Sulfanilamide benzotriazole tetrazole inhibits neuronal apoptosis in neonatal rats by targeting JNK and p38 MAPK pathways

Purpose: To investigate the neuroprotective effect of sulfanilamide benzotriazole tetrazole (SBT) in neonatal rats exposed to isoflurane, and also to elucidate the underlying mechanism. Methods: Rat pups (n = 60) were randomly assigned to six groups of 10 pups each: normal control group, negative control group, 5 mg/kg SBT group, 10 mg/kg SBT group, 15 mg/kg SBT group, and 20 mg/kg SBT group. With exception of normal control group, pups were exposed to isoflurane (0.75 %) for 6 h on postnatal day 7. The negative control group was not treated, while pups in the four treatment groups received 5, 10, 15 and 20 mg/kg SBT, respectively, 1 h after exposure to anaesthesia. TUNEL assay was used to determine the extent of apoptosis in cornu ammonis area-1 (CA-1), cornu ammonis area-3 (CA-3) and dentate gyrus of rat hippocampal tissues. Expressions of apoptotic and anti-apoptotic proteins were determined using Western blotting. Evaluation of learning and memorizing ability was done using Morris water maze test. Results: Isoflurane significantly increased the extent of apoptosis in CA-1, CA-3 and dentate gyrus of rat hippocampal tissues (p < 0.05). However, treatment with SBT significantly and dose-dependently reduced neuronal apoptosis (p < 0.05). The expression of caspase 3 was significantly upregulated by isoflurane, but was significantly and dose-dependently down-regulated by SBT (p < 0.05). Isoflurane significantly increased Bax expression, and decreased the expression of bcl-2 (p < 0.05). The effects of isoflurane on the expression of these proteins were significantly and dose-dependently reversed by SBT (p < 0.05). The expression of bcl xL in rat hippocampal tissues was significantly down-regulated by isoflurane, but was significantly and dose-dependently upregulated by SBT (p < 0.05). The escape latency of pups was significantly higher in negative control group than in normal control group, but SBT treatment significantly and dose-dependently reversed this trend (p < 0.05). Conclusion: These results suggest that SBT prevents neuronal apoptosis, and improves the ability to learn and memorize in neonatal rats exposed to isoflurane via regulation of apoptotic, JNK and p38 MAPK protein expressions

Effect of Leeway and Drift Angle of Ship Navigation and Determination Method

The wind and the current is an important factor affecting the safety of navigation of ships at sea. This article focuses on the influence of wind and flow of ships sailing and Predicted drift angle of dead reckoning tracer method, which plays an active role in ensuring the safety of navigation, and plays a guiding role in the determination of the leeway and drift angle for the staff on board and in solving the problems of students in navigation schools

CPIN:Comprehensive present-interest network for CTR prediction

Personalized recommendation is a popular research direction in both industry and academia. Some research on recommender systems utilizes the users’ interaction history on items to represent the users’ interests, which has achieved remarkable success. Users’ interests in the real world are dynamically changing and have a strong correlation with the interaction sequence. However, sometimes users’ interests are less relevant to the order of the current interaction sequence, but are more relevant to certain items in the user interaction history. In this paper, a novel deep neural network model is proposed to deal with this situation. The developed model consists of two parts: the present interest relevant to the order of the interaction sequence and the comprehensive interest relevant to some items in the interaction sequence. An ancillary multi-layer perceptron (MLP) is constructed to improve the training of our model. Experiments on public and industrial datasets are conducted. The experimental results show that our proposed model outperforms the state-of-the-art models which demonstrates the effectiveness of the ancillary MLP

Genome-Wide Network-Based Analysis of Colorectal Cancer Identifies Novel Prognostic Factors and an Integrative Prognostic Index

