Bacterial Association Networks From Healthy And Cancer-Associated Gut Microbiomes,
2021
University of Central Florida
Bacterial Association Networks From Healthy And Cancer-Associated Gut Microbiomes, Mark Loftus
Electronic Theses and Dissertations, 2020-2023
The human gastrointestinal tract is colonized by a diverse community of symbiotic microorganisms, mainly bacteria, that are known to play essential roles in maintaining the health of their human host. Disruption of this bacterial community has been associated with numerous diseases, including Colorectal Cancer (CRC). CRC is one of the leading causes of cancer-related deaths worldwide. As such, focus has been placed on the modulation of the bacterial community within the cancer-associated gut microbiome as the next step in possible CRC treatment and prevention strategies. To use the bacterial community for these purposes, a better understanding of the associations that …
Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors,
2021
West Virginia University Health Sciences Center
Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls
Graduate Theses, Dissertations, and Problem Reports (ETD)
This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …
The Effect Of Cxcl12 Ligand On Internalization And Dimerization Of Cxcr4 Receptors In Live Cells,
2021
The University of Akron
The Effect Of Cxcl12 Ligand On Internalization And Dimerization Of Cxcr4 Receptors In Live Cells, Loga Iyer
Williams Honors College, Honors Research Projects
The primary objective of this project was to determine the effect of CXCL12 ligand binding on the CXCR4 receptor, specifically, how it would impact receptor internalization and dimerization. The CXCL12 ligand derives from the stromal cell-derived alpha family [8]. The CXCR4 receptors, known as C-X-C chemokine receptor type 4 play an essential role in controlling cell proliferation. When misregulated, these receptors can drive tumorigenesis and are thus important targets of cancer therapy. These G protein-coupled receptors stimulate a cascade of signaling pathways in specific tissues [1]. These pathways include the positive transcriptional control of CXCR4 via the Nuclear Respiratory Factor-1 …
Traction Force Is Modulated By The Calpain Small Subunit And Secreted Galectin-3,
2021
Wayne State University
Traction Force Is Modulated By The Calpain Small Subunit And Secreted Galectin-3, Imjoo Jang
Wayne State University Dissertations
Cell migration is a fundamental physical process for wound repair, innate immune response, embryonic development, inflammatory responses as well as cancer metastasis. Biochemical and mechanical cues present inside and outside the cell can modulate the mechanical aspects of cell migration. During cell migration, traction forces are generated by the contraction of the actomyosin cytoskeleton and transmitted to the extracellular matrix through integrin-mediated focal adhesions, facilitating the forward movement of the cell. Although regulating traction force is central to achieving successful cell migration, the detailed mechanism of the force production is still largely unclear. The calpain family of proteases has been …
Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice,
2021
West Virginia University
Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish
Graduate Theses, Dissertations, and Problem Reports (ETD)
Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and consistent …
Entry And Replication Of Negative-Strand Rna Viruses,
2021
University of Kentucky
Entry And Replication Of Negative-Strand Rna Viruses, Kerri Boggs
Theses and Dissertations--Molecular and Cellular Biochemistry
Hendra virus (HeV) and human metapneumovirus (HMPV) are negative-sense, singled-stranded RNA viruses. The paramyxovirus HeV is classified as a biosafety level 4 pathogen due to its high fatality rate and the lack of a human vaccine or antiviral treatment. HMPV is a widespread pneumovirus that causes respiratory tract infections which are particularly dangerous for young children, immunocompromised individuals, and the elderly. Like HeV, no vaccines or therapies are available to combat HMPV infections. These viruses fuse their lipid envelopes with a cell to initiate infection. Blocking cell entry is a promising approach for antiviral development, and many vaccines are designed …
Therapeutic Targeting Of Leukemia Stem Cells To Prevent T-Cell Acute Lymphoblastic Leukemia Relapse,
2021
University of Kentucky
Therapeutic Targeting Of Leukemia Stem Cells To Prevent T-Cell Acute Lymphoblastic Leukemia Relapse, Meghan G. Haney
