Evolution of a behavior-linked microsatellite-containing element in the 5' flanking region of the primate AVPR1A gene

<p>Abstract</p> <p>Background</p> <p>The arginine vasopressin V1a receptor (V1aR) modulates social cognition and behavior in a wide variety of species. Variation in a repetitive microsatellite element in the 5' flanking region of the V1aR gene (<it>AVPR1A</it>) in rodents has been associated with variation in brain V1aR expression and in social behavior. In humans, the 5' flanking region of <it>AVPR1A </it>contains a tandem duplication of two ~350 bp, microsatellite-containing elements located approximately 3.5 kb upstream of the transcription start site. The first block, referred to as DupA, contains a polymorphic (GT)₂₅microsatellite; the second block, DupB, has a complex (CT)₄-(TT)-(CT)₈-(GT)₂₄polymorphic motif, known as RS3. Polymorphisms in RS3 have been associated with variation in sociobehavioral traits in humans, including autism spectrum disorders. Thus, evolution of these regions may have contributed to variation in social behavior in primates. We examined the structure of these regions in six ape, six monkey, and one prosimian species.</p> <p>Results</p> <p>Both tandem repeat blocks are present upstream of the <it>AVPR1A </it>coding region in five of the ape species we investigated, while monkeys have only one copy of this region. As in humans, the microsatellites within DupA and DupB are polymorphic in many primate species. Furthermore, both single (lacking DupB) and duplicated alleles (containing both DupA and DupB) are present in chimpanzee (<it>Pan troglodytes</it>) populations with allele frequencies of 0.795 and 0.205 for the single and duplicated alleles, respectively, based on the analysis of 47 wild-caught individuals. Finally, a phylogenetic reconstruction suggests two alternate evolutionary histories for this locus.</p> <p>Conclusion</p> <p>There is no obvious relationship between the presence of the RS3 duplication and social organization in primates. However, polymorphisms identified in some species may be useful in future genetic association studies. In particular, the presence of both single and duplicated alleles in chimpanzees provides a unique opportunity to assess the functional role of this duplication in contributing to variation in social behavior in primates. While our initial studies show no signs of directional selection on this locus in chimps, pharmacological and genetic association studies support a potential role for this region in influencing V1aR expression and social behavior.</p

Employee Stock Ownership and Financial Performance in European Countries: The Moderating Effects of Uncertainty Avoidance and Social Trust

This study investigates how the effect of employee stock ownership on financial performance may hinge on the diverse cultural and societal contexts of European countries. Based on agency and national culture theories, we hypothesize that the positive relationship between employee stock ownership and return on assets (ROA) is stronger in those nations with lower uncertainty avoidance and higher social trust. Using a multisource, time‐lagged, large‐scale dataset of 1,741 firms from 21 countries in Europe, our multilevel, random coefficient modeling analysis found evidence for these hypotheses, suggesting that uncertainty avoidance and social trust serve as important contextual cues in predicting the linkage between employee stock ownership and financial performance. Our supplemental analysis with distinction between the managerial and nonmanagerial employee stock ownership further indicates managerial employee stock ownership has a direct positive effect on ROA. Although nonmanagerial employee stock ownership had a nonsignificant association with ROA, the relationship was positive and significant when uncertainty avoidance was low and social trust was high. This research contributes to the existing literature by illuminating some of the contextual influences altering the effectiveness of employee stock ownership. Our findings also offer practical suggestions for effectively using employee stock ownership

What Does Child Protective Services Investigate as Neglect? A Population-Based Study

Most child protective services (CPS) investigations involve allegations of neglect. Broad and vague definitions have led to concerns that CPS-investigated neglect is driven by poverty-based material hardship. In a representative sample of 295 neglect investigations in California in 2017, structured data and narrative text fields were used to characterize the types of neglect and concurrent parental risk factors investigated by CPS and to assess the rate and nature of investigated physical neglect, defined as inadequate food, housing, or hygiene. The most common types of neglect were inadequate supervision (44%) and failure to protect (29%), followed by physical neglect (14%). Common risk factors identified in neglect investigations were parental substance use (41%), domestic violence (21%), mental illness (18%), and co-reported physical or sexual abuse (29%). Nearly all investigations of physical neglect (99%) included concerns related to substance use, domestic violence, mental illness, co-reported abuse or an additional neglect allegation (i.e., abandonment). Given concerns identified in neglect investigations, economic supports are likely insufficient without an array of behavioral-health supports

Reprogramming human T cell function and specificity with non-viral genome targeting.

Decades of work have aimed to genetically reprogram T cells for therapeutic purposes1,2 using recombinant viral vectors, which do not target transgenes to specific genomic sites3,4. The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells using homology-directed repair5,6. Here we developed a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences (greater than one&nbsp;kilobase) at specific sites in the genomes of primary human T cells, while preserving cell viability and function. This permits individual or multiplexed modification of endogenous genes. First, we applied this strategy to correct a pathogenic IL2RA mutation in cells from patients with monogenic autoimmune disease, and demonstrate improved signalling function. Second, we replaced the endogenous T cell receptor (TCR) locus with a new TCR that redirected T cells to a cancer antigen. The resulting TCR-engineered T cells specifically recognized tumour antigens and mounted productive anti-tumour cell responses in vitro and in vivo. Together, these studies provide preclinical evidence that non-viral genome targeting can enable rapid and flexible experimental manipulation and therapeutic engineering of primary human immune cells

Climatic variability in Mfabeni peatlands (South Africa) since the late Pleistocene

