Autophagy and other vacuolar protein degradation mechanisms

Autophagic degradation of cytoplasm (including protein, RNA etc.) is a non-selective bulk process, as indicated by ultrastructural evidence and by the similarity in autophagic sequestration rates of various cytosolic enzymes with different half-lives. The initial autophagic sequestration step, performed by a poorly-characterized organelle called a phagophore, is subject tofeedback inhibition by purines and amino acids, the effect of the latter being potentiated by insulin and antagonized by glucagon. Epinephrine and other adrenergic agonists inhibit autophagic sequestration through a prazosin-sensitive ₁-adrenergic mechanism. The sequestration is also inhibited by cAMP and by protein phosphorylation as indicated by the effects of cyclic nucleotide analogues, phosphodiesterase inhibitors and okadaic acid.Asparagine specifically inhibits autophagic-lysosomal fusion without having any significant effects on autophagic sequestration, on intralysosomal degradation or on the endocytic pathway. Autophaged material that accumulates in prelysosomal vacuoles in the presence of asparagine is accessible to endocytosed enzymes, revealing the existence of an amphifunctional organelle, the amphisome. Evidence from several cell types suggests that endocytosis may be coupled to autophagy to a variable extent, and that the amphisome may play a central role as a collecting station for material destined for lysosomal degradation.Protein degradation can also take place in a salvage compartment closely associated with the endoplasmic reticulum (ER). In this compartment unassembled protein chains are degraded by uncharacterized proteinases, while resident proteins roturn to the ER and assembled secretory and membrane proteins proceed through the Golgi apparatus. In thetrans-Golgi network some proteins are proteolytically processed by Ca²⁺-dependent proteinases; furthermore, this compartment sorts proteins to lysosomes, various membrane domains, endosomes or secretory vesicles/granules. Processing of both endogenous and exogenous proteins can occurr in endosomes, which may play a particularly important role in antigen processing and presentation. Proteins in endosomes or secretory compartments can either be exocytosed, or channeled to lysosomes for degradation. The switch mechanisms which decide between these options are subject to bioregulation by external agents (hormones and growth factors), and may play an important role in the control of protein uptake and secretion.     

糖类遗传与生命起源

从遗传学角度探讨了糖类与生命起源，讨论了遗传学上的再认识，提出糖类在遗传学上扮演着重要、核心的角色、糖类是生命起源物质，基因是糖类衍生物。生命诞生过程可能是：先有糖类、然后有氨基酸和碱基；磷酸及其盐类既是生命物质的组成部分、也是催化剂，阳光或地热为能源，于是诞生了基因。生命体是分子相互作用、有序组合、自我调控的耗散体系。     

Functions and pathologies of BiP and its interaction partners

The endoplasmic reticulum (ER) is involved in a variety of essential and interconnected processes in human cells, including protein biogenesis, signal transduction, and calcium homeostasis. The central player in all these processes is the ER-lumenal polypeptide chain binding protein BiP that acts as a molecular chaperone. BiP belongs to the heat shock protein 70 (Hsp70) family and crucially depends on a number of interaction partners, including co-chaperones, nucleotide exchange factors, and signaling molecules. In the course of the last five years, several diseases have been linked to BiP and its interaction partners, such as a group of infectious diseases that are caused by Shigella toxin producing E. coli. Furthermore, the inherited diseases Marinesco-Sj?gren syndrome, autosomal dominant polycystic liver disease, Wolcott-Rallison syndrome, and several cancer types can be considered BiP-related diseases. This review summarizes the physiological and pathophysiological characteristics of BiP and its interaction partners. Received 20 November 2008; received after revision 09 December 2008; accepted 12 December 2008     

Identification of susceptibility genes loci associated with type 2 diabetes

In this study, we selected 10 susceptible SNPs loci to investigate their contribution to susceptibility to type 2 diabetes in Han Chinese among Hubei population. We genotyped SNPs rs5219, rs1801282, rs1470579, rs1111875, rs1081661, rs7754840, rs4506565, rs13266634, rs4402960, and rs5643981 by using the method of polymerase chain reaction-ligase detection reaction (PCR-LDR). In a case-control study, we have genotyped the 10 candidate susceptibility SNP loci, and here, we reported that the SNP rs5219 in KCNJ1...     

