Gonadotropin-releasing hormone (GnRH) neurons are able to trigger the release of luteinizing hormone and follicle-stimulating hormone which control the maturation of oocytes and ovulation which is vital for reproduction. They are the most downstream neurons that project to the median eminence into the pituitary portal where they release GnRH. Modulation...
Estradiol (E2) plays a role in positive and negative feedback mechanisms of the hypothalamic-pituitary-gonadal (HPG) axis in female mammals. These mechanisms are regulated by two different populations of kisspeptin (KP)-producing neurons: anteroventral periventricular (AVPV) neurons, which are stimulated by E2, and arcuate (arc) neurons, which are inhibited by E2. AVPV...
Estrogen (E2) is essential for multiple physiological effects in females, ensuring maximum reproductive fitness and maintaining skeletal homeostasis. E2 has been shown to stimulate cancellous bone formation via activation of estrogen receptor alpha (ERα), an effect widely accepted to be mediated directly at bone. A recent landmark study by Herber...
Aging is a major risk factor for the deterioration of biochemical pathways that lead to many chronic neurodegenerative disorders (i.e. Parkinson’s and Alzheimer's Disease). Cellular senescence is a hallmark of aging, a condition characterized by stable growth arrest resulting in a cell that no longer divides, but is metabolically active....
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KathyMagnusson, Committee Member, representing Biomedical Sciences, College of
Veterinary
Zinc is an important micronutrient involved in many cellular processes, including those part of immune function; however, about 15% of the US population is at risk for marginal zinc deficiency. This can lead to immune system complications including the generation of inflammatory cytokines. Aging is another factor that worsens the...
Multicellular coordination in response to environmental stimuli is essential in biology, and this coordination is often achieved by a division of labor to establish leaders and followers in a cell population. This is called emergent leadership, but how a cell adopts its role and effectively exchanges information with peers is...
Radiation exposure to the brain can occur from a variety of events, including space missions, nuclear accidents, and clinical treatments. The effects of high dose radiation are well studied, but those of lower dosage are more elusive. Decline of memory and cognition is observed in patients exposed to low dose...
Age-related diseases have been associated with chronic inflammation and impaired immune response, one of the hallmarks of aging. Aging individuals also have a higher susceptibility to zinc deficiency. The effects of zinc deficiency share many commonalities with the effects of aging on the immune system and zinc deficiency may be...
Gut-brain communication consists of bidirectional routes between cognitive centers of the brain and peripheral intestines. This bidirectional communication is the result of the interplay between enteroendocrine cells (EECs), enteric nervous system, central nervous system, the vagus nerve, and our microbiota. Multiple studies have associated gut microbial dysbiosis with neurological disorders...
Alzheimer’s Disease (AD) is a neurodegenerative pathology currently affecting nearly 44 million individuals worldwide, yet there are not currently any effective treatments or preventions for AD despite the rapid development in our understanding of the disease over the last four decades. The medical and sanitary innovations of the last century...
Otoferlin is a C2-domain, transmembrane protein whose mutated form is responsible for the DFNB9 subtype of prelingual hearing impairment. Mutations in otoferlin cause an autosomal recessive, non-syndromic form of deafness that is characterized by auditory neuropathy/ auditory dissynchrony (AN/AD), meaning that the outer hair cells (OHCs) are normal, and the...
Cervical cancer is the fourth most common cancer in women worldwide with human papillomavirus (HPV) being the main cause of the disease. Currently available treatment methods are limited and emphasize the need for discovery of new therapies that improve patient outcome. Chromosomal amplifications have been identified as a source of...
Cancer is the second leading cause of death in the United States. To date, over 60% of current anticancer drugs were inspired by the discovery of chemical structure from nature, commonly known as a natural product. This work represents the biological characterization of several marine natural product compounds and their...
Cognitive impairment, or cognitive decline, a noticeable and measurable decline in cognitive abilities (e.g. memory and learning) that exceeds those attributed to normal aging, represents an early symptom of neurodegeneration and increased risk for progression to more severe dementias, such as Alzheimer's disease (AD). While the complex etiology of these...
Plethodontid salamanders have served as an informative vertebrate system for studying the role of chemical signals in facilitating social and reproductive behaviors. Individuals produce complex mixtures of chemicals from multiple glandular regions. In total, these secretions convey a wide variety of information, and are important for numerous inter- and intraspecific...
Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by neuromuscular junction decay, motor neuron death, progressive paralysis, and eventually death of the individual, usually by respiratory failure. Oxidative stress is a prominent hallmark of the disease and is often accompanied and exacerbated by mitochondrial dysfunction and neuroinflammation. This...
Cnidarians, such as corals and sea anemones serve as hosts to a variety of organisms including symbiotic dinoflagellates, bacteria, virus, and apicomplexans. As corals are vital to the health and productivity of the reef ecosystem it is important to understand how these organisms interact with each component of the holobiont....
The intracellular mutualism between cnidarians and photosynthetic dinoflagellates (genus Symbiodinium) is responsible for the physical and trophic structure of diverse coral reef ecosystems. This relationship, based on nutrient exchange, allows for high productivity in tropical waters, which are generally nutrient-poor environments. Numerous environmental stressors currently threaten the health of corals,...
EF-hand proteins are a conserved family of proteins that are modulated by divalent cations and regulate diverse cellular activities. In the present study we characterized the molecular determinants of myosin regulatory light chain (RLC) interaction with several subunits of the N-methyl-D-aspartate (NMDA)-type glutamate receptor. Myosin RLC is an EF-hand protein...
Altogether, this dissertation highlights the value of mass spectrometry-based analysis of intact proteins for solving problems related to understanding disease mechanisms and developing new therapeutics.
Mutations to the antioxidant enzyme Cu, Zn Superoxide Dismutase (SOD1) perturb protein structure in vivo to cause 2-5% of amyotrophic lateral sclerosis (ALS) cases. Metal-deficient...
Circadian clocks coordinate molecular, cellular, physiological, and behavioral processes with the 24-hour solar day. While clock functions are well understood in young animals, it is not clear how aging or neurodegenerative disease affects the various levels of the circadian system. A common symptom of many neurodegenerative diseases including Alzheimer’s disease...
Auditory defects and disorders are prevalent at all ages and affect 8% of the population in developed nations including newborns and children. Congenital hearing loss is the most common birth defect and it is estimated that 1 in 1000 children are affected by deafness at birth or before the onset...
The human cathelicidin antimicrobial peptide (CAMP) is a broad spectrum microbicidal agent and modulator of both the innate and adaptive immune system. It is induced by 1,25-dihydroxyvitamin D (1,25(OH)₂D₃) through activation of the vitamin D receptor (VDR) and primary bile salts through activation of the xenobiotic nuclear receptor farnesoid X...
Circadian clocks are endogenous molecular mechanisms that coordinate daily rhythms in gene expression, cellular activities, and physiological functions with external day/night cycles. Breakdown of circadian rhythms such as sleep/wake cycles is associated with the onset of several neurological diseases; however, it is not clear whether disruption of rhythms is a...
Coibamide A is a methyl-stabilized cyclic depsipeptide with a lariat side chain that was isolated from a marine cyanobacterium as part of an International Cooperative Biodiversity Groups program based in Panama. Previous testing of this potent and selective growth-inhibitory agent in the National Cancer Institute (NCI) in vitro 60 human...
Sexual selection can influence the mating system of an organism through multiple mechanisms. These mechanisms result in variation in reproductive success among individuals, and include scramble competition, endurance rivalries, contests, mate choice and cryptic choice, and sperm competition. Understanding the mating system of a species requires the identification of which...
Darwin devised the evolutionary theory of sexual selection to account for the manifold extravagances of courtship behaviors and displays. Mating interactions represent a major evolutionary process driving the elaboration, vibrancy, and peculiarity of these courtship traits. For my dissertation research, I strived to elucidate the dynamics that constitute the complex...
In this dissertation I study evolutionary patterns at genes encoding antimicrobial peptides (AMPs) in frogs. AMPs are short, amphipathic, cationic, secreted proteins that kill bacteria and other pathogens through a non-catalytic mechanism that involves
binding to and disrupting the microbial cell membrane. In many animal taxa, positive selection is much...