Demographic costs of inbreeding revealed by sex-specific genetic rescue effects

<p>Abstract</p> <p>Background</p> <p>Inbreeding can slow population growth and elevate extinction risk. A small number of unrelated immigrants to an inbred population can substantially reduce inbreeding and improve fitness, but little attention has been paid to the sex-specific effects of immigrants on such "genetic rescue". We conducted two subsequent experiments to investigate demographic consequences of inbreeding and genetic rescue in guppies.</p> <p>Results</p> <p>Populations established from pairs of full siblings that were descended either from two generations of full-sibling inbreeding or unrelated outbred guppies did not grow at different rates initially, but when the first generation offspring started breeding, outbred-founded populations grew more slowly than inbred-founded populations. In a second experiment, adding two outbred males to the inbred populations resulted in significantly faster population growth than in control populations where no immigrants were added. Adding females resulted in growth at a rate intermediate to the control and male-immigrant treatments.</p> <p>Conclusion</p> <p>The slower growth of the outbred-founded than inbred-founded populations is the opposite of what would be expected under inbreeding depression unless many deleterious recessive alleles had already been selectively purged in the inbreeding that preceded the start of the experiment, and that significant inbreeding depression occurred when the first generation offspring in outbred-founded populations started to inbreed. The second experiment revealed strong inbreeding depression in the inbred founded populations, despite the apparent lack thereof in these populations earlier on. Moreover, the fact that the addition of male immigrants resulted in the highest levels of population growth suggests that sex-specific genetic rescue may occur in promiscuous species, with male rescue resulting in higher levels of outbreeding than female rescue.</p

The role of working memory for cognitive control in anorexia nervosa versus substance use disorder

Prefrontal cortex executive functions, such as working memory (WM) interact with limbic processes to foster impulse control. Such an interaction is referred to in a growing body of publications by terms such as cognitive control, cognitive inhibition, affect regulation, self-regulation, top-down control, and cognitive-emotion interaction. The rising trend of research into cognitive control of impulsivity, using various related terms reflects the importance of research into impulse control, as failure to employ cognitions optimally may eventually result in mental disorder. Against this background, we take a novel approach using an impulse control spectrum model - where anorexia nervosa (AN) and substance use disorder (SUD) are at opposite extremes - to examine the role of WM for cognitive control. With this aim, we first summarize WM processes in the healthy brain in order to frame a systematic review of the neuropsychological, neural and genetic findings of AN and SUD. In our systematic review of WM/cognitive control, we found n = 15 studies of AN with a total of n = 582 AN and n = 365 HC participants; and n = 93 studies of SUD with n = 9106 SUD and n = 3028 HC participants. In particular, we consider how WM load/capacity may support the neural process of excessive epistemic foraging (cognitive sampling of the environment to test predictions about the world) in AN that reduces distraction from salient stimuli. We also consider the link between WM and cognitive control in people with SUD who are prone to 'jumping to conclusions' and reduced epistemic foraging. Finally, in light of our review, we consider WM training as a novel research tool and an adjunct to enhance treatment that improves cognitive control of impulsivity. © 2017 Brooks, Funk, Young and Schiöth

Rural men and mental health: their experiences and how they managed

There is a growing awareness that a primary source of information about mental health lies with the consumers. This article reports on a study that interviewed rural men with the aim of exploring their mental health experiences within a rural environment. The results of the interviews are a number of stories of resilience and survival that highlight not only the importance of exploring the individuals' perspective of their issues, but also of acknowledging and drawing on their inner strengths. Rural men face a number of challenges that not only increase the risk of mental illness but also decrease the likelihood of them seeking and/or finding professional support. These men's stories, while different from each other, have a common thread of coping. Despite some support from family and friends participants also acknowledged that seeking out professional support could have made the recovery phase easier. Mental health nurses need to be aware, not only of the barrier to professional support but also of the significant resilience that individuals have and how it can be utilised

