The Experts below are selected from a list of 28242 Experts worldwide ranked by ideXlab platform
Meleah A Hickman - One of the best experts on this subject based on the ideXlab platform.
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Ploidy tug of war evolutionary and genetic environments influence the rate of Ploidy drive in a human fungal pathogen
Evolution, 2017Co-Authors: Aleeza C Gerstein, Heekyung Lim, Judith Berman, Meleah A HickmanAbstract:Variation in baseline Ploidy is seen throughout the tree of life, yet the factors that determine why one Ploidy level is maintained over another remain poorly understood. Experimental evolution studies using asexual fungal microbes with manipulated Ploidy levels intriguingly reveals a propensity to return to the historical baseline Ploidy, a phenomenon that we term "Ploidy drive." We evolved haploid, diploid, and polyploid strains of the human fungal pathogen Candida albicans under three different nutrient limitation environments to test whether these conditions, hypothesized to select for low Ploidy levels, could counteract Ploidy drive. Strains generally maintained or acquired smaller genome sizes (measured as total nuclear DNA through flow cytometry) in minimal medium and under phosphorus depletion compared to in a complete medium, while mostly maintained or acquired increased genome sizes under nitrogen depletion. Improvements in fitness often ran counter to changes in genome size; in a number of scenarios lines that maintained their original genome size often increased in fitness more than lines that converged toward diPloidy (the baseline Ploidy of C. albicans). Combined, this work demonstrates a role for both the environment and genotype in determination of the rate of Ploidy drive, and highlights questions that remain about the force(s) that cause genome size variation.
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Ploidy tug of war evolutionary and genetic environments influence the rate of Ploidy drive in a human fungal pathogen
bioRxiv, 2017Co-Authors: Aleeza C Gerstein, Heekyung Lim, Judith Berman, Meleah A HickmanAbstract:Variation in baseline Ploidy is seen throughout the tree of life, yet the factors that determine why one Ploidy level is selected over another remain poorly understood. Experimental evolution studies using asexual fungal microbes with manipulated Ploidy levels intriguingly reveals a propensity to return to the historical baseline Ploidy, a phenomenon that we term "Ploidy drive". We evolved haploid, diploid, and polyploid strains of the human fungal pathogen Candida albicans under three different nutrient limitation environments to test whether these conditions, hypothesized to select for low Ploidy levels, could counteract Ploidy drive. Strains tended to maintain or acquire smaller genome sizes in minimal medium and under phosphorus depletion compared to in a complete medium, yet tended to maintain or acquire increased genome sizes under nitrogen depletion. Surprisingly, improvements in fitness often ran counter to changes in total nuclear genome size; in a number of scenarios lines that maintained their original genome size often increased in fitness more than lines that converged towards diPloidy. Combined, this work demonstrates a role for both the environment and genotype in determination of the rate of Ploidy drive, and highlights questions that remain about the force(s) that cause genome size variation.
Judith Berman - One of the best experts on this subject based on the ideXlab platform.
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Ploidy tug of war evolutionary and genetic environments influence the rate of Ploidy drive in a human fungal pathogen
Evolution, 2017Co-Authors: Aleeza C Gerstein, Heekyung Lim, Judith Berman, Meleah A HickmanAbstract:Variation in baseline Ploidy is seen throughout the tree of life, yet the factors that determine why one Ploidy level is maintained over another remain poorly understood. Experimental evolution studies using asexual fungal microbes with manipulated Ploidy levels intriguingly reveals a propensity to return to the historical baseline Ploidy, a phenomenon that we term "Ploidy drive." We evolved haploid, diploid, and polyploid strains of the human fungal pathogen Candida albicans under three different nutrient limitation environments to test whether these conditions, hypothesized to select for low Ploidy levels, could counteract Ploidy drive. Strains generally maintained or acquired smaller genome sizes (measured as total nuclear DNA through flow cytometry) in minimal medium and under phosphorus depletion compared to in a complete medium, while mostly maintained or acquired increased genome sizes under nitrogen depletion. Improvements in fitness often ran counter to changes in genome size; in a number of scenarios lines that maintained their original genome size often increased in fitness more than lines that converged toward diPloidy (the baseline Ploidy of C. albicans). Combined, this work demonstrates a role for both the environment and genotype in determination of the rate of Ploidy drive, and highlights questions that remain about the force(s) that cause genome size variation.
