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Novel Inducers Of Gliotoxin Production In Aspergillus Fumigatus, Taylor J. Schoberle 2013 The University of Texas Graduate School of Biomedical Sciences at Houston

Novel Inducers Of Gliotoxin Production In Aspergillus Fumigatus, Taylor J. Schoberle

Dissertations & Theses (Open Access)

Secondary metabolites are produced by numerous organisms and can either be benign to humans or harmful. Genes involved in the synthesis and transport of these secondary metabolites are frequently found in gene clusters, which are often located in subtelomeric regions of the chromosome. These clusters are often coordinately regulated, being almost exclusively dependent on transcription factors that are located within the clusters themselves. Secondary metabolites are also regulated by a variety of factors, including nutritional factors, environmental factors and developmental processes. Gliotoxin, which is produced by a variety of Aspergillus species, Trichoderma species, and Penicillium species, exhibits immunosuppressive properties and …


Notch1 Gain Of Function In Germ Cells Causes Failure Of Spermatogenesis In Male Mice, Zaohua Huang, Bryan Rivas, Alexander I. Agoulnik 2013 Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida

Notch1 Gain Of Function In Germ Cells Causes Failure Of Spermatogenesis In Male Mice, Zaohua Huang, Bryan Rivas, Alexander I. Agoulnik

HWCOM Faculty Publications

NOTCH1 is a member of the NOTCH receptor family, a group of single-pass trans-membrane receptors. NOTCH signaling is highly conserved in evolution and mediates communication between adjacent cells. NOTCH receptors have been implicated in cell fate determination, as well as maintenance and differentiation of stem cells. In the mammalian testis expression of NOTCH1 in somatic and germ cells has been demonstrated, however its role in spermatogenesis was not clear. To study the significance of NOTCH1 in germ cells, we applied a cre/loxP approach in mice to induce NOTCH1 gain- or loss-of function specifically in male germ cells. Using a Stra8-icre …


Eradication Of Therapy-Resistant Human Prostate Tumors Using An Ultrasound-Guided Site-Specific Cancer Terminator Virus Delivery Approach, Adelaide Greco, Altomare Benedetto, Candace Howard, Sarah Kelly, Rounak Nande, Yulia Dementieva, Michele Miranda, Arturo Brunetti, Marco Salvatore, Luigi Claudio, Devanand Sarkar, Paul Dent, David Curiel, Paul Fisher, Pier Claudio 2013 Marshall University

Eradication Of Therapy-Resistant Human Prostate Tumors Using An Ultrasound-Guided Site-Specific Cancer Terminator Virus Delivery Approach, Adelaide Greco, Altomare Benedetto, Candace Howard, Sarah Kelly, Rounak Nande, Yulia Dementieva, Michele Miranda, Arturo Brunetti, Marco Salvatore, Luigi Claudio, Devanand Sarkar, Paul Dent, David Curiel, Paul Fisher, Pier Claudio

Yulia Dementieva

Intratumoral injections of a replication-incompetent adenovirus (Ad) expressing melanoma differentiation– associated gene-7/interleukin-24 (Ad.mda-7), a secreted cytokine displaying cancer-selective, apoptosis-inducing properties, profoundly inhibits prostate cancer (PC) growth in immune-incompetent animals. In contrast, Ad.mda-7 is ineffective in PCs overexpressing antiapoptotic proteins such as Bcl-2 or Bcl-x L . However, intratumoral injections of a conditionally replication-competent Ad (CRCA) in which expression of the adenoviral E1A gene is driven by the cancer-specific promoter of progression-elevated gene-3 (PEG-3) and which simultaneously expresses mda-7/interleukin (IL)-24 in the E3 region of the Ad (Ad.PEG-E1A-mda-7), a cancer terminator virus (CTV), is highly active in these cells. A major …


Effect Of Receptor-Selective Retinoids On Growth And Differentiation Pathways In Mouse Melanoma Cells, Sejal H. Desai, Goran Boskovic, Linda L. Eastham, Marcia Dawson, Richard M. Niles 2013 Marshall University

