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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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The tubular structure of the endoplasmic reticulum (ER) appears to be generated by integral membrane proteins, the reticulons and a protein family consisting of DP1 in mammals and Yop1p in yeast. Here, individual members of these families were found to be sufficient to generate membrane tubules. When we purified yeast Yop1p and incorporated it into proteoliposomes, narrow tubules (approximately 15 to 17 nanometers in diameter) were generated. Tubule formation occurred with different lipids; required essentially only the central portion of the protein, including its two long hydrophobic segments; and was prevented by mutations that affected tubule formation in vivo. Tubules were also formed by reconstituted purified yeast Rtn1p. Tubules made in vitro were narrower than normal ER tubules, due to a higher concentration of tubule-inducing proteins. The shape and oligomerization of the "morphogenic" proteins could explain the formation of the tubular ER.  相似文献   
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Marine life has proved to be an invaluable source of new compounds with significant bioactivities, such as xanthones. This review summarizes the advances made in the study of marine-derived xanthones from 2010 to 2021, from isolation towards synthesis, highlighting their biological activities. Most of these compounds were isolated from marine-derived fungi, found in marine sediments, and associated with other aquatic organisms (sponge and jellyfish). Once isolated, xanthones have been assessed for different bioactivities, such as antibacterial, antifungal, and cytotoxic properties. In the latter case, promising results have been demonstrated. Considering the significant bioactivities showed by xanthones, efforts have been made to synthesize these compounds, like yicathins B and C and the secalonic acid D, through total synthesis.  相似文献   
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Different stunning methods (carbon dioxide [CO2] and hypothermia) used in industrial fish processing were compared with asphyxia in air, which is used in traditional fishing, to evaluate the effects of these methods on the stress responses and the meat quality of the Amazon hybrid surubim, Pseudoplatystoma fasciatum female × Leiarius marmoratus male. After the application, blood and behavioral indicators were evaluated. Following death by gill cutting, the fish were gutted, and analyses of muscle pH, rigor mortis, the exudation of the meat, and coloration were performed. Significantly higher levels of cortisol and glucose were exhibited by the fish subjected to asphyxia than by the fish stunned by either CO2 or hypothermia. The fish subjected to asphyxia displayed decreasing muscle pH during the first 2 h after death and showed higher rates of rigor mortis after 3 h than the fish that were stunned by the other two methods. The asphyxia is a practice that exposes fish to suffering by causing an increase in stress responses, which affects meat quality. The immersion of fish in water and ice (hypothermia) for 5 min was more effective stunning method than the use of CO2, resulting in higher loss of sensibility and greater welfare.  相似文献   
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