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Toll-like receptor 4 (TLR4) plays a critical role in the innate immune response to Gram-negative bacterial infection. A large number of the components involved in TLR4 signaling pathways have been identified over the past ten years. Recent studies focusing on the post-translational modification of TLR4 signaling pathways have begun expanding our knowledge of the impact of lysine acetylation on TLR4 signaling cascades. In this review, we will focus on the potential roles of acetylation in TLR4-mediated innate immune responses.

The matching preclusion number of a graph is the minimum number of edges whose deletion results in a graph that has neither perfect matchings nor almost-perfect matchings, and the conditional matching preclusion number of a graph is the minimum number of edges whose deletion leaves a resulting graph with no isolated vertices that has neither perfect matchings nor almost perfect matchings. In this paper, we find these two numbers for the burnt pancake graphs and show that every optimal (conditional) matching preclusion set is trivial.

Background Pharmacogenetic studies aiming to personalize the treatment of depression are based on the assumption that response to antidepressants is a heritable trait, but there is no compelling evidence to support this. Methods We estimate the contribution of common genetic variation to antidepressant response with Genome-Wide Complex Trait Analysis in a combined sample of 2799 antidepressant-treated subjects with major depressive disorder and genome-wide genotype data. Results We find that common genetic variants explain 42% (SE = .180, p = .009) of individual differences in antidepressant response. Conclusions These results suggest that response to antidepressants is a complex trait with substantial contribution from a large number of common genetic variants of small effect.

Considerable controversy exists regarding the association between hyperuricemia and coronary heart disease (CHD). Therefore, we performed a systematic review and dose-response meta-analysis of prospective studies to examine the controversy. Prospective cohort studies with relative risks (RRs) and 95% confidence intervals (CIs) for CHD according to serum uric acid levels in adults were eligible. A random-effects model was used to compute the pooled risk estimate. The search yielded 29 prospective cohort studies (n = 958410 participants). Hyperuricemia was associated with increased risk of CHD morbidity (adjusted RR 1.13; 95% CI 1.05 to 1.21) and mortality (adjusted RR 1.27; 95% CI 1.16 to 1.39). For each increase of 1 mg/dl in uric acid level, the pooled multivariate RR of CHD mortality was 1.13 (95% CI 1.06 to 1.20). Dose-response analysis indicated that the combined RR of CHD mortality for an increase of 1 mg uric acid level per dl was 1.02 (95% CI 0.84 to 1.24) without heterogeneity among males (P = 0.879, I2 = 0%) and 2.44 (95% CI 1.69 to 3.54) without heterogeneity among females (P = 0.526, I2 = 0%). The increased risk of CHD associated with hyperuricemia was consistent across most subgroups. Hyperuricemia may increase the risk of CHD events, particularly CHD mortality in females.

Penioxalicin (1), the first 3-nor-2,3-seco-labdane type diterpene featuring the fission between C-2 and C-3 in the ring A and the decarboxylation at C-3, was isolated from the fungus Penicillium oxalicum TW01-1. Its planar structure and absolute configuration were elucidated mainly by analysis of 1D and 2D-NMR, ECD spectroscopic data, and single-crystal X-ray diffraction. Compound 1 showed moderate cytotoxicity against HL-60 cell line. The possible biosynthetic pathway of 1 was also proposed.

Let [Formula: see text] be a graph of order [Formula: see text] and [Formula: see text] an integer not great than [Formula: see text]. Erdős and Sós conjectured that if [Formula: see text] has at least [Formula: see text] edges, then [Formula: see text] contains all trees of order [Formula: see text]. Loebl, Komlós and Sós conjectured that if at least [Formula: see text] vertices of [Formula: see text] have degree at least [Formula: see text], then [Formula: see text] contains all trees of order [Formula: see text]. In this paper, it is shown that both the conjectures are true for graphs with independence number two, and our results generalize some known results.

