Trust as a mediator in the relationship between childhood sexual abuse and IL-6 level in adulthood

Childhood sexual abuse (CSA) has been shown to predict the coupling of depression and inflammation in adulthood. Trust within intimate relationships, a core element in marital relations, has been shown to predict positive physical and mental health outcomes, but the mediating role of trust in partners in the association between CSA and inflammation in adulthood requires further study. The present study aimed to examine the impact of CSA on inflammatory biomarkers (IL-6 and IL-1β) in adults with depression and the mediating role of trust. A cross-sectional survey data set of adults presenting with mood and sleep disturbance was used in the analysis. CSA demonstrated a significant negative correlation with IL-6 level (r = -0.28, p<0. 01) in adults with clinically significant depression, while trust showed a significant positive correlation with IL-6 level (r = 0.36, p < .01). Sobel test and bootstrapping revealed a significant mediating role for trust between CSA and IL-6 level. CSA and trust in partners were revealed to have significant associations with IL-6 level in adulthood. Counterintuitively, the directions of association were not those expected. Trust played a mediating role between CSA and adulthood levels of IL-6. Plausible explanations for these counterintuitive findings are discussed

KDEL receptors assist dengue virus exit from the endoplasmic reticulum

Membrane receptors at the surface of target cells are key host factors for virion entry; however, it is unknown whether trafficking and secretion of progeny virus requires host intracellular receptors. In this study, we demonstrate that dengue virus (DENV) interacts with KDEL receptors (KDELR), which cycle between the ER and Golgi apparatus, for vesicular transport from ER to Golgi. Depletion of KDELR by siRNA reduced egress of both DENV progeny and recombinant subviral particles (RSPs). Coimmunoprecipitation of KDELR with dengue structural protein prM required three positively charged residues at the N terminus, whose mutation disrupted protein interaction and inhibited RSP transport from the ER to the Golgi. Finally, siRNA depletion of class II Arfs, which results in KDELR accumulation in the Golgi, phenocopied results obtained with mutagenized prME and KDELR knockdown. Our results have uncovered a function for KDELR as an internal receptor involved in DENV trafficking.published_or_final_versio

Photoluminescent properties of ZrO2: Tm3+, Tb3+, Eu3+ powdersd-A combined experimental and theoretical study

Rare-earth (RE) element-based materials for optical applications have received increasing attention owing to the emission properties of RE ions, which render these materials suitable for use in color displays, lasers, and solid-state lighting. In the present work, ZrO2:RE (RE = Tm3+, Tb3+, and Eu3+) powders were obtained via complex polymerization, and characterized by means of X-ray diffraction (XRD), Raman spectroscopy, UV–visible absorption spectroscopy, and photoluminescence measurements. The XRD patterns and Raman spectra revealed the tetragonal phase of ZrO2 co-doped with up to 4 mol.% RE3+ and stabilization of the cubic phase, for up to 8 mol.% RE3+. In addition, the photoluminescence measurements revealed simultaneous emissions in the blue (477 nm), green (496.02 nm and 548.32 nm), and red-orange (597.16 nm and 617.54 nm) regions. These emissions result from the Tm3+, Tb 3+, and Eu3+ ions, respectively. Energy transfers, such as 1G4 levels (Tm3+) → 5D4 (Tb3+) and 5D4 levels (Tb3+) → 5D0 (Eu3+), occurred during the emission process. Calculations based on density functional theory (DFT) were performed, to complement the experimental data. The results revealed that structural order/disorder effects were generated in the cubic and tetragonal ZrO2 phases in the ZrO2:Eu3+ powders, and changes in the electronic structure were manifested as a decrease in the band gap values. The chromaticity coordinates of all the samples were determined from the PL spectrum. The coordinates, x = 0.34 and y = 0.34, of the ZrO2:8%RE sample corresponded to a point located in the white region of the CIE diagram and color correlated temperature (CCT) was found to be 5181 K. More importantly, the present results indicate that ZrO2:RE powders constitute promising photoluminescent materials for use in new lighting devices.The authors gratefully acknowledge the financial support of the Brazilian governmental research funding agencies CAPES, CNPq 402127/2013-7, FAPESP2013/07296-2 and INCTMN2008/57872-1

Discovery of an exosite on the SOCS2-SH2 domain that enhances SH2 binding to phosphorylated ligands

