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Riboswitches are gene control elements typically located in the 5' untranslated regions of bacterial mRNAs where they modulate the expression of associated genes in response to elevated concentrations of cellular metabolites. Metabolite binding stabilizes the evolutionarily conserved receptor domains and affects the folding of the downstream gene-controlling modules. About 20 classes of riboswitches display a large number of RNA sequences perfectly adjusted to bind their cognate cellular metabolites. The question of how riboswitches achieve exquisite specificity for various ligands has been answered for almost all major classes of known riboswitches by structural and biochemical studies of their metabolite-sensing domains. Here I outline the most recent additions to the growing collection of riboswitch structures, review the principles of riboswitch folding and metabolite recognition, and discuss whether this information can help us understand the details of genetic control and metabolite recognition in the riboswitches whose three-dimensional structures are not available.	What process involves metabolite-sensing mRNAs to control gene expression?	Riboswitches are gene control elements typically located in the 5' untranslated regions of bacterial mRNAs where they modulate the expression of associated genes in response to elevated concentrations of cellular metabolites.
Honey bees provision glandular secretions in the form of royal jelly as larval nourishment to developing queens. Exposure to chemicals and nutritional conditions can influence queen development and thus impact colony fitness. Previous research reports that royal jelly remains pesticide-free during colony-level exposure and that chemical residues are buffered by the nurse bees. However, the impacts of pesticides can also manifest in quality and quantity of royal jelly produced by nurse bees. Here, we tested how colony exposure to a multi-pesticide pollen treatment influences the amount of royal jelly provisioned per queen and the additional impacts on royal jelly nutritional quality. We observed differences in the metabolome, proteome, and phytosterol compositions of royal jelly synthesized by nurse bees from multi-pesticide exposed colonies, including significant reductions of key nutrients such as 24-methylenecholesterol, major royal jelly proteins, and 10-hydroxy-2-decenoic acid. Additionally, quantity of royal jelly provisioned per queen was lower in colonies exposed to pesticides, but this effect was colony-dependent. Pesticide treatment had a greater impact on royal jelly nutritional composition than the weight of royal jelly provisioned per queen cell. These novel findings highlight the indirect effects of pesticide exposure on queen developmental nutrition and allude to social consequences of nurse bee glandular degeneration.	Does the royal jelly contain proteins?	We observed differences in the metabolome, proteome, and phytosterol compositions of royal jelly synthesized by nurse bees from multi-pesticide exposed colonies, including significant reductions of key nutrients such as 24-methylenecholesterol, major royal jelly proteins, and 10-hydroxy-2-decenoic acid.
Circular RNAs (circRNAs) are long, non-coding RNAs that result from the non-canonical splicing of linear pre-mRNAs. However, the characteristics and the critical role of circRNA in co-/post-transcriptional regulation were not well recognized until the "microRNA sponge" function of circRNA is discovered. Recent studies have mainly been devoted to the function of the circular RNA sponge for miR-7 (ciRS-7) and sex-determining region Y (SRY) by targeting microRNA-7 (miR-7) and microRNA-138 (miR-138), respectively. In this review, we illustrate the specific role of circRNAs in a wide variety of cancers and in regulating the biological behavior of cancers via miR-7 or miR-138 regulation. Furthermore, circRNA, together with its gene silencing ability, also shows its potential in RNA interference (RNAi) therapy by binding to target RNAs, which provides a novel perspective in cancer treatment. Thus, this review concerns the biogenesis, biological function, oncogenesis, progression and possible therapies for cancer involving circRNAs.	What is the biological function of the SRY circular RNA (circRNA)?	Recent studies have mainly been devoted to the function of the circular RNA sponge for miR-7 (ciRS-7) and sex-determining region Y (SRY) by targeting microRNA-7 (miR-7) and microRNA-138 (miR-138), respectively.
Thyromimetic agents that can treat dyslipidemia without adverse effects like cardiac arrhythmias and osteoporosis are attractive options. Initial experience with desssicated thyroid hormone extract and DT4 were disappointing. Thyroid hormone has nuclear action with four receptor isoforms- TR α1, TRα2, TRβ1, TRβ2. TR α1 has predominant effects on CVS, TRβ2 acts mainly on the pituitary and TRβ1 has hepatoselective action and decrease cholesterol levels. Eprotirome and Sobetirome are 2 thyromimetics that have selective TRβ1 activity. They act in dyslipidemia by multiple mechanisms. They are presumably safe on the pituitary- thyroid axis.	What is the mechanism of action of eprotirome?	Eprotirome and Sobetirome are 2 thyromimetics that have selective TRβ1 activity.
We report the use of the U1 snRNA as a vector for the stable expression of antisense molecules against the splice junctions of specific dystrophin exons. The single-stranded 5' terminus of U1 can be replaced by unrelated sequences as long as 50 nucleotides without affecting both the stability and the ability to assemble into snRNP particles. Effective exon skipping has been obtained for different dystrophin exons by antisense sequences against 5' and 3' splice sites alone or in combination with ESE sequences. The efficacy of these molecules has been studied both in in vitro systems and in animals. In both cases the chimeric molecules, delivered as part of lentiviral or AAV vectors (De Angelis et al. Proc Natl Acad Sci USA 99:9456-9461, 2002; Denti et al. Proc Natl Acad Sci USA 103: 3758-3763, 2006; Denti et al. Hum Gene Ther 17: 565-743, 2006; Denti et al. Hum Gene Ther 19: 601-608, 2008; Incitti et al. Mol Ther 18: 1675-1682, 2010), provided high skipping activity and efficient rescue of dystrophin synthesis. Moreover, the U1-antisense molecules, delivered to mice via systemic injection of recombinant AAV viruses, displayed body wide transduction, long-term expression, dystrophin rescue as well as morphological and functional benefit (Denti et al. Hum Gene Ther 19: 601-608, 2008). In this Chapter we report methods for producing U1-antisense expression cassettes in the backbone of lentiviral constructs and for testing their activity both in patients' derived myoblasts as well as in fibroblasts reprogrammed to muscle differentiation.	How could U1 small nuclear RNA be used in therapeutics?	We report the use of the U1 snRNA as a vector for the stable expression of antisense molecules against the splice junctions of specific dystrophin exons
We study, using simulated experiments inspired by thin-film magnetic domain patterns, the feasibility of phase retrieval in x-ray diffractive imaging in the presence of intrinsic charge scattering given only photon-shot-noise limited diffraction data. We detail a reconstruction algorithm to recover the sample's magnetization distribution under such conditions and compare its performance with that of Fourier transform holography. Concerning the design of future experiments, we also chart out the reconstruction limits of diffractive imaging when photon-shot-noise and the intensity of charge scattering noise are independently varied. This work is directly relevant to the time-resolved imaging of magnetic dynamics using coherent and ultrafast radiation from x-ray free-electron lasers and also to broader classes of diffractive imaging experiments which suffer noisy data, missing data, or both.	Where is X-ray free electron laser used?	This work is directly relevant to the time-resolved imaging of magnetic dynamics using coherent and ultrafast radiation from x-ray free-electron lasers and also to broader classes of diffractive imaging experiments which suffer noisy data, missing data, or both.
