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Articles 601 - 630 of 838
Full-Text Articles in Biology
The Role Of The Ascc Complex In The Alkylation Damage Response, Jennifer Soll
The Role Of The Ascc Complex In The Alkylation Damage Response, Jennifer Soll
Arts & Sciences Graduate Student Theses and Dissertations
DNA alkylation damage is caused by various agents that are present in the environment as well as cellular metabolism and can be induced by certain chemotherapeutic agents. Thus, the repair of damaged DNA is critical for genomic maintenance. The ALKBH family of proteins plays a central role in the repair of specific alkylated lesions, including 1-methyladenine (1meA) and 3-methylcytosine (3meC). A major outstanding question in the field of alkylation repair is the role of associated protein partners in the function of the human AlkB homologues. Here, I demonstrate that the ALKBH3 associated complex ASCC (comprised of ASCC1, ASCC2, and ASCC3) …
Typical And Atypical Development Of The Brain’S Functional Network Architecture, Ashley Nicole Nielsen
Typical And Atypical Development Of The Brain’S Functional Network Architecture, Ashley Nicole Nielsen
Arts & Sciences Graduate Student Theses and Dissertations
The human brain is a complex organ that gives rise to many behaviors. Specialized neural regions cooperate as functional networks that form an intricate functional architecture. Development provides a unique window into how brain functioning and human thinking are affected if the necessary neural features and connections are not fully formed. Similarly, developmental disorders can shed light on atypical trajectories of neural systems that may lead to or be a consequence of symptomatic behavior. A description of the typical and atypical development of functional networks is essential to identify the features of brain organization critical for mature human thinking and …
The Role Of Tumor Stromal Discoidin Domain Receptor 2 (Ddr2) In Breast Cancer Metastasis., Samantha Van Hove Bayer
The Role Of Tumor Stromal Discoidin Domain Receptor 2 (Ddr2) In Breast Cancer Metastasis., Samantha Van Hove Bayer
Arts & Sciences Graduate Student Theses and Dissertations
Characteristics of breast tumor stroma, including altered collagen architecture and increased stiffness, are known to contribute to tumor invasion and metastasis. However, the cellular and molecular mechanisms by which these changes occur are not fully understood. To address this question, we used a mouse genetic model to delete Discoidin Domain Receptor 2 (DDR2) from mouse tumor stromal cells and interrogated breast cancer associated fibroblasts (CAFs) to determine the molecular events downstream of DDR2 action that may lead to changes in the tumor extracellular matrix (ECM). Our work revealed that the action of DDR2 in breast stromal cells is required for …
The Role Of Ifrd1 In The Recruitment And Function Of Reserve Stem Cells In Regeneration And Cancer, Mark Anthony Lewis
The Role Of Ifrd1 In The Recruitment And Function Of Reserve Stem Cells In Regeneration And Cancer, Mark Anthony Lewis
Arts & Sciences Graduate Student Theses and Dissertations
Mature cells can reprogram into a proliferative, progenitor-like state to repair tissue following injury and inflammation. Differentiated cells in diverse tissues can become proliferative via a dedicated, evolutionarily conserved program we termed paligenosis. We detailed how paligenosis occurs, in both gastric chief and pancreatic acinar cells, in a step-wise manner that involves: 1) autodegradation of mature cell components; 2) re-expression of progenitor genes; 3) re-entry into the cell cycle. This process is governed by mTORC1, a fundamental cellular energy sensor and regulator of protein translation. Blocking mTORC1 permitted autophagy and metaplastic gene induction but blocked cell cycle re-entry at S-phase. …
Grammar And Variation: Understanding How Cis-Regulatory Information Is Encoded In Mammalian Genomes, Dana Michele King
Grammar And Variation: Understanding How Cis-Regulatory Information Is Encoded In Mammalian Genomes, Dana Michele King
Arts & Sciences Graduate Student Theses and Dissertations
Understanding how genotype leads to phenotype is key to understand both the development and dysfunction of complex organisms. In the context of regulating the gene expression patterns that contribute to cell identity and function, the goal of my thesis research is to how changes in genome sequence may impact impact gene expression by determining how sequence features contribute to regulatory potential. To accomplish this goal, I first leveraged the key regulatory role of pluripotency transcription factors (TFs) in mouse embryonic stem cells (mESCs) and tested synthetically generated and genomic identified combinations of binding site for four TFs, OCT4, SOX2, KLF4, …
Fast Objective Coupled Planar Illumination Microscopy, Cody Jonathan Greer
Fast Objective Coupled Planar Illumination Microscopy, Cody Jonathan Greer
Arts & Sciences Graduate Student Theses and Dissertations
Among optical imaging techniques light sheet fluorescence microscopy stands out as one of the most attractive for capturing high-speed biological dynamics unfolding in three dimensions. The technique is potentially millions of times faster than point-scanning techniques such as two-photon microscopy. This potential is especially poignant for neuroscience applications due to the fact that interactions between neurons transpire over mere milliseconds within tissue volumes spanning hundreds of cubic microns. However current-generation light sheet microscopes are limited by volume scanning rate and/or camera frame rate. We begin by reviewing the optical principles underlying light sheet fluorescence microscopy and the origin of these …
The Splice Is Not Right: Splice-Site-Creating Mutations In Cancer Genomes, Reyka Glencora Jayasinghe
The Splice Is Not Right: Splice-Site-Creating Mutations In Cancer Genomes, Reyka Glencora Jayasinghe
Arts & Sciences Graduate Student Theses and Dissertations
Accurate interpretation of cancer mutations in individual tumors is a prerequisite for precision medicine. Large-scale sequencing studies, such as The Cancer Genome Atlas (TCGA) project, have worked to address the functional consequences of genomic mutations, with the larger goal of determining the underlying mechanisms of cancer initiation and progression. Many studies have focused on characterizing non-synonymous somatic mutations that alter amino acid sequence, as well as splice disrupting mutations at splice donors and acceptors. Current annotation methods typically classify mutations as disruptors of splicing if they fall on the consensus intronic dinucleotide splice donor, GT, the splice acceptor, AG. Splice …
Modeling The Bioactivation And Subsequent Reactivity Of Drugs, Tyler Brian Hughes
Modeling The Bioactivation And Subsequent Reactivity Of Drugs, Tyler Brian Hughes
Arts & Sciences Graduate Student Theses and Dissertations
Metabolism can convert drugs to harmful reactive metabolites that conjugate to DNA and off-target proteins. Reactive metabolites are a significant driver of both drug candidate attrition and withdrawal from the market of already approved drugs. Unfortunately, reactive metabolites are difficult to study in vivo, because they are transitory and generally do not circulate. Instead, this work computationally models both metabolism and reactivity. Using deep learning, predictive models were developed for the metabolic formation of quinones and epoxides, which together account for about half of known reactive metabolites. Additionally, an accurate model of DNA and protein reactivity was constructed, which predicts …
Protein Structure-Guided Approaches To Identify Functional Mutations In Cancer, Sohini Sengupta
Protein Structure-Guided Approaches To Identify Functional Mutations In Cancer, Sohini Sengupta
Arts & Sciences Graduate Student Theses and Dissertations
Distinguishing driver mutations from passenger mutations within tumor cells continues to be a major challenge in cancer genomics. Many computational tools have been developed to address this challenge; however, they rely heavily on primary protein sequence context and frequency/mutation rate. Rare driver mutations not found in many cancer patients may be missed with these traditional approaches. Additionally, the structural context of mutations on tertiary/quaternary protein structures is not taken into account and may play a more prominent role in determining phenotype and function. This dissertation first presents a novel computational tool called HotSpot3D, which identifies regions of protein structures that …
A Mouse Model Of Börjeson-Forssman-Lehmann Syndrome Reveals A Potential Link With Autism Spectrum Disorder, Cheng Cheng
A Mouse Model Of Börjeson-Forssman-Lehmann Syndrome Reveals A Potential Link With Autism Spectrum Disorder, Cheng Cheng
Arts & Sciences Graduate Student Theses and Dissertations
ABSTRACT OF THE DISSERTATIONA Mouse Model of Börjeson-Forssman-Lehmann Syndrome reveals a potential link with Autism Spectrum DisorderByCheng ChengDoctor of Philosophy in Biology and Biomedical SciencesDevelopmental, Regenerative and Stem Cell BiologyWashington University in St. Louis, 2018Dr. Azad Bonni, ChairIntellectual disability (ID) is a prevalent neurodevelopmental disorder that affects 1% to 3% of the general population. ID is characterized by developmental deficiencies in cognitive function and adaptive behaviors. Lacking effective treatments, ID currently presents an immense burden to affected families and the economy. Therefore, there is an urgent need to elucidate the pathogenesis of ID. Human genetic studies have associated ID with …