Effect Of Receptor-Selective Retinoids On Growth And Differentiation Pathways In Mouse Melanoma Cells, Sejal H. Desai, Goran Boskovic, Linda L. Eastham, Marcia Dawson, Richard M. Niles

Goran Boskovic

Treatment of B16 mouse melanoma cells with all-trans-retinoic acid (ATRA) results in inhibition of cell proliferation and induction of differentiation. Accompanying these events is an induction of retinoic acid receptor β (RARβ) expression, an increase in protein kinase Cα (PKCα) expression, and enhanced activator protein-1 (AP-1) transcriptional activity. These cells express nuclear RARα and RARγ and nuclear retinoid X receptors (RXR) α and β constitutively. We tested the ability of receptor-selective retinoids to induce the biochemical changes found in ATRA-treated melanoma cells and also tested their effectiveness in decreasing anchorage-dependent and -independent growth. The RXR-selective ligand (2E,4E)-6-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)-3,7-dimethyl-2,4,6-octatrienoic acid (SR11246) was …


Effect Of Receptor-Selective Retinoids On Growth And Differentiation Pathways In Mouse Melanoma Cells, Sejal H. Desai, Goran Boskovic, Linda L. Eastham, Marcia Dawson, Richard M. Niles 2013 Marshall University

Effect Of Receptor-Selective Retinoids On Growth And Differentiation Pathways In Mouse Melanoma Cells, Sejal H. Desai, Goran Boskovic, Linda L. Eastham, Marcia Dawson, Richard M. Niles

Richard M. Niles

Treatment of B16 mouse melanoma cells with all-trans-retinoic acid (ATRA) results in inhibition of cell proliferation and induction of differentiation. Accompanying these events is an induction of retinoic acid receptor β (RARβ) expression, an increase in protein kinase Cα (PKCα) expression, and enhanced activator protein-1 (AP-1) transcriptional activity. These cells express nuclear RARα and RARγ and nuclear retinoid X receptors (RXR) α and β constitutively. We tested the ability of receptor-selective retinoids to induce the biochemical changes found in ATRA-treated melanoma cells and also tested their effectiveness in decreasing anchorage-dependent and -independent growth. The RXR-selective ligand (2E,4E)-6-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)-3,7-dimethyl-2,4,6-octatrienoic acid (SR11246) was …


Effect Of Receptor-Selective Retinoids On Growth And Differentiation Pathways In Mouse Melanoma Cells, Sejal H. Desai, Goran Boskovic, Linda L. Eastham, Marcia Dawson, Richard M. Niles 2013 Marshall University

Effect Of Receptor-Selective Retinoids On Growth And Differentiation Pathways In Mouse Melanoma Cells, Sejal H. Desai, Goran Boskovic, Linda L. Eastham, Marcia Dawson, Richard M. Niles

Linda L. Eastham

Treatment of B16 mouse melanoma cells with all-trans-retinoic acid (ATRA) results in inhibition of cell proliferation and induction of differentiation. Accompanying these events is an induction of retinoic acid receptor β (RARβ) expression, an increase in protein kinase Cα (PKCα) expression, and enhanced activator protein-1 (AP-1) transcriptional activity. These cells express nuclear RARα and RARγ and nuclear retinoid X receptors (RXR) α and β constitutively. We tested the ability of receptor-selective retinoids to induce the biochemical changes found in ATRA-treated melanoma cells and also tested their effectiveness in decreasing anchorage-dependent and -independent growth. The RXR-selective ligand (2E,4E)-6-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)-3,7-dimethyl-2,4,6-octatrienoic acid (SR11246) was …


Expression Of The Chemokine Receptor, Cxcr4, And Its Ligand, Sdf-1, Are Increased In Purkinje Cells Of The Multiple System Atrophy Cerebellum, Megan Welter 2013 Western Michigan University

