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Articles 61 - 90 of 1126
Full-Text Articles in Biology
Acquisition Algorithms For Protein Mass Spectrometry And Their Application To Clinical Proteomics, Nathan Wamsley
Acquisition Algorithms For Protein Mass Spectrometry And Their Application To Clinical Proteomics, Nathan Wamsley
Arts & Sciences Graduate Student Theses and Dissertations
Bottom-up protein mass spectrometry aims for the identification and quantification of protein species by proxy of their proteolytic peptides. This dissertation presents methodological advances in three areas of protein mass spectrometry: acquisition methods, clinical appli- cations, and data analysis algorithms. The second chapter presents an optimized internal standard-triggered parallel reaction monitoring (OIS-PRM) method and demonstrates its application to study prognostic biomarkers in head and neck squamous cell carcinoma (HN- SCC). OIS-PRM uses intelligent scan scheduling and real-time monitoring of peptide elution profiles to reduce cycle-times and improve quantitative precision and accuracy. The assay measured NRF2 activation in both cell lines …
Examing The Role Of Complement Signaling In Viral Neuroinflammatory Responses, Marlene Kanmogne
Examing The Role Of Complement Signaling In Viral Neuroinflammatory Responses, Marlene Kanmogne
Arts & Sciences Graduate Student Theses and Dissertations
The complement system is an ancient pathway that serves dual roles as a key regulator of neuroinflammation and a critical regulator of neural networks. Few studies have addressed how these two pathways may interact during infection of the central nervous system. While some components of complement are expressed in the healthy developing brain, complement component 3a receptor (C3aR) is a G protein coupled receptor that is expressed by astrocytes, microglia and infiltrating immune cells during inflammatory states. We previously found that C3aR is required for engulfment of synaptic material by activated microglia during neuroinvasive viral infection. Here, we used a …
Mutant-Specific Analysis Of Tumor Cell Heterogeneity In Glioblastoma, Patrick Desouza
Mutant-Specific Analysis Of Tumor Cell Heterogeneity In Glioblastoma, Patrick Desouza
Arts & Sciences Graduate Student Theses and Dissertations
Glioblastoma (GBM) is an aggressive brain tumor driven by the interplay between tumor cell-intrinsic and -extrinsic heterogeneity, enabling rapid evolution. To investigate how canonical GBM mutations promote functional plasticity, we developed an isogenic human neural stem cell (NSC) model of GBM by sequential addition of TERT promoter, TP53, and PDGFRA point mutations. TP53 loss-of-function increased TERT expression during serial mutagenesis, but only triple mutant NSCs reliably formed lethal brain tumors in vivo that recapitulate GBM. Tumor cell evolution triggered stress-related metabolic changes and transitioned toward a neuronal progenitor network driven by transcription factor INSM1. INSM1 is highly expressed in human …
Role Of The Small Intestinal Microbiota In The Pathogenesis Of Environmental Enteric Dysfunction In Undernourished Children And Mothers, Clara Kao
Arts & Sciences Graduate Student Theses and Dissertations
Undernutrition in women and its propagation in their children remains a major global health challenge. Worldwide, one in five children under five years of age manifests undernutrition as impaired linear growth, or stunting. Stunting, defined as having a length-for-age z-score (LAZ) <-2, is associated with poor developmental outcomes, including impaired neurodevelopment and immune responses. Furthermore, stunting and its long-term sequelae persist across generations, contributing to an intergenerational cycle of undernutrition. Existing nutritional interventions fail to substantially improve stunting, highlighting the need to (i) better understand other factors contributing to stunting and (ii) focus clinical efforts towards treating maternal undernutrition. Environmental enteric dysfunction (EED) is a subclinical inflammatory enteropathy of the small intestine proposed to contribute to stunting. EED is diagnosed histologically