Combining Footprinting Mass Spectrometry And Molecular Dynamics Simulation For Structural Studies In Membrane Proteins, Fengbo Zhou
Arts & Sciences Graduate Student Theses and Dissertations
Membrane proteins are essential in many cellular processes and represent ~60% of all current drug targets. Due to technical limits, membrane proteins of various types were not studied extensively in the past and the biochemistry and functionality of them remain unclear. The structural biology methodologies require pure isolated protein samples for us to resolve their structure and study their biochemical functions. For such in vitro studies, however, membrane proteins often become unstable when isolated from their native lipid bilayer environment. To overcome the challenge, I employed a novel methodology of solubilizing membrane proteins in solution without detergent. I reconstituted ferroportin, …
The Role Of Fibrillin-1 In Eye Development And Disease, Wendell Brooks Jones
The Role Of Fibrillin-1 In Eye Development And Disease, Wendell Brooks Jones
Arts & Sciences Graduate Student Theses and Dissertations
The ciliary zonule of the human eye consists of a circumferential array of fibers that connect the ocular lens to the nonpigmented ciliary epithelium (NPCE) located at the inner wall of the eye. Zonular fibers consist of bundles of beaded filaments called microfibrils. Microfibrils are major structural elements of the extracellular matrix and are present in pure form in the ciliary zonule. Microfibrils are composed principally of fibrillin-1 (FBN-1); a large extracellular matrix glycoprotein. In humans, mutations in FBN1 underlie Marfan syndrome; a pleiotropic connective tissue disorder that profoundly affects the eye. Ocular manifestations include ectopia lentis (dislocated lenses), cataracts, …
Sequence Analysis Methods For The Design Of Cancer Vaccines That Target Tumor-Specific Mutant Antigens (Neoantigens), Jasreet Hundal
Sequence Analysis Methods For The Design Of Cancer Vaccines That Target Tumor-Specific Mutant Antigens (Neoantigens), Jasreet Hundal
Arts & Sciences Graduate Student Theses and Dissertations
The human adaptive immune system is programmed to distinguish between self and non-self proteins and if trained to recognize markers unique to a cancer, it may be possible to stimulate the selective destruction of cancer cells. Therapeutic cancer vaccines aim to boost the immune system by selectively increasing the population of T cells specifically targeted to the tumor-unique antigens, thereby initiating cancer cell death.. In the past, this approach has primarily focused on targeted selection of ‘shared’ tumor antigens, found across many patients. The advent of massively parallel sequencing and specialized analytical approaches has enabled more efficient characterization of tumor-specific …
The Essential Roles Of The Chromatin Factor Gon4l In Heart Development, Terin Elise Budine
The Essential Roles Of The Chromatin Factor Gon4l In Heart Development, Terin Elise Budine
Arts & Sciences Graduate Student Theses and Dissertations
Heart development and the genetic pathways underlying it are highly conserved among vertebrates. During heart development, an embryo must induce mesoderm formation, pattern the mesoderm, specify cardiomyocytes, increase the population of cardiomyocytes through proliferation, and pattern the cardiac chambers. It is becoming increasingly clear that chromatin modifications help mediate the complex processes of heart development by providing spatiotemporal regulation of gene expression. My thesis work focuses on characterizing functions of the chromatin factor Gonad-4-like (Gon4l), encoded by the gene ugly duckling (udu), in zebrafish heart development. Previous works established a requirement for Gon4l in the formation of many mesoderm derivatives …
Genetic Basis Of Thermal Divergence In Saccharomyces Species, Xueying C. Li
Genetic Basis Of Thermal Divergence In Saccharomyces Species, Xueying C. Li
Arts & Sciences Graduate Student Theses and Dissertations
The genetic architecture of phenotypic divergence is a central question in evolutionary biology. Genetic architecture is impacted by whether evolution occurs through accumulation of many small-effect or a few large-effect changes, the relative contribution of coding and cis-regulatory changes, and the prevalence of epistatic effects. Our empirical understanding of the genetic basis of evolutionary change remains incomplete, largely because reproductive barriers limit genetic analysis to those phenotypes that distinguish closely related species. In this dissertation, I use hybrid genetic analysis to examine the basis of thermal divergence between two post-zygotically isolated species, Saccharomyces cerevisiae and S. uvarum. S. cerevisiae is …
A Recombinant Virus And Reporter Mouse System To Study Chronic Chikungunya Virus Pathogenesis, Alissa Roxanne Young
