Plos One
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Heat shock protein 90 (HSP90) is a molecular chaperone which stabilizes client proteins with important roles in tumor growth. 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90 ATPase activity, occupies the ATP binding site of HSP90 causing a conformational change which destabilizes client proteins and directs them towards proteosomal degradation. Malignant melanomas have active RAF-MEK-ERK signaling which can occur either through an activating mutation in BRAF (BRAFV600E) or through activation of signal transduction upstream of BRAF. Prior work showed that 17-AAG inhibits cell growth in BRAFV600E and BRAF wildtype (BRAFWT) melanomas, although there were conflicting reports about the dependence of BRAFV600E and BRAFWT upon HSP90 activity for stability. ⋯ Surprisingly, 17-AAG also stimulated melanin production in SK-Mel-30 cells and enhanced TYRP1 and DCT expression without stimulating TYR production in all three BRAFWT cell lines studied as well as in B16F10 mouse melanoma cells. In vivo, the combination of 17-AAG and cellular immunotherapy directed against Tyrp1 enhanced the inhibition of tumor growth compared to either therapy alone. Our studies support a role for 17-AAG and HSP90 inhibition in enhancing cellular immunotherapy for melanoma.
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The aim of the present study was to evaluate the ability of the ratios of central venous to arterial carbon dioxide content and tension to arteriovenous oxygen content to predict an increase in oxygen consumption (VO2) upon fluid challenge (FC). ⋯ Our results showed that the ratios of central venous to arterial carbon dioxide content and tension to arteriovenous oxygen content were not predictive of VO2 changes following fluid challenge in postoperative cardiac surgery patients.
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The relationship between decreased bone mineral density (BMD) and chronic kidney disease (CKD) is controversial. The associations among metabolic syndrome (MetS), serum uric acid and CKD are also unclear. We aimed to investigate the relationship between decreased BMD, MetS, serum uric acid and CKD in a general population. ⋯ Decreased BMD, uric acid and MetS were significantly associated with CKD.. Further large and prospective cohort studies are necessary to investigate whether management of osteoporosis, hyperuricemia, or MetS might prevent the progression of CKD.
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The brown marmorated stink bug, Halyomorpha halys, is an agricultural and urban pest that has become widely established as an invasive species of major concern in the USA and across Europe. This species forms large aggregations when entering diapause, and it is often these aggregations that are found by officials conducting inspections of internationally shipped freight. Identifying the presence of diapausing aggregations of H. halys using their emissions of volatile organic compounds (VOCs) may be a potential means for detecting and intercepting them during international freight inspections. ⋯ Diapausing groups were significantly more likely to release defensive odors than diapause-disrupted groups. The predominant compounds consistently found from both groups were tridecane, (E)-2-decenal, and 4-oxo-(E)-2-hexenal, with a small abundance of dodecane. Our findings show that diapausing H. halys do release defensive compounds, and suggest that volatile sampling may be feasible to detect H. halys in freight.
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[This corrects the article DOI: 10.1371/journal.pone.0161062.].