Gene expression allelic imbalance in ovine brown adipose tissue impacts energy homeostasis

Heritable trait variation within a population of organisms is largely governed by DNA variations that impact gene transcription and protein function. Identifying genetic variants that affect complex functional traits is a primary aim of population genetics studies, especially in the context of human disease and agricultural production traits. The identification of alleles directly altering mRNA expression and thereby biological function is challenging due to difficulty in isolating direct effects of cis-acting genetic variations from indirect trans-acting genetic effects. Allele specific gene expression or allelic imbalance in gene expression (AI) occurring at heterozygous loci provides an opportunity to identify genes directly impacted by cis-acting genetic variants as indirect trans-acting effects equally impact the expression of both alleles. However, the identification of genes showing AI in the context of the expression of all genes remains a challenge due to a variety of technical and statistical issues. The current study focuses on the discovery of genes showing AI using single nucleotide polymorphisms as allelic reporters. By developing a computational and statistical process that addressed multiple analytical challenges, we ranked 5,809 genes for evidence of AI using RNA-Seq data derived from brown adipose tissue samples from a cohort of late gestation fetal lambs and then identified a conservative subgroup of 1,293 genes. Thus, AI was extensive, representing approximately 25% of the tested genes. Genes associated with AI were enriched for multiple Gene Ontology (GO) terms relating to lipid metabolism, mitochondrial function and the extracellular matrix. These functions suggest that cis-acting genetic variations causing AI in the population are preferentially impacting genes involved in energy homeostasis and tissue remodelling. These functions may contribute to production traits likely to be under genetic selection in the population.Shila Ghazanfar, Tony Vuocolo, Janna L. Morrison, Lisa M. Nicholas, Isabella C. McMillen, Jean Y. H. Yang, ... et al

Complex and unexpected dynamics in simple genetic regulatory networks

Peer reviewedPublisher PD

Expression of Emotion: When It Causes Trauma and When It Helps

The idea that clients should be encouraged to express strong emotion regarding the traumas they have suffered is widely assumed. This paper asks whether the empirical literature supports the underlying assumption that emotional expression leads to positive outcomes (better health and dissipation of distress). Studies in which individuals who have been given an opportunity to express emotions about past traumas are compared with subjects placed in appropriate control conditions are reviewed. The empirical literature suggests that eliciting emotion is harmful when it is not associated with reappraisal of past trauma, but helpful when the reappraisal occurs. The following guideline emerges: if trauma is to be revisited, it should be accompanied by reappraisal. Since this is sometimes difficult to engineer, alternative approaches for working with victims of trauma, not involving revisiting the trauma, are offered. Additionally, it is suggested that it can be helpful to identify the nature of the problem arising from the traumatic experience, and then provide therapeutic intervention that addresses the problem

A Compilation of Strategies for Implementing Clinical Innovations in Health and Mental Health

Efforts to identify, develop, refine, and test strategies to disseminate and implement evidence-based treatments have been prioritized in order to improve the quality of health and mental healthcare delivery. However, this task is complicated by an implementation science literature characterized by inconsistent language use and inadequate descriptions of implementation strategies. This article brings more depth and clarity to implementation research and practice by presenting a consolidated compilation of discrete implementation strategies, based upon a review of 205 sources published between 1995 and 2011. The resulting compilation includes 68 implementation strategies and definitions, which are grouped according to six key implementation processes: planning, educating, financing, restructuring, managing quality, and attending to the policy context. This consolidated compilation can serve as a reference to stakeholders who wish to implement clinical innovations in health and mental healthcare and can facilitate the development of multifaceted, multilevel implementation plans that are tailored to local contexts

Intergenerational Transmission of Glucose Intolerance and Obesity by In Utero Undernutrition in Mice

OBJECTIVE—Low birth weight (LBW) is associated with increased risk of obesity, diabetes, and cardiovascular disease during adult life. Moreover, this programmed disease risk can progress to subsequent generations. We previously described a mouse model of LBW, produced by maternal caloric undernutrition (UN) during late gestation. LBW offspring (F1-UN generation) develop progressive obesity and impaired glucose tolerance (IGT) with aging. We aimed to determine whether such metabolic phenotypes can be transmitted to subsequent generations in an experimental model, even in the absence of altered nutrition during the second pregnancy

Mental Health and School Functioning for Girls in the Child Welfare System : the Mediating Role of Future Orientation and School Engagement

This study investigated the association between mental health problems and academic and behavioral school functioning for adolescent girls in the child welfare system and determined whether school engagement and future orientation meditated the relationship. Participants were 231 girls aged between 12 and 19 who had been involved with the child welfare system. Results indicated that 39% of girls reported depressive symptoms in the clinical range and 54% reported posttraumatic symptoms in the clinical range. The most common school functioning problems reported were failing a class (41%) and physical fights with other students (35%). Participants reported a mean number of 1.7 school functioning problems. Higher levels of depression and PTSD were significantly associated with more school functioning problems. School engagement fully mediated the relationship between depression and school functioning and between PTSD and school functioning, both models controlling for age, race, and placement stability. Future orientation was not significantly associated with school functioning problems at the bivariate level. Findings suggest that school engagement is a potentially modifiable target for interventions aiming to ameliorate the negative influence of mental health problems on school functioning for adolescent girls with histories of abuse or neglect

Ecto-5’-nucleotidase: Structure function relationships

Ecto-5’-nucleotidase (ecto-5’-NT) is attached via a GPI anchor to the extracellular membrane, where it hydrolyses AMP to adenosine and phosphate. Related 5’-nucleotidases exist in bacteria, where they are exported into the periplasmic space. X-ray structures of the 5’-nucleotidase from E. coli showed that the enzyme consists of two domains. The N-terminal domain coordinates two catalytic divalent metal ions, whereas the C-terminal domain provides the substrate specificity pocket for the nucleotides. Thus, the substrate binds at the interface of the two domains. Here, the currently available structural information on ecto-5’NT is reviewed in relation to the catalytic properties and enzyme function

Fifty Years of Urban Accessibility: The Impact of Urban Railway Network on the Land Gradient in Industrializing Berlin

As the first to use an archival data set on historical land values of Berlin, Germany, from 1890 to 1936, we exploit exogenous variation in transport technology in order to test the validity of the monocentric city model. Endogenously determining the CBD, we conduct cross-section and time-difference analysis and model the land gradient in terms of straight-line distance and travel times. A counterfactual scenario indicates that a large proportion of urban decentralization is attributable to improvements in transport infrastructure. Controlling for spatial dependency, results suggest that the monocentric model fitted the city structure until the mid 20th century