The cytochrome P450 (CYP) 2C192 loss-of-function allele has been associated with impaired clopidogrel response and worse prognosis in clopidogrel-treated patients. The benefit of tailored therapy according to platelet function test results remains unclear, and the potential effect of genotypes on this benefit has not been addressed in unstable patients. The present study was designed to evaluate the benefit of tailored therapy with a higher maintenance dose according to CYP2C19 genotypes in patients identified as nonresponders who underwent percutaneous coronary intervention for non-ST-segment elevation acute coronary syndromes. Three hundred forty-six consecutive patients were enrolled and received a loading dose of 600 mg, including 86 2 carriers (13 homozygotes and 73 heterozygotes) and 260 2 noncarriers. Clopidogrel response, assessed with platelet reactivity index vasoactive-stimulated phosphoprotein, was significantly affected by genotype, with lower clopidogrel response in CYP2C192 allele carriers (p = 0.01). Accordingly, the rate of clopidogrel nonresponse was higher in CYP2C192 allele carriers (53% vs 41%, p = 0.04). All clopidogrel nonresponders (n = 151), including 105 2 noncarriers and 46 2 carriers, received high 150-mg clopidogrel maintenance doses at discharge to overcome initial low response. After 1 month, high maintenance doses overcame clopidogrel low response in only 44% of the whole population and significantly less frequently in 2 carriers than in noncarriers (28% vs 50%, p = 0.01). In conclusion, higher clopidogrel maintenance doses were able to overcome clopidogrel low response in fewer than half of clopidogrel low responders who underwent percutaneous coronary intervention for non-ST-segment elevation acute coronary syndromes. The benefit of this tailored therapy was significantly reduced in CYP2C19*2 carriers. Therefore, these patients might require alternative strategies with new P2Y₁₂ blockers.	What gene test is recommended for clopidogrel?	The cytochrome P450 (CYP) 2C19*2 loss-of-function allele has been associated with impaired clopidogrel response and worse prognosis in clopidogrel-treated patients.
The cell division control protein (Cdc2) kinase is a catalytic subunit of a protein kinase complex, called the M phase promoting factor, which induces entry into mitosis and is universal among eukaryotes. This protein is believed to play a major role in cell division and control. The lives of biological cells are controlled by proteins interacting in metabolic and signaling pathways, in complexes that replicate genes and regulate gene activity, and in the assembly of the cytoskeletal infrastructure. Our knowledge of protein-protein (P-P) interactions has been accumulated from biochemical and genetic experiments, including the widely used yeast two-hybrid test. In this paper we examine if P-P interactions in regenerating tissues and cells of the anuran Xenopus laevis can be discovered from biomedical literature using computational and literature mining techniques. Using literature mining techniques, we have identified a set of implicitly interacting proteins in regenerating tissues and cells of Xenopus laevis that may interact with Cdc2 to control cell division. Genome sequence based bioinformatics tools were then applied to validate a set of proteins that appear to interact with the Cdc2 protein. Pathway analysis of these proteins suggests that Myc proteins function as the regulator of M phase initiation by controlling expression of the Akt1 molecule that ultimately inhibits the Cdc2-cyclin B complex in cells. P-P interactions that are implicitly appearing in literature can be effectively discovered using literature mining techniques. By applying evolutionary principles on the P-P interacting pairs, it is possible to quantitatively analyze the significance of the associations with biological relevance. The developed BioMap system allows discovering implicit P-P interactions from large quantity of biomedical literature data. The unique similarities and differences observed within the interacting proteins can lead to the development of the new hypotheses that can be used to design further laboratory experiments.	Which are the available biomedical text mining tools for the detection of protein-protein interactions?	The developed BioMap system allows discovering implicit P-P interactions from large quantity of biomedical literature data.
Immunocompromised adults can have prolonged acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive RT-PCR results, long after the initial diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to determine if SARS-CoV-2 virus can be recovered in viral cell culture from immunocompromised adults with persistently positive SARS-CoV-2 RT-PCR tests. We obtained 20 remnant SARS-CoV-2 PCR positive nasopharyngeal swabs from 20 immunocompromised adults with a positive RT-PCR test ≥14 days after the initial positive test. The patients' 2 test samples underwent SARS-CoV-2 antigen testing, and culture with Vero-hACE2-TMPRSS2 cells. Viral RNA and cultivable virus were recovered from the cultured cells after qRT-PCR and plaque assays. Of 20 patients, 10 (50%) had a solid organ transplant and 5 (25%) had a hematologic malignancy. For most patients, RT-PCR Ct values increased over time. There were 2 patients with positive viral cell cultures; one patient had chronic lymphocytic leukemia treated with venetoclax and obinutuzumab who had a low viral titer of 27 PFU/mL. The second patient had marginal zone lymphoma treated with bendamustine and rituximab who had a high viral titer of 2 x 10 PFU/mL. Most samples collected ≥7 days after an initial positive SARS-CoV-2 RT-PCR had negative viral cell cultures. The 2 patients with positive viral cell cultures had hematologic malignancies treated with chemotherapy and B cell depleting therapy. One patient had a high concentration titer of cultivable virus. Further data are needed to determine risk factors for persistent viral shedding and methods to prevent SARS-CoV-2 transmission from immunocompromised hosts.	What is the significance of a persistently positive RT-PCR for weeks after illness?	Immunocompromised adults can have prolonged acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive RT-PCR results, long after the initial diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to determine if SARS-CoV-2 virus can be recovered in viral cell culture from immunocompromised adults with persistently positive SARS-CoV-2 RT-PCR tests.
Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, and characterized by typical face, moderate-to-severe mental retardation, epilepsy, Hirschsprung disease, and multiple congenital anomalies, including genital anomalies (particularly hypospadias in males), congenital heart defects, agenesis of the corpus callosum, and eye defects. Since the first delineation by Mowat et al. [Mowat et al. (1998); J Med Genet 35:617-623], approximately 179 patients with ZEB2 mutations, deletions or cytogenetic abnormalities have been reported primarily from Europe, Australia and the United States. Genetic defects include chromosome 2q21-q23 microdeletions (or different chromosome rearrangements) in few patients, and ZEB2 mutations in most. We report on clinical and genetic data from 19 Italian patients, diagnosed within the last 5 years, including six previously published, and compare them with patients already reported. The main purpose of this review is to underline a highly consistent phenotype and to highlight the phenotypic evolution occurring with age, particularly of the facial characteristics. The prevalence of MWS is likely to be underestimated. Knowledge of the phenotypic spectrum of MWS and of its changing phenotype with age can improve the detection rate of this condition.	Have mutations in the ZEB2 gene been found in any human syndrome?	owat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene
The change in the colour of urine is a known occurrence in an intensive care setting and is always a cause of concern to the clinicians who have to differentiate between benign and pathological causes. Herein, we present a case of 62-year-old postoperative lady, noticed to be passing green coloured urine believed to be due to intravenous Propofol administration for induction of general anaesthesia. The green colour of urine due to Propofol occurs when clearance of Propofol exceeds hepatic elimination, and extrahepatic elimination of Propofol occurs. This discolouration of urine is a rare (less than 1% cases) but a benign side effect of Propofol, which is non-nephrotoxic and gets reversed after discontinuation of the drug.	Can propofol cause green urine?	green colour of urine due to Propofol occurs when clearance of Propofol exceeds hepatic elimination, and extrahepatic elimination of Propofol occurs. Thi
Activation of the superoxide-producing NADPH oxidase Nox1 requires both the organizer protein Noxo1 and the activator protein Noxa1. Here we describe an alternative splicing form of Noxo1, Noxo1gamma, which is expressed in the testis and fetal brain. The Noxo1gamma protein contains an additional five amino acids in the N-terminal PX domain, a phosphoinositide-binding module; the domain plays an essential role in supporting superoxide production by NADPH oxidase (Nox) family oxidases including Nox1, gp91(phox)/Nox2, and Nox3, as shown in this study. The PX domain isolated from Noxo1gamma shows a lower affinity for phosphoinositides than that from the classical splicing form Noxo1beta. Consistent with this, in resting cells, Noxo1gamma is poorly localized to the membrane, and thus less effective in activating Nox1 than Noxo1beta, which is constitutively present at the membrane. On the other hand, cell stimulation with phorbol 12-myristate 13-acetate (PMA), an activator of Nox1-3, facilitates membrane translocation of Noxo1gamma; as a result, Noxo1gamma is equivalent to Noxo1beta in Nox1 activation in PMA-stimulated cells. The effect of the five-amino-acid insertion in the Noxo1 PX domain appears to depend on the type of Nox; in activation of gp91(phox)/Nox2, Noxo1gamma is less active than Noxo1beta even in the presence of PMA, whereas Noxo1gamma and Noxo1beta support the superoxide-producing activity of Nox3 to the same extent in a manner independent of cell stimulation.	Which NADPH oxidase family member requires interaction with NOXO1 for function?	Activation of the superoxide-producing NADPH oxidase Nox1 requires both the organizer protein Noxo1 and the activator protein Noxa1.
Angiotensin convertase inhibitor (Enalapril) was used in 51 children aged 4 days up to 18 years (mean 4.3 +/- 5.5, years). As many as 27 subjects were newborns (4) and infants (23). The patients suffered from circulatory insufficiency due to congestive cardiomyopathy (13 cases). 6 treated subjects suffered from circulatory insufficiency due to congenital heart malformations before cardiac surgery and 22 after it (including complex malformations operated according to Fontan method). 10 children were treated because of arterial hypertension. 4 subjects suffered form life-threatening arrhythmias coexisting with circulatory insufficiency. (These subjects were already mentioned among the patients suffering from circulatory insufficiency). Enalapril (mainly as a drug named Benalapril) was used in the mean dose of 0.21 mg/kg of body mass daily. 4 patients (8%) died during treatment but their deaths can not be related to angiotensin convertase inhibitor therapy. In the other children (82%) the beneficial influence of angiotensin convertase inhibitor use was found (improvement in comparison with the state before convertase inhibitor introduction). In 10% of subjects enalapril did not show any significant therapeutic effect. According to authors' opinion enalapril use is exceptionally profitable in the subjects surgically treated for complex heart malformations (Fontan operation). The beneficial effect was also found in majority of children suffering from congestive cardiomyopathy. Convertase inhibitor was always successfully used as the unique antihypertensive drug in children suffering from arterial hypertension. In the other cases treatment was combined (mainly with digitalis). This combination seems to be exceptionally useful in children suffering from congestive cardiomyopathy. Only in 1 case unserious side effect was found (persistent cough).	In what proportion of children with heart failure has Enalapril been shown to be safe and effective?	4 patients (8%) died during treatment but their deaths can not be related to angiotensin convertase inhibitor therapy. In the other children (82%) the beneficial influence of angiotensin convertase inhibitor use was found (improvement in comparison with the state before convertase inhibitor introduction). In 10% of subjects enalapril did not show any significant therapeutic effect
All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras, that promote oncogenesis when they are mutationally activated at codon 12, 13, or 61. Although there is a high degree of similarity among the isoforms, K-Ras mutations are far more frequently observed in cancer, and each isoform displays preferential coupling to particular cancer types. We examined the mutational spectra of Ras isoforms curated from large-scale tumor profiling and found that each isoform exhibits surprisingly distinctive codon mutation and amino-acid substitution biases. These findings were unexpected given that these mutations occur in regions that share 100% amino-acid sequence identity among the 3 isoforms. Of importance, many of these mutational biases were not due to differences in exposure to mutagens, because the patterns were still evident when compared within specific cancer types. We discuss potential genetic and epigenetic mechanisms, as well as isoform-specific differences in protein structure and signaling, that may promote these distinct mutation patterns and differential coupling to specific cancers.	Which are the different members/isoforms of the Ras oncogenes?	All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras
Tourette syndrome (TS) is characterized by tics, sensorimotor gating deficiencies, and abnormalities of cortico-basal ganglia circuits. A mutation in histidine decarboxylase (Hdc), the key enzyme for the biosynthesis of histamine (HA), has been implicated as a rare genetic cause. Hdc knockout mice exhibited potentiated tic-like stereotypies, recapitulating core phenomenology of TS; these were mitigated by the dopamine (DA) D2 antagonist haloperidol, a proven pharmacotherapy, and by HA infusion into the brain. Prepulse inhibition was impaired in both mice and humans carrying Hdc mutations. HA infusion reduced striatal DA levels; in Hdc knockout mice, striatal DA was increased and the DA-regulated immediate early gene Fos was upregulated. DA D2/D3 receptor binding was altered both in mice and in humans carrying the Hdc mutation. These data confirm histidine decarboxylase deficiency as a rare cause of TS and identify HA-DA interactions in the basal ganglia as an important locus of pathology.	Which mutated genes are associated with the Tourette's syndrome?	A mutation in histidine decarboxylase (Hdc), the key enzyme for the biosynthesis of histamine (HA), has been implicated as a rare genetic cause.
