Cmah deficiency may lead to age-related hearing loss by influencing miRNA-PPAR mediated signaling pathway

Background Previous evidence has indicated CMP-Neu5Ac hydroxylase (Cmah) disruption inducesaging-related hearing loss (AHL). However, its function mechanisms remain unclear. This study was to explore the mechanisms of AHL by using microarray analysis in the Cmah deficiency animal model. Methods Microarray dataset GSE70659 was available from the Gene Expression Omnibus database, including cochlear tissues from wild-type and Cmah-null C57BL/6J mice with old age (12 months, n = 3). Differentially expressed genes (DEGs) were identified using the Linear Models for Microarray data method and a protein–protein interaction (PPI) network was constructed using data from the Search Tool for the Retrieval of Interacting Genes database followed by module analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery. The upstream miRNAs and potential small-molecule drugs were predicted by miRwalk2.0 and Connectivity Map, respectively. Results A total of 799 DEGs (449 upregulated and 350 downregulated) were identified. Upregulated DEGs were involved in Cell adhesion molecules (ICAM1, intercellular adhesion molecule 1) and tumor necrosis factor (TNF) signaling pathway (FOS, FBJ osteosarcoma oncogene; ICAM1), while downregulated DEGs participated in PPAR signaling pathway (PPARG, peroxisome proliferator-activated receptor gamma). A PPI network was constructed, in which FOS, ICAM1 and PPARG were ranked as hub genes and PPARG was a transcription factor to regulate other target genes (ICAM1, FOS). Function analysis of two significant modules further demonstrated PPAR signaling pathway was especially important. Furthermore, mmu-miR-130b-3p, mmu-miR-27a-3p, mmu-miR-27b-3p and mmu-miR-721 were predicted to regulate PPARG. Topiramate were speculated to be a potential small-molecule drug to reverse DEGs in AHL. Conclusions PPAR mediated signaling pathway may be an important mechanism for AHL. Downregulation of the above miRNAs and use of topiramate may be potential treatment strategies for ALH by upregulating PPARG

EALink: An Efficient and Accurate Pre-trained Framework for Issue-Commit Link Recovery

Issue-commit links, as a type of software traceability links, play a vital role in various software development and maintenance tasks. However, they are typically deficient, as developers often forget or fail to create tags when making commits. Existing studies have deployed deep learning techniques, including pretrained models, to improve automatic issue-commit link recovery.Despite their promising performance, we argue that previous approaches have four main problems, hindering them from recovering links in large software projects. To overcome these problems, we propose an efficient and accurate pre-trained framework called EALink for issue-commit link recovery. EALink requires much fewer model parameters than existing pre-trained methods, bringing efficient training and recovery. Moreover, we design various techniques to improve the recovery accuracy of EALink. We construct a large-scale dataset and conduct extensive experiments to demonstrate the power of EALink. Results show that EALink outperforms the state-of-the-art methods by a large margin (15.23%-408.65%) on various evaluation metrics. Meanwhile, its training and inference overhead is orders of magnitude lower than existing methods.Comment: 13 pages, 6 figures, published to AS

Study of Salicylic Acid Influence on Seedling Growth and Nitrogen Metabolism in Watermelon (Citrullus lanatus L.)

Salicylic acid is involved in the regulation of metabolic activity and defense mechanism in plants under various stress conditions. Present study was conducted to determine the effects of salicylic acid (10 to 500 μM) on seedling growth, development and nitrogen use efficiency in watermelon (Citrullus lanatus L.) plants with or without nitrogen nutrient. Salicylic acid increased contents of chlorophyll, total non-structural carbohydrate and total nitrogen, as well as nitrate assimilation through the induction of nitrate reductase (EC 1.6.6.1) activity in isolated watermelon cotyledons. Accumulation of salicylic acid was two-fold higher in cotyledons without nitrate supply in comparison to that with nitrate supply. Further 50 μM of SA induced enhancement in seed germination and growth characteristics. However higher salicylic acid concentrations inhibited above physiological characteristics. Results show that, field application of salicylic acid need optimum physiological concentration (e.g., 50 μM) to increase nitrogen use efficiency particularly during germination and seedling growth