by blunted intestinal villi, epithelial barrier disruption and an immunoinflammatory infiltrate in the lamina propria. However, the pathophysiology of EED remains poorly defined. Furthermore, the small intestinal microbiota remains understudied due to difficulties in sampling. Evidence that the small intestinal microbiota contributes to EED pathogenesis comes in part from our collaborative work with colleagues at icddr,b (the International Centre for Diarrhoeal Disease Research, Bangladesh) who oversaw the Bangladesh EED (BEED) study. In this study children, aged 12-18 months residing in an urban slum in the Mirpur district of Dhaka who failed a nutritional intervention for their stunting, underwent esophago-gastroduodenoscopy (EGD) to obtain duodenal mucosal biopsies, aspirates of duodenal luminal fluid and plasma samples. A set of 14 bacteria taxa (defined by 16S rRNA amplicon sequencing) were identified in the duodenal microbiota of >80% of children with EED. Moreover, the absolute abundances of these ‘core taxa’ were positively correlated with duodenal mucosal and systemic inflammation in study participants and negatively correlated with linear growth. Our lab showed that introduction of a consortium of bacteria cultured from these duodenal aspirates, including these core taxa, produced small intestinal inflammation in young adult gnotobiotic, providing …
Parsing Heterogeneity In Depression, Kayla Hannon
Parsing Heterogeneity In Depression, Kayla Hannon
Arts & Sciences Graduate Student Theses and Dissertations
Depression is a highly prevalent mental health disorder that often requires treatment. While current treatments are effective for a large portion of patients generally, the exact medication that works for any specific person is unclear, leading to large delays in symptom remittance if at all. This hurdle has motivated substantial efforts to identify markers of depression that might predict treatment outcomes. However, large sources of heterogeneity in depression have stymied progress on identifying robust and replicable neuroimaging markers. Parsing this heterogeneity is crucial but mired with challenges. My dissertation work has elucidated several key barriers in parsing the heterogeneity of …
Exploring Ddr2’S Role In Caf Extracellular Matrix Production And Tumor Progression, Favour Ayomide Akinjiyan
Exploring Ddr2’S Role In Caf Extracellular Matrix Production And Tumor Progression, Favour Ayomide Akinjiyan
Arts & Sciences Graduate Student Theses and Dissertations
Ovarian cancer has poor survival outcomes particularly for advanced stage, metastatic disease. Metastasis is promoted by interactions of stromal cells, such as cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), with tumor cells. CAFs play a key role in tumor progression by remodeling the TME and extracellular matrix (ECM) to result in a more permissive environment for tumor progression. It has been shown that fibroblasts, in particular myofibroblasts, utilize metabolism to support ECM remodeling. However, the intricate mechanisms by which CAFs support collagen production and tumor progression are poorly understood. In this study, we show that the fibrillar collagen receptor, …
Effects Of Pharmacologic And Genetic Manipulation Of Gaba-A Receptors On Network Activity, Peter Michael Lambert
Effects Of Pharmacologic And Genetic Manipulation Of Gaba-A Receptors On Network Activity, Peter Michael Lambert
Arts & Sciences Graduate Student Theses and Dissertations
GABAA receptors (GABAARs) are the primary inhibitory neurotransmitter receptors in the central nervous system. A rich diversity of receptor subtypes are produced by the combination of various GABA receptor subunits into a heteropentameric chloride channel. Inhibitory signaling through GABAARs occurs on timescales ranging from fast synaptic events lasting milliseconds to tonically active receptors providing standing inhibitory tone. GABAARs are modulated by many clinically important drugs including anesthetic, hypnotic, anxiolytic, and antidepressant agents. Of note, GABAARs are modulated by neurosteroids, which have recently been developed as novel therapeutic agents for psychiatric disease. The synchronized activation of GABAARs through coordinated activity of …