Expression Of The Chemokine Receptor, Cxcr4, And Its Ligand, Sdf-1, Are Increased In Purkinje Cells Of The Multiple System Atrophy Cerebellum, Megan Welter

Masters Theses

Multiple System Atrophy (MSA) is a sporadic, neurodegenerative disease that consists of three conditions: autonomic dysfunction, Parkinsonism and cerebellar ataxia. Our lab conducted an Affymetrix global gene expression analysis using pons tissue of MSA patients to determine genes that are differentially expressed when compared to non- MSA controls. This study identified upregulated genes, including the C-X-C chemokine receptor type 4, CXCR4, to which stromal cell-derived factor-I (SDF-1) is the natural ligand. The CXCR4/SDF-1 signaling pair has been sho.wn to play multiple roles in the brain, such as inducing neuronal apoptosis and promoting leukocyte recruitment during inflammation. The MSA cerebellum presents …


Assessing Methods For Assigning Snps To Genes In Gene-Based Tests Of Association Using Common Variants, Ashley Petersen, Carolina Alvarez, Scott DeClaire, Nathan L. Tintle 2013 University of Washington

Assessing Methods For Assigning Snps To Genes In Gene-Based Tests Of Association Using Common Variants, Ashley Petersen, Carolina Alvarez, Scott Declaire, Nathan L. Tintle

Department of Biostatistics Faculty Publications

Gene-based tests of association are frequently applied to common SNPs (MAF>5%) as an alternative to single-marker tests. In this analysis we conduct a variety of simulation studies applied to five popular gene-based tests investigating general trends related to their performance in realistic situations. In particular, we focus on the impact of non-causal SNPs and a variety of LD structures on the behavior of these tests. Ultimately, we find that non-causal SNPs can significantly impact the power of all gene-based tests. On average, we find that the “noise” from 6–12 non-causal SNPs will cancel out the “signal” of one causal …


Assembly And Function Of Myosin Ii On Ultraviolet/Ozone Patterned Trimethylchlorosilane Substrates, Hideyo Takatsuki, Madhukar Kolli, Kevin Rice, B. Day, Shinichi Asano, Mashiur Rahman, Yue Zhang, Ryoki Ishikawa, Kazuhiro Kohama, Eric Blough 2013 Marshall University

Assembly And Function Of Myosin Ii On Ultraviolet/Ozone Patterned Trimethylchlorosilane Substrates, Hideyo Takatsuki, Madhukar Kolli, Kevin Rice, B. Day, Shinichi Asano, Mashiur Rahman, Yue Zhang, Ryoki Ishikawa, Kazuhiro Kohama, Eric Blough

Kevin M Rice

The study of biomolecular motors represents a rapidly and progressing field of nanobiotechnology. Here, we present a simple method for patterning myosin II on a microstructured surface. Our findings indicate that UV/ozone treatment can be used to alter the hydrophobicity of trimethyl-chloro-silane (TMCS) coated glass surfaces, to alter protein binding, and effectively produce localized motor activity. Taken together, these data suggest that photoreactive patterning may be useful for the selective localization of functional myosin II motor tracks.


Age-Associated Changes In Hearts Of Male Fischer 344/Brown Norway F1 Rats, Ernest M. Walker Jr., Michael S. Nillas, Elsa I. Mangiarua, Sylvestre Cansino, Ryan G. Morrison, Romaine R. Perdue, William E. Triest, Gary L. Wright, Mark Studeny, Paulette Wehner, Kevin M. Rice, Eric R. Blough 2013 Marshall University

Age-Associated Changes In Hearts Of Male Fischer 344/Brown Norway F1 Rats, Ernest M. Walker Jr., Michael S. Nillas, Elsa I. Mangiarua, Sylvestre Cansino, Ryan G. Morrison, Romaine R. Perdue, William E. Triest, Gary L. Wright, Mark Studeny, Paulette Wehner, Kevin M. Rice, Eric R. Blough