On the Quality of HY-2A Scatterometer Wind

Presentación para el International Ocean Vector Winds Science Team (2015 IOVWST) Meeting, 19-21 May 2015, Portland, Oregon.-- 39 pagesPeer Reviewe

Associations between genetic variations in the FURIN gene and hypertension

<p>Abstract</p> <p>Background</p> <p>Hypertension is a complex disease influenced by multiple genetic and environmental factors. The Kazakh ethnic group is characterized by a relatively high prevalence of hypertension. Previous research indicates that the FURIN gene may play a pivotal role in the renin-angiotensin system and maintaining the sodium-electrolyte balance. Because these systems influence blood pressure regulation, we considered FURIN as a candidate gene for hypertension. The purpose of this study was to systematically investigate the association between genetic variations in the FURIN gene and essential hypertension in a Xinjiang Kazakh population.</p> <p>Methods</p> <p>We sequenced all exons and the promoter regions of the FURIN gene in 94 hypertensive individuals to identify genetic variations associated with the disorder. Genotyping was performed using the TaqMan polymerase chain reaction method for four representative common single nucleotide polymorphisms (SNPs, -7315C > T, 1970C > G, 5604C > G, 6262C > T) in 934 Kazakh Chinese people. One SNP (1970C > G) was replicated in 1,219 Uygur Chinese people.</p> <p>Results</p> <p>Nine novel and seven known single nucleotide polymorphisms were identified in the FURIN gene. The results suggest that 1970C > G was associated with a hypertension phenotype in Kazakh Chinese (additive model, <it>P </it>= 0.091; dominant model, <it>P = </it>0.031, allele model, <it>P </it>= 0.030), and after adjustment with logistic regression analysis, ORs were 1.451 (95%CI 1.106-1.905, <it>P </it>= 0.008) and 1.496 (95% 1.103-2.028, <it>P </it>= 0.01) in additive and dominant models, respectively. In addition, the association between 1970C > G and hypertension was replicated in Uygur subjects (additive model, <it>P </it>= 0.042; dominant model, <it>P </it>= 0.102; allele model, <it>P </it>= 0.027) after adjustment in additive and dominant models, ORs were 1.327 (95% 1.07-1.646), <it>P </it>= 0.01 and 1.307 (95%CI 1.015-1.681, <it>P </it>= 0.038), respectively. G allele carriers exhibited significant lower urinary Na⁺excretion rate than non-carriers in the Kazakh Chinese population (152.45 ± 76.04 uM/min vs 173.33 ± 90.02 uM/min, <it>P </it>= 0.007).</p> <p>Conclusion</p> <p>Our results suggest that the FURIN gene may be a candidate gene involved in human hypertension, and that the G allele of 1970C > G may be a modest risk factor for hypertension in Xinjiang Kazakh and Uygur populations.</p

The everchanging epidemiology of meningococcal disease worldwide and the potential for prevention through vaccination.

Neisseria meningitidis is a major cause of bacterial meningitis and septicaemia worldwide and is associated with high case fatality rates and serious life-long complications among survivors. Twelve serogroups are recognised, of which six (A, B, C, W, X and Y) are responsible for nearly all cases of invasive meningococcal disease (IMD). The incidence of IMD and responsible serogroups vary widely both geographically and over time. For the first time, effective vaccines against all these serogroups are available or nearing licensure. Over the past two decades, IMD incidence has been declining across most parts of the world through a combination of successful meningococcal immunisation programmes and secular trends. The introduction of meningococcal C conjugate vaccines in the early 2000s was associated with rapid declines in meningococcal C disease, whilst implementation of a meningococcal A conjugate vaccine across the African meningitis belt led to near-elimination of meningococcal A disease. Consequently, other serogroups have become more important causes of IMD. In particular, the emergence of a hypervirulent meningococcal group W clone has led many countries to shift from monovalent meningococcal C to quadrivalent ACWY conjugate vaccines in their national immunisation programmes. Additionally, the recent licensure of two protein-based, broad-spectrum meningococcal B vaccines finally provides protection against the most common group responsible for childhood IMD across Europe and Australia. This review describes global IMD epidemiology across each continent and trends over time, the serogroups responsible for IMD, the impact of meningococcal immunisation programmes and future needs to eliminate this devastating disease