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.     

Melatonin and mitochondrial function during ischemia/reperfusion injury

Ischemia/reperfusion (IR) injury occurs in many organs and tissues, and contributes to morbidity and mortality worldwide. Melatonin, an endogenously produced indolamine, provides a strong defense against IR injury. Mitochondrion, an organelle for ATP production and a decider for cell fate, has been validated to be a crucial target for melatonin to exert its protection against IR injury. In this review, we first clarify the mechanisms underlying mitochondrial dysfunction during IR and melatonin’s protection of mitochondria under this condition. Thereafter, special focus is placed on the protective actions of melatonin against IR injury in brain, heart, liver, and others. Finally, we explore several potential future directions of research in this area. Collectively, the information compiled here will serve as a comprehensive reference for the actions of melatonin in IR injury identified to date and will hopefully aid in the design of future research and increase the potential of melatonin as a therapeutic agent.     

Wigner-Ville distribution and cross Wigner-Ville distribution of noisy signals

The Wigner-Ville distribution （WVD） and the cross Wigner-Ville distribution （XWVD） have been shown to be efficient in the estimation of instantaneous frequency （IF）. But the statistical result of the IF estimation from XWVD peak is much better than using WVD peak. The reason is given from a statistical point of view. Theoretical studies show that XWVD of the analyzed signal can be estimated from XWVD of the noise-contaminated signal. The estimation is unbiased, and the variance is equal to that of noise. In this case, WVD cannot be estimated from W-VD of the noise-contaminated signal. Therefore, higher SNR is required when WVD is used to analyze signals.     

求解变分不等式与不动点问题的惯性次梯度外梯度算法

提出了一种求解变分不等式与不动点问题的惯性次梯度外梯度算法,证明了其弱收敛性定理,通过数值实验验证所得的理论结果.     

Effects of maternal aging on localizations and expression levels of DNA methyltransferases and chromosome architecture in in-vivo matured mouse oocytes

This paper investigated the age-related changes in the expression patterns of maintenance methyltransferase (DNMT1) and de novo methyltransferases (DNMT3a, 3b, 3L) and the chromosome architecture in in-vivo matured mouse oocytes using two-photon laser-scanning microscope. Our results showed that (1) DNMT1 and DNMT3a, 3b, 3L in the oocytes of pubertal mice were located in the cortical region of oocyte cytoplasm. In aging groups, DNMT1 was also located in the cortical region. However, DNMT3a, 3b, 3L had a relatively wider distribution in the oocyte cytoplasm and appeared near the chromosomes. These differences between pubertal and aging groups suggested that aging might affect DNA methylation; (2) the expression of DNMT1, and DNMT3a, 3b in aging groups increased significantly compared to pubertal groups, while, the expression of DNMT3L decreased. These results might be explained by the compensation mechanism among DNMTs, which might be impervious to aging; (3) aging caused increased errors in the distribution and three-dimensional morphology of chromosomes, including the increased total volume and surface area, the high ratio of height to diameter of a circular cylinder enclosing the chromosomes (H/D). Our work provided morphological information for the studies of age-related decline in oocyte qualities.     

法语在法国对外文化政策的地位及其在中国的表现

法语的推广在法国对外文化推广中的作用是非常重要的.文章将对法国对外文化政策的起源、社会背景、法语的重要地位以及结合中国实际进行了综合分析研究.     

面具下的荒诞——《路的尽头》之真相

约翰·巴思是当代美国最有影响力的后现代主义小说家之一,他的第二部作品《路的尽头》充分讨论了＂面具＂的深刻含义。人格面具是一把双刃剑：它是人适应社会的重要条件,但在整个人格中也会产生负面影响。运用面具理论,分析小说中主人公雅各布·霍纳错综复杂的思想,探讨人格面具对他生活所造成的影响;分析导致霍纳人格面具膨胀和人格分裂的深层社会原因。可以发现,巴思正是试图通过借助霍纳所戴的面具,嘲讽当时虚无、荒诞和存在焦虑的社会思潮。     

K148与K149对黑曲霉NRRL3135植酸酶A与植酸结合机制的影响

为了研究黑曲霉NRRL3135植酸酶A K148与K149对底物与酶的结合反应的影响,构建了一个单位点突变体(K148E)和一个双位点突变体(K148E和K149E),由于带电的氨基酸残基发生变化,造成这2个突变体的酶活性都有不同程度的减少,利用InsightII软件模拟了2种突变体酶的3-D结构,发现酶分子突变位置的表面电势有明显的改变.这2个α-螺旋(141～160)位点的改变可能降低了活性中心附近的底物浓度,减缓了底物与活性中心的反应速度.     

Sequence similarity analysis of non-self CTL epitopes and mouse proteins using sequence alignment

This research analyzed amino acid sequence similarity between non-self T cell epitopes recognized by mouse antibodies and mouse proteins. Using sequence alignment,we found that only 8 of 1 108 epitopes are highly similar to mouse protein sequences. The result shows that non-self T cell epitopes are not similar or have little similarity to mouse protein sequences. Furthermore,reviewing the related literature,we also found that the eight epitopes would trigger immune responses in some particular environment,which are ignored by T cells in normal condition. The result suggests that no or low-similarity peptide vaccines can reduce the chance of collateral cross-reactions and enhance the antigen-specific immune response to vaccine.