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Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. | The beneficial effect of the selective estrogen receptor (ER) modulator tamoxifen in the treatment and prevention of breast cancer is assumed to be through its ability to antagonize the stimulatory actions of estrogen; although tamoxifen can also have some estrogen-like agonist effects. Here; we report that; in addition to these mixed agonist/antagonist actions; tamoxifen can also selectively regulate a unique set of >60 genes; which are minimally regulated by estradiol (E2) or raloxifene in ERalpha-positiv | 16849584 | [
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Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. | e MCF-7 human breast cancer cells. This gene regulation by tamoxifen is mediated by ERalpha and reversed by E2 or ICI 182;780. Introduction of ERbeta into MCF-7 cells reverses tamoxifen action on approximately 75% of these genes. To examine whether these genes might serve as markers of tamoxifen sensitivity and/or the development of resistance; their expression level was examined in breast cancers of women who had received adjuvant therapy with tamoxifen. High expression of two of the tamoxifen-stimulated g | 16849584 | [
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Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. | enes; YWHAZ/14-3-3z and LOC441453; was found to correlate significantly with disease recurrence following tamoxifen treatment in women with ER-positive cancers and hence seem to be markers of a poor prognosis. Our data indicate a new dimension in tamoxifen action; involving gene expression regulation that is tamoxifen preferential; and identify genes that might serve as markers of tumor responsiveness or resistance to tamoxifen therapy. This may have a potential effect on the choice of tamoxifen versus arom | 16849584 | [
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Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer. | Until recently; it was generally accepted that vascularization of tumors arises exclusively from endothelial sprouting. Whether circulating bone marrow-derived endothelial progenitor cells (EPC) participate in the progression of non-small cell lung cancer (NSCLC) has not yet been evaluated. EPCs labeled with CD34; CD133; and vascular endothelial growth factor receptor-2 (VEGFR2) antibodies were counted by flow cytometry in the peripheral blood of 53 NSCLC patients. Furthermore; by means of a quantitative re | 16849585 | [
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Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer. | verse transcription-PCR approach; we measured VEGFR2; CD133; CD34; and VE-cadherin mRNA in the peripheral blood samples of the same patient population. EPCs in tumor samples were identified by confocal microscopy using CD31; CD34; CD133; and VEGFR2 antibodies. Although immunofluorescent labeling of microvessels made clear that incorporation of EPCs is a rare phenomenon in NSCLC tissue (9 of 22 cases); circulating EPC levels before therapeutic intervention were increased in NSCLC patients (P < 0.002; versus | 16849585 | [
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Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer. | healthy controls); and high pretreatment circulating EPC numbers correlated with poor overall survival (P < 0.001). Furthermore; in the subgroup of responders to treatment; the posttreatment EPC numbers in the peripheral blood were significantly lower compared with nonresponding patients. Interestingly; pretreatment mRNA levels of CD133; VE-cadherin; and CD34 were not significantly increased in NSCLC patients; whereas VEGFR2 expression was increased by 80-fold. Moreover; posttreatment VEGFR2 mRNA level in t | 16849585 | [
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Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer. | he peripheral blood was significantly higher in the subgroup of nonresponding patients when compared with posttreatment level of patients responding to antitumor therapy. Circulating levels of bone marrow-derived EPCs are significantly increased in NSCLC patients and correlate with clinical behavior. | 16849585 | [
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Peroxisome proliferator-activated receptor gamma as a molecular target of resveratrol-induced modulation of polyamine metabolism. | Previous results indicate that the polyphenol resveratrol inhibits cell growth of colon carcinoma cells via modulation of polyamine metabolic key enzymes. The aim of this work was to specify the underlying molecular mechanisms and to identify a possible role of transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma). Cell growth was determined by bromodeoxyuridine incorporation and crystal violet staining. Protein levels were examined by Western blot analysis. Spermine/spermidine a | 16849586 | [
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Peroxisome proliferator-activated receptor gamma as a molecular target of resveratrol-induced modulation of polyamine metabolism. | cetyltransferase (SSAT) activity was determined by a radiochemical assay. PPARgamma ligand-dependent transcriptional activity was measured by a luciferase assay. A dominant-negative PPARgamma mutant was transfected in Caco-2 cells to suppress PPARgamma-mediated functions. Resveratrol inhibits cell growth of both Caco-2 and HCT-116 cells in a dose- and time-dependent manner (P < 0.001). In contrast to Caco-2-wild type cells (P < 0.05); resveratrol failed to increase SSAT activity in dominant-negative PPARgam | 16849586 | [
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Peroxisome proliferator-activated receptor gamma as a molecular target of resveratrol-induced modulation of polyamine metabolism. | ma cells. PPARgamma involvement was further confirmed via ligand-dependent activation (P < 0.01) as well as by induction of cytokeratin 20 (P < 0.001) after resveratrol treatment. Coincubation with SB203580 abolished SSAT activation significantly in Caco-2 (P < 0.05) and HCT-116 (P < 0.01) cells. The involvement of p38 mitogen-activated protein kinase (MAPK) was further confirmed by a resveratrol-mediated phosphorylation of p38 protein in both cell lines. Resveratrol further increased the expression of PPAR | 16849586 | [
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Peroxisome proliferator-activated receptor gamma as a molecular target of resveratrol-induced modulation of polyamine metabolism. | gamma coactivator PGC-1alpha (P < 0.05) as well as SIRT1 (P < 0.01) in a dose-dependent manner after 24 hours of incubation. Based on our findings; p38 MAPK and transcription factor PPARgamma can be considered as molecular targets of resveratrol in the regulation of cell proliferation and SSAT activity; respectively; in a cell culture model of colon cancer. | 16849586 | [