Exploring the neural substrates of misinformation processing

It is well known that information that is initially thought to be correct but then revealed to be false, often continues to influence human judgement and decision making despite people being aware of the retraction. Yet little research has examined the underlying neural substrates of this phenomenon, which is known as the ‘continued influence effect of misinformation’ (CIEM). It remains unclear how the human brain processes critical information that retracts prior claims. To address this question in further detail, 26 healthy adults underwent functional magnetic resonance imaging (fMRI) while listening to brief narratives which either involved a retraction of prior information or not. Following each narrative, subjects’ comprehension of the narrative, including their inclination to rely on retracted information, was probed. As expected, it was found that retracted information continued to affect participants’ narrative-related reasoning. In addition, the fMRI data indicated that the continued influence of retracted information may be due to a breakdown of narrative-level integration and coherence-building mechanisms implemented by the precuneus and posterior cingulate gyrus

Keeping track of ‘alternative facts’: The neural correlates of processing misinformation corrections

Upon receiving a correction, initially presented misinformation often continues to influence people's judgment and reasoning. Whereas some researchers believe that this so-called continued influence effect of misinformation (CIEM) simply arises from the insufficient encoding and integration of corrective claims, others assume that it arises from a competition between the correct information and the initial misinformation in memory. To examine these possibilities, we conducted two functional magnetic resonance imaging (fMRI) studies. In each study, participants were asked to (a) read a series of brief news reports that contained confirmations or corrections of prior information and (b) evaluate whether subsequently presented memory probes matched the reports' correct facts rather than the initial misinformation. Both studies revealed that following correction-containing news reports, participants struggled to refute mismatching memory probes, especially when they referred to initial misinformation (as opposed to mismatching probes with novel information). We found little evidence, however, that the encoding of confirmations and corrections produced systematic neural processing differences indicative of distinct encoding strategies. Instead, we discovered that following corrections, participants exhibited increased activity in the left angular gyrus and the bilateral precuneus in response to mismatching memory probes that contained prior misinformation, compared to novel mismatch probes. These findings favour the notion that people's susceptibility to the CIEM arises from the concurrent retention of both correct and incorrect information in memory

Intrinsic androgen-dependent gene expression patterns revealed by comparison of genital fibroblasts from normal males and individuals with complete and partial androgen insensitivity syndrome

<p>Abstract</p> <p>Background</p> <p>To better understand the molecular programs of normal and abnormal genital development, clear-cut definition of androgen-dependent gene expression patterns, without the influence of genotype (46, XX vs. 46, XY), is warranted. Previously, we have identified global gene expression profiles in genital-derived fibroblasts that differ between 46, XY males and 46, XY females with complete androgen insensitivity syndrome (CAIS) due to inactivating mutations of the androgen receptor (AR). While these differences could be due to cell autonomous changes in gene expression induced by androgen programming, recent work suggests they could also be influenced by the location from which the fibroblasts were harvested (topology). To minimize the influence of topology, we compared gene expression patterns of fibroblasts derived from identical urogenital anlagen: the scrotum in normally virilized 46, XY males and the labia majora from completely feminized 46, XY individuals with CAIS.</p> <p>Results</p> <p>612 transcripts representing 440 unique genes differed significantly in expression levels between scrotum and CAIS labia majora, suggesting the effects of androgen programming. While some genes coincided with those we had identified previously (TBX3, IGFBP5, EGFR, CSPG2), a significant number did not, implying that topology had influenced gene expression in our previous experiments. Supervised clustering of gene expression data derived from a large set of fibroblast cultures from individuals with partial AIS revealed that the new, topology controlled data set better classified the specimens.</p> <p>Conclusion</p> <p>Inactivating mutations of the AR, in themselves, appear to induce lasting changes in gene expression in cultured fibroblasts, independent of topology and genotype. Genes identified are likely to be relevant candidates to decipher androgen-dependent normal and abnormal genital development.</p

Allocating the Burdens of Climate Action: Consumption-Based Carbon Accounting and the Polluter-Pays Principle

