The baryon density at z=0.9-1.9 - Tracing the warm-hot intergalactic medium with broad Lyman alpha absorption

We present an analysis of the Lyman alpha forests of five quasar spectra in the near UV. Properties of the intergalactic medium (IGM) at an intermediate redshift interval (0.9 < z < 1.9) are studied. The amount of baryons in the diffuse photoionised IGM and the warm-hot intergalactic medium (WHIM) are traced to get constraints on the redshift evolution of the different phases of the intergalactic gas. The baryon density of the diffuse IGM is determined with photoionisation calculations under the assumption of local hydrostatic equilibrium. We assume that the gas is ionised by a metagalactic background radiation with a Haardt & Madau (2001) spectrum. The WHIM is traced with broad Lyman alpha (BLA) absorption. The properties of a number of BLA detections are studied. Under the assumption of collisional ionisation equilibrium a lower limit to the baryon density could be estimated. It is found that the diffuse photoionised IGM contains at least 25% of the total baryonic matter at redshifts 1 < z < 2. For the WHIM a lower limit of 2.4% could be determined. Furthermore the data indicates that the intergalactic gas is in a state of evolution at z=1.5. We confirm that a considerable part of the WHIM is created between z=1 and z=2.Comment: 6 pages, 1 figure, accepted for publication in A&

Iatrogenic effects of Reboot/ NoFap on public health: A preregistered survey study

“Reboot,” especially NoFap, promotes abstinence from masturbation and/or pornography to treat “pornography addiction,” an unrecognized diagnosis. While the intention of Reboot/NoFap is to decrease distress, qualitative studies have consistently suggested that “Reboots” paradoxically cause more distress. The distress appears to occur in response to (1) the abstinence goal, which recasts common sexual behaviors as personal “failures,” and (2) problematic and inaccurate Reboot/NoFap forum messaging regarding sexuality and addiction. This preregistered survey asked men about their experience with perceived “relapse” and NoFap forums. Participants reported that their most recent relapse was followed by feeling shameful, worthless, sad, a desire to commit suicide, and other negative emotions. A novel predictor of identifying as a pornography addict in this lower religiosity sample was higher narcissism. Participants reported that NoFap forums contained posts that were misogynist (73.7% of participants), bullying (49.1%), anti-LGBT (42.9%), antisemitic (32.0%), instructing followers to harm or kill themselves (23.5%), or threats to hurt someone else (21.1%). More engagement in NoFap online forums was associated with worse symptoms of erectile dysfunction, depression, anxiety, and more sex negativity. Results support and expand previously documented harms and problems with Reboot/NoFap claims of treating pornography addiction from qualitative research

Asexuality: Classification and characterization

This is a post-print version of the article. The official published version can be obtaineed at the link below.The term “asexual” has been defined in many different ways and asexuality has received very little research attention. In a small qualitative study (N = 4), individuals who self-identified as asexual were interviewed to help formulate hypotheses for a larger study. The second larger study was an online survey drawn from a convenience sample designed to better characterize asexuality and to test predictors of asexual identity. A convenience sample of 1,146 individuals (N = 41 self-identified asexual) completed online questionnaires assessing sexual history, sexual inhibition and excitation, sexual desire, and an open-response questionnaire concerning asexual identity. Asexuals reported significantly less desire for sex with a partner, lower sexual arousability, and lower sexual excitation but did not differ consistently from non-asexuals in their sexual inhibition scores or their desire to masturbate. Content analyses supported the idea that low sexual desire is the primary feature predicting asexual identity

Disgust trumps lust:women’s disgust and attraction towards men is unaffected by sexual arousal

