id
stringlengths 40
40
| source
stringclasses 9
values | title
stringlengths 2
345
| clean_text
stringlengths 35
1.63M
| raw_text
stringlengths 4
1.63M
| url
stringlengths 4
498
| overview
stringlengths 0
10k
|
|---|---|---|---|---|---|---|
b366aaa050b9bb80c4d39a15152e8e47148f056a | wikidoc | CSMD1 | CSMD1
CSMD1 CUB and Sushi multiple domains 1 is a protein that in humans is encoded by the CSMD1 gene.
# Structure
CSMD1 contains 14 N-terminal CUB domains that are separated from each other by a Sushi domains followed by an additional 15 tandem Sushi domain segment.
# Function
Based on analogy to other proteins that contain Sushi domains, it is believed that the gene product of CSMD1 functions as a Complement control protein.
# Clinical significance
It is a potential tumour suppressor, the deletion of which may result in head and neck carcinomas behaving more aggressively. CSMD1 protein expression was found to be reduced in patients with invasive breast cancer. Functional studies showed that CSMD1 reduction causes cells to transform to a cancer form by increasing their ability to divide, migrate and invade. In a three dimensional model of breast ducts, reduced CSMD1 expression failed breast duct formation. | CSMD1
CSMD1 CUB and Sushi multiple domains 1 is a protein that in humans is encoded by the CSMD1 gene.[1]
# Structure
CSMD1 contains 14 N-terminal CUB domains that are separated from each other by a Sushi domains followed by an additional 15 tandem Sushi domain segment.[2]
# Function
Based on analogy to other proteins that contain Sushi domains, it is believed that the gene product of CSMD1 functions as a Complement control protein.[2]
# Clinical significance
It is a potential tumour suppressor, the deletion of which may result in head and neck carcinomas behaving more aggressively.[3] CSMD1 protein expression was found to be reduced in patients with invasive breast cancer.[4] Functional studies showed that CSMD1 reduction causes cells to transform to a cancer form by increasing their ability to divide, migrate and invade. In a three dimensional model of breast ducts, reduced CSMD1 expression failed breast duct formation.[5] | https://www.wikidoc.org/index.php/CSMD1 | |
bdd4ded37e8d0685508fc36e77078c8f32210c87 | wikidoc | CSPG4 | CSPG4
Chondroitin sulfate proteoglycan 4, also known as melanoma-associated chondroitin sulfate proteoglycan (MCSP) or neuron-glial antigen 2 (NG2), is a chondroitin sulfate proteoglycan that in humans is encoded by the CSPG4 gene.
CSPG4 plays a role in stabilizing cell-substratum interactions during early events of melanoma cell spreading on endothelial basement membranes. It represents an integral membrane chondroitin sulfate proteoglycan expressed by human malignant melanoma cells.
CSPG4/NG2 is also a hallmark protein of oligodendrocyte progenitor cells (OPCs) and OPC dysfunction has been implicated as a candidate pathophysiological mechanism of familial schizophrenia. A research group investigating the role of genetics in schizophrenia, reported, two rare missense mutations in CSPG4 gene, segregating within families (CSPG4A131T and CSPG4V901G mutations). The researchers also demonstrate that the induced pluripotent stem cells (iPSCs)-derived OPCs from CSPG4A131T mutation carriers exhibited abnormal post-translational processing, subcellular localization of the mutant NG2 protein, aberrant cellular morphology, and a decreased cell viability and myelination potential. In vivo diffusion tensor imaging of the brain of CSPG4A131T mutation carriers demonstrated a reduced white matter integrity compared to the unaffected sibling and matched general population controls. | CSPG4
Chondroitin sulfate proteoglycan 4, also known as melanoma-associated chondroitin sulfate proteoglycan (MCSP) or neuron-glial antigen 2 (NG2), is a chondroitin sulfate proteoglycan that in humans is encoded by the CSPG4 gene.[1][2][3]
CSPG4 plays a role in stabilizing cell-substratum interactions during early events of melanoma cell spreading on endothelial basement membranes. It represents an integral membrane chondroitin sulfate proteoglycan expressed by human malignant melanoma cells.[3]
CSPG4/NG2 is also a hallmark protein of oligodendrocyte progenitor cells (OPCs)[4] and OPC dysfunction has been implicated as a candidate pathophysiological mechanism of familial schizophrenia.[5] A research group investigating the role of genetics in schizophrenia, reported, two rare missense mutations in CSPG4 gene, segregating within families (CSPG4A131T and CSPG4V901G mutations). The researchers also demonstrate that the induced pluripotent stem cells (iPSCs)-derived OPCs from CSPG4A131T mutation carriers exhibited abnormal post-translational processing, subcellular localization of the mutant NG2 protein, aberrant cellular morphology, and a decreased cell viability and myelination potential. In vivo diffusion tensor imaging of the brain of CSPG4A131T mutation carriers demonstrated a reduced white matter integrity compared to the unaffected sibling and matched general population controls.[6] | https://www.wikidoc.org/index.php/CSPG4 | |
ec622b3cb94d8361cbec1abc68762017260c6850 | wikidoc | CSRP3 | CSRP3
Cysteine and glycine-rich protein 3 gene codes for the Muscle LIM Protein (MLP) or CSRP3, a small 194 amino acid protein, which is specifically expressed in skeletal muscles and cardiac muscle. Since the identification of MLP, 20 years ago, a multitude of studies have focused on delineating its functional significance.
# Gene
The CSRP3 gene was discovered in rat in 1994. In humans it was mapped to chromosome 11p15.1, where it spans a 20kb genomic region, organized in 6 exons. The full length transcript is 0.8kb, while a splice variant, originating from the alternative splicing of exons 3 and 4, was recently identified and designated MLP-b.
# Structure
MLP contains two LIM domains (LIM1 and LIM2), each being surrounded by glycine-rich regions, and the two separated by more than 50 residues. LIM domains offer a remarkable ability for protein-protein interactions. Furthermore, MLP carries a nuclear localization signal at amino acid positions 64-69 MLP can be acetylated/deacetylated at the position 69 lysine residue (K69), by acetyltransferase (PCAF) and histone deacetylase 4 (HDAC4), respectively. In myocytes, MLP has the ability to oligomerize, forming dimers, trimers and tetramers, an attribute that impacts its interactions, localization and function.
# Protein interactions and localization
MLP has been identified to bind to an increasing list of proteins, exhibiting variable subcellular localization and diverse functional properties. In particular, MLP interacts with proteins at the:
- Z-line, including telethonin (T-cap), alpha-actinin (ACTN), cofilin-2 (CFL2), calcineurin, HDAC4, MLP-b as well as to MLP itself;
- costameres, where it binds to zyxin, integrin linked kinase (ILK) and beta1-spectrin;
- intercalated discs, where it associates with the nebulin-related anchoring protein (NRAP);
- nucleus, where it binds to the transcription factors MyoD, myogenin and MRF4.
M-line as well as plasma membrane localization of MLP has also been observed, however, the protein associations mediating this subcellular distribution are currently unknown.
These diverse localization patterns and binding partners of MLP suggest a multitude of roles relating both to the striated myocyte cytoskeleton and the nucleus. The role of MLP in each of these two cellular compartments appears to be dynamic, with studies demonstrating nucleocytoplasmic shuttling, driven by its nuclear localization signal, over time and under different conditions.
# Functions
In the nucleus, MLP acts as a positive regulator of myogenesis and promotes myogenic differentiation. Overexpression of MLP enhances myotube differentiation, an effect attributed to the direct association of MLP with muscle specific transcription factors such as MyoD, myogenin and MRF4 and consequently the transcriptional control of fundamental muscle-specific genes.
In the cytoplasm, MLP is an important scaffold protein, implicated in various cytoskeletal macromolecular complexes, at the sarcomeric Z-line, the costameres, and the microfilaments. At the Z-line, MLP interacts with different Z-line components and acts as a scaffold protein promoting the assembly of macromolecular complexes along sarcomeres and actin-based cytoskeleton Moreover, since the Z-line acts as a stretch sensor, MLP is believed to be involved in mechano-signaling processes. Indeed, cardiomyocytes from MLP transgenic or knock-out mouse exhibit defective intrinsic stretch responses, due to selective loss of passive stretch sensing.
At the costameres, another region implicated in force transmission, MLP is thought to be contributing in mechanosensing through its interactions with β1 spectrin and zyxin. However, the precise role of MLP at the costameres has not been extensively investigated yet.
At the microfilaments, MLP is implicated in actin remodeling (or actin dynamics) through its interaction with cofilin-2 (CFL2). Binding of MLP to CFL2 enhances the CFL2-dependent F-actin depolymerization, with a recent study demonstrating that MLP can act directly on actin cytoskeleton dynamics through direct binding that stabilizes and crosslinks actin filaments into bundles.
Additionally, MLP is indirectly related to calcium homeostasis and energy metabolism. Specifically, acetylation of MLP increases the calcium sensitivity of myofilaments and regulates contractility, while the absence of MLP causes alterations in calcium signaling (intracellular calcium handling) with defects in excitation-contraction coupling. Furthermore, lack of MLP leads to local loss of mitochondria and energy deficiency.
# Clinical significance
MLP is directly associated with striated muscle diseases. Mutations in the CSRP3 gene have been detected in patients with dilated cardiomyopathy (DCM) , and hypertrophic cardiomyopathy (HCM) , while the most frequent MLP mutation, W4R, has been found in both of these patient populations. Biochemical and functional studies have been performed for some of these mutant proteins, and reveal aberrant localization and interaction patterns, leading to impaired molecular and cellular functions. For example, the W4R mutation abolishes the MLP/T-cap interaction, leading to mislocalization of T-cap, Z-line instability and severe sarcomeric structural defects. The C58G mutation causes reduced protein stability due to enhanced ubiquitin-dependent proteasome degradation while the K69L mutation, which is within the predicted nuclear localization signal of MLP, abolishes the MLP/α-actinin interaction and causes altered subcellular distribution of the mutant protein, showing predominant perinuclear localization.
Alterations in the protein expression levels of MLP, its oligomerization or splicing have also been described in human cardiac and skeletal muscle diseases: both MLP protein levels and oligomerization are down-regulated in human heart failure, while MLP levels are significantly changed in different skeletal myopathies, including facioscapulohumeral muscular dystrophy, nemaline myopathy and limb girdle muscular dystrophy type 2B. Moreover, significant changes in MLP-b protein expression levels, as well as deregulation of the MLP:MLP-b ratio have been detected in limb girdle muscular dystrophy type 2A, Duchenne muscular dystrophy and dermatomyositis patients.
# Animal models
Animal models are providing valuable insight on MLP’s functional significance in striated muscle pathophysiology. Ablation of Mlp (MLP-/-) in mice affects all striated muscles, although the cardiac phenotype is more severe, leading to alterations in cardiac pressure and volume, aberrant contractility, development of dilated cardiomyopathy with hypertrophy and progressive heart failure. At the histological level there is dramatic disruption of the cardiomyocyte cytoarchitecture at multiple levels, and pronounced fibrosis. Other cellular changes included alterations in intracellular calcium handling, local loss of mitochondria and energy deficiency.
Crossing MLP-/- mice with phospholamban (PLN) -/-, or β2-adrenergic receptor (β2-AR) -/-, or angiotensin II type 1a receptor (AT1a) -/-, or β-adrenergic receptor kinase 1 inhibitor (bARK1) -/- mice, as well as overexpressing calcineurin rescued their cardiac function, through a series of only partly understood molecular mechanisms. Conversely crossing MLP-/- mice with β1-adrenergic receptor (β1-AR) -/- mice was lethal, while crossing MLP-/- mice with calcineurin -/- mice, enhanced fibrosis and cardiomyopathy. A gene knockin mouse model harboring the human MLP-W4R mutation developed HCM and heart failure, while ultrastructural analysis of its cardiac tissue revealed myocardial disarray and significant fibrosis, increased nuclear localization of MLP concomitantly with reduced sarcomeric Z-line distribution.
Alterations in MLP nucleocytoplasmic shuttling, which are possibly modulated by changes in its oligomerization status, have also been implicated in hypertrophy and heart failure, independently of mutations.
Studies in Drosophila revealed that genetic ablation of Mlp84B, the Drosophila homolog of MLP, was associated with pupal lethality and impaired muscle function. Mechanical studies of Mlp84B-null flight muscles indicate that loss of Mlp84B results in decreased muscle stiffness and power generation. Cardiac-specific ablation of Mlp84B caused decreased lifespan, impaired diastolic function and disturbances in cardiac rhythm.
Overall, these animal models have provided critical evidence on the functional significance of MLP in striated muscle physiology and pathophysiology. | CSRP3
Cysteine and glycine-rich protein 3 gene codes for the Muscle LIM Protein (MLP) or CSRP3, a small 194 amino acid protein, which is specifically expressed in skeletal muscles and cardiac muscle.[1][2] Since the identification of MLP, 20 years ago,[3] a multitude of studies have focused on delineating its functional significance.
# Gene
The CSRP3 gene was discovered in rat in 1994.[3] In humans it was mapped to chromosome 11p15.1,[4][5] where it spans a 20kb genomic region, organized in 6 exons. The full length transcript is 0.8kb,[4][6] while a splice variant, originating from the alternative splicing of exons 3 and 4, was recently identified and designated MLP-b.[7]
# Structure
MLP contains two LIM domains (LIM1 and LIM2), each being surrounded by glycine-rich regions, and the two separated by more than 50 residues.[8] LIM domains offer a remarkable ability for protein-protein interactions.[9] Furthermore, MLP carries a nuclear localization signal at amino acid positions 64-69 [10] MLP can be acetylated/deacetylated at the position 69 lysine residue (K69), by acetyltransferase (PCAF) and histone deacetylase 4 (HDAC4), respectively.[11] In myocytes, MLP has the ability to oligomerize, forming dimers, trimers and tetramers, an attribute that impacts its interactions, localization and function.[12]
# Protein interactions and localization
MLP has been identified to bind to an increasing list of proteins, exhibiting variable subcellular localization and diverse functional properties. In particular, MLP interacts with proteins at the:
- Z-line, including telethonin (T-cap), alpha-actinin (ACTN), cofilin-2 (CFL2), calcineurin, HDAC4, MLP-b as well as to MLP itself;[6][7][11][13][14][15][16]
- costameres, where it binds to zyxin, integrin linked kinase (ILK) and beta1-spectrin;[13][17][18]
- intercalated discs, where it associates with the nebulin-related anchoring protein (NRAP);[19]
- nucleus, where it binds to the transcription factors MyoD, myogenin and MRF4.[20]
M-line as well as plasma membrane localization of MLP has also been observed, however, the protein associations mediating this subcellular distribution are currently unknown.[12][21]
These diverse localization patterns and binding partners of MLP suggest a multitude of roles relating both to the striated myocyte cytoskeleton and the nucleus.[22] The role of MLP in each of these two cellular compartments appears to be dynamic, with studies demonstrating nucleocytoplasmic shuttling, driven by its nuclear localization signal, over time and under different conditions.[22]
# Functions
In the nucleus, MLP acts as a positive regulator of myogenesis and promotes myogenic differentiation.[3] Overexpression of MLP enhances myotube differentiation, an effect attributed to the direct association of MLP with muscle specific transcription factors such as MyoD, myogenin and MRF4 and consequently the transcriptional control of fundamental muscle-specific genes.[3][7][20]
In the cytoplasm, MLP is an important scaffold protein, implicated in various cytoskeletal macromolecular complexes, at the sarcomeric Z-line, the costameres, and the microfilaments.[6][7][11][13][14][15][16] At the Z-line, MLP interacts with different Z-line components [6][7][11][13][14][15][16][23][24] and acts as a scaffold protein promoting the assembly of macromolecular complexes along sarcomeres and actin-based cytoskeleton [6][17][19][25][26] Moreover, since the Z-line acts as a stretch sensor,[27][28][29][30] MLP is believed to be involved in mechano-signaling processes. Indeed, cardiomyocytes from MLP transgenic or knock-out mouse exhibit defective intrinsic stretch responses, due to selective loss of passive stretch sensing.[6][21]
At the costameres, another region implicated in force transmission, MLP is thought to be contributing in mechanosensing through its interactions with β1 spectrin and zyxin. However, the precise role of MLP at the costameres has not been extensively investigated yet.
At the microfilaments, MLP is implicated in actin remodeling (or actin dynamics) through its interaction with cofilin-2 (CFL2). Binding of MLP to CFL2 enhances the CFL2-dependent F-actin depolymerization,[14] with a recent study demonstrating that MLP can act directly on actin cytoskeleton dynamics through direct binding that stabilizes and crosslinks actin filaments into bundles.[31]
Additionally, MLP is indirectly related to calcium homeostasis and energy metabolism. Specifically, acetylation of MLP increases the calcium sensitivity of myofilaments and regulates contractility,[11] while the absence of MLP causes alterations in calcium signaling (intracellular calcium handling) with defects in excitation-contraction coupling.[32][33][34] Furthermore, lack of MLP leads to local loss of mitochondria and energy deficiency.[35]
# Clinical significance
MLP is directly associated with striated muscle diseases. Mutations in the CSRP3 gene have been detected in patients with dilated cardiomyopathy (DCM) [e.g. G72R and K69R], and hypertrophic cardiomyopathy (HCM) [e.g. L44P, S46R, S54R/E55G, C58G, R64C, Y66C, Q91L, K42/fs165], while the most frequent MLP mutation, W4R, has been found in both of these patient populations.[6][10][21][36][37][38][39] Biochemical and functional studies have been performed for some of these mutant proteins, and reveal aberrant localization and interaction patterns, leading to impaired molecular and cellular functions. For example, the W4R mutation abolishes the MLP/T-cap interaction, leading to mislocalization of T-cap, Z-line instability and severe sarcomeric structural defects.[6] The C58G mutation causes reduced protein stability due to enhanced ubiquitin-dependent proteasome degradation[36] while the K69L mutation, which is within the predicted nuclear localization signal of MLP, abolishes the MLP/α-actinin interaction and causes altered subcellular distribution of the mutant protein, showing predominant perinuclear localization.[39]
Alterations in the protein expression levels of MLP, its oligomerization or splicing have also been described in human cardiac and skeletal muscle diseases: both MLP protein levels and oligomerization are down-regulated in human heart failure,[12][15] while MLP levels are significantly changed in different skeletal myopathies, including facioscapulohumeral muscular dystrophy, nemaline myopathy and limb girdle muscular dystrophy type 2B.[40][41][42] Moreover, significant changes in MLP-b protein expression levels, as well as deregulation of the MLP:MLP-b ratio have been detected in limb girdle muscular dystrophy type 2A, Duchenne muscular dystrophy and dermatomyositis patients.[7]
# Animal models
Animal models are providing valuable insight on MLP’s functional significance in striated muscle pathophysiology. Ablation of Mlp (MLP-/-) in mice affects all striated muscles, although the cardiac phenotype is more severe, leading to alterations in cardiac pressure and volume, aberrant contractility, development of dilated cardiomyopathy with hypertrophy and progressive heart failure.[26][32][43] At the histological level there is dramatic disruption of the cardiomyocyte cytoarchitecture at multiple levels, and pronounced fibrosis.[19][26][34][44] Other cellular changes included alterations in intracellular calcium handling, local loss of mitochondria and energy deficiency.[32][33][34]
Crossing MLP-/- mice with phospholamban (PLN) -/-, or β2-adrenergic receptor (β2-AR) -/-, or angiotensin II type 1a receptor (AT1a) -/-, or β-adrenergic receptor kinase 1 inhibitor (bARK1) -/- mice, as well as overexpressing calcineurin rescued their cardiac function, through a series of only partly understood molecular mechanisms.[45][46][47][48][49] Conversely crossing MLP-/- mice with β1-adrenergic receptor (β1-AR) -/- mice was lethal, while crossing MLP-/- mice with calcineurin -/- mice, enhanced fibrosis and cardiomyopathy.[45][46] A gene knockin mouse model harboring the human MLP-W4R mutation developed HCM and heart failure, while ultrastructural analysis of its cardiac tissue revealed myocardial disarray and significant fibrosis, increased nuclear localization of MLP concomitantly with reduced sarcomeric Z-line distribution.[21]
Alterations in MLP nucleocytoplasmic shuttling, which are possibly modulated by changes in its oligomerization status, have also been implicated in hypertrophy and heart failure, independently of mutations.[12][22]
Studies in Drosophila revealed that genetic ablation of Mlp84B, the Drosophila homolog of MLP, was associated with pupal lethality and impaired muscle function.[23] Mechanical studies of Mlp84B-null flight muscles indicate that loss of Mlp84B results in decreased muscle stiffness and power generation.[50] Cardiac-specific ablation of Mlp84B caused decreased lifespan, impaired diastolic function and disturbances in cardiac rhythm.[51]
Overall, these animal models have provided critical evidence on the functional significance of MLP in striated muscle physiology and pathophysiology. | https://www.wikidoc.org/index.php/CSRP3 | |
592e083698acf07b1605f7f8e1d62738faa8f06a | wikidoc | CSTF2 | CSTF2
Cleavage stimulation factor 64 kDa subunit is a protein that in humans is encoded by the CSTF2 gene.
This gene encodes a nuclear protein with an RRM (RNA recognition motif) domain. The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3' end cleavage and polyadenylation of pre-mRNAs. Specifically, this protein binds GU-rich elements within the 3'-untranslated region of mRNAs.
# Interactions
CSTF2 has been shown to interact with CSTF3, SUB1, SYMPK, BARD1 and BRCA1. | CSTF2
Cleavage stimulation factor 64 kDa subunit is a protein that in humans is encoded by the CSTF2 gene.[1][2]
This gene encodes a nuclear protein with an RRM (RNA recognition motif) domain. The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3' end cleavage and polyadenylation of pre-mRNAs. Specifically, this protein binds GU-rich elements within the 3'-untranslated region of mRNAs.[2]
# Interactions
CSTF2 has been shown to interact with CSTF3,[3] SUB1,[4] SYMPK,[3] BARD1[5][6] and BRCA1.[5][6] | https://www.wikidoc.org/index.php/CSTF2 | |
eed981658839e8ece0325d07d07667bee51cd528 | wikidoc | CTBP1 | CTBP1
C-terminal-binding protein 1 also known as CtBP1 is a protein that in humans is encoded by the CTBP1 gene.
# Function
The CtBP1 protein was originally identified as a human protein that bound a PLDLS motif in the C-terminus of adenovirus E1A proteins. It and the related protein CTBP2 were later shown to function as transcriptional corepressors. That is, regulatory proteins that bind to sequence-specific DNA-binding proteins and help turn genes off. CtBPs do this by recruiting histone modifying enzymes that add repressive histone marks and remove activating marks. CtBP proteins can also self-associate and presumably bring together gene regulatory complexes.
CtBP1 is broadly expressed from embryo to adult, while CtBP2 has a somewhat more restricted pattern of expression. CtBPs have multiple biological roles and appear to be most important in regulating the epithelial to mesenchymal transition, as well as influencing metabolism. They do the latter by binding NADH in preference to NAD+, thereby sensing the NADH/NAD+ ratio. When bound it undergoes a conformational change that allows it to dimerize and associate with its partner proteins and silence specific genes.
During skeletal and T cell development, CtBP1 and CtBP2 associate with the PLDLSL domain of δEF1, a cellular zinc finger-homeodomain protein, and thereby enhances δEF1-induced transcriptional silencing. CtBP also binds the Kruppel-like factors family of zinc finger proteins KLF3, KLF8 and KLF12. In addition, CtBP complexes with CtIP, a 125 kDa protein that recognizes distinctly different protein motifs from CtBP. CtIP binds to the BRCT repeats within the breast cancer gene BRCA1 and enables CtBP to influence BRCA1 activity. Both proteins can also interact with a polycomb group protein complex which participates in regulation of gene expression during development. Alternative splicing of transcripts from this gene results in multiple transcript variants.
# Interactions
CTBP1 has been shown to interact with:
- ACTL6B,
- ARF,
- EVI1
- FOXP2,
- HDAC1,
- IKZF1,
- IKZF4,
- KLF3,
- KLF8,
- Mdm2,
- MLL,
- NRIP1,
- Pinin,
- RBBP8, and
- TGIF1.
- GATA1. | CTBP1
C-terminal-binding protein 1 also known as CtBP1 is a protein that in humans is encoded by the CTBP1 gene.[1]
# Function
The CtBP1 protein was originally identified as a human protein that bound a PLDLS motif in the C-terminus of adenovirus E1A proteins. It and the related protein CTBP2 were later shown to function as transcriptional corepressors.[2] That is, regulatory proteins that bind to sequence-specific DNA-binding proteins and help turn genes off. CtBPs do this by recruiting histone modifying enzymes that add repressive histone marks and remove activating marks. CtBP proteins can also self-associate and presumably bring together gene regulatory complexes.[3]
CtBP1 is broadly expressed from embryo to adult, while CtBP2 has a somewhat more restricted pattern of expression. CtBPs have multiple biological roles and appear to be most important in regulating the epithelial to mesenchymal transition, as well as influencing metabolism. They do the latter by binding NADH in preference to NAD+, thereby sensing the NADH/NAD+ ratio. When bound it undergoes a conformational change that allows it to dimerize and associate with its partner proteins and silence specific genes.
During skeletal and T cell development, CtBP1 and CtBP2 associate with the PLDLSL domain of δEF1, a cellular zinc finger-homeodomain protein, and thereby enhances δEF1-induced transcriptional silencing. CtBP also binds the Kruppel-like factors family of zinc finger proteins KLF3, KLF8 and KLF12. In addition, CtBP complexes with CtIP, a 125 kDa protein that recognizes distinctly different protein motifs from CtBP. CtIP binds to the BRCT repeats within the breast cancer gene BRCA1 and enables CtBP to influence BRCA1 activity. Both proteins can also interact with a polycomb group protein complex which participates in regulation of gene expression during development. Alternative splicing of transcripts from this gene results in multiple transcript variants.[4]
# Interactions
CTBP1 has been shown to interact with:
- ACTL6B,[5]
- ARF,[6]
- EVI1[7][8]
- FOXP2,[9]
- HDAC1,[10][11][12]
- IKZF1,[13]
- IKZF4,[14]
- KLF3,[2]
- KLF8,[15]
- Mdm2,[16]
- MLL,[17]
- NRIP1,[18][19]
- Pinin,[20]
- RBBP8,[1][21] and
- TGIF1.[11]
- GATA1.[22][23] | https://www.wikidoc.org/index.php/CTBP1 | |
d018776237845fd8af9471da4b2aaded3dbf5c90 | wikidoc | CTBP2 | CTBP2
C-terminal-binding protein 2 also known as CtBP2 is a protein that in humans is encoded by the CTBP2 gene.
# Function
The CtBPs - CtBP1 and CtBP2 in mammals - are among the best characterized transcriptional corepressors. They typically turn their target genes off. They do this by binding to sequence-specific DNA-binding proteins that carry a short motif of the general form Proline-Isoleucine-Aspartate-Leucine-Serine (the PIDLS motif). They then recruit histone modifying enzymes, histone deacetylases, histone methylases and histone demethylases. These enzymes are thought to work together to remove activating and add repressive histone marks. For example, histone deacetylase 1 (HDAC1) and HDAC2 can remove the activating mark histone 3 acetyl lysine 9 (H3K9Ac), then the histone methylase G9a can add methyl groups, while the histone demethylase lysine specific demethylase 1 (LSD1) can remove the activating mark H3K4me.
The CtBPs bind to many different DNA-binding proteins and also bind to co-repressors that are themselves bound to DNA-binding proteins, such as Friend of GATA (Fog). CtBPs can also dimerize and multimerize to bridge larger transcriptional complexes. They appear to be primarily scaffold proteins that allow the assembly of gene repression complexes.
One interesting aspect of CtBPs is their ability to bind to NADH and to a lesser extent NAD+. It has been proposed that this will enable them to sense the metabolic status of the cell and to regulate genes in response to changes in the NADH/NAD+ ratio. Accordingly, CtBPs have been found to be important in fat biology, binding to key proteins such as PRDM16, NRIP, and FOG2.
The full functional roles of CtBP proteins in mammals have been difficult to evaluate because of partial redundancy between CtBP1 and CtBP2. Similarly, the early lethality of the CtBP2 knockout and of double knockout mice has precluded detailed analysis of the cellular effects of deleting these proteins. Important results have emerged from model organisms where there is only a single CtBP gene. In Drosophila CtBP is involved in development and in circadian rhythms. In the worm C. elegans CtBP is involved in life span. Both circadian rhythms and life span appear to be linked to metabolism supporting the role for CtBPs in metabolic sensing.
The mammalian CtBP2 gene produces alternative transcripts encoding two distinct proteins. In addition to the transcriptional repressor (corepressor) discussed above, there is a longer isoform that is a major component of specialized synapses known as synaptic ribbons. Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases. A portion of the 3'-untranslated region was used to map this gene to chromosome 21q21.3; however, it was noted that similar loci elsewhere in the genome are likely. Blast analysis shows that this gene is present on chromosome 10.
# Interactions
CTBP2 has been shown to interact with:
- FHL3,
- KLF3,
- KLF8,
- Mdm2,
- NRIP1,
- SOX6, and
- ZFPM2. | CTBP2
C-terminal-binding protein 2 also known as CtBP2 is a protein that in humans is encoded by the CTBP2 gene.[1][2][3]
# Function
The CtBPs - CtBP1 and CtBP2 in mammals - are among the best characterized transcriptional corepressors.[4] They typically turn their target genes off. They do this by binding to sequence-specific DNA-binding proteins that carry a short motif of the general form Proline-Isoleucine-Aspartate-Leucine-Serine (the PIDLS motif). They then recruit histone modifying enzymes, histone deacetylases, histone methylases and histone demethylases. These enzymes are thought to work together to remove activating and add repressive histone marks. For example, histone deacetylase 1 (HDAC1) and HDAC2 can remove the activating mark histone 3 acetyl lysine 9 (H3K9Ac), then the histone methylase G9a can add methyl groups, while the histone demethylase lysine specific demethylase 1 (LSD1) can remove the activating mark H3K4me.[5]
The CtBPs bind to many different DNA-binding proteins and also bind to co-repressors that are themselves bound to DNA-binding proteins, such as Friend of GATA (Fog).[6] CtBPs can also dimerize and multimerize to bridge larger transcriptional complexes. They appear to be primarily scaffold proteins that allow the assembly of gene repression complexes.
One interesting aspect of CtBPs is their ability to bind to NADH and to a lesser extent NAD+. It has been proposed that this will enable them to sense the metabolic status of the cell and to regulate genes in response to changes in the NADH/NAD+ ratio. Accordingly, CtBPs have been found to be important in fat biology, binding to key proteins such as PRDM16, NRIP, and FOG2.[7]
The full functional roles of CtBP proteins in mammals have been difficult to evaluate because of partial redundancy between CtBP1 and CtBP2.[8] Similarly, the early lethality of the CtBP2 knockout and of double knockout mice has precluded detailed analysis of the cellular effects of deleting these proteins. Important results have emerged from model organisms where there is only a single CtBP gene. In Drosophila CtBP is involved in development and in circadian rhythms.[9] In the worm C. elegans CtBP is involved in life span.[10] Both circadian rhythms and life span appear to be linked to metabolism supporting the role for CtBPs in metabolic sensing.
The mammalian CtBP2 gene produces alternative transcripts encoding two distinct proteins. In addition to the transcriptional repressor (corepressor) discussed above, there is a longer isoform that is a major component of specialized synapses known as synaptic ribbons. Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases. A portion of the 3'-untranslated region was used to map this gene to chromosome 21q21.3; however, it was noted that similar loci elsewhere in the genome are likely. Blast analysis shows that this gene is present on chromosome 10.[3]
# Interactions
CTBP2 has been shown to interact with:
- FHL3,[11]
- KLF3,[1][11]
- KLF8,[12]
- Mdm2,[13]
- NRIP1,[14][15]
- SOX6,[16] and
- ZFPM2.[17] | https://www.wikidoc.org/index.php/CTBP2 | |
51bd9f397763dac665fd4f486b31f40afb60b31f | wikidoc | CTDP1 | CTDP1
RNA polymerase II subunit A C-terminal domain phosphatase is an enzyme that in humans is encoded by the CTDP1 gene.
This gene encodes a protein which interacts with the carboxy-terminus of transcription initiation factor TFIIF, a transcription factor which regulates elongation as well as initiation by RNA polymerase II. The protein may also represent a component of an RNA polymerase II holoenzyme complex. Alternative splicing of this gene results in two transcript variants encoding 2 different isoforms.
# Interactions
CTDP1 has been shown to interact with WD repeat-containing protein 77, GTF2F1 and POLR2A. | CTDP1
RNA polymerase II subunit A C-terminal domain phosphatase is an enzyme that in humans is encoded by the CTDP1 gene.[1][2][3]
This gene encodes a protein which interacts with the carboxy-terminus of transcription initiation factor TFIIF, a transcription factor which regulates elongation as well as initiation by RNA polymerase II. The protein may also represent a component of an RNA polymerase II holoenzyme complex. Alternative splicing of this gene results in two transcript variants encoding 2 different isoforms.[3]
# Interactions
CTDP1 has been shown to interact with WD repeat-containing protein 77,[4] GTF2F1[2] and POLR2A.[5] | https://www.wikidoc.org/index.php/CTDP1 | |
99149ca3aa7801db8af55bb1c66753e024f9745d | wikidoc | CUL4B | CUL4B
Cullin-4B is a protein that in humans is encoded by the CUL4B gene which is located on the X chromosome. CUL4B has high sequence similarity with CUL4A, with which it shares certain E3 ubiquitin ligase functions. CUL4B is largely expressed in the nucleus and regulates several key functions including: cell cycle progression, chromatin remodeling and neurological and placental development in mice. In humans, CUL4B has been implicated in X-linked intellectual disability and is frequently mutated in pancreatic adenocarcinomas and a small percentage of various lung cancers. Viruses such as HIV can also co-opt CUL4B-based complexes to promote viral pathogenesis. CUL4B complexes containing Cereblon are also targeted by the teratogenic drug thalidomide.
# Structure
Human CUL4B is 913 amino acids long and shares a high degree of sequence identity (84%) with CUL4A with the exception of its unique N-terminal region. The extreme N-terminus of CUL4B is disordered and, currently, it is unclear what structural and functional qualities it possesses. CUL4B binds to the beta-propeller of the DDB1 adaptor protein which interacts with numerous DDB1-CUL4-Associated Factors (DCAFs). This interaction is crucial for the recruitment of substrates to the ubiquitin ligase complex. At the C-terminal end, CUL4B interacts with the RBX1/ROC1 protein via its RING domain. RBX1 is a core component of Cullin-RING ubiquitin ligase (CRL) complexes and functions to recruit E2 ubiquitin conjugating enzymes. Therefore, the C-terminus of CUL4B - along with RBX1 and activated E2 enzymes - compose the catalytic core of CRL4B complexes. CUL4B is also modified by covalent attachment of a NEDD8 molecule at a highly conserved lysine residue in the C-terminal region. This modification appears to induce conformational changes which promotes flexibility in the RING domain of cullin proteins and enhanced ubiquitin ligase activity.
# Functions
## Cell cycle regulation and chromatin remodeling
CUL4B-based E3 ubiquitin ligase complexes often demonstrate overlapping activity with CUL4A-based complexes. Both CRL4 complexes utilize Cdt2 and the DNA processivity factor PCNA to induce the ubiquitination and degradation of replication licensing factor Cdt1 and cyclin-dependent kinase inhibitor p21 in a proteasome-dependent manner. CRL4Cdt2 also degrades PCNA-bound PR-Set7/SET8, which is a histone 4 methyltransferase, and the p12 subunit of DNA polymerase δ, which is crucial for DNA replication. As a result, CRL4 complexes are able to control the onset of DNA replication, chromatin remodeling and progression through the cell cycle.
## Mammalian embryonic development
Loss of Cul4b in mice causes embryonic lethality and defects in placental development. The extra-embryonic tissue of these developing mice also showed increased rates of apoptosis and a decrease in cell proliferation. When Cul4b deletion was limited to the epiblast (only in Sox2-expressing tissue), it was possible to generate living mice.
## Neurological development
Mice that do not express CUL4B in epiblast tissue demonstrate normal brain morphology but decrease number of parvalbumin (PV)-positive GABAergic interneurons - particularly in the dentate gyrus. In these mice, certain dendritic features of hippocampal neurons were also affected by Cul4b loss, which may explain the observed increases in epileptic susceptibility and spatial learning defects. These phenotypes resembled features seen in patients with X-linked intellectual disability (see below).
# Clinical significance
## X-linked intellectual disability
Loss-of-function CUL4B mutation events have been discovered in numerous patients with X-linked intellectual disability , which is characterized by aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus and tremor. CUL4B mutations have also been associated with malformations of cortical development.
## Viral pathogenesis
After HIV infects a cell, the virus "hijacks" either the CUL4B-DDB1 complex or the CUL4A-DDB1 complex via the same mechanism. Essentially, HIV proteins such as Vpr and Vpx bind to VPRBP (a DDB1-binding substrate receptor protein) and induce the ubiquitination and degradation of SAMHD1 and UNG2 to promote viral replication. These proteins are not degraded by CRL4 complexes in the absence of virus.
## Cancer
According to data from The Cancer Genome Atlas, CUL4B is mutated in 21% of pancreatic carcinomas with a recurring truncating mutation at amino acid 143. CUL4B is also mutated or amplified in 3-5% of lung cancers. The significance of these observed mutations has not been determined.
## Thalidomide treatment
In 2010, Ito et al. reported that Cereblon, a DCAF protein, was a major target of the teratogenic compound thalidomide. Thalidomide and other derivatives such as pomalidomide and lenalidomide are known as immunomodulatory drugs (or IMiDs) and have been investigated as therapeutic agents for autoimmune diseases and several cancers - particularly myelomas. Recent reports show that IMiDs bind to CRL4CRBN and promote the degradation of IKZN1 and IKZN3 transcription factors, which are not normally targeted by CRL4 complexes.
# Interactions and substrates
Human CUL4B forms direct interactions with:
- RBX1
- CAND1
- DDB1 and
- the COP9 signalosome
Human CUL4B-DDB1-RBX1 complexes promote the ubiquitination of:
- Cdt1
- p21
- PR-Set7/SET8
- p12 subunit of DNA polymerase δ
- SAMHD1†
- UNG2†
- IKZF1§
- IKZF3§
†protein is a CRL4 substrate only when directed by viral proteins
§protein is a CRL4 substrate only when directed by IMiDs
# Notes | CUL4B
Cullin-4B is a protein that in humans is encoded by the CUL4B gene which is located on the X chromosome.[1][2] CUL4B has high sequence similarity with CUL4A, with which it shares certain E3 ubiquitin ligase functions. CUL4B is largely expressed in the nucleus and regulates several key functions including: cell cycle progression, chromatin remodeling and neurological and placental development in mice. In humans, CUL4B has been implicated in X-linked intellectual disability and is frequently mutated in pancreatic adenocarcinomas and a small percentage of various lung cancers. Viruses such as HIV can also co-opt CUL4B-based complexes to promote viral pathogenesis. CUL4B complexes containing Cereblon are also targeted by the teratogenic drug thalidomide.
# Structure
Human CUL4B is 913 amino acids long and shares a high degree of sequence identity (84%) with CUL4A with the exception of its unique N-terminal region.[3] The extreme N-terminus of CUL4B is disordered and, currently, it is unclear what structural and functional qualities it possesses. CUL4B binds to the beta-propeller of the DDB1 adaptor protein which interacts with numerous DDB1-CUL4-Associated Factors (DCAFs). This interaction is crucial for the recruitment of substrates to the ubiquitin ligase complex. At the C-terminal end, CUL4B interacts with the RBX1/ROC1 protein via its RING domain. RBX1 is a core component of Cullin-RING ubiquitin ligase (CRL) complexes and functions to recruit E2 ubiquitin conjugating enzymes. Therefore, the C-terminus of CUL4B - along with RBX1 and activated E2 enzymes - compose the catalytic core of CRL4B complexes. CUL4B is also modified by covalent attachment of a NEDD8 molecule at a highly conserved lysine residue in the C-terminal region. This modification appears to induce conformational changes which promotes flexibility in the RING domain of cullin proteins and enhanced ubiquitin ligase activity.[4]
# Functions
## Cell cycle regulation and chromatin remodeling
CUL4B-based E3 ubiquitin ligase complexes often demonstrate overlapping activity with CUL4A-based complexes. Both CRL4 complexes utilize Cdt2 and the DNA processivity factor PCNA to induce the ubiquitination and degradation of replication licensing factor Cdt1 and cyclin-dependent kinase inhibitor p21 in a proteasome-dependent manner.[5][6] CRL4Cdt2 also degrades PCNA-bound PR-Set7/SET8, which is a histone 4 methyltransferase, and the p12 subunit of DNA polymerase δ, which is crucial for DNA replication.[7][8] As a result, CRL4 complexes are able to control the onset of DNA replication, chromatin remodeling and progression through the cell cycle.
## Mammalian embryonic development
Loss of Cul4b in mice causes embryonic lethality and defects in placental development. The extra-embryonic tissue of these developing mice also showed increased rates of apoptosis and a decrease in cell proliferation. When Cul4b deletion was limited to the epiblast (only in Sox2-expressing tissue), it was possible to generate living mice.[9]
## Neurological development
Mice that do not express CUL4B in epiblast tissue demonstrate normal brain morphology but decrease number of parvalbumin (PV)-positive GABAergic interneurons - particularly in the dentate gyrus.[10] In these mice, certain dendritic features of hippocampal neurons were also affected by Cul4b loss, which may explain the observed increases in epileptic susceptibility and spatial learning defects. These phenotypes resembled features seen in patients with X-linked intellectual disability (see below).
# Clinical significance
## X-linked intellectual disability
Loss-of-function CUL4B mutation events have been discovered in numerous patients with X-linked intellectual disability , which is characterized by aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus and tremor.[11][12][13] CUL4B mutations have also been associated with malformations of cortical development.[14]
## Viral pathogenesis
After HIV infects a cell, the virus "hijacks" either the CUL4B-DDB1 complex or the CUL4A-DDB1 complex via the same mechanism. Essentially, HIV proteins such as Vpr and Vpx bind to VPRBP (a DDB1-binding substrate receptor protein) and induce the ubiquitination and degradation of SAMHD1 and UNG2 to promote viral replication.[15] These proteins are not degraded by CRL4 complexes in the absence of virus.
## Cancer
According to data from The Cancer Genome Atlas, CUL4B is mutated in 21% of pancreatic carcinomas with a recurring truncating mutation at amino acid 143. CUL4B is also mutated or amplified in 3-5% of lung cancers. The significance of these observed mutations has not been determined.
## Thalidomide treatment
In 2010, Ito et al. reported that Cereblon, a DCAF protein, was a major target of the teratogenic compound thalidomide.[16] Thalidomide and other derivatives such as pomalidomide and lenalidomide are known as immunomodulatory drugs (or IMiDs) and have been investigated as therapeutic agents for autoimmune diseases and several cancers - particularly myelomas. Recent reports show that IMiDs bind to CRL4CRBN and promote the degradation of IKZN1 and IKZN3 transcription factors, which are not normally targeted by CRL4 complexes.[17][18]
# Interactions and substrates
Human CUL4B forms direct interactions with:
- RBX1[19]
- CAND1[20]
- DDB1[21] and
- the COP9 signalosome[22]
Human CUL4B-DDB1-RBX1 complexes promote the ubiquitination of:
- Cdt1[5][23]
- p21[6][24]
- PR-Set7/SET8[7]
- p12 subunit of DNA polymerase δ[8]
- SAMHD1†[15]
- UNG2†[15]
- IKZF1§[17][18]
- IKZF3§[17][18]
†protein is a CRL4 substrate only when directed by viral proteins
§protein is a CRL4 substrate only when directed by IMiDs
# Notes | https://www.wikidoc.org/index.php/CUL4B | |
76643b5bbc159905cb1cf9cc9dc367885c987f92 | wikidoc | CUTL1 | CUTL1
Cux1 (CUTL1, CDP, CDP/Cux) is a homeodomain protein that in humans is encoded by the CUX1 gene.
# Function
The protein encoded by this gene is a member of the homeodomain family of DNA binding proteins. It regulates gene expression, morphogenesis, and differentiation and it also plays a role in cell cycle progression, particularly at S-phase. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined, and the p200 isoform of Cux1 is processed proteolytically to smaller active isoforms, such as p110. Cux1 DNA binding is stimulated by activation of the PAR2/F2RL1 cell-surface G-protein-coupled receptor in fibroblasts and breast-cancer epithelial cells to regulate Matrix metalloproteinase 10, Interleukin1-alpha, and Cyclo-oxygenase 2 (COX2) genes.
# Role in tumor growth
Genetic data from over 7,600 cancer patients shows that over 1% has the deactivated CUX1 which links to progression of tumor growth. Researchers from the Wellcome Trust Sanger Institute reported that the mutation of CUX1 reduces the inhibitory effects of a biological inhibitor, PIK3IP1 (phosphoinositide-3-kinase interacting protein 1), resulted in higher activity of the growth promoting enzyme, phosphoinositide 3-kinase (PI3K) which leads to tumor progression. Although CUX1 is mutated at a lower rate compared to other known gene mutations that cause cancer, this deactivated gene is found across many cancer types in this study to be the underlying cause of the disease.
# CASP
Tne CUX1 gene Alternatively Spliced Product was first reported in 1997. The CUX1 gene has up to 33 exons. CASP mRNA includes exons 1 through 14 and 25 through 33. The human CASP protein is predicted to contain 678 amino acids, of which 400 are shared with CUTL1. CASP protein is approximately 80 kD. It lacks the DNA binding region of CUTL1, but instead contains a trans-membrane domain that allows it to insert into lipid bilayers. It has been localized to the Golgi apparatus.
CASP has been reported to be part of a complex with Golgin 84 that tethers COPI vesicles and is important for retrograde transport in the Golgi and between the Golgi and endoplasmic reticulum. The targeting of vesicles involves tethers and SNAREs.
# Interactions
Cux1 (CUTL1, CDP, CDP/Cux) has been shown to interact with:
- CREB binding protein,
- Retinoblastoma protein, and
- SATB1
These physical interactions are reported in BioPlex 2.0
- MAGEA10
- EXT2
- RAB30
- HLA-DQA1
- STX6
- WDR83
- SLC39A4
- LAMP1
- POTEB
- SLC39A12
# Notes
- ↑ This CASP is not the same as the scaffolding protein called CASP for Cytohesin/ARNO ... Scaffolding Protein | CUTL1
Cux1 (CUTL1, CDP, CDP/Cux) is a homeodomain protein that in humans is encoded by the CUX1 gene.[1][2][3][4]
# Function
The protein encoded by this gene is a member of the homeodomain family of DNA binding proteins. It regulates gene expression, morphogenesis, and differentiation and it also plays a role in cell cycle progression, particularly at S-phase. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined, and the p200 isoform of Cux1 is processed proteolytically to smaller active isoforms, such as p110.[4] Cux1 DNA binding is stimulated by activation of the PAR2/F2RL1 cell-surface G-protein-coupled receptor in fibroblasts and breast-cancer epithelial cells to regulate Matrix metalloproteinase 10, Interleukin1-alpha, and Cyclo-oxygenase 2 (COX2) genes.[5]
# Role in tumor growth
Genetic data from over 7,600 cancer patients shows that over 1% has the deactivated CUX1 which links to progression of tumor growth. Researchers from the Wellcome Trust Sanger Institute reported that the mutation of CUX1 reduces the inhibitory effects of a biological inhibitor, PIK3IP1 (phosphoinositide-3-kinase interacting protein 1), resulted in higher activity of the growth promoting enzyme, phosphoinositide 3-kinase (PI3K) which leads to tumor progression. Although CUX1 is mutated at a lower rate compared to other known gene mutations that cause cancer, this deactivated gene is found across many cancer types in this study to be the underlying cause of the disease.[6][7]
# CASP
Tne CUX1 gene Alternatively Spliced Product was first reported in 1997.[9][lower-alpha 1] The CUX1 gene has up to 33 exons. CASP mRNA includes exons 1 through 14 and 25 through 33.[11] The human CASP protein is predicted to contain 678 amino acids, of which 400 are shared with CUTL1.[9] CASP protein is approximately 80 kD.[9] It lacks the DNA binding region of CUTL1,[9][12] but instead contains a trans-membrane domain that allows it to insert into lipid bilayers.[12] It has been localized to the Golgi apparatus.[12]
CASP has been reported to be part of a complex with Golgin 84 that tethers COPI vesicles and is important for retrograde transport in the Golgi and between the Golgi and endoplasmic reticulum.[13] The targeting of vesicles involves tethers and SNAREs.[13]
# Interactions
Cux1 (CUTL1, CDP, CDP/Cux) has been shown to interact with:
- CREB binding protein,[14]
- Retinoblastoma protein,[15] and
- SATB1[16]
These physical interactions are reported in BioPlex 2.0
- MAGEA10
- EXT2
- RAB30
- HLA-DQA1
- STX6
- WDR83
- SLC39A4
- LAMP1
- POTEB
- SLC39A12
# Notes
- ↑ This CASP is not the same as the scaffolding protein called CASP[10] for Cytohesin/ARNO ... Scaffolding Protein | https://www.wikidoc.org/index.php/CUTL1 | |
e840ce6790a120db98f2488da8e0965945221d38 | wikidoc | CXCL1 | CXCL1
The chemokine (C-X-C motif) ligand 1 (CXCL1) is a small cytokine belonging to the CXC chemokine family that was previously called GRO1 oncogene, GROα, KC, neutrophil-activating protein 3 (NAP-3) and melanoma growth stimulating activity, alpha (MGSA-α). In humans, this protein is encoded by the Cxcl1.
# Function
CXCL1 is secreted by human melanoma cells, has mitogenic properties and is implicated in melanoma pathogenesis.
CXCL1 is expressed by macrophages, neutrophils and epithelial cells, and has neutrophil chemoattractant activity. CXCL1 plays a role in spinal cord development by inhibiting the migration of oligodendrocyte precursors and is involved in the processes of angiogenesis, arteriogenesis, inflammation, wound healing, and tumorigenesis.
This chemokine elicits its effects by signaling through the chemokine receptor CXCR2. The gene for CXCL1 is located on human chromosome 4 amongst genes for other CXC chemokines. An initial study in mice showed evidence that CXCL1 decreased the severity of multiple sclerosis and may offer a neuro-protective function. | CXCL1
The chemokine (C-X-C motif) ligand 1 (CXCL1) is a small cytokine belonging to the CXC chemokine family that was previously called GRO1 oncogene, GROα, KC, neutrophil-activating protein 3 (NAP-3) and melanoma growth stimulating activity, alpha (MGSA-α). In humans, this protein is encoded by the Cxcl1.[1]
# Function
CXCL1 is secreted by human melanoma cells, has mitogenic properties and is implicated in melanoma pathogenesis.[2][3]
CXCL1 is expressed by macrophages, neutrophils and epithelial cells,[4][5] and has neutrophil chemoattractant activity.[6][7] CXCL1 plays a role in spinal cord development by inhibiting the migration of oligodendrocyte precursors and is involved in the processes of angiogenesis, arteriogenesis, inflammation, wound healing, and tumorigenesis.[8][9][10][11][12]
This chemokine elicits its effects by signaling through the chemokine receptor CXCR2.[8] The gene for CXCL1 is located on human chromosome 4 amongst genes for other CXC chemokines.[13] An initial study in mice showed evidence that CXCL1 decreased the severity of multiple sclerosis and may offer a neuro-protective function.[14] | https://www.wikidoc.org/index.php/CXCL1 | |
263baa29ea56c80026e57e566c9a6b3b3071f388 | wikidoc | CXCL5 | CXCL5
C-X-C motif chemokine 5 (CXCL5 or ENA78) is a protein that in humans is encoded by the CXCL5 gene.
# Function
The protein encoded by this gene, CXCL5 is a small cytokine belonging to the CXC chemokine family that is also known as epithelial-derived neutrophil-activating peptide 78 (ENA-78). It is produced following stimulation of cells with the inflammatory cytokines interleukin-1 or tumor necrosis factor-alpha. Expression of CXCL5 has also been observed in eosinophils, and can be inhibited with the type II interferon IFN-γ. This chemokine stimulates the chemotaxis of neutrophils possessing angiogenic properties. It elicits these effects by interacting with the cell surface chemokine receptor CXCR2. The gene for CXCL5 is encoded on four exons and is located on human chromosome 4 amongst several other CXC chemokine genes. CXCL5 has been implicated in connective tissue remodelling. CXCL5 has been also described to regulate neutrophil homeostasis.
# Clinical significance
CXCL5 plays a role in reducing sensitivity to sunburn pain in some subjects, and is a "potential target which can be utilized to understand more about pain in other inflammatory conditions like arthritis and cystitis.". CXCL5 is well known to have chemotactic and activating functions on neutrophil, mainly during acute inflammatory responses. However CXCL5 expression is also higher in atherosclerosis (a chronic inflammatory condition) but is not associated with neutrophil infiltration. Instead CXCL5 has a protective role in atherosclerosis by directly controlling macrophage foam cell formation. | CXCL5
C-X-C motif chemokine 5 (CXCL5 or ENA78) is a protein that in humans is encoded by the CXCL5 gene.[1][2]
# Function
The protein encoded by this gene, CXCL5 is a small cytokine belonging to the CXC chemokine family that is also known as epithelial-derived neutrophil-activating peptide 78 (ENA-78). It is produced following stimulation of cells with the inflammatory cytokines interleukin-1 or tumor necrosis factor-alpha.[3] Expression of CXCL5 has also been observed in eosinophils, and can be inhibited with the type II interferon IFN-γ.[4] This chemokine stimulates the chemotaxis of neutrophils possessing angiogenic properties. It elicits these effects by interacting with the cell surface chemokine receptor CXCR2.[4] The gene for CXCL5 is encoded on four exons and is located on human chromosome 4 amongst several other CXC chemokine genes.[3][5] CXCL5 has been implicated in connective tissue remodelling.[4] CXCL5 has been also described to regulate neutrophil homeostasis.[6]
# Clinical significance
CXCL5 plays a role in reducing sensitivity to sunburn pain in some subjects, and is a "potential target which can be utilized to understand more about pain in other inflammatory conditions like arthritis and cystitis.".[7] CXCL5 is well known to have chemotactic and activating functions on neutrophil, mainly during acute inflammatory responses. However CXCL5 expression is also higher in atherosclerosis (a chronic inflammatory condition) but is not associated with neutrophil infiltration. Instead CXCL5 has a protective role in atherosclerosis by directly controlling macrophage foam cell formation.[8] | https://www.wikidoc.org/index.php/CXCL5 | |
e1d798df4b8b6f4a2f4072c8e3396dfee6a2c042 | wikidoc | CXCL9 | CXCL9
Chemokine (C-X-C motif) ligand 9 (CXCL9) is a small cytokine belonging to the CXC chemokine family that is also known as Monokine induced by gamma interferon (MIG). CXCL9 is a T-cell chemoattractant, which is induced by IFN-γ. It is closely related to two other CXC chemokines called CXCL10 and CXCL11, whose genes are located near the gene for CXCL9 on human chromosome 4. CXCL9, CXCL10 and CXCL11 all elicit their chemotactic functions by interacting with the chemokine receptor CXCR3.
Neutrophil collagenase/matrix metalloproteinase 8 (MMP-8) degrades CXCL9 and cleaves CXCL10 at two positions.
Gelatinase B/matrix metalloproteinase 9 (MMP-9) degrades CXCL10 and cleaves CXCL9 at three different sites in its extended carboxy-terminal region.
# Biomarkers
CXCL9, -10, -11 have proven to be valid biomarkers for the development of heart failure and left ventricular dysfunction, suggesting an underlining pathophysiological relation between levels of these chemokines and the development of adverse cardiac remodeling.
This chemokine has also been associated as a biomarker for diagnosing Q fever infections.
# Interactions
CXCL9 has been shown to interact with CXCR3. | CXCL9
Chemokine (C-X-C motif) ligand 9 (CXCL9) is a small cytokine belonging to the CXC chemokine family that is also known as Monokine induced by gamma interferon (MIG). CXCL9 is a T-cell chemoattractant, which is induced by IFN-γ. It is closely related to two other CXC chemokines called CXCL10 and CXCL11, whose genes are located near the gene for CXCL9 on human chromosome 4.[1][2] CXCL9, CXCL10 and CXCL11 all elicit their chemotactic functions by interacting with the chemokine receptor CXCR3.[3]
Neutrophil collagenase/matrix metalloproteinase 8 (MMP-8) degrades CXCL9 and cleaves CXCL10 at two positions.
Gelatinase B/matrix metalloproteinase 9 (MMP-9) degrades CXCL10 and cleaves CXCL9 at three different sites in its extended carboxy-terminal region.
# Biomarkers
CXCL9, -10, -11 have proven to be valid biomarkers for the development of heart failure and left ventricular dysfunction, suggesting an underlining pathophysiological relation between levels of these chemokines and the development of adverse cardiac remodeling.[4][5]
This chemokine has also been associated as a biomarker for diagnosing Q fever infections.[6]
# Interactions
CXCL9 has been shown to interact with CXCR3.[7][8] | https://www.wikidoc.org/index.php/CXCL9 | |
ad6a23c4ebf337814b0f6cf7a540076d7827be94 | wikidoc | CXCR3 | CXCR3
Chemokine receptor CXCR3 is a Gαi protein-coupled receptor in the CXC chemokine receptor family. Other names for CXCR3 are G protein-coupled receptor 9 (GPR9) and CD183. There are three isoforms of CXCR3 in humans: CXCR3-A, CXCR3-B and chemokine receptor 3-alternative (CXCR3-alt). CXCR3-A binds to the CXC chemokines CXCL9 (MIG), CXCL10 (IP-10), and CXCL11 (I-TAC) whereas CXCR3-B can also bind to CXCL4 in addition to CXCL9, CXCL10, and CXCL11.
# Expression
CXCR3 is expressed primarily on activated T lymphocytes and NK cells, and some epithelial cells. CXCR3 and CCR5 are preferentially expressed on Th1 cells, whereas Th2 cells favor the expression of CCR3 and CCR4. CXCR3 ligands that attract Th1 cells can concomitantly block the migration of Th2 cells in response to CCR3 ligands, thus enhancing the polarization of effector T cell recruitment.
# Signal transduction
Binding of CXCL9, CXCL10, and CXCL11 to CXCR3 is able to elicit increases in intracellular Ca2++ levels and activate phosphoinositide 3-kinase and mitogen-activated protein kinase (MAPK). Detailed signaling pathway has not yet been established, but may include the same enzymes that were identified in the signaling cascade induced by other chemokine receptors.
# Function
CXCR3 is able to regulate leukocyte trafficking. Binding of chemokines to CXCR3 induces various cellular responses, most notably integrin activation, cytoskeletal changes and chemotactic migration. CXCR3-ligand interaction attracts Th1 cells and promotes Th1 cell maturation.
As a consequence of chemokine-induced cellular desensitization (phosphorylation-dependent receptor internalization), cellular responses are typically rapid and short in duration. Cellular responsiveness is restored after dephosphorylation of intracellular receptors and subsequent recycling to the cell surface. A hallmark of CXCR3 is its prominent expression in in vitro cultured effector/memory T cells, and in T cells present in many types of inflamed tissues. In addition, CXCL9, CXCL10 and CXCL11 are commonly produced by local cells in inflammatory lesion, suggesting that CXCR3 and its chemokines participate in the recruitment of inflammatory cells. Additionally, CXCR3 has been implicated in wound healing.
# Clinical significance
CXCR3 has been implicated in the following diseases atherosclerosis, multiple sclerosis, pulmonary fibrosis, type 1 diabetes, autoimmune myasthenia gravis, nephrotoxic nephritis, acute cardiac allograft rejection, allergic contact dermatitis, and possibly Celiac Disease. Development of agents to block CXCR3-ligand interactions may provide new ways to treat these diseases.
# Cardiovascular implications
Evidence from pre-clinical and clinical investigations has revealed the involvement of CXCR3 and its ligands in several cardiovascular diseases (CVDs) of diverse etiologies including atherosclerosis, hypertension, Kawasaki disease, myocarditis, dilated cardiomyopathies, Chagas, cardiac hypertrophy and heart failure, as well as in heart transplant rejection and transplant coronary artery disease (CAD).
CXCL9-10-11 have been recognized to be valid biomarkers for the development of heart failure and left ventricular dysfunction in two pilot studies, suggesting an underlining correlation between levels of the interferon (IFN)-γ-inducible chemokines and the development of adverse cardiac remodeling.
# Pharmacology
Recent reports indicate that there is a significant interest for the identification of small-molecule antagonists of CXCR3. Several small molecules were found to constitute a promising series of functional antagonists of CXCR3 that could be developed into new therapeutic agents for the treatment of inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and diabetes. More recently the first QSAR study concerning antagonists of CXCR3 has been published in the literature. The in silico model provides a time- and cost-effective tool for the screening of existing and virtual libraries of small molecules as well as for designing of novel molecules of desired activity. | CXCR3
Chemokine receptor CXCR3 is a Gαi protein-coupled receptor in the CXC chemokine receptor family. Other names for CXCR3 are G protein-coupled receptor 9 (GPR9) and CD183. There are three isoforms of CXCR3 in humans: CXCR3-A, CXCR3-B and chemokine receptor 3-alternative (CXCR3-alt).[1] CXCR3-A binds to the CXC chemokines CXCL9 (MIG), CXCL10 (IP-10), and CXCL11 (I-TAC)[2] whereas CXCR3-B can also bind to CXCL4 in addition to CXCL9, CXCL10, and CXCL11.[3]
# Expression
CXCR3 is expressed primarily on activated T lymphocytes and NK cells,[4] and some epithelial cells. CXCR3 and CCR5 are preferentially expressed on Th1 cells, whereas Th2 cells favor the expression of CCR3 and CCR4. CXCR3 ligands that attract Th1 cells can concomitantly block the migration of Th2 cells in response to CCR3 ligands, thus enhancing the polarization of effector T cell recruitment.
# Signal transduction
Binding of CXCL9, CXCL10, and CXCL11 to CXCR3 is able to elicit increases in intracellular Ca2++ levels and activate phosphoinositide 3-kinase and mitogen-activated protein kinase (MAPK).[5] Detailed signaling pathway has not yet been established, but may include the same enzymes that were identified in the signaling cascade induced by other chemokine receptors.
# Function
CXCR3 is able to regulate leukocyte trafficking. Binding of chemokines to CXCR3 induces various cellular responses, most notably integrin activation, cytoskeletal changes and chemotactic migration. CXCR3-ligand interaction attracts Th1 cells and promotes Th1 cell maturation.
As a consequence of chemokine-induced cellular desensitization (phosphorylation-dependent receptor internalization), cellular responses are typically rapid and short in duration. Cellular responsiveness is restored after dephosphorylation of intracellular receptors and subsequent recycling to the cell surface. A hallmark of CXCR3 is its prominent expression in in vitro cultured effector/memory T cells, and in T cells present in many types of inflamed tissues. In addition, CXCL9, CXCL10 and CXCL11 are commonly produced by local cells in inflammatory lesion, suggesting that CXCR3 and its chemokines participate in the recruitment of inflammatory cells.[6] Additionally, CXCR3 has been implicated in wound healing.[7]
# Clinical significance
CXCR3 has been implicated in the following diseases atherosclerosis,[8] multiple sclerosis,[9] pulmonary fibrosis,[10] type 1 diabetes,[11] autoimmune myasthenia gravis, nephrotoxic nephritis,[12] acute cardiac allograft rejection[13], allergic contact dermatitis,[14] and possibly Celiac Disease.[15] Development of agents to block CXCR3-ligand interactions may provide new ways to treat these diseases.
# Cardiovascular implications
Evidence from pre-clinical and clinical investigations has revealed the involvement of CXCR3 and its ligands in several cardiovascular diseases (CVDs) of diverse etiologies including atherosclerosis, hypertension, Kawasaki disease, myocarditis, dilated cardiomyopathies, Chagas, cardiac hypertrophy and heart failure, as well as in heart transplant rejection and transplant coronary artery disease (CAD).[1][16]
CXCL9-10-11 have been recognized to be valid biomarkers for the development of heart failure and left ventricular dysfunction in two pilot studies, suggesting an underlining correlation between levels of the interferon (IFN)-γ-inducible chemokines and the development of adverse cardiac remodeling.[17]
[18]
# Pharmacology
Recent reports indicate that there is a significant interest for the identification of small-molecule antagonists of CXCR3.[19] Several small molecules [20] were found to constitute a promising series of functional antagonists of CXCR3 that could be developed into new therapeutic agents for the treatment of inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and diabetes. More recently the first QSAR study concerning antagonists of CXCR3 has been published in the literature. The in silico model provides a time- and cost-effective tool for the screening of existing and virtual libraries of small molecules as well as for designing of novel molecules of desired activity.[21] | https://www.wikidoc.org/index.php/CXCR3 | |
f4e48949132585bf87443acec11bb14a6277b211 | wikidoc | CXCR4 | CXCR4
C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the CXCR4 gene.
# Function
CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. CXCR4 is one of several chemokine receptors that HIV can use to infect CD4+ T cells. HIV isolates that use CXCR4 are traditionally known as T-cell tropic isolates. Typically, these viruses are found late in infection. It is unclear as to whether the emergence of CXCR4-using HIV is a consequence or a cause of immunodeficiency.
CXCR4 is upregulated during the implantation window in natural and hormone replacement therapy cycles in the endometrium, producing, in presence of a human blastocyst, a surface polarization of the CXCR4 receptors suggesting that this receptor is implicated in the adhesion phase of human implantation.
CXCR4's ligand SDF-1 is known to be important in hematopoietic stem cell homing to the bone marrow and in hematopoietic stem cell quiescence. It has been also shown that CXCR4 signalling regulates the expression of CD20 on B cells. Until recently, SDF-1 and CXCR4 were believed to be a relatively monogamous ligand-receptor pair (other chemokines are promiscuous, tending to use several different chemokine receptors). Recent evidence demonstrates ubiquitin is also a natural ligand of CXCR4. Ubiquitin is a small (76-amino acid) protein highly conserved among eukaryotic cells. It is best known for its intracellular role in targeting ubiquitylated proteins for degradation via the ubiquitin proteasome system. Evidence in numerous animal models suggests ubiquitin is anti-inflammatory immune modulator and endogenous opponent of proinflammatory damage associated molecular pattern molecules. It is speculated this interaction may be through CXCR4 mediated signalling pathways. MIF is an additional ligand of CXCR4
CXCR4 is present in newly generated neurons during embryogenesis and adult life where it plays a role in neuronal guidance. The levels of the receptor decrease as neurons mature. CXCR4 mutant mice have aberrant neuronal distribution. This has been implicated in disorders such as epilepsy.
# Clinical significance
Drugs that block the CXCR4 receptor appear to be capable of "mobilizing" hematopoietic stem cells into the bloodstream as peripheral blood stem cells. Peripheral blood stem cell mobilization is very important in hematopoietic stem cell transplantation (as a recent alternative to transplantation of surgically harvested bone marrow) and is currently performed using drugs such as G-CSF. G-CSF is a growth factor for neutrophils (a common type of white blood cells), and may act by increasing the activity of neutrophil-derived proteases such as neutrophil elastase in the bone marrow leading to proteolytic degradation of SDF-1. Plerixafor (AMD3100) is a drug, approved for routine clinical use, which directly blocks the CXCR4 receptor. It is a very efficient inducer of hematopoietic stem cell mobilization in animal and human studies. In a small human clinical trial to evaluate the safety and efficacy of fucoidan ingestion (brown seaweed extract), 3g daily of 75% w/w oral fucoidan for 12 days increased the proportion of CD34+CXCR4+ from 45 to 90% and the serum SDF-1 levels, which could be useful in CD34+ cells homing/mobilization via SDF-1/CXCR4 axis.
It has been associated with WHIM syndrome. WHIM like mutations in CXCR4 were recently identified in patients with Waldenstrom's macroglobulinemia, a B-cell malignancy. The presence of CXCR4 WHIM mutations has been associated with clinical resistance to ibrutinib in patients with Waldenstrom's Macroglobulinemia.
While CXCR4’s expression is low or absent in many healthy tissues, it was demonstrated to be expressed in over 23 types of cancer, including breast cancer, ovarian cancer, melanoma, and prostate cancer. Expression of this receptor in cancer cells has been linked to metastasis to tissues containing a high concentration of CXCL12, such as lungs, liver and bone marrow. However, in breast cancer where SDF1/CXCL12 is also expressed by the cancer cells themselves along with CXCR4, CXCL12 expression is positively correlated with disease free (metastasis free) survival. CXCL12 (over-)expressing cancers might not sense the CXCL12 gradient released from the metastasis target tissues since the receptor, CXCR4, is saturated with the ligand produced in an autocrine manner. Another explanation of this observation is provided by a study that shows the ability of CXCL12 (and CCL2) producing tumors to entrain neutrophils that inhibit seeding of tumor cells in the lung.
# Drug response
Chronic exposure to THC has been shown to increase T lymphocyte CXCR4 expression on both CD4+ and CD8+ T lymphocytes in rhesus macaques. It has been shown that BCR signalling inhibitors also affect CXCR4 pathway and thus CD20 expression.
# Interactions
CXCR4 has been shown to interact with USP14. | CXCR4
C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the CXCR4 gene.[1][2]
# Function
CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. CXCR4 is one of several chemokine receptors that HIV can use to infect CD4+ T cells. HIV isolates that use CXCR4 are traditionally known as T-cell tropic isolates. Typically, these viruses are found late in infection. It is unclear as to whether the emergence of CXCR4-using HIV is a consequence or a cause of immunodeficiency.
CXCR4 is upregulated during the implantation window in natural and hormone replacement therapy cycles in the endometrium, producing, in presence of a human blastocyst, a surface polarization of the CXCR4 receptors suggesting that this receptor is implicated in the adhesion phase of human implantation.
CXCR4's ligand SDF-1 is known to be important in hematopoietic stem cell homing to the bone marrow and in hematopoietic stem cell quiescence. It has been also shown that CXCR4 signalling regulates the expression of CD20 on B cells. Until recently, SDF-1 and CXCR4 were believed to be a relatively monogamous ligand-receptor pair (other chemokines are promiscuous, tending to use several different chemokine receptors). Recent evidence demonstrates ubiquitin is also a natural ligand of CXCR4.[3] Ubiquitin is a small (76-amino acid) protein highly conserved among eukaryotic cells. It is best known for its intracellular role in targeting ubiquitylated proteins for degradation via the ubiquitin proteasome system. Evidence in numerous animal models suggests ubiquitin is anti-inflammatory immune modulator and endogenous opponent of proinflammatory damage associated molecular pattern molecules.[4] It is speculated this interaction may be through CXCR4 mediated signalling pathways. MIF is an additional ligand of CXCR4[5]
CXCR4 is present in newly generated neurons during embryogenesis and adult life where it plays a role in neuronal guidance. The levels of the receptor decrease as neurons mature. CXCR4 mutant mice have aberrant neuronal distribution. This has been implicated in disorders such as epilepsy.[6]
# Clinical significance
Drugs that block the CXCR4 receptor appear to be capable of "mobilizing" hematopoietic stem cells into the bloodstream as peripheral blood stem cells. Peripheral blood stem cell mobilization is very important in hematopoietic stem cell transplantation (as a recent alternative to transplantation of surgically harvested bone marrow) and is currently performed using drugs such as G-CSF. G-CSF is a growth factor for neutrophils (a common type of white blood cells), and may act by increasing the activity of neutrophil-derived proteases such as neutrophil elastase in the bone marrow leading to proteolytic degradation of SDF-1. Plerixafor (AMD3100) is a drug, approved for routine clinical use,[7] which directly blocks the CXCR4 receptor. It is a very efficient inducer of hematopoietic stem cell mobilization in animal and human studies. In a small human clinical trial to evaluate the safety and efficacy of fucoidan ingestion (brown seaweed extract), 3g daily of 75% w/w oral fucoidan for 12 days increased the proportion of CD34+CXCR4+ from 45 to 90% and the serum SDF-1 levels, which could be useful in CD34+ cells homing/mobilization via SDF-1/CXCR4 axis.[8]
It has been associated with WHIM syndrome.[9] WHIM like mutations in CXCR4 were recently identified in patients with Waldenstrom's macroglobulinemia, a B-cell malignancy.[10] The presence of CXCR4 WHIM mutations has been associated with clinical resistance to ibrutinib in patients with Waldenstrom's Macroglobulinemia.[11]
While CXCR4’s expression is low or absent in many healthy tissues, it was demonstrated to be expressed in over 23 types of cancer, including breast cancer, ovarian cancer, melanoma, and prostate cancer. Expression of this receptor in cancer cells has been linked to metastasis to tissues containing a high concentration of CXCL12, such as lungs, liver and bone marrow.[12][13] However, in breast cancer where SDF1/CXCL12 is also expressed by the cancer cells themselves along with CXCR4, CXCL12 expression is positively correlated with disease free (metastasis free) survival. CXCL12 (over-)expressing cancers might not sense the CXCL12 gradient released from the metastasis target tissues since the receptor, CXCR4, is saturated with the ligand produced in an autocrine manner.[14] Another explanation of this observation is provided by a study that shows the ability of CXCL12 (and CCL2) producing tumors to entrain neutrophils that inhibit seeding of tumor cells in the lung.[15]
# Drug response
Chronic exposure to THC has been shown to increase T lymphocyte CXCR4 expression on both CD4+ and CD8+ T lymphocytes in rhesus macaques.[16] It has been shown that BCR signalling inhibitors also affect CXCR4 pathway and thus CD20 expression.
# Interactions
CXCR4 has been shown to interact with USP14.[17] | https://www.wikidoc.org/index.php/CXCR4 | |
42294de23a34d09b63a9002ca94dc61be0f3ed23 | wikidoc | CYR61 | CYR61
Cysteine-rich angiogenic inducer 61 (CYR61) or CCN family member 1 (CCN1), is a matricellular protein that in humans is encoded by the CYR61 gene.
CYR61 is a secreted, extracellular matrix (ECM)-associated signaling protein of the CCN family (CCN intercellular signaling protein). CYR61 is capable of regulating a broad range of cellular activities, including cell adhesion, migration, proliferation, differentiation, apoptosis, and senescence through interaction with cell surface integrin receptors and heparan sulfate proteoglycans. During embryonic development, CYR61 is critical for cardiac septal morphogenesis, blood vessel formation in placenta, and vascular integrity. In adulthood CYR61 plays important roles in inflammation and tissue repair, and is associated with diseases related to chronic inflammation, including rheumatoid arthritis, atherosclerosis, diabetes-related nephropathy and retinopathy, and many different forms of cancers.
# CCN protein family
CYR61 was first identified as a protein encoded by a serum-inducible gene in mouse fibroblasts. Other highly conserved homologs were later identified to comprise the CCN protein family (CCN intercellular signaling protein). The CCN acronym is derived from the first three members of the family identified, namely CYR61 (CCN1), CTGF (connective tissue growth factor, or CCN2), and NOV (nephroblastoma overexpressed, or CCN3). These proteins, together with WISP1 (CCN4), WISP2 (CCN5), and WISP3 (CCN6) comprise the six members of the family in vertebrates and have been renamed CCN1-6 in order of their discovery by international consensus. CCN proteins function as matricellular proteins, which are extracellular matrix proteins that play regulatory roles, particularly in the context of wound repair.
# Gene structure and regulation
CYR61 is located at human chromosome 1p22.3, whereas the mouse Cyr61 gene is located at chromosome 3, 72.9cM. The mouse CYR61 coding region spans ~3.2 Kb, containing 5 exons interspaced with 4 introns. The first exon encodes 5’-UTR sequence and the first several amino acids in the secretory signal peptide. The remaining four exons each encode a distinct CCN1 domain. The 5th exon also contains the 3’-UTR sequences, which has 5 copies of AU-rich elements that confers a short mRNA half life, and a mir-155 target site.
The CYR61 promoter is a TATA box containing promoter, with binding sites for many transcription factors including AP1, ATF, E2F, HNF3b, NF1, NFκB, SP1, and SRF, and 2 poly(CA) stretches that may form Z-DNA structure. Transcriptional activation of CYR61 is exquisitely sensitive to a wide range of environmental perturbations, including stimulation by platelet-derived growth factor and basic fibroblast growth factor, transforming growth factor β1 (TGF-β1), growth hormone, the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), cAMP, vitamin D3, estrogen and tamoxifen, angiotensin II, hypoxia, UV light, and mechanical stretch.
# Protein structure and function
## Structural domains
Full-length CYR61 protein contains 381 amino acids with an N-terminal secretory signal peptide followed by four structurally distinct domains. The four CYR61 domains are, from N- to C-termini, the insulin-like growth factor binding protein (IGFBP) domain, von Willebrand type C repeats (vWC) domain, thrombospondin type 1 repeat domain (TSR), and the C-terminal (CT) domain that contains a cysteine-knot motif. CCN1 has unusually high cysteine residue content (10% or 38 in total). The number and spacing of cysteine residues are completely conserved among CYR61 (CCN1), CTGF (CCN2), NOV (CCN3), and WISP-1 (CCN4), and are largely conserved with WISP-2 (CCN5), which lacks precisely the CT domain, and WISP3 (CCN6), which lacks 4 cysteines in the vWC domain. CYR61 is glycosylated, although the regulation and function of gylcosylation are unknown.
## Integrin binding
CYR61 binds directly to various integrin receptors in a cell type-dependent manner, including integrin αvβ3 in endothelial cells, α6β1 and heparan sulfate proteoglycans (HSPGs) in fibroblasts and smooth muscle cells αIIbβ3 in activated platelets, αMβ2 in monocytes and macrophages, and αDβ2 in macrophage foam cells. Where examined, syndecan-4 has been identified as the HSPG critical for CCN1 functions. The CYR61 binding sites for some of these integrins have been mapped (Figure 1). Due to the cell type specificity of integrin expression, CYR61 acts through distinct integrins to mediate specific functions in different types of cells. For example, CYR61 induces angiogenic functions in endothelial cells through αvβ3, and in fibroblasts promotes cellular senescence and enables TNFα to induce apoptosis through binding to α6β1-HSPGs. However, CYR61 supports cell adhesion through all of the integrins identified above.
## Cell signaling and function
As a cell adhesive substrate, CYR61 induces the activation of focal adhesion kinase, paxillin, RAC, and sustained activation of MAPK/ERK1-2. In macrophages, CYR61 also activates the transcription factor NFκB and stimulates M1 polarization. CYR61 activates Akt signaling in thymic epithelial cells, promoting their proliferation and thus thymic size growth. CYR61 has potent angiogenic activity upon endothelial cells and induces neovascularization, first demonstrated in a corneal micropocket implant assay and subsequently confirmed in a rabbit ischemic hindlimb model. CYR61 also accelerates and promotes the chondrogenic differentiation of mouse limb bud mesenchymal cells, and stimulates osteoblast differentiation but inhibits osteoclastogenesis. Cyr61 is a strong inducer of reactive oxygen species accumulation in fibroblastic cells, and this activity underlies many CYR61-induced apoptosis and senescence. CYR61 is able to support cell adhesion, stimulate cell migration, promote growth factor-induced cell proliferation and differentiation in some cell types, promote apoptosis in synergy with TNF family cytokines, and induce cellular senescence in fibroblasts.
# Embryonic development
During embryo development in mice, Cyr61 is highly expressed in the cardiovascular, skeletal, and neuronal systems. Cyr61 knockout mice are embryonic lethal due to defects in cardiac septal morphogenesis, deficient blood vessel formation in placenta, and compromised vascular integrity. In Xenopus laevis, Cyr61 is required for normal gastrulation and modulation of Wnt signaling.
# Clinical relevance
CYR61 is highly expressed at sites of inflammation and wound repair, and is associated with diseases involving chronic inflammation and tissue injury.
## Wound healing and fibrosis
In skin wound healing, CYR61 is highly expressed in the granulation tissue by myofibroblasts, which proliferate and rapidly synthesize ECM to maintain tissue integrity and to promote regeneration of parenchymal cells. However, excessive matrix deposition can lead to fibrosis, scarring, and loss of tissue function. In skin wounds, CYR61 accumulates in the granulation tissue as myofibroblasts proliferate, and eventually reaches a sufficiently high level to drive the myofibroblasts themselves into senescence, whereupon these cells cease to proliferate and express matrix-degrading enzymes. Thus, CYR61 limits synthesis and deposition of ECM by myofibroblasts, reducing the risk of fibrosis during wound healing. In addition to skin wound healing, CYR61 expression is elevated in remodeling cardiomyocytes after myocardial infarction, in vascular injury, and in the long bones during fracture repair. Blockade of CYR61 by antibodies inhibits bone fracture healing in mice. In the kidney, CYR61 is expressed in podocytes in normal adult and embryonic glomeruli, but expression is decreased in IgA nephropathy, diabetic nephropathy, and membranous nephropathy, particularly in diseased kidneys with severe mesangial expansion.
## Inflammation
CYR61 promotes the apoptotic functions of inflammatory cytokines such as TNFα, FasL, and TRAIL. It also reprograms macrophages towards M1 polarization through αMβ2-mediated activation of NF-κB. CYR61 is upregulated in patients with Crohn's disease and ulcerative colitis. CYR61 supports the patrolling behavior of murine resident Ly6Clow monocytes along the endothelial in the steady state and is required for their accumulation under viral-mimicking vascular inflammation.
## Arthritis
CYR61 is highly expressed in collagen-induced arthritis in rodents, and inhibition of CCN1 expression correlates with suppression of inflammatory arthritis. CYR61 is also found in articular cartilage from patients with osteoarthritis and appears to suppress ADAMTS4 (aggrecanase) activity, possibly leading to cartilage cell (chondrocyte) cloning.
## Vascular diseases
CYR61 is overexpressed in vascular smooth muscle cells of atherosclerotic lesions and in the neointima of restenosis after balloon angioplasty, both in rodent models and in humans. Suppression of CYR61 expression results in reduced neointimal hyperplasia after balloon angioplasty, an effect that is reversed by delivery of CYR61 via gene transfer In a mouse model of oxygen-induced retinopathy, expression of CYR61 in the vitreous humor produced significant beneficial effects in repairing damaged vasculature.
## Cancer
Angiogenesis is essential for the supply of oxygen and nutrients to nourish the growing tumor. CYR61 is a powerful angiogenic inducer in vivo, and it can also promote cancer cell proliferation, invasion, survival, epithelial–mesenchymal transition, and metastasis. Accordingly, forced overexpression of CYR61 enhanced tumor growth in xenografts of breast cancer cells, prostate cancer cells, ovarian carcinoma cells, and squamous carcinoma cells. Clinically, CYR61 expression correlates with the tumor stage, tumor size, lymph node positivity, and poor prognosis in several cancers, including breast cancer, prostate cancer, glioma, gastric adenocarcinoma, and squamous cell carcinoma.
However, CYR61 can also induce apoptosis and cellular senescence, two well-established mechanisms of tumor suppression Thus, whereas CYR61 can promote the proliferation of prostate cancer cells, it can also exacerbate apoptosis of these cells in the presence of the immune surveillance molecule TRAIL. CYR61 has an inhibitory effect on some cancers, and suppresses tumor growth of non-small-cell lung cancer (NSCLC) cells, endometrial adenocarcinoma cells, and in melanoma cells. | CYR61
Cysteine-rich angiogenic inducer 61 (CYR61) or CCN family member 1 (CCN1), is a matricellular protein that in humans is encoded by the CYR61 gene.[1]
CYR61 is a secreted, extracellular matrix (ECM)-associated signaling protein of the CCN family (CCN intercellular signaling protein).[2][3] CYR61 is capable of regulating a broad range of cellular activities, including cell adhesion, migration, proliferation, differentiation, apoptosis, and senescence through interaction with cell surface integrin receptors and heparan sulfate proteoglycans. During embryonic development, CYR61 is critical for cardiac septal morphogenesis, blood vessel formation in placenta, and vascular integrity. In adulthood CYR61 plays important roles in inflammation and tissue repair, and is associated with diseases related to chronic inflammation, including rheumatoid arthritis, atherosclerosis, diabetes-related nephropathy and retinopathy, and many different forms of cancers.
# CCN protein family
CYR61 was first identified as a protein encoded by a serum-inducible gene in mouse fibroblasts.[2][4] Other highly conserved homologs were later identified to comprise the CCN protein family (CCN intercellular signaling protein).[5][6][7] The CCN acronym is derived from the first three members of the family identified, namely CYR61 (CCN1), CTGF (connective tissue growth factor, or CCN2), and NOV (nephroblastoma overexpressed, or CCN3). These proteins, together with WISP1 (CCN4), WISP2 (CCN5), and WISP3 (CCN6) comprise the six members of the family in vertebrates and have been renamed CCN1-6 in order of their discovery by international consensus.[8] CCN proteins function as matricellular proteins, which are extracellular matrix proteins that play regulatory roles, particularly in the context of wound repair.[9]
# Gene structure and regulation
CYR61 is located at human chromosome 1p22.3, whereas the mouse Cyr61 gene is located at chromosome 3, 72.9cM.[10] The mouse CYR61 coding region spans ~3.2 Kb, containing 5 exons interspaced with 4 introns.[11] The first exon encodes 5’-UTR sequence and the first several amino acids in the secretory signal peptide. The remaining four exons each encode a distinct CCN1 domain. The 5th exon also contains the 3’-UTR sequences, which has 5 copies of AU-rich elements that confers a short mRNA half life, and a mir-155 target site.[12]
The CYR61 promoter is a TATA box containing promoter, with binding sites for many transcription factors including AP1, ATF, E2F, HNF3b, NF1, NFκB, SP1, and SRF, and 2 poly(CA) stretches that may form Z-DNA structure. Transcriptional activation of CYR61 is exquisitely sensitive to a wide range of environmental perturbations, including stimulation by platelet-derived growth factor and basic fibroblast growth factor, transforming growth factor β1 (TGF-β1), growth hormone, the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), cAMP, vitamin D3, estrogen and tamoxifen, angiotensin II, hypoxia, UV light, and mechanical stretch.[3][7]
# Protein structure and function
## Structural domains
Full-length CYR61 protein contains 381 amino acids with an N-terminal secretory signal peptide followed by four structurally distinct domains.[13] The four CYR61 domains are, from N- to C-termini, the insulin-like growth factor binding protein (IGFBP) domain, von Willebrand type C repeats (vWC) domain, thrombospondin type 1 repeat domain (TSR), and the C-terminal (CT) domain that contains a cysteine-knot motif. CCN1 has unusually high cysteine residue content (10% or 38 in total). The number and spacing of cysteine residues are completely conserved among CYR61 (CCN1), CTGF (CCN2), NOV (CCN3), and WISP-1 (CCN4), and are largely conserved with WISP-2 (CCN5), which lacks precisely the CT domain, and WISP3 (CCN6), which lacks 4 cysteines in the vWC domain. CYR61 is glycosylated, although the regulation and function of gylcosylation are unknown.
## Integrin binding
CYR61 binds directly to various integrin receptors in a cell type-dependent manner, including integrin αvβ3 in endothelial cells,[14] α6β1 and heparan sulfate proteoglycans (HSPGs) in fibroblasts and smooth muscle cells[15][16] αIIbβ3 in activated platelets,[17] αMβ2 in monocytes and macrophages,[18][19] and αDβ2 in macrophage foam cells.[20] Where examined, syndecan-4 has been identified as the HSPG critical for CCN1 functions.[21][22] The CYR61 binding sites for some of these integrins have been mapped (Figure 1). Due to the cell type specificity of integrin expression, CYR61 acts through distinct integrins to mediate specific functions in different types of cells. For example, CYR61 induces angiogenic functions in endothelial cells through αvβ3,[23] and in fibroblasts promotes cellular senescence and enables TNFα to induce apoptosis through binding to α6β1-HSPGs.[22][24] However, CYR61 supports cell adhesion through all of the integrins identified above.
## Cell signaling and function
As a cell adhesive substrate, CYR61 induces the activation of focal adhesion kinase, paxillin, RAC, and sustained activation of MAPK/ERK1-2.[25] In macrophages, CYR61 also activates the transcription factor NFκB and stimulates M1 polarization.[19] CYR61 activates Akt signaling in thymic epithelial cells, promoting their proliferation and thus thymic size growth.[26] CYR61 has potent angiogenic activity upon endothelial cells and induces neovascularization, first demonstrated in a corneal micropocket implant assay[27] and subsequently confirmed in a rabbit ischemic hindlimb model.[28] CYR61 also accelerates and promotes the chondrogenic differentiation of mouse limb bud mesenchymal cells,[29] and stimulates osteoblast differentiation but inhibits osteoclastogenesis.[30][31][32] Cyr61 is a strong inducer of reactive oxygen species accumulation in fibroblastic cells, and this activity underlies many CYR61-induced apoptosis and senescence.[22][24] CYR61 is able to support cell adhesion, stimulate cell migration, promote growth factor-induced cell proliferation and differentiation in some cell types, promote apoptosis in synergy with TNF family cytokines, and induce cellular senescence in fibroblasts.
# Embryonic development
During embryo development in mice, Cyr61 is highly expressed in the cardiovascular, skeletal, and neuronal systems.[33][34] Cyr61 knockout mice are embryonic lethal due to defects in cardiac septal morphogenesis, deficient blood vessel formation in placenta, and compromised vascular integrity.[35][36] In Xenopus laevis, Cyr61 is required for normal gastrulation and modulation of Wnt signaling.[37]
# Clinical relevance
CYR61 is highly expressed at sites of inflammation and wound repair, and is associated with diseases involving chronic inflammation and tissue injury.[3]
## Wound healing and fibrosis
In skin wound healing, CYR61 is highly expressed in the granulation tissue by myofibroblasts, which proliferate and rapidly synthesize ECM to maintain tissue integrity and to promote regeneration of parenchymal cells.[38][39] However, excessive matrix deposition can lead to fibrosis, scarring, and loss of tissue function. In skin wounds, CYR61 accumulates in the granulation tissue as myofibroblasts proliferate, and eventually reaches a sufficiently high level to drive the myofibroblasts themselves into senescence, whereupon these cells cease to proliferate and express matrix-degrading enzymes.[24] Thus, CYR61 limits synthesis and deposition of ECM by myofibroblasts, reducing the risk of fibrosis during wound healing.[40] In addition to skin wound healing, CYR61 expression is elevated in remodeling cardiomyocytes after myocardial infarction,[41] in vascular injury,[16] and in the long bones during fracture repair.[42][43] Blockade of CYR61 by antibodies inhibits bone fracture healing in mice.[44] In the kidney, CYR61 is expressed in podocytes in normal adult and embryonic glomeruli, but expression is decreased in IgA nephropathy, diabetic nephropathy, and membranous nephropathy, particularly in diseased kidneys with severe mesangial expansion.[45]
## Inflammation
CYR61 promotes the apoptotic functions of inflammatory cytokines such as TNFα, FasL, and TRAIL.[22][46][47] It also reprograms macrophages towards M1 polarization through αMβ2-mediated activation of NF-κB.[19] CYR61 is upregulated in patients with Crohn's disease and ulcerative colitis.[48] CYR61 supports the patrolling behavior of murine resident Ly6Clow monocytes along the endothelial in the steady state and is required for their accumulation under viral-mimicking vascular inflammation.[49]
## Arthritis
CYR61 is highly expressed in collagen-induced arthritis in rodents, and inhibition of CCN1 expression correlates with suppression of inflammatory arthritis.[50] CYR61 is also found in articular cartilage from patients with osteoarthritis and appears to suppress ADAMTS4 (aggrecanase) activity, possibly leading to cartilage cell (chondrocyte) cloning.[51]
## Vascular diseases
CYR61 is overexpressed in vascular smooth muscle cells of atherosclerotic lesions and in the neointima of restenosis after balloon angioplasty, both in rodent models and in humans.[16][18][52][53] Suppression of CYR61 expression results in reduced neointimal hyperplasia after balloon angioplasty, an effect that is reversed by delivery of CYR61 via gene transfer[54][55] In a mouse model of oxygen-induced retinopathy, expression of CYR61 in the vitreous humor produced significant beneficial effects in repairing damaged vasculature.[56]
## Cancer
Angiogenesis is essential for the supply of oxygen and nutrients to nourish the growing tumor.[57] CYR61 is a powerful angiogenic inducer in vivo,[27][28] and it can also promote cancer cell proliferation, invasion, survival, epithelial–mesenchymal transition, and metastasis.[58][59][60][61] Accordingly, forced overexpression of CYR61 enhanced tumor growth in xenografts of breast cancer cells,[62] prostate cancer cells,[59] ovarian carcinoma cells,[63] and squamous carcinoma cells.[64] Clinically, CYR61 expression correlates with the tumor stage, tumor size, lymph node positivity, and poor prognosis in several cancers, including breast cancer,[62][65][66][67][68] prostate cancer,[69] glioma,[70] gastric adenocarcinoma,[71] and squamous cell carcinoma.[64]
However, CYR61 can also induce apoptosis and cellular senescence,[21][24][72] two well-established mechanisms of tumor suppression[73] Thus, whereas CYR61 can promote the proliferation of prostate cancer cells, it can also exacerbate apoptosis of these cells in the presence of the immune surveillance molecule TRAIL.[47][59][74] CYR61 has an inhibitory effect on some cancers, and suppresses tumor growth of non-small-cell lung cancer (NSCLC) cells,[75] endometrial adenocarcinoma cells,[76] and in melanoma cells.[77] | https://www.wikidoc.org/index.php/CYR61 | |
299b21e002d3ce1a763d8c9202403244144442b1 | wikidoc | CYTH2 | CYTH2
Cytohesin-2 is a protein that in humans is encoded by the CYTH2 gene.
# Function
Cytohesin-2 (CYTH2), formerly known as Pleckstrin homology, Sec7 and coiled/coil domains 2 (PSCD2), is a member of the cytohesin family. Members of this family have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of CYTHs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. CYTH2 exhibits GEP activity in vitro with ARF1, ARF3, and ARF6. CYTH2 protein is 83% homologous to CYTH1. Two transcript variants encoding different isoforms have been found for this gene.
# Interactions
CYTH2 has been shown to interact with Arrestin beta 2 and Arrestin beta 1. | CYTH2
Cytohesin-2 is a protein that in humans is encoded by the CYTH2 gene.[1][2][3]
# Function
Cytohesin-2 (CYTH2), formerly known as Pleckstrin homology, Sec7 and coiled/coil domains 2 (PSCD2), is a member of the cytohesin family. Members of this family have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of CYTHs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. CYTH2 exhibits GEP activity in vitro with ARF1, ARF3, and ARF6. CYTH2 protein is 83% homologous to CYTH1. Two transcript variants encoding different isoforms have been found for this gene.[3]
# Interactions
CYTH2 has been shown to interact with Arrestin beta 2[4] and Arrestin beta 1. [4] | https://www.wikidoc.org/index.php/CYTH2 | |
1bb76dce3569ad9904a26e7851fa883ace2aa409 | wikidoc | CYTL1 | CYTL1
Cytokine-like 1 (CYTL1) is a protein that in humans is encoded by the CYTL1 gene.
# Function
C17 is a cytokine-like protein specifically expressed in bone marrow and cord blood mononuclear cells that bear the CD34 surface marker. Functionally, C17 was identified as a secretory protein expressed in CD34+ haemopoietic cells. CYTL1 seems to regulate chondrogenesis and is required for the maintenance of cartilage homeostasis and might, additionally, work as a regulatory factor in embryo implantation in the stage of early pregnancy.
This family of proteins, C17, is found in vertebrates. Proteins have two conserved sequence motifs: PPTCYSR and DDC. | CYTL1
Cytokine-like 1 (CYTL1) is a protein that in humans is encoded by the CYTL1 gene.[1]
# Function
C17 is a cytokine-like protein specifically expressed in bone marrow and cord blood mononuclear cells that bear the CD34 surface marker.[2] Functionally, C17 was identified as a secretory protein expressed in CD34+ haemopoietic cells.[2] CYTL1 seems to regulate chondrogenesis and is required for the maintenance of cartilage homeostasis and might, additionally, work as a regulatory factor in embryo implantation in the stage of early pregnancy.[3]
This family of proteins, C17, is found in vertebrates. Proteins have two conserved sequence motifs: PPTCYSR and DDC. | https://www.wikidoc.org/index.php/CYTL1 | |
6fadf604ce1aa4449fc43081a55172dba5b400c6 | wikidoc | CYYR1 | CYYR1
Cysteine and tyrosine-rich protein 1 is a protein that in humans is encoded by the CYYR1 gene and is located on chromosome 21, location 21q21.2. This protein has a function that is not presently understood.