Roles Of Cpsa And Slamf1 In The Innate Immune Response To Mycobacterium Tuberculosis, Steven Grigsby
Roles Of Cpsa And Slamf1 In The Innate Immune Response To Mycobacterium Tuberculosis, Steven Grigsby
Arts & Sciences Graduate Student Theses and Dissertations
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), possesses an arsenal of virulence factors to evade host immunity. Not only is Mtb able to evade innate immunity, but adaptive immunity also often fails to adequately control Mtb infection. A mechanistic understanding of how Mtb establishes infection and evades immunity is critical to the development of a protective vaccine and novel therapeutics. The Mtb protein CpsA protects Mtb against the host NADPH oxidase and LC3-asociated phagocytosis of the innate immune system. Consequently, a ΔcpsA mutant is initially attenuated in vivo but eventually reaches the same bacterial burden in the lungs …
Novel Therapeutics For Myeloid Malignancies, Tim Kong
Novel Therapeutics For Myeloid Malignancies, Tim Kong
Arts & Sciences Graduate Student Theses and Dissertations
Myeloid malignancies are a group of heterogenous and clonal disorders that include myeloproliferative neoplasms (MPNs) and acute myeloid leukemia (AML). These blood cancers are driven by characteristic oncogenes and propagated by pro-inflammatory niches; MPNs demonstrate hyperactive JAK-STAT signaling and upregulate cytokines including TNF, IL-6, and IL-8. Current therapeutics such as ruxolitinib targeting JAK2 providing symptomatic benefit to MPN patients but are not curative and do not prevent disease transformation to acute myeloid leukemia (AML). As such, greater understanding of the underlying disease biology is still required with means of uncover cancer dependencies. Here, we utilize a series of multi-omic approaches …
Senescent Cancer-Associated Fibroblasts Mediate Immunosuppression And Promote Breast Cancer Progression, Jiayu Ye
Arts & Sciences Graduate Student Theses and Dissertations
Breast cancer is the most frequently diagnosed cancer among women worldwide, and aging is the largest risk factor for breast cancer development. The process of aging is typically accompanied by a progressive accumulation of senescent cells, which are characterized by a series of markers such as p16INKA4 (p16) positivity and a distinctive profile of secretory factors including mitogens, cytokines, and extracellular matrix (ECM) proteins that are collectively recognized as senescence-associated secretory phenotype (SASP). Numerous data so far have shown that senescent stromal cells play critical roles in modulating tumor microenvironment and progression. For example, senescent fibroblasts induced in vitro could …
Models And Mechanisms Of Chemotherapy-Induced Side Effects, Junwei Du
Models And Mechanisms Of Chemotherapy-Induced Side Effects, Junwei Du
McKelvey School of Engineering Graduate Student Theses & Dissertations
Cancer is among the leading causes of death worldwide. Chemotherapy remains a cornerstone in the treatment of various cancers; however, it often leads to a range of debilitating side effects that compromise its efficacy and profoundly impact patients' quality of life and psychosocial well-being. These side effects can be broadly categorized into short-term effects, such as nausea, vomiting, fatigue, hair loss, and neutropenia, and long-term effects which can persist months or even years after treatment, including peripheral neuropathies, cognitive impairment, cardiotoxicity, nephrotoxicity and ototoxicity. Among the most common and dose-limiting side effects are chemotherapy-induced peripheral neuropathy (CIPN) and cardiotoxicity (CTX). …
Biology Department Publications: 2024, Sam Lindgren
Biology Department Publications: 2024, Sam Lindgren
Biology Department Bibliographies
This document is a non-comprehensive list of publications made by graduate students, post-doctoral researchers, and faculty members in the Biology Department in 2024. It indexes those publications available through PubMed, and serves as an archival record of the Department's robust scholarly contributions.