Kevin M Rice

Aging is associated with left ventricular hypertrophy, dilatation, and fibrosis of the heart. The Fischer 344/Brown Norway F1 (F344/BNF1) rat is recommended for age-related studies by the National Institutes on Aging because this hybrid rat lives longer and has a lower rate of pathological conditions than inbred rats. However, little is known about age-associated changes in cardiac and aortic function and structure in this model. This study evaluated age-related cardiac changes in male F344/BNF1 rats using ECHO, gross, and microscopic examinations. Rats aged 6-, 30-, and 36-mo were anesthetized and two-dimensional ECHO measurements, two-dimensional guided M-mode, Doppler M-mode, and other …


Effect Of Aging On Cellular Mechanotransduction, Miaozong Wu, Jacqueline Fannin, Kevin M. Rice, Bin Wang, Eric R. Blough 2013 Marshall University

Effect Of Aging On Cellular Mechanotransduction, Miaozong Wu, Jacqueline Fannin, Kevin M. Rice, Bin Wang, Eric R. Blough

Kevin M Rice

Aging is becoming a critical heath care issue and a burgeoning economic burden on society. Mechanotransduction is the ability of the cell to sense, process, and respond to mechanical stimuli and is an important regulator of physiologic function that has been found to play a role in regulating gene expression, protein synthesis, cell differentiation, tissue growth, and most recently, the pathophysiology of disease. Here we will review some of the recent findings of this field and attempt, where possible, to present changes in mechanotransduction that are associated with the aging process in several selected physiological systems, including musculoskeletal, cardiovascular, neuronal, …


Virologic Factors Contributing To The Genetic Diversification Of Influenza Viruses Circulating In North American Swine, Thomas Paul Fabrizio II 2013 University of Tennessee Health Science Center

Virologic Factors Contributing To The Genetic Diversification Of Influenza Viruses Circulating In North American Swine, Thomas Paul Fabrizio Ii

Theses and Dissertations (ETD)

The purpose of this study was to determine mechanisms of reassortment of swine influenza viruses and determine if certain reassortant gene combinations can drive evolution and host adaptation in the context of the triple reassortant internal gene (TRIG) cassette. The TRIG contains a unique combination of a human polymerase basic 1 (PB1) gene with avian polymerase basic 2 (PB2) and polymerase acidic (PA) genes. The remaining internal genes, nucleoprotein (NP), matrix (M), and non-structural (NS) are of swine origin. This differs considerably from classical swine lineage viruses which are drifted variants of the 1918 pandemic with all swine origin genes. …


Functional Study Of Hemogen Knockout Mouse Model, Peng Gao 2013 University of Tennessee Health Science Center

Functional Study Of Hemogen Knockout Mouse Model, Peng Gao

Theses and Dissertations (ETD)

Mouse Hemogen (Hemgn) is regarded as a homologue of human Erythroid Differentiation Associated Gene (EDAG). EDAG overexpression has been postulated for association with some leukemia cases. Meanwhile, Hemgn has been found to contribute to Hoxb4 mediated hematopoietic stem cell expansion. Based on these postulations and evidences, a Hemgn knockout mouse model has been generated to study its function in normal and stress hematopoiesis. I confirmed the Hemgn expression in hematopoietic organs including bone marrow and spleen, as well as round spematids in testis. Hemgn is expressed in mouse hematopoietic stem cells and erythroid progenitor cells. Moreover, Hemgn was also found …


Identification Of Anziaic Acid, A Lichen Depside From Hypotrachyna Sp., As A New Topoisomerase Poison Inhibitor, Bokun Cheng, Shugeng Cao, Victor Vasquez, Thirunavukkarasu Annamalai, Giselle Tamayo-Castillo, Yuk-Ching Tse-Dinh 2013 Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York

Identification Of Anziaic Acid, A Lichen Depside From Hypotrachyna Sp., As A New Topoisomerase Poison Inhibitor, Bokun Cheng, Shugeng Cao, Victor Vasquez, Thirunavukkarasu Annamalai, Giselle Tamayo-Castillo, Yuk-Ching Tse-Dinh