# Protein
The product of the gene is a single pass type 1 transmembrane protein with four exons and a very large intron of 85.8 kb and coding for a protein containing 154 amino acids. The most prominent feature identified in the protein is a central, unique cysteine and tyrosine-rich protein domain, on portion of the protein which is located inside the cell. This domain is found to be strongly conserved from lower vertebrates (fishes) to humans but is absent in bacteria and invertebrates.
## Properties and Domains
Bioinformatic analysis predicted the following properties for CYYR1:
- Molecular Weight = 16.6kdal
- Isoelectric Point = 8.28
The amino acid sequence is 153 amino acids long and contains 3 domains.
Using bioinformatic tools the following domains were determined:
- Signal Peptide - Position 1-29
- Transmembrane Domain - Position 62-82
- Poly-Proline Domain - Position 144-149
## Orthologs
Multiple sequence alignments were done with orthologs of the CYYR1 gene and they show that the protein sequence is highly conserved throughout all vertebrates.
There are no known or predicted paralogs in homo sapiens.
## Interactions
CYYR1 has been shown to increase glutathione level in yeast cells when complementing a defect in GSH uptake in yeast cells that lack Hgt1p, the primary yeast GSH uptake transporter. However, the CYYR1 gene is not naturally found in yeast, so function of CYYR1 is still unknown. | CYYR1
Cysteine and tyrosine-rich protein 1 is a protein that in humans is encoded by the CYYR1 gene[1][2][3] and is located on chromosome 21, location 21q21.2. This protein has a function that is not presently understood.
# Protein
The product of the gene is a single pass type 1 transmembrane protein with four exons and a very large intron of 85.8 kb and coding for a protein containing 154 amino acids.[4] The most prominent feature identified in the protein is a central, unique cysteine and tyrosine-rich protein domain, on portion of the protein which is located inside the cell. This domain is found to be strongly conserved from lower vertebrates (fishes) to humans but is absent in bacteria and invertebrates.[2]
## Properties and Domains
Bioinformatic analysis predicted the following properties for CYYR1:
- Molecular Weight = 16.6kdal
- Isoelectric Point = 8.28
The amino acid sequence is 153 amino acids long and contains 3 domains.[5]
Using bioinformatic tools the following domains were determined:
- Signal Peptide[4] - Position 1-29
- Transmembrane Domain[4] - Position 62-82
- Poly-Proline Domain[4] - Position 144-149
## Orthologs
Multiple sequence alignments were done with orthologs of the CYYR1 gene and they show that the protein sequence is highly conserved throughout all vertebrates.
There are no known or predicted paralogs in homo sapiens.
## Interactions
CYYR1 has been shown to increase glutathione level in yeast cells when complementing a defect in GSH uptake in yeast cells that lack Hgt1p, the primary yeast GSH uptake transporter.[7] However, the CYYR1 gene is not naturally found in yeast, so function of CYYR1 is still unknown. | https://www.wikidoc.org/index.php/CYYR1 | |
ba7fdd58d731f3d2d58707897284fa3092613d00 | wikidoc | CaBIG | CaBIG
# Overview
caBIG is the Cancer Biomedical Informatics Grid, a National Cancer Institute (USA) initiative to link cancer researchers and their data. caBIG refers both to the computing infrastructure that will provide interoperability between the NCI-designated Cancer Center community, although the intention is that any organization should be able to participate in, and take advantage of, the tools and data made available through the initiative. There are currently (2006) 800 people from 80 organizations involved in the program, which was initiated in 2004 by the National Cancer Institute's Center for Bioinformatics (NCICB).
One of the primary goals of caBIG is to create a grid infrastructure that supports semantic interoperability. This will enable data and analytical tools provided by the participating cancer research centers and public and private participants to be shared in a manner that is federated and scalable. Currently this is not possible because each research site uses different data definitions and standards, making useful exchange difficult. This effort is in some ways similar to work being done on the Semantic Web project.
The chosen method for implementing semantic interoperability within caBIG is the use of standard vocabularies and ontologies and heavy use of a metadata repository. The National Cancer Institute has built tools that provide these functionalities and service as a common point for creating interoperability.
# Resources
- Public Information Web Site
- Official web site
- NCI Center for Bioinformatics | CaBIG
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
caBIG is the Cancer Biomedical Informatics Grid, a National Cancer Institute (USA) initiative to link cancer researchers and their data. caBIG refers both to the computing infrastructure that will provide interoperability between the NCI-designated Cancer Center community, although the intention is that any organization should be able to participate in, and take advantage of, the tools and data made available through the initiative. There are currently (2006) 800 people from 80 organizations involved in the program, which was initiated in 2004 by the National Cancer Institute's Center for Bioinformatics (NCICB).
One of the primary goals of caBIG is to create a grid infrastructure that supports semantic interoperability. This will enable data and analytical tools provided by the participating cancer research centers and public and private participants to be shared in a manner that is federated and scalable. Currently this is not possible because each research site uses different data definitions and standards, making useful exchange difficult. This effort is in some ways similar to work being done on the Semantic Web project.
The chosen method for implementing semantic interoperability within caBIG is the use of standard vocabularies and ontologies and heavy use of a metadata repository. The National Cancer Institute has built tools that provide these functionalities and service as a common point for creating interoperability.
# Resources
- Public Information Web Site
- Official web site
- NCI Center for Bioinformatics | https://www.wikidoc.org/index.php/CaBIG | |
4d371d33fb29b9845ce00b11285e001acb46bad2 | wikidoc | Cecum | Cecum
# Overview
The cecum or caecum (from the Latin caecus meaning blind) is a pouch connected to the ascending colon of the large intestine and the ileum. It is separated from the ileum by the ileocecal valve (ICV) or Bauhin's valve, and is considered to be the beginning of the large intestine. It is also separated from the colon by the cecocolic junction.
# Variation across species
The cecum is present in mammals, and two ceca are present in most birds, and some reptiles.
Most herbivores have a relatively large cecum, hosting a large number of bacteria, which aid in the enzymatic breakdown of plant materials such as cellulose.
Exclusive carnivores, whose diets contain little or no plant material, have a reduced cecum, often partially or wholly replaced by the vermiform appendix.
# Etymology
The term cecum comes from the Latin, meaning blind gut or cul de sac.
In dissections by the Greek philosophers, the connection between the ileum of the small intestines and the cecum was not fully understood. Most of the studies of the digestive tract were done on animals and the results were compared to human structures.
The junction between the small intestines and the colon, called the ileocecal valve, is so small in some animals that it was not considered to be a connection between the small and large intestines. During a dissection, the colon could be traced from the rectum, to the sigmoid colon, through the descending, transverse, and ascending sections. The colon seemed to dead-end into the cecum, or cul-de-sac.
However, the connection between the end of the small intestines, ileum, and the start of the colon, cecum are now clearly understood, but the name has not changed. | Cecum
# Overview
Template:Infobox Anatomy
The cecum or caecum (from the Latin caecus meaning blind) is a pouch connected to the ascending colon of the large intestine and the ileum. It is separated from the ileum by the ileocecal valve (ICV) or Bauhin's valve, and is considered to be the beginning of the large intestine. It is also separated from the colon by the cecocolic junction.
# Variation across species
The cecum is present in mammals, and two ceca are present in most birds, and some reptiles.
Most herbivores have a relatively large cecum, hosting a large number of bacteria, which aid in the enzymatic breakdown of plant materials such as cellulose.
Exclusive carnivores, whose diets contain little or no plant material, have a reduced cecum, often partially or wholly replaced by the vermiform appendix.
# Etymology
The term cecum comes from the Latin, meaning blind gut or cul de sac.
In dissections by the Greek philosophers, the connection between the ileum of the small intestines and the cecum was not fully understood. Most of the studies of the digestive tract were done on animals and the results were compared to human structures.
The junction between the small intestines and the colon, called the ileocecal valve, is so small in some animals that it was not considered to be a connection between the small and large intestines. During a dissection, the colon could be traced from the rectum, to the sigmoid colon, through the descending, transverse, and ascending sections. The colon seemed to dead-end into the cecum, or cul-de-sac.
However, the connection between the end of the small intestines, ileum, and the start of the colon, cecum are now clearly understood, but the name has not changed. | https://www.wikidoc.org/index.php/Caecum | |
9e77cbed07aa20fc90a8170a1afb7e336dfaa9fb | wikidoc | Heart | Heart
# Overview
The heart is a muscular organ responsible for pumping blood through the blood vessels by repeated, rhythmic contractions, or a similar structure in the annelids, mollusks, and arthropods. The term cardiac (as in cardiology) means "related to the heart" and comes from the Greek καρδία, kardia, for "heart." The heart is composed of cardiac muscle, an involuntary muscle tissue which is found only within this organ. The average human heart beating at 72 BPM, will beat approximately 2.5 billion times during a lifetime of 66 years.
# Early development
The human embryonic heart begins beating about 21 days after conception, or five weeks after the last normal menstrual period (LMP), which is the date normally used to date pregnancy. The human heart begins beating at a rate near the mother’s, about 75-80 beats per minute (BPM). The embryonic heart rate (EHR) then accelerates linearly for the first month of beating, peaking at 165-185 BPM during the early 7th week, (early 9th week after the LMP). This acceleration is approximately 3.3 BPM per day, or about 10 BPM every three days, an increase of 100 BPM in the first month.
After peaking at about 9.5 weeks after the LMP, it decelerates to about 152 BPM (+/-25 BPM) during the 15th week after the LMP. After the 15th week the deceleration slows reaching an average rate of about 145 (+/-25 BPM) BPM at term. The regression formula which describes this acceleration before the embryo reaches 25 mm in crown-rump length or 9.2 LMP weeks is Age in days = EHR(0.3)+6
There is no difference in male and female heart rates before birth.
# Structure
In the human body, the heart is usually situated in the middle of the thorax with the largest part of the heart slightly offset to the left (although sometimes it is on the right, see dextrocardia), underneath the breastbone (see diagrams). The heart is usually felt to be on the left side because the left heart (left ventricle) is stronger (it pumps to all body parts). The left lung is smaller than the right lung because the heart occupies more of the left hemithorax. The heart is enclosed by a sac known as the pericardium and is surrounded by the lungs. The pericardium is a double membrane structure containing a serous fluid to reduce friction during heart contractions. The mediastinum, a subdivision of the thoracic cavity, is the name of the heart cavity.
The apex is the blunt point situated in an inferior (pointing down and left) direction. A stethoscope can be placed directly over the apex so that the beats can be counted. It is located posterior to the 5th intercostal space in the left mid-clavicular line. In normal adults, the mass of the heart is 250-350 g (9-12 oz), or about three quarters the size of a clenched fist, but extremely diseased hearts can be up to 1000 g (2 lb) in mass due to hypertrophy. It consists of four chambers, the two upper atria (singular: atrium
) and the two lower ventricles. Below, on the right, is a picture of a fresh human heart which was removed from a 64-year-old British male.
- At 21 days after conception, the human heart begins beating at 70 to 80 beats per minute and accelerates linearly for the first month of beating.
- Anterior (frontal) view of the opened heart. Arrows indicate normal blood flow. Image provided courtesy of www.3dscience.com.
- Human heart
# Functioning
The function of the right side of the heart (see right heart) is to collect de-oxygenated blood, in the right atrium, from the body and pump it, via the right ventricle, into the lungs (pulmonary circulation) so that carbon dioxide can be dropped off and oxygen picked up (gas exchange). This happens through a passive process called diffusion. The left side (see left heart) collects oxygenated blood from the lungs into the left atrium. From the left atrium the blood moves to the left ventricle which pumps it out to the body. On both sides, the lower ventricles are thicker and stronger than the upper atria.
The muscle wall surrounding the left ventricle is thicker than the wall surrounding the right ventricle due to the higher force needed to pump the blood through the systemic circulation.
Starting in the right atrium, the blood flows through the tricuspid valve to the right ventricle. Here it is pumped out the pulmonary semilunar valve and travels through the pulmonary artery to the lungs. From there, blood flows back through the pulmonary vein to the left atrium. It then travels through the bicuspid valve to the left ventricle and on to through the aortic semilunar valve to the aorta. The aorta forks, and the blood is divided between major arteries which supply the upper and lower body. The blood travels the arteries to the smaller arterioles, then finally to the tiny capillaries which feed each cell. The (relatively) deoxygenated blood then travels to the venules, which coalesce into veins, then to the inferior and superior vena cavae and finally back to the right atrium where the process began.
The heart is effectively a syncytium, a meshwork of cardiac muscle cells interconnected by contiguous cytoplasmic bridges. This relates to electrical stimulation of one cell spreading to neighboring cells
# First aid
See cardiac arrest for emergencies involving the heart
If a person is encountered in cardiac arrest (no heartbeat), cardiopulmonary resuscitation (CPR) should be started and help called. If an automated external defibrillator is available, this device may automatically administer defibrillation if this is indicated. Usually, if there is enough time, the person can be rushed to the hospital where he or she will be cared for by a cardiologist, a doctor who specializes in the heart and lungs. | Heart
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
The heart is a muscular organ responsible for pumping blood through the blood vessels by repeated, rhythmic contractions, or a similar structure in the annelids, mollusks, and arthropods.[1] The term cardiac (as in cardiology) means "related to the heart" and comes from the Greek καρδία, kardia, for "heart." The heart is composed of cardiac muscle, an involuntary muscle tissue which is found only within this organ.[2] The average human heart beating at 72 BPM, will beat approximately 2.5 billion times during a lifetime of 66 years.
# Early development
The human embryonic heart begins beating about 21 days after conception, or five weeks after the last normal menstrual period (LMP), which is the date normally used to date pregnancy. The human heart begins beating at a rate near the mother’s, about 75-80 beats per minute (BPM). The embryonic heart rate (EHR) then accelerates linearly for the first month of beating, peaking at 165-185 BPM during the early 7th week, (early 9th week after the LMP). This acceleration is approximately 3.3 BPM per day, or about 10 BPM every three days, an increase of 100 BPM in the first month.[3]
After peaking at about 9.5 weeks after the LMP, it decelerates to about 152 BPM (+/-25 BPM) during the 15th week after the LMP. After the 15th week the deceleration slows reaching an average rate of about 145 (+/-25 BPM) BPM at term. The regression formula which describes this acceleration before the embryo reaches 25 mm in crown-rump length or 9.2 LMP weeks is Age in days = EHR(0.3)+6
There is no difference in male and female heart rates before birth.[4]
# Structure
In the human body, the heart is usually situated in the middle of the thorax with the largest part of the heart slightly offset to the left (although sometimes it is on the right, see dextrocardia), underneath the breastbone (see diagrams). The heart is usually felt to be on the left side because the left heart (left ventricle) is stronger (it pumps to all body parts). The left lung is smaller than the right lung because the heart occupies more of the left hemithorax. The heart is enclosed by a sac known as the pericardium and is surrounded by the lungs. The pericardium is a double membrane structure containing a serous fluid to reduce friction during heart contractions. The mediastinum, a subdivision of the thoracic cavity, is the name of the heart cavity.
The apex is the blunt point situated in an inferior (pointing down and left) direction. A stethoscope can be placed directly over the apex so that the beats can be counted. It is located posterior to the 5th intercostal space in the left mid-clavicular line. In normal adults, the mass of the heart is 250-350 g (9-12 oz), or about three quarters the size of a clenched fist, but extremely diseased hearts can be up to 1000 g (2 lb) in mass due to hypertrophy. It consists of four chambers, the two upper atria (singular: atrium
) and the two lower ventricles. Below, on the right, is a picture of a fresh human heart which was removed from a 64-year-old British male.
- At 21 days after conception, the human heart begins beating at 70 to 80 beats per minute and accelerates linearly for the first month of beating.
- Anterior (frontal) view of the opened heart. Arrows indicate normal blood flow. Image provided courtesy of www.3dscience.com.
- Human heart
# Functioning
The function of the right side of the heart (see right heart) is to collect de-oxygenated blood, in the right atrium, from the body and pump it, via the right ventricle, into the lungs (pulmonary circulation) so that carbon dioxide can be dropped off and oxygen picked up (gas exchange). This happens through a passive process called diffusion. The left side (see left heart) collects oxygenated blood from the lungs into the left atrium. From the left atrium the blood moves to the left ventricle which pumps it out to the body. On both sides, the lower ventricles are thicker and stronger than the upper atria.
The muscle wall surrounding the left ventricle is thicker than the wall surrounding the right ventricle due to the higher force needed to pump the blood through the systemic circulation.
Starting in the right atrium, the blood flows through the tricuspid valve to the right ventricle. Here it is pumped out the pulmonary semilunar valve and travels through the pulmonary artery to the lungs. From there, blood flows back through the pulmonary vein to the left atrium. It then travels through the bicuspid valve to the left ventricle and on to through the aortic semilunar valve to the aorta. The aorta forks, and the blood is divided between major arteries which supply the upper and lower body. The blood travels the arteries to the smaller arterioles, then finally to the tiny capillaries which feed each cell. The (relatively) deoxygenated blood then travels to the venules, which coalesce into veins, then to the inferior and superior vena cavae and finally back to the right atrium where the process began.
The heart is effectively a syncytium, a meshwork of cardiac muscle cells interconnected by contiguous cytoplasmic bridges. This relates to electrical stimulation of one cell spreading to neighboring cells
# First aid
See cardiac arrest for emergencies involving the heart
If a person is encountered in cardiac arrest (no heartbeat), cardiopulmonary resuscitation (CPR) should be started and help called. If an automated external defibrillator is available, this device may automatically administer defibrillation if this is indicated. Usually, if there is enough time, the person can be rushed to the hospital where he or she will be cared for by a cardiologist, a doctor who specializes in the heart and lungs. | https://www.wikidoc.org/index.php/Cardiac | |
2aadf4736fc74b5daf0836451df2ae4fd63d8607 | wikidoc | Casts | Casts
Cast may refer to:
- Casting, a process by which a material is introduced into a mould while liquid, and allowed to solidify into a specific shape
- Casting (performing arts), a pre-production process for selecting a cast of actors and other talent
Cast member, (c.1631) a group of performers in a play, movie, or performing arts
- Cast member, (c.1631) a group of performers in a play, movie, or performing arts
- Orthopedic cast, a protective shell to hold a broken bone in place until it has healed
- In archaeology, a cavity formed by the decomposition of wood furnishings or human or animal remains, previously covered due to volcanic ash fall
- The casting of Spell_(paranormal)|magic spells
- The Center for Advanced Spatial Technologies (CAST) at the University of Arkansas, Fayetteville
- Orthopedic cast, a shell which is used to help heal broken bones by holding the limb in place
In popular culture:
- Cast (comic)|Cast (comic), a comic series published in the Philippines
In music:
- Cast (band), an English rock and roll band from the 1990s
- Cast (Mexican band), a progressive Mexican rock band
Other
- Cast, Finistère, a commune of the Finistère département, in France
- Cast (earthworm), mineral-rich organic matter that is excreted by earthworms
- Urinary casts, tubules found in urine
- Casting (tails), a process whereby animals can 'drop' their tail, which may or may not regenerate
- Cast (archery), the distance a bow can shoot its arrow
- Type conversion, a programming language method for changing data types | Casts
Cast may refer to:
- Casting, a process by which a material is introduced into a mould while liquid, and allowed to solidify into a specific shape
- Casting (performing arts), a pre-production process for selecting a cast of actors and other talent
Cast member, (c.1631) a group of performers in a play, movie, or performing arts
- Cast member, (c.1631) a group of performers in a play, movie, or performing arts
- Orthopedic cast, a protective shell to hold a broken bone in place until it has healed
- In archaeology, a cavity formed by the decomposition of wood furnishings or human or animal remains, previously covered due to volcanic ash fall
- The casting of Spell_(paranormal)|magic spells
- The Center for Advanced Spatial Technologies (CAST) at the University of Arkansas, Fayetteville
- Orthopedic cast, a shell which is used to help heal broken bones by holding the limb in place
In popular culture:
- Cast (comic)|Cast (comic), a comic series published in the Philippines
In music:
- Cast (band), an English rock and roll band from the 1990s
- Cast (Mexican band), a progressive Mexican rock band
Other
- Cast, Finistère, a commune of the Finistère département, in France
- Cast (earthworm), mineral-rich organic matter that is excreted by earthworms
- Urinary casts, tubules found in urine
- Casting (tails), a process whereby animals can 'drop' their tail, which may or may not regenerate
- Cast (archery), the distance a bow can shoot its arrow
- Type conversion, a programming language method for changing data types | https://www.wikidoc.org/index.php/Casts | |
8d62d89ab2c31688575ef755eba456953992fd35 | wikidoc | Cedax | Cedax
CEDAX is an antibiotic known as ceftibuten. Each capsule contains 400 mg of ceftibuten.
Indications: CEDAX is active against:
Haemophilus influenzae
Moraxella catarralhis
Escherichia coli (K. pneumoniae, K. oxytoca)
Proteus vulgaris, P. mirabils, P. providence
Species of Salmonella and Shigellas
Species of Enterobacter
Streptococcus
CEDAX is indicated for acute bronchitis, pneumonias and urinary track infections, enteritis and gastroenteritis.
Dosage: 5 to 10 days. Adults recommended dose is 400 mg/day.
Children 9 mg/kg/day (max. 400 mg). Best taken in an empty stomach
( at least 1 hour before a meal, or at least 2 hours after a meal).
Adverse reactions: In studies made in 3,000 patients CEDAX was well tolerated . Most frequent reactions were gastrointestinal and nauseas.
Warning: Must be prescribed with extreme caution in individuals with allergy to penicillins.
Sources: Medicohomepage, Cedax | Cedax
CEDAX is an antibiotic known as ceftibuten. Each capsule contains 400 mg of ceftibuten.
Indications: CEDAX is active against:
Haemophilus influenzae
Moraxella catarralhis
Escherichia coli (K. pneumoniae, K. oxytoca)
Proteus vulgaris, P. mirabils, P. providence
Species of Salmonella and Shigellas
Species of Enterobacter
Streptococcus
CEDAX is indicated for acute bronchitis, pneumonias and urinary track infections, enteritis and gastroenteritis.
Dosage: 5 to 10 days. Adults recommended dose is 400 mg/day.
Children 9 mg/kg/day (max. 400 mg). Best taken in an empty stomach
( at least 1 hour before a meal, or at least 2 hours after a meal).
Adverse reactions: In studies made in 3,000 patients CEDAX was well tolerated . Most frequent reactions were gastrointestinal and nauseas.
Warning: Must be prescribed with extreme caution in individuals with allergy to penicillins.
Sources: Medicohomepage, Cedax
Template:WS | https://www.wikidoc.org/index.php/Cedax | |
3e2961eec88bf8bcef0ff07b5bc8850298158ea5 | wikidoc | Lysis | Lysis
Lysis (Greek Template:Polytonic, lusis from luein = to separate) refers to the death of a cell by breaking of the cellular membrane, often by viral or osmotic mechanisms that compromise its integrity. A solution containing the contents of lysed cells is called a "lysate".
# Applications
Cell lysis is used mostly in western blotting to analyse the composition of specific proteins, lipids and nucleic acids individually or as complexes. Depending upon the detergent that is used either all membranes are lysed or certain membranes are lysed, leaving other membranes intact. For example if the cell membrane only is lysed then gradient centrifugation can be used to collect certain organelles - nuclei, mitochondria, lysosomes, chloroplasts and endoplasmic reticulum. The isolated organelles can then be analysed by electron microscopy or western blotting.
# Cytolysis
Cytolysis is the lysis of cells in a hypotonic environment. Cytolysis is caused by excessive osmosis, or movement of water, towards the inside of a cell (hyperhydration). The cell membrane cannot withstand the osmotic pressure of the water inside, and so it explodes. Osmosis occurs from a region of high water potential to a region of low water potential passing through a semipermeable membrane, so these bursting cells are located in hypotonic environments.
Cytolysis can be prevented by several different mechanisms, including the contractile vacuole that exists in some paramecia which rapidly pump water out of the system of the cell.
Cytolysis does not occur under normal conditions in plant cells because plant cells have a strong cell wall that contains the osmotic pressure, or turgor pressure, that would otherwise cause cytolysis to occur.
# Plasmolysis
Plasmolysis is the contraction of cells within plants due to the loss of water through osmosis. In a hypertonic environment, the cell membrane peels off of the cell wall and the vacuole collapses. These cells will eventually wilt and die unless the flow of water caused by osmosis can stop the contraction of the cell membrane. | Lysis
Lysis (Greek Template:Polytonic, lusis from luein = to separate) refers to the death of a cell by breaking of the cellular membrane, often by viral or osmotic mechanisms that compromise its integrity.[citation needed] A solution containing the contents of lysed cells is called a "lysate".
# Applications
Cell lysis is used mostly in western blotting to analyse the composition of specific proteins, lipids and nucleic acids individually or as complexes. Depending upon the detergent that is used either all membranes are lysed or certain membranes are lysed, leaving other membranes intact. For example if the cell membrane only is lysed then gradient centrifugation can be used to collect certain organelles - nuclei, mitochondria, lysosomes, chloroplasts and endoplasmic reticulum. The isolated organelles can then be analysed by electron microscopy or western blotting.
# Cytolysis
Cytolysis is the lysis of cells in a hypotonic environment. Cytolysis is caused by excessive osmosis, or movement of water, towards the inside of a cell (hyperhydration). The cell membrane cannot withstand the osmotic pressure of the water inside, and so it explodes. Osmosis occurs from a region of high water potential to a region of low water potential passing through a semipermeable membrane, so these bursting cells are located in hypotonic environments.
Cytolysis can be prevented by several different mechanisms, including the contractile vacuole that exists in some paramecia which rapidly pump water out of the system of the cell.
Cytolysis does not occur under normal conditions in plant cells because plant cells have a strong cell wall that contains the osmotic pressure, or turgor pressure, that would otherwise cause cytolysis to occur.
# Plasmolysis
Plasmolysis is the contraction of cells within plants due to the loss of water through osmosis. In a hypertonic environment, the cell membrane peels off of the cell wall and the vacuole collapses. These cells will eventually wilt and die unless the flow of water caused by osmosis can stop the contraction of the cell membrane. | https://www.wikidoc.org/index.php/Cell_lysate | |
8b8c4228de5a525216e2a59c7cdaaac827bd1fa1 | wikidoc | Cheek | Cheek
Cheeks (Latin: maxilla, also malā: "jaw") constitute the area of the face below the eyes and between the nose and the left or right ear.
It is fleshy in humans and other mammals, the skin being suspended by the chin and the jaws, and forming the lateral wall of the human mouth, visibly touching the cheekbone below the eye.
In vertebrates, markings on the cheek area (malar stripes/spots/...), particularly immediately beneath the eye, often serve as important distinguishing features between species or individuals.
"Buccal" means relating to the cheek.
In humans, the region is innervated by the buccal nerve.
ar:وجنة
de:Wange
dv:ކޯ
eo:Vango
id:Pipi
it:Guancia
la:Mala
nl:Wang (anatomie)
sv:Kind
tl:Pisngi | Cheek
Template:Infobox Anatomy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Cheeks (Latin: maxilla, also malā: "jaw") constitute the area of the face below the eyes and between the nose and the left or right ear.
It is fleshy in humans and other mammals, the skin being suspended by the chin and the jaws, and forming the lateral wall of the human mouth, visibly touching the cheekbone below the eye.
In vertebrates, markings on the cheek area (malar stripes/spots/...), particularly immediately beneath the eye, often serve as important distinguishing features between species or individuals.
"Buccal" means relating to the cheek.
In humans, the region is innervated by the buccal nerve.
Template:Human anatomical features
Template:Head and neck general
ar:وجنة
de:Wange
dv:ކޯ
eo:Vango
id:Pipi
it:Guancia
la:Mala
nl:Wang (anatomie)
sv:Kind
tl:Pisngi
Template:WH
Template:WS
Template:Jb1 | https://www.wikidoc.org/index.php/Cheek | |
3ea1368dad48517a1306e7fdaa842d9131aa899c | wikidoc | Chest | Chest
# Overview
The chest is a part of the anatomy of humans and various other animals.
# Human chest anatomy
In human, the chest is the region of the body between the neck and the abdomen, along with its internal organs and other contents. It is mostly protected and supported by the ribcage, spine, and shoulder girdle. Contents of the chest include the following:
- organs
heart
lungs
- heart
- lungs
- muscles
major and minor pectoral muscles
trapezius muscles and neck
- major and minor pectoral muscles
- trapezius muscles and neck
- internal structures
diaphragm
esophagus
trachea
xiphoid process
- diaphragm
- esophagus
- trachea
- xiphoid process
- arteries and veins
aorta
superior vena cava
inferior vena cava
pulmonary artery
- aorta
- superior vena cava
- inferior vena cava
- pulmonary artery
- bones
the shoulder socket containing the upper part of the humerus
scapula
sternum
thoracic portion of the spine
collarbone
ribcage
Floating ribs
- the shoulder socket containing the upper part of the humerus
- scapula
- sternum
- thoracic portion of the spine
- collarbone
- ribcage
- Floating ribs
- external structures
nipples
mammary glands
- nipples
- mammary glands
- thoracic abdomen (stomach, kidney/adrenal, pancreas, spleen, and lower oesophagus)
In humans, the portion of the chest protected by the ribcage is also called the thorax.
# Chest injury
Injury to the chest (also referred to as chest trauma, thoracic injury, or thoracic trauma) results in up to ¼ of all deaths due to trauma in the United States.
In the human body, the chest is the body region between the neck and diaphragm in the front of the body. The corresponding area in an animal can be referred to as the chest. The chest holds many important internal, and is protected by the ribcage.
It is important to realize that the shape of the chest does not correspond to that of the bony thorax which encloses the heart and lungs; all the breadth of the shoulders is due to the shoulder girdle, and contains the axilla and the head of the humerus. In the middle line the suprasternal notch is seen above, while about three fingers' breadth below it a transverse ridge can be felt, which is known as (Ludovic's angle) and marks the junction between the manubrium and gladiolus of the sternum. Level with this line the second ribs join the sternum, and when these are found the lower ribs may be easily counted in a moderately thin subject. At the lower part of the sternum, where the seventh or last true ribs join it, the ensiform cartilage begins, and over this there is often a depression popularly known as the pit of the stomach.
The nipple in the male is situated in front of the fourth rib or a little below; vertically it lies a little external to a line drawn down from the middle of the clavicle; in the female it is not so constant. A little below it the lower limit of the great pectoral muscle is seen running upward and outward to the axilla; in the female this is obscured by the breast, which extends from the second to the sixth rib vertically and from the edge of the sternum to the mid-axillary line laterally. The female nipple is surrounded for half an inch by a more or less pigmented disc, the areola. The apex of a normal heart is in the fifth left intercostal space, three and a half inches from the mid-line. | Chest
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
The chest is a part of the anatomy of humans and various other animals.
# Human chest anatomy
In human, the chest is the region of the body between the neck and the abdomen, along with its internal organs and other contents. It is mostly protected and supported by the ribcage, spine, and shoulder girdle. Contents of the chest include the following:
- organs
heart
lungs
- heart
- lungs
- muscles
major and minor pectoral muscles
trapezius muscles and neck
- major and minor pectoral muscles
- trapezius muscles and neck
- internal structures
diaphragm
esophagus
trachea
xiphoid process
- diaphragm
- esophagus
- trachea
- xiphoid process
- arteries and veins
aorta
superior vena cava
inferior vena cava
pulmonary artery
- aorta
- superior vena cava
- inferior vena cava
- pulmonary artery
- bones
the shoulder socket containing the upper part of the humerus
scapula
sternum
thoracic portion of the spine
collarbone
ribcage
Floating ribs
- the shoulder socket containing the upper part of the humerus
- scapula
- sternum
- thoracic portion of the spine
- collarbone
- ribcage
- Floating ribs
- external structures
nipples
mammary glands
- nipples
- mammary glands
- thoracic abdomen (stomach, kidney/adrenal, pancreas, spleen, and lower oesophagus)
In humans, the portion of the chest protected by the ribcage is also called the thorax.
# Chest injury
Injury to the chest (also referred to as chest trauma, thoracic injury, or thoracic trauma) results in up to ¼ of all deaths due to trauma in the United States.[1]
In the human body, the chest is the body region between the neck and diaphragm in the front of the body. The corresponding area in an animal can be referred to as the chest. The chest holds many important internal, and is protected by the ribcage.
It is important to realize that the shape of the chest does not correspond to that of the bony thorax which encloses the heart and lungs; all the breadth of the shoulders is due to the shoulder girdle, and contains the axilla and the head of the humerus. In the middle line the suprasternal notch is seen above, while about three fingers' breadth below it a transverse ridge can be felt, which is known as (Ludovic's angle) and marks the junction between the manubrium and gladiolus of the sternum. Level with this line the second ribs join the sternum, and when these are found the lower ribs may be easily counted in a moderately thin subject. At the lower part of the sternum, where the seventh or last true ribs join it, the ensiform cartilage begins, and over this there is often a depression popularly known as the pit of the stomach.
The nipple in the male is situated in front of the fourth rib or a little below; vertically it lies a little external to a line drawn down from the middle of the clavicle; in the female it is not so constant. A little below it the lower limit of the great pectoral muscle is seen running upward and outward to the axilla; in the female this is obscured by the breast, which extends from the second to the sixth rib vertically and from the edge of the sternum to the mid-axillary line laterally. The female nipple is surrounded for half an inch by a more or less pigmented disc, the areola. The apex of a normal heart is in the fifth left intercostal space, three and a half inches from the mid-line. | https://www.wikidoc.org/index.php/Chest | |
e2b87c895ccd73916ec9c24da3498b7fff6cc4cb | wikidoc | Chick | Chick
Chick may refer to one of these topics:
- A chicken (Gallus gallus animal)
- A young bird (originally a dialectal form of chicken)
In falconry, chick may mean:
- A day-old cockerel
- A young bird of prey at the fluffy downy stage
Chick could also be a reference to one of the following:
- Harriette Chick (1875–1977), a British nutritionist
- Jack Chick (born 1924), an American publisher who runs Chick Publications
- Chick Hearn (1916-2002), an American sportscaster
- Chick Corea (1941-present), an American jazz pianist
- Chick Webb (1905-1939), Jazz drummer and band leader
- Chick - A 90's one hit wonder band
- Chick - A clothing line by Nicky Hilton
- Chick Young, a Scottish football journalist
Chick appears in these other article titles, but would not by itself ever be a reference to these topics:
- Chick flick, slang for a movie made for, or appealing primarily to, women
- Chick-fil-A, a fast food restaurant chain
- Chick lit, a contemporary genre of literature
- Chick pea, an edible pulse (Legume)
- Dixie Chicks, a country music group
- The Hot Chick, a 2002 comedy film starring Rob Schneider
- Grand Rapids Chicks, formerly the Milwaukee Chicks, a women's professional baseball team
de:Chick | Chick
Template:Wiktionarypar
Chick may refer to one of these topics:
- A chicken (Gallus gallus animal)
- A young bird (originally a dialectal form of chicken)
In falconry, chick may mean:
- A day-old cockerel
- A young bird of prey at the fluffy downy stage
Chick could also be a reference to one of the following:
- Harriette Chick (1875–1977), a British nutritionist
- Jack Chick (born 1924), an American publisher who runs Chick Publications
- Chick Hearn (1916-2002), an American sportscaster
- Chick Corea (1941-present), an American jazz pianist
- Chick Webb (1905-1939), Jazz drummer and band leader
- Chick - A 90's one hit wonder band
- Chick - A clothing line by Nicky Hilton
- Chick Young, a Scottish football journalist
Chick appears in these other article titles, but would not by itself ever be a reference to these topics:
- Chick flick, slang for a movie made for, or appealing primarily to, women
- Chick-fil-A, a fast food restaurant chain
- Chick lit, a contemporary genre of literature
- Chick pea, an edible pulse (Legume)
- Dixie Chicks, a country music group
- The Hot Chick, a 2002 comedy film starring Rob Schneider
- Grand Rapids Chicks, formerly the Milwaukee Chicks, a women's professional baseball team
Template:Disambig
de:Chick
Template:WH
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Chick | |
9a4d2f0cf8234c29ce1c4b45ca9ad6eb02d13190 | wikidoc | Child | Child
A child (plural: children) is a human being between birth and puberty. The term may also define a relationship with a parent or authority figure, or signify group membership in a clan, tribe, or religion; or it can signify being strongly affected by a specific time, place, or circumstance, as in "a child of nature" or "a child of the Sixties."
# Legal definition
The United Nations Convention on the Rights of the Child defines a child as "every human being below the age of 18 years unless under the law applicable to the child, majority is attained earlier".
In a New York court ruling in 2006 on the eviction of a pregnant woman, the court declared that her child was equally protected under the law although the eviction notice was served before the child was born.
# Biological definition
Biologically, a child is anyone in the developmental stage of childhood, between infancy and adulthood.
# Attitudes toward children
Social attitudes toward children differ around the world, and these attitudes have changed over time. One study has found that children in the United States are coddled and overprotected.
A 1988 study on European attitudes toward the centrality of children found that Italy was more child-centric and Holland less child-centric, with other countries (Austria, Great Britain, Ireland, and West Germany) falling in between.
# Age of responsibility
The age at which children are considered responsible for their own actions has also changed over time, and this is reflected in the way they are treated in courts of law. In Roman times, children were regarded as not culpable for crimes, a position later adopted by the Church. In the nineteenth century, children younger than seven years old were believed incapable of crime. Children from the age of seven were considered responsible for their actions. Hence, they could face criminal charges, be sent to adult prisons, and be punished like adults by whipping, branding or hanging. | Child
A child (plural: children) is a human being between birth and puberty.[1] The term may also define a relationship with a parent or authority figure, or signify group membership in a clan, tribe, or religion; or it can signify being strongly affected by a specific time, place, or circumstance, as in "a child of nature" or "a child of the Sixties."[2]
# Legal definition
The United Nations Convention on the Rights of the Child defines a child as "every human being below the age of 18 years unless under the law applicable to the child, majority is attained earlier".[3]
In a New York court ruling in 2006 on the eviction of a pregnant woman, the court declared that her child was equally protected under the law although the eviction notice was served before the child was born.[4]
# Biological definition
Biologically, a child is anyone in the developmental stage of childhood, between infancy and adulthood.
# Attitudes toward children
Social attitudes toward children differ around the world, and these attitudes have changed over time. One study has found that children in the United States are coddled and overprotected.[5]
A 1988 study on European attitudes toward the centrality of children found that Italy was more child-centric and Holland less child-centric, with other countries (Austria, Great Britain, Ireland, and West Germany) falling in between.[6]
# Age of responsibility
The age at which children are considered responsible for their own actions has also changed over time, and this is reflected in the way they are treated in courts of law. In Roman times, children were regarded as not culpable for crimes, a position later adopted by the Church. In the nineteenth century, children younger than seven years old were believed incapable of crime. Children from the age of seven were considered responsible for their actions. Hence, they could face criminal charges, be sent to adult prisons, and be punished like adults by whipping, branding or hanging.[7] | https://www.wikidoc.org/index.php/Child | |
4d9740fc189a15b2deb0a70156578d733a1eca90 | wikidoc | Cigar | Cigar
A cigar is a tightly rolled bundle of dried and fermented tobacco, one end of which is ignited so that its smoke may be drawn into the smoker's mouth through the other end. Most cigar smokers do not inhale the smoke, and in some circles doing so is considered to be poor form.
The English word cigar is from the Spanish word cigarro, which in turn derives from the Mayan word for tobacco, siyar. (See entry at the Spanish Royal Academy's online dictionary ).
A poor-quality cigar is often referred to as a dog rocket.
Cigar tobacco is grown in significant quantities in such nations as Brazil, The Philippines, Cameroon, Cuba, Dominican Republic, Honduras, Indonesia, Mexico, Nicaragua and the United States, with Cuban cigars in particular being somewhat of an icon for cigars.
# History
The indigenous inhabitants of the islands of the Caribbean Sea and Mesoamerica have smoked cigars since as early as the 10th century, as evidenced by the discovery of a ceramic vessel at a Mayan archaeological site in Uaxactún, Guatemala, decorated with the painted figure of a man smoking a primitive cigar. Explorer Christopher Columbus is generally credited with the introduction of smoking to Europe.
Two of Columbus's crewmen during his 1492 journey, Rodrigo de Jerez and Luis de Torres, are said to have disembarked in Cuba and taken puffs of tobacco wrapped in maize husks, thus becoming the first European cigar smokers.
Towards the end of the 16th Century, 1592, the Spanish galleon "San Clemente" brought to the Philippines over the Acapulco - Manila Trade Route some 50 kgs of Cuban tobacco seed. This was then distributed among the Roman Catholic missions. The good churchmen found excellent climates and soils for growing with top class seed high quality tobacco on Philippine soil.
In the 19th century, cigar smoking was common while cigarettes were still comparatively rare. The cigar business was an important industry, and factories employed many people before mechanized manufacturing of cigars became practical. Many modern cigars, as a matter of prestige, are still rolled by hand; some boxes bear the phrase Totalmente a mano, "Totally by hand," as proof.
# Manufacture
Tobacco leaves are harvested and aged using a process that combines use of heat and shade to reduce sugar and water content without causing the large leaves to rot. This first part of the process, called curing, takes between 25 and 45 days and varies substantially based upon climatic conditions as well as the construction of sheds or barns used to store harvested tobacco. The curing process is manipulated based upon the type of tobacco, and the desired color of the leaf. The second part of the process, called fermentation, is carried out under conditions designed to help the leaf die slowly and gracefully. Temperature and humidity are controlled to ensure that the leaf continues to ferment, without rotting or disintegrating. This is where the flavor, burning, and aroma characteristics are primarily brought out in the leaf.
Once the leaves have aged properly, they are sorted for use as filler or wrapper based upon their appearance and overall quality. During this process, the leaves are continually moistened and handled carefully to ensure each leaf is best used according to its individual qualities. The leaf will continue to be baled, inspected, unbaled, reinspected, and baled again repeatedly as it continues its aging cycle. When the leaf has matured according to the manufacturer's specifications, it will be used in the production of a cigar.
The creation of a quality cigar is still performed by hand. An experienced cigar roller can produce hundreds of exceptional, nearly identical cigars per day. The rollers keep the tobacco moist-- especially the wrapper, and use specially designed crescent-shaped knives, called a chaveta, to form the filler and wrapper leaves quickly and accurately. Once rolled, the cigars are stored in wooden forms as they dry, in which their uncapped ends are cut to a uniform size. From this stage, the cigar is a complete product that can be "laid down" and aged for decades if kept as close to 70 degrees Fahrenheit (21 degrees Celsius), and 70% relative humidity, as the environment will allow. According to some experts,Template:Who however, long-term cigar aging requires significantly lower storage temperatures (for example, 40 degrees Fahrenheit is recommended for a 50 year storage). The higher temperatures which are usually used in standard cigar storage will cause the deterioration of the cigar after several years, resulting an eventual corruption of the cigar's flavor. Once cigars have been purchased, proper storage is usually accomplished by keeping the cigars in a specialized wooden box, or humidor, where conditions can be carefully controlled for long periods of time. Even if a cigar becomes dry, it can be successfully re-humidified so long as it has not been handled carelessly.
Some cigars, especially premium brands, use different varieties of tobacco for the filler and the wrapper.
"Long filler cigars" are a far higher quality of cigar, using long leaves throughout. These cigars also use a third variety of tobacco leaf, a "binder", between the filler and the outer wrapper. This permits the makers to use more delicate and attractive leaves as a wrapper. These high-quality cigars almost always blend varieties of tobacco. Even Cuban long-filler cigars will combine tobaccos from different parts of the island to incorporate several different flavors.
In low-grade cigars, chopped up tobacco leaves are used for the filler, and long leaves or even a type of "paper" made from tobacco pulp is used for the wrapper which binds the cigar together.
Historically, a lector or reader was always employed to entertain the cigar factory workers. This practice became obsolete once audio books for portable players became available, but it is still practiced in some Cuban factories. The name for the Montecristo cigar brand may have arisen from this practice. (See Cigar Brands).
## Families in the cigar industry
A unique part of the premium cigar industry is that nearly all modern cigar makers are either members of long-standing cigar families -- or purport themselves to be of one. Families dominate the cigar industry as the art and skill of hand making premium cigars has been passed down to each generation through family lines.
Families are such an integral part of the cigar industry that families are highlighted in the majority of cigar advertisements and in product packaging. When cigar lovers purchase a premium cigar, not only do they purchase a roll of fine, aged tobacco, but they also purchase a product of hand craftsmanship that is infused with the history and care of the family and roller that created it.
In 1992, Cigar Aficionado magazine created the "Cigar Hall of Fame" to recognize families in the cigar industry. To date, six individuals have been inducted into the Hall of Fame for their families' contributions to the cigar industry:
- Edgar M. Cullman, Chairman, General Cigar Company, New York
- Zino Davidoff, Founder, Davidoff et Cie., Geneva
- Carlos Fuente, Sr., Chairman, Tabacalera A. Fuente y Cia., Ybor City, Tampa
- Frank Llaneza, Chairman, Villazon & Co., Ybor City, Tampa
- Stanford J. Newman, Chairman, J.C. Newman Cigar Company, Ybor City, Tampa
- Angel Oliva, Sr., Founder, Oliva Tobacco Co., Ybor City, Tampa
The oldest family-owned premium cigar company in America is the J.C. Newman Cigar Company, a four generation family who has been making their Diamond Crown, Cuesta-Rey and Maximus cigars since 1895 and are headquartered in Tampa's famous Ybor City cigar district.
Perhaps the best known cigar family in the world is the Arturo Fuente family. Now led by father and son Carlos Fuente, Sr. and Jr., the Fuente Family has been rolling their Arturo Fuente, Fuente Fuente OpusX, and Montesino cigars since 1916.
The oldest Dominican Republic cigar maker is the León family, who have been making their León Jimenes and La Aurora cigars on the island since 1905.
Not only are premium cigar makers typically families, but so are those who grow the premium cigar tobacco. The Oliva Family has been growing cigar tobacco since 1934 and their family's tobacco is found in nearly every major cigar brand sold on the American market.
Some families, such as the well-known Padrons, have crossed over from tobacco leaf grower to cigar maker. While the Padron family has been growing tobacco since the 1850s, they began making cigars that bear their family's name in 1964.
Like the Padrons, the Carlos Torano family first began growing tobacco in 1916 before they started rolling their own family's brands, which also bear the family name, in the 1990s.
Even the premium cigars made by the cigar industry's two corporate conglomerates, Altadis and Swedish Match, are overseen by members of two cigar families, Altadis' Benjamin Menendez and Swedish Match's Ernesto Perez-Carrillo.
Families are such an important part of the premium cigar industry that the term "Cigar Family" is a registered trademark of the Arturo Fuente and J.C. Newman families and is used to distinguish and identify their families, premium cigar brands, and charitable foundation.
# Composition
Cigars are composed of three types of tobacco leaves, whose variations determine smoking and flavor characteristics:
## Wrappers
A cigar's outermost leaves, or wrapper, come from the widest part of the plant. The wrapper determines much of the cigar's character and flavor, and as such its color is often used to describe the cigar as a whole. Colors are designated as follows, from lightest to darkest:
- Double Claro – very light, slightly greenish (also called Candela, American Market Selection or jade); achieved by picking leaves before maturity and drying quickly; often grown in Connecticut
- Claro – light tan or yellowish. Indicative of shade-grown tobacco.
- Natural – light brown to brown; generally sun-grown.
- Colorado Claro – mid-brown; particularly associated with tobacco grown in the Dominican Republic or in Cuba
- Colorado – reddish-brown (also called Rosado)
- Colorado Maduro – dark brown; particularly associated with Honduras or Cuba-grown tobacco
- Maduro – dark brown to very dark brown
- Oscuro – a.k.a. "Double Maduro", black, often oily in appearance; tend to be grown in Cuba, Nicaragua, Brazil, Mexico, or Connecticut
Some manufacturers use an alternate designation:
- American Market Selection (AMS) – synonymous with Double Claro
- English Market Selection (EMS) – can refer to any color stronger than Double Claro but milder than Maduro
- Spanish Market Selection (SMS) – either of the two darkest colors, Maduro and Oscuro
It is often thought, mistakenly, that the darker the wrapper, the fuller the flavor. In fact it is the blend of the filler which dictates the flavour. If anything, dark wrappers add a touch of sweetness and light ones a hint of dryness to the taste.
## Fillers
The majority of a cigar is made up of fillers, wrapped-up bunches of leaves in its interior. Fillers of various strengths are usually blended to produce unique cigar flavors. The more oils present in the tobacco leaf, the stronger (less dry) the filler. Types range from the minimally-flavored Volado taken from the bottom of the plant, through the light-flavored (dry) Seco taken from the middle of the plant, and on to the strong Ligero from the upper leaves exposed to the most sunlight. Large-gauge cigars have a greater capacity to contain filler, and thus have greater potential to provide a full body and/or complex flavor. When used, Ligero is always folded into the middle of the filler because it burns slowly.
Fillers can be either long or short; long filler uses whole leaves and is of a better quality, while short filler, also called "mixed," uses chopped up leaves as well as stems and other bits. Recently some manufacturers have created what they term "medium filler" cigars. They do not use whole leaves but part of the leaves. The quality is usually much better than short filler cigars because the leaves are not chopped up and there are no stems and bits in the filler. Short filler cigars are easy to identify when smoked since they often burn hotter and the smoker will be spitting out bits and pieces from the smoking end. Long filled cigars of high quality should burn evenly and consistently. Also available is a filler called "Sandwich" (sometimes "Cuban Sandwich") which is a method of rolling a cigar using both long and short filler and using long outer leaf to sandwich the short in between.
## Binders
Binders are elastic leaves used to hold together the bunches of fillers.
# Size and shape
Cigars are commonly categorized by the size and shape of the cigar, which together are known as a vitola.
The size of a cigar is measured by two dimensions: its ring gauge (its diameter in sixty-fourths of an inch) and its length (in inches). For example, most non-Cuban robustos have a ring gauge of approximately 50 and a length of approximately 5 inches. Robustos which are of Cuban origin always have a ring gauge of 50 and a length of 4 7/8 inches.
See also Factory Name.
## Parejo
The most common shape is the parejo, which has a cylindrical body, straight sides, one end open, and a round cap on the other end which is either snipped off, sliced perpendicularly (a V-cut), or punched through before smoking.
Parejos are designated by the following terms:
- Coronas
Rothschilds (4 1/2" x 50) after the Rothschild family
Robusto (4 7/8" x 50)
Hermosos No. 4 (5" x 48)
Mareva/Petit Corona (5 1/8" x 42)
Corona (5 1/2" x 42)
Corona Gorda (5 5/8" x 46)
Toro (6" x 50)
Corona Grande (6 1/8" x 42)
Cervantes/Lonsdale (6 1/2" x 42), named for Hugh Cecil Lowther, 5th Earl of Lonsdale
Dalia (6 3/4" x 43)
Julieta, also known as Churchill (7" x 47), named for Winston Churchill
Prominente/Double Corona (7 5/8" x 49)
Presidente (8" x 50)
Gran Corona ("A") (9 1/4" x 47)
- Rothschilds (4 1/2" x 50) after the Rothschild family
- Robusto (4 7/8" x 50)
- Hermosos No. 4 (5" x 48)
- Mareva/Petit Corona (5 1/8" x 42)
- Corona (5 1/2" x 42)
- Corona Gorda (5 5/8" x 46)
- Toro (6" x 50)
- Corona Grande (6 1/8" x 42)
- Cervantes/Lonsdale (6 1/2" x 42), named for Hugh Cecil Lowther, 5th Earl of Lonsdale
- Dalia (6 3/4" x 43)
- Julieta, also known as Churchill (7" x 47), named for Winston Churchill
- Prominente/Double Corona (7 5/8" x 49)
- Presidente (8" x 50)
- Gran Corona ("A") (9 1/4" x 47)
- Panatelas – longer and generally thinner than Coronas
Small Panatela (5" x 33)
Carlota (5 5/8" x 35)
Short Panatela (5" x 38)
Slim Panatela (6" x 34)
Panatela (6" x 38)
Deliciados/Laguito No. 1 (7 1/4" x 38)
- Small Panatela (5" x 33)
- Carlota (5 5/8" x 35)
- Short Panatela (5" x 38)
- Slim Panatela (6" x 34)
- Panatela (6" x 38)
- Deliciados/Laguito No. 1 (7 1/4" x 38)
## Figurado
Irregularly-shaped cigars are known as figurados and are sometimes considered of higher quality because they are more difficult to make.
Historically, especially during the 19th century, figurados were the most popular shapes, however, by the 1930s, they had fallen out of fashion and all but disappeared.
They have, however, recently received a small resurgence in popularity, and there are currently many brands(manufacturers) that produce figurados alongside the simpler parejos. The Cuban cigar brand Cuaba only has figurados in their range.
Figurados include the following:
- Torpedo - Like a parejo except that the cap is pointed.
- Pyramid - Has a broad foot and evenly narrows to a pointed cap.
- Perfecto - Narrow at both ends and bulged in the middle.
- Presidente/Diadema - shaped like a parejo but considered a figurado because of its enormous size and occasional closed foot akin to a perfecto.
- Culebras - Three long, pointed cigars braided together.
- Tuscanian - The typical Italian cigar, created in the early nineteenth century when Kentucky tobacco was hybridized with local varieties and used to create a long, tough, slim cigar thicker in the middle and tapered at the ends, with a very strong aroma. It is also known as a cheroot, which is the largest selling cigar shape in the United States.
Arturo Fuente, a large cigar manufacturer based in the Dominican Republic, has also manufactured figurados in exotic shapes ranging from chili peppers to baseball bats and American footballs. They are highly collectible and extremely expensive, when publicly available. In practice, the terms Torpedo and Pyramid are often used interchangeably, even among very knowledgeable cigar smokers. Min Ron Nee, the Hong Kong-based cigar expert whose work "An Illustrated Encyclopaedia of Post-Revolution Havana Cigars" is considered to be the definitive work on cigars and cigar terms, defines Torpedo as "cigar slang." Nee thinks the majority is right (because slang is defined by majority usage) and torpedoes are pyramids by another name.
# Flavour
Virtually all cigar aficionados enjoy the practice because of the rich and varied flavours one observes when smoking, although some eschew the connoisseurial qualities in favour of other factors. For those drawn by taste, each brand and type of cigar carries different qualities of taste. The wrapper does not, as is commonly thought, dictate the flavour of the cigar. However, darker wrappers tend to produce a sweetness, while lighter wrappers usually have a drier taste to them. Flavours of cigars whether mild, medium, or full bodied are not indicators of quality. Like all kinds of flavors they are highly personal.
Unlike cigarettes, cigars taste very little of smoke, and usually very much of tobacco with nuances of other tastes. Some cigar enthusiasts use a vocabulary similar to that of wine-tasters to describe the overtones and undertones observed while smoking a cigar. A fine cigar can have virtually no taste of smoke whatsoever.
Some of the more common flavours one observes while smoking a cigar include:
- Spice
- Cocoa / chocolate
- Peat / moss / earth
- Coffee
- Nut
- Wood
- Berry
- Honey
- Vanilla
Many different things affect the scent of cigar smoke: quality of the cigar, added flavours, tobacco type, cigar age, cigar humidity, production method (handmade vs. machine-made) and more.
Non-smokers subjected to second-hand cigar smoke have many different opinions about the scent of cigar smoke. Some enjoy the cigar smoke, noticing the difference between cigar smoke and the more common scent of cigarette smoke. However, other non-smokers do not appreciate or enjoy the scent of cigar smoke.
The most ardent enjoyers of cigar smoking will sometimes keep personal journals of cigars they've enjoyed, complete with personal ratings, description of flavors observed, sizes, brands, etc. The qualities and characteristics of cigar tasting are very similar to those of wine, bourbon, Scotch, beer, cognacs and tequila. Within a given specification, there are endless varieties. This dynamic is part of the appeal to which cigar smokers are continually drawn.
# Cuban Cigars
Cigars manufactured in Cuba are widely considered to be without peer, although many experts believe that the best offerings from Honduras and Nicaragua rival those from Cuba. The Cuban reputation is thought to arise from the unique characteristics of the Vuelta Abajo district in the Pinar del Río Province at the west of the island, where the microclimate allows high-quality tobacco to be grown.
Cuban cigars are rolled from tobacco leaves found throughout the country of Cuba. The filler, binder, and wrapper may come from different portions of the island. All cigar production in Cuba is controlled by the Cuban government, and each brand may be rolled in several different factories in Cuba. Cuban cigar rollers are claimed to be the most skilled rollers in the world.
Habanos SA and Cubatabaco do all the work relating to Cuban cigars,
including quality control, promoting and distributing and exportation.
Cuban cigars are either hand made, or machine made. All bear the statement Hecho en Cuba, on the box or label, regardless of method of production. Hand-finished cigars previously bunched by machine add Hecho a mano, while fully hand-made cigars say Totalmente a mano in stylized text. Some cigars show a TC or Tripa Corta - meaning short filler and cuttings were used in the hand-rolling process.
## List of current notable Cuban cigar brands
- Bolivar
- Cohiba
- Cuaba
- Diplomaticos
- El Rey Del Mundo
- Fonseca
- Guantanamera
- H. Upmann
- Hoyo de Monterrey
- Jose L. Piedra
- Juan Lopez
- La Gloria Cubana
- Macanudo
- Montecristo
- Partagas
- Por Larranaga
- Punch
- Quai D'Orsay
- Quintero
- Rafael Gonzalez
- Ramon Allones
- Romeo y Julieta
- Saint Luis Rey
- San Cristobal de la Habana
- Sancho Panza
- Trinidad
- Vegas Robaina
- Vegueros.
## United States embargo against Cuba
The cigar became inextricably intertwined with U.S. political history on February 7, 1962, when United States President John F. Kennedy, intending to sanction Fidel Castro's communist government, imposed a trade embargo on Cuba. Americans were thus prohibited from purchasing what were at the time considered the finest cigars on the market, and Cuba was deprived of a large portion of its customers. According to Pierre Salinger, then Kennedy's press secretary, the president ordered him on the evening of February 6 to obtain a thousand H. Upmann brand petit corona Cuban cigars; upon Salinger's arrival with the cigars the following morning, Kennedy signed the executive order which put the embargo into effect. Cigars (and tobacco leaves) imported prior to the embargo are not considered contraband, and are known as "pre-embargo Cubans."
In the United States, authentic Cuban-made cigars often carry a mystique among some aficionados for being perceived as "the best smoking experience" of all cigars, and for being "forbidden fruit" for Americans to purchase. Some aficionados consider Cuban cigars to be superior in quality to similar cigars made in other countries such as the Dominican Republic, Honduras, and Nicaragua. In fact, many of the major brand name cigars from these countries are manufactured under the supervision of Cigar Family members (see Families in the cigar industry below) who descended from those that formerly operated cigar factories in Cuba.
As of 2007, it remains illegal for Americans to purchase or import Cuban cigars, although they are readily available across the Northern border in Canada and small quantities can be brought back without trouble from US Customs if the bands are removed prior to crossing. However, there is a lively smuggling trade in Cuban cigars, coupled with inflated prices and rampant counterfeiting. Cuban cigars purchased in overseas ports such as Jamaica and other Caribbean islands, or Mexico, are almost always counterfeit. Because of the increased use of home computers and the advent of the Internet, it has become much easier for people in the United States to purchase illegal cigars online from neighboring countries such as Canada where there is no embargo against Cuba. The full impact of computers and the Internet on the embargo is not known. As with all black market internet purchases, there is a high risk of being scammed, either from receiving inferior counterfeit goods, or nothing.
## Cigars Specific to Other Countries
Italy produces the typical "Sigaro Toscano" (Tuscan Cigar).
Burma and India are traditionally associated with the cheroot.
# Popular culture
Cigars are often presented as stereotypical rich man's accessory. Cigars are often smoked to celebrate good fortune, like the birth of a child, a graduation, a big business accomplishment, etc. Some buy and keep a cigar 'for luck' with regard to a bet, with the intention of smoking it after winning the bet. The expression "Close but no cigar", has its origins in cigars being given out as prizes in games of chance at fairgrounds.
King Edward VII enjoyed smoking cigarettes and cigars, much to the chagrin of his mother, Queen Victoria. After her death, legend has it, King Edward said to his male guests at the end of a dinner party, "Gentlemen, you may smoke." In his name, a line of inexpensive American cigars has long been named King Edward.
Two men who died during the zenith of the cigar's popularity owing ultimately to nicotine addiction and the consequent cancer were President Ulysses S. Grant of the USA (throat cancer) and Dr. Sigmund Freud (mouth cancer). Both these men were noted for regularly smoking an entire box (20 cigars) a day.
Although Grant was able for the duration of the Civil War to stop drinking, he was most often seen with a cigar and after his Presidency, Grant contracted cancer. Not wishing to leave his wife Julia penniless, Grant decided to write and publish his memoirs while in great pain.
Freud likewise succumbed in the 1930s to a habit which he seems to have been reluctant to psychoanalyze. Challenged on the "phallic" shape of the cigar, Freud is supposed to have replied, "Sometimes, a cigar is just a cigar."
Winston Churchill was a famous cigar smoker, while his time as Britain's wartime leader was he rarely seen without one. Churchill also had a cigar size named in his honour.
Karl Marx the philosopher, and Groucho Marx the comedian were both heavy cigar smokers. When Groucho was ill with appendicitis, his brother Zeppo stood in for him onstage. Apparently, few people noticed the difference, but Zeppo admitted that the cigars he had to smoke made him sick.
Fellow Vaudevillian George Burns also smoked cigars as part of his "shtick." Comedians have often used cigar smoking as part of their comic timing.
Famous quotes about the cigar include not only Freud's but also from a Rudyard Kipling poem: "A woman is only a woman: but a good cigar is a smoke." Also: "What this country needs is a good five cent cigar." The cigar was also a staple for vaudeville jokes and slapstick, from the overexcited new father who says "have a baby, my wife just had a cigar" to the exploding cigar which may have been a coded proletarian gesture of resistance to the cigar, which with the top hat and tails was the semiotic for "capitalism" in the early 20th century.
Since apart from certain forms of heavily cured and strong snuff, the cigar is the most potent form of self-dosing with tobacco, it has long had associations of being a male rite of passage, as it may have had during the pre-Columbian era in America. Its fumes and rituals have in American and European cultures established a "men's hut"; in the 19th century, men would retire to the "smoking room" after dinner, to discuss serious issues.
Famous jazz musicians, most notably Miles Davis, were proud cigar smokers, appreciating their fine flavor & aroma, though never did they smoke on major stage. According to Davis, his favourite brand was Augusta, a rare brand only sold in restaurants & coffee shops, or directly to certain famous people, like himself.
One of the most recent developments in the cigar industry is to laser engrave right onto the outer cigar leaf (wrapper). This process uses modern lasers to remove the dark pigment from the leaf, leaving a white or tan print on the cigar itself. The process allows for personalization and improved logo visibility on these signature stogies. Cigars such as the Oliva Master Blend 2 have licensed the patented process; patent #'s: 6,180,914 and 6,172,328.
# Cigar-related charities
In 2001, the Arturo Fuente and J.C. Newman cigar families created the 501(c)(3) Cigar Family Charitable Foundation to help the impoverished communities surrounding the Fuente's Chateau de la Fuente cigar tobacco fields. To date, it has built schools, medical clinics, recreations facilities, and clean water filtration stations.
In 2004, Altadis founded the World of Montecristo Relief Organization, another 501(c)(3) charity that raises funds to help provide aid to the cigar-related regions in the Caribbean damaged by hurricanes.
As Cigar Aficionado reported, a number of other cigar makers have made charitable contributions an important part of the cigar industry. Since the Dominican Republic, Honduras, Nicaragua and Cuba, the four places where the vast majority of premium cigars are made, are frequently ravaged by storms, many cigar makers work to help those affected by storms in their areas. | Cigar
A cigar is a tightly rolled bundle of dried and fermented tobacco, one end of which is ignited so that its smoke may be drawn into the smoker's mouth through the other end. Most cigar smokers do not inhale the smoke, and in some circles doing so is considered to be poor form.
The English word cigar is from the Spanish word cigarro, which in turn derives from the Mayan word for tobacco, siyar. (See entry at the Spanish Royal Academy's online dictionary [1]).
A poor-quality cigar is often referred to as a dog rocket[2].
Cigar tobacco is grown in significant quantities in such nations as Brazil, The Philippines, Cameroon, Cuba, Dominican Republic, Honduras, Indonesia, Mexico, Nicaragua and the United States, with Cuban cigars in particular being somewhat of an icon for cigars.
# History
The indigenous inhabitants of the islands of the Caribbean Sea and Mesoamerica have smoked cigars since as early as the 10th century, as evidenced by the discovery of a ceramic vessel at a Mayan archaeological site in Uaxactún, Guatemala, decorated with the painted figure of a man smoking a primitive cigar. Explorer Christopher Columbus is generally credited with the introduction of smoking to Europe.
Two of Columbus's crewmen during his 1492 journey, Rodrigo de Jerez and Luis de Torres, are said to have disembarked in Cuba and taken puffs of tobacco wrapped in maize husks, thus becoming the first European cigar smokers.
Towards the end of the 16th Century, 1592, the Spanish galleon "San Clemente" brought to the Philippines over the Acapulco - Manila Trade Route some 50 kgs of Cuban tobacco seed. This was then distributed among the Roman Catholic missions. The good churchmen found excellent climates and soils for growing with top class seed high quality tobacco on Philippine soil.
In the 19th century, cigar smoking was common while cigarettes were still comparatively rare. The cigar business was an important industry, and factories employed many people before mechanized manufacturing of cigars became practical. Many modern cigars, as a matter of prestige, are still rolled by hand; some boxes bear the phrase Totalmente a mano, "Totally by hand," as proof.
# Manufacture
Tobacco leaves are harvested and aged using a process that combines use of heat and shade to reduce sugar and water content without causing the large leaves to rot. This first part of the process, called curing, takes between 25 and 45 days and varies substantially based upon climatic conditions as well as the construction of sheds or barns used to store harvested tobacco. The curing process is manipulated based upon the type of tobacco, and the desired color of the leaf. The second part of the process, called fermentation, is carried out under conditions designed to help the leaf die slowly and gracefully. Temperature and humidity are controlled to ensure that the leaf continues to ferment, without rotting or disintegrating. This is where the flavor, burning, and aroma characteristics are primarily brought out in the leaf.
Once the leaves have aged properly, they are sorted for use as filler or wrapper based upon their appearance and overall quality. During this process, the leaves are continually moistened and handled carefully to ensure each leaf is best used according to its individual qualities. The leaf will continue to be baled, inspected, unbaled, reinspected, and baled again repeatedly as it continues its aging cycle. When the leaf has matured according to the manufacturer's specifications, it will be used in the production of a cigar.
The creation of a quality cigar is still performed by hand. An experienced cigar roller can produce hundreds of exceptional, nearly identical cigars per day. The rollers keep the tobacco moist-- especially the wrapper, and use specially designed crescent-shaped knives, called a chaveta, to form the filler and wrapper leaves quickly and accurately. Once rolled, the cigars are stored in wooden forms as they dry, in which their uncapped ends are cut to a uniform size. From this stage, the cigar is a complete product that can be "laid down" and aged for decades if kept as close to 70 degrees Fahrenheit (21 degrees Celsius), and 70% relative humidity, as the environment will allow. According to some experts,Template:Who however, long-term cigar aging requires significantly lower storage temperatures (for example, 40 degrees Fahrenheit is recommended for a 50 year storage). The higher temperatures which are usually used in standard cigar storage will cause the deterioration of the cigar after several years, resulting an eventual corruption of the cigar's flavor. Once cigars have been purchased, proper storage is usually accomplished by keeping the cigars in a specialized wooden box, or humidor, where conditions can be carefully controlled for long periods of time. Even if a cigar becomes dry, it can be successfully re-humidified so long as it has not been handled carelessly.
Some cigars, especially premium brands, use different varieties of tobacco for the filler and the wrapper.
"Long filler cigars" are a far higher quality of cigar, using long leaves throughout. These cigars also use a third variety of tobacco leaf, a "binder", between the filler and the outer wrapper. This permits the makers to use more delicate and attractive leaves as a wrapper. These high-quality cigars almost always blend varieties of tobacco. Even Cuban long-filler cigars will combine tobaccos from different parts of the island to incorporate several different flavors.
In low-grade cigars, chopped up tobacco leaves are used for the filler, and long leaves or even a type of "paper" made from tobacco pulp is used for the wrapper which binds the cigar together.
Historically, a lector or reader was always employed to entertain the cigar factory workers. This practice became obsolete once audio books for portable players became available, but it is still practiced in some Cuban factories. The name for the Montecristo cigar brand may have arisen from this practice. (See Cigar Brands).
## Families in the cigar industry
A unique part of the premium cigar industry is that nearly all modern cigar makers are either members of long-standing cigar families -- or purport themselves to be of one. Families dominate the cigar industry as the art and skill of hand making premium cigars has been passed down to each generation through family lines.
Families are such an integral part of the cigar industry that families are highlighted in the majority of cigar advertisements and in product packaging. When cigar lovers purchase a premium cigar, not only do they purchase a roll of fine, aged tobacco, but they also purchase a product of hand craftsmanship that is infused with the history and care of the family and roller that created it.
In 1992, Cigar Aficionado magazine created the "Cigar Hall of Fame"[1] to recognize families in the cigar industry. To date, six individuals have been inducted into the Hall of Fame for their families' contributions to the cigar industry:
- Edgar M. Cullman, Chairman, General Cigar Company, New York
- Zino Davidoff, Founder, Davidoff et Cie., Geneva
- Carlos Fuente, Sr., Chairman, Tabacalera A. Fuente y Cia., Ybor City, Tampa
- Frank Llaneza, Chairman, Villazon & Co., Ybor City, Tampa
- Stanford J. Newman, Chairman, J.C. Newman Cigar Company, Ybor City, Tampa
- Angel Oliva, Sr., Founder, Oliva Tobacco Co., Ybor City, Tampa
The oldest family-owned premium cigar company in America is the J.C. Newman Cigar Company, a four generation family who has been making their Diamond Crown, Cuesta-Rey and Maximus cigars since 1895 and are headquartered in Tampa's famous Ybor City cigar district.
Perhaps the best known cigar family in the world is the Arturo Fuente family. Now led by father and son Carlos Fuente, Sr. and Jr., the Fuente Family has been rolling their Arturo Fuente, Fuente Fuente OpusX, and Montesino cigars since 1916.
The oldest Dominican Republic cigar maker is the León family, who have been making their León Jimenes and La Aurora cigars on the island since 1905.
Not only are premium cigar makers typically families, but so are those who grow the premium cigar tobacco. The Oliva Family has been growing cigar tobacco since 1934 and their family's tobacco is found in nearly every major cigar brand sold on the American market.
Some families, such as the well-known Padrons, have crossed over from tobacco leaf grower to cigar maker. While the Padron family has been growing tobacco since the 1850s, they began making cigars that bear their family's name in 1964.
Like the Padrons, the Carlos Torano family first began growing tobacco in 1916 before they started rolling their own family's brands, which also bear the family name, in the 1990s.
Even the premium cigars made by the cigar industry's two corporate conglomerates, Altadis and Swedish Match, are overseen by members of two cigar families, Altadis' Benjamin Menendez and Swedish Match's Ernesto Perez-Carrillo.
Families are such an important part of the premium cigar industry that the term "Cigar Family" is a registered trademark of the Arturo Fuente and J.C. Newman families and is used to distinguish and identify their families, premium cigar brands, and charitable foundation.
# Composition
Cigars are composed of three types of tobacco leaves, whose variations determine smoking and flavor characteristics:
## Wrappers
A cigar's outermost leaves, or wrapper, come from the widest part of the plant. The wrapper determines much of the cigar's character and flavor, and as such its color is often used to describe the cigar as a whole. Colors are designated as follows, from lightest to darkest:
- Double Claro – very light, slightly greenish (also called Candela, American Market Selection or jade); achieved by picking leaves before maturity and drying quickly; often grown in Connecticut
- Claro – light tan or yellowish. Indicative of shade-grown tobacco.
- Natural – light brown to brown; generally sun-grown.
- Colorado Claro – mid-brown; particularly associated with tobacco grown in the Dominican Republic or in Cuba
- Colorado – reddish-brown (also called Rosado)
- Colorado Maduro – dark brown; particularly associated with Honduras or Cuba-grown tobacco
- Maduro – dark brown to very dark brown
- Oscuro – a.k.a. "Double Maduro", black, often oily in appearance; tend to be grown in Cuba, Nicaragua, Brazil, Mexico, or Connecticut
Some manufacturers use an alternate designation:
- American Market Selection (AMS) – synonymous with Double Claro
- English Market Selection (EMS) – can refer to any color stronger than Double Claro but milder than Maduro
- Spanish Market Selection (SMS) – either of the two darkest colors, Maduro and Oscuro
It is often thought, mistakenly, that the darker the wrapper, the fuller the flavor. In fact it is the blend of the filler which dictates the flavour. If anything, dark wrappers add a touch of sweetness and light ones a hint of dryness to the taste.
## Fillers
The majority of a cigar is made up of fillers, wrapped-up bunches of leaves in its interior. Fillers of various strengths are usually blended to produce unique cigar flavors. The more oils present in the tobacco leaf, the stronger (less dry) the filler. Types range from the minimally-flavored Volado taken from the bottom of the plant, through the light-flavored (dry) Seco taken from the middle of the plant, and on to the strong Ligero from the upper leaves exposed to the most sunlight. Large-gauge cigars have a greater capacity to contain filler, and thus have greater potential to provide a full body and/or complex flavor. When used, Ligero is always folded into the middle of the filler because it burns slowly.
Fillers can be either long or short; long filler uses whole leaves and is of a better quality, while short filler, also called "mixed," uses chopped up leaves as well as stems and other bits. Recently some manufacturers have created what they term "medium filler" cigars. They do not use whole leaves but part of the leaves. The quality is usually much better than short filler cigars because the leaves are not chopped up and there are no stems and bits in the filler. Short filler cigars are easy to identify when smoked since they often burn hotter and the smoker will be spitting out bits and pieces from the smoking end. Long filled cigars of high quality should burn evenly and consistently. Also available is a filler called "Sandwich" (sometimes "Cuban Sandwich") which is a method of rolling a cigar using both long and short filler and using long outer leaf to sandwich the short in between.
## Binders
Binders are elastic leaves used to hold together the bunches of fillers.
# Size and shape
Cigars are commonly categorized by the size and shape of the cigar, which together are known as a vitola.
The size of a cigar is measured by two dimensions: its ring gauge (its diameter in sixty-fourths of an inch) and its length (in inches). For example, most non-Cuban robustos have a ring gauge of approximately 50 and a length of approximately 5 inches. Robustos which are of Cuban origin always have a ring gauge of 50 and a length of 4 7/8 inches.[citation needed]
See also Factory Name.
## Parejo
The most common shape is the parejo, which has a cylindrical body, straight sides, one end open, and a round cap on the other end which is either snipped off, sliced perpendicularly (a V-cut), or punched through before smoking.
Parejos are designated by the following terms:
- Coronas
Rothschilds (4 1/2" x 50) after the Rothschild family
Robusto (4 7/8" x 50)
Hermosos No. 4 (5" x 48)
Mareva/Petit Corona (5 1/8" x 42)
Corona (5 1/2" x 42)
Corona Gorda (5 5/8" x 46)
Toro (6" x 50)
Corona Grande (6 1/8" x 42)
Cervantes/Lonsdale (6 1/2" x 42), named for Hugh Cecil Lowther, 5th Earl of Lonsdale
Dalia (6 3/4" x 43)
Julieta, also known as Churchill (7" x 47), named for Winston Churchill
Prominente/Double Corona (7 5/8" x 49)
Presidente (8" x 50)
Gran Corona ("A") (9 1/4" x 47)
- Rothschilds (4 1/2" x 50) after the Rothschild family
- Robusto (4 7/8" x 50)
- Hermosos No. 4 (5" x 48)
- Mareva/Petit Corona (5 1/8" x 42)
- Corona (5 1/2" x 42)
- Corona Gorda (5 5/8" x 46)
- Toro (6" x 50)
- Corona Grande (6 1/8" x 42)
- Cervantes/Lonsdale (6 1/2" x 42), named for Hugh Cecil Lowther, 5th Earl of Lonsdale
- Dalia (6 3/4" x 43)
- Julieta, also known as Churchill (7" x 47), named for Winston Churchill
- Prominente/Double Corona (7 5/8" x 49)
- Presidente (8" x 50)
- Gran Corona ("A") (9 1/4" x 47)
- Panatelas – longer and generally thinner than Coronas
Small Panatela (5" x 33)
Carlota (5 5/8" x 35)
Short Panatela (5" x 38)
Slim Panatela (6" x 34)
Panatela (6" x 38)
Deliciados/Laguito No. 1 (7 1/4" x 38)
- Small Panatela (5" x 33)
- Carlota (5 5/8" x 35)
- Short Panatela (5" x 38)
- Slim Panatela (6" x 34)
- Panatela (6" x 38)
- Deliciados/Laguito No. 1 (7 1/4" x 38)
## Figurado
Irregularly-shaped cigars are known as figurados and are sometimes considered of higher quality because they are more difficult to make.
Historically, especially during the 19th century, figurados were the most popular shapes, however, by the 1930s, they had fallen out of fashion and all but disappeared.
They have, however, recently received a small resurgence in popularity, and there are currently many brands(manufacturers) that produce figurados alongside the simpler parejos. The Cuban cigar brand Cuaba only has figurados in their range.
Figurados include the following:
- Torpedo - Like a parejo except that the cap is pointed.
- Pyramid - Has a broad foot and evenly narrows to a pointed cap.
- Perfecto - Narrow at both ends and bulged in the middle.
- Presidente/Diadema - shaped like a parejo but considered a figurado because of its enormous size and occasional closed foot akin to a perfecto.
- Culebras - Three long, pointed cigars braided together.
- Tuscanian - The typical Italian cigar, created in the early nineteenth century when Kentucky tobacco was hybridized with local varieties and used to create a long, tough, slim cigar thicker in the middle and tapered at the ends, with a very strong aroma. It is also known as a cheroot, which is the largest selling cigar shape in the United States.
Arturo Fuente, a large cigar manufacturer based in the Dominican Republic, has also manufactured figurados in exotic shapes ranging from chili peppers to baseball bats and American footballs. They are highly collectible and extremely expensive, when publicly available. In practice, the terms Torpedo and Pyramid are often used interchangeably, even among very knowledgeable cigar smokers. Min Ron Nee, the Hong Kong-based cigar expert whose work "An Illustrated Encyclopaedia of Post-Revolution Havana Cigars" is considered to be the definitive work on cigars and cigar terms, defines Torpedo as "cigar slang." Nee thinks the majority is right (because slang is defined by majority usage) and torpedoes are pyramids by another name.
# Flavour
Virtually all cigar aficionados enjoy the practice because of the rich and varied flavours one observes when smoking, although some eschew the connoisseurial qualities in favour of other factors. For those drawn by taste, each brand and type of cigar carries different qualities of taste. The wrapper does not, as is commonly thought, dictate the flavour of the cigar. However, darker wrappers tend to produce a sweetness, while lighter wrappers usually have a drier taste to them. Flavours of cigars whether mild, medium, or full bodied are not indicators of quality. Like all kinds of flavors they are highly personal.
Unlike cigarettes, cigars taste very little of smoke, and usually very much of tobacco with nuances of other tastes. Some cigar enthusiasts use a vocabulary similar to that of wine-tasters to describe the overtones and undertones observed while smoking a cigar. A fine cigar can have virtually no taste of smoke whatsoever.
Some of the more common flavours one observes while smoking a cigar include:
- Spice
- Cocoa / chocolate
- Peat / moss / earth
- Coffee
- Nut
- Wood
- Berry
- Honey
- Vanilla
Many different things affect the scent of cigar smoke: quality of the cigar, added flavours, tobacco type, cigar age, cigar humidity, production method (handmade vs. machine-made) and more.
Non-smokers subjected to second-hand cigar smoke have many different opinions about the scent of cigar smoke. Some enjoy the cigar smoke, noticing the difference between cigar smoke and the more common scent of cigarette smoke. However, other non-smokers do not appreciate or enjoy the scent of cigar smoke.
The most ardent enjoyers of cigar smoking will sometimes keep personal journals of cigars they've enjoyed, complete with personal ratings, description of flavors observed, sizes, brands, etc. The qualities and characteristics of cigar tasting are very similar to those of wine, bourbon, Scotch, beer, cognacs and tequila. Within a given specification, there are endless varieties. This dynamic is part of the appeal to which cigar smokers are continually drawn.
# Cuban Cigars
Cigars manufactured in Cuba are widely considered to be without peer, although many experts believe that the best offerings from Honduras and Nicaragua rival those from Cuba. The Cuban reputation is thought to arise from the unique characteristics of the Vuelta Abajo district in the Pinar del Río Province at the west of the island, where the microclimate allows high-quality tobacco to be grown.
Cuban cigars are rolled from tobacco leaves found throughout the country of Cuba. The filler, binder, and wrapper may come from different portions of the island. All cigar production in Cuba is controlled by the Cuban government, and each brand may be rolled in several different factories in Cuba. Cuban cigar rollers are claimed to be the most skilled rollers in the world.
Habanos SA and Cubatabaco do all the work relating to Cuban cigars,
including quality control, promoting and distributing and exportation.
Cuban cigars are either hand made, or machine made. All bear the statement Hecho en Cuba, on the box or label, regardless of method of production. Hand-finished cigars previously bunched by machine add Hecho a mano, while fully hand-made cigars say Totalmente a mano in stylized text. Some cigars show a TC or Tripa Corta - meaning short filler and cuttings were used in the hand-rolling process.
## List of current notable Cuban cigar brands
- Bolivar
- Cohiba
- Cuaba
- Diplomaticos
- El Rey Del Mundo
- Fonseca
- Guantanamera
- H. Upmann
- Hoyo de Monterrey
- Jose L. Piedra
- Juan Lopez
- La Gloria Cubana
- Macanudo
- Montecristo
- Partagas
- Por Larranaga
- Punch
- Quai D'Orsay
- Quintero
- Rafael Gonzalez
- Ramon Allones
- Romeo y Julieta
- Saint Luis Rey
- San Cristobal de la Habana
- Sancho Panza
- Trinidad
- Vegas Robaina
- Vegueros.
## United States embargo against Cuba
The cigar became inextricably intertwined with U.S. political history on February 7, 1962, when United States President John F. Kennedy, intending to sanction Fidel Castro's communist government, imposed a trade embargo on Cuba. Americans were thus prohibited from purchasing what were at the time considered the finest cigars on the market, and Cuba was deprived of a large portion of its customers. According to Pierre Salinger, then Kennedy's press secretary, the president ordered him on the evening of February 6 to obtain a thousand H. Upmann brand petit corona Cuban cigars; upon Salinger's arrival with the cigars the following morning, Kennedy signed the executive order which put the embargo into effect.[2] Cigars (and tobacco leaves) imported prior to the embargo are not considered contraband, and are known as "pre-embargo Cubans."
In the United States, authentic Cuban-made cigars often carry a mystique among some aficionados for being perceived as "the best smoking experience" of all cigars, and for being "forbidden fruit" for Americans to purchase. Some aficionados consider Cuban cigars to be superior in quality to similar cigars made in other countries such as the Dominican Republic, Honduras, and Nicaragua. In fact, many of the major brand name cigars from these countries are manufactured under the supervision of Cigar Family members (see Families in the cigar industry below) who descended from those that formerly operated cigar factories in Cuba.
As of 2007, it remains illegal for Americans to purchase or import Cuban cigars[3], although they are readily available across the Northern border in Canada and small quantities can be brought back without trouble from US Customs if the bands are removed prior to crossing. However, there is a lively smuggling trade in Cuban cigars, coupled with inflated prices and rampant counterfeiting. Cuban cigars purchased in overseas ports such as Jamaica and other Caribbean islands, or Mexico, are almost always counterfeit. Because of the increased use of home computers and the advent of the Internet, it has become much easier for people in the United States to purchase illegal cigars online from neighboring countries such as Canada where there is no embargo against Cuba. The full impact of computers and the Internet on the embargo is not known. As with all black market internet purchases, there is a high risk of being scammed, either from receiving inferior counterfeit goods, or nothing.
## Cigars Specific to Other Countries
Italy produces the typical "Sigaro Toscano" (Tuscan Cigar).
Burma and India are traditionally associated with the cheroot.
# Popular culture
Cigars are often presented as stereotypical rich man's accessory. Cigars are often smoked to celebrate good fortune, like the birth of a child, a graduation, a big business accomplishment, etc. Some buy and keep a cigar 'for luck' with regard to a bet, with the intention of smoking it after winning the bet. The expression "Close but no cigar", has its origins in cigars being given out as prizes in games of chance at fairgrounds.
King Edward VII enjoyed smoking cigarettes and cigars, much to the chagrin of his mother, Queen Victoria. After her death, legend has it, King Edward said to his male guests at the end of a dinner party, "Gentlemen, you may smoke." In his name, a line of inexpensive American cigars has long been named King Edward.
Two men who died during the zenith of the cigar's popularity owing ultimately to nicotine addiction and the consequent cancer were President Ulysses S. Grant of the USA (throat cancer) and Dr. Sigmund Freud (mouth cancer). Both these men were noted for regularly smoking an entire box (20 cigars) a day.
Although Grant was able for the duration of the Civil War to stop drinking, he was most often seen with a cigar and after his Presidency, Grant contracted cancer. Not wishing to leave his wife Julia penniless, Grant decided to write and publish his memoirs while in great pain.
Freud likewise succumbed in the 1930s to a habit which he seems to have been reluctant to psychoanalyze. Challenged on the "phallic" shape of the cigar, Freud is supposed to have replied, "Sometimes, a cigar is just a cigar."[4]
Winston Churchill was a famous cigar smoker, while his time as Britain's wartime leader was he rarely seen without one. Churchill also had a cigar size named in his honour.
Karl Marx the philosopher, and Groucho Marx the comedian were both heavy cigar smokers. When Groucho was ill with appendicitis, his brother Zeppo stood in for him onstage. Apparently, few people noticed the difference, but Zeppo admitted that the cigars he had to smoke made him sick.
Fellow Vaudevillian George Burns also smoked cigars as part of his "shtick." Comedians have often used cigar smoking as part of their comic timing.
Famous quotes about the cigar include not only Freud's but also from a Rudyard Kipling poem: "A woman is only a woman: but a good cigar is a smoke." Also: "What this country needs is a good five cent cigar." The cigar was also a staple for vaudeville jokes and slapstick, from the overexcited new father who says "have a baby, my wife just had a cigar" to the exploding cigar which may have been a coded proletarian gesture of resistance to the cigar, which with the top hat and tails was the semiotic for "capitalism" in the early 20th century.
Since apart from certain forms of heavily cured and strong snuff, the cigar is the most potent form of self-dosing with tobacco, it has long had associations of being a male rite of passage, as it may have had during the pre-Columbian era in America. Its fumes and rituals have in American and European cultures established a "men's hut"; in the 19th century, men would retire to the "smoking room" after dinner, to discuss serious issues.
Famous jazz musicians, most notably Miles Davis, were proud cigar smokers, appreciating their fine flavor & aroma, though never did they smoke on major stage. According to Davis, his favourite brand was Augusta, a rare brand only sold in restaurants & coffee shops, or directly to certain famous people, like himself.
One of the most recent developments in the cigar industry is to laser engrave right onto the outer cigar leaf (wrapper). This process uses modern lasers to remove the dark pigment from the leaf, leaving a white or tan print on the cigar itself. The process allows for personalization and improved logo visibility on these signature stogies. Cigars such as the Oliva Master Blend 2 have licensed the patented process; patent #'s: 6,180,914 and 6,172,328.
# Cigar-related charities
In 2001, the Arturo Fuente and J.C. Newman cigar families created the 501(c)(3) Cigar Family Charitable Foundation to help the impoverished communities surrounding the Fuente's Chateau de la Fuente cigar tobacco fields. To date, it has built schools, medical clinics, recreations facilities, and clean water filtration stations.
In 2004, Altadis founded the World of Montecristo Relief Organization, another 501(c)(3) charity that raises funds to help provide aid to the cigar-related regions in the Caribbean damaged by hurricanes.
As Cigar Aficionado reported,[5] a number of other cigar makers have made charitable contributions an important part of the cigar industry. Since the Dominican Republic, Honduras, Nicaragua and Cuba, the four places where the vast majority of premium cigars are made, are frequently ravaged by storms, many cigar makers work to help those affected by storms in their areas. | https://www.wikidoc.org/index.php/Cigar | |
e118f18760abe5c9b126046b4ef67d6b33fb5a73 | wikidoc | Clade | Clade
A clade is a taxonomic group of organisms comprising a single common ancestor and all the descendants of that ancestor. Any such group is considered to be a monophyletic group of organisms, and can be represented by both a phylogenetic analysis, as in a tree diagram, and by a cladogram (see cladistics), or simply as a taxonomic reference.
If a clade proves robust in different cladistic analyses using different sets of data, it may be adopted into taxonomy and become a taxon. Not all taxa, however, are considered to be clades. Reptiles, for example, are a paraphyletic group because they do not include aves (birds), which are thought to also have evolved from the common ancestor of the reptiles.
In cladistics, a clade that is located within another more inclusive clade is said to be "nested" within that clade. Nested clade analysis is beneficial in many ways. For instance, it enables the detection of range expansions in isolated geographic areas.
# Phylogenetic nomenclature
Phylogenetic nomenclature is formulated in terms of evolution and common descent rather than the type specimens, categorical ranks, and morphological characters. The latter is used most commonly in cladistic analysis. Taxon names are strictly connected to phylogenetic tree topology and evolutionary history. In taxonomy, each name is attached to a clade taxonomic group containing a common ancestor and all its descendants. Phylogenetic nomenclature discards categorical ranks. The problem with ranks are evident when one considers biodiversity lineages and clades. Questions like "how many lineages are there?" or "how many clades are there?" become pointless, since there are no answers. These are relative concepts, illustrating the fractal nature of the tree of life and the need to let a phylogenetic hypothesis be the focus, rather than the categories, when biodiversity is quantified. Phylogenetic nomenclature helps to put focus on phylogenetic trees by offering an explicit link between names and parts of species history, that is, clades.
# Traditional binomial nomenclature
In phylogenetics, binomial names are associated with the relationships of each described species. But this creates a problem because it makes assumptions about relationships about the description of the species identification. It suggests that species or genera are a unique category, and this contradicts the idea of recognizing only clades and lineages.
# Phylogenetic alternatives
To avoid the pitfalls of traditional Linnaean taxonomy in phylogenetic nomenclature, three new methods of phylogenetic naming have been proposed: node-, stem-, and apomorphy-based. In node-based naming, taxon name A might refer to the least inclusive clade containing X and Y. In stem-based naming, A would refer to the most inclusive clade containing X and Y but not Z. In apomorphy (derived feature)-based naming, A would refer to the clade identified by a feature synapomorphic (sharing a derivation) with a feature in specimen (taxon) X. Differences between a traditional approach and these phylogenetic alternatives become obvious when the phylogenetic hypothesis changes. Comparison between the traditional Linnaean approach to nomenclature and a phylogenetic alternative (node-based naming). Suppose that all we want to do is to give a name ("A") to a clade containing X and Y. In the Linnaean system this means that we have to introduce names for sister taxa, assigning all taxa to the categories species, genus, and family, and designate type species. No explicit reference to phylogeny is made. The phylogenetic alternative provides an explicit reference to evolutionary history, and nothing but the clade containing X and Y needs to be named. When the hypothesis of relationship changes, the phylogenetic alternative is cleaner and more explicit about what it refers to. | Clade
A clade is a taxonomic group of organisms comprising a single common ancestor and all the descendants of that ancestor. Any such group is considered to be a monophyletic group of organisms, and can be represented by both a phylogenetic analysis, as in a tree diagram, and by a cladogram (see cladistics), or simply as a taxonomic reference.
If a clade proves robust in different cladistic analyses using different sets of data, it may be adopted into taxonomy and become a taxon. Not all taxa, however, are considered to be clades. Reptiles, for example, are a paraphyletic group because they do not include aves (birds), which are thought to also have evolved from the common ancestor of the reptiles.
In cladistics, a clade that is located within another more inclusive clade is said to be "nested" within that clade. Nested clade analysis is beneficial in many ways. For instance, it enables the detection of range expansions in isolated geographic areas.
# Phylogenetic nomenclature
Phylogenetic nomenclature is formulated in terms of evolution and common descent rather than the type specimens, categorical ranks, and morphological characters. The latter is used most commonly in cladistic analysis. Taxon names are strictly connected to phylogenetic tree topology and evolutionary history. In taxonomy, each name is attached to a clade taxonomic group containing a common ancestor and all its descendants. Phylogenetic nomenclature discards categorical ranks. The problem with ranks are evident when one considers biodiversity lineages and clades. Questions like "how many lineages are there?" or "how many clades are there?" become pointless, since there are no answers. These are relative concepts, illustrating the fractal nature of the tree of life and the need to let a phylogenetic hypothesis be the focus, rather than the categories, when biodiversity is quantified. Phylogenetic nomenclature helps to put focus on phylogenetic trees by offering an explicit link between names and parts of species history, that is, clades.
# Traditional binomial nomenclature
In phylogenetics, binomial names are associated with the relationships of each described species. But this creates a problem because it makes assumptions about relationships about the description of the species identification. It suggests that species or genera are a unique category, and this contradicts the idea of recognizing only clades and lineages.
# Phylogenetic alternatives
To avoid the pitfalls of traditional Linnaean taxonomy in phylogenetic nomenclature, three new methods of phylogenetic naming have been proposed: node-, stem-, and apomorphy-based. In node-based naming, taxon name A might refer to the least inclusive clade containing X and Y. In stem-based naming, A would refer to the most inclusive clade containing X and Y but not Z. In apomorphy (derived feature)-based naming, A would refer to the clade identified by a feature synapomorphic (sharing a derivation) with a feature in specimen (taxon) X. Differences between a traditional approach and these phylogenetic alternatives become obvious when the phylogenetic hypothesis changes. Comparison between the traditional Linnaean approach to nomenclature and a phylogenetic alternative (node-based naming). Suppose that all we want to do is to give a name ("A") to a clade containing X and Y. In the Linnaean system this means that we have to introduce names for sister taxa, assigning all taxa to the categories species, genus, and family, and designate type species. No explicit reference to phylogeny is made. The phylogenetic alternative provides an explicit reference to evolutionary history, and nothing but the clade containing X and Y needs to be named. When the hypothesis of relationship changes, the phylogenetic alternative is cleaner and more explicit about what it refers to.
Template:Phylo
Template:Evolution
# External links
- Evolving Thoughts: Clade
- DM Hillis, D Zwickl & R Gutell: ~3000 species Tree of Life A cladogram?
- Phylogenetic systematics, a.k.a. evolutionary trees University of California, Berkeley
ca:Clade
eo:Klado
it:Clade
hu:Klád
ms:Klad
nl:Clade
no:Klade
fi:Kliini
sv:Klad
uk:Клада
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Clade | |
f3e3f60d62b3537bc0c98fb3aad21750280f1159 | wikidoc | Ergot | Ergot
# Overview
Ergot is the common name of a fungus in the genus Claviceps that is parasitic on certain grains and grasses. The form the fungus takes to winter-over is called a sclerotium, and this small structure is what is usually referred to as 'ergot', although referring to the members of the Claviceps genus as 'ergot' is also correct. There are about 50 known species of Claviceps, most of them in the tropical regions. Economically important species are Claviceps purpurea (parasitic on grass and cereals), C. fusiformis (on pearl millet, buffel grass), C. paspali (on dallis grass), and C. africana. C. purpurea can affect a number of cereals including rye (its most common host), triticale, wheat and barley. It affects oats only rarely.
There are three races or varieties of C. purpurea, differing in their host specificity :
- G1 — land grasses of open meadows and fields;
- G2 — grasses from moist, forest, and mountain habitats;
- G3 (C. purpurea var. spartinae) — salt marsh grasses (Spartina, Distichlis).
# Life cycle of the fungus
An ergot kernel called a sclerotium develops when a floret of flowering grass or cereal is infected by a spore of Claviceps fungus. The infection process mimics a pollen grain growing into an ovary during fertilization. The fungus then destroys the plant ovary and attaches itself to a vascular bundle originally intended for seed nutrition. The first stage of ergot infection manifests itself as a white soft tissue (known as sphacelia) producing sugary honeydew, which often drops out of the grass florets. This honeydew contains millions of asexual spores (conidia) which are dispersed to other florets by insects. Later, the sphacelia convert into a hard dry sclerotium inside the husk of the floret. At this stage, alkaloids and lipids accumulate in the sclerotium.
