Early star-forming galaxies and the reionization of the Universe

Star forming galaxies represent a valuable tracer of cosmic history. Recent observational progress with Hubble Space Telescope has led to the discovery and study of the earliest-known galaxies corresponding to a period when the Universe was only ~800 million years old. Intense ultraviolet radiation from these early galaxies probably induced a major event in cosmic history: the reionization of intergalactic hydrogen. New techniques are being developed to understand the properties of these most distant galaxies and determine their influence on the evolution of the universe.Comment: Review article appearing in Nature. This posting reflects a submitted version of the review formatted by the authors, in accordance with Nature publication policies. For the official, published version of the review, please see http://www.nature.com/nature/archive/index.htm

A regression analysis of gene expression in ES cells reveals two gene classes that are significantly different in epigenetic patterns

<p>Abstract</p> <p>Background</p> <p>To understand the gene regulatory system that governs the self-renewal and pluripotency of embryonic stem cells (ESCs) is an important step for promoting regenerative medicine. In it, the role of several core transcription factors (TFs), such as Oct4, Sox2 and Nanog, has been intensively investigated, details of their involvement in the genome-wide gene regulation are still not well clarified.</p> <p>Methods</p> <p>We constructed a predictive model of genome-wide gene expression in mouse ESCs from publicly available ChIP-seq data of 12 core TFs. The tag sequences were remapped on the genome by various alignment tools. Then, the binding density of each TF is calculated from the genome-wide bona fide TF binding sites. The TF-binding data was combined with the data of several epigenetic states (DNA methylation, several histone modifications, and CpG island) of promoter regions. These data as well as the ordinary peak intensity data were used as predictors of a simple linear regression model that predicts absolute gene expression. We also developed a pipeline for analyzing the effects of predictors and their interactions.</p> <p>Results</p> <p>Through our analysis, we identified two classes of genes that are either well explained or inefficiently explained by our model. The latter class seems to be genes that are not directly regulated by the core TFs. The regulatory regions of these gene classes show apparently distinct patterns of DNA methylation, histone modifications, existence of CpG islands, and gene ontology terms, suggesting the relative importance of epigenetic effects. Furthermore, we identified statistically significant TF interactions correlated with the epigenetic modification patterns.</p> <p>Conclusions</p> <p>Here, we proposed an improved prediction method in explaining the ESC-specific gene expression. Our study implies that the majority of genes are more or less directly regulated by the core TFs. In addition, our result is consistent with the general idea of relative importance of epigenetic effects in ESCs.</p

Hepatitis Vaccination of Men Who Have Sex with Men at Gay Pride Events

Prevention researchers have advocated primary prevention such as vaccination in alternative venues. However, there have been major questions about both the attendance of, and the ability to, vaccinate high-risk individuals in such settings. The current study seeks to assess the feasibility of vaccinating high-risk men who have sex with men (MSM) at Gay Pride events. The research questions are: Do gay men who are sampled at Gay Pride events engage in more or less risky behavior than gay men sampled at other venues? Do the gay men who receive hepatitis vaccinations at Gay Pride engage in more or less risky behavior than gay men at Gay Pride who do not receive hepatitis vaccination? Of the 3689 MSM that completed the Field Risk Assessment (FRA), 1095/3689 = 29.68% were recruited at either the 2006 or 2007 Long Beach, California Gay Pride events. The remaining, 2594/3689 = 70.32% were recruited at Long Beach gay bars, gay community organizations and institutions, and through street recruitment in various gay enclaves in the Long Beach area. Logistic regression analysis yielded eight factors that were associated with non-attendance of Gay Pride: Age, had sex while high in the last 12 months, had unprotected anal intercourse (UAI) in the last 12 months, had sex for drugs/money in the last 12 months, been diagnosed with a sexually transmitted infection (STI) in the last 12 months, used nitrites (poppers) in the last 12 months, and used methamphetamine in the last 12 months. Identifying as White, Asian, or African American compared to Hispanic was also associated with non-attendance. Bivariate analysis indicated that, of the MSM sampled at Gay Pride, 280/1095 = 25.57% received a hepatitis vaccination there. The MSM sampled at Gay Pride who reported engaging in UAI or having used any stimulant (cocaine, crack-cocaine, or methamphetamine) in the last 12 months were more likely to receive hepatitis vaccination on-site. The results provide evidence for the viability of successfully vaccinating high-risk MSM at Gay Pride events. However, it is vital that no-cost vaccinations are also funded in other community settings such as STI clinics, drug treatment programs, prisons, universities, and other community resource centers in order to reach those additional high-risk MSM who do not attend Gay Pride

Employment of ex-prisoners with mental health problems, a realistic evaluation protocol