A Recombinant Virus And Reporter Mouse System To Study Chronic Chikungunya Virus Pathogenesis, Alissa Roxanne Young
Arts & Sciences Graduate Student Theses and Dissertations
Chikungunya virus (CHIKV) is an arthritogenic alphavirus that during acute disease causes fever as well as severe joint and muscle pain. Chronic joint and muscle pain persists in a significant subset of patients, yet we still have a poor understanding of what drives this chronic disease. While replicating virus has not been detected in the joints of patients with chronic arthritis or in various animal models at chronic time points, persistent viral RNA can be detected for months after acute infection.To identify the cells that could be contributing to chronic CHIKV pathogenesis, we developed recombinant viruses that express Cre recombinase …
Mechanistic Characterization Of Resistome And Microbiome Dynamics Across Diverse Microbial Habitats, Andrew John Gasparrini
Mechanistic Characterization Of Resistome And Microbiome Dynamics Across Diverse Microbial Habitats, Andrew John Gasparrini
Arts & Sciences Graduate Student Theses and Dissertations
Increasing antibiotic resistance in pathogens is a serious public health challenge, with over two million antibiotic resistant infections in the United States leading to at least 23,000 deaths and an estimated $55 billion in excess healthcare and societal costs. Antibiotic resistance has risen steadily in both pathogenic and benign bacteria since antibiotics’ introduction to agriculture and medicine 70 years ago. A dramatic reduction in the number of antibiotics approved for human use has accompanied this rise in antibiotic resistance, leading to the alarming prospect of a post-antibiotic era. Understanding the evolutionary origins, genetic contexts, and molecular mechanisms of antibiotic resistance …
The Role Of Apolipoprotein E In Regulating Tau Pathogenesis And Neurodegeneration In A Tauopathy Mouse Model, Yang Shi
Arts & Sciences Graduate Student Theses and Dissertations
APOE4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). APOE4 increases brain amyloid-β (Aβ) pathology relative to other APOE isoforms. However, whether APOE independently influences tau pathology, the other pathological hallmark of AD and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human APOE knock in (KI) or APOE knockout (KO) background, we show that the presence of human APOE, regardless of APOE isoforms, leads to various degrees of brain atrophy in 9-month old P301S mice, whereas APOE ablation strongly protects against neurodegeneration. In particular, P301S/E4 mice develop …
A Tail Of Two Pancancer Projects: Somatic Variant Identification And Driver Gene Discovery Using Tcga, Matthew Hawkins Bailey
A Tail Of Two Pancancer Projects: Somatic Variant Identification And Driver Gene Discovery Using Tcga, Matthew Hawkins Bailey
Arts & Sciences Graduate Student Theses and Dissertations
The implementation of next-generation genomic sequencing has exploded over the past dozen years. Large consortia, such as The Cancer Genome Atlas (TCGA); the International Cancer Genetics Consortium (ICGC); and the Pediatric Cancer Genome Projects (PCGP), made great strides in democratizing big data for the scientific community. These data sets provide a rich resource to build tools for somatic variant discovery and exploratory analysis. Public repositories hold the answer to many novel biological and clinical revelations i.e., the discovery of complex indels, splice creating mutations, alternative super enhancer binding sites, machine learning models to predict mutation impact, and cancer subtype classification …
Neural Mechanisms Of Drosophila Circadian Rhythms, Xitong Liang
Neural Mechanisms Of Drosophila Circadian Rhythms, Xitong Liang
Arts & Sciences Graduate Student Theses and Dissertations
Animals show circadian rhythms in a variety of physiological functions and behaviors. In Drosophila melanogaster, behavioral rhythms are driven by circadian clock genes that are oscillating in ~150 circadian pacemaker neurons. To explain how circadian neurons encode time and regulate different behavioral rhythms, I performed 24-hour in vivo whole-brain calcium imaging using light-sheet microscopy. First, I found that different groups of circadian neurons show circadian rhythms in spontaneous neural activity with diverse phases. The neural activity phases of the M and E pacemaker groups, which are associated with the morning and evening locomotor activities respectively, occur ~4 hours before their …
The Costs Of A Big Brain: How Region Scaling And Energetic Costs Influence Brain Size Evolution In Weakly Electric African Fishes (Mormyridae), Kimberley Varunee Sukhum
The Costs Of A Big Brain: How Region Scaling And Energetic Costs Influence Brain Size Evolution In Weakly Electric African Fishes (Mormyridae), Kimberley Varunee Sukhum
