Crystal structure of a cholera toxin-related heat-labile enterotoxin from E. coli

Examination of the structure of Escherichia coli heat-labile enterotoxin in the AB5 complex at a resolution of 2.3A reveals that the doughnut-shaped B pentamer binds the enzymatic A subunit using a hairpin of the A2 fragment, through a highly charged central pore. Putative ganglioside GM1-binding sites on the B subunits are more than 20A removed from the membrane-crossing A1 subunit. This ADP-ribosylating (A1) fragment of the toxin has structural homology with the catalytic region of exotoxin A and hence also to diphtheria toxin.     

Requirement for a functional Rb-1 gene in murine development.

Human retinoblastomas can occur both as hereditary and as sporadic cases. Knudson's proposal that they result from two mutational events, of which one is present in the germ line in hereditary cases, has been confirmed by more recent molecular analysis, which has shown both events to involve loss or mutational inactivation of the same gene, RB-1 (ref. 2). RB-1 heterozygosity also predisposes to osteosarcoma, and RB-1 allele losses are seen in sporadic lung, breast, prostate and bladder carcinomas. RB-1 is expressed in most, if not all, tissues and codes for a nuclear phosphoprotein which becomes hypophosphorylated in the G0 growth arrest state and in the G1 phase of the cell cycle. To gain a further insight into the role of RB-1 we and other groups have generated mice carrying an inactivated allele of the homologous gene, Rb-1 (ref. 10), by gene targeting. We report here that young heterozygous mice do not appear abnormal and do not develop retinoblastoma at a detectable frequency. However, homozygous mutant embryos fail to reach term and show a number of abnormalities in neural and haematopoietic development. Broadly similar results are reported by the other groups.     

用于数据库新兴应用程序的逻辑

逻辑与数据库及信息系统之间的关系是广泛和长期存在的。对于数据库理论家而言，逻辑是一个统一的框架。在该框架内可以理解数据模型和查询语言的语义学；允许对它们的可表达性进行比较；并且应用高度开发的数学逻辑工具给出深入的理解。随着数据库系统管理的信息类型日益丰富．数据库和信息系统的逻辑价值也就更加突出。异构和分布式数据源包括了从遗传序列到具有丰富时态的结构；从结合文本与数据的半结构文件到有关复杂组织协同进程的信息。     

Adaptation of Industrial Organisations to the Environment Grounded in Evolutionary Models

Yes, we perceive that the environment in which comp an ies operate, is changing at higher speeds then before. Globalisation, higher inn ovation rates, customisation, more intense competition, technological developmen ts account for these changes effecting the way industrial companies operate and eventually their structures and processes. Companies have to adapt themselves to these changes. The question arose whether the approach of the Section Industria l Organisation and Management that it has practised ...     

Zu Einsteins letzter Vorlesung — Beobachtbarkeit,Realität und Vollständigkeit in Quanten- und Relativitätstheorie

Ohne Zusammenfassung Vorgelegt von J. D. North     

Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group.

Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS; MIM 260920) is a rare, apparently monogenic, autosomal recessive disorder characterized by recurrent episodes of fever accompanied with lymphadenopathy, abdominal distress, joint involvement and skin lesions. All patients have high serum IgD values (>100 U/ml) and HIDS 'attacks' are associated with an intense acute phase reaction whose exact pathophysiology remains obscure. Two other hereditary febrile disorders have been described. Familial Mediterranean fever (MIM 249100) is an autosomal recessive disorder affecting mostly populations from the Mediterranean basin and is caused by mutations in the gene MEFV (refs 5,6). Familial Hibernian fever (MIM 142680), also known as autosomal dominant familial recurrent fever, is caused by missense mutations in the gene encoding type I tumour necrosis factor receptor. Here we perform a genome-wide search to map the HIDS gene. Haplotype analysis placed the gene at 12q24 between D12S330 and D12S79. We identified the gene MVK, encoding mevalonate kinase (MK, ATP:mevalonate 5-phosphotransferase; EC 2.7.1.36), as a candidate gene. We characterized 3 missense mutations, a 92-bp loss stemming from a deletion or from exon skipping, and the absence of expression of one allele. Functional analysis demonstrated diminished MK activity in fibroblasts from HIDS patients. Our data establish MVK as the gene responsible for HIDS.     

Metamodeling: The epistemology of system science

The Metasystem Paradigm postulates a hierarchy of at least three inquiring systems: at the lowest level of abstraction, an inquiring system devoted to IMPLEMENTATION; at the object level, an inquiring system devoted to MODELING; and finally, at the metalevel, an inquiring system devoted to METAMODELING. System Design is incomplete without the intervention of these three inquiring systems, each of which plays a role in System Design. System Science draws its paradigm and its epistemology from the metalevel inquiring system. Furthermore, this inquiring system is dedicated to a methodology called METAMODELING which provides MODELING (at the next-lower inquiring system) with its source of knowledge and its reasoning methods. A design is incomplete unless it takes into account both MODELING and METAMODELING. METAMODELING is to MODELING what the Theory of Design is to Design, or what Decision Making ABOUT Decision Making is to Decision Making, or what Learning to Learn is to Learning. The consequences of using an obsolete modeling paradigm are explored in relation to the discipline of operations research.     

Reconciling complexity with stability in naturally assembling food webs

Understanding how complex food webs assemble through time is fundamental both for ecological theory and for the development of sustainable strategies of ecosystem conservation and restoration. The build-up of complexity in communities is theoretically difficult, because in random-pattern models complexity leads to instability. There is growing evidence, however, that nonrandom patterns in the strengths of the interactions between predators and prey strongly enhance system stability. Here we show how such patterns explain stability in naturally assembling communities. We present two series of below-ground food webs along natural productivity gradients in vegetation successions. The complexity of the food webs increased along the gradients. The stability of the food webs was captured by measuring the weight of feedback loops of three interacting 'species' locked in omnivory. Low predator-prey biomass ratios in these omnivorous loops were shown to have a crucial role in preserving stability as productivity and complexity increased during succession. Our results show the build-up of food-web complexity in natural productivity gradients and pin down the feedback loops that govern the stability of whole webs. They show that it is the heaviest three-link feedback loop in a network of predator-prey effects that limits its stability. Because the weight of these feedback loops is kept relatively low by the biomass build-up in the successional process, complexity does not lead to instability.