Salidroside (p-hydroxyphenethyl-beta-d-glucoside), which is present in all species of the genus Rhodiola, has been reported to have a broad spectrum of pharmacological properties. The present study, for the first time, focused on evaluating the effects of the purified salidroside on the proliferation of various human cancer cell lines derived from different tissues, and further investigating its possible molecular mechanisms. Cell viability assay and [(3)H] thymidine incorporation were used to evaluate the cytotoxic effects of salidroside on cancer cell lines, and flow cytometry analyzed the change of cell cycle distribution induced by salidroside. Western immunoblotting further studied the expression changes of cyclins (cyclin D1 and cyclin B1), cyclin-dependent kinases (CDK4 and Cdc2), and cyclin-dependent kinase inhibitors (p21(Cip1) and p27(Kip1)). The results showed that salidroside inhibited the growth of various human cancer cell lines in concentration- and time-dependent manners, and the sensitivity to salidroside was different in those cancer cell lines. Salidroside could cause G1-phase or G2-phase arrest in different cancer cell lines, meanwhile, salidroside resulted in a decrease of CDK4, cyclin D1, cyclin B1 and Cdc2, and upregulated the levels of p27(Kip1) and p21(Cip1). Taken together, salidroside could inhibit the growth of cancer cells by modulating CDK4-cyclin D1 pathway for G1-phase arrest and/or modulating the Cdc2-cyclin B1 pathway for G2-phase arrest.

Based on the comprehensive study of core samples, well testing data, and reservoir fluid properties, the construction and the distribution of the abnormal pressure systems of the Huatugou oil field in Qaidam Basin are discussed. The correlation between the pressure systems and hydrocarbon accumulation is addressed by analyzing the corresponding fluid characteristics. The results show that the Huatugou oil field as a whole has low formation pressure and low fluid energy; therefore, the hydrocarbons are hard to migrate, which facilitates the forming of primary reservoirs. The study reservoirs, located at the Xiayoushashan Formation (N21) and the Shangganchaigou Formation (N1) are relatively shallow and have medium porosity and low permeability. They are abnormal low-pressure reservoirs with an average formation pressure coefficient of 0.61 and 0.72 respectively. According to the pressure coefficient and geothermal anomaly, the N1 and N21 Formations belong to two independent temperature-pressure systems, and the former has slightly higher energy. The low-pressure compartments consist of a distal bar as the main body, prodelta mud as the top boundary, and shore and shallow lake mud or algal mound as the bottom boundary. They are vertically overlapped and horizontally paralleled. The formation water is abundant in the Cl− ion and can be categorized as CaCl2 type with high salinity, which indicates that the abnormal low-pressure compartments are in good sealing condition and beneficial for oil and gas accumulation and preservation.

The insulin-like growth factor-I receptor (IGF-IR) pathway is required for the maintenance of the transformed phenotype in neoplastic cells and hence has been the subject of intensive drug discovery efforts. A key aspect of successful clinical development of targeted therapies directed against IGF-IR will be identification of responsive patient populations. Toward that end, we have endeavored to identify predictive biomarkers of response to an anti-IGF-IR-targeting monoclonal antibody in preclinical models of breast and colorectal cancer. We find that levels of the IGF-IR itself may have predictive value in these tumor types and identify other gene expression predictors of in vitro response. Studies in breast cancer models suggest that IGF-IR expression is both correlated and functionally linked with estrogen receptor signaling and provide a basis for both patient stratification and rational combination therapy with antiestrogen-targeting agents. In addition, we find that levels of other components of the signaling pathway such as the adaptor proteins IRS1 and IRS2, as well as the ligand IGF-II, have predictive value and report on the development of a pathway-focused panel of diagnostic biomarkers that could be used to test these hypotheses during clinical development of IGF-IR-targeting therapies. [Mol Cancer Ther 2009;8(8):2110–21]

Breast cancers can be divided into subtypes with important implications for prognosis and treatment. We set out to characterize the genetic alterations observed in different breast cancer subtypes and to identify specific candidate genes and pathways associated with subtype biology. mRNA expression levels of estrogen receptor, progesterone receptor, and HER2 were shown to predict marker status determined by immunohistochemistry and to be effective at assigning samples to subtypes. HER2+ cancers were shown to have the greatest frequency of high-level amplification (independent of the ERBB2 amplicon itself), but triple-negative cancers had the highest overall frequencies of copy gain. Triple-negative cancers also were shown to have more frequent loss of phosphatase and tensin homologue and mutation of RB1, which may contribute to genomic instability. We identified and validated seven regions of copy number alteration associated with different subtypes, and used integrative bioinformatics analysis to identify candidate oncogenes and tumor suppressors, including ERBB2, GRB7, MYST2, PPM1D, CCND1, HDAC2, FOXA1, and RASA1. We tested the candidate oncogene MYST2 and showed that it enhances the anchorage-independent growth of breast cancer cells. The genome-wide and region-specific differences between subtypes suggest the differential activation of oncogenic pathways. (Mol Cancer Res 2009;7(4):511–22)

Breast cancer is a heterogeneous disease with distinct molecular subtypes characterized by differential response to targeted and chemotherapeutic agents. Enhanced understanding of the genetic alterations characteristic of different subtypes is needed to pave the way for more personalized administration of therapeutic agents. We have taken a functional genomics approach using a well-characterized panel of breast cancer cell lines to identify putative biomarkers of resistance to antimitotic agents such as paclitaxel and monomethyl-auristatin-E (MMAE). In vitro studies revealed a striking difference in sensitivity to these agents between cell lines from different subtypes, with basal-like cell lines being significantly more sensitive to both agents than luminal or HER2-amplified cell lines. Genome-wide association studies using copy number data from Affymetrix single nucleotide polymorphism arrays identified amplification of the chromosome 17q21 region as being highly associated with resistance to both paclitaxel and MMAE. An unbiased approach consisting of RNA interference and high content analysis was used to show that amplification and concomitant overexpression of the gene encoding the ABCC3 drug transporter is responsible for conferring in vitro resistance to paclitaxel and MMAE. We also show that amplification of ABCC3 is present in primary breast tumors and that it occurs predominantly in HER2-amplified and luminal tumors, and we report on development of a specific fluorescence in situ hybridization assay that may have utility as a predictive biomarker of taxane resistance in breast cancer. [Cancer Res 2008;68(13):5380–9]

Penioxalamine A (1), a novel prenylated spiro-oxindole alkaloid having a unique seven-membered nitrogen heterocycle system, was isolated from the fungus Penicillium oxalicum TW01-1. The structure of 1 was elucidated on the basis of the spectral data, single-crystal X-ray diffraction, and CD analysis. Compound 1 showed moderate cytotoxicity against HL-60 cell line. The possible biosynthetic pathway of 1 was also proposed.

The minor allele of the R620W missense single-nucleotide polymorphism (SNP) (rs2476601) in the hematopoietic-specific protein tyrosine phosphatase gene, PTPN22, has been associated with multiple autoimmune diseases, including rheumatoid arthritis (RA). These genetic data, combined with biochemical evidence that this SNP affects PTPN22 function, suggest that this phosphatase is a key regulator of autoimmunity. To determine whether other genetic variants in PTPN22 contribute to the development of RA, we sequenced the coding regions of this gene in 48 white North American patients with RA and identified 15 previously unreported SNPs, including 2 coding SNPs in the catalytic domain. We then genotyped 37 SNPs in or near PTPN22 in 475 patients with RA and 475 individually matched controls (sample set 1) and selected a subset of markers for replication in an additional 661 patients with RA and 1,322 individually matched controls (sample set 2). Analyses of these results predict 10 common (frequency >1%) PTPN22 haplotypes in white North Americans. The sole haplotype found to carry the previously identified W620 risk allele was strongly associated with disease in both sample sets, whereas another haplotype, identical at all other SNPs but carrying the R620 allele, showed no association. R620W, however, does not fully explain the association between PTPN22 and RA, since significant differences between cases and controls persisted in both sample sets after the haplotype data were stratified by R620W. Additional analyses identified two SNPs on a single common haplotype that are associated with RA independent of R620W, suggesting that R620W and at least one additional variant in the PTPN22 gene region influence RA susceptibility.