Background Offenders with a mental illness are routinely excluded from vocational services due to their mental health. Employment has shown to be very important in improving mental health, reducing recidivism, and connecting people to society. This study examines the effectiveness of an established intervention which is relatively untested in this population, Individual Placement and Support (IPS), to help offenders with mental health problems into competitive employment. The overall research question is whether IPS is effective in gaining and sustaining competitive employment for offenders with a Severe Mental Illness (SMI). The context is an English criminal justice setting across different populations. The study will also measure non-vocational outcomes such as recidivism, mental health and social stability. Methods/Design A Realistic Evaluation (RE) design will address the questions “What works, for whom, and in what circumstances?” This study includes pre and post comparisons for a cohort of approximately 20 people taking part in IPS, and a similar number of controls, over a one year period. The RE also consists of interviews with practitioners and offenders in order to understand how IPS works and develops within the criminal justice system (CJS). By applying this framework the research can go from discovering whether IPS works, to how and why (or why not) IPS works. This is achieved by examining where the intervention is occurring (Context (C)), the mechanisms (M) that create particular behaviours, and how the outcomes (O) from the intervention all come together (CMOs). Employment outcomes will also be examined for all participants. Discussion By applying RE the research will permit inferences to be drawn about how and why (or why not) IPS works, by examining context, mechanisms and outcomes. IPS has never been implemented within the CJS in the United Kingdom. As a result, this evaluative research will not only provide a novel insight into the core research areas, but also how the intervention can be improved for others in the future

Conduct disorder in girls: neighborhoods, family characteristics, and parenting behaviors

<p>Abstract</p> <p>Background</p> <p>Little is known about the social context of girls with conduct disorder (CD), a question of increasing importance to clinicians and researchers. The purpose of this study was to examine the associations between three social context domains (neighborhood, family characteristics, and parenting behaviors) and CD in adolescent girls, additionally testing for race moderation effects. We predicted that disadvantaged neighborhoods, family characteristics such as parental marital status, and parenting behaviors such as negative discipline would characterize girls with CD. We also hypothesized that parenting behaviors would mediate the associations between neighborhood and family characteristics and CD.</p> <p>Methods</p> <p>We recruited 93 15–17 year-old girls from the community and used a structured psychiatric interview to assign participants to a CD group (n = 52) or a demographically matched group with no psychiatric disorder (n = 41). Each girl and parent also filled out questionnaires about neighborhood, family characteristics, and parenting behaviors.</p> <p>Results</p> <p>Neighborhood quality was not associated with CD in girls. Some family characteristics (parental antisociality) and parenting behaviors (levels of family activities and negative discipline) were characteristic of girls with CD, but notll. There was no moderation by race. Our hypothesis that the association between family characteristics and CD would be mediated by parenting behaviors was not supported.</p> <p>Conclusion</p> <p>This study expanded upon previous research by investigating multiple social context domains in girls with CD and by selecting a comparison group who were not different in age, social class, or race. When these factors are thus controlled, CD in adolescent girls is not significantly associated with neighborhood, but is associated with some family characteristics and some types of parental behaviors. However, the mechanisms underlying these relationships need to be further investigated. We discuss possible explanations for our findings and suggest directions for future research.</p

Active Suppression of Early Immune Response in Tobacco by the Human Pathogen Salmonella Typhimurium

The persistence of enteric pathogens on plants has been studied extensively, mainly due to the potential hazard of human pathogens such as Salmonella enterica being able to invade and survive in/on plants. Factors involved in the interactions between enteric bacteria and plants have been identified and consequently it was hypothesized that plants may be vectors or alternative hosts for enteric pathogens. To survive, endophytic bacteria have to escape the plant immune systems, which function at different levels through the plant-bacteria interactions. To understand how S. enterica survives endophyticaly we conducted a detailed analysis on its ability to elicit or evade the plant immune response. The models of this study were Nicotiana tabacum plants and cells suspension exposed to S. enterica serovar Typhimurium. The plant immune response was analyzed by looking at tissue damage and by testing oxidative burst and pH changes. It was found that S. Typhimurium did not promote disease symptoms in the contaminated plants. Live S. Typhimurium did not trigger the production of an oxidative burst and pH changes by the plant cells, while heat killed or chloramphenicol treated S. Typhimurium and purified LPS of Salmonella were significant elicitors, indicating that S. Typhimurium actively suppress the plant response. By looking at the plant response to mutants defective in virulence factors we showed that the suppression depends on secreted factors. Deletion of invA reduced the ability of S. Typhimurium to suppress oxidative burst and pH changes, indicating that a functional SPI1 TTSS is required for the suppression. This study demonstrates that plant colonization by S. Typhimurium is indeed an active process. S. Typhimurium utilizes adaptive strategies of altering innate plant perception systems to improve its fitness in the plant habitat. All together these results suggest a complex mechanism for perception of S. Typhimurium by plants