Department of Chemistry and Biochemistry

Topoisomerase inhibitors are effective for antibacterial and anticancer therapy because they can lead to the accumulation of the intermediate DNA cleavage complex formed by the topoisomerase enzymes, which trigger cell death. Here we report the application of a novel enzyme-based high-throughput screening assay to identify natural product extracts that can lead to increased accumulation of the DNA cleavage complex formed by recombinant Yersinia pestistopoisomerase I as part of a larger effort to identify new antibacterial compounds. Further characterization and fractionation of the screening positives from the primary assay led to the discovery of a depside, anziaic acid, from the lichen …


Age-Associated Changes In Hearts Of Male Fischer 344/Brown Norway F1 Rats, Ernest M. Walker Jr., Michael S. Nillas, Elsa I. Mangiarua, Sylvestre Cansino, Ryan G. Morrison, Romaine R. Perdue, William E. Triest, Gary L. Wright, Mark Studeny, Paulette Wehner, Kevin M. Rice, Eric R. Blough 2013 Marshall University

Age-Associated Changes In Hearts Of Male Fischer 344/Brown Norway F1 Rats, Ernest M. Walker Jr., Michael S. Nillas, Elsa I. Mangiarua, Sylvestre Cansino, Ryan G. Morrison, Romaine R. Perdue, William E. Triest, Gary L. Wright, Mark Studeny, Paulette Wehner, Kevin M. Rice, Eric R. Blough

Elsa I. Mangiarua

Aging is associated with left ventricular hypertrophy, dilatation, and fibrosis of the heart. The Fischer 344/Brown Norway F1 (F344/BNF1) rat is recommended for age-related studies by the National Institutes on Aging because this hybrid rat lives longer and has a lower rate of pathological conditions than inbred rats. However, little is known about age-associated changes in cardiac and aortic function and structure in this model. This study evaluated age-related cardiac changes in male F344/BNF1 rats using ECHO, gross, and microscopic examinations. Rats aged 6-, 30-, and 36-mo were anesthetized and two-dimensional ECHO measurements, two-dimensional guided M-mode, Doppler M-mode, and other …


Instability Of Ctg Repeats Is Governed By The Position Of A Dna Base Lesion Through Base Excision Repair, Yanhao Lai, Meng Xu, Zunzhen Zhang, Yuan Liu 2013 Department of Chemistry and Biochemistry, Florida International University, Miami, Florida; Department of Environmental and Occupational Health, West China School of Public Health, Sichuan University, Chengdu, People’s Republic of China

Instability Of Ctg Repeats Is Governed By The Position Of A Dna Base Lesion Through Base Excision Repair, Yanhao Lai, Meng Xu, Zunzhen Zhang, Yuan Liu

Department of Chemistry and Biochemistry

Trinucleotide repeat (TNR) expansions and deletions are associated with human neurodegeneration and cancer. However, their underlying mechanisms remain to be elucidated. Recent studies have demonstrated that CAG repeat expansions can be initiated by oxidative DNA base damage and fulfilled by base excision repair (BER), suggesting active roles for oxidative DNA damage and BER in TNR instability. Here, we provide the first evidence that oxidative DNA damage can induce CTG repeat deletions along with limited expansions in human cells. Biochemical characterization of BER in the context of (CTG)20 repeats further revealed that repeat instability correlated with the position of a base …


Effect Of Aging On Cellular Mechanotransduction, Miaozong Wu, Jacqueline Fannin, Kevin M. Rice, Bin Wang, Eric R. Blough 2013 Marshall University

Effect Of Aging On Cellular Mechanotransduction, Miaozong Wu, Jacqueline Fannin, Kevin M. Rice, Bin Wang, Eric R. Blough

