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Full-Text Articles in Biology

Superoxide Dismutase 1: Novel Insights On Disease Models And Tissue Specificity In Amyotrophic Lateral Sclerosis, Matthew James Crisp May 2016

Superoxide Dismutase 1: Novel Insights On Disease Models And Tissue Specificity In Amyotrophic Lateral Sclerosis, Matthew James Crisp

Arts & Sciences Graduate Student Theses and Dissertations

Mutations in superoxide dismutase 1 (SOD1) are known to cause dominantly-inherited amyotrophic lateral sclerosis (ALS), a rapidly-fatal adult-onset neurodegenerative disorder defined by motor neuron loss and progressive paralysis. In the past twenty years, research into the disorder has been driven by the creation of numerous transgenic animal models that have yielded multiple theories on the pathogenesis of the disease. Patients and animal models with SOD1 mutations express the defective protein in every cell, yet the disease only affects tissues in the neuromuscular axis. In this dissertation, I present original work exploring two aspects of SOD1 ALS. The first details the …


The Role Of Dnmt3a In Acute Myeloid Leukemia Pathogenesis, Christopher Browning Cole May 2016

The Role Of Dnmt3a In Acute Myeloid Leukemia Pathogenesis, Christopher Browning Cole

Arts & Sciences Graduate Student Theses and Dissertations

Loss of function mutations in the DNA methyltransferase DNMT3A are highly recurrent in acute myeloid leukemia (AML). DNMT3A and the highly homologous gene DNMT3B encode the two methyltransferases that are primarily responsible for mediating de novo methylation of specific DNA sequences during cellular differentiation. DNMT3A mutations are mutually exclusive of several translocations that create oncogenic fusion genes (PML-RARA, RUNX1-RUNX1T1, CBFB-MYH11, and MLL-X), suggesting that these fusions may require functional DNMT3A to initiate leukemogenesis. Using bone marrow cells from a constitutive Dnmt3a null mouse, we show that loss of Dnmt3a caused a striking loss of DNA methylation throughout the genome of …


Understanding The Interactions Of Developing Thymocytes And Antigen Presenting Cells In The Thymic Medulla, Justin Shaun Arnold Perry May 2016

Understanding The Interactions Of Developing Thymocytes And Antigen Presenting Cells In The Thymic Medulla, Justin Shaun Arnold Perry

Arts & Sciences Graduate Student Theses and Dissertations

Various thymic APC subsets have been invoked in deletional tolerance and Treg cell induction, but previous studies either assessed total T cell numbers or used TCR transgenic lines, obscuring roles that individual thymic APC subsets might serve for particular antigen-specific T cell populations. Utilizing T cell receptor sequencing, we found that medullary thymic epithelial cells (mTECs) and bone marrow-derived (BM) APCs delete or select unique conventional and Treg cell TCR repertoires, demonstrating distinct roles for these APCs. We show that BM APCs and mTECs each contribute to Aire-dependent T cell tolerance development, albeit through either cooperative or autologous antigen presentation …


Refining Associations Between Targeted Genes And The Development Of Substance Use Disorders, Emily Olfson May 2016

Refining Associations Between Targeted Genes And The Development Of Substance Use Disorders, Emily Olfson

Arts & Sciences Graduate Student Theses and Dissertations

Recent genome-wide association studies (GWAS) provide strong evidence for the contribution of a few specific genes to alcohol and nicotine dependence. Chapter 2 explores numerous previously identified candidate genes for alcohol dependence using a publicly available GWAS. I found that many candidate loci do not replicate, highlighting the utility of GWAS for focusing on disease associated genes. Chapters 3-5 dissect associations between three genome-wide significant genes and substance use disorders. Chapter 3 focuses on a functional variant in alcohol dehydrogenase (ADH) 1B. Through examining 1,550 adolescent drinkers in the Collaborative Study on the Genetics of Alcoholism (COGA), I extended adult …


