OGR1/GPR68 Modulates the Severity of Experimental Autoimmune Encephalomyelitis and Regulates Nitric Oxide Production by Macrophages.

Ovarian cancer G protein-coupled receptor 1 (OGR1) is a proton-sensing molecule that can detect decreases in extracellular pH that occur during inflammation. Although OGR1 has been shown to have pro-inflammatory functions in various diseases, its role in autoimmunity has not been examined. We therefore sought to determine whether OGR1 has a role in the development of T cell autoimmunity by contrasting the development of experimental autoimmune encephalomyelitis between wild type and OGR1-knockout mice. OGR1-knockout mice showed a drastically attenuated clinical course of disease that was associated with a profound reduction in the expansion of myelin oligodendrocyte glycoprotein 35-55-reactive T helper 1 (Th1) and Th17 cells in the periphery and a reduced accumulation of Th1 and Th17 effectors in the central nervous system. We determined that these impaired T cell responses in OGR1-knockout mice associated with a reduced frequency and number of dendritic cells in draining lymph nodes during EAE and a higher production of nitric oxide by macrophages. Our studies suggest that OGR1 plays a key role in regulating T cell responses during autoimmunity

Genomic and Transcriptomic Landscape and Evolutionary Dynamics of Heat Shock Proteins in Spotted Sea Bass (Lateolabrax maculatus) under Salinity Change and Alkalinity Stress

The heat shock protein (Hsp) superfamily has received accumulated attention because it is ubiquitous and conserved in almost all living organisms and is involved in a wide spectrum of cellular responses against diverse environmental stresses. However, our knowledge about the Hsp co-chaperon network is still limited in non-model organisms. In this study, we provided the systematic analysis of 95 Hsp genes (LmHsps) in the genome of spotted sea bass (Lateolabrax maculatus), an important aquaculture species in China that can widely adapt to diverse salinities from fresh to sea water, and moderately adapt to high alkaline water. Through in silico analysis using transcriptome and genome database, we determined the expression profiles of LmHsps in response to salinity change and alkalinity stress in L. maculatus gills. The results revealed that LmHsps were sensitive in response to alkalinity stress, and the LmHsp40-70-90 members were more actively regulated than other LmHsps and may also be coordinately interacted as co-chaperons. This was in accordance with the fact that members of LmHsp40, LmHsp70, and LmHsp90 evolved more rapidly in L. maculatus than other teleost lineages with positively selected sites detected in their functional domains. Our results revealed the diverse and cooperated regulation of LmHsps under alkaline stress, which may have arisen through the functional divergence and adaptive recruitment of the Hsp40-70-90 co-chaperons and will provide vital insights for the development of L. maculatus cultivation in alkaline water

Trend Prediction of Event Popularity from Microblogs

Owing to rapid development of the Internet and the rise of the big data era, microblog has become the main means for people to spread and obtain information. If people can accurately predict the development trend of a microblog event, it will be of great significance for the government to carry out public relations activities on network event supervision and guide the development of microblog event reasonably for network crisis. This paper presents effective solutions to deal with trend prediction of microblog events’ popularity. Firstly, by selecting the influence factors and quantifying the weight of each factor with an information entropy algorithm, the microblog event popularity is modeled. Secondly, the singular spectrum analysis is carried out to decompose and reconstruct the time series of the popularity of microblog event. Then, the box chart method is used to divide the popularity of microblog event into various trend spaces. In addition, this paper exploits the Bi-LSTM model to deal with trend prediction with a sequence to label model. Finally, the comparative experimental analysis is carried out on two real data sets crawled from Sina Weibo platform. Compared to three comparative methods, the experimental results show that our proposal improves F1-score by up to 39%

Mechanism of Mutation-Induced Effects on the Catalytic Function of TEV Protease: A Molecular Dynamics Study

Tobacco etch virus protease (TEVp) is wildly exploited for various biotechnological applications. These applications take advantage of TEVp’s ability to cleave specific substrate sequences to study protein function and interactions. A major limitation of this enzyme is its relatively slow catalytic rate. In this study, MD simulations were conducted on TEV enzymes and known highly active mutants (eTEV and uTEV3) to explore the relationship between mutation, conformation, and catalytic function. The results suggest that mutations distant from the active site can influence the substrate-binding pocket through interaction networks. MD analysis of eTEV demonstrates that, by stabilizing the orientation of the substrate at the catalytic site, mutations that appropriately enlarge the substrate-binding pocket will be beneficial for Kcat, enhancing the catalytic efficiency of the enzyme. On the contrary, mutations in uTEV3 reduced the flexibility of the active pocket and increased the hydrogen bonding between the substrate and enzyme, resulting in higher affinity. At the same time, the MD simulation demonstrates that mutations outside of the active site residues could affect the dynamic movement of the binding pocket by altering residue networks and communication pathways, thereby having a profound impact on reactivity. These findings not only provide a molecular mechanistic explanation for the excellent mutants, but also serve as a guiding framework for rational computational design

The Prognostic Significance of miR-21 Expression among Surgically Resected Hepatocellular Carcinoma Patients: Evidence from a Meta-Analysis and Retrospective Cohort Study

Background. To date, microRNA-21 (miR-21) has been reported to be associated with the prognosis of hepatocellular carcinoma (HCC) in various studies, yet the results were inconsistent. The purpose of this two-part study, consisting of a retrospective cohort study and a meta-analysis, sets out to determine the prognostic role of miR-21 expression among HCC patients who underwent surgical resection. Methods. In this study, we first detected miR-21 expression in HCC patients by quantitative real-time PCR (qRT-PCR). Patients were divided into a high miR-21 expression group and a low miR-21 expression group according to the median level of miR-21 expression in tumor tissues. The survival outcomes of the two groups were analyzed by the Kaplan-Meier method with the log-rank test. Multivariate analysis of the prognostic factors was performed with the Cox regression model. Subsequently, eligible studies were obtained by searching on PubMed, Cochrane Library, and Web of Science, and a meta-analysis was performed to assess the prognostic role of miR-21 expression among HCC. Results. The qRT-PCR analysis results of our cohort study showed miR-21 expression was significantly upregulated in HCC tissues when compared with adjacent nontumor tissues. Multivariate analysis suggested that miR-21 expression was an independent prognostic factor for overall survival (OS) (hazard ratio, HR=2.361) and disease-free survival (DFS) (HR=2.024) in HCC patients who underwent surgical resection. A total of 10 studies with 969 patients were enrolled in the meta-analysis, consisting of 9 studies from the database search and our cohort study. We observed that elevated miR-21 expression can predict poor OS (HR=2.24, 95%CI=1.73‐2.91, P<0.001) and DFS/recurrence-free survival (RFS) (HR=2.44, 95%CI=1.62‐3.67, P<0.001) in surgically resected HCC patients. Conclusions. Our study demonstrated that miR-21 high expression among surgically resected HCC patients is a prognostic factor that indicated adverse survival

On the motion of a falling circular cylinder in flows after water entry

This paper reports an experimental investigation on the motion of a circular cylinder after it horizontally enters into a water flow with a certain slamming speed. A smart cylinder-releasing mechanism is designed to enable repeatable release of the cylinder. A high-speed camera is used to record the cylinder’s motion. The effects of three factors are investigated, including the cylinder-to-water density ratio, water speed and slamming speed of the cylinder. Data for several cases with either a solid cylinder or a hollow cylinder are obtained and compared. Variations of both horizontal and vertical displacements against these factors are presented and analyzed. It is found that the trajectories of the hollow cylinder collapse at the initial stage of submerging in water when the velocity ratios are the same.Published versio

Steroidogenic Effects of Salinity Change on the Hypothalamus&ndash;Pituitary&ndash;Gonad (HPG) Axis of Male Chinese Sea Bass (Lateolabrax maculatus)

As lower vertebrates, teleost species could be affected by dynamic aquatic environments and may respond to environmental changes through the hypothalamus&ndash;pituitary&ndash;gonad (HPG) axis to ensure their normal growth and sexual development. Chinese sea bass (Lateolabrax maculatus), euryhaline marine teleosts, have an extraordinary ability to deal with a wide range of salinity changes, whereas the salinity decrease during their sex-maturation season may interfere with the HPG axis and affect their steroid hormone metabolism, resulting in abnormal reproductive functioning. To this end, in this study, 40 HPG axis genes in the L. maculatus genome were systematically characterized and their copy numbers, phylogenies, gene structures, and expression patterns were investigated, revealing the conservation of the HPG axis among teleost lineages. In addition, freshwater acclimation was carried out with maturing male L. maculatus, and their serum cortisol and 11-ketotestosterone (11-KT) levels were both increased significantly after the salinity change, while their testes were found to be partially degraded. After salinity reduction, the expression of genes involved in cortisol and 11-KT synthesis (cyp17a, hsd3b1, cyp21a, cyp11c, hsd11b2, and hsd17b3) showed generally upregulated expression in the head kidneys and testes, respectively. Moreover, cyp11c and hsd11b2 were involved in the synthesis and metabolism of both cortisol and 11-KT, and after salinity change their putative interaction may contribute to steroid hormone homeostasis. Our results proved the effects of salinity change on the HPG axis and steroidogenic pathway in L. maculatus and revealed the gene interactions involved in the regulation of steroid hormone levels. The coordinated interaction of steroidogenic genes provides comprehensive insights into steroidogenic pathway regulation, as well as sexual development, in teleost species