Publications by authors named "Mitchell Thomas"

Lipopolysaccharide (LPS) has long been known to enhance innate and adaptive immune responses; however, its extreme toxicity precludes its use in clinical settings. The combined toxicity and adjuvanticity of LPS have contributed to the view that immunological adjuvants need to be highly inflammatory to be maximally effective. Here, we compared the effects of LPS with its less-toxic derivatives, monophosphoryl lipid A (MPL) and a chemical mimetic, RC529, on CD4+ T cell clonal expansion, long-term survival, and T helper cell type 1 (Th1) differentiation.

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Cryptococcus gattii is a group of exogenous, neurotropic yeasts that possess the capsular serotype B or C. Isolates of serotype C are extremely rare and, until recently, were known to infect only immunocompetent individuals. We genotyped 176 isolates of Cryptococcus from patients in sub-Saharan Africa who had AIDS; 22 (13.

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A report on the 23rd Fungal Genetics Conference, Pacific Grove, USA, 15-20 March 2005.

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Cryptococcus neoformans is a fungal pathogen that has evolved over the past 40 million years into three distinct varieties or sibling species (gattii, grubii, and neoformans). Each variety manifests differences in epidemiology and disease, and var. grubii strains are responsible for the vast majority of human disease.

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The study of quantitative traits provides a window on the interactions between multiple unlinked genetic loci. The interaction between hosts and pathogenic microbes, such as fungi, involves aspects of quantitative genetics for both partners in this dynamic equilibrium. One important pathogenic fungus is Cryptococcus neoformans, a basidiomycete yeast that can infect the human brain and whose mating system has two mating type alleles, a and alpha.

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Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating the molecular basis of fungal disease of plants. Here, we report the draft sequence of the M. grisea genome.

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Background: Recent advances in sequencing techniques leading to cost reduction have resulted in the generation of a growing number of sequenced eukaryotic genomes. Computational tools greatly assist in defining open reading frames and assigning tentative annotations. However, gene functions cannot be asserted without biological support through, among other things, mutational analysis.

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Large chromosomal events such as translocations and segmental duplications enable rapid adaptation to new environments. Here we marshal genomic, genetic, meiotic mapping, and physical evidence to demonstrate that a chromosomal translocation and segmental duplication occurred during construction of a congenic strain pair in the fungal human pathogen Cryptococcus neoformans. Two chromosomes underwent telomere-telomere fusion, generating a dicentric chromosome that broke to produce a chromosomal translocation, forming two novel chromosomes sharing a large segmental duplication.

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Cryptococcus neoformans is a major, global cause of meningoencephalitis in immunocompromised patients. Despite advances in the molecular epidemiology of C. neoformans, its population structure and mode of reproduction are not well understood.

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Cryptococcus neoformans is a basidiomycetous yeast ubiquitous in the environment, a model for fungal pathogenesis, and an opportunistic human pathogen of global importance. We have sequenced its approximately 20-megabase genome, which contains approximately 6500 intron-rich gene structures and encodes a transcriptome abundant in alternatively spliced and antisense messages. The genome is rich in transposons, many of which cluster at candidate centromeric regions.

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We describe a method to characterize the effects that immunological adjuvants have on in vivo lymphocyte proliferation at the level of daughter cell accumulation. We used standard 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeling techniques to follow T cells through multiple rounds of division in experimentally treated mice and measured both the fold-increase in cell number and average number of divisions undergone by each cell. These data were then incorporated into a calculation to determine the average number of daughter cells that accumulated from each round of mitosis, termed the daughter cell accumulation index.

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Hemiascomycetes are species of yeasts within the order Saccharomycetales. The order encompasses disparate genera with a variety of life styles, including opportunistic human pathogens (e.g.

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Trichoderma reesei is an important industrial fungus known for its ability to efficiently secrete large quantities of protein as well as its wide variety of biomass degrading enzymes. Past research on this fungus has primarily focused on extending its protein production capabilities, leaving the structure of its 33 Mb genome essentially a mystery. To begin to address these deficiencies and further our knowledge of T.

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A unique form of needle-free drug and vaccine delivery is under investigation. The principle of the concept is to accelerate pharmaceuticals in particle form to a momentum sufficient to penetrate the outer layer of the human skin for a pharmacological effect. The relationship between the key particle impact parameters and particle penetration depth in excised human skin has been experimentally determined.

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To construct a genetic linkage map of the heterothallic yeast, Cryptococcus neoformans (Filobasidiella neoformans), we crossed two mating-compatible strains and analyzed 94 progeny for the segregation of 301 polymorphic markers, consisting of 228 restriction site polymorphisms, 63 microsatellites, two indels, and eight mating-type (MAT)-associated markers. All but six markers showed no significant (P < 0.05) segregation distortion.

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The effectiveness of ballistic particle delivery to the skin is often dependent upon breaching the stratum corneum (SC) and targeting cells within defined layers of the viable epidermis. This paper experimentally determines the influence of relative humidity (RH) and temperature on the ballistic delivery of particles to the skin. Gold particles of radius 0.

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The number of immunocompromised patients and subsequent invasive fungal infections continues to rise. However, the education of future medical mycologists to engage this growing problem is diminishing. While there are an increasing number of publications and grants awarded in mycology, the time and detail devoted to teaching medical mycology in United States medical schools are inadequate.

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The most common cause of fungal meningitis in humans, Cryptococcus neoformans serotype A, is a basidiomycetous yeast with a bipolar mating system. However, the vast majority (>99.9%) of C.

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Reactive oxygen species (ROS) mediate apoptosis in many different cell types. We have previously shown that the antioxidant Mn(III) tetrakis(5,10,15,20-benzoic acid)porphyrin (MnTBAP) decreased intracellular ROS and prevented the apoptosis of activated T cells in vitro. To determine the mechanism(s) by which MnTBAP afforded such protection, we used Affymetrix (Santa Clara, CA) gene arrays to compare gene expression in T cells activated with staphylococcal enterotoxin B in vivo then cultured with or without MnTBAP.

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Intracellular accumulation of PHFtau in Alzheimer's disease (AD) disrupts the neuronal cytoskeleton and other neuronal machinery and contributes to axonal and dendritic degeneration, and neuronal death. Furthermore, amyloid-beta (Abeta) has been reported to be toxic to neurons and neurites. While loss of presynaptic elements is an established feature of AD, the nature and extent of dendritic degeneration has been infrequently studied.

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Background: Cannabinoid use could potentially alter HIV RNA levels by two mechanisms: immune modulation or cannabinoid-protease inhibitor interactions (because both share cytochrome P-450 metabolic pathways).

Objective: To determine the short-term effects of smoked marijuana on the viral load in HIV-infected patients.

Design: Randomized, placebo-controlled, 21-day intervention trial.

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SUMMARY The rice blast fungus Magnaporthe grisea causes one of the most destructive diseases of rice. To initiate the infection of host tissues, conidia elaborate germ tubes that differentiate specialized infection structures called appressoria. Microarrays composed of 3500 cDNAs of M.

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Cryptococcus neoformans is a major pathogen of humans throughout the world. Using commercial monoclonal antibodies to capsular epitopes, strains of C. neoformans manifest five serotypes: A, B, C, D and AD.

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The filamentous fungus Trichoderma reesei produces and secretes profuse quantities of enzymes that act synergistically to degrade cellulase and related biomass components. We partially sequenced over 5100 random T. reesei cDNA clones.

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