Application Of Genomic Technologies To Study Infertility, Nicholas Rui Yuan Ho May 2016

Application Of Genomic Technologies To Study Infertility, Nicholas Rui Yuan Ho

Arts & Sciences Graduate Student Theses and Dissertations

An estimated one in eight couples in the United States are diagnosed with infertility. There is a significant genetic contribution to infertility, with estimates of heritability ranging from 0.2 to 0.5. We know surprisingly little about the genetic causes, with only slightly more than a hundred genes known to cause human infertility. I have been translating recent advances in genomics to study infertility in a more efficient manner, in order to improve our knowledge of the genetic causes. By using high throughput genomics and proteomics datasets from other groups, I was able to feed that into a machine learning algorithm …


Granulocyte-Colony Stimulating Factor Reprograms The Bone Marrow Microenvironment To Suppress B Lymphopoiesis, Ryan Brent Day May 2016

Granulocyte-Colony Stimulating Factor Reprograms The Bone Marrow Microenvironment To Suppress B Lymphopoiesis, Ryan Brent Day

Arts & Sciences Graduate Student Theses and Dissertations

The production of hematopoietic cells in the bone marrow is tightly and dynamically regulated in response to environmental stimuli. In response to infection, the bone marrow increases granulopoiesis at the expense of lymphopoiesis. The mechanisms mediating this shift are poorly understood. We show that treatment with granulocyte-colony stimulating factor (G-CSF), which is often induced during infection, results in marked decline of B lymphocytes at multiple stages of bone marrow B cell development. Transgenic mouse models show that G-CSF acts in a non-cell intrinsic fashion through cells of the monocyte-macrophage lineage to suppress B lymphopoiesis by downregulating important B trophic factors …


A Novel Ultrashort Pulsed Laser Method For Pathogen Inactivation, Shaw-Wei David Tsen May 2016

A Novel Ultrashort Pulsed Laser Method For Pathogen Inactivation, Shaw-Wei David Tsen

Arts & Sciences Graduate Student Theses and Dissertations

Emerging viral pathogens represent a constant and prominent threat to human health worldwide. There is a dire need to develop new pathogen inactivation techniques that can be used to safeguard the blood supply and to generate inactivated vaccines against these emerging viruses. Unfortunately, current techniques are inadequate because they introduce toxic/carcinogenic chemicals or alter the structure of the products, leading to loss of safety and efficacy. We have developed a novel, chemical-free ultrashort pulsed laser treatment system capable of inactivating a broad spectrum of both enveloped and non-enveloped viruses. We found that ultrashort pulsed laser treatment targets the vibrational modes …


Mechanism Of Calcium-Dependent Chloride Channel Activation By The Secreted Regulator Clca1, Zeynep Yurtsever May 2016

Mechanism Of Calcium-Dependent Chloride Channel Activation By The Secreted Regulator Clca1, Zeynep Yurtsever

Arts & Sciences Graduate Student Theses and Dissertations

The calcium-activated chloride channel regulator (CLCA) proteins are key signaling molecules, which are implicated in various diseases through their tissue-specific expression. Human CLCA1 protein, overexpressed in airway epithelia under pathophysiological conditions, is centrally involved in the manifestation of IL-13-driven mucus cell metaplasia (MCM), a hallmark feature of asthma and chronic obstructive pulmonary disease (COPD), for which there are currently no available therapeutics. Elucidating the poorly understood molecular basis of CLCA1 function is thus required to design specific inhibitors of CLCA1 activity to treat MCM in asthma and COPD. Originally misannotated as ion channels, CLCA proteins are secreted soluble proteins that …


The Murine Accessory Olfactory Bulb As A Model Chemosensory System: Experimental And Computational Analysis Of Chemosensory Representations, Gary Francis Hammen May 2016

The Murine Accessory Olfactory Bulb As A Model Chemosensory System: Experimental And Computational Analysis Of Chemosensory Representations, Gary Francis Hammen