Theses and Dissertations--Molecular and Cellular Biochemistry
The survival rate of T-cell Acute Lymphoblastic Leukemia (T-ALL) relapse is a dismal 10% of affected adults and 30% of children, largely due to the relapsed disease being more aggressive and treatment resistant than the initial disease. Relapse is thought to occur because conventional chemotherapies are unable to reliably eliminate a unique cell type known as leukemia stem (or propagating) cells (LSCs). LSCs are the only cells within the leukemia with the ability to self-renew and remake or replenish the ALL from a single cell. Currently, the pathways governing self-renewal in LSCs are largely unknown, precluding our ability to successfully …
Reversible Glucan Phosphorylation In The Red Alga, Cyanidioschyzon Merolae,
2021
University of Kentucky
Reversible Glucan Phosphorylation In The Red Alga, Cyanidioschyzon Merolae, Corey Owen Brizzee
Theses and Dissertations--Molecular and Cellular Biochemistry
Starch and glycogen are an essential component for the majority of species and have been developed to maintain homeostasis in response to environmental changes. Water-soluble glycogen is an excellent source of quick, short-term energy in response to energy demands. In contrast, plants and algae have developed the macromolecule starch that is elegantly suitable for their dependence on external circumstances. Semi-crystalline starch is water-insoluble and inaccessible to most amylolytic enzymes, thus plants and algae have developed a coordinated system so that these enzymes can gain access to the denser starch energy cache. Starch-like semi-crystalline polysaccharides are also found in red algae, …
Regulation Of Osseous Healing By Macrophage-Derived Wnt Ligands,
2021
Virginia Commonwealth University
Regulation Of Osseous Healing By Macrophage-Derived Wnt Ligands, Jefferson Overlin Abaricia
Theses and Dissertations
Osseous healing is regulated by various classes of cells and signaling mechanisms. Of these, Wnt signaling has long been known to be critically important in directing the differentiation of mesenchymal stem cells (MSCs) into osteoblasts during bone healing. However, the source of these Wnt ligands is not known. Recently, a body of literature has arisen finding both beneficial and detrimental effects of macrophage-derived Wnt ligands on the regeneration of other tissues (liver, kidney, heart, and intestine), often by regulating inflammatory activation and stem cell behavior. As macrophages have been well-characterized as orchestrators of healing, their use of Wnt signaling to …
Nuclear Aurora-A Kinase-Induced Hypoxia Signaling Drives Dissemination And Metastasis In Breast Cancer.,
2021
West Virginia University
Nuclear Aurora-A Kinase-Induced Hypoxia Signaling Drives Dissemination And Metastasis In Breast Cancer., Kristina Marinak Whately
Graduate Theses, Dissertations, and Problem Reports (ETD)
Metastatic breast cancer causes the vast majority of cancer-associated deaths, especially in triple negative breast cancers (TNBC). TNBC is still poorly understood and has no effective treatment. Here we reveal that presence of Aurora-A Kinase (AURKA) in the nucleus and metastatic dissemination are molecularly connected through HIF1 (Hypoxia induced factor-1) signaling. The nuclear AURKA in the complex with constitutively expressed HIF-1β subunit activates transcription of “hypoxia induced genes” under normoxic conditions (the phenomenon called pseudohypoxia) without upregulation of oxygen-sensitive HIF-1α subunit. We uncover that AURKA preferentially binds to and phosphorylates HIF-1β, and co-localizes with HIF complex on DNA. The mass …
The Origin Of Novel Trait Inferred From Transcriptomic Analysis And A Targeted Gene Approach In The Beetle Horns.,
2021
West Virginia University
The Origin Of Novel Trait Inferred From Transcriptomic Analysis And A Targeted Gene Approach In The Beetle Horns., Naureen Fatima
Graduate Theses, Dissertations, and Problem Reports (ETD)
The origin of the evolutionary new trait (evolutionary novelty) and its subsequent evolution is of great interest for biologists in various fields, and beetle horns have been used to address this fundamental biological question. Previous studies on one of the horned beetle species, Onthophagus taurus, that utilized comparative gene expression analyses, suggested legs to be a strong candidate of the origin of horns. At the same time, their horns are secondary sexual traits whose development is regulated by the same gene (doublesex) as genitalia, which also originates from paired appendages such as legs. However, little is known …
