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Articles 1 - 6 of 6
Full-Text Articles in Genetics and Genomics
Exploiting Fission Yeast Genetic Interaction Data To Identify Disease-Specific Drug Targets For Tuberous Sclerosis Complex, Ashyad Rayhan
Exploiting Fission Yeast Genetic Interaction Data To Identify Disease-Specific Drug Targets For Tuberous Sclerosis Complex, Ashyad Rayhan
Electronic Thesis and Dissertation Repository
Tuberous sclerosis complex (TSC) is an inherited genetic disorder caused by loss-of-function mutations in either TSC1 or TSC2. Their respective gene products regulate the mechanistic target of rapamycin (mTOR) signaling pathway, which serves as an activator of cellular proliferation, metabolism, and cell survival. Orthologs of the TSC1 and TSC2 genes exist in a wide range of organisms, including the commonly used and genetically tractable model eukaryote, Schizosaccharomyces pombe. To better understand the functional roles of S. pombe tsc1 and tsc2, I exploited recent advances in genetic interaction biology to identify and characterize genes that modulate the phenotypic …
Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque
Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque
Electronic Thesis and Dissertation Repository
Maternal alcohol consumption during pregnancy results in a spectrum of behavioural and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD). Currently, little is know about if and how the external environment may modulate these deficits. I have used C57BL/6 mice to study this interaction between prenatal alcohol exposure and the postnatal environment. Alcohol exposure during synaptogenesis produces high levels of anxiety-like traits and decreased memory performance. Alcohol-exposed mice (and matched unexposed controls) were put in 'environmentally-enriched' conditions of voluntary exercise, physical activities and cognitive stimulation to ascertain the effects of a positive postnatal environment. The results show that …
Accurate Cytogenetic Biodosimetry Through Automated Dicentric Chromosome Curation And Metaphase Cell Selection, Jin Liu, Yanxin Li, Ruth Wilkins, Canadian Nuclear Laboratories, Joan H. Knoll, Peter Rogan
Accurate Cytogenetic Biodosimetry Through Automated Dicentric Chromosome Curation And Metaphase Cell Selection, Jin Liu, Yanxin Li, Ruth Wilkins, Canadian Nuclear Laboratories, Joan H. Knoll, Peter Rogan
Biochemistry Publications
Accurate digital image analysis of abnormal microscopic structures relies on high quality images and on minimizing the rates of false positive (FP) and negative objects in images. Cytogenetic biodosimetry detects dicentric chromosomes (DCs) that arise from exposure to ionizing radiation, and determines radiation dose received based on DC frequency. Improvements in automated DC recognition increase the accuracy of dose estimates by reclassifying FP DCs as monocentric chromosomes or chromosome fragments. We also present image segmentation methods to rank high quality digital metaphase images and eliminate suboptimal metaphase cells. A set of chromosome morphology segmentation methods selectively filtered out FP DCs …
Functional Characteristics Of Four Novel Lone Atrial Fibrillation-Linked Connexin40 Mutants, Mahmoud Noureldin
Functional Characteristics Of Four Novel Lone Atrial Fibrillation-Linked Connexin40 Mutants, Mahmoud Noureldin
Electronic Thesis and Dissertation Repository
Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Recently, four novel heterozygous Cx40 mutations, K107R, L223M, Q236H, and I257L were identified in 4 of 310 unrelated AF patients. To study possible alterations associated with these mutants, we studied their localization and function using gap junction (GJ)-deficient model cells. Cell pairs expressing Q236H alone or together with wildtype Cx43 showed a significantly lower coupling conductance. Impaired GJ function and dominant negative action on Cx43 of this mutant are consistent with previous findings on the majority of AF-linked Cx40 mutants. The remaining three novel AF-linked mutants did not show …
The Cdk-Resistant Prb-E2f1 Complex Recruits Chromatin-Organizing Proteins To Repetitive Dna Sequences, Charles A. Ishak
The Cdk-Resistant Prb-E2f1 Complex Recruits Chromatin-Organizing Proteins To Repetitive Dna Sequences, Charles A. Ishak
Electronic Thesis and Dissertation Repository
This thesis investigates mechanistic links between genome integrity and the recruitment of chromatin organizing proteins to repetitive DNA sequences mediated by the retinoblastoma tumor suppressor protein (pRB). I demonstrate that a CDK-resistant interaction between the pRB C-terminus and the E2F1 coiled-coil marked box domain establishes a scaffold that facilitates recruitment of multiple chromatin-organizing proteins to repetitive sequences across the genome throughout the cell cycle. Specifically, pRB recruits the enhancer-of-zeste-homologue 2 (EZH2) histone methyltransferase to establish repressive facultative heterochromatin at repetitive sequences, and the Condensin II complex to ensure proper DNA replication and mitotic progression. To disrupt the CDK-resistant pRB-E2F1 interaction …
Hsp90 And Its Co-Chaperones Modify Tdp-43 Localization, Aggregation, And Toxicity, Lilian T. Lin
Hsp90 And Its Co-Chaperones Modify Tdp-43 Localization, Aggregation, And Toxicity, Lilian T. Lin
Electronic Thesis and Dissertation Repository
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with protein misfolding and protein aggregation. In particular, the TAR DNA-binding protein (TDP-43) is often found in the pathological inclusions in neurons of ALS patient brains and spinal cords. This phenomenon is known as TDP-43 proteinopathy, the mislocalization of TDP-43 from the cell nucleus and the formation of aggregates in the cytoplasm. Numerous mutations in the gene encoding TDP-43 have also been linked to familial cases of ALS (fALS) and cause TDP-43 proteinopathy. This study attempts to decipher how the molecular chaperone Hsp90 and its co-chaperones, Aha1, Sti1, and Cdc37, modulate …