Background/Aims: Colorectal cancer (CRC) is one of leading cancers in both incidence and mortality rate. The 5-year survival rate varies considerably depending on the pathological stage of the tumor. Although prominent progress has been made through screening for survival-associated factors from a certain type of genetic or epigenetic modifications, few attempts have been made to apply a network-based approach in prognostic factor identification, which could prove valuable for a complex, multi-faceted disease such as CRC. Methods: In this study, a TCGA dataset of 379 CRC patients was subjected to a network-based analysis strategy consisting of multivariate regression, co-expression network and gene regulatory network analyses, and survival analyses. Both genetic and epigenetic aberrations, including those in gene expression and DNA methylation at specific sites, were screened for significant association with patient survival. A prognostic index (PI) integrating all potential prognostic factors was subsequently validated for its prognostic value. Results: A collection of six miRNAs, eleven mRNAs, and nine DNA methylation sites were identified as potential prognostic factors. The low- and high-risk patient groups assigned based on PI level showed significant difference in overall survival (hazard ratio = 1.32, 95% confidence interval 1.29-1.36, p < 0.0001). Patients in the low- and high-risk groups can be further divided into a total of four subgroups, based on pathological staging. In the two high-risk subgroups (PI > 0), there was significant different (Cox p < 0.0001) in OS between the earlier (stages I/II) and later stages (stages III/IV). However, in the two low-risk subgroups (PI < 0), earlier (stages I/II) and later stages (stages III/IV) showed no significant difference in OS (Cox p = 0.185). On the other hand, there were significant differences in OS between the low- and high-risk subgroups when both subgroups were of earlier stages (Cox p < 0.001) or of later stages (Cox p < 0.0001). Conclusion: The novel network-based, integrative analysis adopted in this study was efficient in screening for prognostic predictors. Along with PI, the set of 6 miRNAs, 11 mRNAs, and 9 DNA methylation sites could serve as the basis for improved prognosis estimation for CRC patients in future clinical practice

Rapid Assembly of Multiple-Exon cDNA Directly from Genomic DNA

Backgrouud. Polymerase chain reaction (PCR) is extensively applied in gene cloning. But due to the existence of introns, low copy number of particular genes and high complexity of the eukaryotic genome, it is usually impossible to amplify and clone a gene as a full-length sequence directly from the genome by ordinary PCR based techniques. Cloning of cDNA instead of genomic DNA involves multiple steps: harvest of tissues that express the gene of interest, RNA isolation, cDNA synthesis (reverse transcription), and PCR amplification. To simplify the cloning procedures and avoid the problems caused by ubiquitously distributed durable RNases, we have developed a novel strategy allowing the cloning of any cDNA or open reading frame (ORF) with wild type sequence in any spliced form from a single genomic DNA preparation. Methodology. Our Genomic DNA Splicing technique contains the following steps: first, all exons of the gene are amplified from a genomic DNA preparation, using software-optimized, highly efficient primers residing in flanking introns. Next, the tissue-specific exon sequences are assembled into one full-length sequence by overlapping PCR with deliberately designed primers located at the splicing sites. Finally, software-optimized outmost primers are exploited for efficient amplification of the assembled full-length products. Conclusions. The Genomic DNA Splicing protocol avoids RNA preparation and reverse transcription steps, and the entire assembly process can be finished within hours, Since genamic DNA is more stable than RNA, it may be a more practical cloning strategy for many genes, especially the ones that are very large and difficult to generate a full length cDNA using oligo-dT primed reverse transcription. With this technique, we successfully doned the full-length wild type coding sequence of human polymeric immunoglobulin receptor, which is 2295 bp in length and composed of 10 exons. © 2007 An et al.published_or_final_versio

The transcriptional coactivator TAZ regulates reciprocal differentiation of T(h)17 cells and T(reg) cells

