The role of posttranslational modification in moonlighting glyceraldehyde-3-phosphate dehydrogenase structure and function

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a moonlighting protein exhibiting distinct activities apart from its classical role in glycolysis. Regulation of its moonlighting functions and its subcellular localization may be dependent on its posttranslational modification (PTM). The latter include its phosphorylation, which is required for its role in intermembrane trafficking, synaptic transmission and cancer survival; nitrosylation, which is required for its function in apoptosis, heme metabolism and the immune response; acetylation which is necessary for its modulation of apoptotic gene regulation; and N-acetylglucosamine modification which may induce changes in GAPDH oligomeric structure. These findings suggest a structure function relationship between GAPDH posttranslational modification and its diverse moonlighting activities.

     

WHO at country level--a little impact,no strategy.

The acid test of WHO''s effect on the world''s health is its impact at country level. Unless it has an impact there, all of its declarations, its debates at the World Health Assembly, its conferences, its pamphlets, its political manouvering in Geneva and the regions, all of these come to nothing. Working as it does through national governments, WHO insists that it has no role in directly managing or delivering health care. Judging WHO''s impact in individual countries is therefore difficult--its approaches are largely indirect, and initiatives may take years to bear fruit. But from the meagre resources that WHO makes available at country level it is clear why its country operations are criticised as the weakest link in an already weak chain of influence from its headquarters in Geneva to the people in its member states. Poorly funded, undertrained, and with no clear strategy to follow, its staff at country level stand little chance of making an impact.     

Water? What's so special about it?

What is so special about water? Why does it have the properties it has, and how might these reasons be relevant to its apparent biological importance? By exploring the structure and dynamics of water, from the isolated molecule and its interactions, through its many crystalline phases and to its so-called anomalous liquid phase, some of its apparently unusual behaviour is rationalized. The way in which it interacts with some relatively simple interfaces is also discussed. As a result of this exploration, a checklist of possible molecular-level reasons for its biological importance is devised.     

Stress-free state of the red blood cell membrane and the deformation of its skeleton

The response of a red blood cell (RBC) to deformation depends on its membrane, a composite of a lipid bilayer and a skeleton, which is a closed, twodimensional network of spectrin tetramers as its bonds. The deformation of the skeleton and its lateral redistribution are studied in terms of the RBC resting state for a fixed geometry of the RBC, partially aspirated into a micropipette. The geometry of the RBC skeleton in its initial state is taken to be either two concentric circles, a references biconcave shape or a sphere. It is assumed that in its initial state the skeleton is distributed laterally in a homogeneous manner with its bonds either unstressed, presenting its stress-free state, or prestressed. The lateral distribution was calculated using a variational calculation. It was assumed that the spectrin tetramer bonds exhibit a linear elasticity. The results showed a significant effect of the initial skeleton geometry on its lateral distribution in the deformed state. The proposed model is used to analyze the measurements of skeleton extension ratios by the method of applying two modes of RBC micropipette aspiration.     

Male‐female differences in family size preferences among college students

Abstract

Three dimensions of isolated spousal separation largely determine its fertility impact: (1) length, (2) “completeness” (degree to which it is eliminating fecundability during fecundable months), and (3) its timing as defined by the reproductive state of the wife at its start. While it is obvious that by starting when the wife is in the fecundable state its net delaying of next conception is maximized, it is much less clear with which reproductive state its start should coincide in order to minimize its fertility impact. By means of a simple model, it is shown that for minimum impact a separation should start later in a pregnancy the longer is post‐partum anovulation, the higher is the level of intrauterine mortality, and the shorter is the period of separation. Conditions of natural fertility are assumed.     

High-frequency P element loss in Drosophila is homolog dependent

P transposable elements in Drosophila melanogaster can undergo precise loss at a rate exceeding 13% per generation. The process is similar to gene conversion in its requirement for a homolog that is wild type at the insertion site and in its reduced frequency when pairing between the homologs is inhibited. However, it differs from classical gene conversion by its high frequency, its requirement for P transposase, its unidirectionality, and its occurrence in somatic and premeiotic cells. Our results suggest a model of P element transposition in which jumps occur by a "cut-and-paste" mechanism but are followed by double-strand gap repair to restore the P element at the donor site. The results also suggest a technique for site-directed mutagenesis in Drosophila.     

沙冬青淀粉粒及其与叶绿体发育的关系

沙冬青叶绿体中的淀粉粒一般为１－３个,主要有４种类型。第１种外周部分电子密度较高,中央部分较低,但每个部分的电子密度十分均匀。它们近似椭圆形,附近的类囊体形态正常,结构清晰。第２种电子密度由外向内逐渐变低,多为椭圆形,附近的类囊体较清晰。第３种外周部分的电子密度很高,中央部分不均匀,形状多种多样,附近的类囊体有的不清晰。第４种电子密度很低,十分均匀,形状不规则,附近的类囊体已经解体或正在解体。分析表明,淀粉的形态变化明显与叶绿体发育有关。     

Acetylcholinesterase: how is structure related to function?

In accordance with its biological role, termination of neurotransmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter, acetylcholine, acetylcholinesterase is one of nature's most efficient enzymes. Solution of its three-dimensional structure revealed that its active site is located at the bottom of a deep and narrow gorge. Such an architecture was unanticipated in view of its high turnover number. The present review examines how the highly specialized structure of acetylcholinesterase, with its sequestered active site, contributes to its catalytic efficacy, and discusses how the traffic of substrate and products to and from the active site is controlled.     

甲壳素及其衍生物在医药卫生领域中的应用

甲壳素是自然界储存量仅次于纤维素的第二大天然多糖化合物 ,本文综述了其药理作用、在医药卫生方面的应用研究情况 ,如甲壳素抗感染、抗凝血、抗癌及降血脂等作用及在制剂方面的应用等     

世界麦双尾蚜研究进展：分布、

The Russian wheat aphid (RWA), Diuraphis noxia (Mordvilko), has become a worldwide cereal pest with its dispersion to over 30 countries in this century. According to the natural history of its occurrence around the world, it is postulated RWA originated from western or central Asia. The aphid dispersed gradually to Europe and northern Africa, but its big jump across the ocean to North America is still a mystery. There are two overwintering strategies in RWA. The anholocyclic biotype, often reproducing earlier and more offsprings than the holocyclic one, has greater impact on crops in South Africa and United States. According to the experiments on its thermal response, RWA could withstand temperatures below -20℃, while temperatures above 30℃ would be harmful to its survival. The preference to colder condition may determine its distribution on the world. RWA has made great damages to cereal crops worldwide. It caused loss in crop yield by directly feeding on plant nutrition and disturbing the plant metabolism. But its status as plant virus transporter is open to question. By now, the aphid is still a serious pest in many countries and its invasion to more countries and areas maybe continues. Therefore, the research on its biological characteristics as well as its dispersion apparently needs to be enhanced in the future.     

Regulation and roles of phosphoenolpyruvate carboxykinase in plants

Phosphoenolpyruvate carboxykinase (PCK) is probably ubiquitous in flowering plants, but is confined to certain cells or tissues. It is regulated by phosphorylation, which renders it less active by altering both its substrate affinities and its sensitivity to regulation by adenylates. In the leaves of some C4 plants, such as Panicum maximum, dephosphorylation increases its activity in the light. In other tissues such regulation probably avoids futile cycling between phosphoenolpyruvate and oxaloacetate. Although PCK generally acts as a decarboxylase in plants, its affinity for CO2 measured at physiological concentrations of metal ions is high and would allow it to be freely reversible in vivo. While its function in gluconeogenesis in seeds postgermination and in leaves of C4 and crassulacean acid metabolism plants is clearly established, the possible functions of PCK in other plant cells are discussed, drawing parallels with those in animals, including its integrated function in cataplerosis, nitrogen metabolism, pH regulation, and gluconeogenesis.     

Homology and structure-function correlations between alpha 1-acid glycoprotein and serum retinol-binding protein and its relatives

Although the serum protein alpha 1-acid glycoprotein (AGP) or orosomucoid has been extensively studied, its relationships with other proteins have been controversial and its precise physiological function has remained unclear. It is shown here that AGP is significantly similar in amino acid sequence and in the locations of introns in its structural gene to members of a protein superfamily that includes serum retinol-binding protein (RBP), beta-lactoglobulin (LG), alpha 2u-globulin, and protein HC (alpha 1-microglobulin). The view that the three-dimensional structure of AGP is closely similar to the published structures of RBP and LG is supported by its homology with these proteins, similarities in disulfide bond arrangements, and its secondary structure profile, predicted from the amino acid sequence. The relationship of AGP with this particular protein family indicates that its well-characterized ability to bind lipophilic drugs and certain steroids is a reflection of its true biological role. It is proposed that AGP and the other members of this extensive group of proteins should be designated lipocalins to reflect a common ability to bind lipophiles by enclosure within their structures in a manner that minimizes solvent contact.     

中国兰科植物四个新记录种

报道了中国兰科植物四个新记录种,反瓣叉柱兰(Cheirostylis thailandica),短茎对叶兰(Listerabrevi-caulis),凹唇石仙桃(Pholidota recurva),绿花大苞兰(Sunipia annamensis)。短茎对叶兰(Listera brevicaulis)二枚叶贴地着生,唇瓣先端二裂,裂片下翻并靠合;凹唇石仙桃(Pholidota recurva)的假鳞茎圆柱形,首尾相连,花偏向一侧,花序在中部向下弯,唇瓣前端略凹陷;绿花大苞兰(Sunipia annamensis)的花序长于叶,唇瓣心形,肉质,边缘向上翻卷。     

Comparative aspects of the area postrema: fine-structural considerations help to determine its function

The area postrema is a circumventricular organ of the fourth ventricle of the mammalian brain. Although there are distinct gross anatomical differences in the appearance of this organ between "lower" mammals such as rodents and lagomorphs and "higher" mammals such as carnivores and primates, its fine structure is remarkably similar in all species studied. There are many suggestions in the literature for a specific function for this area of the brain, ranging from its being a chemoreceptive trigger zone for the emetic response to its being a regulatory nucleus for the sleep cycle. The present report describes some comparative studies on the ultrastructure of this organ. This information is discussed in relation to what is known about the neurochemistry of the area postrema and its connections with other brain regions and visceral structures. A suggestion is offered that our current knowledge of the area postrema is consistent with its performing many of its proposed functions in the context of a regulatory ("fine-tuning") center for many autonomic functions.     

Construction of proteolysis resistant human interleukin-2 by fusion to its protective single chain antibody

Interleukin-2 (IL-2) is a 15 kDa cytokine secreted by T-cells. Consequence to its natural function as locally secreted short-term messenger, its half-life in circulation is short and provided mainly by fast renal clearance due to its low molecular weight and its proteolytic susceptibility. These are common characteristics for most cytokines, resulting in low clinical utility. In this study we report the construction of an IL-2 fusion-protein comprising a protective anti-hIL-2 single chain antibody that was selected from a phage display library and the hIL-2. This IL-2 fusion-protein is fully human and resistant to inactivation by the ubiquitous lysosomal protease-cathepsin D, which is implicated in the in vivo inactivation of IL-2. In contrast, the native IL-2 lost practically all of its activity under these conditions. This resistance is due to the interaction of the single chain domain with its epitope on IL-2 thus masking possible cleavage sites. We suggest that this 45 kDa proteolysis resistant IL-2 fusion-protein upon further increase of its molecular weight by common fusion techniques to at least 75 kDa will exhibit significantly longer half-life in vivo and a higher clinical utility than either the native IL-2 or any of its reported long T/2 derivatives.     

A facile method for the preparation of deuterium labeled salvinorin A: synthesis of [2,2,2-2H3]-salvinorin A

Salvinorin A is a novel hallucinogen isolated from the widely available leaves of Salvia divinorum. Based on its mechanism of action, salvinorin A has shown potential as a stimulant abuse therapeutic. However, there are no methods for the detection of salvinorin A or its metabolites in biological fluids. In order to begin developing salvinorin A as a potential therapeutic, an understanding of its metabolism is needed. Here, a straightforward synthesis of a deuterium labeled analog of salvinorin A and its utility as an internal standard for the detection of salvinorin A and its metabolites in biological fluids by LC-MS is described.     

Endothelin-1 as a neuropeptide: neurotransmitter or neurovascular effects?

Endothelin-1 (ET-1) is an endothelium-derived peptide that also possesses potent mitogenic activity. There is also a suggestion the ET-1 is a neuropeptide, based mainly on its histological identification in both the central and peripheral nervous system in a number of species, including man. A neuropeptide role for ET-1 is supported by studies showing a variety of effects caused following its administration into different regions of the brain and by application to peripheral nerves. In addition there are studies proposing that ET-1 is implicated in a number of neural circuits where its transmitter affects range from a role in pain and temperature control to its action on the hypothalamo-neurosecretory system. While the effect of ET-1 on nerve tissue is beyond doubt, its action on nerve blood flow is often ignored. Here, we review data generated in a number of species and using a variety of experimental models. Studies range from those showing the distribution of ET-1 and its receptors in nerve tissue to those describing numerous neurally-mediated effects of ET-1.     

Structure-function studies of DNA polymerase lambda

DNA polymerase lambda is a member of the X family of polymerases that is implicated in non-homologous end-joining of double-strand breaks in DNA and in base excision repair of DNA damage. To better understand the roles of DNA polymerase lambda in these repair pathways, here we review its structure and biochemical properties, with emphasis on its gap-filling polymerization activity, its dRP lyase activity and its unusual DNA synthetic (in)fidelity.     

Three new species of Potamothrix (Oligochaeta, Naididae, Tubificinae) from Fuxian Lake, the deepest lake of Yunnan Province, Southwest China

Three new species of Potamothrix Vejdovsky & Mrázek, 1902 (Oligochaeta: Tubificinae), Potamothrix praeprostatussp. n., Potamothrix paramoldaviensissp. n. and Potamothrix parabedotisp. n., are reported from Fuxian Lake of Yunnan Province, Southwest China. Potamothrix praeprostatusdiffers from its allies by its prostate glands joining atria in its proximal to middle portion, and spermathecal chaetae. Potamothrix paramoldaviensis is distinguishable from its allies by having penial chaeta but no penes, and differs from Potamothrix moldaviensisby its homogenous atrium. Potamothrix parabedoti is distinctive in the position of its reproductive organs, and differs from Potamothrix bedoti by its homogenous atrium. Hitherto, 34 freshwater oligochaete species have been recorded in Yunnan Province, including nine endemic species from the plateau lakes.