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Detection of low molecular weight derivatives of cyclin E1 is a function of cyclin E1 protein levels in breast cancer. | Cyclin E1 regulates the initiation of the S phase program in the mammalian cell division cycle. In normal cells; cyclin E1 protein expression is tightly controlled through a combination of transcriptional and proteolytic regulatory processes. However; in many types of human tumor; cyclin E1 expression is frequently dysregulated; including overexpression; nonperiodic expression relative to cell division; and generation of low molecular weight (LMW) derivatives. LMW derivatives of cyclin E1 have been proposed | 16849587 | [
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Detection of low molecular weight derivatives of cyclin E1 is a function of cyclin E1 protein levels in breast cancer. | to be generated by the in vivo proteolytic cleavage of the full-length cyclin E1 protein by a yet to be identified tumor-specific protease. Recently; it was suggested that overexpression of full-length or LMW derivatives of cyclin E1 are independent variables associated with poor outcome in patients with breast cancer. However; we have extensively analyzed cyclin E1 protein expression in primary breast tumors and breast tumor-derived cell lines and found that the ability to detect LMW derivatives of cyclin | 16849587 | [
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Detection of low molecular weight derivatives of cyclin E1 is a function of cyclin E1 protein levels in breast cancer. | E1 correlates only with the level of cyclin E1 protein. When cyclin E1 levels on Western blots are normalized; LMW derivatives of cyclin E1 were observed at roughly equal levels in all primary breast tumors; breast tumor-derived cell lines; immortalized nontransformed human mammary epithelial cells; and normal breast tissue. Therefore; the detection of LMW derivatives of cyclin E1 is likely a function of cyclin E1 protein levels; and the activity of the proteolytic machinery responsible for their generatio | 16849587 | [
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Detection of low molecular weight derivatives of cyclin E1 is a function of cyclin E1 protein levels in breast cancer. | n is not a tumor-specific property. | 16849587 | [
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Prohibitin is a novel target gene of vitamin D involved in its antiproliferative action in breast cancer cells. | Previously; we showed that N-methyl-N-nitrosourea-transformed MCF12F breast epithelial cells exhibited differential expression of several genes; including up-regulation of prohibitin and elevated sensitivity to a relatively noncalcemic vitamin D analogue; 1alpha-hydroxyvitamin D5 [1alpha(OH)D5]. In this report; we evaluated the functional significance of prohibitin in relation to the cellular response to vitamin D. The in silico screening for putative transcription factor binding sites identified two vitami | 16849588 | [
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Prohibitin is a novel target gene of vitamin D involved in its antiproliferative action in breast cancer cells. | n D receptor (VDR)/retinoid X receptor binding sites in the 1-kb promoter region of prohibitin. Prohibitin up-regulation by 1alpha(OH)D5 treatment at both transcriptional and translational levels was confirmed by real-time reverse transcription-PCR and Western blot analysis in breast cancer cells; identifying prohibitin as a vitamin D target gene. Confocal microscopic analysis showed that prohibitin was localized in the nuclei of MCF-7 cells and a portion of prohibitin was colocalized with VDR; but direct p | 16849588 | [
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Prohibitin is a novel target gene of vitamin D involved in its antiproliferative action in breast cancer cells. | hysical interaction between VDR and prohibitin in cell lysates was not detectable. In MCF-7 cells expressing tetracycline-inducible prohibitin (Tet-On model); the overexpression of prohibitin inhibited cell proliferation and enhanced vitamin D-induced antiproliferative activity. Knockdown of prohibitin was accompanied by increased number of cells incorporating bromodeoxyuridine in the whole population and increased cell distribution in the S phase of cell cycle. In addition; prohibitin level had no signific | 16849588 | [
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Prohibitin is a novel target gene of vitamin D involved in its antiproliferative action in breast cancer cells. | ant effect on the vitamin D-induced transactivation of CYP24; a VDR target gene. This is the first report to suggest that prohibitin serves as a novel vitamin D target gene; which is involved in the antiproliferative action of vitamin D without affecting CYP24 transactivation in breast cancer cells. | 16849588 | [
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Chemoprevention of familial adenomatous polyposis by low doses of atorvastatin and celecoxib given individually and in combination to APCMin mice. | Preclinical and clinical studies have established evidence that cyclooxygenase-2 (COX-2) inhibitors and statins [hydroxy-3-methylglutaryl CoA reductase (HMGR) inhibitors] inhibit colon carcinogenesis. Chronic use of high doses of COX-2 inhibitors may induce side effects; and combining the low doses of agents may be an effective way to increase their efficacy and minimize the side effects. We assessed the chemopreventive efficacy of atorvastatin (Lipitor) and celecoxib individually or in combination in an an | 16849589 | [
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Chemoprevention of familial adenomatous polyposis by low doses of atorvastatin and celecoxib given individually and in combination to APCMin mice. | imal model of familial adenomatous polyposis. Six-week-old male C57BL/6J-APCmin/+ mice were either fed diets containing 0 or 100 ppm atorvastatin or 300 ppm celecoxib; or a combination of both for approximately 80 days. Mice were sacrificed; and their intestines were scored for tumors. Normal-seeming mucosa and intestinal tumors were harvested and assayed for apoptosis (terminal deoxynucleotidyl transferase-mediated nick-end labeling) and HMGR and COX-2 protein expression and activity. We observed that 100 | 16849589 | [
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Chemoprevention of familial adenomatous polyposis by low doses of atorvastatin and celecoxib given individually and in combination to APCMin mice. | ppm atorvastatin significantly (P < 0.002) suppressed intestinal polyp formation. As anticipated; 300 ppm celecoxib decreased the rate of formation of intestinal polyps by approximately 70% (P < 0.0001). Importantly; the combination of 100 ppm atorvastatin and 300 ppm celecoxib in the diet suppressed the colon polyps completely and small intestinal polyps by >86% (P < 0.0001) compared with the control group. The inhibition of tumor formation by the atorvastatin and celecoxib combination was significant (P < | 16849589 | [