Characterization Of Long-Noncoding Rnas In Prostate And Pancreatic Cancer Through Single Cell Transcriptomics, Debanjan Saha
Characterization Of Long-Noncoding Rnas In Prostate And Pancreatic Cancer Through Single Cell Transcriptomics, Debanjan Saha
Arts & Sciences Graduate Student Theses and Dissertations
Metastatic castration resistant prostate cancer (mCRPC) is a subtype of prostate cancer that develops after metastasis and resistance to hormone therapy, thereby carrying a poor prognosis. Likewise, pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies due to its propensity to present at advanced, unresectable stages in patients. Recent genomic studies have identified molecular features of mCRPC and PDAC, such as the existence of mutations in key driver genes, the extensive transcriptomic intra-tumoral heterogeneity, the role of regulatory elements in dictating driver gene expression, mechanisms of treatment resistance, and the interactions with the immunosuppressive and stromal tumor- microenvironment …
Pilrα Sustains Microglial Capacity To Process Myelin In A Mouse Model Of Demyelination, Kent Lin
Pilrα Sustains Microglial Capacity To Process Myelin In A Mouse Model Of Demyelination, Kent Lin
Arts & Sciences Graduate Student Theses and Dissertations
Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles, and neurodegeneration. Microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in AD pathogenesis by containing the spreading of Aβ plaques. Genetic studies have associated a variant of the receptor Paired Immunoglobulin-like Type 2 Receptor Alpha (PILRα) with reduced risk for AD. PILRα is a receptor found on myeloid cells, such as microglia, that binds to endogenous cell surface glycoproteins and sends inhibitory signals within the cell. Additionally, it serves as an entry receptor for Herpes Simplex Virus 1. To elucidate the role …
Understanding Strain-Level Dynamics In Gut Commensal-Pathogen-Host Interactions, Anna Louise Deveaux
Understanding Strain-Level Dynamics In Gut Commensal-Pathogen-Host Interactions, Anna Louise Deveaux
Arts & Sciences Graduate Student Theses and Dissertations
The human gut microbiome is a consortium of trillions of bacteria, archaea, fungi, and viruses that colonizes the gastrointestinal tract and promotes health under homeostatic conditions. This microbial community trains the immune system, modulates inflammation and anticancer immunity, promotes cardiometabolic health, enables nutrient extraction, and prevents pathogen overgrowth. The latter function manifests through colonization resistance, in which microbes occupy spatial and nutritional niches thereby excluding pathogens from the community entirely, and through limiting pathogen population growth if colonization occurs. These roles are facilitated by complex host-microbe and microbe-microbe interactions that underlie differences in susceptibility to microbiome-mediated infectious diseases. The strain-level …
Dissecting The Contribution Of Stmn2 To Als Pathogenesis, Kelsey Krus
Dissecting The Contribution Of Stmn2 To Als Pathogenesis, Kelsey Krus
Arts & Sciences Graduate Student Theses and Dissertations
TDP-43 is required for splicing of Stathmin-2 (STMN2) transcript, so STMN2 is reduced in most ALS patients. TDP-43 does not regulate STMN2 in mice as it does in humans. Thus, mouse models of ALS do not reflect patient loss of STMN2. To test the hypothesis that a reduction in STMN2 contributes to ALS pathogenesis, we generated STMN2 knockout mice. Constitutive STMN2 loss induces an early sensory and motor neuropathy with disrupted motor behavior and dramatic distal neuromuscular junction (NMJ) denervation. This NMJ pathology occurs in fast-fatigable motor units, which are the most vulnerable in ALS. In contrast, motoneurons and axons …
Barriers And Breakthroughs In The Evolution Of Aggregative Multicellularity, Israt Jahan
Barriers And Breakthroughs In The Evolution Of Aggregative Multicellularity, Israt Jahan
Arts & Sciences Graduate Student Theses and Dissertations
