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Articles 811 - 838 of 838
Full-Text Articles in Biology
Molecular And Epigenetic Regulation Of Stem Cell Radiosensitivity, Keith Michael Jacobs
Molecular And Epigenetic Regulation Of Stem Cell Radiosensitivity, Keith Michael Jacobs
Arts & Sciences Graduate Student Theses and Dissertations
Normal tissue injury resulting from ionizing radiation (IR) during cancer radiotherapy has been attributed to reduced regenerative capacity of stem cell compartments. Utilizing multiple in vivo tissue niches and primary culture models, we demonstrate that normal stem cells are highly radiosensitive while their isogenic, directly differentiated progeny are radioresistant. Stem cell dropout is therefore likely responsible for the resulting radiation injury in these niches. This differential radiosensitivity is independent of proliferation status, and increased IR-induced apoptosis in stem cells is more broadly distributed across the cell cycle.We elucidate that stem cells exhibit an attenuated DDR resulting in aberrant cell cycle …
Melittin-Derived Peptides For Sirna Delivery: Mechanisms Of Efficient Cytoplasmic Release, Kirk Kohwa Hou
Melittin-Derived Peptides For Sirna Delivery: Mechanisms Of Efficient Cytoplasmic Release, Kirk Kohwa Hou
Arts & Sciences Graduate Student Theses and Dissertations
The development of small molecules as therapeutic agents for targeted disease treatment is unable to keep up with the rapid expansion of databases cataloguing disease-causing proteins enabled by high throughput analysis of patient samples. As an alternative, the use of small interfering RNA (siRNA) provides a simple means of efficiently and specifically silencing the expression of these pathogenic proteins without the need for screening and development required of small molecules. Unfortunately, the delivery of siRNA is not trivial, and existing technology is characterized by either poor siRNA transfection efficiency or induction of cytotoxicity. Detailed work by many groups has supported …
The Effects Of Hpa Axis Genetic Variation And Early Life Stress On Cortisol Levels In Preschool Age Children And On Amygdala And Hippocampus Volumes, Reactivity, And Connectivity At School Age, David Pagliaccio
Arts & Sciences Graduate Student Theses and Dissertations
Internalizing psychopathology has been linked to increased cortisol reactivity and alterations in limbic brain structure and function, yet the mechanisms underlying these alterations are unclear. One key hypothesis is that stress plays a major causal role in these mechanisms. Animal studies find that chronic stress or glucocorticoid administration lead to alterations in hippocampal and amygdala structure and function. Relatedly, life stress is a major risk factors for depression while candidate gene studies have related variation in hypothalamic-pituitary-adrenal (HPA) axis genes to increased prevalence and severity of depression. The present work tested the hypothesis that genetic profile scores combining variance across …
Viral And Innate Immune Factors Controlling Disease Susceptibility During Chikungunya Virus Infection, Anjali Rohatgi
Viral And Innate Immune Factors Controlling Disease Susceptibility During Chikungunya Virus Infection, Anjali Rohatgi
Arts & Sciences Graduate Student Theses and Dissertations
Chikungunya virus (CHIKV) is a re-emerging pathogen that causes a high fever, painful arthritis and a macular rash. The current outbreak began in Kenya in 2004 and spread throughout the Indian Ocean area and Southeast Asia, infecting millions. During this outbreak, more severe disease manifestations, including lethality, were reported for the first time. To understand one possible reason for this change in severity, we explored the impact of genetic changes in the virus on disease pathogenesis. In addition, we dissected the role of type I interferon (IFN) subtypes in CHIKV infection. From these studies, we have gained important insight into …
The Attentional Control Of Reading: Insights From Behavior, Imaging And Development, Sarah Ihnen
The Attentional Control Of Reading: Insights From Behavior, Imaging And Development, Sarah Ihnen
Arts & Sciences Graduate Student Theses and Dissertations