苏铁在种子植物进化中的位置：分子生物学的证据

用大分子rRNA快速测序法测定了苏铁(Cycas revoluta Thunb.)、水松[Glyptos-trobus pensilis(Staunt.)Koch]和南方红豆杉[Taxus mairei(Lemee et Levl)S.Y.Hu]三种裸子植物Ls-rRNA5′端区108个核苷酸的序列。用这些数据构建的rRNA系统树揭示了苏铁与水松和南方红豆杉构成一个关系密切的姐妹群,而所分析的被子植物都为另一自然类群。另以绿藻作为种子植物群外参照物种,表明苏铁这一位置并不是由于一个特异的进化速度所造成的。这一结果支持了苏铁与松杉类为一自然群类,它们的分歧发生在裸子植物与被子植物分歧之后的假说。     

核糖与运动能力

核糖是合成ATP的起始分子,是核酸的重要组成部分。在体内,核糖主要通过磷酸戊糖途径生成。由于核糖是合成嘌呤核苷酸的重要前体物质,所以它是骨骼肌和心肌通过从头和补救途径合成能量物质的重要原料。由于核糖可以加快骨骼肌和心肌PRPP的合成速度,消除了磷酸戊糖途径中葡萄糖-6-磷酸脱氢酶活性低的限制,使嘌呤核苷酸的合成速度成倍增加,所以补充核糖可以提高运动能力。研究证明,核糖是一种安全、有效的运动营养补充品。     

核酸序列的模糊聚类与分子进化

将核酸序列(编码区)分成几类,求出每类的平均信息参数(D_L),用模糊聚类的方法研究它们的相似性和同源性,求出各级相似分岔值并导出动态聚类图.证明了短程相似分岔与序列进化有明显的相性,即L=2-5的一级相似分岔值与物种出现地质年代的对数保持较好的线性关系.     

Roles of the DNA mismatch repair and nucleotide excision repair proteins during meiosis

Numerous proteins are involved in the nucleotide excision repair (NER) and DNA mismatch repair (MMR) pathways. The function and specificity of these proteins during the mitotic cell cycle has been actively investigated, in large part due to the involvement of these systems in human diseases. In contrast, comparatively little is known about their functioning during meiosis. At least three repair pathways operate during meiosis in the yeast Saccharomyces cerevisiae to repair mismatches that occur as a consequence of heteroduplex formation in recombination. The first pathway is similar to the one acting during postreplicative mismatch repair in mitotically dividing cells, while two pathways are responsible for the repair of large loops during meiosis, using proteins from MMR and NER systems. Some MMR proteins also help prevent recombination between diverged sequences during meiosis, and act late in recombination to affect the resolution of crossovers. This review will discuss the current status of DNA mismatch repair and nucleotide excision repair proteins during meiosis, especially in the yeast S. cerevisiae. Received 21 September 1998; received after revision 23 November 1998; accepted 23 November 1998     

Scanning for sisnatures of geosraphically restricted selection based on population genomics analysis

Natural selection, as the driving force of human evolution, has direct impact on population differentiation. However, it is still unclear to what extent the genetic differentiation has been caused by natural selection. To explore this question, we performed a genome-wide scan with single nucleotide polymorphism （SNP） data from the International HapMap Project. Single locus FsTanalysis was applied to assess the frequency difference among populations in autosomes. Based on the empirical distribution of FsT, we identified 12669 SNPs correlating to population differentiation and 1853 candidate genes subjected to geographic restricted natural selection. Further interpretation of gene ontogeny revealed 121 categories of biological process with the enrichments of candidate genes. Our results suggest that natural selection may play an important role in human population differentiation. In addition, our analysis provides new clues as well as research methods for our understanding of population differentiation and natural selection.