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Chemoprevention of familial adenomatous polyposis by low doses of atorvastatin and celecoxib given individually and in combination to APCMin mice. | 0.005) when compared with tumor inhibition by celecoxib alone. In addition; increased rates of apoptosis in intestinal tumors (P < 0.01-0.0001) were observed in animals fed with atorvastatin and celecoxib and more so with the combinations. Tumors of animals fed atorvastatin showed a significant decrease in HMGR-R activity. Similarly; tumors of mice exposed to celecoxib showed significantly lower levels of COX-2 activity. These observations show that atorvastatin inhibits intestinal tumorigenesis and that; | 16849589 | [
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Chemoprevention of familial adenomatous polyposis by low doses of atorvastatin and celecoxib given individually and in combination to APCMin mice. | importantly; when given together with low doses of celecoxib; it significantly increases the chemopreventive efficacy in an APC(min) mice. | 16849589 | [
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German human methylome project started. | nan | 16849590 | [
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Potential sperm donors', recipients' and their partners' opinions towards the release of identifying information in Western Australia. | The aim of this study was to examine Western Australian potential sperm donors' and recipients' opinions towards the release of identifying information and their intentions to disclose.Forty-five potential sperm donors; 33 recipients and 12 partners completed an anonymous questionnaire regarding their opinions on the release of identifying information; whether a child should be told about the manner of their conception; the level of expected contact of donor with future donor offspring and the importance of | 16849591 | [
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Potential sperm donors', recipients' and their partners' opinions towards the release of identifying information in Western Australia. | anonymity in their decision to donate.Slightly less than one-half (48.9%) of potential donors indicated that they would still donate if their identity was revealed to future offspring. When asked whether they would consider contact with offspring; 80% responded positively; with 42% favouring one-off contact. The majority of recipients (82%) and partners (92%) were planning to inform their offspring about the manner of their conception; with 69% of recipients believing that the offspring should receive iden | 16849591 | [
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Potential sperm donors', recipients' and their partners' opinions towards the release of identifying information in Western Australia. | tifying information about the donor. Recipients were ambivalent about the level of contact between their offspring and the donor.These results suggest that the move to an open-identity donor system in Western Australia will benefit the majority of recipient parents who are intending to disclose; however; it also suggests a 50% decline in the number of potential sperm donors. | 16849591 | [
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Inhibition of Ca2+ influx is required for mitochondrial reactive oxygen species-induced endoplasmic reticulum Ca2+ depletion and cell death in leukemia cells. | Disturbances of endoplasmic reticulum (ER) Ca2+ homeostasis or protein processing can lead to ER stress-induced cell death. Increasing evidence suggests that oxidative stress (OS) plays an important role in a variety of cell death mechanisms. To investigate the role of OS in ER stress; we measured OS in response to three ER stress agents: econazole (Ec); which stimulates ER Ca2+ release and blocks Ca2+ influx; thapsigargin (Tg); a sarco(endo)plasmic reticulum Ca2+ ATPase inhibitor that releases ER Ca2+ and | 16849592 | [
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Inhibition of Ca2+ influx is required for mitochondrial reactive oxygen species-induced endoplasmic reticulum Ca2+ depletion and cell death in leukemia cells. | stimulates Ca2+ influx; and tunicamycin (Tu); a glycosylation inhibitor that causes protein accumulation in the ER. Ec; but not Tg or Tu; caused a rapid increase in OS. Reactive oxygen species (ROS) generation was observed within mitochondria immediately after exposure to Ec. Furthermore; Ec hyperpolarized the mitochondrial membrane and inhibited adenine nucleotide transport in cell-free mitochondria; suggesting a mitochondrial target. Antimycin A; an inhibitor of complex III in electron transport; reversed | 16849592 | [
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Inhibition of Ca2+ influx is required for mitochondrial reactive oxygen species-induced endoplasmic reticulum Ca2+ depletion and cell death in leukemia cells. | mitochondrial hyperpolarization; OS generation; ER Ca2+ depletion; and cell death by Ec; suggesting complex III dependence for these effects. Antioxidants butylated hydroxytoluene and N-Acetyl-L-cysteine prevented ER Ca2+ depletion and cell death by Ec. However; inhibition of Ca2+ influx by Ec was unaffected by either antimycin A or the antioxidants; suggesting that this target is distinct from the mitochondrial target of Ec. Atractyloside; an adenine nucleotide transport inhibitor; generated ROS and stimu | 16849592 | [
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Inhibition of Ca2+ influx is required for mitochondrial reactive oxygen species-induced endoplasmic reticulum Ca2+ depletion and cell death in leukemia cells. | lated ER Ca2+ release; but it did not block Ca2+ influx; deplete the ER or induce cell death. Taken together; these results demonstrate that combined mitochondrial ROS generation and Ca2+ influx blockade by Ec is required for cell death. | 16849592 | [
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Dustiness testing of materials handled at workplaces. | nan | 16849593 | [
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Site-specific amino acid frequency, fitness and the mutational landscape model of adaptation in human immunodeficiency virus type 1. | Analysis of the intensely studied HIV-1 gp120 V3 protein region reveals that the among-population mean site-specific frequency of an amino acid is a measure of its relative marginal fitness. This surprising result may arise if populations are displaced from mutation-selection equilibrium by fluctuating selection and if the probability of fixation of a beneficial amino acid is proportional to its selection coefficient. | 16849594 | [
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An efficient genetic screen in Drosophila to identify nuclear-encoded genes with mitochondrial function. | We conducted a screen for glossy-eye flies that fail to incorporate BrdU in the third larval instar eye disc but exhibit normal neuronal differentiation and isolated 23 complementation groups of mutants. These same phenotypes were previously seen in mutants for cytochrome c oxidase subunit Va. We have molecularly characterized six complementation groups and; surprisingly; each encodes a mitochondrial protein. Therefore; we believe our screen to be an efficient method for identifying genes with mitochondrial | 16849596 | [
