Interpretation of recent Southern Hemisphere climate change

Climate variability in the high-latitude Southern Hemisphere (SH) is dominated by the SH annular mode, a large-scale pattern of variability characterized by fluctuations in the strength of the circumpolar vortex. We present evidence that recent trends in the SH tropospheric circulation can be interpreted as a bias toward the high-index polarity of this pattern, with stronger westerly flow encircling the polar cap. It is argued that the largest and most significant tropospheric trends can be traced to recent trends in the lower stratospheric polar vortex, which are due largely to photochemical ozone losses. During the summer-fall season, the trend toward stronger circumpolar flow has contributed substantially to the observed warming over the Antarctic Peninsula and Patagonia and to the cooling over eastern Antarctica and the Antarctic plateau.     

Hepatic glucose sensing via the CREB coactivator CRTC2

Chronic hyperglycemia contributes to the development of diabetes-associated complications. Increases in the concentration of circulating glucose activate the hexosamine biosynthetic pathway (HBP) and promote the O-glycosylation of proteins by O-glycosyl transferase (OGT). We show that OGT triggered hepatic gluconeogenesis through the O-glycosylation of the transducer of regulated cyclic adenosine monophosphate response element-binding protein (CREB) 2 (TORC2 or CRTC2). CRTC2 was O-glycosylated at sites that normally sequester CRTC2 in the cytoplasm through a phosphorylation-dependent mechanism. Decreasing amounts of O-glycosylated CRTC2 by expression of the deglycosylating enzyme O-GlcNAcase blocked effects of glucose on gluconeogenesis, demonstrating the importance of the HBP in the development of glucose intolerance.     

Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi

Hsp90 is a molecular chaperone for many signal transducers and may influence evolution by releasing previously silent genetic variation in response to environmental change. In fungi separated by approximately 800 million years of evolution, Hsp90 potentiated the evolution of drug resistance in a different way, by enabling new mutations to have immediate phenotypic consequences. Resistance was abrogated by Hsp90 inhibitors and by febrile temperatures, suggesting new therapeutic strategies and a clinical benefit of fever. During selection in a human host, drug resistance that was initially Hsp90-dependent evolved toward independence. Thus, Hsp90 can act in diverse ways to couple environmental contingency to the emergence and fixation of new traits.     

Yeast genes that enhance the toxicity of a mutant huntingtin fragment or alpha-synuclein

Genome-wide screens were performed in yeast to identify genes that enhance the toxicity of a mutant huntingtin fragment or of alpha-synuclein. Of 4850 haploid mutants containing deletions of nonessential genes, 52 were identified that were sensitive to a mutant huntingtin fragment, 86 that were sensitive to alpha-synuclein, and only one mutant that was sensitive to both. Genes that enhanced toxicity of the mutant huntingtin fragment clustered in the functionally related cellular processes of response to stress, protein folding, and ubiquitin-dependent protein catabolism, whereas genes that modified alpha-synuclein toxicity clustered in the processes of lipid metabolism and vesicle-mediated transport. Genes with human orthologs were overrepresented in our screens, suggesting that we may have discovered conserved and nonoverlapping sets of cell-autonomous genes and pathways that are relevant to Huntington's disease and Parkinson's disease.