Exposure to 4-tert-octylphenol accelerates sexual differentiation and disrupts expression of steroidogenic factor 1 in developing bullfrogs.

Sex-specific gonadal steroidogenesis during development is critical to differentiation of the sexually dimorphic phenotype and reproductive function of adult organisms. Environmental contaminants may affect the process of sexual differentiation through disruption of steroid production and/or action. Control of the steroidogenic metabolic pathway is regulated partly by P450 cytochrome hydroxylases, and the expression of many of these enzymes is controlled by the orphan nuclear receptor, steroidogenic factor-1 (SF-1). In mammals, SF-1 expression is critical for development of the reproductive axis and adult reproductive function. In the bullfrog Rana catesbeiana, during sequential stages of development encompassing sexual differentiation, SF-1 protein expression becomes elevated in ovaries of sexually differentiating females, whereas expression in testes decreases. We exposed tadpoles to the industrial pollutant octylphenol (OP) for 24 hr before and during the critical stages of sexual differentiation to determine whether this known endocrine disruptor affects sex differentiation and SF-1 expression. We found that both females and males treated with an environmentally relevant low dose (10(-9)M) of OP underwent early gonadal differentiation. Furthermore, OP exposure disrupted the sexually dimorphic expression of SF-1 that occurs during sexual differentiation. Our results suggest that OP exposure may affect developmental processes that could ultimately influence adult reproductive function and that these disruptive effects may be mediated in partly through disturbances in gene regulation by SF-1

Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage

Annexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H2O2), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.Natural Sciences and Engineering Research Council of Canada (NSERC); European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Beatrice Hunter Cancer Research Institute; Terry Fox Foundationinfo:eu-repo/semantics/publishedVersio

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Skewed genomic variability in strains of the toxigenic bacterial pathogen, Clostridium perfringens

Clostridium perfringens is a Gram-positive, anaerobic spore-forming bacterium commonly found in soil, sediments, and the human gastrointestinal tract. C. perfringens is responsible for a wide spectrum of disease, including food poisoning, gas gangrene (clostridial myonecrosis), enteritis necroticans, and non-foodborne gastrointestinal infections. The complete genome sequences of Clostridium perfringens strain ATCC 13124, a gas gangrene isolate and the species type strain, and the enterotoxin-producing food poisoning strain SM101, were determined and compared with the published C. perfringens strain 13 genome. Comparison of the three genomes revealed considerable genomic diversity with >300 unique "genomic islands" identified, with the majority of these islands unusually clustered on one replichore. PCR-based analysis indicated that the large genomic islands are widely variable across a large collection of C. perfringens strains. These islands encode genes that correlate to differences in virulence and phenotypic characteristics of these strains. Significant differences between the strains include numerous novel mobile elements and genes encoding metabolic capabilities, strain-specific extracellular polysaccharide capsule, sporulation factors, toxins, and other secreted enzymes, providing substantial insight into this medically important bacterial pathogen. ©2006 by Cold Spring Harbor Laboratory Press

Gender comparisons of fat talk in the United Kingdom and the United States

This study compared different forms of body talk, including "fat talk," among 231 university men and women in central England (UK; n = 93) and the southeastern United States (US; n = 138). A 2 (gender) by 2 (country) repeated measures ANOVA across types of body talk (negative, self-accepting, positive) and additional Chi-square analyses revealed that there were differences across gender and between the UK and US cultures. Specifically, UK and US women were more likely to report frequently hearing or perceiving pressure to engage in fat talk than men. US women and men were also more likely to report pressure to join in self-accepting body talk than UK women and men

Genetic variability and ontogeny predict microbiome structure in a disease-challenged montane amphibian

Amphibian populations worldwide are at risk of extinction from infectious diseases, including chytridiomycosis caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). Amphibian cutaneous microbiomes interact with Bd and can confer protective benefits to the host. The composition of the microbiome itself is influenced by many environment- and host-related factors. However, little is known about the interacting effects of host population structure, genetic variation and developmental stage on microbiome composition and Bd prevalence across multiple sites. Here we explore these questions in Amietia hymenopus, a disease-affected frog in southern Africa. We use microsatellite genotyping and 16S amplicon sequencing to show that the microbiome associated with tadpole mouthparts is structured spatially, and is influenced by host genotype and developmental stage. We observed strong genetic structure in host populations based on rivers and geographic distances, but this did not correspond to spatial patterns in microbiome composition. These results indicate that demographic and host genetic factors affect microbiome composition within sites, but different factors are responsible for host population structure and microbiome structure at the between-site level. Our results help to elucidate complex within- and among- population drivers of microbiome structure in amphibian populations. That there is a genetic basis to microbiome composition in amphibians could help to inform amphibian conservation efforts against infectious diseases