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An unconventional nuclear localization motif is crucial for function of the Drosophila Wnt/wingless antagonist Naked cuticle. | Wnt/beta-catenin signals orchestrate cell fate and behavior throughout the animal kingdom. Aberrant Wnt signaling impacts nearly the entire spectrum of human disease; including birth defects; cancer; and osteoporosis. If Wnt signaling is to be effectively manipulated for therapeutic advantage; we first must understand how Wnt signals are normally controlled. Naked cuticle (Nkd) is a novel and evolutionarily conserved inducible antagonist of Wnt/beta-catenin signaling that is crucial for segmentation in the | 16849595 | [
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An unconventional nuclear localization motif is crucial for function of the Drosophila Wnt/wingless antagonist Naked cuticle. | model genetic organism; the fruit fly Drosophila melanogaster. Nkd can bind and inhibit the Wnt signal transducer Dishevelled (Dsh); but the mechanism by which Nkd limits Wnt signaling in the fly embryo is not understood. Here we show that nkd mutants exhibit elevated levels of the beta-catenin homolog Armadillo but no alteration in Dsh abundance or distribution. In the fly embryo; Nkd and Dsh are predominantly cytoplasmic; although a recent report suggests that vertebrate Dsh requires nuclear localization | 16849595 | [
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An unconventional nuclear localization motif is crucial for function of the Drosophila Wnt/wingless antagonist Naked cuticle. | for activity in gain-of-function assays. While Dsh-binding regions of Nkd contribute to its activity; we identify a conserved 30-amino-acid motif; separable from Dsh-binding regions; that is essential for Nkd function and nuclear localization. Replacement of the 30-aa motif with a conventional nuclear localization sequence rescued a small fraction of nkd mutant animals to adulthood. Our studies suggest that Nkd targets Dsh-dependent signal transduction steps in both cytoplasmic and nuclear compartments of c | 16849595 | [
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An unconventional nuclear localization motif is crucial for function of the Drosophila Wnt/wingless antagonist Naked cuticle. | ells receiving the Wnt signal. | 16849595 | [
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Why molecular chaperones buffer mutational damage: a case study with a yeast Hsp40/70 system. | The malfunctioning of molecular chaperones may result in uncovering genetic variation. The molecular basis of this phenomenon remains largely unknown. Chaperones rescue proteins unfolded by environmental stresses and therefore they might also help to stabilize mutated proteins and thus mask damages. To test this hypothesis; we carried out a genomewide mutagenesis followed by a screen for mutations that were synthetically harmful when the RAC-Ssb1/2 cytosolic chaperones were inactive. Mutants with such a phe | 16849597 | [
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Why molecular chaperones buffer mutational damage: a case study with a yeast Hsp40/70 system. | notype were found and mapped to single nucleotide substitutions. However; neither the genes identified nor the nature of genetic lesions implied that folding of the mutated proteins was being supported by the chaperones. In a second screen; we identified temperature-sensitive (ts) mutants; a phenotype indicative of structural instability of proteins. We tested these for an association with sensitivity to loss of chaperone activity but found no such correlation as might have been expected if the chaperones a | 16849597 | [
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Why molecular chaperones buffer mutational damage: a case study with a yeast Hsp40/70 system. | ssisted the folding of mutant proteins. Thus; molecular chaperones can mask the negative effects of mutations but the mechanism of such buffering need not be direct. A plausible role of chaperones is to stabilize genetic networks; thus making them more tolerant to malfunctioning of their constituents. | 16849597 | [
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Effects of sex and insulin/insulin-like growth factor-1 signaling on performance in an associative learning paradigm in Caenorhabditis elegans. | Learning is an adaptive change in behavior in response to environmental stimuli. In mammals; there is a distinct female bias to learn skills that is still unprecedented in other animal taxa. Here we have investigated the biological determinants of performance in an associative learning paradigm in the nematode Caenorhabditis elegans. Using an assay of chemotactic reactions associated with food deprivation; wild-type male worms show inferior learning ability relative to hermaphrodites. Sex-based learning dif | 16849598 | [
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Effects of sex and insulin/insulin-like growth factor-1 signaling on performance in an associative learning paradigm in Caenorhabditis elegans. | ference is therefore an ancient evolutionary feature appearing even in relatively simple animals. C. elegans mutants with reduced insulin/IGF-1 signaling also exhibit a greatly reduced learning ability in this assay. In addition; hyperactivation of insulin/IGF-1 signaling through loss-of-function mutations in the PTEN phosphatase daf-18; a negative regulator of insulin/IGF-1 signaling; enhances learning ability beyond that of wild type. According to our epistasis analysis; the effect of DAF-2 on learning ac | 16849598 | [
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Effects of sex and insulin/insulin-like growth factor-1 signaling on performance in an associative learning paradigm in Caenorhabditis elegans. | ts via phosphatidylinositol 3;4;5-trisphosphate (PIP(3)) production; but not the DAF-16 FOXO transcription factor. This implies that the signaling pathway from DAF-2 affecting this learning paradigm branches between PIP(3) production and DAF-16. However; learning capacity of nematodes is lowered by loss-of-function mutations in daf-16; suggesting involvement of noninsulin/IGF-1 signaling-dependent DAF-16 activation in learning. Potentially; sex and insulin/IGF-1 signaling affect performance in this learning | 16849598 | [
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Effects of sex and insulin/insulin-like growth factor-1 signaling on performance in an associative learning paradigm in Caenorhabditis elegans. | assay via effects on the neurobiology of learning. | 16849598 | [