Using Zebrafish To Elucidate The Expression And Gene Regulatory Network Of The Genomic Screen Homeobox Transcription Factors And Bring Innovative Science Learning Experiences To West Virginia,
2021
West Virginia University
Using Zebrafish To Elucidate The Expression And Gene Regulatory Network Of The Genomic Screen Homeobox Transcription Factors And Bring Innovative Science Learning Experiences To West Virginia, Rebecca Ann Coltogirone
Graduate Theses, Dissertations, and Problem Reports (ETD)
Central nervous system (CNS) development requires a code of regionally expressed transcription factors that impart initial neuronal cell identity, connectivity, and function. The absence of a transcription factor code would eliminate the neurodevelopmental logic producing diverse cell types in the CNS. Furthermore, early disruptions in transcription factor expression can affect later connectivity and function of neuronal circuits mediating sensory processing, defects in which are often observed as comorbid with various neurodevelopmental disorders (NDDs). Characterizing transcription factor expression and function is therefore an essential step in discerning the molecular mechanisms underlying human NDDs. genomic screen homeobox 1 and 2 (gsx1 …
From Inner Segment To Outer Segment: Palmitoylation Of Photoreceptor Na+, K+-Atpase And The Importance Of Prcd In Photoreceptor Outer Segment Morphogenesis,
2021
West Virginia University
From Inner Segment To Outer Segment: Palmitoylation Of Photoreceptor Na+, K+-Atpase And The Importance Of Prcd In Photoreceptor Outer Segment Morphogenesis, Emily R. Sechrest
Graduate Theses, Dissertations, and Problem Reports (ETD)
Photoreceptors are specialized neuroepithelial cells which are optimized for efficient capture of light and initiation of visual transduction. These cells have several compartments which are very important for proper visual function and segregation of cellular processes, including the outer segment (OS), inner segment (IS), nucleus, and synapse. The IS houses all of the cellular organelles and biosynthetic molecular machinery the cell requires and is the site of protein synthesis. The light-sensing OS is a highly modified, primary cilium, which contains many stacks of double membranous discs which house proteins required for formation and maintenance of OS structure, as well as …
Molecular Mechanisms Regulating Optic Fissure Fusion During Zebrafish Eye Development,
2021
University of Kentucky
Molecular Mechanisms Regulating Optic Fissure Fusion During Zebrafish Eye Development, Megan Weaver
Theses and Dissertations--Biology
Vertebrate retinal development requires timely and precise fusion of the optic fissure. Failure of this event leads to congenital vision impairment in the form of coloboma. Recent studies have suggested hyaloid vasculature to be involved in OF fusion. In order to examine this link, we analyzed optic fissure fusion and hyaloid vasculogenesis in the zebrafish pax2a noi mutant line. We first determined that pax2a-/- embryos fail to accumulate F-actin in the optic fissure prior to basement membrane (BM) degradation. Furthermore, using 3D and live imaging we observed reduced OF hyaloid vascularization in pax2a-/- embryos. When examining the connection …
Leveraging Transcriptomic Approaches To Identify Differences In Genetic Programming Driving Two Distinct Wound Healing Mechanisms, Regeneration And Fibrosis, In Acomys And Mus,
2021
University of Kentucky
Leveraging Transcriptomic Approaches To Identify Differences In Genetic Programming Driving Two Distinct Wound Healing Mechanisms, Regeneration And Fibrosis, In Acomys And Mus, Shishir K. Biswas
Theses and Dissertations--Biology
Why can some animals and others cannot? This fundamental question has fueled scientists studying regeneration for hundreds of years since early observations in crayfish, salamanders and many other organisms. While most contemporary work in regeneration is done in a handful of species including salamanders, zebrafish and flatforms, these organisms lack a closely-related, non-regenerating sister species from which unique genetic differences can be identified. Additionally, while much has been learned from these organisms, they do not share fundamental biological traits with mammals (endothermy, metabolism and immune system) which limits the ability to translate this research for clinical medicine. To this end, …
Cellular Bioenergetics Regulates Cell Proliferation During Mammalian Regeneration,
2021
University of Kentucky
Cellular Bioenergetics Regulates Cell Proliferation During Mammalian Regeneration, Sandeep Saxena