The evolution of multicellular organization represents a key innovation in the history of life, yet fundamental questions remain about the evolutionary mechanisms that allowed some lineages to achieve remarkable complexity, while constrained others in their elaboration. The widely accepted single-cell bottleneck model provides a compelling explanation for the success of clonal multicellularity by reducing internal conflict and facilitating developmental integration. However, this perspective does not fully account for the stability and repeated evolution of aggregative multicellularity, where cooperation emerges among previously independent cells that may not be genetic relatives. Aggregative multicellularity demonstrates that the evolution of multicellularity is not a …
Barriers And Breakthroughs In The Evolution Of Aggregative Multicellularity, Israt Jahan
Barriers And Breakthroughs In The Evolution Of Aggregative Multicellularity, Israt Jahan
Arts & Sciences Graduate Student Theses and Dissertations
The evolution of multicellular organization represents a key innovation in the history of life, yet fundamental questions remain about the evolutionary mechanisms that allowed some lineages to achieve remarkable complexity, while constrained others in their elaboration. The widely accepted single-cell bottleneck model provides a compelling explanation for the success of clonal multicellularity by reducing internal conflict and facilitating developmental integration. However, this perspective does not fully account for the stability and repeated evolution of aggregative multicellularity, where cooperation emerges among previously independent cells that may not be genetic relatives. Aggregative multicellularity demonstrates that the evolution of multicellularity is not a …
Defining B Cell Responses To Emerging Viral Pathogens, Wafaa Al Soussi
Defining B Cell Responses To Emerging Viral Pathogens, Wafaa Al Soussi
Arts & Sciences Graduate Student Theses and Dissertations
The primary series of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines greatly reduced the burden of the coronavirus disease 2019 (COVID-19) pandemic and saved millions of lives. However, waning levels of circulating neutralizing antibodies and the continuous emergence of SARS-CoV-2 variants with increasing numbers of mutations in the spike (S) protein have decreased vaccine effectiveness and led to a recommendation for booster immunizations. In addition, new vaccines based on circulating variants have been developed to enhance the ability of induced antibodies to combat such variants. However, a critical unanswered question was how prior exposure to the ancestral SARS-CoV-2 strain …
Defining B Cell Responses To Emerging Viral Pathogens, Wafaa Al Soussi
Defining B Cell Responses To Emerging Viral Pathogens, Wafaa Al Soussi
Arts & Sciences Graduate Student Theses and Dissertations
The primary series of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines greatly reduced the burden of the coronavirus disease 2019 (COVID-19) pandemic and saved millions of lives. However, waning levels of circulating neutralizing antibodies and the continuous emergence of SARS-CoV-2 variants with increasing numbers of mutations in the spike (S) protein have decreased vaccine effectiveness and led to a recommendation for booster immunizations. In addition, new vaccines based on circulating variants have been developed to enhance the ability of induced antibodies to combat such variants. However, a critical unanswered question was how prior exposure to the ancestral SARS-CoV-2 strain …
A Role For The Actin Cytoskeleton And Plastin-3 In Osteoblast Mineralization And Mechanosensation, Samantha Meagan Chin
A Role For The Actin Cytoskeleton And Plastin-3 In Osteoblast Mineralization And Mechanosensation, Samantha Meagan Chin
Arts & Sciences Graduate Student Theses and Dissertations
The great diversity in actin network architectures and dynamics is exploited by cells to drive fundamental biological processes including cell migration, intracellular trafficking, and cell division. One such system that relies on the actin cytoskeleton to fulfill its physiological function are osteoblasts, which are mesenchymal lineage bone cells that promote bone formation through depositing a collagen scaffold and subsequently promoting mineralization of this matrix. A number of factors are known to drive osteogenic differentiation of pre-osteoblast cells including extracellular matrix cues such as substrate stiffness, which are primarily detected via mechanosensitive machinery linked to the actin cytoskeleton. Disruptions to β-actin, …