Arts & Sciences Graduate Student Theses and Dissertations

A common challenge across sensory processing modalities is forming meaningful associations between the neural responses and the outside world. These neural representations of the world must then be integrated across different sensory systems contributing to each individuals perceptual experience. While there has been considerable study of sensory representations in the visual system of humans and multiple model organisms, other sensory domains, including olfaction, are less well understood. In this thesis, I set out to better understand the sensory representations of the mouse accessory olfactory system (AOS), a part of the olfactory system. The mouse AOS, our model chemosensory system, comprises …


Functional Consequences Of Cantu Syndrome Associated Mutations In The Atp Sensitive Potassium Channel, Paige Cooper Dec 2015

Functional Consequences Of Cantu Syndrome Associated Mutations In The Atp Sensitive Potassium Channel, Paige Cooper

Arts & Sciences Graduate Student Theses and Dissertations

ATP-sensitive potassium (KATP) channels are composed of inward-rectifying potassium channel pore-forming subunits (Kir6.1 and Kir6.2, encoded by KCNJ8 and KCNJ11, respectively) and regulatory sulfonylurea receptor subunits (SUR1 and SUR2, encoded by ABCC8 and ABCC9, respectively). These channels couple metabolism to excitability in multiple tissues. Mutations in ABCC9 have been linked to Cantú syndrome (CS), a multi-organ disease characterized by congenital hypertrichosis, distinct facial features, osteochondrodysplasia, and cardiac defects. Additionally, two ABCC9 mutation-negative patients, exhibiting clinical hallmarks of CS, have been identified as having KCNJ8 mutations. This body of work is focused on determining the functional consequences and molecular mechanisms of …


Human Immunodeficiency Virus Type 1 Envelope Protein Interaction With Host Cell Coreceptor C-X-C Chemokine Receptor Type 4, Jie Zhang Dec 2015

Human Immunodeficiency Virus Type 1 Envelope Protein Interaction With Host Cell Coreceptor C-X-C Chemokine Receptor Type 4, Jie Zhang

Arts & Sciences Graduate Student Theses and Dissertations

Human Immunodeficiency Virus Type 1 (HIV-1) envelope protein is the sole determinant for viral entry and tropism. The ability of HIV-1 to infect susceptible host cells depends on the ability of its envelope protein to engage host cell receptor CD4 and coreceptor C-C Chemokine Receptor Type 5 (CCR5) and/or C-X-C Chemokine Receptor Type 4 (CXCR4). Most naturally occurring infections start with a single CCR5-tropic virion. In approximately 50% of HIV-1 Clade B infected patients, the viral population spontaneous develops the ability to utilize CXCR4 at a late disease stage, and this coreceptor shift corresponds to a poor prognosis for the …


Ion Selectivity And Allostery In The Nak Channel, Joshua B. Brettmann Dec 2015

Ion Selectivity And Allostery In The Nak Channel, Joshua B. Brettmann

Arts & Sciences Graduate Student Theses and Dissertations

Ion channels require proper ion selectivity and regulated gating in order to perform their cellular functions. Bacterial ion channels serve as excellent model systems to study structure/function relationships concerning the fundamental processes of ion selectivity and gating. NaK, a non-selective cation channel from Bacillus cereus, has the conserved pore structure of K+ channels. However, its non-canonical selectivity filter structure leads to non-selectivity between Na+ and K+. Full selectivity is restored with two mutations that lead to the restoration of a Kcsa-like selectivity filter structure. Many mutations can be made to the selectivity filter of NaK without loss of protein stability …


Lysosomal Rnaset2 Is Required For Metabolic Stress-Mediated Ros Generation And Cell Death, George Caputa Dec 2015

Lysosomal Rnaset2 Is Required For Metabolic Stress-Mediated Ros Generation And Cell Death, George Caputa

