Age-dependent shift in spontaneous excitation-inhibition balance of infralimbic prefrontal layer II/III neurons is accelerated by early life stress, independent of forebrain mineralocorticoid receptor expression

In this study we tested the hypothesis i) that age-dependent shifts in the excitation-inhibition balance of pre-frontal neurons are accelerated by early life stress, a risk factor for the etiology of many psychiatric disorders; and if so, ii) that this process is exacerbated by genetic forebrain-specific downregulation of the mineralocorticoid receptor, a receptor that was earlier found to be a protective factor for negative effects of early life stress in both rodents and humans. In agreement with the literature, an age-dependent downregulation of the excitation inhibition balance was found both with regard to spontaneous and evoked synaptic currents. The age-dependent shift in spontaneous excitatory relative to inhibitory currents was significantly accelerated by early life stress, but this was not exacerbated by reduction in mineralocorticoid receptor expression. The age-dependent changes in the excitation-inhibition balance were mirrored by similar changes in receptor subunit expression and morphological alterations, particularly in spine density, which could thus potentially contribute to the functional changes. However, none of these parameters displayed acceleration by early life stress, nor depended on mineralocorticoid receptor expression. We conclude that, in agreement with the hypothesis, early life stress accelerates the developmental shift of the excitation-inhibition balance but, contrary to expectation, there is no evidence for a putative protective role of the mineralocorticoid receptor in this system. In view of the modest effect of early life stress on the excitation-inhibition balance, alternative mechanisms potentially underlying the development of psychiatric disorders should be further explored

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

A mixed methods evaluation of Girls' Talk+: A sexuality education programme for girls with mild intellectual disabilities

Background: Girls with a mild intellectual disability generally receive less sexuality education than their non-disabled peers, while their needs for sexual knowledge are possibly greater. This study aimed to evaluate the effect and process of a new sexuality education programme (Girls' Talk+), focused on sexual health among girls with a mild intellectual disability in the Netherlands. Methods: A mixed methods approach was applied, using participant questionnaires (n = 249), logs written by trainers (n = 17) and interviews with trainers (n = 10). Descriptive statistics and linear regression models were used to analyse the quantitative data. Several coding phases were used to analyse the interviews. Results and conclusions: This study provides some indication that Girls' Talk+ has positive results on improving knowledge, attitude, and self-efficacy in relation to sexual health as well as trainer and participant satisfaction with the programme

Cold-Water Coral Mound Archive Provides Unique Insights Into Intermediate Water Mass Dynamics in the Alboran Sea During the Last Deglaciation

The Alboran Sea is widely recognized to host numerous cold-water coral ecosystems, including the East Melilla Coral Province. Yet, their development through time and response to climatic variability has still to be fully understood. Based on a combined investigation of benthic foraminiferal assemblages, foraminiferal stable isotope compositions, grain size analysis, sediment geochemistry, and macrofaunal quantification, this study identifies key events and processes having governed coldwater coral development at the East Melilla Coral Province between Greenland Stadial 2.1 and the Early Holocene. The transition from Greenland Stadial 2.1 to Greenland Interstadial 1 is associated to a decline of bryozoan communities and their replacement by cold-water corals, together with changes in benthic foraminiferal assemblages and a decrease in the sediment mean grain size. These results suggest that a rapid decrease in bottom currents and the establishment of dysoxic and mesotrophic conditions at the seafloor, possibly associated to enhanced fluvial input, resulted in the decline of bryozoans as the dominant suspension feeding organisms and their replacement by a thriving cold-water coral community. This transition from a bryozoan to a coral dominated environment is concomitant with the beginning of the African Humid Period, confirming that increasing fluvial input could have been a main factor triggering the establishment of cold-water corals in the East Melilla Coral Province during Greenland Interstadial 1. A change in benthic foraminiferal communities and an increase in the sediment mean grain size mark the passage from the Early to Late Greenland Interstadial 1. The current velocity of intermediate water masses is suggested to have increased during the Early to Late Greenland Interstadial 1, whilst simultaneously fluvial input would have reduced. Such changes suggest that the climate became more arid during the second phase of Greenland Interstadial 1.ISSN:2296-774

Analytical Artefacts Preclude Reliable Isotope Ratio Measurement of Internal Water in Coral Skeletons

Internal water in cold‐water and tropical coral skeletons was extracted and measured for its oxygen and hydrogen isotope ratios. Water was extracted by crushing pieces of coral hard tissue in a percussion device connected to either a cavity ring‐down spectroscopy (CRDS) system or an isotope ratio mass spectrometry (IRMS) system. Despite most samples yielding sufficient water, each analytical system produces distinct isotope patterns. Experiments show that several characteristics specific to biominerals give rise to discrepancies and analytical artefacts that preclude the acquisition of reproducible isotope data. The main complication is that internal water in biogenic carbonates is distributed in an open interconnected micro‐network that readily exchanges with external water and potentially facilitates interaction with hydration water in the finely dispersed organic matrix in the coral skeleton. Furthermore, only an isotopically fractionated part of the internal water is released from the coral skeletons upon crushing. Altogether, isotope ratio measurement of internal water in corals with bulk crushing techniques does not give primary fluid isotope ratios useful for (palaeo‐)environmental or microbiological studies. As the resulting isotope patterns can show systematic behaviour per technique, isotope data may be erroneously interpreted to reflect the original calcifying fluid when using only a single technique to isotopically characterise internal fluids in coral skeletons.Key Points: Free water trapped inside coral skeletons was extracted and isotopically analyzed on two commonly used techniques for fluid inclusion isotope analysis. Measured oxygen and hydrogen isotope ratios do not reproduce between the techniques due to several analytical artefacts. The water extracted from coral skeletons is not of primary origin.Nederlandse Organisatie voor Wetenschappelijk Onderzoek http://dx.doi.org/10.13039/501100003246Western Indian Ocean Marine Science Association http://dx.doi.org/10.13039/50110000910

Age-related loss of axonal regeneration is reflected by the level of local translation.

Regeneration capacity is reduced as CNS axons mature. Using laser-mediated axotomy, proteomics and puromycin-based tagging of newly-synthesized proteins in a human embryonic stem cell-derived neuron culture system that allows isolation of axons from cell bodies, we show here that efficient regeneration in younger axons (d45 in culture) is associated with local axonal protein synthesis (local translation). Enhanced regeneration, promoted by co-culture with human glial precursor cells, is associated with increased axonal synthesis of proteins, including those constituting the translation machinery itself. Reduced regeneration, as occurs with the maturation of these axons by d65 in culture, correlates with reduced levels of axonal proteins involved in translation and an inability to respond by increased translation of regeneration promoting axonal mRNAs released from stress granules. Together, our results provide evidence that, as in development and in the PNS, local translation contributes to CNS axon regeneration