Pituitary Adenylate Cyclase Activating Polypeptide And Its Receptor As Novel Therapeutic Targets For Opioid Induced Hyperalgesia, Elizaveta Mangutov
Pituitary Adenylate Cyclase Activating Polypeptide And Its Receptor As Novel Therapeutic Targets For Opioid Induced Hyperalgesia, Elizaveta Mangutov
Arts & Sciences Graduate Student Theses and Dissertations
Opioids are commonly prescribed for the treatment of pain and headache disorders. However, chronic opioid use can result in a paradoxical increased sensitivity to pain as well as an extension of pain area known as opioid-induced hyperalgesia (OIH). One field OIH has been clearly identified is migraine, known as medication overuse headache (MOH). While opioids may provide acute relief, chronic use results in increased migraine pain severity and progression of migraine from an episodic to chronic state. The primary treatment is opioid cessation, which is difficult to implement as patients are reluctant to stop treatment they believe is helping them, …
Pituitary Adenylate Cyclase Activating Polypeptide And Its Receptor As Novel Therapeutic Targets For Opioid Induced Hyperalgesia, Elizaveta Mangutov
Pituitary Adenylate Cyclase Activating Polypeptide And Its Receptor As Novel Therapeutic Targets For Opioid Induced Hyperalgesia, Elizaveta Mangutov
Arts & Sciences Graduate Student Theses and Dissertations
Opioids are commonly prescribed for the treatment of pain and headache disorders. However, chronic opioid use can result in a paradoxical increased sensitivity to pain as well as an extension of pain area known as opioid-induced hyperalgesia (OIH). One field OIH has been clearly identified is migraine, known as medication overuse headache (MOH). While opioids may provide acute relief, chronic use results in increased migraine pain severity and progression of migraine from an episodic to chronic state. The primary treatment is opioid cessation, which is difficult to implement as patients are reluctant to stop treatment they believe is helping them, …
A Role For The Actin Cytoskeleton And Plastin-3 In Osteoblast Mineralization And Mechanosensation, Samantha Meagan Chin
A Role For The Actin Cytoskeleton And Plastin-3 In Osteoblast Mineralization And Mechanosensation, Samantha Meagan Chin
Arts & Sciences Graduate Student Theses and Dissertations
The great diversity in actin network architectures and dynamics is exploited by cells to drive fundamental biological processes including cell migration, intracellular trafficking, and cell division. One such system that relies on the actin cytoskeleton to fulfill its physiological function are osteoblasts, which are mesenchymal lineage bone cells that promote bone formation through depositing a collagen scaffold and subsequently promoting mineralization of this matrix. A number of factors are known to drive osteogenic differentiation of pre-osteoblast cells including extracellular matrix cues such as substrate stiffness, which are primarily detected via mechanosensitive machinery linked to the actin cytoskeleton. Disruptions to β-actin, …
Leveraging Arginine Catabolism To Treat Metabolic Complications, Yiming Zhang
Leveraging Arginine Catabolism To Treat Metabolic Complications, Yiming Zhang
Arts & Sciences Graduate Student Theses and Dissertations
Fasting and caloric restriction are effective to treat patients with pre-diabetes or metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), but intensive lifestyle changes are difficult for many to implement and sustain. Therefore, by identifying and studying fasting-mediated signals, we hope to elicit and convey the therapeutic effects of fasting against MASLD without actual physiological fasting. We discovered a key pathway in the liver through unbiased transcriptomic screening in fasted mice, a novel glucose fasting-activated effector: the amino acid hydrolase, arginase 2 (ARG2). Our previously published data demonstrates that forced hepatocyte-specific Arg2 overexpression is …
A Mechanistic Exploration Of How Neighborhood Crime Exposure Relates To Neonatal Brain Function, Early Externalizing Behaviors, And Callous-Unemotional Traits, Rebecca Brady
Arts & Sciences Graduate Student Theses and Dissertations
Pregnancy through early childhood is a period of tremendous neural and behavioral development. Neuronal birth and migration occur prenatally and result in the formation of neonatal functional and structural networks. These early brain networks are a building block for postnatal development wherein infants rapidly learn a variety of new skills, including socioemotional skills such as emotion regulation and moral understanding. During the acquisition of these skills, even typically developing toddlers can act aggressively or impulsively; however, toddlers with high levels of externalizing behaviors are more likely to develop clinical externalizing disorders later in childhood and adolescence. As such, it is …
Examination Of Protective Mucosal Immune Responses To Viral Sexually Transmitted Infections, Aisha Lee
Examination Of Protective Mucosal Immune Responses To Viral Sexually Transmitted Infections, Aisha Lee
Arts & Sciences Graduate Student Theses and Dissertations
Sexually transmitted infections (STI) are a prominent global health issue that affect the sexual and reproductive health of billions worldwide. Viral STIs present a particular challenge due to limited availability of treatment options and their frequent establishment of lifelong infection. One of the most common viral STIs is genital herpes, a recurrent ulcerative disease caused by chronic infection with the human alphaherpesviruses, HSV-1 or HSV-2. Women are particularly susceptible to morbidities of infection ranging from increased risk of HIV-1 acquisition to vertical transfer to neonates, for whom infection can be fatal. Previous efforts to develop a prophylactic vaccine for genital …
Exploring The Homeostatic Functions And Driving Forces Of Lymphatic Outflow Pathways From The Central Nervous System, Zachary Matthew Papadopoulos
Exploring The Homeostatic Functions And Driving Forces Of Lymphatic Outflow Pathways From The Central Nervous System, Zachary Matthew Papadopoulos
Arts & Sciences Graduate Student Theses and Dissertations
Lymphatic drainage from the central nervous system (CNS) has been noted and described for several hundred years, yet its physiological roles have remained unclear. The fluid homeostasis of the CNS has long stood as an area of scientific interest due to primary disorders including hydrocephalus. However, the early days of neuroimmunology leaned on the lack of lymphatic vasculature in the CNS as a contributing explanation for ‘immune privilege’ in the CNS. As a result, the importance of lymphatics in CNS homeostasis has remained poorly understood and controversial. Following a renaissance in interest in the contribution of lymphatics to CNS homeostasis, …
Mechanism Of Impaired Cd8+ T Cell Activation During Ross River Virus Infection, Christopher Bullock
Mechanism Of Impaired Cd8+ T Cell Activation During Ross River Virus Infection, Christopher Bullock
Arts & Sciences Graduate Student Theses and Dissertations
Ross River virus (RRV) is a mosquito transmitted virus endemic to Australia that infects humans and causes acute symptoms of rash, fever, myalgia, and fatigue. Although systemic viral infection subsides within a few weeks, joint pain lingers in many patients for months. Active viral replication is not readily detected in this chronic phase, although persistent viral RNA has been found in the synovial fluid of patients. This can be studied in mice, which can be productively infected with RRV when inoculated in the foot. Like in humans, in the chronic phase of disease, viral RNA is still present in the …
Cytoplasmic And Mitochondrial Calcium Influences Retinal Ganglion Cell Survival To Axon Injury, Sean Mccracken
Cytoplasmic And Mitochondrial Calcium Influences Retinal Ganglion Cell Survival To Axon Injury, Sean Mccracken
Arts & Sciences Graduate Student Theses and Dissertations
Retinal Ganglion Cell (RGC) death is the final outcome in optic neuropathies like glaucoma and traumatic optic nerve injury, which represent the leading cause of irreversible blindness worldwide. There are currently no treatments for these diseases targeting RGCs directly, and mechanisms underlying RGC death are unclear. Calcium ion (Ca2+) dysregulation occurs in almost all neurodegenerative conditions, including glaucoma, which has been studied in rodents using a robust injury model of traumatic axon injury, optic nerve crush (ONC). However, the impact of homeostatic Ca2+ regulation in RGCs response to glaucoma or ONC is unknown. Furthermore, while some mechanisms that regulate Ca2+ …