Functional proteins from a random-sequence library

Functional primordial proteins presumably originated from random sequences, but it is not known how frequently functional, or even folded, proteins occur in collections of random sequences. Here we have used in vitro selection of messenger RNA displayed proteins, in which each protein is covalently linked through its carboxy terminus to the 3' end of its encoding mRNA, to sample a large number of distinct random sequences. Starting from a library of 6 x 1012 proteins each containing 80 contiguous random amino acids, we selected functional proteins by enriching for those that bind to ATP. This selection yielded four new ATP-binding proteins that appear to be unrelated to each other or to anything found in the current databases of biological proteins. The frequency of occurrence of functional proteins in random-sequence libraries appears to be similar to that observed for equivalent RNA libraries.     

Functional analysis of schistosomes EF-hand domain-containing tegument proteins

Schistosomes cause schistosomiasis disease which severely threatens human health. Little is known about the functions of EF-hand domain containing schistosomes tegument proteins other than as an-tigens. More possible functions of these tegument proteins were investigated with in silico analyses including protein-protein functional interaction,site-specific variation and glycosylation modification. The analysis results suggested that schistosomes could actively modulate host immune responses for its own favor through functional interactions with host proteins with immunomodulatory function,and passively regulate host immune responses through sequence variation under positive selection and glycosylating the recognition sites of host immune attack. In addition,the analysis of the C-terminal domain of these tegument proteins indicated that they could assist schistosomes in escaping host immune attacks through inhibiting chemotaxis and non-complement fixing antibody (IgG4) responses. In summary,our results suggested that these tegument antigen proteins could assist schistosomes in escaping and modulating host immune responses for self-protection during the process of host-para-site interaction.     

中文文档与源代码间关联关系提取方法的研究

文章提出了一种提取中文软件文档与源代码间的关联关系的方法,根据中文软件文档和源代码的一些特征,在潜在语义索引模型的基础上使用了3种策略:引入项目数据词典辅助中文分词和中英文的翻译、将文档按类型分层以实现反馈、调整代码中的特征项的权值。实验结果表明,同时使用3种策略可以在提取阀值C相同的情况下,提高查全率4%~28%,在查全率不变的情况下,提高查准率8%~30%。     

浅析功能饮料之战

功能性饮料崛起的原因在于国际红火的市场前景与国内有利的市场契机,通过对该品类饮料营销策略中的产品定位策略与媒体投放策略的分析,指出制约功能饮料发展的瓶颈在于该类产品不够平民化以及缺乏相应的行业标准。     

Functional interactions between receptors in bacterial chemotaxis

Bacterial chemotaxis is a model system for signal transduction, noted for its relative simplicity, high sensitivity, wide dynamic range and robustness. Changes in ligand concentrations are sensed by a protein assembly consisting of transmembrane receptors, a coupling protein (CheW) and a histidine kinase (CheA). In Escherichia coli, these components are organized at the cell poles in tight clusters that contain several thousand copies of each protein. Here we studied the effects of variation in the composition of clusters on the activity of the kinase and its sensitivity to attractant stimuli, monitoring responses in vivo using fluorescence resonance energy transfer. Our results indicate that assemblies of bacterial chemoreceptors work in a highly cooperative manner, mimicking the behaviour of allosteric proteins. Conditions that favour steep responses to attractants in mutants with homogeneous receptor populations also enhance the sensitivity of the response in wild-type cells. This is consistent with a number of models that assume long-range cooperative interactions between receptors as a general mechanism for signal integration and amplification.     

Functional proteomic identification of DNA replication proteins by induced proteolysis in vivo

Evolutionarily diverse eukaryotic cells share many conserved proteins of unknown function. Some are essential for cell viability, emphasising their importance for fundamental processes of cell biology but complicating their analysis. We have developed an approach to the large-scale characterization of such proteins, based on conditional and rapid degradation of the target protein in vivo, so that the immediate consequences of bulk protein depletion can be examined. Budding yeast strains have been constructed in which essential proteins of unknown function have been fused to a 'heat-inducible-degron' cassette that targets the protein for proteolysis at 37 degrees C (ref. 4). By screening the collection for defects in cell-cycle progression, here we identify three DNA replication factors that interact with each other and that have uncharacterized homologues in human cells. We have used the degron strains to show that these proteins are required for the establishment and normal progression of DNA replication forks. The degron collection could also be used to identify other, essential, proteins with roles in many other processes of eukaryotic cell biology.     

