PGB pair production at LHC and ILC as a probe of the topcolor-assisted technicolor models

The topcolor-assisted technicolor (TC2) model predicts some light pseudo goldstone bosons (PGBs), which may be accessible at the LHC or ILC. In this work we study the pair productions of the charged or neutral PGBs at the LHC and ILC. For the productions at the LHC we consider the processes proceeding through gluon-gluon fusion and quark-antiquark annihilation, while for the productions at the ILC we consider both the electron-positron collision and the photon-photon collision. We find that in a large part of parameter space the production cross sections at both colliders can be quite large compared with the low standard model backgrounds. Therefore, in future experiments these productions may be detectable and allow for probing TC2 model.Comment: 26 pages, 16 figures. slight changes in the text; notations for curves changed; references adde

Human Ovarian Tumor Cells Escape γδ T Cell Recognition Partly by Down Regulating Surface Expression of MICA and Limiting Cell Cycle Related Molecules

Background: Mechanisms of human Vc2Vd2 T cell-mediated tumor immunity have yet to be fully elucidated. Methods and Findings: At least some tumor cell recognition is mediated by NKG2D-MICA interactions. Herein, by using MTT assay and PI-BrdU co-staining and Western-blot, we show that these Vc2Vd2 T cells can limit the proliferation of ovarian tumor cells by down regulation of apoptosis and cell cycle related molecules in tumor cells. Cell-to-cell contact is critical. cd T cell-resistant, but not susceptible ovarian tumor cells escape cd T cell-mediated immune recognition by up-regulating pErk1/2, thereby decreasing surface MICA levels. Erk1/2 inhibitor pretreatment or incubation prevents this MICA decrease, while up-regulating key cell cycle related molecules such as CDK2, CDK4 and Cyclin D1, as well as apoptosis related molecules making resistant tumor cells now vulnerable to cd T cell-mediated lysis. Conclusion: These findings demonstrate novel effects of cdT cells on ovarian tumor cells

Criminal Justice Reform as HIV and TB Prevention in African Prisons

Katherine Todrys and Joseph Amon argue for criminal justice system reforms in sub-Saharan Africa to reduce HIV and TB transmission in prisons and to guarantee detainees' human rights and health

Identification of Direct Target Genes Using Joint Sequence and Expression Likelihood with Application to DAF-16

A major challenge in the post-genome era is to reconstruct regulatory networks from the biological knowledge accumulated up to date. The development of tools for identifying direct target genes of transcription factors (TFs) is critical to this endeavor. Given a set of microarray experiments, a probabilistic model called TRANSMODIS has been developed which can infer the direct targets of a TF by integrating sequence motif, gene expression and ChIP-chip data. The performance of TRANSMODIS was first validated on a set of transcription factor perturbation experiments (TFPEs) involving Pho4p, a well studied TF in Saccharomyces cerevisiae. TRANSMODIS removed elements of arbitrariness in manual target gene selection process and produced results that concur with one's intuition. TRANSMODIS was further validated on a genome-wide scale by comparing it with two other methods in Saccharomyces cerevisiae. The usefulness of TRANSMODIS was then demonstrated by applying it to the identification of direct targets of DAF-16, a critical TF regulating ageing in Caenorhabditis elegans. We found that 189 genes were tightly regulated by DAF-16. In addition, DAF-16 has differential preference for motifs when acting as an activator or repressor, which awaits experimental verification. TRANSMODIS is computationally efficient and robust, making it a useful probabilistic framework for finding immediate targets

Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein

BACKGROUND: We previously described the selection of a T20-dependent human immunodeficiency virus type-1 (HIV-1) variant in a patient on T20 therapy. The fusion inhibitor T20 targets the viral envelope (Env) protein by blocking a conformational switch that is critical for viral entry into the host cell. T20-dependent viral entry is the result of 2 mutations in Env (GIA-SKY), creating a protein that undergoes a premature conformational switch, and the presence of T20 prevents this premature switch and rescues viral entry. In the present study, we performed 6 independent evolution experiments with the T20-dependent HIV-1 variant in the absence of T20, with the aim to identify second site compensatory changes, which may provide new mechanistic insights into Env function and the T20-dependence mechanism. RESULTS: Escape variants with improved replication capacity appeared within 42 days in 5 evolution cultures. Strikingly, 3 cultures revealed the same single amino acid change in the CD4 binding region of Env (glycine at position 431 substituted for arginine: G431R). This mutation was sufficient to abolish the T20-dependence phenotype and restore viral replication in the absence of T20. The GIA-SKY-G431R escape variant produces an Env protein that exhibits reduced syncytia formation and reduced cell-cell fusion activity. The escape variant was more sensitive to an antibody acting on an early gp41 intermediate, suggesting that the G431R mutation helps preserve a pre-fusion Env conformation, similar to T20 action. The escape variant was also less sensitive to soluble CD4, suggesting a reduced CD4 receptor affinity. CONCLUSION: The forced evolution experiments indicate that the premature conformational switch of the T20-dependent HIV-1 Env variant (GIA-SKY) can be corrected by a second site mutation in Env (GIA-SKY-G431R) that affects the interaction with the CD4 receptor

BCAA catabolism in brown fat controls energy homeostasis through SLC25A44.

Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes systemic BCAA clearance in mice and humans. In turn, a BAT-specific defect in BCAA catabolism attenuates systemic BCAA clearance, BAT fuel oxidation and thermogenesis, leading to diet-induced obesity and glucose intolerance. Mechanistically, active BCAA catabolism in BAT is mediated by SLC25A44, which transports BCAAs into mitochondria. Our results suggest that BAT serves as a key metabolic filter that controls BCAA clearance via SLC25A44, thereby contributing to the improvement of metabolic health

Abrogated Inflammatory Response Promotes Neurogenesis in a Murine Model of Japanese Encephalitis

Japanese encephalitis virus (JEV) induces neuroinflammation with typical features of viral encephalitis, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. The detrimental effects of inflammation on neurogenesis have been reported in various models of acute and chronic inflammation. We investigated whether JEV-induced inflammation has similar adverse effects on neurogenesis and whether those effects can be reversed using an anti-inflammatory compound minocycline.Here, using in vitro studies and mouse models, we observed that an acute inflammatory milieu is created in the subventricular neurogenic niche following Japanese encephalitis (JE) and a resultant impairment in neurogenesis occurs, which can be reversed with minocycline treatment. Immunohistological studies showed that proliferating cells were replenished and the population of migrating neuroblasts was restored in the niche following minocycline treatment. In vitro, we checked for the efficacy of minocycline as an anti-inflammatory compound and cytokine bead array showed that production of cyto/chemokines decreased in JEV-activated BV2 cells. Furthermore, mouse neurospheres grown in the conditioned media from JEV-activated microglia exhibit arrest in both proliferation and differentiation of the spheres compared to conditioned media from control microglia. These effects were completely reversed when conditioned media from JEV-activated and minocycline treated microglia was used.This study provides conclusive evidence that JEV-activated microglia and the resultant inflammatory molecules are anti-proliferative and anti-neurogenic for NSPCs growth and development, and therefore contribute to the viral neuropathogenesis. The role of minocycline in restoring neurogenesis may implicate enhanced neuronal repair and attenuation of the neuropsychiatric sequelae in JE survivors

FITBAR: a web tool for the robust prediction of prokaryotic regulons

<p>Abstract</p> <p>Background</p> <p>The binding of regulatory proteins to their specific DNA targets determines the accurate expression of the neighboring genes. The <it>in silico </it>prediction of new binding sites in completely sequenced genomes is a key aspect in the deeper understanding of gene regulatory networks. Several algorithms have been described to discriminate against false-positives in the prediction of new binding targets; however none of them has been implemented so far to assist the detection of binding sites at the genomic scale.</p> <p>Results</p> <p>FITBAR (Fast Investigation Tool for Bacterial and Archaeal Regulons) is a web service designed to identify new protein binding sites on fully sequenced prokaryotic genomes. This tool consists in a workbench where the significance of the predictions can be compared using different statistical methods, a feature not found in existing resources. The Local Markov Model and the Compound Importance Sampling algorithms have been implemented to compute the P-value of newly discovered binding sites. In addition, FITBAR provides two optimized genomic scanning algorithms using either log-odds or entropy-weighted position-specific scoring matrices. Other significant features include the production of a detailed genomic context map for each detected binding site and the export of the search results in spreadsheet and portable document formats. FITBAR discovery of a high affinity <it>Escherichia coli </it>NagC binding site was validated experimentally <it>in vitro </it>as well as <it>in vivo </it>and published.</p> <p>Conclusions</p> <p>FITBAR was developed in order to allow fast, accurate and statistically robust predictions of prokaryotic regulons. This feature constitutes the main advantage of this web tool over other matrix search programs and does not impair its performance. The web service is available at <url>http://archaea.u-psud.fr/fitbar</url>.</p

Application of ordinal logistic regression analysis in determining risk factors of child malnutrition in Bangladesh

<p>Abstract</p> <p>Background</p> <p>The study attempts to develop an ordinal logistic regression (OLR) model to identify the determinants of child malnutrition instead of developing traditional binary logistic regression (BLR) model using the data of Bangladesh Demographic and Health Survey 2004.</p> <p>Methods</p> <p>Based on weight-for-age anthropometric index (Z-score) child nutrition status is categorized into three groups-severely undernourished (< -3.0), moderately undernourished (-3.0 to -2.01) and nourished (≥-2.0). Since nutrition status is ordinal, an OLR model-proportional odds model (POM) can be developed instead of two separate BLR models to find predictors of both malnutrition and severe malnutrition if the proportional odds assumption satisfies. The assumption is satisfied with low p-value (0.144) due to violation of the assumption for one co-variate. So partial proportional odds model (PPOM) and two BLR models have also been developed to check the applicability of the OLR model. Graphical test has also been adopted for checking the proportional odds assumption.</p> <p>Results</p> <p>All the models determine that age of child, birth interval, mothers' education, maternal nutrition, household wealth status, child feeding index, and incidence of fever, ARI & diarrhoea were the significant predictors of child malnutrition; however, results of PPOM were more precise than those of other models.</p> <p>Conclusion</p> <p>These findings clearly justify that OLR models (POM and PPOM) are appropriate to find predictors of malnutrition instead of BLR models.</p

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu