Biochemistry, Biophysics, and Structural Biology Commons^™

The Role Of Irf1 In The Brain And In Adaptive Responses Of Astrocytes, Andrew Hoskins

Theses and Dissertations

In neurodegenerative diseases, the CNS becomes inflamed through activation of pathways, including the NF-B pathway. Some of the therapies for those diseases target neuroinflammatory pathways. Here, we explore the mechanisms for the upregulation of a subset of genes following a restimulation of the NF-B pathway. We discover that this upregulation occurs independent of IRF1 expression and type 1 interferon signaling. A knockdown of IRF1 using siRNA and an inhibition of JAK proteins using inhibitor AG490 both had no effect on priming. A secreted factor was found to upregulate the expression of both this subset of genes and genes encoding pro-inflammatory …

Cellular Mechanisms By Which Alcohol Promotes Hiv Protease Inhibitor-Induced Hepatotoxicity, Michael Hinton

Theses and Dissertations

CELLULAR MECHANISMS BY WHICH ALCOHOL PROMOTES HIV PROTEASE INHIBITOR-INDUCED HEPATOTOXICITY

Michael Hinton, B.S.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University

Virginia Commonwealth University, 2019

Major Director: Huiping Zhou

Professor, Department of Microbiology and Immunology

The development of highly-active-antiretroviral therapy(HAART) has allowed management of HIV and extended the lives of those infected. Alcohol abuse, which is very common in HIV-1 infected patients, is one of the most important co-morbid risk factors for liver injury and has been associated with the occurrence of serious metabolic syndrome and subsequent discontinuation …

Genotyping For Response To Physical Training, Stacy Simmons

Browse all Theses and Dissertations

Understanding the inter-individual variability in physical fitness performance has been the focus of scientific research for decades especially in the United States military. Injury and physical inadequacy cost the U.S military millions of dollars every year. The project PHITE (Precision High Intensity Training through Epigenetics) was funded to investigate this personal complex trait by combing the genetic and epigenetic (non-shared environmental factors) contributions into a single model for physical training response. This project is set up as having 150 male and female recruits between the ages of 18-27 years old. Each participant is randomly put blind into either a high …

∆Np63Α Positively Regulates Erk3 Expression In Non-Melanoma Skin Cancer, Eid Salem Alshammari

Browse all Theses and Dissertations

Non-melanoma skin cancer (NMSC) is a group of skin cancer that includes basal cell carcinoma of the skin (BCC), squamous cell carcinoma of the skin (SCC), actinic keratoses, a precursor to SCC, and other rare cutaneous carcinomas. p63, a member of the p53 gene family, is an important regulator for epithelial tissue growth and development. ∆Np63α, a main isoform of p63, is highly expressed in NMSC and plays essential roles in NMSCs development. Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the MAPK family. It possesses a single phosphorylation site (serine 189) in its activation loop, which makes …

The Functional Role Of Rna Binding Protein Rbms3 As A Tumor Promoter In Triple-Negative Breast Cancer Cells, Yuting Zhou

Theses and Dissertations--Molecular and Cellular Biochemistry

RBMS3 belongs to the family of c-myc gene single-strand binding proteins (MSSPs) that play important roles in transcriptional regulation. Here, we show that RBMS3 functions as a tumor promoter in triple-negative breast cancer (TNBC), a highly aggressive BC subtype. Analysis of RBMS3 expression shows that RBMS3 is upregulated at both mRNA and protein levels in TNBC cells. Functionally, overexpression of RBMS3 increases cell migration, invasion and cancer stem cell (CSC) behaviors. Moreover, RBMS3 induces expression of epithelial-mesenchymal transition (EMT) and CSC markers. Conversely, loss of RBMS3 in TNBC BT549 cells inhibits cell proliferation, migration and mesenchymal phenotype. Correlation analysis shows …

Biochemical Approaches For The Diagnosis And Treatment Of Lafora Disease, Mary Kathryn Brewer

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is the sole carbohydrate storage molecule found in mammalian cells and plays an important role in cellular metabolism in nearly all tissues, including the brain. Defects in glycogen metabolism underlie the glycogen storage diseases (GSDs), genetic disorders with variable clinical phenotypes depending on the mutation type and affected gene(s). Lafora disease (LD) is a fatal form of progressive myoclonus epilepsy and a non-classical GSD. LD typically manifests in adolescence with tonic-clonic seizures, myoclonus, and a rapid, insidious progression. Patients experience increasingly severe and frequent epileptic episodes, loss of speech and muscular control, disinhibited dementia, and severe cognitive decline; death …

Pancreas Of Coxsackievirus-Infected Dams And Their Challenged Pups: A Complex Issue, Sona Sarmirova, Maria Borsanyiova, Brigita Benkoova, Michaela Pospisilova, Rajkumar Rajasekaran, Katarina Berakova, Pavol Gomolcak, Jay Reddy, Shubhada Bopegamage

School of Veterinary and Biomedical Sciences: Faculty Publications

Enteroviral infections are frequent, often asymptomatic in humans and during gravidity. The present study is an extension of our previous investigations where we had shown pancreatitis in challenged pups of CVB4-E2-infected dams. Present investigation describes the effect of gestational infection with this virus on the pancreas of both dams and their challenged pups. Gravid CD1 outbred mice were orally infected with CVB4-E2 virus at different gestation times. Pups were challenged orally with the same virus after 25 days of birth. Organs were collected at selected intervals postinfection (p.i.), and replicating virus and viral-RNA copies were analyzed. Additional readouts included histopathology …

The Role Of Isothiocyanates As Cancer Chemo‐Preventive, Chemo‐Therapeutic And Anti‐Melanoma Agents, Melina Mitsiogianni, Georgios Koutsidis, Nikos Mavroudis, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Vasilis Zoumpourlis, Tom Amery, Alex Galanis, Aglaia Pappa, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

Many studies have shown evidence in support of the beneficial effects of phytochemicals in preventing chronic diseases, including cancer. Among such phytochemicals, sulphur‐containing compounds (e.g., isothiocyanates (ITCs)) have raised scientific interest by exerting unique chemopreventive properties against cancer pathogenesis. ITCs are the major biologically active compounds capable of mediating the anticancer effect of cruciferous vegetables. Recently, many studies have shown that a higher intake of cruciferous vegetables is associated with reduced risk of developing various forms of cancers primarily due to a plurality of effects, including (i) metabolic activation and detoxification, (ii) inflammation, (iii) angiogenesis, (iv) metastasis and (v) regulation …

Viral Emergence In Marine Mammals In The North Pacific May Be Linked To Arctic Sea Ice Reduction, Elizabeth Vanwormer, J. A.K. Mazet, A. Hall, V. A. Gill, P. L. Boveng, J. M. London, T. Gelatt, B. S. Fadely, M. E. Lander, J. Sterling, V. N. Burkanov, R. R. Ream, P. M. Brock, L. D. Rea, B. R. Smith, A. Jeffers, M. Henstock, M. J. Rehberg, K. A. Burek-Huntington, S. L. Crosby, J. A, Hammond, T. Goldstein

School of Veterinary and Biomedical Sciences: Faculty Publications

Climate change-driven alterations in Arctic environments can influence habitat availability, species distributions and interactions, and the breeding, foraging, and health of marine mammals. Phocine distemper virus (PDV), which has caused extensive mortality in Atlantic seals, was confirmed in sea otters in the North Pacific Ocean in 2004, raising the question of whether reductions in sea ice could increase contact between Arctic and sub-Arctic marine mammals and lead to viral transmission across the Arctic Ocean. Using data on PDV exposure and infection and animal movement in sympatric seal, sea lion, and sea otter species sampled in the North Pacific Ocean from …

Visualizing The Invisible: A Guide To Designing, Printing, And Incorporating Dynamic 3d Molecular Models To Teach Structure–Function Relationships, Michelle Howell, Karin Van Dijk, Christine S. Booth, Tomáš Helikar, Brain A. Couch, Rebecca Roston

Department of Biochemistry: Faculty Publications

Understanding the intricate relationship between macromolecular structure and function represents a central goal of undergraduate biology education (1–3). In teaching complex three-dimensional (3D) concepts, instructors typically depend on static two-dimensional (2D) textbook images or computer-based visualization software, which can lead to unintended misconceptions (4–6). While chemical and molecular kits exist, these models cannot handle the size and detail of macromolecules. Consequently, students may graduate in the life sciences without understanding how structure underlies function or acquiring skills to translate between 2D and 3D molecular models (5, 7). Building on recent technological advances, 3D printing (3DP) potentiates an era in which …

Autophagy In Adipocyte Browning: Emerging Drug Target For Intervention In Obesity, Seung-Hyun Ro, Yura Jang, Jiyoung Bae, Isaac M. Kim, Cameron Schaecher, Zachery D. Shomo

