gsp癌基因在国人肢端肥大症患者中的表达

ｇｓｐ癌基因是肢端肥大症患者发生垂体肿瘤的重要原因,这是由于编码刺激性Ｇ蛋白α亚基（Ｇｓα）的基因存在突变,导致细胞内ｃＡＭＰ水平持速升高所致。令人惊讶的是,来自日本的报导ｇｓｐ癌基因的发病率（４～９％）明显低于西方（４０％）,推测为种族差异所至。为了进一步观察,我们检测了ｇｓｐ癌基因在我国肢端肥大患者中的表达率。材料与方法：检测了１０例国人肢端肥大患者（男６例,女４例,年龄２３～５４岁,其中３例表现有巨人症,肿瘤直径为１１～４０ｍｍ,６例肿瘤有侵袭性）。从肿瘤组织中提取ＤＮＡ,经ＰＣＲ扩增Ｇｓα基因,ＰＣＲ－ＤＮＡ直接进行序列分析来检测ｇｓｐ癌基因突变位点。结果：４例（４０％）肿瘤ｇａｓ癌基因为阳性,３例突变位点位于编码Ｇｓα基因的２０１号密码子上,精氨酸被替换为半胱氨酸（ＣＧＴ→ＴＧＴ）,１例位于２２７号密码子,甘氨酸被替换为亮氨酸（ＣＡＧ→ＣＴＧ）。讨论：结果显示,ｇｓｐ癌基因在中国肢端肥大症患者中的发病率与西方一致,其与日本研究结果的差异似乎不是种族不同所致     

Relative fitness can decrease in evolving asexual populations of S. cerevisiae

It is generally accepted from the darwinian theory of evolution that a progressive increase in population adaptation will occur in populations containing genetic variation in fitness, until a stable equilibrium is reached and/or the additive genetic variation is exhausted. However, the theoretical literature of population genetics documents exceptions where mean population fitness may decrease in response to evolutionary changes in gene frequency, due to varying selective coefficients, sexual selection or to epistatic interactions between loci. Until now, no examples of such exceptions have been documented from fitness estimates in either natural or experimental populations. We present here direct evidence that, as a result of epistatic interactions between adaptive mutations, mean population fitness can decrease in asexual evolving populations of the yeast Saccharomyces cerevisiae.     

Sequence identification of 2,375 human brain genes.

We recently described a new approach for the rapid characterization of expressed genes by partial DNA sequencing to generate 'expressed sequence tags'. From a set of 600 human brain complementary DNA clones, 348 were informative nuclear-encoded messenger RNAs. We have now partially sequenced 2,672 new, independent cDNA clones isolated from four human brain cDNA libraries to generate 2,375 expressed sequence tags to nuclear-encoded genes. These sequences, together with 348 brain expressed sequence tags from our previous study, comprise more than 2,500 new human genes and 870,769 base pairs of DNA sequence. These data represent an approximate doubling of the number of human genes identified by DNA sequencing and may represent as many as 5% of the genes in the human genome.     

Crude-oil biodegradation via methanogenesis in subsurface petroleum reservoirs

Biodegradation of crude oil in subsurface petroleum reservoirs has adversely affected the majority of the world's oil, making recovery and refining of that oil more costly. The prevalent occurrence of biodegradation in shallow subsurface petroleum reservoirs has been attributed to aerobic bacterial hydrocarbon degradation stimulated by surface recharge of oxygen-bearing meteoric waters. This hypothesis is empirically supported by the likelihood of encountering biodegraded oils at higher levels of degradation in reservoirs near the surface. More recent findings, however, suggest that anaerobic degradation processes dominate subsurface sedimentary environments, despite slow reaction kinetics and uncertainty as to the actual degradation pathways occurring in oil reservoirs. Here we use laboratory experiments in microcosms monitoring the hydrocarbon composition of degraded oils and generated gases, together with the carbon isotopic compositions of gas and oil samples taken at wellheads and a Rayleigh isotope fractionation box model, to elucidate the probable mechanisms of hydrocarbon degradation in reservoirs. We find that crude-oil hydrocarbon degradation under methanogenic conditions in the laboratory mimics the characteristic sequential removal of compound classes seen in reservoir-degraded petroleum. The initial preferential removal of n-alkanes generates close to stoichiometric amounts of methane, principally by hydrogenotrophic methanogenesis. Our data imply a common methanogenic biodegradation mechanism in subsurface degraded oil reservoirs, resulting in consistent patterns of hydrocarbon alteration, and the common association of dry gas with severely degraded oils observed worldwide. Energy recovery from oilfields in the form of methane, based on accelerating natural methanogenic biodegradation, may offer a route to economic production of difficult-to-recover energy from oilfields.     