The whisker-reinforced polymer composites have good friction and wear properties and widely used in many fields. Potassium titanate (K2Ti6O13) whiskers have good properties, lower prices and show good foreground in whisker-reinforced polymer matrix composites. The surface properties of the whisker are vital for the performance of the reinforced composites. In this paper, the friction and wear properties of potassium titanate whiskers reinforced bismaleimide copmposites and the surfaces of whiskers treated by coupling agents were studied. Two coupling agents, a silane compound (KH550) and a titanate (NDZ311) were selected to treat the surface of K2Ti6O13 whiskers, respectively. Three whisker-reinforced BMI composites, K2Ti6O13/BMI, K2Ti6O13 (KH550)/BMI and K2Ti6O13 (NDZ311)/BMI, were prepared and their tribological behaviors were investigated. Results show that the wear-resistance of the matrix improved by the incorporation of whiskers into the matrix, while the improvement efficiency is depended on the nature of the surface of whiskers and whisker content. The composite containing KH550 treated whiskers has the best wear-resistance, and that containing untreated whiskers has the poorest wear-resistance among the three composites. Experiment results were explained from the point of the interfacial adhesion between the matrix and whiskers as well as the surface morphologies of worn surface and wear particles of the matrix and composites.

Aluminum-borate-whiskers-reinforced bismaleimide (BMI/Al18B4O33) composites were prepared, and the mechanical and thermal properties were investigated. Results show that the coupling agent used for surface treatment of whiskers has a great effect on the properties of these materials. Composites containing surface-untreated whiskers, or silane-compound-KH 921-treated whiskers, exhibited initially only a slight increase in the flexural strength when the whiskers weight content increased up to 5 wt%; thereafter, they showed a sharp decrease when the whiskers content was higher than 5 wt%. On the other hand, impact strength tests showed that the addition of the two kinds of whiskers decreased the impact strength of the composites. However, studies of the composite containing borate (BE4)-treated whiskers showed that its flexural strength greatly increased with increasing whisker content. Moreover, the composite showed initially an increase in impact strength with a whisker content up to 10 wt%, then showing a slight decrease when the whisker content reached 15 wt%. Scanning electron microscopy observations revealed that the two coupling agents (KH 921 and BE4) employed in this work tend to change the fracture features of the composites from brittleness to that of ductile behaviour. Copyright © 2004 Society of Chemical Industry

Aluminum borate (Al18B4O33) whisker–reinforced composites based on a epoxy resin, which was made up of a trifunctional epoxy resin, TDE 85, and methyl nadic anhydride (MNA), were prepared, and the effects of the whiskers on the processing, reactivity, and typical mechanical properties of the composites were investigated. Two coupling agents, aluminate (DL411A) and borate (BE4), were used to surface treat the whiskers. Results show that the addition of the whiskers does not change the reactivity of the matrix, while increasing the viscosity of the resin, but when the whisker content is less than 5 wt %, the increased viscosity does not obviously influence the processing characteristics of the resin. Mechanical properties are greatly dependent on the chemistry and concentration of the coupling agent for treating the whiskers. A good coupling agent, which has good interaction with the whiskers and the matrix, can effectively improve the compatibility between the whiskers and the matrix, and thus result in great improvement of mechanical properties. BE4 proved to be better than DL411A for treating the whiskers. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 1950–1954, 2004

The Ordovician deposition is characterized by a thick carbonate in the Tarim Basin. In northwestern section of the basin, rocks are chiefly deposited in a carbonate ramp. Twelve microfacies have been distinguished on the basis of their depositional textures and petrographic analysis. Four depositional belts such as tidal flat, lagoon, shoal and open marine can be identified.

