Life Sciences Commons^™

The Influence Of Metacommunity Size On Species Diversity Across Spatial Scales, Lauren Woods

Arts & Sciences Electronic Theses and Dissertations

This dissertation explores the influence of metacommunity size and landscape level processes, such as dispersal, on species diversity. A metacommunity is a group of local communities, or patches, connected by dispersal, and metacommunity size can be defined as the number of discrete local patches within a metacommunity. In chapter 1, I developed a framework to predict the effects of habitat destruction, or a reduction in metacommunity size, on the species richness of local patches of different sizes by integrating metacommunity theory with the equilibrium theory of island biogeography. The effect of metacommunity size on species richness in small and large …

Modulation Of Nmda Receptor Activity During Physiological And Pathophysiological Events, Christine Marie Emnett

Arts & Sciences Electronic Theses and Dissertations

N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors that serve crucial signaling and neurotrophic functions throughout the central nervous system. Both hyperfunction and hypofunction of NMDARs are associated with neurological and neuropsychiatric conditions. Thus, both positive and negative pharmacological NMDAR modulators are of clinical interest as treatments. Understanding drug mechanisms could lead to more rational drug design. Memantine and ketamine are NMDAR open channel blockers that exhibit similar pharmacodynamics at NMDARs but have different clinical uses. Memantine improves cognitive decline during Alzheimer's disease. Ketamine is an anesthetic and analgesic with psychotomimetic effects, but it is also a rapid acting and long-lived …

The Genetic Architecture And Evolution Of Brain Cortical Folding In A Pedigreed Primate Population, Elizabeth Grace Atkinson

Arts & Sciences Electronic Theses and Dissertations

Elevated neurological faculty, related to the dramatic increase in brain volume, is a hallmark of the primates. Cognitive capacity, the processing power and speed of the brain, is directly related to the number of neurons in the cerebral cortex and the connectivity network underlying information processing in the brain. Increased cortical folding (gyrification) allows for more neurons to be contained within the volume of the braincase and the arrangement of folds and ridges across the cerebral cortex is an indication of the underlying neural network connecting regions. The goal of this dissertation is to develop a better understanding of the …

Development Of Polarizable Force Field Models For Transition Metal Ions, Jin Yu Xiang

Arts & Sciences Electronic Theses and Dissertations

This dissertation focuses on the development of polarizable molecular mechanics (MM) force field models for the third-row transition metal (TM) ions. These TM ions perform important structural and chemical functions in a wide range of organic and biological environments because of the unique properties of the 3d orbitals. Being able study these systems in silico can provide a tremendous amount of information that is difficult to obtain through experiments. However, the standard treatment of ions in traditional MM models has shown to be insufficient for describing the d-shell electronic effects. In this work, empirical models for TM electronic effects are …

Type 1 Diabetes And The Male Reproductive Axis, Erica Schoeller

Arts & Sciences Electronic Theses and Dissertations

Glucose regulation is important in both spermatogenesis as well as mature sperm function. The impact of diabetes on sperm function is becoming increasingly clear, though much work is still needed to elucidate the mechanism by which diabetes impairs spermatogenesis. Diabetes causes disruptions in the hypothalamic pituitary gonadal (HPG) axis, the regulatory system that controls reproduction. The HPG axis functions by secreting GnRH pulses from the hypothalamus, which bind to receptors on the pituitary and cause secretion of follicle stimulating hormone and luteinizing hormone, which then bind to receptors in the testes and facilitate spermatogenesis. Type 1 diabetes can severely impact …

Dysfunctional Gene Regulation Of The Meiotic Program In An Interspecific Yeast Hybrid, Devjanee Swain Lenz

Arts & Sciences Electronic Theses and Dissertations

Speciation, the evolutionary process by which species arise, is a fundamental biological concept. One of the major goals of evolutionary genetics is to understand the genetic basis of reproductive isolation (RI), a collection of barriers that prevents two species from forming viable or fertile hybrids. Given the lack of viable or fertile hybrid progeny, identifying genes that impact RI as well as their functions has been difficult. Thus we lack a view of the total genetic contribution to RI. Recently the budding yeast Saccharomyces has served as an evolutionary model, as abundant sequence, expression, and phenotypic data exist for the …

The Uropathogenic Escherichia Coli Effector Ybcl Modulates The Innate Immune Response In The Urinary Tract, Megan Elizabeth Lau

Arts & Sciences Electronic Theses and Dissertations

Uropathogenic Escherichia coli (UPEC) are the primary etiology of urinary tract infections (UTIs), one of the most common bacterial infections afflicting the human population. While UPEC cause disease throughout the urinary tract, bladder infection, or cystitis, is most prevalent. A key aspect of UPEC pathogenesis in the bladder is the modulation of the host inflammatory response. At acute time points, UPEC delay the arrival of immune cells, such as neutrophils, to the bladder. The lack of neutrophils in the bladder lumen enables UPEC to replicate freely in the urine and invade the bladder epithelium, a requirement for bacterial persistence, in …

Post-Translational Regulation Of Fas-Mediated Pparα Activation, Anne Patricia Louise Jensen-Urstad

Arts & Sciences Electronic Theses and Dissertations

The liver is a central organ to whole-body metabolism and mediates many of the adaptive responses to changes in nutrient availability, such that the appropriate energy sources are used and blood glucose levels maintained, whether directly after a meal or after a twelve-hour fast. The adaptive responses to fasting in liver are largely mediated by the nuclear receptor peroxisome proliferator-activated receptor α, or PPARα.

PPARα can be activated by a de novo synthesized lipid ligand—16:0/18:1- glycerophosphocholine (16:0/18:1-GPC)—the synthesis of which is dependent on fatty acid synthase (FAS), but little is known about the regulation of this pathway. My thesis focused …

The Natural Variants Of The Streptococcus Nad+-Glycohydrolase Spn Modulate Divergent Host Cell Signaling Pathways And Death, Sukantha Chandrasekaran

Arts & Sciences Electronic Theses and Dissertations

Streptococcus pyogenes has an arsenal of virulence factors that promote its ability to cause a broad range of diseases and fight host defenses. One of these factors is the S. pyogenes NAD+-glycohydrolase (SPN), which is secreted from the bacterial cell and translocated into the host cell cytosol where it contributes to cell death. Every strain examined to date has SPN and recent studies suggest that SPN is continuing to evolve diverging into two variants that correlate with tissue tropism, one of which lacks the signature NADase activity. SPN's roles in both cytotoxicity and niche selection are unknown. To gain insight …

Quantification Of Conformational Heterogeneity And Its Role In Protein Aggregation And Unfolding, Nicholas J. Lyle

Arts & Sciences Electronic Theses and Dissertations

Proteins can exhibit significant conformational heterogeneity either under denaturing conditions or in aqueous solutions. The latter is true for a class of proteins whose sequences predispose them to form heterogeneous ensembles of conformations. Characterization of conformational heterogeneity in a protein ensemble requires the quantification of the amplitudes of spontaneous fluctuations in conjunction with information regarding coarse grain measures that report on the average sizes, shapes, and densities. This often demands multiplexed experimental approaches whose readouts are interpreted or annotated using ensembles drawn from atomistic or coarse grain computational simulations. Efforts to characterize conformational heterogeneity contribute directly to our understanding of …

Urine Trouble: A Molecular And Anatomical Examination Of Bladder Pain, Lara Wiley Crock

Arts & Sciences Electronic Theses and Dissertations

Interstitial cystitis or painful bladder syndrome (IC/PBS) is a chronic pain syndrome affecting 3-6% of women in the US. Some evidence suggests urothelial injury may cause some cases of IC/PBS. To examine how urothelial injury modulates bladder pain, three injury models were used: Infection with uropathogenic Escherichia coli (UPEC, inflammatory), Protamine sulfate (PS, non-inflammatory chemical), and lipopolysaccharide (LPS, non-infectious and inflammatory) treatment. Surprisingly, injury with PS decreased, while UPEC alone increased the pain response to bladder distention. These data suggest that changes in the urothelium may modulate some forms of IC/PBS. However, in most cases, patients with IC/PBS have no …

A Ranksum Statistics Based Framework To Decipher Transcription Regulation, Iuan-Bor Chen

Arts & Sciences Electronic Theses and Dissertations

The unbiased generation of specific and meaningful hypotheses from the deluge of data generated by modern genomic methods remains a challenge. These datasets require increasing level of expertise to analyze fully, and are often underutilized even in the originating lab. It would be desirable to have a computational strategy that is easy to implement, robust against outliers and missing data, and broadly applicable to diverse experimental designs. In this dissertation, I present a set of ranksum statistics-based analytical methods as a framework to extract testable hypotheses from large and complex datasets. To illustrate its utility, this framework was applied to …

Cell Culture Models Of Genetic Variation, Joshua T. Witten

Arts & Sciences Electronic Theses and Dissertations

Studying genetic variation presents a dilemma. While the genetic variation of greatest interest is that causing variation in traits and disease risk in natural populations, natural populations have characteristics that make them challenging to study. In this work, I have assessed the use of cell culture methods as a solution to some of these challenges. In particular, I studied genetic variation in the budding yeast Saccharomyces cerevisiae that was generated by selection in the lab as a model for natural genetic variation. I have found that even simplistic selection programs in the laboratory, including the use of chemical mutagenesis to …

Identifying And Characterizing Arabidopsis Jasmonate Signaling Components Manipulated By Pseudomonas Syringae, Neva Laurie-Berry

Arts & Sciences Electronic Theses and Dissertations

Jasmonate signaling is critical for susceptibility of Arabidopsis thaliana to the bacterial pathogen Pseudomonas syringae, as demonstrated by the reduced susceptibility of coil mutant plants. The infection responses of another jasmonate-insensitive mutant, jinl, had previously been unknown. This work demonstrates that susceptibility to P. syringae requires activity of the transcription factor JTN1/MYC2. Reduced susceptibility correlates with reduced sensitivity to the P. syringae phytotoxin coronatine, a molecular mimic of the endogenous jasmonate JA-Ile. The reduced susceptibility of jinl mutant plants correlates with increased salicylic acid (SA)-dependent signaling. Analysis of jinl plants carrying the sidl mutation, resulting in decreased S A synthesis …