Action must be taken to combat climate change. Yet, how the costs of climate action should be allocated among states remains a question. One popular answer—the polluter-pays principle (PPP)—stipulates that those responsible for causing the problem should pay to address it. While intuitively plausible, the PPP has been subjected to withering criticism in recent years. It is timely, following the Paris Agreement, to develop a new version: one that does not focus on historical production-based emissions but rather allocates climate burdens in proportion to each state’s annual consumption-based emissions. This change in carbon accounting results in a fairer and more environmentally effective principle for distributing climate duties

Optimization and evaluation of a live virus SARS-CoV-2 neutralization assay

Virus neutralization assays provide a means to quantitate functional antibody responses that block virus infection. These assays are instrumental in defining vaccine and therapeutic antibody potency, immune evasion by viral variants, and post-infection immunity. Here we describe the development, optimization and evaluation of a live virus microneutralization assay specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this assay, SARS-CoV-2 clinical isolates are pre-incubated with serial diluted antibody and added to Vero E6 cells. Replicating virus is quantitated by enzyme-linked immunosorbent assay (ELISA) targeting the SARS-CoV-2 nucleocapsid protein and the standardized 50% virus inhibition titer calculated. We evaluated critical test parameters that include virus titration, assay linearity, number of cells, viral dose, incubation period post-inoculation, and normalization methods. Virus titration at 96 hours was determined optimal to account for different growth kinetics of clinical isolates. Nucleocapsid protein levels directly correlated with virus inoculum, with the strongest correlation at 24 hours post-inoculation. Variance was minimized by infecting a cell monolayer, rather than a cell suspension. Neutralization titers modestly decreased with increasing numbers of Vero E6 cells and virus amount. Application of two different normalization models effectively reduced the intermediate precision coefficient of variance to <16.5%. The SARS-CoV-2 microneutralization assay described and evaluated here is based on the influenza virus microneutralization assay described by WHO, and are proposed as a standard assay for comparing neutralization investigations

Alichur Dome, South Pamir, Western India-Asia Collisional Zone: Detailing the Neogene Shakhdara-Alichur Syn-collisional Gneiss-Dome Complex and Connection to Lithospheric Processes

Neogene, syn‐collisional extensional exhumation of Asian lower–middle crust produced the Shakhdara–Alichur gneiss‐dome complex in the South Pamir. The <1 km‐thick, mylonitic–brittle, top‐NNE, normal‐sense Alichur shear zone (ASZ) bounds the 125 × 25 km Alichur dome to the north. The Shakhdara dome is bounded by the <4 km‐thick, mylonitic–brittle, top‐SSE South Pamir normal‐sense shear zone (SPSZ) to the south, and the dextral Gunt wrench zone to its north. The Alichur dome comprises Cretaceous granitoids/gneisses cut by early Miocene leucogranites; its hanging wall contains non/weakly metamorphosed rocks. The 22–17 Ma Alichur‐dome‐injection‐complex leucogranites transition from foliation‐parallel, centimeter‐ to meter‐thick sheets within the ASZ into discordant intrusions that may comprise half the volume of the dome core. Secondary fluid inclusions in mylonites and mylonitization‐temperature constraints suggest Alichur‐dome exhumation from 10–15 km depth. Thermochronologic dates bracket footwall cooling between ~410–130 °C from ~16–4 Ma; tectonic cooling/exhumation rates (~42 °C/Myr, ~1.1 km/Myr) contrast with erosion‐dominated rates in the hanging wall (~2 °C/Myr, <0.1 km/Myr). Dome‐scale boudinage, oblique divergence of the ASZ and SPSZ hanging walls, and dextral wrenching reflect minor approximately E–W material flow out of the orogen. We attribute broadly southward younging extensional exhumation across the central South Pamir between ~20–4 Ma to: (i) Mostly northward, foreland‐directed flow of hot crust into a cold foreland during the growth of the Pamir orocline; and (ii) Contrasting effects of basal shear related to underthrusting Indian lithosphere, enhancing extension in the underthrust South Pamir and inhibiting extension in the non‐underthrust Central Pamir