Theses and Dissertations--Biology
Mammalian system consists of stress-sensing molecules that regulates their cellular response against damage, injury and oncogenic stress. During vertebrate regeneration, cells responding to injury re-enter the cell cycle and proliferate to form new tissue. Cell cycle re-entry or arrest is at least partly regulated by cellular senescence which negatively impacts the proliferative pool of cells during regeneration. What remains unclear is whether cells in regenerating systems possess an increased propensity to proliferate and are refractory to signals that induce senescence. My thesis work has focused on how fibroblasts from the ear pinna differentially regulate healing in highly regenerative mammals (e.g., …
Special Issue: Shiga Toxin-Producing Escherichia Coli,
2021
University of Nebraska - Lincoln
Special Issue: Shiga Toxin-Producing Escherichia Coli, Rodney A. Moxley
School of Veterinary and Biomedical Sciences: Faculty Publications
Globally, Shiga toxin-producing Escherichia coli (STEC) is an important cause of diarrheal disease, most notably hemorrhagic colitis, and post-diarrheal sequela, such as hemolytic-uremic syndrome (HUS) [1]. Cattle are a major reservoir of STEC, with approx- imately half of the cases in humans attributable to foodborne exposure [2]. Prevention of human illness has mainly been through food safety measures [2]. Despite extensive research, no other generally accepted and effective preventive measures or therapies for STEC infections in human patients are available [3]. Many questions remain about STEC virulence factors, pathogenesis, detection, and other aspects that necessitate a continua- tion of basic …
Tetraspanins As Potential Therapeutic Candidates For Targeting Flaviviruses,
2021
Old Dominion University
Tetraspanins As Potential Therapeutic Candidates For Targeting Flaviviruses, Waqas Ahmed, Girish Neelakanta, Hameeda Sultana
Biological Sciences Faculty Publications
Tetraspanin family of proteins participates in numerous fundamental signaling pathways involved in viral transmission, virus-specific immunity, and virus-mediated vesicular trafficking. Studies in the identification of novel therapeutic candidates and strategies to target West Nile virus, dengue and Zika viruses are highly warranted due to the failure in development of vaccines. Recent evidences have shown that the widely distributed tetraspanin proteins may provide a platform for the development of novel therapeutic approaches. In this review, we discuss the diversified and important functions of tetraspanins in exosome/extracellular vesicle biology, virus-host interactions, virus-mediated vesicular trafficking, modulation of immune mechanism(s), and their possible role(s) …
Tick Extracellular Vesicles Enable Arthropod Feeding And Promote Distinct Outcomes Of Bacterial Infection,
2021
Old Dominion University
Tick Extracellular Vesicles Enable Arthropod Feeding And Promote Distinct Outcomes Of Bacterial Infection, Adela S. Oliva Chávez, Xiaowei Wang, Liron Marnin, Nathan K. Archer, Holly L. Hammond, Erin E. Mcclure Carroll, Dana K. Shaw, Brenden G. Tully, Amanda D. Buskirk, Shelby L. Ford, L. Rainer Butler, Preeti Shahi, Kateryna Morozova, Cristina C. Clement, Lauren Lawres, Anya J. O'Neal, Choukri Ben Mamoun, Kathleen L. Mason, Brandi E. Hobbs, Glen A. Scoles, Eileen M. Barry, Daniel E. Sonenshine, Utpal Pal, Jesus G. Valenzuela, Marcelo B. Sztein, Marcela F. Pasetti, Michael L. Levin, Michail Kotsyfakis, Steven M. Jay, Jason F. Huntley, Lloyd S. Miller, Laura Santambrogio, Joao H.F. Pedra
Biological Sciences Faculty Publications
Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting …
Microrna In The Mammalian Growth Plate: Matrix Vesicles And 1Α,25-Dihydroxyvitamin D3,
2021
Virginia Commonwealth University
Microrna In The Mammalian Growth Plate: Matrix Vesicles And 1Α,25-Dihydroxyvitamin D3, Niels C. Asmussen
Theses and Dissertations
Growth plate chondrocytes are the driving force of long bone elongation and they accomplish this vital task, in part, by producing, remodeling, and finally mineralizing the cartilage tissue that makes up the growth plate. This mineralized tissue is turned over again as bone forming cells invade and began the process of turning mineralized cartilage into bone. Chondrocytes undergo a distinct series of observable phases as they move through this process transitioning from a stage of proliferation to one of hypertrophy and finally capillary invasion. Chondrocytes produce matrix vesicles (MVs) that they release into the growth plate and that attach to …