Department of Biochemistry: Faculty Publications

Autophagy, lipophagy, and mitophagy are considered to be the major recycling processes for protein aggregates, excess fat, and damaged mitochondria in adipose tissues in response to nutrient status-associated stress, oxidative stress, and genotoxic stress in the human body. Obesity with increased body weight is often associated with white adipose tissue (WAT) hypertrophy and hyperplasia and/or beige/brown adipose tissue atrophy and aplasia, which significantly contribute to the imbalance in lipid metabolism, adipocytokine secretion, free fatty acid release, and mitochondria function. In recent studies, hyperactive autophagy in WAT was observed in obese and diabetic patients, and inhibition of adipose autophagy through targeted …

Dna Uptake By Type Iv Filaments, Kurt H. Piepenbrink

Department of Biochemistry: Faculty Publications

Bacterial uptake of DNA through type IV filaments is an essential component of natural competence in numerous gram-positive and gram-negative species. Recent advances in the field have broadened our understanding of the structures used to take up extracellular DNA. Here, we review seminal experiments in the literature describing DNA binding by type IV pili, competence pili and the flp pili of Micrococcus luteus; collectively referred to here as type IV filaments. We compare the current state of the field on mechanisms of DNA uptake for these three appendage systems and describe the current mechanistic understanding of both DNA-binding and …

Student Understanding Of Dna Structure–Function Relationships Improves From Using 3d Learning Modules With Dynamic 3d Printed Models, Michelle E. Howell, Christine S. Booth, Sharmin M. Sikich, Tomáš Helikar, Rebecca Roston, Brain A. Couch, Karin Van Dijk

Department of Biochemistry: Faculty Publications

Understanding the relationship between molecular structure and function represents an important goal of undergraduate life sciences. Although evidence suggests that handling physical models supports gains in student understanding of structure–function relationships, such models have not been widely implemented in biochemistry classrooms. Three-dimensional (3D) printing represents an emerging cost-effective means of producing molecular models to help students investigate structure–function concepts. We developed three interactive learning modules with dynamic 3D printed models to help biochemistry students visualize biomolecular structures and address particular misconceptions. These modules targeted specific learning objectives related to DNA and RNA structure, transcription factor-DNA interactions, and DNA supercoiling dynamics. …

Winter Hardiness Of Miscanthus (Iii): Genome‐Wide Association And Genomic Prediction For Overwintering Ability In Miscanthus Sinensis, Hongxu Dong, Lindsay V. Clark, Alexander E. Lipka, Joe E. Brummer, Katarzyna Glowacka, Megan C. Hall, Kweon Heo, Xiaoli Jin, Junhua Peng, Toshihiko Yamada, Bimal Kumar Ghimire, Ji Hye Yoo, Chang Yeon Yu, Hua Zhao, Stephen P. Long, Erik J. Sacks

Department of Biochemistry: Faculty Publications

Overwintering ability is an important selection criterion for Miscanthus breeding in temperate regions. Insufficient overwintering ability of the currently leading Miscanthus biomass cultivar, M. ×giganteus (M×g) ‘1993–1780’, in regions where average annual minimum temperatures are −26.1°C (USDA hardiness zone 5) or lower poses a pressing need to develop new cultivars with superior cold tolerance. To facilitate breeding of Miscanthus, this study characterized phenotypic and genetic variation of overwintering ability in an M. sinensis germplasm panel consisting of 564 accessions, evaluated in field trials at three locations in North America and two in Asia. Genome‐wide association (GWA) and genomic …

Chronic Alcohol Exposure Alters Circulating Insulin And Ghrelin Levels: Role Of Ghrelin In Hepatic Steatosis, Karuna Rasineni, Paul G. Thomes, Jacy L. Kubik, Edward N. Harris, Kusum K. Kharbanda, Carol A. Casey

Department of Biochemistry: Faculty Publications

Fatty liver is the earliest response of the liver to excessive ethanol consumption. Central in the development of alcoholic steatosis is increased mobilization of nonesterified free fatty acids (NEFAs) to the liver from the adipose tissue. In this study, we hypothesized that ethanol-induced increase in ghrelin by impairing insulin secretion, could be responsible for the altered lipid metabolism observed in adipose and liver tissue. Male Wistar rats were fed for 5–8 wk with control or ethanol Lieber-DeCarli diet, followed by biochemical analyses in serum and liver tissues. In addition, in vitro studies were conducted on pancreatic islets isolated from experimental …

The Mitochondrial Nad+ Transporter (Ndt1) Plays Important Roles In Cellular Nad+ Homeostasis In Arabidopsis Thaliana, Izabel De Souza Chaves, Elias Feitosa-Araujo, Alexandra Florian, David B. Medeiros, Paula Da Fonseca-Pereira, Lennart Charton, Elmien Heyneke, Jorge A. C. Apfata, Marcel V. Pires, Tabea Mettler-Altmann, Wagner L. Arajuo, H. Ekkehard Neuhaus, Ferdinando Palmieri, Toshihiro Obata, Andreas P. M. Weber, Nicole Linka, Alisdair R. Femie, Adriano Nunes-Nesi