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Ploidy tug of war evolutionary and genetic environments influence the rate of Ploidy drive in a human fungal pathogen
bioRxiv, 2017Co-Authors: Aleeza C Gerstein, Heekyung Lim, Judith Berman, Meleah A HickmanAbstract:Variation in baseline Ploidy is seen throughout the tree of life, yet the factors that determine why one Ploidy level is selected over another remain poorly understood. Experimental evolution studies using asexual fungal microbes with manipulated Ploidy levels intriguingly reveals a propensity to return to the historical baseline Ploidy, a phenomenon that we term "Ploidy drive". We evolved haploid, diploid, and polyploid strains of the human fungal pathogen Candida albicans under three different nutrient limitation environments to test whether these conditions, hypothesized to select for low Ploidy levels, could counteract Ploidy drive. Strains tended to maintain or acquire smaller genome sizes in minimal medium and under phosphorus depletion compared to in a complete medium, yet tended to maintain or acquire increased genome sizes under nitrogen depletion. Surprisingly, improvements in fitness often ran counter to changes in total nuclear genome size; in a number of scenarios lines that maintained their original genome size often increased in fitness more than lines that converged towards diPloidy. Combined, this work demonstrates a role for both the environment and genotype in determination of the rate of Ploidy drive, and highlights questions that remain about the force(s) that cause genome size variation.
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Rapid Mechanisms for Generating Genome Diversity: Whole Ploidy Shifts, AneuPloidy, and Loss of Heterozygosity
Cold Spring Harbor perspectives in medicine, 2014Co-Authors: Richard J. Bennett, Anja Forche, Judith BermanAbstract:Human fungal pathogens can exist in a variety of Ploidy states, including euploid and aneuploid forms. Ploidy change has a major impact on phenotypic properties, including the regulation of interactions with the human host. In addition, the rapid emergence of drug-resistant isolates is often associated with the formation of specific supernumerary chromosomes. Pathogens such as Candida albicans and Cryptococcus neoformans appear particularly well adapted for propagation in multiple Ploidy states with novel pathways driving Ploidy variation. In both species, heterozygous cells also readily undergo loss of heterozygosity (LOH), leading to additional phenotypic changes such as altered drug resistance. Here, we examine the sexual and parasexual cycles that drive Ploidy variation in human fungal pathogens and discuss Ploidyand LOH events with respect to their far-reaching roles in fungal adaptation and pathogenesis.
M Robinson - One of the best experts on this subject based on the ideXlab platform.
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dysplasia and dna Ploidy to prognosticate clinical outcome in oral potentially malignant disorders
Journal of Oral Pathology & Medicine, 2021Co-Authors: Hans Prakash Sathasivam, Deepa Nayar, Philip Sloan, P J Thomson, Edward Odell, M RobinsonAbstract:Background: Oral potentially malignant disorders are a clinical conundrum as there are no reliable methods to predict their behaviour. We combine conventional oral epithelial dysplasia grading with DNA Ploidy analysis to examine the validity of this approach to risk assessment in a cohort of patients with known clinical outcomes. Methods: Sections from diagnostic biopsies were assessed for oral epithelial dysplasia using the WHO grading system, and DNA Ploidy analysis was performed using established methods. Patients reviewed for a minimum of 5 years who did not develop oral squamous cell carcinoma were classified as “non-transforming” cases. Patients that developed oral squamous cell carcinoma ≥ 6 months after the initial diagnostic biopsy were classified as having “malignant transformation.” Results: Ninety cases were included in the study. Seventy cases yielded informative DNA Ploidy results. Of these 70 cases, 31 progressed to cancer. Oral epithelial dysplasia grading and DNA Ploidy status were both significantly associated with clinical outcome (P < 0.05). Severe dysplasia had a hazard ratio of 3.50 (CI: 1.46, 8.45; P = 0.005) compared to cases with mild dysplasia. AneuPloidy had a hazard ratio of 2.09 (CI: 1.01, 4.32; P = 0.046) compared to cases with a diploid/tetraploid status. Receiver operating characteristic analysis gave an area under the curve of 0.617 for DNA Ploidy status and 0.688 when DNA Ploidy status was combined with dysplasia grading. Conclusion: Our findings suggest that combining dysplasia grading with DNA Ploidy status has clinical utility which could be used to develop novel management algorithms.
Edward Odell - One of the best experts on this subject based on the ideXlab platform.