Modulation of Mrp1 (ABCc1) and Pgp (ABCb1) by Bilirubin at the Blood-CSF and Blood-Brain Barriers in the Gunn Rat

Accumulation of unconjugated bilirubin (UCB) in the brain causes bilirubin encephalopathy. Pgp (ABCb1) and Mrp1 (ABCc1), highly expressed in the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) respectively, may modulate the accumulation of UCB in brain. We examined the effect of prolonged exposure to elevated concentrations of UCB on expression of the two transporters in homozygous, jaundiced (jj) Gunn rats compared to heterozygous, not jaundiced (Jj) littermates at different developmental stages (2, 9, 17 and 60 days after birth). BBB Pgp protein expression was low in both jj and Jj pups at 9 days (about 16–27% of adult values), despite the up-regulation in jj animals (2 and 1.3 fold higher than age matched Jj animals at P9 and P17–P60, respectively); Mrp1 protein expression was barely detectable. Conversely, at the BCSFB Mrp1 protein expression was rather high (60–70% of the adult values) in both jj and Jj at P2, but was markedly (50%) down-regulated in jj pups starting at P9, particularly in the 4th ventricle choroid plexuses: Pgp was almost undetectable. The Mrp1 protein down regulation was accompanied by a modest up-regulation of mRNA, suggesting a translational rather than a transcriptional inhibition. In vitro exposure of choroid plexus epithelial cells obtained from normal rats to UCB, also resulted in a down-regulation of Mrp1 protein. These data suggest that down-regulation of Mrp1 protein at the BSCFB, resulting from a direct effect of UCB on epithelial cells, may impact the Mrp1-mediated neuroprotective functions of the blood-cerebrospinal fluid barrier and actually potentiate UCB neurotoxicity

The Microbiota Mediates Pathogen Clearance from the Gut Lumen after Non-Typhoidal Salmonella Diarrhea

Many enteropathogenic bacteria target the mammalian gut. The mechanisms protecting the host from infection are poorly understood. We have studied the protective functions of secretory antibodies (sIgA) and the microbiota, using a mouse model for S. typhimurium diarrhea. This pathogen is a common cause of diarrhea in humans world-wide. S. typhimurium (S. tmatt, sseD) causes a self-limiting gut infection in streptomycin-treated mice. After 40 days, all animals had overcome the disease, developed a sIgA response, and most had cleared the pathogen from the gut lumen. sIgA limited pathogen access to the mucosal surface and protected from gut inflammation in challenge infections. This protection was O-antigen specific, as demonstrated with pathogens lacking the S. typhimurium O-antigen (wbaP, S. enteritidis) and sIgA-deficient mice (TCRβ−/−δ−/−, JH−/−, IgA−/−, pIgR−/−). Surprisingly, sIgA-deficiency did not affect the kinetics of pathogen clearance from the gut lumen. Instead, this was mediated by the microbiota. This was confirmed using ‘L-mice’ which harbor a low complexity gut flora, lack colonization resistance and develop a normal sIgA response, but fail to clear S. tmatt from the gut lumen. In these mice, pathogen clearance was achieved by transferring a normal complex microbiota. Thus, besides colonization resistance ( = pathogen blockage by an intact microbiota), the microbiota mediates a second, novel protective function, i.e. pathogen clearance. Here, the normal microbiota re-grows from a state of depletion and disturbed composition and gradually clears even very high pathogen loads from the gut lumen, a site inaccessible to most “classical” immune effector mechanisms. In conclusion, sIgA and microbiota serve complementary protective functions. The microbiota confers colonization resistance and mediates pathogen clearance in primary infections, while sIgA protects from disease if the host re-encounters the same pathogen. This has implications for curing S. typhimurium diarrhea and for preventing transmission

Dark Matter in the Milky Way's Dwarf Spheroidal Satellites

The Milky Way's dwarf spheroidal satellites include the nearest, smallest and least luminous galaxies known. They also exhibit the largest discrepancies between dynamical and luminous masses. This article reviews the development of empirical constraints on the structure and kinematics of dSph stellar populations and discusses how this phenomenology translates into constraints on the amount and distribution of dark matter within dSphs. Some implications for cosmology and the particle nature of dark matter are discussed, and some topics/questions for future study are identified.Comment: A version with full-resolution figures is available at http://www.cfa.harvard.edu/~mwalker/mwdsph_review.pdf; 70 pages, 22 figures; invited review article to be published in Vol. 5 of the book "Planets, Stars, and Stellar Systems", published by Springe