2 resultados para Candida albicans morphology and interaction with Pseudomonas aeruginosa

em DigitalCommons@University of Nebraska - Lincoln


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The role of social cognition in severe mental illness (SMI) has gained much attention, especially over the last decade. The impact of deficits in socio-cognitive functioning has been found to have detrimental effects on key areas of day-to-day functioning in individuals with SMI, such as gaining and maintaining employment and overall experienced quality of life. Treatment of individuals with SMI is challenging, as the presentation of individual signs and symptoms is rather heterogeneous. There are several treatment approaches addressing deficits ranging from broader social and interpersonal functioning to neurocognitive and more intrapersonal functioning. As research in the domain of social cognition continues to identify specific deficits and its functional detriments, treatment options need to evolve to better target identified functional deficits. Social Cognition and Interaction Training (SCIT) was recently developed to address specific socio-cognitive deficits in an inpatient population of individuals with schizophrenia-spectrum disorders. This study applied SCIT in an outpatient SMI population as many deficits remain after individuals’ symptoms are less severe and overall functioning is more stable than during the acute inpatient phase of their rehabilitation. Specifically, this study has two objectives. First, to demonstrate that deficits in social cognition persist after the acute phase of illness has abated. Second, to demonstrate that these deficits can be ameliorated via targeted treatment such as SCIT. Data was gathered in local outpatient treatment settings serving a heterogeneous SMI population. Adviser: William D. Spaulding

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Candida albicans is a common opportunistic, dimorphic human fungal pathogen. One of its virulence factors is the morphological switch between yeasts and hyphal or pseudohyphal forms, which can invade tissues and cause damage. Our studies focus on factors regulating pseudohyphae and epigenetic modifications of C. albicans. Regulating factors of pseudohyphae are aromatic alcohols and high phosphate. At low concentrations, exogenous aromatic alcohols induced pseudohyphae, as did high phosphate. For addressing the pathways involved in inducing pseudohyphae by aromatic alcohols or high phosphate, we used mutants defective in cAMP dependent PKA pathway (efg1/efg1), MAP kinase pathway (cph1/cph1), or both (cph1/cph1/efg1/efg1). These mutants failed to produce either hyphae or pseudohyphae in the presence of aromatic alcohols; but high phosphate still stimulated pseudohyphae. Gcn4, a transcription activator of more than 500 amino acid related genes, is turned-on in response to amino acid starvation. The accumulation of aromatic alcohols sends nitrogen starvation signals, which inhibit eIF2B, which in turn derepresses Gcn4p. High phosphate also induces pseudohyphae by derepressing Gcn4p, although the pathways involved are still unknown. In sum, aromatic alcohols and high phosphate induce pseudohyphae by derepressing Gcn4. In this study we found a novel posttranslational histone modification in C. albicans, which is biotinylation. Western blot and Mass spectrometry techniques were used to find that Histones H2B and H4 were biotinylated at every condition tested such as yeast vs. hyphae, aerobic growth vs. anaerobic growth, rich medium vs. defined medium. In C. albicans lysines K8, K11 in histone H4 and lysines K17, K18, K31 in histone H2B are biotin attachment sites as found using mass spectrometry. Biotin was also found to enhance the germ tube formation of C. albicans. Germ tube formation assays with biotin-starved cells as inoculum showed low percent of germ tubes (1-5%). Addition of biotin to the media showed 100% germ tubes. Biotinylation of histones were not detected from biotin-starved cells. Appendix-A details work related to Farnesol quantification assays in several strains of C.albicans and Ceratocystis ulmi, and growth studies of class E VPS strains of Saccharomyces Cerevisiae. Adviser: Kenneth W. Nickerson