Arts & Sciences Graduate Student Theses and Dissertations

Ectopic lipid deposition in non-adipose tissues is a hallmark of metabolic diseases, such as obesity and diabetes, and associated with cell dysfunction, cell death, and organ dysfunction. However, the molecular mechanisms linking excess free fatty acid to cell death are poorly understood. In order to identify genes critical for lipotoxicity, our lab performed a genetic screen in Chinese hamster ovary cells and isolated mutants that were resistant to lipotoxic death. In one of the lines, mutant 2B1, an allele encoding RNASET2, a ribonuclease of the T2 family, was disrupted by proviral insertion. We found that RNASET2 is induced during lipotoxicity …


Characterizing The Role Of Sialylated Milk Glycans And The Infant Gut Microbiota In Growth And Metabolism, Mark Richard Charbonneau Dec 2015

Characterizing The Role Of Sialylated Milk Glycans And The Infant Gut Microbiota In Growth And Metabolism, Mark Richard Charbonneau

Arts & Sciences Graduate Student Theses and Dissertations

Undernutrition is a pressing and pervasive global health problem. The pathogenesis of this disease remains unclear, but epidemiologic studies indicate that it is not due to food insecurity alone. Moreover, current therapeutic interventions have limited efficacy in preventing or ameliorating the long-term sequelae of undernutrition, including stunting and cognitive deficits. Recent culture-independent studies have demonstrated that the normal postnatal pattern of gut microbiota development is disrupted in children with undernutrition, leading to the proposal that perturbations in gut microbiota development impairs healthy growth of the host. Human breast milk contains a diverse repertoire of free and conjugated human milk oligosaccharides …


The Identification Of Alkaloid Pathway Genes From Non-Model Plant Species In The Amaryllidaceae, Matthew B. Kilgore Dec 2015

The Identification Of Alkaloid Pathway Genes From Non-Model Plant Species In The Amaryllidaceae, Matthew B. Kilgore

Arts & Sciences Graduate Student Theses and Dissertations

Secondary metabolites are often restricted in their distribution to different groups of organisms. For this reason, attempts to study these often useful and interesting products of metabolism require an ability to work in a diversity of non-model species. Methods for gene discovery with low investment and high efficiency are needed to effectively identify the biosynthetic genes in these diverse pathways. During this work, a workflow for efficiently identifying biosynthetic genes was developed and applied to Amaryllidaceae alkaloid biosynthesis. Genes discovered during this work include a norbelladine 4’-O-methyltransferase, a cytochrome P450 capable of phenol-phenol coupling 4’-O-methylnorbelladine to noroxomaritidine, and a short-chain …


Behavioral And Fmri-Based Characterization Of Cognitive Processes Supporting Learning And Retrieval Of Memory For Words In Young Adults, Binyam Nardos Dec 2015

Behavioral And Fmri-Based Characterization Of Cognitive Processes Supporting Learning And Retrieval Of Memory For Words In Young Adults, Binyam Nardos

Arts & Sciences Graduate Student Theses and Dissertations

A novel word is rarely defined explicitly during the first encounter. With repeated exposure, a decontextualized meaning of the word is integrated into semantic memory. With the overarching goal of characterizing the functional neuroanatomy of semantic processing in young adults, we employed a contextual word learning paradigm, creating novel synonyms for common animal/artifact nouns that, along with additional real words, served as stimuli for the lexical-decision based functional MRI (fMRI) experiment. Young adults (n=28) were given two types of word learning training administered in multiple sessions spread out over three days. The first type of training provided perceptual form-only training …