自身免疫性疾病是一类机体对自身抗原发生免疫反应而导致自身多器官、组织受累的慢性炎症性疾病。目前大量研究表明机体内促炎症的TH17细胞和抑制炎症Treg细胞在类群数量和活化状态的失衡是造成自身免疫疾病的主要致病因素。陈兰芬教授和周大旺教授团队的前期研究发现小鼠中Hippo信号通路中激酶Mst1/2缺失导致免疫缺陷，机体易受病原体感染并伴随着严重自身免疫疾病。该研究揭示了Hippo 信号通路转录共激活因子TAZ在决定CD4+初始T细胞分化为促进炎症的TH17效应细胞和抑制免疫反应的Treg调节性细胞过程中发挥着关键作用，拓展了当前对于Hippo信号通路的相关研究内容。 陈兰芬，博士，厦门大学生命科学学院教授。【Abstraact】An imbalance in the lineages of immunosuppressive regulatory T cells (Treg cells) and the inflammatory TH17 subset of helper T cells leads to the development of autoimmune and/or inflammatory disease. Here we found that TAZ, a coactivator of TEAD transcription factors of Hippo signaling, was expressed under T H17 cell–inducing conditions and was required for TH17 differentiation and TH17 cell–mediated inflammatory diseases. TAZ was a critical co-activator of the TH17-defining transcription factor RORγt. In addition, TAZ attenuated Treg cell development by decreasing acetylation of the Treg cell master regulator Foxp3 mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for proteasomal degradation. In contrast, under T regcell–skewing conditions, TEAD1 expression and sequestration of TAZ from the transcription factors RORγt and Foxp3 promoted Treg cell differentiation. Furthermore, deficiency in TAZ or overexpression of TEAD1 induced Treg cell differentiation, whereas expression of a transgene encoding TAZ or activation of TAZ directed TH17 cell differentiation. Our results demonstrate a pivotal role for TAZ in regulating the differentiation of Treg cells and TH17 cells.J. Avruch for comments on the manuscript.Supported by the National Basic Research Program (973) of China (2015CB910502 to L.C.), the National Natural Science Foundation of China (81422018 to L.C.; 31625010 and U1505224 to D.Z.; U1405225 and 81372617 to L.C.; J1310027 to D.Z.; 81472229 to L.H.; and 31600698 to J. Geng), the 111 Projects (B12001 and B06016), China's 1000 Young Talents Program (D.Z., and L.C.), the Fundamental Research Funds for the Central Universities of China-Xiamen University (20720160071 to D.Z. and 20720160054 to L.H.) and Major disease research projects of Xiamen (3502Z20149029 to L.C.)

Genomic mapping of phosphorothioates reveals partial modification of short consensus sequences

Bacterial phosphorothioate (PT) DNA modifications are incorporated by Dnd proteins A-E and often function with DndF-H as a restriction-modification (R-M) system, as in Escherichia coli B7A. However, bacteria such as Vibrio cyclitrophicus FF75 lack dndF-H, which points to other PT functions. Here we report two novel, orthogonal technologies to map PTs across the genomes of B7A and FF75 with >90% agreement: single molecule, real-time sequencing and deep sequencing of iodine-induced cleavage at PT (ICDS). In B7A, we detect PT on both strands of G[subscript ps]AAC/G[subscript ps]TTC motifs, but with only 12% of 40,701 possible sites modified. In contrast, PT in FF75 occurs as a single-strand modification at C[subscript ps]CA, again with only 14% of 160,541 sites modified. Single-molecule analysis indicates that modification could be partial at any particular genomic site even with active restriction by DndF-H, with direct interaction of modification proteins with GAAC/GTTC sites demonstrated with oligonucleotides. These results point to highly unusual target selection by PT-modification proteins and rule out known R-M mechanisms.National Natural Science Foundation (China)Ministry of Science and Technology of the People's Republic of China (973 and 863 Programs)Shanghai Municipal Council of Science and Technology. Shanghai Pujiang ProgramNational Science Foundation (U.S.) (CHE-1019990)National Institute of Environmental Health Sciences (ES002109)Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology