Computational analysis of the formation mechanisms of carbazoles

Journal of Molecular Modeling - The organoselenium compound ebselen has recently been investigated as a treatment for COVID-19; however, efforts to model ebselen in silico have been hampered by the...     

Agomelatine modulates calcium signaling through protein kinase C and phospholipase C-mediated mechanisms in rat sensory neurons

Agomelatine, a novel antidepressant exerting its effects through melatonergic and serotonergic systems, implicated to be effective against pain including neuropathic pain but without any knowledge of mechanism of action. To explore the possible role of agomelatine on nociceptive transmission at the peripheral level, the effects of agomelatine on intracellular calcium ([Ca²⁺]_i) signaling in peripheral neurons were investigated in cultured rat dorsal root ganglion (DRG) neurons. Using the fura-2-based calcium imaging technique, the effects of agomelatine on [Ca²⁺]_i and roles of the second messenger-mediated pathways were assessed. Agomelatine caused [Ca²⁺]_i signaling in a dose-dependent manner when tested at 10 and 100 μM concentration. Luzindole, a selective melatonin receptor antagonist, almost completely blocked the agomelatine-induced calcium signals. The agomelatine-induced calcium transients were also nearly abolished following pretreatment with the 100 ng/ml pertussis toxin, a Gi/o protein inhibitor. The stimulatory effects of agomelatine on [Ca²⁺]_i transients were significantly reduced by applications of phospholipase C (PLC) and protein kinase C (PKC) blockers, 10 μM U73122, and 10 μM chelerythrine chloride, respectively. The obtained results of agomelatine-induced [Ca²⁺]_i signals indicates that peripheral mechanisms are involved in analgesic effects of agomelatine. These mechanisms seems to involve G-protein-coupled receptor activation and PLC and PKC mediated mechanisms.     

Changes in Liver Tissue Trace Element Concentrations During Hepatitis B Viral Infection Treatment

Biological Trace Element Research - Approximately 350–400 million people in the world have Hbs Ag (hepatitis B virus surface antigen) positivity. In the international guidelines, the...     

Predictors of the paroxysmal atrial fibrillation recurrence following cryoballoon-based pulmonary vein isolation: Assessment of left atrial volume,left atrial volume index,galectin-3 level and neutrophil-to-lymphocyte ratio

Background

Cryoballoon-based pulmonary vein isolation (PVI) is a treatment option for atrial fibrillation (AF). Left atrial volume (LAV) and left atrial volume index (LAVi) are important parameters for long term success of PVI. Galectin-3 (Gal-3) and neutrophil to lymphocyte ratio (N/L ratio) are biomarkers to demonstrate the cardiac fibrosis and remodelling.

Boron ameliorates arsenic‐induced DNA damage,proinflammatory cytokine gene expressions,oxidant/antioxidant status,and biochemical parameters in rats

Arsenic, an element found in nature, causes hazardous effects on living organisms. Meanwhile, natural compounds exhibit protective effects against hazardous substances. This study evaluated the effects of boron against arsenic‐induced genotoxicity and altered biochemical parameters in rats. Thirty‐five male Wistar albino rats were equally divided into five groups, and the experimental period lasted 30 days. One group was used as the control, and another group was treated with 100 mg/L arsenic in drinking water. The other groups were orally treated with 5, 10, and 20 mg/kg boron plus arsenic (100 mg/L via drinking water). Arsenic caused changes in biochemical parameters, total oxidant/antioxidant status, and DNA damage in mononuclear leukocytes. Moreover, it increased IFN‐γ, IL‐1β, TNF‐α, and NFκB mRNA expression levels in rat tissue. However, boron treatment improved arsenic‐induced alterations in biochemical parameters and increases in DNA damage and proinflammatory cytokine gene expressions.     

Offspring sex is not related to maternal allocation of yolk steroids in the lizard Bassiana duperreyi (Scincidae)

The eggs of birds and reptiles contain detectable levels of several steroid hormones, and experimental application of such steroids can reverse genetically determined sex of the offspring. However, any causal influence of maternally derived yolk steroids on sex determination in birds and reptiles remains controversial. We measured yolk hormones (dihydrotestosterone, testosterone, and 17 beta-estradiol) in newly laid eggs of the montane scincid lizard Bassiana duperreyi. This species is well suited to such an analysis because (1) offspring sex is influenced by incubation temperatures and egg size as well as by sex chromosomes, suggesting that yolk hormones might somehow be involved in the complex pathways of sex determination, and (2) experimental application of either estradiol or fadrozole to such eggs strongly influences offspring sex. We obtained yolk by biopsy, before incubating the eggs at a temperature that produces a 50:50 sex ratio. Yolk steroid levels varied over a threefold range between eggs from different clutches, but there were no significant differences in yolk steroids, or in relative composition of steroids, between eggs destined to become male versus female. Further, yolk steroid concentrations were not significantly related to egg size. Thus, yolk steroid hormones do not appear to play a critical role in sex determination for B. duperreyi.     