The Genetics Core of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), formally established in 2009, aims to provide resources and facilitate research related to genetic predictors of multidimensional Alzheimer’s disease (AD)-related phenotypes. Here, we provide a systematic review of genetic studies published between 2009 and 2012 where either ADNI APOE genotype or genome-wide association study (GWAS) data were used. We review and synthesize ADNI genetic associations with disease status or quantitative disease endophenotypes including structural and functional neuroimaging, fluid biomarker assays, and cognitive performance. We also discuss the diverse analytical strategies used in these studies, including univariate and multivariate analysis, meta-analysis, pathway analysis, and interaction and network analysis. Finally, we perform pathway and network enrichment analyses of these ADNI genetic associations to highlight key mechanisms that may drive disease onset and trajectory. Major ADNI findings included all the top 10 AD genes and several of these (e.g., APOE, BIN1, CLU, CR1, and PICALM) were corroborated by ADNI imaging, fluid and cognitive phenotypes. ADNI imaging genetics studies discovered novel findings (e.g., FRMD6) that were later replicated on different data sets. Several other genes (e.g., APOC1, FTO, GRIN2B, MAGI2, and TOMM40) were associated with multiple ADNI phenotypes, warranting further investigation on other data sets. The broad availability and wide scope of ADNI genetic and phenotypic data has advanced our understanding of the genetic basis of AD and has nominated novel targets for future studies employing next-generation sequencing and convergent multi-omics approaches, and for clinical drug and biomarker development. Electronic supplementary material The online version of this article (doi:10.1007/s11682-013-9262-z) contains supplementary material, which is available to authorized users.

It is imperative to provide a more uniform method to improve the validity of prevalence studies on multimorbidity. However, the status of prevalence studies on multimorbidity of chronic disease is still yet to be confirmed in China. The objective of the present systematic review was to evaluate the variance across prevalence studies and to explore possible explanations for variations in China. Published literature was obtained from four databases. The studies that described the prevalence of multimorbidity on chronic disease based on the general population were considered. We assessed the risk of bias by a preplanned checklist referring to STROBE (Strengthening the Reporting of Observational Studies in Epidemiology). The heterogeneity among eligible studies was estimated by I(2) statistic and P-value using MetaAnalyst software. Nine studies were eligible for this systematic review. The prevalence of multimorbidity among the population aged 60 years or more ranged from 6.4% (95% CI 5.1-8.0) to 76.5% (95%CI 73.6-79.2). However, just two of nine studies could be judged as having a low risk of bias. It was shown that key items introducing the risk of bias included inconsistent sampling method, lacking of uniform measure indices and data source based on self-report. Heterogeneity test showed I(2) = 50% (P0.001), which showed there was substantial variation among individual studies. Therefore, only a narrative summary rather than meta-analysis was carried out. Marked methodology heterogeneity exists among prevalence studies on multimorbidity. Suggested methodological aspects that should be considered in future studies include sampling method, measure indices of multimorbidity and data source.

Women during pregnancy or puerperium have a higher risk of venous thromboembolism (VTE). The reported incidence of pregnancy-associated VTE from literature varied considerably. To summarize the overall incidence of the disease, we conducted this meta-analysis.We searched PubMed, EMBase and CNKI (China National Knowledge Infrastructure) for studies that reported the incidence of VTE during pregnancy or puerperium. The quality of included studies was assessed using the Newcastle-Ottawa scale and the meta-analysis was conducted using R software and Meta analyst Beta 3.13. Sensitivity analyses were performed to analyze the robustness of the results and publication bias was assessed using Egger's test.Twenty-seven articles met the inclusion criteria. The pooled incidence rate was 1.4‰ (1.0-1.8‰) for VTE, 1.1‰ (1.0-1.3‰) for deep vein thrombosis (DVT) and 0.3‰ (0.2-0.4‰) for pulmonary embolism (PE). The weighted proportion of VTE postpartum was 57.5% and the pooled proportion of right-sided DVT was 27.9%. We noted substantial heterogeneity among individual studies.Women during pregnancy or puerperium are associated with a higher morbidity of VTE. Physicians should be of high vigilance to pregnancy-associated VTE, especially for women postpartum.

To determine whether the supplementation of ω-3 polyunsaturated fatty acids in parenteral nutrition (PN) confers treatment benefits to outcomes of septic patients.The databases of MEDLINE, EMBASE, Cochrane central register of controlled trials, the CNKI and the Wanfang biomedicine were searched to identify prospective randomized controlled trials (RCTs) which compared the ω-3 polyunsaturated fatty acids supplemented with the standard PN on outcomes of adult patients with sepsis from January 1996 to June 2013. The methodological quality of the included studies was evaluated, and the Cochrane Collaboration RevMan 5.0 was used for data analysis.A total of 12 studies enrolling 721 patients were included. Significant reduction in 28-day mortality [relative risk (RR) 0.77, 95% confidence interval (95%CI) 0.59 to 0.99, P=0.04], short intensive care unit [ICU, weighted mean difference (WMD)=-3.10, 95%CI -5.98 to -0.21, P=0.04] and hospital length of stay (WMD=-3.12, 95%CI -4.65 to -1.60, P0.000 1) were observed in patients receiving ω-3 polyunsaturated fatty acids supplemented PN. There was no differences in days of mechanical ventilation between patients with or without adding ω-3 polyunsaturated fatty acids in PN (WMD=1.33, 95%CI -5.09 to 7.75, P=0.69).Meta-analysis results demonstrated that PN supplemented with ω-3 polyunsaturated fatty acids was beneficial in improving the outcomes of patients with sepsis. However, this conclusion must be interpreted with caution due to the low quality of the enrolled trials.

Testing whether genetic information could inform the selection of the best drug for patients with depression, Rudolf Uher and colleagues searched for genetic variants that could predict clinically meaningful responses to two major groups of antidepressants., Background It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way. Methods and Findings The NEWMEDS consortium, an academia–industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p, Editors' Summary Background Genetic and environmental factors can influence a person's response to medications. Taking advantage of the recent advancements in genetics, scientists are working to match specific gene variations with responses to particular medications. Knowing whether a patient is likely to respond to a drug or have serious side effects would allow doctors to select the best treatment up front. Right now, there are only a handful of examples where a patient's version of a particular gene predicts their response to a particular drug. Some scientists believe that there will be many more such matches between genetic variants and treatment responses. Others think that because the action of most drugs is influenced by many different genes, a variant in one of those genes is unlikely to have measurable effect in most cases. Why Was This Study Done? One of the areas where patients' responses to available drugs vary widely is severe depression (or major depressive disorder). Prescription of an antidepressant is often the first step in treating the disease. However, less than half of patients get well taking the first antidepressant prescribed. Those who don't respond to the first drug need to, together with their doctors, try multiple courses of treatment to find the right drug and the right dose for them. For some patients none of the existing drugs work well. To see whether genetic information could help improve the choice of antidepressant, researchers from universities and the pharmaceutical industry joined forces in this large study. They examined two ways to use genetic information to improve the treatment of depression. First, they searched all genes for common genetic variants that could predict which patients would not respond to the two major groups of antidepressants (serotonin reuptake inhibitors, or SRIs, and noradrenaline reuptake inhibitors, or NRIs). They hoped that this would help with the development of new drugs that could help these patients. Second, they looked for common genetic variants in all genes that could identify patients who responded to one of the two major groups of antidepressants. Such predictors would make it possible to know which drug to prescribe for which patient. What Did the Researchers Do and Find? The researchers selected 1,790 patients with severe depression who had participated in one of several research studies; 1,222 of the patients had been treated with an SRI, the remaining 568 with an NRI, and it was recorded how well the drugs worked for each patient. The researchers also had a detailed picture of the genetic make-up of each patient, with information for over half a million genetic variants. They then looked for an association between genetic variants and responses to drugs. They found not a single genetic variant that could predict clearly whether a person would respond to antidepressants in general, to one of the two main groups (SRIs and NRIs), or much better to one than the other. They also didn't find any combination of variants in groups of genes that work together that could predict responses. Combining their data with those from another large study did not yield any robust predictors either. What Do These Findings Mean? This study was large enough that it should have been possible to find common genetic variants that by themselves could predict a clinically meaningful response to SRIs and/or NRIs, had such variants existed. The fact that the study failed to find such variants suggests that such variants do not exist. It is still possible, however, that variants that are less common could predict response, or that combinations of variants could. To find those, if they do exist, even larger studies will need to be done. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001326 The National Institute of General Medical Sciences at the US National Institutes of Health has a fact sheet on personalized medicine PubMed Health at the US National Library of Medicine has a page on major depressive disorder Wikipedia has pages on major depressive disorder and pharmacogenetics, the study of how genetic variation affects response to certain drugs (note that Wikipedia is a free online encyclopedia that anyone can edit) The UK National Health Service has comprehensive information pages on depression

