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Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis; however, treatment options remain limited. Here we report the construction of 264 signature-tagged gene-deletion strains for 129 putative kinases, and examine their phenotypic traits under 30 distinct in vitro growth conditions and in two different hosts (insect larvae and mice). Clustering analysis of in vitro phenotypic traits indicates that several of these kinases have roles in known signalling pathways, and identifies hitherto uncharacterized signalling cascades. Virulence assays in the insect and mouse models provide evidence of pathogenicity-related roles for 63 kinases involved in the following biological categories: growth and cell cycle, nutrient metabolism, stress response and adaptation, cell signalling, cell polarity and morphology, vacuole trafficking, transfer RNA (tRNA) modification and other functions. Our study provides insights into the pathobiological signalling circuitry of C. neoformans and identifies potential anticryptococcal or antifungal drug targets.

Chemically bonded graphene/carbon nanotube composites as flexible supercapacitor electrode materials are synthesized by amide bonding. Carbon nanotubes attached along the edges and onto the surface of graphene act as spacers to increase the electrolyte-accessible surface area. Our lamellar structure electrodes demonstrate the largest volumetric capacitance (165 F cm(-3) ) ever shown by carbon-based electrodes.

Wnt/␤-catenin signaling contributes to diverse cellular functions, such as Drosophila wing development and colon carcinogenesis. Recently, stabilizing mutations of ␤-catenin, a hallmark of Wnt signaling, were documented in significant numbers of primary hepatocellular carcinomas (HCC). However, whether the ␤-catenin mutation leads to the activation of Wnt/␤-catenin signaling in hepatoma cells has not been established. We found that Wnt/ ␤-catenin signaling could be activated by ectopic expression of Wnt-1 in some hepatoma cells, such as Hep3B and PLC/PRF/5 cells, but not in others, such as Huh7 and Chang cells. Importantly, we noted that the former were derived from hepatitis B virus (HBV)-infected livers, whereas the latter were derived from HBV-negative livers. It was then speculated that HBx, a viral regulatory protein of HBV, is involved in activating Wnt/␤-catenin signaling in hepatoma cells. In agreement with this notion, ectopic expression of HBx along with Wnt-1 activated Wnt/␤-catenin signaling in Huh7 cells by stabilizing cytoplasmic ␤-catenin. Further, we showed that such stabilization of ␤-catenin by HBx was achieved by suppressing glycogen synthase kinase 3 activity via the activation of Src kinase. In conclusion, the data suggest that Wnt-1 is necessary but insufficient to activate Wnt/␤-catenin signaling in hepatoma cells and the enhanced stabilization of ␤-catenin by HBx, in addition to Wnt-1, is essential for the activation of Wnt/␤-catenin signaling in hepatoma cells. (HEPATOLOGY 2004;