Comprehensive analysis of the chromatin landscape in Drosophila melanogaster.

Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function

Animal-related factors associated with moderate-to-severe diarrhea in children younger than five years in western Kenya: A matched case-control study

Background Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years. Exposure to domestic animals may be a risk factor for diarrheal disease. The objectives of this study were to identify animal-related exposures associated with cases of moderate-to-severe diarrhea (MSD) in children in rural western Kenya, and to identify the major zoonotic enteric pathogens present in domestic animals residing in the homesteads of case and control children. Methodology/Principal findings We characterized animal-related exposures in a subset of case and control children (n = 73 pairs matched on age, sex and location) with reported animal presence at home enrolled in the Global Enteric Multicenter Study in western Kenya, and analysed these for an association with MSD. We identified potentially zoonotic enteric pathogens in pooled fecal specimens collected from domestic animals resident at children’s homesteads. Variables that were associated with decreased risk of MSD were washing hands after animal contact (matched odds ratio [MOR] = 0.2; 95% CI 0.08–0.7), and presence of adult sheep that were not confined in a pen overnight (MOR = 0.1; 0.02–0.5). Variables that were associated with increased risk of MSD were increasing number of sheep owned (MOR = 1.2; 1.0–1.5), frequent observation of fresh rodent excreta (feces/urine) outside the house (MOR = 7.5; 1.5–37.2), and participation of the child in providing water to chickens (MOR = 3.8; 1.2–12.2). Of 691 pooled specimens collected from 2,174 domestic animals, 159 pools (23%) tested positive for one or more potentially zoonotic enteric pathogens (Campylobacter jejuni, C. coli, non-typhoidal Salmonella, diarrheagenic E. coli, Giardia, Cryptosporidium, or rotavirus). We did not find any association between the presence of particular pathogens in household animals, and MSD in children. Conclusions and significance Public health agencies should continue to promote frequent hand washing, including after animal contact, to reduce the risk of MSD. Future studies should address specific causal relations of MSD with sheep and chicken husbandry practices, and with the presence of rodents

Probing genetic control of swine responses to PRRSV infection: current progress of the PRRS host genetics consortium

<p>Abstract</p> <p>Background</p> <p>Understanding the role of host genetics in resistance to porcine reproductive and respiratory syndrome virus (PRRSV) infection, and the effects of PRRS on pig health and related growth, are goals of the PRRS Host Genetics Consortium (PHGC).</p> <p>Methods</p> <p>The project uses a nursery pig model to assess pig resistance/susceptibility to primary PRRSV infection. To date, 6 groups of 200 crossbred pigs from high health farms were donated by commercial sources. After acclimation, the pigs were infected with PRRSV in a biosecure facility and followed for 42 days post infection (dpi). Blood samples were collected at 0, 4, 7, 10, 14, 21, 28, 35 and 42 dpi for serum and whole blood RNA gene expression analyses; weekly weights were recorded for growth traits. All data have been entered into the PHGC relational database. Genomic DNAs from all PHGC1-6 pigs were prepared and genotyped with the Porcine SNP60 SNPchip.</p> <p>Results</p> <p>Results have affirmed that all challenged pigs become PRRSV infected with peak viremia being observed between 4-21 dpi. Multivariate statistical analyses of viral load and weight data have identified PHGC pigs in different virus/weight categories. Sera are now being compared for factors involved in recovery from infection, including speed of response and levels of immune cytokines. Genome-wide association studies (GWAS) are underway to identify genes and chromosomal locations that identify PRRS resistant/susceptible pigs and pigs able to maintain growth while infected with PRRSV.</p> <p>Conclusions</p> <p>Overall, the PHGC project will enable researchers to discover and verify important genotypes and phenotypes that predict resistance/susceptibility to PRRSV infection. The availability of PHGC samples provides a unique opportunity to continue to develop deeper phenotypes on every PRRSV infected pig.</p

The Expression and Localization of N-Myc Downstream-Regulated Gene 1 in Human Trophoblasts

The protein N-Myc downstream-regulated gene 1 (NDRG1) is implicated in the regulation of cell proliferation, differentiation, and cellular stress response. NDRG1 is expressed in primary human trophoblasts, where it promotes cell viability and resistance to hypoxic injury. The mechanism of action of NDRG1 remains unknown. To gain further insight into the intracellular action of NDRG1, we analyzed the expression pattern and cellular localization of endogenous NDRG1 and transfected Myc-tagged NDRG1 in human trophoblasts exposed to diverse injuries. In standard conditions, NDRG1 was diffusely expressed in the cytoplasm at a low level. Hypoxia or the hypoxia mimetic cobalt chloride, but not serum deprivation, ultraviolet (UV) light, or ionizing radiation, induced the expression of NDRG1 in human trophoblasts and the redistribution of NDRG1 into the nucleus and cytoplasmic membranes associated with the endoplasmic reticulum (ER) and microtubules. Mutation of the phosphopantetheine attachment site (PPAS) within NDRG1 abrogated this pattern of redistribution. Our results shed new light on the impact of cell injury on NDRG1 expression patterns, and suggest that the PPAS domain plays a key role in NDRG1's subcellular distribution. © 2013 Shi et al

Evaluation of efalizumab using safe psoriasis control

BACKGROUND: Safe Psoriasis Control (SPC) is an important comprehensive measure that is validated for the assessment of benefit:risk of psoriasis treatments, combining efficacy, quality of life, and safety measures. The objective of this analysis was to assess the benefit:risk of efalizumab, a novel biologic agent indicated for the treatment of moderate-to-severe plaque psoriasis, by applying the SPC to data from randomized, placebo-controlled clinical studies of efalizumab. METHODS: SPC was applied to week 12 data from four placebo-controlled, Phase III studies: three retrospective and one prospective, the latter including a cohort of "high-need" patients for whom existing therapies were inadequate or unsuitable. RESULTS: In the retrospective analysis, 39.4% of patients achieved SPC after 12 weeks of treatment with efalizumab, compared with 10.4% for placebo. In the prospective analysis, 34.3% of patients achieved SPC after 12 weeks of treatment with efalizumab, compared with 7.3% on placebo. Among high-need patients, 33.0% achieved SPC, compared with 3.4% on placebo. CONCLUSION: Efalizumab has a favorable benefit:risk profile using the comprehensive outcome measure SPC

Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes.

Heterogeneity in early language development in autism spectrum disorder (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here, we identified a large-scale association between multiple coordinated blood leukocyte gene coexpression modules and the multivariate functional neuroimaging (fMRI) response to speech. Gene coexpression modules associated with the multivariate fMRI response to speech were different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and poor versus good early language outcome. Associated coexpression modules were enriched in genes that are broadly expressed in the brain and many other tissues. These coexpression modules were also enriched in ASD-associated, prenatal, human-specific, and language-relevant genes. This work highlights distinctive neurobiology in ASD subtypes with different early language outcomes that is present well before such outcomes are known. Associations between neuroimaging measures and gene expression levels in blood leukocytes may offer a unique in vivo window into identifying brain-relevant molecular mechanisms in ASD

Physical, Psychological and Emotional Benefits of Green Physical Activity: An Ecological Dynamics Perspective

© 2015 Springer International Publishing Switzerland Increasing evidence supports the multiple benefits to physical, psychological and emotional wellbeing of green physical activity, a topic of increasing interest in the past decade. Research has revealed a synergistic benefit of green physical activity, which includes all aspects of exercise and physical activity in the presence of nature. Our theoretical analysis suggests there are three distinct levels of engagement in green physical activity, with each level reported to have a positive effect on human behaviours. However, the extent to which each level of green physical activity benefits health and wellbeing is assumed to differ, requiring confirmation in future research. This elucidation of understanding is needed because previous literature has tended to focus on recording empirical evidence rather than developing a sound theoretical framework to understand green physical activity effects. Here we propose an ecological dynamics rationale to explain how and why green physical activity might influence health and wellbeing of different population groups. This framework suggests a number of unexplored, interacting constraints related to types of environment and population groups, which shape reported levels of benefit of green physical activity. Further analysis is needed to clarify the explicit relationship between green physical activity and health and wellbeing, including levels of engagement, types of environmental constraints, levels of physical activity, adventure effects, skill effects and sampling of different populations

Effective resting-state connectivity in severe unipolar depression before and after electroconvulsive therapy

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depressive disorders. A recent multi-center study found no consistent changes in correlation-based (undirected) resting-state connectivity after ECT. Effective (directed) connectivity may provide more insight into the working mechanism of ECT. OBJECTIVE: We investigated whether there are consistent changes in effective resting-state connectivity. METHODS: This multi-center study included data from 189 patients suffering from severe unipolar depression and 59 healthy control participants. Longitudinal data were available for 81 patients and 24 healthy controls. We used dynamic causal modeling for resting-state functional magnetic resonance imaging to determine effective connectivity in the default mode, salience and central executive networks before and after a course of ECT. Bayesian general linear models were used to examine differences in baseline and longitudinal effective connectivity effects associated with ECT and its effectiveness. RESULTS: Compared to controls, depressed patients showed many differences in effective connectivity at baseline, which varied according to the presence of psychotic features and later treatment outcome. Additionally, effective connectivity changed after ECT, which was related to ECT effectiveness. Notably, treatment effectiveness was associated with decreasing and increasing effective connectivity from the posterior default mode network to the left and right insula, respectively. No effects were found using correlation-based (undirected) connectivity. CONCLUSIONS: A beneficial response to ECT may depend on how brain regions influence each other in networks important for emotion and cognition. These findings further elucidate the working mechanisms of ECT and may provide directions for future non-invasive brain stimulation research

Common Functional Correlates of Head-Strike Behavior in the Pachycephalosaur Stegoceras validum (Ornithischia, Dinosauria) and Combative Artiodactyls

BACKGROUND: Pachycephalosaurs were bipedal herbivorous dinosaurs with bony domes on their heads, suggestive of head-butting as seen in bighorn sheep and musk oxen. Previous biomechanical studies indicate potential for pachycephalosaur head-butting, but bone histology appears to contradict the behavior in young and old individuals. Comparing pachycephalosaurs with fighting artiodactyls tests for common correlates of head-butting in their cranial structure and mechanics. METHODS/PRINCIPAL FINDINGS: Computed tomographic (CT) scans and physical sectioning revealed internal cranial structure of ten artiodactyls and pachycephalosaurs Stegoceras validum and Prenocephale prenes. Finite element analyses (FEA), incorporating bone and keratin tissue types, determined cranial stress and strain from simulated head impacts. Recursive partition analysis quantified strengths of correlation between functional morphology and actual or hypothesized behavior. Strong head-strike correlates include a dome-like cephalic morphology, neurovascular canals exiting onto the cranium surface, large neck muscle attachments, and dense cortical bone above a sparse cancellous layer in line with the force of impact. The head-butting duiker Cephalophus leucogaster is the closest morphological analog to Stegoceras, with a smaller yet similarly rounded dome. Crania of the duiker, pachycephalosaurs, and bighorn sheep Ovis canadensis share stratification of thick cortical and cancellous layers. Stegoceras, Cephalophus, and musk ox crania experience lower stress and higher safety factors for a given impact force than giraffe, pronghorn, or the non-combative llama. CONCLUSIONS/SIGNIFICANCE: Anatomy, biomechanics, and statistical correlation suggest that some pachycephalosaurs were as competent at head-to-head impacts as extant analogs displaying such combat. Large-scale comparisons and recursive partitioning can greatly refine inference of behavioral capability for fossil animals

Type D Personality, Temperament, and Mental Health in Military Personnel Awaiting Deployment

Type D personality, temperament, and mental health in military personnel awaitin