Mating is a double-edged sword. It can have great adaptive benefits, but also high costs, depending on the mate. Disgust is an avoidance reaction that serves the function of discouraging costly mating decisions, for example if the risk of pathogen transmission is high. It should, however, be temporarily inhibited in order to enable potentially adaptive mating. We therefore tested the hypothesis that sexual arousal inhibits disgust if a partner is attractive, but not if he is unattractive or shows signs of disease. In an online experiment, women rated their disgust towards anticipated behaviors with men depicted on photographs. Participants did so in a sexually aroused state and in a control state. The faces varied in attractiveness and the presence of disease cues (blemishes). We found that disease cues and attractiveness, but not sexual arousal, influenced disgust. The results suggest that women feel disgust at sexual contact with unattractive or diseased men independently of their sexual arousal

Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity

Metformin, the first-line drug to treat type 2 diabetes (T2D), inhibits mitochondrial glycerolphosphate dehydrogenase in the liver to suppress gluconeogenesis. However, the direct target and the underlying mechanisms by which metformin increases glucose uptake in peripheral tissues remain uncharacterized. Lipid phosphatase Src homology 2 domain-containing inositol-5-phosphatase 2 (SHIP2) is upregulated in diabetic rodent models and suppresses insulin signaling by reducing Akt activation, leading to insulin resistance and diminished glucose uptake. Here, we demonstrate that metformin directly binds to and reduces the catalytic activity of the recombinant SHIP2 phosphatase domain in vitro. Metformin inhibits SHIP2 in cultured cells and in skeletal muscle and kidney of db/db mice. In SHIP2-overexpressing myotubes, metformin ameliorates reduced glucose uptake by slowing down glucose transporter 4 endocytosis. SHIP2 overexpression reduces Akt activity and enhances podocyte apoptosis, and both are restored to normal levels by metformin. SHIP2 activity is elevated in glomeruli of patients with T2D receiving nonmetformin medication, but not in patients receiving metformin, compared with people without diabetes. Furthermore, podocyte loss in kidneys of metformin-treated T2D patients is reduced compared with patients receiving nonmetformin medication. Our data unravel a novel molecular mechanism by which metformin enhances glucose uptake and acts renoprotectively by reducing SHIP2 activity.Polianskyte-Prause, Z., Tolvanen, T. A., Lindfors, S., Dumont, V., Van, M., Wang, H., Dash, S. N., Berg, M., Naams, J.-B., Hautala, L. C., Nisen, H., Mirtti, T., Groop, P.-H., Wahala, K., Tienari, J., Lehtonen, S. Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity.Peer reviewe

Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding

Insufficient insulin secretion is a hallmark of type 2 diabetes and has been attributed to beta cell identity loss characterized by decreased expression of several key beta cell genes. The pro-inflammatory factor BMP-2 is upregulated in islets of Langerhans from individuals with diabetes and acts as an inhibitor of beta cell function and proliferation. Exposure to BMP-2 induces expression of Id1-4, Hes-1, and Hey-1 which are transcriptional regulators associated with loss of differentiation. The aim of this study was to investigate the mechanism by which BMP-2 induces beta cell dysfunction and loss of cell maturity. Mouse islets exposed to BMP-2 for 10 days showed impaired glucose-stimulated insulin secretion and beta cell proliferation. BMP-2-induced beta cell dysfunction was associated with decreased expression of cell maturity and proliferation markers specific to the beta cell such as Ins1, Ucn3, and Ki67 and increased expression of Id1-4, Hes-1, and Hey-1. The top 30 most regulated proteins significantly correlated with corresponding mRNA expression. BMP-2-induced gene expression changes were associated with a predominant reduction in acetylation of H3K27 and a decrease in NeuroD1 chromatin binding activity. These results show that BMP-2 induces loss of beta cell maturity and suggest that remodeling of H3K27ac and decreased NeuroD1 DNA binding activity participate in the effect of BMP-2 on beta cell dysfunction

Scholars’ open debate paper on the World Health Organization ICD-11 gaming disorder proposal