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dysplasia and dna Ploidy to prognosticate clinical outcome in oral potentially malignant disorders
Journal of Oral Pathology & Medicine, 2021Co-Authors: Hans Prakash Sathasivam, Deepa Nayar, Philip Sloan, P J Thomson, Edward Odell, M RobinsonAbstract:Background: Oral potentially malignant disorders are a clinical conundrum as there are no reliable methods to predict their behaviour. We combine conventional oral epithelial dysplasia grading with DNA Ploidy analysis to examine the validity of this approach to risk assessment in a cohort of patients with known clinical outcomes. Methods: Sections from diagnostic biopsies were assessed for oral epithelial dysplasia using the WHO grading system, and DNA Ploidy analysis was performed using established methods. Patients reviewed for a minimum of 5 years who did not develop oral squamous cell carcinoma were classified as “non-transforming” cases. Patients that developed oral squamous cell carcinoma ≥ 6 months after the initial diagnostic biopsy were classified as having “malignant transformation.” Results: Ninety cases were included in the study. Seventy cases yielded informative DNA Ploidy results. Of these 70 cases, 31 progressed to cancer. Oral epithelial dysplasia grading and DNA Ploidy status were both significantly associated with clinical outcome (P < 0.05). Severe dysplasia had a hazard ratio of 3.50 (CI: 1.46, 8.45; P = 0.005) compared to cases with mild dysplasia. AneuPloidy had a hazard ratio of 2.09 (CI: 1.01, 4.32; P = 0.046) compared to cases with a diploid/tetraploid status. Receiver operating characteristic analysis gave an area under the curve of 0.617 for DNA Ploidy status and 0.688 when DNA Ploidy status was combined with dysplasia grading. Conclusion: Our findings suggest that combining dysplasia grading with DNA Ploidy status has clinical utility which could be used to develop novel management algorithms.
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predictive value of dysplasia grading and dna Ploidy in malignant transformation of oral potentially malignant disorders
Cancer Prevention Research, 2013Co-Authors: Marcelo Sperandio, Amy Louise Brown, Claire Lock, Peter Morgan, Victoria H Coupland, Peter B Madden, Saman Warnakulasuriya, Henrik Moller, Edward OdellAbstract:Dysplasia grading is widely used to assess risk of transformation in oral potentially malignant disorders despite limited data on predictive value. DNA Ploidy analysis has been proposed as an alternative. This study examines the prognostic value for both tests used in a routine diagnostic setting to inform clinical management. A retrospective study of conventional dysplasia grading was conducted on 1,401 patients. DNA Ploidy analysis was conducted on a subset of 273 patients and results correlated with clinical information, pathologic diagnosis, and outcome over 5 to 15 years. Malignant transformation occurred in 32 of 273 patients (12%) and, of these, 20 (63%) of preexisting index lesions were aneuploid. Of 241 patients not developing carcinoma, only 39 (16%) of index lesions were aneuploid. Epithelial dysplasia correlated with DNA Ploidy status (P < 0.001). The overall positive predictive value for malignant transformation by DNA aneuPloidy was 38.5% (sensitivity 65.2% and specificity 75%) and by severe dysplasia grade 39.5% (sensitivity 30% and specificity 98%). DNA diploid and tetraploid status had negative predictive value of 90% to 96%. Combining DNA Ploidy analysis with dysplasia grading gives a higher predictive value than either technique alone. Each of three traditional dysplasia grades predicts a significantly different risk of carcinoma development and time to transformation. DNA Ploidy analysis had equivalent predictive value and also detected additional risk lesions in the absence of dysplasia.
Hans Prakash Sathasivam - One of the best experts on this subject based on the ideXlab platform.
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dysplasia and dna Ploidy to prognosticate clinical outcome in oral potentially malignant disorders
Journal of Oral Pathology & Medicine, 2021Co-Authors: Hans Prakash Sathasivam, Deepa Nayar, Philip Sloan, P J Thomson, Edward Odell, M RobinsonAbstract:Background: Oral potentially malignant disorders are a clinical conundrum as there are no reliable methods to predict their behaviour. We combine conventional oral epithelial dysplasia grading with DNA Ploidy analysis to examine the validity of this approach to risk assessment in a cohort of patients with known clinical outcomes. Methods: Sections from diagnostic biopsies were assessed for oral epithelial dysplasia using the WHO grading system, and DNA Ploidy analysis was performed using established methods. Patients reviewed for a minimum of 5 years who did not develop oral squamous cell carcinoma were classified as “non-transforming” cases. Patients that developed oral squamous cell carcinoma ≥ 6 months after the initial diagnostic biopsy were classified as having “malignant transformation.” Results: Ninety cases were included in the study. Seventy cases yielded informative DNA Ploidy results. Of these 70 cases, 31 progressed to cancer. Oral epithelial dysplasia grading and DNA Ploidy status were both significantly associated with clinical outcome (P < 0.05). Severe dysplasia had a hazard ratio of 3.50 (CI: 1.46, 8.45; P = 0.005) compared to cases with mild dysplasia. AneuPloidy had a hazard ratio of 2.09 (CI: 1.01, 4.32; P = 0.046) compared to cases with a diploid/tetraploid status. Receiver operating characteristic analysis gave an area under the curve of 0.617 for DNA Ploidy status and 0.688 when DNA Ploidy status was combined with dysplasia grading. Conclusion: Our findings suggest that combining dysplasia grading with DNA Ploidy status has clinical utility which could be used to develop novel management algorithms.
