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. PUBLICATION ABSTRACT
Regulation of gene expression is an important way cells adapt to changes in their surroundings. Glucose repression of gene expression in the bakers yeast, Saccharomyces cerevisiae, has proven to be a ...useful model of how the environment can influence gene expression. Glucose represses the transcription of many genes not required for glucose metabolism, including genes required for the utilization of galactose, sucrose, and other carbon sources. The presence of glucose is sensed and a signal transmitted to a DNA-binding transcriptional repressor, Mig1. The goal of the work reported in this dissertation was to understand how Mig1 is regulated by this signal. The function of Mig1 is controlled by regulation of its subcellular localization: in the presence of glucose it is in the nucleus; in the absence of glucose it is in the cytoplasm. Transport into and out of the nucleus in response to glucose is rapid. Nuclear export of Mig1 requires its phosphorylation by the Snf1 protein kinase, which stimulates its interaction with a nuclear export receptor, Msn5. These observations suggest the following model for glucose regulation of Mig1 dependent repression: In the presence of glucose Snf1 is inactive, and Mig1 remains unphosphorylated. The result is that Mig1 is transported into the nucleus where it binds to its target genes and represses transcription. Upon glucose removal Snf1 is activated and Mig1 becomes phosphorylated at multiple sites. This promotes an interaction with Msn5, which transports Mig1 to the cytoplasm, relieving transcriptional repression.
This study investigated the recycling of solid waste residues from rock asphalt extraction via 5-h calcination at 900 °C and indirect carbon mineralization. The calcined powder was first dissolved at ...60 °C in 2 M CH3COOH, carbonized in NH4HCO3, and agitated at 1200 rpm in 2 M NaOH for 30 minutes at 30–60 °C and pH 12. The precipitated calcium carbonate (PCC) results are calcite (24.4–56.3 wt%) and vaterite (75.6–3.7 wt%), as confirmed by XRD analysis, carbonate FTIR spectra, and SEM images of prismatic calcite and spherical vaterite. This high-value PCC product has potential industrial applications, such as paper and plastics.