Bin Wang

Aging is becoming a critical heath care issue and a burgeoning economic burden on society. Mechanotransduction is the ability of the cell to sense, process, and respond to mechanical stimuli and is an important regulator of physiologic function that has been found to play a role in regulating gene expression, protein synthesis, cell differentiation, tissue growth, and most recently, the pathophysiology of disease. Here we will review some of the recent findings of this field and attempt, where possible, to present changes in mechanotransduction that are associated with the aging process in several selected physiological systems, including musculoskeletal, cardiovascular, neuronal, …


Effect Of Aging On Cellular Mechanotransduction, Miaozong Wu, Jacqueline Fannin, Kevin Rice, Bin Wang, Eric Blough 2013 Marshall University

Effect Of Aging On Cellular Mechanotransduction, Miaozong Wu, Jacqueline Fannin, Kevin Rice, Bin Wang, Eric Blough

Eric Blough

Aging is becoming a critical heath care issue and a burgeoning economic burden on society. Mechanotransduction is the ability of the cell to sense, process, and respond to mechanical stimuli and is an important regulator of physiologic function that has been found to play a role in regulating gene expression, protein synthesis, cell differentiation, tissue growth, and most recently, the pathophysiology of disease. Here we will review some of the recent findings of this field and attempt, where possible, to present changes in mechanotransduction that are associated with the aging process in several selected physiological systems, including musculoskeletal, cardiovascular, neuronal, …


Assembly And Function Of Myosin Ii On Ultraviolet/Ozone Patterned Trimethylchlorosilane Substrates, Hideyo Takatsuki, Madhukar Kolli, Kevin Rice, B. Day, Shinichi Asano, Mashiur Rahman, Yue Zhang, Ryoki Ishikawa, Kazuhiro Kohama, Eric Blough 2013 Marshall University

Assembly And Function Of Myosin Ii On Ultraviolet/Ozone Patterned Trimethylchlorosilane Substrates, Hideyo Takatsuki, Madhukar Kolli, Kevin Rice, B. Day, Shinichi Asano, Mashiur Rahman, Yue Zhang, Ryoki Ishikawa, Kazuhiro Kohama, Eric Blough

Eric Blough

The study of biomolecular motors represents a rapidly and progressing field of nanobiotechnology. Here, we present a simple method for patterning myosin II on a microstructured surface. Our findings indicate that UV/ozone treatment can be used to alter the hydrophobicity of trimethyl-chloro-silane (TMCS) coated glass surfaces, to alter protein binding, and effectively produce localized motor activity. Taken together, these data suggest that photoreactive patterning may be useful for the selective localization of functional myosin II motor tracks.


Age-Associated Changes In Hearts Of Male Fischer 344/Brown Norway F1 Rats, Ernest M. Walker Jr., Michael S. Nillas, Elsa I. Mangiarua, Sylvestre Cansino, Ryan G. Morrison, Romaine R. Perdue, William E. Triest, Gary L. Wright, Mark Studeny, Paulette Wehner, Kevin M. Rice, Eric R. Blough 2013 Marshall University

Age-Associated Changes In Hearts Of Male Fischer 344/Brown Norway F1 Rats, Ernest M. Walker Jr., Michael S. Nillas, Elsa I. Mangiarua, Sylvestre Cansino, Ryan G. Morrison, Romaine R. Perdue, William E. Triest, Gary L. Wright, Mark Studeny, Paulette Wehner, Kevin M. Rice, Eric R. Blough

Eric Blough

Aging is associated with left ventricular hypertrophy, dilatation, and fibrosis of the heart. The Fischer 344/Brown Norway F1 (F344/BNF1) rat is recommended for age-related studies by the National Institutes on Aging because this hybrid rat lives longer and has a lower rate of pathological conditions than inbred rats. However, little is known about age-associated changes in cardiac and aortic function and structure in this model. This study evaluated age-related cardiac changes in male F344/BNF1 rats using ECHO, gross, and microscopic examinations. Rats aged 6-, 30-, and 36-mo were anesthetized and two-dimensional ECHO measurements, two-dimensional guided M-mode, Doppler M-mode, and other …


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