Functional interactions between the gut microbiota and host metabolism

The link between the microbes in the human gut and the development of obesity, cardiovascular disease and metabolic syndromes, such as type 2 diabetes, is becoming clearer. However, because of the complexity of the microbial community, the functional connections are less well understood. Studies in both mice and humans are helping to show what effect the gut microbiota has on host metabolism by improving energy yield from food and modulating dietary or the host-derived compounds that alter host metabolic pathways. Through increased knowledge of the mechanisms involved in the interactions between the microbiota and its host, we will be in a better position to develop treatments for metabolic disease.     

混合序列加权和的完全收敛性及a.s.收敛性

在新的条件下讨论了不同分布的混合序列加权和的完全收敛性,获得了混合序列完全收敛的两个充分条件及Marcinkiewicz-Zygmund型的强大数定律.     

爆破大块率与爆破主参数之间的函数关系

在众多影响爆破大块率的因素中，爆破参数对大块率影响的不确定性因素最大，在实践操作中最难把握，事前对爆破的效果也很难估计。前人的研究仅对爆破大块率与爆破参数之间的关系作了定性的分析。从定性分析开始，经过定量分析，找出了它们之间的函数关系，从而指导生产实践。     

Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products

Ataxia-telangiectasia (A-T) and Nijmegen breakage syndrome (NBS) are recessive genetic disorders with susceptibility to cancer and similar cellular phenotypes. The protein product of the gene responsible for A-T, designated ATM, is a member of a family of kinases characterized by a carboxy-terminal phosphatidylinositol 3-kinase-like domain. The NBS1 protein is specifically mutated in patients with Nijmegen breakage syndrome and forms a complex with the DNA repair proteins Rad50 and Mrel1. Here we show that phosphorylation of NBS1, induced by ionizing radiation, requires catalytically active ATM. Complexes containing ATM and NBS1 exist in vivo in both untreated cells and cells treated with ionizing radiation. We have identified two residues of NBS1, Ser 278 and Ser 343 that are phosphorylated in vitro by ATM and whose modification in vivo is essential for the cellular response to DNA damage. This response includes S-phase checkpoint activation, formation of the NBS1/Mrel1/Rad50 nuclear foci and rescue of hypersensitivity to ionizing radiation. Together, these results demonstrate a biochemical link between cell-cycle checkpoints activated by DNA damage and DNA repair in two genetic diseases with overlapping phenotypes.     

Functional identity between murine gamma interferon and macrophage activating factor

We have previously suggested that two lymphokine activities-macrophage activating factor (MAF) and gamma interferon (IFN-gamma)-are mediated by the same molecule. Striking similarities were noted in their cellular biosynthesis, rate of inactivation with acid treatment and heating, and elution profiles on Sephacryl S-200. In addition, highly specific polyclonal antibodies to murine IFN-gamma neutralized MAF and IFN-gamma to a similar degree. However, definitive studies require a pure product and we now report that murine IFN-gamma that had been cloned and expressed in a simian nonlymphoid cell line shows MAF activity. But it is not yet known whether IFN-gamma is responsible for all the MAF activity in media conditioned by T cells as the possibility for MAF heterogeneity remains.     

函数关系已知的混沌系统的广义外同步

针对具有未知参数的两个不同混沌系统,在函数关系给定的情况下,对它们达到广义外同步进行了分析,并通过Barbalat's引理,给出了达到广义外同步的一个充分条件;同时,也给出了达到广义外同步所满足的自适应控制器和参数自适应律,数值仿真进一步验证了理论的正确性和有效性.     

Misfolded proteins partition between two distinct quality control compartments

The accumulation of misfolded proteins in intracellular amyloid inclusions, typical of many neurodegenerative disorders including Huntington's and prion disease, is thought to occur after failure of the cellular protein quality control mechanisms. Here we examine the formation of misfolded protein inclusions in the eukaryotic cytosol of yeast and mammalian cell culture models. We identify two intracellular compartments for the sequestration of misfolded cytosolic proteins. Partition of quality control substrates to either compartment seems to depend on their ubiquitination status and aggregation state. Soluble ubiquitinated misfolded proteins accumulate in a juxtanuclear compartment where proteasomes are concentrated. In contrast, terminally aggregated proteins are sequestered in a perivacuolar inclusion. Notably, disease-associated Huntingtin and prion proteins are preferentially directed to the perivacuolar compartment. Enhancing ubiquitination of a prion protein suffices to promote its delivery to the juxtanuclear inclusion. Our findings provide a framework for understanding the preferential accumulation of amyloidogenic proteins in inclusions linked to human disease.