Syntrophin proteins as Santa Claus: role(s) in cell signal transduction

Syntrophins are a family of cytoplasmic membrane-associated adaptor proteins, characterized by the presence of a unique domain organization comprised of a C-terminal syntrophin unique (SU) domain and an N-terminal pleckstrin homology (PH) domain that is split by insertion of a PDZ domain. Syntrophins have been recognized as an important component of many signaling events, and they seem to function more like the cell’s own personal ‘Santa Claus’ that serves to ‘gift’ various signaling complexes with precise proteins that they ‘wish for’, and at the same time care enough for the spatial, temporal control of these signaling events, maintaining overall smooth functioning and general happiness of the cell. Syntrophins not only associate various ion channels and signaling proteins to the dystrophin-associated protein complex (DAPC), via a direct interaction with dystrophin protein but also serve as a link between the extracellular matrix and the intracellular downstream targets and cell cytoskeleton by interacting with F-actin. They play an important role in regulating the postsynaptic signal transduction, sarcolemmal localization of nNOS, EphA4 signaling at the neuromuscular junction, and G-protein mediated signaling. In our previous work, we reported a differential expression pattern of alpha-1-syntrophin (SNTA1) protein in esophageal and breast carcinomas. Implicated in several other pathologies, like cardiac dys-functioning, muscular dystrophies, diabetes, etc., these proteins provide a lot of scope for further studies. The present review focuses on the role of syntrophins in membrane targeting and regulation of cellular proteins, while highlighting their relevance in possible development and/or progression of pathologies including cancer which we have recently demonstrated.     

Vγ9Vδ2 T cell activation by strongly agonistic nucleotidic phosphoantigens

Human Vγ9Vδ2 T cells can sense through their TCR tumor cells producing the weak endogenous phosphorylated antigen isopentenyl pyrophosphate (IPP), or bacterially infected cells producing the strong agonist hydroxyl dimethylallyl pyrophosphate (HDMAPP). The recognition of the phosphoantigen is dependent on its binding to the intracellular B30.2 domain of butyrophilin BTN3A1. Most studies have focused on pyrophosphate phosphoantigens. As triphosphate nucleotide derivatives are naturally co-produced with IPP and HDMAPP, we analyzed their specific properties using synthetic nucleotides derived from HDMAPP. The adenylated, thymidylated and uridylated triphosphate derivatives were found to activate directly Vγ9Vδ2 cell lines as efficiently as HDMAPP in the absence of accessory cells. These antigens were inherently resistant to terminal phosphatases, but apyrase, when added during a direct stimulation of Vγ9Vδ2 cells, abrogated their stimulating activity, indicating that their activity required transformation into strong pyrophosphate agonists by a nucleotide pyrophosphatase activity which is present in serum. Tumor cells can be sensitized with nucleotide phosphoantigens in the presence of apyrase to become stimulatory, showing that this can occur before their hydrolysis into pyrophosphates. Whereas tumors sensitized with HDMAPP rapidly lost their stimulatory activity, sensitization with nucleotide derivatives, in particular with the thymidine derivative, induced long-lasting stimulating ability. Using isothermal titration calorimetry, binding of some nucleotide derivatives to BTN3A1 intracellular domain was found to occur with an affinity similar to that of IPP, but much lower than that of HDMAPP. Thus, nucleotide phosphoantigens are precursors of pyrophosphate antigens which can deliver strong agonists intracellularly resulting in prolonged and strengthened activity.     

Requirement of yeast fimbrin for actin organization and morphogenesis in vivo

The SAC6 gene was found by suppression of a yeast actin mutation. Its protein product, Sac6p (previously referred to as ABP67), was independently isolated by actin-filament affinity chromatography and colocalizes with actin in vivo. Thus Sac6p binds to actin in vitro, and functionally associates with actin structures involved in the development and maintenance of cell polarity in vivo. We report here that Sac6p is an actin-filament bundling protein 43% identical in amino-acid sequence to the vertebrate bundling protein fimbrin. This yeast fimbrin homologue contains two putative actin-binding regions homologous to domains of dystrophin, beta-spectrin, filamin, actin-gelation protein and alpha-actinin. Mutants lacking Sac6p do not form normal actin structures and are defective in morphogenesis. These findings demonstrate an in vivo role for the well-documented biochemical interaction between fimbrin and actin.     

Identifying and incorporating change in information systems

The difficulty of identifying future requirements and the inflexibility of information systems make what is normally called the maintenance process difficult and costly, and may lead to information systems failure or obsolescence. This paper addresses the problem in a number of ways. It discusses three techniques which might be used to help identify future requirements. Two of these techniques are drawn from other disciplines; the third is not used widely in the information systems domain. All the techniques have broader applicability than maintenance alone, in that they are concerned with reducing uncertainty. The paper outlines some tenets of good applications software design, drawn from a number of sources, which will facilitate change by making the software design more flexible. Finally, these tenets are incorporated into information systems design through a proposed modification of the information systems life cycle framework. This framework—part of a “code of good practice” for information systems developers—could be incorporated into information systems development methodologies.