Neural processing of criticism and positive comments from relatives in individuals with schizotypal personality traits

Objectives. High negative expressed emotion by family members towards schizophrenia patients increases the risk of subsequent relapse. The study aimed to determine whether individuals with high schizotypy (HS) and low schizotypy (LS) would differ in activation of brain areas involved in cognitive control when listening to relative criticism

Optimized two-dimensional thin layer chromatography to monitor the intracellular concentration of acetyl phosphate and other small phosphorylated molecules

Acetyl phosphate (acetyl-P) serves critical roles in coenzyme A recycling and ATP synthesis. It is the intermediate of the Pta-AckA pathway that inter-converts acetyl-coenzyme A and acetate. Acetyl-P also can act as a global signal by donating its phosphoryl group to specific two-component response regulators. This ability derives from its capacity to store energy in the form of a high-energy phosphate bond. This bond, while critical to its function, also destabilizes acetyl-P in cell extracts. This lability has greatly complicated biochemical analysis, leading in part to widely varying acetyl-P measurements. We therefore developed an optimized protocol based on two-dimensional thin layer chromatography that includes metabolic labeling under aerated conditions and careful examination of the integrity of acetyl-P within extracts. This protocol results in greatly improved reproducibility, and thus permits precise measurements of the intracellular concentration of acetyl-P, as well as that of other small phosphorylated molecules

Urinary Exosomal microRNA-451-5p Is a Potential Early Biomarker of Diabetic Nephropathy in Rats

Non-invasive renal signatures can help in serial monitoring of diabetic patients. We tested whether urinary exosomal (UE) microRNA (miR) analysis could non-invasively predict renal pathology in diabetic rats during the course of diabetes. Diabetes mellitus (DM) was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg body weight). Non-diabetic control (CTRL) rats were injected with vehicle. Insulin (INS) treatment (5U/d, s.c.) was provided to 50% of the DM rats. Urine samples were collected at weeks 3, 6, and 9 following injections and UE prepared. An increase in miR-451-5p and miR-16, observed by pilot small RNA sequencing of UE RNA, was confirmed by quantitative real-time polymerase chain reaction (qPCR) and selected for further study. Subsets of rats were euthanized after 3, 6, and 9 weeks of diabetes for renal pathology analysis, including determination of the tubulointerstitial fibrotic index (TFI) and glomerulosclerotic index (GI) scores. qPCR showed a substantial rise in miR-451-5p in UE from DM rats during thecourse of diabetes, with a significant rise (median fold change >1000) between 3 and 6 weeks. Moreover, UE miR-451-5p at 6 weeks predicted urine albumin at 9 weeks (r = 0.76). A delayed but significant rise was also observed for miR-16. In contrast, mean urine albumin only increased 21% between 3 and 6 weeks (non-significant rise), and renal TFI and GI were unchanged till 9 weeks. Renal expression of miR-451-5p and miR-16 (at 10 weeks) did not correlate with urine levels, and moreover, was negatively associated with indices of renal pathology (r�-0.70, p = 0.005 for TFI and r�-0.6, p�0.02 for GI). Overall, a relative elevation in renal miR-451-5p and miR-16 in diabetes appeared protective against diabetes- induced kidney fibrosis; while UE miR-451-5p may hold prognostic value as an earlyand sensitive non-invasive indicator of renal diseas

Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF∼0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10 -3 ), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies

Recent developments in mushrooms as anti-cancer therapeutics: a review

From time immemorial, mushrooms have been valued by humankind as a culinary wonder and folk medicine in Oriental practice. The last decade has witnessed the overwhelming interest of western research fraternity in pharmaceutical potential of mushrooms. The chief medicinal uses of mushrooms discovered so far are as anti-oxidant, anti-diabetic, hypocholesterolemic, anti-tumor, anti-cancer, immunomodulatory, anti-allergic, nephroprotective, and anti-microbial agents. The mushrooms credited with success against cancer belong to the genus Phellinus, Pleurotus, Agaricus, Ganoderma, Clitocybe, Antrodia, Trametes, Cordyceps, Xerocomus, Calvatia, Schizophyllum, Flammulina, Suillus, Inonotus, Inocybe, Funlia, Lactarius, Albatrellus, Russula, and Fomes. The anti-cancer compounds play crucial role as reactive oxygen species inducer, mitotic kinase inhibitor, anti-mitotic, angiogenesis inhibitor, topoisomerase inhibitor, leading to apoptosis, and eventually checking cancer proliferation. The present review updates the recent findings on the pharmacologically active compounds, their anti-tumor potential, and underlying mechanism of biological action in order to raise awareness for further investigations to develop cancer therapeutics from mushrooms. The mounting evidences from various research groups across the globe, regarding anti-tumor application of mushroom extracts unarguably make it a fast-track research area worth mass attention

