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Sexual Dimorphism In A Mouse Model Of Dry Eye Disease, Neal Mecum

Electronic Theses and Dissertations

Dry eye can result from multiple causes, including a reduction in the quantity or altered composition of tears. The lacrimal gland is the major supplier of the aqueous tear components, including water, electrolytes, and proteins. Reduced output from the lacrimal glands results in aqueous tear deficiency, a specific subclass of dry eye disease (DED) marked by inadequate tear volume. The prevalence of DED is 1.5-2 times greater in women than men, yet a comprehensive comparison of dry eye symptoms in male and female animals in an animal model of DED has not been performed. We excised the lacrimal gland to …

Spruce Budworm Defoliation Dynamics And Its Influence On The Acadian Forest, Cen Chen

Electronic Theses and Dissertations

Spruce budworm (SBW; Choristoneura fumiferana (Clem.)) is the primary forest defoliator in North America. SBW defoliation has affected tens of millions ha of forests during its periodic outbreaks and caused severe growth reduction and mortality of spruce-fir (Picea-Abies) species. Evaluating these damaging effects of SBW defoliation requires understandings of the variation and dynamics of defoliation, as well as trees' variable responses to defoliation in consideration of various tree- stand-, and site-level factors. In this dissertation, we developed statistical models to 1) evaluate influences of SBW defoliation on spruce-fir stand dynamics of annual volume net growth, mortality, …

Towards A Unified Disease Mechanism For Trna Synthetase-Mediated Peripheral Neuropathy, Emily L. Spaulding

Electronic Theses and Dissertations

Charcot-Marie-Tooth disease (CMT) is a debilitating inherited peripheral neuropathy resulting in progressive distal muscle atrophy and loss of sensation. CMT is genetically heterogeneous, with mutations in over 80 different genes leading to demyelinating or axonal forms. There are genetically similar subgroups, including the largest protein family implicated in the disease, the tRNA synthetases (ARSs). ARSs are responsible for aminoacylation of tRNAs during translation and are therefore ubiquitously expressed and essential proteins. Dominant mutations in at least five ARSs cause axonal forms of CMT. How mutations in ARSs cause CMT is unclear, however, the similar clinical presentation of patients suggests shared …

Genetic Analysis Of A Novel Ftsk Homolog, Hfka, In Streptomyces Coelicolor Development-Associated Chromosome Segregation, Sumedha Sethi

Electronic Theses and Dissertations

A quintessential phenomenon occurring during prokaryotic development is accurate segregation of the replicated genomes into the daughter cells. Key energy-dependent processes like chromosome condensation and subcellular partitioning of the genomes are driven by conserved proteins like SMC, ParB, FtsK. During its complex developmental cycle, Streptomyces coelicolor segregates its genomes into chains of unicellular spores when its multigenomic syncytial aerial hyphae undergo division.

A novel ftsK-like gene, hfkA (Homolog of FtsK protein A), was examined for function and localization during development-associated chromosome segregation. Individual deletions did not affect segregation, but a ΔhfkA ΔftsK mutant exhibited 8% anucleate …

Transcription Regulation Of Human Il1b Gene In Monocytes And Lymphoid Cd4 T Cells, Sree H. Pulugulla

Electronic Theses and Dissertations

Cytokines are key regulators of the inflammatory response and play an important role in facilitating intercellular communication between various immune cell types. Interleukin‑1β (IL‑1β) is a potent pro-inflammatory cytokine that is required for robust initiation of innate immune response and subsequent development of adaptive immunity. IL-1β is first synthesized as an inactive cytoplasmic, non‑glycosylated, precursor molecule (proIL‑1β) by monocytes and macrophages in response to invading pathogenic microbes. The activation of caspase‑1 by inflammasomes cleaves proIL-1β into mature biologically active IL-1β that is released from cells via a non-classical, endoplasmic reticulum‑independent secretory pathway directly from the cytoplasm via Gasdermin D membrane …

State-Dependent Mapping Of Glyr-Cholesterol Interactions By Coupling Crosslinking With Mass Spectrometry, Nicholas Ferraro

Electronic Theses and Dissertations

The glycine receptor (GlyR) belongs to a superfamily of pentameric ligand-gated ion channels (pLGICs) that mediate fast neurotransmission. GlyR typically modulates inhibitory transmission by antagonizing membrane depolarization through anion influx. Allosteric interactions between the receptor and its lipid surroundings affect receptor function, and cholesterol is essential for pLGIC activity. Human α1 GlyR was purified from baculovirus infected insect cells and reconstituted in unilamellar vesicles at cholesterol: lipid ratios below and above the cholesterol activity threshold with aliquots of azi-cholesterol. State-dependent crosslinking studies of receptors primarily in its resting (no glycine), desensitized (10mM glycine) and open (F207A/A288G, 30nM ivermectin) states were …

Genetic And Biochemical Analysis Of A Conserved, Multi-Gene System Regulation Spore-Associated Proteins In Streptomyces Coelicolor, Joseph Sallmen

Electronic Theses and Dissertations

Streptomyces coelicolor is a Gram positive, filamentous soil dwelling bacterium that exhibits a complex life cycle including the transition from a vegetative mycelium to a sporulating, aerial mycelium. Early genetic studies identified two classes of genes that resulted in developmental blocks, bald and white. The bald (bld) phenotype occurs when colonies cannot produce aerial hyphae. White (whi) colonies exhibit incomplete sporulation and/or loss of production of the concurrently produced grey pigment. While some of the original mutants have been explored, the developmental functions of many of the identified genes are not well understood. Of particular interest …

Nanomedicine-Driven Neuropathic Pain Relief In Rat Model Is Associated With Macrophage Polarity And Mast Cell Activation, Muzamil Saleem

Electronic Theses and Dissertations

We explored the immune neuropathology underlying multi-day relief from neuropathic pain in a rat model initiated at the sciatic nerve by using a nanoemulsion-based nanomedicine as a biological probe. The nanomedicine is theranostic: both therapeutic (containing celecoxib drug) and diagnostic (containing near-infrared fluorescent (NIRF) dye) and is small enough to be phagocytosed by circulating monocytes. A model of neuropathic pain is initiated by tying four 1mm spaced knots around the sciatic nerve with chromic gut suture, which results in neuroinflammation, and a resultant pain-like behavior manifests. We show that pain-like behavior reaches a plateau of maximum hypersensitivity 8 days post-surgery, …

Characterization Of The Effect Of Exercise Dose And Integrative Nonpharmacological Therapies In The Treatment Of Chronic Pain, Anna M. Polaski

Electronic Theses and Dissertations

Chronic pain includes debilitating conditions affecting large populations of people throughout the world. These diseases are further complicated by comorbid psychological disorders which make chronic pain conditions difficult to treat. Nonpharmacological treatment options have more recently become an important mainstay of effective therapies and are currently being used to supplement or replace traditional pharmacological treatment methods. Exercise-based therapies in particular are of interest due to their demonstrated success in reducing pain symptoms as well as improving psychological outcomes. Dose is an important factor in being able to effectively prescribe treatments in the context of specific exercise interventions and specific pain …

The Potential For Dickeya Dianthicola To Be Vectored By Two Common Insect Pests Of Potatoes, Jonas K. Insinga

Electronic Theses and Dissertations

Dickeya dianthicola (Samson) causing blackleg and soft rot was first detected in potatoes grown in Maine in 2014. Previous work has suggested that insects, particularly aphids, may be able to vector bacteria in this genus between plants, but no conclusive work has been done to confirm this theory. In order to determine whether insect-mediated transmission is likely to occur in potato fields, two model potato pests common in Maine were used: the Colorado potato beetle (Leptinotarsa decimlineata Say) and the green peach aphids (Myzus persicae Sulzer). Olfactometry and recruitment experiments evaluated if either insect discriminates between infected and …

The Effects Of Sediment Acidification And Temperature On The Immune Capacity Of The Atlantic Jackknife (Razor) Clam (Ensis Leei M. Huber, 2015), Brian Preziosi

Electronic Theses and Dissertations

Sediment acidification has been shown to negatively impact clams of economic importance such as the soft-shell clam, Mya arenaria Linnaeus, 1758, and hard clam, Mercenaria mercenaria (Linnaeus, 1758). Effects of sediment acidification on razor clams, including the Atlantic jackknife clam Ensis leei M. Huber, 2015, are unknown. E. leei has been identified as a species with potential for aquaculture operations on the New England coast. E. leei may be resilient to acidification and thus persist in acidified sediments where other clams cannot. To this end, the impact of acidified surface sediment on the internal immune capacity of adult (mean shell …

Validation Of A Fluorescence-Based Bacteria Enumeration And Viability Determination Method Using Image Cytometry, Matthew R. Hodgkin

Electronic Theses and Dissertations

Craft beer production in the United States has been increasing significantly in recent years. As production and participation in the industry increases, so have consumer demands for more beer options. Breweries have met this call with experimentation of ingredients in their beer and also the styles they brew. One such beer, the sour beer, is an example of this experimentation and new product development. Sour beers are a style that differ from most other beers by how they are manufactured. Instead of being fermented with only yeast, both a lactic acid-producing bacteria and yeast are used. With increased competition amongst …

Evaluating The Occurrence Of Age-Related Peripheral Neuropathy In Het3 Mice And Development Of A Whole Tissue Imaging Technique For Analyzing Total Innervation In The Subcutaneous Adipose Depot, Jake Willows

Electronic Theses and Dissertations

Adipose tissue can be characterized as either being a white (energy storing) depot or a brown (energy expending) depot and both have been found to contain dense networks of neural innervation. This adipose nerve supply regulates numerous metabolic functions and likely plays an important role in the function of adipose blood vessels. Recently our lab has shown in the C57BL/6 mouse model that peripheral neuropathy, or the dying back and dysfunction of the nerves in the superficial tissues such as the skin, can extend into the subcutaneous adipose tissue in conditions commonly associated with the neuropathic phenotype (i.e. diabetes, obesity, …

Long-Term Study Of Prescribed Fire Effects On Stand Dynamics And Oak Regeneration Potentials In Degraded Upland Oak-Hickory Stands In Northwestern Arkansas, Mason C. Danheim, Kathryn R. Kidd Dr, Hal O. Liechty Dr, Brian P. Oswald Dr

Electronic Theses and Dissertations

Upland oak-hickory forests in the Ozark Mountains of northwestern Arkansas and south central Missouri were impacted by oak decline during the early 2000s. This decline event was caused by predisposing (e.g., mature, dense stand conditions), inciting (i.e., drought), and contributing (e.g., red oak borer, E. rufulus H., outbreak) factors. Immediately following onset of the decline, substantial crown dieback and tree mortality, particularly for two red oak species (northern red oak, Quercus rubra Michx. and black oak, Q. velutina Lam.), were observed. In addition, densities of advanced oak regeneration were inadequate at this time, resulting in poor regeneration potentials for …

Fish Passage And Hydropower: Investigating Resource Agency Decision-Making During The Ferc Hydropower Relicensing Process, Sarah Vogel

Electronic Theses and Dissertations

Hydropower dams represent a significant challenge for the successful migration of sea-run fish, many species of which are in decline. Most hydropower dams in the United States are regulated by the Federal Energy Regulatory Commission (FERC), an independent federal agency responsible for granting 30 to 50-year licenses to projects for their continued operation. Licenses typically include conditions for the conservation of sea-run fish such as fish passage construction, operational changes, monitoring of effectiveness, and other mitigative conditions. While FERC remains the primary authority in licensing, the current regulatory framework stipulates input from other federal and state resource and regulatory agencies, …

Getting Over The Dam: Overcoming Institutional Barriers To The Recovery Of Atlantic Salmon By Navigating The Social-Science/Policy Interface, Melissa E. Flye

Electronic Theses and Dissertations

The term governance has undergone somewhat of an evolution since its inception, originally describing the act of governing, it has come to represent a more collaborative form of governing which is distinct from hierarchical control models (Marin and Mayntz, 1991). Collaborative governance refers to the systems associated with public policy decision making and resource management which span the jurisdictional boundaries of public agencies, levels of government, and/or public and private spheres in order to pursue a public policy goal or outcome (Emerson et al., 2012). Environmental management is often considered an inherently collaborative effort, as ecological systems and species rarely …

Identification Of Chromatin Regulators Perturbed In Hematopoietic Stem And Progenitor Cell Aging, Eraj S. Khokhar

Electronic Theses and Dissertations

As lifespan is increasing globally, there is a critical need to identify strategies to extend healthspan and prevent chronic diseases into older age. The long-term goal of my research is to identify novel strategies to ameliorate aging-induced decline in hematopoietic stem cell (HSC) function. HSCs give rise to all mature blood and immune cells. With age, HSCs undergo defects in their differentiation ability which correlates with a decline in immune function. Comprehensive knowledge of gene regulatory and epigenetic mechanisms underlying this defect is a barrier to developing therapies to ameliorate aging-associated decline in HSC function. Therefore, my project focuses on …

Spatial And Temporal Variation In The Aquatic Invertebrate Community Structure Of Rock Pools Along The Penobscot River, Maine, Chase R. Gagne

Electronic Theses and Dissertations

Pools of water that form in the fissures and depressions of rock outcrops, known as rock pools, are fairly common aquatic habitats that can easily be found along the rocky banks of many of Maine’s major rivers. In general, rock pools and the aquatic invertebrates inhabiting them have received little research attention and, though ubiquitous, have never been studied in Maine. My research addressed this knowledge gap by surveying 40 rock pools at four sites along the Penobscot River in Maine. The rock pools themselves had highly variable environmental characteristics and differed across sites and over time, especially in hydroperiod. …

Exploration Of Ataxia Telangiectasia And Rad3-Related’S (Atr’S) Role In Cell Death Regulation: Implications In Development, Cancer, And Stroke, Brian Cartwright

Electronic Theses and Dissertations

From gametogenesis until death an organism’s genome is under constant bombardment from endogenous and exogenous sources of DNA damage. To maintain genomic integrity amid this damage, cells have evolved responses which allow them to either preserve viability for recovery or initiate self-destructive pathways depending on the severity of DNA damage. One protein involved in initiating and carrying out these responses is the protein kinase ataxia telangiectasia and Rad3-related (ATR). ATR is known primarily for its regulatory role in initiating the checkpoint-signaling cascade following DNA damage and replicative stress. These signaling events lead to cell cycle arrest, DNA repair, or apoptosis …

Age And Seasonal Change In The Chronobiology Of A Spider With An Exceptionally Long-Period Circadian Clock, Shae Crain

Electronic Theses and Dissertations

This study examines locomotor activity in samples of Frontinella pyramitela collected over its active season (April-October) to investigate whether seasonality and/or age may help explain the exceptional variability typically found in spider clock systems. Despite its noteworthy variability (%CV= 7.7), we have found that Frontinella has a mean free-running period of 28.4±2.18 hours that does not significantly vary over time. There is no correlation between day length and free-running period, indicating that varying length of FRP is not a function of photoperiod length. In LD 12:12 h, the window of activity is significantly smaller in April, gradually widening as the …

A Possible Luxr Solo Type Regulator Of An Antibiotic-Like Compound From The Soil Bacterium Rhodococcus, Katelyn Sellick

Electronic Theses and Dissertations

Rhodococcus, a species of bacteria commonly found in the soil, is an under-explored producer of small bioactive compounds including siderophores, pigments and antibiotics. MTM3W5.2 is a strain of Rhodococcus that was previously discovered to produce an antibiotic-like compound that has inhibitory effects on other Rhodococcus strains, including the veterinary pathogen, R. equi. The biosynthetic gene cluster responsible for production of the antibiotic has been identified, and a small gene, BTZ20_3964 at the start of the operon is believed to be a luxR solo regulator of the gene cluster. The goal of this project was to determine this gene’s …

Therapeutic Potential Of Withaferin A Against Non-Small Cell Lung Cancer., Al Hassan Kyakulaga

Electronic Theses and Dissertations

Lung cancer is the leading cause of cancer-related deaths worldwide and in the United States. Despite recent advancements in treatment approaches, chemoresistance and metastasis remain a major therapeutic challenge. Withaferin A (WFA), a plant-derived compound has recently emerged as a promising antitumor agent. In the present study, we explored the therapeutic potential of WFA against advanced NSCLC. Briefly, WFA was evaluated for its efficacy, toxicity and pharmacokinetic properties against advanced NSCLC using in vitro and in vivo models. Two human NSCLC cell lines, H1299 and A549 were used in cell culture to determine the anticancer properties of WFA. Repeat dose …

Understanding Object Motion Encoding In The Mammalian Retina., Victor Julian Depiero

Electronic Theses and Dissertations

Phototransduction, transmission of visual information down the optic nerve incurs delays on the order of 50 – 100ms. This implies that the neuronal representation of a moving object should lag behind the object’s actual position. However, studies have demonstrated that the visual system compensates for neuronal delays using a predictive mechanism called phase advancing, which shifts the population response toward the leading edge of a moving object’s retinal image. To understand how this compensation is achieved in the retina, I investigated cellular and synaptic mechanisms that drive phase advancing. I used three approaches, each testing phase advancing at a …

The Identification Of Long Non-Coding Rna Zfas1 Through An Exploratory Rna-Sequencing Analysis And Its Association With Epithelial-To-Mesenchymal Transition In Colon Cancer Adenocarcinoma., Stephen J. O'Brien

Electronic Theses and Dissertations

Colorectal adenocarcinoma is the fourth most common cancer diagnosed worldwide and is a significant cause of morbidity and mortality. This dissertation performed an exploratory RNA-sequencing analysis comparing gene expression between colon adenocarcinoma tissue and paired normal colon epithelium. After identification of a number of lncRNAs that were increased in expression in colon adenocarcinoma compared to normal colon epithelium, we aimed to validate the expression and investigate their function in vitro. Specifically, we focused on the lncRNA ZFAS1 and its association with epithelial-to-mesenchymal transition. These studies found the following: 1. Seven candidate lncRNAs were identified from the exploratory RNA-sequencing analysis to …

Investigation Of Phosphoserine Aminotransferase 1(Psat1) In Breast Cancer Progression., Stephanie Metcalf

Electronic Theses and Dissertations

This dissertation describes my research into the involvement of phosphoserine aminotransferase 1 (PSAT1) in breast cancer progression; specifically, in triple negative breast cancer (TNBC) metastasis and endocrine resistance in estrogen receptor positive breast cancer (ER+BC). Breast cancer is the most common tumor diagnosis among women. While the overall 5-year survival for breast cancer is reaching 90%, the 5-year survival for metastatic disease is only 22%. Metastasis and endocrine resistance combined can affect over 50% of patients. One of the proteins and pathways implicated in both metastasis and endocrine resistance in breast cancer is phosphoserine aminotransferase 1 (PSAT1) and the serine …

Characterizing The Roles Of Neutral Ceramidase In Cisplatin-Induced Kidney Injury., Sophia M. Sears

Electronic Theses and Dissertations

Cisplatin is a commonly used chemotherapeutic agent with a dose-limiting nephrotoxicity. 30% of patients given cisplatin develop acute kidney injury (AKI). AKI increases risk of chronic kidney disease (CKD) development and mortality. Patients that don’t develop clinical AKI are still at risk for long term declines in renal function. Currently, there are no FDA approved agents to treat or prevent cisplatin-induced kidney injury (CDDP-KI). In this study, we demonstrated that neutral ceramidase (nCDase) knockout provides protection from AKI in the high-dose model of CDDP-KI. However, in the repeated low dose cisplatin (RLDC) model of injury and we found nCDase knockout …

The Training Of A Para Powerlifter: A Case Study Of Adaptive Monitoring, Training And Overcoming, Derek Wilcox

Electronic Theses and Dissertations

Paralympic athletes (PA) appear to be more prone to chronic overuse injuries from daily wheelchair or crutch use. Over half of these injuries are shoulder related which can deleteriously impact quality of life. Adaptive powerlifters (AP) are a subdivision of Paralympic athletes and are at a higher risk for catastrophic injuries as compared to their counterparts, due to the compound of fatigue and lifting of maximal weights. For this reason, it is vital to have well-designed training plans for these athletes in order to preserve quality of life and maximize performance in competition. Unfortunately, there is a lack of literature …

Role Of Topoisomerase Ii Alpha In Dna Topology And T Cell Responses During Chronic Viral Infections, Stella Chinyere Ogbu

Electronic Theses and Dissertations

The clearance of viruses is largely dependent upon the activation of T cells to generate a robust immune response. However, host responses are suppressed during chronic viral infections. In this thesis, we explored the role of Top2α in DNA topology in individuals with chronic HBV, HCV, and HIV infections. We found that Top2α protein expression and activity were low in T cells derived from chronically virus-infected individuals compared to healthy subjects. Using CD4⁺ T cells treated with Top2α inhibitor or poisoner as a model, we demonstrated that Top2α inhibition disrupts the DNA topology, suppresses DNA repair kinase (ATM), and …

Visitor Characteristics, Attitudes, And Management Preferences Of The Bob Marshall Wilderness Complex, Samuel J. Rhodes

Electronic Theses and Dissertations

The Bob Marshall Wilderness Complex (BMWC) encompasses 3 federal wilderness areas and spans over 1.5 million acres of iconic mountains and valleys in northwestern Montana. Here visitors can find a plethora of recreation opportunity that give access to some of the most rugged country that can be found in the lower 48 states. However, managing wilderness areas comes with the challenge of both preserving the natural resources found within their borders and enabling opportunities for recreational experiences. Wilderness social scientists always have striven to determine the type of visitors coming to wilderness, and see what sorts of experiences they pursue. …

Dynamic Regulation Of G-Protein Signaling, William C. Simke

Electronic Theses and Dissertations

G protein-coupled receptors (GPCRs) are involved in numerous signaling processes ranging from neuronal growth to immune cells tracking invaders. GPCR signaling plays a role in many human diseases and thus GPCRs are important drug targets. Yeast respond to mating pheromone using a GPCR signaling system homologous to those used in humans to polarize their cytoskeleton toward the pheromone source. This is accomplished by initializing a MAPK signaling cascade to arrest the cells in mitosis and upregulate expression of chemotropic proteins. Pathway desensitization is accomplished by the Regulator of G-protein Signaling (RGS). RGS abrogates signaling by binding to the active GPCR, …