Developing Synthetic Strategies For Multifaceted Applications Of Stable Gold-Based Complexes,
2021
University of Kentucky
Developing Synthetic Strategies For Multifaceted Applications Of Stable Gold-Based Complexes, Randall Tyler Mertens
Theses and Dissertations--Chemistry
Development of stable gold-based complexes has been a rapidly advancing field due to the popularity of gold complexes, particularly for use in biomedical research and catalytic transformations. Given that auranofin, a gold(I) complex with FDA approval for the treatment of rheumatoid arthritis is used in the clinic, the development of stable gold-based molecules of clinical relevance is urgently needed. Herein are reported, synthetic strategies used for the development of new classes of gold(I) and gold(III) complexes for advancement in mitochondrial modulation for use as chemotherapeutics as well as application to gold catalysis due to the unique geometry of complexes presented …
An Investigation Of The Role Of Basigin-Variant-1 In The Immune Response Within The Retina,
2021
University of North Florida
An Investigation Of The Role Of Basigin-Variant-1 In The Immune Response Within The Retina, Abigail D. Tompa
UNF Graduate Theses and Dissertations
The neural retina is considered an immune privileged area, in that the eye attempts to suppress the inflammatory response to preserve vision. If there is damage to the blood-retina barrier, such as in diabetes or macular degeneration, it is possible for monocytes to travel out of the blood vessels and into the retina. While studying retinoblastoma, a research group determined that the protein, Basigin, through its extracellular domain, elicits an immune response by enhancing transcription of the pro-inflammatory cytokine interleukin-6 (IL-6). Basigin is cell adhesion molecule that belongs to the immunoglobulin superfamily. The Basigin gene has two main transcripts, that …
Characterization Of Alcohol-Mediated Promotion Of Breast Cancer Stem Cells,
2021
Loyola University Chicago
Characterization Of Alcohol-Mediated Promotion Of Breast Cancer Stem Cells, Mckenna Below
Master's Theses
Breast cancer is the leading cause of cancer-related death in women globally, and one in eight women will be diagnosed with breast cancer at some point in her life. Alcohol consumption has been linked to increase breast cancer risk and increased risk of tumor recurrence. Understanding the molecular mechanisms of modifiable lifestyle factors such as alcohol consumption will help to lower these risks and design more effective therapeutic approaches. Estrogen Receptor positive (ER+) breast cancer comprises approximately 70% of all breast cancers, and these tumors are effectively targeted by endocrine therapy in the form of estrogen deprivation with aromatase inhibitors, …
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 …
Prolactin Drives A Dynamic Stat5a/Hdac6/Hmgn2 Cis-Regulatory Landscape Exploitable In Er+ Breast Cancer,
2021
Virginia Commonwealth University
Prolactin Drives A Dynamic Stat5a/Hdac6/Hmgn2 Cis-Regulatory Landscape Exploitable In Er+ Breast Cancer, Justin M. Craig
Theses and Dissertations
The hormone prolactin has been implicated in breast cancer pathogenesis and regulates chromatin engagement by the transcription factor, STAT5A. STAT5A is known to inducibly bind promoters and cis-regulatory elements genome-wide, though the mechanisms by which it exerts specificity and regulation of target gene expression remain enigmatic. We previously identified HDAC6 and HMGN2 as cofactors that facilitate prolactin induced, STAT5A mediated gene expression. Here, multi-condition STAT5A, HDAC6, and HMGN2 ChIP-seq with parallel condition RNA-seq are utilized to reveal the cis-regulatory landscape and cofactor dynamics underlying prolactin stimulated gene expression in breast cancer. We find that prolactin regulated genes are …
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 …
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 …
Development Of Adjunctive Agents For Difluoromethylornithine Anti-Cancer Therapy,
2021
University of Central Florida
Development Of Adjunctive Agents For Difluoromethylornithine Anti-Cancer Therapy, Aiste Dobrovolskaite
Electronic Theses and Dissertations, 2020-2023
The native polyamines putrescine, spermidine, and spermine are small positively-charged molecules that can interact with negatively-charged macromolecules like DNA, RNA and proteins. These interactions aid in nucleic acid and protein conformational stability, thereby, making polyamines essential building blocks for cells. Polyamines are involved in various cellular functions including gene regulation, protein synthesis, and cell proliferation. Rapidly-proliferating cells, such as cancer cells, utilize high polyamine levels for cell growth. Targeting the polyamine addiction of cancers is a validated anti-cancer strategy. To achieve the maximal reduction of polyamine levels, polyamine blocking therapy (PBT) employs several compounds in combination. First, one can inhibit …