Suppressor of cytokine signaling (SOCS)2 protein is a key negative regulator of the growth hormone (GH) and Janus kinase (JAK)-Signal Transducers and Activators of Transcription (STAT) signaling cascade. The central SOCS2-Src homology 2 (SH2) domain is characteristic of the SOCS family proteins and is an important module that facilitates recognition of targets bearing phosphorylated tyrosine (pTyr) residues. Here we identify an exosite on the SOCS2-SH2 domain which, when bound to a non-phosphorylated peptide (F3), enhances SH2 affinity for canonical phosphorylated ligands. Solution of the SOCS2/F3 crystal structure reveals F3 as an α-helix which binds on the opposite side of the SH2 domain to the phosphopeptide binding site. F3:exosite binding appears to stabilise the SOCS2-SH2 domain, resulting in slower dissociation of phosphorylated ligands and consequently, enhances binding affinity. This biophysical enhancement of SH2:pTyr binding affinity translates to increase SOCS2 inhibition of GH signaling

Viral subversion of selective autophagy is critical for biogenesis of virus replication organelles

Infection by many (+)RNA viruses is accompanied by ER-expansion and membrane remodelling to form viral replication organelles, followed by assembly and secretion of viral progenies. We previously identified that virus-triggered lipophagy was critical for flaviviral assembly, and is driven by the lipid droplet associated protein Ancient ubiquitin protein 1 (Aup1). A ubiquitin conjugating protein Ube2g2 that functions as a co-factor for Aup1 was identified as a host dependency factor in our study. Here we characterized its function: Ube2g2-deficient cells displayed a dramatic reduction in virus production, which could be rescued by reconstituting the wild-type but not the catalytically deficient (C89K) mutant of Ube2g2, suggesting that its enzymatic activity is necessary. Ube2g2 deficiency did not affect entry of virus particles but resulted in a profound loss in formation of replication organelles, and production of infectious progenies. This phenomenon resulted from its dual activity in (i) triggering lipophagy in conjunction with Aup1, and (ii) degradation of ER chaperones such as Herpud1, SEL1L, Hrd1, along with Sec62 to restrict ER-phagy upon Xbp1-IRE1 triggered ER expansion. Our results therefore underscore an exquisite fine-tuning of selective autophagy by flaviviruses that drive host membrane reorganization during infection to enable biogenesis of viral replication organelles

The K\"ahler-Ricci flow on surfaces of positive Kodaira dimension

The existence of K\"ahler-Einstein metrics on a compact K\"ahler manifold has been the subject of intensive study over the last few decades, following Yau's solution to Calabi's conjecture. The Ricci flow, introduced by Richard Hamilton has become one of the most powerful tools in geometric analysis. We study the K\"ahler-Ricci flow on minimal surfaces of Kodaira dimension one and show that the flow collapses and converges to a unique canonical metric on its canonical model. Such a canonical is a generalized K\"ahler-Einstein metric. Combining the results of Cao, Tsuji, Tian and Zhang, we give a metric classification for K\"aher surfaces with a numerical effective canonical line bundle by the K\"ahler-Ricci flow. In general, we propose a program of finding canonical metrics on canonical models of projective varieties of positive Kodaira dimension

Drug Repurposing for the Treatment of COVID-19: A Knowledge Graph Approach

Identifying effective drug treatments for COVID-19 is essential to reduce morbidity and mortality. Although a number of existing drugs have been proposed as potential COVID-19 treatments, effective data platforms and algorithms to prioritize drug candidates for evaluation and application of knowledge graph for drug repurposing have not been adequately explored. A COVID-19 knowledge graph by integrating 14 public bioinformatic databases containing information on drugs, genes, proteins, viruses, diseases, symptoms and their linkages is developed. An algorithm is developed to extract hidden linkages connecting drugs and COVID-19 from the knowledge graph, to generate and rank proposed drug candidates for repurposing as treatments for COVID-19 by integrating three scores for each drug: motif scores, knowledge graph PageRank scores, and knowledge graph embedding scores. The knowledge graph contains over 48 000 nodes and 13 37 000 edges, including 13 563 molecules in the DrugBank database. From the 5624 molecules identified by the motif-discovery algorithms, ranking results show that 112 drug molecules had the top 2% scores, of which 50 existing drugs with other indications approved by health administrations reported. The proposed drug candidates serve to generate hypotheses for future evaluation in clinical trials and observational studies