Endogenous Protection In Subarachnoid Hemorrhage, Eric Milner Dec 2015

Endogenous Protection In Subarachnoid Hemorrhage, Eric Milner

Arts & Sciences Graduate Student Theses and Dissertations

Vasospasm-induced delayed cerebral ischemia (DCI) remains a major source of morbidity in patients with aneurysmal subarachnoid hemorrhage (SAH). Moreover, cognitive dysfunction is the primary driver of poor long-term outcome in SAH survivors; modeling such deficits preclinically is thus key for mechanistic and translational investigation. We hypothesized that activating innate neurovascular protective mechanisms by conditioning may represent a novel therapeutic approach against SAH-induced DCI, short-term, neurological deficits, and long-term neurocognitive deficits; and, secondarily, that the neurovascular protection it provides is mediated by endothelial nitric oxide synthase (eNOS) and hypoxia-inducible factor 1α (HIF-1α).In Experiment 1, wild-type C57BL/6 mice were subjected to hypoxic …


Transcriptional Regulation Of The Endoplasmic Reticulum In Dedicated Secretory Cells, Benjamin David Moore Dec 2015

Transcriptional Regulation Of The Endoplasmic Reticulum In Dedicated Secretory Cells, Benjamin David Moore

Arts & Sciences Graduate Student Theses and Dissertations

Differentiating cells express subsets of genes to build the cellular machinery necessary to perform their specific function as they acquire their mature fate. These subsets of genes are regulated by networks of transcription factors as cells progress through their developmental program. In secretory tissue, highly-specialized cells establish a complex secretory apparatus and scale up their cellular architecture to facilitate the production and secretion of large amounts of protein. Here, we identify a network of transcription factors responsible for the development of this cellular machinery in these professional secretory cells, and develop new tools to better study the molecular networks that …


Molecular Mechanisms Of Axon Growth And Regeneration, Dana Watt Dec 2015

Molecular Mechanisms Of Axon Growth And Regeneration, Dana Watt

Arts & Sciences Graduate Student Theses and Dissertations

Neurons are cells with unique and extremely polarized morphologies. The axon allows communication between the cell soma and the distantly located synaptic terminal and can extend up to one meter in humans. This exceptional cellular structure therefore has specialized biological processes dedicated to its growth, maintenance and regeneration. The structure that carries out axon elongation during development and regeneration is the growth cone, which features a cytoskeletal structure that is both highly dynamic yet consistent in overall organization. The growth cone coordinates a leading edge of dynamic actin with the microtubules of the growing axon, enabling directed outgrowth while maintaining …


The Mechanism And Regulation Of Mammalian Photoreceptor Dark Adaptation, Yunlu Xue Dec 2015

The Mechanism And Regulation Of Mammalian Photoreceptor Dark Adaptation, Yunlu Xue

Arts & Sciences Graduate Student Theses and Dissertations

The visual perception of vertebrates begins in rod and cone photoreceptors. Both photoreceptors require visual pigments to detect light. At the first step of light detection, a chromophore molecule (i.e. 11-cis retinal), which is conjugated to the visual pigment in photoreceptor outer segment, absorbs a photon. Photoisomerization of the chromophore activates the visual pigment, triggers the phototransduction cascade, and produces electrical signals. After photoisomerization, the chromophore is ultimately converted to all-trans retinol, which must be recycled to regenerate the visual pigment. This visual pigment regeneration process is called the visual cycle. It is the rate-limiting step of the photoreceptor dark …


Neural Mechanisms Of Working Memory Cortical Networks, Charalampos Papadimitriou Aug 2015

Neural Mechanisms Of Working Memory Cortical Networks, Charalampos Papadimitriou

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation is aimed at understanding the cortical networks that maintain working memory information. By leveraging patterns of information degradation in spatial working memory encoding we reveal new neural mechanisms that support working memory function and challenge existing models of working memory circuits.First we examine how interference from previous memoranda influences memory of a currently remembered location. We find that memory for a currently remembered location is biased toward the previously memorized location. This interference is graded, not all-or-none. Interference is strongest when the previous and current targets are close and activate overlapping populations of neurons. Contrary to the attractive …


Spatial And Epigenetic Regulation Of T-Cell Receptor Beta Gene Assembly, Kinjal Majumder Aug 2015

