Social creatures: model animal systems for studying the neuroendocrine mechanisms of social behaviour

Work was supported by grants awarded to ML (BBSRC BB/S000224/1), OJB (BO 1958/8-2, GRK 2174), KEB (Wellcome Trust 109614/Z/15/Z, MRC MR/N004574/1), AJ (BBSRC BB/S000801) and GL (Israel Science Foundation #1511/16; United States-Israel Binational Science Foundation #2017325; Nella and Leon Benoziyo Center for Neurological Diseases, Richard F. Goodman Yale/Weizmann Exchange Program and Estate of Emile Mimran).The interaction of animals with conspecifics, termed social behaviour, has a major impact on the survival of many vertebrate species. Neuropeptide hormones modulate the underlying physiology that governs social interactions, and many findings concerning the neuroendocrine mechanisms of social behaviours have been extrapolated from animal models to humans. Neurones expressing neuropeptides show similar distribution patterns within the hypothalamic nucleus, even when evolutionarily distant species are compared. During evolution, hypothalamic neuropeptides and releasing hormones have retained not only their structures, but also their biological functions, including their effects on behaviour. Here, we review the current understanding of the mechanisms of social behaviours in several classes of animals, such as worms, insects and fish, as well as laboratory, wild and domesticated mammals.Publisher PDFPeer reviewe

Associations between epigenetic aging and childhood peer victimization, depression, and suicidal ideation in adolescence and adulthood: A study of two population-based samples

Background: Prior studies indicate that peer victimization (including bullying) is associated with higher risk for depression and suicidal ideation across the life course. However, molecular mechanisms underlying these associations remain unclear. This two-cohort study proposes to test whether epigenetic aging and pace of aging, as well as a DNA methylation marker of responsive to glucocorticoids, are associated to childhood peer victimization and later depressive symptoms, or suicidal ideation. Methods: Cohort 1: Epigenome-wide DNA methylation (EPIC array) was measured in saliva collected when participants were 10.47 years (standard deviation = 0.35) in a subsample of the Quebec Longitudinal Study of Child Development (QLSCD, n = 149 participants), with self-reported peer victimization at 6-8 years, depressive symptoms (mean symptoms, and dichotomized top 30% symptoms) and suicidal ideation at 15-17 years. Cohort 2: Epigenome-wide DNA methylation (EPIC array) was measured in blood collected from participants aged 45.13 years (standard deviation = 0.37) in a subsample of the 1958 British Birth cohort (1958BBC, n = 238 participants) with information on mother-reported peer victimization at 7-11 years, self-reported depressive symptoms at 50 years, and suicidal ideation at 45 years. Five epigenetic indices were derived: three indicators of epigenetic aging [Horvath's pan-tissue (Horvath1), Horvath's Skin-and-Blood (Horvath2), Pediatric-Buccal-Epigenetic age (PedBE)], pace of aging (DunedinPACE), and stress response reactivity (Epistress). Results: Peer victimization was not associated with the epigenetic indices in either cohort. In the QLSCD, higher PedBE epigenetic aging and a slower pace of aging as measured by DunedinPACE predicted higher depressive symptoms scores. In contrast, neither the Horvath1, or Horvath2 epigenetic age estimates, nor the Epistress score were associated with depressive symptoms in either cohort, and none of the epigenetic indices predicted suicidal ideation. Conclusion: The findings are consistent with epigenome-wide and candidate gene studies suggesting that these epigenetic indices did not relate to peer victimization, challenging the hypothesis that cumulative epigenetic aging indices could translate vulnerability to depressive symptoms and suicidal ideation following peer victimization. Since some indices of epigenetic aging and pace of aging signaled higher risk for depressive symptoms, future studies should pursue this investigation to further evaluate the robustness and generalization of these preliminary findings

String theoretic QCD axions in the light of PLANCK and BICEP2

The QCD axion solving the strong CP problem may originate from antisymmetric tensor gauge fields in compactified string theory, with a decay constant around the GUT scale. Such possibility appears to be ruled out now by the detection of tensor modes by BICEP2 and the PLANCK constraints on isocurvature density perturbations. A more interesting and still viable possibility is that the string theoretic QCD axion is charged under an anomalous U(1)_A gauge symmetry. In such case, the axion decay constant can be much lower than the GUT scale if moduli are stabilized near the point of vanishing Fayet-Illiopoulos term, and U(1)_A-charged matter fields get a vacuum value far below the GUT scale due to a tachyonic SUSY breaking scalar mass. We examine the symmetry breaking pattern of such models during the inflationary epoch with the Hubble expansion rate 10^{14} GeV, and identify the range of the QCD axion decay constant, as well as the corresponding relic axion abundance, consistent with known cosmological constraints. In addition to the case that the PQ symmetry is restored during inflation, there are other viable scenarios, including that the PQ symmetry is broken during inflation at high scales around 10^{16}-10^{17} GeV due to a large Hubble-induced tachyonic scalar mass from the U(1)_A D-term, while the present axion scale is in the range 10^{9}-5\times 10^{13} GeV, where the present value larger than 10^{12} GeV requires a fine-tuning of the axion misalignment angle. We also discuss the implications of our results for the size of SUSY breaking soft masses.Comment: 29 pages, 1 figure; v3: analysis updated including the full anharmonic effects, references added, version accepted for publication in JHE