Claviceps species from tropic and subtropic regions produce macro- and microconidia in their honeydew. Macroconidia differ in shape and size between the species, whereas microconidia are rather uniform, oval to globose (5x3μm). Macroconidia are able to produce secondary conidia. A germ tube emerges from a macroconidium through the surface of a honeydew drop and a secondary conidium of the oval to pearlike shape is formed to which the contents of the original macroconidium migrates. Secondary conidia form white frost-like surface on honeydew drops and are spread by wind. No such process occurs in Claviceps purpurea, Claviceps grohii, Claviceps nigricans, and Claviceps zizaniae, all from North temperate regions.
When a mature sclerotium drops to the ground, the fungus remains dormant until proper conditions trigger its fruiting phase (onset of spring, rain period, etc.). It germinates, forming one or several fruiting bodies with head and stipe, variously colored (resembling a tiny mushroom). In the head, threadlike sexual spores are formed, which are ejected simultaneously, when suitable grass hosts are flowering. Ergot infection causes a reduction in the yield and quality of grain and hay produced, and if infected grain or hay is fed to livestock it may cause a disease called ergotism.
Black and protruding sclerotia of C. purpurea are well known. However, many tropical ergots have brown or greyish sclerotia, mimicking the shape of the host seed. For this reason, the infection is often overlooked.
# Effects on humans and animals
The ergot sclerotium contains high concentrations (up to 2% of dry mass) of ergotamine, a complex molecule consisting of a tripeptide-derived cyclol-lactam ring connected via amide linkage to a lysergic acid (ergoline) moiety, and other alkaloids of the ergoline group that are biosynthesized by the fungus. Ergot alkaloids have a wide range of biological activities including effects on circulation and neurotransmission.
Ergotism is the name for sometimes severe pathological syndromes affecting humans or animals that have ingested ergot alkaloid-containing plant material, such as ergot-contaminated grains. The common name for ergotism is "St. Anthony's fire" referring to the symptoms, such as severe burning sensations in the limbs. These are caused by effects of ergot alkaloids on the vascular system due to vasoconstriction of blood vessels, sometimes leading to gangrene and loss of limbs due to severely restricted blood circulation. The neurotropic activities of the ergot alkaloids may also cause hallucinations and attendant irrational behaviour, convulsions, and even death. Other symptoms include strong uterine contractions, nausea, seizures, and unconsciousness. Monks of the order of St. Anthony the Great specialized in treating ergotism victims with balms containing tranquilizing and blood circulation-stimulating plants; they were also skilled in amputations.
In addition to ergot alkaloids, Claviceps paspali also produces tremorgens (paspalitrem) causing "paspalum staggers" in cattle. Ergot alkaloids are also produced by fungi of the genera Penicillium and Aspergillus, notably by some isolates of the human pathogen Aspergillus fumigatus , and have been isolated from plants in the family Convolvulaceae, of which morning glory is best known.
Historically, controlled doses of ergot were used to induce abortions and to stop maternal bleeding after childbirth, but simple ergot extract is no longer used as a pharmaceutical.
Ergot contains no lysergic acid diethylamide (LSD) but instead contains ergotamine which is used to synthesize lysergic acid which is then used for lysergic acid diethylamide synthesis. Moreover, lysergic acid, a molecule used in the synthesis of LSD, can be isolated from ergot.
In the January 4, 2007 edition of the New England Journal of Medicine, a paper was published documenting a British study of over 11,000 Parkinson's Disease patients, which found that two commonly used Parkinson's drugs derived from ergot, Pergolide and Cabergoline, may increase the risk of leaky heart valves by up to 700%.
# Speculations
The disease cycle of the ergot fungus was first described in the 1800s, but the connection with ergot and epidemics among people and animals was known several hundred years before that.
Human poisoning due to the consumption of rye bread made from ergot-infected grain was common in Europe in the Middle Ages. The epidemic was known as St. Anthony's Fire or ignis sacer.
It has also been posited — though speculatively — that the Salem Witch Trials were initiated by young women who had consumed ergot-tainted rye. The Great Fear in France during the Revolution has also been linked by some historians to the influence of ergot.
British author John Grigsby claims that the presence of ergot in the stomachs of some of the so called 'bog-bodies' - Iron Age human remains from peat bogs N E Europe such as Tollund man - reveals that ergot was once a ritual drink in a prehistoric fertility cult akin to that at Eleusis in Greece. In his book Beowulf and Grendel he argues that the Anglo-Saxon poem Beowulf is based on a memory of the quelling of this fertility cult by followers of Odin. He states that Beowulf, meaning barley-wolf, suggests a connection to ergot which in German was known as the 'tooth of the wolf'.
Poisonings due to consumption of seeds treated with mercury compounds are sometimes misidentified as ergotism, such as the case of mass-poisoning in the French village Pont-Saint-Esprit in 1951:
The mass poisoning which took place in the French town of Pont-St. Esprit in 1951 has been widely presented in the lay and scientific press as an example of ergotism. While the poisoning was traced to bread, ergotism was not the cause of the syndrome, which was due to a toxic mercury compound used to disinfect grain to be planted as seed. Some sacks of grain treated with the fungicide were inadvertently ground into flour and baked into bread. Albert Hofmann arrived at this conclusion after visiting Pont-St. Esprit, and analyzing samples of the bread (which contained no ergot alkaloids) and autopsy samples of four of the victims who succumbed (Hofmann 1980; Hofmann 1991). On the other hand, Swedish toxicologist Bo Holmstedt insists the poisoning was in fact due to ergotism (Holmstedt 1978).…
As Dr. Simon Cotton (member of the Chemistry Department of Uppingham School, U.K.) notes, there have been numerous cases of mass-poisoning due to consumption of mercury-treated seeds:
More horrifying than this were epidemics of poisoning, caused by people eating treated seed grains. There was a serious epidemic in Iraq in 1956 and again in 1960, whilst use of seed wheat (which had been treated with a mixture of C2H5HgCl and C6H5HgOCOCH3) for food, caused the poisoning of about 100 people in West Pakistan in 1961. Another outbreak happened in Guatemala in 1965. Most serious was the disaster in Iraq in 1971–2, when according to official figures 459 died. Grain had been treated with methyl mercury compounds as a fungicide and should have been planted. Instead it was sold for milling and made into bread. It had been dyed red as a warning and also had warning labels in English and Spanish that no one could understand.
Kykeon, the beverage consumed by participants in the ancient Greek mystery of Eleusinian Mysteries, might have been based on hallucinogens from ergot.
Currently, rye grain is infected repeatedly to produce ergot. | Ergot
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Ergot is the common name of a fungus in the genus Claviceps that is parasitic on certain grains and grasses. The form the fungus takes to winter-over is called a sclerotium, and this small structure is what is usually referred to as 'ergot', although referring to the members of the Claviceps genus as 'ergot' is also correct. There are about 50 known species of Claviceps, most of them in the tropical regions. Economically important species are Claviceps purpurea (parasitic on grass and cereals), C. fusiformis (on pearl millet, buffel grass), C. paspali (on dallis grass), and C. africana[2](on sorghum). C. purpurea can affect a number of cereals including rye (its most common host), triticale, wheat and barley. It affects oats only rarely.
There are three races or varieties of C. purpurea, differing in their host specificity [3]:
- G1 — land grasses of open meadows and fields;
- G2 — grasses from moist, forest, and mountain habitats;
- G3 (C. purpurea var. spartinae) — salt marsh grasses (Spartina, Distichlis).
# Life cycle of the fungus
An ergot kernel called a sclerotium develops when a floret of flowering grass or cereal is infected by a spore of Claviceps fungus. The infection process mimics a pollen grain growing into an ovary during fertilization. The fungus then destroys the plant ovary and attaches itself to a vascular bundle originally intended for seed nutrition. The first stage of ergot infection manifests itself as a white soft tissue (known as sphacelia) producing sugary honeydew, which often drops out of the grass florets. This honeydew contains millions of asexual spores (conidia) which are dispersed to other florets by insects. Later, the sphacelia convert into a hard dry sclerotium inside the husk of the floret. At this stage, alkaloids and lipids accumulate in the sclerotium.
Claviceps species from tropic and subtropic regions produce macro- and microconidia in their honeydew. Macroconidia differ in shape and size between the species, whereas microconidia are rather uniform, oval to globose (5x3μm). Macroconidia are able to produce secondary conidia. A germ tube emerges from a macroconidium through the surface of a honeydew drop and a secondary conidium of the oval to pearlike shape is formed to which the contents of the original macroconidium migrates. Secondary conidia form white frost-like surface on honeydew drops and are spread by wind. No such process occurs in Claviceps purpurea, Claviceps grohii, Claviceps nigricans, and Claviceps zizaniae, all from North temperate regions.
When a mature sclerotium drops to the ground, the fungus remains dormant until proper conditions trigger its fruiting phase (onset of spring, rain period, etc.). It germinates, forming one or several fruiting bodies with head and stipe, variously colored (resembling a tiny mushroom). In the head, threadlike sexual spores are formed, which are ejected simultaneously, when suitable grass hosts are flowering. Ergot infection causes a reduction in the yield and quality of grain and hay produced, and if infected grain or hay is fed to livestock it may cause a disease called ergotism.
Black and protruding sclerotia of C. purpurea are well known. However, many tropical ergots have brown or greyish sclerotia, mimicking the shape of the host seed. For this reason, the infection is often overlooked.
# Effects on humans and animals
The ergot sclerotium contains high concentrations (up to 2% of dry mass) of ergotamine, a complex molecule consisting of a tripeptide-derived cyclol-lactam ring connected via amide linkage to a lysergic acid (ergoline) moiety, and other alkaloids of the ergoline group that are biosynthesized by the fungus.[1] Ergot alkaloids have a wide range of biological activities including effects on circulation and neurotransmission. [2]
Ergotism is the name for sometimes severe pathological syndromes affecting humans or animals that have ingested ergot alkaloid-containing plant material, such as ergot-contaminated grains. The common name for ergotism is "St. Anthony's fire" referring to the symptoms, such as severe burning sensations in the limbs[4]. These are caused by effects of ergot alkaloids on the vascular system due to vasoconstriction of blood vessels, sometimes leading to gangrene and loss of limbs due to severely restricted blood circulation. The neurotropic activities of the ergot alkaloids may also cause hallucinations and attendant irrational behaviour, convulsions, and even death. [1][2] Other symptoms include strong uterine contractions, nausea, seizures, and unconsciousness. Monks of the order of St. Anthony the Great specialized in treating ergotism victims with balms containing tranquilizing and blood circulation-stimulating plants; they were also skilled in amputations.
In addition to ergot alkaloids, Claviceps paspali also produces tremorgens (paspalitrem) causing "paspalum staggers" in cattle. Ergot alkaloids are also produced by fungi of the genera Penicillium and Aspergillus, notably by some isolates of the human pathogen Aspergillus fumigatus [3], and have been isolated from plants in the family Convolvulaceae, of which morning glory is best known.
Historically, controlled doses of ergot were used to induce abortions and to stop maternal bleeding after childbirth, but simple ergot extract is no longer used as a pharmaceutical.
Ergot contains no lysergic acid diethylamide (LSD) but instead contains ergotamine which is used to synthesize lysergic acid which is then used for lysergic acid diethylamide synthesis. Moreover, lysergic acid, a molecule used in the synthesis of LSD, can be isolated from ergot.
In the January 4, 2007 edition of the New England Journal of Medicine, a paper was published documenting a British study of over 11,000 Parkinson's Disease patients, which found that two commonly used Parkinson's drugs derived from ergot, Pergolide and Cabergoline, may increase the risk of leaky heart valves by up to 700%.
# Speculations
The disease cycle of the ergot fungus was first described in the 1800s, but the connection with ergot and epidemics among people and animals was known several hundred years before that.
Human poisoning due to the consumption of rye bread made from ergot-infected grain was common in Europe in the Middle Ages. The epidemic was known as St. Anthony's Fire or ignis sacer.
It has also been posited — though speculatively — that the Salem Witch Trials were initiated by young women who had consumed ergot-tainted rye. The Great Fear in France during the Revolution has also been linked by some historians to the influence of ergot.
British author John Grigsby claims that the presence of ergot in the stomachs of some of the so called 'bog-bodies' - Iron Age human remains from peat bogs N E Europe such as Tollund man - reveals that ergot was once a ritual drink in a prehistoric fertility cult akin to that at Eleusis in Greece. In his book Beowulf and Grendel he argues that the Anglo-Saxon poem Beowulf is based on a memory of the quelling of this fertility cult by followers of Odin. He states that Beowulf, meaning barley-wolf, suggests a connection to ergot which in German was known as the 'tooth of the wolf'.
Poisonings due to consumption of seeds treated with mercury compounds are sometimes misidentified as ergotism, such as the case of mass-poisoning in the French village Pont-Saint-Esprit in 1951:
The mass poisoning which took place in the French town of Pont-St. Esprit in 1951 has been widely presented in the lay and scientific press as an example of ergotism. While the poisoning was traced to bread, ergotism was not the cause of the syndrome, which was due to a toxic mercury compound used to disinfect grain to be planted as seed. Some sacks of grain treated with the fungicide were inadvertently ground into flour and baked into bread. Albert Hofmann arrived at this conclusion after visiting Pont-St. Esprit, and analyzing samples of the bread (which contained no ergot alkaloids) and autopsy samples of four of the victims who succumbed (Hofmann 1980; Hofmann 1991). On the other hand, Swedish toxicologist Bo Holmstedt insists the poisoning was in fact due to ergotism (Holmstedt 1978).…[4]
As Dr. Simon Cotton (member of the Chemistry Department of Uppingham School, U.K.) notes, there have been numerous cases of mass-poisoning due to consumption of mercury-treated seeds:
More horrifying than this were epidemics of poisoning, caused by people eating treated seed grains. There was a serious epidemic in Iraq in 1956 and again in 1960, whilst use of seed wheat (which had been treated with a mixture of C2H5HgCl and C6H5HgOCOCH3) for food, caused the poisoning of about 100 people in West Pakistan in 1961. Another outbreak happened in Guatemala in 1965. Most serious was the disaster in Iraq in 1971–2, when according to official figures 459 died. Grain had been treated with methyl mercury compounds as a fungicide and should have been planted. Instead it was sold for milling and made into bread. It had been dyed red as a warning and also had warning labels in English and Spanish that no one could understand.[5]
Kykeon, the beverage consumed by participants in the ancient Greek mystery of Eleusinian Mysteries, might have been based on hallucinogens from ergot.
Currently, rye grain is infected repeatedly to produce ergot. | https://www.wikidoc.org/index.php/Claviceps_purpurea | |
5efa91a8defc85cfc4b5fd184ae42d89446d3c75 | wikidoc | Clove | Clove
Cloves (Syzygium aromaticum, syn. Eugenia aromaticum or Eugenia caryophyllata) are the aromatic dried flower buds of a tree in the family Myrtaceae. Cloves are native to Indonesia and used as a spice in cuisine all over the world. The name derives from French clou, a nail, as the buds vaguely resemble small irregular nails in shape. Cloves are harvested primarily in Zanzibar, Indonesia and Madagascar; it is also grown in Pakistan, India, and Sri Lanka.
The clove tree is an evergreen which grows to a height ranging from 10-20 m, having large oval leaves and crimson flowers in numerous groups of terminal clusters. The flower buds are at first of a pale color and gradually become green, after which they develop into a bright red, when they are ready for collecting. Cloves are harvested when 1.5-2 cm long, and consist of a long calyx, terminating in four spreading sepals, and four unopened petals which form a small ball in the centre.
# Uses
According to FAO, Indonesia produced almost 80% of the world's clove output in 2005 followed at a distance by Madagascar and Tanzania.
Cloves can be used in cooking either whole or in a ground form, but as they are extremely strong, they are used sparingly. The spice is used throughout Europe and Asia and is smoked in a type of cigarettes locally known as kretek in Indonesia. Cloves are also an important incense material in Chinese and Japanese culture.
Cloves have historically been used in Indian cuisine (both North Indian and South Indian) as well as in Mexican cuisine, where it is often paired together with cumin and canela (cinnamon). In the north Indian cuisine, it is used in almost every sauce or side dish made, mostly ground up along with other spices. They are also a key ingredient in tea along with green cardamoms. In the south Indian cuisine, it finds extensive use in the biryani dish (similar to the pilaf, but with the addition of local spice taste), and is normally added whole to enhance the presentation and flavor of the rice.
# Medicinal uses
Cloves are used in Ayurveda called Lavang in India, Chinese medicine and western herbalism and dentistry where the essential oil is used as an anodyne (painkiller) for dental emergencies. Cloves are used as a carminative, to increase hydrochloric acid in the stomach and to improve peristalsis. Cloves are also said to be a natural antihelmintic. The essential oil is used in aromatherapy when stimulation and warming is needed, especially for digestive problems. Topical application over the stomach or abdomen will warm the digestive tract.
In Chinese medicine cloves or ding xiang are considered acrid, warm and aromatic, entering the kidney, spleen and stomach meridians, and are notable in their ability to warm the middle, direct stomach qi downward, to treat hiccough and to fortify the kidney yang. Because the herb is so warming it is contraindicated in any persons with fire symptoms and according to classical sources should not be used for anything except cold from yang deficiency. As such it is used in formulas for impotence or clear vaginal discharge from yang deficiency, for morning sickness together with ginseng and patchouli, or for vomiting and diarrhea due to spleen and stomach coldness. This would translate to hypochlorhydria.
Ayurvedic herbalist K.P. Khalsa, RH (AHG), uses cloves internally as a tea and topically as an oil for hypotonic muscles, including for multiple sclerosis. This is also found in Tibetan medicine. Ayurvedic herbalist Alan Tilotson, RH (AHG) suggests avoiding more than occasional use of cloves internally in the presence of pitta inflammation such as is found in acute flares of autoimmune diseases.
In West Africa, the Yorubas use cloves infused in water as a treatment for stomach upsets, vomitting and diarrhoea.The infusion is called Ogun Jedi-jedi.
Western studies have supported the use of cloves and clove oil for dental pain, and to a lesser extent for fever reduction, as a mosquito repellent and to prevent premature ejaculation. Clove may reduce blood sugar levels.
# Toxicity
Large amounts should be avoided in pregnancy.
Cloves can be irritating to the gastrointestinal tract, and should be avoided by people with gastric ulcers, colitis, or irritable bowel syndrome. In overdoses, cloves can cause vomiting, nausea, diarrhea, and upper gastrointestinal hemorrhage.
Severe cases can lead to changes in liver function, dyspnea, loss of consciousness, hallucination, and even death. The internal use of the essential oil should be restricted to 3 drops per day for an adult as excessive use can cause severe kidney damage.
# History
Until modern times, cloves grew only on a few islands in the Maluku Islands (historically called the Spice Islands), including Bacan, Makian, Moti, Ternate, and Tidore. Nevertheless, they found their way west to the Middle East and Europe well before the first century CE. Archeologists found cloves within a ceramic vessel in Syria along with evidence dating the find to within a few years of 1721 BC.
Cloves, along with nutmeg and pepper, were highly prized in Roman times, and Pliny the Elder once famously complained that "there is no year in which India does not drain the Roman Empire of fifty million sesterces". Cloves were traded by Arabs during the Middle Ages in the profitable Indian Ocean trade. In the late fifteenth century, Portugal took over the Indian Ocean trade, including cloves, due to the Treaty of Tordesillas with Spain and a separate treaty with the sultan of Ternate. The Portuguese brought large quantities of cloves to Europe, mainly from the Maluku Islands. Clove was then one of the most valuable spices, a kg costing around 7 g of gold.
The trade later became dominated by the Dutch in the seventeenth century. With great difficulty the French succeeded in introducing the clove tree into Mauritius in the year 1770; subsequently their cultivation was introduced into Guiana, Brazil, most of the West Indies, and Zanzibar, where the majority of cloves are grown today.
In Britain in the seventeenth and eighteenth centuries, cloves were worth at least their weight in gold, due to the high price of importing them.
The clove has become a commercial 'success', with products including clove drops being released and enjoyed by die-hard clove fans.
# Active compounds
The compound responsible for the cloves' aroma is eugenol. It is the main component in the essential oil extracted from cloves, comprising 72-90%. Eugenol has pronounced antiseptic and anaesthetic properties. Other important constituents include essential oils acetyl eugenol, beta-caryophylline and vanillin; crategolic acid; tannins, gallotannic acid, methyl salicylate (painkiller); the flavanoids eugenin, kaempferol, rhamnetin, and eugenitin; triterpenoids like oleanolic acid, stigmasterol and campesterol; and several sesquiterpenes.
# Notes and references
- ↑ Dorenburg, Andrew and Page, Karen. "The New American Chef: Cooking with the Best Flavors and Techniques from Around the World", John Wiley and Sons Inc., ©2003.
- ↑ Balch, Phyllis and Balch, James. Prescription for Nutritional Healing, 3rd ed., Avery Publishing, ©2000, pg. 94.
- ↑ Chinese Herbal Medicine: Materia Medica, Third Edition by Dan Bensky, Steven Clavey, Erich Stoger, and Andrew Gamble 2004
- ↑ Chinese Herbal Medicine: Materia Medica, Third Edition by Dan Bensky, Steven Clavey, Erich Stoger, and Andrew Gamble 2004
- ↑ TibetMed - Question: Multiple Sclerosis
- ↑ Tilotson, Alan. Special Diets for Illness
- ↑ National Institutes of Health, Medicine Plus. Clove (Eugenia aromatica) and Clove oil (Eugenol)
- ↑ Chinese Herbal Medicine: Materia Medica, Third Edition by Dan Bensky, Steven Clavey, Erich Stoger, and Andrew Gamble 2004
- ↑ Jump up to: 9.0 9.1 Turner, Jack (2004). Spice: The History of a Temptation. Vintage Books. pp. p. xv. ISBN 0-375-70705-0.CS1 maint: Extra text (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Chinese Herbal Medicine: Materia Medica, Third Edition by Dan Bensky, Steven Clavey, Erich Stoger, and Andrew Gamble. 2004
bg:Карамфил (подправка)
ca:Clavell d'espècia
cs:Hřebíček
co:Viulaccia
de:Gewürznelke
el:Γαριφαλόδενδρο
et:Nelk_(vürts)
eo:Kariofilo
id:Cengkeh
it:Eugenia caryophyllata
he:ציפורן (תבלין)
ht:Jiwòf
la:Syzygium aromaticum
lb:Neelcheskapp
lt:Kvapnusis gvazdikmedis
li:Groffelsnagel
hu:Szegfűszeg
nl:Kruidnagel
no:Kryddernellik
nn:Nelliktre
ksh:Jrovvötsnäähl
fi:Mausteneilikka
sv:Kryddnejlika
ta:கிராம்பு
uk:Гвоздика (пряність)
wa:Djirofe | Clove
Cloves (Syzygium aromaticum, syn. Eugenia aromaticum or Eugenia caryophyllata) are the aromatic dried flower buds of a tree in the family Myrtaceae. Cloves are native to Indonesia and used as a spice in cuisine all over the world. The name derives from French clou, a nail, as the buds vaguely resemble small irregular nails in shape. Cloves are harvested primarily in Zanzibar, Indonesia and Madagascar; it is also grown in Pakistan, India, and Sri Lanka.
The clove tree is an evergreen which grows to a height ranging from 10-20 m, having large oval leaves and crimson flowers in numerous groups of terminal clusters. The flower buds are at first of a pale color and gradually become green, after which they develop into a bright red, when they are ready for collecting. Cloves are harvested when 1.5-2 cm long, and consist of a long calyx, terminating in four spreading sepals, and four unopened petals which form a small ball in the centre.
# Uses
According to FAO, Indonesia produced almost 80% of the world's clove output in 2005 followed at a distance by Madagascar and Tanzania.
Cloves can be used in cooking either whole or in a ground form, but as they are extremely strong, they are used sparingly. The spice is used throughout Europe and Asia and is smoked in a type of cigarettes locally known as kretek in Indonesia. Cloves are also an important incense material in Chinese and Japanese culture.
Cloves have historically been used in Indian cuisine (both North Indian and South Indian) as well as in Mexican cuisine, where it is often paired together with cumin and canela (cinnamon).[1] In the north Indian cuisine, it is used in almost every sauce or side dish made, mostly ground up along with other spices. They are also a key ingredient in tea along with green cardamoms. In the south Indian cuisine, it finds extensive use in the biryani dish (similar to the pilaf, but with the addition of local spice taste), and is normally added whole to enhance the presentation and flavor of the rice.
# Medicinal uses
Cloves are used in Ayurveda called Lavang in India, Chinese medicine and western herbalism and dentistry where the essential oil is used as an anodyne (painkiller) for dental emergencies. Cloves are used as a carminative, to increase hydrochloric acid in the stomach and to improve peristalsis. Cloves are also said to be a natural antihelmintic.[2] The essential oil is used in aromatherapy when stimulation and warming is needed, especially for digestive problems. Topical application over the stomach or abdomen will warm the digestive tract.
In Chinese medicine cloves or ding xiang are considered acrid, warm and aromatic, entering the kidney, spleen and stomach meridians, and are notable in their ability to warm the middle, direct stomach qi downward, to treat hiccough and to fortify the kidney yang.[3] Because the herb is so warming it is contraindicated in any persons with fire symptoms and according to classical sources should not be used for anything except cold from yang deficiency. As such it is used in formulas for impotence or clear vaginal discharge from yang deficiency, for morning sickness together with ginseng and patchouli, or for vomiting and diarrhea due to spleen and stomach coldness.[4] This would translate to hypochlorhydria.
Ayurvedic herbalist K.P. Khalsa, RH (AHG), uses cloves internally as a tea and topically as an oil for hypotonic muscles, including for multiple sclerosis. This is also found in Tibetan medicine.[5] Ayurvedic herbalist Alan Tilotson, RH (AHG) suggests avoiding more than occasional use of cloves internally in the presence of pitta inflammation such as is found in acute flares of autoimmune diseases.[6]
In West Africa, the Yorubas use cloves infused in water as a treatment for stomach upsets, vomitting and diarrhoea.The infusion is called Ogun Jedi-jedi.
Western studies have supported the use of cloves and clove oil for dental pain, and to a lesser extent for fever reduction, as a mosquito repellent and to prevent premature ejaculation. Clove may reduce blood sugar levels.[7]
# Toxicity
Large amounts should be avoided in pregnancy.[citation needed]
Cloves can be irritating to the gastrointestinal tract, and should be avoided by people with gastric ulcers, colitis, or irritable bowel syndrome. In overdoses, cloves can cause vomiting, nausea, diarrhea, and upper gastrointestinal hemorrhage.[citation needed]
Severe cases can lead to changes in liver function, dyspnea, loss of consciousness, hallucination, and even death.[8] The internal use of the essential oil should be restricted to 3 drops per day for an adult as excessive use can cause severe kidney damage.[citation needed]
# History
Until modern times, cloves grew only on a few islands in the Maluku Islands (historically called the Spice Islands), including Bacan, Makian, Moti, Ternate, and Tidore.[9] Nevertheless, they found their way west to the Middle East and Europe well before the first century CE. Archeologists found cloves within a ceramic vessel in Syria along with evidence dating the find to within a few years of 1721 BC.[9]
Cloves, along with nutmeg and pepper, were highly prized in Roman times, and Pliny the Elder once famously complained that "there is no year in which India does not drain the Roman Empire of fifty million sesterces". Cloves were traded by Arabs during the Middle Ages in the profitable Indian Ocean trade. In the late fifteenth century, Portugal took over the Indian Ocean trade, including cloves, due to the Treaty of Tordesillas with Spain and a separate treaty with the sultan of Ternate. The Portuguese brought large quantities of cloves to Europe, mainly from the Maluku Islands. Clove was then one of the most valuable spices, a kg costing around 7 g of gold[citation needed].
The trade later became dominated by the Dutch in the seventeenth century. With great difficulty the French succeeded in introducing the clove tree into Mauritius in the year 1770; subsequently their cultivation was introduced into Guiana, Brazil, most of the West Indies, and Zanzibar, where the majority of cloves are grown today.
In Britain in the seventeenth and eighteenth centuries, cloves were worth at least their weight in gold, due to the high price of importing them.[citation needed]
The clove has become a commercial 'success', with products including clove drops being released and enjoyed by die-hard clove fans.
# Active compounds
The compound responsible for the cloves' aroma is eugenol. It is the main component in the essential oil extracted from cloves, comprising 72-90%. Eugenol has pronounced antiseptic and anaesthetic properties. Other important constituents include essential oils acetyl eugenol, beta-caryophylline and vanillin; crategolic acid; tannins, gallotannic acid, methyl salicylate (painkiller); the flavanoids eugenin, kaempferol, rhamnetin, and eugenitin; triterpenoids like oleanolic acid, stigmasterol and campesterol; and several sesquiterpenes.[10]
# Notes and references
- ↑ Dorenburg, Andrew and Page, Karen. "The New American Chef: Cooking with the Best Flavors and Techniques from Around the World", John Wiley and Sons Inc., ©2003.
- ↑ Balch, Phyllis and Balch, James. Prescription for Nutritional Healing, 3rd ed., Avery Publishing, ©2000, pg. 94.
- ↑ Chinese Herbal Medicine: Materia Medica, Third Edition by Dan Bensky, Steven Clavey, Erich Stoger, and Andrew Gamble 2004
- ↑ Chinese Herbal Medicine: Materia Medica, Third Edition by Dan Bensky, Steven Clavey, Erich Stoger, and Andrew Gamble 2004
- ↑ TibetMed - Question: Multiple Sclerosis
- ↑ http://oneearthherbs.squarespace.com/diseases/special-diets-for-illness.html Tilotson, Alan. Special Diets for Illness
- ↑ http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-clove.html National Institutes of Health, Medicine Plus. Clove (Eugenia aromatica) and Clove oil (Eugenol)
- ↑ Chinese Herbal Medicine: Materia Medica, Third Edition by Dan Bensky, Steven Clavey, Erich Stoger, and Andrew Gamble 2004
- ↑ Jump up to: 9.0 9.1 Turner, Jack (2004). Spice: The History of a Temptation. Vintage Books. pp. p. xv. ISBN 0-375-70705-0.CS1 maint: Extra text (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Chinese Herbal Medicine: Materia Medica, Third Edition by Dan Bensky, Steven Clavey, Erich Stoger, and Andrew Gamble. 2004
Template:Herbs & spices
bg:Карамфил (подправка)
ca:Clavell d'espècia
cs:Hřebíček
co:Viulaccia
de:Gewürznelke
el:Γαριφαλόδενδρο
et:Nelk_(vürts)
eo:Kariofilo
id:Cengkeh
it:Eugenia caryophyllata
he:ציפורן (תבלין)
ht:Jiwòf
la:Syzygium aromaticum
lb:Neelcheskapp
lt:Kvapnusis gvazdikmedis
li:Groffelsnagel
hu:Szegfűszeg
nl:Kruidnagel
no:Kryddernellik
nn:Nelliktre
ksh:Jrovvötsnäähl
fi:Mausteneilikka
sv:Kryddnejlika
ta:கிராம்பு
uk:Гвоздика (пряність)
wa:Djirofe | https://www.wikidoc.org/index.php/Clove | |
a06ce6c79ec022a3cc48efd2b2cb11c9685f50e8 | wikidoc | Cocoa | Cocoa
Cocoa is the dried and partially fermented fatty seed of the cacao tree from which chocolate is made. "Cocoa" can often also refer to cocoa powder, the dry powder made by grinding cocoa seeds and removing the cocoa butter from the dark, bitter cocoa solids; or it may refer to the combination of both cocoa powder and cocoa butter together .
A cocoa pod has a rough leathery rind about 3 cm thick (this varies with the origin and variety of pod). It is filled with sweet, mucilaginous pulp called 'baba de cacao' in South America, enclosing 30 to 50 large almond-like seeds (beans) that are fairly soft and pinkish or purplish in color.
Cocoa should not be confused with the coca plant which is used to create cocaine.
# History
The cacao tree may have originated in the foothills of the Andes in the Amazon and Orinoco basins of South America where today, examples of wild cacao still can be found. However, it may have had a larger range in the past, evidence for which may be obscured because of its cultivation in these areas long before, as well as after, the Spanish arrived. It may have been introduced into Central America by the ancientMayas, and cultivated in Mexico by the Toltecs and later by the Aztecs. It was a common currency throughout MesoAmerica and the Caribbean before the Spanish conquests.
Cacao trees will grow in a limited geographical zone, of approximately 20 degrees to the north and south of the Equator. Nearly 70% of the world crop is grown in West Africa.
Cocoa was an important commodity in Pre-Columbian Mesoamerica. Spanish chroniclers of the conquest of Mexico by Hernán Cortés relate that when Montezuma II, emperor of the Aztecs, dined he took no other beverage than chocolate, served in a golden goblet and eaten with a golden spoon. Flavored with vanilla and spices, his chocolate was whipped into a froth that dissolved in the mouth. No fewer than 50 pitchers of it were prepared for the emperor each day, and 2000 more for nobles of his court.
Chocolate was introduced to Europe by the Spaniards and became a popular beverage by the mid 1500s. They also introduced the cacao tree into the West Indies and the Philippines.
The cacao plant was first given its botanical name by Swedish natural scientist Carolus Linnaeus in his original classification of the plant kingdom, who called it "Theobroma ("food of the gods") cacao".
# Production
## World production
About 3,000,000 tonnes of cocoa is grown each year. The global production was
This is an increase of 131.7% in 30 years.
There are three main varieties of the Theobroma cacao: Forastero, Criollo, and Trinitario. The first comprises 95% of the world production of cacao, and is the most widely used. Overall, the highest quality of cacao comes from the Criollo variety and is considered a delicacy; however, Criollo is harder to produce, hence very few countries produce it, with the majority of production coming from Venezuela (Chuao and Porcelana). The Trinitario is a mix between Criollo and Forastero.
The Netherlands is the leading cocoa processing country, followed by the U.S..
Cocoa and its products (including chocolate) are used world-wide. Belgium had the highest per-capita consumption at 5.5 kg in 1995/96, 10 times the world average .
## Harvesting
When the pods ripen, they are harvested from the trunks and branches of the Cocoa tree with a curved knife on a long pole. The pod itself is green when ready to harvest, rather than red or orange. Normally, red or orange pods are considered of a lesser quality because their flavors and aromas are poorer; these are used for industrial chocolate. The pods are either opened on the field and the seeds extracted and carried to the fermentation area on the plantation, or the whole pods are taken to the fermentation area.
## Processing
The harvested pods are opened with a machete, the pulp and cocoa seeds are removed and the rind is discarded. The pulp and seeds are then piled in heaps, placed in bins, or laid out on grates for several days. During this time, the seeds and pulp undergo "sweating", where the thick pulp liquifies as it ferments. The fermented pulp trickles away, leaving cocoa seeds behind to be collected. Sweating is important for the quality of the beans, which originally have a strong bitter taste. If sweating is interrupted, the resulting cocoa may be ruined; if underdone the cocoa seed maintains a flavor similar to raw potatoes and becomes susceptible to mildew.
The liquified pulp is used by some cocoa producing countries to distill alcoholic spirits.
- Boy collecting cacao
Boy collecting cacao
- Cacao drying under the sun
Cacao drying under the sun
- Cacao drying square in front of church, Chuao, Venezuela.
Cacao drying square in front of church, Chuao, Venezuela.
- Woman drying cacao
Woman drying cacao
The fermented beans are dried by spreading them out over a large surface and constantly raking them. In large plantations, this is done on huge trays under the sun or by using artificial heat. Small plantations may dry their harvest on little trays or on cowhides. Finally, the beans are trodden and shuffled about (often using bare human feet) and sometimes, during this process, red clay mixed with water is sprinkled over the beans to obtain a finer color, polish, and protection against molds during shipment to factories in the United States, the Netherlands, United Kingdom, and other countries. Drying in the sun is preferable to drying by artificial means, as no extraneous flavors such as smoke or oil are introduced which might otherwise taint the flavor.
## Chocolate production
To make 1 kg (2.2 pounds) of chocolate, about 300 to 600 beans are processed, depending on the desired cocoa content. In a factory, the beans are washed and roasted. Next they are de-hulled by a "nibber" machine that also removes the germ. The nibs are what is left of the bean after this process, and are ground between three sets of stones into a thick creamy paste, known as chocolate liquor. This "liquor" is separated into cocoa powder and cocoa fat (cocoa butter) using a hydraulic press or the Broma process. This process produces around 50% cocoa butter and 50% cocoa powder. Standard cocoa powder has a fat content of approximately 10-12 percent. Cocoa butter is used in chocolate bar manufacture, other confectionery, soaps, and cosmetics.
Adding an alkali produces Dutch process cocoa powder, which is less acidic, darker and more mellow in flavor than what is generally available in most of the world. Regular (nonalkalized) cocoa is acidic, so when added to an alkaline ingredient like baking soda, the two react and leave a byproduct.
# Problems in the use of cocoa as a commodity
- Cocoa farmers in many countries lack information on production and marketing practices to help them improve their livelihoods. Charities such as the World Cocoa Foundation helps to support sustainable cocoa efforts through public-private partnerships in cocoa growing regions.
- Child slavery has commonly been used in its production to cover the lower profit margin. According to the U.S. Department of State, more than 109,000 children were working on cocoa farms in Côte d'Ivoire (Ivory Coast) in 'the worst forms of child labor' in 2002. See Cocoa Protocol for an effort to end this practice. The Cocoa Protocol has been critiqued by a number of groups including the International Labor Rights Fund since it is an industry initiative which has failed to meet its goals of phasing out child labor in the industry.
- Natural pollination is exclusively by midges, which may be affected by pesticides. Pollination is also carried out manually.
- Many cocoa farmers receive a low price for their production. This has led to cocoa and chocolate being available as fairtrade items in some countries. However, this fair trade remains as a tiny percentage of the total trade.
# Cocoa trading
Cocoa beans, Cocoa butter and cocoa powder are traded on two world exchanges: London and New York. The London market is based on West African cocoa and New York on cocoa predominantly from South East Asia. Cocoa is the world's smallest soft commodity market.
The futures price of cocoa butter and cocoa powder is determined by multiplying the bean price by a ratio. The combined butter and powder ratio has tended to be around 3.5. If the combined ratio falls below around 3.2, production ceases to be economically viable and some factories cease extraction of butter and powder and trade exclusively in cocoa liquor.
File:WikCOCOA.jpg
# Health benefits of cocoa consumption
Chocolate and cocoa contain a high level of flavonoids, specifically epicatechin, which may have beneficial cardiovascular effects on health.
The ingestion of flavonol-rich cocoa is associated with acute elevation of circulating Nitrous oxide, enhanced flow-mediated vasodilation, and augmented microcirculation.
Prolonged intake of flavonol-rich cocoa has been linked to cardiovascular health benefits, though it should be noted that this refers to plain cocoa. Milk chocolate's addition of whole milk reduces the overall cocoa content per ounce while increasing saturated fat levels, possibly negating some of cocoa's heart-healthy potential benefits. Nevertheless, studies have still found short term benefits in LDL cholesterol levels from dark chocolate consumption.
Hollenberg and colleagues of Harvard Medical School studied the effects of cocoa and flavanols on Panama's Kuna Indian population, who are heavy consumers of cocoa. The researchers found that the Kuna Indians living on the islands had significantly lower rates of heart disease and cancer compared to those on the mainland who do not drink cocoa as on the islands. It is believed that the improved blood flow after consumption of flavanol-rich cocoa may help to achieve health benefits in hearts and other organs. In particular, the benefits may extend to the brain and have important implications for learning and memory.
Foods rich in cocoa appear to reduce blood pressure but drinking green and black tea may not, according to an analysis of previously published research in the April 9, 2007 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
# Non-human animal consumption
Chocolate is a food product with appeal not only to the human population, but to many different animals as well. However, chocolate and cocoa contain a high level of xanthines, specifically theobromine and to a much lesser extent caffeine, that are detrimental to the health of many animals, including dogs and cats. While these compounds have desirable effects in humans, they cannot be efficiently metabolized in many animals and can lead to cardiac and nervous system problems, and if consumed in high quantities, even lead to death. However, since the mid-2000s, some cocoa derivatives with a low concentration of xanthines, have been designed by specialized industry to be suitable for pet consumption, enabling the pet food industry to offer animal safe chocolate and cocoa flavored products. It results in products with a high concentration of fiber and proteins, while maintaining low concentrations of sugar and other carbohydrates; thus enabling it to be used to create healthy functional cocoa pet products. | Cocoa
Cocoa is the dried and partially fermented fatty seed of the cacao tree from which chocolate is made. "Cocoa" can often also refer to cocoa powder, the dry powder made by grinding cocoa seeds and removing the cocoa butter from the dark, bitter cocoa solids; or it may refer to the combination of both cocoa powder and cocoa butter together [1].
A cocoa pod has a rough leathery rind about 3 cm thick (this varies with the origin and variety of pod). It is filled with sweet, mucilaginous pulp called 'baba de cacao' in South America, enclosing 30 to 50 large almond-like seeds (beans) that are fairly soft and pinkish or purplish in color.
Cocoa should not be confused with the coca plant which is used to create cocaine.
# History
The cacao tree may have originated in the foothills of the Andes in the Amazon and Orinoco basins of South America where today, examples of wild cacao still can be found. However, it may have had a larger range in the past, evidence for which may be obscured because of its cultivation in these areas long before, as well as after, the Spanish arrived. It may have been introduced into Central America by the ancientMayas, and cultivated in Mexico by the Toltecs and later by the Aztecs. It was a common currency throughout MesoAmerica and the Caribbean before the Spanish conquests.
Cacao trees will grow in a limited geographical zone, of approximately 20 degrees to the north and south of the Equator. Nearly 70% of the world crop is grown in West Africa.
Cocoa was an important commodity in Pre-Columbian Mesoamerica. Spanish chroniclers of the conquest of Mexico by Hernán Cortés relate that when Montezuma II, emperor of the Aztecs, dined he took no other beverage than chocolate, served in a golden goblet and eaten with a golden spoon. Flavored with vanilla and spices, his chocolate was whipped into a froth that dissolved in the mouth. No fewer than 50 pitchers of it were prepared for the emperor each day, and 2000 more for nobles of his court.
Chocolate was introduced to Europe by the Spaniards and became a popular beverage by the mid 1500s. They also introduced the cacao tree into the West Indies and the Philippines.
The cacao plant was first given its botanical name by Swedish natural scientist Carolus Linnaeus in his original classification of the plant kingdom, who called it "Theobroma ("food of the gods") cacao".
# Production
## World production
Template:Agricultural production box
About 3,000,000 tonnes of cocoa is grown each year. The global production was
This is an increase of 131.7% in 30 years.
There are three main varieties of the Theobroma cacao: Forastero, Criollo, and Trinitario. The first comprises 95% of the world production of cacao, and is the most widely used. Overall, the highest quality of cacao comes from the Criollo variety and is considered a delicacy[2]; however, Criollo is harder to produce, hence very few countries produce it, with the majority of production coming from Venezuela (Chuao and Porcelana). The Trinitario is a mix between Criollo and Forastero[3].
The Netherlands is the leading cocoa processing country, followed by the U.S..
Cocoa and its products (including chocolate) are used world-wide. Belgium had the highest per-capita consumption at 5.5 kg in 1995/96, 10 times the world average [1].
## Harvesting
When the pods ripen, they are harvested from the trunks and branches of the Cocoa tree with a curved knife on a long pole. The pod itself is green when ready to harvest, rather than red or orange. Normally, red or orange pods are considered of a lesser quality because their flavors and aromas are poorer; these are used for industrial chocolate. The pods are either opened on the field and the seeds extracted and carried to the fermentation area on the plantation, or the whole pods are taken to the fermentation area.
## Processing
The harvested pods are opened with a machete, the pulp and cocoa seeds are removed and the rind is discarded. The pulp and seeds are then piled in heaps, placed in bins, or laid out on grates for several days. During this time, the seeds and pulp undergo "sweating", where the thick pulp liquifies as it ferments. The fermented pulp trickles away, leaving cocoa seeds behind to be collected. Sweating is important for the quality of the beans, which originally have a strong bitter taste. If sweating is interrupted, the resulting cocoa may be ruined; if underdone the cocoa seed maintains a flavor similar to raw potatoes and becomes susceptible to mildew.
The liquified pulp is used by some cocoa producing countries to distill alcoholic spirits.
- Boy collecting cacao
Boy collecting cacao
- Cacao drying under the sun
Cacao drying under the sun
- Cacao drying square in front of church, Chuao, Venezuela.
Cacao drying square in front of church, Chuao, Venezuela.
- Woman drying cacao
Woman drying cacao
The fermented beans are dried by spreading them out over a large surface and constantly raking them. In large plantations, this is done on huge trays under the sun or by using artificial heat. Small plantations may dry their harvest on little trays or on cowhides. Finally, the beans are trodden and shuffled about (often using bare human feet) and sometimes, during this process, red clay mixed with water is sprinkled over the beans to obtain a finer color, polish, and protection against molds during shipment to factories in the United States, the Netherlands, United Kingdom, and other countries. Drying in the sun is preferable to drying by artificial means, as no extraneous flavors such as smoke or oil are introduced which might otherwise taint the flavor.
## Chocolate production
To make 1 kg (2.2 pounds) of chocolate, about 300 to 600 beans are processed, depending on the desired cocoa content. In a factory, the beans are washed and roasted. Next they are de-hulled by a "nibber" machine that also removes the germ. The nibs are what is left of the bean after this process, and are ground between three sets of stones into a thick creamy paste, known as chocolate liquor. This "liquor" is separated into cocoa powder and cocoa fat (cocoa butter) using a hydraulic press or the Broma process. This process produces around 50% cocoa butter and 50% cocoa powder. Standard cocoa powder has a fat content of approximately 10-12 percent. Cocoa butter is used in chocolate bar manufacture, other confectionery, soaps, and cosmetics.
Adding an alkali produces Dutch process cocoa powder, which is less acidic, darker and more mellow in flavor than what is generally available in most of the world. Regular (nonalkalized) cocoa is acidic, so when added to an alkaline ingredient like baking soda, the two react and leave a byproduct.
# Problems in the use of cocoa as a commodity
- Cocoa farmers in many countries lack information on production and marketing practices to help them improve their livelihoods. Charities such as the World Cocoa Foundation helps to support sustainable cocoa efforts through public-private partnerships in cocoa growing regions.
- Child slavery has commonly been used in its production to cover the lower profit margin. According to the U.S. Department of State, more than 109,000 children were working on cocoa farms in Côte d'Ivoire (Ivory Coast) in 'the worst forms of child labor' in 2002.[2] See Cocoa Protocol for an effort to end this practice. The Cocoa Protocol has been critiqued by a number of groups including the International Labor Rights Fund since it is an industry initiative which has failed to meet its goals of phasing out child labor in the industry.
- Natural pollination is exclusively by midges, which may be affected by pesticides. Pollination is also carried out manually.
- Many cocoa farmers receive a low price for their production. This has led to cocoa and chocolate being available as fairtrade items in some countries. However, this fair trade remains as a tiny percentage of the total trade.
# Cocoa trading
Cocoa beans, Cocoa butter and cocoa powder are traded on two world exchanges: London and New York. The London market is based on West African cocoa and New York on cocoa predominantly from South East Asia. Cocoa is the world's smallest soft commodity market.
The futures price of cocoa butter and cocoa powder is determined by multiplying the bean price by a ratio. The combined butter and powder ratio has tended to be around 3.5. If the combined ratio falls below around 3.2, production ceases to be economically viable and some factories cease extraction of butter and powder and trade exclusively in cocoa liquor.
File:WikCOCOA.jpg
# Health benefits of cocoa consumption
Chocolate and cocoa contain a high level of flavonoids, specifically epicatechin, which may have beneficial cardiovascular effects on health[citation needed].
The ingestion of flavonol-rich cocoa is associated with acute elevation of circulating Nitrous oxide, enhanced flow-mediated vasodilation, and augmented microcirculation[citation needed].
Prolonged intake of flavonol-rich cocoa has been linked to cardiovascular health benefits[citation needed], though it should be noted that this refers to plain cocoa. Milk chocolate's addition of whole milk reduces the overall cocoa content per ounce while increasing saturated fat levels, possibly negating some of cocoa's heart-healthy potential benefits. Nevertheless, studies have still found short term benefits in LDL cholesterol levels from dark chocolate consumption.
[4]
Hollenberg and colleagues of Harvard Medical School studied the effects of cocoa and flavanols on Panama's Kuna Indian population, who are heavy consumers of cocoa. The researchers found that the Kuna Indians living on the islands had significantly lower rates of heart disease and cancer compared to those on the mainland who do not drink cocoa as on the islands. It is believed that the improved blood flow after consumption of flavanol-rich cocoa may help to achieve health benefits in hearts and other organs. In particular, the benefits may extend to the brain and have important implications for learning and memory.[5][6]
Foods rich in cocoa appear to reduce blood pressure but drinking green and black tea may not, according to an analysis of previously published research in the April 9, 2007 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.[7]
# Non-human animal consumption
Chocolate is a food product with appeal not only to the human population, but to many different animals as well. However, chocolate and cocoa contain a high level of xanthines, specifically theobromine and to a much lesser extent caffeine, that are detrimental to the health of many animals, including dogs and cats. While these compounds have desirable effects in humans, they cannot be efficiently metabolized in many animals and can lead to cardiac and nervous system problems, and if consumed in high quantities, even lead to death. However, since the mid-2000s, some cocoa derivatives with a low concentration of xanthines, have been designed by specialized industry to be suitable for pet consumption, enabling the pet food industry to offer animal safe chocolate and cocoa flavored products.[citation needed] It results in products with a high concentration of fiber and proteins, while maintaining low concentrations of sugar and other carbohydrates; thus enabling it to be used to create healthy functional cocoa pet products. | https://www.wikidoc.org/index.php/Cocoa | |
f8cf8b3b5351ce028c0ad0f11deec7f0954f6760 | wikidoc | Colic | Colic
# Overview
Colic is a form of pain which starts and stops abruptly. It is often due to expansion of a viscus.
Types of Colic include:
- Baby colic, a condition, usually in infants, characterized by incessant crying
- Renal colic, a pain in the flank, characteristic of kidney stones
- Biliary colic, blockage by a gallstone of the common bile duct or the duct leading into it from the gallbladder
- Devon colic, an affliction caused by lead poisoning
- Painter's colic or lead poisoning | Colic
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Template:Editor help
# Overview
Colic is a form of pain which starts and stops abruptly. It is often due to expansion of a viscus.
Types of Colic include:
- Baby colic, a condition, usually in infants, characterized by incessant crying
- Renal colic, a pain in the flank, characteristic of kidney stones
- Biliary colic, blockage by a gallstone of the common bile duct or the duct leading into it from the gallbladder
- Devon colic, an affliction caused by lead poisoning
- Painter's colic or lead poisoning
Template:WikiDoc help menu
Template:WikiDoc sources | https://www.wikidoc.org/index.php/Colic | |
007682e50d85e4b56a6cd2285b77309033a22d6b | wikidoc | Color | Color
Color or colour is the visual perceptual property corresponding in humans to the categories called red, yellow, blue, black, etc. Color derives from the spectrum of light (distribution of light energy versus wavelength) interacting in the eye with the spectral sensitivities of the light receptors. Color categories and physical specifications of color are also associated with objects, materials, light sources, etc., based on their physical properties such as light absorption, reflection, or emission spectra.
Typically, only features of the composition of light that are detectable by humans (wavelength spectrum from 400 nm to 700 nm, roughly) are included, thereby objectively relating the psychological phenomenon of color to its physical specification.
Because perception of color stems from the varying sensitivity of different types of cone cells in the retina to different parts of the spectrum, colors may be defined and quantified by the degree to which they stimulate these cells. These physical or physiological quantifications of color, however, do not fully explain the psychophysical perception of color appearance.
The science of color is sometimes called chromatics. It includes the perception of color by the human eye and brain, the origin of color in materials, color theory in art, and the physics of electromagnetic radiation in the visible range (that is, what we commonly refer to simply as Light).
# Physics of color
Electromagnetic radiation is characterized by its wavelength (or frequency) and its intensity. When the wavelength is within the visible spectrum (the range of wavelengths humans can perceive, approximately from 380 nm to 740 nm), it is known as "visible light".
Most light sources emit light at many different wavelengths; a source's spectrum is a distribution giving its intensity at each wavelength. Although the spectrum of light arriving at the eye from a given direction determines the color sensation in that direction, there are many more possible spectral combinations than color sensations. In fact, one may formally define a color as a class of spectra that give rise to the same color sensation, although such classes would vary widely among different species, and to a lesser extent among individuals within the same species. In each such class the members are called metamers of the color in question.
## Spectral colors
The familiar colors of the rainbow in the spectrum – named using the Latin word for appearance or apparition by Isaac Newton in 1671 – include all those colors that can be produced by visible light of a single wavelength only, the pure spectral or monochromatic colors. The table at right shows approximate frequencies (in terahertz) and wavelengths (in nanometers) for various pure spectral colors. The wavelengths are measured in vacuum (see refraction).
The color table should not be interpreted as a definitive list – the pure spectral colors form a continuous spectrum, and how it is divided into distinct colors is a matter of culture, taste, and language. A common list identifies six main bands: red, orange, yellow, green, blue, and violet. Newton's conception included a seventh color, indigo, between blue and violet – but most people do not distinguish it, and most color scientists do not recognize it as a separate color; it is sometimes designated as wavelengths of 420–440 nm.
The intensity of a spectral color may alter its perception considerably; for example, a low-intensity orange-yellow is brown, and a low-intensity yellow-green is olive-green.
As discussed in the section on color vision, a light source need not actually be of one single wavelength to be perceived as a pure spectral color.
For discussion of non-spectral colors, see below.
## Color of objects
The color of an object depends on both the physics of the object in its environment and the characteristics of the perceiving eye and brain. Physically, objects can be said to have the color of the light leaving their surfaces, which normally depends on the spectrum of that light and of the incident illumination, as well as potentially on the angles of illumination and viewing. Some objects not only reflect light, but also transmit light or emit light themselves (see below), which contribute to the color also. And a viewer's perception of the object's color depends not only on the spectrum of the light leaving its surface, but also on a host of contextual cues, so that the color tends to be perceived as relatively constant: that is, relatively independent of the lighting spectrum, viewing angle, etc. This effect is known as color constancy.
Some generalizations of the physics can be drawn, neglecting perceptual effects for now:
- Light arriving at an opaque surface is either reflected "specularly" (that is, in the manner of a mirror), scattered (that is, reflected with diffuse scattering), or absorbed – or some combination of these.
- Opaque objects that do not reflect specularly (which tend to have rough surfaces) have their color determined by which wavelengths of light they scatter more and which they scatter less (with the light that is not scattered being absorbed). If objects scatter all wavelengths, they appear white. If they absorb all wavelengths, they appear black.
- Opaque objects that specularly reflect light of different wavelengths with different efficiencies look like mirrors tinted with colors determined by those differences. An object that reflects some fraction of impinging light and absorbs the rest may look black but also be faintly reflective; examples are black objects coated with layers of enamel or lacquer.
- Objects that transmit light are either translucent (scattering the transmitted light) or transparent (not scattering the transmitted light). If they also absorb (or reflect) light of varying wavelengths differentially, they appear tinted with a color determined by the nature of that absorption (or that reflectance).
- Objects may emit light that they generate themselves, rather than merely reflecting or transmitting light. They may do so because of their elevated temperature (they are then said to be incandescent), as a result of certain chemical reactions (a phenomenon called chemoluminescence), or for other reasons (see the articles Phosphorescence and List of light sources).
- Objects may absorb light and then as a consequence emit light that has different properties. They are then called fluorescent (if light is emitted only while light is absorbed) or phosphorescent (if light is emitted even after light ceases to be absorbed; this term is also sometimes loosely applied to light emitted due to chemical reactions).
For further treatment of the color of objects, see structural color, below.
To summarize, the color of an object is a complex result of its surface properties, its transmission properties, and its emission properties, all of which factors contribute to the mix of wavelengths in the light leaving the surface of the object. The perceived color is then further conditioned by the nature of the ambient illumination, and by the color properties of other objects nearby, via the effect known as color constancy and via other characteristics of the perceiving eye and brain.
# Color perception
## Development of theories of color vision
Although Aristotle and other ancient scientists had already written on the nature of light and color vision, it was not until Newton that light was identified as the source of the color sensation. In 1810, Goethe published his comprehensive Theory of Colors. In 1801 Thomas Young proposed his trichromatic theory, based on the observation that any color could be matched with a combination of three lights. This theory was later refined by James Clerk Maxwell and Hermann von Helmholtz. As Helmholtz puts it, "the principles of Newton's law of mixture were experimentally confirmed by Maxwell in 1856. Young's theory of color sensations, like so much else that this marvellous investigator achieved in advance of his time, remained unnoticed until Maxwell directed attention to it."
At the same time as Helmholtz, Ewald Hering developed the opponent process theory of color, noting that color blindness and afterimages typically come in opponent pairs (red-green, blue-yellow, and black-white). Ultimately these two theories were synthesized in 1957 by Hurvich and Jameson, who showed that retinal processing corresponds to the trichromatic theory, while processing at the level of the lateral geniculate nucleus corresponds to the opponent theory.
In 1931, an international group of experts known as the Commission Internationale d'Eclairage (CIE) developed a mathematical color model, which mapped out the space of observable colors and assigned a set of three numbers to each.
## Color in the eye
The ability of the human eye to distinguish colors is based upon the varying sensitivity of different cells in the retina to light of different wavelengths. The retina contains three types of color receptor cells, or cones. One type, relatively distinct from the other two, is most responsive to light that we perceive as violet, with wavelengths around 420 nm. (Cones of this type are sometimes called short-wavelength cones, S cones, or, misleadingly, blue cones.) The other two types are closely related genetically and chemically. One of them (sometimes called long-wavelength cones, L cones, or, misleadingly, red cones) is most sensitive to light we perceive as yellowish-green, with wavelengths around 564 nm; the other type (sometimes called middle-wavelength cones, M cones, or, misleadingly, green cones) is most sensitive to light perceived as green, with wavelengths around 534 nm.
Light, no matter how complex its composition of wavelengths, is reduced to three color components by the eye. For each location in the visual field, the three types of cones yield three signals based on the extent to which each is stimulated. These values are sometimes called tristimulus values.
The response curve as a function of wavelength for each type of cone is illustrated above. Because the curves overlap, some tristimulus values do not occur for any incoming light combination. For example, it is not possible to stimulate only the mid-wavelength/"green" cones; the other cones will inevitably be stimulated to some degree at the same time. The set of all possible tristimulus values determines the human color space. It has been estimated that humans can distinguish roughly 10 million different colors.
The other type of light-sensitive cell in the eye, the rod, has a different response curve. In normal situations, when light is bright enough to strongly stimulate the cones, rods play virtually no role in vision at all. On the other hand, in dim light, the cones are understimulated leaving only the signal from the rods, resulting in a colorless response. (Furthermore, the rods are barely sensitive to light in the "red" range.) In certain conditions of intermediate illumination, the rod response and a weak cone response can together result in color discriminations not accounted for by cone responses alone.
## Color in the brain
While the mechanisms of color vision at the level of the retina are well-described in terms of tristimulus values (see above), color processing after that point is organized differently. A dominant theory of color vision proposes that color information is transmitted out of the eye by three opponent processes, or opponent channels, each constructed from the raw output of the cones: a red-green channel, a blue-yellow channel and a black-white "luminance" channel. This theory has been supported by neurobiology, and accounts for the structure of our subjective color experience. Specifically, it explains why we cannot perceive a "reddish green" or "yellowish blue," and it predicts the color wheel: it is the collection of colors for which at least one of the two color channels measures a value at one of its extremes.
The exact nature of color perception beyond the processing already described, and indeed the status of color as a feature of the perceived world or rather as a feature of our perception of the world, is a matter of complex and continuing philosophical dispute (see qualia).
## Nonstandard color perception
### Color deficiency
If one or more types of a person's color-sensing cones are missing or less responsive than normal to incoming light, that person can distinguish fewer colors and is said to be color deficient or color blind (though this latter term can be misleading; almost all color deficient individuals can distinguish at least some colors). Some kinds of color deficiency are caused by anomalies in the number or nature of cones in the retina. Others (like central or cortical achromatopsia) are caused by neural anomalies in those parts of the brain where visual processing takes place.
### Tetrachromacy
While most humans are trichromatic (having three types of color receptors), many animals, known as tetrachromats, have four types. These include some species of spiders, most marsupials, birds, reptiles, and many species of fish. Other species are sensitive to only two axes of color or do not perceive color at all; these are called dichromats and monochromats respectively. A distinction is made between retinal tetrachromacy (having four pigments in cone cells in the retina, compared to three in trichromats) and functional tetrachromacy (having the ability to make enhanced color discriminations based on that retinal difference). As many as half of all women, but only a small percentage of men, are retinal tetrachromats. The phenomenon arises when an individual receives two slightly different copies of the gene for either the medium- or long-wavelength cones, which are carried on the x-chromosome, accounting for the differences between genders. For some of these retinal tetrachromats, color discriminations are enhanced, making them functional tetrachromats.
### Synesthesia
In certain forms of synesthesia, perceiving letters and numbers (grapheme–color synesthesia) or hearing musical sounds (music–color synesthesia) will lead to the unusual additional experiences of seeing colors. Behavioral and functional neuroimaging experiments have demonstrated that these color experiences lead to changes in behavioral tasks and lead to increased activation of brain regions involved in color perception, thus demonstrating their reality, and similarity to real color percepts, albeit evoked through a non-standard route.
## Afterimages
After exposure to strong light in their sensitivity range, photoreceptors of a given type become desensitized. For a few seconds after the light ceases, they will continue to signal less strongly than they otherwise would. Colors observed during that period will appear to lack the color component detected by the desensitized photoreceptors. This effect is responsible for the phenomenon of afterimages, in which the eye may continue to see a bright figure after looking away from it, but in a complementary color.
Afterimage effects have also been utilized by artists, including Vincent van Gogh.
## Color constancy
There is an interesting phenomenon which occurs when an artist uses a limited color palette: the eye tends to compensate by seeing any grey or neutral color as the color which is missing from the color wheel. E.g., in a limited palette consisting of red, yellow, black and white, a mixture of yellow and black will appear as a variety of green, a mixture of red and black will appear as a variety of purple, and pure grey will appear bluish.
The trichromatric theory discussed above is strictly true only if the whole scene seen by the eye is of one and the same color, which of course is unrealistic. In reality, the brain compares the various colors in a scene, in order to eliminate the effects of the illumination. If a scene is illuminated with one light, and then with another, as long as the difference between the light sources stays within a reasonable range, the colors of the scene will nevertheless appear constant to us. This was studied by Edwin Land in the 1970s and led to his retinex theory of color constancy.
## Color naming
Colors vary in several different ways, including hue (red vs. orange vs. blue), saturation, brightness, and gloss. Some color words are derived from the name of an object of that color, such as "orange" or "salmon", while others are abstract, like "red".
Different cultures have different terms for colors, and may also assign some color names to slightly different parts of the spectrum: for instance, the Chinese character 青 (rendered as qīng in Mandarin and ao in Japanese) has a meaning that covers both blue and green; blue and green are traditionally considered shades of "青."
In the 1969 study Basic Color Terms: Their Universality and Evolution, Brent Berlin and Paul Kay describe a pattern in naming "basic" colors (like "red" but not "red-orange" or "dark red" or "blood red", which are "shades" of red). All languages that have two "basic" color names distinguish dark/cool colors from bright/warm colors. The next colors to be distinguished are usually red and then blue or green. All languages with six "basic" colors include black, white, red, green, blue and yellow. The pattern holds up to a set of twelve: black, grey, white, pink, red, orange, yellow, green, blue, purple, brown, and azure (distinct from blue in Russian and Italian but not English).
# Associations
Individual colors have a variety of cultural associations such as national colors (in general described in individual color articles and color symbolism). The field of color psychology attempts to identify the effects of color on human emotion and activity. Chromotherapy is a form of alternative medicine attributed to various Eastern traditions.
# Health effects
When the color spectrum of artificial lighting is mismatched to that of sunlight, material health effects may arise including increased incidence of headache. This phenomenon is often coupled with adverse effects of over-illumination, since many of the same interior spaces that have color mismatch also have higher light intensity than desirable for the task being conducted in that space.
# Measurement and reproduction of color
## Relation to spectral colors
Most light sources are mixtures of various wavelengths of light. However, many such sources can still have a spectral color insofar as the eye cannot distinguish them from monochromatic sources. For example, most computer displays reproduce the spectral color orange as a combination of red and green light; it appears orange because the red and green are mixed in the right proportions to allow the eye's red and green cones to respond the way they do to orange.
A useful concept in understanding the perceived color of a non-monochromatic light source is the dominant wavelength, which identifies the single wavelength of light which produces a sensation most similar to the light source. Dominant wavelength is roughly akin to hue.
Of course, there are many color perceptions that by definition cannot be pure spectral colors due to desaturation or because they are purples (mixtures of red and violet light, from opposite ends of the spectrum). Some examples of necessarily non-spectral colors are the achromatic colors (black, gray and white) and colors such as pink, tan, and magenta.
Two different light spectra which have the same effect on the three color receptors in the human eye will be perceived as the same color. This is exemplified by the white light that is emitted by fluorescent lamps, which typically has a spectrum consisting of a few narrow bands, while daylight has a continuous spectrum. The human eye cannot tell the difference between such light spectra just by looking into the light source, although reflected colors from objects can look different. (This is often exploited e.g. to make fruit or tomatoes look more brightly red in shops.)
Similarly, most human color perceptions can be generated by a mixture of three colors called primaries. This is used to reproduce color scenes in photography, printing, television and other media. There are a number of methods or color spaces for specifying a color in terms of three particular primary colors. Each method has its advantages and disadvantages depending on the particular application.
No mixture of colors, though, can produce a fully pure color perceived as completely identical to a spectral color, although one can get very close for the longer wavelengths, where the chromaticity diagram above has a nearly straight edge. For example, mixing green light (530 nm) and blue light (460 nm) produces cyan light that is slightly desaturated, because response of the red color receptor would be greater to the green and blue light in the mixture than it would be to a pure cyan light at 485 nm that has the same intensity as the mixture of blue and green.
Because of this, and because the primaries in color printing systems generally are not pure themselves, the colors reproduced are never perfectly saturated colors, and so spectral colors cannot be matched exactly. However, natural scenes rarely contain fully saturated colors, thus such scenes can usually be approximated well by these systems. The range of colors that can be reproduced with a given color reproduction system is called the gamut. The CIE chromaticity diagram can be used to describe the gamut.
Another problem with color reproduction systems is connected with the acquisition devices, like cameras or scanners. The characteristics of the color sensors in the devices are often very far from the characteristics of the receptors in the human eye. In effect, acquisition of colors that have some special, often very "jagged," spectra caused for example by unusual lighting of the photographed scene can be relatively poor.
Species that have color receptors different from humans, e.g. birds that may have four receptors, can differentiate some colors that look the same to a human. In such cases, a color reproduction system 'tuned' to a human with normal color vision may give very inaccurate results for the other observers.
The next problem is different color response of different devices. For color information stored and transferred in a digital form, color management technique based on color profiles attached to color data and to devices with different color response helps to avoid deformations of the reproduced colors. The technique works only for colors in gamut of the particular devices, e.g. it can still happen that your monitor is not able to show you real color of your goldfish even if your camera can receive and store the color information properly and vice versa.
## Pigments and reflective media
Pigments are chemicals that selectively absorb and reflect different spectra of light. When a surface is painted with a pigment, light hitting the surface is reflected, minus some wavelengths. This subtraction of wavelengths produces the appearance of different colors. Most paints are a blend of several chemical pigments, intended to produce a reflection of a given color.
Pigment manufacturers assume the source light will be white, or of roughly equal intensity across the spectrum. If the light is not a pure white source (as in the case of nearly all forms of artificial lighting), the resulting spectrum will appear a slightly different color. Red paint, viewed under blue light, may appear black. Red paint is red because it reflects only the red components of the spectrum. Blue light, containing none of these, will create no reflection from red paint, creating the appearance of black.
## Structural color
Structural colors are colors caused by interference effects rather than by pigments. Color effects are produced when a material is scored with fine parallel lines, formed of a thin layer or of two or more parallel thin layers, or otherwise composed of microstructures on the scale of the color's wavelength. If the microstructures are spaced randomly, light of shorter wavelengths will be scattered preferentially to produce Tyndall effect colors: the blue of the sky, the luster of opals, and the blue of human irises. If the microstructures are aligned in arrays, for example the array of pits in a CD, they behave as a diffraction grating: the grating reflects different wavelengths in different directions due to interference phenomena, separating mixed "white" light into light of different wavelengths. If the structure is one or more thin layers then it will reflect some wavelengths and transmit others, depending on the layers' thickness.
Structural color is responsible for the blues and greens of the feathers of many birds (the blue jay, for example), as well as certain butterfly wings and beetle shells. Variations in the pattern's spacing often give rise to an iridescent effect, as seen in peacock feathers, soap bubbles, films of oil, and mother of pearl, because the reflected color depends upon the viewing angle. Peter Vukusic has carried out research in butterfly wings and beetle shells using electron micrography, and has since helped develop a range of "photonic" cosmetics using structural color.
Structural color is studied in the field of thin-film optics. A layman's term that describes particularly the most ordered or the most changeable structural colors is iridescence.
## Additional terms
- Hue: the color's direction from white, for example in the CIE chromaticity diagram.
- Colorfulness, chroma, or saturation: how "intense" or "concentrated" a color is; also known as chroma or purity.
- Value, brightness, or lightness: how light or dark a color is.
- Tint: a color made lighter by adding white.
- Shade: a color made darker by adding black. | Color
Template:Pp-semi-protected
Template:Two other uses
Template:Redirect6
Color or colour[1] is the visual perceptual property corresponding in humans to the categories called red, yellow, blue, black, etc. Color derives from the spectrum of light (distribution of light energy versus wavelength) interacting in the eye with the spectral sensitivities of the light receptors. Color categories and physical specifications of color are also associated with objects, materials, light sources, etc., based on their physical properties such as light absorption, reflection, or emission spectra.
Typically, only features of the composition of light that are detectable by humans (wavelength spectrum from 400 nm to 700 nm, roughly) are included, thereby objectively relating the psychological phenomenon of color to its physical specification.
Because perception of color stems from the varying sensitivity of different types of cone cells in the retina to different parts of the spectrum, colors may be defined and quantified by the degree to which they stimulate these cells. These physical or physiological quantifications of color, however, do not fully explain the psychophysical perception of color appearance.
The science of color is sometimes called chromatics. It includes the perception of color by the human eye and brain, the origin of color in materials, color theory in art, and the physics of electromagnetic radiation in the visible range (that is, what we commonly refer to simply as Light).
# Physics of color
Electromagnetic radiation is characterized by its wavelength (or frequency) and its intensity. When the wavelength is within the visible spectrum (the range of wavelengths humans can perceive, approximately from 380 nm to 740 nm), it is known as "visible light".
Most light sources emit light at many different wavelengths; a source's spectrum is a distribution giving its intensity at each wavelength. Although the spectrum of light arriving at the eye from a given direction determines the color sensation in that direction, there are many more possible spectral combinations than color sensations. In fact, one may formally define a color as a class of spectra that give rise to the same color sensation, although such classes would vary widely among different species, and to a lesser extent among individuals within the same species. In each such class the members are called metamers of the color in question.
## Spectral colors
The familiar colors of the rainbow in the spectrum – named using the Latin word for appearance or apparition by Isaac Newton in 1671 – include all those colors that can be produced by visible light of a single wavelength only, the pure spectral or monochromatic colors. The table at right shows approximate frequencies (in terahertz) and wavelengths (in nanometers) for various pure spectral colors. The wavelengths are measured in vacuum (see refraction).
The color table should not be interpreted as a definitive list – the pure spectral colors form a continuous spectrum, and how it is divided into distinct colors is a matter of culture, taste, and language. A common list identifies six main bands: red, orange, yellow, green, blue, and violet. Newton's conception included a seventh color, indigo, between blue and violet – but most people do not distinguish it, and most color scientists do not recognize it as a separate color; it is sometimes designated as wavelengths of 420–440 nm.
The intensity of a spectral color may alter its perception considerably; for example, a low-intensity orange-yellow is brown, and a low-intensity yellow-green is olive-green.
As discussed in the section on color vision, a light source need not actually be of one single wavelength to be perceived as a pure spectral color.
For discussion of non-spectral colors, see below.
## Color of objects
The color of an object depends on both the physics of the object in its environment and the characteristics of the perceiving eye and brain. Physically, objects can be said to have the color of the light leaving their surfaces, which normally depends on the spectrum of that light and of the incident illumination, as well as potentially on the angles of illumination and viewing. Some objects not only reflect light, but also transmit light or emit light themselves (see below), which contribute to the color also. And a viewer's perception of the object's color depends not only on the spectrum of the light leaving its surface, but also on a host of contextual cues, so that the color tends to be perceived as relatively constant: that is, relatively independent of the lighting spectrum, viewing angle, etc. This effect is known as color constancy.
Some generalizations of the physics can be drawn, neglecting perceptual effects for now:
- Light arriving at an opaque surface is either reflected "specularly" (that is, in the manner of a mirror), scattered (that is, reflected with diffuse scattering), or absorbed – or some combination of these.
- Opaque objects that do not reflect specularly (which tend to have rough surfaces) have their color determined by which wavelengths of light they scatter more and which they scatter less (with the light that is not scattered being absorbed). If objects scatter all wavelengths, they appear white. If they absorb all wavelengths, they appear black.
- Opaque objects that specularly reflect light of different wavelengths with different efficiencies look like mirrors tinted with colors determined by those differences. An object that reflects some fraction of impinging light and absorbs the rest may look black but also be faintly reflective; examples are black objects coated with layers of enamel or lacquer.
- Objects that transmit light are either translucent (scattering the transmitted light) or transparent (not scattering the transmitted light). If they also absorb (or reflect) light of varying wavelengths differentially, they appear tinted with a color determined by the nature of that absorption (or that reflectance).
- Objects may emit light that they generate themselves, rather than merely reflecting or transmitting light. They may do so because of their elevated temperature (they are then said to be incandescent), as a result of certain chemical reactions (a phenomenon called chemoluminescence), or for other reasons (see the articles Phosphorescence and List of light sources).
- Objects may absorb light and then as a consequence emit light that has different properties. They are then called fluorescent (if light is emitted only while light is absorbed) or phosphorescent (if light is emitted even after light ceases to be absorbed; this term is also sometimes loosely applied to light emitted due to chemical reactions).
For further treatment of the color of objects, see structural color, below.
To summarize, the color of an object is a complex result of its surface properties, its transmission properties, and its emission properties, all of which factors contribute to the mix of wavelengths in the light leaving the surface of the object. The perceived color is then further conditioned by the nature of the ambient illumination, and by the color properties of other objects nearby, via the effect known as color constancy and via other characteristics of the perceiving eye and brain.
# Color perception
## Development of theories of color vision
Although Aristotle and other ancient scientists had already written on the nature of light and color vision, it was not until Newton that light was identified as the source of the color sensation. In 1810, Goethe published his comprehensive Theory of Colors. In 1801 Thomas Young proposed his trichromatic theory, based on the observation that any color could be matched with a combination of three lights. This theory was later refined by James Clerk Maxwell and Hermann von Helmholtz. As Helmholtz puts it, "the principles of Newton's law of mixture were experimentally confirmed by Maxwell in 1856. Young's theory of color sensations, like so much else that this marvellous investigator achieved in advance of his time, remained unnoticed until Maxwell directed attention to it."[3]
At the same time as Helmholtz, Ewald Hering developed the opponent process theory of color, noting that color blindness and afterimages typically come in opponent pairs (red-green, blue-yellow, and black-white). Ultimately these two theories were synthesized in 1957 by Hurvich and Jameson, who showed that retinal processing corresponds to the trichromatic theory, while processing at the level of the lateral geniculate nucleus corresponds to the opponent theory.[4]
In 1931, an international group of experts known as the Commission Internationale d'Eclairage (CIE) developed a mathematical color model, which mapped out the space of observable colors and assigned a set of three numbers to each.
## Color in the eye
The ability of the human eye to distinguish colors is based upon the varying sensitivity of different cells in the retina to light of different wavelengths. The retina contains three types of color receptor cells, or cones. One type, relatively distinct from the other two, is most responsive to light that we perceive as violet, with wavelengths around 420 nm. (Cones of this type are sometimes called short-wavelength cones, S cones, or, misleadingly, blue cones.) The other two types are closely related genetically and chemically. One of them (sometimes called long-wavelength cones, L cones, or, misleadingly, red cones) is most sensitive to light we perceive as yellowish-green, with wavelengths around 564 nm; the other type (sometimes called middle-wavelength cones, M cones, or, misleadingly, green cones) is most sensitive to light perceived as green, with wavelengths around 534 nm.
Light, no matter how complex its composition of wavelengths, is reduced to three color components by the eye. For each location in the visual field, the three types of cones yield three signals based on the extent to which each is stimulated. These values are sometimes called tristimulus values.
The response curve as a function of wavelength for each type of cone is illustrated above. Because the curves overlap, some tristimulus values do not occur for any incoming light combination. For example, it is not possible to stimulate only the mid-wavelength/"green" cones; the other cones will inevitably be stimulated to some degree at the same time. The set of all possible tristimulus values determines the human color space. It has been estimated that humans can distinguish roughly 10 million different colors.[5]
The other type of light-sensitive cell in the eye, the rod, has a different response curve. In normal situations, when light is bright enough to strongly stimulate the cones, rods play virtually no role in vision at all.[6] On the other hand, in dim light, the cones are understimulated leaving only the signal from the rods, resulting in a colorless response. (Furthermore, the rods are barely sensitive to light in the "red" range.) In certain conditions of intermediate illumination, the rod response and a weak cone response can together result in color discriminations not accounted for by cone responses alone.
## Color in the brain
While the mechanisms of color vision at the level of the retina are well-described in terms of tristimulus values (see above), color processing after that point is organized differently. A dominant theory of color vision proposes that color information is transmitted out of the eye by three opponent processes, or opponent channels, each constructed from the raw output of the cones: a red-green channel, a blue-yellow channel and a black-white "luminance" channel. This theory has been supported by neurobiology, and accounts for the structure of our subjective color experience. Specifically, it explains why we cannot perceive a "reddish green" or "yellowish blue," and it predicts the color wheel: it is the collection of colors for which at least one of the two color channels measures a value at one of its extremes.
The exact nature of color perception beyond the processing already described, and indeed the status of color as a feature of the perceived world or rather as a feature of our perception of the world, is a matter of complex and continuing philosophical dispute (see qualia).
## Nonstandard color perception
### Color deficiency
If one or more types of a person's color-sensing cones are missing or less responsive than normal to incoming light, that person can distinguish fewer colors and is said to be color deficient or color blind (though this latter term can be misleading; almost all color deficient individuals can distinguish at least some colors). Some kinds of color deficiency are caused by anomalies in the number or nature of cones in the retina. Others (like central or cortical achromatopsia) are caused by neural anomalies in those parts of the brain where visual processing takes place.
### Tetrachromacy
While most humans are trichromatic (having three types of color receptors), many animals, known as tetrachromats, have four types. These include some species of spiders, most marsupials, birds, reptiles, and many species of fish. Other species are sensitive to only two axes of color or do not perceive color at all; these are called dichromats and monochromats respectively. A distinction is made between retinal tetrachromacy (having four pigments in cone cells in the retina, compared to three in trichromats) and functional tetrachromacy (having the ability to make enhanced color discriminations based on that retinal difference). As many as half of all women, but only a small percentage of men, are retinal tetrachromats.[7] The phenomenon arises when an individual receives two slightly different copies of the gene for either the medium- or long-wavelength cones, which are carried on the x-chromosome, accounting for the differences between genders.[7] For some of these retinal tetrachromats, color discriminations are enhanced, making them functional tetrachromats.[7]
### Synesthesia
In certain forms of synesthesia, perceiving letters and numbers (grapheme–color synesthesia) or hearing musical sounds (music–color synesthesia) will lead to the unusual additional experiences of seeing colors. Behavioral and functional neuroimaging experiments have demonstrated that these color experiences lead to changes in behavioral tasks and lead to increased activation of brain regions involved in color perception, thus demonstrating their reality, and similarity to real color percepts, albeit evoked through a non-standard route.
## Afterimages
After exposure to strong light in their sensitivity range, photoreceptors of a given type become desensitized. For a few seconds after the light ceases, they will continue to signal less strongly than they otherwise would. Colors observed during that period will appear to lack the color component detected by the desensitized photoreceptors. This effect is responsible for the phenomenon of afterimages, in which the eye may continue to see a bright figure after looking away from it, but in a complementary color.
Afterimage effects have also been utilized by artists, including Vincent van Gogh.
## Color constancy
There is an interesting phenomenon which occurs when an artist uses a limited color palette: the eye tends to compensate by seeing any grey or neutral color as the color which is missing from the color wheel. E.g., in a limited palette consisting of red, yellow, black and white, a mixture of yellow and black will appear as a variety of green, a mixture of red and black will appear as a variety of purple, and pure grey will appear bluish.[citation needed]
The trichromatric theory discussed above is strictly true only if the whole scene seen by the eye is of one and the same color, which of course is unrealistic. In reality, the brain compares the various colors in a scene, in order to eliminate the effects of the illumination. If a scene is illuminated with one light, and then with another, as long as the difference between the light sources stays within a reasonable range, the colors of the scene will nevertheless appear constant to us. This was studied by Edwin Land in the 1970s and led to his retinex theory of color constancy.
## Color naming
Colors vary in several different ways, including hue (red vs. orange vs. blue), saturation, brightness, and gloss. Some color words are derived from the name of an object of that color, such as "orange" or "salmon", while others are abstract, like "red".
Different cultures have different terms for colors, and may also assign some color names to slightly different parts of the spectrum: for instance, the Chinese character 青 (rendered as qīng in Mandarin and ao in Japanese) has a meaning that covers both blue and green; blue and green are traditionally considered shades of "青."
In the 1969 study Basic Color Terms: Their Universality and Evolution, Brent Berlin and Paul Kay describe a pattern in naming "basic" colors (like "red" but not "red-orange" or "dark red" or "blood red", which are "shades" of red). All languages that have two "basic" color names distinguish dark/cool colors from bright/warm colors. The next colors to be distinguished are usually red and then blue or green. All languages with six "basic" colors include black, white, red, green, blue and yellow. The pattern holds up to a set of twelve: black, grey, white, pink, red, orange, yellow, green, blue, purple, brown, and azure (distinct from blue in Russian and Italian but not English).
# Associations
Individual colors have a variety of cultural associations such as national colors (in general described in individual color articles and color symbolism). The field of color psychology attempts to identify the effects of color on human emotion and activity. Chromotherapy is a form of alternative medicine attributed to various Eastern traditions.
# Health effects
When the color spectrum of artificial lighting is mismatched to that of sunlight, material health effects may arise including increased incidence of headache. This phenomenon is often coupled with adverse effects of over-illumination, since many of the same interior spaces that have color mismatch also have higher light intensity than desirable for the task being conducted in that space.
# Measurement and reproduction of color
## Relation to spectral colors
Most light sources are mixtures of various wavelengths of light. However, many such sources can still have a spectral color insofar as the eye cannot distinguish them from monochromatic sources. For example, most computer displays reproduce the spectral color orange as a combination of red and green light; it appears orange because the red and green are mixed in the right proportions to allow the eye's red and green cones to respond the way they do to orange.
A useful concept in understanding the perceived color of a non-monochromatic light source is the dominant wavelength, which identifies the single wavelength of light which produces a sensation most similar to the light source. Dominant wavelength is roughly akin to hue.
Of course, there are many color perceptions that by definition cannot be pure spectral colors due to desaturation or because they are purples (mixtures of red and violet light, from opposite ends of the spectrum). Some examples of necessarily non-spectral colors are the achromatic colors (black, gray and white) and colors such as pink, tan, and magenta.
Two different light spectra which have the same effect on the three color receptors in the human eye will be perceived as the same color. This is exemplified by the white light that is emitted by fluorescent lamps, which typically has a spectrum consisting of a few narrow bands, while daylight has a continuous spectrum. The human eye cannot tell the difference between such light spectra just by looking into the light source, although reflected colors from objects can look different. (This is often exploited e.g. to make fruit or tomatoes look more brightly red in shops.)
Similarly, most human color perceptions can be generated by a mixture of three colors called primaries. This is used to reproduce color scenes in photography, printing, television and other media. There are a number of methods or color spaces for specifying a color in terms of three particular primary colors. Each method has its advantages and disadvantages depending on the particular application.
No mixture of colors, though, can produce a fully pure color perceived as completely identical to a spectral color, although one can get very close for the longer wavelengths, where the chromaticity diagram above has a nearly straight edge. For example, mixing green light (530 nm) and blue light (460 nm) produces cyan light that is slightly desaturated, because response of the red color receptor would be greater to the green and blue light in the mixture than it would be to a pure cyan light at 485 nm that has the same intensity as the mixture of blue and green.
Because of this, and because the primaries in color printing systems generally are not pure themselves, the colors reproduced are never perfectly saturated colors, and so spectral colors cannot be matched exactly. However, natural scenes rarely contain fully saturated colors, thus such scenes can usually be approximated well by these systems. The range of colors that can be reproduced with a given color reproduction system is called the gamut. The CIE chromaticity diagram can be used to describe the gamut.
Another problem with color reproduction systems is connected with the acquisition devices, like cameras or scanners. The characteristics of the color sensors in the devices are often very far from the characteristics of the receptors in the human eye. In effect, acquisition of colors that have some special, often very "jagged," spectra caused for example by unusual lighting of the photographed scene can be relatively poor.
Species that have color receptors different from humans, e.g. birds that may have four receptors, can differentiate some colors that look the same to a human. In such cases, a color reproduction system 'tuned' to a human with normal color vision may give very inaccurate results for the other observers.
The next problem is different color response of different devices. For color information stored and transferred in a digital form, color management technique based on color profiles attached to color data and to devices with different color response helps to avoid deformations of the reproduced colors. The technique works only for colors in gamut of the particular devices, e.g. it can still happen that your monitor is not able to show you real color of your goldfish even if your camera can receive and store the color information properly and vice versa.
## Pigments and reflective media
Pigments are chemicals that selectively absorb and reflect different spectra of light. When a surface is painted with a pigment, light hitting the surface is reflected, minus some wavelengths. This subtraction of wavelengths produces the appearance of different colors. Most paints are a blend of several chemical pigments, intended to produce a reflection of a given color.
Pigment manufacturers assume the source light will be white, or of roughly equal intensity across the spectrum. If the light is not a pure white source (as in the case of nearly all forms of artificial lighting), the resulting spectrum will appear a slightly different color. Red paint, viewed under blue light, may appear black. Red paint is red because it reflects only the red components of the spectrum. Blue light, containing none of these, will create no reflection from red paint, creating the appearance of black.
## Structural color
Structural colors are colors caused by interference effects rather than by pigments. Color effects are produced when a material is scored with fine parallel lines, formed of a thin layer or of two or more parallel thin layers, or otherwise composed of microstructures on the scale of the color's wavelength. If the microstructures are spaced randomly, light of shorter wavelengths will be scattered preferentially to produce Tyndall effect colors: the blue of the sky, the luster of opals, and the blue of human irises. If the microstructures are aligned in arrays, for example the array of pits in a CD, they behave as a diffraction grating: the grating reflects different wavelengths in different directions due to interference phenomena, separating mixed "white" light into light of different wavelengths. If the structure is one or more thin layers then it will reflect some wavelengths and transmit others, depending on the layers' thickness.
Structural color is responsible for the blues and greens of the feathers of many birds (the blue jay, for example), as well as certain butterfly wings and beetle shells. Variations in the pattern's spacing often give rise to an iridescent effect, as seen in peacock feathers, soap bubbles, films of oil, and mother of pearl, because the reflected color depends upon the viewing angle. Peter Vukusic has carried out research in butterfly wings and beetle shells using electron micrography, and has since helped develop a range of "photonic" cosmetics using structural color.[8]
Structural color is studied in the field of thin-film optics. A layman's term that describes particularly the most ordered or the most changeable structural colors is iridescence.
## Additional terms
- Hue: the color's direction from white, for example in the CIE chromaticity diagram.
- Colorfulness, chroma, or saturation: how "intense" or "concentrated" a color is; also known as chroma or purity.
- Value, brightness, or lightness: how light or dark a color is.
- Tint: a color made lighter by adding white.
- Shade: a color made darker by adding black. | https://www.wikidoc.org/index.php/Colo | |
a0d2eb5732365fec28589401236b416b6420d658 | wikidoc | Enema | Enema
An enema (plural enemata or enemas) is the procedure of introducing liquids into the rectum and colon via the anus. Enemas can be carried out for medical reasons (as a treatment for constipation), as a remedy for encopresis, as part of alternative health therapies, and also for erotic purposes, particularly as part of BDSM activities. In earlier times, they were often known as clysters, and were probably used more frequently than at present.
# Medical usage
The main medical usages of enemas are:
- As a bowel stimulant, not unlike a laxative -- the main difference being that laxatives are commonly thought of as orally administered while enemas are administered directly into the rectum, and thereafter, into the colon. When the enema injection into the rectum is complete, and after a set "holding time," the patient expels feces along with the enema in the toilet.
- Enemas may also be used to relieve constipation and fecal impaction, although in many professional health-care settings, their use has been largely replaced by oral laxatives and laxative suppositories. In-home use of enemas for constipation and alternative health purposes is somewhat harder to measure.
- Bowel stimulating enemas usually consist of water, which works primarily as a mechanical stimulant, or they may be made up of water with baking soda (sodium bicarbonate) or water with a mild hand soap dissolved in it; sodium phosphate solution, which draws additional water from the bloodstream into the colon and increases the effectiveness of the enema, but which can often be rather irritating to the colon, causing intense cramping or "gripping"; or mineral oil, which functions as a lubricant and stool softener, but which often has the side effect of sporadic seepage from the patient's anus which can soil the patient's undergarments for up to 24 hours. Other types of enema solutions are also used, including equal parts of milk and molasses heated together to slightly above normal body temperature. In the past, castile soap was a common additive in an enema, but it has largely fallen out of use because of its irritating action in the rectum and because of the risk of chemical colitis as well as the ready availability of other enema preparations that are perhaps more effective than soap in stimulating a bowel movement. At the opposite end of the spectrum, an isotonic saline solution is least irritating to the rectum and colon, having a neutral osmotic pressure, and neither leaching electrolytes from the body, as can happen with plain water, nor drawing water into the colon, as with phosphates, nor adding anything to the bloodstream. Thus, a salt water solution can be used when a longer period of retention is desired, such as to soften an impaction.
- Cleansing the lower bowel prior to a surgical procedure such as sigmoidoscopy or colonoscopy. Because of speed and supposed convenience, enemas used for this purpose are commonly the more costly, sodium phosphate variety -- often called a disposable enema. A more pleasant experience preparing for testing procedures can usually be obtained with gently-administered baking soda enemas; cleansing the lower bowel for colonoscopy and other bowel studies can be effectively achieved with water-based, or water with baking soda, enema administration.
- The administration of substances into the bloodstream. This may be done in situations where it is undesirable or impossible to deliver a medication by mouth, such as antiemetics given to reduce nausea (though not many antiemetics are delivered by enema). Additionally, several anti-angiogenic agents, which work better without digestion, can be safely administered via a gentle enema. Medicines for cancer, for arthritis, and for age-related macular degeneration are often given via enema in order to avoid the normally-functioning digestive tract. Interestingly, some water-based enemas are also used as a relieving agent for Irritable Bowel Syndrome, using cayenne pepper to squelch irritation in the colon and rectal area. Finally, an enema may also be used for hydration purposes. See also route of administration.
- The topical administration of medications into the rectum, such as corticosteroids and mesalazine used in the treatment of inflammatory bowel disease. Administration by enema avoids having the medication pass through the entire gastrointestinal tract, therefore simplifying the delivery of the medication to the affected area and limiting the amount that is absorbed into the bloodstream.
- General anesthetic agents for surgical purposes are sometimes administered by way of an enema. Occasionally, anesthetic agents are used rectally to reduce medically-induced vomiting during and after surgical procedures, in an attempt to avoid aspiration of stomach contents.
- A barium enema is used as a contrast substance in the radiological imaging of the bowel. The enema may contain barium sulfate powder, or a water-soluble contrast agent. Barium enemas are sometimes the only practical way to "view" the colon in a relatively safe manner. Following barium enema administration, patients often find that flushing the remaining barium with additional water, baking soda, or saline enemas helps restore normal colon activity without complications of constipation from the administration of the barium sulfate.
In certain countries such as the United States, customary enema usage went well into the 20th century; it was thought a good idea to cleanse the bowel in case of fever; also, pregnant women were given enemas prior to labor, supposedly to reduce the risk of feces being passed during contractions. Under some controversial discussion, pre-delivery enemas were also given to women to speed delivery by inducing contractions. This latter usage has since been largely abandoned, because obstetricians now commonly give oxytocin to induce labor and because women generally found the procedure unpleasant.
# Home usage
Many self-given enemas used at home are the pre-packaged, disposable, sodium phosphate solutions in single-use bottles sold under a variety of brand names, or in generic formats. Costing up to a dollar per use, these units come with a pre-lubricated nozzle attached to the top of the container. Some enemas are administered using so-called disposable bags connected to disposable tubing (despite the names, such units can commonly be used for many months or years without significant deterioration).
Patients who want easier, more gently-accepted enemas often purchase Combination Enema Syringes which are commonly referred to as "closed top" syringes, and which can also be used as old-fashioned hot water bottles, so as to relieve aches and pains via gentle heat administrations to parts of the body. Cost for each enema can be as little as a few pennies for the baking soda added to ordinary tap water.
In medical or hospital environments, reusable enema equipment is now rare because of the expense of disinfecting a water-based solution. For a single-patient stay of short duration, an inexpensive disposable enema bag can be used for several days or weeks, using a simple rinse out procedure after each enema administration. The difficulty comes in from the longer time period (and expense) required of nursing aides to give a gentle, water-based enema to a patient, as compared to the very few minutes it takes the same nursing aide to give the more irritating, cold, pre-packaged sodium phosphate unit.
For home use, disposable enema bottle units are common, but reusable rubber or vinyl bags or enema bulbs may also be used. In former times, enemas were infrequently administered using clyster syringes. If such commercially-available items are not at hand, ordinary water bottles are sometimes used.
# Colonic irrigation
Colonic irrigation or colon hydrotherapy is a large-volume enema which cleanses the whole colon. Colonic irrigation was in vogue for health and hygienic purposes at the beginning of the 20th century (see John Harvey Kellogg) and remains popular as an alternative health therapy in many parts of the world. Advocates believe that, when carried out by trained personnel using clean or sterilized equipment, colonic irrigation is a safe and valuable tool for eliminating toxins from the body and restoring normal muscular activity in the colon. However, there have been a few cases of intestinal perforation due to improperly done colonic irrigations. The actual medical benefit of colonic irrigation is controversial but may have value for many common health conditions.
# Enema Usage in Rectal Drug Administration
In rectal administration of dissolved drugs or alcohol an enema might be used to help increase the rate of absorption by cleaning the colon of feces first .
Enemas have also been used for ritual rectal drug administration such as balché, alcohol, tobacco, peyote, and other hallucinogenic drugs and entheogens, most notably by the Mayans and also some other American Indian tribes. Some tribes continue the practice in the present day.
People who wish to become intoxicated faster have also been known to use enemas as a method to instill alcohol into the bloodstream, absorbed through the membranes of the colon. However, great care must be taken as to the amount of alcohol used. Only a small amount is needed as the intestine absorbs the alcohol more quickly than the stomach. Deaths have resulted due to alcohol poisoning via enema.
For more information on rectal drug administration, see route of administration.
# Recreational usage
The paraphilia directed towards enemas is known as klismaphilia, the enjoyment of enemas. Enemas may be used as part of BDSM activities for either males or females, or as a regular sexual activity for an individual or between partners. In many cities, enemas are available as a service from practitioners in the sex industry to cater to klismaphiliac desires. Enemas can be pleasurable to either sex, and in males, enemas can can stimulate the prostate gland. Unexpected erections are common in medical settings, even if the person would otherwise consider it an unpleasant procedure.
An enema may also be used prior to anal sex or anilingus in order to enhance the sensation of intercourse, or to remove feces prior to sex, possibly reducing bacterial transmission and risk of infection, or just to reduce the possibility of fecal material adhering to the genitals or sex toys used during the following activity.