Department of Biochemistry: Faculty Publications

Nicotinamide adenine dinucleotide (NAD⁺) is an essential coenzyme required for all living organisms. In eukaryotic cells, the final step of NAD⁺ biosynthesis is exclusively cytosolic. Hence, NAD⁺ must be imported into organelles to support their metabolic functions. Three NAD⁺ transporters belonging to the mitochondrial carrier family (MCF) have been biochemically characterized in plants. AtNDT1 (At2g47490), focus of the current study, AtNDT2 (At1g25380), targeted to the inner mitochondrial membrane, and AtPXN (At2g39970), located in the peroxisomal membrane. Although AtNDT1 was presumed to reside in the chloroplast …

Acyltransferases And Methods Of Using, Edgar Cahoon, Umidjon Iskandarov, Hae Jin Kim, Jillian Collins-Silva

Department of Biochemistry: Faculty Publications

Provided herein are novel acyltransferases and methods of using such novel acyltransferases in making medium - chain fatty acids.

Charting A New Frontier Of Science By Integrating Mathematical Modeling To Understand And Predict Complex Biological Systems, Katharine White, Kira Mcentire, Nicole R. Buan, Kingshuk Ghosh, Lecia Robinson, Elisar Barbar

Department of Biochemistry: Faculty Publications

Biological systems are staggeringly complex. To untangle this complexity and make predictions about biological systems is a continuous goal of biological research. One approach to achieve these goals is to emphasize the use of quantitative measures of biological processes. Advances in quantitative biology data collection and analysis across scales (molecular, cellular, organismal, ecological) has transformed how we understand, categorize, and predict complex biological systems. Simultaneously, thanks to increased computational power, mathematicians, engineers and physical scientists -- collectively termed theoreticians -- have developed sophisticated models of biological systems at different scales. But there is still a disconnect between the two fields. …

Fatty Acid Transporter 2 Reprograms Neutrophils In Cancer, Filippo Veglia, Vladimir A. Tyurin, Maria Blasi, Alessandra De Leo, Andrew Kossenkov, Laxminarasimha Donthireddy, To Tsun Ki Jerrick, Zach Schug, Subhasree Basu, Fang Wang, Emanuela Ricciotti, Concetta C. Dirusso, Maureen E. Murphy, Robert H. Vonderheide, Paul M. Lieberman, Charles Mulligan, Brian Nam, Neil Hockstein, Gregory Masters, Michael Guarino, Cindy Lin, Yulia Nefedova, Paul N. Black, Valerian E, Kagan, Dmitry Gabrilovich

Department of Biochemistry: Faculty Publications

Polymorphonuclear myeloid derived suppressor cells (PMN-MDSC) are pathologically activated neutrophils that are critically important for the regulation of immune responses in cancer. They contribute to the failure of cancer therapies and are associated with poor clinical outcomes. Despite the recent advances in understanding of the PMN-MDSC biology, the mechanisms responsible for pathological activation of neutrophils are not well defined, which limits selective targeting of these cells. Here, we report that mouse and human PMN-MDSC exclusively up-regulate fatty acid transporter protein 2 (FATP2). Over-expression of FATP2 in PMN-MDSC was controlled by GM-CSF, through the activation of STAT5 transcription factor. Deletion of …

Arsenite Exposure Suppresses Adipogenesis, Mitochondrial Biogenesis And Thermogenesis Via Autophagy Inhibition In Brown Adipose Tissue, Jiyoung Bae, Yura Jang, Heejeong Kim, Kalika Mahato, Cameron Schaecher, Issac M. Kim, Eunju Kim, Seung-Hyun Ro

Department of Biochemistry: Faculty Publications

Arsenite, a trivalent form of arsenic, is an element that occurs naturally in the environment. Humans are exposed to high dose of arsenite through consuming arsenite-contaminated drinking water and food, and the arsenite can accumulate in the human tissues. Arsenite induces oxidative stress, which is linked to metabolic disorders such as obesity and diabetes. Brown adipocytes dissipating energy as heat have emerging roles for obesity treatment and prevention. therefore, understanding the pathophysiological role of brown adipocytes can provide effective strategies delineating the link between arsenite exposure and metabolic disorders. Our study revealed that arsenite significantly reduced differentiation of murine brown …