Deep carbonate of Tarim Basin has become an important study target of shoal reservoirs at present, and the reservoir capacity and its control factors of high-frequent meter scale cyclic carbonate strata have been the purposes of this study. This research has selected the upper layer of strata of Yingshan formation in Keping area of Tarim Basin as the target stata, and analyzed by anatomying its outcrop, sampling and studying microscopic flakes. The result shows that the strata of Yingshan formation has deposited as high-frequent meter-scale cyclic sequence, and been an aggradational pattern between parasequence sets. Each parasequence set contains four parasequences which limestone was thickening during depositing period, the external style and internal composition between parasequence sets and parasequences are apparent self similarity. Calcarenite and bioclastic debris are the main particle types of shoal reservoirs, and the size gradually has increased up. Cement and means of contact between particles are consistent with the aggradational high-frequency sequences. All of the above fully have proved that the depositional energy increases from the parasequence sets A to C, and the high-energy deposition environment provides the basic condition for forming excellent shoal reservoir. Cracks and fissures are the main reservoir spaces of Yingshan formation shoal reservoir, but deep diagenesis shortly has not conducted to form effective dissolution intergranular pore, and reduced the capacity of quality shoal reservoir as the prerequisite for high-energy environment. As a result, the tectonic uplift has been the leading factor to control Yingshan formation to be II category reservoir.

Our previous proteome analysis showed that the nuclear isoform of dUTP pyrophosphatase (DUT-N) was identified in the culture medium of human amnion FL cells after exposure to the alkylating agent N -methyl- N ′-nitro- N -nitrosoguanidine (MNNG). These results suggest that DUT-N may be a potential early biomarker to assess the risk of alkylating agents exposure. DUT-N is one of the two isoforms of deoxyuridine triphosphate nucleotidohydrolase (dUTPase). Our current knowledge of DUT-N expression in human cells is very limited. In the current study, we first investigated the appearance of DUT-N in the culture medium of different human cell lines in response to a low concentration of MNNG exposure. We verified that the MNNG-induced appearance of DUT-N in the extracellular environment is cell-specific. Western blot analysis confirmed that the intracellular DUT-N changes responded to MNNG in a concentration-dependent and cell-specific manner. Furthermore, subcellular fraction experiments showed that 0.25 μM MNNG treatment dramatically increased the DUT-N expression levels in the cytoplasmic extracts prepared from both FL and HepG2 cells, increased DUT-N levels in nuclear extracts prepared from HepG2 cells, and decreased DUT-N levels in nuclear extracts from FL cells. Morphological studies using immunofluorescence showed that a low concentration of MNNG could alter the distribution of DUT-N in FL and HepG2 cells in different ways. Taken together, these studies indicate a role of DUT-N in alkylating agent-induced cell responses.

Contains fulltext : 87688.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of existing studies to boost statistical power. METHOD: We used data from four projects: a) the Children's Hospital of Philadelphia (CHOP); b) phase I of the International Multicenter ADHD Genetics project (IMAGE); c) phase II of IMAGE (IMAGE II); and d) the Pfizer-funded study from the University of California, Los Angeles, Washington University, and Massachusetts General Hospital (PUWMa). The final sample size consisted of 2,064 trios, 896 cases, and 2,455 controls. For each study, we imputed HapMap single nucleotide polymorphisms, computed association test statistics and transformed them to z-scores, and then combined weighted z-scores in a meta-analysis. RESULTS: No genome-wide significant associations were found, although an analysis of candidate genes suggests that they may be involved in the disorder. CONCLUSIONS: Given that ADHD is a highly heritable disorder, our negative results suggest that the effects of common ADHD risk variants must, individually, be very small or that other types of variants, e.g., rare ones, account for much of the disorder's heritability. 01 september 2010

