Thomsoncoates2601

Peripheral biomarker and post-mortem brains studies have shown alterations of neuronal calcium sensor 1 (Ncs-1) expression in people with bipolar disorder or schizophrenia. However, its engagement by psychiatric medications and potential contribution to behavioral regulation remains elusive. We investigated the effect on Ncs-1 expression of valproic acid (VPA), a mood stabilizer used for the management of bipolar disorder. Treatment with VPA induced Ncs-1 gene expression in cell line while chronic administration of this drug to mice increased both Ncs-1 protein and mRNA levels in the mouse frontal cortex. Inhibition of histone deacetylases (HDACs), a known biochemical effect of VPA, did not alter the expression of Ncs-1. In contrast, pharmacological inhibition or genetic downregulation of glycogen synthase kinase 3β (Gsk3β) increased Ncs-1 expression, whereas overexpression of a constitutively active Gsk3β had the opposite effect. Moreover, adeno-associated virus-mediated Ncs-1 overexpression in mouse frontal cortex caused responses similar to those elicited by VPA or lithium in tests evaluating social and mood-related behaviors. These findings indicate that VPA increases frontal cortex Ncs-1 gene expression as a result of Gsk3 inhibition. Furthermore, behavioral changes induced by Ncs-1 overexpression support a contribution of this mechanism in the regulation of behavior by VPA and potentially other psychoactive medications inhibiting Gsk3 activity.Hip shape is an important determinant of hip osteoarthritis (OA), which occurs more commonly in women. However, it remains unclear to what extent differences in OA prevalence are attributed to sex differences in hip shape. Here, we explore sex differences in proximal femur shape in a cohort of adolescents. Hip morphology was quantified using hip DXA scans from the Avon Longitudinal Study of Parents and Children. Independent modes of variation (hip shape mode (HSM) scores) were generated for each image using an adult reference statistical shape model (N = 19,379). Linear regression was used to examine sex differences for the top ten HSMs, adjusting for age, height, lean and fat mass. Complete outcome and covariate data were available for 4,428 and 4,369 participants at ages 14 and 18 years, respectively. Several HSMs showed sex differences at both time points. The combined effect of sex on hip shape at age 14 reflected flatter femoral head and smaller lesser trochanter in females compared with males and, following adjustment for age and body size, these differences became more pronounced. At age 18, smaller lesser trochanter and femoral neck width (FNW) in females still remained although differences in femoral head, femoral shaft and FNW were largely attenuated following adjustment. Sexual dimorphism in proximal femur shape can be discerned in adolescence and early adulthood. Observed differences in proximal femur shape, particularly at age 14 were largely independent of body size, however to what extent differences in hip shape in early life play a role in predisposing to hip OA in later life remains to be determined.Heme b is an iron-containing cofactor in hemoproteins that participates in the fundamental processes of photosynthesis and respiration in phytoplankton. Heme b concentrations typically decline in waters with low iron concentrations but due to lack of field data, the distribution of heme b in particulate material in the ocean is poorly constrained. Here we report particulate heme b distributions across the Atlantic Ocean (59.9°N to 34.6°S). Heme b concentrations in surface waters ranged from 0.10 to 33.7 pmol L-1 (median = 1.47 pmol L-1, n = 974) and were highest in regions with a high biomass. The ratio of heme b to particulate organic carbon (POC) exhibited a mean value of 0.44 μmol heme b mol-1 POC. We identified the ratio of 0.10 µmol heme b mol-1 POC as the cut-off between heme b replete and heme b deficient (anemic) phytoplankton. By this definition, we observed anemic phytoplankton populations in the Subtropical South Atlantic and Irminger Basin. Comparison of observed and modelled heme b suggested that heme b could account for between 0.17-9.1% of biogenic iron. BI-2493 cost Our large scale observations of heme b relative to organic matter provide further evidence of the impact of changes in iron supply on phytoplankton iron status across the Atlantic Ocean.In the present study we tested the effects of different transcranial direct current stimulation (tDCS) protocols in the formation of visuo-spatial contextual learning (VSCL). The study comprised three experiments designed to evaluate tDCS-induced changes in VSCL measures collected during the execution of a visual search task widely used to examine statistical learning in the visuo-spatial domain. In Experiment 1, we probed for the effects of left-posterior parietal cortex (PPC) anodal-tDCS (AtDCS) at different timings (i.e. offline and online) and intensities (i.e. 3 mA and 1.5 mA). The protocol producing the more robust effect in Experiment 1 was used in Experiment 2 over the right-PPC, while in Experiment 3, cathodal-tDCS (CtDCS) was applied over the left-PPC only at a high intensity (i.e. 3 mA) but varying timing of application (offline and online). Results revealed that high intensity offline AtDCS reduced VSCL regardless of the stimulation side (Experiment 1 and 2), while no significant behavioral changes were produced by both online AtDCS protocols (Experiment 1) and offline/online CtDCS (Experiment 3). The reduced VSCL could result from homeostatic regulatory mechanisms hindering normal task-related neuroplastic phenomena.Individuals at risk for schizophrenia-spectrum disorders display abnormalities related to motivational salience, or the ability of stimuli to elicit attention due to associations with rewards or punishments. However, the nature of these abnormalities is unclear because most focus on responses to stimuli from broad "pleasant" and "unpleasant" categories and ignore the variation of motivational salience within these categories. In two groups at risk for schizophrenia-spectrum disorders-a Social Anhedonia group and a Psychotic-like Experiences group-and a control group, the current study examined event-related potential components sensitive to motivational salience-the Early Posterior Negativity (EPN), reflecting earlier selective attention, and the Late Positive Potential (LPP), reflecting sustained attention. Compared to controls, the Social Anhedonia group showed smaller increases in the EPN in response to erotica and smaller increases in the LPP as the motivational salience of pleasant images increased (exciting less then affiliative less then erotica).