# Precautions
Improper administration of an enema may cause electrolyte imbalance (with repeated enemas) or ruptures to the bowel or rectal tissues resulting in internal bleeding, however these occourances are rare in healthy, sober adults. Internal bleeding or rupture may leave the individual exposed to infections from intestional bacteria. Blood resulting from tears in the colon may not always be visible, but can distinguished if the feces is unusually dark or has red hue. If intestional rupture is suspected, medical assistance should be obtained immediately.
The enema tube and solution may stimulate the vagus nerve, which triggers an arrhythmia such as bradycardia. Enemas should not be used if there is an undiagnosed abdominal pain since the peristalsis of the bowel can cause an inflamed appendix to rupture. | Enema
An enema (plural enemata or enemas) is the procedure of introducing liquids into the rectum and colon via the anus. Enemas can be carried out for medical reasons (as a treatment for constipation), as a remedy for encopresis, as part of alternative health therapies, and also for erotic purposes, particularly as part of BDSM activities. In earlier times, they were often known as clysters, and were probably used more frequently than at present.
# Medical usage
The main medical usages of enemas are:
- As a bowel stimulant, not unlike a laxative -- the main difference being that laxatives are commonly thought of as orally administered while enemas are administered directly into the rectum, and thereafter, into the colon. When the enema injection into the rectum is complete, and after a set "holding time," the patient expels feces along with the enema in the toilet.
- Enemas may also be used to relieve constipation and fecal impaction, although in many professional health-care settings, their use has been largely replaced by oral laxatives and laxative suppositories. In-home use of enemas for constipation and alternative health purposes is somewhat harder to measure.
- Bowel stimulating enemas usually consist of water, which works primarily as a mechanical stimulant, or they may be made up of water with baking soda (sodium bicarbonate) or water with a mild hand soap dissolved in it; sodium phosphate solution, which draws additional water from the bloodstream into the colon and increases the effectiveness of the enema, but which can often be rather irritating to the colon, causing intense cramping or "gripping"; or mineral oil, which functions as a lubricant and stool softener, but which often has the side effect of sporadic seepage from the patient's anus which can soil the patient's undergarments for up to 24 hours. Other types of enema solutions are also used, including equal parts of milk and molasses heated together to slightly above normal body temperature. In the past, castile soap was a common additive in an enema, but it has largely fallen out of use because of its irritating action in the rectum and because of the risk of chemical colitis as well as the ready availability of other enema preparations that are perhaps more effective than soap in stimulating a bowel movement. At the opposite end of the spectrum, an isotonic saline solution is least irritating to the rectum and colon, having a neutral osmotic pressure, and neither leaching electrolytes from the body, as can happen with plain water, nor drawing water into the colon, as with phosphates, nor adding anything to the bloodstream. Thus, a salt water solution can be used when a longer period of retention is desired, such as to soften an impaction.
- Cleansing the lower bowel prior to a surgical procedure such as sigmoidoscopy or colonoscopy. Because of speed and supposed convenience, enemas used for this purpose are commonly the more costly, sodium phosphate variety -- often called a disposable enema. A more pleasant experience preparing for testing procedures can usually be obtained with gently-administered baking soda enemas; cleansing the lower bowel for colonoscopy and other bowel studies can be effectively achieved with water-based, or water with baking soda, enema administration.
- The administration of substances into the bloodstream. This may be done in situations where it is undesirable or impossible to deliver a medication by mouth, such as antiemetics given to reduce nausea (though not many antiemetics are delivered by enema). Additionally, several anti-angiogenic agents, which work better without digestion, can be safely administered via a gentle enema. Medicines for cancer, for arthritis, and for age-related macular degeneration are often given via enema in order to avoid the normally-functioning digestive tract. Interestingly, some water-based enemas are also used as a relieving agent for Irritable Bowel Syndrome, using cayenne pepper to squelch irritation in the colon and rectal area. Finally, an enema may also be used for hydration purposes. See also route of administration.
- The topical administration of medications into the rectum, such as corticosteroids and mesalazine used in the treatment of inflammatory bowel disease. Administration by enema avoids having the medication pass through the entire gastrointestinal tract, therefore simplifying the delivery of the medication to the affected area and limiting the amount that is absorbed into the bloodstream.
- General anesthetic agents for surgical purposes are sometimes administered by way of an enema. Occasionally, anesthetic agents are used rectally to reduce medically-induced vomiting during and after surgical procedures, in an attempt to avoid aspiration of stomach contents.
- A barium enema is used as a contrast substance in the radiological imaging of the bowel. The enema may contain barium sulfate powder, or a water-soluble contrast agent. Barium enemas are sometimes the only practical way to "view" the colon in a relatively safe manner. Following barium enema administration, patients often find that flushing the remaining barium with additional water, baking soda, or saline enemas helps restore normal colon activity without complications of constipation from the administration of the barium sulfate.
In certain countries such as the United States, customary enema usage went well into the 20th century; it was thought a good idea to cleanse the bowel in case of fever; also, pregnant women were given enemas prior to labor, supposedly to reduce the risk of feces being passed during contractions. Under some controversial discussion, pre-delivery enemas were also given to women to speed delivery by inducing contractions. This latter usage has since been largely abandoned, because obstetricians now commonly give oxytocin to induce labor and because women generally found the procedure unpleasant.
# Home usage
Many self-given enemas used at home are the pre-packaged, disposable, sodium phosphate solutions in single-use bottles sold under a variety of brand names, or in generic formats. Costing up to a dollar per use, these units come with a pre-lubricated nozzle attached to the top of the container. Some enemas are administered using so-called disposable bags connected to disposable tubing (despite the names, such units can commonly be used for many months or years without significant deterioration).
Patients who want easier, more gently-accepted enemas often purchase Combination Enema Syringes which are commonly referred to as "closed top" syringes, and which can also be used as old-fashioned hot water bottles, so as to relieve aches and pains via gentle heat administrations to parts of the body. Cost for each enema can be as little as a few pennies for the baking soda added to ordinary tap water.
In medical or hospital environments, reusable enema equipment is now rare because of the expense of disinfecting a water-based solution. For a single-patient stay of short duration, an inexpensive disposable enema bag can be used for several days or weeks, using a simple rinse out procedure after each enema administration. The difficulty comes in from the longer time period (and expense) required of nursing aides to give a gentle, water-based enema to a patient, as compared to the very few minutes it takes the same nursing aide to give the more irritating, cold, pre-packaged sodium phosphate unit.
For home use, disposable enema bottle units are common, but reusable rubber or vinyl bags or enema bulbs may also be used. In former times, enemas were infrequently administered using clyster syringes. If such commercially-available items are not at hand, ordinary water bottles are sometimes used.
# Colonic irrigation
Colonic irrigation or colon hydrotherapy is a large-volume enema which cleanses the whole colon. Colonic irrigation was in vogue for health and hygienic purposes at the beginning of the 20th century (see John Harvey Kellogg) and remains popular as an alternative health therapy in many parts of the world. Advocates believe that, when carried out by trained personnel using clean or sterilized equipment, colonic irrigation is a safe and valuable tool for eliminating toxins from the body and restoring normal muscular activity in the colon. However, there have been a few cases of intestinal perforation due to improperly done colonic irrigations. The actual medical benefit of colonic irrigation is controversial but may have value for many common health conditions.
# Enema Usage in Rectal Drug Administration
In rectal administration of dissolved drugs or alcohol an enema might be used to help increase the rate of absorption by cleaning the colon of feces first [1].
Enemas have also been used for ritual rectal drug administration such as balché, alcohol, tobacco, peyote, and other hallucinogenic drugs and entheogens, most notably by the Mayans and also some other American Indian tribes. Some tribes continue the practice in the present day. [2]
People who wish to become intoxicated faster have also been known to use enemas as a method to instill alcohol into the bloodstream, absorbed through the membranes of the colon. However, great care must be taken as to the amount of alcohol used. Only a small amount is needed as the intestine absorbs the alcohol more quickly than the stomach. Deaths have resulted due to alcohol poisoning via enema. [1]
For more information on rectal drug administration, see route of administration.
# Recreational usage
The paraphilia directed towards enemas is known as klismaphilia, the enjoyment of enemas. Enemas may be used as part of BDSM activities for either males or females, or as a regular sexual activity for an individual or between partners. In many cities, enemas are available as a service from practitioners in the sex industry to cater to klismaphiliac desires. Enemas can be pleasurable to either sex, and in males, enemas can can stimulate the prostate gland. Unexpected erections are common in medical settings, even if the person would otherwise consider it an unpleasant procedure.
An enema may also be used prior to anal sex or anilingus in order to enhance the sensation of intercourse, or to remove feces prior to sex, possibly reducing bacterial transmission and risk of infection, or just to reduce the possibility of fecal material adhering to the genitals or sex toys used during the following activity.
# Precautions
Improper administration of an enema may cause electrolyte imbalance (with repeated enemas) or ruptures to the bowel or rectal tissues resulting in internal bleeding, however these occourances are rare in healthy, sober adults. Internal bleeding or rupture may leave the individual exposed to infections from intestional bacteria. Blood resulting from tears in the colon may not always be visible, but can distinguished if the feces is unusually dark or has red hue. If intestional rupture is suspected, medical assistance should be obtained immediately. [3]
The enema tube and solution may stimulate the vagus nerve, which triggers an arrhythmia such as bradycardia. Enemas should not be used if there is an undiagnosed abdominal pain since the peristalsis of the bowel can cause an inflamed appendix to rupture. | https://www.wikidoc.org/index.php/Colon_hydrotherapy | |
af5248df6839983f3676085153cef7a7685dbb3b | wikidoc | Milia | Milia
Synonyms and keywords:: Milk sports, oil seeds.
# Overview
Milia, also known as milk spots or oil seeds, are benign, keratin-filled cysts that can appear just under the epidermis or on the roof of the mouth. They are commonly associated with newborn babies but can appear on people of all ages. They are usually found around the nose and eyes, and sometimes on the genitalia.
In children milia often disappears within two to four weeks. In adults it may require removal by a physician or a cosmetologist.
Milia can sometimes be a result of harsh face washes or from repeated heat stress from hot showering on people with sensitive skins.
# Physical examination
## Gallery
### Eye
- url = >
- url = >
- url = >
- url = > | Milia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jesus Rosario Hernandez, M.D. [2].
Synonyms and keywords:: Milk sports, oil seeds.
# Overview
Milia, also known as milk spots or oil seeds, are benign, keratin-filled cysts that can appear just under the epidermis or on the roof of the mouth. They are commonly associated with newborn babies but can appear on people of all ages. They are usually found around the nose and eyes, and sometimes on the genitalia.
In children milia often disappears within two to four weeks. In adults it may require removal by a physician or a cosmetologist.
Milia can sometimes be a result of harsh face washes or from repeated heat stress from hot showering on people with sensitive skins.
# Physical examination
## Gallery
### Eye
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=290>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=290>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=290>
- url = http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=290> | https://www.wikidoc.org/index.php/Congenital_hypotrichosis_milia | |
11a3d5faaad2ab7ed93532015c6dc9d33732b1c6 | wikidoc | Corex | Corex
This page is about the cough syrup Corex. For the steel making process, please see COREX.
Corex is a cough syrup sold by Pfizer Inc., a global pharmaceutical company. It is available in India, Pakistan, Bangladesh and a few other South Asian countries. Corex is a prescribed medicine and can only be bought with a prescription from a general physician.
Its active ingredients are chlorpheniramine maleate and codeine phosphate.
Corex is one of the most commonly available over the counter drugs in India, and is used as a cheap and readily available substitute for Codeine.
Legally, Corex can only be obtained by a physician's prescription, but studies show that more than 90% of the product is sold without any prescription.
Corex is not generally a fatal drug substitute, unless taken in extremely high quantities. However, many side effects are common. Corex is known to cause short term memory loss, sleeplessness, tremors and spasms. Muscular pains and dehydration are other common side-effects.
Long term abuse leads to serious kidney damage. Corex has a high sugar content, and may be unsuitable for acute diabetic patients. | Corex
This page is about the cough syrup Corex. For the steel making process, please see COREX.
Corex is a cough syrup sold by Pfizer Inc., a global pharmaceutical company. It is available in India, Pakistan, Bangladesh and a few other South Asian countries. Corex is a prescribed medicine and can only be bought with a prescription from a general physician.
Its active ingredients are chlorpheniramine maleate and codeine phosphate.
Corex is one of the most commonly available over the counter drugs in India, and is used as a cheap and readily available substitute for Codeine.
Legally, Corex can only be obtained by a physician's prescription, but studies show that more than 90% of the product is sold without any prescription.
Corex is not generally a fatal drug substitute, unless taken in extremely high quantities. However, many side effects are common. Corex is known to cause short term memory loss, sleeplessness, tremors and spasms. Muscular pains and dehydration are other common side-effects.
Long term abuse leads to serious kidney damage. Corex has a high sugar content, and may be unsuitable for acute diabetic patients. | https://www.wikidoc.org/index.php/Corex | |
5267610bf823682d2e8417122bebdcc28e2cc7fb | wikidoc | Stent | Stent
# Overview
In medicine, a stent is a tube that is inserted into a natural conduit of the body to prevent or counteract a disease-induced localized flow constriction. The term may also refer to a tube used to temporarily hold such a natural conduit open to allow access for surgery.
# Applications
The main purpose of a stent is to counteract significant decreases in vessel or duct diameter by acutely propping open the conduit by a mechanical scaffold or stent. Stents are often used to alleviate diminished blood flow to organs and extremities beyond an obstruction in order to maintain an adequate delivery of oxygenated blood. Although the most widely known use of stents is in coronary arteries, they are widely used in other natural body conduits, such as central and peripheral arteries and veins, bile ducts, esophagus, colon, trachea or large bronchi, ureters, and urethra.
# Etymology
The origin of the word stent remains unsettled. The verb stenting was used for centuries for the process of stiffening garments (a usage long obsolete, per the Oxford English Dictionary) and some believe this to be the origin. Others attribute the noun stent to Jan F. Esser, a Dutch plastic surgeon who in 1916 used the word to describe a dental impression compound invented in 1856 by the English dentist Charles Stent (1807–1885), which Esser employed to craft a form for facial reconstruction. The full account is described in the Journal of the History of Dentistry. According to the author, from the use of Stent's compound as support for facial tissues grew the eventual use of stent to open various bodily structures.
Worth noting though is that the first "stents" used in medical practice were initially called "Wallstents".
# Types of stent
## Vascular
- Bare Metal Stent
- Covered Stent and Stent Graft
- Drug-eluting stent
First generation stents eluted sirolimus (SES) or paclitaxel (PES)
- First generation stents eluted sirolimus (SES) or paclitaxel (PES)
- Second generation stents are zotarolimus-eluting stent (ZES) and the everolimus-eluting stent (EES). Everolimus (a semi-synthetic derivative of sirolimus). Second generation stents have other enhancements in addition to the choice of drug.
- Second generation stents are zotarolimus-eluting stent (ZES) and the everolimus-eluting stent (EES). Everolimus (a semi-synthetic derivative of sirolimus). Second generation stents have other enhancements in addition to the choice of drug.
In the controlled environment of randomized clinical trials, routine coronary stenting is safe but probably not associated with important reductions in rates of mortality, acute myocardial infarction, or coronary artery bypass surgery compared with standard PTCA with provisional stenting. Coronary stenting is associated with substantial reductions in angiographic restenosis rates and the subsequent need for repeated PTCA, although this benefit may be overestimated because of trial designs. The incremental benefit of routine stenting for reducing repeated angioplasty diminishes as the crossover rate of stenting with conventional PTCA increases.
# Stent implantation versus Coronary bypass surgery
Coronary heart disease (CHD) is a major cause of morbidity and mortality throughout the world, and both surgical revascularisation (coronary artery bypass grafting, CABG) and percutaneous coronary intervention (PCI) are established treatment options. The rapid developments in both surgical and percutaneous techniques have been such that the choice of the optimum revascularisation strategy is changing, often without an established evidence base; this is particularly true in complex conditions including patients with three-vessel and left main stem anatomy. The widespread use of drug eluting stents has resulted in a significant reduction in patients referred for CABG although published data favours the surgical approach in this high-risk group.
- The SYNTAX Trial aims to explore the interface between treatment with CABG and PCI in patients with three-vessel and left main stem disease, comparing CABG using contemporary techniques and PCI using drug eluting TAXUS stents. The aim of the trial is to establish non-inferiority of PCI with CABG. The unique feature of the SYNTAX trial is the ‘all comers’ strategy. A team comprising a cardiac surgeon and an interventional cardiologist assesses each patient; if equivalent revascularisation is applicable using both techniques, the patient is accepted for randomization; if either CABG or PCI is deemed unsuitable for technical reasons or the presence of co-morbidities, then the patient is recruited into one of two parallel registries which will track these patients undergoing either CABG or PCI. The patient will not be included in the randomized cohort. 1800 patients will be randomized (1:1) between CABG and PCI. The primary end-point is a major adverse, cardiac and cerbrovascular event at one year. All patients will be followed for five years. Of the 1800 patients, 710 with left main stem disease will be randomized between CABG and PCI. In this sub-group, repeat cardiac catheterisation will be undertaken after the one-year primary endpoint to determine graft and native vessel patency (the Le Mans sub-study).
- The SYNTAX Trial is one of the most important trials ever undertaken in the field of coronary revascularisation and will provide a rational basis for choosing the optimum revascularisation strategy in patients for many years to come.
- Problems: One of the drawbacks of vascular stents is the potential development of a thick smooth muscle tissue inside the lumen, the so-called neointima. Development of a neointima is variable but can at times be so severe as to re-occlude the vessel lumen (restenosis), especially in the case of smaller diameter vessels, which often results in reintervention. Consequently, current research focuses on the reduction of neointima after stent placement. Considerable improvements have been made, including the use of more bio-compatible materials, anti-inflammatory drug-eluting stents, resorbable stents, and others. Fortunately, even if stents are eventually covered by neointima, the minimally invasive nature of their deployment makes reintervention possible and usually straightforward.
- On September 4, 2007, an international study showed that some heart attack patients would be better off without using drug-coated stents in emergency to open their clogged arteries (patients were 5 times more likely to die after 2 years than those who received metal stents). Dr. Valentin Fuster, director of the Cardiovascular Institute at Mount Sinai School of Medicine in New York said stents are less commonly used in Europe, implanted in only about 15 % of patients there while drug-lined stents are used in up to 30% of Americans having heart attacks. The new research was presented by Dr. Gabriel Steg, of the Hospital Bichat-Claude Bernard in Paris, at a meeting of the European Society of Cardiology in Vienna. Dr. Eckhart Fleck, director of cardiology at the German Heart Institute in Berlin and a spokesman for the European Society of Cardiology said that "Drug-eluting stents are not for everyone."
## Urinary Tract
Ureteral stents are used to ensure the patency of a ureter, which may be compromised, for example, by a kidney stone. This method is sometimes used as a temporary measure, to prevent damage to a blocked kidney, until a procedure to remove the stone can be performed.
A urethral/prostatic stent might be needed if a man is unable to urinate. Often this situation occurs when an enlarged prostate pushes against the urethra, blocking the flow of urine. The placement of a stent can open the obstruction, avoiding the collapse of the urethra.
## Stent Graft
A stent graft is a tubular device, which is composed of special fabric supported by a rigid structure, usually metal. The rigid structure is called a stent. An average stent on its own has no covering, and therefore is usually just a metal mesh. Although there are many types of stent, these stents are used mainly for vascular intervention.
The device is used primarily in Endovascular surgery. Stent grafts are used to support weak points in arteries, commonly known as an aneurysm. Stent grafts are most commonly used in the repair of an abdominal aortic aneurysm, in a procedure called an EVAR. The theory behind the procedure is that once in place inside the aorta, the stent graft acts as a false lumen for blood travel through, instead of into the aneurysm sack.
## Other
- CHD Stent
- Rectal Stent
- Oesophageal Stent
- Biliary Stent
- Pancreatic Stent
# 2009 and 2007 Focused Update: ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (DO NOT EDIT)
## Recommendations for the Use of Stents in STEMI (DO NOT EDIT)
## Drug-Eluting and Bare-Metal Stents (DO NOT EDIT)
# Related Chapters
- Angioplasty
- Bronchoscopy
- Colonoscopy
- Esophagogastroduodenoscopy
- Grommet
- Restenosis | Stent
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
In medicine, a stent is a tube that is inserted into a natural conduit of the body to prevent or counteract a disease-induced localized flow constriction. The term may also refer to a tube used to temporarily hold such a natural conduit open to allow access for surgery.
# Applications
The main purpose of a stent is to counteract significant decreases in vessel or duct diameter by acutely propping open the conduit by a mechanical scaffold or stent. Stents are often used to alleviate diminished blood flow to organs and extremities beyond an obstruction in order to maintain an adequate delivery of oxygenated blood. Although the most widely known use of stents is in coronary arteries, they are widely used in other natural body conduits, such as central and peripheral arteries and veins, bile ducts, esophagus, colon, trachea or large bronchi, ureters, and urethra.
# Etymology
The origin of the word stent remains unsettled. The verb stenting was used for centuries for the process of stiffening garments (a usage long obsolete, per the Oxford English Dictionary) and some believe this to be the origin. Others attribute the noun stent to Jan F. Esser, a Dutch plastic surgeon who in 1916 used the word to describe a dental impression compound invented in 1856 by the English dentist Charles Stent (1807–1885), which Esser employed to craft a form for facial reconstruction. The full account is described in the Journal of the History of Dentistry. [2] According to the author, from the use of Stent's compound as support for facial tissues grew the eventual use of stent to open various bodily structures.
Worth noting though is that the first "stents" used in medical practice were initially called "Wallstents".
# Types of stent
## Vascular
- Bare Metal Stent
- Covered Stent and Stent Graft
- Drug-eluting stent
First generation stents eluted sirolimus (SES) or paclitaxel (PES)[1]
- First generation stents eluted sirolimus (SES) or paclitaxel (PES)[1]
- Second generation stents are zotarolimus-eluting stent (ZES) and the everolimus-eluting stent (EES). Everolimus (a semi-synthetic derivative of sirolimus). Second generation stents have other enhancements in addition to the choice of drug.
- Second generation stents are zotarolimus-eluting stent (ZES) and the everolimus-eluting stent (EES). Everolimus (a semi-synthetic derivative of sirolimus). Second generation stents have other enhancements in addition to the choice of drug.
In the controlled environment of randomized clinical trials, routine coronary stenting is safe but probably not associated with important reductions in rates of mortality, acute myocardial infarction, or coronary artery bypass surgery compared with standard PTCA with provisional stenting. Coronary stenting is associated with substantial reductions in angiographic restenosis rates and the subsequent need for repeated PTCA, although this benefit may be overestimated because of trial designs. The incremental benefit of routine stenting for reducing repeated angioplasty diminishes as the crossover rate of stenting with conventional PTCA increases.[2]
# Stent implantation versus Coronary bypass surgery
Coronary heart disease (CHD) is a major cause of morbidity and mortality throughout the world, and both surgical revascularisation (coronary artery bypass grafting, CABG) and percutaneous coronary intervention (PCI) are established treatment options. The rapid developments in both surgical and percutaneous techniques have been such that the choice of the optimum revascularisation strategy is changing, often without an established evidence base; this is particularly true in complex conditions including patients with three-vessel and left main stem anatomy. The widespread use of drug eluting stents has resulted in a significant reduction in patients referred for CABG although published data favours the surgical approach in this high-risk group.
- The SYNTAX Trial[3] aims to explore the interface between treatment with CABG and PCI in patients with three-vessel and left main stem disease, comparing CABG using contemporary techniques and PCI using drug eluting TAXUS stents. The aim of the trial is to establish non-inferiority of PCI with CABG. The unique feature of the SYNTAX trial is the ‘all comers’ strategy. A team comprising a cardiac surgeon and an interventional cardiologist assesses each patient; if equivalent revascularisation is applicable using both techniques, the patient is accepted for randomization; if either CABG or PCI is deemed unsuitable for technical reasons or the presence of co-morbidities, then the patient is recruited into one of two parallel registries which will track these patients undergoing either CABG or PCI. The patient will not be included in the randomized cohort. 1800 patients will be randomized (1:1) between CABG and PCI. The primary end-point is a major adverse, cardiac and cerbrovascular event at one year. All patients will be followed for five years. Of the 1800 patients, 710 with left main stem disease will be randomized between CABG and PCI. In this sub-group, repeat cardiac catheterisation will be undertaken after the one-year primary endpoint to determine graft and native vessel patency (the Le Mans sub-study).
- The SYNTAX Trial is one of the most important trials ever undertaken in the field of coronary revascularisation and will provide a rational basis for choosing the optimum revascularisation strategy in patients for many years to come.
- Problems: One of the drawbacks of vascular stents is the potential development of a thick smooth muscle tissue inside the lumen, the so-called neointima. Development of a neointima is variable but can at times be so severe as to re-occlude the vessel lumen (restenosis), especially in the case of smaller diameter vessels, which often results in reintervention. Consequently, current research focuses on the reduction of neointima after stent placement. Considerable improvements have been made, including the use of more bio-compatible materials, anti-inflammatory drug-eluting stents, resorbable stents, and others. Fortunately, even if stents are eventually covered by neointima, the minimally invasive nature of their deployment makes reintervention possible and usually straightforward.
- On September 4, 2007, an international study showed that some heart attack patients would be better off without using drug-coated stents in emergency to open their clogged arteries (patients were 5 times more likely to die after 2 years than those who received metal stents). Dr. Valentin Fuster, director of the Cardiovascular Institute at Mount Sinai School of Medicine in New York said stents are less commonly used in Europe, implanted in only about 15 % of patients there while drug-lined stents are used in up to 30% of Americans having heart attacks. The new research was presented by Dr. Gabriel Steg, of the Hospital Bichat-Claude Bernard in Paris, at a meeting of the European Society of Cardiology in Vienna. Dr. Eckhart Fleck, director of cardiology at the German Heart Institute in Berlin and a spokesman for the European Society of Cardiology said that "Drug-eluting stents are not for everyone." [4]
## Urinary Tract
Ureteral stents are used to ensure the patency of a ureter, which may be compromised, for example, by a kidney stone. This method is sometimes used as a temporary measure, to prevent damage to a blocked kidney, until a procedure to remove the stone can be performed.
A urethral/prostatic stent might be needed if a man is unable to urinate. Often this situation occurs when an enlarged prostate pushes against the urethra, blocking the flow of urine. The placement of a stent can open the obstruction, avoiding the collapse of the urethra.
## Stent Graft
A stent graft is a tubular device, which is composed of special fabric supported by a rigid structure, usually metal. The rigid structure is called a stent. An average stent on its own has no covering, and therefore is usually just a metal mesh. Although there are many types of stent, these stents are used mainly for vascular intervention.
The device is used primarily in Endovascular surgery. Stent grafts are used to support weak points in arteries, commonly known as an aneurysm. Stent grafts are most commonly used in the repair of an abdominal aortic aneurysm, in a procedure called an EVAR. The theory behind the procedure is that once in place inside the aorta, the stent graft acts as a false lumen for blood travel through, instead of into the aneurysm sack.
## Other
- CHD Stent
- Rectal Stent
- Oesophageal Stent
- Biliary Stent
- Pancreatic Stent
# 2009 and 2007 Focused Update: ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (DO NOT EDIT)[5][6]
## Recommendations for the Use of Stents in STEMI (DO NOT EDIT)[5]
## Drug-Eluting and Bare-Metal Stents (DO NOT EDIT)[6]
# Related Chapters
- Angioplasty
- Bronchoscopy
- Colonoscopy
- Esophagogastroduodenoscopy
- Grommet
- Restenosis
# External links
- Drug-Eluting Stents — Angioplasty.Org
- Cardiovascular and Interventional Radiological Society of Europe
- How a Dentist's Name Became a Synonym for a Life-saving Device: The Story of Dr. Charles Stent Journal of the History of Dentistry/Vol. 49, No: 2, July 2001
- Cleveland Clinic Webchat - Interventional Procedures - Stents, Angioplasty and New Approaches to Treat Heart Disease with Dr. Samir Kapadia
- Cleveland Clinic Webchat - Interventional Procedures - Questions & Answers about Stents, Angioplasty and New Approaches to Treat Heart Disease with Dr. Stephen Ellis | https://www.wikidoc.org/index.php/Coronary_stent | |
39c43c2a17b8138bc6a899d9c06dbff557d97463 | wikidoc | Cramp | Cramp
Co-Editor-In-Chief: Elliot B. Tapper, M.D., Department of Medicine, Beth Israel Deaconess Medical Center;
Co-Editor-In-Chief: C. Michael Gibson, M.S., M.D.
# Overview
Cramps are unpleasant, often painful, sensations caused by contraction or over shortening of muscles. Cramps have many causes - from overexertion to imbalances of electrolytes (e.g. calcium)or more complex conditions. They can be fleeting or disabling. Cramps can occur in virtually any muscle-bound organ. This is a broad overview of all muscular cramps.
# Classification
## Nocturnal Leg Cramps
Nocturnal leg cramps are involuntary, often very painful muscle contractions that occur in the calves, soles of the feet, or other muscles in the body during the night or (less commonly) while resting. The duration of nocturnal leg cramps is highly variable with cramps sometimes only lasting a few seconds and other times several minutes. Soreness in the muscles may remain for some time after the cramp ends. These leg cramps are a common occurrence in late-term pregnancy and frequently afflict patients cirrhosis and those on dialysis. Most cramps, however, occur outside the context of systemic disease. These cramps are more common in older people but may happen to anyone. In population studies in the Netherlands and Sweden, 36% of all adults reported one or more disabling cramps per year and 2% report weekly cramps. As many as 50-60% of Americans over the age of 65 complain of more than one disabling muscle cramp per week.
The precise cause of these cramps is unclear. Potential contributing factors are believed to include dehydration, low levels of certain minerals (magnesium, potassium, calcium, and sodium), and the reduced blood flow through the muscles attendant in prolonged sitting or lying down. An important cause specific to nocturnal leg cramps is iron deficiency. Through an unknown mechanism, low levels of iron can result in occasional or disabling cramps. It can often manifest as the so-called Restless Legs Syndrome of irresistible nocturnal movement impulses that resolve with standing or walking around. Anyone seeking evaluation for cramps or restless legs should have their hemoglobin or iron levels checked as iron repletion will improve and, often, stop the cramps altogether. There is no role, however, for iron supplementation in patients with a normal ferritin level.
The treatment of cramps can be difficult; there is very sparse data in the literature guiding treatment decisions. The medication with the best data support its use is Quinine, whose effects have been known since the 1940's and are both significant and long lasting. However, Quinine is exceptionally toxic, famously causing Thrombotic Thrombocytopoenic Purpura (TTP), and has been pulled off of the market for this indication.
There are some measures which have been studied and found to be ineffective: stretching, magnesium, vitamin E and gabapentin have all been evaluated with no benefit. Some measures are used by clinicians, but have never been formally evaluated by trial: baclofen, carbamazepine, and oxcarbazepine. Finally, there are a few medications that have proven benefit with small trial data: injected lidocaine (however impractical), vitamin B6, verapamil and diltiazem.
## Smooth Muscle Cramps
Smooth muscle contractions lie at the heart of the cramping (or colicky) pain of internal organs. These include the intestine, uterus, ureter (in kidney stone pain), and various others.
### Menstrual Cramps
Menstruation is also highly likely to cause cramps of varying severity in the abdomen that may radiate to the lower back and thighs. Menstrual cramps can be treated with ibuprofen, acetaminophen or paracetamol, stretching exercises, or the application of heat through such means as warm baths or heating pads. Menstrual cramps that do not respond to self-treatment can be a symptom of endometriosis or other health problems.
## Skeletal Muscle Cramps
Skeletal muscles are muscles that can be voluntarily controlled. Of the skeletal muscles, those which cramp the most often are the calves, thighs, and arches of the foot. These cramps are seemingly associated with strenuous activity and can be intensely painful.
### Self Induced Cramp
Self-induced cramp is brought on purposefully by individuals for the purpose of stretching muscle in a position where standing or greater movement is difficult or impossible. For instance, certain workers or craftsmen may find inducing cramp in the lower legs enables them to stretch desirable muscle groups without the need to physically stand in tight spaces.
## Iatrogenic Causes
Statins are known to cause myalgia and cramps among other side effects. Additional factors increasing probability for this adverse side effects are physical exercise, age, female gender, history of cramps and hypothyroidism. Up to 80% of athletes using statins suffer significant muscular adverse effects including cramps , the rate appears to be approximately 10-25% in typical population using statins . In some cases this adverse effects will disappear after switching to a different statin, however they should not be ignored if they persist as they can rarely develop into a more serious problem. Coenzyme Q10 supplementation can be helpful to avoid some statin related adverse effects but currently there is not enough evidence to prove effectiveness in avoiding myopathy or myalgia .
# Causes
There are numerous causes of cramping: hyperflexion; inadequate oxygenation; exposure to large changes in temperature; dehydration; low blood salt; or low blood calcium. Muscle cramps may also be a symptom/complication of pregnancy, kidney disease, thyroid disease, severe hypokalemia or hypocalcemia, restless legs syndrome, and neurologic disorders like multiple sclerosis or ALS. Cramps can also occur 'idiopathically' with no apparent cause.
Electrolyte disturbance may cause cramping and tetany of muscles, particularly critical hypokalaemia (a low level of potassium) and hypocalcaemia (a low level of calcium). This disturbance arises as the body loses large amounts of interstitial fluid through sweat. This interstitial fluid is composed mostly of water and table salt (NaCl). The loss of osmotically active particles outside muscle cells(NaCl) leads to a disturbance of the osmotic balance and swelling of muscle cells as these contain more osmotically active particles. This causes the calcium pump between the muscle lumen and sarcoplasmic reticulum to short circuit and the calcium ions remain bound to the tropomyosin and the muscle contraction is continued. This may occur when the lactic acid is high in the cells.
## Causes by Organ System
## Causes in Alphabetical Order
# Treatment
Muscle cramps can be treated by applying a soft massage on the cramped muscle, stretching the muscle and applying heat or cold. Heat improves superficial blood circulation and makes muscles more flexible, so some people find that heat is more soothing for muscle cramps. Application of excessive heat or cold to sore muscles may bring on cramps. Pounding on a cramped muscle can increase soreness.
- In the case of inadequate oxygenation, excess lactic acid, produced by anaerobic respiration, builds up and stresses the muscle. In addition to the methods described above, cramps from poor oxygenation can be improved by rapid deep breathing.
- Cramps from lack of water and/or salt can be treated by drinking water and/or increasing salt intake, respectively.
There is no scientific evidence to support the widely held claim by the sports nutrition industry that intake of specially composed electrolyte drinks has any advantage over intake of plain table salt (via drink or food) and water to counter these electrolyte disturbances and muscle cramps in people with a well-functioning renal system.
Eating foods high in potassium can help prevent muscle cramps. Foods with high sources of potassium include, in order from highest to lowest: avocados, potatoes, bananas, broccoli, orange juice, soybeans and apricots, although it is also common in most fruits, vegetables and meats.
Leg cramps may also be due to vitamin D deficiency (also needed for calcium absorption). Due to change in diet, shunning milk because of high cholesterol content, or, in children, preference for soft drinks, and decreased sun exposure, vitamin D deficiency is widespread. Correcting this deficiency will in many cases also eliminate, or reduce, frequency of leg cramps.
# Related Chapters
- Trigger points
- Side Stitch
- Delayed onset muscle soreness | Cramp
Co-Editor-In-Chief: Elliot B. Tapper, M.D., Department of Medicine, Beth Israel Deaconess Medical Center;
Co-Editor-In-Chief: C. Michael Gibson, M.S., M.D.
# Overview
Cramps are unpleasant, often painful, sensations caused by contraction or over shortening of muscles. Cramps have many causes - from overexertion to imbalances of electrolytes (e.g. calcium)or more complex conditions. They can be fleeting or disabling. Cramps can occur in virtually any muscle-bound organ. This is a broad overview of all muscular cramps.
# Classification
## Nocturnal Leg Cramps
Nocturnal leg cramps are involuntary, often very painful muscle contractions that occur in the calves, soles of the feet, or other muscles in the body during the night or (less commonly) while resting. The duration of nocturnal leg cramps is highly variable with cramps sometimes only lasting a few seconds and other times several minutes. Soreness in the muscles may remain for some time after the cramp ends. These leg cramps are a common occurrence in late-term pregnancy and frequently afflict patients cirrhosis and those on dialysis. Most cramps, however, occur outside the context of systemic disease. These cramps are more common in older people but may happen to anyone. In population studies in the Netherlands and Sweden, 36% of all adults reported one or more disabling cramps per year and 2% report weekly cramps.[1] As many as 50-60% of Americans over the age of 65 complain of more than one disabling muscle cramp per week.[2]
The precise cause of these cramps is unclear. Potential contributing factors are believed to include dehydration, low levels of certain minerals (magnesium, potassium, calcium, and sodium), and the reduced blood flow through the muscles attendant in prolonged sitting or lying down. An important cause specific to nocturnal leg cramps is iron deficiency. Through an unknown mechanism, low levels of iron can result in occasional or disabling cramps. It can often manifest as the so-called Restless Legs Syndrome of irresistible nocturnal movement impulses that resolve with standing or walking around.[3] Anyone seeking evaluation for cramps or restless legs should have their hemoglobin or iron levels checked as iron repletion will improve and, often, stop the cramps altogether.[4] There is no role, however, for iron supplementation in patients with a normal ferritin level.[5]
The treatment of cramps can be difficult; there is very sparse data in the literature guiding treatment decisions. The medication with the best data support its use is Quinine, whose effects have been known since the 1940's and are both significant and long lasting.[6][7] However, Quinine is exceptionally toxic, famously causing Thrombotic Thrombocytopoenic Purpura (TTP), and has been pulled off of the market for this indication.
There are some measures which have been studied and found to be ineffective: stretching, magnesium, vitamin E and gabapentin have all been evaluated with no benefit. Some measures are used by clinicians, but have never been formally evaluated by trial: baclofen, carbamazepine, and oxcarbazepine. Finally, there are a few medications that have proven benefit with small trial data: injected lidocaine (however impractical), vitamin B6, verapamil and diltiazem.[8]
## Smooth Muscle Cramps
Smooth muscle contractions lie at the heart of the cramping (or colicky) pain of internal organs. These include the intestine, uterus, ureter (in kidney stone pain), and various others.
### Menstrual Cramps
Menstruation is also highly likely to cause cramps of varying severity in the abdomen that may radiate to the lower back and thighs. Menstrual cramps can be treated with ibuprofen, acetaminophen or paracetamol, stretching exercises, or the application of heat through such means as warm baths or heating pads. Menstrual cramps that do not respond to self-treatment can be a symptom of endometriosis or other health problems.
## Skeletal Muscle Cramps
Skeletal muscles are muscles that can be voluntarily controlled. Of the skeletal muscles, those which cramp the most often are the calves, thighs, and arches of the foot. These cramps are seemingly associated with strenuous activity and can be intensely painful.
### Self Induced Cramp
Self-induced cramp is brought on purposefully by individuals for the purpose of stretching muscle in a position where standing or greater movement is difficult or impossible. For instance, certain workers or craftsmen may find inducing cramp in the lower legs enables them to stretch desirable muscle groups without the need to physically stand in tight spaces.
## Iatrogenic Causes
Statins are known to cause myalgia and cramps among other side effects. Additional factors increasing probability for this adverse side effects are physical exercise, age, female gender, history of cramps and hypothyroidism. Up to 80% of athletes using statins suffer significant muscular adverse effects including cramps [9], the rate appears to be approximately 10-25% in typical population using statins [10][11]. In some cases this adverse effects will disappear after switching to a different statin, however they should not be ignored if they persist as they can rarely develop into a more serious problem. Coenzyme Q10 supplementation can be helpful to avoid some statin related adverse effects but currently there is not enough evidence to prove effectiveness in avoiding myopathy or myalgia [12].
# Causes
There are numerous causes of cramping: hyperflexion; inadequate oxygenation; exposure to large changes in temperature; dehydration; low blood salt; or low blood calcium. Muscle cramps may also be a symptom/complication of pregnancy, kidney disease, thyroid disease, severe hypokalemia or hypocalcemia, restless legs syndrome, and neurologic disorders like multiple sclerosis or ALS.[13] Cramps can also occur 'idiopathically' with no apparent cause.
Electrolyte disturbance may cause cramping and tetany of muscles, particularly critical hypokalaemia (a low level of potassium) and hypocalcaemia (a low level of calcium). This disturbance arises as the body loses large amounts of interstitial fluid through sweat. This interstitial fluid is composed mostly of water and table salt (NaCl). The loss of osmotically active particles outside muscle cells(NaCl) leads to a disturbance of the osmotic balance and swelling of muscle cells as these contain more osmotically active particles. This causes the calcium pump between the muscle lumen and sarcoplasmic reticulum to short circuit and the calcium ions remain bound to the tropomyosin and the muscle contraction is continued. This may occur when the lactic acid is high in the cells.
## Causes by Organ System
## Causes in Alphabetical Order
# Treatment
Muscle cramps can be treated by applying a soft massage on the cramped muscle, stretching the muscle and applying heat or cold. Heat improves superficial blood circulation and makes muscles more flexible, so some people find that heat is more soothing for muscle cramps. Application of excessive heat or cold to sore muscles may bring on cramps. Pounding on a cramped muscle can increase soreness.
- In the case of inadequate oxygenation, excess lactic acid, produced by anaerobic respiration, builds up and stresses the muscle. In addition to the methods described above, cramps from poor oxygenation can be improved by rapid deep breathing.
- Cramps from lack of water and/or salt can be treated by drinking water and/or increasing salt intake, respectively.
There is no scientific evidence to support the widely held claim by the sports nutrition industry that intake of specially composed electrolyte drinks has any advantage over intake of plain table salt (via drink or food) and water to counter these electrolyte disturbances and muscle cramps in people with a well-functioning renal system.
Eating foods high in potassium can help prevent muscle cramps.[14] Foods with high sources of potassium include, in order from highest to lowest: avocados, potatoes, bananas, broccoli, orange juice, soybeans and apricots, although it is also common in most fruits, vegetables and meats.
Leg cramps may also be due to vitamin D deficiency (also needed for calcium absorption). Due to change in diet, shunning milk because of high cholesterol content, or, in children, preference for soft drinks, and decreased sun exposure, vitamin D deficiency is widespread. Correcting this deficiency will in many cases also eliminate, or reduce, frequency of leg cramps.
# Related Chapters
- Trigger points
- Side Stitch
- Delayed onset muscle soreness | https://www.wikidoc.org/index.php/Cramp | |
6d968a530c709046cf2f9799f57becaa0880e3b5 | wikidoc | Skull | Skull
# Overview
The skull is a bony structure found in many animals which serves as the general framework for the head. The skull supports the structures of the face and protects the head against injury.
The skull can be subdivided into two parts: the cranium and the mandible. A skull that is missing a mandible is only a cranium; this is the source of a very commonly made error in terminology. Those animals having skulls are called craniates.
Protection of the brain is only one part of the function of a bony skull. For example, a fixed distance between the eyes is essential for stereoscopic vision, and a fixed position for the ears helps the brain to use auditory cues to judge direction and distance of sounds. In some animals, the skull also has a defensive function (e.g. horned ungulates); the frontal bone is where horns are mounted.
# Human skulls
In humans, the adult skull is normally made up of 22 bones. Except for the mandible, all of the bones of the skull are joined together by sutures, rigid articulations permitting very little movement. Eight bones form the neurocranium (braincase), a protective vault surrounding the brain. Fourteen bones form the splanchnocranium, the bones supporting the face. Encased within the temporal bones are the six ear ossicles of the middle ears, though these are not part of the skull. The hyoid bone, supporting the tongue, is usually not considered as part of the skull either, as it does not articulate with any other bones.
The skull contains the sinus cavities, which are air-filled cavities lined with respiratory epithelium, which also lines the large airways. The exact functions of the sinuses are unclear; they may contribute to lessening the weight of the skull with a minimal reduction in strength,or they may be important in improving the resonance of the voice. In some animals, such as the elephant, the sinuses are extensive. The elephant skull needs to be very large, to form an attachment for muscles of the neck and trunk, but is also unexpectedly light; the comparatively small brain-case is surrounded by large sinuses which reduce the weight.
The meninges are the three layers, or membranes, which surround the structures of the nervous system. They are known as the dura mater, the arachnoid mater and the pia mater. Other than being classified together, they have little in common with each other.
In humans, the anatomical position for the skull is the Frankfurt plane, where the lower margins of the orbits and the upper borders of the ear canals are all in a horizontal plane. This is the position where the subject is standing and looking directly forward. For comparison, the skulls of other species, notably primates and hominids, may sometimes be studied in the Frankfurt plane. However, this does not always equate to a natural posture in life.
# Possible types of skull fractures
# Other skulls
## Temporal Fenestra
The temporal fenestra are anatomical features of the amniote skull, characterised by bilaterally symmetrical holes (fenestrae) in the temporal bone. Depending on the lineage of a given animal, two, one, or no pairs of temporal fenestrae may be present, above or below the postorbital and squamosal bones. The upper temporal fenestrae are also known as the supratemporal fenestrae, and the lower temporal fenestrae are also known as the infratemporal fenestrae. The presence and morphology of the temporal fenestra is critical for taxonomic classification of the synapsids, of which mammals are part.
Physiological speculation associates it with a rise in metabolic rates and an increase in jaw musculature. The earlier amniotes of the Carboniferous did not have temporal fenestrae but the more advanced sauropsids and synapsids did. As time progressed, sauropsids' and synapsids' temporal fenestrae became more modified and larger to make stronger bites and more jaw muscles. Dinosaurs, which are sauropsids, have large advanced openings and their descendants, the birds, have temporal fenestrae which have been modified. Mammals, which are synapsids, possess no fenestral openings in the skull, as the trait has been modified. They do, though, still have the temporal orbit (which resembles an opening) and the temporal muscles. It is a hole in the head and is situated to the rear of the orbit behind the eye. | Skull
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
The skull is a bony structure found in many animals which serves as the general framework for the head. The skull supports the structures of the face and protects the head against injury.
The skull can be subdivided into two parts: the cranium and the mandible. A skull that is missing a mandible is only a cranium; this is the source of a very commonly made error in terminology. Those animals having skulls are called craniates.
Protection of the brain is only one part of the function of a bony skull. For example, a fixed distance between the eyes is essential for stereoscopic vision, and a fixed position for the ears helps the brain to use auditory cues to judge direction and distance of sounds. In some animals, the skull also has a defensive function (e.g. horned ungulates); the frontal bone is where horns are mounted.
# Human skulls
In humans, the adult skull is normally made up of 22 bones. Except for the mandible, all of the bones of the skull are joined together by sutures, rigid articulations permitting very little movement. Eight bones form the neurocranium (braincase), a protective vault surrounding the brain. Fourteen bones form the splanchnocranium, the bones supporting the face. Encased within the temporal bones are the six ear ossicles of the middle ears, though these are not part of the skull. The hyoid bone, supporting the tongue, is usually not considered as part of the skull either, as it does not articulate with any other bones.
The skull contains the sinus cavities, which are air-filled cavities lined with respiratory epithelium, which also lines the large airways. The exact functions of the sinuses are unclear; they may contribute to lessening the weight of the skull with a minimal reduction in strength,or they may be important in improving the resonance of the voice. In some animals, such as the elephant, the sinuses are extensive. The elephant skull needs to be very large, to form an attachment for muscles of the neck and trunk, but is also unexpectedly light; the comparatively small brain-case is surrounded by large sinuses which reduce the weight.
The meninges are the three layers, or membranes, which surround the structures of the nervous system. They are known as the dura mater, the arachnoid mater and the pia mater. Other than being classified together, they have little in common with each other.
In humans, the anatomical position for the skull is the Frankfurt plane, where the lower margins of the orbits and the upper borders of the ear canals are all in a horizontal plane. This is the position where the subject is standing and looking directly forward. For comparison, the skulls of other species, notably primates and hominids, may sometimes be studied in the Frankfurt plane. However, this does not always equate to a natural posture in life.
# Possible types of skull fractures
Template:Seemain
# Other skulls
## Temporal Fenestra
The temporal fenestra are anatomical features of the amniote skull, characterised by bilaterally symmetrical holes (fenestrae) in the temporal bone. Depending on the lineage of a given animal, two, one, or no pairs of temporal fenestrae may be present, above or below the postorbital and squamosal bones. The upper temporal fenestrae are also known as the supratemporal fenestrae, and the lower temporal fenestrae are also known as the infratemporal fenestrae. The presence and morphology of the temporal fenestra is critical for taxonomic classification of the synapsids, of which mammals are part.
Physiological speculation associates it with a rise in metabolic rates and an increase in jaw musculature. The earlier amniotes of the Carboniferous did not have temporal fenestrae but the more advanced sauropsids and synapsids did. As time progressed, sauropsids' and synapsids' temporal fenestrae became more modified and larger to make stronger bites and more jaw muscles. Dinosaurs, which are sauropsids, have large advanced openings and their descendants, the birds, have temporal fenestrae which have been modified. Mammals, which are synapsids, possess no fenestral openings in the skull, as the trait has been modified. They do, though, still have the temporal orbit (which resembles an opening) and the temporal muscles. It is a hole in the head and is situated to the rear of the orbit behind the eye. | https://www.wikidoc.org/index.php/Cranial_bones | |
ae0e1e8243d034a5d58f04b4016859fbc3568968 | wikidoc | Tears | Tears
Tears are a liquid produced by the body's process of lacrimation to clean and lubricate the eyes. The word lacrimation may also be used in a medical or literary sense to refer to crying. Strong emotions, such as sorrow or elation, may lead to crying. Although most land mammals have a lacrimation system to keep their eyes wet, Humans are the only animal generally accepted to cry emotional tears.
# Physiology
In humans, the tear film coating the eye has three distinct layers, from the most outer surface:
- The lipid layer contains oils secreted by the meibomian glands. The outer-most layer of the tear film coats the aqueous layer to provide a hydrophobic barrier that retards evaporation and prevents tears spilling onto the cheek.
- The aqueous layer contains water and other substances such as proteins (e.g. tear lipocalin, lactoferrin, lysozyme and lacritin) secreted by the glands and the lacrimal gland. The aqueous layer serves to promote spreading of the tear film, control of infectious agents and osmotic regulation.
- The mucous layer contains mucin secreted by the conjunctival goblet cells. The inner-most layer of the tear film, it coats the cornea to provide a hydrophilic layer that allows for even distribution of the tear film, as well as mucus covering of the cornea.
Having a thin tear film may prevent you from wearing contact lenses as the amount of oxygen need is higher than normal and contact lenses stop oxygen entering your eye. You will find that your eyes will dry out while wearing contact lenses whilst having a thin tear film. Special eye drops are available for contact lense wearers, also certain types of contact lenses are designed to let more oxygen through.
# Drainage of tear film
One lacrimal gland is located superiortemporally to each eye, behind the upper eyelid. The lacrimal glands secrete lacrimal fluid which flows through the main excretory ducts into the space between the eyeball and lids. When the eyes blink the lacrimal fluid is spread across the surface of the eye. Lacrimal fluid gathers in the lacrimal lake, and is drawn into the puncta by capillary action, then flows through the lacrimal canaliculi at the inner corner of the eyelids through the nasolacrimal duct, and finally into the nasal cavity. An excess of tears, as with strong emotion, can thus cause the nose to run.
# Types of tears
There are three very basic types of tears:
- Basal tears: In healthy mammalian eyes, the cornea is continually kept wet and nourished by basal tears. They lubricate the eye and help to keep it clear of dust. Tear fluid contains water, mucin, lipids, lysozyme, lactoferrin, lipocalin, lacritin, immunoglobulins, glucose, urea, sodium, and potassium. Some of the substances in lacrimal fluid fight against bacterial infection as a part of the immune system.
- Reflex tears: The second type of tears results from irritation of the eye by foreign particles, or from the presence of irritant substances such as onion vapors, tear gas or pepper spray in the eye's environment. These reflex tears attempt to wash out irritants that may have come into contact with the eye.
- Crying or weeping (psychic tears): The third category, generally referred to as crying or weeping, is increased lacrimation due to strong emotional stress, depression or physical pain. This practice is not restricted to negative emotions; many people have been known to cry when extremely happy or when they are laughing. In humans, emotional tears can be accompanied by reddening of the face and sobbing — cough-like, convulsive breathing, sometimes involving spasms of the whole upper body. Tears brought about by emotions have a different chemical make up than those for lubrication. The limbic system is involved in production of basic emotional drives, such as anger, fear, etc. The limbic system, specifically the hypothalamus, also has a degree of control over the autonomic system. The parasympathetic branch of the autonomic system controls the lacrimal glands via the neurotransmitter acetylcholine through both the nicotinic and muscarinic receptors. When these receptors are activated that the lacrimal gland is stimulated to produce tears.
# Diseases and disorders
Quality of vision is affected by the stability of the tear film.
"Crocodile tears syndrome" is an uncommon consequence of recovery from Bell's palsy where faulty regeneration of the facial nerve causes sufferers to shed tears while eating.
Keratoconjunctivitis sicca, more commonly known as dry eye, is a very common disorder of the tear film. Paradoxically, sufferers can experience watering of the eyes which is in fact a response to irritation caused by the original tear film deficiency.
"Leamy Eye" is a condition whereby there is excessive watering of one eye, seemingly for no apparent reason, in response to environmental stimuli.
# Causes
## Drug Induced
- Eribulin
- Naphazoline
# Societal aspects
Most mammals will produce tears in response to extreme pain or other stimuli, but crying as an emotional reaction is considered by many to be a uniquely human phenomenon, possibly due to humans' advanced self-awareness. Some studies suggest that elephants and gorillas may cry as well.
In nearly all cultures, crying is seen as a specific act associated with tears trickling down the cheeks and accompanied by characteristic sobbing sounds. Emotional triggers are most often anger and grief, but crying can also be triggered by sadness, joy, fear, laughter or humor, frustration, or other strongly-experienced emotions.
In many cultures, crying is associated with babies and children. Some cultures consider crying to be undignified and infantile, casting aspersions on those who cry publicly, except if it is due to the death of a close friend or relative. In most cultures, it is more socially acceptable for women to cry than men.
Some modern therapy movements such as Re-evaluation Counseling believe that crying is beneficial to health and mental wellbeing, and positively encourage it.
An insincere display of grief or dishonest remorse is called crocodile tears, from the ancient anecdote that crocodiles would pretend to weep while luring or devouring their prey.
# Spiritual aspects
Transpersonal psychology is scientifically investigating the mechanism and process of sublime tears of spiritual bliss and joy.
Many religions describe gods or prophets as crying:
- According to a hadith, the prophet Muhammad proclaimed: "This (tears) is an expression of the tenderness and compassion, which the Lord hath put into the hearts of His servants. The Lord doth not have compassion on and commiserate with His servants, except such as are tender and full of feeling."
- The shortest verse in English translated Bibles is found in the Gospel of John 11:35, "Jesus wept."
- Jade is sometimes known as "tears of the Buddha".
The Gift of Tears in Shin Buddhism: Tears of joy and grief cleanse our souls. Christians as well may perceive tears as a spiritual gift when they refer to Gospel of Jesus Christ: "Blessed are you that weep now, for you shall laugh" (Luke 6.21), while Weeping Icons are a common feature of the Eastern Christian Traditions. | Tears
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Tears are a liquid produced by the body's process of lacrimation to clean and lubricate the eyes. The word lacrimation may also be used in a medical or literary sense to refer to crying. Strong emotions, such as sorrow or elation, may lead to crying. Although most land mammals have a lacrimation system to keep their eyes wet, Humans are the only animal generally accepted to cry emotional tears. [2][3]
# Physiology
In humans, the tear film coating the eye has three distinct layers, from the most outer surface:
- The lipid layer contains oils secreted by the meibomian glands. The outer-most layer of the tear film coats the aqueous layer to provide a hydrophobic barrier that retards evaporation and prevents tears spilling onto the cheek.
- The aqueous layer contains water and other substances such as proteins (e.g. tear lipocalin, lactoferrin, lysozyme[1] and lacritin) secreted by the glands and the lacrimal gland. The aqueous layer serves to promote spreading of the tear film, control of infectious agents and osmotic regulation.
- The mucous layer contains mucin secreted by the conjunctival goblet cells. The inner-most layer of the tear film, it coats the cornea to provide a hydrophilic layer that allows for even distribution of the tear film, as well as mucus covering of the cornea.
Having a thin tear film may prevent you from wearing contact lenses as the amount of oxygen need is higher than normal and contact lenses stop oxygen entering your eye. You will find that your eyes will dry out while wearing contact lenses whilst having a thin tear film. Special eye drops are available for contact lense wearers, also certain types of contact lenses are designed to let more oxygen through.
# Drainage of tear film
One lacrimal gland is located superiortemporally to each eye, behind the upper eyelid. The lacrimal glands secrete lacrimal fluid which flows through the main excretory ducts into the space between the eyeball and lids. When the eyes blink the lacrimal fluid is spread across the surface of the eye. Lacrimal fluid gathers in the lacrimal lake, and is drawn into the puncta by capillary action, then flows through the lacrimal canaliculi at the inner corner of the eyelids through the nasolacrimal duct, and finally into the nasal cavity. An excess of tears, as with strong emotion, can thus cause the nose to run.
[4]
# Types of tears
There are three very basic types of tears:
- Basal tears: In healthy mammalian eyes, the cornea is continually kept wet and nourished by basal tears. They lubricate the eye and help to keep it clear of dust. Tear fluid contains water, mucin, lipids, lysozyme, lactoferrin, lipocalin, lacritin, immunoglobulins, glucose, urea, sodium, and potassium. Some of the substances in lacrimal fluid fight against bacterial infection as a part of the immune system.
- Reflex tears: The second type of tears results from irritation of the eye by foreign particles, or from the presence of irritant substances such as onion vapors, tear gas or pepper spray in the eye's environment. These reflex tears attempt to wash out irritants that may have come into contact with the eye.
- Crying or weeping (psychic tears): The third category, generally referred to as crying or weeping, is increased lacrimation due to strong emotional stress, depression or physical pain. This practice is not restricted to negative emotions; many people have been known to cry when extremely happy or when they are laughing. In humans, emotional tears can be accompanied by reddening of the face and sobbing — cough-like, convulsive breathing, sometimes involving spasms of the whole upper body. Tears brought about by emotions have a different chemical make up than those for lubrication. The limbic system is involved in production of basic emotional drives, such as anger, fear, etc. The limbic system, specifically the hypothalamus, also has a degree of control over the autonomic system. The parasympathetic branch of the autonomic system controls the lacrimal glands via the neurotransmitter acetylcholine through both the nicotinic and muscarinic receptors. When these receptors are activated that the lacrimal gland is stimulated to produce tears.[2]
# Diseases and disorders
Quality of vision is affected by the stability of the tear film.[3]
"Crocodile tears syndrome" is an uncommon consequence of recovery from Bell's palsy where faulty regeneration of the facial nerve causes sufferers to shed tears while eating.[4]
Keratoconjunctivitis sicca, more commonly known as dry eye, is a very common disorder of the tear film. Paradoxically, sufferers can experience watering of the eyes which is in fact a response to irritation caused by the original tear film deficiency.
"Leamy Eye" is a condition whereby there is excessive watering of one eye, seemingly for no apparent reason, in response to environmental stimuli.
# Causes
## Drug Induced
- Eribulin
- Naphazoline
# Societal aspects
Most mammals will produce tears in response to extreme pain or other stimuli, but crying as an emotional reaction is considered by many to be a uniquely human phenomenon, possibly due to humans' advanced self-awareness. Some studies suggest that elephants and gorillas may cry as well.[5]
In nearly all cultures, crying is seen as a specific act associated with tears trickling down the cheeks and accompanied by characteristic sobbing sounds. Emotional triggers are most often anger and grief, but crying can also be triggered by sadness, joy, fear, laughter or humor, frustration, or other strongly-experienced emotions.
In many cultures, crying is associated with babies and children. Some cultures consider crying to be undignified and infantile, casting aspersions on those who cry publicly, except if it is due to the death of a close friend or relative. In most cultures, it is more socially acceptable for women to cry than men.
Some modern therapy movements such as Re-evaluation Counseling believe that crying is beneficial to health and mental wellbeing, and positively encourage it.[6]
An insincere display of grief or dishonest remorse is called crocodile tears, from the ancient anecdote that crocodiles would pretend to weep while luring or devouring their prey.[7]
# Spiritual aspects
Transpersonal psychology is scientifically investigating the mechanism and process of sublime tears of spiritual bliss and joy.[citation needed]
Many religions describe gods or prophets as crying:
- According to a hadith, the prophet Muhammad proclaimed: "This (tears) is an expression of the tenderness and compassion, which the Lord hath put into the hearts of His servants. The Lord doth not have compassion on and commiserate with His servants, except such as are tender and full of feeling."
- The shortest verse in English translated Bibles is found in the Gospel of John 11:35, "Jesus wept."
- Jade is sometimes known as "tears of the Buddha".
The Gift of Tears in Shin Buddhism: Tears of joy and grief cleanse our souls. Christians as well may perceive tears as a spiritual gift when they refer to Gospel of Jesus Christ: "Blessed are you that weep now, for you shall laugh" (Luke 6.21), while Weeping Icons are a common feature of the Eastern Christian Traditions. | https://www.wikidoc.org/index.php/Crying | |
33b5935d2a8b27c4837f2baba5ec298728d36b02 | wikidoc | Cubam | Cubam
Cubam, is the term used to refer to a multi-ligand receptor located in the terminal ileum, specializing in absorption of vitamin B12. Cubam is essentially composed of amnionless (AMN), and cubilin. Cubilin is essential as a cell receptor recognizing the "vitamin B12-intrinsic factor" complex, whereas amnionless is more involved in the receptor mediated endocytosis of the complex.
# Clinical significance
Vitamin B12 is an essential water-soluble vitamin, the absorption of which relies on a functional secretion of salivary haptocorrin, functional secretion of gastric intrinsic factor, functional cleavage of the haptocorrin via pancreatic protease, and a functional absorption via the Cubam at terminal ileum. As expected, a defect at any point of the aforementioned list, can cause malabsoption of vitamin B12, and subsequent macrocytic anemia. The most common cause of Vitamin B12 deficiency is deficiency of the intrinsic factor (IF) usually due to atrophic gastritis, which reduces the number of parietal cells secreting intrinsic factor. This can lead to pernicious anemia. However, a rare abnormality of AMN can also cause vitamin B12 anemia; this condition is referred to as "Imerslund-Gräsbeck syndrome (IGS)." Autosomal recessive mutations in both components of Cubam (AMN, and cubilin) is responsible for Imerslund-Gräsbeck syndrome, which manifests as macrocytic, megaloblastic anemia.
Severe vitamin B12 deficiency is most commonly caused by an autoimmune mediated deficiency in intrinsic factor. Rarely, a mutations in the gene CUBN, coding for cubilin, or AMN, coding for amnionless cause an autosomal reccessive form of vitamin B12 deficiency, known as the Imerslund-Gräsbeck syndrome. Cubilin and amnionless also play a role in renal tubular function. Cubilin is essential for embryonic development in rodents, but appears not to be essential for normal human embryonic development. | Cubam
Cubam, is the term used to refer to a multi-ligand receptor located in the terminal ileum, specializing in absorption of vitamin B12. Cubam is essentially composed of amnionless (AMN), and cubilin.[1][2] Cubilin is essential as a cell receptor recognizing the "vitamin B12-intrinsic factor" complex, whereas amnionless is more involved in the receptor mediated endocytosis of the complex.
# Clinical significance
Vitamin B12 is an essential water-soluble vitamin, the absorption of which relies on a functional secretion of salivary haptocorrin, functional secretion of gastric intrinsic factor, functional cleavage of the haptocorrin via pancreatic protease, and a functional absorption via the Cubam at terminal ileum. As expected, a defect at any point of the aforementioned list, can cause malabsoption of vitamin B12, and subsequent macrocytic anemia. The most common cause of Vitamin B12 deficiency is deficiency of the intrinsic factor (IF) usually due to atrophic gastritis, which reduces the number of parietal cells secreting intrinsic factor. This can lead to pernicious anemia. However, a rare abnormality of AMN can also cause vitamin B12 anemia; this condition is referred to as "Imerslund-Gräsbeck syndrome (IGS)." Autosomal recessive mutations in both components of Cubam (AMN, and cubilin) is responsible for Imerslund-Gräsbeck syndrome,[3] which manifests as macrocytic, megaloblastic anemia.
Severe vitamin B12 deficiency is most commonly caused by an autoimmune mediated deficiency in intrinsic factor. Rarely, a mutations in the gene CUBN, coding for cubilin, or AMN, coding for amnionless cause an autosomal reccessive form of vitamin B12 deficiency, known as the Imerslund-Gräsbeck syndrome. Cubilin and amnionless also play a role in renal tubular function. Cubilin is essential for embryonic development in rodents, but appears not to be essential for normal human embryonic development.[4] | https://www.wikidoc.org/index.php/Cubam | |
a46a843e3899d463e0958b3f0ad0085e90694ad7 | wikidoc | Cubeb | Cubeb
Cubeb (Piper cubeba), or tailed pepper, is a plant in genus Piper, cultivated for its fruit and essential oil. It is mostly grown in Java and Sumatra, hence sometimes called Java pepper. The fruits are gathered before they are ripe, and carefully dried. Commercial cubebs consist of the dried berries, similar in appearance to black pepper, but with stalks attached — the "tails" in "tailed pepper". The dried pericarp is wrinkled, its color ranges from grayish-brown to black. The seed is hard, white and oily. The odor of cubebs is described as agreeable and aromatic. The taste, pungent, acrid, slightly bitter and persistent. It has been described as tasting like allspice, or like a cross between allspice and black pepper.
Cubeb came to Europe via India through the trade with the Arabs. The name cubeb comes from Arabic kababah (كبابة), which is of unknown origin, by way of Old French quibibes. Cubeb is mentioned in alchemical writings by its Arabic name. In his Theatrum Botanicum, John Parkinson tells that the king of Portugal prohibited the sale of cubeb in order to promote black pepper (Piper nigrum) around 1640. It experienced a brief resurgence in 19th century Europe for medicinal uses, but has practically vanished from the European market since. It continues to be used as a flavoring agent for gins and cigarettes in the West, and as a seasoning for food in Indonesia and Africa.
# History
In the 4th century BC, Theophrastus mentioned komakon, including it with cinnamon and cassia as an ingredient in aromatic confections. Guillaume Budé and Claudius Salmasius have identified komakon with cubeb, probably due to the resemblance which the word bears to the Javanese name of cubeb, kumukus. This is seen as a curious evidence of Greek trade with Java in a time earlier than that of Theophrastus. It is unlikely Greeks acquired them from somewhere else, since Javanese growers protected their monopoly of the trade by sterilizing the berries by scalding, ensuring that the vines were unable to be cultivated elsewhere.
In the Tang Dynasty, cubeb was brought to China from Srivijaya. In India the spice came to be called kabab chini, that is, "Chinese cubeb," possibly because the Chinese had a hand in its trade, but more likely because it was an important item in the trade with China. In China this pepper was called both vilenga, and vidanga, the cognate Sanskrit word. Li Hsun thought it grew on the same tree as black pepper. Tang physicians administered it to restore appetite, cure "demon vapors", darken the hair, and perfume the body. However, there is no evidence showing that cubeb was used as a condiment in China.
The Book of One Thousand and One Nights, compiled in the 9th century, mentions cubeb as a remedy for infertility, showing it was already used by Arabs for medicinal purpose. Cubeb was introduced to Arabic cuisine around the 10th century. The Travels of Marco Polo, written in late 13th century, describes Java as a producer of cubeb, along with other valuable spices. In the 14th century, cubeb was imported into Europe from the Grain Coast, under the name of pepper, by merchants of Rouen and Lippe. A 14th century morality tale exemplifying gluttony by the Franciscan writer Francesc Eiximenis describes the eating habits of a worldly cleric who consumes a bizarre concoction of egg yolks with cinnamon and cubeb after his baths, probably as an aphrodisiac.
Cubeb was thought by the people of Europe to be repulsive to demons, just as it was by the people of China. Ludovico Maria Sinistrari, a Catholic priest who wrote about methods of exorcism in the late 17th century, includes cubeb as an ingredient in an incense to ward off incubus. Even today, his formula for the incense is quoted by neopagan authors, some of whom also claim that cubeb can be used in love sachets and spells.
After the prohibition of sale, culinary use of cubeb decreased dramatically in Europe, and only its medicinal application continued to the 19th century. In the early 20th century, cubeb was regularly shipped from Indonesia to Europe and the United States. The trade gradually diminished to an average of 135 ton annually, and practically ceased after 1940.
# Chemistry
The dried cubeb berries contain essential oil consisting monoterpenes (sabinene 50%, α-thujene, carene, and sesquiterpenes (caryophyllene, copaene, α- and β-cubebene, δ-cadinene, germacrene)., the oxides 1-4 and 1-8 cineole and the alcohol cubebol.
About 15% of a volatile oil is obtained by distilling cubebs with water. Cubebene, the liquid portion, has the formula C15H24. It is a pale green or blue-yellow viscous liquid with a warm woody, slightly camphoraceous odor. After rectification with water, or on keeping, this deposits rhombic crystals of camphor of cubebs (C15H60).
Cubebin (C10H10O3) is a crystalline substance existing in cubebs, discovered by Eugène Soubeiran and Capitaine in 1839. It may be prepared from cubebene, or from the pulp left after the distillation of the oil. The drug, along with gum, fatty oils, and malates of magnesium and calcium, contains also about 1% of cubebic acid, and about 6% of a resin. The dose of the fruit is 30 to 60 grains, and the British Pharmacopoeia contains a tincture with a dose of 4 to 1 dram.
# Use
## Medicinal
In India, Sanskrit texts included cubeb in various remedies. Charaka and Sushruta prescribed a cubeb paste as a mouthwash, and the use of dried cubebs internally for oral and dental diseases, loss of voice, halitosis, fevers, and cough. Unani physicians use a paste of the cubeb berries externally on male and female genitals to intensify sexual pleasure during coitus. Due to this attributed property, cubeb was called "Habb-ul-Uruus".
In traditional Chinese medicine cubeb is used for its alleged warming property. In Tibetan medicine, cubeb (ka ko la in Tibetan) is one of bzang po drug, six fine herbs beneficial to specific organs in the body, with cubeb assigned to the spleen.
Arab physicians of the Middle Ages were usually versed in alchemy, and cubeb was used, under the name kababa, when preparing the water of al butm. The Book of One Thousand and One Nights mentions cubeb as a main ingredient in making an aphrodisiac remedy for infertility:
The mixture, called "seed-thickener", is given to Shams-al-Din, a wealthy merchant who had no child, with the instruction that he must eat the paste two hours before having intercourse with his wife. According to the story, the merchant did get the child he desired after following these instructions. Other Arab authors wrote that cubeb rendered the breath fragrant, cured affections of the bladder, and that eating it "enhances the delight of coitus".
In 1654, Nicholas Culpeper wrote in the London Dispensatorie that cubebs were "hot and dry in the third degree... (snip) they cleanse the head of flegm and strenghthen the brain, they heat the stomach and provoke lust". A later edition in 1826 informed the reader that "the Arabs call them Quabebe, and Quabebe Chine: they grow plentifully in Java, they stir up venery. (snip) ...and are very profitable for cold griefs of the womb".
The modern use of cubeb in England as a drug dates from 1815. There were various preparations, including oleum cubebae (oil of cubeb), tinctures, fluid extracts, oleo-resin compounds, and vapors, which were used for throat complaints. A small percentage of cubeb wase commonly included in lozenges designed to alleviate bronchitis, in which the antiseptic and expectoral properties of the drug are useful. The most important therapeutic application of this drug, however, was in treating gonorrhea, where its antiseptic action was of much value. William Wyatt Squire wrote in 1908 that cubebs "act specifically on the genito-urinary mucous membrane. (They are) given in all stages of gonorrhea". As compared with copaiba in this connection cubeb has the advantages of being less disagreeable to take and somewhat less likely to disturb the digestive apparatus in prolonged administration.
The volatile oil, oleum cubebae, was the form in which cubeb is most commonly used as a drug, the dose being 5 to 20 minims, which may be suspended in mucilage or given after meals in a wafer. The drug exhibited the typical actions of a volatile oil, but exerted some of these to an exceptional degree. As such, it was liable to cause a cutaneous erythema in the course of its excretion by the skin, had a marked diuretic action, and was a fairly efficient disinfectant of the urinary passages. Its administration caused the appearance in the urine of a salt of cubebic acid which was precipitated by heat or nitric acid, and was therefore liable to be mistaken for albumin, when these two most common tests for the occurrence of albuminuria were applied.
The National Botanic Pharmacopoeia printed in 1921 tells that cubeb wase "an excellent remedy for flour albus or whites."
## Culinary
In Europe, cubeb was one of the valuable spices during the Middle Age. It was ground as a seasoning for meat or used in sauces. A medieval recipe includes cubeb in making sauce sarcenes, which consists of almond milk and several spices. As an aromatic confectionery, cubeb was often candied and eaten whole. Candied cubeb is mentioned in Thomas Pynchon's Gravity's Rainbow, set in the 1940s:
Cubeb reached Africa by way of the Arabs. In Moroccan cuisine, cubeb is used in savory dishes and in pastries like markouts, little diamonds of semolina with honey and dates. It also appears occasionally in the list of ingredients for the famed spice mixture Ras el hanout. In West Africa, cubeb turns up in dishes like stews in of Benin, where its use is so frequent that it is referred to as piment pays, pepper of the country. In Indonesian cuisine, especially in Indonesian gulés (curries), cubeb is frequently used. Ocet Kubebowy, a vinegar infused with cubeb, cumin and garlic was used for meat marinades in Poland during the 14th century. Cubeb can still be used to enhance the flavor of savory soups.
## Cigarettes and spirits
Cubeb was frequently used in the form of cigarettes for asthma, chronic pharyngitis and hay fever. Edgar Rice Burroughs, being fond of smoking cubeb cigarettes, humorously stated that if he had not smoked so many cubebs, there might never have been Tarzan. "Marshall's Prepared Cubeb Cigarettes" was a popular brand, with enough sales to still be made during World War II. Occasionally, marijuana-users claimed that smoking marijuana is no more harmful than smoking cubeb.
Cubeb oil was included in the list of ingredients found in cigarettes, published by the Tobacco Prevention and Control Branch of North Carolina's Department of Health and Human Services.
Bombay Sapphire gin is flavored with botanicals including cubeb and grains of paradise. The brand was launched in 1987, but its maker claims that it is based on a secret recipe dating to 1761. Pertsovka, a dark brown Russian pepper vodka with a burning taste, is prepared from infusion of cubeb and capsicum peppers.
## Other
Cubeb is sometimes used to adulterate the essential oil of Patchouli, which requires caution for Patchouli users. In turn, cubeb is adulterated by Piper baccatum (also known as the "climbing pepper of Java") and Piper caninum.
Cubeb berries are used in love-drawing magic spells by practitioners of hoodoo, an African-American form of folk magic.
In 2000, Shiseido, a well-known Japanese cosmetics company patented a line of anti-aging products containing formulas made from several herbs, including cubeb.
In 2001, the Switzerland-based company Firmenich patented cubebol, a compound found in cubeb oil, as a cooling and refreshing agent. The patent describes application of cubebol as a refreshing agent in various products, ranging from chewing gum to sorbets, drinks, toothpaste, and
gelatin-based confectioneries.
# Notes
- ↑ Jump up to: 1.0 1.1 Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv Chapter XXV.
- ↑ Jump up to: 4.0 4.1 Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv. "...Incubus none the less persisted in appearing to her constantly, in the shape of an exceptionally handsome young man. At last, among other learned men, whose advice had been taken on the subject, was a very profound Theologian who, observing that the maiden was of a thoroughly phlegmatic temperament, surmised that that Incubus was an aqueous Demon (there are in fact, as is testified by Guazzo (Compendium Maleficarum, I. 19), igneous, aerial, phlegmatic, earthly, and subterranean demons who avoid the light of day), and so he prescribed a continual suffumigation in the room. A new vessel, made of earthenware and glass, was accordingly introduced, and filled with sweet calamus, cubeb seed, roots of both aristolochies, great and small cardamom, ginger, long-pepper, caryophylleae, cinnamon, cloves, mace, nutmegs, calamite storax, benzoin, aloes-wood and roots, one ounce of fragrant sandal, and three quarts of half brandy and water; the vessel was then set on hot ashes in order to force forth and upwards the fumigating vapour, and the cell was kept closed. As soon as the suffumigation was done, the Incubus came, but never dared enter the cell."
- ↑ Template:Harv.
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv. "Take one pound of tarmantanita, half a pound of honey of which the frost has been removed, one pound of aqua vita, very fine Indian 'and, sandal, in equal parts. Arab samg, juz bawwa, kholanjan root, kababa, reed, mastaqi, qaranfal, sanbal, of each three drachms. They must be pounded well and put into a distilling vessel made of glass, and it must be well covered, and put on a gentle fire. And the first water which will come up will be pure... (snip) And know that the first is called 'the mother of medicine'."
- ↑ Template:Harv. Richard Francis Burton edition gives a different formulae: "So he gave it to him and the broker betook himself to a hashish-seller, of whom he bought two ounces of concentrated Roumi opium and equal-parts of Chinese cubebs, cinnamon, cloves, cardamoms, ginger, white pepper and mountain skink; and, pounding them all together, boiled them in sweet olive oil; after which he added three ounces of male frankincense in fragments and a cupful of coriander-seed; and, macerating the whole, made it into an electuary with Roumi bee honey." Skink refers to a kind of lizard.
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv "Make a thykke mylke of almondys, do hit in a pot with floure of rys, safron, gynger, macys, quibibis, canel, sygure: and rynse the bottom of the disch with fat broth. Boyle the sewe byfore, and messe hit forth."
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv.
- ↑ Template:Harv
- ↑ The list of ingredients found in cigarettes Accessed February 11, 2006.
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Institute of Science in Society News, March 2000 (Accessed 27 February 2006)
- ↑ Leffingwell, John C., Ph.D (2001). "Cool without Menthol & Cooler than Menthol and Cooling Compounds as Insect Repellents". Leffingwell & Associates. Retrieved 2006-09-15..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ U.S. Patent 6,214,788 | Cubeb
Cubeb (Piper cubeba), or tailed pepper, is a plant in genus Piper, cultivated for its fruit and essential oil. It is mostly grown in Java and Sumatra, hence sometimes called Java pepper. The fruits are gathered before they are ripe, and carefully dried. Commercial cubebs consist of the dried berries, similar in appearance to black pepper, but with stalks attached — the "tails" in "tailed pepper". The dried pericarp is wrinkled, its color ranges from grayish-brown to black. The seed is hard, white and oily. The odor of cubebs is described as agreeable and aromatic. The taste, pungent, acrid, slightly bitter and persistent. It has been described as tasting like allspice, or like a cross between allspice and black pepper.
Cubeb came to Europe via India through the trade with the Arabs. The name cubeb comes from Arabic kababah (كبابة), which is of unknown origin,[1] by way of Old French quibibes.[2] Cubeb is mentioned in alchemical writings by its Arabic name. In his Theatrum Botanicum, John Parkinson tells that the king of Portugal prohibited the sale of cubeb in order to promote black pepper (Piper nigrum) around 1640. It experienced a brief resurgence in 19th century Europe for medicinal uses, but has practically vanished from the European market since. It continues to be used as a flavoring agent for gins and cigarettes in the West, and as a seasoning for food in Indonesia and Africa.
# History
In the 4th century BC, Theophrastus mentioned komakon, including it with cinnamon and cassia as an ingredient in aromatic confections. Guillaume Budé and Claudius Salmasius have identified komakon with cubeb, probably due to the resemblance which the word bears to the Javanese name of cubeb, kumukus. This is seen as a curious evidence of Greek trade with Java in a time earlier than that of Theophrastus.[3] It is unlikely Greeks acquired them from somewhere else, since Javanese growers protected their monopoly of the trade by sterilizing the berries by scalding, ensuring that the vines were unable to be cultivated elsewhere.[1]
In the Tang Dynasty, cubeb was brought to China from Srivijaya. In India the spice came to be called kabab chini, that is, "Chinese cubeb," possibly because the Chinese had a hand in its trade, but more likely because it was an important item in the trade with China. In China this pepper was called both vilenga, and vidanga, the cognate Sanskrit word.[4] Li Hsun thought it grew on the same tree as black pepper. Tang physicians administered it to restore appetite, cure "demon vapors", darken the hair, and perfume the body. However, there is no evidence showing that cubeb was used as a condiment in China.[4]
The Book of One Thousand and One Nights, compiled in the 9th century, mentions cubeb as a remedy for infertility, showing it was already used by Arabs for medicinal purpose. Cubeb was introduced to Arabic cuisine around the 10th century.[5] The Travels of Marco Polo, written in late 13th century, describes Java as a producer of cubeb, along with other valuable spices. In the 14th century, cubeb was imported into Europe from the Grain Coast, under the name of pepper, by merchants of Rouen and Lippe. A 14th century morality tale exemplifying gluttony by the Franciscan writer Francesc Eiximenis describes the eating habits of a worldly cleric who consumes a bizarre concoction of egg yolks with cinnamon and cubeb after his baths, probably as an aphrodisiac.
Cubeb was thought by the people of Europe to be repulsive to demons, just as it was by the people of China. Ludovico Maria Sinistrari, a Catholic priest who wrote about methods of exorcism in the late 17th century, includes cubeb as an ingredient in an incense to ward off incubus.[6] Even today, his formula for the incense is quoted by neopagan authors, some of whom also claim that cubeb can be used in love sachets and spells.
After the prohibition of sale, culinary use of cubeb decreased dramatically in Europe, and only its medicinal application continued to the 19th century. In the early 20th century, cubeb was regularly shipped from Indonesia to Europe and the United States. The trade gradually diminished to an average of 135 ton annually, and practically ceased after 1940.[7]
# Chemistry
The dried cubeb berries contain essential oil consisting monoterpenes (sabinene 50%, α-thujene, carene, and sesquiterpenes (caryophyllene, copaene, α- and β-cubebene, δ-cadinene, germacrene)., the oxides 1-4 and 1-8 cineole and the alcohol cubebol.
About 15% of a volatile oil is obtained by distilling cubebs with water. Cubebene, the liquid portion, has the formula C15H24. It is a pale green or blue-yellow viscous liquid with a warm woody, slightly camphoraceous odor.[8] After rectification with water, or on keeping, this deposits rhombic crystals of camphor of cubebs (C15H60).
Cubebin (C10H10O3) is a crystalline substance existing in cubebs, discovered by Eugène Soubeiran and Capitaine in 1839. It may be prepared from cubebene, or from the pulp left after the distillation of the oil. The drug, along with gum, fatty oils, and malates of magnesium and calcium, contains also about 1% of cubebic acid, and about 6% of a resin. The dose of the fruit is 30 to 60 grains, and the British Pharmacopoeia contains a tincture with a dose of 4 to 1 dram.
# Use
## Medicinal
In India, Sanskrit texts included cubeb in various remedies. Charaka and Sushruta prescribed a cubeb paste as a mouthwash, and the use of dried cubebs internally for oral and dental diseases, loss of voice, halitosis, fevers, and cough. Unani physicians use a paste of the cubeb berries externally on male and female genitals to intensify sexual pleasure during coitus. Due to this attributed property, cubeb was called "Habb-ul-Uruus".[9]
In traditional Chinese medicine cubeb is used for its alleged warming property. In Tibetan medicine, cubeb (ka ko la in Tibetan) is one of bzang po drug, six fine herbs beneficial to specific organs in the body, with cubeb assigned to the spleen.[10]
Arab physicians of the Middle Ages were usually versed in alchemy, and cubeb was used, under the name kababa, when preparing the water of al butm.[11] The Book of One Thousand and One Nights mentions cubeb as a main ingredient in making an aphrodisiac remedy for infertility:
The mixture, called "seed-thickener", is given to Shams-al-Din, a wealthy merchant who had no child, with the instruction that he must eat the paste two hours before having intercourse with his wife. According to the story, the merchant did get the child he desired after following these instructions. Other Arab authors wrote that cubeb rendered the breath fragrant, cured affections of the bladder, and that eating it "enhances the delight of coitus".[13]
In 1654, Nicholas Culpeper wrote in the London Dispensatorie that cubebs were "hot and dry in the third degree... (snip) they cleanse the head of flegm and strenghthen the brain, they heat the stomach and provoke lust".[14] A later edition in 1826 informed the reader that "the Arabs call them Quabebe, and Quabebe Chine: they grow plentifully in Java, they stir up venery. (snip) ...and are very profitable for cold griefs of the womb".
The modern use of cubeb in England as a drug dates from 1815. There were various preparations, including oleum cubebae (oil of cubeb), tinctures, fluid extracts, oleo-resin compounds, and vapors, which were used for throat complaints. A small percentage of cubeb wase commonly included in lozenges designed to alleviate bronchitis, in which the antiseptic and expectoral properties of the drug are useful. The most important therapeutic application of this drug, however, was in treating gonorrhea, where its antiseptic action was of much value. William Wyatt Squire wrote in 1908 that cubebs "act specifically on the genito-urinary mucous membrane. (They are) given in all stages of gonorrhea".[15] As compared with copaiba in this connection cubeb has the advantages of being less disagreeable to take and somewhat less likely to disturb the digestive apparatus in prolonged administration.
The volatile oil, oleum cubebae, was the form in which cubeb is most commonly used as a drug, the dose being 5 to 20 minims, which may be suspended in mucilage or given after meals in a wafer. The drug exhibited the typical actions of a volatile oil, but exerted some of these to an exceptional degree. As such, it was liable to cause a cutaneous erythema in the course of its excretion by the skin, had a marked diuretic action, and was a fairly efficient disinfectant of the urinary passages. Its administration caused the appearance in the urine of a salt of cubebic acid which was precipitated by heat or nitric acid, and was therefore liable to be mistaken for albumin, when these two most common tests for the occurrence of albuminuria were applied.
The National Botanic Pharmacopoeia printed in 1921 tells that cubeb wase "an excellent remedy for flour albus or whites."[16]
## Culinary
In Europe, cubeb was one of the valuable spices during the Middle Age. It was ground as a seasoning for meat or used in sauces. A medieval recipe includes cubeb in making sauce sarcenes, which consists of almond milk and several spices.[17] As an aromatic confectionery, cubeb was often candied and eaten whole. Candied cubeb is mentioned in Thomas Pynchon's Gravity's Rainbow, set in the 1940s:
Cubeb reached Africa by way of the Arabs. In Moroccan cuisine, cubeb is used in savory dishes and in pastries like markouts, little diamonds of semolina with honey and dates.[19] It also appears occasionally in the list of ingredients for the famed spice mixture Ras el hanout. In West Africa, cubeb turns up in dishes like stews in of Benin, where its use is so frequent that it is referred to as piment pays, pepper of the country.[20] In Indonesian cuisine, especially in Indonesian gulés (curries), cubeb is frequently used. Ocet Kubebowy, a vinegar infused with cubeb, cumin and garlic was used for meat marinades in Poland during the 14th century.[21] Cubeb can still be used to enhance the flavor of savory soups.
## Cigarettes and spirits
Cubeb was frequently used in the form of cigarettes for asthma, chronic pharyngitis and hay fever. Edgar Rice Burroughs, being fond of smoking cubeb cigarettes, humorously stated that if he had not smoked so many cubebs, there might never have been Tarzan. "Marshall's Prepared Cubeb Cigarettes" was a popular brand, with enough sales to still be made during World War II.[22] Occasionally, marijuana-users claimed that smoking marijuana is no more harmful than smoking cubeb.[23]
Cubeb oil was included in the list of ingredients found in cigarettes, published by the Tobacco Prevention and Control Branch of North Carolina's Department of Health and Human Services.[24]
Bombay Sapphire gin is flavored with botanicals including cubeb and grains of paradise. The brand was launched in 1987, but its maker claims that it is based on a secret recipe dating to 1761. Pertsovka, a dark brown Russian pepper vodka with a burning taste, is prepared from infusion of cubeb and capsicum peppers.[25]
## Other
Cubeb is sometimes used to adulterate the essential oil of Patchouli, which requires caution for Patchouli users.[26] In turn, cubeb is adulterated by Piper baccatum (also known as the "climbing pepper of Java") and Piper caninum.[27]
Cubeb berries are used in love-drawing magic spells by practitioners of hoodoo, an African-American form of folk magic.
In 2000, Shiseido, a well-known Japanese cosmetics company patented a line of anti-aging products containing formulas made from several herbs, including cubeb.[28]
In 2001, the Switzerland-based company Firmenich patented cubebol, a compound found in cubeb oil, as a cooling and refreshing agent.[29] The patent describes application of cubebol as a refreshing agent in various products, ranging from chewing gum to sorbets, drinks, toothpaste, and
gelatin-based confectioneries.[30]
# Notes
- ↑ Jump up to: 1.0 1.1 Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv Chapter XXV.
- ↑ Jump up to: 4.0 4.1 Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv. "...Incubus none the less persisted in appearing to her constantly, in the shape of an exceptionally handsome young man. At last, among other learned men, whose advice had been taken on the subject, was a very profound Theologian who, observing that the maiden was of a thoroughly phlegmatic temperament, surmised that that Incubus was an aqueous Demon (there are in fact, as is testified by Guazzo (Compendium Maleficarum, I. 19), igneous, aerial, phlegmatic, earthly, and subterranean demons who avoid the light of day), and so he prescribed a continual suffumigation in the room. A new vessel, made of earthenware and glass, was accordingly introduced, and filled with sweet calamus, cubeb seed, roots of both aristolochies, great and small cardamom, ginger, long-pepper, caryophylleae, cinnamon, cloves, mace, nutmegs, calamite storax, benzoin, aloes-wood and roots, one ounce of fragrant sandal, and three quarts of half brandy and water; the vessel was then set on hot ashes in order to force forth and upwards the fumigating vapour, and the cell was kept closed. As soon as the suffumigation was done, the Incubus came, but never dared enter the cell."
- ↑ Template:Harv.
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv. "Take one pound of tarmantanita, half a pound of honey of which the frost has been removed, one pound of aqua vita, very fine Indian 'and, sandal, in equal parts. Arab samg, juz bawwa, kholanjan root, kababa, reed, mastaqi, qaranfal, sanbal, of each three drachms. They must be pounded well and put into a distilling vessel made of glass, and it must be well covered, and put on a gentle fire. And the first water which will come up will be pure... (snip) And know that the first is called 'the mother of medicine'."
- ↑ Template:Harv. Richard Francis Burton edition gives a different formulae: "So he gave it to him and the broker betook himself to a hashish-seller, of whom he bought two ounces of concentrated Roumi opium and equal-parts of Chinese cubebs, cinnamon, cloves, cardamoms, ginger, white pepper and mountain skink; and, pounding them all together, boiled them in sweet olive oil; after which he added three ounces of male frankincense in fragments and a cupful of coriander-seed; and, macerating the whole, made it into an electuary with Roumi bee honey." Skink refers to a kind of lizard.
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv "Make a thykke mylke of almondys, do hit in a pot with floure of rys, safron, gynger, macys, quibibis, canel, sygure: and rynse the bottom of the disch with fat broth. Boyle the sewe byfore, and messe hit forth."
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv.
- ↑ Template:Harv
- ↑ The list of ingredients found in cigarettes Accessed February 11, 2006.
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Template:Harv
- ↑ Institute of Science in Society News, March 2000 (Accessed 27 February 2006)
- ↑ Leffingwell, John C., Ph.D (2001). "Cool without Menthol & Cooler than Menthol and Cooling Compounds as Insect Repellents". Leffingwell & Associates. Retrieved 2006-09-15..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ U.S. Patent 6,214,788 | https://www.wikidoc.org/index.php/Cubeb | |
a54f63bc7e3a7985cff6b0e0330529bd67e34849 | wikidoc | Cumin | Cumin
Cumin (Cuminum cyminum) (sometimes spelled cummin) is a flowering plant in the family Apiaceae, native from the east Mediterranean to East India.
It is a herbaceous annual plant, with a slender branched stem 20-30 cm tall. The leaves are 5-10 cm long, pinnate or bipinnate, thread-like leaflets. The flowers are small, white or pink, and borne in umbels. The fruit is a laterall fusiform or ovoid achene 4-5 mm long, containing a single seed. Cumin seeds are similar to fennel seeds, but are smaller and darker in colour.
# Cultivation and uses
Cumin seeds are used as a spice for their distinctive aroma, popular in North African, Middle Eastern, western Chinese, Indian, Cuban and Mexican cuisine.
Cumin's distinctive flavour and strong, warm aroma is due to its essential oil content. Its main constituent and important aroma compound is cuminaldehyde (4-isopropylbenzaldehyde). Important aroma compounds of toasted cumin are the substituted pyrazines, 2-ethoxy-3-isopropylpyrazine, 2-methoxy-3-sec-butylpyrazine, and 2-methoxy-3-methylpyrazine.
Today, cumin is identified with Indian and Mexican cuisine. It is used as an ingredient of curry powder. Cumin can be found in some Dutch cheeses like Leyden cheese, and in some traditional breads from France. In herbal medicine, cumin is classified as stimulant, carminative, and antimicrobial.
Cumin can be used to season many dishes, as it draws out their natural sweetnesses. It is traditionally added to curries, enchiladas, tacos, and other Middle-eastern, Indian, Cuban and Mexican-style foods. It can also be added to salsa to give it extra flavour. Cumin has also been used on meat in addition to other common seasonings. The spice is a familiar taste in Tex-Mex dishes and is extensively used in the cuisines of the Indian subcontinent. Cumin was also used heavily in ancient Roman cuisine.
Cultivation of cumin requires a long, hot summer of 3-4 months, with daytime temperatures around 30°C (86°F); it is drought tolerant, and is mostly grown in mediterranean climates. It is grown from seed sown in spring, and needs a fertile, well-drained soil.
Cumin can be boiled in tea to make "cumin cider", first made by native Mexicans and spread throughout South America.
## Description
Cumin is the dried seed of the herb Cuminum cyminum, a member of the parsley family. The cumin plant grows to 30-50 cm (1-2 ft) tall and is harvested by hand. Cumin is a key component in both chili powder and curry powder.
## Uses
The flavour of cumin plays a major role in Mexican, Thai, Vietnamese, and Indian cuisines. Cumin is a critical ingredient of chili powder, and is found in achiote blends, adobos, garam masala, curry powder, and bahaarat.
## Origins
Historically, Iran has been the principal supplier of cumin, but currently the major sources are India, Sri Lanka, Syria, Pakistan, and Turkey.
## Folklore
Superstition during the Middle Ages cited that cumin kept chickens and lovers from wandering. It was also believed that a happy life awaited the bride and groom who carried cumin seed throughout the wedding ceremony. Cumin is also said to help in treatment of the common cold, when added to hot milk and consumed.
# History
Cumin has been in use since ancient times. Seeds, excavated at the Syrian site Tell ed-Der, have been dated to the second millennium BC. They have also been reported from several New Kingdom levels of ancient Egyptian archaeological sites.
Originally cultivated in Iran and the Mediterranean region, cumin is mentioned in the Bible in both the Old Testament (Isaiah 28:27) and the New Testament (Matthew 23:23). It was also known in ancient Greece and Rome. The Greeks kept cumin at the dining table in its own container (much as pepper is frequently kept today), and this practice continues in Morocco. Cumin fell out of favour in Europe except in Spain and Malta during the Middle Ages. It was introduced to the Americas by Spanish colonists.
Since returned to favour in parts of Europe, today it is mostly grown in Iran, Uzbekistan, Tajikistan, Turkey, Morocco, Egypt, India, Syria, Mexico, and Chile.
## Etymology
The English form is derived from the Latin cuminum and Greek κύμινον. The Greek term itself seems to have been borrowed from a Semitic source; forms of this word are attested in several ancient Semitic languages, including Akkadian. The ultimate source seems to be the Sumerian word gamun .
A folk etymology connects the word with the Persian city Kerman, where, the story goes, most of ancient Persia's cumin was produced. For the Persians the expression "carrying cumin to Kerman" has the same meaning as the English language phrase "carrying coals to Newcastle". Kerman, locally called Kermun, would have became Kumun and then cumin in the European languages.
In India and Pakistan, cumin is known as jeera or jira; in Iran and Central Asia, cumin is known as zira; in northwestern mainland China, cumin is known as ziran. In Arabic, it is known as kamuwn, (الكمــــــــون).
# Confusion with other spices
Cumin is hotter to the taste, lighter in colour, and larger than caraway (Carum carvi), another umbelliferous spice that is sometimes confused with it. Many European languages do not distinquish clearly between the two. For example, in Czech caraway is called 'kmín' while cumin is called 'římský kmín' or "Roman caraway." Some older cookbooks erroneously name ground coriander as the same spice as ground cumin.
The distantly related Bunium persicum and the unrelated Nigella sativa are both sometimes called black cumin (q.v.).
# Images
- Dry, whole cumin fruit (or seed)
Dry, whole cumin fruit (or seed)
- Whole cumin seeds and ground cumin
Whole cumin seeds and ground cumin | Cumin
Cumin (Cuminum cyminum) (sometimes spelled cummin) is a flowering plant in the family Apiaceae, native from the east Mediterranean to East India.
It is a herbaceous annual plant, with a slender branched stem 20-30 cm tall. The leaves are 5-10 cm long, pinnate or bipinnate, thread-like leaflets. The flowers are small, white or pink, and borne in umbels. The fruit is a laterall fusiform or ovoid achene 4-5 mm long, containing a single seed. Cumin seeds are similar to fennel seeds, but are smaller and darker in colour.
# Cultivation and uses
Cumin seeds are used as a spice for their distinctive aroma, popular in North African, Middle Eastern, western Chinese, Indian, Cuban and Mexican cuisine.
Cumin's distinctive flavour and strong, warm aroma is due to its essential oil content. Its main constituent and important aroma compound is cuminaldehyde (4-isopropylbenzaldehyde). Important aroma compounds of toasted cumin are the substituted pyrazines, 2-ethoxy-3-isopropylpyrazine, 2-methoxy-3-sec-butylpyrazine, and 2-methoxy-3-methylpyrazine.
Today, cumin is identified with Indian and Mexican cuisine. It is used as an ingredient of curry powder. Cumin can be found in some Dutch cheeses like Leyden cheese, and in some traditional breads from France. In herbal medicine, cumin is classified as stimulant, carminative, and antimicrobial.
Cumin can be used to season many dishes, as it draws out their natural sweetnesses. It is traditionally added to curries, enchiladas, tacos, and other Middle-eastern, Indian, Cuban and Mexican-style foods. It can also be added to salsa to give it extra flavour. Cumin has also been used on meat in addition to other common seasonings. The spice is a familiar taste in Tex-Mex dishes and is extensively used in the cuisines of the Indian subcontinent. Cumin was also used heavily in ancient Roman cuisine.
Cultivation of cumin requires a long, hot summer of 3-4 months, with daytime temperatures around 30°C (86°F); it is drought tolerant, and is mostly grown in mediterranean climates. It is grown from seed sown in spring, and needs a fertile, well-drained soil.
Cumin can be boiled in tea to make "cumin cider", first made by native Mexicans and spread throughout South America.
## Description
Cumin is the dried seed of the herb Cuminum cyminum, a member of the parsley family. The cumin plant grows to 30-50 cm (1-2 ft) tall and is harvested by hand. Cumin is a key component in both chili powder and curry powder.
## Uses
The flavour of cumin plays a major role in Mexican, Thai, Vietnamese, and Indian cuisines. Cumin is a critical ingredient of chili powder, and is found in achiote blends, adobos, garam masala, curry powder, and bahaarat.
## Origins
Historically, Iran has been the principal supplier of cumin, but currently the major sources are India, Sri Lanka, Syria, Pakistan, and Turkey.
## Folklore
Superstition during the Middle Ages cited that cumin kept chickens and lovers from wandering. It was also believed that a happy life awaited the bride and groom who carried cumin seed throughout the wedding ceremony. Cumin is also said to help in treatment of the common cold, when added to hot milk and consumed.
# History
Cumin has been in use since ancient times. Seeds, excavated at the Syrian site Tell ed-Der, have been dated to the second millennium BC. They have also been reported from several New Kingdom levels of ancient Egyptian archaeological sites.[1]
Originally cultivated in Iran and the Mediterranean region, cumin is mentioned in the Bible in both the Old Testament (Isaiah 28:27) and the New Testament (Matthew 23:23). It was also known in ancient Greece and Rome. The Greeks kept cumin at the dining table in its own container (much as pepper is frequently kept today), and this practice continues in Morocco. Cumin fell out of favour in Europe except in Spain and Malta during the Middle Ages. It was introduced to the Americas by Spanish colonists.
Since returned to favour in parts of Europe, today it is mostly grown in Iran, Uzbekistan, Tajikistan, Turkey, Morocco, Egypt, India, Syria, Mexico, and Chile.
## Etymology
The English form is derived from the Latin cuminum and Greek κύμινον. The Greek term itself seems to have been borrowed from a Semitic source; forms of this word are attested in several ancient Semitic languages, including Akkadian. The ultimate source seems to be the Sumerian word gamun [1].
A folk etymology connects the word with the Persian city Kerman, where, the story goes, most of ancient Persia's cumin was produced. For the Persians the expression "carrying cumin to Kerman" has the same meaning as the English language phrase "carrying coals to Newcastle". Kerman, locally called Kermun, would have became Kumun and then cumin in the European languages.
In India and Pakistan, cumin is known as jeera or jira; in Iran and Central Asia, cumin is known as zira; in northwestern mainland China, cumin is known as ziran. In Arabic, it is known as kamuwn, (الكمــــــــون).
# Confusion with other spices
Cumin is hotter to the taste, lighter in colour, and larger than caraway (Carum carvi), another umbelliferous spice that is sometimes confused with it. Many European languages do not distinquish clearly between the two. For example, in Czech caraway is called 'kmín' while cumin is called 'římský kmín' or "Roman caraway." Some older cookbooks erroneously name ground coriander as the same spice as ground cumin. [2]
The distantly related Bunium persicum and the unrelated Nigella sativa are both sometimes called black cumin (q.v.).
Template:Nutritionalvalue
# Images
- Dry, whole cumin fruit (or seed)
Dry, whole cumin fruit (or seed)
- Whole cumin seeds and ground cumin
Whole cumin seeds and ground cumin | https://www.wikidoc.org/index.php/Cumin | |
37d030dfb90dedba9d09e3832f9f8627b635803b | wikidoc | Wound | Wound
# Overview
In medicine, a wound is a type of physical trauma where in the skin is torn, cut or punctured (an open wound), or where blunt force trauma causes a contusion (a closed wound). In pathology, it specifically refers to a sharp injury which damages the dermis of the skin.
# Classification
Before any medical or paramedical evaluation, a wound is considered as minor when:
- It is superficial (a "flesh wound");
- It is away from natural orifices;
- There is only minor bleeding;
- It was not caused by a tool or an animal.
Any other wound should be considered as severe. If there is any doubt, a wound should be considered as severe. "Severe" does not necessarily mean that it endangers life, but it must at least be seen by a physician. In the case of severe open wounds, there is a risk of blood loss (which could lead to shock), and an increased chance of infection due to bacteria entering a wound that is exposed to air. Due to the risk of infection, wounds should be kept clean, and closed if possible until professional help is available.
Depending on their severity, closed wounds can be just as dangerous as open wounds. An injury to the brain such as a contusion is an extremely dire closed wound, and requires emergency medical attention.
# Types of Wounds
- Superficial bullet wounds
- Wound, sewed with four stitches
- A laceration to the leg
- An abrasion
## Open wounds
Open wounds can be classified into a number of different types, according to the object that caused the wound. The types of open wound are:
- Incisions or incised wounds - caused by a clean, sharp-edged object such as a knife, a razor or a glass splinter. Incisions which involve only the epidermis are legally classified as cuts, rather than wounds.
- Lacerations - Irregular wounds caused by a blunt impact to soft tissue which lies over hard tissue (e.g. laceration of the skin covering the skull) or tearing of skin and other tissues such as caused by childbirth. Lacerations may show bridging, as connective tissue or blood vessels are flattened against the underlying hard surface. Commonly misused in reference to injury with sharp objects, which would not display bridging (connective tissue and blood vessels are severed).
- Abrasions (grazes) - a superficial wound in which the topmost layer of the skin (the epidermis) is scraped off. Often caused by a sliding fall onto a rough surface.
- Puncture wounds - caused by an object puncturing the skin, such as a nail or needle.
- Penetration wounds - caused by an object such as a knife entering the body.
- Gunshot wounds - caused by a bullet or similar projectile driving into or through the body. There may be two wounds, one at the site of entry and one at the site of exit.
In a medical context, all stab wounds and gunshot wounds are considered major wounds.
## Closed wounds
Closed wounds have fewer categories, but are just as dangerous as open wounds. The types of closed wounds are:
- Contusions - (more commonly known as a bruise) - caused by blunt force trauma that damages tissue under the skin.
- Hematoma - (also called a blood tumor) - caused by damage to a blood vessel that in turn causes blood to collect under the skin.
- Crushing Injuries - caused by a great or extreme amount of force applied over a long period of time.
# Healing
To heal a wound, the body undertakes a series of actions collectively known as the wound healing process.
## Infection
Bacterial infection of wound can impede the healing process and lead to life threatening complications. Scientists at Sheffield University have identified a way of using light to rapidly detect the presence of bacteria. They are developing a portable kit in which specially designed molecules emit a light signal when bound to bacteria. Current laboratory-based detection of bacteria can take hours or even days.
## Antimicrobial Regimen
- Wound infection
- 1. Mild to moderate
- Preferred regimen (1): TMP-SMX-DS double strength 1-2 tabs PO bid
- Preferred regimen (2): Clindamycin 300-450 mg PO tid
- Alternative regimen (1): Minocycline 100 mg PO bid
- Alternative regimen (2): Linezolid 600 mg PO bid
- 2. Febrile with sepsis
- Preferred regimen (1): Ticarcillin-clavulanate 3.1 gm IV q4-6h (OR Piperacillin-Tazobactam 3.375 gm q6h) AND Vancomycin 1gm IV q12h
- Preferred regimen (2): Doripenem 500 mg IV q 8hr (OR Imipenem OR Meropenem OR Ertapenem 1gm IV q24h) AND Vancomycin 1gm IV q12h
- Alternative regimen (1): Vancomycin 1 gm IV q12h (OR Daptomycin 6 mg/kg IV q24h) AND Ciprofloxacin 750 mg IV q24h (OR Levofloxacin 750 mg IV q24h)
- Alternative regimen (2): Ceftaroline 600 mg IV q12h AND Ciprofloxacin 750 mg IV q24h (OR Levofloxacin 750 mg IV q24h)
- Alternative regimen (3): Telavancin 10 mg/kg IV q24h AND Ciprofloxacin 750 mg IV q24h (OR Levofloxacin 750 mg IV q24h) | Wound
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
In medicine, a wound is a type of physical trauma where in the skin is torn, cut or punctured (an open wound), or where blunt force trauma causes a contusion (a closed wound). In pathology, it specifically refers to a sharp injury which damages the dermis of the skin.
# Classification
Before any medical or paramedical evaluation, a wound is considered as minor when:
- It is superficial (a "flesh wound");
- It is away from natural orifices;
- There is only minor bleeding;
- It was not caused by a tool or an animal.
Any other wound should be considered as severe. If there is any doubt, a wound should be considered as severe. "Severe" does not necessarily mean that it endangers life, but it must at least be seen by a physician. In the case of severe open wounds, there is a risk of blood loss (which could lead to shock), and an increased chance of infection due to bacteria entering a wound that is exposed to air. Due to the risk of infection, wounds should be kept clean, and closed if possible until professional help is available.
Depending on their severity, closed wounds can be just as dangerous as open wounds. An injury to the brain such as a contusion is an extremely dire closed wound, and requires emergency medical attention.
# Types of Wounds
- Superficial bullet wounds
- Wound, sewed with four stitches
- A laceration to the leg
- An abrasion
## Open wounds
Open wounds can be classified into a number of different types, according to the object that caused the wound. The types of open wound are: [1] [2]
- Incisions or incised wounds - caused by a clean, sharp-edged object such as a knife, a razor or a glass splinter. Incisions which involve only the epidermis are legally classified as cuts, rather than wounds.
- Lacerations - Irregular wounds caused by a blunt impact to soft tissue which lies over hard tissue (e.g. laceration of the skin covering the skull) or tearing of skin and other tissues such as caused by childbirth. Lacerations may show bridging, as connective tissue or blood vessels are flattened against the underlying hard surface. Commonly misused in reference to injury with sharp objects, which would not display bridging (connective tissue and blood vessels are severed).
- Abrasions (grazes) - a superficial wound in which the topmost layer of the skin (the epidermis) is scraped off. Often caused by a sliding fall onto a rough surface.
- Puncture wounds - caused by an object puncturing the skin, such as a nail or needle.
- Penetration wounds - caused by an object such as a knife entering the body.
- Gunshot wounds - caused by a bullet or similar projectile driving into or through the body. There may be two wounds, one at the site of entry and one at the site of exit.
In a medical context, all stab wounds and gunshot wounds are considered major wounds.
## Closed wounds
Closed wounds have fewer categories, but are just as dangerous as open wounds. The types of closed wounds are:
- Contusions - (more commonly known as a bruise) - caused by blunt force trauma that damages tissue under the skin.
- Hematoma - (also called a blood tumor) - caused by damage to a blood vessel that in turn causes blood to collect under the skin.
- Crushing Injuries - caused by a great or extreme amount of force applied over a long period of time.
# Healing
To heal a wound, the body undertakes a series of actions collectively known as the wound healing process.
## Infection
Bacterial infection of wound can impede the healing process and lead to life threatening complications. Scientists at Sheffield University have identified a way of using light to rapidly detect the presence of bacteria. They are developing a portable kit in which specially designed molecules emit a light signal when bound to bacteria. Current laboratory-based detection of bacteria can take hours or even days.[3]
## Antimicrobial Regimen
- Wound infection[4]
- 1. Mild to moderate
- Preferred regimen (1): TMP-SMX-DS double strength 1-2 tabs PO bid
- Preferred regimen (2): Clindamycin 300-450 mg PO tid
- Alternative regimen (1): Minocycline 100 mg PO bid
- Alternative regimen (2): Linezolid 600 mg PO bid
- 2. Febrile with sepsis
- Preferred regimen (1): Ticarcillin-clavulanate 3.1 gm IV q4-6h (OR Piperacillin-Tazobactam 3.375 gm q6h) AND Vancomycin 1gm IV q12h
- Preferred regimen (2): Doripenem 500 mg IV q 8hr (OR Imipenem OR Meropenem OR Ertapenem 1gm IV q24h) AND Vancomycin 1gm IV q12h
- Alternative regimen (1): Vancomycin 1 gm IV q12h (OR Daptomycin 6 mg/kg IV q24h) AND Ciprofloxacin 750 mg IV q24h (OR Levofloxacin 750 mg IV q24h)
- Alternative regimen (2): Ceftaroline 600 mg IV q12h AND Ciprofloxacin 750 mg IV q24h (OR Levofloxacin 750 mg IV q24h)
- Alternative regimen (3): Telavancin 10 mg/kg IV q24h AND Ciprofloxacin 750 mg IV q24h (OR Levofloxacin 750 mg IV q24h) | https://www.wikidoc.org/index.php/Cut | |
fbeb42476e6521f404c1ed7af1f36e261af7984f | wikidoc | DAAM1 | DAAM1
Disheveled-associated activator of morphogenesis 1 is a protein that in humans is encoded by the DAAM1 gene. Evidence of alternative splicing has been observed for this gene but the full-length nature of these variants has not been determined.
# Function
Cell motility, adhesion, and cytokinesis, and other functions of the cell cortex are mediated by the reorganization of the actin cytoskeleton and recent evidence suggests a role for formin homology (FH) proteins in these processes. The protein encoded by this gene contains FH domains and belongs to a novel FH protein subfamily implicated in cell polarity. Wnt/Fz signaling activates the small GTPase Rho, a key regulator of cytoskeleton architecture, to control cell polarity and movement during development. Activation requires Dvl-Rho complex formation, an assembly mediated by this gene product, which is thought to function as a scaffolding protein.
# Clinical significance
The deletion of a single copy of this gene has been associated with congenital heart defects. | DAAM1
Disheveled-associated activator of morphogenesis 1 is a protein that in humans is encoded by the DAAM1 gene.[1][2][3] Evidence of alternative splicing has been observed for this gene but the full-length nature of these variants has not been determined.
# Function
Cell motility, adhesion, and cytokinesis, and other functions of the cell cortex are mediated by the reorganization of the actin cytoskeleton and recent evidence suggests a role for formin homology (FH) proteins in these processes. The protein encoded by this gene contains FH domains and belongs to a novel FH protein subfamily implicated in cell polarity. Wnt/Fz signaling activates the small GTPase Rho, a key regulator of cytoskeleton architecture, to control cell polarity and movement during development. Activation requires Dvl-Rho complex formation, an assembly mediated by this gene product, which is thought to function as a scaffolding protein.[3]
# Clinical significance
The deletion of a single copy of this gene has been associated with congenital heart defects.[4] | https://www.wikidoc.org/index.php/DAAM1 | |
ad1dc2f8e5325462296d1d0e3d1c99b8a4b43fda | wikidoc | DACH1 | DACH1
Dachshund homolog 1, also known as DACH1, is a protein which in humans is encoded by the DACH1 gene. DACH1 has been shown to interact with Ubc9, Smad4, and NCoR.
# Structure
Gene structure . This protein coding gene has 760 amino acid protein, and an observed molecular weight of 52 kDa. Dachshund Family transcription factor 1 is encoded by DACH gene, who spans 400kDa and is encoded by 12 exons. This gene is located, in humans, in chromosome 13 (13q22). It encodes a chromatin-associated protein that associates with other DNA-binding transcription factors to regulate gene expression, mRNA translation, coactivator binding, and cell fate determination during development.
Multiple transcript variants encoding different isoforms have been found for this gene. Four alternatively spliced transcripts encoding different isoforms have been described for this gene.DACH1 mRNA was detected in multiple human tissues, including kidney and heart. Dach1 is located in nuclear and cytoplasmic pools and is considered a cell fate determination factor. Dachshund domain 1 (DD1, also known as Box-N) has a predicted helix–turn–helix family structure. The X-ray crystal structure of the human DACH1 Box-N illustrates that the DACH1 protein contains a domain that is conserved with the pro-oncogenes ski/sno oncogenes, which form an α/β structure similar to that found in the winged helix/forkhead subgroup of DNA binding proteins. This protein is widely expressed including bone marrow, brain, colon, eye, heart, kidney, leucocyte, liver, lung, pancreas, pineal gland, placenta, prostate, retina, skeletal muscle, small intestine, stromal/preosteoblasts and the spleen.
Protein modification. DACH1 is modified by phosphorylation, acetylation, and SUMOYlation. Acetylation of Dach1 determine binding to the p53 tumor suppressor, and thereby governs a subset of p53 functions involved in stem cell restraint and the inhibition of cellular proliferation. SUMOYlation of DACH governs HDAC binding. Phosphorylation of Dach1 contributes to YB-1 binding, subcellular distribution and the induction of EMT via translation of EMT regulatory genes.
# Function
Organismal development. Dach1 is similar to the D. melanogaster dac gene, which encodes a nuclear factor essential for determining cell fates in the eye, leg, and nervous system of the fly. Dach is a member of the Ski gene family and is involved in eye and organismal development. Dach1 deletion mice exhibit early postnatal death, although no developmental defects were detected in any organ system examined, including kidneys. DACH1 plays an important role on this precursor of cell proliferation in retinal and pituitary.
Restrain of Cancer cell growth. DACH1 protein is able to prevent the proliferation of cancerous cells (lung, breast, prostate) and functions as a repressor of estrogen receptor activity in breast cancer cells.
Transcription. DACH1 conducts transcriptional function through interacting with transcription factors including c-Jun, estrogen receptor alpha, the androgen receptor, and the basal transcription apparatus through binding to the co-integrator protein CA150. Curiously, DACH1 selectively bound to the delta domain of c-Jun, which was known to interact with an endogenous cellular repressor. DACH1 binds directly with a Forkhead-like DNA sequence to restrain oncogenic signals from a subset of FKHR proteins. Dach1 governs mRNA translation of an EMT signature and governs Snail1 transcription.
Cell migration. DACH1 inhibits migration of vascular endothelial cells, fibroblasts and prostate epithelial cells wherein DACH1 maintains persistence of migratory directionality via heterotypic signals.
# Disease relevance
## Cancer
DACH1 has been implicated in suppression of tumor growth, and has been proposed as a putatative tumor suppressor although no formal in vivo evidence has been published to date. Supporting evidence includes the finding that Dach1 expression is reduced in human malignancies including breast, lung, prostate and brain tumors. DACH1 inhibits Cyclin D1 expression and thereby reduces breast cancer cell line cell growth. Normal cells and some breast cancer cells have receptors that bind estrogen and progesterone. These two hormones often promote the growth of breast cancer cells. Approximately 70% of breast cancers are ERa+, DACH1 expression decreases when the cancer is more invasive and the level of estrogen is high.
## Nephropathy
Renal hypodysplasia (RHD) is characterized by small and/or disorganized kidneys following abnormal organogenesis. Double homozygous missense mutations of DACH1 and BMP4 occurred in a patient with bilateral cystic dysplasia. Functional analysis of the DACH1 mutation (p.R684C). demonstrated enhanced suppression of the TGF-β pathway. Dach1 is highly expressed in the adult podocyte, with transcripts showing an approximate tenfold enrichment compared to total kidney cortex. It is also more widely expressed in the earlier developing kidney, but again including definite podocyte expression.
## Diabetes
Hepatocyte the abundance of DACH1 Is Increased in the hepatocytes of Obese patients. Dach1 promotes hepatic insulin resistance via Nuclear Exclusion of HDAC4. | DACH1
Dachshund homolog 1, also known as DACH1, is a protein which in humans is encoded by the DACH1 gene.[1][2][3] DACH1 has been shown to interact with Ubc9,[4] Smad4,[5] and NCoR.[5][6]
# Structure
Gene structure . This protein coding gene has 760 amino acid protein, and an observed molecular weight of 52 kDa. Dachshund Family transcription factor 1 is encoded by DACH gene, who spans 400kDa and is encoded by 12 exons. This gene is located, in humans, in chromosome 13 (13q22). It encodes a chromatin-associated protein that associates with other DNA-binding transcription factors to regulate gene expression,[5][7][8][6][9][10] mRNA translation,[11] coactivator binding,[12] and cell fate determination during development.[13][14]
Multiple transcript variants encoding different isoforms have been found for this gene. Four alternatively spliced transcripts encoding different isoforms have been described for this gene.DACH1 mRNA was detected in multiple human tissues, including kidney and heart. Dach1 is located in nuclear and cytoplasmic pools and is considered a cell fate determination factor.[13][14] Dachshund domain 1 (DD1, also known as Box-N) has a predicted helix–turn–helix family structure. The X-ray crystal structure of the human DACH1 Box-N illustrates that the DACH1 protein contains a domain that is conserved with the pro-oncogenes ski/sno oncogenes, which form an α/β structure similar to that found in the winged helix/forkhead subgroup of DNA binding proteins.[10] This protein is widely expressed including bone marrow, brain, colon, eye, heart, kidney, leucocyte, liver, lung, pancreas, pineal gland, placenta, prostate, retina, skeletal muscle, small intestine, stromal/preosteoblasts and the spleen.[6][17][16]
Protein modification. DACH1 is modified by phosphorylation,[11] acetylation,[18] and SUMOYlation.[19] Acetylation of Dach1 determine binding to the p53 tumor suppressor, and thereby governs a subset of p53 functions involved in stem cell restraint and the inhibition of cellular proliferation.[18] SUMOYlation of DACH governs HDAC binding.[20] Phosphorylation of Dach1 contributes to YB-1 binding, subcellular distribution and the induction of EMT via translation of EMT regulatory genes.[11]
# Function
Organismal development. Dach1 is similar to the D. melanogaster dac gene, which encodes a nuclear factor essential for determining cell fates in the eye, leg, and nervous system of the fly.[2] Dach is a member of the Ski gene family and is involved in eye and organismal development.[14][22] Dach1 deletion mice exhibit early postnatal death, although no developmental defects were detected in any organ system examined, including kidneys. DACH1 plays an important role on this precursor of cell proliferation in retinal and pituitary.[3][13][23]
Restrain of Cancer cell growth. DACH1 protein is able to prevent the proliferation of cancerous cells (lung, breast, prostate[7][8][6][9][10]) and functions as a repressor of estrogen receptor activity in breast cancer cells.[7][9]
Transcription. DACH1 conducts transcriptional function through interacting with transcription factors including c-Jun,[7] estrogen receptor alpha,[9] the androgen receptor,[6] and the basal transcription apparatus through binding to the co-integrator protein CA150. Curiously, DACH1 selectively bound to the delta domain of c-Jun, which was known to interact with an endogenous cellular repressor. DACH1 binds directly with a Forkhead-like DNA sequence to restrain oncogenic signals from a subset of FKHR proteins.[10] Dach1 governs mRNA translation of an EMT signature[11] and governs Snail1 transcription.[11]
Cell migration. DACH1 inhibits migration of vascular endothelial cells,[20][24] fibroblasts[25] and prostate epithelial cells[24] wherein DACH1 maintains persistence of migratory directionality via heterotypic signals.
# Disease relevance
## Cancer
DACH1 has been implicated in suppression of tumor growth, and has been proposed as a putatative tumor suppressor although no formal in vivo evidence has been published to date. Supporting evidence includes the finding that Dach1 expression is reduced in human malignancies including breast,[23][11] lung,[8] prostate[6] and brain tumors.[26] DACH1 inhibits Cyclin D1 expression and thereby reduces breast cancer cell line cell growth.[25] Normal cells and some breast cancer cells have receptors that bind estrogen and progesterone. These two hormones often promote the growth of breast cancer cells. Approximately 70% of breast cancers are ERa+, DACH1 expression decreases when the cancer is more invasive and the level of estrogen is high.[9]
## Nephropathy
Renal hypodysplasia (RHD) is characterized by small and/or disorganized kidneys following abnormal organogenesis. Double homozygous missense mutations of DACH1 and BMP4 occurred in a patient with bilateral cystic dysplasia.[27] Functional analysis of the DACH1 mutation (p.R684C). demonstrated enhanced suppression of the TGF-β pathway. Dach1 is highly expressed in the adult podocyte, with transcripts showing an approximate tenfold enrichment compared to total kidney cortex. It is also more widely expressed in the earlier developing kidney, but again including definite podocyte expression.
## Diabetes
Hepatocyte the abundance of DACH1 Is Increased in the hepatocytes of Obese patients. Dach1 promotes hepatic insulin resistance via Nuclear Exclusion of HDAC4.[20] | https://www.wikidoc.org/index.php/DACH1 | |
ef11fe037aae7ca2cd87908c7b353bb6a3df10e9 | wikidoc | DAPK1 | DAPK1
Death-associated protein kinase 1 is an enzyme that in humans is encoded by the DAPK1 gene.
# Function
Death-associated protein kinase 1 is a positive mediator of gamma-interferon induced programmed cell death. DAPK1 encodes a structurally unique 160-kD calmodulin dependent serine-threonine kinase that carries 8 ankyrin repeats and 2 putative P-loop consensus sites. It is a tumor suppressor candidate.
In melanocytic cells DAPK1 gene expression may be regulated by MITF.
# As a drug target
Depletion of DAPK1 results in inhibition of tumor cell count and volume growth in cellular and animal models of triple receptor-negative breast cancer, from individuals with p53-mutant cancers. This has not been demonstrated in actual patients. | DAPK1
Death-associated protein kinase 1 is an enzyme that in humans is encoded by the DAPK1 gene.[1]
# Function
Death-associated protein kinase 1 is a positive mediator of gamma-interferon induced programmed cell death. DAPK1 encodes a structurally unique 160-kD calmodulin dependent serine-threonine kinase that carries 8 ankyrin repeats and 2 putative P-loop consensus sites. It is a tumor suppressor candidate.[2]
In melanocytic cells DAPK1 gene expression may be regulated by MITF.[3]
# As a drug target
Depletion of DAPK1 results in inhibition of tumor cell count and volume growth in cellular and animal models of triple receptor-negative breast cancer, from individuals with p53-mutant cancers.[4] This has not been demonstrated in actual patients. | https://www.wikidoc.org/index.php/DAPK1 | |
c3a7b61d248eee28c27c43b2c81d763dce6332ba | wikidoc | DAPK3 | DAPK3
Death-associated protein kinase 3 is an enzyme that in humans is encoded by the DAPK3 gene.
# Function
Death-associated protein kinase 3 (DAPK3) induces morphological changes in apoptosis when overexpressed in mammalian cells. These results suggest that DAPK3 may play a role in the induction of apoptosis.
Unlike most other mammalian genes, murine (rat and mouse) DAPK3 has undergone accelerated evolution and diverged from the tightly conserved consensus that is maintained from fish to human.
# Interactions
DAPK3 has been shown to interact with PAWR and Death associated protein 6. | DAPK3
Death-associated protein kinase 3 is an enzyme that in humans is encoded by the DAPK3 gene.[1][2]
# Function
Death-associated protein kinase 3 (DAPK3) induces morphological changes in apoptosis when overexpressed in mammalian cells. These results suggest that DAPK3 may play a role in the induction of apoptosis.[2]
Unlike most other mammalian genes, murine (rat and mouse) DAPK3 has undergone accelerated evolution and diverged from the tightly conserved consensus that is maintained from fish to human.[3]
# Interactions
DAPK3 has been shown to interact with PAWR[4] and Death associated protein 6.[4] | https://www.wikidoc.org/index.php/DAPK3 | |
47de2315d286e4d83aa85ebbca618d61f6334f93 | wikidoc | DCDC2 | DCDC2
Doublecortin domain-containing protein 2 is a protein that in humans is encoded by the DCDC2 gene.
# Function
This gene encodes a protein with two doublecortin peptide domains. This domain has been demonstrated to bind tubulin and enhance microtubule polymerization.
# Clinical significance
Mutations in this gene have been associated with reading disability (RD), also referred to as developmental dyslexia. But this is controverse since a recent study proposed that there is a "low likelihood of a direct deletion effect on reading skills."
Changes in the DCDC2 gene are frequently found among dyslexics. Altered alleles often occur among children with reading and writing difficulties. The gene appears to have a strong linkage with the processing of speech information when writing. | DCDC2
Doublecortin domain-containing protein 2 is a protein that in humans is encoded by the DCDC2 gene.[1][2][3]
# Function
This gene encodes a protein with two doublecortin peptide domains. This domain has been demonstrated to bind tubulin and enhance microtubule polymerization.[3]
# Clinical significance
Mutations in this gene have been associated with reading disability (RD), also referred to as developmental dyslexia.[3][4] But this is controverse since a recent study proposed that there is a "low likelihood of a direct deletion effect on reading skills." [5]
Changes in the DCDC2 gene are frequently found among dyslexics. Altered alleles often occur among children with reading and writing difficulties. The gene appears to have a strong linkage with the processing of speech information when writing.[6][7][8] | https://www.wikidoc.org/index.php/DCDC2 | |
ba0f0f517daf1067fae34a6aa4e0c7d8331fdec2 | wikidoc | DCHS1 | DCHS1
Protein dachsous homolog 1, also known as protocadherin-16 (PCDH16) or cadherin-19 (CDH19) or cadherin-25 (CDH25) or fibroblast cadherin-1 (FIB1), is a protein that in humans is encoded by the DCHS1 gene.
# Function
This gene is a member of the cadherin superfamily whose members encode calcium-dependent cell-cell adhesion molecules. The encoded protein has a signal peptide, 27 cadherin repeat domains and a unique cytoplasmic region. This particular cadherin family member is expressed in fibroblasts but not in melanocytes or keratinocytes. The cell-cell adhesion of fibroblasts is thought to be necessary for wound healing.
# Clinical significance
Mutations in this gene have been shown to cause mitral valve prolapse | DCHS1
Protein dachsous homolog 1, also known as protocadherin-16 (PCDH16) or cadherin-19 (CDH19) or cadherin-25 (CDH25) or fibroblast cadherin-1 (FIB1), is a protein that in humans is encoded by the DCHS1 gene.[1][2]
# Function
This gene is a member of the cadherin superfamily whose members encode calcium-dependent cell-cell adhesion molecules. The encoded protein has a signal peptide, 27 cadherin repeat domains and a unique cytoplasmic region. This particular cadherin family member is expressed in fibroblasts but not in melanocytes or keratinocytes. The cell-cell adhesion of fibroblasts is thought to be necessary for wound healing.[1]
# Clinical significance
Mutations in this gene have been shown to cause mitral valve prolapse[3] | https://www.wikidoc.org/index.php/DCHS1 | |
ba59c83c04fdfe1b5860c203ec9189f239a497d6 | wikidoc | DCP1A | DCP1A
mRNA-decapping enzyme 1A is a protein that in humans is encoded by the DCP1A gene.
Decapping is a key step in general and regulated mRNA decay. The protein encoded by this gene is a decapping enzyme. This protein and another decapping enzyme form a decapping complex, which interacts with the nonsense-mediated decay factor hUpf1 and may be recruited to mRNAs containing premature termination codons. This protein also participates in the TGF-beta signaling pathway.
# Interactions
DCP1A has been shown to interact with DCP2 and UPF1. It has also been shown to interact with GW182, a P-body marker. | DCP1A
mRNA-decapping enzyme 1A is a protein that in humans is encoded by the DCP1A gene.[1]
Decapping is a key step in general and regulated mRNA decay. The protein encoded by this gene is a decapping enzyme. This protein and another decapping enzyme form a decapping complex, which interacts with the nonsense-mediated decay factor hUpf1 and may be recruited to mRNAs containing premature termination codons. This protein also participates in the TGF-beta signaling pathway.[1]
# Interactions
DCP1A has been shown to interact with DCP2[2] and UPF1.[2] It has also been shown to interact with GW182, a P-body marker.[3] | https://www.wikidoc.org/index.php/DCP1A | |
9d25b36dd240e5272369b799f67cfb87bb4e4c37 | wikidoc | DCTN1 | DCTN1
Dynactin subunit 1 is a protein that in humans is encoded by the DCTN1 gene.
# Function
This gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 23 subunits (11 individual proteins ranging in size from 22 to 150 kD). Dynactin binds to cytoplasmic dynein, dynein cargo adaptors, and microtubules. It is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis.
This subunit is commonly referred to p150-glued. It is present in two copies per dynactin complex and forms an ~75nm long flexible arm that extends from the main body of dynactin. The p150-glued arm contains binding sites for microtubules, the microtubule plus tip binding protein EB1, and the N-terminus of the dynein intermediate chain.
Alternative splicing of this gene results in at least 2 functionally distinct isoforms: a ubiquitously expressed one and a brain-specific one. Based on its cytogenetic location, this gene is considered as a candidate gene for limb-girdle muscular dystrophy.
# Interactions
DCTN1 has been shown to interact with:
- BBS4,
- Dystonin,
- Grb2, and
- RAB6A. | DCTN1
Dynactin subunit 1 is a protein that in humans is encoded by the DCTN1 gene.[1]
# Function
This gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 23 subunits (11 individual proteins ranging in size from 22 to 150 kD)[2]. Dynactin binds to cytoplasmic dynein, dynein cargo adaptors, and microtubules[3]. It is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis.
This subunit is commonly referred to p150-glued[1]. It is present in two copies per dynactin complex and forms an ~75nm long flexible arm that extends from the main body of dynactin[2]. The p150-glued arm contains binding sites for microtubules[4], the microtubule plus tip binding protein EB1[5], and the N-terminus of the dynein intermediate chain[6][7].
Alternative splicing of this gene results in at least 2 functionally distinct isoforms: a ubiquitously expressed one and a brain-specific one. Based on its cytogenetic location, this gene is considered as a candidate gene for limb-girdle muscular dystrophy.[8]
# Interactions
DCTN1 has been shown to interact with:
- BBS4,[9]
- Dystonin,[10]
- Grb2,[11] and
- RAB6A.[12] | https://www.wikidoc.org/index.php/DCTN1 | |
0c38a902095cf1b665a997300fe9f6d5d2be1fbf | wikidoc | DCTN5 | DCTN5
Dynactin 5 (p25) is a protein that in humans is encoded by the DCTN5 gene.
This gene encodes a subunit of dynactin, a component of the cytoplasmic dynein motor machinery involved in minus-end-directed transport. The encoded protein is a component of the pointed-end subcomplex and is thought to bind membranous cargo. A pseudogene of this gene is located on the long arm of chromosome 1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.
# Model organisms
Model organisms have been used in the study of DCTN5 function. A conditional knockout mouse line, called Dctn5tm2a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and three significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and abnormal lens morphology (including cataracts) was observed in female animals. | DCTN5
Dynactin 5 (p25) is a protein that in humans is encoded by the DCTN5 gene.[1]
This gene encodes a subunit of dynactin, a component of the cytoplasmic dynein motor machinery involved in minus-end-directed transport. The encoded protein is a component of the pointed-end subcomplex and is thought to bind membranous cargo. A pseudogene of this gene is located on the long arm of chromosome 1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.[1]
# Model organisms
Model organisms have been used in the study of DCTN5 function. A conditional knockout mouse line, called Dctn5tm2a(KOMP)Wtsi[7][8] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[9][10][11]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty five tests were carried out on mutant mice and three significant abnormalities were observed.[5] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and abnormal lens morphology (including cataracts) was observed in female animals.[5] | https://www.wikidoc.org/index.php/DCTN5 | |
80d8db0eeda9ea99da097d3cbd84e33786373fef | wikidoc | DDIT4 | DDIT4
DNA-damage-inducible transcript 4 (DDIT4) protein also known as protein regulated in development and DNA damage response 1 (REDD1) is a protein that in humans is encoded by the DDIT4 gene.
# Function
DDIT4 acts as a negative regulator of mTOR, a serine/threonine kinase that regulates a variety of cellular functions such as growth, proliferation and autophagy. In particular, upregulation of HIF-1 in response to hypoxia upregulates DDIT4, leading to activation of Tsc1/2 via 14–3–3 shuttling and subsequent downregulation of mTOR via Rheb. In addition to hypoxia, DDIT4 expression has also been shown to be activated by DNA damage and energy stress.
# Clinical significance
Clinical interest in DDIT4 is based primarily on its effect on mTOR, which has been associated with aging and linked with diseases such as tuberous sclerosis, lymphangioleiomyomatosis, diabetes, and cancer. In particular, the overactivation of mTOR in many cancer types has led to the development of mTOR inhibitors for cancer treatment. DDIT4 has begun to receive attention in this regard via the diabetes drug Metformin which has been shown to reduce cancer risk and increase DDIT4 expression. | DDIT4
DNA-damage-inducible transcript 4 (DDIT4) protein also known as protein regulated in development and DNA damage response 1 (REDD1) is a protein that in humans is encoded by the DDIT4 gene.[1][2]
# Function
DDIT4 acts as a negative regulator of mTOR,[3] a serine/threonine kinase that regulates a variety of cellular functions such as growth, proliferation and autophagy.[4] In particular, upregulation of HIF-1 in response to hypoxia upregulates DDIT4,[1] leading to activation of Tsc1/2 via 14–3–3 shuttling [5] and subsequent downregulation of mTOR via Rheb.[6] In addition to hypoxia, DDIT4 expression has also been shown to be activated by DNA damage[7] and energy stress.[8]
# Clinical significance
Clinical interest in DDIT4 is based primarily on its effect on mTOR, which has been associated with aging[9] and linked with diseases such as tuberous sclerosis, lymphangioleiomyomatosis,[10] diabetes,[9] and cancer. In particular, the overactivation of mTOR in many cancer types[4] has led to the development of mTOR inhibitors for cancer treatment. DDIT4 has begun to receive attention in this regard via the diabetes drug Metformin which has been shown to reduce cancer risk and increase DDIT4 expression.[11] | https://www.wikidoc.org/index.php/DDIT4 | |
b56be4b6013573b1c7f513dfab0b95bb9fb7d317 | wikidoc | DDX11 | DDX11
Probable ATP-dependent RNA helicase DDX11 is an enzyme that in humans is encoded by the DDX11 gene.
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly.
Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is an enzyme that possesses both ATPase and DNA helicase activities. This gene is a homolog of the yeast CHL1 gene, and may function to maintain chromosome transmission fidelity and genome stability. Alternative splicing results in multiple transcript variants encoding distinct isoforms. | DDX11
Probable ATP-dependent RNA helicase DDX11 is an enzyme that in humans is encoded by the DDX11 gene.[1]
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly.
Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is an enzyme that possesses both ATPase and DNA helicase activities. This gene is a homolog of the yeast CHL1 gene, and may function to maintain chromosome transmission fidelity and genome stability. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[1] | https://www.wikidoc.org/index.php/DDX11 | |
63ba0657fa403f096cdc0f1611d570310df658c9 | wikidoc | DDX20 | DDX20
Probable ATP-dependent RNA helicase DDX20, also known as DEAD-box helicase 20 and gem-associated protein 3 (GEMIN3), is an enzyme that in humans is encoded by the DDX20 gene.
# Function
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which has an ATPase activity and is a component of the survival of motor neuron (SMN) complex. This DEAD box protein is one of the gem-associated proteins (GEMIN3) that interacts directly with SMN.
SMN is the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs.
# Biological Implication
Previous research has revealed that DDX20 may act as a tumor suppressor in hepatocellular carcinoma and as a tumor promoter in breast cancer. DDX20 deficiency enhances NF-κB activity by impairing the NF-κB-suppressive action of microRNAs, and suggest that dysregulation of the microRNA machinery components may also be involved in pathogenesis in various human diseases. Such as miRNA-140 which acts as a liver tumor suppressor, and due to a deficiency of DDX20, miRNA-140 function gets impair, this subsequent functional impairment of miRNAs could lead to hepatocarcinogenesis.Similarly, DDX20 may promote the progression of Prostate cancer (PCa) through the NF-κB pathway. In a clinical based study it has been observed that positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. It makes DP103 has potential as a therapeutic target for breast cancer treatment.
# Interactions
DDX20 has been shown to interact with:
- EIF2C2,
- GEMIN4,
- GEMIN5,
- LSM2,
- SMN1,
- SNRPB,
- SNRPD3 and
- SNRPG,
- SNRPD1,
- SNRPD2,
- SNRPE,
- SNRPF, and
- SIP1. | DDX20
Probable ATP-dependent RNA helicase DDX20, also known as DEAD-box helicase 20 and gem-associated protein 3 (GEMIN3), is an enzyme that in humans is encoded by the DDX20 gene.[1][2]
# Function
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which has an ATPase activity and is a component of the survival of motor neuron (SMN) complex.[2] This DEAD box protein is one of the gem-associated proteins (GEMIN3) that interacts directly with SMN.[3]
SMN is the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs.[2]
# Biological Implication
Previous research has revealed that DDX20 may act as a tumor suppressor in hepatocellular carcinoma and as a tumor promoter in breast cancer. DDX20 deficiency enhances NF-κB activity by impairing the NF-κB-suppressive action of microRNAs, and suggest that dysregulation of the microRNA machinery components may also be involved in pathogenesis in various human diseases.[4] Such as miRNA-140 which acts as a liver tumor suppressor, and due to a deficiency of DDX20, miRNA-140 function gets impair, this subsequent functional impairment of miRNAs could lead to hepatocarcinogenesis.Similarly,[5] DDX20 may promote the progression of Prostate cancer (PCa) through the NF-κB pathway.[6] In a clinical based study it has been observed that positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. It makes DP103 has potential as a therapeutic target for breast cancer treatment.[7]
# Interactions
DDX20 has been shown to interact with:
- EIF2C2,[8][9]
- GEMIN4,[8][10][11]
- GEMIN5,[8][12]
- LSM2,[13]
- SMN1,[8][10][13][14]
- SNRPB,[13]
- SNRPD3[13] and
- SNRPG,[13]
- SNRPD1,[13]
- SNRPD2,[13]
- SNRPE,[13]
- SNRPF,[13] and
- SIP1.[8][13] | https://www.wikidoc.org/index.php/DDX20 | |
7ce7d515562f69fc9f7b649d4eac95c3f2049e70 | wikidoc | DDX27 | DDX27
DEAD (Asp-Glu-Ala-Asp) box polypeptide 27, also known as DDX27, is a human gene.
The protein encoded by this gene belongs to the family of DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), and are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, the function of which has not been determined.
# Model organisms
Model organisms have been used in the study of DDX27 function. A conditional knockout mouse line, called Ddx27tm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program, a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty seven tests were carried out and two phenotypes were reported. No homozygous mutant embryos were identified during gestation, and in a separate study only 1% survived until weaning (significantly less than the Mendelian ratio). The remaining tests were carried out on heterozygous mutant adult mice; no significant abnormalities were observed in these animals. | DDX27
DEAD (Asp-Glu-Ala-Asp) box polypeptide 27, also known as DDX27, is a human gene.[1]
The protein encoded by this gene belongs to the family of DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), and are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, the function of which has not been determined.[1]
# Model organisms
Model organisms have been used in the study of DDX27 function. A conditional knockout mouse line, called Ddx27tm1a(KOMP)Wtsi[6][7] was generated as part of the International Knockout Mouse Consortium program, a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[8][9][10]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[4][11] Twenty seven tests were carried out and two phenotypes were reported. No homozygous mutant embryos were identified during gestation, and in a separate study only 1% survived until weaning (significantly less than the Mendelian ratio). The remaining tests were carried out on heterozygous mutant adult mice; no significant abnormalities were observed in these animals.[4] | https://www.wikidoc.org/index.php/DDX27 | |
90575a77749a69a96d38b4f4e94ca1bdc74463c4 | wikidoc | DDX3X | DDX3X
ATP-dependent RNA helicase DDX3X is an enzyme that in humans is encoded by the DDX3X gene.
# Function
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which interacts specifically with hepatitis C virus core protein resulting a change in intracellular location. This gene has a homolog located in the nonrecombining region of the Y chromosome. The protein sequence is 91% identical between this gene and the Y-linked homolog.
# Role in cancer
DDX3X is involved in many different types of cancer. For example, it is abnormally expressed in breast epithelial cancer cells in which its expression is activated by HIF1A during hypoxia. Increased expression of DDX3X by HIF1A in hypoxia is initiated by the direct binding of HIF1A to the HIF1A response element, as verified with chromatin immunoprecipitation and luciferase reporter assay. Since the expression of DDX3X is affected by the activity of HIF1A, the co-localization of these proteins has also been demonstrated in MDA-MB-231 xenograft tumor samples.
In HeLa cells DDX3X is reported to control cell cycle progression through Cyclin E1. More specifically, DDX3X was shown to directly bind to the 5´ UTR of Cyclin E1 and thereby facilitating the translation of the protein. Increased protein levels of Cyclin E1 was demonstrated to mediate the transition of S phase entry.
# Clinical significance
Mutations of the DDX3X gene are also associated with medulloblastoma. | DDX3X
ATP-dependent RNA helicase DDX3X is an enzyme that in humans is encoded by the DDX3X gene.[1][2][3]
# Function
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which interacts specifically with hepatitis C virus core protein resulting a change in intracellular location. This gene has a homolog located in the nonrecombining region of the Y chromosome. The protein sequence is 91% identical between this gene and the Y-linked homolog.[3]
# Role in cancer
DDX3X is involved in many different types of cancer. For example, it is abnormally expressed in breast epithelial cancer cells in which its expression is activated by HIF1A during hypoxia.[4] Increased expression of DDX3X by HIF1A in hypoxia is initiated by the direct binding of HIF1A to the HIF1A response element,[4] as verified with chromatin immunoprecipitation and luciferase reporter assay. Since the expression of DDX3X is affected by the activity of HIF1A, the co-localization of these proteins has also been demonstrated in MDA-MB-231 xenograft tumor samples.[4]
In HeLa cells DDX3X is reported to control cell cycle progression through Cyclin E1.[5] More specifically, DDX3X was shown to directly bind to the 5´ UTR of Cyclin E1 and thereby facilitating the translation of the protein. Increased protein levels of Cyclin E1 was demonstrated to mediate the transition of S phase entry.[5]
# Clinical significance
Mutations of the DDX3X gene are also associated with medulloblastoma.[6][7][8] | https://www.wikidoc.org/index.php/DDX3X | |
922587c7d3a001d422629c2dc076f0386feab003 | wikidoc | DDX42 | DDX42
ATP-dependent RNA helicase DDX42 is an enzyme that in humans is encoded by the DDX42 gene.
# Function
This gene encodes a member of the Asp-Glu-Ala-Asp (DEAD) box protein family. Members of this protein family are putative RNA helicases, and are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. Two transcript variants encoding the same protein have been identified for this gene.
# Interactions
DDX42 has been shown to interact with SF3B1.
# Model organisms
Model organisms have been used in the study of DDX42 function. A conditional knockout mouse line called Ddx42tm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping | DDX42
ATP-dependent RNA helicase DDX42 is an enzyme that in humans is encoded by the DDX42 gene.[1][2]
# Function
This gene encodes a member of the Asp-Glu-Ala-Asp (DEAD) box protein family. Members of this protein family are putative RNA helicases, and are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. Two transcript variants encoding the same protein have been identified for this gene.[2]
# Interactions
DDX42 has been shown to interact with SF3B1.[3]
# Model organisms
Model organisms have been used in the study of DDX42 function. A conditional knockout mouse line called Ddx42tm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[4] Male and female animals underwent a standardized phenotypic screen[5] to determine the effects of deletion.[6][7][8][9] Additional screens performed: - In-depth immunological phenotyping[10] | https://www.wikidoc.org/index.php/DDX42 | |
59cf7ef8f87d9ca1a1c025715c0e8d5594bf8098 | wikidoc | DEFA1 | DEFA1
Defensin, alpha 1 also known as human alpha defensin 1, human neutrophil peptide 1 (HNP-1) or neutrophil defensin 1 is a human protein that is encoded by the DEFA1 gene. Human alpha defensin 1 belongs to the alpha defensin family of antimicrobial peptides.
# Function
Defensins are a family of microbicidal and cytotoxic peptides thought to be involved in host defense. They are abundant in the granules of neutrophils and also found in the epithelia of mucosal surfaces such as those of the intestine, respiratory tract, urinary tract, and vagina. Members of the defensin family are highly similar in protein sequence and distinguished by a conserved cysteine motif. Several alpha defensin genes are clustered on chromosome 8. The protein encoded by this gene, defensin, alpha 1, is found in the microbicidal granules of neutrophils and likely plays a role in phagocyte-mediated host defense. It differs from the defensins, alpha 2 and alpha 3 by only one amino acid.
# Biosynthesis
HNPs are generated as 94 amino acids preproHNPs, which are co-translationally cleaved to 75 amino acids pro-peptides with a N-terminal prosegment having a negative charge that neutralizes the highly positively charged C terminal peptide. Processing of proHNPs occurs mainly in late promyelocytes, where the 75 amino acids proHNPs are cleaved to a 56 amino acids intermediate form and onward to 29-30 amino acids mature peptides designated HNPs. Cationic 29-30 amino acids HNPs associate with the negatively charged proteoglycan serglycin and translocate to azurophil granules. At later stages of granulocytic differentiation in which HNP expression peaks (i.e. myelocytes and metamyelocytes), proHNPs are not cleaved, rendering the peptides overall neutral. This prevents binding to serglycin and most proHNP is accordingly secreted into the bone marrow plasma although some is retained in specific granules. | DEFA1
Defensin, alpha 1 also known as human alpha defensin 1, human neutrophil peptide 1 (HNP-1) or neutrophil defensin 1 is a human protein that is encoded by the DEFA1 gene.[1][2][3] Human alpha defensin 1 belongs to the alpha defensin family of antimicrobial peptides.
# Function
Defensins are a family of microbicidal and cytotoxic peptides thought to be involved in host defense. They are abundant in the granules of neutrophils and also found in the epithelia of mucosal surfaces such as those of the intestine, respiratory tract, urinary tract, and vagina. Members of the defensin family are highly similar in protein sequence and distinguished by a conserved cysteine motif. Several alpha defensin genes are clustered on chromosome 8. The protein encoded by this gene, defensin, alpha 1, is found in the microbicidal granules of neutrophils and likely plays a role in phagocyte-mediated host defense. It differs from the defensins, alpha 2 and alpha 3 by only one amino acid.[3]
# Biosynthesis
HNPs are generated as 94 amino acids preproHNPs, which are co-translationally cleaved to 75 amino acids pro-peptides with a N-terminal prosegment having a negative charge that neutralizes the highly positively charged C terminal peptide. Processing of proHNPs occurs mainly in late promyelocytes, where the 75 amino acids proHNPs are cleaved to a 56 amino acids intermediate form and onward to 29-30 amino acids mature peptides designated HNPs.[4][5] Cationic 29-30 amino acids HNPs associate with the negatively charged proteoglycan serglycin and translocate to azurophil granules.[6] At later stages of granulocytic differentiation in which HNP expression peaks (i.e. myelocytes and metamyelocytes), proHNPs are not cleaved, rendering the peptides overall neutral. This prevents binding to serglycin and most proHNP is accordingly secreted into the bone marrow plasma although some is retained in specific granules.[7] | https://www.wikidoc.org/index.php/DEFA1 | |
c5525ba35352c0a909be507f83ca010c16137242 | wikidoc | DEFA6 | DEFA6
Defensin, alpha 6 (DEFA6) also known as human alpha defensin 6 (HD6) is a human protein that is encoded by the DEFA6 gene. DEFA6 is expressed in the Paneth cells of the ileum.
# Function
The alpha defensins are a family of microbicidal and cytotoxic peptides that defend the host against bacteria and viruses. HD6 has poor antibacterial potency. However, HD6 affords protection against invasion by enteric bacterial pathogens by self-assembly to form fibrils and nanonets that surround and entangle bacteria.
Several alpha defensin genes, including DEFA6, are clustered on chromosome 8. | DEFA6
Defensin, alpha 6 (DEFA6) also known as human alpha defensin 6 (HD6) is a human protein that is encoded by the DEFA6 gene.[1][2] DEFA6 is expressed in the Paneth cells of the ileum.[3]
# Function
The alpha defensins are a family of microbicidal and cytotoxic peptides that defend the host against bacteria and viruses. HD6 has poor antibacterial potency.[4] However, HD6 affords protection against invasion by enteric bacterial pathogens by self-assembly to form fibrils and nanonets that surround and entangle bacteria.[5]
Several alpha defensin genes, including DEFA6, are clustered on chromosome 8.[1] | https://www.wikidoc.org/index.php/DEFA6 | |
798d9655fe3bb50d23bbfe67778128efc9f1644d | wikidoc | DFNA5 | DFNA5
Non-syndromic hearing impairment protein 5 is a protein that in humans is encoded by the DFNA5 gene.
# Function
Hearing impairment is a heterogeneous condition with over 40 loci described. The protein encoded by this gene is expressed in fetal cochlea, however, its function is not known. Nonsyndromic hearing impairment is associated with a mutation in this gene.
The observation that DFNA5 is epigenetically inactivated in a large number of cancers of frequent types (gastric, colorectal, and breast) is another important finding and is in line with its apoptosis-inducing properties. Indeed, if apoptosis is an intrinsic feature of DFNA5, shutting the gene down in tumor cells makes them more susceptible to uncontrolled cellular growth. Moreover, the fact that DFNA5 is regulated by P53 strongly suggests that DFNA5 is a tumor suppressor gene. | DFNA5
Non-syndromic hearing impairment protein 5 is a protein that in humans is encoded by the DFNA5 gene.[1][2][3]
# Function
Hearing impairment is a heterogeneous condition with over 40 loci described. The protein encoded by this gene is expressed in fetal cochlea, however, its function is not known. Nonsyndromic hearing impairment is associated with a mutation in this gene.[3]
The observation that DFNA5 is epigenetically inactivated in a large number of cancers of frequent types (gastric, colorectal, and breast) is another important finding and is in line with its apoptosis-inducing properties. Indeed, if apoptosis is an intrinsic feature of DFNA5, shutting the gene down in tumor cells makes them more susceptible to uncontrolled cellular growth. Moreover, the fact that DFNA5 is regulated by P53 strongly suggests that DFNA5 is a tumor suppressor gene.[4] | https://www.wikidoc.org/index.php/DFNA5 | |
b8597d4052ad02d9dd097287a8a12dd47f8e9050 | wikidoc | DGCR8 | DGCR8
The DGCR8 microprocessor complex subunit (DiGeorge syndrome chromosomal region 8) is a protein that in humans is encoded by the DGCR8 gene. In other animals, particularly the common model organisms Drosophila melanogaster and Caenorhabditis elegans, the protein is known as Pasha (partner of Drosha). It is a required component of the RNA interference pathway.
# Function
DGCR8 is localized to the cell nucleus and is required for microRNA (miRNA) processing. It binds to Drosha, an RNase III enzyme, to form the Microprocessor complex that cleaves a primary transcript known as pri-miRNA to a characteristic stem-loop structure known as a pre-miRNA, which is then further processed to miRNA fragments by the enzyme Dicer. DGCR8 contains an RNA-binding domain and is thought to bind pri-miRNA to stabilize it for processing by Drosha.
DGCR8 is also required for some types of DNA repair. Removal of UV-induced DNA photoproducts, during transcription coupled nucleotide excision repair (TC-NER), depends on JNK phosphorylation of DGCR8 on serine 153. While DGCR8 is known to function in microRNA biogenesis, this activity is not required for DGCR8-dependent removal of UV-induced photoproducts. Nucleotide excision repair is also needed for repair of oxidative DNA damage due to hydrogen peroxide (H2O2), and DGCR8 depleted cells are sensitive to H2O2. | DGCR8
The DGCR8 microprocessor complex subunit (DiGeorge syndrome chromosomal [or critical] region 8) is a protein that in humans is encoded by the DGCR8 gene.[1] In other animals, particularly the common model organisms Drosophila melanogaster and Caenorhabditis elegans, the protein is known as Pasha (partner of Drosha).[2] It is a required component of the RNA interference pathway.
# Function
DGCR8 is localized to the cell nucleus and is required for microRNA (miRNA) processing. It binds to Drosha, an RNase III enzyme, to form the Microprocessor complex that cleaves a primary transcript known as pri-miRNA to a characteristic stem-loop structure known as a pre-miRNA, which is then further processed to miRNA fragments by the enzyme Dicer. DGCR8 contains an RNA-binding domain and is thought to bind pri-miRNA to stabilize it for processing by Drosha.[3]
DGCR8 is also required for some types of DNA repair. Removal of UV-induced DNA photoproducts, during transcription coupled nucleotide excision repair (TC-NER), depends on JNK phosphorylation of DGCR8 on serine 153.[4] While DGCR8 is known to function in microRNA biogenesis, this activity is not required for DGCR8-dependent removal of UV-induced photoproducts.[4] Nucleotide excision repair is also needed for repair of oxidative DNA damage due to hydrogen peroxide (H2O2), and DGCR8 depleted cells are sensitive to H2O2.[4] | https://www.wikidoc.org/index.php/DGCR8 | |
eeb6a8793387dd9c97240fbd1f44f165b127c642 | wikidoc | DHRS1 | DHRS1
Dehydrogenase/reductase SDR family member 1, also known as Short chain dehydrogenase/reductase family 19C member 1 is an enzyme that in humans is encoded by the DHRS1 gene located on chromosome 14.
# Structure
The DHRS1 gene is located on the chromosome 14q21.3 region and contains 9 exons. It encodes a 314-amino-acid, 33-kDa protein that is thought to be located to the endoplasmic reticulum and the mitochondrial inner membrane inside the cell.
# Function
The DHRS1 protein is thought to have oxidoreductase activity based on sequence similarity and conserved catalytic sites with other short-chain oxidoreductase enzymes. The enzyme is found to be expressed in the fetal brain.
# Interactions
The DHRS1 protein is thought to interact with the protein phospholipid scrambase 1 (PLSCR1). | DHRS1
Dehydrogenase/reductase SDR family member 1, also known as Short chain dehydrogenase/reductase family 19C member 1 is an enzyme that in humans is encoded by the DHRS1 gene located on chromosome 14.[1][2][3]
# Structure
The DHRS1 gene is located on the chromosome 14q21.3 region and contains 9 exons. It encodes a 314-amino-acid, 33-kDa protein that is thought to be located to the endoplasmic reticulum and the mitochondrial inner membrane inside the cell.
# Function
The DHRS1 protein is thought to have oxidoreductase activity based on sequence similarity and conserved catalytic sites with other short-chain oxidoreductase enzymes. The enzyme is found to be expressed in the fetal brain.[4]
# Interactions
The DHRS1 protein is thought to interact with the protein phospholipid scrambase 1 (PLSCR1).[5] | https://www.wikidoc.org/index.php/DHRS1 | |
1db3ac481743972491f89bec12c48cec474264a6 | wikidoc | DHX29 | DHX29
DExH-box helicase 29 (DHX29) is a 155 kDa protein that in humans is encoded by the DHX29 gene.
# Function
This gene encodes a member of the DEAH (Asp-Glu-Ala-His) subfamily of proteins, part of the DEAD (Asp-Glu-Ala-Asp) box family of RNA helicases. The encoded protein functions in translation initiation, and is specifically required for ribosomal scanning across stable mRNA secondary structures during initiation codon selection. This protein may also play a role in sensing virally derived cytosolic nucleic acids. Knockdown of this gene results in reduced protein translation and impaired proliferation of cancer cells.
# Interactions
DHX29 has been shown to interact with the eukaryotic small ribosomal subunit (40S) and eIF3. | DHX29
DExH-box helicase 29 (DHX29) is a 155 kDa protein that in humans is encoded by the DHX29 gene.[1]
# Function
This gene encodes a member of the DEAH (Asp-Glu-Ala-His) subfamily of proteins, part of the DEAD (Asp-Glu-Ala-Asp) box family of RNA helicases. The encoded protein functions in translation initiation, and is specifically required for ribosomal scanning across stable mRNA secondary structures during initiation codon selection.[2] This protein may also play a role in sensing virally derived cytosolic nucleic acids.[3] Knockdown of this gene results in reduced protein translation and impaired proliferation of cancer cells.[4]
# Interactions
DHX29 has been shown to interact with the eukaryotic small ribosomal subunit (40S) and eIF3.[5][6][7][8] | https://www.wikidoc.org/index.php/DHX29 | |
9ca5c552f4883a44dfb40c75e2eb61d6bb2c007d | wikidoc | DHX36 | DHX36
Probable ATP-dependent RNA helicase DHX36 also known as DEAH box protein 36 (DHX36) or MLE-like protein 1 (MLEL1) or G4 resolvase 1 (G4R1) or RNA helicase associated with AU-rich elements (RHAU) is an enzyme that in humans is encoded by the DHX36 gene.
# Structure
Structurally, DHX36 is a 1008 amino acid-long modular protein that has been crystallized in a complex with a DNA G-quadruplex. It consists of a ~440-amino acid helicase core comprising all signature motifs of the DEAH/RHA family of helicases with N- and C-terminal flanking regions of ~180 and ~380 amino acids, respectively. Part of the N-terminal flanking region forms an alpha-helix called the DHX36-specific motif, which recognizes the 5'-most G-quadruplex quartet. The OB-fold domain binds to the 3'-most G-tract sugar-phosphate backbone. Like all the DEAH/RHA helicases, the helicase associated domain is located adjacent to the helicase core region and occupies 75% of the C-terminal region.
# Function
DEAH/RHA proteins are RNA and DNA helicases typically characterized by low processivity translocation on substrates and the capability to bind/unwind non-canonical nucleic acid secondary structures. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAH/RHA protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division.
DHX36 exhibits a unique ATP-dependent guanine-quadruplex (G4) resolvase activity and specificity for its substrate in vitro. DHX36 displays repetitive unwinding activity as a function of the thermal stability of the G-quadruplex substrate, characteristic of a number of other G-quadruplex resolvases such as the BLM/WRN helicases. DHX36 binds G4-nucleic acid with sub-nanomolar affinity and unwinds G4 structures much more efficiently than double-stranded nucleic acid. Consistent with these biochemical observations, DHX36 was also identified as the major source of tetramolecular RNA-resolving activity in HeLa cell lysates.
Previous work showed that DHX36 associates with mRNAs and re-localises to stress granules (SGs) upon translational arrest induced by various environmental stresses. A region of the first 105 amino acid was shown to be critical for RNA binding and re-localisation to SGs. | DHX36
Probable ATP-dependent RNA helicase DHX36 also known as DEAH box protein 36 (DHX36) or MLE-like protein 1 (MLEL1) or G4 resolvase 1 (G4R1) or RNA helicase associated with AU-rich elements (RHAU) is an enzyme that in humans is encoded by the DHX36 gene.[1][2]
# Structure
Structurally, DHX36 is a 1008 amino acid-long modular protein that has been crystallized in a complex with a DNA G-quadruplex.[3] It consists of a ~440-amino acid helicase core comprising all signature motifs of the DEAH/RHA family of helicases with N- and C-terminal flanking regions of ~180 and ~380 amino acids, respectively. Part of the N-terminal flanking region forms an alpha-helix called the DHX36-specific motif, which recognizes the 5'-most G-quadruplex quartet. The OB-fold domain binds to the 3'-most G-tract sugar-phosphate backbone.[4] Like all the DEAH/RHA helicases, the helicase associated domain is located adjacent to the helicase core region and occupies 75% of the C-terminal region.[5]
# Function
DEAH/RHA proteins are RNA and DNA helicases typically characterized by low processivity translocation on substrates and the capability to bind/unwind non-canonical nucleic acid secondary structures.[6] They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAH/RHA protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division.[1]
DHX36 exhibits a unique ATP-dependent guanine-quadruplex (G4) resolvase activity and specificity for its substrate in vitro.[7][8] DHX36 displays repetitive unwinding activity as a function of the thermal stability of the G-quadruplex substrate, characteristic of a number of other G-quadruplex resolvases such as the BLM/WRN helicases.[9][10] DHX36 binds G4-nucleic acid with sub-nanomolar affinity and unwinds G4 structures much more efficiently than double-stranded nucleic acid. Consistent with these biochemical observations, DHX36 was also identified as the major source of tetramolecular RNA-resolving activity in HeLa cell lysates.
Previous work showed that DHX36 associates with mRNAs and re-localises to stress granules (SGs) upon translational arrest induced by various environmental stresses.[11][12] A region of the first 105 amino acid was shown to be critical for RNA binding and re-localisation to SGs. | https://www.wikidoc.org/index.php/DHX36 | |
832f99b2c0e43b4c16363238cc49d38c6006f04e | wikidoc | DISC1 | DISC1
Disrupted in schizophrenia 1 is a protein that in humans is encoded by the DISC1 gene. In coordination with a wide array of interacting partners, DISC1 has been shown to participate in the regulation of cell proliferation, differentiation, migration, neuronal axon and dendrite outgrowth, mitochondrial transport, fission and/or fusion, and cell-to-cell adhesion. Several studies have shown that unregulated expression or altered protein structure of DISC1 may predispose individuals to the development of schizophrenia, clinical depression, bipolar disorder, and other psychiatric conditions. The cellular functions that are disrupted by permutations in DISC1, which lead to the development of these disorders, have yet to be clearly defined and are the subject of current ongoing research. However, recent genetic studies of large schizophrenia cohorts have failed to implicate DISC1 as a risk gene.
# Discovery
In 1970, researchers from the University of Edinburgh performing cytogenetic research on a group of juvenile offenders in Scotland found an abnormal translocation in chromosome 1 of one of the boys, who also displayed characteristics of an affective psychological disorder. After this initial observation, the boy's family was studied and it was found that 34 out of 77 family members displayed the same translocation. According to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (or DSM-IV) criteria, sixteen of the 34 individuals identified as having the genetic mutation were diagnosed with psychiatric problems. In contrast, five of the 43 unaffected family members were identified to have psychological indispositions. The psychiatric illnesses observed in the family ranged from schizophrenia and major depression to bipolar disorder and adolescent conduct disorder (which the original research subject had). After studying this large Scottish family for four generations, in 2000, this gene was given the name "DISC1". The name was derived from the basis of the molecular nature of the mutation: the translocation directly disrupts the gene.
## Importance of genetic studies
The implication of genetics in psychiatric illnesses is not unique to schizophrenia, though the heritability of schizophrenia has been calculated as high as 80%. The continued research of the family following the discovery of the translocation yielded statistical analysis of the probability of observing the simultaneous occurrence, or co-inheritance, of psychological afflictions and the translocation. This concept was measured quantitatively using the LOD, or logarithm of the odds value. The higher the LOD value, the stronger the correlation between the presence of the translocation and given disease(s) is thought to be. The LOD for the chromosome 1 translocation and identification of schizophrenia alone in the Scottish family was found to be 3.6. The LOD value of the translocation and a broader number of diagnoses (including schizophrenia, schizoaffective disorder, bipolar affective disorder, and recurrent major depression) was found to be 7.1.
Besides large familial-based studies in which the pedigrees of various family members are examined, twin studies have also been a source of support for researchers in the investigation of DISC1. In a meta-analysis of twin studies, twelve out of fourteen were found to support the fact that from a genetic perspective, schizophrenia is a complex trait that depends on both genetic and environmental factors. Such findings have encouraged researchers to continue with both macro-analysis of the disorders afflicting individuals with the mutation, as well as explore the micro-level.
# Gene location and transcription
The DISC1 gene is situated at chromosome 1q42.1 and overlaps with DISC2 open reading frame. Multiple DISC1 isoforms have been identified at the RNA level, including a TSNAX-DISC1 transgene splice variant, and at the protein level. Of the isolated RNA isomers, 4 have been confirmed to be translated namely Long form (L), Long variant isoform (Lv), Small isoform (S), and Especially small isoform (Es). Human DISC1 is transcribed as two major splice variants, L form and Lv isoform. The L and Lv transcripts utilize distal and proximal splice sites, respectively, within exon 11. The L and Lv protein isoforms differ by only 22 amino acids within the C-terminus.
Alternate transcriptional splice variants, encoding different isoforms, have been characterized.
DISC1 homologues have been identified in all major vertebrate families including the common chimpanzee, the rhesus monkey, the house mouse, the brown rat, zebrafish, pufferfish, cattle, and dogs; additionally homologue's have been described for invertebrate and plant phyla.
# Protein structure and subcellular distribution
The protein encoded by this gene is predicted to contain a coiled coil motif rich C-terminal domain, and a N-terminal globular domain. The N-terminus contains two putative nuclear localization signals, and a serine-phenylalanine-rich motif of unknown significance. The C-terminus contains multiple regions with coiled-coil forming potential, and two leucine zippers that may mediate protein-protein interactions.
The protein locates to the nucleus, centrosome, cytoplasm, mitochondria, axons and synapses. Mitochondria are the predominant site of endogenous DISC1 expression, with at least two isoforms occupying internal mitochondrial locations. No known functional homologues exist for this protein in humans, although it does have broad homology to scaffold proteins. The DISC1 protein function appears to be highly diverse and its functional role in cellular processes is dependent upon the cellular domain it is located in. The presence or absence of certain protein interaction domains or targeting motifs may confer specific functions and influence sub cellular targeting, therefore it is probable that alternative splicing codetermines both the function and the intracellular location of DISC1.
# Function
Many studies have provided insight into the normal function of the DISC1 protein, though much remains to be clearly defined. DISC1 is functionally involved in several processes that regulate neural development and brain maturation such as neuronal proliferation, differentiation, migration, cAMP signaling, cytoskeletal modulation, and translational regulation via various signaling pathways. Much of what is understood about the normal function of DISC1 has been uncovered through studies on zebrafish and mice as model organisms. In zebrafish, DISC1 is essential for forebrain development and GSK3/β-catenin signaling, while in mice the DISC1-GSK3 pathway regulates proliferation of neural progenitor cells in the cortex and adult dentate gyrus. This data suggests a direct DISC1 GSK3/β-catenin interaction.
DISC1 functions through a rich protein-protein interaction network, named the “DISC1 interactome” by researchers. Among its known interaction partners are 14-3-3ε, LIS1 and the PDE4B enzyme. DISC1 may play an important role in neuroplasticity via interactions with molecules of the cytoskeleton and centrosome, such as NUDEL and LIS1. The protein also enables the activity of dynein, a microtubule protein. Controlling transport of microtubules is involved in neuronal migration, neurite outgrowth, and axon formation.
DISC1 is highly expressed during critical periods of brain development, particularly in the embryonic ventricular and subventricular zones of the cortex, where neural progenitor cells are found. This localization suggests that DISC1 is an important regulator of embryonic and adult neurogenesis, and may regulate proliferation and/or differentiation. Levels of the protein in cycling neural progenitor cells affects whether they differentiate into neurons or remain as progenitors. Expression profile is highest in the hippocampus during development and remains highly expressed in the adult dentate gyrus and olfactory bulb, regions where adult neurogenesis is present. DISC1 has also been shown to regulate tempo of neuronal integration into the brain and guidance of positioning of new neurons.
Due to localization of the protein found at the synapse, DISC1 is also likely to play a key role in postsynaptic density, however this novel role is not yet fully understood.
# Protein interactions
The DISC1 protein has no known enzymatic activity; rather it exerts its effect on multiple proteins through interactions to modulate their functional states and biological activities in time and space. These include:
## DISC1
DISC1 has been shown to self-associate, to form dimers, multimers, and oligomers. The ability of DISC1 to form complexes with itself may be important in regulating its affinity for interacting partners such as NDEL1. In postmortem brain samples of Schizophrenia patients there is an increase in insoluble DISC1 oligomer aggregates, indicative of a common link with other neurological disorders characterised by protein aggregation, namely Alzheimer's disease, Parkinson's disease, and Huntington's disease.
## ATF4/ATF5
ATF4 and ATF5 are members of the leucine zipper activating transcription factor / CREB family. They are known to bind to and regulate the function of GABAB receptors in synapses and are involved in signal transduction from the cell membrane to the nucleus. Both proteins interact with DISC1 and GABAB receptors via their second C-terminal leucine zipper domain, therefore DISC1 is able to regulate GABAB receptor function through its interaction with ATF4/ATF5.
## FEZ1
DISC1 participates in neurite outgrowth through its interaction with the fasciculation and elongation protein ζ-1 (FEZ1). FEZ1 is a mammalian homolog of the C. elegans UNC-76 protein involved in axonal outgrowth and fasciculation. The C-terminal region of FEZ1 (aa 247-392) is required for interaction with DISC1. A DISC1 region (aa 446-633), containing two stretches with coiled-coil-forming potential is critical for its interaction with FEZ1. DISC1-FEZ1 interaction is enhanced during neuro-differentiation, and expression of the FEZ1-binding domain of DISC1 has a dominant negative effect on neurite outgrowth, which implies co-operation of DISC1 and FEZ1 in this process.
## Kalirin-7
The DISC1 protein plays a role in the process of regulating spine form and function through its interactions with kalirin-7 (kal-7). Kal-7 is a regulator of spine morphology and synaptic plasticity in association with neuronal activity. Kal-7-dependent regulation of spine formation occurs through its activity as a GDP/GTP exchange factor for Rac1. Activation of rac1 by kal-7 leads to increased spine size and synaptic strength through regulation of the actin cytoskeleton by rac1. DISC1 is able to bind to kal-7, confining its access to rac1, and in turn regulate spinal formation. Activation of NMDA receptors causes dissociation of DISC1 and kal-7, leaving kal-7 available to activate rac1.
## MAP1A
DISC1 shows strong interaction with the microtubule-associated protein MAP1A that controls the polymerization and stabilization of microtubule networks in neurons, and thereby influence cell shape and intracellular transport of vesicles and organelles. MAP1A binds to the far N-terminus (aa 293-696) of DISC1, and the amino terminus of DISC1 binds to the LC2 subunit of MAP1A. The LC2 subunit of MAP1A contains an actin-binding domain and is necessary and sufficient for microtubule binding and polymerization, therefore DISC1 is able to regulate the ability of MAP1A to polymerize and stabilize microtubules and traffic proteins to their correct localization in the synaptic architecture.
## NDEL1/NUDEL
DISC1 is localized to the centrosome, the primary microtubule organizing center of the cell, via interaction with nuclear distribution gene homologue-like 1 (NDEL1, also called NUDEL), where it is part of a protein complex involved in cytoskeletal processes of neuronal migration, including nucleokinesis and neurite outgrowth. NUDEL is also known to play a role in axon regeneration and has an additional DISC1-modulated function as a cysteine endopeptidase. Localization of NUDEL to axons is dependent on expression of DISC1. NUDEL binds to a 100 amino acid domain of DISC1 (aa 598-697) containing a coiled coil domain and a leucine zipper. The amino acid domain of NUDEL that binds DISC1 is the carboxyl terminal 100 amino acids of the protein (aa 241-345), which contains a cytoplasmic dynein binding site.
## PCM1/Pericentriolar material
The protein Pericentriolar Material 1 (PCM1) which is associated with cilia development in the CNS interacts directly with the Disrupted-In-Schizophrenia 1 (DISC1) and calmodulin 1 (CALM1)proteins. Kamiya et al. have shown that PCM1, DISC1 and BBS4 can all disrupt neuronal organisation in the mouse when their expression is down-regulated. Markers at the pericentriolar material 1 gene (PCM1) have shown genetic association with schizophrenia in several schizophrenia case control studies. Resequencing of the genomic DNA from research volunteers who had inherited haplotypes associated with schizophrenia showed a threonine an isoleucine mis-sense mutation in exon 24 which may change the structure and function of PCM1 (rs370429). This mutation was found only as a heterozygote in ninety eight schizophrenic research subjects and controls out of a total sample of 2,246 case and control research subjects. Amongst the ninety eight carriers of rs370429 sixty seven were affected with schizophrenia. The same alleles and haplotypes were associated with schizophrenia in both London and Aberdeen samples. Another potential aetiological base pair change in PCM1 was rs445422 which altered a splice site signal. A further mutation, rs208747, was shown by electrophoretic mobility shift assays to create or destroy a promoter transcription factor site. Five further non-synonymous changes in exons were also found. Given the number and identity of the haplotypes associated with schizophrenia further aetiological base pair changes must exist within and around the PCM1 gene. The findings in relation to PCM1 support the role of DISC1 also being a susceptibility locus for schizophrenia.
Other interactions include: ACTN2, CEP63, EIF3A, RANBP9, and SPTBN4.
# Clinical implications
Aberrations of DISC1 are considered a generalized risk factor in major psychiatric diseases and have also been implicated in memory deficits and abnormal patterns of brain activity. DISC1 translocation increases the risk of developing schizophrenia, bipolar disorder, or major depression by about 50-fold in comparison to the general population. Efforts to model DISC1 disease biology in transgenic mice, Drosophila, and zebrafish have provided psychiatric disease implications related to DISC1 mutations. However, no specific variant is consistently associated with development of mental disorders, indicating allelic heterogeneity in psychiatric disease. The impact of variants in the DISC1 gene on expression and protein function is not yet clearly defined and associated variants are not necessarily causative.
## Schizophrenia
Schizophrenia affects 1% of the general population and is highly heritable, providing an indication of a genetic basis. DISC1 has been associated with neurological abnormalities such as delusions, deficits in long term and working memory, diminution of gray matter volume in hippocampal and prefrontal regions. These abnormalities are also seen as symptoms of schizophrenia. As DISC1 function is involved in neurogenesis and neuroplasticity, vulnerability to schizophrenia may involve dysfunction in the hippocampus, a brain region in which adult neurogenesis occurs.
## Autism and Asperger’s syndrome
In 2008, a genetic screen of 97 Finnish families affected by autism and Asperger’s syndrome revealed repeated DNA sequences within the DISC1 gene in those diagnosed with autism. Furthermore, a single nucleotide change in the gene was found to be present in 83% of family members with Asperger’s syndrome. A recent family study has reported a large chromosome 1 deletion that includes loss of DISC1 in a young boy diagnosed with autism. A link between DISC1 duplication and autism has also been suggested by the finding of a seven-gene duplication that includes DISC1 carried by two brothers with autism and mild retardation. These alterations in people with the disorder are rare, however, as none were found in a screening of 260 Belgians with autism.
Transgenic model organism strains generated with mutated or absent DISC1 suggest that the gene may contribute to at least some autistic abnormalities. Mice with lowered levels of DISC1 expression exhibit abnormal response to electrical stimulation, a decrease of dopamine synthesis, and an inability to filter unnecessary sensory information. Studies of expression of mutant DISC1 prenatally and postnatally have demonstrated varying effects, indicating the possibility that early postnatal expression of mutant DISC1 causes features of autism. Many more studies are necessary to confirm these suggestions.
## Bipolar disorder
Linkage studies in extended families multiply affected with bipolar disorder also provide evidence for DISC1 as a genetic factor in the etiology of bipolar disorder. In 1998, a follow-up study was conducted of the large Scottish family in which DISC1 was first discovered. Additional family members with the original translocation who developed major psychotic illness, including bipolar disorder, were identified.
# Research directions
As DISC1 investigation continues to be an emerging area of study, many unanswered questions regarding the biological function of the protein and its implications in psychiatric disorders remain. In depth understanding of DISC1 as a genetic risk factor for psychiatric disorders provides a possible target for developing new drug therapies and preventative measures. The pathways regulated by DISC1 interaction may provide possible avenues for therapeutic opportunities to reverse related deficits. Definitive genetic architecture, risk distribution, and their correlation with prognosis is crucial to determining response to new drug treatments.
In addition to DISC1, the antisense partner has been identified as DISC2, a noncoding RNA gene that may be involved in regulating the gene locus. However, structure and function of DISC2 remain unknown and may provide insight into how DISC1 is regulated.
Rare mutations in DISC1 other than the original translocation have been discovered and require further investigation. Furthermore, posttranslational processing and its effect on isoform expression, which also contributes to protein function and may be involved in some forms of disease, remains to be studied. The ability to predict the impact of different types of mutations on protein function and resulting psychiatric phenotype is crucial for the development of targeted treatments.
Family studies continue to provide an important approach towards deepening understanding of the biological nature of the gene and its clinical implications. While the original Scottish family in which DISC1 was discovered is still being considered, other familial populations in different countries have also become the focus of research in the past decade. In 2005, an American family was found to also possess a frameshift mutation in the DISC1 gene, which again co-segregated with schizophrenia and schizoaffective disorder. Characterized by a deletion of four base-pairs, the mutation was found in two siblings, one with schizophrenia and the other with schizoaffective disorder. Similar studies have also been done with Taiwanese and Finnish families. | DISC1
Disrupted in schizophrenia 1 is a protein that in humans is encoded by the DISC1 gene.[1] In coordination with a wide array of interacting partners, DISC1 has been shown to participate in the regulation of cell proliferation, differentiation, migration, neuronal axon and dendrite outgrowth, mitochondrial transport, fission and/or fusion, and cell-to-cell adhesion. Several studies have shown that unregulated expression or altered protein structure of DISC1 may predispose individuals to the development of schizophrenia, clinical depression, bipolar disorder, and other psychiatric conditions. The cellular functions that are disrupted by permutations in DISC1, which lead to the development of these disorders, have yet to be clearly defined and are the subject of current ongoing research. However, recent genetic studies of large schizophrenia cohorts have failed to implicate DISC1 as a risk gene. [2]
# Discovery
In 1970, researchers from the University of Edinburgh performing cytogenetic research on a group of juvenile offenders in Scotland found an abnormal translocation in chromosome 1 of one of the boys, who also displayed characteristics of an affective psychological disorder.[3] After this initial observation, the boy's family was studied and it was found that 34 out of 77 family members displayed the same translocation. According to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (or DSM-IV) criteria, sixteen of the 34 individuals identified as having the genetic mutation were diagnosed with psychiatric problems. In contrast, five of the 43 unaffected family members were identified to have psychological indispositions. The psychiatric illnesses observed in the family ranged from schizophrenia and major depression to bipolar disorder and adolescent conduct disorder (which the original research subject had).[4] After studying this large Scottish family for four generations, in 2000, this gene was given the name "DISC1". The name was derived from the basis of the molecular nature of the mutation: the translocation directly disrupts the gene.[1]
## Importance of genetic studies
The implication of genetics in psychiatric illnesses is not unique to schizophrenia, though the heritability of schizophrenia has been calculated as high as 80%.[5] The continued research of the family following the discovery of the translocation yielded statistical analysis of the probability of observing the simultaneous occurrence, or co-inheritance, of psychological afflictions and the translocation. This concept was measured quantitatively using the LOD, or logarithm of the odds value.[6] The higher the LOD value, the stronger the correlation between the presence of the translocation and given disease(s) is thought to be. The LOD for the chromosome 1 translocation and identification of schizophrenia alone in the Scottish family was found to be 3.6.[6] The LOD value of the translocation and a broader number of diagnoses (including schizophrenia, schizoaffective disorder, bipolar affective disorder, and recurrent major depression) was found to be 7.1.[6]
Besides large familial-based studies in which the pedigrees of various family members are examined, twin studies have also been a source of support for researchers in the investigation of DISC1.[5] In a meta-analysis of twin studies, twelve out of fourteen were found to support the fact that from a genetic perspective, schizophrenia is a complex trait that depends on both genetic and environmental factors.[5] Such findings have encouraged researchers to continue with both macro-analysis of the disorders afflicting individuals with the mutation, as well as explore the micro-level.
# Gene location and transcription
The DISC1 gene is situated at chromosome 1q42.1 and overlaps with DISC2 open reading frame. Multiple DISC1 isoforms have been identified at the RNA level, including a TSNAX-DISC1 transgene splice variant, and at the protein level.[7] Of the isolated RNA isomers, 4 have been confirmed to be translated namely Long form (L), Long variant isoform (Lv), Small isoform (S), and Especially small isoform (Es). Human DISC1 is transcribed as two major splice variants, L form and Lv isoform. The L and Lv transcripts utilize distal and proximal splice sites, respectively, within exon 11. The L and Lv protein isoforms differ by only 22 amino acids within the C-terminus.[8]
Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[9]
DISC1 homologues have been identified in all major vertebrate families including the common chimpanzee, the rhesus monkey, the house mouse, the brown rat, zebrafish, pufferfish, cattle, and dogs; additionally homologue's have been described for invertebrate and plant phyla.[10][11]
# Protein structure and subcellular distribution
The protein encoded by this gene is predicted to contain a coiled coil motif rich C-terminal domain, and a N-terminal globular domain.[10] The N-terminus contains two putative nuclear localization signals, and a serine-phenylalanine-rich motif of unknown significance. The C-terminus contains multiple regions with coiled-coil forming potential, and two leucine zippers that may mediate protein-protein interactions.
The protein locates to the nucleus, centrosome, cytoplasm, mitochondria, axons and synapses. Mitochondria are the predominant site of endogenous DISC1 expression, with at least two isoforms occupying internal mitochondrial locations. No known functional homologues exist for this protein in humans, although it does have broad homology to scaffold proteins. The DISC1 protein function appears to be highly diverse and its functional role in cellular processes is dependent upon the cellular domain it is located in. The presence or absence of certain protein interaction domains or targeting motifs may confer specific functions and influence sub cellular targeting, therefore it is probable that alternative splicing codetermines both the function and the intracellular location of DISC1.[8]
# Function
Many studies have provided insight into the normal function of the DISC1 protein, though much remains to be clearly defined. DISC1 is functionally involved in several processes that regulate neural development and brain maturation such as neuronal proliferation, differentiation, migration, cAMP signaling, cytoskeletal modulation, and translational regulation via various signaling pathways.[12] Much of what is understood about the normal function of DISC1 has been uncovered through studies on zebrafish and mice as model organisms. In zebrafish, DISC1 is essential for forebrain development and GSK3/β-catenin signaling, while in mice the DISC1-GSK3 pathway regulates proliferation of neural progenitor cells in the cortex and adult dentate gyrus. This data suggests a direct DISC1 GSK3/β-catenin interaction.[13]
DISC1 functions through a rich protein-protein interaction network, named the “DISC1 interactome” by researchers.[13] Among its known interaction partners are 14-3-3ε, LIS1 and the PDE4B enzyme.[14] DISC1 may play an important role in neuroplasticity via interactions with molecules of the cytoskeleton and centrosome, such as NUDEL and LIS1. The protein also enables the activity of dynein, a microtubule protein. Controlling transport of microtubules is involved in neuronal migration, neurite outgrowth, and axon formation.[15]
DISC1 is highly expressed during critical periods of brain development, particularly in the embryonic ventricular and subventricular zones of the cortex, where neural progenitor cells are found. This localization suggests that DISC1 is an important regulator of embryonic and adult neurogenesis, and may regulate proliferation and/or differentiation. Levels of the protein in cycling neural progenitor cells affects whether they differentiate into neurons or remain as progenitors.[13] Expression profile is highest in the hippocampus during development and remains highly expressed in the adult dentate gyrus and olfactory bulb, regions where adult neurogenesis is present.[15] DISC1 has also been shown to regulate tempo of neuronal integration into the brain and guidance of positioning of new neurons.[15]
Due to localization of the protein found at the synapse, DISC1 is also likely to play a key role in postsynaptic density, however this novel role is not yet fully understood.[13]
# Protein interactions
The DISC1 protein has no known enzymatic activity; rather it exerts its effect on multiple proteins through interactions to modulate their functional states and biological activities in time and space.[16] These include:
## DISC1
DISC1 has been shown to self-associate, to form dimers, multimers, and oligomers. The ability of DISC1 to form complexes with itself may be important in regulating its affinity for interacting partners such as NDEL1. In postmortem brain samples of Schizophrenia patients there is an increase in insoluble DISC1 oligomer aggregates, indicative of a common link with other neurological disorders characterised by protein aggregation, namely Alzheimer's disease, Parkinson's disease, and Huntington's disease.[17][18]
## ATF4/ATF5
ATF4 and ATF5 are members of the leucine zipper activating transcription factor / CREB family. They are known to bind to and regulate the function of GABAB receptors in synapses and are involved in signal transduction from the cell membrane to the nucleus. Both proteins interact with DISC1 and GABAB receptors via their second C-terminal leucine zipper domain, therefore DISC1 is able to regulate GABAB receptor function through its interaction with ATF4/ATF5.[16][19]
## FEZ1
DISC1 participates in neurite outgrowth through its interaction with the fasciculation and elongation protein ζ-1 (FEZ1). FEZ1 is a mammalian homolog of the C. elegans UNC-76 protein involved in axonal outgrowth and fasciculation. The C-terminal region of FEZ1 (aa 247-392) is required for interaction with DISC1. A DISC1 region (aa 446-633), containing two stretches with coiled-coil-forming potential is critical for its interaction with FEZ1.[20] DISC1-FEZ1 interaction is enhanced during neuro-differentiation, and expression of the FEZ1-binding domain of DISC1 has a dominant negative effect on neurite outgrowth, which implies co-operation of DISC1 and FEZ1 in this process.[16]
## Kalirin-7
The DISC1 protein plays a role in the process of regulating spine form and function through its interactions with kalirin-7 (kal-7). Kal-7 is a regulator of spine morphology and synaptic plasticity in association with neuronal activity. Kal-7-dependent regulation of spine formation occurs through its activity as a GDP/GTP exchange factor for Rac1. Activation of rac1 by kal-7 leads to increased spine size and synaptic strength through regulation of the actin cytoskeleton by rac1. DISC1 is able to bind to kal-7, confining its access to rac1, and in turn regulate spinal formation. Activation of NMDA receptors causes dissociation of DISC1 and kal-7, leaving kal-7 available to activate rac1.[13][16]
## MAP1A
DISC1 shows strong interaction with the microtubule-associated protein MAP1A that controls the polymerization and stabilization of microtubule networks in neurons, and thereby influence cell shape and intracellular transport of vesicles and organelles. MAP1A binds to the far N-terminus (aa 293-696) of DISC1, and the amino terminus of DISC1 binds to the LC2 subunit of MAP1A. The LC2 subunit of MAP1A contains an actin-binding domain and is necessary and sufficient for microtubule binding and polymerization, therefore DISC1 is able to regulate the ability of MAP1A to polymerize and stabilize microtubules and traffic proteins to their correct localization in the synaptic architecture.[19]
## NDEL1/NUDEL
DISC1 is localized to the centrosome, the primary microtubule organizing center of the cell, via interaction with nuclear distribution gene homologue-like 1 (NDEL1, also called NUDEL), where it is part of a protein complex involved in cytoskeletal processes of neuronal migration, including nucleokinesis and neurite outgrowth. NUDEL is also known to play a role in axon regeneration and has an additional DISC1-modulated function as a cysteine endopeptidase. Localization of NUDEL to axons is dependent on expression of DISC1.[16] NUDEL binds to a 100 amino acid domain of DISC1 (aa 598-697) containing a coiled coil domain and a leucine zipper. The amino acid domain of NUDEL that binds DISC1 is the carboxyl terminal 100 amino acids of the protein (aa 241-345), which contains a cytoplasmic dynein binding site.[19]
## PCM1/Pericentriolar material
The protein Pericentriolar Material 1 (PCM1) which is associated with cilia development in the CNS interacts directly with the Disrupted-In-Schizophrenia 1 (DISC1) and calmodulin 1 (CALM1)proteins. Kamiya et al. have shown that PCM1, DISC1 and BBS4 can all disrupt neuronal organisation in the mouse when their expression is down-regulated.[21] Markers at the pericentriolar material 1 gene (PCM1) have shown genetic association with schizophrenia in several schizophrenia case control studies.[22][23] Resequencing of the genomic DNA from research volunteers who had inherited haplotypes associated with schizophrenia showed a threonine an isoleucine mis-sense mutation in exon 24 which may change the structure and function of PCM1 (rs370429).[24] This mutation was found only as a heterozygote in ninety eight schizophrenic research subjects and controls out of a total sample of 2,246 case and control research subjects. Amongst the ninety eight carriers of rs370429 sixty seven were affected with schizophrenia. The same alleles and haplotypes were associated with schizophrenia in both London and Aberdeen samples. Another potential aetiological base pair change in PCM1 was rs445422 which altered a splice site signal. A further mutation, rs208747, was shown by electrophoretic mobility shift assays to create or destroy a promoter transcription factor site. Five further non-synonymous changes in exons were also found. Given the number and identity of the haplotypes associated with schizophrenia further aetiological base pair changes must exist within and around the PCM1 gene.[24] The findings in relation to PCM1 support the role of DISC1 also being a susceptibility locus for schizophrenia.
Other interactions include: ACTN2,[19] CEP63,[19] EIF3A,[19] RANBP9,[19] and SPTBN4.[19]
# Clinical implications
Aberrations of DISC1 are considered a generalized risk factor in major psychiatric diseases and have also been implicated in memory deficits and abnormal patterns of brain activity.[12][25] DISC1 translocation increases the risk of developing schizophrenia, bipolar disorder, or major depression by about 50-fold in comparison to the general population.[13] Efforts to model DISC1 disease biology in transgenic mice, Drosophila, and zebrafish have provided psychiatric disease implications related to DISC1 mutations.[13] However, no specific variant is consistently associated with development of mental disorders, indicating allelic heterogeneity in psychiatric disease. The impact of variants in the DISC1 gene on expression and protein function is not yet clearly defined and associated variants are not necessarily causative.[26]
## Schizophrenia
Schizophrenia affects 1% of the general population and is highly heritable, providing an indication of a genetic basis.[15] DISC1 has been associated with neurological abnormalities such as delusions, deficits in long term and working memory, diminution of gray matter volume in hippocampal and prefrontal regions.[15] These abnormalities are also seen as symptoms of schizophrenia. As DISC1 function is involved in neurogenesis and neuroplasticity, vulnerability to schizophrenia may involve dysfunction in the hippocampus, a brain region in which adult neurogenesis occurs.[15]
## Autism and Asperger’s syndrome
In 2008, a genetic screen of 97 Finnish families affected by autism and Asperger’s syndrome revealed repeated DNA sequences within the DISC1 gene in those diagnosed with autism.[25] Furthermore, a single nucleotide change in the gene was found to be present in 83% of family members with Asperger’s syndrome. A recent family study has reported a large chromosome 1 deletion that includes loss of DISC1 in a young boy diagnosed with autism. A link between DISC1 duplication and autism has also been suggested by the finding of a seven-gene duplication that includes DISC1 carried by two brothers with autism and mild retardation. These alterations in people with the disorder are rare, however, as none were found in a screening of 260 Belgians with autism.[25]
Transgenic model organism strains generated with mutated or absent DISC1 suggest that the gene may contribute to at least some autistic abnormalities.[25] Mice with lowered levels of DISC1 expression exhibit abnormal response to electrical stimulation, a decrease of dopamine synthesis, and an inability to filter unnecessary sensory information. Studies of expression of mutant DISC1 prenatally and postnatally have demonstrated varying effects, indicating the possibility that early postnatal expression of mutant DISC1 causes features of autism. Many more studies are necessary to confirm these suggestions.[25]
## Bipolar disorder
Linkage studies in extended families multiply affected with bipolar disorder also provide evidence for DISC1 as a genetic factor in the etiology of bipolar disorder.[27] In 1998, a follow-up study was conducted of the large Scottish family in which DISC1 was first discovered. Additional family members with the original translocation who developed major psychotic illness, including bipolar disorder, were identified.[27]
# Research directions
As DISC1 investigation continues to be an emerging area of study, many unanswered questions regarding the biological function of the protein and its implications in psychiatric disorders remain. In depth understanding of DISC1 as a genetic risk factor for psychiatric disorders provides a possible target for developing new drug therapies and preventative measures.[27] The pathways regulated by DISC1 interaction may provide possible avenues for therapeutic opportunities to reverse related deficits.[13] Definitive genetic architecture, risk distribution, and their correlation with prognosis is crucial to determining response to new drug treatments.[26]
In addition to DISC1, the antisense partner has been identified as DISC2, a noncoding RNA gene that may be involved in regulating the gene locus. However, structure and function of DISC2 remain unknown and may provide insight into how DISC1 is regulated.[26]
Rare mutations in DISC1 other than the original translocation have been discovered and require further investigation.[13] Furthermore, posttranslational processing and its effect on isoform expression, which also contributes to protein function and may be involved in some forms of disease, remains to be studied.[13][26] The ability to predict the impact of different types of mutations on protein function and resulting psychiatric phenotype is crucial for the development of targeted treatments.[26]
Family studies continue to provide an important approach towards deepening understanding of the biological nature of the gene and its clinical implications. While the original Scottish family in which DISC1 was discovered is still being considered, other familial populations in different countries have also become the focus of research in the past decade. In 2005, an American family was found to also possess a frameshift mutation in the DISC1 gene, which again co-segregated with schizophrenia and schizoaffective disorder.[28] Characterized by a deletion of four base-pairs, the mutation was found in two siblings, one with schizophrenia and the other with schizoaffective disorder. Similar studies have also been done with Taiwanese and Finnish families.[28] | https://www.wikidoc.org/index.php/DISC1 | |
dfd5089f94efa6211c06603ce65b5cfc8417584d | wikidoc | PARK7 | PARK7
Protein deglycase DJ-1, also known as Parkinson disease protein 7, is a protein which in humans is encoded by the PARK7 gene.
