Hypomanic Defence: Investigating the relationship between depression, response styles and vulnerability to mania

Background: The purpose of this study was to investigate the role of response styles to negative affect in mediating the relationship between depression and vulnerability to experiencing mania. Methods: A cross-sectional correlational design was utilized to examine 217 participants’ responses to an online survey comprising the Hypomanic Personality Scale (HPS), Response Styles Questionnaire (RSQ), and Personal Health Questionaire (PHQ-8). Results: After controlling for covariates (age, gender, ethnicity & depression), rumination, risk-taking and adaptive-coping were all positive predictors of hypomanic personality. Parallel mediation analysis demonstrated that rumination and risk-taking positively mediated the relationship between depression and hypomanic personality, whilst adaptive-coping negatively mediated this relationship. Serial mediation analysis revealed evidence for a sequence of causal mediators, demonstrating that rumination independently predicted risk-taking, which subsequently predicted hypomanic personality. Adaptive-coping continued to supress the relationship between depression and hypomanic personality after including risk-taking in the mediation analysis. Limitations: An unstratified volunteer sampling technique was utilised, introducing potential bias regarding the tendency to adopt maladaptive response styles. Utilising a three-factor response styles solution may lack face validity due to the wide variety of behaviours that encompass adaptive-coping strategies such as pleasant distraction and problem solving. Conclusions: Our findings support the maladaptive role of rumination and risk-taking in mediating the relationship between depression and vulnerability to experience mania, and further substantiates the protective function of adaptive-coping. Clinical interventions may endeavour to diminish the use of rumination and risk-taking, whilst promoting adaptive-coping strategies such as pleasant distraction and problem-solving

The Cost of Male Aggression and Polygyny in California Sea Lions (Zalophus californianus)

In polygynous mating systems, males often increase their fecundity via aggressive defense of mates and/or resources necessary for successful mating. Here we show that both male and female reproductive behavior during the breeding season (June–August) affect female fecundity, a vital rate that is an important determinant of population growth rate and viability. By using 4 years of data on behavior and demography of California sea lions (Zalophus californianus), we found that male behavior and spatial dynamics—aggression and territory size—are significantly related to female fecundity. Higher rates of male aggression and larger territory sizes were associated with lower estimates of female fecundity within the same year. Female aggression was significantly and positively related to fecundity both within the same year as the behavior was measured and in the following year. These results indicate that while male aggression and defense of territories may increase male fecundity, such interactions may cause a reduction in the overall population growth rate by lowering female fecundity. Females may attempt to offset male-related reductions in female fecundity by increasing their own aggression—perhaps to defend pups from incidental injury or mortality. Thus in polygynous mating systems, male aggression may increase male fitness at the cost of female fitness and overall population viability

Estimates of Particulate Organic Carbon Flowing from the Pelagic Environment to the Benthos through Sponge Assemblages

Despite the importance of trophic interactions between organisms, and the relationship between primary production and benthic diversity, there have been few studies that have quantified the carbon flow from pelagic to benthic environments as a result of the assemblage level activity of suspension-feeding organisms. In this study, we examine the feeding activity of seven common sponge species from the Taputeranga marine reserve on the south coast of Wellington in New Zealand. We analysed the diet composition, feeding efficiency, pumping rates, and the number of food particles (specifically picoplanktonic prokaryotic cells) retained by sponges. We used this information, combined with abundance estimates of the sponges and estimations of the total amount of food available to sponges in a known volume of water (89,821 m3), to estimate: (1) particulate organic carbon (POC) fluxes through sponges as a result of their suspension-feeding activities on picoplankton; and (2) the proportion of the available POC from picoplankton that sponges consume. The most POC acquired by the sponges was from non-photosynthetic bacterial cells (ranging from 0.09 to 4.69 g C d−1 with varying sponge percentage cover from 0.5 to 5%), followed by Prochlorococcus (0.07 to 3.47 g C d−1) and then Synechococcus (0.05 to 2.34 g C d−1) cells. Depending on sponge abundance, the amount of POC that sponges consumed as a proportion of the total POC available was 0.2–12.1% for Bac, 0.4–21.3% for Prochlo, and 0.3–15.8% for Synecho. The flux of POC for the whole sponge assemblage, based on the consumption of prokaryotic picoplankton, ranged from 0.07–3.50 g C m2 d−1. This study is the first to estimate the contribution of a sponge assemblage (rather than focusing on individual sponge species) to POC flow from three groups of picoplankton in a temperate rocky reef through the feeding activity of sponges and demonstrates the importance of sponges to energy flow in rocky reef environments