Concerns about problematic gaming behaviors deserve our full attention. However, we claim that it is far from clear that these problems can or should be attributed to a new disorder. The empirical basis for a Gaming Disorder proposal, such as in the new ICD-11, suffers from fundamental issues. Our main concerns are the low quality of the research base, the fact that the current operationalization leans too heavily on substance use and gambling criteria, and the lack of consensus on symptomatology and assessment of problematic gaming. The act of formalizing this disorder, even as a proposal, has negative medical, scientific, public-health, societal, and human rights fallout that should be considered. Of particular concern are moral panics around the harm of video gaming. They might result in premature application of diagnosis in the medical community and the treatment of abundant false-positive cases, especially for children and adolescents. Second, research will be locked into a confirmatory approach, rather than an exploration of the boundaries of normal versus pathological. Third, the healthy majority of gamers will be affected negatively. We expect that the premature inclusion of Gaming Disorder as a diagnosis in ICD-11 will cause significant stigma to the millions of children who play video games as a part of a normal, healthy life. At this point, suggesting formal diagnoses and categories is premature: the ICD-11 proposal for Gaming Disorder should be removed to avoid a waste of public health resources as well as to avoid causing harm to healthy video gamers around the world

A weak scientific basis for gaming disorder: let us err on the side of caution

We greatly appreciate the care and thought that is evident in the 10 commentaries that discuss our debate paper, the majority of which argued in favor of a formalized ICD-11 gaming disorder. We agree that there are some people whose play of video games is related to life problems. We believe that understanding this population and the nature and severity of the problems they experience should be a focus area for future research. However, moving from research construct to formal disorder requires a much stronger evidence base than we currently have. The burden of evidence and the clinical utility should be extremely high, because there is a genuine risk of abuse of diagnoses. We provide suggestions about the level of evidence that might be required: transparent and preregistered studies, a better demarcation of the subject area that includes a rationale for focusing on gaming particularly versus a more general behavioral addictions concept, the exploration of non-addiction approaches, and the unbiased exploration of clinical approaches that treat potentially underlying issues, such as depressive mood or social anxiety first. We acknowledge there could be benefits to formalizing gaming disorder, many of which were highlighted by colleagues in their commentaries, but we think they do not yet outweigh the wider societal and public health risks involved. Given the gravity of diagnostic classification and its wider societal impact, we urge our colleagues at the WHO to err on the side of caution for now and postpone the formalization

CD8 positive T cells express IL-17 in patients with chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible chronic inflammatory disease of the lung. The nature of the immune reaction in COPD raises the possibility that IL-17 and related cytokines may contribute to this disorder. This study analyzed the expression of IL-17A and IL-17F as well as the phenotype of cells producing them in bronchial biopsies from COPD patients.</p> <p>Methods</p> <p>Bronchoscopic biopsies of the airway were obtained from 16 COPD subjects (GOLD stage 1-4) and 15 control subjects. Paraffin sections were used for the investigation of IL-17A and IL-17F expression in the airways by immunohistochemistry, and frozen sections were used for the immunofluorescence double staining of IL-17A or IL-17F paired with CD4 or CD8. In order to confirm the expression of IL-17A and IL-17F at the mRNA level, a quantitative RT-PCR was performed on the total mRNA extracted from entire section or CD8 positive cells selected by laser capture microdissection.</p> <p>Results</p> <p>IL-17F immunoreactivity was significantly higher in the bronchial biopsies of COPD patients compared to control subjects (<it>P </it>< 0.0001). In the submucosa, the absolute number of both IL-17A and IL-17F positive cells was higher in COPD patients (<it>P </it>< 0.0001). After adjusting for the total number of cells in the submucosa, we still found that more cells were positive for both IL-17A (<it>P </it>< 0.0001) and IL-17F (<it>P </it>< 0.0001) in COPD patients compared to controls. The mRNA expression of IL-17A and IL-17F in airways of COPD patients was confirmed by RT-PCR. The expression of IL-17A and IL-17F was co-localized with not only CD4 but also CD8, which was further confirmed by RT-PCR on laser capture microdissection selected CD8 positive cells.</p> <p>Conclusion</p> <p>These findings support the notion that Th17 cytokines could play important roles in the pathogenesis of COPD, raising the possibility of using this mechanism as the basis for novel therapeutic approaches.</p