Silver staining is used to detect proteins after electrophoretic separation on polyacrylamide gels. It -combines excellent sensitivity (in the low nanogram range) with the use of very simple and cheap equipment and chemicals. For its use in proteomics, two important additional features must be considered, compatibility with mass spectrometry and quantitative response. Both features are discussed in this chapter, and optimized silver staining protocols are proposed.	List protein gel staining methods visualizing the entire protein set.	Silver staining is used to detect proteins after electrophoretic separation on polyacrylamide gels
Heterochromatin assembly in fission yeast depends on the Clr4 histone methyltransferase, which targets H3K9. We show that the histone deacetylase Sir2 is required for Clr4 activity at telomeres, but acts redundantly with Clr3 histone deacetylase to maintain centromeric heterochromatin. However, Sir2 is critical for Clr4 function during de novo centromeric heterochromatin assembly. We identified new targets of Sir2 and tested if their deacetylation is necessary for Clr4-mediated heterochromatin establishment. Sir2 preferentially deacetylates H4K16Ac and H3K4Ac, but mutation of these residues to mimic acetylation did not prevent Clr4-mediated heterochromatin establishment. Sir2 also deacetylates H3K9Ac and H3K14Ac. Strains bearing H3K9 or H3K14 mutations exhibit heterochromatin defects. H3K9 mutation blocks Clr4 function, but why H3K14 mutation impacts heterochromatin was not known. Here, we demonstrate that recruitment of Clr4 to centromeres is blocked by mutation of H3K14. We suggest that Sir2 deacetylates H3K14 to target Clr4 to centromeres. Further, we demonstrate that Sir2 is critical for de novo accumulation of H3K9me2 in RNAi-deficient cells. These analyses place Sir2 and H3K14 deacetylation upstream of Clr4 recruitment during heterochromatin assembly.	What is the function of yeast Clr4 on chromatin?	These analyses place Sir2 and H3K14 deacetylation upstream of Clr4 recruitment during heterochromatin assembly.
An individual with normal male habitus, body proportions, and secondary sexual characteristics was admitted to the hospital with head trauma. A routine blood smear demonstrated that 36% of the granulocytes had "drumsticks". Chromosomal analysis revealed a 46,XYqh+ karyotype. the extremely large Y chromosome was located by quinacrine fluorescence in the "drumstick" of the polymorphonuclear granulocytes. The presence of a large Y chromosome may thus produce pseudo-drumsticks. Fluorescent staining can distinguish between true drumsticks bearing the inactive X of normal females and the pseudo-drumsticks in a normal male produced by a large Y chromosome.	What is the relationship between the X chromosome and a neutrophil drumstick?	Fluorescent staining can distinguish between true drumsticks bearing the inactive X of normal females and the pseudo-drumsticks in a normal male produced by a large Y chromosome.
Expressions of EphB4 and EphrinB2 proteins may be related to differentiation degree of tumor cells.	Do ephrins play a role in brain cancer?	Expressions of EphB4 and EphrinB2 proteins may be related to differentiation degree of tumor cells
The vascular endothelial growth factor (VEGF) pathway is associated with the promotion of endothelial cell proliferation, migration, and survival necessary for angiogenesis. VEGF and its three receptor isoforms are often overexpressed in many human solid tumors. Tivozanib is a potent, selective inhibitor of VEGF receptors 1, 2, and 3, with a long half-life. The purpose of these studies was to evaluate the effect of ketoconazole, a potent inhibitor of CYP3A4, and rifampin, a potent inducer of CYP3A4, on the pharmacokinetics of tivozanib. Two phase I, open-label, 2-period, single-sequence studies evaluated the effect of steady-state ketoconazole (NCT01363778) or rifampin (NCT01363804) on the pharmacokinetic profile, safety, and tolerability of a single oral 1.5-mg dose of tivozanib. Tivozanib was well tolerated in both studies. Steady-state ketoconazole did not cause a clinically significant change in the pharmacokinetics of a single dose of tivozanib; therefore, dosing of tivozanib with a CYP3A4 pathway inhibitor should not cause a clinically significant change in serum tivozanib levels. However, coadministration of tivozanib with rifampin caused a significant decrease in the area under the curve from 0 to infinity and half-life and an increase in clearance of tivozanib, which suggest increased clearance via the enhanced CYP3A4-mediated metabolism of tivozanib.	Which receptor is inhibited by Tivozanib?	Tivozanib is a potent, selective inhibitor of VEGF receptors 1, 2, and 3, with a long half-life.
Alpha interferon (IFN-α) controls homeostasis of hematopoietic stem cells, regulates antiviral resistance, inhibits angiogenesis, and suppresses tumor growth. This cytokine is often used to treat cancers and chronic viral infections. The extent of cellular responses to IFN-α is limited by the IFN-induced ubiquitination and degradation of the IFN-α/β receptor chain 1 (IFNAR1) chain of the cognate receptor. IFNAR1 ubiquitination is facilitated by the βTrcp E3 ubiquitin ligase that is recruited to IFNAR1 upon its degron phosphorylation, which is induced by the ligand. Here we report identification of protein kinase D2 (PKD2) as a kinase that mediates the ligand-inducible phosphorylation of IFNAR1 degron and enables binding of βTrcp to the receptor. Treatment of cells with IFN-α induces catalytic activity of PKD2 and stimulates its interaction with IFNAR1. Expression and kinase activity of PKD2 are required for the ligand-inducible stimulation of IFNAR1 ubiquitination and endocytosis and for accelerated proteolytic turnover of IFNAR1. Furthermore, inhibition or knockdown of PKD2 robustly augments intracellular signaling induced by IFN-α and increases the efficacy of its antiviral effects. The mechanisms of the ligand-inducible elimination of IFNAR1 are discussed, along with the potential medical significance of this regulation.	Which E3 ubiquitin ligase mediates the ubiquitination and degradation of the interferon receptor type 1 (IFNAR1)?	IFNAR1 ubiquitination is facilitated by the βTrcp E3 ubiquitin ligase that is recruited to IFNAR1 upon its degron phosphorylation, which is induced by the ligand.
Isotretinoin is a potent retinoic acid used in the treatment of skin disorders. Though very effective, it is teratogenic if administered during pregnancy, and its teratogenic effect may be related to the normal activity of retinoids as signalling molecules in the embryo. Although its exact mechanism of action is unknown, it has been suggested that it causes its characteristic pattern of defects that includes heart defects, by inhibiting the migration of neural crest cells. However, other effects on cells are known. We studied early cardiac cell proliferation using incorporation of bromodeoxyuridine (BrdU) and detection with a monoclonal anti-BrdU. Proliferation in heart tissue of whole embryo cultures was inhibited in medium with 10(-6) M isotretinoin to 62% of the control level in myocardium. We studied its effects in culture on precardiac explant development in the absence of the neural crests. Culture of precardiac mesodermal-endodermal explants revealed that development of heart vesicles from the mesoderm was little affected, but the development of heartbeat was inhibited depending on dose in the 10(-5) to 10(-7) M range. The effect on development of contractions was augmented in the presence of serum; it could be duplicated by all-trans-retinoic acid, and it was reversible. Synthesis of the alpha-actin isotype, analyzed by isoelectric focusing, was found to be inhibited or delayed. The results suggest multiple effects of retinoids on growth, morphogenesis, and differentiation of early cardiac tissue, and are discussed in relation to the potential role of retinoids in early embryogenesis.	Is it safe to take isotretinoin during pregnancy?	The results suggest multiple effects of retinoids on growth, morphogenesis, and differentiation of early cardiac tissue, and are discussed in relation to the potential role of retinoids in early embryogenesis.
Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by systemic iron overload with consequent tissue damage. The vast majority of HH patients are homozygous for the C282Y mutation in HFE, a non-classical MHC class-I gene located in chromosome 6, whose role in the regulation of systemic iron metabolism is still not completely understood. Iron enhances the formation of reactive oxygen species, with increasing risk of DNA damage induced by oxidative stress, and consequently an increased susceptibility to chromosome instability. In the present work we examined spontaneous and diepoxybutane (DEB)-induced chromosome instability in PHA-stimulated lymphocyte cultures from 23 HH patients, all homozygous for the C282Y HFE mutation, in comparison to 29 normal controls. In addition, three patients with secondary forms of iron overload, not related to HFE, were studied as controls to test the role of iron overload on DEB-induced chromosome instability. Our results show a significantly higher frequency of spontaneous chromosome breaks in lymphocytes from the HH patients, when compared with lymphocytes from normal controls (p<0.0001). In addition, there is a significant correlation between the percentage of cells with spontaneous chromosomal breaks and the transferrin saturation (r=0.53, p=0.0041) or serum-ferritin levels (r=0.66, p=0.0001) in patients. Surprisingly, the frequency of DEB-induced chromosome breaks was significantly lower in lymphocytes from HH patients than in lymphocytes from both controls and patients with secondary forms of hemochromatosis (p=0.0029). No correlation was observed between the percentage of cells with DEB-induced chromosome breaks and the transferrin saturation or serum-ferritin values. These results suggest that lymphocytes from HH patients may have an increased capacity to respond to DEB-induced chromosome breakage, and that this capacity is somehow related to the presence of the C282Y HFE mutation.	Which conditions is caused by mutations in HFE?	These results suggest that lymphocytes from HH patients may have an increased capacity to respond to DEB-induced chromosome breakage, and that this capacity is somehow related to the presence of the C282Y HFE mutation.
In 1958, Kearns and Sayre described a multisystem entity, now known as Kearns-Sayre syndrome (KSS). The syndrome is defined as exhibiting a triad of thus far unexplained degenerative conditions: progressive external ophthalmoplegia, retinal pigmentary degeneration, and heart block. Commonly accompanying findings include cerebellar dysfunction and CSF protein levels above 100 mg/dl. Symptoms usually appear in early childhood, but the onset has been seen occasionally in young adults. KSS is a mitochondrial disorder that occurs rarely; the actual incidence is unknown. Ocular findings consist of bilateral ptosis, chronic progressive external ophthalmoplegia, and pigmentary retinopathy. Corneal clouding and optic neuritis are infrequent. We herein report a classic case of Kearns Sayre syndrome and discuss the findings.	What is Kearns-Sayre syndrome (KSS)?	KSS is a mitochondrial disorder that occurs rarely; the actual incidence is unknown.
Nodular-type DTS on MRI studies might be associated with non-Grade I tumors. The range of dural resection for convexity meningiomas should be 2.5 cm from the tumor base, and if this extent of resection is not feasible, the type of DTS should be considered. However, for skull base meningiomas, in which mostly Simpson Grade II resection is achieved, the use of this classification should be further validated. The classification of DTS enables the surgeon to predict preoperatively and then to achieve the optimal range of dural resection that might significantly reduce the recurrence rate of meningiomas.	Simpson grading is used to describe resection of which brain tumor?	However, for skull base meningiomas, in which mostly Simpson Grade II resection is achieved, the use of this classification should be further validated.
Imminent death donation (IDD) is described as living organ donation prior to a planned withdrawal of life-sustaining care in an imminently dying patient. Although IDD was ethically justified by United Network for Organ Sharing, the concept remains controversial due to presumed lack of public support. The aim of this study was to evaluate the public's attitudes towards IDD. A cross-sectional survey was conducted of US adults age >18 years (n = 2644). The survey included a case scenario of a patient with a devastating brain injury. Responses were assessed on a 5-point Likert scale. Results showed that 68% - 74% of participants agreed or strongly agreed with IDD when posed as a general question and in relation to the case scenario. Participants were concerned about "recovery after a devastating brain injury" (34%), and that "doctors would not try as hard to save a patient's life" (33%). Only 9% of participants would be less likely to trust the organ donation process. In conclusion, our study demonstrates strong public support for IDD in the case of a patient with a devastating brain injury. Notably, participants were not largely concerned with losing trust in the organ donation process. These results justify policy change towards imminent death donation.	What is IDD in relation to organ transplantation?	Imminent death donation (IDD) is described as living organ donation prior to a planned withdrawal of life-sustaining care in an imminently dying patient
Clofarabine (2-chloro-2'-fluoro-2'-deoxyarabinosyladenine, ClF) is a second-generation 2'-deoxyadenosine analogue that is structurally related to cladribine (2-chloro-2'-deoxyadenosine, 2CdA) and fludarabine (9-beta-d-arabinosyl-2-fluoroadenine, F-ara-A). It demonstrates potent antitumour activity at much lower doses than parent compounds with high therapeutic efficacy in paediatric blood cancers. Our previous studies in breast cancer cells indicate that 2CdA and F-ara-A are involved in epigenetic regulation of gene transcription. We therefore investigated whether ClF influences methylation and expression of selected tumour suppressor genes, such as adenomatous polyposis coli (APC), phosphatase and tensin homologue (PTEN), and retinoic acid receptor beta 2 (RARbeta2), as well as expression of p53, p21 and DNA methyltransferase 1 (DNMT1) in MCF-7 and MDA-MB-231 breast cancer cell lines with different invasive potential. Promoter methylation and gene expression were estimated using methylation-sensitive restriction analysis (MSRA) and real-time PCR, respectively. ClF demonstrated potent growth inhibitory activity in MCF-7 and MDA-MB-231 cells after 96h treatment with IC50 determined as equal to 640nM and 50nM, respectively. In both breast cancer cell lines, ClF led to hypomethylation and up-regulation of APC, PTEN and RARbeta2 as well as increase in p21 expression. Only in non-invasive MCF-7 cells, these changes were associated with down-regulation of DNMT1. Our results provide first evidence of ClF implications in epigenetic regulation of transcriptional activity of selected tumour suppressor genes in breast cancer. It seems to be a new important element of ClF anticancer activity and may indicate its potential efficacy in epigenetic therapy of solid tumours, especially at early stages of carcinogenesis.	What genes are related to breast cancer?	Our previous studies in breast cancer cells indicate that 2CdA and F-ara-A are involved in epigenetic regulation of gene transcription
Fanconi anaemia (FA) is a rare recessive disorder marked by developmental abnormalities, bone marrow failure, and a high risk for the development of leukaemia and solid tumours. The inactivation of FA genes, in particular FANCF, has also been documented in sporadic tumours in non-FA patients. To study whether there is a causal relationship between FA pathway defects and tumour development, we have generated a mouse model with a targeted disruption of the FA core complex gene Fancf. Fancf-deficient mouse embryonic fibroblasts displayed a phenotype typical for FA cells: they showed an aberrant response to DNA cross-linking agents as manifested by G(2) arrest, chromosomal aberrations, reduced survival, and an inability to monoubiquitinate FANCD2. Fancf homozygous mice were viable, born following a normal Mendelian distribution, and showed no growth retardation or developmental abnormalities. The gonads of Fancf mutant mice functioned abnormally, showing compromised follicle development and spermatogenesis as has been observed in other FA mouse models and in FA patients. In a cohort of Fancf-deficient mice, we observed decreased overall survival and increased tumour incidence. Notably, in seven female mice, six ovarian tumours developed: five granulosa cell tumours and one luteoma. One mouse had developed tumours in both ovaries. High-resolution array comparative genomic hybridization (aCGH) on these tumours suggests that the increased incidence of ovarian tumours correlates with the infertility in Fancf-deficient mice and the genomic instability characteristic of FA pathway deficiency.	Is there a mouse model for Fanconi anemia?	Fancf-deficient mouse embryonic fibroblasts displayed a phenotype typical for FA cells: they showed an aberrant response to DNA cross-linking agents as manifested by G(2) arrest, chromosomal aberrations, reduced survival, and an inability to monoubiquitinate FANCD2
NADPH oxidases are the major sources of reactive oxygen species in cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents. Because Nox isoforms in renal proximal tubules (RPTs) are involved in the pathogenesis of hypertension, we tested the hypothesis that NOX5 is differentially expressed in RPT cells from normotensive (NT) and hypertensive subjects (HT). We found that NOX5 mRNA, total NOX5 protein, and apical membrane NOX5 protein were 4.2±0.7-fold, 5.2±0.7-fold, and 2.8±0.5-fold greater in HT than NT. Basal total NADPH oxidase activity was 4.5±0.2-fold and basal NOX5 activity in NOX5 immunoprecipitates was 6.2±0.2-fold greater in HT than NT (P=<0.001, n=6-14/group). Ionomycin increased total NOX and NOX5 activities in RPT cells from HT (P<0.01, n=4, ANOVA), effects that were abrogated by pre-treatment of the RPT cells with diphenylene-iodonium or superoxide dismutase. Silencing NOX5 using NOX5-siRNA decreased NADPH oxidase activity (-45.1±3.2% vs. mock-siRNA, n=6-8) in HT. D1-like receptor stimulation decreased NADPH oxidase activity to a greater extent in NT (-32.5±1.8%) than HT (-14.8±1.8). In contrast to the marked increase in expression and activity of NOX5 in HT, NOX1 mRNA and protein were minimally increased in HT, relative to NT; total NOX2 and NOX4 proteins were not different between HT and NT, while the increase in apical RPT cell membrane NOX1, NOX2, and NOX4 proteins in HT, relative to NT, was much less than those observed with NOX5. Thus, we demonstrate, for the first time, that NOX5 is expressed in human RPT cells and to greater extent than the other Nox isoforms in HT than NT. We suggest that the increased expression of NOX5, which may be responsible for the increased oxidative stress in RPT cells in human essential hypertension, is caused, in part, by a defective renal dopaminergic system.	Is NADPH oxidase 5 expressed in rodents?	NADPH oxidases are the major sources of reactive oxygen species in cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents.
Chromosomes are not packed randomly in the nucleus. The Rabl orientation is an example of the non-random arrangement of chromosomes, centromeres are grouped in a limited area near the nuclear periphery and telomeres are located apart from centromeres. This orientation is established during mitosis and maintained through subsequent interphase in a range of species. We report that a Rabl-like configuration can be formed de novo without a preceding mitosis during the transition from the sexual phase to the vegetative phase of the life cycle in fission yeast. In this process, each of the dispersed centromeres is often associated with a novel Sad1-containing body that is contacting a cytoplasmic microtubule laterally (Sad1 is a component of the spindle pole body (SPB)). The Sad1-containing body was colocalized with other known SPB components, Kms1 and Spo15 but not with Cut12, indicating that it represents a novel SPB-related complex. The existence of the triplex structure (centromere-microtubule-Sad1 body) suggests that the clustering of centromeres is controlled by a cytoplasmic microtubular system. Accordingly, when microtubules are destabilized, clustering is markedly reduced.	Where do centromeres locate according to the Rabl orientation of eukaryotic nuclei?	The Rabl orientation is an example of the non-random arrangement of chromosomes, centromeres are grouped in a limited area near the nuclear periphery and telomeres are located apart from centromeres.
NF-κB transcription factors are pivotal players in controlling inflammatory and immune responses, as well as cell proliferation and apoptosis. Aberrant regulation of NF-κB and the signaling pathways that regulate its activity have been involved in various pathologies, particularly cancers, as well as inflammatory and autoimmune diseases. NF-κB activation is tightly regulated by the IκB kinase (IKK) complex, which is composed of two catalytic subunits IKKα and IKKβ, and a regulatory subunit IKKγ/NEMO. Although IKKα and IKKβ share structural similarities, IKKα has been shown to have distinct biological functions. However, the molecular mechanisms that modulate IKKα activity have not yet been fully elucidated. To understand better the regulation of IKKα activity, we purified IKKα-associated proteins and identified ABIN-2. Here, we demonstrate that IKKα and IKKβ both interact with ABIN-2 and impair its constitutive degradation by the proteasome. Nonetheless, ABIN-2 enhances IKKα- but not IKKβ-mediated NF-κB activation by specifically inducing IKKα autophosphorylation and kinase activity. Furthermore, we found that ABIN-2 serine 146 is critical for the ABIN-2-dependent IKKα transcriptional up-regulation of specific NF-κB target genes. These results imply that ABIN-2 acts as a positive regulator of NF-κB-dependent transcription by activating IKKα.	Which are the subunits of the IkB protein kinase (IKK)?	NF-κB activation is tightly regulated by the IκB kinase (IKK) complex, which is composed of two catalytic subunits IKKα and IKKβ, and a regulatory subunit IKKγ/NEMO.
The interpretation of non-coding variants still constitutes a major challenge in the application of whole-genome sequencing in Mendelian disease, especially for single-nucleotide and other small non-coding variants. Here we present Genomiser, an analysis framework that is able not only to score the relevance of variation in the non-coding genome, but also to associate regulatory variants to specific Mendelian diseases. Genomiser scores variants through either existing methods such as CADD or a bespoke machine learning method and combines these with allele frequency, regulatory sequences, chromosomal topological domains, and phenotypic relevance to discover variants associated to specific Mendelian disorders. Overall, Genomiser is able to identify causal regulatory variants as the top candidate in 77% of simulated whole genomes, allowing effective detection and discovery of regulatory variants in Mendelian disease.	Which method is available for whole genome identification of pathogenic regulatory variants in mendelian disease?	Genomiser scores variants through either existing methods such as CADD or a bespoke machine learning method and combines these with allele frequency, regulatory sequences, chromosomal topological domains, and phenotypic relevance to discover variants associated to specific Mendelian disorders.
Although Gaucher disease is a rare disorder, recent developments in novel means for therapeutic intervention have invigorated both academic research and pharmaceutical industry discovery programmes. The common mutations found in the lysosomal enzyme deficient in Gaucher disease, beta-glucocerebrosidase, earmark these proteins for destruction by the endoplasmic reticulum-localised protein folding machinery, resulting in enzyme insufficiency, lysosomal glycolipid storage and subsequent pathology. However, many of these mutants can be rescued from global misfolding to preserve glycolipid substrate binding and eventual catalysis in the lysosome, by the addition of subinhibitory concentrations of pharmacologically active small molecules. This novel, chaperon-mediated approach has benefited from insights into the molecular understanding of beta-glucocerebrosidase structure, drug design and development in cellular models for disease.	Which enzyme is deficient in Gaucher's disease?	The common mutations found in the lysosomal enzyme deficient in Gaucher disease, beta-glucocerebrosidase, earmark these proteins for destruction by the endoplasmic reticulum-localised protein folding machinery, resulting in enzyme insufficiency, lysosomal glycolipid storage and subsequent pathology
Unintentional acupuncture needling of the thoracic spinal canal produced a spinal epidural hematoma and subarachnoid hemorrhage. This case demonstrates that patients are sometimes reluctant to disclose folk medical treatments to Western physicians, and the proper diagnosis may depend upon the prowess of the neuroradiologist.	Can acupuncture cause spinal epidural hematoma?	Unintentional acupuncture needling of the thoracic spinal canal produced a spinal epidural hematoma and subarachnoid hemorrhage
The transcription factor NF-kappaB is composed of homodimeric and heterodimeric complexes of Rel/NF-kappaB-family polypeptides, which include Rel-A, c-Rel, Rel-B, NF-kappaB/p50 and NF-kappaB2/p52 . The NF-kappaB1 gene encodes a larger precursor protein, p105, from which p50 is produced constitutively by proteasome-mediated removal of the p105 carboxy terminus. The p105 precursor also acts as an NFkappaB-inhibitory protein, retaining associated p50, c-Rel and Rel-A proteins in the cytoplasm through its carboxy terminus. Following cell stimulation by agonists, p105 is proteolysed more rapidly and released Rel subunits translocate into the nucleus. Here we show that TPL-2 , which is homologous to MAP-kinase-kinase kinases in its catalytic domain, forms a complex with the carboxy terminus of p105. TPL-2 was originally identified, in a carboxy-terminal-deleted form, as an oncoprotein in rats and is more than 90% identical to the human oncoprotein COT. Expression of TPL-2 results in phosphorylation and increased degradation of p105 while maintaining p50 production. This releases associated Rel subunits or p50-Rel heterodimers to generate active nuclear NF-kappaB. Furthermore, kinase-inactive TPL-2 blocks the degradation of p105 induced by tumour-necrosis factor-alpha. TPL-2 is therefore a component of a new signalling pathway that controls proteolysis of NF-kappaB1 p105.	Which proteins are the different members of the NF-kappaB family of transcription factors?	The transcription factor NF-kappaB is composed of homodimeric and heterodimeric complexes of Rel/NF-kappaB-family polypeptides, which include Rel-A, c-Rel, Rel-B, NF-kappaB/p50 and NF-kappaB2/p52 .
Early investigations into the immune surveillance of chemically-induced sarcomas led to two important concepts in tumour immunobiology: one, tumour rejection can be elicited by immune recognition of tumour antigens; and two, tumours express unique sets of antigens, which are known as tumour-specific antigens. The pioneering studies of Srivastava and colleagues led to the proposal that heat-shock proteins (HSPs) function as ubiquitous tumour-specific antigens, with the specificity residing in a population of bound peptides that identify the tissue of origin of the HSP. However, recent findings, including new data on the cell biology of peptide generation and trafficking, have called into question the specificity of tumour rejection that is induced by HSPs.	Are tumour specific antigens originating from known protein coding genes?	The pioneering studies of Srivastava and colleagues led to the proposal that heat-shock proteins (HSPs) function as ubiquitous tumour-specific antigens, with the specificity residing in a population of bound peptides that identify the tissue of origin of the HSP.
The secretion of dopamine and serotonin is increased in cholangiocarcinoma, which has growth-promoting effects. Monoamine oxidase A (MAOA), the degradation enzyme of serotonin and dopamine, is suppressed in cholangiocarcinoma via an unknown mechanism. The aims of this study were to (i) correlate MAOA immunoreactivity with pathophysiological parameters of cholangiocarcinoma, (ii) determine the mechanism by which MAOA expression is suppressed and (iii) evaluate the consequences of restored MAOA expression in cholangiocarcinoma. MAOA expression was assessed in cholangiocarcinoma and nonmalignant controls. The control of MAOA expression by promoter hypermethylation was evaluated and the contribution of interleukin-6 (IL-6) signaling to the suppression of MAOA expression was determined. The effects of MAOA overexpression on cholangiocarcinoma growth and invasion were also assessed. MAOA expression is correlated with differentiation, invasion and survival in cholangiocarcinoma. The MAOA promoter was hypermethylated immediately upstream of the start codon in cholangiocarcinoma samples and cell lines but not in nonmalignant counterparts. IL-6 signaling also decreased MAOA expression via a mechanism independent of hypermethylation, involving the regulation of the balance between SP-1 transcriptional activity and its inhibitor, R1 repressor. Inhibition of both IL-6 signaling and DNA methylation restored MAOA levels to those observed in cholangiocytes. Forced MAOA overexpression inhibited cholangiocarcinoma growth and invasion. MAOA expression is suppressed by the coordinated control of promoter hypermethylation and IL-6 signaling. MAOA may be a useful prognostic marker in the management of cholangiocarcinoma, and therapies designed to increase MAOA expression might prove beneficial in the treatment of cholangiocarcinoma.	Is the gene MAOA epigenetically modified by methylation?	The MAOA promoter was hypermethylated immediately upstream of the start codon in cholangiocarcinoma samples and cell lines but not in nonmalignant counterparts.
5-Fluorouracil (5-FU) is an antimetabolite that acts during the S phase of the cell cycle. The active metabolite, 5-fluorodeoxyuridine monophosphate inhibits thymidylate synthase (TS), thus preventing DNA synthesis, which leads to imbalanced cell growth and ultimately cell death. 5-FU and its oral prodrug capecitabine are used in the treatment of a number of solid tumors, including colorectal, breast, gastric, pancreatic, prostate, and bladder cancers. Common side effects include leukopenia, diarrhea, stomatitis, nausea, vomiting, and alopecia. Hand-foot syndrome (HFS) is a relatively common side effect of cytotoxic chemotherapy. It is more frequently associated with 5-FU, capecitabine, and cytarabine. This article reports on the case of a 55-year-old black man with metastatic colorectal carcinoma that was refractory to recommended treatment measures who developed grade 3 HFS after treatment with modified FOLFOX6 (leucovorin [LV]/5-FU/oxaliplatin) and bFOL (bolus 5-FU/LV/oxaliplatin) regimens. Treatment was discontinued despite excellent response to chemotherapy. The patient had progression of disease on IROX (irinotecan/oxaliplatin) and irinotecan/cetuximab regimens. He was started on gemcitabine/capecitabine and developed HFS again, which was controlled with aggressive skin care and vitamin B6 treatment. Full sequencing of the dihydropyrimidine dehydrogenase (DPYD) gene and analysis of the human TS gene (TYMS) promoter region was performed. Pharmacogenetic testing revealed 2R/2R genotype of TYMS gene, which is associated with up to a 2.5-fold risk of toxicity to 5-FU therapy. Hand-foot syndrome has proven to be a dose-limiting toxicity of 5-FU, especially of capecitabine, leading to significant morbidity. Hand-foot syndrome seems to be dose dependent, and both peak drug concentration and total cumulative dose determine its occurrence. Genetic variations such as polymorphic abnormality of TYMS are potential causative factors for a significant portion of serious adverse reactions to 5-FU-based therapy.	Which drugs are included in the IROX regimen for colorectal cancer?	isease on IROX (irinotecan/oxaliplatin) and irinotecan/cetuximab regimens. He was started on gemcitabine/ca
Molluscum contagiosum virus (MCV) is a poxvirus that causes tumor-like skin lesions. New evidence indicates that plasmacytoid dendritic cells, type I interferon production, and interferon-induced dendritic cells have prominent roles in anti-MCV responses, and these features characterize the inflammatory response in lesions that will likely undergo spontaneous regression.	Which virus type causes Molluscum contagiosum?	Molluscum contagiosum virus (MCV) is a poxvirus that causes tumor-like skin lesions
This study reports a microfluidic-based optical sensing device for label-free detection of circulating tumor cells (CTCs), a rare cell species in blood circulation. Based on the metabolic features of cancer cells, live CTCs can be quantified indirectly through their lactic acid production. Compared with the conventional schemes for CTC detection, this label-free approach could prevent the biological bias due to the heterogeneity of the surface antigens on cancer cells. In this study, a microfluidic device was proposed to generate uniform water-in-oil cell-encapsulating micro-droplets, followed by the fluorescence-based optical detection of lactic acid produced within the micro-droplets. To test its feasibility to quantify cancer cells, experiments were carried out. Results showed that the detection signals were proportional to the number of cancer cells within the micro-droplets, whereas such signals were insensitive to the existence and number of leukocytes within. To further demonstrate its feasibility for cancer cell detection, the cancer cells with known cell number in a cell suspension was detected based on the method. Results revealed that there was no significant difference between the detected number and the real number of cancer cells. As a whole, the proposed method opens up a new route to detect live CTCs in a label-free manner.	How rare are CTCs (circulating tumour cells) in the plasma of patients?	This study reports a microfluidic-based optical sensing device for label-free detection of circulating tumor cells (CTCs), a rare cell species in blood circulation.