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

Influence of ovarian hormones deprivation on gene expression in the lower urinary tract of rats

OBJECTIVE: Identify the influence of ovarian hormone deprivation in expression genes on the lower urinary tract of rats. MATERIALS AND METHODS: This study deals with gene screening on lower urinary tract of rats. Fifty isogenic rats divided in two groups of twenty-five animals have their lower urinary tract surgically removed: group I, ovariectomized rats 30 days prior to surgery; group II, non-ovariectomized rats. Total RNA was isolated from bladder and urethra, and differential expression of genes was analyzed quantitative, qualitative and comparatively by array technology and RT-PCR. RESULTS: A total of 76 candidate genes were identified as differentially expressed between the groups, 26 being lower expressed in group II, and 50 in group I. Among them, differential expression validation was confirmed by RT-PCR for three lower expressed genes in group I: Vascular Endothelial Growth Factor (VEGF), Beta-2 Microglobulin (B2M) and Cytochrome c Oxidase subunit I (COX I). CONCLUSION: Ovarian hormone deprivation influences the expression genes on lower urinary tract. We demonstrated that a 30-day period of castration down regulate the expression of VEGF, B2M and COX I in adult rats which are involved in activities of angiogenesis, immune responses and cellular metabolism respectively.Federal University of São Paulo Department of GynecologyUNIFESP, Department of GynecologySciEL

Impact of surface adhesion and sample heterogeneity on the multiscale mechanical characterisation of soft biomaterials

Funding from the Engineering and Physical Sciences Research Council (EP/L505602/1) is gratefully acknowledged

Substance use risk profiles and associations with early substance use in adolescence

We examined whether anxiety sensitivity, hopelessness, sensation seeking, and impulsivity (i.e., revised version of the Substance Use Risk Profile Scale) would be related to the lifetime prevalence and age of onset of alcohol, tobacco, and cannabis use, and to polydrug use in early adolescence. Baseline data of a broader effectiveness study were used from 3,783 early adolescents aged 11–15 years. Structural equation models showed that hopelessness and sensation seeking were indicative of ever-used alcohol, tobacco or cannabis and for the use of more than one substance. Furthermore, individuals with higher levels of hopelessness had a higher chance of starting to use alcohol or cannabis at an earlier age, but highly anxiety sensitive individuals were less likely to start using alcohol use at a younger age. Conclusively, early adolescents who report higher levels of hopelessness and sensation seeking seem to be at higher risk for an early onset of substance use and poly substance use

Genome Wide Association Identifies PPFIA1 as a Candidate Gene for Acute Lung Injury Risk Following Major Trauma

Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated B-lymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research

Motivations for participating in a non-interventional gender-based violence survey in a low-income setting in South Africa

Abstract Background Qualitative study of motivations to participate in research into violence and other sensitive issues can help interpretation of findings from community based quantitative surveys. It is equally important to conduct research that may enable a deeper understanding on what motivates people to participate in GBV studies. To date, not much research has been conducted to investigate the factors that influence non-enrolment and enrolment in GBV studies from the viewpoint of the real participants. The present study sought to explore people’s reasons for participating in a non-intervention GBV community-based survey in Gauteng province, South Africa. Methods Twenty-two qualitative in-depth interviews were conducted with adult black African men and women who had participated in a gender-based violence survey conducted in a low-income setting in South Africa. Results Some participants reported motives for survey participation which could be interpreted as altruistic. Their motives included a desire to contribute to advancement of knowledge and to share life experiences so that unknown others could learn from these experiences. Yet, some participants hoped their participation will result in personal benefit or that they may be helped with their socio-economic challenges. The analysis further revealed a complex relationship between altruism and self-interest motives for participating in the survey amongst some of the participants. Conclusion We conclude that it is difficult to discern which motive was primary or preceded the other. This is because such motives are not fixed, probably multiple and owing to their fluidity, may shift in people’s minds at different times and depending on the nature of the conversation. Moreover, there may be a shift in the weight given to different motives over time

The role of impulsivity in the aetiology of drug dependence: reward sensitivity versus automaticity

Journal ArticleResearch Support, Non-U.S. Gov'tCopyright © The Author(s) 2011.RATIONALE: Impulsivity has long been known as a risk factor for drug dependence, but the mechanisms underpinning this association are unclear. Impulsivity may confer hypersensitivity to drug reinforcement which establishes higher rates of instrumental drug-seeking and drug-taking behaviour, or may confer a propensity for automatic (non-intentional) control over drug-seeking/taking and thus intransigence to clinical intervention. METHOD: The current study sought to distinguish these two accounts by measuring Barratt Impulsivity and craving to smoke in 100 smokers prior to their completion of an instrumental concurrent choice task for tobacco (to measure the rate of drug-seeking) and an ad libitum smoking test (to measure the rate of drug-taking-number of puffs consumed). RESULTS: The results showed that impulsivity was not associated with higher rates of drug-seeking/taking, but individual differences in smoking uptake and craving were. Rather, nonplanning impulsivity moderated (decreased) the relationship between craving and drug-taking, but not drug-seeking. CONCLUSIONS: These data suggest that whereas the uptake of drug use is mediated by hypervaluation of the drug as an instrumental goal, the orthogonal trait nonplanning impulsivity confers a propensity for automatic control over well-practiced drug-taking behaviour.MR

Fetal and infant origins of asthma

Previous studies have suggested that asthma, like other common diseases, has at least part of its origin early in life. Low birth weight has been shown to be associated with increased risks of asthma, chronic obstructive airway disease, and impaired lung function in adults, and increased risks of respiratory symptoms in early childhood. The developmental plasticity hypothesis suggests that the associations between low birth weight and diseases in later life are explained by adaptation mechanisms in fetal life and infancy in response to various adverse exposures. Various pathways leading from adverse fetal and infant exposures to growth adaptations and respiratory health outcomes have been studied, including fetal and early infant growth patterns, maternal smoking and diet, children’s diet, respiratory tract infections and acetaminophen use, and genetic susceptibility. Still, the specific adverse exposures in fetal and early postnatal life leading to respiratory disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life, and their epigenetic mechanisms may underlie the complex associations of low birth weight with respiratory disease in later life. New well-designed epidemiological studies are needed to identify the specific underlying mechanisms. This review is focused on specific adverse fetal and infant growth patterns and exposures, genetic susceptibility, possible respiratory adaptations and perspectives for new studies