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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.  相似文献   
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A prion disease of cervids: chronic wasting disease   总被引:1,自引:0,他引:1  
Chronic wasting disease (CWD) is a prion disease of deer, elk, and moose, initially recognized in Colorado mule deer. The discovery of CWD beyond the borders of Colorado and Wyoming, in Canada and as far east as New York, has led to its emergence as a prion disease of international importance. Epidemiological studies indicate that CWD is horizontally transmitted among free-ranging animals, potentially indirectly by prion-containing secreta or excreta contaminating the environment. Experimental CWD transmission attempts to other wild and domestic mammals and to transgenic mice expressing the prion protein of cattle, sheep, and humans have shed light on CWD species barriers. Transgenic mice expressing the cervid prion protein have proven useful for assessing the genetic influences of Prnp polymorphisms on CWD susceptibility. Accumulating evidence of CWD pathogenesis indicates that the misfolded prion protein or prion infectivity seems to be widely disseminated in many nonneural organs and in blood. This review highlights contemporary research findings in this prion disease of free-ranging wildlife.  相似文献   
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When tropical shrimps are kept in recirculating aquaculture systems (RAS), one of the limiting factors is the maintenance of a sufficient water quality, and therefore, often disinfectants like peracetic acid (PAA) are added to the water either as prophylactic or treatment measure. In this study, PAA in concentrations of 0.1 mg/L, 1 mg/L and 10 mg/L was applied continuously for 56 days to small-scale seawater RAS stocked with Litopenaeus vannamei. Treatment with 0.1 mg/L did not result in a reduction in the total bacterial amount and therefore was not effective. A concentration of 10 mg/L led to significant changes in the chemical water parameters already after 2 days and was therefore not recommendable. A concentration of 1 mg/L led to increased levels of ammonia and nitrite within 2 days and to a significant increase in the bacterial amount in the water, most probably due to an enhanced growth of heterotrophic bacteria. The microflora showed significant fluctuations, and there were indications that the welfare of the shrimps was affected. Using 1 mg PAA/L for prophylactic use is therefore also not recommendable but might be an alternative option for short-term treatment in cases of disease outbreaks.  相似文献   
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International Aquatic Research - This work makes a comparative evaluation of the biochemical profile of three sea commercial cucumber species (Holothuria mammata, H. polii and H. tubulosa) caught...  相似文献   
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Agricultural industrialization and the subsequent reliance on pesticides has resulted in numerous unintended consequences, such as impacts upon the environment and by extension human health. Eco‐efficiency is a strategy for sustainably increasing production, while simultaneously decreasing these externalities on ecological systems. Eco‐efficiency is defined as the ratio of production to environmental impacts. It has been widely adopted to improve chemical production, but we investigate the challenges of applying eco‐efficiency to pesticide use. Eco‐efficiency strategies include technological innovation, investment in research and development, improvement of business processes, and accounting for market forces. These components are often part of integrated pest management (IPM) systems that include alternatives to pesticides, but its implementation is often thwarted by commercial realities and technical challenges. We propose the creation and adoption of an eco‐efficiency index for pesticide use so that the broad benefits of eco‐efficient strategies such as IPM can be more readily quantified. We propose an index based upon the ratio of crop yield to a risk quotient (RQ) calculated from pesticide toxicity. Eco‐efficiency is an operational basis for optimizing pest management for sustainability. It naturally favors adoption of IPM and should be considered by regulators, researchers, and practitioners involved in pest management. © 2019 Society of Chemical Industry  相似文献   
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