The emerging link between O-GlcNAcylation and neurological disorders

O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is involved in the regulation of many cellular cascades and neurological diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke. In the brain, the expression of O-GlcNAcylation is notably heightened, as is that of O-linked N-acetylglucosaminyltransferase (OGT) and β-N-acetylglucosaminidase (OGA), the presence of which is prominent in many regions of neurological importance. Most importantly, O-GlcNAcylation is believed to contribute to the normal functioning of neurons; conversely, its dysregulation participates in the pathogenesis of neurological disorders. In neurodegenerative diseases, O-GlcNAcylation of the brain’s key proteins, such as tau and amyloid-β, interacts with their phosphorylation, thereby triggering the formation of neurofibrillary tangles and amyloid plaques. An increase of O-GlcNAcylation by pharmacological intervention prevents neuronal loss. Additionally, O-GlcNAcylation is stress sensitive, and its elevation is cytoprotective. Increased O-GlcNAcylation ameliorated brain damage in victims of both trauma-hemorrhage and stroke. In this review, we summarize the current understanding of O-GlcNAcylation’s physiological and pathological roles in the nervous system and provide a foundation for development of a therapeutic strategy for neurological disorders.     

A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis

To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.     

Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.     

Fixed Point Theorems for φ-Probabilistic Contraction in Hausdorff Fuzzy Metric Spaces

In this paper,we discuss the common fixed point with respect to several self-mappings on fuzzy metric space.Recently many authors put forward some relevant comm...     

五味子有效成分保护心室重构的研究进展

五味子对心血管、免疫系统及CNS具有调节作用,阐述了五味子中有效成分木脂素和多糖保护心室重构的作用.     

A New Adaptive Formant Vocoder

A new type of vocoder system based upon formant analysis is presented in this paper. The LMS adaptive algorithm is used for tracking formants of speech signals. The results of computer simulation show that the new vocoder has better synthesized speech quality.     

炼油厂废水处理污泥热解制油技术研究

对炼油厂废水处理污泥进行了催化热解产油实验,考察了温度（170－300℃）和反应时间（0－90min)对产油率的影响。温度越高,产油率越高,在300℃时,产油率达54．6％,经60min反应接近平衡。讨论了系统质量与能量平衡。     

祛寒逐风合剂治 疗尢 王痹(类风湿性关节炎)的研究

祛寒逐风合剂是以1972年由甘肃武威出土的汉代医简中“伤寒逐风方”为基础方配制而成的中药制剂,供临床使用。方中有制附片、川椒、细辛、白术、川芎、制鳖甲等,以温经散寒为主,佐以祛风除湿、活血止痛、补益肝肾,尊《黄帝内经》中“寒者热之”、“治寒以热”之大法,主要用于治疗wang痹（类风湿性关节炎）之辩证为风寒湿阻者。几年来临床观察120例,其中治愈23例,好转95例,临床验证取得了满意疗效,与宝光牌风湿液治病该病作对照,其疗效结果经统计学处理,治疗组优于对照组（P＜0．01）,且该药对中医辩证为风寒湿阻之各种痹证,包括西医诊断之风湿性关节炎、类风湿性关节炎、强直性脊柱炎、增生性关节炎、各种腰腿痛等都有很好的疗效,有望成为治疗风湿病的一种有效药物。     

萍乡市古籍保存及利用状况分析

通过对萍乡市古籍保存及利用状况的调查与分析,指出应进一步加强对古籍的保护,并针对古籍的特点对其进行合理的开发与利用,从而最大限度地为本地区政治、经济、文化事业的可持续发展服务。     

民主的悖论--对法国福利制度的思考

法国是一个高福利的国家,高福利制度为法国人民提供了保障,但也有不少弊病.它造成产品的高成本和国际竞争力的降低,从而使法国经济陷于长期的不景气状态,并且出现了高失业率.同时,福利经费也赤字累累,难以为继.但在法国现行的政治体制下,高福利制度难以进行根本的改革,消除它的弊端,这是我们必须引以为鉴的.