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Regulation of the Drosophila melanogaster protein, enhancer of rudimentary, by casein kinase II. | The Drosophila melanogaster gene enhancer of rudimentary; e(r); encodes a conserved protein; ER. Most ER homologs share two casein kinase II (CKII) target sites. In D. melanogaster; these sites are T18 and S24. A third CKII site; T63; has been seen only in drosophilids. The conservation of these CKII sites; particularly T18 and S24; suggests a role for these residues in the function of the protein. To test this hypothesis; these positions were mutated either to alanine as a nonphosphorylated mimic or to glu | 16849599 | [
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Regulation of the Drosophila melanogaster protein, enhancer of rudimentary, by casein kinase II. | tamic acid as a phosphorylated mimic. The mutations were tested individually or in double or triple combinations for their ability to rescue either a wing truncation characteristic of the genotype e(r)(p1) r(hd1-12) or the synthetic lethal interaction between e(r)(p2) and the Notch allele N(nd-p). All of the substitutions as single mutations rescued both mutant phenotypes; arguing that individually the phosphorylation of the three residues does not affect ER activity. The double mutants T18A-S24A and T18E-S | 16849599 | [
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Regulation of the Drosophila melanogaster protein, enhancer of rudimentary, by casein kinase II. | 24E and the triple mutants T18A-S24A-T63A and T18E-S24E-T63E failed to rescue. Together the data support the following model for the regulation of ER by CKII. ER that is unphosphorylated at both T18A and S24 is inactive. CKII activates ER by phosphorylating either T18 or S24. Further phosphorylation to produce the doubly phosphorylated protein inactivates ER. | 16849599 | [
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Arabidopsis SHORT INTEGUMENTS 2 is a mitochondrial DAR GTPase. | The Arabidopsis short integuments 2-1 (sin2-1) mutant produces ovules with short integuments due to early cessation of cell division in these structures. SIN2 was isolated and encodes a putative GTPase sharing features found in the novel DAR GTPase family. DAR proteins share a signature DAR motif and a unique arrangement of the four conserved GTPase G motifs. We found that DAR GTPases are present in all examined prokaryotes and eukaryotes and that they have diversified into four paralogous lineages in highe | 16849600 | [
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Arabidopsis SHORT INTEGUMENTS 2 is a mitochondrial DAR GTPase. | r eukaryotes. Eukaryotic members of the SIN2 clade of DAR GTPases have been found to localize to mitochondria and are related to eubacterial proteins that facilitate essential steps in biogenesis of the large ribosomal subunit. We propose a similar role for SIN2 in mitochondria. A sin2 insertional allele has ovule effects similar to sin2-1; but more pronounced pleiotropic effects on vegetative and floral development. The diverse developmental effects of the mitochondrial SIN2 GTPase support a mitochondrial | 16849600 | [
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Modeling extent and distribution of zygotic disequilibrium: implications for a multigenerational canine pedigree. | Unlike gametic linkage disequilibrium defined for a random-mating population; zygotic disequilibrium describes the nonrandom association between different loci in a nonequilibrium population that deviates from Hardy-Weinberg equilibrium. Zygotic disequilibrium specifies five different types of disequilibria simultaneously that are (1) Hardy-Weinberg disequilibria at each locus; (2) gametic disequilibrium (including two alleles in the same gamete; each from a different locus); (3) nongametic disequilibrium ( | 16849601 | [
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Modeling extent and distribution of zygotic disequilibrium: implications for a multigenerational canine pedigree. | including two alleles in different gametes; each from a different locus); (4) trigenic disequilibrium (including a zygote at one locus and an allele at the other); and (5) quadrigenic disequilibrium (including two zygotes each from a different locus). However; because of the uncertainty on the phase of the double heterozygote; gametic and nongametic disequilibria need to be combined into a composite digenic disequilibrium and further define a composite quadrigenic disequilibrium together with the quadrigeni | 16849601 | [
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Modeling extent and distribution of zygotic disequilibrium: implications for a multigenerational canine pedigree. | c disequilibrium. To investigate the extent and distribution of zygotic disequilibrium across the canine genome; a total of 148 dogs were genotyped at 247 microsatellite markers located on 39 pairs of chromosomes for an outbred multigenerational pedigree; initiated with a limited number of unrelated founders. A major portion of zygotic disequilibrium was contributed by the composite digenic and quadrigenic disequilibrium whose values and numbers of significant marker pairs are both greater than those of tri | 16849601 | [
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Modeling extent and distribution of zygotic disequilibrium: implications for a multigenerational canine pedigree. | genic disequilibrium. All types of disequilibrium are extensive in the canine genome; although their values tend to decrease with extended map distances; but with a greater slope for trigenic disequilibrium than for the other types of disequilibrium. Considerable variation in the pattern of disequilibrium reduction was observed among different chromosomes. The results from this study provide scientific guidance about the determination of the number of markers used for whole-genome association studies. | 16849601 | [
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Regulation of DNA replication machinery by Mrc1 in fission yeast. | Faithful replication of chromosomes is crucial to genome integrity. In yeast; the ORC binds replication origins throughout the cell cycle. However; Cdc45 binds these before S-phase; and; during replication; it moves along the DNA with MCM helicase. When replication progression is inhibited; checkpoint regulation is believed to stabilize the replication fork; the detailed mechanism; however; remains unclear. To examine the relationship between replication initiation and elongation defects and the response to | 16849602 | [
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Regulation of DNA replication machinery by Mrc1 in fission yeast. | replication elongation block; we used fission yeast mutants of Orc1 and Cdc45--orp1-4 and sna41-928; respectively--at their respective semipermissive temperatures with regard to BrdU incorporation. Both orp1 and sna41 cells exhibited HU hypersensitivity in the absence of Chk1; a DNA damage checkpoint kinase; and were defective in full activation of Cds1; a replication checkpoint kinase; indicating that normal replication is required for Cds1 activation. Mrc1 is required to activate Cds1 and prevent the rep | 16849602 | [
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Regulation of DNA replication machinery by Mrc1 in fission yeast. | lication machinery from uncoupling from DNA synthesis. We observed that; while either the orp1 or the sna41 mutation partially suppressed HU sensitivity of cds1 cells; sna41 specifically suppressed that of mrc1 cells. Interestingly; sna41 alleviated the defect in recovery from HU arrest without increasing Cds1 activity. In addition to sna41; specific mutations of MCM suppressed the HU sensitivity of mrc1 cells. Thus; during elongation; Mrc1 may negatively regulate Cdc45 and MCM helicase to render stalled fo | 16849602 | [
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Regulation of DNA replication machinery by Mrc1 in fission yeast. | rks capable of resuming replication. | 16849602 | [
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A stochastic model for cancer risk. | We propose a simple stochastic model based on the two successive mutations hypothesis to compute cancer risks. Assume that only stem cells are susceptible to the first mutation and that there are a total of D stem cell divisions over the lifetime of the tissue with a first mutation probability mu(1) per division. Our model predicts that cancer risk will be low if m = mu(1)D is low even in the case of very advantageous mutations. Moreover; if mu(1)D is low the mutation probability of the second mutation is p | 16849605 | [
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A stochastic model for cancer risk. | ractically irrelevant to the cancer risk. These results are in contrast with existing models but in agreement with a conjecture of Cairns. In the case where m is large our model predicts that the cancer risk depends crucially on whether the first mutation is advantageous or not. A disadvantageous or neutral mutation makes the risk of cancer drop dramatically. | 16849605 | [
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Maternal gametophytic baseless1 is required for development of the central cell and early endosperm patterning in maize (Zea mays). | In angiosperms; double fertilization of an egg cell and a central cell with two sperm cells results in the formation of a seed containing a diploid embryo and a triploid endosperm. The extent to which the embryo sac controls postfertilization events in the seed is unknown. The novel gametophytic maternal-effect maize mutation; baseless1 (bsl1) affects central cell development within the embryo sac; frequently by altering the position of the two polar nuclei. Despite this irregularity; fertilization is as ef | 16849604 | [
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Maternal gametophytic baseless1 is required for development of the central cell and early endosperm patterning in maize (Zea mays). | ficient as in wild type. The spatial expression of basal endosperm-specific transcripts is altered in free-nuclear and cellular mutant endosperms. At later stages of seed development; bsl1 predominantly affects development of the basal endosperm transfer layer (BETL). When bsl1/+ diploid plants were pollinated by wild-type tetraploid plants; the BETL abnormalities observed in bsl1/bsl1/+/+ tetraploid endosperms were diverse and of variable severity. Moreover; the frequency of kernels with severely perturbed | 16849604 | [
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Maternal gametophytic baseless1 is required for development of the central cell and early endosperm patterning in maize (Zea mays). | BETL development correlated with the percentage of severely affected bsl1 central cells. Therefore; BSL1 is likely required in the central cell before fertilization for correct BETL patterning to occur. These findings provide new genetic evidence that a maternal gametophytic component is necessary for correct endosperm patterning. | 16849604 | [
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Effects on production traits of haplotypes among casein genes in Norwegian goats and evidence for a site of preferential recombination. | In goat milk the most abundant proteins are the casein genes; CSN1S1; CSN2; CSN1S2; and CSN3. Mutations have been identified within these genes affecting the level of gene expression; and effects on milk production traits have been reported. The aim of this study was to detect polymorphisms (SNPs) in the casein genes of Norwegian goats; resolve haplotype structures within the loci; and assess the effect of these haplotypes on milk production traits. Four hundred thirty-six Norwegian bucks were genotyped for | 16849606 | [
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Effects on production traits of haplotypes among casein genes in Norwegian goats and evidence for a site of preferential recombination. | 39 polymorphic sites across the four loci. The numbers of unique haplotypes present in each locus were 10; 6; 4; and 8 for CSN1S1; CSN2; CSN1S2; and CSN3; respectively. The effects of the CSN1S1 haplotypes on protein percentage and fat kilograms were significant; as were the effects of CSN3 haplotypes on fat percentage and protein percentage. A deletion in exon 12 of CSN1S1; unique to the Norwegian goat population; explained the effects of CSN1S1 haplotypes on fat kilograms; but not protein percentage. Inv | 16849606 | [
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Effects on production traits of haplotypes among casein genes in Norwegian goats and evidence for a site of preferential recombination. | estigation of linkage disequilibrium between all possible pairs of SNPs revealed higher levels of linkage disequilbrium for SNP pairs within casein loci than for SNP pairs between casein loci; likely reflecting low levels of intragenic recombination. Further; there was evidence for a site of preferential recombination between CSN2 and CSN1S2. The value of the haplotypes for haplotype-assisted selection (HAS) is discussed. | 16849606 | [
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The period gene Thr-Gly polymorphism in Australian and African Drosophila melanogaster populations: implications for selection. | The period gene is a key regulator of biological rhythmicity in Drosophila melanogaster. The central part of the gene encodes a dipeptide Thr-Gly repeat that has been implicated in the evolution of both circadian and ultradian rhythms. We have previously observed that length variation in the repeat follows a latitudinal cline in Europe and North Africa; so we have sought to extend this observation to the southern hemisphere. We observe a parallel cline in Australia for one of the two major length variants a | 16849607 | [