Spatial And Epigenetic Regulation Of T-Cell Receptor Beta Gene Assembly, Kinjal Majumder

Arts & Sciences Graduate Student Theses and Dissertations

The adaptive immune system endows mammals with a sophisticated mechanism to recognize foreign proteins via surface antigen receptors that are expressed on the surface of all lymphocytes. This defense network is generated by V(D)J recombination, a set of sequentially controlled DNA cleavage and repair events that assembles functional antigen receptor genes from distally located Variable (V), Diversity (D) and Joining (J) gene segments. However, the recombination process must be stringently regulated to prevent formation of chromosomal translocations, which can lead to tumors. The process of V(D)J recombination is controlled at the levels of tissue, stage and allele specificity by a …


Adaptive Mechanisms Of Niche Remodeling In Streptococcus Pyogenes, Elyse Paluscio Aug 2015

Adaptive Mechanisms Of Niche Remodeling In Streptococcus Pyogenes, Elyse Paluscio

Arts & Sciences Graduate Student Theses and Dissertations

The Gram-positive bacterium Streptococcus pyogenes is a remarkably successful pathogen, capable of infecting numerous tissue sites within its human host. The ability of S. pyogenes to invade these different niches is, in part, due to the species’ ability to monitor various physical and chemical signals in its environment and alter its transcriptional profile in response to these differential conditions. As a member of the lactic acid bacteria, S. pyogenes has a simple fermentative metabolism and relies exclusively on a combination of homo-lactic and mixed acid fermentation as a means of generating energy in the cell. As a consequence of its …


Dna Damage Responses Regulate Macrophage Function During Innate Immune Responses, Abigail Rodriguez Morales Aug 2015

Dna Damage Responses Regulate Macrophage Function During Innate Immune Responses, Abigail Rodriguez Morales

Arts & Sciences Graduate Student Theses and Dissertations

Activated macrophages produce genotoxins such as reactive oxygen and nitrogen intermediates that are critical for the eradication of pathogens. Here we show that one of these agents, nitric oxide (NO), damages macrophage genomic DNA, resulting in the activation of DNA damage responses (DDR). The DDR is primarily initiated through DNA double-strand break (DSB) intermediates and depends on the PI3-like kinases ATM and DNA-PKcs. In response to Listeria monocytogenes infection, ATM and DNA-PKcs regulate a tissue-specific genetic program that includes the expression of inflammatory cytokines, chemokines and cell surface receptors, several of which are critical for cell migration during immune responses …


The Role Of Reversible Palmitoylation In Regulating Diverse Biological Processes, Mohammad H. Maktabi Aug 2015

The Role Of Reversible Palmitoylation In Regulating Diverse Biological Processes, Mohammad H. Maktabi

Arts & Sciences Graduate Student Theses and Dissertations

It is well established that covalent lipid-modification of proteins can play an important role in the spatial and temporal organization of many intracellular signaling proteins. In particular, protein palmitoylation, the thioester linkage of a palmitate moiety to a cysteine residue, plays a critical role in promoting membrane binding. It also serves as a versatile sorting signal for membrane trafficking and precise microdomain partitioning. Classical studies using metabolic labeling have revealed that palmitoylation is dynamic, in which many substrates undergo palmitate cycling, and that turnover is regulated by extracellular signals. As such, the kinetics of palmitoylation cycling is dependent on the …


Programming The Myocardium: The Notch-Wnt Axis, Benjamin S. Gillers Aug 2015

Programming The Myocardium: The Notch-Wnt Axis, Benjamin S. Gillers

Arts & Sciences Graduate Student Theses and Dissertations

Heart related deaths are the number one cause of death in the United States. While heart failure and other mechanical issues are common, arrhythmias account for the majority of these deaths. By understanding the genetic architecture that patterns the normal cardiac conduction system, we can further deepen our understanding of how arrhythmias arise and develop targeted therapies to treat this deadly class of disease. I have found that canonical Wnt signaling is necessary for development of the atrioventricular junction. Furthermore, absence of myocardial Wnt signaling leads to tricuspid atresia. Overexpression of Wnt signaling leads to development of ectopic atrioventricular junction …


Host Immune Signals Regulate Blood-Brain Barrier Function During Central Nervous System Infection And Autoimmunity, Brian Daniels Aug 2015

Host Immune Signals Regulate Blood-Brain Barrier Function During Central Nervous System Infection And Autoimmunity, Brian Daniels

Arts & Sciences Graduate Student Theses and Dissertations

A major hallmark of neuroinflammatory diseases is the breakdown of the blood-brain barrier (BBB). This barrier between the hematogenous circulation and the parenchyma of the central nervous system (CNS) is a multicellular interface made up of endothelial cells joined by tight and adherens junctions (TJs and AJs), along with pericytes and the endfeet projections of astroglia. Together, these cells tightly restrict the movement of solutes and cells from the circulation into the CNS in a manner crucial for proper CNS homeostasis. Regulation of BBB function occurs dynamically during neuroinflammatory diseases such as infection and CNS autoimmunity, resulting in both protective …


Essential Roles Of Stat3 In Zebrafish Development, Yinzi Liu Aug 2015

Essential Roles Of Stat3 In Zebrafish Development, Yinzi Liu

Arts & Sciences Graduate Student Theses and Dissertations

Vertebrate gastrulation is a fundamental morphogenetic process during which germ layers are formed, patterned and shaped into a body plan with organ rudiments. Among the conserved gastrulation movements, convergence and extension (C&E) occur concurrently to narrow the germ layers mediolaterally and elongate them along the anteroposterior embryonic axis. C&E are largely driven by cell migration and cell intercalation, while cell proliferation has been considered dispensable and even incompatible with gastrulation movements and morphogenesis. Signal transducer and activator of transcription 3 (Stat3) has been implicated by antisense morpholino loss-of-function study in regulation of zebrafish C&E movements in part by promoting non …


Escherichia Coli Iron Acquisition Paradigms And Host Responses In The Human Urinary Milieu, Robin Reid Shields-Cutler Aug 2015

Escherichia Coli Iron Acquisition Paradigms And Host Responses In The Human Urinary Milieu, Robin Reid Shields-Cutler

Arts & Sciences Graduate Student Theses and Dissertations

Urinary tract infections (UTIs) are some of the most common bacterial infections worldwide and are increasingly complicated by high antibiotic resistance and recurrence rates. Explanations for the marked individual differences in UTI susceptibility remain incomplete. In this thesis we show that urinary colonization by uropathogenic E. coli (UPEC) is influenced by urine composition and the activity of an important innate immune protein, siderocalin (SCN; also called lipocalin 2 or neutrophil gelatinase-associated lipocalin/NGAL). During UTI, host factors limit the availability of iron, an essential nutrient for the invading pathogen. In response, UPEC modify the urinary environment with metal binding siderophores, some …


Dissection Of Affective Catecholamine Circuits Using Traditional And Wireless Optogenetics, Jordan Gary Mccall Aug 2015

Dissection Of Affective Catecholamine Circuits Using Traditional And Wireless Optogenetics, Jordan Gary Mccall

Arts & Sciences Graduate Student Theses and Dissertations

Parsing the complexity of the mammalian brain has challenged neuroscientists for thousands of years. In the early 21st century, advances in materials science and neuroscience have enabled unprecedented control of neural circuitry. In particular, cell-type selective manipulations, such as those with optogenetics and chemogenetics, routinely provide answers to previously intractable neurobiological questions in the intact, behaving animal.In this two-part dissertation, I first introduce new minimally invasive, wireless technology to perturb neural activity in the ventral tegmental area dopaminergic system of freely moving animals. I report a series of novel devices for studying and perturbing intact neural systems through optogenetics, microfluidic …