Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene

Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin tolerance tests. The PTP-1B-/- mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B-/- and PTP-1B+/- mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+ mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity.     

Erythropoiesis in the rat: differential rates of DNA synthesis and cell proliferation

Direct in vivo estimates of DNA synthesis time in early and late erythroblasts were obtained by using the H(3)- and C(14)-thymidine double-la-beling technique. A double-emulsion autoradiographic procedure was used to resolve the two isotopes. Early erythroblasts were found to proliferate at a rate about five times that of late cells. This results primarily from a shorter mean DNA synthesis time in early cells (2.5 hours) than in late cells (6.5 hours).     

Hypertensive action of 18-hydroxydeoxycorticosterone

18-Hydroxydeoxycorticosterone is an adrenal steroid hormone causing salt and water retention and is secreted in greatly increased amounts in response to the pituitary hormone adrenocorticotropic hormone. Its production is abnormally high in some forms of hypertension in man and rat. Direct proof that 18-hydroxydeoxycorticosterone is capable of causing hypertension is present. Daily subcutaneous injections of 200 micrograms, a low physiological dose, significantly increase the blood pressure of unilaterally nephrectomized saline-treated rats after 2 weeks. This strengthens the hypothesis that 18-hydroxydeoxycorticosterone contributes to the etiology of hypertension, possibly by a mechanism involving stressinduced release of adrenocorticotropic hormone.     

Inactivation of TNF signaling by rationally designed dominant-negative TNF variants

Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.     

PEST domain-enriched tyrosine phosphatase (PEP) regulation of effector/memory T cells

Protein tyrosine kinases and phosphatases cooperate to regulate normal immune cell function. We examined the role of PEST domain-enriched tyrosine phosphatase (PEP) in regulating T cell antigen-receptor function during thymocyte development and peripheral T cell differentiation. Although normal na?ve T cell functions were retained in pep-deficient mice, effector/memory T cells demonstrated enhanced activation of Lck. In turn, this resulted in increased expansion and function of the effector/memory T cell pool, which was also associated with spontaneous development of germinal centers and elevated serum antibody levels. These results revealed a central role for PEP in negatively regulating specific aspects of T cell development and function.     

A persistent oxygen anomaly reveals the fate of spilled methane in the deep Gulf of Mexico

Methane was the most abundant hydrocarbon released during the 2010 Deepwater Horizon oil spill in the Gulf of Mexico. Beyond relevancy to this anthropogenic event, this methane release simulates a rapid and relatively short-term natural release from hydrates into deep water. Based on methane and oxygen distributions measured at 207 stations throughout the affected region, we find that within ~120 days from the onset of release ~3.0 × 10(10) to 3.9 × 10(10) moles of oxygen were respired, primarily by methanotrophs, and left behind a residual microbial community containing methanotrophic bacteria. We suggest that a vigorous deepwater bacterial bloom respired nearly all the released methane within this time, and that by analogy, large-scale releases of methane from hydrate in the deep ocean are likely to be met by a similarly rapid methanotrophic response.     

DUBA: a deubiquitinase that regulates type I interferon production

Production of type I interferon (IFN-I) is a critical host defense triggered by pattern-recognition receptors (PRRs) of the innate immune system. Deubiquitinating enzyme A (DUBA), an ovarian tumor domain-containing deubiquitinating enzyme, was discovered in a small interfering RNA-based screen as a regulator of IFN-I production. Reduction of DUBA augmented the PRR-induced IFN-I response, whereas ectopic expression of DUBA had the converse effect. DUBA bound tumor necrosis factor receptor-associated factor 3 (TRAF3), an adaptor protein essential for the IFN-I response. TRAF3 is an E3 ubiquitin ligase that preferentially assembled lysine-63-linked polyubiquitin chains. DUBA selectively cleaved the lysine-63-linked polyubiquitin chains on TRAF3, resulting in its dissociation from the downstream signaling complex containing TANK-binding kinase 1. A discrete ubiquitin interaction motif within DUBA was required for efficient deubiquitination of TRAF3 and optimal suppression of IFN-I. Our data identify DUBA as a negative regulator of innate immune responses.     

Magnetic resonance studies of lunar samples

Electron spin resonance searches at 9.5 gigahertz on several fines samples and portions of several rocks have yielded signals whose lineshapes and temperature dependences show that the samples are principally ferromagnetic in nature. Proton magnetic resonance searches at 60 megahertz of these samples have not revealed any signals ascribable to water or any other types of hydrogen in concentrations greater than 0.0001 percent by weight contained in narrow lines (5 oersteds wide or less) and 0.01 percent by weight in wide lines (as wide as 100 oersteds).     

包头市全巴图工业污染区盐渍土特征研究

包头市西南全巴图工业污水排放地区,在水文地质、气候等因素综合作用下,形成以草甸盐土为主的盐渍土,土壤中含盐量0.32～19.02％,是中度-强度盐渍化土或盐土,盐害较重,在进行改良后才能利用。盐土盐分以表层最高,土层中下部浓度变低,尤其改良地淡化过程明显(表3)。在本区盐渍土地上,采取合理的改良措施后,可以逐步地进行防污林带营造等保护生态环境的工程。     

Emergence of anoxia in the California current large marine ecosystem

Eastern boundary current systems are among the world's most productive large marine ecosystems. Because upwelling currents transport nutrient-rich but oxygen-depleted water onto shallow seas, large expanses of productive continental shelves can be vulnerable to the risk of extreme low-oxygen events. Here, we report the novel rise of water-column shelf anoxia in the northern California Current system, a large marine ecosystem with no previous record of such extreme oxygen deficits. The expansion of anoxia highlights the potential for rapid and discontinuous ecosystem change in productive coastal systems that sustain a major portion of the world's fisheries.