模拟微重力对人脑神经组织细胞骨架和凋亡的影响

探讨模拟微重力效应对神经组织形态结构、骨架系统和凋亡的影响.原代培养人脑癌旁细胞7 d后,一组回转,另一组静置.倒置显微镜和透射电镜观察细胞大体形态及超微结构,扫描电镜观察细胞表面微细形貌;用TRITC标记的二抗和FITC标记的鬼笔环肽分别显示β-tubulin和F-actin的分布.回转时间延长至7、14 d后细胞体明显变大,细胞对基底的贴附能力显著下降.14 d回转组胞浆内细胞器结构变少,线粒体断裂同时相互离散,并有大量空泡.回转组胞质内β-tubulin和F-actin表达明显减少,F-actin绕核呈环,分布紊乱,且1个细胞核解离成几个微核.结果表明,模拟微重力一周能明显影响神经组织细胞的大体形态及超微结构,同时引起骨架蛋白的高度紊乱并伴随细胞凋亡的发生.     

Stem cells and their extracellular vesicles as natural and bioinspired carriers for the treatment of neurological disorders

One of the most explored strategies to cure neurological disorders is the transplantation of stem cells and their derived products. Different stem cells, as well as their extracellular vesicles (EV), modified or not, have been administrated in a large array of preclinical neurological disorder models. EV represent the hope of a “cell-free” therapy that would combine the therapeutic potential of stem cells without their drawbacks. Stem cells and EV showed various degrees of efficiency but, overall, provided benefits and improvements. The administration route has a considerable impact on stem cell and EV safety and therapeutic effect. However, despite evidences of preclinical success, the different strategies developed based on stem cells to treat neurological disorders do not exactly recapitulate in clinical trials. Discrepancies between preclinical and clinical experimental conditions and settings, cell availability and difficulties to scale up and to produce cells and EV in a Good Manufacturing Practices (GMP) environment limit translation.     

The Function of Selenium in Central Nervous System: Lessons from MsrB1 Knockout Mouse Models

MsrB1 used to be named selenoprotein R, for it was first identified as a selenocysteine containing protein by searching for the selenocysteine insert sequence (SECIS) in the human genome. Later, it was found that MsrB1 is homologous to PilB in Neisseria gonorrhoeae, which is a methionine sulfoxide reductase (Msr), specifically reducing L-methionine sulfoxide (L-Met-O) in proteins. In humans and mice, four members constitute the Msr family, which are MsrA, MsrB1, MsrB2, and MsrB3. MsrA can reduce free or protein-containing L-Met-O (S), whereas MsrBs can only function on the L-Met-O (R) epimer in proteins. Though there are isomerases existent that could transfer L-Met-O (S) to L-Met-O (R) and vice-versa, the loss of Msr individually results in different phenotypes in mice models. These observations indicate that the function of one Msr cannot be totally complemented by another. Among the mammalian Msrs, MsrB1 is the only selenocysteine-containing protein, and we recently found that loss of MsrB1 perturbs the synaptic plasticity in mice, along with the astrogliosis in their brains. In this review, we summarized the effects resulting from Msr deficiency and the bioactivity of selenium in the central nervous system, especially those that we learned from the MsrB1 knockout mouse model. We hope it will be helpful in better understanding how the trace element selenium participates in the reduction of L-Met-O and becomes involved in neurobiology.     

震级与震中烈度转换方法的进一步研究

进一步研究了地震震级与震中烈度的转换方法,在神经网络理论应用算法的实现上,采用了函数增强的输入模式,并对输出元进行了简化处理,使得网络结构简单,加快了计算速度,且提高了准确程度,研究结果表明,神经网络模拟结果的形式具有不唯一性,因而,能灵活地处理复杂系统,并按照具体情况给出系统的某种规律。     