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

Chemistry courses as the turning point for premedical students

Previous research has documented that negative experiences in chemistry courses are a major factor that discourages many students from continuing in premedical studies. This adverse impact affects women and students from under-represented minority (URM) groups disproportionately. To determine if chemistry courses have a similar effect at a large public university, we surveyed 1,036 students from three entering cohorts at the University of California, Berkeley. We surveyed students at the beginning of their first year at the university and again at the end of their second year. All subjects had indicated an interest in premedical studies at the time they entered the university. We conducted follow-up interviews with a stratified sub-set of 63 survey respondents to explore the factors that affected their level of interest in premedical studies. Using a 10-point scale, we found that the strength of interest in premedical studies declined for all racial/ethnic groups. In the follow-up interviews, students identified chemistry courses as the principal factor contributing to their reported loss of interest. URM students especially often stated that chemistry courses caused them to abandon their hopes of becoming a physician. Consistent with reports over more than 50 years, it appears that undergraduate courses in chemistry have the effect of discouraging otherwise qualified students, as reflected in their admission to one of the most highly selective public universities in the US, from continuing in premedical studies, especially in the case of URM students. Reassessment of this role for chemistry courses may be overdue

Effect of Prenatal Exposure to Airborne Polycyclic Aromatic Hydrocarbons on Neurodevelopment in the First 3 Years of Life among Inner-City Children

Our prospective cohort study of nonsmoking African-American and Dominican mothers and children in New York City is evaluating the role of prenatal exposure to urban pollutants, including polycyclic aromatic hydrocarbons (PAHs), environmental tobacco smoke (ETS), and pesticides, in the pathogenesis of neurobehavioral disorders. We used the Bayley Scales of Infant Development to evaluate the effects on child mental and psychomotor development of prenatal exposure to airborne PAHs monitored during pregnancy by personal air sampling. Behavioral development was assessed by the Child Behavior Checklist. We adjusted for potential confounders including sociodemographic factors and prenatal exposure to ETS and chlorpyrifos. Prenatal exposure to PAHs was not associated with psychomotor development index or behavioral problems. However, high prenatal exposure to PAHs (upper quartile) was associated with lower mental development index at age 3 [β= –5.69; 95% confidence interval (CI), –9.05 to –2.33; p < 0.01]. The odds of cognitive developmental delay were also significantly greater for children with high prenatal exposure (odds ratio = 2.89; 95% CI, 1.33 to 6.25; p = 0.01). General estimated equation analysis showed a significant age × PAH effect on mental development (p = 0.01), confirming the age-specific regression findings. Further adjustment for lead did not alter the relationships. There were no differences in effect sizes by ethnicity. The results require confirmation but suggest that environmental PAHs at levels recently encountered in New York City air may adversely affect children’s cognitive development at 3 years of age, with implications for school performance

What\u27s new in online news?

This paper examines aspects of the field of Information Systems (IS) concerned with its diversity and with the rapid changes within the discipline that have been incurred by the continued evolution of the IS artefact. This examination is done in order to establish the suitability of the Cynefin framework, developed for knowledge management, as a suitable tool for sense-making in IS. A description and assessment of the Cynefin framework is provided with its varied applications in both organisational practice and research. The paper then applies the framework to make sense of some historical trends and contemporary issues of IS emphasising their diversity and changing nature. We conclude with speculation on how this approach may help guide future sense-making in IS research

Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer

Phenomenological Implications of Deflected Mirage Mediation: Comparison with Mirage Mediation

We compare the collider phenomenology of mirage mediation and deflected mirage mediation, which are two recently proposed "mixed" supersymmetry breaking scenarios motivated from string compactifications. The scenarios differ in that deflected mirage mediation includes contributions from gauge mediation in addition to the contributions from gravity mediation and anomaly mediation also present in mirage mediation. The threshold effects from gauge mediation can drastically alter the low energy spectrum from that of pure mirage mediation models, resulting in some cases in a squeezed gaugino spectrum and a gluino that is much lighter than other colored superpartners. We provide several benchmark deflected mirage mediation models and construct model lines as a function of the gauge mediation contributions, and discuss their discovery potential at the LHC.Comment: 29 pages, 9 figure

A Novel Redox Method for Rapid Production of Functional Bi-Specific Antibodies For Use in Early Pilot Studies

We demonstrate here a rapid alternative method for the production of functional bi-specific antibodies using the mild reducing agent 2-mercaptoethanesulfonic acid sodium salt (MESNA). Following reduction of a mixture of two monoclonal antibodies with MESNA to break inter heavy chain bonds, this solution is dialysed under oxidising conditions and antibodies are allowed to reform. During this reaction a mixture of antibodies is formed, including parental antibodies and bi-specific antibody. Bi-specific antibodies are purified over two sequential affinity columns. Following purification, bi-specificity of antibodies is determined in enzyme-linked immunosorbent assays and by flow cytometry. Using this redox method we have been successful in producing hybrid and same-species bi-specific antibodies in a time frame of 6–10 working days, making this production method a time saving alternative to the time-consuming traditional heterohybridoma technology for the production of bi-specific antibodies for use in early pilot studies. The use of both rat and mouse IgG antibodies forming a rat/mouse bi-specific antibody as well as producing a pure mouse bi-specific antibody and a pure rat bi-specific antibody demonstrates the flexibility of this production method