It has been postulated that a bipolar seesaw interhemispheric mechanism dominated the relationship between the Northern and Southern hemisphere climates since the late Pleistocene. A key test for this proposition would be to undertake palaeoenvironmental studies on terrestrial archives in climatically sensitive regions. Southern Africa's contemporary C-3 and C-4 terrestrial plant distributions display a definitive geographical pattern dictated by different growing season rainfall and temperature zones; however, the region is generally archive poor due to its overall semi-arid climate and high relief topography. The Mfabeni peatland, with a basal age of c. 47 k yrs calibrated before present (kcal yr BP), is one of the oldest continuous coastal peat deposits in Southern Africa. Molecular leaf wax isotopes (delta C-13(wax)) were generated for a 810 cm long core, and combined with previously published bulk geochemical (delta C-13(bulk), %TOC), palynological, and stratigraphic data, to reconstruct the late Pleistocene and Holocene palaeoenvironments. We interpreted environmental shifts associated with the Heinrich 4, Last Glacial Maximum, deglacial and Holocene periods, which are consistent with adjacent Indian Ocean sea surface temperature records. However, the other shorter climate perturbations during the Heinrich 5, 3, 2, 1, Antarctic cold reversal and Younger Dryas, were muted, most likely due to local hydrological overprinting on the Mfabeni record. A general anti-phase sequence was observed between the Mfabeni record and better established Northern Hemisphere events, underpinning the bipolar seesaw interhemispheric mechanism proposed for global climate forcing since the Late Pleistocene

Borderline Personality Disorder Symptoms in College Students: The Complex Interplay between Alexithymia, Emotional Dysregulation and Rumination.

Both Emotional Cascade Theory and Linehan's Biosocial Theory suggest dysregulated behaviors associated with Borderline Personality Disorder (BPD) emerge, in part, because of cycles of rumination, poor emotional recognition and poor emotion regulation. In this study we examined relationships between rumination, alexithymia, and emotion regulation in predicting dysregulated behaviors associated with BPD (e.g. self-harm, substance use, aggression), and explored both indirect and moderating effects among these variables. The sample comprised 2261 college students who completed self-report measures of the aforementioned constructs. BPD symptoms, stress, family psychological illness, and alexithymia exerted direct effects on behaviors. Symptoms had an indirect effect on behaviors through rumination, alexithymia and emotional dysregulation. In addition, the relationship between symptoms and dysregulated behaviors was conditional on level of rumination and alexithymia. Implications for early identification and treatment of BPD and related behaviors in college settings are discussed

The Children’s Data Network

The Children's Data Network (CDN) is a data and research collaborative focused on the linkage and analysis of administrative records. In partnership with public agencies, philanthropic funders, affiliated researchers, and community stakeholders, we seek to generate knowledge and advance evidence-rich policies that improve the health, safety, and well-being of the children of California. Given our experience negotiating access to and working with existing administrative data (and importantly, data stewards), the CDN has demonstrated its ability to perform cost-effective and rigorous record linkage, answer time-sensitive policy- and program-related questions, and build the public sector's capacity to do the same. Owing to steadfast and generous infrastructure and project support, close collaboration with public partners, and strategic analyses and engagements, the CDN has promoted a person-level and longitudinal understanding of children and families in California and in so doing, informed policy and program development nationwide. We sincerely hope that our experience—and lessons learned—can advance and inform work in other fields and jurisdictions

Regional disparities in the effect of training on employment

In this paper we investigate one particular aspect of human capital formation: the relative effectiveness of training, as reflected in its effect on the probability of securing continued employment during the recent financial crisis. We use a panel on 3,983 individuals for the period 2008-2011 and focus on how the effects of training differ between the South and the North of Italy and across workers with different levels of education. Our most striking result is that the effect of training on continued employment is notably stronger in the South than in the North of the country

Preliminary Evidence for Cell Membrane Amelioration in Children with Cystic Fibrosis by 5-MTHF and Vitamin B12 Supplementation: A Single Arm Trial

Cystic fibrosis (CF) is one of the most common fatal autosomal recessive disorders in the Caucasian population caused by mutations of gene for the cystic fibrosis transmembrane conductance regulator (CFTR). New experimental therapeutic strategies for CF propose a diet supplementation to affect the plasma membrane fluidity and to modulate amplified inflammatory response. The objective of this study was to evaluate the efficacy of 5-methyltetrahydrofolate (5-MTHF) and vitamin B12 supplementation for ameliorating cell plasma membrane features in pediatric patients with cystic fibrosis.A single arm trial was conducted from April 2004 to March 2006 in an Italian CF care centre. 31 children with CF aged from 3 to 8 years old were enrolled. Exclusion criteria were diabetes, chronic infections of the airways and regular antibiotics intake. Children with CF were supplemented for 24 weeks with 5-methyltetrahydrofolate (5-MTHF, 7.5 mg /day) and vitamin B12 (0.5 mg/day). Red blood cells (RBCs) were used to investigate plasma membrane, since RBCs share lipid, protein composition and organization with other cell types. We evaluated RBCs membrane lipid composition, membrane protein oxidative damage, cation content, cation transport pathways, plasma and RBCs folate levels and plasma homocysteine levels at baseline and after 24 weeks of 5-MTHF and vitamin B12 supplementation. In CF children, 5-MTHF and vitamin B12 supplementation (i) increased plasma and RBC folate levels; (ii) decreased plasma homocysteine levels; (iii) modified RBC membrane phospholipid fatty acid composition; (iv) increased RBC K(+) content; (v) reduced RBC membrane oxidative damage and HSP70 membrane association.5-MTHF and vitamin B12 supplementation might ameliorate RBC membrane features of children with CF.ClinicalTrials.gov NCT00730509