基于BP人工神经网络的上市公司财务评估分析

叙述了人工神经网络的基本原理,建立对上市公司财务评估的神经网络模型,并结合实例,通过对比因子分析法的结果,验证了模型的可靠性和准确性。     

γ-氨基丁酸类似物的合成新进展

γ-氨基丁酸(GABA)类似物有着强烈而有趣的生理活性,有些已应用于中枢神经系统疾病的临床治疗。综述了近二十几年以来γ-氨基酸类似物的不同合成方法。     

神经系统中心理信息运作过程和机理

生命的本能是能够把非实体信息转换成实体信息,并以此主动地支配和调节生命主体的行为,这应该就是生命奥秘的关键。心理信息内容作为实体信息被直接固化到神经子网络系统中,该实体信息能够完全替代外来信息表现心理内容。神经系统能够在心理信息运行的过程中自然而然地形成必要的记忆,人体内的精巧机制能够控制心理信息有目的地运行。     

Interactions among Endothelial Nitric Oxide Synthase,Cardiovascular System,and Nociception during Physiological and Pathophysiological States

Nitric oxide synthase (NOS) plays important roles within the cardiovascular system in physiological states as well as in pathophysiologic and specific cardiovascular (CV) disease states, such as hypertension (HTN), arteriosclerosis, and cerebrovascular accidents. This review discusses the roles of the endothelial NOS (eNOS) and its effect on cardiovascular responses that are induced by nociceptive stimuli. The roles of eNOS enzyme in modulating CV functions while experiencing pain will be discussed. Nociception, otherwise known as the subjective experience of pain through sensory receptors, termed “nociceptors”, can be stimulated by various external or internal stimuli. In turn, events of various cascade pathways implicating eNOS contribute to a plethora of pathophysiological responses to the noxious pain stimuli. Nociception pathways involve various regions of the brain and spinal cord, including the dorsolateral periaqueductal gray matter (PAG), rostral ventrolateral medulla (RVLM), caudal ventrolateral medulla, and intermediolateral column of the spinal cord. These pathways can interrelate in nociceptive responses to pain stimuli. The alterations in CV responses that affect GABAergic and glutamatergic pathways will be discussed in relation to mechanical and thermal (heat and cold) stimuli. Overall, this paper will discuss the aggregate recent and past data regarding pain pathways and the CV system.     

Assessment of autonomic nervous system activity by heart rate recovery response

The assessment of autonomic nervous system (ANS) activity is a tool for diagnosing or predicting cardiovascular diseases,while heart rate recovery response (HRRR) after exercise has been promoted as a process under the regulation of ANS (sympathetic and parasympathetic nervous systems).Therefore,assessment of ANS activity was performed by HRRR in this study.Firstly,HRRR signal was extracted based on wavelet decomposition and difference curve of coarse component from heart rate signal.Then,HRRR was divided into quickly descending interval (QDI) and slowly descending interval (SDI).Finally,3 groups of indexes (Difference,Exponential and Quadratic Groups) from QDI and SDI were compared between 50 normotensive and 61 hypertensive subjects.The results showed that the indexes of Difference Group were better choices than others in analyzing the features of HRRR.Furthermore,parasympathetic activity is dominant in QDI,while sympathetic and parasympathetic activities affect SDI together.In conclusion,the proposed method was effective to assess ANS activity.     

E-pharmacophore-based screening of mGluR5 negative allosteric modulators for central nervous system disorder

Glutamate, a major neurotransmitter in the central nervous system of human, plays a crucial role in various neurological pathways by activating the ligand-gated ion channels such as mGluR and iGluR. Dysfunction of mGluR 5 can cause Alzheimer’s disease, Parkinson’s disease, epilepsy, depression, anxiety, etc. In the current study, we have developed the energetically optimized pharmacophore model to screen the eMolecules database having more than 6 million compounds with the help of reported cocrystal structure with 3-chloro-5-[6-(5-fluoropyridin-2 yl)pyrimidin-4-yl]benzonitrile (PDB ID: 5CGD). The obtained hits were docked into the allosteric site of the target and further validation of E-pharmacophore was done by enrichment calculations followed by the molecular dynamics simulations to analyze the specific amino acid interactions with the compound present in the allosteric site of the receptor.