Prolonged diet-induced obesity in mice modifies the inflammatory response and leads to worse outcome after stroke

BACKGROUND: Obesity increases the risk for ischaemic stroke and is associated with worse outcome clinically and experimentally. Most experimental studies have used genetic models of obesity. Here, a more clinically relevant model, diet-induced obesity, was used to study the impact of obesity over time on the outcome and inflammatory response after stroke. METHODS: Male C57BL/6 mice were maintained on a high-fat (60% fat) or control (12% fat) diet for 2, 3, 4 and 6 months when experimental stroke was induced by transient occlusion of the middle cerebral artery (MCAo) for either 20 (6-month diet) or 30 min (2-, 3-, 4- and 6-month diet). Ischaemic damage, blood-brain barrier (BBB) integrity, neutrophil number and chemokine expression in the brain were assessed at 24 h. Plasma chemokine levels (at 4 and 24 h) and neutrophil number in the liver (at 24 h) were measured. Physiological parameters (body weight and blood glucose) were measured in naïve control- and high-fat-fed mice at all time points and blood pressure at 3 and 6 months. Blood cell counts were also assessed in naïve 6-month control- and high-fat-fed mice. RESULTS: Mice fed a high-fat diet for 6 months had greater body weight, blood glucose and white and red blood cell count but no change in systolic blood pressure. After 4 and 6 months of high-fat feeding, and in the latter group with a 30-min (but not 20-min) occlusion of the MCA, obese mice had greater ischaemic brain damage. An increase in blood-brain barrier permeability, chemokine expression (CXCL-1 and CCL3), neutrophil number and microglia/macrophage cells was observed in the brains of 6-month high-fat-fed mice after 30-min MCAo. In response to stroke, chemokine (CXCL-1) expression in the plasma and liver was significantly different in obese mice (6-month high-fat fed), and a greater number of neutrophils were detected in the liver of control but not obese mice. CONCLUSIONS: The detrimental effects of diet-induced obesity on stroke were therefore dependent on the severity of obesity and length of ischaemic challenge. The altered inflammatory response in obese mice may play a key role in its negative impact on stroke

Search for strongly interacting massive particles generating trackless jets in proton-proton collisions at s = 13 TeV

A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 16.1 fb - 1 , collected with the CMS detector in 2016. No significant excess of events is observed above the expected background. For the simplified dark matter model under consideration, SIMPs with masses up to 100 GeV are excluded and further sensitivity is explored towards higher masses

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into different pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, , and tb) or third-generation leptons (τν and ττ) are included in this kind of combination for the first time. A simplified model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confidence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion

Measurement and interpretation of same-sign W boson pair production in association with two jets in pp collisions at s = 13 TeV with the ATLAS detector

This paper presents the measurement of fducial and diferential cross sections for both the inclusive and electroweak production of a same-sign W-boson pair in association with two jets (W±W±jj) using 139 fb−1 of proton-proton collision data recorded at a centre-of-mass energy of √s = 13 TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed by selecting two same-charge leptons, electron or muon, and at least two jets with large invariant mass and a large rapidity diference. The measured fducial cross sections for electroweak and inclusive W±W±jj production are 2.92 ± 0.22 (stat.) ± 0.19 (syst.)fb and 3.38±0.22 (stat.)±0.19 (syst.)fb, respectively, in agreement with Standard Model predictions. The measurements are used to constrain anomalous quartic gauge couplings by extracting 95% confdence level intervals on dimension-8 operators. A search for doubly charged Higgs bosons H±± that are produced in vector-boson fusion processes and decay into a same-sign W boson pair is performed. The largest deviation from the Standard Model occurs for an H±± mass near 450 GeV, with a global signifcance of 2.5 standard deviations