# Structure
## Gene
The gene PARK7, also known as DJ-1, encodes a protein of the peptidase C56 family. The human gene PARK7 has 8 Exons and locates at chromosome band 1p36.23.
## Protein
The human protein deglycase DJ-1 is 20 kDa in size and composed of 189 amino acids with seven β-strands and nine α-helices in total and is present as a dimer. It belongs to the peptidase C56 family of proteins.
The protein structures of human protein DJ-1, Escherichia coli chaperone Hsp31, YhbO and YajL and an Archaea protease are evolutionarily conserved.
# Function
Under an oxidative condition, protein deglycase DJ-1 inhibits the aggregation of α-synuclein via its chaperone activity, thus functions as a redox-sensitive chaperone and as a sensor for oxidative stress. Accordingly, DJ-1 apparently protects neurons against oxidative stress and cell death. In parallel, Protein DJ-1 acts as a positive regulator of androgen receptor-dependent transcription.
Pyrroloquinoline quinone (PQQ) has been shown to reduce the self-oxidation of the DJ-1 protein, an early step in the onset of some forms of Parkinson's disease.
Functional DJ-1 protein has been shown to bind metals and protect against metal-induced cytotoxicity from copper and mercury.
# Clinical significance
Defects in this gene are the cause of autosomal recessive early-onset Parkinson's disease 7.
# Interactions
PARK7 has been shown to interact with:
- CASK,
- EFCAB6, and
- PIAS2. | PARK7
Protein deglycase DJ-1, also known as Parkinson disease protein 7, is a protein which in humans is encoded by the PARK7 gene.[1]
# Structure
## Gene
The gene PARK7, also known as DJ-1, encodes a protein of the peptidase C56 family. The human gene PARK7 has 8 Exons and locates at chromosome band 1p36.23.[1]
## Protein
The human protein deglycase DJ-1 is 20 kDa in size and composed of 189 amino acids with seven β-strands and nine α-helices in total and is present as a dimer.[2][3][4] It belongs to the peptidase C56 family of proteins.
The protein structures of human protein DJ-1, Escherichia coli chaperone Hsp31, YhbO and YajL and an Archaea protease are evolutionarily conserved.[5]
# Function
Under an oxidative condition, protein deglycase DJ-1 inhibits the aggregation of α-synuclein via its chaperone activity,[6][7] thus functions as a redox-sensitive chaperone and as a sensor for oxidative stress. Accordingly, DJ-1 apparently protects neurons against oxidative stress and cell death.[1] In parallel, Protein DJ-1 acts as a positive regulator of androgen receptor-dependent transcription.
Pyrroloquinoline quinone (PQQ) has been shown to reduce the self-oxidation of the DJ-1 protein, an early step in the onset of some forms of Parkinson's disease.[8]
Functional DJ-1 protein has been shown to bind metals and protect against metal-induced cytotoxicity from copper and mercury.[9]
# Clinical significance
Defects in this gene are the cause of autosomal recessive early-onset Parkinson's disease 7.[1][10]
# Interactions
PARK7 has been shown to interact with:
- CASK,[11]
- EFCAB6,[12] and
- PIAS2.[13] | https://www.wikidoc.org/index.php/DJ-1 | |
f1972a92f57b5dcbf23f93b663eae691edc36ecf | wikidoc | DMAC1 | DMAC1
Transmembrane protein 261 is a protein that in humans is encoded by the TMEM261 gene located on chromosome 9. TMEM261 is also known as C9ORF123 and DMAC1, Chromosome 9 Open Reading Frame 123 and Transmembrane Protein C9orf123 and Distal membrane-arm assembly complex protein 1.
# Gene Features
TMEM261 is located at 9p24.1, its length is 91,891 base pairs (bp) on the reverse strand. Its neighbouring gene is PTPRD located at 9p23-p24.3 also on the reverse strand and encodes protein tyrosine phosphatase receptor type delta.
TMEM261 has 2 exons and 1 intron, and 6 primary transcript variants; the largest mRNA transcript variant consisting of 742bp with a protein 129 amino acids (aa) in length and 13,500 Daltons (Da) in size, and the smallest coding transcript variant being 381bp with a protein 69aa long and 6,100 Da in size.
# Protein Features
TMEM261 is a protein consisting out of 112 amino acids, with a molecular weight of 11.8 kDa. The isoelectric point is predicted to be 10.2, whilst its posttranslational modification value is 9.9.
## Structure
TMEM261 contains a domain of unknown function, DUF4536 (pfam15055), predicted as a helical membrane spanning domain about 45aa (Cys 47- Ser 92) in length with no known domain relationships. Two further transmembrane helical domains are predicted of lengths 18aa (Val 52-Ala 69) and 23aa (Pro 81-Ala 102]). There is also a low complexity region spanning 25aa (Thr 14-Ala 39). The tertiary structure for TMEM261 has not yet been determined. However, its protein secondary structure is mostly composed of coiled-coil regions with beta strands and alpha helices found within the transmembrane and domain of unknown function regions. The N-terminal region of TMEM261 is composed of a disordered region which contains the low complexity region that is not highly conserved amongst orthologues.
## Modifications
A N-myristoylation domain is shown to be present in most TMEM261 protein variants. Post-translational modifications include myristoylation of the N-terminal Glycine residue (Gly2) of the TMEM261 protein as well as phosphorylation of Threonine 31.
## Interactions
Proteins shown to interact with TMEM261 include NAAA (protein-protein interaction), QTRT1 (RNA-protein interaction),ZC4H2(DNA-protein interaction) and ZNF454(DNA-protein interaction). It has also shown to interact with APP(protein-protein interaction), ARHGEF38(protein-protein interaction) and HNRNPD(RNA-protein interaction).
Additional transcription factor binding sites (DNA-protein interaction) predicted include one binding site for MEF2C a monocyte-specific enhancement factor that is involved in muscle-cell regulation particularly in the cardiovascular system and two binding sites for GATA1 which is a globin transcription factor 1 involved in erythroblast development regulation.
# Expression
TMEM261 shows ubiquitous expression in humans and is detected in almost all tissue types. It shows tissue-enriched gene (TEG) expression when compared to housekeeping gene (HKG) expression. Its highest expression is seen in the heart (overall relative expression 94%) particularly in heart fibroblast cells, thymus (overall relative expression 90%), and thyroid (overall relative expression 93%) particularly in thyroid glandular cells. Staining intensity of cancer cells showed intermediate to high expression in breast, colorectal, ovarian, skin, urothelial, head and neck cells.
# Function
Currently the function for TMEM261 is unknown. However, gene amplification and rearrangements of its locus have been associated with various cancers including colorectal cancer,
breast cancer and lymphomas.
# Evolution
## Orthologues
The orthologues and homologues of TMEM261 are limited to vertebrates, its oldest homologue dates to that of the cartilaginous fishes which diverged from Homo sapiens 462.5 million years ago. The protein primary structure of TMEM261 shows higher overall conservation in mammals, however high conservation of the domain of unknown function (DUF4536) to the C-terminus region is seen in all orthologues, including distant homologues. The protein structure of TMEM261 shows conservation across most orthologues.
## Paralogues
TMEM261 has no known paralogs. | DMAC1
Transmembrane protein 261 is a protein that in humans is encoded by the TMEM261 gene located on chromosome 9.[1] TMEM261 is also known as C9ORF123 and DMAC1, Chromosome 9 Open Reading Frame 123 and Transmembrane Protein C9orf123[2] and Distal membrane-arm assembly complex protein 1[3].
# Gene Features
TMEM261 is located at 9p24.1, its length is 91,891 base pairs (bp) on the reverse strand.[2] Its neighbouring gene is PTPRD located at 9p23-p24.3 also on the reverse strand and encodes protein tyrosine phosphatase receptor type delta.[1][2]
TMEM261 has 2 exons and 1 intron, and 6 primary transcript variants; the largest mRNA transcript variant consisting of 742bp with a protein 129 amino acids (aa) in length and 13,500 Daltons (Da) in size, and the smallest coding transcript variant being 381bp with a protein 69aa long and 6,100 Da in size.[4][5]
# Protein Features
TMEM261 is a protein consisting out of 112 amino acids, with a molecular weight of 11.8 kDa.[6] The isoelectric point is predicted to be 10.2,[7] whilst its posttranslational modification value is 9.9.[5]
## Structure
TMEM261 contains a domain of unknown function, DUF4536 (pfam15055), predicted as a helical membrane spanning domain about 45aa (Cys 47- Ser 92) in length with no known domain relationships.[8][9] Two further transmembrane helical domains are predicted of lengths 18aa (Val 52-Ala 69) and 23aa (Pro 81-Ala 102]).[10][11] There is also a low complexity region spanning 25aa (Thr 14-Ala 39).[12] The tertiary structure for TMEM261 has not yet been determined. However, its protein secondary structure is mostly composed of coiled-coil regions with beta strands and alpha helices found within the transmembrane and domain of unknown function regions. The N-terminal region of TMEM261 is composed of a disordered region[13][14] which contains the low complexity region[12] that is not highly conserved amongst orthologues.[15][16]
## Modifications
A N-myristoylation domain is shown to be present in most TMEM261 protein variants.[5] Post-translational modifications include myristoylation of the N-terminal Glycine residue (Gly2)[5][17] of the TMEM261 protein as well as phosphorylation of Threonine 31.[18]
## Interactions
Proteins shown to interact with TMEM261 include NAAA (protein-protein interaction), QTRT1 (RNA-protein interaction),ZC4H2(DNA-protein interaction)[19] and ZNF454(DNA-protein interaction).[20][21] It has also shown to interact with APP(protein-protein interaction),[22] ARHGEF38(protein-protein interaction)[23] and HNRNPD(RNA-protein interaction).[24][25]
Additional transcription factor binding sites (DNA-protein interaction) predicted include one binding site for MEF2C a monocyte-specific enhancement factor that is involved in muscle-cell regulation particularly in the cardiovascular system [2][27] and two binding sites for GATA1 which is a globin transcription factor 1 involved in erythroblast development regulation.[28][29][30]
# Expression
TMEM261 shows ubiquitous expression in humans and is detected in almost all tissue types.[31][32] It shows tissue-enriched gene (TEG) expression when compared to housekeeping gene (HKG) expression.[26] Its highest expression is seen in the heart (overall relative expression 94%) particularly in heart fibroblast cells, thymus (overall relative expression 90%), and thyroid (overall relative expression 93%) particularly in thyroid glandular cells.[26][31] Staining intensity of cancer cells showed intermediate to high expression in breast, colorectal, ovarian, skin, urothelial, head and neck cells.[31]
# Function
Currently the function for TMEM261 is unknown.[33] However, gene amplification and rearrangements of its locus have been associated with various cancers including colorectal cancer,[34]
breast cancer[35] and lymphomas.[36][37]
# Evolution
## Orthologues
The orthologues and homologues of TMEM261 are limited to vertebrates, its oldest homologue dates to that of the cartilaginous fishes[38] which diverged from Homo sapiens 462.5 million years ago.[39] The protein primary structure of TMEM261 shows higher overall conservation in mammals, however high conservation of the domain of unknown function (DUF4536) to the C-terminus region is seen in all orthologues, including distant homologues. The protein structure of TMEM261 shows conservation across most orthologues.[15][16]
## Paralogues
TMEM261 has no known paralogs.[38] | https://www.wikidoc.org/index.php/DMAC1 | |
c105932896530afcbb152fa38a4dbcdbd14e2f8d | wikidoc | DMBT1 | DMBT1
Deleted in malignant brain tumors 1 protein is a protein that in humans is encoded by the DMBT1 gene.
# Function
Loss of sequences from human chromosome 10q has been associated with the progression of human cancers. The gene DMBT1 was originally isolated based on its deletion in a medulloblastoma cell line. DMBT1 is expressed with transcripts of 6.0, 7.5, and 8.0 kb in fetal lung and with one transcript of 8.0 kb in adult lung, although the 7.5 kb transcript has not been characterized. The DMBT1 protein is a glycoprotein containing multiple scavenger receptor cysteine-rich (SRCR) domains separated by SRCR-interspersed domains (SID). Transcript variant 2 (8.0 kb) has been shown to bind surfactant protein D independently of carbohydrate recognition. This indicates that DMBT1 may not be a classical tumor suppressor gene, but rather play a role in the interaction of tumor cells and the immune system.
# Pattern recognition and potential use of DMBT1 in nanomedicine
At epithelial barriers molecular pattern recognition mechanisms act as minesweepers against harmful environmental factors and thereby play a crucial role in the defense against invading bacterial and viral pathogens. However, it became evident that some of the proteins participating in these host defense processes may simultaneously function as regulators of tissue regeneration when in the extracellular matrix, thus coupling defense functions with regulation of stem cells. Although molecular pattern recognition has complex physiological roles and we just begin to understand its various functions, the simplicity of the underlying principles for recognition of specific classes of molecules may generate novel starting points for nanomedical approaches in drug delivery across epithelial barriers. The protein DMBT1, showed pattern recognition activity for poly-sulfated and poly-phosphorylated ligands, including nucleic acids, and the ability to aggregate ligands. This raises the interesting question in how far these properties can be utilized to assemble nucleic acidpeptide nano-complexes and whether this can be exploited to modulate the pharmacological properties of nucleic acids and/or for nucleic acid delivery to target cells Recently, DMBT1-derived peptides have been successfully harnessed for siRNA intracellular delivery.
# Interactions
DMBT1 has been shown to interact with Surfactant protein D. DMBT1-derived peptides also interacts with nucleic acids. | DMBT1
Deleted in malignant brain tumors 1 protein is a protein that in humans is encoded by the DMBT1 gene.[1][2]
# Function
Loss of sequences from human chromosome 10q has been associated with the progression of human cancers. The gene DMBT1 was originally isolated based on its deletion in a medulloblastoma cell line. DMBT1 is expressed with transcripts of 6.0, 7.5, and 8.0 kb in fetal lung and with one transcript of 8.0 kb in adult lung, although the 7.5 kb transcript has not been characterized. The DMBT1 protein is a glycoprotein containing multiple scavenger receptor cysteine-rich (SRCR) domains separated by SRCR-interspersed domains (SID). Transcript variant 2 (8.0 kb) has been shown to bind surfactant protein D independently of carbohydrate recognition. This indicates that DMBT1 may not be a classical tumor suppressor gene, but rather play a role in the interaction of tumor cells and the immune system.[3]
# Pattern recognition and potential use of DMBT1 in nanomedicine
At epithelial barriers molecular pattern recognition mechanisms act as minesweepers against harmful environmental factors and thereby play a crucial role in the defense against invading bacterial and viral pathogens. However, it became evident that some of the proteins participating in these host defense processes may simultaneously function as regulators of tissue regeneration when in the extracellular matrix, thus coupling defense functions with regulation of stem cells. Although molecular pattern recognition has complex physiological roles and we just begin to understand its various functions, the simplicity of the underlying principles for recognition of specific classes of molecules may generate novel starting points for nanomedical approaches in drug delivery across epithelial barriers. The protein DMBT1, showed pattern recognition activity for poly-sulfated and poly-phosphorylated ligands, including nucleic acids, and the ability to aggregate ligands. This raises the interesting question in how far these properties can be utilized to assemble nucleic acidpeptide nano-complexes and whether this can be exploited to modulate the pharmacological properties of nucleic acids and/or for nucleic acid delivery to target cells [4] Recently, DMBT1-derived peptides have been successfully harnessed for siRNA intracellular delivery. [5]
# Interactions
DMBT1 has been shown to interact with Surfactant protein D.[6][7] DMBT1-derived peptides also interacts with nucleic acids. [5] | https://www.wikidoc.org/index.php/DMBT1 | |
e77675e7584e1c32720727335ec3e1900cb9be89 | wikidoc | DMRT1 | DMRT1
Doublesex and mab-3 related transcription factor 1, also known as DMRT1, is a protein which in humans is encoded by the DMRT1 gene.
# Function
This gene is found in a cluster with two other members of the gene family, having in common a zinc finger-like DNA-binding motif (DM domain). The DM domain is an ancient, conserved component of the vertebrate sex-determining pathway that is also a key regulator of male development in flies and nematodes, and is found to be the key sex-determining factor in chickens.
This gene exhibits a gonad-specific and sexually dimorphic expression pattern, just like the related doublesex gene in fruit flies. Defective testicular development and XY feminization occur when this gene is hemizygous.
The DMRT1 gene is located at the end of the 9th chromosome. This gene is a dose sensitive transcription factor protein that regulates Sertoli cells and germ cell. The majority DMRT1 protein is located in the testicular cord and Sertoli cells, with a small amount in the germ cells. Two copies of the DMRT1 gene are required for normal sexual development. When a DMRT1 gene is lost the most common disease is chromosome 9p deletion, which causes abnormal testicular formation and feminization. The DMRT1 gene is critical in the male sex determination and without this gene the default female characteristic takes over and male characteristic is slight or non-existent. In the knockout model of this gene, the mice showed changes in both Sertoli and germ cells soon after the gonadal ridge was formed. The main defects associated with this knockout gene were developmental arrest, excess proliferation of germ cells, and failure to undergo meiosis, mitosis, or migration. Thus, the knockout model shows that loss of the DMRT1 gene is associated with incomplete germ cell development leading to infertility, abnormal testicular formation, and/or feminization of the affected individual. | DMRT1
Doublesex and mab-3 related transcription factor 1, also known as DMRT1, is a protein which in humans is encoded by the DMRT1 gene.[1][2][3]
# Function
This gene is found in a cluster with two other members of the gene family, having in common a zinc finger-like DNA-binding motif (DM domain). The DM domain is an ancient, conserved component of the vertebrate sex-determining pathway that is also a key regulator of male development in flies and nematodes, and is found to be the key sex-determining factor in chickens.[4]
This gene exhibits a gonad-specific and sexually dimorphic expression pattern, just like the related doublesex gene in fruit flies. Defective testicular development and XY feminization occur when this gene is hemizygous.[1]
The DMRT1 gene is located at the end of the 9th chromosome. This gene is a dose sensitive transcription factor protein that regulates Sertoli cells and germ cell. The majority DMRT1 protein is located in the testicular cord and Sertoli cells, with a small amount in the germ cells. Two copies of the DMRT1 gene are required for normal sexual development. When a DMRT1 gene is lost the most common disease is chromosome 9p deletion, which causes abnormal testicular formation and feminization. The DMRT1 gene is critical in the male sex determination and without this gene the default female characteristic takes over and male characteristic is slight or non-existent. In the knockout model of this gene, the mice showed changes in both Sertoli and germ cells soon after the gonadal ridge was formed. The main defects associated with this knockout gene were developmental arrest, excess proliferation of germ cells, and failure to undergo meiosis, mitosis, or migration. Thus, the knockout model shows that loss of the DMRT1 gene is associated with incomplete germ cell development leading to infertility, abnormal testicular formation, and/or feminization of the affected individual. | https://www.wikidoc.org/index.php/DMRT1 | |
7cf0976fb87dc39963cae0a797679178ffc23936 | wikidoc | DMXL2 | DMXL2
Dmx-like 2 is a protein that in humans is encoded by the DMXL2 gene.
# Function
This gene encodes a protein with 12 WD domains. Proteins with WD domains are involved in many functions including participation in signal transduction pathways. Participation of the encoded protein in regulation of the Notch signaling pathway has been demonstrated in vitro using several human cell lines (.mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}PMID 20810660). A gene encoding a similar protein is located on chromosome 5. Multiple transcript variants encoding different isoforms have been found for this gene.
# Clinical relevance
Haplosufficiency of Dmxl2 has been identified as the cause of Polyendocrine-polyneuropathy syndrome, and delayed puberty. Research has indicated that this is a result of altered function of CNS synapses (in which the protein product of Dmxl2 is expressed) causing altered activation of the GnRH neurons of the hypothalamus. | DMXL2
Dmx-like 2 is a protein that in humans is encoded by the DMXL2 gene.
[1]
# Function
This gene encodes a protein with 12 WD domains. Proteins with WD domains are involved in many functions including participation in signal transduction pathways. Participation of the encoded protein in regulation of the Notch signaling pathway has been demonstrated in vitro using several human cell lines (.mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}PMID 20810660). A gene encoding a similar protein is located on chromosome 5. Multiple transcript variants encoding different isoforms have been found for this gene.
# Clinical relevance
Haplosufficiency of Dmxl2 has been identified as the cause of Polyendocrine-polyneuropathy syndrome, and delayed puberty. Research has indicated that this is a result of altered function of CNS synapses (in which the protein product of Dmxl2 is expressed) causing altered activation of the GnRH neurons of the hypothalamus. | https://www.wikidoc.org/index.php/DMXL2 | |
445f133b71042c125252f2203b93427de8ce7603 | wikidoc | DNAI2 | DNAI2
Dynein intermediate chain 2, axonemal, also known as axonemal dynein intermediate chain 2, is a protein that in humans is encoded by the DNAI2 gene.
# Function
The protein encoded by this gene belongs to the dynein intermediate chain family, and is part of the dynein complex of respiratory cilia and sperm flagella.
# Clinical significance
Mutations in the DNAI2 gene are associated with primary ciliary dyskinesia. | DNAI2
Dynein intermediate chain 2, axonemal, also known as axonemal dynein intermediate chain 2, is a protein that in humans is encoded by the DNAI2 gene.[1][2]
# Function
The protein encoded by this gene belongs to the dynein intermediate chain family, and is part of the dynein complex of respiratory cilia and sperm flagella.[1]
# Clinical significance
Mutations in the DNAI2 gene are associated with primary ciliary dyskinesia.[3] | https://www.wikidoc.org/index.php/DNAI2 | |
a2e3811c7ecdeeb2b58a83f94f56acef465e9fdc | wikidoc | DNAL1 | DNAL1
Dynein light chain 1, axonemal is a protein that in humans is encoded by the DNAL1 gene.
# Function
DNAL1 is a component of outer dynein arms, which contain the molecular motors for ATP-dependent cilia movement.
# Clinical significance
Mutations in the DNAL1 gene are associated with primary ciliary dyskinesia. | DNAL1
Dynein light chain 1, axonemal is a protein that in humans is encoded by the DNAL1 gene.[1][2]
# Function
DNAL1 is a component of outer dynein arms, which contain the molecular motors for ATP-dependent cilia movement.[1][2]
# Clinical significance
Mutations in the DNAL1 gene are associated with primary ciliary dyskinesia.[3] | https://www.wikidoc.org/index.php/DNAL1 | |
477a4efe691fef9038d25ff21537771e1464df43 | wikidoc | DNM1L | DNM1L
Dynamin-1-like protein is a GTPase that regulates mitochondrial fission. In humans, dynamin-1-like protein, which is typically referred to as dynamin-related protein 1 (Drp1), is encoded by the DNM1L gene.
# Structure
Drp1, which is a member of the dynamin superfamily of proteins, consists of a GTPase and GTPase effector domain that are separated from each other by a helical segment of amino acids. There are 3 mouse and 6 human isoforms of Drp1, including a brain-specific variant. Drp1 exists as homooligomers and its function relies on its oligomerization ability.
# Function
Mitochondria routinely undergo fission and fusion events that maintain a dynamic reticular network. Drp1 is a fundamental component of mitochondrial fission. Indeed, Drp1 deficient neurons have large, strongly interconnected mitochondria., due to dysfunctional fission machinery. Fission helps facilitate mitophagy, which is the breakdown and recycling of damaged mitochondria. Dysfunction in the DRP activity may result in mutated DNA or malfunctioning proteins diffusing throughout the mitochondrial system. In addition, fission results in fragmented mitochondria more capable of producing of reactive oxygen species, which can disrupt normal biochemical processes inside of cells. ROS can be formed from incomplete transfer of electrons through the electron transport chain. Furthermore, fission influences calcium flux within the cell, linking Drp1 to apoptosis and cancer.
Several studies have indicated that Drp1 is essential for proper embryonic development. Drp1 knockout mice exhibit abnormal brain development and die around embryonic day 12. In neural specific Drp1 knockout mice, brain size is reduced and apoptosis is increased. Synapse formation and neurite growth are also impaired. A second group of researchers generated another neural specific knockout mouse line. They found that knocking out Drp1 resulted in the appearance of large mitochondria in Purkinje cells and prevented neural tube formation.
In humans, loss of Drp1 function affects brain development and is also associated with early mortality.
# Interactions
The majority of knowledge about mitochondrial fission comes from studies with yeast. The yeast homolog of Drp1 is dynamin-1 (Dnm1), which interacts with Fis1 through Mdv1. This interaction causes Dnm1 to oligomerize and form rings around dividing mitochondria at the so-called "constriction point". Drp1 has also been shown to interact with GSK3B. In mammals, Drp1 receptors include Mff, Mid49 and Mid51
Post-translational modifications to Drp1 (e.g. phosphorylation) can alter its activity and affect the rate of fission.
Drp1 has two major phosphorylation sites. The CDK phosphorylation site is S579, and the PKA site is S600 in Drp1 isoform 3. Phosphorylation by CDK is thought to be activating, whereas PKA phosphorylation is thought to be inhibitory. Recently, CaMKII was shown to phosphorylate Drp1 at S616. This was shown to occur in response to chronic Beta-adrenergic stimulation and to promote mPTP opening. Other post-translational modifications include S-nitrosylation, sumoylation, and ubiquitination. Higher S- nitrosylation modifications of Drp1, which enhances Drp1 activity, have been observed in Alzheimer’s Disease. Furthermore, Drp1 has been shown to interact with Aβ monomers, thought to play an important role in Alzheimer’s Disease, exacerbating the disease and its symptoms. Drp1 has been linked to a number of pathways and processes including cell division, apoptosis, and necrosis. Drp1 has been shown to stabilize p53 during oxidative stress, promoting its translocation to the mitochondria and encouraging mitochondrial- related necrosis. In addition, cyclin B1- CDK activates Drp1, causing fragmentation and ensuring mitochondria are distributed to each daughter cell after mitosis. Likewise, different transcriptional controllers are able to alter Drp1 activity through gene expression and regulation. For example, PPARGC1A and regulated Drp1 activity through gene expression.
# Therapy
Inhibition of Drp1 has been considered for possible therapeutics for a variety of diseases. The most studied inhibitor is a small molecule named mitochondrial division inhibitor 1 (mdivi¬1) which in fact inhibits complex 1 on the mitochondrial respiratory chain. The inhibitors putative function is preventing the GTPase activity of Drp1. Preventing the activation and localization to the mitochondria. Midiv-1 has been demonstrated to attenuate the effects of ischemia reperfusion injury after cardiac arrest. The treatment prevented both mitochondria fragmentation and increased cell viability. Similarly, midiv-1 has demonstrated neuroprotective effects by greatly reducing neuron death due to seizure. Furthermore, the study showed midiv-1 was capable to preventing the activation of caspase 3 by reversing the release of cytochrome c in intrinsic apoptosis. Whether mdivi-1 inhibits Drp1 or not, it's therapeutic potential is certainly evident. Other than directly inhibiting Drp1, certain inhibitors of proteins involved in the posttranslational modifications of Drp1 have been studied. FK506 is a calcineurin inhibitor, which functions to dephosphorylate the serine 637 position of Drp1, encouraging translocation to the mitochondria and fragmentation. FK506 was shown to also preserve mitochondrial morphology after reperfusion injury. | DNM1L
Dynamin-1-like protein is a GTPase that regulates mitochondrial fission. In humans, dynamin-1-like protein, which is typically referred to as dynamin-related protein 1 (Drp1), is encoded by the DNM1L gene.[1][2][3]
# Structure
Drp1, which is a member of the dynamin superfamily of proteins, consists of a GTPase and GTPase effector domain that are separated from each other by a helical segment of amino acids.[4] There are 3 mouse and 6 human isoforms of Drp1, including a brain-specific variant.[5] Drp1 exists as homooligomers and its function relies on its oligomerization ability.[6]
# Function
Mitochondria routinely undergo fission and fusion events that maintain a dynamic reticular network. Drp1 is a fundamental component of mitochondrial fission.[7] Indeed, Drp1 deficient neurons have large, strongly interconnected mitochondria.,[8] due to dysfunctional fission machinery. Fission helps facilitate mitophagy, which is the breakdown and recycling of damaged mitochondria. Dysfunction in the DRP activity may result in mutated DNA or malfunctioning proteins diffusing throughout the mitochondrial system. In addition, fission results in fragmented mitochondria more capable of producing of reactive oxygen species, which can disrupt normal biochemical processes inside of cells.[9] ROS can be formed from incomplete transfer of electrons through the electron transport chain. Furthermore, fission influences calcium flux within the cell, linking Drp1 to apoptosis and cancer.[10]
Several studies have indicated that Drp1 is essential for proper embryonic development. Drp1 knockout mice exhibit abnormal brain development and die around embryonic day 12. In neural specific Drp1 knockout mice, brain size is reduced and apoptosis is increased. Synapse formation and neurite growth are also impaired. A second group of researchers generated another neural specific knockout mouse line. They found that knocking out Drp1 resulted in the appearance of large mitochondria in Purkinje cells and prevented neural tube formation.[5]
In humans, loss of Drp1 function affects brain development and is also associated with early mortality.[4]
# Interactions
The majority of knowledge about mitochondrial fission comes from studies with yeast. The yeast homolog of Drp1 is dynamin-1 (Dnm1), which interacts with Fis1 through Mdv1. This interaction causes Dnm1 to oligomerize and form rings around dividing mitochondria at the so-called "constriction point".[4][11] Drp1 has also been shown to interact with GSK3B.[2] In mammals, Drp1 receptors include Mff, Mid49 and Mid51[12][13]
Post-translational modifications to Drp1 (e.g. phosphorylation) can alter its activity and affect the rate of fission.[14]
Drp1 has two major phosphorylation sites. The CDK phosphorylation site is S579, and the PKA site is S600 in Drp1 isoform 3. Phosphorylation by CDK is thought to be activating, whereas PKA phosphorylation is thought to be inhibitory. Recently, CaMKII was shown to phosphorylate Drp1 at S616. This was shown to occur in response to chronic Beta-adrenergic stimulation and to promote mPTP opening.[15] Other post-translational modifications include S-nitrosylation, sumoylation, and ubiquitination. Higher S- nitrosylation modifications of Drp1, which enhances Drp1 activity, have been observed in Alzheimer’s Disease. Furthermore, Drp1 has been shown to interact with Aβ monomers, thought to play an important role in Alzheimer’s Disease, exacerbating the disease and its symptoms.[16] Drp1 has been linked to a number of pathways and processes including cell division, apoptosis, and necrosis. Drp1 has been shown to stabilize p53 during oxidative stress, promoting its translocation to the mitochondria and encouraging mitochondrial- related necrosis.[17] In addition, cyclin B1- CDK activates Drp1, causing fragmentation and ensuring mitochondria are distributed to each daughter cell after mitosis. Likewise, different transcriptional controllers are able to alter Drp1 activity through gene expression and regulation. For example, PPARGC1A and [HIF1A] regulated Drp1 activity through gene expression.[9]
# Therapy
Inhibition of Drp1 has been considered for possible therapeutics for a variety of diseases. The most studied inhibitor is a small molecule named mitochondrial division inhibitor 1 (mdivi¬1) which in fact inhibits complex 1 on the mitochondrial respiratory chain.[18] The inhibitors putative function is preventing the GTPase activity of Drp1. Preventing the activation and localization to the mitochondria.[9] Midiv-1 has been demonstrated to attenuate the effects of ischemia reperfusion injury after cardiac arrest. The treatment prevented both mitochondria fragmentation and increased cell viability.[19] Similarly, midiv-1 has demonstrated neuroprotective effects by greatly reducing neuron death due to seizure. Furthermore, the study showed midiv-1 was capable to preventing the activation of caspase 3 by reversing the release of cytochrome c in intrinsic apoptosis.[20] Whether mdivi-1 inhibits Drp1 or not, it's therapeutic potential is certainly evident. Other than directly inhibiting Drp1, certain inhibitors of proteins involved in the posttranslational modifications of Drp1 have been studied. FK506 is a calcineurin inhibitor, which functions to dephosphorylate the serine 637 position of Drp1, encouraging translocation to the mitochondria and fragmentation. FK506 was shown to also preserve mitochondrial morphology after reperfusion injury.[19] | https://www.wikidoc.org/index.php/DNM1L | |
f62064537d8eafd52abe8b48af272a38462fe93a | wikidoc | DNPEP | DNPEP
Aspartyl aminopeptidase is an enzyme that in humans is encoded by the DNPEP gene.
# Function
The protein encoded by this gene is an aminopeptidase which prefers acidic amino acids, and specifically favors aspartic acid over glutamic acid. It is thought to be a cytosolic protein involved in general metabolism of intracellular proteins.
# Model organisms
Model organisms have been used in the study of DNPEP function. A conditional knockout mouse line called Dnpeptm1e(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping | DNPEP
Aspartyl aminopeptidase is an enzyme that in humans is encoded by the DNPEP gene.[1][2]
# Function
The protein encoded by this gene is an aminopeptidase which prefers acidic amino acids, and specifically favors aspartic acid over glutamic acid. It is thought to be a cytosolic protein involved in general metabolism of intracellular proteins.[2]
# Model organisms
Model organisms have been used in the study of DNPEP function. A conditional knockout mouse line called Dnpeptm1e(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[3] Male and female animals underwent a standardized phenotypic screen[4] to determine the effects of deletion.[5][6][7][8] Additional screens performed: - In-depth immunological phenotyping[9] | https://www.wikidoc.org/index.php/DNPEP | |
34dcdb1416917cdffca23b58c8ec52a7b4adaf30 | wikidoc | DORN1 | DORN1
DORN1 refers to a purinergic receptor found in green plants, which is involved in extracellular ATP detection. Through the process of signal transduction, DORN1 couples ATP binding (which occurs during cellular stress) to downstream signalling and ultimately gene expression, which is thought to aid in plant survival.
# Molecular properties
In contrast to animal purinergic receptors (which are G protein-coupled receptors), DORN1 is a lectin receptor kinase (LecRK), and is part of the L type lectin receptor kinases, due to its legume-like extracellular domain.
In green plants such as Arabidopsis thaliana, several mutants lacking the DORN1 receptors are unable to phosphorylate mitogen-activated protein kinases after ATP stimulation.
# Function
DORN1 receptors may play a role in mediating wound-induced inflammatory responses in green plants, with ATP acting as a damage-associated molecular pattern molecule. In response to cell lysis, ATP is discharged and binds onto the extracellular lectin domain of the DORN1 receptor. The intracellular DORN1 kinase domain is subsequently activated, resulting in several cellular responses such as mitogen-activated protein kinase activation, increased cytosolic calcium concentration and reactive oxygen species (ROS) production, ultimately leading to the induction of defence gene expression. | DORN1
DORN1 refers to a purinergic receptor found in green plants, which is involved in extracellular ATP detection.[1] Through the process of signal transduction, DORN1 couples ATP binding (which occurs during cellular stress) to downstream signalling and ultimately gene expression, which is thought to aid in plant survival.[1] [2]
# Molecular properties
In contrast to animal purinergic receptors (which are G protein-coupled receptors), DORN1 is a lectin receptor kinase (LecRK)[2], and is part of the L type lectin receptor kinases, due to its legume-like extracellular domain. [3]
In green plants such as Arabidopsis thaliana, several mutants lacking the DORN1 receptors are unable to phosphorylate mitogen-activated protein kinases after ATP stimulation.[4]
# Function
DORN1 receptors may play a role in mediating wound-induced inflammatory responses in green plants, with ATP acting as a damage-associated molecular pattern molecule. In response to cell lysis, ATP is discharged and binds onto the extracellular lectin domain of the DORN1 receptor. The intracellular DORN1 kinase domain is subsequently activated, resulting in several cellular responses such as mitogen-activated protein kinase activation, increased cytosolic calcium concentration and reactive oxygen species (ROS) production, ultimately leading to the induction of defence gene expression.[2] [5] | https://www.wikidoc.org/index.php/DORN1 | |
11207d608367b0d81d604fc05e26d0fbbb803581 | wikidoc | DOT1L | DOT1L
DOT1-like (Disruptor of telomeric silencing 1-like), histone H3K79 methyltransferase (S. cerevisiae), also known as DOT1L, is a protein found in humans, as well as other eukaryotes.
The methylation of histone H3 lysine 79 (H3K79) by DOT1L which is a conserved epigenetic mark in many eukaryotic epigenomes, increases progressively along the aging process, suggesting that "DOT1L might function as a vital clock, ticking the hours impassively".
DOT1L has been reported to play an important role in the processes of mixed-lineage leukemia (MLL)-rearranged leukemias
Small molecule inhibitors of Dot1L catalytic activity have been developed. | DOT1L
DOT1-like (Disruptor of telomeric silencing 1-like), histone H3K79 methyltransferase (S. cerevisiae), also known as DOT1L, is a protein found in humans, as well as other eukaryotes.[1][2]
The methylation of histone H3 lysine 79 (H3K79) by DOT1L which is a conserved epigenetic mark in many eukaryotic epigenomes, increases progressively along the aging process, suggesting that "DOT1L might function as a vital clock, ticking the hours impassively".[3]
DOT1L has been reported to play an important role in the processes of mixed-lineage leukemia (MLL)-rearranged leukemias[4]
Small molecule inhibitors of Dot1L catalytic activity have been developed.[5][6] | https://www.wikidoc.org/index.php/DOT1L | |
cc489844d0b96549804b32422887fd4c6be53766 | wikidoc | DPP10 | DPP10
Inactive dipeptidyl peptidase 10 is a protein that in humans is encoded by the DPP10 gene. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.
# Function
This gene encodes a single-pass type II membrane protein that is a member of the S9B family in clan SC of the serine proteases. This protein has no detectable protease activity, most likely due to the absence of the conserved serine residue normally present in the catalytic domain of serine proteases. However, it does bind specific voltage-gated potassium channels and alters their expression and biophysical properties.
# Clinical significance
Mutations in this gene have been associated with asthma and autism spectrum disorders. | DPP10
Inactive dipeptidyl peptidase 10 is a protein that in humans is encoded by the DPP10 gene.[1][2][3] Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[3]
# Function
This gene encodes a single-pass type II membrane protein that is a member of the S9B family in clan SC of the serine proteases. This protein has no detectable protease activity, most likely due to the absence of the conserved serine residue normally present in the catalytic domain of serine proteases. However, it does bind specific voltage-gated potassium channels and alters their expression and biophysical properties.[3]
# Clinical significance
Mutations in this gene have been associated with asthma[3] and autism spectrum disorders.[4] | https://www.wikidoc.org/index.php/DPP10 | |
bc7a03cb29fc64289ecbedb747688295b8a41cbc | wikidoc | DSCR1 | DSCR1
Down syndrome critical region gene 1, also known as DSCR1, is a protein that in humans is encoded by the DSCR1 gene.
RCAN1 is a gene that in humans encodes the protein DSCR1.
# Gene Location and Sequencing
DSCR1 in human is located at the centromeric border of the DSCR and encodes an inhibitor of calcineurin/ NFAT (nuclear factor activated T cells) signalling.
DSCR1 genomic sequence of total 45 kb contain 7 exons and 6 introns , different cDNA analysis yield first four exons are alternative and code for two isoforms of 197 amino acids, and one isoform code for 171 amino acids which differ in their N terminal . While the rest of the 168 residues are common. There is also alternative promotor region with about 900 bp between exon 3 and 4 suggesting that the fourth isoform might be penetrated from another promotor.
# Function
The protein encoded by this gene interacts with calcineurin A and inhibits calcineurin-dependent signaling pathways of genetic transcription, possibly affecting central nervous system development. Three transcript variants encoding three different isoforms have been found for this gene. In endothelial cells, VEGF stimulates RCAN1.4 expression which regulates gene expression, cell migration and tubular morphogenesis.
# Protein Structure
DSCR1 Consist of putative functional motifs and calcineurin binding domain. DSCR1 contains two proline-rich SH3 binding domain, usually named proline-rich domain (PRD), which defines the protein family. SH3 domains or PRD are very important to allow the binding of the protein to endocytosis-related proteins such as ITSN1 and amphiphysin 1 and 2.
# Clinical significance
This gene is located in the minimal candidate region for the Down syndrome phenotype, and is overexpressed in the brain of Down syndrome fetuses. Chronic overexpression of this gene may lead to neurofibrillary tangles such as those associated with Alzheimer's disease.
# Associated diseases
## Alzheimer disease and Down syndrome disease
All Down syndrome (DS) patients progress neuropathological changes identical to the pathogenesis of Alzheimer disease (AD) after their middle age, such as neurotic plaques and neuronal loss in their brain, Therefor, DS patients are perfect models to study AD pathogenesis.
Chronic DSCR1 overexpression is related with DS and, while its shortage is reported in Huntington’s disease. DSCR1 expressed excessively in the Central nervous system of embryos during their development, this protein is later overexpressed in differentiating neurons regions such as Brains of DS patients. However, neurotrophic peptide PACAP (or Pituitary adenylate cyclase-activating peptide) which is responsible for the development, differentiation, and survival, and various parts of memory and learning, Target RCNA1 in a Down syndrome related gene, induces the expression of regulator of calcineurin 1, through activation of the PKA-CREB pathway, and this is important to understand the mechanisms of neural differentiation and aim for proper expression of RCAN1.
## Cancer risk
It is suggested that the reason patients with Down's Syndrome are less predisposed to certain cancers is due to the impact of this gene of reducing blood supply to tumour cells.
It is also proposed by epidemiological studies that DS patients are in greater risk of Leukaemia , on the other hand they are at lower risk of cancer and other angiogenesis related diseases such as Diabetic retinopathy and Atherosclerosis , indicating that one or more trisomic genes on chromosome 21 is responsible for protecting DS patients against cancer, and this cancer defence could be a result of angiogenesis suppression.
# Interactions
DSCR1 has been shown to interact with Calcineurin.
Hydrogen peroxide (H2O2) increases the overexpression of protein RCAN1. However, anti-oxidants and inhibitors of mitogen-activated protein kinases (MAPK) treatment block the increased expression of RCAN1 by H2O2. Demonstrating that the increased expression is a result of generating reactive oxygen species and activation of MAPK. Furthermore, phosphorylation is important to regulator RCAN1 protein expression. Because phosphorylation of RCAN1 expression by H2O2 increases of the half-life of the protein. | DSCR1
Down syndrome critical region gene 1, also known as DSCR1, is a protein that in humans is encoded by the DSCR1 gene.[1]
RCAN1 is a gene that in humans encodes the protein DSCR1.
# Gene Location and Sequencing
DSCR1 in human is located at the centromeric border of the DSCR and encodes an inhibitor of calcineurin/ NFAT (nuclear factor activated T cells) signalling.[2]
DSCR1 genomic sequence of total 45 kb contain 7 exons and 6 introns , different cDNA analysis yield first four exons are alternative and code for two isoforms of 197 amino acids, and one isoform code for 171 amino acids which differ in their N terminal . While the rest of the 168 residues are common. There is also alternative promotor region with about 900 bp between exon 3 and 4 suggesting that the fourth isoform might be penetrated from another promotor.[3]
# Function
The protein encoded by this gene interacts with calcineurin A and inhibits calcineurin-dependent signaling pathways of genetic transcription, possibly affecting central nervous system development. Three transcript variants encoding three different isoforms have been found for this gene.[1] In endothelial cells, VEGF stimulates RCAN1.4 expression which regulates gene expression, cell migration and tubular morphogenesis.[4]
# Protein Structure
DSCR1 Consist of putative functional motifs and calcineurin binding domain. DSCR1 contains two proline-rich SH3 binding domain, usually named proline-rich domain (PRD), which defines the protein family. SH3 domains or PRD are very important to allow the binding of the protein to endocytosis-related proteins such as ITSN1 and amphiphysin 1 and 2.[5]
# Clinical significance
This gene is located in the minimal candidate region for the Down syndrome phenotype, and is overexpressed in the brain of Down syndrome fetuses. Chronic overexpression of this gene may lead to neurofibrillary tangles such as those associated with Alzheimer's disease.[1][6]
# Associated diseases
## Alzheimer disease and Down syndrome disease
All Down syndrome (DS) patients progress neuropathological changes identical to the pathogenesis of Alzheimer disease (AD) after their middle age, such as neurotic plaques and neuronal loss in their brain, Therefor, DS patients are perfect models to study AD pathogenesis.[7]
Chronic DSCR1 overexpression is related with DS and, while its shortage is reported in Huntington’s disease. DSCR1 expressed excessively in the Central nervous system of embryos during their development, this protein is later overexpressed in differentiating neurons regions such as Brains of DS patients. However, neurotrophic peptide PACAP (or Pituitary adenylate cyclase-activating peptide) which is responsible for the development, differentiation, and survival, and various parts of memory and learning, Target RCNA1 in a Down syndrome related gene, induces the expression of regulator of calcineurin 1, through activation of the PKA-CREB pathway, and this is important to understand the mechanisms of neural differentiation and aim for proper expression of RCAN1.[8]
## Cancer risk
It is suggested that the reason patients with Down's Syndrome are less predisposed to certain cancers is due to the impact of this gene of reducing blood supply to tumour cells.[9]
It is also proposed by epidemiological studies that DS patients are in greater risk of Leukaemia , on the other hand they are at lower risk of cancer and other angiogenesis related diseases such as Diabetic retinopathy and Atherosclerosis , indicating that one or more trisomic genes on chromosome 21 is responsible for protecting DS patients against cancer, and this cancer defence could be a result of angiogenesis suppression.[10]
# Interactions
DSCR1 has been shown to interact with Calcineurin.[11]
Hydrogen peroxide (H2O2) increases the overexpression of protein RCAN1. However, anti-oxidants and inhibitors of mitogen-activated protein kinases (MAPK) treatment block the increased expression of RCAN1 by H2O2. Demonstrating that the increased expression is a result of generating reactive oxygen species and activation of MAPK. Furthermore, phosphorylation is important to regulator RCAN1 protein expression. Because phosphorylation of RCAN1 expression by H2O2 increases of the half-life of the protein.[12] | https://www.wikidoc.org/index.php/DSCR1 | |
fb9519b982f951cf887a9a0d8fc0f6217a7fd469 | wikidoc | DUSP1 | DUSP1
Dual specificity protein phosphatase 1 is an enzyme that in humans is encoded by the DUSP1 gene.
# Function
The expression of DUSP1 gene is induced in human skin fibroblasts by oxidative/heat stress and growth factors. It specifies a protein with structural features similar to members of the non-receptor-type protein-tyrosine phosphatase family, and which has significant amino-acid sequence similarity to a Tyr/Ser-protein phosphatase encoded by the late gene H1 of vaccinia virus. The bacterially expressed and purified DUSP1 protein has intrinsic phosphatase activity, and specifically inactivates mitogen-activated protein (MAP) kinase in vitro by the concomitant dephosphorylation of both its phosphothreonine and phosphotyrosine residues. Furthermore, it suppresses the activation of MAP kinase by oncogenic ras in extracts of Xenopus oocytes. Thus, DUSP1 may play an important role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation.
# Interactions
DUSP1 has been shown to interact with MAPK14, MAPK1 and MAPK8. | DUSP1
Dual specificity protein phosphatase 1 is an enzyme that in humans is encoded by the DUSP1 gene.[1][2]
# Function
The expression of DUSP1 gene is induced in human skin fibroblasts by oxidative/heat stress and growth factors. It specifies a protein with structural features similar to members of the non-receptor-type protein-tyrosine phosphatase family, and which has significant amino-acid sequence similarity to a Tyr/Ser-protein phosphatase encoded by the late gene H1 of vaccinia virus. The bacterially expressed and purified DUSP1 protein has intrinsic phosphatase activity, and specifically inactivates mitogen-activated protein (MAP) kinase in vitro by the concomitant dephosphorylation of both its phosphothreonine and phosphotyrosine residues. Furthermore, it suppresses the activation of MAP kinase by oncogenic ras in extracts of Xenopus oocytes. Thus, DUSP1 may play an important role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation.[3]
# Interactions
DUSP1 has been shown to interact with MAPK14,[4][5] MAPK1[5][6] and MAPK8.[5] | https://www.wikidoc.org/index.php/DUSP1 | |
2131ea05cbebb9186be888aa43f01b47cf6aa4bf | wikidoc | DUSP3 | DUSP3
Dual specificity protein phosphatase 3 is an enzyme that in humans is encoded by the DUSP3 gene.
The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene maps in a region that contains the BRCA1 locus which confers susceptibility to breast and ovarian cancer. Although DUSP3 is expressed in both breast and ovarian tissues, mutation screening in breast cancer pedigrees and in sporadic tumors was negative, leading to the conclusion that this gene is not BRCA1.
# Model organisms
Model organisms have been used in the study of DUSP3 function. A conditional knockout mouse line, called Dusp3tm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and four significant abnormalities were observed. Homozygous mutants had an increased percent of body fat, abnormal humerus morphology and an increased susceptibility to bacterial infection. Corpus callosum area, hippocampus area and total brain section area was increased, while length of pyramidal cell layer was reduced.
# Interactions
DUSP3 has been shown to interact with MAPK3 and MAPK1. | DUSP3
Dual specificity protein phosphatase 3 is an enzyme that in humans is encoded by the DUSP3 gene.[1][2]
The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene maps in a region that contains the BRCA1 locus which confers susceptibility to breast and ovarian cancer. Although DUSP3 is expressed in both breast and ovarian tissues, mutation screening in breast cancer pedigrees and in sporadic tumors was negative, leading to the conclusion that this gene is not BRCA1.[2]
# Model organisms
Model organisms have been used in the study of DUSP3 function. A conditional knockout mouse line, called Dusp3tm1a(KOMP)Wtsi[10][11] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[12][13][14]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[8][15] Twenty five tests were carried out on mutant mice and four significant abnormalities were observed.[8] Homozygous mutants had an increased percent of body fat, abnormal humerus morphology and an increased susceptibility to bacterial infection. Corpus callosum area, hippocampus area and total brain section area was increased, while length of pyramidal cell layer was reduced.[8]
# Interactions
DUSP3 has been shown to interact with MAPK3[16] and MAPK1.[16] | https://www.wikidoc.org/index.php/DUSP3 | |
815398adbced55b5e74114d7c247bbcd2c2b57a6 | wikidoc | DUSP4 | DUSP4
Dual specificity protein phosphatase 4 is an enzyme that in humans is encoded by the DUSP4 gene.
# Function
The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1, ERK2 and JNK, is expressed in a variety of tissues, and is localized in the nucleus. Two alternatively spliced transcript variants, encoding distinct isoforms, have been observed for this gene. In addition, multiple polyadenylation sites have been reported.
In melanocytic cells DUSP4 gene expression may be regulated by MITF. | DUSP4
Dual specificity protein phosphatase 4 is an enzyme that in humans is encoded by the DUSP4 gene.[1][2][3]
# Function
The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1, ERK2 and JNK, is expressed in a variety of tissues, and is localized in the nucleus. Two alternatively spliced transcript variants, encoding distinct isoforms, have been observed for this gene. In addition, multiple polyadenylation sites have been reported.[3]
In melanocytic cells DUSP4 gene expression may be regulated by MITF.[4] | https://www.wikidoc.org/index.php/DUSP4 | |
d25d14af83f088dd9dc04f8425536b97a7798940 | wikidoc | DUSP5 | DUSP5
Dual specificity protein phosphatase 5 is an enzyme that in humans is encoded by the DUSP5 gene.
# Function
The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1/2, is expressed in a variety of tissues with the highest levels in pancreas and brain, and is localized in the nucleus.
# Model organisms
Model organisms have been used in the study of DUSP5 function. A conditional knockout mouse line called Dusp5tm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping | DUSP5
Dual specificity protein phosphatase 5 is an enzyme that in humans is encoded by the DUSP5 gene.[1][2]
# Function
The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1/2, is expressed in a variety of tissues with the highest levels in pancreas and brain, and is localized in the nucleus.[2]
# Model organisms
Model organisms have been used in the study of DUSP5 function. A conditional knockout mouse line called Dusp5tm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[3] Male and female animals underwent a standardized phenotypic screen[4] to determine the effects of deletion.[5][6][7][8] Additional screens performed: - In-depth immunological phenotyping[9] | https://www.wikidoc.org/index.php/DUSP5 | |
402b29642b3adb7799405ea4f824564642590545 | wikidoc | DUSP7 | DUSP7
Dual specificity protein phosphatase 7 is an enzyme that in humans is encoded by the DUSP7 gene.
# Function
Dual-specificity phosphatases (DUSPs) constitute a large heterogeneous subgroup of the type I cysteine-based protein-tyrosine phosphatase superfamily. DUSPs are characterized by their ability to de-phosphorylate both tyrosine (EC 3.1.3.48) and serine / threonine (EC 3.1.3.16) residues. DUSP7 belongs to a class of DUSPs, designated MKPs, that dephosphorylate MAPK (mitogen-activated protein kinase) proteins ERK, JNK, and p38 with specificity distinct from that of individual MKP proteins. MKPs contain a highly conserved C-terminal catalytic domain and an N-terminal Cdc25-like (CH2) domain. MAPK activation cascades mediate various physiologic processes, including cellular proliferation, apoptosis, differentiation, and stress responses.
It is known to bind and dephosphorylate ErkII, and as it, along with the other members of the DUSP family expresses high selectively for MAP kinases, it has been suggested that it functions as a method for selectively activating/deactivating different members of that family. | DUSP7
Dual specificity protein phosphatase 7 is an enzyme that in humans is encoded by the DUSP7 gene.[1][2][3]
# Function
Dual-specificity phosphatases (DUSPs) constitute a large heterogeneous subgroup of the type I cysteine-based protein-tyrosine phosphatase superfamily. DUSPs are characterized by their ability to de-phosphorylate both tyrosine (EC 3.1.3.48) and serine / threonine (EC 3.1.3.16) residues. DUSP7 belongs to a class of DUSPs, designated MKPs, that dephosphorylate MAPK (mitogen-activated protein kinase) proteins ERK, JNK, and p38 with specificity distinct from that of individual MKP proteins. MKPs contain a highly conserved C-terminal catalytic domain and an N-terminal Cdc25-like (CH2) domain. MAPK activation cascades mediate various physiologic processes, including cellular proliferation, apoptosis, differentiation, and stress responses.[3][4]
It is known to bind and dephosphorylate ErkII, and as it, along with the other members of the DUSP family expresses high selectively for MAP kinases, it has been suggested that it functions as a method for selectively activating/deactivating different members of that family.[5] | https://www.wikidoc.org/index.php/DUSP7 | |
8633712ef9b55f82fa214ae1351cc1dbdb34e7f0 | wikidoc | LRRK2 | LRRK2
Leucine-rich repeat kinase 2 (LRRK2), also known as dardarin (from the Basque word "dardara" which means trembling), is an enzyme that in humans is encoded by the PARK8 gene. LRRK2 is a member of the leucine-rich repeat kinase family. Variants of this gene are associated with an increased risk of Parkinson's disease and also Crohn's disease.
# Function
The LRRK2 gene encodes a protein with an armadillo repeats (ARM) region, an ankyrin repeat (ANK) region, a leucine-rich repeat (LRR) domain, a kinase domain, a RAS domain, a GTPase domain, and a WD40 domain. The protein is present largely in the cytoplasm but also associates with the mitochondrial outer membrane.
LRRK2 interacts with the C-terminal R2 RING finger domain of parkin, and parkin interacted with the COR domain of LRRK2. Expression of mutant LRRK2 induced apoptotic cell death in neuroblastoma cells and in mouse cortical neurons.
Expression of LRRK2 mutants implicated in autosomal dominant Parkinson's disease causes shortening and simplification of the dendritic tree in vivo and in cultured neurons. This is mediated in part by alterations in macroautophagy, and can be prevented by protein kinase A regulation of the autophagy protein LC3. The G2019S and R1441C mutations elicit post-synaptic calcium imbalance, leading to excess mitochondrial clearance from dendrites by mitophagy. LRRK2 is also a substrate for chaperone-mediated autophagy.
# Clinical significance
Mutations in this gene have been associated with Parkinson's disease type 8.
The Gly2019Ser mutation in LRRK2 is a relatively common cause of familial Parkinson's disease in Caucasians. It may also cause sporadic Parkinson's disease. The mutated Gly amino acid is conserved in all kinase domains of all species.
The Gly2019Ser mutation is one of a small number of LRRK2 mutations proven to cause Parkinson's disease. Of these, Gly2019Ser is the most common in the Western World, accounting for ~2% of all Parkinson's disease cases in North American Caucasians. This mutation is enriched in certain populations, being found in approximately 20% of all Ashkenazi Jewish Parkinson's disease patients and in approximately 40% of all Parkinson's disease patients of North African Berber Arab ancestry.
Unexpectedly, genomewide association studies have found an association between LRRK2 and Crohn's disease as well as with Parkinson's disease, suggesting that the two diseases share common pathways.
Attempts have been made to grow crystals of the LRRK2 aboard the International Space Station, as the low-gravity environment renders the crystals less susceptible to sedimentation and convection, and thus easier to map.
Mutations in the LRRK2 gene is the main factor in contributing to the genetic development of Parkinson's disease, and over 100 mutations in this gene have been shown to increase the chance of PD development. These mutations are most commonly seen in Jewish, North African Arab Berber, Chinese, and Japanese populations | LRRK2
Leucine-rich repeat kinase 2 (LRRK2), also known as dardarin (from the Basque word "dardara" which means trembling), is an enzyme that in humans is encoded by the PARK8 gene.[1] LRRK2 is a member of the leucine-rich repeat kinase family. Variants of this gene are associated with an increased risk of Parkinson's disease and also Crohn's disease.[1][2]
# Function
The LRRK2 gene encodes a protein with an armadillo repeats (ARM) region, an ankyrin repeat (ANK) region, a leucine-rich repeat (LRR) domain, a kinase domain, a RAS domain, a GTPase domain, and a WD40 domain. The protein is present largely in the cytoplasm but also associates with the mitochondrial outer membrane.
LRRK2 interacts with the C-terminal R2 RING finger domain of parkin, and parkin interacted with the COR domain of LRRK2. Expression of mutant LRRK2 induced apoptotic cell death in neuroblastoma cells and in mouse cortical neurons.[3]
Expression of LRRK2 mutants implicated in autosomal dominant Parkinson's disease causes shortening and simplification of the dendritic tree in vivo and in cultured neurons.[4] This is mediated in part by alterations in macroautophagy,[5][6][7][8][9] and can be prevented by protein kinase A regulation of the autophagy protein LC3.[10] The G2019S and R1441C mutations elicit post-synaptic calcium imbalance, leading to excess mitochondrial clearance from dendrites by mitophagy.[11] LRRK2 is also a substrate for chaperone-mediated autophagy.[12]
# Clinical significance
Mutations in this gene have been associated with Parkinson's disease type 8.[13]
The Gly2019Ser mutation in LRRK2 is a relatively common cause of familial Parkinson's disease in Caucasians.[14] It may also cause sporadic Parkinson's disease. The mutated Gly amino acid is conserved in all kinase domains of all species.
The Gly2019Ser mutation is one of a small number of LRRK2 mutations proven to cause Parkinson's disease. Of these, Gly2019Ser is the most common in the Western World, accounting for ~2% of all Parkinson's disease cases in North American Caucasians. This mutation is enriched in certain populations, being found in approximately 20% of all Ashkenazi Jewish Parkinson's disease patients and in approximately 40% of all Parkinson's disease patients of North African Berber Arab ancestry.[citation needed]
Unexpectedly, genomewide association studies have found an association between LRRK2 and Crohn's disease as well as with Parkinson's disease, suggesting that the two diseases share common pathways.[15][16]
Attempts have been made to grow crystals of the LRRK2 aboard the International Space Station, as the low-gravity environment renders the crystals less susceptible to sedimentation and convection, and thus easier to map.[17]
Mutations in the LRRK2 gene is the main factor in contributing to the genetic development of Parkinson's disease, and over 100 mutations in this gene have been shown to increase the chance of PD development. These mutations are most commonly seen in Jewish, North African Arab Berber, Chinese, and Japanese populations[18] | https://www.wikidoc.org/index.php/Dardarin | |
b3889b645f75d78a2cb0a06966760d6aa8c57fb8 | wikidoc | Urine | Urine
Steven C. Campbell, M.D., Ph.D. Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.
Synonyms and keywords: Urinary findings; Urinary abnormalities; Findings on urine exam; Urine; Urine composition; Urine output
# Overview
Urine is a fluid produced by humans through the kidney, collected in the bladder, and excreted through the genital urethra. Urine formation helps to maintain the balance of minerals and other substances in the body. Urinary findings may be qualitative or quantitative. Qualitative urinary findings are often analyzed on urinalysis and urine culture. Quantitative urinary findings depends on urine output. A urinalysis (U) is an array of tests performed on urine and is one of the most common methods of medical diagnosis. A part of a urinalysis can be performed by using urine dipsticks, in which the test results can be read as color changes.
# Composition of Urine
The following is a list of normal urine constituents:
- Non-organic substances: bicarbonate, chloride, phosphorus, sulphur, bromide, fluoride, iodide, rhodanide, potassium, natron, calcium, magnesium, iron, copper, zinc, cobalt, selenium, arsenium, lead, and mercury.
- Nitrogenous substances: nitrogen, urea, creatine, creatinine, guanidine, choline, carnitine, piperidine, spermidine, dopamine, epinephrine, norepinephrine, serotonin, tryptamine, levulinique amino-acid, and bilirubin
- Non-nitrogenous organic acids
- Amino acids: alanine, carnosine, glycine, histidine, leucine, lysine, methionine, phenylalanine, serine, tyrosine, valine, hydroxyloproline, galactosylhydroxylyzine, xylosylserine, and others.
- Proteins: albumin, haptoglobin, transferrin, immunoglobulins IgG, IgA, IgM, and others.
- Enzymes: lactadehydrogenase, gamma-glutamyl transferase, alpha amylase, uropepsinogene, lysozyme, beta-N-acetylglucosaminidase, urokinase, protease, and others.
- Carbohydrates: arabinose, xyloseribose, fucose, rhammose, ketopentose, glucose, galactose, mannose, fructose, lactose, sucrose, fucosylglucose, raffinose, and others.
- Vitamins: thiamine (vitamin B1), riboflavin (vitamin B2), vitamin B6, 4-pyridoxique acid, nicotinic acid, vitamin B12, biopterine, ascorbic acid (vitamin C) and others.
- Hormones: gonadotropin, corticotropin, prolactin, lactogeniques hormones, oxytocin, vasopressin, thyroxine, catecholamines (epinephrine, norepinephrine, dopamine), insulin, erythropoietin, corticosteroids (aldosterone, corticosterone, cortisone), testosterone, progesterone, estrogen and others.
- Agglutinins and precipitines: neutralizing action on the polio virus and other viruses.
- Antineoplaston: selectively prevents the development of cancer cells without affecting healthy cells that
- Allantoin: nitrogen crystalline substance that promotes healing, from the oxidation of uric acid. It is used in the manufacture of many skin creams.
- DHEA (dehydroepiandrosterone): steroid secreted by the adrenal glands, present in large quantities in male urine. It prevents obesity, prolongs the life of animals and is a possible treatment against anemia, diabetes and breast cancer. DHEA stimulates the development of the bone marrow and increases its production of red blood cells, monocytes, macrophages and lymphocytes. A low level of DHEA seems to be associated with aging.
- Gastric antisecretory products: prevent the onset and development of stomach ulcers.
- Glucoronic acid: produced by the liver, kidneys and intestines, it has a major secretory function.
- H-11: inhibits the growth of cancer cells and reduces the existing tumors without disrupting the recovery process.
- H.U.D. HUD (Human’s urine derivative): demonstrates remarkable anticancer properties.
- Interleukin-1: a positive influence on the auxiliary and inhibitory substances. Can send a signal to the hypothalamus to trigger fever.
- Trimethyl-glyoxal: destroys cancer cells.
- Prostaglandine: a hormonal substance that dilates the blood vessels, lowers tension, relaxes the muscle walls of the bronchi, stimulates contractions during labor, and many metabolic functions.
- Proteoglobulines: plasma proteins containing anti-bodies against certain allergens, they are identical to the proteins of immoglobulines blood serum.
- Prosteoses: immunological products assets allergic reactions.
# Algorithm of Common Urinary Findings
# Urine Odor
Urine is usually odorless but can produce pungent smells following the consumption of certain foods (e.g. asparagus)
# Urine Color and Turbidity
## Color
Below is a table that lists common urine discolorations and their associated conditions.
To view a complete comprehensive list of causes that are are associated with urine discoloration, click here
## Turbidity
- Normal urine is usually clear
- Turbid urine may be a manifestation of urinary bacterial infection, hematuria, proteinuria, pyuria, or presence of crystals and casts.
# Urine Specific Gravity and Osmolality
## Urine Specific Gravity
- Normal urine specific gravity (density) ranges between 1.003 and 1.035 g.cm-3.
- Specific gravity outside the normal range may sometimes be associated with urinary disorders.
## Urine Osmolality
- In healthy individuals with restricted fluid intake, urine osmolality should be > than 800mOsm/kg.
- 24-hour urine osmolality normally ranges between 500 and 800 mOsm/kg.
- Random urine osmolality normally ranges between 50 and 1400 mOsm/kg.
### Increased urine osmolality
- Acidosis
- Addison's Disease
- Congestive Heart Failure
- Hepatic cirrhosis
- Hypernatremia
- Shock
- Syndrome of Inappropriate Anti Diuretic Hormone (SIADH)
### Decreased urine osmolality
- Aldosteronism
- Amyloidosis
- Chronic Interstitial Nephritis
- Chronic pyelonephritis
- Diabetes Insipidus
- Primary polydypsia
- Glomerulonephritis
- Hypercalcemia
- Hypokalemia
- Lithium nephrotoxicity
- Nephrogenic diabetes insipidus
- Polycystic kidneys
- Renal Tubular Necrosis
# Urinary pH
- The pH of urine is normally close to neutral pH = 6 to 7 (Range: 4.5 to 8.2).
- Strongly acidic or alkaline urine may be manifestations of the following:
## Renal and urologic diseases
- Urinary tract infection
- Acute kidney injury
- Chronic kindey disease
- Renal tubular acidosis
## Systemic diseases
- Diabetes Mellitus
- Diarrhea
- Vomiting
- Fanconi's Syndrome
- Increased protein catabolism
- Lupus erythematosus
- Metabolic/respiratory alkalosis or acidosis
- Protein rich diet
## Drug administration
- Acetazolamide
- Aldosteronism
- Amyloidosis
- Antibiotics
- Sodium acetate
- Sodium bicarbonate
- Sodium lactate
# Hematuria
- Microscopic hematuria
- Gross hematuria
# Pyuria
Pyuria is defined as the presence of 10 or more white cells per cubic millimeter in a urine specimen, 3 or more white cells per high-power field of unspun urine, a positive result on Gram’s stain of an unspun urine specimen, or a urinary dipstick test that is positive for leukocyte esterase
Pyuria may first be classified based on gross/microscopic examination
- Microscopic pyuria
- Gross pyuria
Pyuria may also be classified based on the presence/absence of detectable infection
- Bacteriuria (detectable bacteria in urine)
- Sterile pyuria (non-infectious cause or an infection that is undetected on regular gram-stain and urine culture)
# Proteinuria
- Albuminuria
Microalbuminuria
Macroalbuminuria
- Microalbuminuria
- Macroalbuminuria
- Paraproteinuria
# Cells
- Benign
- Malignant
# Casts and Crystals
## Casts
To view a comprehensive list of urinary cast types and the characteristics of each cast type, click here
### Acellular casts
- Hyaline casts
- Granular casts
- Waxy casts
- Fatty casts
- Pigment casts
- Crystal casts
### Cellular casts
- RBC casts
- WBC casts
- Bacterial casts
- Epithelial cell casts
## Crystals
- Struvite crystals (magnesium-ammonium-phosphate)
- Bilirubin crystals
- Calcium carbonate crystals
- Amorphous crystals
- Calcium oxalate dihydrate crystals
- Cystine crystals
# Other
## Urinary beta-HCG (urinary pregnancy test)
## Myoglobinuria
## Glucosuria
## Ketonuria
## Bilirubinuria
## Eosinophiluria
- Acute interstitial nephritis
- Atheroembolic renal disease
- Rapidly progressive glomerulonephritis
- Urinary tract infection
To view a comprehensive list of causes of eosinophiluria, click here
## Bacterial antigens
## Sperm
## Urinary drug concentration
- Drug testing uses urinalysis to test for certain chemicals which are typically present in the urine only after recreational drug use.
- These tests must be requested specifically or as part of a toxicology screen, and are not part of a routine urinalysis.
## Dissolved electrolytes or heavy metals
Calciuria (urinary calcium) differential diagnosis:
- Bone metastases
- Diets low in calcium
- Hypervitaminosis
- Idiopathic hypercalciuria
- Increased calcium intake
- Multiple Myeloma
- Paget's Disease
- Primary hyperparathyroidism
- Prolonged immobilization
- Pseudoparahypothyroidism
- Renal Tubular Acidosis
- Renal osteodystrophy
- Sarcoidosis
- Steroids
- Vitamin D deficiency
- Vitamin D resistant ricketts
## Catecholamines
### Differential Diagnosis of urinary catecholamines
- Medication-induced
- Ganglioma
- Multiple endocrine neoplasia type 2
- Neuroblastoma
- Pheochromocytoma
- Stress
# Urine Culture
Normal urine is sterile. Presence of microorganisms in urine culture may be associated with urinary infections or colonization.
- Bacteria: Bacteriuria
- Fungi: Funguria
# Urine Quantity (Volume)
- The amount of urine produced depends on hydration (volume of fluid intake), physical activity, environmental factors, body surface area, and general health condition.
- In adult humans, the average urine production is approximately 1 L to 2 L per 24 hours.
## High Urine Output
- Polyuria: Excessive urinary production > 2.5 L per 24 hours
## Low Urine Output
Low urine output may be either oliguria or anuria:
- Oliguria: Urine production < 400 mL / 24 hours in adults. A more specific definition includes the following:
Infants: oliguria is defined as urine output < 1 mL/kg/hr
Children: Oliguria is defined as urine output < 0.5 mL/kg/hr.
Aduults: Oliguria is defined as urine output < 17 to 21 ml/hr.
- Infants: oliguria is defined as urine output < 1 mL/kg/hr
- Children: Oliguria is defined as urine output < 0.5 mL/kg/hr.
- Aduults: Oliguria is defined as urine output < 17 to 21 ml/hr.
For a detailed explanation of oliguria, click here.
- Anuria: Urine production < 100 mL / 24 hr in adults.
For a detailed explanation of anuria, click here. | Urine
Steven C. Campbell, M.D., Ph.D. Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.
Synonyms and keywords: Urinary findings; Urinary abnormalities; Findings on urine exam; Urine; Urine composition; Urine output
# Overview
Urine is a fluid produced by humans through the kidney, collected in the bladder, and excreted through the genital urethra. Urine formation helps to maintain the balance of minerals and other substances in the body. Urinary findings may be qualitative or quantitative. Qualitative urinary findings are often analyzed on urinalysis and urine culture. Quantitative urinary findings depends on urine output. A urinalysis (U) is an array of tests performed on urine and is one of the most common methods of medical diagnosis. A part of a urinalysis can be performed by using urine dipsticks, in which the test results can be read as color changes.
# Composition of Urine
The following is a list of normal urine constituents:
- Non-organic substances: bicarbonate, chloride, phosphorus, sulphur, bromide, fluoride, iodide, rhodanide, potassium, natron, calcium, magnesium, iron, copper, zinc, cobalt, selenium, arsenium, lead, and mercury.
- Nitrogenous substances: nitrogen, urea, creatine, creatinine, guanidine, choline, carnitine, piperidine, spermidine, dopamine, epinephrine, norepinephrine, serotonin, tryptamine, levulinique amino-acid, and bilirubin
- Non-nitrogenous organic acids
- Amino acids: alanine, carnosine, glycine, histidine, leucine, lysine, methionine, phenylalanine, serine, tyrosine, valine, hydroxyloproline, galactosylhydroxylyzine, xylosylserine, and others.
- Proteins: albumin, haptoglobin, transferrin, immunoglobulins IgG, IgA, IgM, and others.
- Enzymes: lactadehydrogenase, gamma-glutamyl transferase, alpha amylase, uropepsinogene, lysozyme, beta-N-acetylglucosaminidase, urokinase, protease, and others.
- Carbohydrates: arabinose, xyloseribose, fucose, rhammose, ketopentose, glucose, galactose, mannose, fructose, lactose, sucrose, fucosylglucose, raffinose, and others.
- Vitamins: thiamine (vitamin B1), riboflavin (vitamin B2), vitamin B6, 4-pyridoxique acid, nicotinic acid, vitamin B12, biopterine, ascorbic acid (vitamin C) and others.
- Hormones: gonadotropin, corticotropin, prolactin, lactogeniques hormones, oxytocin, vasopressin, thyroxine, catecholamines (epinephrine, norepinephrine, dopamine), insulin, erythropoietin, corticosteroids (aldosterone, corticosterone, cortisone), testosterone, progesterone, estrogen and others.
- Agglutinins and precipitines: neutralizing action on the polio virus and other viruses.
- Antineoplaston: selectively prevents the development of cancer cells without affecting healthy cells that
- Allantoin: nitrogen crystalline substance that promotes healing, from the oxidation of uric acid. It is used in the manufacture of many skin creams.
- DHEA (dehydroepiandrosterone): steroid secreted by the adrenal glands, present in large quantities in male urine. It prevents obesity, prolongs the life of animals and is a possible treatment against anemia, diabetes and breast cancer. DHEA stimulates the development of the bone marrow and increases its production of red blood cells, monocytes, macrophages and lymphocytes. A low level of DHEA seems to be associated with aging.
- Gastric antisecretory products: prevent the onset and development of stomach ulcers.
- Glucoronic acid: produced by the liver, kidneys and intestines, it has a major secretory function.
- H-11: inhibits the growth of cancer cells and reduces the existing tumors without disrupting the recovery process.
- H.U.D. HUD (Human’s urine derivative): demonstrates remarkable anticancer properties.
- Interleukin-1: a positive influence on the auxiliary and inhibitory substances. Can send a signal to the hypothalamus to trigger fever.
- Trimethyl-glyoxal: destroys cancer cells.
- Prostaglandine: a hormonal substance that dilates the blood vessels, lowers tension, relaxes the muscle walls of the bronchi, stimulates contractions during labor, and many metabolic functions.
- Proteoglobulines: plasma proteins containing anti-bodies against certain allergens, they are identical to the proteins of immoglobulines blood serum.
- Prosteoses: immunological products assets allergic reactions.
# Algorithm of Common Urinary Findings
# Urine Odor
Urine is usually odorless but can produce pungent smells following the consumption of certain foods (e.g. asparagus)
# Urine Color and Turbidity
## Color
Below is a table that lists common urine discolorations and their associated conditions.
To view a complete comprehensive list of causes that are are associated with urine discoloration, click here
## Turbidity
- Normal urine is usually clear
- Turbid urine may be a manifestation of urinary bacterial infection, hematuria, proteinuria, pyuria, or presence of crystals and casts.
# Urine Specific Gravity and Osmolality
## Urine Specific Gravity
- Normal urine specific gravity (density) ranges between 1.003 and 1.035 g.cm-3.
- Specific gravity outside the normal range may sometimes be associated with urinary disorders.
## Urine Osmolality
- In healthy individuals with restricted fluid intake, urine osmolality should be > than 800mOsm/kg.
- 24-hour urine osmolality normally ranges between 500 and 800 mOsm/kg.
- Random urine osmolality normally ranges between 50 and 1400 mOsm/kg.
### Increased urine osmolality
- Acidosis
- Addison's Disease
- Congestive Heart Failure
- Hepatic cirrhosis
- Hypernatremia
- Shock
- Syndrome of Inappropriate Anti Diuretic Hormone (SIADH)
### Decreased urine osmolality
- Aldosteronism
- Amyloidosis
- Chronic Interstitial Nephritis
- Chronic pyelonephritis
- Diabetes Insipidus
- Primary polydypsia
- Glomerulonephritis
- Hypercalcemia
- Hypokalemia
- Lithium nephrotoxicity
- Nephrogenic diabetes insipidus
- Polycystic kidneys
- Renal Tubular Necrosis
# Urinary pH
- The pH of urine is normally close to neutral pH = 6 to 7 (Range: 4.5 to 8.2).
- Strongly acidic or alkaline urine may be manifestations of the following:
## Renal and urologic diseases
- Urinary tract infection
- Acute kidney injury
- Chronic kindey disease
- Renal tubular acidosis
## Systemic diseases
- Diabetes Mellitus
- Diarrhea
- Vomiting
- Fanconi's Syndrome
- Increased protein catabolism
- Lupus erythematosus
- Metabolic/respiratory alkalosis or acidosis
- Protein rich diet
## Drug administration
- Acetazolamide
- Aldosteronism
- Amyloidosis
- Antibiotics
- Sodium acetate
- Sodium bicarbonate
- Sodium lactate
# Hematuria
- Microscopic hematuria
- Gross hematuria
# Pyuria
Pyuria is defined as the presence of 10 or more white cells per cubic millimeter in a urine specimen, 3 or more white cells per high-power field of unspun urine, a positive result on Gram’s stain of an unspun urine specimen, or a urinary dipstick test that is positive for leukocyte esterase[1]
Pyuria may first be classified based on gross/microscopic examination
- Microscopic pyuria
- Gross pyuria
Pyuria may also be classified based on the presence/absence of detectable infection
- Bacteriuria (detectable bacteria in urine)
- Sterile pyuria (non-infectious cause or an infection that is undetected on regular gram-stain and urine culture)
# Proteinuria
- Albuminuria
Microalbuminuria
Macroalbuminuria
- Microalbuminuria
- Macroalbuminuria
- Paraproteinuria
# Cells
- Benign
- Malignant
# Casts and Crystals
## Casts
To view a comprehensive list of urinary cast types and the characteristics of each cast type, click here
### Acellular casts
- Hyaline casts
- Granular casts
- Waxy casts
- Fatty casts
- Pigment casts
- Crystal casts
### Cellular casts
- RBC casts
- WBC casts
- Bacterial casts
- Epithelial cell casts
## Crystals
- Struvite crystals (magnesium-ammonium-phosphate)
- Bilirubin crystals
- Calcium carbonate crystals
- Amorphous crystals
- Calcium oxalate dihydrate crystals
- Cystine crystals
# Other
## Urinary beta-HCG (urinary pregnancy test)
## Myoglobinuria
## Glucosuria
## Ketonuria
## Bilirubinuria
## Eosinophiluria
- Acute interstitial nephritis
- Atheroembolic renal disease
- Rapidly progressive glomerulonephritis
- Urinary tract infection
To view a comprehensive list of causes of eosinophiluria, click here
## Bacterial antigens
## Sperm
## Urinary drug concentration
- Drug testing uses urinalysis to test for certain chemicals which are typically present in the urine only after recreational drug use.
- These tests must be requested specifically or as part of a toxicology screen, and are not part of a routine urinalysis.
## Dissolved electrolytes or heavy metals
Calciuria (urinary calcium) differential diagnosis:
- Bone metastases
- Diets low in calcium
- Hypervitaminosis
- Idiopathic hypercalciuria
- Increased calcium intake
- Multiple Myeloma
- Paget's Disease
- Primary hyperparathyroidism
- Prolonged immobilization
- Pseudoparahypothyroidism
- Renal Tubular Acidosis
- Renal osteodystrophy
- Sarcoidosis
- Steroids
- Vitamin D deficiency
- Vitamin D resistant ricketts
## Catecholamines
### Differential Diagnosis of urinary catecholamines
- Medication-induced
- Ganglioma
- Multiple endocrine neoplasia type 2
- Neuroblastoma
- Pheochromocytoma
- Stress
# Urine Culture
Normal urine is sterile. Presence of microorganisms in urine culture may be associated with urinary infections or colonization.
- Bacteria: Bacteriuria
- Fungi: Funguria
# Urine Quantity (Volume)
- The amount of urine produced depends on hydration (volume of fluid intake), physical activity, environmental factors, body surface area, and general health condition.
- In adult humans, the average urine production is approximately 1 L to 2 L per 24 hours.
## High Urine Output
- Polyuria: Excessive urinary production > 2.5 L per 24 hours
## Low Urine Output
Low urine output may be either oliguria or anuria:
- Oliguria: Urine production < 400 mL / 24 hours in adults. A more specific definition includes the following:
Infants: oliguria is defined as urine output < 1 mL/kg/hr[2]
Children: Oliguria is defined as urine output < 0.5 mL/kg/hr.
Aduults: Oliguria is defined as urine output < 17 to 21 ml/hr.
- Infants: oliguria is defined as urine output < 1 mL/kg/hr[2]
- Children: Oliguria is defined as urine output < 0.5 mL/kg/hr.
- Aduults: Oliguria is defined as urine output < 17 to 21 ml/hr.
For a detailed explanation of oliguria, click here.
- Anuria: Urine production < 100 mL / 24 hr in adults.
For a detailed explanation of anuria, click here. | https://www.wikidoc.org/index.php/Dark_urine | |
077d3eafc098d277e27c230c161cac6292abbefc | wikidoc | Feces | Feces
# Overview
Feces, faeces, or fæces (see spelling differences) is a waste product from an animal's digestive tract expelled through the anus (or cloaca) during defecation. The word faeces is the plural of the Latin word fæx meaning "dregs". There is no singular form in the English language, making it a plurale tantum.
# Etymology
Due to the nature of feces, several synonyms have developed. Of these, some are generally used as profanity (such as shit and crap) while others have been deemed inoffensive (such as poo, poop, and dookie). Other terms (such as dung) are normally used for animal feces rather than human feces.
# Ecology
After an animal has digested eaten material, the remains of it is excreted from its body as waste. Though it is lower in energy than the food it came from, feces may still contain a large amount of energy, often 50% of that of the original food. This means that of all food eaten, a significant amount of energy remains for the decomposers of ecosystems. Many organisms feed on feces, from bacteria to fungi to insects such as dung beetles, which can sense odors from long distances. Some may specialize in feces, while others may eat other foods as well. Feces serve not only as a basic food, but also a supplement to the usual diet of some animals. This is known as coprophagia, and occurs in various animal species such as young elephants eating their mother's feces to gain essential gut flora, or by other animals such as monkeys.
Feces are also an important as a signal. Kestrels for instance are able to detect the feces of their prey (which reflect ultraviolet), allowing them to identify areas where there are large numbers of voles, for example. This adaptation is essential in prey detection, as voles are expert at hiding from such predators. Some caterpillars even shoot their feces away from themselves in an explosive burst, helping them to avoid predators taking advantage of the olfactory signal it creates. In a non-predatory example, dominant wildebeest bulls defend territories marked with feces and pheromones produced by scent glands.
Seeds may also be found in feces. Animals which eat fruit are known as frugivores. The advantage in having fruit for a plant is that animals will eat the fruit and unknowingly disperse the seed in doing so. This mode of seed dispersal is highly successful, as seeds dispersed around the base of a plant are unlikely to succeed and are often subject to heavy predation. Provided the seed can withstand the pathway through the digestive system, it is not only likely to be far away from the parent plant, but is even provided with its own fertilizer.
Organisms which subsist on dead organic matter or detritus are known as detritivores, and play an important role in ecosystems by recycling organic matter back into a simpler form which plants and other autotrophs may once again absorb. This cycling of matter is known as the biogeochemical cycle. To maintain nutrients in soil it is therefore important that feces return to the area from which they came, which is not always the case in human society where food may be transported from rural areas to urban populations and then feces disposed of into a river or sea.
# Human feces
In humans, defecation may occur (depending on the individual and the circumstances) from once every two or three days to several times a day. Hardening of the feces may cause prolonged interruption in the routine and is called constipation.
Human fecal matter varies significantly in appearance, depending on diet and health. Normally it is semisolid, with a mucus coating. Its brown coloration comes from a combination of bile and bilirubin, which comes from dead red blood cells.
In newborn babies, fecal matter is initially yellow/green after the meconium. This coloration comes from the presence of bile alone. In time, as the body starts expelling bilirubin from dead red blood cells, it acquires its familiar brown appearance, unless the baby is breast feeding, in which case it remains soft, pale yellowish, and not-unpleasantly scented until the baby begins to eat significant amounts of other food.
Throughout the life of an ordinary human, one may experience many types of feces. A "green" stool is from rapid transit of feces through the intestines (or the consumption of certain blue or green food dyes in quantity), and "clay-like" appearance to the feces is the result of a lack of bilirubin.
Bile overload is very rare, and not a health threat. Problems as simple as serious diarrhea can cause blood in one's stool. Black stools caused by blood usually indicate a problem in the intestines (the black is digested blood), whereas red streaks of blood in stool are usually caused by bleeding in the rectum or anus.
Food may sometimes make an appearance in the feces. Common undigested foods found in human feces are seeds, nuts, corn and beans, mainly because of their high dietary fiber content. Artificial food coloring in some processed foods such as highly colorful packaged breakfast cereals can also cause unusual feces coloring if eaten in sufficient quantities.
## Differential Diagnosis of Causes of Feces Consistency
### Slimy
- Allergic diarrhea
- Amebic dysentery
- Chronic enterocolitis
- Colitis mucosa
- Gastroenteritis
- Pellagra
### Thin
- Constipation
- Rectal carcinoma
### Watery
- Acute gastroenteritis
- Carcinoid syndrome
- Cholera
- Intoxication
## Differential Diagnosis of Causes of Feces Color
Stool color can provide insight into the pathophysiologic basis of disease.
### Black Stool
- Melena, often the source is the upper GI tract as acid contents cause the stool to turn black. associated with acharacteristic foul smell. BUN will often be increased due to absorption of nitrogenous products in the upper GI tract.
### Bright Red
- Lower GI bleed
- Hemorrhoids
### Light Grey
- After radiocontrast use
- Bile duct occlusion
- Fatty stool
- Viral Hepatitis
## Personal hygiene
All cultures practice some form of personal cleansing after expelling feces.
- In Western society, the use of toilet paper is widespread.
- Other paper products were also historically used (before the advent of flush toilets).
- Before paper was cheap to produce, a "toilet rag" made of cloth was used, with a separate rag assigned to each family member.
- Several companies market toilet tissue or wipes for babies and campers.
- In some European countries, the use of a bidet for additional cleaning is common.
- In South Asia, showers are provided for use in toilets.
- In Islam, washing is prescribed by ritual cleansing with water, of which washing of the anus is part of the ablutions. The "act" of passing toilet, in Islam, requires ritual cleansing with water using the left hand. As religion is often practiced by widely differing cultural groups, Islamic tradition involves washing of the hands using soap and water after ablutions after using the toilet, to using of tissue paper to dry-off hands and other "wet" parts of the body to showers after each toilet use. In many Muslim countries, piped water is supplied inside toilets for both bathing and washing in addition to flushing of faecal matter. Such toilets are also common in Greece, Spain and parts of Eastern Europe.
- In India, the anus is also washed with water using the left hand. As with all such practices, hand washing after use of the toilet has become a very important public health issue.
- In England, there was historically much fascination with the act of going to the toilet, with royals appointing lesser mortals to assist with the removal of faeces and cleansing of the body parts using towels. The Indian toilet was adapted as the WC or water closet and widely deployed in England during the reign of Queen Victoria. London was the stage for several instances of food poisoning resulting from workers handling food after using the toilet. Cleansing of the anus was an arbitrary practice left to personal choice and facility available.
- In Ancient Rome, a communal sponge was used, which was then rinsed in a bucket of salt water.
- In Japan, flat sticks were used in ancient times, being replaced by toilet paper as the country became more "westernized." Toilets that include built-in bidets have now become widely popular in private homes.
## Bristol Stool Scale
Consistency and shape of stools may be classified medically according to the Bristol Stool Scale.
Pica, a disorder where non-food items are eaten, can cause unusual stool. Intestinal parasites and their ova (eggs) can sometimes be visible to the naked eye.
# Odor
The distinctive odor of feces is due to bacterial action. Gut flora produce compounds such as indole, skatole, and thiols (sulfur-containing compounds), as well as the inorganic gas hydrogen sulfide. These are the same compounds that are responsible for the odor of flatulence. Consumption of foods with spices may result in the spices being undigested and adding to the odor of feces. Certain commercial products exist that claim to reduce the odor of feces. The perceived bad odor of feces has been hypothesized to be a deterrent for humans, as consumption or touching it may result in sickness or infection. Of course, human perception of the odor is a subjective matter; an animal that eats feces may be attracted to its odor.
# Pets
Pets can be trained to use litter boxes or wait to be let out via several methods, such as crate training for dogs. Several companies market carpet cleaning products aimed at pet owners. However pet feces can be cleaned with just dishwashing detergent or liquid soap.
# Uses
The feces of animals is often used as fertilizer; see manure.
Some animal feces, especially those of the camel, bison and cow, is used as fuel when dried out.
Animal dung, besides being used as fuel, is occasionally used as a cement to make adobe mud brick huts or even in throwing sports such as cow pat throwing or camel dung throwing contests.
See also Fewmets for the use of faeces in Venery, or Hunting in the Middle_Ages
See also Kopi Luwak
Kopi Luwak (pronounced ) or Civet coffee is coffee made from coffee berries which have been eaten by and passed through the digestive tract of the Asian Palm Civet (Paradoxurus hermaphroditus). | Feces
# Overview
Feces, faeces, or fæces (see spelling differences) is a waste product from an animal's digestive tract expelled through the anus (or cloaca) during defecation. The word faeces is the plural of the Latin word fæx meaning "dregs". There is no singular form in the English language, making it a plurale tantum. [1]
# Etymology
Due to the nature of feces, several synonyms have developed. Of these, some are generally used as profanity (such as shit and crap) while others have been deemed inoffensive (such as poo, poop, and dookie). Other terms (such as dung) are normally used for animal feces rather than human feces.
# Ecology
After an animal has digested eaten material, the remains of it is excreted from its body as waste. Though it is lower in energy than the food it came from, feces may still contain a large amount of energy, often 50% of that of the original food.[2] This means that of all food eaten, a significant amount of energy remains for the decomposers of ecosystems. Many organisms feed on feces, from bacteria to fungi to insects such as dung beetles, which can sense odors from long distances.[3] Some may specialize in feces, while others may eat other foods as well. Feces serve not only as a basic food, but also a supplement to the usual diet of some animals. This is known as coprophagia, and occurs in various animal species such as young elephants eating their mother's feces to gain essential gut flora, or by other animals such as monkeys.
Feces are also an important as a signal. Kestrels for instance are able to detect the feces of their prey (which reflect ultraviolet), allowing them to identify areas where there are large numbers of voles, for example. This adaptation is essential in prey detection, as voles are expert at hiding from such predators.[4] Some caterpillars even shoot their feces away from themselves in an explosive burst, helping them to avoid predators taking advantage of the olfactory signal it creates. In a non-predatory example, dominant wildebeest bulls defend territories marked with feces and pheromones produced by scent glands.
Seeds may also be found in feces. Animals which eat fruit are known as frugivores. The advantage in having fruit for a plant is that animals will eat the fruit and unknowingly disperse the seed in doing so. This mode of seed dispersal is highly successful, as seeds dispersed around the base of a plant are unlikely to succeed and are often subject to heavy predation. Provided the seed can withstand the pathway through the digestive system, it is not only likely to be far away from the parent plant, but is even provided with its own fertilizer.
Organisms which subsist on dead organic matter or detritus are known as detritivores, and play an important role in ecosystems by recycling organic matter back into a simpler form which plants and other autotrophs may once again absorb. This cycling of matter is known as the biogeochemical cycle. To maintain nutrients in soil it is therefore important that feces return to the area from which they came, which is not always the case in human society where food may be transported from rural areas to urban populations and then feces disposed of into a river or sea.
# Human feces
In humans, defecation may occur (depending on the individual and the circumstances) from once every two or three days to several times a day. Hardening of the feces may cause prolonged interruption in the routine and is called constipation.
Human fecal matter varies significantly in appearance, depending on diet and health. Normally it is semisolid, with a mucus coating. Its brown coloration comes from a combination of bile and bilirubin, which comes from dead red blood cells.
In newborn babies, fecal matter is initially yellow/green after the meconium. This coloration comes from the presence of bile alone. In time, as the body starts expelling bilirubin from dead red blood cells, it acquires its familiar brown appearance, unless the baby is breast feeding, in which case it remains soft, pale yellowish, and not-unpleasantly scented until the baby begins to eat significant amounts of other food.
Throughout the life of an ordinary human, one may experience many types of feces. A "green" stool is from rapid transit of feces through the intestines (or the consumption of certain blue or green food dyes in quantity), and "clay-like" appearance to the feces is the result of a lack of bilirubin.
Bile overload is very rare, and not a health threat. Problems as simple as serious diarrhea can cause blood in one's stool. Black stools caused by blood usually indicate a problem in the intestines (the black is digested blood), whereas red streaks of blood in stool are usually caused by bleeding in the rectum or anus.
Food may sometimes make an appearance in the feces. Common undigested foods found in human feces are seeds, nuts, corn and beans, mainly because of their high dietary fiber content. Artificial food coloring in some processed foods such as highly colorful packaged breakfast cereals can also cause unusual feces coloring if eaten in sufficient quantities.
## Differential Diagnosis of Causes of Feces Consistency
### Slimy
- Allergic diarrhea
- Amebic dysentery
- Chronic enterocolitis
- Colitis mucosa
- Gastroenteritis
- Pellagra
### Thin
- Constipation
- Rectal carcinoma
### Watery
- Acute gastroenteritis
- Carcinoid syndrome
- Cholera
- Intoxication
## Differential Diagnosis of Causes of Feces Color
Stool color can provide insight into the pathophysiologic basis of disease.
### Black Stool
- Melena, often the source is the upper GI tract as acid contents cause the stool to turn black. associated with acharacteristic foul smell. BUN will often be increased due to absorption of nitrogenous products in the upper GI tract.
### Bright Red
- Lower GI bleed
- Hemorrhoids
### Light Grey
- After radiocontrast use
- Bile duct occlusion
- Fatty stool
- Viral Hepatitis
## Personal hygiene
All cultures practice some form of personal cleansing after expelling feces.
- In Western society, the use of toilet paper is widespread.
- Other paper products were also historically used (before the advent of flush toilets).
- Before paper was cheap to produce, a "toilet rag" made of cloth was used, with a separate rag assigned to each family member.
- Several companies market toilet tissue or wipes for babies and campers.
- In some European countries, the use of a bidet for additional cleaning is common.
- In South Asia, showers are provided for use in toilets.
- In Islam, washing is prescribed by ritual cleansing with water, of which washing of the anus is part of the ablutions. The "act" of passing toilet, in Islam, requires ritual cleansing with water using the left hand. As religion is often practiced by widely differing cultural groups, Islamic tradition involves washing of the hands using soap and water after ablutions after using the toilet, to using of tissue paper to dry-off hands and other "wet" parts of the body to showers after each toilet use. In many Muslim countries, piped water is supplied inside toilets for both bathing and washing in addition to flushing of faecal matter. Such toilets are also common in Greece, Spain and parts of Eastern Europe.
- In India, the anus is also washed with water using the left hand. As with all such practices, hand washing after use of the toilet has become a very important public health issue.
- In England, there was historically much fascination with the act of going to the toilet, with royals appointing lesser mortals to assist with the removal of faeces and cleansing of the body parts using towels. The Indian toilet was adapted as the WC or water closet and widely deployed in England during the reign of Queen Victoria. London was the stage for several instances of food poisoning resulting from workers handling food after using the toilet. Cleansing of the anus was an arbitrary practice left to personal choice and facility available.
- In Ancient Rome, a communal sponge was used, which was then rinsed in a bucket of salt water.
- In Japan, flat sticks were used in ancient times, being replaced by toilet paper as the country became more "westernized." Toilets that include built-in bidets have now become widely popular in private homes.
## Bristol Stool Scale
Consistency and shape of stools may be classified medically according to the Bristol Stool Scale.
Pica, a disorder where non-food items are eaten, can cause unusual stool. Intestinal parasites and their ova (eggs) can sometimes be visible to the naked eye.
# Odor
The distinctive odor of feces is due to bacterial action. Gut flora produce compounds such as indole, skatole, and thiols (sulfur-containing compounds), as well as the inorganic gas hydrogen sulfide. These are the same compounds that are responsible for the odor of flatulence. Consumption of foods with spices may result in the spices being undigested and adding to the odor of feces. Certain commercial products exist that claim to reduce the odor of feces. The perceived bad odor of feces has been hypothesized to be a deterrent for humans, as consumption or touching it may result in sickness or infection. [5] Of course, human perception of the odor is a subjective matter; an animal that eats feces may be attracted to its odor.
# Pets
Pets can be trained to use litter boxes or wait to be let out via several methods, such as crate training for dogs. Several companies market carpet cleaning products aimed at pet owners. However pet feces can be cleaned with just dishwashing detergent or liquid soap. [6]
# Uses
The feces of animals is often used as fertilizer; see manure.
Some animal feces, especially those of the camel, bison and cow, is used as fuel when dried out.[7]
Animal dung, besides being used as fuel, is occasionally used as a cement to make adobe mud brick huts [8] or even in throwing sports such as cow pat throwing or camel dung throwing contests.[9]
See also Fewmets for the use of faeces in Venery, or Hunting in the Middle_Ages
See also Kopi Luwak
Kopi Luwak (pronounced [ˈkopi ˈluwak]) or Civet coffee is coffee made from coffee berries which have been eaten by and passed through the digestive tract of the Asian Palm Civet (Paradoxurus hermaphroditus). | https://www.wikidoc.org/index.php/Ddx:Feces_Color | |
ec13f257a42b1ae9ac63350d65b597c390760ca9 | wikidoc | Debye | Debye
# Overview
The debye (symbol: D) is a non-SI, CGS unit of electrical dipole moment. It is defined as 1Template:E statcoulomb centimeter (or 1Template:E esu m, or 1Template:E Fr cm). In SI units, 1 D equals approximately 3.33564Template:E coulomb-meter (exactly 1Template:E C m2/s divided by c, the speed of light in vacuum). Conversely 1 C m = 2.9979Template:E D.
It is named after the physicist Peter J. W. Debye.
Historically the debye was defined as the dipole moment resulting from two charges of opposite sign but an equal magnitude of 10-10 statcoulomb (generally called esu in older literature), which were separated by 1 angstrom (10-8 cm or 10-10m).
Note that
10-10 statcoulomb is 0.48 units of elementary charge.
This gave a convenient unit for molecular dipole moments. Typical dipole moments for simple diatomic molecules are in the range of 0 - 11D, where symmetric homoatomic species, e.g. chlorine, Cl2, have a dipole moment of 0D and highly ionic molecular species such as gas phase potassium bromide, KBr have a dipole moment of 10.5D.
The debye is still used in atomic physics and chemistry because SI units are inconveniently large, particularly since the smallest prefix is Template:E (e.g., 2.54 D = 8.47Template:E yCm). Note that SI disallows the application of prefixes to both members of a compound unit (e.g., 2.54 D = 8.47 fC·fm) or the compounding of prefixes (e.g., 2.54 D = 8.47 µyCm), so there is currently no satisfactory solution to this problem of notation. | Debye
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
The debye (symbol: D) is a non-SI, CGS unit of electrical dipole moment. It is defined as 1Template:E statcoulomb centimeter (or 1Template:E esu m, or 1Template:E Fr cm). In SI units, 1 D equals approximately 3.33564Template:E coulomb-meter (exactly 1Template:E C m2/s divided by c, the speed of light in vacuum). Conversely 1 C m = 2.9979Template:E D.
It is named after the physicist Peter J. W. Debye.
Historically the debye was defined as the dipole moment resulting from two charges of opposite sign but an equal magnitude of 10-10 statcoulomb (generally called esu in older literature), which were separated by 1 angstrom (10-8 cm or 10-10m).
</math>
Note that
10-10 statcoulomb is 0.48 units of elementary charge.
This gave a convenient unit for molecular dipole moments. Typical dipole moments for simple diatomic molecules are in the range of 0 - 11D, where symmetric homoatomic species, e.g. chlorine, Cl2, have a dipole moment of 0D and highly ionic molecular species such as gas phase potassium bromide, KBr have a dipole moment of 10.5D.[1]
The debye is still used in atomic physics and chemistry because SI units are inconveniently large, particularly since the smallest prefix is Template:E (e.g., 2.54 D = 8.47Template:E yCm). Note that SI disallows the application of prefixes to both members of a compound unit (e.g., 2.54 D = 8.47 fC·fm) or the compounding of prefixes (e.g., 2.54 D = 8.47 µyCm), so there is currently no satisfactory solution to this problem of notation. | https://www.wikidoc.org/index.php/Debye | |
10ae3d78f994c12fd6cb0a7a870be9b17f747034 | wikidoc | Liter | Liter
# Overview
The litre or liter (see spelling differences) is a unit of volume. There are two official symbols: the Latin letter L in lower (l) and upper case (L). The liter appears in several versions of the metric system; although not an SI unit, it is accepted for use with the SI. The international unit of volume is the cubic meter (m³). One liter is denoted as 1 cubic decimeter (dm³).
# Origin
The word "liter" is derived from an older French unit, the litron, whose name came from Greek via Latin. The original metric system used the liter as a base unit.
# Definition
A liter is defined as a special name for a cubic decimeter (1 L = 1 dm³). Hence 1 L ≡ 0.001 m³ (exactly).
So 1000 L = 1 m3
# SI prefixes applied to the liter
The liter may be used with any SI prefix. The more often used terms are in bold in the table below.
## Milliliter (milliliter)
The milliliter is defined as one cubic centimeter and one-thousandth of a liter. It is a commonly used measurement, especially in medicine and cooking. Acceptable symbols for the milliliter are mL and ml.
# Non-metric conversions
## Rough conversions
A liter is the volume of a cube with sides of 10 cm, which is slightly less than a cube of sides 4 inches (or one-third of a foot). Twenty-seven cubes "one-third of a foot on each side" would fit in one cubic foot, which is within 5% of the actual value of exactly 28.316846592 liters.
One liter is also slightly more than one U.S. liquid quart and slightly less than one Imperial quart or the less common U.S. dry quart.
A measured cup is roughly 237 mL. However, this number is usually rounded to 250 mL to ease metrication of recipies using English units of measurement.
# Explanation
Liters are most commonly used for items measured by the capacity or size of their container (such as fluids and berries), whereas cubic meters (and derived units) are most commonly used for items measured either by their dimensions or their displacements. The liter is often also used in some calculated measurements, such as density (kg/L), allowing an easy comparison with the density of water.
One liter of water has a mass of almost exactly one kilogram. Similarly: 1 milliliter of water has about 1 g of mass; 1,000 liters of water has about 1,000 kg (1 ton) of mass. This relationship is because the gram was originally defined as the mass of 1 mL of water. However, this definition was abandoned in 1964 because the density of water changes with pressure and the units of pressure are dependent on the definition of mass.
# Symbol
Originally, the only symbol for the liter was l (lowercase letter l), following the SI convention that only those unit symbols that abbreviate the name of a person start with a capital letter.
In many English-speaking countries, the most common shape of a handwritten Arabic digit 1 is just a vertical stroke, that is it lacks the upstroke added in many other cultures. Therefore, the digit 1 may easily be confused with the letter l. On some typewriters, particularly older ones, the unshifted L key had to be used to type the numeral 1. Further, even in some computer typefaces, the two characters are barely distinguishable at all. This caused some concern, especially in the medical community. As a result, L (uppercase letter L) was adopted as an alternative symbol for liter in 1979. The United States National Institute of Standards and Technology now recommends the use of the uppercase letter L, a practice that is also widely followed in Canada and Australia. In these countries, the symbol L is also used with prefixes, as in mL and µL, instead of the traditional ml and µl used in Europe. In the UK and Ireland, lowercase l is used with prefixes, though whole liters are often written in full (so, "750 ml" on a wine bottle, but often "1 liter" on a juice carton).
Prior to 1979, the symbol Template:Unicode (script small l, U+2113), came into common use in some countries; for example, it was recommended by South African Bureau of Standards publication M33 and Canada in the 1970s. This symbol can still be encountered occasionally in some English-speaking countries, and its use is ubiquitous in Japan and South Korea. Nevertheless, it is no longer used in most countries and no longer officially recognised by the Bureau International des Poids et Mesures, the International Organization for Standardization due to confusion and because it is often not (anyway) available in many documentation systems.
# History
In 1795, the liter was introduced in France as one of the new "Republican Measures", and defined as one cubic decimeter.
In 1879, the Comité International des Poids et Mesures adopted the definition of the liter, and the symbol l (lowercase letter L).
In 1901, at the 3rd General Conference on Weights and Measures conference, the liter was redefined as the space occupied by 1 kg of pure water at the temperature of its maximum density (3.98 °C) under a pressure of 1 atm. This made the liter equal to about 1.000 028 dm³ (earlier reference works usually put it at 1.000 027 dm³).
In 1964, at the 12th General Conference on Weights and Measures conference, the original definition was reverted to, and thus the liter was once again defined in exact relation to the meter, as another name for the cubic decimeter, that is, exactly 1 dm³.
In 1979, at the 16th General Conference on Weights and Measures conference, the alternative symbol L (uppercase letter L) was adopted. It also expressed a preference that in the future only one of these two symbols should be retained, but in 1990 said it was still too early to do so.
# Colloquial and practical usage
In spoken English, the abbreviation "mL" (for milliliter) is often pronounced as "mil", which is homophonous with the term "mil", meaning "one thousandth of an inch". This generally does not create confusion, because the context is usually sufficient — one being a volume, the other a linear measurement. The colloquial use of "mil" for millimeter for an ambiguous topic as in "5 mils of rain fell since 9am" may, however, be confusing.
The abbreviation cc (for cubic centimeter, equal to a milliliter or mL)) is a unit of the cgs system, that preceded the MKS system, that later evolved into the SI system. The abbreviation cc is still commonly used in many fields including (for example) sizing for motorcycle and related sports for combustion engine displacement.
In European countries where the metric system was established well before the adoption of the SI standard, there is still carry-over of usage from the precursor cgs and MKS systems. In the SI system, use of prefixes for multiples of 1,000 is preferred and all other multiples discouraged. However, in countries where these other multiples were already established, their use remains common. In particular, use of the centi (10-2), deci (10-1), deca (10+1), and hecto (10+2) prefixes are still common. For example, in many European countries, the hectoliter is the typical unit for production and export volumes of beverages (milk, beer, soft drinks, etc); deciliters are found in cookbooks; centiliters indicate the capacity of drinking glasses and of small bottles. In colloquial Dutch in Belgium, a 'vijfentwintiger' and a 'drieëndertiger' (literally 'twenty-fiver' and 'thirty-threer') are the common beer glasses, the corresponding bottles mention 25 cL or 33 cL. Bottles may also be 75 cL or half size at 37.5 cL for 'artisanal' brews or 70 cL for wines or spirits. Cans come in 25 cL, 33 cL and 50 cL aka 0.5 L. Family size bottles as for soft drinks or drinking water use the liter (0.5 L, 1 L, 1.5 L, 2 L), and so do beer barrels (50 L, or the half sized 25 L). This unit is most common for all other household size containers of liquids, from thermocans, by buckets, to bath tubs; as well as for fuel tanks and consumption for heating or by vehicles.
In countries where where the metric system was adopted as the official measuring system after the SI standard was established, common usage more closely follow contemporary SI conventions. For example, in Canada where the metric system is now in wide-spread use, consumer beverages are labelled almost exclusively using liters and milliliters. Hectoliters sometimes appear in industry, but centiliters and deciliters are rarely, if ever, used. Larger volumes are usually given in cubic meters (equivalent to 1 kL), or thousands or millions of cubic meters. The situation is similar in Australia, although kiloliters, megaliters and gigaliters are commonly used for measuring water consumption, reservoir capacities and river flows.
For larger volumes of fluids, such as annual consumption of tap water, lorry (truck) tanks, or swimming pools, the cubic meter is the general unit, as it is for all volumes of a non-liquid nature. There are a few exceptions in which the liter is used for rather large volumes, such as the irregularly shaped boot of a car or the internal size of a microwave oven. | Liter
# Overview
The litre or liter (see spelling differences) is a unit of volume. There are two official symbols: the Latin letter L in lower (l) and upper case (L). The liter appears in several versions of the metric system; although not an SI unit, it is accepted for use with the SI. The international unit of volume is the cubic meter (m³). One liter is denoted as 1 cubic decimeter (dm³).
# Origin
The word "liter" is derived from an older French unit, the litron, whose name came from Greek via Latin. The original metric system used the liter as a base unit.
# Definition
A liter is defined as a special name for a cubic decimeter (1 L = 1 dm³). Hence 1 L ≡ 0.001 m³ (exactly).
So 1000 L = 1 m3
# SI prefixes applied to the liter
The liter may be used with any SI prefix. The more often used terms are in bold in the table below.
## Milliliter (milliliter)
The milliliter is defined as one cubic centimeter and one-thousandth of a liter. It is a commonly used measurement, especially in medicine and cooking. Acceptable symbols for the milliliter are mL and ml.
# Non-metric conversions
## Rough conversions
A liter is the volume of a cube with sides of 10 cm, which is slightly less than a cube of sides 4 inches (or one-third of a foot). Twenty-seven cubes "one-third of a foot on each side" would fit in one cubic foot, which is within 5% of the actual value of exactly 28.316846592 liters.
One liter is also slightly more than one U.S. liquid quart and slightly less than one Imperial quart or the less common U.S. dry quart.
A measured cup is roughly 237 mL. However, this number is usually rounded to 250 mL to ease metrication of recipies using English units of measurement.
# Explanation
Liters are most commonly used for items measured by the capacity or size of their container (such as fluids and berries), whereas cubic meters (and derived units) are most commonly used for items measured either by their dimensions or their displacements. The liter is often also used in some calculated measurements, such as density (kg/L), allowing an easy comparison with the density of water.
One liter of water has a mass of almost exactly one kilogram. Similarly: 1 milliliter of water has about 1 g of mass; 1,000 liters of water has about 1,000 kg (1 ton) of mass. This relationship is because the gram was originally defined as the mass of 1 mL of water. However, this definition was abandoned in 1964 because the density of water changes with pressure and the units of pressure are dependent on the definition of mass.
# Symbol
Originally, the only symbol for the liter was l (lowercase letter l), following the SI convention that only those unit symbols that abbreviate the name of a person start with a capital letter.
In many English-speaking countries, the most common shape of a handwritten Arabic digit 1 is just a vertical stroke, that is it lacks the upstroke added in many other cultures. Therefore, the digit 1 may easily be confused with the letter l. On some typewriters, particularly older ones, the unshifted L key had to be used to type the numeral 1. Further, even in some computer typefaces, the two characters are barely distinguishable at all. This caused some concern, especially in the medical community. As a result, L (uppercase letter L) was adopted as an alternative symbol for liter in 1979. The United States National Institute of Standards and Technology now recommends the use of the uppercase letter L, a practice that is also widely followed in Canada and Australia. In these countries, the symbol L is also used with prefixes, as in mL and µL, instead of the traditional ml and µl used in Europe. In the UK and Ireland, lowercase l is used with prefixes, though whole liters are often written in full (so, "750 ml" on a wine bottle, but often "1 liter" on a juice carton).
Prior to 1979, the symbol Template:Unicode (script small l, U+2113), came into common use in some countries; for example, it was recommended by South African Bureau of Standards publication M33 and Canada in the 1970s. This symbol can still be encountered occasionally in some English-speaking countries, and its use is ubiquitous in Japan and South Korea. Nevertheless, it is no longer used in most countries and no longer officially recognised by the Bureau International des Poids et Mesures, the International Organization for Standardization due to confusion and because it is often not (anyway) available in many documentation systems.
# History
In 1795, the liter was introduced in France as one of the new "Republican Measures", and defined as one cubic decimeter.
In 1879, the Comité International des Poids et Mesures adopted the definition of the liter, and the symbol l (lowercase letter L).
In 1901, at the 3rd General Conference on Weights and Measures conference, the liter was redefined as the space occupied by 1 kg of pure water at the temperature of its maximum density (3.98 °C) under a pressure of 1 atm. This made the liter equal to about 1.000 028 dm³ (earlier reference works usually put it at 1.000 027 dm³).
In 1964, at the 12th General Conference on Weights and Measures conference, the original definition was reverted to, and thus the liter was once again defined in exact relation to the meter, as another name for the cubic decimeter, that is, exactly 1 dm³. [1]
In 1979, at the 16th General Conference on Weights and Measures conference, the alternative symbol L (uppercase letter L) was adopted. It also expressed a preference that in the future only one of these two symbols should be retained, but in 1990 said it was still too early to do so.[2]
# Colloquial and practical usage
In spoken English, the abbreviation "mL" (for milliliter) is often pronounced as "mil", which is homophonous with the term "mil", meaning "one thousandth of an inch". This generally does not create confusion, because the context is usually sufficient — one being a volume, the other a linear measurement. The colloquial use of "mil" for millimeter for an ambiguous topic as in "5 mils of rain fell since 9am" may, however, be confusing.
The abbreviation cc (for cubic centimeter, equal to a milliliter or mL)) is a unit of the cgs system, that preceded the MKS system, that later evolved into the SI system. The abbreviation cc is still commonly used in many fields including (for example) sizing for motorcycle and related sports for combustion engine displacement.
In European countries where the metric system was established well before the adoption of the SI standard, there is still carry-over of usage from the precursor cgs and MKS systems. In the SI system, use of prefixes for multiples of 1,000 is preferred and all other multiples discouraged. However, in countries where these other multiples were already established, their use remains common. In particular, use of the centi (10-2), deci (10-1), deca (10+1), and hecto (10+2) prefixes are still common. For example, in many European countries, the hectoliter is the typical unit for production and export volumes of beverages (milk, beer, soft drinks, etc); deciliters are found in cookbooks; centiliters indicate the capacity of drinking glasses and of small bottles. In colloquial Dutch in Belgium, a 'vijfentwintiger' and a 'drieëndertiger' (literally 'twenty-fiver' and 'thirty-threer') are the common beer glasses, the corresponding bottles mention 25 cL or 33 cL. Bottles may also be 75 cL or half size at 37.5 cL for 'artisanal' brews or 70 cL for wines or spirits. Cans come in 25 cL, 33 cL and 50 cL aka 0.5 L. Family size bottles as for soft drinks or drinking water use the liter (0.5 L, 1 L, 1.5 L, 2 L), and so do beer barrels (50 L, or the half sized 25 L). This unit is most common for all other household size containers of liquids, from thermocans, by buckets, to bath tubs; as well as for fuel tanks and consumption for heating or by vehicles.
In countries where where the metric system was adopted as the official measuring system after the SI standard was established, common usage more closely follow contemporary SI conventions. For example, in Canada where the metric system is now in wide-spread use, consumer beverages are labelled almost exclusively using liters and milliliters. Hectoliters sometimes appear in industry, but centiliters and deciliters are rarely, if ever, used. Larger volumes are usually given in cubic meters (equivalent to 1 kL), or thousands or millions of cubic meters. The situation is similar in Australia, although kiloliters, megaliters and gigaliters are commonly used for measuring water consumption, reservoir capacities and river flows.
For larger volumes of fluids, such as annual consumption of tap water, lorry (truck) tanks, or swimming pools, the cubic meter is the general unit, as it is for all volumes of a non-liquid nature. There are a few exceptions in which the liter is used for rather large volumes, such as the irregularly shaped boot of a car or the internal size of a microwave oven. | https://www.wikidoc.org/index.php/Decilitre | |
d5457fa276ece969681704364cb895ba33e93347 | wikidoc | Sleep | Sleep
Sleep is a natural state of bodily rest observed throughout the animal kingdom. It is common to all mammals and birds, and is also seen in many reptiles, amphibians and fish.
In humans, other mammals, and a substantial majority of other animals which have been studied — such as fish, birds, ants, and fruit-flies — regular sleep is essential for survival. However its purposes are only partly clear and are the subject of intense research.
# Physiology
In mammals and birds the measurement of eye movement during sleep is used to divide sleep into two broad types:
- rapid eye movement (REM) and
- non-rapid eye movement (NREM) sleep.
Each type has a distinct set of associated physiological, neurological and psychological features.
Sleep proceeds in cycles of REM and the four stages of NREM, the order normally being:
In humans this cycle is on average 90 to 110 minutes, with a greater amount of stages 3 and 4 early in the night and more REM later in the night. Each phase may have a distinct physiological function.
Drugs such as sleeping pills and alcoholic beverages can suppress certain stages of sleep (see Sleep deprivation). This can result in a sleep that exhibits loss of consciousness but does not fulfill its physiological functions.
Rechtschaffen and Kales originally outlined the criteria for staging sleep in 1968. The American Academy of Sleep Medicine (AASM) updated the staging rules in 2007.
## Stages of sleep
Criteria for REM sleep include not only rapid eye movements but also a rapid low voltage EEG. In mammals, at least, low muscle tone is also seen. Most memorable dreaming occurs in this stage.
NREM accounts for 75–80% of total sleep time in normal human adults. In NREM sleep, there is relatively little dreaming. Non-REM encompasses four stages; stages 1 and 2 are considered 'light sleep', and 3 and 4 'deep sleep' or slow-wave sleep, SWS. They are differentiated solely using EEG, unlike REM sleep which is characterized by rapid eye movements and relative absence of muscle tone. In non-REM sleep there are often limb movements, and parasomnias such as sleepwalking may occur.
A cyclical alternating pattern may sometimes be observed during a stage.
NREM consists of four stages according to the 2007 AASM standards:
- During Stage N1 the brain transitions from alpha waves (common to people who are awake and having a frequency of 8 to 13 Hz) to theta waves (frequency of 4 to 7 Hz). This stage is sometimes referred to as somnolence, or "drowsy sleep". Associated with the onset of sleep during N1 may be sudden twitches and hypnic jerks. Some people may also experience hypnagogic hallucinations during this stage, which can be more troublesome to the subject. During N1 the subject loses some muscle tone, and conscious awareness of the external environment.
- Stage N2, is characterized by "sleep spindles" (12 to 16 Hz) and "K-complexes." During this stage, muscular activity as measured by electromyography (EMG) lowers and conscious awareness of the external environment disappears. This stage occupies 45 to 55% of total sleep.
- In Stage N3, the delta waves, also called delta rhythms (0.5 to 4 Hz) make up less than 50% of the total wave-patterns. This is considered part of deep or slow-wave sleep (SWS) and appears to function primarily as a transition into stage N4. This is the stage in which night terrors, bedwetting, sleepwalking and sleep-talking occur.
- In Stage N4, delta-waves make up more than 50% of the wave-patterns. Stages N3 and N4 are the deepest forms of sleep; N4 is effectively a deeper version of N3, in which the deep-sleep characteristics, such as delta-waves, are more pronounced.
Both REM sleep and NREM sleep stages 3 and 4 are homeostatically driven; that is, if a person or animal is selectively deprived of one of these, it rebounds once uninhibited sleep again is allowed. This suggests that both are essential to the functions of the sleep process.
## Sleep timing
Sleep timing is controlled by the circadian clock, by homeostasis and, in humans, by willed behavior.
The circadian clock, an inner time-keeping, temperature-fluctuating, enzyme-controlling device, works in tandem with adenosine, a neurotransmitter which inhibits many of the bodily processes that are associated with wakefulness. Adenosine is created over the course of the day; high levels of adenosine lead to sleepiness. In diurnal animals, sleepiness occurs as the circadian element causes the release of the hormone melatonin and a gradual decrease in core body temperature. The timing is affected by one's chronotype. It is the circadian rhythm which determines the ideal timing of a correctly structured and restorative sleep episode.
Homeostatic sleep propensity, the need for sleep as a function of the amount of time elapsed since the last adequate sleep episode, is also important and must be balanced against the circadian element for satisfactory sleep. Along with corresponding messages from the circadian clock, this tells the body it needs to sleep.
Sleep offset, awakening, is primarily determined by circadian rhythm. A normal person who regularly awakens at an early hour will generally not be able to sleep much later than the person's normal waking time, even if moderately sleep deprived.
## Optimal amount in humans
### Adults
The optimal amount of sleep is not a meaningful concept unless the timing of that sleep is seen in relation to an individual's circadian rhythms. A person's major sleep episode is relatively inefficient and inadequate when it occurs at the "wrong" time of day. The timing is correct when the following two circadian markers occur after the middle of the sleep episode but before awakening:
- maximum concentration of the hormone melatonin, and
- minimum core body temperature.
The National Sleep Foundation in the United States maintains that eight to nine hours of sleep for adult humans is optimal and that sufficient sleep benefits alertness, memory and problem solving, and overall health, as well as reducing the risk of accidents. A widely publicized 2003 study performed at the University of Pennsylvania School of Medicine demonstrated that cognitive performance declines with fewer than eight hours of sleep.
However, a University of California, San Diego psychiatry study of more than one million adults found that people who live the longest self-report sleeping for six to seven hours each night. Another study of sleep duration and mortality risk in women showed similar results. Other studies show that "sleeping more than 7 to 8 hours per day has been consistently associated with increased mortality"
Causal links are currently speculative: the available data may only reflect comorbid depression, socioeconomic status, or even alcohol use, for example. These studies cannot be used to determine optimal sleep habits, only correlation — and empirically observed correlation is a necessary but not sufficient condition for causality. A need for nine or ten hours of sleep a day, or only five to six, may or may not have the same cause as the shortened life span. In other words, long or short sleep duration itself has not been shown to be a cause of early death.
Researchers from the University of Warwick and University College London have found that lack of sleep can more than double the risk of death from cardiovascular disease, but that too much sleep can also double the risk of death. Professor Francesco Cappuccio said: “Short sleep has been shown to be a risk factor for weight gain, hypertension and Type 2 diabetes sometimes leading to mortality but in contrast to the short sleep-mortality association it appears that no potential mechanisms by which long sleep could be associated with increased mortality have yet been investigated. Some candidate causes for this include depression, low socioeconomic status and cancer-related fatigue. In terms of prevention, our findings indicate that consistently sleeping around 7 hours per night is optimal for health and a sustained reduction may predispose to ill-health.”
### Hours by age
Children need a greater amount of sleep per day than adults to develop and function properly: up to 18 hours for newborn babies, with a declining rate as a child ages. A newborn baby spends almost half of its sleep time in REM-sleep. By the age of five or so, only a bit over two hours are spent in REM.
## Sleep debt
Sleep debt is the effect of not getting enough rest and sleep; a large debt causes mental and physical fatigue. Scientists do not agree on how much sleep debt it is possible to accumulate, nor on whether the prevalence of sleep debt among adults has changed appreciably in the industrialized world in recent decades. It is likely that children are sleeping less than previously in Western societies.
# Functions
The multiple theories proposed to explain the function of sleep are reflective of the as yet incomplete understanding of the subject.
It is likely that sleep evolved to fulfill some primeval function, but has taken over multiple functions over time as organisms have evolved. An analogy would be that of the larynx, which performs multiple functions such as controlling the passage of food and air, phonation for communicating and social purposes, etc. These are all functions of the larynx but just one of them likely represents the original function. Some of the many proposed functions of sleep are as follows:
## Restoration
Wound healing has been shown to be affected by sleep. A study conducted by Gumustekin et al. in 2004 shows sleep deprivation hindering the healing of burns on rats.
It has also been shown that sleep deprivation affects the immune system and metabolism. In a study by Zager et al in 2007, rats were deprived of sleep for 24 hours. When compared with a control group, the sleep-deprived rats' blood tests indicated a 20% decrease in white blood cell count, a significant change in the immune system.
A study by Bonnet and Arand in 2003 indicates that sleep affects metabolism. Comparing normal human sleepers and sleepers with sleep state misperception insomnia, where patients complain of poor sleep but have normal sleep by electroencephalographic (EEG) criteria, the researchers found significantly greater metabolism values for the normal sleepers.
It has yet to be clearly proven that sleep duration affects somatic growth. One study by Jenni et al in 2007 recorded growth, height and weight, as correlated to parent-reported time-in-bed in 305 children over a period of nine years (age 1-10). It was found that "the variation of sleep duration among children does not seem to have an effect on growth". It has been shown that sleep, more specifically slow-wave sleep (SWS), does affect growth hormone levels in adult men. During eight hours sleep, Van Cauter, Leproult, and Plat found that the men with a high percentage of SWS (average 24%) also had high growth hormone secretion, while subjects with a low percentage of SWS (average 9%) had low growth hormone secretion.
There are multiple arguments supporting the restorative function of sleep. We feel rested after sleeping, and it is natural to assume that this is a basic purpose of sleep. Overall metabolic rate goes down during sleep and certain anabolic hormones such as growth hormones as mentioned above are secreted preferentially during sleep. Sleep among species is, in general, inversely related to the animal size and basal metabolic rate. Rats with a very high basal metabolic rate sleep for up to 14 hours a day whereas elephants and giraffes with lower BMRs sleep only 3-4 hours per day.
Energy conservation could as well have been accomplished by resting quiescent without shutting off the organism from the environment, potentially a dangerous situation. A sedentary non-sleeping animal is more likely to survive predators, while still preserving energy. Sleep therefore does something else other than conserving energy. Most interestingly, hibernating animals, when they wake up from hibernation go into rebound sleep because of lack of sleep during the hibernation period. They are definitely well rested and are conserving energy during hibernation, but need sleep for something else.
One study that was conducted kept rats awake indefinitely. They started dying after 5 days.
## Anabolic/catabolic
Non-REM sleep may be an anabolic state marked by physiological processes of growth and rejuvenation of the organism's immune, nervous, muscular, and skeletal systems (but see above). Wakefulness may perhaps be viewed as a cyclical, temporary, hyperactive catabolic state during which the organism acquires nourishment and procreates.
## Ontogenesis
According to the ontogenetic hypothesis of REM sleep, the activity occurring during neonatal REM sleep (or active sleep) seems to be particularly important to the developing organism (Marks et al., 1995). Studies investigating the effects of deprivation of active sleep have shown that deprivation early in life can result in behavioral problems, permanent sleep disruption, decreased brain mass (Mirmiran et al. 1983), and an abnormal amount of neuronal cell death (Morrissey, Duntley & Anch, 2004).
REM sleep appears to be important for development of the brain. REM sleep occupies majority of time of sleep of infants, which spend most of their time sleeping. Among different species, the more immature the baby is born, the more time it spends in REM sleep. Proponents also suggest that REM-induced muscle inhibition in the presence of brain activation exists to allow for brain development by activating the synapses yet without any motor consequences which may get the infant in trouble. Additionally, REM deprivation results in developmental abnormalities later in life.
However, this does not explain why older adults still need REM sleep, and why the fraction of time spent does not change significantly as one ages. Aquatic mammal infants do not have REM sleep in infancy. REM sleep in those animals increases as they age. Obviously, REM sleep is not needed for development in these animals.
## Memory processing
Scientists have shown numerous ways in which sleep is related to memory. In a study conducted by Turner, Drummond, Salamat, and Brown working memory was shown to be affected by sleep deprivation. Working memory is important because it keeps information active for further processing and supports higher-level cognitive functions such as decision making, reasoning, and episodic memory. Turner et al. allowed 18 women and 22 men to sleep only 26 minutes per night over a 4-day period. Subjects were given initial cognitive tests while well rested and then tested again twice a day during the 4 days of sleep deprivation. On the final test the average working memory span of the sleep deprived group had dropped by 38% in comparison to the control group.
Memory also seems to be affected differently by certain stages of sleep such as REM and slow-wave sleep (SWS). In one study cited in Born, Rasch, and Gais multiple groups of human subjects were used: wake control groups and sleep test groups. Sleep and wake groups were taught a task and then tested on it both on early and late nights, with the order of nights balanced across participants. When the subject’s brains were scanned during sleep, hypnograms revealed that SWS was the dominant sleep stage during the early night representing around 23% on average for sleep stage activity. The early night test group performed 16% better on the declarative memory test than the control group. During late night sleep, REM became the most active sleep stage at about 24%, and the late night test group performed 25% better on the procedural memory test than the control group. This indicates that procedural memory benefits from late REM-rich sleep where as declarative memory benefits from early SWS-rich sleep.
Another study conducted by Datta indirectly supports these results. The subjects chosen were 22 male rats. A box was constructed where a single rat could move freely from one end to the other. The bottom of the box was made of a steel grate. A light would shine in the box accompanied by a sound. After a 5 second delay an electrical shock would be applied. Once the shock commenced the rat could move to the other end of the box, ending the shock immediately. The rat could also use the 5 second delay to move to the other end of the box and avoid the shock entirely. The length of the shock never exceeded 5 seconds. This was repeated 30 times for half the rats. The other half, the control group, was placed in the same trial but the rats were shocked regardless of their reaction. After each of the training sessions the rat would be placed in a recording cage for 6 hours of polygraphic recordings. This process was repeated for 3 consecutive days. This study found that during the post-trial sleep recording session rats spent 25.47% more time in REM sleep after learning trials than after control trials. These trials support the results of the Born et al. study, indicating an obvious correlation between REM sleep and procedural knowledge.
Another interesting observation of the Datta study is that the learning group spent 180% more time in SWS than did the control group during the post-trial sleep-recording session. This phenomenon is supported by a study performed by Kudrimoti, Barnes, and McNaughton. This study shows that after spatial exploration activity, patterns of hippocampal place cells are reactivated during SWS following the experiment. In a study by Kudrimoti et al seven rats were run through a linear track using rewards on either end. The rats would then be placed in the track for 30 minutes to allow them to adjust (PRE), then they ran the track with reward based training for 30 minutes (RUN), and then they were allowed to rest for 30 minutes. During each of these three periods EEG data was collected for information on the rats’ sleep stages. Kudrimoti et al computed the mean firing rates of hippocampal place cells during pre-behavior SWS (PRE) and three 10 min intervals in post-behavior SWS (POST) by averaging across 22 track-running sessions from seven rats. The results showed that 10 min after the trial RUN session there was a 12% increase in the mean firing rate of hippocampal place cells from the PRE level, however after 20 minutes the mean firing rate returned rapidly toward the PRE level. The elevated firing of hippocampal place cells during SWS after spatial exploration could explain why there were elevated levels of SWS sleep in Datta’s study as it also dealt with a form of spatial exploration.
The different studies all suggest that there is a correlation between sleep and the many complex functions of memory.
## Preservation
The "Preservation and Protection" theory holds that sleep serves an adaptive function. It protects the person during that portion of the 24-hour day in which being awake, and hence roaming around, would place the individual at greatest risk. Organisms do not require 24 hours to feed themselves and meet other necessities. From this perspective of adaptation, organisms are safer by staying out of harm's way where potentially they could be prey to other, stronger organisms. They sleep at times that maximize their safety, given their physical capacities and their habitats. (Allison & Cicchetti, 1976; Webb, 1982).
However, this theory fails to explain why the brain disengages from the external environment during normal sleep. Another argument against the theory is that sleep is not simply a passive consequence of removing the animal from the environment, but is a "drive": animals alter their behaviors in order to obtain sleep. Therefore, circadian regulation is more than sufficient to explain periods of activity and quiescence that are adaptive to an organism, but the more peculiar specializations of sleep probably serve different and unknown functions.
Moreover, the preservation theory does not explain why carnivores like lions, which are on top of the food chain, sleep the most. By the preservation logic, these top carnivores should not need any sleep at all. Preservation does not explain why aquatic mammals sleep while moving. Lethargy during these vulnerable hours would do the same, and will be more advantageous because the animal will be quiescent but still be able to respond to environmental challenges like predators etc. Sleep rebound that occurs after a sleepless night will be maladaptive, but still occurs for a reason. For example, a zebra falling asleep the day after it spent the sleeping time running from a lion is more and not less vulnerable to predation.
# Dreaming
Dreaming is the perception of sensory images during sleep, in a sequence which the sleeper/dreamer usually perceives more as an apparent participant than an observer. Dreaming is stimulated by the pons and mostly occurs during the REM phase of sleep.
People have proposed many hypotheses about the functions of dreaming. Sigmund Freud postulated that dreams are the symbolic expression of frustrated desires that had been relegated to the subconscious, and he used dream interpretation in the form of psychoanalysis to uncover these desires. Scientists have become skeptical about the Freudian interpretation, and place more emphasis on dreaming as a requirement for organization and consolidation of recent memory and experience. See Freud:The Interpretation of Dreams
Rosalind Cartwright stated that "One Function of dreams may be to restore our sense of competence...it is also probable that in many times of stress, dreams have more work to do in resolving our problems and are thus more salient and memorable."Template:Citequote
J. Allan Hobson's and Robert McCarley's activation synthesis theory proposes that dreams are caused by the random firing of neurons in the cerebral cortex during the REM period. According to the theory, the forebrain then creates a story in an attempt to reconcile and make sense of the nonsensical sensory information presented to it, hence the odd nature of many dreams.
# Effect of food and drink on sleep
## Drowsiness
- Tryptophan
The amino acid tryptophan is a building block of the protein found in foods. It contributes to sleepiness. Carbohydrates make tryptophan more available to the brain, which is why carbohydrate-heavy meals containing tryptophan tend to cause drowsiness.
- Melatonin
Melatonin is a naturally occurring hormone that regulates sleepiness. It is made in the brain where tryptophan is converted into serotonin and then into melatonin, which is released at night by the pineal gland to induce and maintain sleep. Melatonin supplementation may be used as a sleep aid, both as a hypnotic and as a chronobiotic (see phase response curve, PRC).
- The "Post-Lunch Dip"
Many people have a temporary drop in alertness in early afternoon, commonly known as the post-lunch dip. While a large meal, rich in carbohydrates, can make a person feel sleepy, the post-lunch dip is mostly an effect of the biological clock. People naturally feel most sleepy (have the greatest "drive for sleep") at two times of the day about 12 hours apart, for example at 2:00 AM and 2:00 PM. At those two times, the body clock "kicks in". At about 2 p.m. (14:00), it overrides the homeostatic build-up of sleep debt, allowing several more hours of wakefulness. At about 2 a.m. (02:00), with the daily sleep debt paid off, it "kicks in" again to ensure a few more hours of sleep.
- Alcohol
Alcoholic beverages aid relaxation and commonly are used as a sleep aid. Alcohol tends, however, to disrupt sleep throughout the night and can prevent the deeper stages of sleep from occurring.
## Stimulation
- Caffeine
Caffeine is a stimulant that works by slowing the action of the hormones in the brain that cause sleepiness. Effective dosage is individual, in part dependent on prior usage. It can cause a rapid reduction in alertness as it wears off.
- Amphetamines
Amphetamines are often used to treat narcolepsy, the most common effects are decreased appetite, decreased stamina, and physical energy.
- Energy Drinks
The stimulating effects of energy drinks comes from natural stimulants such as caffeine, sugars, and essential amino acids, and eventually will create a rapid reduction in alertness similar to that of caffeine.
Further reading: National Sleep Foundation - Topics: A to Zzzzs
# Causes of difficulty in sleeping
There are a great many possible reasons for sleeping poorly. Following sleep hygienic principles may solve problems of physical or emotional discomfort. When pain, illness, drugs or stress are the culprit, the cause must be treated. Sleep disorders, including the sleep apneas, narcolepsy, primary insomnia, periodic limb movement disorder (PLMD), restless leg syndrome (RLS) and the circadian rhythm sleep disorders, are treatable.
Elderly people may to some degree lose the ability to consolidate sleep. They need the same amount per day as they've always needed, but may need to take some of their sleep as daytime naps.
# Anthropology of sleep
Recent research suggests that sleep patterns vary significantly across human cultures. The most striking differences are between societies that have plentiful artificial light and ones that do not. Cultures without artificial light have more broken-up sleep patterns. This is called polyphasic sleep or segmented sleep and has led to expressions such as "first sleep," "watch," and "second sleep" which appear in literature from all over the world.
Some cultures have fragmented sleep patterns in which people sleep at all times of the day, and for shorter periods at night. For example, many Mediterranean and Latin American cultures have a siesta, in which people sleep for a period in the afternoon. In many nomadic or hunter-gatherer societies people sleep off and on throughout the day or night depending on what is happening.
# Sleep in non-humans
Horses and other herbivorous ungulates can sleep while standing, but must necessarily lie down for REM sleep (which causes muscular atony) for short periods - giraffes, for example, only need to lie down for REM sleep for a few minutes at a time. Bats sleep while hanging upside down. Some aquatic mammals and some birds can sleep with one half of the brain, while the other half is awake, so called unihemispheric slow-wave sleep. Birds and mammals have cycles of non-REM and REM sleep as described above for humans, though birds’ cycles are much shorter and they do not lose muscle tone (go limp) to the same extent that most mammals do.
Many animals sleep, but neurological sleep states are difficult to define in lower order animals. In these animals, sleep is defined using behavioral characteristics such as minimal movement, postures typical for the species and reduced responsiveness to external stimulation. It is quickly reversible, as opposed to hibernation or coma, and sleep deprivation is followed by longer and/or deeper sleep.
Many species of mammals sleep for a large proportion of each 24-hour period when they are very young. However, killer whales and some dolphins do not sleep during the first month after they are born.
# Longest period without sleep
Depending on how sleep is defined, there are several people who can claim the record for having gone the longest without sleep:
- Thai Ngoc, born 1942, claimed in 2006 to have been awake for 33 years or 11,700 nights, according to Vietnamese news organization Thanh Nien. It was said that Ngoc acquired the ability to go without sleep after a bout of fever in 1973, but other reports indicate he stopped sleeping in 1976 with no known trigger. At the time of the Thanh Nien report, Ngoc suffered from no apparent ill effect (other than a minor decline in liver function), was mentally sound and could carry 100 kg of pig feed down a 4 km road, but another report indicates that he was healthy before the sleepless episode but that now he was not feeling well because of the lack of sleep.
- In January 2005, the RIA Novosti published an article about Fyodor Nesterchuk from the Ukrainian town of Kamen-Kashirsky who claimed to have not slept in more than 20 years. Local doctor Fyodor Koshel, chief of the Lutsk city health department, claimed to have examined him extensively and failed to make him sleep. Koshel also said however that Nesterchuck did not suffer any of the normally deleterious effects of sleep deprivation. Several bloggers have commented that people who claim not to sleep are usually shown to sleep when studied in sleep laboratories with EEG. Another blog stated that Ananova's reprinting of the story is indicative of their having a reputation for not being a credible source of news. The "problem" may lie in that Nesterchuck and people like him don't remember sleeping, which may be cause for further study. Whether he doesn't sleep or doesn't remember sleeping, either event indicates a condition not present in most humans. Nesterchuck reports experiencing drowsiness at night, commenting that he attempts to sleep "in vain" when he notices his eyelids drooping. Many people also experience microsleep episodes during sleep deprivation, in which they sleep for periods of seconds to fractions of a second and frequently don't remember these episodes. Because microsleep is frequently not remembered, microsleep or a related phenomenon may be responsible for lack of sleep and/or lack of memory in individuals like Nesterchuk and Thai Ngoc.
- Randy Gardner holds the Guinness World Record for intentionally having gone the longest without sleep. In 1965, Gardner, then 18, stayed awake for 264 hours (about 11 days) for a high school science project. He experienced significant deficits in concentration, motivation, perception and other higher mental processes during his sleep deprivation. However, he recovered normal cognitive functions after a few nights' sleep.
- On May 25 2007 the BBC reported that Tony Wright beat the Guinness World Record by staying awake for 11 days and nights. The Guinness Book of Records has, however, withdrawn its backing of a sleep deprivation class because of the associated health risks.
- A 3-year-old boy named Rhett Lamb of St. Petersburg Florida has a rare condition and has only slept for one to two hours per day in the past three years. He has a rare abnormality called an Arnold-Chiari malformation where brain tissue protrudes into the spinal canal. The skull puts pressure on the protruding part of the brain. It is not yet known if the brain malformation is directly related to his sleep deprivation. Rhett checked into a hospital for an experimental surgery to relieve the issue. | Sleep
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Sleep is a natural state of bodily rest observed throughout the animal kingdom. It is common to all mammals and birds, and is also seen in many reptiles, amphibians and fish.
In humans, other mammals, and a substantial majority of other animals which have been studied — such as fish, birds, ants, and fruit-flies — regular sleep is essential for survival. However its purposes are only partly clear and are the subject of intense research.[1]
# Physiology
In mammals and birds the measurement of eye movement during sleep is used to divide sleep into two broad types:
- rapid eye movement (REM) and
- non-rapid eye movement (NREM) sleep.
Each type has a distinct set of associated physiological, neurological and psychological features.
Sleep proceeds in cycles of REM and the four stages of NREM, the order normally being:
In humans this cycle is on average 90 to 110 minutes,[2] with a greater amount of stages 3 and 4 early in the night and more REM later in the night. Each phase may have a distinct physiological function.
Drugs such as sleeping pills and alcoholic beverages can suppress certain stages of sleep (see Sleep deprivation). This can result in a sleep that exhibits loss of consciousness but does not fulfill its physiological functions.
Rechtschaffen and Kales originally outlined the criteria for staging sleep in 1968. The American Academy of Sleep Medicine (AASM) updated the staging rules in 2007.
## Stages of sleep
Criteria for REM sleep include not only rapid eye movements but also a rapid low voltage EEG. In mammals, at least, low muscle tone is also seen. Most memorable dreaming occurs in this stage.
NREM accounts for 75–80% of total sleep time in normal human adults. In NREM sleep, there is relatively little dreaming. Non-REM encompasses four stages; stages 1 and 2 are considered 'light sleep', and 3 and 4 'deep sleep' or slow-wave sleep, SWS. They are differentiated solely using EEG, unlike REM sleep which is characterized by rapid eye movements and relative absence of muscle tone. In non-REM sleep there are often limb movements, and parasomnias such as sleepwalking may occur.
A cyclical alternating pattern may sometimes be observed during a stage.
NREM consists of four stages according to the 2007 AASM standards:
- During Stage N1 the brain transitions from alpha waves (common to people who are awake and having a frequency of 8 to 13 Hz) to theta waves (frequency of 4 to 7 Hz). This stage is sometimes referred to as somnolence, or "drowsy sleep". Associated with the onset of sleep during N1 may be sudden twitches and hypnic jerks. Some people may also experience hypnagogic hallucinations during this stage, which can be more troublesome to the subject. During N1 the subject loses some muscle tone, and conscious awareness of the external environment.
- Stage N2, is characterized by "sleep spindles" (12 to 16 Hz) and "K-complexes." During this stage, muscular activity as measured by electromyography (EMG) lowers and conscious awareness of the external environment disappears. This stage occupies 45 to 55% of total sleep.
- In Stage N3, the delta waves, also called delta rhythms (0.5 to 4 Hz) make up less than 50% of the total wave-patterns. This is considered part of deep or slow-wave sleep (SWS) and appears to function primarily as a transition into stage N4. This is the stage in which night terrors, bedwetting, sleepwalking and sleep-talking occur.
- In Stage N4, delta-waves make up more than 50% of the wave-patterns. Stages N3 and N4 are the deepest forms of sleep; N4 is effectively a deeper version of N3, in which the deep-sleep characteristics, such as delta-waves, are more pronounced.[3]
Both REM sleep and NREM sleep stages 3 and 4 are homeostatically driven; that is, if a person or animal is selectively deprived of one of these, it rebounds once uninhibited sleep again is allowed. This suggests that both are essential to the functions of the sleep process.
## Sleep timing
Sleep timing is controlled by the circadian clock, by homeostasis and, in humans, by willed behavior.
The circadian clock, an inner time-keeping, temperature-fluctuating, enzyme-controlling device, works in tandem with adenosine, a neurotransmitter which inhibits many of the bodily processes that are associated with wakefulness. Adenosine is created over the course of the day; high levels of adenosine lead to sleepiness. In diurnal animals, sleepiness occurs as the circadian element causes the release of the hormone melatonin and a gradual decrease in core body temperature. The timing is affected by one's chronotype. It is the circadian rhythm which determines the ideal timing of a correctly structured and restorative sleep episode.[4]
Homeostatic sleep propensity, the need for sleep as a function of the amount of time elapsed since the last adequate sleep episode, is also important and must be balanced against the circadian element for satisfactory sleep. Along with corresponding messages from the circadian clock, this tells the body it needs to sleep.[5]
Sleep offset, awakening, is primarily determined by circadian rhythm. A normal person who regularly awakens at an early hour will generally not be able to sleep much later than the person's normal waking time, even if moderately sleep deprived.
## Optimal amount in humans
### Adults
The optimal amount of sleep is not a meaningful concept unless the timing of that sleep is seen in relation to an individual's circadian rhythms. A person's major sleep episode is relatively inefficient and inadequate when it occurs at the "wrong" time of day. The timing is correct when the following two circadian markers occur after the middle of the sleep episode but before awakening:[6]
- maximum concentration of the hormone melatonin, and
- minimum core body temperature.
The National Sleep Foundation in the United States maintains that eight to nine hours of sleep for adult humans is optimal and that sufficient sleep benefits alertness, memory and problem solving, and overall health, as well as reducing the risk of accidents.[7] A widely publicized 2003 study[8] performed at the University of Pennsylvania School of Medicine demonstrated that cognitive performance declines with fewer than eight hours of sleep.
However, a University of California, San Diego psychiatry study of more than one million adults found that people who live the longest self-report sleeping for six to seven hours each night.[9] Another study of sleep duration and mortality risk in women showed similar results.[10] Other studies show that "sleeping more than 7 to 8 hours per day has been consistently associated with increased mortality"[11]
Causal links are currently speculative: the available data may only reflect comorbid depression, socioeconomic status, or even alcohol use, for example.[12] These studies cannot be used to determine optimal sleep habits, only correlation — and empirically observed correlation is a necessary but not sufficient condition for causality. A need for nine or ten hours of sleep a day, or only five to six, may or may not have the same cause as the shortened life span. In other words, long or short sleep duration itself has not been shown to be a cause of early death.
Researchers from the University of Warwick and University College London have found that lack of sleep can more than double the risk of death from cardiovascular disease, but that too much sleep can also double the risk of death.[13][14] Professor Francesco Cappuccio said: “Short sleep has been shown to be a risk factor for weight gain, hypertension and Type 2 diabetes sometimes leading to mortality but in contrast to the short sleep-mortality association it appears that no potential mechanisms by which long sleep could be associated with increased mortality have yet been investigated. Some candidate causes for this include depression, low socioeconomic status and cancer-related fatigue. [...] In terms of prevention, our findings indicate that consistently sleeping around 7 hours per night is optimal for health and a sustained reduction may predispose to ill-health.”
### Hours by age
Children need a greater amount of sleep per day than adults to develop and function properly: up to 18 hours for newborn babies, with a declining rate as a child ages.[7][15] A newborn baby spends almost half of its sleep time in REM-sleep. By the age of five or so, only a bit over two hours are spent in REM.[16]
## Sleep debt
Sleep debt is the effect of not getting enough rest and sleep; a large debt causes mental and physical fatigue. Scientists do not agree on how much sleep debt it is possible to accumulate, nor on whether the prevalence of sleep debt among adults has changed appreciably in the industrialized world in recent decades. It is likely that children are sleeping less than previously in Western societies.[17]
# Functions
The multiple theories proposed to explain the function of sleep are reflective of the as yet incomplete understanding of the subject.
It is likely that sleep evolved to fulfill some primeval function, but has taken over multiple functions over time as organisms have evolved. An analogy would be that of the larynx, which performs multiple functions such as controlling the passage of food and air, phonation for communicating and social purposes, etc. These are all functions of the larynx but just one of them likely represents the original function. Some of the many proposed functions of sleep are as follows:
## Restoration
Wound healing has been shown to be affected by sleep. A study conducted by Gumustekin et al.[18] in 2004 shows sleep deprivation hindering the healing of burns on rats.
It has also been shown that sleep deprivation affects the immune system and metabolism. In a study by Zager et al in 2007,[19] rats were deprived of sleep for 24 hours. When compared with a control group, the sleep-deprived rats' blood tests indicated a 20% decrease in white blood cell count, a significant change in the immune system.
A study by Bonnet and Arand[20] in 2003 indicates that sleep affects metabolism. Comparing normal human sleepers and sleepers with sleep state misperception insomnia, where patients complain of poor sleep but have normal sleep by electroencephalographic (EEG) criteria, the researchers found significantly greater metabolism values for the normal sleepers.
It has yet to be clearly proven that sleep duration affects somatic growth. One study by Jenni et al[21] in 2007 recorded growth, height and weight, as correlated to parent-reported time-in-bed in 305 children over a period of nine years (age 1-10). It was found that "the variation of sleep duration among children does not seem to have an effect on growth". It has been shown that sleep, more specifically slow-wave sleep (SWS), does affect growth hormone levels in adult men. During eight hours sleep, Van Cauter, Leproult, and Plat[22] found that the men with a high percentage of SWS (average 24%) also had high growth hormone secretion, while subjects with a low percentage of SWS (average 9%) had low growth hormone secretion.
There are multiple arguments supporting the restorative function of sleep. We feel rested after sleeping, and it is natural to assume that this is a basic purpose of sleep. Overall metabolic rate goes down during sleep and certain anabolic hormones such as growth hormones as mentioned above are secreted preferentially during sleep. Sleep among species is, in general, inversely related to the animal size and basal metabolic rate. Rats with a very high basal metabolic rate sleep for up to 14 hours a day whereas elephants and giraffes with lower BMRs sleep only 3-4 hours per day.
Energy conservation could as well have been accomplished by resting quiescent without shutting off the organism from the environment, potentially a dangerous situation. A sedentary non-sleeping animal is more likely to survive predators, while still preserving energy. Sleep therefore does something else other than conserving energy. Most interestingly, hibernating animals, when they wake up from hibernation go into rebound sleep because of lack of sleep during the hibernation period. They are definitely well rested and are conserving energy during hibernation, but need sleep for something else.[23]
One study that was conducted kept rats awake indefinitely. They started dying after 5 days.
## Anabolic/catabolic
Non-REM sleep may be an anabolic state marked by physiological processes of growth and rejuvenation of the organism's immune, nervous, muscular, and skeletal systems (but see above). Wakefulness may perhaps be viewed as a cyclical, temporary, hyperactive catabolic state during which the organism acquires nourishment and procreates.
## Ontogenesis
According to the ontogenetic hypothesis of REM sleep, the activity occurring during neonatal REM sleep (or active sleep) seems to be particularly important to the developing organism (Marks et al., 1995). Studies investigating the effects of deprivation of active sleep have shown that deprivation early in life can result in behavioral problems, permanent sleep disruption, decreased brain mass (Mirmiran et al. 1983), and an abnormal amount of neuronal cell death (Morrissey, Duntley & Anch, 2004).
REM sleep appears to be important for development of the brain. REM sleep occupies majority of time of sleep of infants, which spend most of their time sleeping. Among different species, the more immature the baby is born, the more time it spends in REM sleep. Proponents also suggest that REM-induced muscle inhibition in the presence of brain activation exists to allow for brain development by activating the synapses yet without any motor consequences which may get the infant in trouble. Additionally, REM deprivation results in developmental abnormalities later in life.
However, this does not explain why older adults still need REM sleep, and why the fraction of time spent does not change significantly as one ages. Aquatic mammal infants do not have REM sleep in infancy. REM sleep in those animals increases as they age. Obviously, REM sleep is not needed for development in these animals.
## Memory processing
Scientists have shown numerous ways in which sleep is related to memory. In a study conducted by Turner, Drummond, Salamat, and Brown[24] working memory was shown to be affected by sleep deprivation. Working memory is important because it keeps information active for further processing and supports higher-level cognitive functions such as decision making, reasoning, and episodic memory. Turner et al. allowed 18 women and 22 men to sleep only 26 minutes per night over a 4-day period. Subjects were given initial cognitive tests while well rested and then tested again twice a day during the 4 days of sleep deprivation. On the final test the average working memory span of the sleep deprived group had dropped by 38% in comparison to the control group.
Memory also seems to be affected differently by certain stages of sleep such as REM and slow-wave sleep (SWS). In one study cited in Born, Rasch, and Gais[25] multiple groups of human subjects were used: wake control groups and sleep test groups. Sleep and wake groups were taught a task and then tested on it both on early and late nights, with the order of nights balanced across participants. When the subject’s brains were scanned during sleep, hypnograms revealed that SWS was the dominant sleep stage during the early night representing around 23% on average for sleep stage activity. The early night test group performed 16% better on the declarative memory test than the control group. During late night sleep, REM became the most active sleep stage at about 24%, and the late night test group performed 25% better on the procedural memory test than the control group. This indicates that procedural memory benefits from late REM-rich sleep where as declarative memory benefits from early SWS-rich sleep.
Another study conducted by Datta[26] indirectly supports these results. The subjects chosen were 22 male rats. A box was constructed where a single rat could move freely from one end to the other. The bottom of the box was made of a steel grate. A light would shine in the box accompanied by a sound. After a 5 second delay an electrical shock would be applied. Once the shock commenced the rat could move to the other end of the box, ending the shock immediately. The rat could also use the 5 second delay to move to the other end of the box and avoid the shock entirely. The length of the shock never exceeded 5 seconds. This was repeated 30 times for half the rats. The other half, the control group, was placed in the same trial but the rats were shocked regardless of their reaction. After each of the training sessions the rat would be placed in a recording cage for 6 hours of polygraphic recordings. This process was repeated for 3 consecutive days. This study found that during the post-trial sleep recording session rats spent 25.47% more time in REM sleep after learning trials than after control trials. These trials support the results of the Born et al. study, indicating an obvious correlation between REM sleep and procedural knowledge.
Another interesting observation of the Datta study is that the learning group spent 180% more time in SWS than did the control group during the post-trial sleep-recording session. This phenomenon is supported by a study performed by Kudrimoti, Barnes, and McNaughton.[27] This study shows that after spatial exploration activity, patterns of hippocampal place cells are reactivated during SWS following the experiment. In a study by Kudrimoti et al seven rats were run through a linear track using rewards on either end. The rats would then be placed in the track for 30 minutes to allow them to adjust (PRE), then they ran the track with reward based training for 30 minutes (RUN), and then they were allowed to rest for 30 minutes. During each of these three periods EEG data was collected for information on the rats’ sleep stages. Kudrimoti et al computed the mean firing rates of hippocampal place cells during pre-behavior SWS (PRE) and three 10 min intervals in post-behavior SWS (POST) by averaging across 22 track-running sessions from seven rats. The results showed that 10 min after the trial RUN session there was a 12% increase in the mean firing rate of hippocampal place cells from the PRE level, however after 20 minutes the mean firing rate returned rapidly toward the PRE level. The elevated firing of hippocampal place cells during SWS after spatial exploration could explain why there were elevated levels of SWS sleep in Datta’s study as it also dealt with a form of spatial exploration.
The different studies all suggest that there is a correlation between sleep and the many complex functions of memory.
## Preservation
The "Preservation and Protection" theory holds that sleep serves an adaptive function. It protects the person during that portion of the 24-hour day in which being awake, and hence roaming around, would place the individual at greatest risk. Organisms do not require 24 hours to feed themselves and meet other necessities. From this perspective of adaptation, organisms are safer by staying out of harm's way where potentially they could be prey to other, stronger organisms. They sleep at times that maximize their safety, given their physical capacities and their habitats. (Allison & Cicchetti, 1976; Webb, 1982).
However, this theory fails to explain why the brain disengages from the external environment during normal sleep. Another argument against the theory is that sleep is not simply a passive consequence of removing the animal from the environment, but is a "drive": animals alter their behaviors in order to obtain sleep. Therefore, circadian regulation is more than sufficient to explain periods of activity and quiescence that are adaptive to an organism, but the more peculiar specializations of sleep probably serve different and unknown functions.
Moreover, the preservation theory does not explain why carnivores like lions, which are on top of the food chain, sleep the most. By the preservation logic, these top carnivores should not need any sleep at all. Preservation does not explain why aquatic mammals sleep while moving. Lethargy during these vulnerable hours would do the same, and will be more advantageous because the animal will be quiescent but still be able to respond to environmental challenges like predators etc. Sleep rebound that occurs after a sleepless night will be maladaptive, but still occurs for a reason. For example, a zebra falling asleep the day after it spent the sleeping time running from a lion is more and not less vulnerable to predation.
# Dreaming
Dreaming is the perception of sensory images during sleep, in a sequence which the sleeper/dreamer usually perceives more as an apparent participant than an observer. Dreaming is stimulated by the pons and mostly occurs during the REM phase of sleep.
People have proposed many hypotheses about the functions of dreaming. Sigmund Freud postulated that dreams are the symbolic expression of frustrated desires that had been relegated to the subconscious, and he used dream interpretation in the form of psychoanalysis to uncover these desires. Scientists have become skeptical about the Freudian interpretation, and place more emphasis on dreaming as a requirement for organization and consolidation of recent memory and experience. See Freud:The Interpretation of Dreams
Rosalind Cartwright stated that "One Function of dreams may be to restore our sense of competence...it is also probable that in many times of stress, dreams have more work to do in resolving our problems and are thus more salient and memorable."Template:Citequote
J. Allan Hobson's and Robert McCarley's activation synthesis theory proposes that dreams are caused by the random firing of neurons in the cerebral cortex during the REM period. According to the theory, the forebrain then creates a story in an attempt to reconcile and make sense of the nonsensical sensory information presented to it, hence the odd nature of many dreams.[28]
# Effect of food and drink on sleep
## Drowsiness
- Tryptophan
The amino acid tryptophan is a building block of the protein found in foods. It contributes to sleepiness. Carbohydrates make tryptophan more available to the brain, which is why carbohydrate-heavy meals containing tryptophan tend to cause drowsiness.
- Melatonin
Melatonin is a naturally occurring hormone that regulates sleepiness. It is made in the brain where tryptophan is converted into serotonin and then into melatonin, which is released at night by the pineal gland to induce and maintain sleep. Melatonin supplementation may be used as a sleep aid, both as a hypnotic and as a chronobiotic (see phase response curve, PRC).
- The "Post-Lunch Dip"
Many people have a temporary drop in alertness in early afternoon, commonly known as the post-lunch dip. While a large meal, rich in carbohydrates, can make a person feel sleepy, the post-lunch dip is mostly an effect of the biological clock. People naturally feel most sleepy (have the greatest "drive for sleep") at two times of the day about 12 hours apart, for example at 2:00 AM and 2:00 PM. At those two times, the body clock "kicks in". At about 2 p.m. (14:00), it overrides the homeostatic build-up of sleep debt, allowing several more hours of wakefulness. At about 2 a.m. (02:00), with the daily sleep debt paid off, it "kicks in" again to ensure a few more hours of sleep.
- Alcohol
Alcoholic beverages aid relaxation and commonly are used as a sleep aid. Alcohol tends, however, to disrupt sleep throughout the night and can prevent the deeper stages of sleep from occurring.
## Stimulation
- Caffeine
Caffeine is a stimulant that works by slowing the action of the hormones in the brain that cause sleepiness. Effective dosage is individual, in part dependent on prior usage. It can cause a rapid reduction in alertness as it wears off.
- Amphetamines
Amphetamines are often used to treat narcolepsy, the most common effects are decreased appetite, decreased stamina, and physical energy.
- Energy Drinks
The stimulating effects of energy drinks comes from natural stimulants such as caffeine, sugars, and essential amino acids, and eventually will create a rapid reduction in alertness similar to that of caffeine.
Further reading: National Sleep Foundation - Topics: A to Zzzzs
# Causes of difficulty in sleeping
There are a great many possible reasons for sleeping poorly. Following sleep hygienic principles may solve problems of physical or emotional discomfort.[29] When pain, illness, drugs or stress are the culprit, the cause must be treated. Sleep disorders, including the sleep apneas, narcolepsy, primary insomnia, periodic limb movement disorder (PLMD), restless leg syndrome (RLS) and the circadian rhythm sleep disorders, are treatable.
Elderly people may to some degree lose the ability to consolidate sleep. They need the same amount per day as they've always needed, but may need to take some of their sleep as daytime naps.
# Anthropology of sleep
Recent research suggests that sleep patterns vary significantly across human cultures.[30][31] The most striking differences are between societies that have plentiful artificial light and ones that do not. Cultures without artificial light have more broken-up sleep patterns. This is called polyphasic sleep or segmented sleep and has led to expressions such as "first sleep," "watch," and "second sleep" which appear in literature from all over the world.
Some cultures have fragmented sleep patterns in which people sleep at all times of the day, and for shorter periods at night. For example, many Mediterranean and Latin American cultures have a siesta, in which people sleep for a period in the afternoon. In many nomadic or hunter-gatherer societies people sleep off and on throughout the day or night depending on what is happening.
# Sleep in non-humans
Horses and other herbivorous ungulates can sleep while standing, but must necessarily lie down for REM sleep (which causes muscular atony) for short periods - giraffes, for example, only need to lie down for REM sleep for a few minutes at a time. Bats sleep while hanging upside down. Some aquatic mammals and some birds can sleep with one half of the brain, while the other half is awake, so called unihemispheric slow-wave sleep.[32] Birds and mammals have cycles of non-REM and REM sleep as described above for humans, though birds’ cycles are much shorter and they do not lose muscle tone (go limp) to the same extent that most mammals do.
Many animals sleep, but neurological sleep states are difficult to define in lower order animals. In these animals, sleep is defined using behavioral characteristics such as minimal movement, postures typical for the species and reduced responsiveness to external stimulation. It is quickly reversible, as opposed to hibernation or coma, and sleep deprivation is followed by longer and/or deeper sleep.
Many species of mammals sleep for a large proportion of each 24-hour period when they are very young.[33] However, killer whales and some dolphins do not sleep during the first month after they are born.[34]
# Longest period without sleep
Depending on how sleep is defined, there are several people who can claim the record for having gone the longest without sleep:
- Thai Ngoc, born 1942, claimed in 2006 to have been awake for 33 years or 11,700 nights, according to Vietnamese news organization Thanh Nien. It was said that Ngoc acquired the ability to go without sleep after a bout of fever in 1973,[35] but other reports indicate he stopped sleeping in 1976 with no known trigger.[36] At the time of the Thanh Nien report, Ngoc suffered from no apparent ill effect (other than a minor decline in liver function), was mentally sound and could carry 100 kg of pig feed down a 4 km road,[35] but another report indicates that he was healthy before the sleepless episode but that now he was not feeling well because of the lack of sleep.[36]
- In January 2005, the RIA Novosti published an article about Fyodor Nesterchuk from the Ukrainian town of Kamen-Kashirsky who claimed to have not slept in more than 20 years. Local doctor Fyodor Koshel, chief of the Lutsk city health department, claimed to have examined him extensively and failed to make him sleep. Koshel also said however that Nesterchuck did not suffer any of the normally deleterious effects of sleep deprivation.[37] Several bloggers have commented that people who claim not to sleep are usually shown to sleep when studied in sleep laboratories with EEG.[38] Another blog stated that Ananova's reprinting of the story is indicative of their having a reputation for not being a credible source of news.[39] The "problem" may lie in that Nesterchuck and people like him don't remember sleeping, which may be cause for further study. Whether he doesn't sleep or doesn't remember sleeping, either event indicates a condition not present in most humans. Nesterchuck reports experiencing drowsiness at night, commenting that he attempts to sleep "in vain" when he notices his eyelids drooping. Many people also experience microsleep episodes during sleep deprivation, in which they sleep for periods of seconds to fractions of a second and frequently don't remember these episodes. Because microsleep is frequently not remembered, microsleep or a related phenomenon may be responsible for lack of sleep and/or lack of memory in individuals like Nesterchuk and Thai Ngoc.
- Randy Gardner holds the Guinness World Record for intentionally having gone the longest without sleep. In 1965, Gardner, then 18, stayed awake for 264 hours (about 11 days) for a high school science project.[40] He experienced significant deficits in concentration, motivation, perception and other higher mental processes during his sleep deprivation. However, he recovered normal cognitive functions after a few nights' sleep.
- On May 25 2007 the BBC reported that Tony Wright beat the Guinness World Record by staying awake for 11 days and nights.[41] The Guinness Book of Records has, however, withdrawn its backing of a sleep deprivation class because of the associated health risks.
- A 3-year-old boy named Rhett Lamb of St. Petersburg Florida has a rare condition and has only slept for one to two hours per day in the past three years. He has a rare abnormality called an Arnold-Chiari malformation where brain tissue protrudes into the spinal canal. The skull puts pressure on the protruding part of the brain. It is not yet known if the brain malformation is directly related to his sleep deprivation. Rhett checked into a hospital for an experimental surgery to relieve the issue. | https://www.wikidoc.org/index.php/Delta_sleep | |
90dc91552c350e77730613c01b88630fb94bb2ef | wikidoc | Mange | Mange
Mange (from Middle English manjeue, from Old French manjue, from mangier, meaning to eat) is a parasitic infestation of the skin of animals. Common symptoms include hair loss, itching and inflammation, all of which are caused by microscopic mites. Mange is most commonly found in dogs and other canines, but it can occur in other domestic and wild animals.
Similar skin infestations in humans are not usually called mange but Demodicidosis which may have a rosacea-like appearance.
The mites embed themselves in the hair follicles or skin, depending on the type. Both detection and treatment can be difficult and generally require consultation with a veterinarian.
Two types of mites produce canine mange, and each type has characteristic symptoms.
# Demodectic mange
Also called demodicosis or Red Mange, demodectic mange in dogs is caused by a sensitivity to and overpopulation of Demodex canis as the animal's immune system is unable to keep the mites in check. This is a mite that occurs naturally in the hair follicles of most dogs in low numbers around the face and other areas of the body. In most dogs, these mites never cause problems. However, in certain situations, such as an under-developed immune system, an impaired immune system, intense stress, or malnutrition, the mites can reproduce rapidly, causing symptoms in sensitive dogs that range from mild irritation and hair loss on a small patch of skin to severe and widespread inflammation, secondary infection, and--in rare cases--a life-threatening condition. Small patches of demodicosis often correct themselves over time as the dog's immune system matures , although treatment is usually recommended.
Minor cases of demodectic mange usually do not cause much itching but might cause pustules on the dog's skin, redness, scaling, hair loss, or any combination of these. It most commonly appears first on the face, around the eyes, or at the corners of the mouth, and on the forelimbs and paws.
In the more severe form, hair loss can occur in patches all over the body and might be accompanied by crusting, pain, enlarged lymph nodes, and deep skin infections.
Demodectic mange is not generally contagious to people, other animals, or even other dogs (except from mother to pup); these mites thrive only on very specific hosts (dogs) and transmission usually occurs only from the mother to nursing puppies during the first few days after birth. The transmission of these mites from mother to pup is normal (which is why the mites are normal inhabitants of the dog's skin), but some individuals are sensitive to the mites, which can lead to the development of demodectic mange.
Some breeds appear to have an increased risk of mild cases as young dogs, including the Afghan Hound, American Staffordshire Terrier, Boston Terrier, Boxer, Chihuahua, Shar Pei, Collie, Dalmatian, Doberman Pinscher, Bulldog, German Shepherd Dog, Great Dane, Old English Sheepdog, American Pit Bull Terrier, West Highland White Terrier, rat terrier, and Pug. There is strong evidence that a predilection for juvenile demodectic mange is inherited, and those suffering from this form should not be bred.
Demodectic mange also occurs in other domestic and wild animals. The mites are specific to their hosts, and each mammal species is host to one or two unique species of Demodex mites. There are two types of Demodectic mange in cats. Demodex cati causes follicular mange, similar to that seen in dogs, though it is much less common. Demodex gatoi is a more superficial form of mange, causes an itchy skin condition, and is contagious amongst cats.
## Treatment
Minor, localized cases are often treated with medicated shampoos and not treated with agents aimed at killing mites as these infestations often resolve within several weeks in young dogs.
Demodectic mange with secondary infection is treated with antibiotics and medicated shampoos as well as parasiticidal agents. Amitraz is a parasiticidal rinse that is licensed for use in many countries for treating canine demodicosis. It is applied weekly or biweekly, for several weeks, until no mites can be detected by skin scrapings.
Demodectic mange in dogs can also be managed with ivermectins, although there are few countries which license these drugs, which are given by mouth, daily, for this use. Ivermectin is used most frequently; collie-like herding breeds often do not tolerate this drug due to a defect in the blood-brain barrier, though not all of them have this defect. Other avermectin drugs that can be used include doramectin and milbemycin.
Cats with Demodex gatoi must be treated with weekly or bi-weekly sulfurated lime rinses. Demodex cati is treated similarly to canine demodicosis.
# Sarcoptic mange
Also known as canine scabies, sarcoptic mange is a highly contagious infestation of Sarcoptes scabiei canis, a burrowing mite. The canine sarcoptic mite can also infest humans and cats, pigs, horses, sheep and various other species.
These mites dig into and through the skin, causing intense itching and crusting that can quickly become infected. Hair loss and crusting frequently appear first on elbows and ears. Skin damage can occur from the dog's intense scratching and biting and secondary skin infection is common. Dogs with chronic sarcoptic mange are often in poor condition.
## Treatment
Affected dogs need to be isolated from other dogs and their bedding, and places they have occupied must be thoroughly cleaned. Other dogs in contact with a diagnosed case should be evaluated and treated.
There are a number of parasiticidal treatments useful in treating canine scabies. Sulfurated lime rinses applied weekly or bi-weekly are effective. Selamectin is licensed for treatment by veterinary prescription in several countries; it is applied as a drip-on directly to the skin. Unlicensed, but frequently used, ivermectin, given by mouth for two to four weekly treatments; this drug is not safe to use on some collie-like herding dogs, however. Other avermectin drugs are also effective, but none is licensed for use on dogs.
# Diagnosis
Veterinarians usually attempt diagnosis with skin scrapings from multiple areas, which are then examined under a microscope for mites. Sarcoptes, because they may be present in relatively low numbers, and because they are often removed by dogs chewing at themselves, may be difficult to demonstrate. As a result, diagnosis in Sarcoptic mange is often based on symptoms rather than actual confirmation of the presence of mites. A common and simple way of determining if a dog has mange is if it displays what is called a "Pedal-Pinna reflex", which is when the dog moves one of its hind legs in a scratching motion as the ear is being manipulated and scratched gently by the examiner; because the mites proliferate on the ear margins in nearly all cases at some point, this method works over 95% of the time. It is helpful in cases where all symptoms of mange are present but no mites are observed with a microscope. In some countries, a serologic test is available that may be useful in diagnosis.
For demodectic mange, properly performed deep skin scrapings generally allow the veterinarian to identify the microscopic mites. However because the mite is a normal inhabitant of the dog's skin, the presence of the mites does not conclusively mean the dog suffers from demodex. Rather abnormally high numbers of the mite are more useful. In breeds such as the West Highland White Terrier, relatively minor skin irritation which would otherwise be considered allergy should be carefully scraped because of the predilection of these dogs to demodectic mange. Skin scrapings may be used to follow the progress of treatment in demodectic mange. | Mange
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Mange (from Middle English manjeue, from Old French manjue, from mangier, meaning to eat)[1] is a parasitic infestation of the skin of animals. Common symptoms include hair loss, itching and inflammation, all of which are caused by microscopic mites. Mange is most commonly found in dogs and other canines, but it can occur in other domestic and wild animals.
Similar skin infestations in humans are not usually called mange but Demodicidosis which may have a rosacea-like appearance.[2]
The mites embed themselves in the hair follicles or skin, depending on the type. Both detection and treatment can be difficult and generally require consultation with a veterinarian.
Two types of mites produce canine mange, and each type has characteristic symptoms.
# Demodectic mange
Also called demodicosis or Red Mange, demodectic mange in dogs is caused by a sensitivity to and overpopulation of Demodex canis as the animal's immune system is unable to keep the mites in check. This is a mite that occurs naturally in the hair follicles of most dogs in low numbers around the face and other areas of the body. In most dogs, these mites never cause problems. However, in certain situations, such as an under-developed immune system, an impaired immune system, intense stress, or malnutrition, the mites can reproduce rapidly, causing symptoms in sensitive dogs that range from mild irritation and hair loss on a small patch of skin to severe and widespread inflammation, secondary infection, and--in rare cases--a life-threatening condition. Small patches of demodicosis often correct themselves over time as the dog's immune system matures , although treatment is usually recommended.
Minor cases of demodectic mange usually do not cause much itching but might cause pustules on the dog's skin, redness, scaling, hair loss, or any combination of these. It most commonly appears first on the face, around the eyes, or at the corners of the mouth, and on the forelimbs and paws.
In the more severe form, hair loss can occur in patches all over the body and might be accompanied by crusting, pain, enlarged lymph nodes, and deep skin infections.
Demodectic mange is not generally contagious to people, other animals, or even other dogs (except from mother to pup); these mites thrive only on very specific hosts (dogs) and transmission usually occurs only from the mother to nursing puppies during the first few days after birth. The transmission of these mites from mother to pup is normal (which is why the mites are normal inhabitants of the dog's skin), but some individuals are sensitive to the mites, which can lead to the development of demodectic mange.
Some breeds appear to have an increased risk of mild cases as young dogs, including the Afghan Hound, American Staffordshire Terrier, Boston Terrier, Boxer, Chihuahua, Shar Pei, Collie, Dalmatian, Doberman Pinscher, Bulldog, German Shepherd Dog, Great Dane, Old English Sheepdog, American Pit Bull Terrier, West Highland White Terrier, rat terrier, and Pug. There is strong evidence that a predilection for juvenile demodectic mange is inherited, and those suffering from this form should not be bred.
Demodectic mange also occurs in other domestic and wild animals. The mites are specific to their hosts, and each mammal species is host to one or two unique species of Demodex mites. There are two types of Demodectic mange in cats. Demodex cati causes follicular mange, similar to that seen in dogs, though it is much less common. Demodex gatoi is a more superficial form of mange, causes an itchy skin condition, and is contagious amongst cats.
## Treatment
Minor, localized cases are often treated with medicated shampoos and not treated with agents aimed at killing mites as these infestations often resolve within several weeks in young dogs.
Demodectic mange with secondary infection is treated with antibiotics and medicated shampoos as well as parasiticidal agents. Amitraz is a parasiticidal rinse that is licensed for use in many countries for treating canine demodicosis. It is applied weekly or biweekly, for several weeks, until no mites can be detected by skin scrapings.
Demodectic mange in dogs can also be managed with ivermectins, although there are few countries which license these drugs, which are given by mouth, daily, for this use. Ivermectin is used most frequently; collie-like herding breeds often do not tolerate this drug due to a defect in the blood-brain barrier, though not all of them have this defect. Other avermectin drugs that can be used include doramectin and milbemycin.
Cats with Demodex gatoi must be treated with weekly or bi-weekly sulfurated lime rinses. Demodex cati is treated similarly to canine demodicosis.
# Sarcoptic mange
Also known as canine scabies, sarcoptic mange is a highly contagious infestation of Sarcoptes scabiei canis, a burrowing mite. The canine sarcoptic mite can also infest humans and cats, pigs, horses, sheep and various other species.
These mites dig into and through the skin, causing intense itching and crusting that can quickly become infected. Hair loss and crusting frequently appear first on elbows and ears. Skin damage can occur from the dog's intense scratching and biting and secondary skin infection is common. Dogs with chronic sarcoptic mange are often in poor condition.
## Treatment
Affected dogs need to be isolated from other dogs and their bedding, and places they have occupied must be thoroughly cleaned. Other dogs in contact with a diagnosed case should be evaluated and treated.
There are a number of parasiticidal treatments useful in treating canine scabies. Sulfurated lime rinses applied weekly or bi-weekly are effective. Selamectin is licensed for treatment by veterinary prescription in several countries; it is applied as a drip-on directly to the skin. Unlicensed, but frequently used, ivermectin, given by mouth for two to four weekly treatments; this drug is not safe to use on some collie-like herding dogs, however. Other avermectin drugs are also effective, but none is licensed for use on dogs.
# Diagnosis
Veterinarians usually attempt diagnosis with skin scrapings from multiple areas, which are then examined under a microscope for mites. Sarcoptes, because they may be present in relatively low numbers, and because they are often removed by dogs chewing at themselves, may be difficult to demonstrate. As a result, diagnosis in Sarcoptic mange is often based on symptoms rather than actual confirmation of the presence of mites. A common and simple way of determining if a dog has mange is if it displays what is called a "Pedal-Pinna reflex", which is when the dog moves one of its hind legs in a scratching motion as the ear is being manipulated and scratched gently by the examiner; because the mites proliferate on the ear margins in nearly all cases at some point, this method works over 95% of the time.[3] It is helpful in cases where all symptoms of mange are present but no mites are observed with a microscope. In some countries, a serologic test is available that may be useful in diagnosis.
For demodectic mange, properly performed deep skin scrapings generally allow the veterinarian to identify the microscopic mites. However because the mite is a normal inhabitant of the dog's skin, the presence of the mites does not conclusively mean the dog suffers from demodex. Rather abnormally high numbers of the mite are more useful. In breeds such as the West Highland White Terrier, relatively minor skin irritation which would otherwise be considered allergy should be carefully scraped because of the predilection of these dogs to demodectic mange. Skin scrapings may be used to follow the progress of treatment in demodectic mange. | https://www.wikidoc.org/index.php/Demodicidosis | |
dcc25416d91ed9a169d342c200e2a45e6417d68b | wikidoc | Densa | Densa
Densa is a fictional parody association of Mensa International. "Densa" is a play on the words: "Mensa" and "dense." It is a fictional society analgous to Mensa. Just as Mensa is a society for people who have an exceptionally high IQ, Densa would be a society for people with an exceptionally low IQ. The word is usually used for comical or satirical effect. For example, some one might say a member of Mensa is a member of Densa or should be a member of Densa for doing something dumb. It is almost always used in a light-hearted manner with a wink and a nod.
The concept of an organization for the mentally dense originated in "Boston & Outskirts Mensa Bulletin (BOMB)", August, 1974, in "A-Bomb-inable Puzzle II" by John D. Coons. The puzzle involved "The Boston chapter of Densa, the low IQ society." Subsequent issues had additional puzzles with gags about the group, and were widely reprinted by the bulletins of other Mensa groups, before the concept of a low IQ group gained wider circulation in the 1970s, with other people creating quizzes, etc.
A humor book called the The Densa Quiz: The Official & Complete Dq Test of the International Densa Society was written in 1983 by Stephen Price and J. Webster Shields.
cite news | last = McGowan | first = William | title = A Sense of Belonging | publisher = The New York Times | date = 1987-08-23 | url = | accessdate = 2007-06-28 }}
Not available through New York Times archival service, but available through Proquest. | Densa
Densa is a fictional parody association of Mensa International. "Densa" is a play on the words: "Mensa" and "dense." It is a fictional society analgous to Mensa. Just as Mensa is a society for people who have an exceptionally high IQ, Densa would be a society for people with an exceptionally low IQ. The word is usually used for comical or satirical effect. For example, some one might say a member of Mensa is a member of Densa or should be a member of Densa for doing something dumb. It is almost always used in a light-hearted manner with a wink and a nod. [1][2][3][4][5]
The concept of an organization for the mentally dense originated in "Boston & Outskirts Mensa Bulletin (BOMB)", August, 1974, in "A-Bomb-inable Puzzle II" by John D. Coons. The puzzle involved "The Boston chapter of Densa, the low IQ society." Subsequent issues had additional puzzles with gags about the group, and were widely reprinted by the bulletins of other Mensa groups, before the concept of a low IQ group gained wider circulation in the 1970s, with other people creating quizzes, etc.[6]
A humor book called the The Densa Quiz: The Official & Complete Dq Test of the International Densa Society was written in 1983 by Stephen Price and J. Webster Shields.[7]
cite news | last = McGowan | first = William | title = A Sense of Belonging | publisher = The New York Times | date = 1987-08-23 | url = http://proquest.umi.com/pqdweb?did=956947011&sid=6&Fmt=2&clientId=76566&RQT=309&VName=PQD | accessdate = 2007-06-28 }}
Not available through New York Times archival service, but available through Proquest.</ref> | https://www.wikidoc.org/index.php/Densa | |
b1c8e15065d81f42b39d7b016492db2a864f008b | wikidoc | Dicer | Dicer
Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an enzyme that in humans is encoded by the DICER1 gene. Being part of the RNase III family, Dicer cleaves double-stranded RNA (dsRNA) and pre-microRNA (pre-miRNA) into short single-stranded RNA fragments called small interfering RNA and microRNA, respectively. These fragments are approximately 20-25 base pairs long with a two-base overhang on the 3' end. Dicer facilitates the activation of the RNA-induced silencing complex (RISC), which is essential for RNA interference. RISC has a catalytic component argonaute, which is an endonuclease capable of degrading messenger RNA (mRNA).
# Discovery
Dicer was given its name in 2001 by Emily Bernstein, a graduate student in Gregory Hannon's lab at Cold Spring Harbor Laboratory, who sought to discover the enzyme responsible for generating small RNA fragments from double-stranded RNA. Dicer's ability to generate ~22 nucleotide RNA fragments was discovered by separating it from the RISC enzyme complex after initiating the RNAi pathway with dsRNA transfection. This experiment showed that RISC was not responsible for generating the observable small nucleotide fragments. Subsequent experiments testing RNase III family enzymes abilities to create RNA fragments narrowed the search to Drosophila CG4792, now named Dicer.
Dicer orthologs are present in many other organisms. In the moss Physcomitrella patens DCL1b, one of four DICER proteins, is not involved in miRNA biogenesis but in dicing miRNA target transcripts. Thus, a novel mechanism for regulation of gene expression, the epigenetic silencing of genes by miRNAs, was discovered.
In terms of crystal structure, the first Dicer to be explored was that from the protozoan Giardia intestinalis. A PAZ domain and two RNase III domains were discovered by X-ray crystallography. The protein size is 82 kDa, while it is larger in other organisms; for example, it is 219 kDa in humans. The difference in size from humans to G. intestinalis Dicer is due to at least five different domains being present within human Dicer. These domains are important in Dicer activity regulation, dsRNA processing, and RNA interference protein factor functioning.
# Functional domains
Human dicer (also known as hsDicer or DICER1) is classified a Ribonuclease III because it contains both helicase and PAZ (Piwi/Argonaute/Zwille) domains. In addition to these domains, hsDicer contains four other functional domains: two RNaseIII domains and two double stranded RNA binding domains (DUF283 and dsRBD).
Current research suggests the PAZ domain is capable of binding the 2 nucleotide 3' overhang of dsRNA while the RNaseIII catalytic domains form a pseudo-dimer around the dsRNA to initiate cleavage of the strands. This results in a functional shortening of the dsRNA strand. The distance between the PAZ and RNaseIII domains is determined by the angle of the connector helix and influences the length of the micro RNA product. The dsRBD domain binds the dsRNA, although the specific binding site of the domain has not been defined. It is possible that this domain works as part of a complex with other regulator proteins (TRBP in humans, R2D2, Loqs in Drosophila) in order to effectively position the RNaseIII domains and thus control the specificity of the sRNA products. The helicase domain has been implicated in processing long substrates.
# Role in RNA interference
## Micro RNA
RNA interference is a process where the breakdown of RNA molecules into miRNA inhibits gene expression of specific host mRNA sequences. miRNA is produced within the cell starting from primary miRNA (pri-miRNA) in the nucleus. These long sequences are cleaved into smaller precursor miRNA (pre-miRNA), which are usually 70 nucleotides with a hairpin structure. Pri-miRNA are identified by DGCR8 and cleaved by Drosha to form the pre-miRNA, a process that occurs in the nucleus. These pre-miRNA are then exported to the cytoplasm, where they are cleaved by Dicer to form mature miRNA.
## Small Interfering RNA
Small interfering RNA (siRNA) are produced and function in a similar manner to miRNA by cleaving double-stranded RNA with Dicer into smaller fragments, 21 to 23 nucleotides in length. Both miRNAs and siRNAs activate the RNA-induced silencing complex (RISC), which finds the complementary target mRNA sequence and cleaves the RNA using RNase. This in turn silences the particular gene by RNA interference. siRNAs and miRNAs differ in the fact that siRNAs are typically specific to the mRNA sequence while miRNAs aren't completely complementary to the mRNA sequence. miRNAs can interact with targets that have similar sequences, which inhibits translation of different genes. In general, RNA interference is an essential part of normal processes within organisms such as humans, and it is an area being researched as a diagnostic and therapeutic tool for cancer targets.
# Disease
## Macular degeneration
Age related macular degeneration is a prominent cause of blindness in developed countries. Dicer's role in this disease became apparent after it was discovered that affected patients showed decreased levels of Dicer in their retinal pigment epithelium (RPE). Mice with Dicer knocked out, lacking Dicer only in their RPE, exhibited similar symptoms. However, other mice lacking important RNAi pathway proteins like Drosha and Pasha, did not have symptoms of macular degeneration as Dicer-knockout mice. This observation suggested a Dicer specific role in retinal health that was independent of the RNAi pathway and thus not a function of si/miRNA generation. A form of RNA called Alu RNA (the RNA transcripts of alu elements)) was found to be elevated in patients with insufficient Dicer levels. These non coding strands of RNA can loop forming dsRNA structures that would be degraded by Dicer in a healthy retina. However, with insufficient Dicer levels, the accumulation of alu RNA leads to the degeneration of RPE as a result of inflammation.
## Cancer
Altered miRNA expression profiles in malignant cancers suggest a pivotal role of miRNA and thus dicer in cancer development and prognosis. miRNAs can function as tumor suppressors and therefore their altered expression may result in tumorigenesis. In analysis of lung and ovarian cancer, poor prognosis and decreased patient survival times correlate with decreased dicer and drosha expression. Decreased dicer mRNA levels correlate with advanced tumor stage. However, high dicer expression in other cancers, like prostate and esophageal, has been shown to correlate with poor patient prognosis. This discrepancy between cancer types suggests unique RNAi regulatory processes involving dicer differ amongst different tumor types.
Dicer is also involved in DNA repair. DNA damage increases in mammalian cells with decreased Dicer expression as a result of decreased efficiency of DNA damage repair and other mechanisms. For example, siRNA from double strand breaks (produced by Dicer) may act as guides for protein complexes involved in the double strand break repair mechanisms and can also direct chromatin modifications. Additionally, miRNAs expression patterns change as a result of DNA damage caused by ionizing or ultraviolet radiation. RNAi mechanisms are responsible for transposon silencing and in their absence, as when Dicer is knocked out/down, can lead to activated transposons that cause DNA damage. Accumulation of DNA damage may result in cells with oncogenic mutations and thus the development of a tumor.
## Viral pathogenesis
Infection by RNA viruses can trigger the RNAi cascade. It is likely dicer is involved in viral immunity as viruses that infect both plant and animal cells contain proteins designed to inhibit the RNAi response. In humans, the viruses HIV-1, influenza, and vaccinia encode such RNAi suppressing proteins. Inhibition of dicer is beneficial to the virus as dicer is able to cleave viral dsRNA and load the product onto RISC resulting in targeted degradation of viral mRNA; thus fighting the infection. Another potential mechanism for viral pathogenesis is the blockade of dicer as a way to inhibit cellular miRNA pathways.
## In insects
Insects can use Dicer as a potent antiviral. This finding is especially significant given that mosquitoes are responsible for the transmission of many viral diseases including the potentially deadly arboviruses: West Nile virus, dengue fever and yellow fever. While mosquitoes, more specifically the Aedes aegypti species, serve as the vectors for these viruses, they are not the intended host of the virus. Transmission occurs as a result of the female mosquito's need for vertebrate blood to develop her eggs. The RNAi pathway in insects is very similar to that of other animals; Dicer-2 cleaves viral RNA and loads it onto the RISC complex where one strand serves as a template for the production of RNAi products and the other is degraded. Insects with mutations leading to non-functional components of their RNAi pathway show increased viral loads for viruses they carry or increased susceptibility to viruses for which they are hosts. Similarly to humans, insect viruses have evolved mechanisms to avoid the RNAi pathway. As an example, Drosophila C virus encodes for protein 1A which binds to dsRNA thus protecting it from dicer cleavage as well as RISC loading. Heliothis virescens ascovirus 3a encodes an RNase III enzyme similar to the RNase III domains of dicer which may compete for dsRNA substrate as well as degrade siRNA duplexes to prevent RISC loading.
# Diagnostic and therapeutic applications
Dicer can be used to identify whether tumors are present within the body based on the expression level of the enzyme. A study showed that many patients that had cancer had decreased expression levels of Dicer. The same study showed that lower Dicer expression correlated with lower patient survival length. Along with being a diagnostic tool, Dicer can be used for treating patients by injecting foreign siRNA intravenously to cause gene silencing.
The siRNA was shown to be delivered in two ways in mammalian species such as mice. One way would be to directly inject into the system, which would not require Dicer function. Another way would be to introduce it by plasmids that encode for short hairpin RNA, which are cleaved by Dicer into siRNA.
One of the advantages of using Dicer to produce siRNA therapeutically would be the specificity and diversity of targets it can affect compared to what is currently being used such as antibodies or small molecular inhibitors. In general, small molecular inhibitors are difficult in terms of specificity along with unendurable side effects. Antibodies are as specific as siRNA, but it is limited by only being able to be used against ligands or surface receptors. On the other hand, low efficiency of intracellular uptake is the main obstacle of injection of siRNA. Injected SiRNA has poor stability in blood and causes stimulations of non-specific immunity. Also, producing miRNA therapeutically lacks in specificity because only 6-8 nucleotide base pairing is required for miRNA to attach to mRNA.
# Dicer-like proteins
Plant genomes encode for dicer like proteins with similar functions and protein domains as animal and insect dicer. For example, in the model organism Arabidopsis thaliana, four dicer like proteins are made and are designated DCL1 to DCL4. DCL1 is involved with miRNA generation and sRNA production from inverted repeats. DCL2 creates siRNA from cis-acting antisense transcripts which aid in viral immunity and defense. DCL3 generates siRNA which aids in chromatin modification and DCL4 is involved in trans-acting siRNA metabolism and transcript silencing at the post-transcriptional level. Additionally, DCL 1 and 3 are important for Arabidopsis flowering. In Arabidopsis, DCL knockout does not cause severe developmental problems.
Rice and grapes also produce DCLs as the dicer mechanism is a common defense strategy of many organisms. Rice has evolved other functions for the 5 DCLs it produces and they play a more important role in function and development than in Arabidopsis. Additionally, expression patterns differ among the different plant cell types of rice while expression in Arabidopsis is more homogeneous. Rice DCL expression can be effected by biological stress conditions including drought, salinity, and cold, thus, these stressors may decrease a plants viral resistance. Unlike Arabidopsis, loss of function of DCL proteins causes developmental defects in rice. | Dicer
Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an enzyme that in humans is encoded by the DICER1 gene. Being part of the RNase III family, Dicer cleaves double-stranded RNA (dsRNA) and pre-microRNA (pre-miRNA) into short single-stranded RNA fragments called small interfering RNA and microRNA, respectively. These fragments are approximately 20-25 base pairs long with a two-base overhang on the 3' end. Dicer facilitates the activation of the RNA-induced silencing complex (RISC), which is essential for RNA interference. RISC has a catalytic component argonaute, which is an endonuclease capable of degrading messenger RNA (mRNA).
