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).     

磺酰脲除草剂对不同作物的敏感度测定

经室内药剂对种子胚根长度抑制测定，结果表明：玉主胚根是甲磺隆、绿磺隆、苯磺隆的敏感试材。１４个小麦品种对甲磺隆、烟嘧磺隆的敏感程度不同，经方差分析差异显著。烟农１５对甲磺隆最敏感，其ＩＣ５０值为０．１１７１ｍｇ／ｋｇ；河农１号对甲磺隆最不敏感，其ＩＣ５０值为５．３１４０ｍｇ／ｋｇ。河农３２６对烟嘧磺隆最敏感，其ＩＣ５０值为０．０４５３ｍｇ／ｋｇ；河北２００对烟嘧磺隆最不敏感，其ＩＣ５０值为６．９２     

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.     

不同氮素水平下生菜累积硝酸盐能力的品种差异分析

利用盆栽试验研究了生菜3个不同品种(苦苣、大速生、油麦)在不同氮素供应水平(0、0.2、0.4、0.6gN/kg土)下硝酸盐累积能力的差异。研究结果表明:同一氮肥水平下不同品种生菜硝酸盐含量和硝酸还原酶活性均存在显著性差异;在不同氮肥水平下,生菜各个品种硝酸盐含量具有显著差异性,且随氮肥水平的升高,其硝酸盐含量、硝酸还原酶活性呈递增趋势。因此,实际生产中选择降低硝酸盐措施时应将降低氮肥施用量及筛选低硝酸盐含量品种同时加以考虑。     

Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor

Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.