Monitoring Stem Cell Differentiation Using Raman Microspectroscopy: Chondrogenic Differentiation, Towards Cartilage Formation,
2021
Technological University Dublin
Monitoring Stem Cell Differentiation Using Raman Microspectroscopy: Chondrogenic Differentiation, Towards Cartilage Formation, Francesca Ravera, Esen Efeoglu, Hugh Byrne
Articles
Mesenchymal Stem Cells (MSCs) have the ability to differentiate into chondrocytes, the only cellular components of cartilage and are therefore ideal candidates for cartilage and tissue repair technologies. Chondrocytes are surrounded by cartilage-like extracellular matrix (ECM), a complex network rich in glycosaminoglycans, proteoglycans, and collagen, which, together with a multitude of intracellular signalling molecules, trigger the chondrogenesis and allow the chondroprogenitor to acquire the spherical morphology of the chondrocytes. However, although the mechanisms of the differentiation of MSCs have been extensively explored, it has been difficult to provide a holistic picture of the process, in situ. Raman Micro Spectroscopy (RMS) …
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 …
Nucleus Type-Specific Dna Methylomics Reveals Epigenetic “Memory” Of Prior Adaptation In Skeletal Muscle,
2021
University of Kentucky
Nucleus Type-Specific Dna Methylomics Reveals Epigenetic “Memory” Of Prior Adaptation In Skeletal Muscle, Yuan Wen, Cory M. Dungan, C. Brooks Mobley, Taylor Valentino, Ferdinand Von Walden, Kevin A. Murach
Health, Human Performance and Recreation Faculty Publications and Presentations
Using a mouse model of conditional and inducible in vivo fluorescent myonuclear labeling (HSA-GFP), sorting purification of nuclei, low-input reduced representation bisulfite sequencing (RRBS), and a translatable and reversible model of exercise (progressive weighted wheel running, PoWeR), we provide the first nucleus type-specific epigenetic information on skeletal muscle adaptation and detraining. Adult (>4 mo) HSA-GFP mice performed PoWeR for 8 wk then detrained for 12 wk; age-matched untrained mice were used to control for the long duration of the study. Myonuclei and interstitial nuclei from plantaris muscles were isolated for RRBS. Relative to untrained, PoWeR caused similar myonuclear CpG …
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 …
Investigating The Antitumor Effects Of A Dsrna-Nanoparticle Complex In An In Vitro Ovarian Cancer Model,
2021
Wilfrid Laurier University
Investigating The Antitumor Effects Of A Dsrna-Nanoparticle Complex In An In Vitro Ovarian Cancer Model, Aaron Lewis
Theses and Dissertations (Comprehensive)
An estimated 1 in 70 women will be diagnosed with ovarian cancer in their lifetime. Despite advanced detection and treatment methods, it remains a silent killer with an expected survival rate of 50%. A developing method in cancer treatment is the use of compounds that stimulate the immune system to aid in the body's fight against the disease. This project focused on the use of the potent immune stimulant double-stranded RNA (dsRNA), commercially available as polyinosinic:polycytidylic acid, poly(I:C), to induce cytotoxicity in two ovarian cancer cell lines; SKOV-3 and OVCAR-3. Some challenges exist with the delivery of dsRNA due to …
Visual Arts Enhance Instruction In Observation And Analysis Of Microscopic Forms In Developmental And Cell Biology,
2020
Loyola Marymount University
Visual Arts Enhance Instruction In Observation And Analysis Of Microscopic Forms In Developmental And Cell Biology, Max Ezin, Christina Noravian, Amira Mahomed, Adam Lyle, Aveleen Gill, Tamira Elul
The Transdisciplinary STEAM+ Journal
Two important skills for scientists in developmental and cell biology, as well as in fields such as neurobiology, histology and pathology, are: 1) observation of features and details in microscopic images of cells, and 2) quantification of cellular features observed in microscopic images. However, current training in developmental and cell biology does not emphasize observation and quantitative analysis of microscopic images, and it is unclear how best to teach students these skills. Here, we describe our experiences applying visual artistic approaches to instruct undergraduate and graduate students in how to observe and analyze cellular forms in microscopic images. At Loyola …
Epidemiology Of Non-Alcoholic Fatty Liver Disease And Risk Of Hepatocellular Carcinoma Progression,
2020
Sentara Virginia Beach General Hospital
Epidemiology Of Non-Alcoholic Fatty Liver Disease And Risk Of Hepatocellular Carcinoma Progression, Krishna Chaitanya Thandra, Adam Barsouk, Kalyan Saginala, John Sukumar Aluru, Prashanth Rawla, Alexander Barsouk
Kimmel Cancer Center Faculty Papers
Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. Its incidence has grown alongside the increasing global prevalence of type 2 diabetes, obesity, and metabolic syndrome. The risk of progression to hepatocellular carcinoma for nonalcoholic steatohepatitis patients over 5 years is 8%, and despite targeted and immunotherapy treatment advances, HCC maintains a bleak 5-year survival of 19%. NAFLD’s primary risk factors are components of metabolic syndrome as well as possible sleep disturbances. NAFLD is most common among men 50-60 years of age, though incidence in women catches up after menopause. In the US, Hispanics are …
Molecular Signatures Of Sexual Communication In The Phlebotomine Sand Flies,
2020
University of Kentucky
Molecular Signatures Of Sexual Communication In The Phlebotomine Sand Flies, Paul V. Hickner, Nataliya Timoshevskaya, Ronald J. Nowling, Frédéric Labbé, Andrew D. Nguyen, Mary Ann Mcdowell, Carolina N. Spiegel, Zainulabeuddin Syed
Biology Faculty Publications
Phlebotomine sand flies employ an elaborate system of pheromone communication wherein males produce pheromones that attract other males to leks (thus acting as an aggregation pheromone) and females to the lekking males (sex pheromone). In addition, the type of pheromone produced varies among populations. Despite the numerous studies on sand fly chemical communication, little is known of their chemosensory genome. Chemoreceptors interact with chemicals in an organism’s environment to elicit essential behaviors such as the identification of suitable mates and food sources. Thus, they play important roles during adaptation and speciation. Major chemoreceptor gene families, odorant receptors (ORs), gustatory receptors …
Modeling By Disruption And A Selected-For Partner For The Nude Locus,
2020
State University of New York Downstate Health Sciences University
Modeling By Disruption And A Selected-For Partner For The Nude Locus, Jian Li, Yun-Kyoung Lee, Wenyu Fu, Anne M. Whalen, Mario C. Estable, Laurel A. Raftery, Kristin White, Lorin Weiner, Janice L. Brissette
Life Sciences Faculty Research
A long‐standing problem in biology is how to dissect traits for which no tractable model exists. Here, we screen for genes like the nude locus (Foxn1)—genes central to mammalian hair and thymus development—using animals that never evolved hair, thymi, or Foxn1. Fruit flies are morphologically disrupted by the FOXN1 transcription factor and rescued by weak reductions in fly gene function, revealing molecules that potently synergize with FOXN1 to effect dramatic, chaotic change. Strong synergy/effectivity in flies is expected to reflect strong selection/functionality (purpose) in mammals; the more disruptive a molecular interaction is in alien contexts (flies), the more beneficial it …
Arp2/3-Independent Wave/Scar Pathway And Class Xi Myosin Control Sperm Nuclear Migration In Flowering Plants,
2020
University of Kentucky
Arp2/3-Independent Wave/Scar Pathway And Class Xi Myosin Control Sperm Nuclear Migration In Flowering Plants, Mohammad F. Ali, Umma Fatema, Xiongbo Peng, Samuel W. Hacker, Daisuke Maruyama, Meng-Xiang Sun, Tomokazu Kawashima
Plant and Soil Sciences Faculty Publications
After eukaryotic fertilization, gamete nuclei migrate to fuse parental genomes in order to initiate development of the next generation. In most animals, microtubules control female and male pronuclear migration in the zygote. Flowering plants, on the other hand, have evolved actin filament (F-actin)-based sperm nuclear migration systems for karyogamy. Flowering plants have also evolved a unique double-fertilization process: two female gametophytic cells, the egg and central cells, are each fertilized by a sperm cell. The molecular and cellular mechanisms of how flowering plants utilize and control F-actin for double-fertilization events are largely unknown. Using confocal microscopy live-cell imaging with a …
A Molecular Toolset For The In Vivo Detection Of A Sulfolobus Islandicus Leucyl Trna Synthetase Paralog,
2020
Illinois State University
A Molecular Toolset For The In Vivo Detection Of A Sulfolobus Islandicus Leucyl Trna Synthetase Paralog, Nicholas Michael Bretz
Theses and Dissertations
An ancient and ubiquitous set of enzymes known as the aminoacyl-tRNA synthetases are required for the viability of all organisms. The aminoacyl-tRNA synthetases catalyze the attachment of amino acids onto tRNA molecules. The aminoacylated, or charged, tRNA is then transported and utilized at the ribosome for the synthesis of proteins. The genome of the hyperthermophilic microorganism Sulfolobus islandicus (S. islandicus) harbors a unique leucyl-tRNA synthetase paralog, LeuRS-I, of unknown function. While its duplicate, LeuRS-F, carries out all the classical functions of LeuRS-family enzymes, LeuRS-I fails to charge leucine onto tRNALeu, despite its ability to activate this amino acid and bind …