# Discovery
Dicer was given its name in 2001 by Emily Bernstein, a graduate student in Gregory Hannon's lab at Cold Spring Harbor Laboratory, who sought to discover the enzyme responsible for generating small RNA fragments from double-stranded RNA. Dicer's ability to generate ~22 nucleotide RNA fragments was discovered by separating it from the RISC enzyme complex after initiating the RNAi pathway with dsRNA transfection. This experiment showed that RISC was not responsible for generating the observable small nucleotide fragments. Subsequent experiments testing RNase III family enzymes abilities to create RNA fragments narrowed the search to Drosophila CG4792, now named Dicer.[1]
Dicer orthologs are present in many other organisms.[2] In the moss Physcomitrella patens DCL1b, one of four DICER proteins, is not involved in miRNA biogenesis but in dicing miRNA target transcripts. Thus, a novel mechanism for regulation of gene expression, the epigenetic silencing of genes by miRNAs, was discovered.[3]
In terms of crystal structure, the first Dicer to be explored was that from the protozoan Giardia intestinalis. A PAZ domain and two RNase III domains were discovered by X-ray crystallography. The protein size is 82 kDa, while it is larger in other organisms; for example, it is 219 kDa in humans. The difference in size from humans to G. intestinalis Dicer is due to at least five different domains being present within human Dicer. These domains are important in Dicer activity regulation, dsRNA processing, and RNA interference protein factor functioning.[4]
# Functional domains
Human dicer (also known as hsDicer or DICER1) is classified a Ribonuclease III because it contains both helicase and PAZ (Piwi/Argonaute/Zwille) domains.[6][7] In addition to these domains, hsDicer contains four other functional domains: two RNaseIII domains and two double stranded RNA binding domains (DUF283 and dsRBD).[4][8]
Current research suggests the PAZ domain is capable of binding the 2 nucleotide 3' overhang of dsRNA while the RNaseIII catalytic domains form a pseudo-dimer around the dsRNA to initiate cleavage of the strands. This results in a functional shortening of the dsRNA strand. The distance between the PAZ and RNaseIII domains is determined by the angle of the connector helix and influences the length of the micro RNA product.[5] The dsRBD domain binds the dsRNA, although the specific binding site of the domain has not been defined. It is possible that this domain works as part of a complex with other regulator proteins (TRBP in humans, R2D2, Loqs in Drosophila) in order to effectively position the RNaseIII domains and thus control the specificity of the sRNA products.[9] The helicase domain has been implicated in processing long substrates.[9]
# Role in RNA interference
## Micro RNA
RNA interference is a process where the breakdown of RNA molecules into miRNA inhibits gene expression of specific host mRNA sequences. miRNA is produced within the cell starting from primary miRNA (pri-miRNA) in the nucleus. These long sequences are cleaved into smaller precursor miRNA (pre-miRNA), which are usually 70 nucleotides with a hairpin structure. Pri-miRNA are identified by DGCR8 and cleaved by Drosha to form the pre-miRNA, a process that occurs in the nucleus. These pre-miRNA are then exported to the cytoplasm, where they are cleaved by Dicer to form mature miRNA.[11]
## Small Interfering RNA
Small interfering RNA (siRNA) are produced and function in a similar manner to miRNA by cleaving double-stranded RNA with Dicer into smaller fragments, 21 to 23 nucleotides in length.[9] Both miRNAs and siRNAs activate the RNA-induced silencing complex (RISC), which finds the complementary target mRNA sequence and cleaves the RNA using RNase.[12] This in turn silences the particular gene by RNA interference.[13] siRNAs and miRNAs differ in the fact that siRNAs are typically specific to the mRNA sequence while miRNAs aren't completely complementary to the mRNA sequence. miRNAs can interact with targets that have similar sequences, which inhibits translation of different genes.[14] In general, RNA interference is an essential part of normal processes within organisms such as humans, and it is an area being researched as a diagnostic and therapeutic tool for cancer targets.[11]
# Disease
## Macular degeneration
Age related macular degeneration is a prominent cause of blindness in developed countries. Dicer's role in this disease became apparent after it was discovered that affected patients showed decreased levels of Dicer in their retinal pigment epithelium (RPE). Mice with Dicer knocked out, lacking Dicer only in their RPE, exhibited similar symptoms. However, other mice lacking important RNAi pathway proteins like Drosha and Pasha, did not have symptoms of macular degeneration as Dicer-knockout mice. This observation suggested a Dicer specific role in retinal health that was independent of the RNAi pathway and thus not a function of si/miRNA generation. A form of RNA called Alu RNA (the RNA transcripts of alu elements)) was found to be elevated in patients with insufficient Dicer levels. These non coding strands of RNA can loop forming dsRNA structures that would be degraded by Dicer in a healthy retina. However, with insufficient Dicer levels, the accumulation of alu RNA leads to the degeneration of RPE as a result of inflammation.[15][16]
## Cancer
Altered miRNA expression profiles in malignant cancers suggest a pivotal role of miRNA and thus dicer in cancer development and prognosis. miRNAs can function as tumor suppressors and therefore their altered expression may result in tumorigenesis.[17] In analysis of lung and ovarian cancer, poor prognosis and decreased patient survival times correlate with decreased dicer and drosha expression. Decreased dicer mRNA levels correlate with advanced tumor stage. However, high dicer expression in other cancers, like prostate[18] and esophageal, has been shown to correlate with poor patient prognosis. This discrepancy between cancer types suggests unique RNAi regulatory processes involving dicer differ amongst different tumor types.[11]
Dicer is also involved in DNA repair. DNA damage increases in mammalian cells with decreased Dicer expression as a result of decreased efficiency of DNA damage repair and other mechanisms. For example, siRNA from double strand breaks (produced by Dicer) may act as guides for protein complexes involved in the double strand break repair mechanisms and can also direct chromatin modifications. Additionally, miRNAs expression patterns change as a result of DNA damage caused by ionizing or ultraviolet radiation. RNAi mechanisms are responsible for transposon silencing and in their absence, as when Dicer is knocked out/down, can lead to activated transposons that cause DNA damage. Accumulation of DNA damage may result in cells with oncogenic mutations and thus the development of a tumor.[11]
## Viral pathogenesis
Infection by RNA viruses can trigger the RNAi cascade. It is likely dicer is involved in viral immunity as viruses that infect both plant and animal cells contain proteins designed to inhibit the RNAi response. In humans, the viruses HIV-1, influenza, and vaccinia encode such RNAi suppressing proteins. Inhibition of dicer is beneficial to the virus as dicer is able to cleave viral dsRNA and load the product onto RISC resulting in targeted degradation of viral mRNA; thus fighting the infection. Another potential mechanism for viral pathogenesis is the blockade of dicer as a way to inhibit cellular miRNA pathways.[19]
## In insects
Insects can use Dicer as a potent antiviral. This finding is especially significant given that mosquitoes are responsible for the transmission of many viral diseases including the potentially deadly arboviruses: West Nile virus, dengue fever and yellow fever.[20] While mosquitoes, more specifically the Aedes aegypti species, serve as the vectors for these viruses, they are not the intended host of the virus. Transmission occurs as a result of the female mosquito's need for vertebrate blood to develop her eggs. The RNAi pathway in insects is very similar to that of other animals; Dicer-2 cleaves viral RNA and loads it onto the RISC complex where one strand serves as a template for the production of RNAi products and the other is degraded. Insects with mutations leading to non-functional components of their RNAi pathway show increased viral loads for viruses they carry or increased susceptibility to viruses for which they are hosts. Similarly to humans, insect viruses have evolved mechanisms to avoid the RNAi pathway. As an example, Drosophila C virus encodes for protein 1A which binds to dsRNA thus protecting it from dicer cleavage as well as RISC loading. Heliothis virescens ascovirus 3a encodes an RNase III enzyme similar to the RNase III domains of dicer which may compete for dsRNA substrate as well as degrade siRNA duplexes to prevent RISC loading.[21]
# Diagnostic and therapeutic applications
Dicer can be used to identify whether tumors are present within the body based on the expression level of the enzyme. A study showed that many patients that had cancer had decreased expression levels of Dicer. The same study showed that lower Dicer expression correlated with lower patient survival length.[11] Along with being a diagnostic tool, Dicer can be used for treating patients by injecting foreign siRNA intravenously to cause gene silencing.[22]
The siRNA was shown to be delivered in two ways in mammalian species such as mice. One way would be to directly inject into the system, which would not require Dicer function. Another way would be to introduce it by plasmids that encode for short hairpin RNA, which are cleaved by Dicer into siRNA.[23]
One of the advantages of using Dicer to produce siRNA therapeutically would be the specificity and diversity of targets it can affect compared to what is currently being used such as antibodies or small molecular inhibitors. In general, small molecular inhibitors are difficult in terms of specificity along with unendurable side effects. Antibodies are as specific as siRNA, but it is limited by only being able to be used against ligands or surface receptors. On the other hand, low efficiency of intracellular uptake is the main obstacle of injection of siRNA.[11] Injected SiRNA has poor stability in blood and causes stimulations of non-specific immunity.[24] Also, producing miRNA therapeutically lacks in specificity because only 6-8 nucleotide base pairing is required for miRNA to attach to mRNA.[25]
# Dicer-like proteins
Plant genomes encode for dicer like proteins with similar functions and protein domains as animal and insect dicer. For example, in the model organism Arabidopsis thaliana, four dicer like proteins are made and are designated DCL1 to DCL4. DCL1 is involved with miRNA generation and sRNA production from inverted repeats. DCL2 creates siRNA from cis-acting antisense transcripts which aid in viral immunity and defense. DCL3 generates siRNA which aids in chromatin modification and DCL4 is involved in trans-acting siRNA metabolism and transcript silencing at the post-transcriptional level. Additionally, DCL 1 and 3 are important for Arabidopsis flowering. In Arabidopsis, DCL knockout does not cause severe developmental problems.
Rice and grapes also produce DCLs as the dicer mechanism is a common defense strategy of many organisms. Rice has evolved other functions for the 5 DCLs it produces and they play a more important role in function and development than in Arabidopsis. Additionally, expression patterns differ among the different plant cell types of rice while expression in Arabidopsis is more homogeneous. Rice DCL expression can be effected by biological stress conditions including drought, salinity, and cold, thus, these stressors may decrease a plants viral resistance. Unlike Arabidopsis, loss of function of DCL proteins causes developmental defects in rice.[26] | https://www.wikidoc.org/index.php/Dicer | |
2904c8efe76fde7f6507f061da68c779d21dc4a2 | wikidoc | Water | Water
# Definition and basic characteristics
Water is a common chemical substance that is essential for the survival of all known forms of life.
In typical usage, water refers only to its liquid form or state, but the substance also has a solid state, ice, and a gaseous state, water vapor. About 1.460 petatonnes (Pt) of water covers 71% of the Earth's surface, mostly in oceans and other large water bodies, with 1.6% of water below ground in aquifers and 0.001% in the air as vapor, clouds (formed of solid and liquid water particles suspended in air), and precipitation. Some of the Earth's water is contained within man-made and natural objects near the Earth's surface such as water towers, animal and plant bodies, manufactured products, and food stores.
Saltwater oceans hold 97% of surface water, glaciers and polar ice caps 2.4%, and other land surface water such as rivers, lakes and ponds 0.6%. Water moves continually through a cycle of evaporation or transpiration (evapotranspiration), precipitation, and runoff, usually reaching the sea. Winds carry water vapor over land at the same rate as runoff into the sea, about 36 Tt per year. Over land, evaporation and transpiration contribute another 71 Tt per year to the precipitation of 107 Tt per year over land. Some water is trapped for varying periods in ice caps, glaciers, aquifers, or in lakes, sometimes providing fresh water for life on land. Clean, fresh water is essential to human and other life. However, in many parts of the world - especially developing countries - it is in short supply. Water is a solvent for a wide variety of chemical substances.
# Types of water
Water can appear in three phases. Water takes many different forms on Earth: water vapor and clouds in the sky; seawater and rarely icebergs in the ocean; glaciers and rivers in the mountains; and aquifers in the ground.
Water can dissolve many different substances, giving it different tastes and odors. In fact, humans and other animals have developed senses to be able to evaluate the potability of water: animals generally dislike the taste of salty sea water and the putrid swamps and favor the purer water of a mountain spring or aquifer. Humans also tend to prefer cold water rather than lukewarm, as cold water is likely to contain less microbes. The taste advertised in spring water or mineral water derives from the minerals dissolved in it, as pure H2O is tasteless. As such, purity in spring and mineral water refers to purity from toxins, pollutants, and microbes.
Because of the importance of precipitation to agriculture, and to mankind in general, different names are given to its various forms:
- according to phase
solid - ice
liquid - water, (supercooled water)
gaseous - water vapor
- solid - ice
- liquid - water, (supercooled water)
- gaseous - water vapor
- according to meteorology:
hydrometeor
precipitation
- hydrometeor
precipitation
- precipitation
- levitating particles
clouds
fog
BR (according to METAR)
ascending particles (drifted by wind)
spindrift
stirred snow
- levitating particles
clouds
fog
BR (according to METAR)
- clouds
- fog
- BR (according to METAR)
- ascending particles (drifted by wind)
spindrift
stirred snow
- spindrift
- stirred snow
- according to occurrence
groundwater
meltwater
meteoric water
fresh water
mineral water – contains much minerals
brackish water
dead water – strange phenomenon which can occur when a layer of fresh or brackish water rests on top of more dense salt water, without the two layers mixing. It is dangerous for ship traveling.
seawater
brine
- groundwater
- meltwater
- meteoric water
- fresh water
- mineral water – contains much minerals
- brackish water
- dead water – strange phenomenon which can occur when a layer of fresh or brackish water rests on top of more dense salt water, without the two layers mixing. It is dangerous for ship traveling.
- seawater
- brine
- according to uses
tap water
bottled water
drinking water or potable water – useful for everyday drinking, without fouling, it contains balanced minerals that are not harmful to health (see below)
purified water, laboratory-grade, analytical-grade or reagent-grade water – water which has been highly purified for specific uses in science or engineering. Often broadly classified as Type I, Type II, or Type III, this category of water includes, but is not limited to the following:
distilled water
double distilled water
deionized water
- tap water
- bottled water
- drinking water or potable water – useful for everyday drinking, without fouling, it contains balanced minerals that are not harmful to health (see below)
- purified water, laboratory-grade, analytical-grade or reagent-grade water – water which has been highly purified for specific uses in science or engineering. Often broadly classified as Type I, Type II, or Type III, this category of water includes, but is not limited to the following:
distilled water
double distilled water
deionized water
- distilled water
- double distilled water
- deionized water
- according to other features
soft water – contains less minerals
hard water – from underground, contains more minerals
distilled water, double distilled water, deionized water - contains no minerals
heavy water – made from heavy atoms of hydrogen - deuterium. It is in nature in normal water in very low concentration. It was used in construction of first nuclear reactors.
tritiated water
- soft water – contains less minerals
- hard water – from underground, contains more minerals
- distilled water, double distilled water, deionized water - contains no minerals
- heavy water – made from heavy atoms of hydrogen - deuterium. It is in nature in normal water in very low concentration. It was used in construction of first nuclear reactors.
- tritiated water
- according to microbiology
drinking water
wastewater
stormwater or surface water
- drinking water
- wastewater
- stormwater or surface water
- according to religion
holy water
- holy water
# Chemical and physical properties
Water is the chemical substance with chemical formula H2O: one molecule of water has two hydrogen atoms covalently bonded to a single oxygen atom.
The major chemical and physical properties of water are:
- Water is a tasteless, odorless liquid at ambient temperature and pressure. The color of water and ice are, intrinsically, a very light blue hue, although water appears colorless in small quantities. Ice also appears colorless, and water vapor is essentially invisible as a gas.
- Water is transparent, and thus aquatic plants can live within the water because sunlight can reach them. Only strong UV light is slightly absorbed.
- Water is a liquid under standard conditions.
- Since oxygen has a higher electronegativity than hydrogen, water is a polar molecule. The oxygen has a slight negative charge while the hydrogens have a slight positive charge giving the article a strong effective dipole moment. The interactions between the different dipoles of each molecule cause a net attraction force associated with water's high amount of surface tension.
- Another very important force that causes the water molecules to stick to one another is the hydrogen bond.
- The boiling point of water (and all other liquids) is directly related to the barometric pressure. For example, on the top of Mt. Everest water boils at about 68 °C (Expression error: Missing operand for *. ), compared to 100 °C (Expression error: Missing operand for *. ) at sea level. Conversely, water deep in the ocean near geothermal vents can reach temperatures of hundreds of degrees and remain liquid.
- Water sticks to itself. Water has a high surface tension caused by the strong cohesion between water molecules because it is polar. The apparent elasticity caused by surface tension drives the capillary waves.
- Water also has high adhesion properties because of its polar nature.
- Capillary action refers to the tendency of water to move up a narrow tube against the force of gravity.
- Water is a very strong solvent, referred to as the universal solvent, dissolving many types of substances. Substances that will mix well and dissolve in water, e.g. salts, sugars, acids, alkalis, and some gases: especially oxygen, carbon dioxide (carbonation), are known as "hydrophilic" (water-loving) substances, while those that do not mix well with water (e.g. fats and oils), are known as "hydrophobic" (water-fearing) substances.
- All the major components in cells (proteins, DNA and polysaccharides) are also dissolved in water.
- Pure water has a low electrical conductivity, but this increases significantly upon solvation of a small amount of ionic material such as sodium chloride.
- Water has the second highest specific heat capacity of any known chemical compound, after ammonia, as well as a high heat of vaporization (40.65 kJ mol−1), both of which are a result of the extensive hydrogen bonding between its molecules. These two unusual properties allow water to moderate Earth's climate by buffering large fluctuations in temperature.
- The maximum density of water is at 3.98 °C (Expression error: Missing operand for *. ). Water becomes even less dense upon freezing, expanding 9%. This causes an unusual phenomenon: ice floats upon water, and so water organisms can live inside a partly frozen pond because the water on the bottom has a temperature of around 4 °C (Expression error: Missing operand for *. ).
- Water is miscible with many liquids, for example ethanol, in all proportions, forming a single homogeneous liquid. On the other hand, water and most oils are immiscible usually forming layers according to increasing density from the top. As a gas, water vapor is completely miscible with air.
- Water forms an azeotrope with many other solvents.
- Some substances (sodium, lithium, calcium, potassium) emit a flammable gas (hydrogen) when wet, or react violently with water.
# Distribution of water in nature
## Water in the Universe
Much of the universe's water may be produced as a byproduct of star formation. When stars are born, their birth is accompanied by a strong outward wind of gas and dust. When this outflow of material eventually impacts the surrounding gas, the shock waves that are created compress and heat the gas. The water observed is quickly produced in this warm dense gas.
Water has been detected in interstellar clouds within our galaxy, the Milky Way. It is believed that water exists in abundance in other galaxies too, because its components, hydrogen and oxygen, are among the most abundant elements in the universe. Interstellar clouds eventually condense into solar nebulae and solar systems, such as ours.
Water vapor is on:
- Mercury - 3.4% in the atmosphere
- Venus - 0.002% in the atmosphere
- Earth - trace in the atmosphere (varies with climate)
- Mars - 0.03% in the atmosphere
- Jupiter - 0.0004% in the atmosphere
- Saturn - in ices only
- Enceladus (moon of Saturn) - 91% in the atmosphere
- exoplanets known as HD 189733 b and HD 209458 b.
Liquid water is on:
- Earth - 71% of surface
Strong evidence suggests that liquid water is present just under the surface of Saturn's moon Enceladus. Probably some liquid water is on Europa.
Water ice is on:
- Earth - mainly on ice sheets
- polar ice caps on Mars
- Titan
- Europa
- Enceladus
Probability or possibility of distribution of water ice is at: lunar ice on the Moon, Ceres (dwarf planet), Tethys (moon). Ice is probably in internal structure of Uranus, Neptune, and Pluto and on comets.
## Water and habitable zone
The existence of liquid water, and to a lesser extent its gaseous and solid forms, on Earth is vital to the existence of life on Earth as we know it. The Earth is located in the habitable zone of the solar system; if it were slightly closer to or further from the Sun (about 5%, or 8 million kilometres or so), the conditions which allow the three forms to be present simultaneously would be far less likely to exist.
Earth's mass allows gravity to hold an atmosphere. Water vapor and carbon dioxide in the atmosphere provide a greenhouse effect which helps maintain a relatively steady surface temperature. If Earth were smaller, a thinner atmosphere would cause temperature extremes preventing the accumulation of water except in polar ice caps (as on Mars).
It has been proposed that life itself may maintain the conditions that have allowed its continued existence. The surface temperature of Earth has been relatively constant through geologic time despite varying levels of incoming solar radiation (insolation), indicating that a dynamic process governs Earth's temperature via a combination of greenhouse gases and surface or atmospheric albedo. This proposal is known as the Gaia hypothesis.
The state of water also depends on a planet's gravity. If a planet is sufficiently massive, the water on it may be solid even at high temperatures, because of the high pressure caused by gravity.
There are various theories about origin of water on Earth.
# Water on Earth
Hydrology is the study of the movement, distribution, and quality of water throughout the Earth. The study of the distribution of water is hydrography. The study of the distribution and movement of groundwater is hydrogeology, of glaciers is glaciology, of inland waters is limnology and distribution of oceans is oceanography. Ecological processes with hydrology are in focus of ecohydrology.
The collective mass of water found on, under, and over the surface of a planet is called hydrosphere. Earth's approximate water volume (the total water supply of the world) is 1 360 000 000 km³ (326 000 000 mi³). Of this volume:
- 1 320 000 000 km³ (316 900 000 mi³ or 97.2%) is in the oceans.
- 25 000 000 km³ (6 000 000 mi³ or 1.8%) is in glaciers, ice caps and ice sheets.
- 13 000 000 km³ (3,000,000 mi³ or 0.9%) is groundwater.
- 250 000 km³ (60,000 mi³ or 0.02%) is fresh water in lakes, inland seas, and rivers.
- 13 000 km³ (3,100 mi³ or 0.001%) is atmospheric water vapor at any given time.
Groundwater and fresh water are useful or potentially useful to humans as water resources.
Liquid water is found in bodies of water, such as an ocean, sea, lake, river, stream, canal, pond, or puddle. The majority of water on Earth is sea water. Water is also present in the atmosphere in solid, liquid, and vapor phases. It also exists as groundwater in aquifers.
The most important geological processes caused by water are: chemical weathering, water erosion, water sediment transport and sedimentation, mudflows, ice erosion and sedimentation by glacier.
## Water cycle
The water cycle (known scientifically as the hydrologic cycle) refers to the continuous exchange of water within the hydrosphere, between the atmosphere, soil water, surface water, groundwater, and plants.
Water moves perpetually through each of these regions in the water cycle consisting of following transfer processes:
- evaporation from oceans and other water bodies into the air and transpiration from land plants and animals into air.
- precipitation, from water vapor condensing from the air and falling to earth or ocean.
- runoff from the land usually reaching the sea.
Most water vapor over the oceans returns to the oceans, but winds carry water vapor over land at the same rate as runoff into the sea, about 36 Tt per year. Over land, evaporation and transpiration contribute another 71 Tt per year. Precipitation, at a rate of 107 Tt per year over land, has several forms: most commonly rain, snow, and hail, with some contribution from fog and dew. Condensed water in the air may also refract sunlight to produce rainbows.
Water runoff often collects over watersheds flowing into rivers. A mathematical model used to simulate river or stream flow and calculate water quality parameters is hydrological transport model. Some of water is diverted to irrigation for agriculture. Rivers and seas offer opportunity for travel and commerce. Through erosion, runoff shapes the environment creating river valleys and deltas which provide rich soil and level ground for the establishment of population centers. A flood occurs when an area of land, usually low-lying, is covered with water. It is when a river overflows its banks or flood from the sea. A drought is an extended period of months or years when a region notes a deficiency in its water supply. This occurs when a region receives consistently below average precipitation.
## Fresh water storage
Some runoff water is trapped for periods, for example in lakes.
At high altitude, during winter, and in the far north and south, snow collects in ice caps, snow pack and glaciers.
Water also infiltrates the ground and goes into aquifers. This groundwater later flows back to the surface in springs, or more spectacularly in hot springs and geysers. Groundwater is also extracted artificially in wells.
This water storage is important, since clean, fresh water is essential to human and other land-based life. In many parts of the world, it is in short supply.
## Tides
Tides are the cyclic rising and falling of Earth's ocean surface caused by the tidal forces of the Moon and the Sun acting on the oceans. Tides cause changes in the depth of the marine and estuarine water bodies and produce oscillating currents known as tidal streams.
The changing tide produced at a given location is the result of the changing positions of the Moon and Sun relative to the Earth coupled with the effects of Earth rotation and the local bathymetry. The strip of seashore that is submerged at high tide and exposed at low tide, the intertidal zone, is an important ecological product of ocean tides.
# Effects on life
From a biological standpoint, water has many distinct properties that are critical for the proliferation of life that set it apart from other substances. It carries out this role by allowing organic compounds to react in ways that ultimately allow replication. All known forms of life depend on water. Water is vital both as a solvent in which many of the body's solutes dissolve and as an essential part of many metabolic processes within the body. Metabolism is the sum total of anabolism and catabolism. In anabolism, water is removed from molecules (through energy requiring enzymatic chemical reactions) in order to grow larger molecules (e.g. starches, triglycerides and proteins for storage of fuels and information). In catabolism, water is used to break bonds in order to generate smaller molecules (e.g. glucose, fatty acids and amino acids to be used for fuels for energy use or other purposes). Water is thus essential and central to these metabolic processes. Therefore, without water, these metabolic processes would cease to exist, leaving us to muse about what processes would be in its place, such as gas absorption, dust collection, etc.
Water is also central to photosynthesis and respiration. Photosynthetic cells use the sun's energy to split off water's hydrogen from oxygen. Hydrogen is combined with CO2 (absorbed from air or water) to form glucose and release oxygen. All living cells use such fuels and oxidize the hydrogen and carbon to capture the sun's energy and reform water and CO2 in the process (cellular respiration).
Water is also central to acid-base neutrality and enzyme function. An acid, a hydrogen ion (H+, that is, a proton) donor, can be neutralized by a base, a proton acceptor such as hydroxide ion (OH−) to form water. Water is considered to be neutral, with a pH (the negative log of the hydrogen ion concentration) of 7. Acids have pH values less than 7 while bases have values greater than 7. Stomach acid (HCl) is useful to digestion. However, its corrosive effect on the esophagus during reflux can temporarily be neutralized by ingestion of a base such as aluminum hydroxide to produce the neutral molecules water and the salt aluminum chloride. Human biochemistry that involves enzymes usually performs optimally around a biologically neutral pH of 7.4.
For example a cell of Escherichia coli contains 70% of water, a human body 60-70%, plant body up to 90% and the body of an adult jellyfish is made up of 94–98% water.
## Aquatic life forms
Earth's waters are filled with life. The earliest life forms appeared in water; nearly all fish live exclusively in water, and there are many types of marine mammals, such as dolphins and whales that also live in the water. Some kinds of animals, such as amphibians, spend portions of their lives in water and portions on land. Plants such as kelp and algae grow in the water and are the basis for some underwater ecosystems. Plankton is generally the foundation of the ocean food chain.
Aquatic animals must obtain oxygen to survive, and they do so in various ways. Fish have gills instead of lungs, although some species of fish, such as the lungfish, have both. Marine mammals, such as dolphins, whales, otters, and seals need to surface periodically to breathe air. Smaller life forms are able to absorb oxygen through their skin.
# Effects on human civilization
Civilization has historically flourished around rivers and major waterways; Mesopotamia, the so-called cradle of civilization, was situated between the major rivers Tigris and Euphrates; the ancient society of the Egyptians depended entirely upon the Nile. Large metropolises like Rotterdam, London, Montreal, Paris, New York City, Shanghai, Tokyo, Chicago, and Hong Kong owe their success in part to their easy accessibility via water and the resultant expansion of trade. Islands with safe water ports, like Singapore, have flourished for the same reason. In places such as North Africa and the Middle East, where water is more scarce, access to clean drinking water was and is a major factor in human development.
## Health and pollution
Water fit for human consumption is called drinking water or potable water. Water that is not potable can be made potable by filtration or distillation (heating it until it becomes water vapor, and then capturing the vapor without any of the impurities it leaves behind), or by other methods (chemical or heat treatment that kills bacteria). Sometimes the term safe water is applied to potable water of a lower quality threshold (i.e., it is used effectively for nutrition in humans that have weak access to water cleaning processes, and does more good than harm). Water that is not fit for drinking but is not harmful for humans when used for swimming or bathing is called by various names other than potable or drinking water, and is sometimes called safe water, or "safe for bathing". Chlorine is a skin and mucous membrane irritant that is used to make water safe for bathing or drinking. Its use is highly technical and is usually monitored by government regulations (typically 1 part per million (ppm) for drinking water, and 1-2 ppm of chlorine not yet reacted with impurities for bathing water).
This natural resource is becoming scarcer in certain places, and its availability is a major social and economic concern. Currently, about 1 billion people around the world routinely drink unhealthy water. Most countries accepted the goal of halving by 2015 the number of people worldwide who do not have access to safe water and sanitation during the 2003 G8 Evian summit. Even if this difficult goal is met, it will still leave more than an estimated half a billion people without access to safe drinking water and over 1 billion without access to adequate sanitation. Poor water quality and bad sanitation are deadly; some 5 million deaths a year are caused by polluted drinking water. Water, however, is not a finite resource, but rather re-circulated as potable water in precipitation in quantities many degrees of magnitude higher than human consumption. Therefore, it is the relatively small quantity of water in reserve in the earth (about 1% of our drinking water supply, which is replenished in aquifers around every 1 to 10 years), that is a non-renewable resource, and it is, rather, the distribution of potable and irrigation water which is scarce, rather than the actual amount of it that exists on the earth. Water-poor countries use importation of goods as the primary method of importing water (to leave enough for local human consumption), since the manufacturing process uses around 10 to 100 times products' masses in water.
In the developing world, 90% of all wastewater still goes untreated into local rivers and streams. Some 50 countries, with roughly a third of the world’s population, also suffer from medium or high water stress, and 17 of these extract more water annually than is recharged through their natural water cycles. The strain not only affects surface freshwater bodies like rivers and lakes, but it also degrades groundwater resources.
## Human uses
### Agriculture
The most important use of water in agriculture is for an irrigation and irrigation is key component to produce enough food. Irrigation takes up to 90% of water withdrawn in some developing countries.
### As a scientific standard
On 7 April 1795, the gram was defined in France to be equal to "the absolute weight of a volume of pure water equal to a cube of one hundredth of a meter, and to the temperature of the melting ice." For practical purposes though, a metallic reference standard was required, one thousand times more massive, the kilogram. Work was therefore commissioned to determine precisely how massive one liter of water was. In spite of the fact that the decreed definition of the gram specified water at 0 °C—a highly stable temperature point—the scientists chose to redefine the standard and to perform their measurements at the most stable density point: the temperature at which water reaches maximum density, which was measured at the time as 4 °C.
The Kelvin temperature scale of the SI system is based on the triple point of water. The scale is a more accurate development of the Celsius temperature scale, which is defined by the boiling point (100 °C) and melting point (0 °C) of water.
Natural water consists mainly of the isotopes hydrogen-1 and oxygen-16, but there is also small quantity of heavier hydrogen-2 (deuterium). The amount of deuterium oxides or heavy water is very small, but it still affects the properties of water. Water from rivers and lakes tends to contain less deuterium than seawater. Therefore, a standard water called Vienna Standard Mean Ocean Water is defined as the standard water.
### For drinking
The human body is anywhere from 55% to 78% water depending on body size. To function properly, the body requires between one and seven liters of water per day to avoid dehydration; the precise amount depends on the level of activity, temperature, humidity, and other factors. Most of this is ingested through foods or beverages other than drinking straight water. It is not clear how much water intake is needed by healthy people, though most advocates agree that 6–7 glasses of water (approximately 2 litres) daily is the minimum to maintain proper hydration. Medical literature favors a lower consumption, typically 1 liter of water for an average male, excluding extra requirements due to fluid loss from exercise or warm weather. For those who have healthy kidneys, it is rather difficult to drink too much water, but (especially in warm humid weather and while exercising) it is dangerous to drink too little. People can drink far more water than necessary while exercising, however, putting them at risk of water intoxication (hyperhydration), which can be fatal. The "fact" that a person should consume eight glasses of water per day cannot be traced back to a scientific source. There are other myths such as the effect of water on weight loss and constipation that have been dispelled.
An original recommendation for water intake in 1945 by the Food and Nutrition Board of the National Research Council read: "An ordinary standard for diverse persons is 1 milliliter for each calorie of food. Most of this quantity is contained in prepared foods." The latest dietary reference intake report by the United States National Research Council in general recommended (including food sources): 2.7 liters of water total for women and 3.7 liters for men. Specifically, pregnant and breastfeeding women need additional fluids to stay hydrated. According to the Institute of Medicine—who recommend that, on average, women consume 2.2 litres and men 3.0 litres—this is recommended to be 2.4 litres (approx. 9 cups) for pregnant women and 3 litres (approx. 12.5 cups) for breastfeeding women since an especially large amount of fluid is lost during nursing. Also noted is that normally, about 20 percent of water intake comes from food, while the rest comes from drinking water and beverages (caffeinated included). Water is excreted from the body in multiple forms; through urine and feces, through sweating, and by exhalation of water vapor in the breath. With physical exertion and heat exposure, water loss will increase and daily fluid needs may increase as well.
Humans require water that does not contain too many impurities. Common impurities include metal salts and/or harmful bacteria, such as Vibrio. Some solutes are acceptable and even desirable for taste enhancement and to provide needed electrolytes.
The single largest freshwater resource suitable for drinking is Lake Baikal in Siberia, which has a very low salt and calcium content and is very clean.
### As a dissolving agent or solvent
Dissolving (or suspending) is used to wash everyday items such as the human body, clothes, floors, cars, food, and pets. Also, human wastes are carried by water in the sewage system. Its use as a cleaning solvent consumes most of water in industrialized countries.
Water can facilitate the chemical processing of wastewater. An aqueous environment can be favourable to the breakdown of pollutants, due to the ability to gain an homogenous solution that is pumpable and flexible to treat. Aerobic treatment can be used by applying oxygen or air to a solution reduce the reactivity of substances within it.
Water also facilitates biological processing of waste that have been dissolved within it. Microorganisms that live within water can access dissolved wastes and can feed upon them breaking them down into less polluting substances. Reedbeds and anaerobic digesters are both examples of biological systems that are particularly suited to the treatment of effluents.
Typically from both chemical and biological treatment of wastes, there is often a solid residue or cake that is left over from the treatment process. Depending upon its constituent parts, this 'cake' may be dried and spread on land as a fertilizer if it has beneficial properties, or alternatively disposed of in landfill or incinerated.
Water is the most abundant molecule in organisms.Fruits shrink when they are dried because they consist primarly of water.
### As a heat transfer fluid
Water and steam are used as heat transfer fluids in diverse heat exchange systems, due to its availability and high heat capacity, both as a coolant and for heating. Cool water may even be naturally available from a lake or the sea. Condensing steam is a particularly efficient heating fluid because of the large heat of vaporization. A disadvantage is that water and steam are somewhat corrosive. In almost all electric power plants, water is the coolant, which vaporizes and drives steam turbines to drive generators.
In the nuclear industry, water can also be used as a neutron moderator. In a pressurized water reactor, water is both a coolant and a moderator. This provides a passive safety measure, as removing the water from the reactor also slows the nuclear reaction down.
### Extinguishing fires
Water has a high heat of vaporization and is relatively inert, which makes it a good fire extinguishing fluid. The evaporation of water carries heat away from the fire. However, water cannot be used to fight fires of electric equipment, because impure water is electrically conductive, or of oils and organic solvents, because they float on water and the explosive boiling of water tends to spread the burning liquid.
Decomposition of water may have played a role in the Chernobyl disaster. Initially, cooling of the incandescent reactor was attempted, but the result was an explosion, when the extreme heat caused water to flash into steam, thus leading to a steam explosion; it may also have decomposed water into hydrogen and oxygen, which subsequently exploded.
### Chemical uses
Organic reactions are usually quenched with water or a water solution of a suitable acid, base or buffer. Water is generally effective in removing inorganic salts. In inorganic reactions, water is a common solvent. In organic reactions, it is usually not used as a reaction solvent, because it does not dissolve the reactants well and is amphoteric (acidic and basic) and nucleophilic. Nevertheless, these properties are sometimes desirable. Also, acceleration of Diels-Alder reactions by water has been observed. Supercritical water has recently been a topic of research. Oxygen-saturated supercritical water combusts organic pollutants efficiently.
### Recreation
Humans use water for many recreational purposes, as well as for exercising and for sports. Some of these include swimming, waterskiing, boating, and diving. In addition, some sports, like ice hockey and ice skating, are played on ice.
Lakesides, beaches and waterparks are popular places for people to go to relax and enjoy recreation. Many find the sound of flowing water to be calming, too. Some keep fish and other life in aquariums or ponds for show, fun, and companionship. Humans also use water for snow sports i.e. skiing or snowboarding, which requires the water to be frozen.
People may also use water for play fighting such as with snowballs, water guns or water balloons.
They may also make fountains and use water in their public or private decorations.
### Water industry
The water industry provides drinking water and wastewater services (including sewage treatment) to households and industry.
Water supply facilities includes for example water wells cisterns for rainwater harvesting, water supply network, water purification facilities, water tanks, water towers, water pipes including old aqueducts. Atmospheric water generator is in development.
Drinking water is often collected at springs, extracted from artificial borings in the ground, or wells. Building more wells in adequate places is thus a possible way to produce more water, assuming the aquifers can supply an adequate flow. Other water sources are rainwater and river or lake water. This surface water, however, must be purified for human consumption. This may involve removal of undissolved substances, dissolved substances and harmful microbes. Popular methods are filtering with sand which only removes undissolved material, while chlorination and boiling kill harmful microbes. Distillation does all three functions. More advanced techniques exist, such as reverse osmosis. Desalination of abundant ocean or seawater is a more expensive solution used in coastal arid climates.
The distribution of drinking water is done through municipal water systems or as bottled water. Governments in many countries have programs to distribute water to the needy at no charge. Others argue that the market mechanism and free enterprise are best to manage this rare resource and to finance the boring of wells or the construction of dams and reservoirs.
Reducing waste by using drinking water only for human consumption is another option. In some cities such as Hong Kong, sea water is extensively used for flushing toilets citywide in order to conserve fresh water resources.
Polluting water may be the biggest single misuse of water; to the extent that a pollutant limits other uses of the water, it becomes a waste of the resource, regardless of benefits to the polluter. Like other types of pollution, this does not enter standard accounting of market costs, being conceived as externalities for which the market cannot account. Thus other people pay the price of water pollution, while the private firms' profits are not redistributed to the local population victim of this pollution. Pharmaceuticals consumed by humans often end up in the waterways and can have detrimental effects on aquatic life if they bioaccumulate and if they are not biodegradable.
Wastewater facilities are sewers and wastewater treatment plants. Another way to remove pollution from surface runoff water is bioswale.
### Industrial applications
Water is used in power generation. Hydroelectricity is electricity obtained from hydropower. Hydroelectric power comes from water driving a water turbine connected to a generator. Hydroelectricity is a low-cost, non-polluting, renewable energy source. The energy is supplied by the sun. Heat from the sun evaporates water, which condenses as rain in higher altitudes, from where it flows down.
Pressurized water is used in water blasting and water jet cutters. Also, very high pressure water guns are used for precise cutting. It works very well, is relatively safe, and is not harmful to the environment. It is also used in the cooling of machinery to prevent over-heating, or prevent saw blades from over-heating.
Water is also used in many industrial processes and machines, such as the steam turbine and heat exchanger, in addition to its use as a chemical solvent. Discharge of untreated water from industrial uses is pollution. Pollution includes discharged solutes (chemical pollution) and discharged coolant water (thermal pollution). Industry requires pure water for many applications and utilizes a variety of purification techniques both in water supply and discharge.
### Food processing
Water plays many critical roles within the field of food science. It is important for a food scientist to understand the roles that water plays within food processing to ensure the success of their products.
Solutes such as salts and sugars found in water affect the physical properties of water. The boiling and freezing points of water is affected by solutes. One mole of sucrose (sugar) raises the boiling point of water by 0.52 °C, and one mole of salt raises the boiling point by 1.04 °C while lowering the freezing point of water in a similar way. Solutes in water also affect water activity which affects many chemical reactions and the growth of microbes in food. Water activity can be described as a ratio of the vapor pressure of water in a solution to the vapor pressure of pure water. Solutes in water lower water activity. This is important to know because most bacterial growth ceases at low levels of water activity. Not only does microbial growth affect the safety of food but also the preservation and shelf life of food.
Water hardness is also a critical factor in food processing. It can dramatically affect the quality of a product as well as playing a role in sanitation. Water hardness is classified based on the amounts of removable calcium carbonate salt it contains per gallon. Water hardness is measured in grains; 0.064 g calcium carbonate is equivalent to one grain of hardness. Water is classified as soft if it contains 1 to 4 grains, medium if it contains 5 to 10 grains and hard if it contains 11 to 20 grains. The hardness of water may be altered or treated by using a chemical ion exchange system. The hardness of water also affects its pH balance which plays a critical role in food processing. For example, hard water prevents successful production of clear beverages. Water hardness also affects sanitation; with increasing hardness, there is a loss of effectiveness for its use as a sanitizer.
Boiling, steaming, and simmering are popular cooking methods that often require immersing food in water or its gaseous state, steam. While cooking water is used for dishwashing too.
# Water politics and water crisis
Water politics is politics affected by water and water resources. Because of overpopulation, mass consumption, misuse, and water pollution, the availability of drinking water per capita is inadequate and shrinking as of the year 2006. For this reason, water is a strategic resource in the globe and an important element in many political conflicts. It causes health impacts and damage to biodiversity. The serious worldwide water situation is called water crisis.
UNESCO's World Water Development Report (WWDR, 2003) from its World Water Assessment Program indicates that, in the next 20 years, the quantity of water available to everyone is predicted to decrease by 30%. 40% of the world's inhabitants currently have insufficient fresh water for minimal hygiene. More than 2.2 million people died in 2000 from waterborne diseases (related to the consumption of contaminated water) or drought. In 2004, the UK charity WaterAid reported that a child dies every 15 seconds from easily preventable water-related diseases; often this means lack of sewage disposal; see toilet.
To halve, by 2015, the proportion of people without sustainable access to safe drinking water is one of the Millennium Development Goals.
Fresh water — now more precious than ever in our history for its extensive use in agriculture, high-tech manufacturing, and energy production — is increasingly receiving attention as a resource requiring better water management and sustainable use.
Organizations concerned in water protection include International Water Association (IWA), WaterAid, Water 1st, American Water Resources Association. Water related conventions are United Nations Convention to Combat Desertification (UNCCD), International Convention for the Prevention of Pollution from Ships, United Nations Convention on the Law of the Sea and Ramsar Convention. World Day for Water takes place at March 22 and World Ocean Day at June 8.
Water used in the production of a good or service is virtual water.
# Religion, philosophy, and literature
Water is considered a purifier in most religions. Major faiths that incorporate ritual washing (ablution) include Christianity, Hinduism, Rastafarianism, Islam, Shinto, Taoism, and Judaism. Immersion (or aspersion or affusion) of a person in water is a central sacrament of Christianity (where it is called baptism); it is also a part of the practice of other religions, including Judaism (mikvah) and Sikhism (Amrit Sanskar). In addition, a ritual bath in pure water is performed for the dead in many religions including Judaism and Islam. In Islam, the five daily prayers can be done in most cases after completing washing certain parts of the body using clean water (wudu). In Shinto, water is used in almost all rituals to cleanse a person or an area (e.g., in the ritual of misogi). Water is mentioned in the Bible 442 times in the New International Version and 363 times in the King James Version: 2 Peter 3:5(b) states, "The earth was formed out of water and by water" (NIV).
Some faiths use water especially prepared for religious purposes (holy water in some Christian denominations, Amrita in Sikhism and Hinduism). Many religions also consider particular sources or bodies of water to be sacred or at least auspicious; examples include Lourdes in Roman Catholicism, the Jordan River (at least symbolically) in some Christian churches, the Zamzam Well in Islam and the River Ganges (among many others) in Hinduism.
Water is often believed to have spiritual powers. In Celtic mythology, Sulis is the local goddess of thermal springs; in Hinduism, the Ganges is also personified as a goddess, while Saraswati have been referred to as goddess in Vedas. Also water is one of the "panch-tatva"s (basic 5 elements, others including fire, earth, space, air). Alternatively, gods can be patrons of particular springs, rivers, or lakes: for example in Greek and Roman mythology, Peneus was a river god, one of the three thousand Oceanids. In Islam, not only does water give life, but every life is itself made of water: "We made from water every living thing".
The Ancient Greek philosopher Empedocles held that water is one of the four classical elements along with fire, earth and air, and was regarded as the ylem, or basic substance of the universe. Water was considered cold and moist. In the theory of the four bodily humors, water was associated with phlegm. Water was also one of the five elements in traditional Chinese philosophy, along with earth, fire, wood, and metal.
Water also plays an important role in literature as a symbol of purification. Examples include the critical importance of a river in As I Lay Dying by William Faulkner and the drowning of Ophelia in Hamlet. | Water
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Definition and basic characteristics
Water is a common chemical substance that is essential for the survival of all known forms of life.[1]
In typical usage, water refers only to its liquid form or state, but the substance also has a solid state, ice, and a gaseous state, water vapor. About 1.460 petatonnes (Pt) of water covers 71% of the Earth's surface, mostly in oceans and other large water bodies, with 1.6% of water below ground in aquifers and 0.001% in the air as vapor, clouds (formed of solid and liquid water particles suspended in air), and precipitation.[2] Some of the Earth's water is contained within man-made and natural objects near the Earth's surface such as water towers, animal and plant bodies, manufactured products, and food stores.
Saltwater oceans hold 97% of surface water, glaciers and polar ice caps 2.4%, and other land surface water such as rivers, lakes and ponds 0.6%. Water moves continually through a cycle of evaporation or transpiration (evapotranspiration), precipitation, and runoff, usually reaching the sea. Winds carry water vapor over land at the same rate as runoff into the sea, about 36 Tt per year. Over land, evaporation and transpiration contribute another 71 Tt per year to the precipitation of 107 Tt per year over land. Some water is trapped for varying periods in ice caps, glaciers, aquifers, or in lakes, sometimes providing fresh water for life on land. Clean, fresh water is essential to human and other life. However, in many parts of the world - especially developing countries - it is in short supply. Water is a solvent for a wide variety of chemical substances.
# Types of water
Water can appear in three phases. Water takes many different forms on Earth: water vapor and clouds in the sky; seawater and rarely icebergs in the ocean; glaciers and rivers in the mountains; and aquifers in the ground.
Water can dissolve many different substances, giving it different tastes and odors. In fact, humans and other animals have developed senses to be able to evaluate the potability of water: animals generally dislike the taste of salty sea water and the putrid swamps and favor the purer water of a mountain spring or aquifer. Humans also tend to prefer cold water rather than lukewarm, as cold water is likely to contain less microbes. The taste advertised in spring water or mineral water derives from the minerals dissolved in it, as pure H2O is tasteless. As such, purity in spring and mineral water refers to purity from toxins, pollutants, and microbes.
Because of the importance of precipitation to agriculture, and to mankind in general, different names are given to its various forms:
- according to phase
solid - ice
liquid - water, (supercooled water)
gaseous - water vapor
- solid - ice
- liquid - water, (supercooled water)
- gaseous - water vapor
- according to meteorology:
hydrometeor
precipitation
- hydrometeor
precipitation
- precipitation
- levitating particles
clouds
fog
BR (according to METAR)
ascending particles (drifted by wind)
spindrift
stirred snow
- levitating particles
clouds
fog
BR (according to METAR)
- clouds
- fog
- BR (according to METAR)
- ascending particles (drifted by wind)
spindrift
stirred snow
- spindrift
- stirred snow
- according to occurrence
groundwater
meltwater
meteoric water
fresh water
mineral water – contains much minerals
brackish water
dead water – strange phenomenon which can occur when a layer of fresh or brackish water rests on top of more dense salt water, without the two layers mixing. It is dangerous for ship traveling.
seawater
brine
- groundwater
- meltwater
- meteoric water
- fresh water
- mineral water – contains much minerals
- brackish water
- dead water – strange phenomenon which can occur when a layer of fresh or brackish water rests on top of more dense salt water, without the two layers mixing. It is dangerous for ship traveling.
- seawater
- brine
- according to uses
tap water
bottled water
drinking water or potable water – useful for everyday drinking, without fouling, it contains balanced minerals that are not harmful to health (see below)
purified water, laboratory-grade, analytical-grade or reagent-grade water – water which has been highly purified for specific uses in science or engineering. Often broadly classified as Type I, Type II, or Type III, this category of water includes, but is not limited to the following:
distilled water
double distilled water
deionized water
- tap water
- bottled water
- drinking water or potable water – useful for everyday drinking, without fouling, it contains balanced minerals that are not harmful to health (see below)
- purified water, laboratory-grade, analytical-grade or reagent-grade water – water which has been highly purified for specific uses in science or engineering. Often broadly classified as Type I, Type II, or Type III, this category of water includes, but is not limited to the following:
distilled water
double distilled water
deionized water
- distilled water
- double distilled water
- deionized water
- according to other features
soft water – contains less minerals
hard water – from underground, contains more minerals
distilled water, double distilled water, deionized water - contains no minerals
heavy water – made from heavy atoms of hydrogen - deuterium. It is in nature in normal water in very low concentration. It was used in construction of first nuclear reactors.
tritiated water
- soft water – contains less minerals
- hard water – from underground, contains more minerals
- distilled water, double distilled water, deionized water - contains no minerals
- heavy water – made from heavy atoms of hydrogen - deuterium. It is in nature in normal water in very low concentration. It was used in construction of first nuclear reactors.
- tritiated water
- according to microbiology
drinking water
wastewater
stormwater or surface water
- drinking water
- wastewater
- stormwater or surface water
- according to religion
holy water
- holy water
# Chemical and physical properties
Water is the chemical substance with chemical formula H2O: one molecule of water has two hydrogen atoms covalently bonded to a single oxygen atom.
The major chemical and physical properties of water are:
- Water is a tasteless, odorless liquid at ambient temperature and pressure. The color of water and ice are, intrinsically, a very light blue hue, although water appears colorless in small quantities. Ice also appears colorless, and water vapor is essentially invisible as a gas.[3]
- Water is transparent, and thus aquatic plants can live within the water because sunlight can reach them. Only strong UV light is slightly absorbed.
- Water is a liquid under standard conditions.
- Since oxygen has a higher electronegativity than hydrogen, water is a polar molecule. The oxygen has a slight negative charge while the hydrogens have a slight positive charge giving the article a strong effective dipole moment. The interactions between the different dipoles of each molecule cause a net attraction force associated with water's high amount of surface tension.
- Another very important force that causes the water molecules to stick to one another is the hydrogen bond.
- The boiling point of water (and all other liquids) is directly related to the barometric pressure. For example, on the top of Mt. Everest water boils at about 68 °C (Expression error: Missing operand for *. ), compared to 100 °C (Expression error: Missing operand for *. ) at sea level. Conversely, water deep in the ocean near geothermal vents can reach temperatures of hundreds of degrees and remain liquid.
- Water sticks to itself. Water has a high surface tension caused by the strong cohesion between water molecules because it is polar. The apparent elasticity caused by surface tension drives the capillary waves.
- Water also has high adhesion properties because of its polar nature.
- Capillary action refers to the tendency of water to move up a narrow tube against the force of gravity.
- Water is a very strong solvent, referred to as the universal solvent, dissolving many types of substances. Substances that will mix well and dissolve in water, e.g. salts, sugars, acids, alkalis, and some gases: especially oxygen, carbon dioxide (carbonation), are known as "hydrophilic" (water-loving) substances, while those that do not mix well with water (e.g. fats and oils), are known as "hydrophobic" (water-fearing) substances.
- All the major components in cells (proteins, DNA and polysaccharides) are also dissolved in water.
- Pure water has a low electrical conductivity, but this increases significantly upon solvation of a small amount of ionic material such as sodium chloride.
- Water has the second highest specific heat capacity of any known chemical compound, after ammonia, as well as a high heat of vaporization (40.65 kJ mol−1), both of which are a result of the extensive hydrogen bonding between its molecules. These two unusual properties allow water to moderate Earth's climate by buffering large fluctuations in temperature.
- The maximum density of water is at 3.98 °C (Expression error: Missing operand for *. )[4]. Water becomes even less dense upon freezing, expanding 9%. This causes an unusual phenomenon: ice floats upon water, and so water organisms can live inside a partly frozen pond because the water on the bottom has a temperature of around 4 °C (Expression error: Missing operand for *. ).
- Water is miscible with many liquids, for example ethanol, in all proportions, forming a single homogeneous liquid. On the other hand, water and most oils are immiscible usually forming layers according to increasing density from the top. As a gas, water vapor is completely miscible with air.
- Water forms an azeotrope with many other solvents.
- Some substances (sodium, lithium, calcium, potassium) emit a flammable gas (hydrogen) when wet, or react violently with water.
# Distribution of water in nature
## Water in the Universe
Much of the universe's water may be produced as a byproduct of star formation. When stars are born, their birth is accompanied by a strong outward wind of gas and dust. When this outflow of material eventually impacts the surrounding gas, the shock waves that are created compress and heat the gas. The water observed is quickly produced in this warm dense gas.[5]
Water has been detected in interstellar clouds within our galaxy, the Milky Way. It is believed that water exists in abundance in other galaxies too, because its components, hydrogen and oxygen, are among the most abundant elements in the universe. Interstellar clouds eventually condense into solar nebulae and solar systems, such as ours.
Water vapor is on:
- Mercury - 3.4% in the atmosphere
- Venus - 0.002% in the atmosphere
- Earth - trace in the atmosphere (varies with climate)
- Mars - 0.03% in the atmosphere
- Jupiter - 0.0004% in the atmosphere
- Saturn - in ices only
- Enceladus (moon of Saturn) - 91% in the atmosphere
- exoplanets known as HD 189733 b[6] and HD 209458 b.[7]
Liquid water is on:
- Earth - 71% of surface
Strong evidence suggests that liquid water is present just under the surface of Saturn's moon Enceladus. Probably some liquid water is on Europa.
Water ice is on:
- Earth - mainly on ice sheets
- polar ice caps on Mars
- Titan
- Europa
- Enceladus
Probability or possibility of distribution of water ice is at: lunar ice on the Moon, Ceres (dwarf planet), Tethys (moon). Ice is probably in internal structure of Uranus, Neptune, and Pluto and on comets.
## Water and habitable zone
The existence of liquid water, and to a lesser extent its gaseous and solid forms, on Earth is vital to the existence of life on Earth as we know it. The Earth is located in the habitable zone of the solar system; if it were slightly closer to or further from the Sun (about 5%, or 8 million kilometres or so), the conditions which allow the three forms to be present simultaneously would be far less likely to exist.[8]
Earth's mass allows gravity to hold an atmosphere. Water vapor and carbon dioxide in the atmosphere provide a greenhouse effect which helps maintain a relatively steady surface temperature. If Earth were smaller, a thinner atmosphere would cause temperature extremes preventing the accumulation of water except in polar ice caps (as on Mars).
It has been proposed that life itself may maintain the conditions that have allowed its continued existence. The surface temperature of Earth has been relatively constant through geologic time despite varying levels of incoming solar radiation (insolation), indicating that a dynamic process governs Earth's temperature via a combination of greenhouse gases and surface or atmospheric albedo. This proposal is known as the Gaia hypothesis.
The state of water also depends on a planet's gravity. If a planet is sufficiently massive, the water on it may be solid even at high temperatures, because of the high pressure caused by gravity.
There are various theories about origin of water on Earth.
# Water on Earth
Hydrology is the study of the movement, distribution, and quality of water throughout the Earth. The study of the distribution of water is hydrography. The study of the distribution and movement of groundwater is hydrogeology, of glaciers is glaciology, of inland waters is limnology and distribution of oceans is oceanography. Ecological processes with hydrology are in focus of ecohydrology.
The collective mass of water found on, under, and over the surface of a planet is called hydrosphere. Earth's approximate water volume (the total water supply of the world) is 1 360 000 000 km³ (326 000 000 mi³). Of this volume:
- 1 320 000 000 km³ (316 900 000 mi³ or 97.2%) is in the oceans.
- 25 000 000 km³ (6 000 000 mi³ or 1.8%) is in glaciers, ice caps and ice sheets.
- 13 000 000 km³ (3,000,000 mi³ or 0.9%) is groundwater.
- 250 000 km³ (60,000 mi³ or 0.02%) is fresh water in lakes, inland seas, and rivers.
- 13 000 km³ (3,100 mi³ or 0.001%) is atmospheric water vapor at any given time.
Groundwater and fresh water are useful or potentially useful to humans as water resources.
Liquid water is found in bodies of water, such as an ocean, sea, lake, river, stream, canal, pond, or puddle. The majority of water on Earth is sea water. Water is also present in the atmosphere in solid, liquid, and vapor phases. It also exists as groundwater in aquifers.
The most important geological processes caused by water are: chemical weathering, water erosion, water sediment transport and sedimentation, mudflows, ice erosion and sedimentation by glacier.
## Water cycle
The water cycle (known scientifically as the hydrologic cycle) refers to the continuous exchange of water within the hydrosphere, between the atmosphere, soil water, surface water, groundwater, and plants.
Water moves perpetually through each of these regions in the water cycle consisting of following transfer processes:
- evaporation from oceans and other water bodies into the air and transpiration from land plants and animals into air.
- precipitation, from water vapor condensing from the air and falling to earth or ocean.
- runoff from the land usually reaching the sea.
Most water vapor over the oceans returns to the oceans, but winds carry water vapor over land at the same rate as runoff into the sea, about 36 Tt per year. Over land, evaporation and transpiration contribute another 71 Tt per year. Precipitation, at a rate of 107 Tt per year over land, has several forms: most commonly rain, snow, and hail, with some contribution from fog and dew. Condensed water in the air may also refract sunlight to produce rainbows.
Water runoff often collects over watersheds flowing into rivers. A mathematical model used to simulate river or stream flow and calculate water quality parameters is hydrological transport model. Some of water is diverted to irrigation for agriculture. Rivers and seas offer opportunity for travel and commerce. Through erosion, runoff shapes the environment creating river valleys and deltas which provide rich soil and level ground for the establishment of population centers. A flood occurs when an area of land, usually low-lying, is covered with water. It is when a river overflows its banks or flood from the sea. A drought is an extended period of months or years when a region notes a deficiency in its water supply. This occurs when a region receives consistently below average precipitation.
## Fresh water storage
Some runoff water is trapped for periods, for example in lakes.
At high altitude, during winter, and in the far north and south, snow collects in ice caps, snow pack and glaciers.
Water also infiltrates the ground and goes into aquifers. This groundwater later flows back to the surface in springs, or more spectacularly in hot springs and geysers. Groundwater is also extracted artificially in wells.
This water storage is important, since clean, fresh water is essential to human and other land-based life. In many parts of the world, it is in short supply.
## Tides
Template:Imageframe
Tides are the cyclic rising and falling of Earth's ocean surface caused by the tidal forces of the Moon and the Sun acting on the oceans. Tides cause changes in the depth of the marine and estuarine water bodies and produce oscillating currents known as tidal streams.
The changing tide produced at a given location is the result of the changing positions of the Moon and Sun relative to the Earth coupled with the effects of Earth rotation and the local bathymetry. The strip of seashore that is submerged at high tide and exposed at low tide, the intertidal zone, is an important ecological product of ocean tides.
# Effects on life
From a biological standpoint, water has many distinct properties that are critical for the proliferation of life that set it apart from other substances. It carries out this role by allowing organic compounds to react in ways that ultimately allow replication. All known forms of life depend on water. Water is vital both as a solvent in which many of the body's solutes dissolve and as an essential part of many metabolic processes within the body. Metabolism is the sum total of anabolism and catabolism. In anabolism, water is removed from molecules (through energy requiring enzymatic chemical reactions) in order to grow larger molecules (e.g. starches, triglycerides and proteins for storage of fuels and information). In catabolism, water is used to break bonds in order to generate smaller molecules (e.g. glucose, fatty acids and amino acids to be used for fuels for energy use or other purposes). Water is thus essential and central to these metabolic processes. Therefore, without water, these metabolic processes would cease to exist, leaving us to muse about what processes would be in its place, such as gas absorption, dust collection, etc.
Water is also central to photosynthesis and respiration. Photosynthetic cells use the sun's energy to split off water's hydrogen from oxygen. Hydrogen is combined with CO2 (absorbed from air or water) to form glucose and release oxygen. All living cells use such fuels and oxidize the hydrogen and carbon to capture the sun's energy and reform water and CO2 in the process (cellular respiration).
Water is also central to acid-base neutrality and enzyme function. An acid, a hydrogen ion (H+, that is, a proton) donor, can be neutralized by a base, a proton acceptor such as hydroxide ion (OH−) to form water. Water is considered to be neutral, with a pH (the negative log of the hydrogen ion concentration) of 7. Acids have pH values less than 7 while bases have values greater than 7. Stomach acid (HCl) is useful to digestion. However, its corrosive effect on the esophagus during reflux can temporarily be neutralized by ingestion of a base such as aluminum hydroxide to produce the neutral molecules water and the salt aluminum chloride. Human biochemistry that involves enzymes usually performs optimally around a biologically neutral pH of 7.4.
For example a cell of Escherichia coli contains 70% of water, a human body 60-70%, plant body up to 90% and the body of an adult jellyfish is made up of 94–98% water.
## Aquatic life forms
Earth's waters are filled with life. The earliest life forms appeared in water; nearly all fish live exclusively in water, and there are many types of marine mammals, such as dolphins and whales that also live in the water. Some kinds of animals, such as amphibians, spend portions of their lives in water and portions on land. Plants such as kelp and algae grow in the water and are the basis for some underwater ecosystems. Plankton is generally the foundation of the ocean food chain.
Aquatic animals must obtain oxygen to survive, and they do so in various ways. Fish have gills instead of lungs, although some species of fish, such as the lungfish, have both. Marine mammals, such as dolphins, whales, otters, and seals need to surface periodically to breathe air. Smaller life forms are able to absorb oxygen through their skin.
# Effects on human civilization
Civilization has historically flourished around rivers and major waterways; Mesopotamia, the so-called cradle of civilization, was situated between the major rivers Tigris and Euphrates; the ancient society of the Egyptians depended entirely upon the Nile. Large metropolises like Rotterdam, London, Montreal, Paris, New York City, Shanghai, Tokyo, Chicago, and Hong Kong owe their success in part to their easy accessibility via water and the resultant expansion of trade. Islands with safe water ports, like Singapore, have flourished for the same reason. In places such as North Africa and the Middle East, where water is more scarce, access to clean drinking water was and is a major factor in human development.
## Health and pollution
Water fit for human consumption is called drinking water or potable water. Water that is not potable can be made potable by filtration or distillation (heating it until it becomes water vapor, and then capturing the vapor without any of the impurities it leaves behind), or by other methods (chemical or heat treatment that kills bacteria). Sometimes the term safe water is applied to potable water of a lower quality threshold (i.e., it is used effectively for nutrition in humans that have weak access to water cleaning processes, and does more good than harm). Water that is not fit for drinking but is not harmful for humans when used for swimming or bathing is called by various names other than potable or drinking water, and is sometimes called safe water, or "safe for bathing". Chlorine is a skin and mucous membrane irritant that is used to make water safe for bathing or drinking. Its use is highly technical and is usually monitored by government regulations (typically 1 part per million (ppm) for drinking water, and 1-2 ppm of chlorine not yet reacted with impurities for bathing water).
This natural resource is becoming scarcer in certain places, and its availability is a major social and economic concern. Currently, about 1 billion people around the world routinely drink unhealthy water. Most countries accepted the goal of halving by 2015 the number of people worldwide who do not have access to safe water and sanitation during the 2003 G8 Evian summit.[9] Even if this difficult goal is met, it will still leave more than an estimated half a billion people without access to safe drinking water and over 1 billion without access to adequate sanitation. Poor water quality and bad sanitation are deadly; some 5 million deaths a year are caused by polluted drinking water. Water, however, is not a finite resource, but rather re-circulated as potable water in precipitation in quantities many degrees of magnitude higher than human consumption. Therefore, it is the relatively small quantity of water in reserve in the earth (about 1% of our drinking water supply, which is replenished in aquifers around every 1 to 10 years), that is a non-renewable resource, and it is, rather, the distribution of potable and irrigation water which is scarce, rather than the actual amount of it that exists on the earth. Water-poor countries use importation of goods as the primary method of importing water (to leave enough for local human consumption), since the manufacturing process uses around 10 to 100 times products' masses in water.
In the developing world, 90% of all wastewater still goes untreated into local rivers and streams.[10] Some 50 countries, with roughly a third of the world’s population, also suffer from medium or high water stress, and 17 of these extract more water annually than is recharged through their natural water cycles.[11] The strain not only affects surface freshwater bodies like rivers and lakes, but it also degrades groundwater resources.
## Human uses
### Agriculture
The most important use of water in agriculture is for an irrigation and irrigation is key component to produce enough food. Irrigation takes up to 90% of water withdrawn in some developing countries.[12]
### As a scientific standard
On 7 April 1795, the gram was defined in France to be equal to "the absolute weight of a volume of pure water equal to a cube of one hundredth of a meter, and to the temperature of the melting ice."[13] For practical purposes though, a metallic reference standard was required, one thousand times more massive, the kilogram. Work was therefore commissioned to determine precisely how massive one liter of water was. In spite of the fact that the decreed definition of the gram specified water at 0 °C—a highly stable temperature point—the scientists chose to redefine the standard and to perform their measurements at the most stable density point: the temperature at which water reaches maximum density, which was measured at the time as 4 °C.[14]
The Kelvin temperature scale of the SI system is based on the triple point of water. The scale is a more accurate development of the Celsius temperature scale, which is defined by the boiling point (100 °C) and melting point (0 °C) of water.
Natural water consists mainly of the isotopes hydrogen-1 and oxygen-16, but there is also small quantity of heavier hydrogen-2 (deuterium). The amount of deuterium oxides or heavy water is very small, but it still affects the properties of water. Water from rivers and lakes tends to contain less deuterium than seawater. Therefore, a standard water called Vienna Standard Mean Ocean Water is defined as the standard water.
### For drinking
The human body is anywhere from 55% to 78% water depending on body size.[15] To function properly, the body requires between one and seven liters of water per day to avoid dehydration; the precise amount depends on the level of activity, temperature, humidity, and other factors. Most of this is ingested through foods or beverages other than drinking straight water. It is not clear how much water intake is needed by healthy people, though most advocates agree that 6–7 glasses of water (approximately 2 litres) daily is the minimum to maintain proper hydration.[16] Medical literature favors a lower consumption, typically 1 liter of water for an average male, excluding extra requirements due to fluid loss from exercise or warm weather.[17] For those who have healthy kidneys, it is rather difficult to drink too much water, but (especially in warm humid weather and while exercising) it is dangerous to drink too little. People can drink far more water than necessary while exercising, however, putting them at risk of water intoxication (hyperhydration), which can be fatal. The "fact" that a person should consume eight glasses of water per day cannot be traced back to a scientific source.[18] There are other myths such as the effect of water on weight loss and constipation that have been dispelled.[19]
An original recommendation for water intake in 1945 by the Food and Nutrition Board of the National Research Council read: "An ordinary standard for diverse persons is 1 milliliter for each calorie of food. Most of this quantity is contained in prepared foods."[20] The latest dietary reference intake report by the United States National Research Council in general recommended (including food sources): 2.7 liters of water total for women and 3.7 liters for men.[21] Specifically, pregnant and breastfeeding women need additional fluids to stay hydrated. According to the Institute of Medicine—who recommend that, on average, women consume 2.2 litres and men 3.0 litres—this is recommended to be 2.4 litres (approx. 9 cups) for pregnant women and 3 litres (approx. 12.5 cups) for breastfeeding women since an especially large amount of fluid is lost during nursing.[22] Also noted is that normally, about 20 percent of water intake comes from food, while the rest comes from drinking water and beverages (caffeinated included). Water is excreted from the body in multiple forms; through urine and feces, through sweating, and by exhalation of water vapor in the breath. With physical exertion and heat exposure, water loss will increase and daily fluid needs may increase as well.
Humans require water that does not contain too many impurities. Common impurities include metal salts and/or harmful bacteria, such as Vibrio. Some solutes are acceptable and even desirable for taste enhancement and to provide needed electrolytes. [23]
The single largest freshwater resource suitable for drinking is Lake Baikal in Siberia, which has a very low salt and calcium content and is very clean.
### As a dissolving agent or solvent
Dissolving (or suspending) is used to wash everyday items such as the human body, clothes, floors, cars, food, and pets. Also, human wastes are carried by water in the sewage system. Its use as a cleaning solvent consumes most of water in industrialized countries.
Water can facilitate the chemical processing of wastewater. An aqueous environment can be favourable to the breakdown of pollutants, due to the ability to gain an homogenous solution that is pumpable and flexible to treat. Aerobic treatment can be used by applying oxygen or air to a solution reduce the reactivity of substances within it.
Water also facilitates biological processing of waste that have been dissolved within it. Microorganisms that live within water can access dissolved wastes and can feed upon them breaking them down into less polluting substances. Reedbeds and anaerobic digesters are both examples of biological systems that are particularly suited to the treatment of effluents.
Typically from both chemical and biological treatment of wastes, there is often a solid residue or cake that is left over from the treatment process. Depending upon its constituent parts, this 'cake' may be dried and spread on land as a fertilizer if it has beneficial properties, or alternatively disposed of in landfill or incinerated.
Water is the most abundant molecule in organisms.Fruits shrink when they are dried because they consist primarly of water.
### As a heat transfer fluid
Water and steam are used as heat transfer fluids in diverse heat exchange systems, due to its availability and high heat capacity, both as a coolant and for heating. Cool water may even be naturally available from a lake or the sea. Condensing steam is a particularly efficient heating fluid because of the large heat of vaporization. A disadvantage is that water and steam are somewhat corrosive. In almost all electric power plants, water is the coolant, which vaporizes and drives steam turbines to drive generators.
In the nuclear industry, water can also be used as a neutron moderator. In a pressurized water reactor, water is both a coolant and a moderator. This provides a passive safety measure, as removing the water from the reactor also slows the nuclear reaction down.
### Extinguishing fires
Water has a high heat of vaporization and is relatively inert, which makes it a good fire extinguishing fluid. The evaporation of water carries heat away from the fire. However, water cannot be used to fight fires of electric equipment, because impure water is electrically conductive, or of oils and organic solvents, because they float on water and the explosive boiling of water tends to spread the burning liquid.
Decomposition of water may have played a role in the Chernobyl disaster. Initially, cooling of the incandescent reactor was attempted, but the result was an explosion, when the extreme heat caused water to flash into steam, thus leading to a steam explosion; it may also have decomposed water into hydrogen and oxygen, which subsequently exploded.
### Chemical uses
Organic reactions are usually quenched with water or a water solution of a suitable acid, base or buffer. Water is generally effective in removing inorganic salts. In inorganic reactions, water is a common solvent. In organic reactions, it is usually not used as a reaction solvent, because it does not dissolve the reactants well and is amphoteric (acidic and basic) and nucleophilic. Nevertheless, these properties are sometimes desirable. Also, acceleration of Diels-Alder reactions by water has been observed. Supercritical water has recently been a topic of research. Oxygen-saturated supercritical water combusts organic pollutants efficiently.
### Recreation
Humans use water for many recreational purposes, as well as for exercising and for sports. Some of these include swimming, waterskiing, boating, and diving. In addition, some sports, like ice hockey and ice skating, are played on ice.
Lakesides, beaches and waterparks are popular places for people to go to relax and enjoy recreation. Many find the sound of flowing water to be calming, too. Some keep fish and other life in aquariums or ponds for show, fun, and companionship. Humans also use water for snow sports i.e. skiing or snowboarding, which requires the water to be frozen.
People may also use water for play fighting such as with snowballs, water guns or water balloons.
They may also make fountains and use water in their public or private decorations.
### Water industry
The water industry provides drinking water and wastewater services (including sewage treatment) to households and industry.
Water supply facilities includes for example water wells cisterns for rainwater harvesting, water supply network, water purification facilities, water tanks, water towers, water pipes including old aqueducts. Atmospheric water generator is in development.
Drinking water is often collected at springs, extracted from artificial borings in the ground, or wells. Building more wells in adequate places is thus a possible way to produce more water, assuming the aquifers can supply an adequate flow. Other water sources are rainwater and river or lake water. This surface water, however, must be purified for human consumption. This may involve removal of undissolved substances, dissolved substances and harmful microbes. Popular methods are filtering with sand which only removes undissolved material, while chlorination and boiling kill harmful microbes. Distillation does all three functions. More advanced techniques exist, such as reverse osmosis. Desalination of abundant ocean or seawater is a more expensive solution used in coastal arid climates.
The distribution of drinking water is done through municipal water systems or as bottled water. Governments in many countries have programs to distribute water to the needy at no charge. Others argue that the market mechanism and free enterprise are best to manage this rare resource and to finance the boring of wells or the construction of dams and reservoirs.
Reducing waste by using drinking water only for human consumption is another option. In some cities such as Hong Kong, sea water is extensively used for flushing toilets citywide in order to conserve fresh water resources.
Polluting water may be the biggest single misuse of water; to the extent that a pollutant limits other uses of the water, it becomes a waste of the resource, regardless of benefits to the polluter. Like other types of pollution, this does not enter standard accounting of market costs, being conceived as externalities for which the market cannot account. Thus other people pay the price of water pollution, while the private firms' profits are not redistributed to the local population victim of this pollution. Pharmaceuticals consumed by humans often end up in the waterways and can have detrimental effects on aquatic life if they bioaccumulate and if they are not biodegradable.
Wastewater facilities are sewers and wastewater treatment plants. Another way to remove pollution from surface runoff water is bioswale.
### Industrial applications
Water is used in power generation. Hydroelectricity is electricity obtained from hydropower. Hydroelectric power comes from water driving a water turbine connected to a generator. Hydroelectricity is a low-cost, non-polluting, renewable energy source. The energy is supplied by the sun. Heat from the sun evaporates water, which condenses as rain in higher altitudes, from where it flows down.
Pressurized water is used in water blasting and water jet cutters. Also, very high pressure water guns are used for precise cutting. It works very well, is relatively safe, and is not harmful to the environment. It is also used in the cooling of machinery to prevent over-heating, or prevent saw blades from over-heating.
Water is also used in many industrial processes and machines, such as the steam turbine and heat exchanger, in addition to its use as a chemical solvent. Discharge of untreated water from industrial uses is pollution. Pollution includes discharged solutes (chemical pollution) and discharged coolant water (thermal pollution). Industry requires pure water for many applications and utilizes a variety of purification techniques both in water supply and discharge.
### Food processing
Water plays many critical roles within the field of food science. It is important for a food scientist to understand the roles that water plays within food processing to ensure the success of their products.
Solutes such as salts and sugars found in water affect the physical properties of water. The boiling and freezing points of water is affected by solutes. One mole of sucrose (sugar) raises the boiling point of water by 0.52 °C, and one mole of salt raises the boiling point by 1.04 °C while lowering the freezing point of water in a similar way.[24] Solutes in water also affect water activity which affects many chemical reactions and the growth of microbes in food.[25] Water activity can be described as a ratio of the vapor pressure of water in a solution to the vapor pressure of pure water.[24] Solutes in water lower water activity. This is important to know because most bacterial growth ceases at low levels of water activity.[25] Not only does microbial growth affect the safety of food but also the preservation and shelf life of food.
Water hardness is also a critical factor in food processing. It can dramatically affect the quality of a product as well as playing a role in sanitation. Water hardness is classified based on the amounts of removable calcium carbonate salt it contains per gallon. Water hardness is measured in grains; 0.064 g calcium carbonate is equivalent to one grain of hardness.[24] Water is classified as soft if it contains 1 to 4 grains, medium if it contains 5 to 10 grains and hard if it contains 11 to 20 grains.[24] The hardness of water may be altered or treated by using a chemical ion exchange system. The hardness of water also affects its pH balance which plays a critical role in food processing. For example, hard water prevents successful production of clear beverages. Water hardness also affects sanitation; with increasing hardness, there is a loss of effectiveness for its use as a sanitizer.[24]
Boiling, steaming, and simmering are popular cooking methods that often require immersing food in water or its gaseous state, steam. While cooking water is used for dishwashing too.
# Water politics and water crisis
Water politics is politics affected by water and water resources. Because of overpopulation, mass consumption, misuse, and water pollution, the availability of drinking water per capita is inadequate and shrinking as of the year 2006. For this reason, water is a strategic resource in the globe and an important element in many political conflicts. It causes health impacts and damage to biodiversity. The serious worldwide water situation is called water crisis.
UNESCO's World Water Development Report (WWDR, 2003) from its World Water Assessment Program indicates that, in the next 20 years, the quantity of water available to everyone is predicted to decrease by 30%. 40% of the world's inhabitants currently have insufficient fresh water for minimal hygiene. More than 2.2 million people died in 2000 from waterborne diseases (related to the consumption of contaminated water) or drought. In 2004, the UK charity WaterAid reported that a child dies every 15 seconds from easily preventable water-related diseases; often this means lack of sewage disposal; see toilet.
To halve, by 2015, the proportion of people without sustainable access to safe drinking water is one of the Millennium Development Goals.
Fresh water — now more precious than ever in our history for its extensive use in agriculture, high-tech manufacturing, and energy production — is increasingly receiving attention as a resource requiring better water management and sustainable use.
Organizations concerned in water protection include International Water Association (IWA), WaterAid, Water 1st, American Water Resources Association. Water related conventions are United Nations Convention to Combat Desertification (UNCCD), International Convention for the Prevention of Pollution from Ships, United Nations Convention on the Law of the Sea and Ramsar Convention. World Day for Water takes place at March 22 and World Ocean Day at June 8.
Water used in the production of a good or service is virtual water.
# Religion, philosophy, and literature
Water is considered a purifier in most religions. Major faiths that incorporate ritual washing (ablution) include Christianity, Hinduism, Rastafarianism, Islam, Shinto, Taoism, and Judaism. Immersion (or aspersion or affusion) of a person in water is a central sacrament of Christianity (where it is called baptism); it is also a part of the practice of other religions, including Judaism (mikvah) and Sikhism (Amrit Sanskar). In addition, a ritual bath in pure water is performed for the dead in many religions including Judaism and Islam. In Islam, the five daily prayers can be done in most cases after completing washing certain parts of the body using clean water (wudu). In Shinto, water is used in almost all rituals to cleanse a person or an area (e.g., in the ritual of misogi). Water is mentioned in the Bible 442 times in the New International Version and 363 times in the King James Version: 2 Peter 3:5(b) states, "The earth was formed out of water and by water" (NIV).
Some faiths use water especially prepared for religious purposes (holy water in some Christian denominations, Amrita in Sikhism and Hinduism). Many religions also consider particular sources or bodies of water to be sacred or at least auspicious; examples include Lourdes in Roman Catholicism, the Jordan River (at least symbolically) in some Christian churches, the Zamzam Well in Islam and the River Ganges (among many others) in Hinduism.
Water is often believed to have spiritual powers. In Celtic mythology, Sulis is the local goddess of thermal springs; in Hinduism, the Ganges is also personified as a goddess, while Saraswati have been referred to as goddess in Vedas. Also water is one of the "panch-tatva"s (basic 5 elements, others including fire, earth, space, air). Alternatively, gods can be patrons of particular springs, rivers, or lakes: for example in Greek and Roman mythology, Peneus was a river god, one of the three thousand Oceanids. In Islam, not only does water give life, but every life is itself made of water: "We made from water every living thing".[26]
The Ancient Greek philosopher Empedocles held that water is one of the four classical elements along with fire, earth and air, and was regarded as the ylem, or basic substance of the universe. Water was considered cold and moist. In the theory of the four bodily humors, water was associated with phlegm. Water was also one of the five elements in traditional Chinese philosophy, along with earth, fire, wood, and metal.
Water also plays an important role in literature as a symbol of purification. Examples include the critical importance of a river in As I Lay Dying by William Faulkner and the drowning of Ophelia in Hamlet. | https://www.wikidoc.org/index.php/Dihydrogen_monoxide | |
2a0eb328db6671afd5e5e7bfd5cbfaa5b9881848 | wikidoc | Dimer | Dimer
A dimer is a chemical or biological entity consisting of two subunits called monomers, which are held together by either intramolecular forces (covalent bonds) or weaker intermolecular forces.
# Chemistry
An example of a molecular dimer (i.e. held together by intramolecular forces) is dicyclopentadiene, wherein two cyclopentadiene molecules have reacted to give the product.
Molecular dimers are often formed by the reaction of two identical compounds e.g.: 2A → A-A.
In this example, monomer "A" is said to dimerise to give the dimer "A-A". Diaminocarbenes are another example which dimerise, to give tetraaminoethylenes.
An example of an intermolecular or physical dimer is acetic acid wherein hydrogen bonds hold the two molecules together. The water dimer is another such dimer.
The term homodimer is used when the two molecules are identical (e.g. A-A) and heterodimer when they are not (e.g. A-B).
The reverse of dimerisation is often called disassociation.
# Biochemistry
In biochemistry and molecular biology, dimers of macromolecules like proteins and nucleic acids are often observed. The dimerization of identical subunits is called homodimerization; the dimerization of different subunits or unrelated monomers is called heterodimerization. Most dimers in biochemistry are not connected by covalent bonds with the exception of disulfide bridges.
An example of this would be the enzyme reverse transcriptase, which is made of two different amino acid chains.
## Examples
- Nucleic acids:
DNA
- DNA
- DNA Polymerase
- Proteins:
Antibodies
Protein kinases:
Receptor tyrosine kinases
Transcription factors
Leucine zipper motif proteins
Nuclear receptors
14-3-3 proteins
G protein-coupled receptors
G protein βγ-subunit dimer
Kinesin
Triosephosphateisomerase (TIM)
Alcohol dehydrogenase
Factor XI
Factor XIII
Toll-like receptor
Fibrinogen
- Antibodies
- Protein kinases:
Receptor tyrosine kinases
- Receptor tyrosine kinases
- Transcription factors
Leucine zipper motif proteins
Nuclear receptors
- Leucine zipper motif proteins
- Nuclear receptors
- 14-3-3 proteins
- G protein-coupled receptors
- G protein βγ-subunit dimer
- Kinesin
- Triosephosphateisomerase (TIM)
- Alcohol dehydrogenase
- Factor XI
- Factor XIII
- Toll-like receptor
- Fibrinogen | Dimer
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
A dimer is a chemical or biological entity consisting of two subunits called monomers, which are held together by either intramolecular forces (covalent bonds) or weaker intermolecular forces.
# Chemistry
An example of a molecular dimer (i.e. held together by intramolecular forces) is dicyclopentadiene, wherein two cyclopentadiene molecules have reacted to give the product.
Molecular dimers are often formed by the reaction of two identical compounds e.g.: 2A → A-A.
In this example, monomer "A" is said to dimerise to give the dimer "A-A". Diaminocarbenes are another example which dimerise, to give tetraaminoethylenes.
An example of an intermolecular or physical dimer is acetic acid wherein hydrogen bonds hold the two molecules together. The water dimer is another such dimer.
The term homodimer is used when the two molecules are identical (e.g. A-A) and heterodimer when they are not (e.g. A-B).
The reverse of dimerisation is often called disassociation.
# Biochemistry
In biochemistry and molecular biology, dimers of macromolecules like proteins and nucleic acids are often observed. The dimerization of identical subunits is called homodimerization; the dimerization of different subunits or unrelated monomers is called heterodimerization. Most dimers in biochemistry are not connected by covalent bonds with the exception of disulfide bridges.
An example of this would be the enzyme reverse transcriptase, which is made of two different amino acid chains.
## Examples
- Nucleic acids:
DNA
- DNA
- DNA Polymerase
- Proteins:
Antibodies
Protein kinases:
Receptor tyrosine kinases
Transcription factors
Leucine zipper motif proteins
Nuclear receptors
14-3-3 proteins
G protein-coupled receptors
G protein βγ-subunit dimer
Kinesin
Triosephosphateisomerase (TIM)
Alcohol dehydrogenase
Factor XI
Factor XIII
Toll-like receptor
Fibrinogen
- Antibodies
- Protein kinases:
Receptor tyrosine kinases
- Receptor tyrosine kinases
- Transcription factors
Leucine zipper motif proteins
Nuclear receptors
- Leucine zipper motif proteins
- Nuclear receptors
- 14-3-3 proteins
- G protein-coupled receptors
- G protein βγ-subunit dimer
- Kinesin
- Triosephosphateisomerase (TIM)
- Alcohol dehydrogenase
- Factor XI
- Factor XIII
- Toll-like receptor
- Fibrinogen | https://www.wikidoc.org/index.php/Dimer | |
95079c47ba45d462c922256d1105531957b93bd8 | wikidoc | Dock2 | Dock2
Dock2 (Dedicator of cytokinesis 2), also known as DOCK2, is a large (~180 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-A subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock2 specifically activates isoforms of the small G protein Rac.
# Discovery
Dock2 was first characterised as one of a number of proteins which shared high sequence similarity with the previously described protein Dock180, the archetypal member of the DOCK family. Whereas Dock180 expression is near ubiquitous in mammals, Dock2 appears to be expressed specifically in leukocytes and is considered to be the principal DOCK family member in these cells.
# Structure and Function
Dock2 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins. In their resting state G proteins are bound to Guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphosphate (GTP). GEFs activate G proteins by promoting this nucleotide exchange.
Dock2 and other DOCK family proteins differ from other GEFs in that they do not possess the canonical structure of tandem DH-PH domains known to elicit nucleotide exchange. Instead they possess a DHR2 domain which mediates Rac activation by stabilising it in its nucleotide-free state. They also contain a DHR1 domain which binds phospholipids and is required for the interaction between Dock2 and the plasma membrane. As with other members of the DOCK-A and DOCK-B subfamilies, Dock2 contains an N-terminal SH3 domain which is involved in binding to ELMO proteins (see below). Dock180 contains a C-terminal proline rich region which mediates binding to Crk, however, Dock2 lacks this feature despite the fact that it is able to bind the Crk-like protein CrkL.
# Regulation of Dock2 activity
Efficient Dock180 GEF activity in a cellular context is known to require the formation of a complex between Dock180 and its cognate adaptor proteins, which assist its translocation to the plasma membrane and binding to Rac. Similarly, Dock2 has been shown to form a complex with the well described DOCK-binding protein ELMO1 and this interaction is required for Dock2-mediated Rac activation in lymphocyte cell lines. ELMO proteins contain a C-terminal proline-rich region which binds to the N-terminal SH3 domain of DOCK proteins and mediates their recruitment to sites of high Rac availability (primarily the plasma membrane). ELMO proteins also contain a PH domain which appears to induce conformational changes in DOCK and thus allow binding to Rac.
# Signalling downstream of Dock2
Like other DOCK-A and DOCK-B subfamily proteins Dock2 GEF activity is specific for Rac. Leukocytes express both Rac1 and Rac2 and Dock2 has been shown to bind and promote nucleotide exchange on both of these isoforms. Rac isoforms regulate a multitude of processes in leukocytes and studies so far have shown that Dock2-dependent Rac activation regulates the neutrophil NADPH oxidase and is also important for chemotaxis in neutrophils, lymphocytes and plasmacytoid dendritic cells. Dock2-dependent NADPH oxidase activation was reported in response to the soluble agonist fMLP, which acts via G protein-coupled receptors in neutrophils. Dock2-dependent chemotaxis has been reported in response to the chemokines CXCL12/SDF-1 in T lymphocytes, CXCL13/BLC in B lymphocytes and CCL19/ELC in thymocytes (immature lymphocytes) emigrating from the thymus as well as CCL21/SLC in ex vivo plasmacytoid dendritic cells. In neutrophil chemotaxis Dock2 signals downstream of the C5a and CXCL8/IL-8 receptors. Additional receptors which signal through Dock2 include the T cell receptor/TCR and EDG1, a sphingosine-1-phosphate (S1P) receptor. The HIV-1 protein Nef is able to constitutively activate Dock2 in T lymphocytes which disrupts chemotaxis and immunological synapse formation thereby inhibiting the antiviral immune response.
# Interactions
Dock2 has been shown to interact with CRKL. | Dock2
Dock2 (Dedicator of cytokinesis 2), also known as DOCK2, is a large (~180 kDa) protein involved in intracellular signalling networks.[1] It is a member of the DOCK-A subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock2 specifically activates isoforms of the small G protein Rac.
# Discovery
Dock2 was first characterised as one of a number of proteins which shared high sequence similarity with the previously described protein Dock180, the archetypal member of the DOCK family. Whereas Dock180 expression is near ubiquitous in mammals, Dock2 appears to be expressed specifically in leukocytes and is considered to be the principal DOCK family member in these cells.[2]
# Structure and Function
Dock2 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins. In their resting state G proteins are bound to Guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphosphate (GTP). GEFs activate G proteins by promoting this nucleotide exchange.
Dock2 and other DOCK family proteins differ from other GEFs in that they do not possess the canonical structure of tandem DH-PH domains known to elicit nucleotide exchange. Instead they possess a DHR2 domain which mediates Rac activation by stabilising it in its nucleotide-free state.[3] They also contain a DHR1 domain which binds phospholipids and is required for the interaction between Dock2 and the plasma membrane.[4] As with other members of the DOCK-A and DOCK-B subfamilies, Dock2 contains an N-terminal SH3 domain which is involved in binding to ELMO proteins (see below).[5] Dock180 contains a C-terminal proline rich region which mediates binding to Crk, however, Dock2 lacks this feature[2] despite the fact that it is able to bind the Crk-like protein CrkL.[6]
# Regulation of Dock2 activity
Efficient Dock180 GEF activity in a cellular context is known to require the formation of a complex between Dock180 and its cognate adaptor proteins, which assist its translocation to the plasma membrane and binding to Rac.[7][8] Similarly, Dock2 has been shown to form a complex with the well described DOCK-binding protein ELMO1 and this interaction is required for Dock2-mediated Rac activation in lymphocyte cell lines.[5] ELMO proteins contain a C-terminal proline-rich region which binds to the N-terminal SH3 domain of DOCK proteins and mediates their recruitment to sites of high Rac availability (primarily the plasma membrane).[8] ELMO proteins also contain a PH domain which appears to induce conformational changes in DOCK and thus allow binding to Rac.[9]
# Signalling downstream of Dock2
Like other DOCK-A and DOCK-B subfamily proteins Dock2 GEF activity is specific for Rac. Leukocytes express both Rac1 and Rac2 and Dock2 has been shown to bind and promote nucleotide exchange on both of these isoforms.[2] Rac isoforms regulate a multitude of processes in leukocytes and studies so far have shown that Dock2-dependent Rac activation regulates the neutrophil NADPH oxidase[4] and is also important for chemotaxis in neutrophils,[4][10] lymphocytes[11] and plasmacytoid dendritic cells.[12] Dock2-dependent NADPH oxidase activation was reported in response to the soluble agonist fMLP, which acts via G protein-coupled receptors in neutrophils.[4] Dock2-dependent chemotaxis has been reported in response to the chemokines CXCL12/SDF-1 in T lymphocytes, CXCL13/BLC in B lymphocytes and CCL19/ELC in thymocytes (immature lymphocytes) emigrating from the thymus[11] as well as CCL21/SLC in ex vivo plasmacytoid dendritic cells.[12] In neutrophil chemotaxis Dock2 signals downstream of the C5a and CXCL8/IL-8 receptors.[4][10] Additional receptors which signal through Dock2 include the T cell receptor/TCR[13] and EDG1, a sphingosine-1-phosphate (S1P) receptor.[14] The HIV-1 protein Nef is able to constitutively activate Dock2 in T lymphocytes which disrupts chemotaxis and immunological synapse formation thereby inhibiting the antiviral immune response.[15]
# Interactions
Dock2 has been shown to interact with CRKL.[16] | https://www.wikidoc.org/index.php/Dock2 | |
04ace6d911122f96bfe5bae3780a2f290311c60c | wikidoc | Dock3 | Dock3
Dock3 (Dedicator of cytokinesis 3), also known as MOCA (modifier of cell adhesion) and PBP (presenilin-binding protein), is a large (~180 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-B subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock3 specifically activates the small G protein Rac.
# Discovery
Dock3 was originally discovered in a screen for proteins that bind presenilin (a transmembrane protein which is mutated in early onset Alzheimer's disease). Dock3 is specifically expressed in neurones (primarily in the cerebral cortex and hippocampus).
# Structure and function
Dock3 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins. In their resting state G proteins are bound to Guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphosphate (GTP). GEFs activate G proteins by promoting this nucleotide exchange.
Dock3 exhibits the same domain arrangement as Dock180 (a member of the DOCK-A subfamily and the archetypal member of the DOCK family) and these proteins share a considerable (40%) degree of sequence similarity.
# Regulation of Dock3 activity
Since Dock3 shares the same domain arrangement as Dock180 it is predicted to have a similar array of binding partners, although this has yet to be demonstrated. It contains an N-terminal SH3 domain, which in Dock180 binds ELMO (a family of adaptor proteins which mediate recruitment and efficient GEF activity of Dock180), and a C-terminal proline-rich region which, in Dock180, binds the adaptor protein CRK.
# Signalling downstream of Dock3
Dock3 GEF activity is directed specifically at Rac1. Dock3 has not been shown to interact with Rac3, another Rac protein which is expressed in neuronal cells, and this may be because Rac3 is primarily located in the perinuclear region. In fact, Rac1 and Rac3 appear to have distinct and antagonistic roles in these cells. Dock3-mediated Rac1 activation promotes reorganisation of the cytoskeleton in SH-SY5Y neuroblastoma cells and primary cortical neurones as well as morphological changes in fibroblasts. It has also been shown to regulate neurite outgrowth and cell-cell adhesion in B103 and PC12 cells.
# Dock3 in neurological disorders
The first indication that Dock3 might be involved in neurological disorders came when Dock3 was shown to bind to presenilin, a transmembrane enzyme involved in the generation of beta amyloid (Aβ), accumulation of which is an important step in the development of Alzheimer's disease. Dock3 has been shown to undergo redistribution and association with neurofibrillary tangles in brain samples from Alzheimers patients. A mutation in Dock3 was also identified in a family displaying a phenotype resembling attention-deficit hyperactivity disorder (ADHD). | Dock3
Dock3 (Dedicator of cytokinesis 3), also known as MOCA (modifier of cell adhesion) and PBP (presenilin-binding protein), is a large (~180 kDa) protein involved in intracellular signalling networks.[1] It is a member of the DOCK-B subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock3 specifically activates the small G protein Rac.
# Discovery
Dock3 was originally discovered in a screen for proteins that bind presenilin (a transmembrane protein which is mutated in early onset Alzheimer's disease).[2] Dock3 is specifically expressed in neurones (primarily in the cerebral cortex and hippocampus).
# Structure and function
Dock3 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins. In their resting state G proteins are bound to Guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphosphate (GTP). GEFs activate G proteins by promoting this nucleotide exchange.
Dock3 exhibits the same domain arrangement as Dock180 (a member of the DOCK-A subfamily and the archetypal member of the DOCK family) and these proteins share a considerable (40%) degree of sequence similarity.[3]
# Regulation of Dock3 activity
Since Dock3 shares the same domain arrangement as Dock180 it is predicted to have a similar array of binding partners, although this has yet to be demonstrated. It contains an N-terminal SH3 domain, which in Dock180 binds ELMO (a family of adaptor proteins which mediate recruitment and efficient GEF activity of Dock180), and a C-terminal proline-rich region which, in Dock180, binds the adaptor protein CRK.[3][4]
# Signalling downstream of Dock3
Dock3 GEF activity is directed specifically at Rac1. Dock3 has not been shown to interact with Rac3, another Rac protein which is expressed in neuronal cells, and this may be because Rac3 is primarily located in the perinuclear region. In fact, Rac1 and Rac3 appear to have distinct and antagonistic roles in these cells.[5] Dock3-mediated Rac1 activation promotes reorganisation of the cytoskeleton in SH-SY5Y neuroblastoma cells and primary cortical neurones as well as morphological changes in fibroblasts.[6] It has also been shown to regulate neurite outgrowth and cell-cell adhesion in B103 and PC12 cells.[7]
# Dock3 in neurological disorders
The first indication that Dock3 might be involved in neurological disorders came when Dock3 was shown to bind to presenilin, a transmembrane enzyme involved in the generation of beta amyloid (Aβ),[2] accumulation of which is an important step in the development of Alzheimer's disease. Dock3 has been shown to undergo redistribution and association with neurofibrillary tangles in brain samples from Alzheimers patients.[8] A mutation in Dock3 was also identified in a family displaying a phenotype resembling attention-deficit hyperactivity disorder (ADHD).[9] | https://www.wikidoc.org/index.php/Dock3 |
Subsets and Splits
No saved queries yet
Save your SQL queries to embed, download, and access them later. Queries will appear here once saved.