The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat

Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder characterized by bilateral renal cystic dysplasia, developmental defects of the central nervous system (most commonly occipital encephalocele), hepatic ductal dysplasia and cysts and polydactyly. MKS is genetically heterogeneous, with three loci mapped: MKS1, 17q21-24 (ref. 4); MKS2, 11q13 (ref. 5) and MKS3 (ref. 6). We have refined MKS3 mapping to a 12.67-Mb interval (8q21.13-q22.1) that is syntenic to the Wpk locus in rat, which is a model with polycystic kidney disease, agenesis of the corpus callosum and hydrocephalus. Positional cloning of the Wpk gene suggested a MKS3 candidate gene, TMEM67, for which we identified pathogenic mutations for five MKS3-linked consanguineous families. MKS3 is a previously uncharacterized, evolutionarily conserved gene that is expressed at moderate levels in fetal brain, liver and kidney but has widespread, low levels of expression. It encodes a 995-amino acid seven-transmembrane receptor protein of unknown function that we have called meckelin.     

Digenic inheritance of severe insulin resistance in a human pedigree

Impaired insulin action is a key feature of type 2 diabetes and is also found, to a more extreme degree, in familial syndromes of insulin resistance. Although inherited susceptibility to insulin resistance may involve the interplay of several genetic loci, no clear examples of interactions among genes have yet been reported. Here we describe a family in which five individuals with severe insulin resistance, but no unaffected family members, were doubly [corrected] heterozygous with respect to frameshift/premature stop mutations in two unlinked genes, PPARG and PPP1R3A these encode peroxisome proliferator activated receptor gamma, which is highly expressed in adipocytes, and protein phosphatase 1, regulatory subunit 3, the muscle-specific regulatory subunit of protein phosphatase 1, which are centrally involved in the regulation of carbohydrate and lipid metabolism, respectively. That mutant molecules primarily involved in either carbohydrate or lipid metabolism can combine to produce a phenotype of extreme insulin resistance provides a model of interactions among genes that may underlie common human metabolic disorders such as type 2 diabetes.     

Adrenal weight in relation to duration of pregnancy in the indian desert hareLepus nigricollis dayanus blanford

Résumé La grossesse dans le lièvre,Lepus nigricollis dayanus Blanford, n'a pas d'influence directe sur le poid des glandes surrénales. Le poid surrénal n'augmente pas la grossesse.

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Thanks are due to the retired DirectorC. P. Bhimaya for his keen interest in the work and for providing facilities, and to Dr.P. K. Ghosh, Animal Physiologist, for suggestions.     

Effect of phytic acid on diamine oxidase activity in germinating pea seeds

Summary Diamine oxidase present in the cotyledons of germinating pea seeds is induced by phytic acid but the embryo enzyme is not affected. Polyamines have no effect on phytase activity of the cotyledon or embryo.We thank Dr S. K. Srivastava for his helpful suggestions.     

Inhibitory activity of benzoyl hydrazides and hydrazine on the growth of influenza virus in chick embryo lung tissue culture

Zusammenfassung Hydrazin, wie auch verschiedene Benzoylhydrazide, hemmen das Wachstum des Influenzavirus in Kulturen embryonalen Hühnerlungengewebes. Anthranilsäurehydrazid konnte die Virusvermehrung bis 6 h nach Viruszugabe hemmen.

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This investigation was supported by a contract with the Office of Naval Research.

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From a thesis submitted in partial fulfillment for the degree of Doctor of Philosophy.

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Deceased, October 6, 1960.     

Sur la présence deβ-alanine dans les tissus des plantes supérieures

Summary -alanine has always been found in peptide hydrolysates of various higher plants, but never in protein hydrolysates. An assumption that the-alanine so found is a constituent of coenzyme A has been suggested.     

Enhancement of ethylemethane sulfonate-induced mutation frequency inDrosophila by dimethyl sulphoxide

Zusammenfassung Die mutagene Wirkung von Aethylenmethansulfonat inDrosophila-Männchen wird durch DMSO um 46% erhöht. DMSO allein kann keine Mutation über die Spontanrate hinaus induzieren.     

Mutagenic insertion and chromosome engineering resource (MICER)

Embryonic stem cell technology revolutionized biology by providing a means to assess mammalian gene function in vivo. Although it is now routine to generate mice from embryonic stem cells, one of the principal methods used to create mutations, gene targeting, is a cumbersome process. Here we describe the indexing of 93,960 ready-made insertional targeting vectors from two libraries. 5,925 of these vectors can be used directly to inactivate genes with an average targeting efficiency of 28%. Combinations of vectors from the two libraries can be used to disrupt both alleles of a gene or engineer larger genomic changes such as deletions, duplications, translocations or inversions. These indexed vectors constitute a public resource (Mutagenic Insertion and Chromosome Engineering Resource; MICER) for high-throughput, targeted manipulation of the mouse genome.     

Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins

Interferon-gamma is an immunomodulatory substance that induces the expression of many genes to orchestrate a cellular response and establish the antiviral state of the cell. Among the most abundant antiviral proteins induced by interferon-gamma are guanylate-binding proteins such as GBP1 and GBP2. These are large GTP-binding proteins of relative molecular mass 67,000 with a high-turnover GTPase activity and an antiviral effect. Here we have determined the crystal structure of full-length human GBP1 to 1.8 A resolution. The amino-terminal 278 residues constitute a modified G domain with a number of insertions compared to the canonical Ras structure, and the carboxy-terminal part is an extended helical domain with unique features. From the structure and biochemical experiments reported here, GBP1 appears to belong to the group of large GTP-binding proteins that includes Mx and dynamin, the common property of which is the ability to undergo oligomerization with a high concentration-dependent GTPase activity.     

从碳到氢能源:昨天、今天、明天

简述了近期能源的发展动向,特别以氢能源为重点,就产氢、储氢及利用氢三个方面进行阐述。氢气作为高能量密度的燃料载体在提供能量的过程中可实现或接近实现无碳排放。作者及团队发现,将分散式电解水产氢技术应用在燃料电池模型汽车上,模型车的运行速度及里程可提高30%以上。