Arts & Sciences Graduate Student Theses and Dissertations
Brains control an organismճ ability to sense, remember, and respond to the frequently changing world. Brains are composed of multiple regions and systems, which are associated with different processes. These regions are homologous across all vertebrates yet vary greatly in size and shape across clades. While regions can function independently, they also interact extensively. These characteristics make it difficult to predict whether regions can change in size independently from other regions in response to selection (mosaic evolution hypothesis), or whether the brain evolves as a single concerted organ (concerted evolution hypothesis). Further, many traits such as cognition, behavioral flexibility, and …
The Role Of Mesenchymal Stromal Cells And Classical Dendritic Cells In The Maintenance And Regulation Of The Bone Marrow Niche, Jingzhu Zhang
The Role Of Mesenchymal Stromal Cells And Classical Dendritic Cells In The Maintenance And Regulation Of The Bone Marrow Niche, Jingzhu Zhang
Arts & Sciences Graduate Student Theses and Dissertations
The bone marrow niche is an important microenvironment for the regulation of normal and malignant hematopoiesis. The first discovered niche component is mesenchymal stromal cells, which are the major source for the production and secretion of multiple niche factors. Mesenchymal stromal cells are heterogeneous and various transgenes have been used to target non-identical but overlapping subpopulations. To further characterize the heterogeneity of mesenchymal stromal cells, we tested the targeting specificity of three tissue-specific Cre-recombinase transgenes. We show that in addition to osteoblasts, Ocn-Cre targets a majority of Cxcl12-abundant reticular (CAR) cells and arteriolar pericytes. Surprisingly, Dmp1-Cre also targets a subset …
Evaluation Of Neurobiological Risk Factors For Alcohol Consumption; Convergent Evidence For Predispositional Effects Of Brain Volume, David Baranger
Evaluation Of Neurobiological Risk Factors For Alcohol Consumption; Convergent Evidence For Predispositional Effects Of Brain Volume, David Baranger
Arts & Sciences Graduate Student Theses and Dissertations
Alcohol is one of the most widely used psychoactive substances and accounts for 5% of global disease burden. The goal of the present work is to help advance efforts to both identify prognostic markers of risk, and to understand the mechanisms by which alcohol consumption impacts health. Early life stress is one of the strongest predictors of mental illness, including alcohol dependence, and has been hypothesized to impact risk via modulation of striatal reward functions and reward learning. Studies examined the effect of stress on reward learning and processing, and tested for moderation by genetic and environmental risk. Results were …
Cd4 T Cell Interaction With Intestinal Microbes Under Homeostasis And Inflammation, Jiani Chai
Cd4 T Cell Interaction With Intestinal Microbes Under Homeostasis And Inflammation, Jiani Chai
Arts & Sciences Graduate Student Theses and Dissertations
Specific gut commensal bacteria improve host health by eliciting mutualistic regulatory T (Treg) cells responses. However, the bacteria that induce effector T (Teff) cells during inflammation are unclear. Here, we addressed this by analyzing bacterial-reactive T cell receptor (TCR) transgenic cells and TCR repertoires in a murine colitis model. Unexpectedly, we found that mucosal-associated Helicobacter species triggered both Treg responses during homeostasis and Teff responses during colitis, as suggested by an increased overlap between the Teff/Treg TCR repertoires with colitis. In fact, 4/6 Treg TCRs tested recognized mucosal-associated Helicobacter species in vitro and in vivo. By contrast, the marked expansion …
A Mechanism Of Antimicrobial Resistance And A Mitigation Strategy, Christopher Bulow
A Mechanism Of Antimicrobial Resistance And A Mitigation Strategy, Christopher Bulow
Arts & Sciences Graduate Student Theses and Dissertations
ABSTRACT OF THE DISSERTATIONA Mechanism of Antimicrobial Resistance and a Mitigation StrategybyChristopher BulowDoctor of Philosophy in Biology and Biomedical SciencesMolecular Genetics and GenomicsWashington University in St. Louis, 2018Professor Gautam Dantas, ChairThe ability to treat infections, perform surgery, and administer immunosuppressants and chemotherapy depends on effective antibiotics. The emergence and spread of antimicrobial resistance is far outpacing the development of new therapies1-3 threatening to thrust medicine into a post-antibiotic era4. Many mechanisms of antimicrobial action and of antimicrobial resistance remain poorly understood as drug development struggles to keep pace. As resistance develops, the human gut serves as a reservoir and provides …
A High-Content Screen Identifies Hsp90 As A Component Of Axon Injury Signaling, Scott Karney-Grobe
A High-Content Screen Identifies Hsp90 As A Component Of Axon Injury Signaling, Scott Karney-Grobe
Arts & Sciences Graduate Student Theses and Dissertations
Axons are unique compartments of neurons that extend tremendous distances throughout the body. Neurodegenerative or traumatic damage to axons destroys neuronal function and thus necessitates axonal repair. Mammalian peripheral neurons can regrow their axons following injury, providing a robust system to study the molecular mechanisms of axon regeneration. Injury induces a large transcriptional program that drives regeneration. While many regeneration-associated genes are known, the mechanisms by which injury activates them are less well understood. Identification of new injury signals has been limited by in vivo approaches. To address this challenge, I developed and performed a loss-of-function pharmacological screen in cultured …
Preventing Extinction Of At-Risk Plant Species In A Complex World, Holly Lee Bernardo
Preventing Extinction Of At-Risk Plant Species In A Complex World, Holly Lee Bernardo
Arts & Sciences Graduate Student Theses and Dissertations
Earthճ current biodiversity crisis is now considered a true mass extinction event, with species level extinction rates well above background rates and population level extinction rates orders of magnitude more common that species extinctions. There are many threats driving this loss of biodiversity. How each threat impacts the viability of a species is highly context dependent, but all are anthropogenic in origin and so as the human population continues to increase, so too will the pressure of these threats on our natural systems. Ultimately, how much a threat decreases the viability of a species depends on how that threat influences …
Viral Mhc Class I Evasion Affects Anti-Viral T Cell Development And Responses, Elvin James Lauron
Viral Mhc Class I Evasion Affects Anti-Viral T Cell Development And Responses, Elvin James Lauron
Arts & Sciences Graduate Student Theses and Dissertations
Cytotoxic CD8+ T cells (CTLs) play a critical role in protective immunity against viruses, a fact underscored by the evolution of viral CTL evasion mechanisms. For instance, many viruses commonly target the major histocompatibility complex class I (MHCI) antigen presentation pathway to prevent CTLs from recognizing infected cells. A striking example of this is cowpox virus (CPXV), which interferes with MHCI antigen presentation through two distinct mechanisms. One mechanism of CPXV-mediated MHCI inhibition is to retain MHCI molecules in the endoplasmic reticulum (ER). The second mechanism is to prevent antigen peptide loading onto MHCI molecules. When combined these mechanisms result …
The Mechanism Of Hyper Daptomycin Resistance In Corynebacterium Striatum And Daptomycinճ Mechanism Of Action, Nicholas Kevork Goldner
The Mechanism Of Hyper Daptomycin Resistance In Corynebacterium Striatum And Daptomycinճ Mechanism Of Action, Nicholas Kevork Goldner
Arts & Sciences Graduate Student Theses and Dissertations
Daptomycin, a last line-of-defense antibiotic for treating Gram-positive infections, is experiencing clinical failure against important infectious agents, including Corynebacterium striatum. The recent transition of daptomycin to generic antibiotic status is projected to dramatically increase availability, use, and clinical failure. Despite daptomycinճ more than 30-year history as an important antibiotic, four major questions were left unanswered. 1) How do bacteria become hyper-resistant to daptomycin? 2) What is the in vivo membrane target of daptomycin? 3) How does daptomycin interact with the membrane? 4) What is daptomycinճ mechanism of killing? These four questions have plagued the daptomycin field, and even now conflicting …
The Role Of Membrane Excitability In Insulin Regulation, Christopher Howard Emfinger
The Role Of Membrane Excitability In Insulin Regulation, Christopher Howard Emfinger
Arts & Sciences Graduate Student Theses and Dissertations
In mammals, ATP-sensitive K+ (KATP) channels are essential regulators of insulin secretion from pancreatic islet [beta]-cells, illustrated by the finding that gain-of-function mutations in KATP channels (KATP-GOF) cause neonatal diabetes mellitus (NDM). However, variability in symptom severity and effectiveness of treatment is seen in NDM, even for those with the same mutation and in the same family. Short-term treatment of mice expressing KATP-GOF mutations in [beta]-cells (KATP-GOF mice) with the KATP blocker glibenclamide during disease onset results in two outcomes: one subset becomes severely diabetic (non-remitters), whereas the other subset remains below the glucose levels at which significant side effects …