Recently, salidroside (p-hydroxyphenethyl-beta-d-glucoside) has been identified as one of the most potent compounds isolated from plants of the Rhodiola genus used widely in traditional Chinese medicine, but pharmacokinetic data on the compound are unavailable. We were the first to report the cytotoxic effects of salidroside on cancer cell lines derived from different tissues, and we found that human breast cancer MDA-MB-231 cells (estrogen receptor negative) were sensitive to the inhibitory action of low-concentration salidroside. To further investigate the cytotoxic effects of salidroside on breast cancer cells and reveal possible ER-related differences in response to salidroside, we used MDA-MB-231 cells and MCF-7 cells (estrogen receptor-positive) as models to study possible molecular mechanisms; we evaluated the effects of salidroside on cell growth characteristics, such as proliferation, cell cycle duration, and apoptosis, and on the expression of apoptosis-related molecules. Our results demonstrated for the first time that salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells and may be a promising candidate for breast cancer treatment.

A well-established extension to Nusselt-Rohsenow theory has been used by many investigators to model laminar filmwise condensation from quiescent pure vapors onto isothermal bodies. However, when there is a vapor velocity, shear at the liquid-vapor interface and pressure gradient effects can be important. Although these effects have been studied for some geometries (flat plates and circular cylinders), they have not been studied for the general axisymmetric case. The purpose of this work is to summarize an earlier analysis of condensation from flowing vapors onto axisymmetric bodies and report new experimental results. The experiment employed flowing trichlorotrifluorethane (CFC 113) vapor, which condensed onto a copper sphere. The apparatus, procedures, and data interpretation are discussed, and heat transfer results are compared to a correlation derived from the analytical approach. After correcting for the use of the asymptotic shear approximation, the theory underpredicts the experimental results by about 15%. However, these results do confirm the general utility of the approach and are the first reported for this geometry. It is conjectured that surface waves and boundary layer separation may be responsible for the underprediction. A correlation for practical use is proposed for condensation from a flowing vapor onto a sphere.

Analysis of polymorphism and divergence in the non-coding portion of the human genome yields crucial information about factors driving the evolution of gene regulation. Candidate cis-regulatory regions spanning more than 15,000 genes in 15 African Americans and 20 European Americans were re-sequenced and aligned to the chimpanzee genome in order to identify potentially functional polymorphism and to characterize and quantify departures from neutral evolution. Distortions of the site frequency spectra suggest a general pattern of selective constraint on conserved non-coding sites in the flanking regions of genes (CNCs). Moreover, there is an excess of fixed differences that cannot be explained by a Gamma model of deleterious fitness effects, suggesting the presence of positive selection on CNCs. Extensions of the McDonald-Kreitman test identified candidate cis-regulatory regions with high probabilities of positive and negative selection near many known human genes, the biological characteristics of which exhibit genome-wide trends that differ from patterns observed in protein-coding regions. Notably, there is a higher probability of positive selection in candidate cis-regulatory regions near genes expressed in the fetal brain, suggesting that a larger portion of adaptive regulatory changes has occurred in genes expressed during brain development. Overall we find that natural selection has played an important role in the evolution of candidate cis-regulatory regions throughout hominid evolution., Author Summary It has been suggested that changes in gene expression may have played a more important role in the evolution of modern humans than changes in protein-coding sequences. In order to identify signatures of natural selection on candidate cis-regulatory regions, we examined single nucleotide polymorphisms obtained from the complete re-sequencing of conserved non-coding sites (CNCs) in the flanking regions of over 15,000 genes in 35 humans. Patterns of allele frequencies in CNCs indicate the presence of both positive and negative selection acting on standing variation within these candidate cis-regulatory regions, particularly for the 5′ and 3′ UTRs of genes. Gene-specific tests comparing levels of polymorphism and divergence identify several genes with strong signatures of selection on candidate cis-regulatory regions and suggest that the biological characteristics of genes subject to selection are different between coding and candidate cis-regulatory regions with respect to gene expression and function. For example, we find stronger signatures of positive selection in candidate cis-regulatory regions near genes expressed in the fetal brain, which we do not observe in a concurrent analysis on protein-coding regions. Our results suggest that both positive and negative selection have acted on candidate cis-regulatory regions and that the evolution of non-coding DNA has played an important role throughout hominid evolution.