Open Access. Powered by Scholars. Published by Universities.®
- Discipline
-
- Life Sciences (75)
- Medical Immunology (69)
- Allergy and Immunology (68)
- Immunology and Infectious Disease (68)
- Medical Specialties (68)
-
- Neurosciences (23)
- Microbiology (20)
- Cell and Developmental Biology (12)
- Biochemistry, Biophysics, and Structural Biology (9)
- Biology (8)
- Virology (8)
- Cell Biology (7)
- Genetics (7)
- Genetics and Genomics (7)
- Neuroscience and Neurobiology (7)
- Molecular Biology (6)
- Developmental Biology (5)
- Oncology (5)
- Bioinformatics (3)
- Biochemistry (2)
- Parasitology (2)
- Physiology (2)
- Psychology (2)
- Social and Behavioral Sciences (2)
- Biological Psychology (1)
- Biophysics (1)
- Congenital, Hereditary, and Neonatal Diseases and Abnormalities (1)
- Developmental Neuroscience (1)
- Keyword
-
- Immunotherapy (5)
- Macrophages (5)
- Cancer (4)
- Hematopoiesis (4)
- Microbiota (4)
-
- Dendritic cells (3)
- Inflammation (3)
- Natural killer cells (3)
- T cell (3)
- Tuberculosis (3)
- Virus (3)
- Alzheimer's disease (2)
- Bhlhe40 (2)
- Bladder (2)
- Colon (2)
- Cowpox (2)
- Dendritic Cells (2)
- Dendritic cell (2)
- Flavivirus (2)
- Genomics (2)
- Helicobacter (2)
- Host-pathogen interactions (2)
- IL-10 (2)
- Immunity (2)
- Innate immunity (2)
- Macrophage (2)
- Memory B cell (2)
- Metabolism (2)
- Microbiome (2)
- Microglia (2)
- Publication Year
Articles 1 - 30 of 92
Full-Text Articles in Medical Sciences
Characterization Of Subcellular Functional Domains In The Vesicular Glutamate Transporter 3-Expressing Retinal Amacrine Cell Using Correlative Light And Electron Microscopy, Karl Friedrichsen
Arts & Sciences Electronic Theses and Dissertations
The following work seeks to better understand how neurons process multiple streams of information within the branches of their dendritic arbors. We use correlated light and electron microscopy to capture both live subcellular calcium responses and detailed morphology and synaptic connectivity in a unique retinal amacrine cell in order to directly study the relationship between structure and function. The vesicular glutamate transporter 3-expressing amacrine cell (VG3) selectively integrates and segregates visual information within its arbor branches and provides multiple target neuron types with appropriate excitatory or inhibitory synaptic inputs. By reconstructing VG3 arbor branches, synapses, and connected cell types, we …
Sik3 & Wnk Signals Through Fray To Regulate Glial K+ Buffering And Seizure Susceptibility In Drosophila Models Of Hyperexcitability, Lorenzo Laronn Lones
Sik3 & Wnk Signals Through Fray To Regulate Glial K+ Buffering And Seizure Susceptibility In Drosophila Models Of Hyperexcitability, Lorenzo Laronn Lones
Arts & Sciences Electronic Theses and Dissertations
K+ homeostasis is important for maintaining healthy, physiological levels of neuronal activity. Glial cells play a central role in maintaining homeostatic ion gradients. In previous work from our lab, we unravel a glial K+ buffering program that is centered on a key kinase, salt-inducible kinase 3 (SIK3). SIK3-HDAC4 signaling in glial regulates the transcription of channels and transporters involved in water and ion transport. Defects in this pathway lead to peripheral nerve edema, neuronal hyperactivity, and seizure sensitivity. In an hyperexcitability mutant, eag Shaker, we show this pathway is downregulated and genetic activation suppresses seizure behavior. In this thesis, I …
Contributions Of Specific Retinal Circuits And Their Respective Projections To Visual Behaviors, Jenna Mackenzie Krizan
Contributions Of Specific Retinal Circuits And Their Respective Projections To Visual Behaviors, Jenna Mackenzie Krizan
Arts & Sciences Electronic Theses and Dissertations
The survival of a species is inextricably linked to its ability to successfully navigate and interact with its surroundings, whether to seek safety from predators or gain sustenance from prey. Both functions are performed by mice, guided by vision, and rely on intricate processing in the retina and subcortical targets in the brain. This dissertation addresses how specific features of the visual environment and specific retinal ganglion cell circuits that sample a particular space in the visual environment are used to guide efficient predation in mice.Recent studies have begun to link the ability to detect, track, and ultimately capture prey …
The Bidirectional Relationship Between The Circadian Clock And Alzheimer’S Disease, Patrick Sheehan
The Bidirectional Relationship Between The Circadian Clock And Alzheimer’S Disease, Patrick Sheehan
Arts & Sciences Electronic Theses and Dissertations
The circadian clock and inflammation have a well-described bidirectional relationship in the peripheral immune system: the circadian clock regulates inflammatory responses, but inflammation also impacts oscillatory gene transcription controlled by the clock. The purpose of this thesis work is to understand if manipulation of the circadian clock can impact Alzheimer’s disease pathology, and if pathology itself can alter the circadian clock and its outputs. Here, I show that astrocyte-specific disruption of the circadian clock via deletion of the clock gene Bmal1 surprisingly decreased intra-neuronal protein pathologies. Further investigation found that deletion of the circadian clock resulted in a transcriptomic profile …
Extensive Behavioral Phenotyping Of Williams Syndrome Locus Relevant Mouse Models To Assess Contributions Of Oxytocin And Gtf2ird1, Kayla Rose Nygaard
Extensive Behavioral Phenotyping Of Williams Syndrome Locus Relevant Mouse Models To Assess Contributions Of Oxytocin And Gtf2ird1, Kayla Rose Nygaard
Arts & Sciences Electronic Theses and Dissertations
The Williams Syndrome Critical Region (WSCR) at chromosome 7q11.23 provides a unique opportunity to untangle the relationship between genotype and phenotype in complex behaviors, from fear and anxiety to sociability and sensorimotor processing. Copy number variations (CNVs) in this region result in two syndromes, Williams Syndrome (WS) and Duplication 7q11.23 Syndrome (Dup7), which display phenotypes that may align, indicating a common disruption of a system, or diverge, reflecting an underlying gene dosage-dependent effect. While case studies of atypical deletions resulting in WS have implicated telomeric genes Gtf2ird1 and Gtf2i in the cognitive and behavioral profiles of WS, proving causation requires …
The Effects Of Nmda Antagonism On Neuronal Activity And Neurovascular Coupling In Non-Human Primate Cortex, Benjamin Thomas Acland
The Effects Of Nmda Antagonism On Neuronal Activity And Neurovascular Coupling In Non-Human Primate Cortex, Benjamin Thomas Acland
Arts & Sciences Electronic Theses and Dissertations
The N-methyl-D-aspartate receptor (NMDAR) plays a variety of important roles in the development and function of primate central nervous systems. This thesis describes three nonhuman primate studies that, together, demonstrate that pharmacologically reducing NMDAR activity not only causes dramatic changes in neural activity in cortex, but also changes the relationship between that activity and a key signal often used as its proxy in human studies, the blood-oxygen-level-dependent (BOLD) signal. The first study reveals that NMDA antagonism is sufficient to induce powerful low-frequency modulation of spiking activity and extracellular local field potential (LFP) and discusses the implications of this finding for …
Tissue Resident Macrophages Drive Fibrosis During Pancreas Inflammatory Injury And Pancreatic Ductal Adenocarcinoma, John Baer
Arts & Sciences Electronic Theses and Dissertations
The immune system, and especially macrophages, are central in responding to infections, as well as providing a wide array of functions in other pathologies, especially in responding to inflammation. It is established that macrophages will accumulate within tissues during inflammation, many times secreting cytokines and chemokines central to the inflammatory response. This is particularly true during pancreatitis, or inflammation of the pancreas, where it has been shown that macrophages and monocytes accumulate in the pancreas to have various roles in further promoting inflammation. It is not well established, however, whether there are divergent roles for the distinct macrophage subsets that …
Validation, Categorizing, And Prediction Of Upper Limb Outcomes After Stroke, Jessica Barth
Validation, Categorizing, And Prediction Of Upper Limb Outcomes After Stroke, Jessica Barth
Arts & Sciences Electronic Theses and Dissertations
The incidence and costs of stroke in the United States are projected to rise over the next decade because of the aging population. Declining stroke mortality over the past few decades means that more people survive stroke and live with physical, cognitive, and emotional disability. Stroke remains one of the leading causes of disability in the United States because very few survivors experience a full recovery of their upper limb. Upper limb recovery after stroke is critical to performing activities of daily living and physical and occupational therapies are one of the only treatment options to address these challenges. The …
Functional And Anatomical Characterization Of Descending Periaqueductal Gray (Pag) Projections And Their Role In Pain Modulation, Jose Gabriel Grajales
Functional And Anatomical Characterization Of Descending Periaqueductal Gray (Pag) Projections And Their Role In Pain Modulation, Jose Gabriel Grajales
Arts & Sciences Electronic Theses and Dissertations
Endogenous analgesic pathways embody a potential target for the development for chronic pain therapies. Previous studies have demonstrated the role of the ventrolateral periaqueductal gray (vlPAG) in descending pain modulation. It has been proposed that tonic GABAergic neurotransmission at the level of the vlPAG serves to inhibit efferent excitatory projections that mediate descending analgesia. Disinhibition of these projection neurons allows subsequent activation of rostral ventromedial medulla (RVM) neurons that inhibit nociception at the level of the spinal cord. However, lack of cell-type specificity in these studies has prevented the determination of the role of specific subsets of vlPAG neurons in …
Defining The Role Of Rare Genetic Variants That Drive Risk And Pathogenesis Of Alzheimer’S Disease, Matthew James Rosene
Defining The Role Of Rare Genetic Variants That Drive Risk And Pathogenesis Of Alzheimer’S Disease, Matthew James Rosene
Arts & Sciences Electronic Theses and Dissertations
Alzheimer’s disease (AD) is the leading cause of dementia and is pathologically defined by the aggregation of extracellular amyloid plaques and intracellular neurofibrillary tangles. Rare heritable mutations within the genes for amyloid precursor protein (APP) and presenilin 1 (PSEN1), and presenilin 2 (PSEN2) cause early onset AD and account for approximately 1% of AD cases. While the majority of AD cases are late-onset (LOAD), which is defined by a markedly more complex genetic architecture that is comprised of many genetic risk factors that influence AD through multiple cellular pathways. The advent of deep sequencing analyses have allowed for the identification …
Vcp: A Gatekeeper For Intracellular Proteopathic Seeding, Jiang Zhu
Vcp: A Gatekeeper For Intracellular Proteopathic Seeding, Jiang Zhu
Arts & Sciences Electronic Theses and Dissertations
Protein inclusions such as β-amyloid, tau, α-synuclein, and TDP-43 are considered the pathologic hallmarks of many neurodegenerative diseases. These proteins are prone to misfold, aggregate, and template new aggregates. Accumulating evidence suggests that those proteins in their high-molecular-weight forms can serve as a "seed", spread through an interconnected brain network, and induce new inclusions. Therefore, it is essential to understand the mechanism of proteopathic seeding. In this dissertation, we performed a whole genomic CRISPR-Cas9 KO screening to identify gene modifiers of αS seeding. Within the screening, we found several hits of endolysosomal function and trafficking, including VCP. VCP is a …
Understanding The Influence Of Individual-Level Sources Of Pathology Variation On Neuroimaging Measures Of Alzheimer Disease, Austin Andrew Mccullough
Understanding The Influence Of Individual-Level Sources Of Pathology Variation On Neuroimaging Measures Of Alzheimer Disease, Austin Andrew Mccullough
Arts & Sciences Electronic Theses and Dissertations
The overall goal of this dissertation is to gain a better understanding of how current Alzheimer disease pathologic progression models interact with sources of individual-level variation in pathology to influence overall disease progression in a clinically meaningful way. Many sources of variation, both internal (e.g., genetic mutations, heterogeneity of tau pathology) and external (e.g., diet and exercise, sleep quality), are known to influence disease progression and symptom onset in AD. With the advent of therapies that have shown successful reduction of amyloid load in trials and the rapid progression of anti-tau therapies, we hypothesize that a better understanding of how …
Disuse-Driven Plasticity In The Human Brain, Dillan James Newbold
Disuse-Driven Plasticity In The Human Brain, Dillan James Newbold
Arts & Sciences Electronic Theses and Dissertations
Brain circuits are shaped and maintained by active use. We blocked use of motor circuits in three adult participants by constraining the dominant upper extremity in a cast for two weeks, causing loss of strength and fine motor function. Daily resting-state functional magnetic resonance imaging (rs-fMRI) collected for 42-64 days before, during and after casting revealed two sets of changes in brain function. First, large, spontaneous pulses of activity occurred in the disused motor circuits. Pulses showed a consistent pattern of propagation through the disused circuits— occurring earliest in the dorsal anterior cingulate cortex (dACC) and supplementary motor area (SMA), …
Influence Of Focal Activity On Macroscale Brain Dynamics In Health And Disease, Zachary Pollack Rosenthal
Influence Of Focal Activity On Macroscale Brain Dynamics In Health And Disease, Zachary Pollack Rosenthal
Arts & Sciences Electronic Theses and Dissertations
Macroscopic recordings of brain activity (e.g. fMRI, EEG) are a sensitive biomarker of the neural networks supporting neurocognitive function. However, it remains largely unclear what mechanisms mediate changes in macroscale networks after focal brain injuries like stroke, seizure, and TBI. Recently, optical neuroimaging in animal models has emerged as a powerful tool to begin addressing these questions. Using widefield imaging of cortical calcium dynamics in mice, this dissertation investigates the mechanisms by which focal disruptions in activity alter brain-wide functional dynamics. In two chapters, I demonstrate 1) that focal sensory stimulation elicits state-dependent, global slow waves propagating from primary somatosensory …
The Role Of Neuronal Atp-Sensitive Potassium Channels In Learning And Memory, Shaul Vladimir Yahil
The Role Of Neuronal Atp-Sensitive Potassium Channels In Learning And Memory, Shaul Vladimir Yahil
Arts & Sciences Electronic Theses and Dissertations
ATP-sensitive potassium (KATP) channels link cellular metabolism and membrane excitability in many tissues, including brain and pancreas. Gain-of-function (GOF) mutations to KATP channels cause neonatal diabetes, with some patients exhibiting developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome. Diabetic symptoms have been attributed to loss of membrane excitability and insulin secretion in pancreatic β-cells, though the origin of neurological deficits and the effects of neuronal KATP-GOF mutations more generally remain elusive. In this dissertation, I will present evidence that mice expressing KATP-GOF mutations pan-neuronally (nKATP-GOF) demonstrated sensorimotor and cognitive deficits, whereas hippocampus-specific hKATP-GOF mice exhibited predominantly learning and memory deficits. …
Defining The Epigenetic And Transcriptional Regulatory Mechanisms By Which Hrsv Ns1 Alters Host Transcriptional Response, Nina Rose Beri
Defining The Epigenetic And Transcriptional Regulatory Mechanisms By Which Hrsv Ns1 Alters Host Transcriptional Response, Nina Rose Beri
Arts & Sciences Electronic Theses and Dissertations
No abstract provided.
On Arousal And The Internal Regulation Of Brain Function: Theory And Evidence Across Modalities And Species, Ryan Raut
Arts & Sciences Electronic Theses and Dissertations
The brain is an organ. It is subject to the same physiological regulatory processes that engage the rest of the body’s organs, sculpted over hundreds of millions of years to sustain life so effectively. The central message of this thesis is that the holistic functioning of the brain, rather than operating at some level above or independent from these systemic regulatory processes, is deeply related to them. In short, as our limited attention spans might suggest: brain function is internally regulated. I propose that this internal regulation is a primary function of intrinsic brain activity. Chapter 2 provides a theoretical …
Influence Of Aging And Cerebrovascular Disease On Neuroimaging Measures Of Alzheimer Disease, Lauren Nicole Koenig
Influence Of Aging And Cerebrovascular Disease On Neuroimaging Measures Of Alzheimer Disease, Lauren Nicole Koenig
Arts & Sciences Electronic Theses and Dissertations
The overall goal of this dissertation is to gain a better understanding of how Alzheimer disease relates to normal aging and cerebrovascular disease to impact neuroimaging measures in a clinically meaningful way. Both aging and cerebrovascular disease are known to influence measures of Alzheimer disease, making it difficult to separate what changes are attributable specifically to Alzheimer disease. We hypothesize that a better understanding of these relationships will allow future studies to appropriately take these factors into account. In Chapters 2 and 3 we attempt to separate out the influences of normal aging and Alzheimer disease on measures of atrophy. …
Identification Of Multi-Tissue Protein Quantitative Trait Loci And Causal Inference Of Protein Effects In Neurological And Other Complex Human Diseases Via Mendelian Randomization, Chengran Yang
Arts & Sciences Electronic Theses and Dissertations
Alzheimer disease (AD) is the most common neurodegenerative disease, affecting 6.2 million people mostly aged 65 years or older in the United States as of early 2021. AD has been widely studied and characterized worldwide, but there is still no effective treatment or cure. Even the latest FDA-approved treatment, Aducanumab, cannot stop decline or improve cognition. To develop a truly effective treatments, researchers keep discovering genetic and molecular mechanisms underlying the disease. Protein biomarkers are keys to bridge the mechanisms to disease. Here, I first used a high-throughput proteomic dataset from three tissues (CSF, plasma, and brain) with array-based genotype …
Genetic Risk Factors For Neurodevelopmental Disorders: Insights From Hipsc-Cerebral Organoids, Michelle L. Wegscheid
Genetic Risk Factors For Neurodevelopmental Disorders: Insights From Hipsc-Cerebral Organoids, Michelle L. Wegscheid
Arts & Sciences Electronic Theses and Dissertations
Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder (NDD) characterized by remarkable phenotypic variability, where affected children manifest a spectrum of central nervous system (CNS) abnormalities, including brain tumors, impairments in attention, behavior, learning disabilities, and an increased incidence of autism spectrum disorder (ASD). A significant barrier to the implementation of precision medicine strategies for children with NF1 is a lack of prognostic risk factors to guide clinical management. However, emerging population-based genotype-phenotype association studies have suggested that the germline NF1 gene mutation may represent one clinically actionable risk factor for NF1-associated neurodevelopmental abnormalities. As a critical step in …
Causal Function And Bias Correlation Of The Orbitofrontal Cortex In Economic Choices, Shi Weikang
Causal Function And Bias Correlation Of The Orbitofrontal Cortex In Economic Choices, Shi Weikang
Arts & Sciences Electronic Theses and Dissertations
Economic choices entail two mental processes, value calculation and value comparison (Niehans, 1990). Studies in the last twenty years have shown that neurons in the orbitofrontal cortex (OFC) could support both processes. Namely, in the studies in which monkeys chose between two juice options with various amounts, three functional cell groups had been found in the OFC: offer value cells encode the value of individual juices, chosen juice cells encode the choice in a binary way and chosen value cells encode the value of the chosen juice (Padoa-Schioppa and Assad, 2006). These results suggest a decision circuit within OFC with …
Slo2.1 Channels: A New Molecular Mechanism To Regulate Uterine Excitability, Juan Jose Ferreira
Slo2.1 Channels: A New Molecular Mechanism To Regulate Uterine Excitability, Juan Jose Ferreira
Arts & Sciences Electronic Theses and Dissertations
At the end of pregnancy, the uterus transitions from a non-contractile state to a highly contractile state. Two processes primarily drive this transition. First, from the 28th week of pregnancy until labor, the resting membrane potential of uterine (myometrial) smooth muscle cells (MSMCs) gradually becomes more positive (depolarizes) (Parkington et al. 1999). Second, at the end of pregnancy, MSMCs express more oxytocin receptors and become more sensitive to oxytocin (Kimura et al. 1996). However, the detailed mechanisms by which these processes occur have not been determined. My central hypothesis was that the Na+-activated K+ channel SLO2.1 plays a key role …
Role Of 4r Tau In Astrocyte-Mediated Neuronal Toxicity And The Progression Of Neurodegenerative Disease, Lubov Alexandra Ezerskiy
Role Of 4r Tau In Astrocyte-Mediated Neuronal Toxicity And The Progression Of Neurodegenerative Disease, Lubov Alexandra Ezerskiy
Arts & Sciences Electronic Theses and Dissertations
The microtubule-binding protein tau is associated with neurodegenerative diseases, including Alzheimer’s disease, progressive supranuclear palsy, and a subset of frontotemporal dementias. In these tauopathies, tau becomes hyperphosphorylated and forms intracellular neurofibrillary tau tangles, contributing to synaptic dysfunction, neuronal death, and severe astrogliosis. Tau can be classified as having a 3-repeat (3R) or 4-repeat (4R) structure, resulting from alternative splicing of exon 10 within the MAPT gene. While the higher deposition of 4R tau characterizes many primary tauopathies, the role of 4R tau in neurodegenerative disease pathogenesis remains unclear. To investigate the role of tau isoforms in disease, we created tau …
Metabolic Control And Immune Barriers Of Hematopoietic Stem Cells, Hannah Pizzato
Metabolic Control And Immune Barriers Of Hematopoietic Stem Cells, Hannah Pizzato
Arts & Sciences Electronic Theses and Dissertations
Hematopoietic stem cells (HSCs) have the unique ability to self-renew for life, to differentiate into mature blood lineages, and to readily engraft upon intravenous transplantation. As such, they are the only types of stem cells in routine clinical use. Understanding HSCs and hematopoietic development can provide many lessons for other types of stem cells as they near clinical utility. Through bone marrow transplantation, it was discovered that cells exist with regenerative potential. This led to the search to purify these cells and to determine the function of other hematopoietic cells. By isolating and transplanting cells expressing different combinations of surface …
Investigating The Role Of Bladder Epithelial Stem Cells In Bladder Mucosal Remodeling And Defense Against Infection, Seongmi Kim Russell
Investigating The Role Of Bladder Epithelial Stem Cells In Bladder Mucosal Remodeling And Defense Against Infection, Seongmi Kim Russell
Arts & Sciences Electronic Theses and Dissertations
Urinary tract infections (UTIs) can be highly recurrent, and the mechanism(s) governing recurrence susceptibility are mostly unknown. Here I demonstrate bladder epithelial (urothelial)-intrinsic trained immunity as part of a differential mucosal remodeling response to an initial UTI. I established urothelial stem cell (USC) lines from isogenic mice with different UTI histories (naïve, chronic, or self-resolving) and discovered 2880 differential genome-accessible regions, indicating differential epigenetic reprogramming dependent on infection history. Differentiation of USC lines in vitro resulted in polarized urothelial cultures that recapitulated distinct remodeling morphologies seen in vivo and exhibited altered gene expression, including genes involved in cell death pathways. …
Regulation Of Host-Microbe Interactions In Autoimmunity And Antiviral Immunity By Cytosolic Nucleic Acid Sensing And Interferon Signaling, Derek Jerome Platt
Regulation Of Host-Microbe Interactions In Autoimmunity And Antiviral Immunity By Cytosolic Nucleic Acid Sensing And Interferon Signaling, Derek Jerome Platt
Arts & Sciences Electronic Theses and Dissertations
Cytosolic nucleic acid sensing and interferon (IFN) signaling are central to the host immune response to microbial pathogens. However, dysregulation of immunological pathways such as these can result in devastating autoimmune disease. In order to provide a robust immune response to pathogen without causing harm to self, the host immune system must engage in a delicate balancing act, interacting with microbes and determining whether they are commensal or pathogenic. The cGAS-STING pathway is a key regulator of host-microbe interactions by cytosolic nucleic sensing and IFN signaling. Loss of function in the cGAS-STING pathway leads to increased susceptibility to pathogenic threats, …
Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc
Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc
Arts & Sciences Electronic Theses and Dissertations
Rapid cell proliferation is a hallmark feature of adaptive immune cells lymphocytes. It is essential for the establishment of diverse antigen receptor repertoires and amplification of antigen-specific immune responses. While such proliferation is beneficial for host protection from infections and cancers, it inevitably elevates the risk of oncogenic transformation. In developing and germinal center B lymphocytes, the risk is further increased by endogenous, genomic insults due to antigen receptor rearrangements and somatic mutations, with which expression of the proto-oncogene c-MYC is closely associated. Nonetheless, frequencies of cancers originated from B lymphocytes are relatively low, suggesting that they are protected from …
The Immunoregulation Of Autoimmune Diabetes, Hao Hu
The Immunoregulation Of Autoimmune Diabetes, Hao Hu
Arts & Sciences Electronic Theses and Dissertations
How autoimmune diseases are regulated is a long-term research topic in the autoimmunity field. We use autoimmune diabetes as a model to study this. Autoimmune diabetes is a T cell-dependent autoimmune syndrome. The functions of T cells are regulated during their development and activation. Developmentally, T cells will undergo a stringent thymic selection: a process that self-reactive T cells are tolerized to become thymic derived Tregs or can be deleted by apoptosis based on binding affinity and avidity between the TCRs and self-peptide:MHC complexes. After T cells mature, they can also be tolerized in the periphery in many other ways, …
Investigation Of Ifnγ-Induced Control Of Intracellular Pathogens, Michael Mcallaster
Investigation Of Ifnγ-Induced Control Of Intracellular Pathogens, Michael Mcallaster
Arts & Sciences Electronic Theses and Dissertations
Genes required for the lysosomal degradation pathway of autophagy play key roles in topologically distinct cellular processes with significant physiologic importance. One of the first-described of these ATG gene-dependent processes is the requirement for a subset of ATG genes in interferon-γ (IFNγ)-induced inhibition of norovirus and Toxoplasma gondii replication. In this dissertation we identified novel components that are required for or that negatively regulate this immune mechanism. Enzymes involved in the conjugation of UFM1 to target proteins including UFC1 and UBA5, negatively regulated IFNγ-induced inhibition of norovirus replication via effects of Ern1. We identified and confirmed that IFNγ-induced inhibition of …
Peripheral Nerve Macrophages And Their Implications In Neuroimmunity, Peter Leon Wang
Peripheral Nerve Macrophages And Their Implications In Neuroimmunity, Peter Leon Wang
Arts & Sciences Electronic Theses and Dissertations
Macrophages are innate immune cells that protect against pathogens and maintain tissue integrity. In vertebrates, macrophages reside in every tissue where they perform specific functions from early development through adulthood. While macrophages provide important functions across all tissues, a major focus in recent years has been the role of resident brain macrophages, known as microglia, in neurodegeneration. As microglia have been shown to affect brain development, homeostasis, and disease, they demonstrate how immune cells critically mediate neurological health and point to the broader significance of neuroimmune interactions, or the coordinated actions of the nervous and immune systems for maintaining tissue …