Collagen’s primary structure determines collagen:HSP47 complex stoichiometry

Collagens play important roles in development and homeostasis in most higher organisms. In order to function, collagens require the specific chaperone HSP47 for proper folding and secretion. HSP47 is known to bind to the collagen triple helix, but the exact positions and numbers of binding sites are not clear. Here, we employed a collagen II peptide library to characterize high-affinity binding sites for HSP47. We show that many previously predicted binding sites have very low affinities due to the presence of a negatively charged amino acid in the binding motif. In contrast, large hydrophobic amino acids such as phenylalanine at certain positions in the collagen sequence increase binding strength. For further characterization, we determined two crystal structures of HSP47 bound to peptides containing phenylalanine or leucine. These structures deviate significantly from previously published ones in which different collagen sequences were used. They reveal local conformational rearrangements of HSP47 at the binding site to accommodate the large hydrophobic side chain from the middle strand of the collagen triple helix and, most surprisingly, possess an altered binding stoichiometry in the form of a 1:1 complex. This altered stoichiometry is explained by steric collisions with the second HSP47 molecule present in all structures determined thus far caused by the newly introduced large hydrophobic residue placed on the trailing strand. This exemplifies the importance of considering all three sites of homotrimeric collagen as independent interaction surfaces and may provide insight into the formation of higher oligomeric complexes at promiscuous collagen-binding sites.     

Vavien: an algorithm for prioritizing candidate disease genes based on topological similarity of proteins in interaction networks

Genome-wide linkage and association studies have demonstrated promise in identifying genetic factors that influence health and disease. An important challenge is to narrow down the set of candidate genes that are implicated by these analyses. Protein-protein interaction (PPI) networks are useful in extracting the functional relationships between known disease and candidate genes, based on the principle that products of genes implicated in similar diseases are likely to exhibit significant connectivity/proximity. Information flow?based methods are shown to be very effective in prioritizing candidate disease genes. In this article, we utilize the topology of PPI networks to infer functional information in the context of disease association. Our approach is based on the assumption that PPI networks are organized into recurrent schemes that underlie the mechanisms of cooperation among different proteins. We hypothesize that proteins associated with similar diseases would exhibit similar topological characteristics in PPI networks. Utilizing the location of a protein in the network with respect to other proteins (i.e., the "topological profile" of the proteins), we develop a novel measure to assess the topological similarity of proteins in a PPI network. We then use this measure to prioritize candidate disease genes based on the topological similarity of their products and the products of known disease genes. We test the resulting algorithm, Vavien, via systematic experimental studies using an integrated human PPI network and the Online Mendelian Inheritance in Man (OMIM) database. Vavien outperforms other network-based prioritization algorithms as shown in the results and is available at www.diseasegenes.org.     

亚洲半干旱区碳水通量时空格局及驱动因素

亚洲半干旱区生态系统敏感,环境问题突出,作为全球近30年来碳水通量变化最大的区域,明确其碳水通量的时空分布格局和驱动因素对区域资源管理与可持续发展、全球气候变化等领域具有重要意义。基于植被与土壤湿度的联合同化产品(LPJ-Vegetation and soil moisture Joint Assimilation, LPJ-VSJA),结合研究区植被及气象数据,分析了亚洲半干旱区2010—2018年碳水通量植被总初级生产力(GPP)、蒸散发(ET)和水分利用效率(WUE)的时空变化、年际变化贡献率以及驱动因素。结果表明：(1)2010—2018年亚洲半干旱区年均GPP、ET、WUE空间格局总体呈“双夹型”,中高纬度与低纬度地区的碳水通量值大于中纬度区域。(2)2010—2018年GPP、ET和WUE的年际变化总体都呈现增长趋势,但只有GPP呈现显著增长趋势(P<0.05),增速为7.82 g C m^-2 a^-1。(3)WUE的年际变化表现为总体先增加后减少,正值中农田对WUE年际变化贡献率最大(54.6%),森林生态系统在面积占比仅有...