The process by which the initially attention-requiring task of transforming scribbles into meaningful concepts eventually becomes facile remains a central riddle of cognitive neuroscience. This body of work represents an effort to provide forward movement in answering the question of how attentional control mediates the process of reading, both by considering different stages of reading competence (development) and by seeking convergence between types of evidence (behavior and imaging).Inspired by a study published by Balota and colleagues in 2000, the paradigm used throughout this work involves comparing a simple speeded reading task vs. a regularize ("sound out") task (Balota et al. …
The Intrinsic Apoptotic Cascade In Hematopoiesis And Susceptibility To Therapy-Related Leukemia, Elise Peterson Lu
The Intrinsic Apoptotic Cascade In Hematopoiesis And Susceptibility To Therapy-Related Leukemia, Elise Peterson Lu
Arts & Sciences Graduate Student Theses and Dissertations
Apoptosis and the DNA damage response have been implicated in hematopoietic development and differentiation, as well as in the pathogenesis of myelodysplastic syndrome (MS) and leukemia. However, the specific roles of direct mediators of apoptosis, such as caspases, in hematopoiesis and leukemogenesis have not been elucidated. In order to address this, we studied the effects of loss of Caspase-9, the initiator caspase of the intrinsic apoptotic cascade, and Apaf1, the key component of the apoptosome, on fetal and adult hematopoiesis. We first found that loss of these key regulators has significant effects on the hematopoietic stem and progenitor compartment, with …
Understanding Escherichia Coli Urinary Tract Infection: A Niche Perspective, Drew Joel Schwartz
Understanding Escherichia Coli Urinary Tract Infection: A Niche Perspective, Drew Joel Schwartz
Arts & Sciences Graduate Student Theses and Dissertations
Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, costing greater than $2 billion in healthcare costs and lost wages yearly in America alone. The lifetime risk for a woman exceeds 50% with 25-40% of these suffering recurrent infections. Two of the most important risk factors for recurrent UTI are prior UTIs and sexual intercourse. Over 80% of UTIs are caused by uropathogenic Escherichia coli (UPEC), which binds and invades superficial facet cells lining the bladder surface. UPEC expresses extracellular fibers called type 1 pili with a terminal mannose-binding adhesin, FimH, which interacts with mannosylated uroplakin residues …
The U1a/U2b"/Snf Family Of Rna Binding Proteins: Evolution Of Rna Binding Specificity And Contributions Of Heterotropic Linkage To Snrnp Protein Partitioning, Sandra Gisela Williams
The U1a/U2b"/Snf Family Of Rna Binding Proteins: Evolution Of Rna Binding Specificity And Contributions Of Heterotropic Linkage To Snrnp Protein Partitioning, Sandra Gisela Williams
Arts & Sciences Graduate Student Theses and Dissertations
The U1A/U2B"/SNF is a family of RNA binding proteins that is a highly conserved throughout eukaryotes. These proteins are found in the U1 and/or U2 splicing snRNPs (small nuclear ribonucleoprotein particles). In humans, U1A and U2B" specifically bind to the U1 and U2 snRNAs, respectively. The Drosophila genome codes for SNF, an essential protein that localizes to both the U1 and U2 snRNP. While a specific splicing functions for these proteins have not been determined, their conserved snRNP localization suggests an important splicing-related function.The difference in protein number and partitioning between Drosophila and humans suggested that these proteins may use …
The Roles Of Mist1 And Rab26 In Zymogenic (Chief) Cell Differentiation And Subcellular Organization, Ramon Jin
The Roles Of Mist1 And Rab26 In Zymogenic (Chief) Cell Differentiation And Subcellular Organization, Ramon Jin
Arts & Sciences Graduate Student Theses and Dissertations
Little is known about how differentiating cells reorganize their cellular structure to perform specialized physiological functions. Specifically, exocrine cells like pancreatic acinar and zymogenic chief cells have a highly developed secretory architecture that is rapidly established upon differentiation. What is known in these cells is that the evolutionarily conserved transcription factor MIST1 is required for final maturation. We hypothesized that MIST1 directly regulates specific subcellular components that facilitate functional maturation of secretory cells.We show that MIST1 binds to conserved CATATG E-boxes to activate transcription of 6 genes, including the small GTPases RAB26 and RAB3D. We next demonstrate that RAB26 and …
An Essential Role For Self-Pmhc Throughout The Life Of A Cd4 T Cell: Contributions In The Thymus And Periphery, Stephanie Rodriguez
An Essential Role For Self-Pmhc Throughout The Life Of A Cd4 T Cell: Contributions In The Thymus And Periphery, Stephanie Rodriguez
Arts & Sciences Graduate Student Theses and Dissertations
It is well established that self-peptide Major Histocompatibility Complexes (hereafter self-pMHC) are essential for the development of a broad repertoire of mature, self-tolerant CD4 and CD8 T cells. Despite clear knowledge that the pool of self-ligands is critical for positive and negative selection, the exact kinetics and dynamic nature of thymocyte interaction with self-pMHC class II (self-pMHCII) bearing antigen-presenting cells (APCs) during development is still largely a mystery. The enigmatic nature of selecting self-pMHC is not unique to the thymic environment; increasingly evident is the dependence of peripheral T cells on extra-thymic self-pMHC expression, specifically selecting self-pMHC, for their homeostatic …
Modulation Of Nmda Receptor Activity During Physiological And Pathophysiological Events, Christine Marie Emnett
Modulation Of Nmda Receptor Activity During Physiological And Pathophysiological Events, Christine Marie Emnett
Arts & Sciences Graduate Student 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 …
Origin Of Maternal Age Effect In Congenital Heart Disease Risk For Offspring, Claire Elaine Schulkey
Origin Of Maternal Age Effect In Congenital Heart Disease Risk For Offspring, Claire Elaine Schulkey
Arts & Sciences Graduate Student Theses and Dissertations
Increasing maternal age is widely acknowledged to lead to greater likelihood of pregnancy complications and congenital abnormalities, but the basis of this effect has not been well studied. Often dismissed as the product of oocyte ageing, the mechanistic basis of this maternal age effect is likely more complex.Congenital heart disease is a classic complex disease with multiple genetic and environmental modifiers, including maternal age. Maternal ageing is a known risk-factor in humans, and has been shown to exist in an Nkx2-5 haploinsufficient mouse model for the disease. This mouse model's maternal age risk is dependent upon strain background, with C57BL/6N …
The Influence Of Metacommunity Size On Species Diversity Across Spatial Scales, Lauren Woods
The Influence Of Metacommunity Size On Species Diversity Across Spatial Scales, Lauren Woods
Arts & Sciences Graduate Student 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 …
Evolution Of Ecological Dominance Of Yeast Species In High-Sugar Environments, Kathryn Marie Williams
Evolution Of Ecological Dominance Of Yeast Species In High-Sugar Environments, Kathryn Marie Williams
Arts & Sciences Graduate Student Theses and Dissertations
Two challenging goals of evolutionary biology are to understand how evolutionary innovations evolve and how they contribute to the success of lineages. Evolutionary innovations may arise following whole genome duplication (WGD) events and they are suspected to contribute to the success of lineages by creating ecological opportunity. However, direct evidence for duplicated genes involved in evolutionary innovations remains rare, and the relationship between evolutionary innovations and the success of lineages may be very complex. In this study, I explore the relationship of evolutionary innovation, WGD, and the ecological dominance of yeast species in high-sugar environments. In budding yeast, a major …
Characterizing The Fitness Landscapes Of Gut Symbionts In Defined Community And Diet Contexts, Meng Wu
Characterizing The Fitness Landscapes Of Gut Symbionts In Defined Community And Diet Contexts, Meng Wu
Arts & Sciences Graduate Student Theses and Dissertations
A species' niche is the description of all the environmental conditions required to permit a population of that species to persist, including the effects of the population on those conditions. This definition includes the species' resource requirements, as well as stress tolerances and interactions with other species acting as competitors, predators, parasites, and mutualists. The human gut microbiota serves as a microbial `metabolic organ' tasked in part with the biotransformation of many components of our diet. Relatively little is known about the factors that allow members of the human gut microbiota to persist in a habitat that experiences marked changes …
The Genetic Architecture And Evolution Of Brain Cortical Folding In A Pedigreed Primate Population, Elizabeth Grace Atkinson
The Genetic Architecture And Evolution Of Brain Cortical Folding In A Pedigreed Primate Population, Elizabeth Grace Atkinson
Arts & Sciences Graduate Student 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 …
The Uropathogenic Escherichia Coli Effector Ybcl Modulates The Innate Immune Response In The Urinary Tract, Megan Elizabeth Lau
The Uropathogenic Escherichia Coli Effector Ybcl Modulates The Innate Immune Response In The Urinary Tract, Megan Elizabeth Lau
Arts & Sciences Graduate Student 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 …
The Natural Variants Of The Streptococcus Nad+-Glycohydrolase Spn Modulate Divergent Host Cell Signaling Pathways And Death, Sukantha Chandrasekaran
The Natural Variants Of The Streptococcus Nad+-Glycohydrolase Spn Modulate Divergent Host Cell Signaling Pathways And Death, Sukantha Chandrasekaran
Arts & Sciences Graduate Student 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 …
Type 1 Diabetes And The Male Reproductive Axis, Erica Schoeller
Type 1 Diabetes And The Male Reproductive Axis, Erica Schoeller
Arts & Sciences Graduate Student 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
Dysfunctional Gene Regulation Of The Meiotic Program In An Interspecific Yeast Hybrid, Devjanee Swain Lenz
Arts & Sciences Graduate Student 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 …
Development Of Polarizable Force Field Models For Transition Metal Ions, Jin Yu Xiang
Development Of Polarizable Force Field Models For Transition Metal Ions, Jin Yu Xiang
Arts & Sciences Graduate Student 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 …
Quantification Of Conformational Heterogeneity And Its Role In Protein Aggregation And Unfolding, Nicholas J. Lyle
Quantification Of Conformational Heterogeneity And Its Role In Protein Aggregation And Unfolding, Nicholas J. Lyle
Arts & Sciences Graduate Student 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 …
Post-Translational Regulation Of Fas-Mediated Pparα Activation, Anne Patricia Louise Jensen-Urstad
Post-Translational Regulation Of Fas-Mediated Pparα Activation, Anne Patricia Louise Jensen-Urstad
Arts & Sciences Graduate Student 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 …
Urine Trouble: A Molecular And Anatomical Examination Of Bladder Pain, Lara Wiley Crock
Urine Trouble: A Molecular And Anatomical Examination Of Bladder Pain, Lara Wiley Crock
Arts & Sciences Graduate Student 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
A Ranksum Statistics Based Framework To Decipher Transcription Regulation, Iuan-Bor Chen
Arts & Sciences Graduate Student 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
Cell Culture Models Of Genetic Variation, Joshua T. Witten
Arts & Sciences Graduate Student 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
Identifying And Characterizing Arabidopsis Jasmonate Signaling Components Manipulated By Pseudomonas Syringae, Neva Laurie-Berry
Arts & Sciences Graduate Student 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 …
Rna Metabolism In Escherichia Coli During Bacteriophage T4 Infection, Amino Acid Starvation And Complete Inhibition Of Protein Synthesis, Elizabeth Anne Craig
Rna Metabolism In Escherichia Coli During Bacteriophage T4 Infection, Amino Acid Starvation And Complete Inhibition Of Protein Synthesis, Elizabeth Anne Craig
Arts & Sciences Graduate Student Theses and Dissertations
Three classes of RNA are made in exponentially growing E. coli cells: messenger RNA (mRNA), ribosomal RNA (rRNA) and transfer RNA (tRNA). mRNA possesses the characteristics which were first proposed by Jacob and Monod (1961) as necessary for an intermediary in the transfer of information from DNA to protein.