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81.
Metastasis is a defining feature of malignant tumors and is the most common cause of cancer-related death, yet the genetics of metastasis are poorly understood. We used exome capture coupled with massively parallel sequencing to search for metastasis-related mutations in highly metastatic uveal melanomas of the eye. Inactivating somatic mutations were identified in the gene encoding BRCA1-associated protein 1 (BAP1) on chromosome 3p21.1 in 26 of 31 (84%) metastasizing tumors, including 15 mutations causing premature protein termination and 5 affecting its ubiquitin carboxyl-terminal hydrolase domain. One tumor harbored a frameshift mutation that was germline in origin, thus representing a susceptibility allele. These findings implicate loss of BAP1 in uveal melanoma metastasis and suggest that the BAP1 pathway may be a valuable therapeutic target.  相似文献   
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In this study three different approaches were employed to identify key odorants in Sauvignon blanc wines. First, the concentrations of the odorants were compared to their respective aroma detection thresholds. The resulting odor activity values (OAV) were transformed into a normalized and weighted measure that allows the aroma profiles of different wines to be compared and the contribution of a single aroma in a complex mixture to be evaluated. Based on their OAV, 3-mercaptohexanol and 3-mercaptohexyl acetate were the two most important aroma compounds in many Marlborough Sauvignon blanc wines. Due to limitations with the OAV approach, the study was extended to include aroma extract dilution analysis (AEDA), which revealed that β-damascenone, together with the varietal thiols, esters, and higher alcohols, are key odorants in Sauvignon blanc wines. The final approach undertaken was aroma reconstitution and omission tests using a deodorized wine base and the creation of a model Marlborough Sauvignon blanc. Single compounds and groups of compounds were omitted from the model to study their impact on the sensory properties of the model wine. Reconstitution and omission confirmed that varietal thiols, esters, terpenes, and β-damascenone are all important contributors to Sauvignon blanc aroma. The methoxypyrazines showed an important but relatively low impact in all three of the approaches undertaken in this study.  相似文献   
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Water, Air, &; Soil Pollution - Effective and reliable treatment is needed to treat selenium (Se) in petroleum refinery effluents to meet water discharge limits established under the Clean Water...  相似文献   
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Papuamide A is representative of a class of marine derived cyclic depsipeptides, reported to have cytoprotective activity against HIV-1 in vitro. We show here that papuamide A acts as an entry inhibitor, preventing human immunodeficiency virus infection of host cells and that this inhibition is not specific to R5 or X4 tropic virus. This inhibition of viral entry was determined to not be due to papuamide A binding to CD4 or HIV gp120, the two proteins involved in the cell-virus recognition and binding. Furthermore, papuamide A was able to inhibit HIV pseudotype viruses expressing envelope glycoproteins from vesicular stomatitis virus or amphotropic murine leukemia virus indicating the mechanism of viral entry inhibition is not HIV-1 envelope glycoprotein specific. Time delayed addition studies with the pseudotyped viruses show that papuamide A inhibits viral infection only at the initial stage of the viral life cycle. Additionally, pretreatment studies revealed that the virus, and not the cell, is the target of papuamide A’s action. Together, these results suggest a direct virucidal mechanism of HIV-1 inhibition by papuamide A. We also demonstrate here that the other papuamides (B-D) are able to inhibit viral entry indicating that the free amino moiety of 2,3-diaminobutanoic acid residue is not required for the virucidal activity.  相似文献   
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Soil adjacent to new brick veneer work is likely to have a higher pH owing to the mixture of cement with the soil. In the Gainesville, FL, area, soil samples taken from such locations had a range of pH values from 9.0 to 10.1; similar soils used in bioassays had a pH of 5.6 before the addition of cement. Addition of 15 mg of Portland cement to 33 g of soil increased the pH to 6, and addition of 291 mg of Portland cement increased the pH to 9. The pH of soil amended with cement was stable for the first 5 months. After 10 months, soil pH values decreased from alkaline to near neutral in all cases. Eastern subterranean termite workers, Reticulitermes flavipes (Kollar), were exposed to the treated soil at pH 6-9 for 24 h, and percentage mortality was recorded at 5 days, 5 months and 10 months. Termite mortality significantly decreased at higher soil pHs for bifenthrin, chlorpyrifos, fipronil and imidacloprid treatments at 5 months and similarly for bifenthrin, permethrin, chlorpyrifos, fipronil and imidacloprid treatments at 10 months. There was an inverse linear relationship between soil pH and mortality. Increased soil pH diminished residual activity of termiticide in the following order: imidacloprid > fipronil > chlorpyrifos = bifenthrin > permethrin > cypermethrin.  相似文献   
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The objective of this cross-sectional study was to evaluate the presence of infectious disease in newly arrived cattle on dairy farms in Ontario. Cattle that were more than 2 years old and arrived at dairy farms within the previous year were tested. A total 321 cattle from 56 dairy farms were sampled and had blood submitted to a diagnostic laboratory. Of all sampled cattle, 0.0%, 39.6%, 2.2%, and 1.3% tested positive for Anaplasma, bovine leukemia virus, Mycobacterium avium subsp. paratuberculosis, and Salmonella Dublin, respectively. Based on these results, it is imperative that dairy producers are vigilant to ensure they do not purchase animals with these important and untreatable infectious diseases.  相似文献   
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