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The period gene Thr-Gly polymorphism in Australian and African Drosophila melanogaster populations: implications for selection. | nd find higher levels of some Thr-Gly length variants; particularly at the tropical latitudes; that are extremely rare in Europe. In addition we examined >40 haplotypes from sub-Saharan Africa and find a very different and far more variable profile of Thr-Gly sequences. Statistical analysis of the periodicity and codon content of the repeat from all three continents reveals a possible mechanism that may explain how the repeat initially arose in the ancestors of the D. melanogaster subgroup of species. Our r | 16849607 | [
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The period gene Thr-Gly polymorphism in Australian and African Drosophila melanogaster populations: implications for selection. | esults further reinforce the view that thermal selection may have contributed to shaping the continental patterns of Thr-Gly variability. | 16849607 | [
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The Tribolium castaneum ortholog of Sex combs reduced controls dorsal ridge development. | In insects; the boundary between the embryonic head and thorax is formed by the dorsal ridge; a fused structure composed of portions of the maxillary and labial segments. However; the mechanisms that promote development of this unusual structure remain a mystery. In Drosophila; mutations in the Hox genes Sex combs reduced and Deformed have been reported to cause abnormal dorsal ridge formation; but the significance of these abnormalities is not clear. We have identified three mutant allele classes of Cephal | 16849608 | [
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The Tribolium castaneum ortholog of Sex combs reduced controls dorsal ridge development. | othorax; the Tribolium castaneum (red flour beetle) ortholog of Sex combs reduced; each of which has a different effect on dorsal ridge development. By using Engrailed expression to monitor dorsal ridge development in these mutants; we demonstrate that Cephalothorax promotes the fusion and subsequent dorsolateral extension of the maxillary and labial Engrailed stripes (posterior compartments) during dorsal ridge formation. Molecular and genetic analysis of these alleles indicates that the N terminus of Ceph | 16849608 | [
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The Tribolium castaneum ortholog of Sex combs reduced controls dorsal ridge development. | alothorax is important for the fusion step; but is dispensable for Engrailed stripe extension. Thus; we find that specific regions of Cephalothorax are required for discrete steps in dorsal ridge formation. | 16849608 | [
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The maize Ab10 meiotic drive system maps to supernumerary sequences in a large complex haplotype. | The meiotic drive system on maize abnormal chromosome 10 (Ab10) is contained within a terminal domain of chromatin that extends the long arm of Ab10 to approximately 1.3 times the size of normal chromosome 10L. Ab10 type I (Ab10-I) does not recombine with normal chromosome 10 (N10) over an approximately 32-cM terminal region of the long arm. Comparative RFLP mapping demonstrates that multiple independent rearrangements are responsible for the current organization of Ab10-I; including a set of nested inversi | 16849609 | [
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The maize Ab10 meiotic drive system maps to supernumerary sequences in a large complex haplotype. | ons and at least one long supernumerary segment at the end of the chromosome. Four major meiotic drive functions; i.e.; the recombination effect; smd3; 180-bp neocentromere activity; and the distal tip function; all map to the distal supernumerary segment. TR-1-mediated neocentromere activity (the fifth known drive function) is nonessential in the type II variant of Ab10 and maps to a central region that may include a second supernumerary insertion. Both neocentromere activity and the recombination effect b | 16849609 | [
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The maize Ab10 meiotic drive system maps to supernumerary sequences in a large complex haplotype. | ehave as dominant gain-of-function mutations; consistent with the view that meiotic drive involves new or alien gene products. These and other data suggest that the Ab10 meiotic drive system was initially acquired from a related species and that a complex haplotype evolved around it. | 16849609 | [
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Activation of sterol regulatory element-binding proteins (SREBPs) is critical in IL-8-induced angiogenesis. | Angiogenesis is essential in many physiological and pathological processes and can be stimulated by many different factors. To better understand and to manipulate this process more effectively; it would be beneficial to identify molecules common to the signaling pathways stimulated by different classes of angiogenic factors. Sterol regulatory element-binding proteins (SREBPs) are involved in the metabolism of cholesterol and fatty acids; molecules that are critical in membrane biology; and hence; many of th | 16849610 | [
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Activation of sterol regulatory element-binding proteins (SREBPs) is critical in IL-8-induced angiogenesis. | e processes involved in angiogenesis. Here; we show that angiogenic factors of different families; such as basic fibroblast growth factor; thrombin; and interleukin (IL)-8; stimulate SREBP activation; whereas nonangiogenic factors; such as transforming growth factor-beta1; do not. We focused our detailed studies on IL-8 in vitro and in vivo; as this chemokine is also involved in inflammation and hence; has the potential to be critical in inflammation-induced angiogenesis; a process common to many diseases. | 16849610 | [
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Activation of sterol regulatory element-binding proteins (SREBPs) is critical in IL-8-induced angiogenesis. | Using human microvascular endothelial cells; a rabbit skin wound-healing model; and the chorioallantoic membrane assay; we show that IL-8 stimulates the activation of SREBP-1 and -2; and this activation is specific and receptor-mediated. SREBP activation leads to activation of RhoA through 3-hydroxy-3-methylglutaryl CoA reductase. RhoA is a small guanosinetriphosphatase; important in cytoskeletal functions; which in turn; are critical in many of the cellular processes needed for angiogenesis. Given that div | 16849610 | [
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Activation of sterol regulatory element-binding proteins (SREBPs) is critical in IL-8-induced angiogenesis. | erse; angiogenic factors use different cell-surface receptors; identification of this common step in the signal-transduction pathway provides the opportunity for novel approaches for prevention and treatment of diseases involving abnormal angiogenesis. | 16849610 | [
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The dermal microenvironment induces the expression of the alternative activation marker CD301/mMGL in mononuclear phagocytes, independent of IL-4/IL-13 signaling. | Recently; we have shown that mononuclear phagocytes comprise the majority of interstitial cells in the mouse dermis; as indicated by their phenotypic and functional characteristics. In particular; these cells express the mouse macrophage galactose-/N-acetylgalactosamine-specific-lectin (mMGL)/CD301; identified by the monoclonal antibody ER-MP23; as well as other macrophage markers. As expression of mMGL is induced by IL-4 or IL-13 and is therefore a marker of alternatively activated macrophages; we asked wh | 16849611 | [
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The dermal microenvironment induces the expression of the alternative activation marker CD301/mMGL in mononuclear phagocytes, independent of IL-4/IL-13 signaling. | ether dermal mononuclear phagocytes are genuinely alternatively activated. We observed that these cells expressed; next to mMGL; two other alternative activation markers; namely; the mannose receptor/CD206 and Dectin-1. Yet; as this expression profile was similar in IL-4 receptor alpha knockout mice; neither IL-4 nor IL-13 signaling appeared to be required for this phenotype. We also found that Langerhans cells (LC); which showed only a low level of mMGL in the epidermis; up-regulated mMGL expression upon m | 16849611 | [
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The dermal microenvironment induces the expression of the alternative activation marker CD301/mMGL in mononuclear phagocytes, independent of IL-4/IL-13 signaling. | igration through the dermis; allowing these cells to internalize limited amounts of mMGL ligands. LC isolated from epidermal preparations did not show this up-regulation when cultured in standard medium; but whole skin-conditioned medium did stimulate mMGL expression by LC. The vast majority of mMGL molecules was present in the cytoplasm; however. LC; which arrived in skin-draining lymph nodes; quickly down-regulated mMGL expression; and dermally derived cells retained significant mMGL levels. Taken togethe | 16849611 | [
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The dermal microenvironment induces the expression of the alternative activation marker CD301/mMGL in mononuclear phagocytes, independent of IL-4/IL-13 signaling. | r; these data suggest that the dermal microenvironment induces mononuclear phagocyte subpopulations to express mMGL and possibly other markers of alternatively activated macrophages; independent of IL-4/IL-13 signaling. | 16849611 | [
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Leukocytes, inflammation, and angiogenesis in cancer: fatal attractions. | Leukocytes are cells of defense. Their main function is to protect our body against invading microorganisms. Some leukocytes; in particular; polymorphonuclear and monocytes; accumulate at sites of infection and neutralize pathogens through innate mechanisms. The blood and lymphatic vascular system are essential partners in this defensive reaction: Activated endothelial cells promote leukocyte recruitment at inflammatory sites; new blood vessel formation; a process called angiogenesis; sustains chronic infla | 16849612 | [
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Leukocytes, inflammation, and angiogenesis in cancer: fatal attractions. | mmation; and lymphatic vessels transport antigens and antigen-presenting cells to lymph nodes; where they stimulate naive T and B lymphocytes to elicit an antigen-specific immune response. In contrast; leukocytes and lymphocytes are far less efficient in protecting us from cancer; the "enemy from within." Worse; cancer can exploit inflammation to its advantage. The role of angiogenesis; leukocytes; and inflammation in tumor progression was discussed at the second Monte Verità Conference; Tumor Host Interact | 16849612 | [
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Leukocytes, inflammation, and angiogenesis in cancer: fatal attractions. | ion and Angiogenesis: Basic Mechanisms and Therapeutic Perspectives; held in Ascona; Switzerland; October 1-5; 2005. (Conference chairs were K. Alitalo; M. Aguet; C. Rüegg; and I. Stamenkovic.) Eight articles reporting about topics presented at the conference are featured in this issue of the Journal of Leukocyte Biology. | 16849612 | [
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Comment: pharmacist critique was ill-informed. | nan | 16849613 | [
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HHS-CDC NEWS: update: influenza activity--US and worldwide, 2005-2006 season, and composition of the 2006-2007 influenza vaccine. | nan | 16849615 | [
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Comment: pharmacist critique was ill-informed. | nan | 16849617 | [
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Pharmacologic expulsive treatment of ureteral calculi. | To evaluate the role of nifedipine and the alpha(1)-adrenoreceptor antagonists tamsulosin; terazosin; and doxazosin in the expulsive treatment of ureteral calculi.Literature was searched via MEDLINE (1966-February 2006) with subsequent bibliographic review. MeSH headings included ureteral calculi; nifedipine; doxazosin; and adrenergic alpha-antagonists. Key terms were ureteral calculi; nifedipine; tamsulosin; terazosin; and doxazosin.Trials evaluating nifedipine; tamsulosin; terazosin; and doxazosin for exp | 16849614 | [
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Pharmacologic expulsive treatment of ureteral calculi. | ulsion of ureteral stones were reviewed. All were published in English-language; peer-reviewed journals.Several trials have evaluated the effects of nifedipine and tamsulosin on ureteral stone passage rates and mean time to stone passage in stones no larger than 15 mm. In 28 day trials; the rates of ureteral stone passage were 35-70% in the control groups compared with 77.1-80% in patients treated with nifedipine and 79.3-100% in patients treated with tamsulosin. Average number of days to stone passage in t | 16849614 | [
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Pharmacologic expulsive treatment of ureteral calculi. | he control groups was 4.6-20; and the time to stone passage was only 5-9.3 days in patients receiving nifedipine and 2.7-7.9 days in those receiving tamsulosin. The stone passage rates and time to stone passage appeared to be similar in one trial that compared tamsulosin with terazosin and doxazosin. Limited data suggest that these agents may have a role as adjuncts to shock wave lithotripsy. Adverse drug reactions were uncommon.Nifedipine; tamsulosin; terazosin; and doxazosin are safe and effective options | 16849614 | [
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Pharmacologic expulsive treatment of ureteral calculi. | in enhancing ureteral stone expulsion in selected patients with uncomplicated presentations. | 16849614 | [
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Comment: pharmacist critique was ill-informed. | nan | 16849616 | [
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