Variations on a theme: diversification of cuticular hydrocarbons in a clade of cactophilic Drosophila

<p>Abstract</p> <p>Background</p> <p>We characterized variation and chemical composition of epicuticular hydrocarbons (CHCs) in the seven species of the <it>Drosophila buzzatii </it>cluster with gas chromatography/mass spectrometry. Despite the critical role of CHCs in providing resistance to desiccation and involvement in communication, such as courtship behavior, mating, and aggregation, few studies have investigated how CHC profiles evolve within and between species in a phylogenetic context. We analyzed quantitative differences in CHC profiles in populations of the <it>D. buzzatii </it>species cluster in order to assess the concordance of CHC differentiation with species divergence.</p> <p>Results</p> <p>Thirty-six CHC components were scored in single fly extracts with carbon chain lengths ranging from C₂₉to C₃₉, including methyl-branched alkanes, <it>n</it>-alkenes, and alkadienes. Multivariate analysis of variance revealed that CHC amounts were significantly different among all species and canonical discriminant function (CDF) analysis resolved all species into distinct, non-overlapping groups. Significant intraspecific variation was found in different populations of <it>D. serido </it>suggesting that this taxon is comprised of at least two species. We summarized CHC variation using CDF analysis and mapped the first five CHC canonical variates (CVs) onto an independently derived <it>period </it>(<it>per</it>) gene + chromosome inversion + mtDNA COI gene for each sex. We found that the COI sequences were not phylogenetically informative due to introgression between some species, so only <it>per </it>+ inversion data were used. Positive phylogenetic signal was observed mainly for CV1 when parsimony methods and the test for serial independence (TFSI) were used. These results changed when no outgroup species were included in the analysis and phylogenetic signal was then observed for female CV3 and/or CV4 and male CV4 and CV5. Finally, removal of divergent populations of <it>D. serido </it>significantly increased the amount of phylogenetic signal as up to four out of five CVs then displayed positive phylogenetic signal.</p> <p>Conclusions</p> <p>CHCs were conserved among species while quantitative differences in CHC profiles between populations and species were statistically significant. Most CHCs were species-, population-, and sex-specific. Mapping CHCs onto an independently derived phylogeny revealed that a significant portion of CHC variation was explained by species' systematic affinities indicating phylogenetic conservatism in the evolution of these hydrocarbon arrays, presumptive waterproofing compounds and courtship signals as in many other drosophilid species.</p

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies

Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009

Insulin resistance is a hallmark of type 2 diabetes mellitus and is associated with a metabolic and cardiovascular cluster of disorders (dyslipidaemia, hypertension, obesity [especially visceral], glucose intolerance, endothelial dysfunction), each of which is an independent risk factor for cardiovascular disease (CVD). Multiple prospective studies have documented an association between insulin resistance and accelerated CVD in patients with type 2 diabetes, as well as in non-diabetic individuals. The molecular causes of insulin resistance, i.e. impaired insulin signalling through the phosphoinositol-3 kinase pathway with intact signalling through the mitogen-activated protein kinase pathway, are responsible for the impairment in insulin-stimulated glucose metabolism and contribute to the accelerated rate of CVD in type 2 diabetes patients. The current epidemic of diabetes is being driven by the obesity epidemic, which represents a state of tissue fat overload. Accumulation of toxic lipid metabolites (fatty acyl CoA, diacylglycerol, ceramide) in muscle, liver, adipocytes, beta cells and arterial tissues contributes to insulin resistance, beta cell dysfunction and accelerated atherosclerosis, respectively, in type 2 diabetes. Treatment with thiazolidinediones mobilises fat out of tissues, leading to enhanced insulin sensitivity, improved beta cell function and decreased atherogenesis. Insulin resistance and lipotoxicity represent the missing links (beyond the classical cardiovascular risk factors) that help explain the accelerated rate of CVD in type 2 diabetic patients

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC