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Articles 211 - 240 of 1126

Full-Text Articles in Biology

Modeling X-Linked Dystonia Parkinsonism (Xdp) In Patient-Derived Medium Spiny Neurons, Shivani Aryal Dec 2023

Modeling X-Linked Dystonia Parkinsonism (Xdp) In Patient-Derived Medium Spiny Neurons, Shivani Aryal

Arts & Sciences Graduate Student Theses and Dissertations

X-linked dystonia-parkinsonism (XDP) is an adult-onset neurodegenerative disorder that results in the loss of striatal medium spiny neurons (MSNs). XDP is an X-linked disorder caused by disease-specific mutations around the TAF1 gene. This thesis highlights the utility of directly reprogrammed MSNs from fibroblasts of affected XDP as a platform that captures cellular and epigenetic phenotypes associated with XDP neurodegeneration. In addition, this thesis demonstrates the neuroprotective effect of SAK3 currently tested in other neurodegenerative diseases. XDP fibroblasts from three independent patients as well as age- and sex-matched control fibroblasts were used to generate MSNs using miRNA-9/9*-124 and the transcription factors …


Development Of Computational And Experimental Approaches For Rna Virus Serology, Brittany Kaye Smith Dec 2023

Development Of Computational And Experimental Approaches For Rna Virus Serology, Brittany Kaye Smith

Arts & Sciences Graduate Student Theses and Dissertations

Neutralization assays like the plaque reduction neutralization test (PRNT) and focus reduction neutralization test (FRNT) are the most specific ways to measure neutralizing antibodies, which provide a good estimate of protection for RNA viruses. However, these assays are time-consuming, labor-intensive, and low-throughput. Alternative methods that are faster and convenient are necessary to quantify antibody responses in large-scale studies. In this dissertation, I develop a mix of computational and experimental methods to quantify antibody responses to dengue viruses (DENV) and SARS-CoV-2. DENV is the most significant mosquito-borne viral infection in humans. Four serotypes of DENV exist. Traditionally, infection with one serotype …


Structural Basis Of Gating In Msl Channels, Jingying Zhang Dec 2023

Structural Basis Of Gating In Msl Channels, Jingying Zhang

Arts & Sciences Graduate Student Theses and Dissertations

All living organisms experience exogenous and endogenous mechanical stress that are fundamental to their growth, survival, and development. A prominent strategy to manage these stresses and ensure efficient physiological responses is through mechanosensitive (MS) ion channels by transforming mechanical forces into electrochemical signaling. However, given their structural diversity and the inherent challenges of applying membrane tension during structural study, how MS channels sense mechanical force and transit into different functional states remain unclear. MSL channels in plants, members of the mechanosensitive ion channel of small conductance (MscS) superfamily, provide a compelling avenue for studying the structural basis for gating of …


Inhibiting Notch Signaling In Mins Improves Neurite Extension & Investigating The Epigenome Of Alzheimer’S Disease, Kyle Foster Burbach Nov 2023

Inhibiting Notch Signaling In Mins Improves Neurite Extension & Investigating The Epigenome Of Alzheimer’S Disease, Kyle Foster Burbach

Arts & Sciences Graduate Student Theses and Dissertations

Improvements to models of age-associated neurodegenerative diseases are increasingly important as our population ages and their prevalence increases. Overexpression of microRNAs-9/9* and 124 (miR-9/9*-124) convert human adult fibroblasts into neurons (miNs) by silencing non-neuronal networks, allowing the neuronal program to take over. However, improvements to this paradigm are still necessary to bring this system as close to in vivo investigation as possible. Structure equals function is one of the core tenants of molecular and cellular biology, and it applies to the morphology of neurons more so than most cells in the body. To identify drivers of morphometric reprogramming of miNs, …


Antibiotic Resistance At Sequence, Population, And Global Scales, Kevin Blake Nov 2023

Antibiotic Resistance At Sequence, Population, And Global Scales, Kevin Blake

Arts & Sciences Graduate Student Theses and Dissertations

Antibiotic resistance (AR) can be studied at multiple scales. The smallest is at the level of the DNA or amino acid sequence of AR genes, characterizing how AR genes are encoded, regulated, and expressed. Next is the level of protein structure, deciphering the 3D shape of AR proteins and how that shape affects function. The next higher scale is that of biochemistry, studying the kinetics of these proteins’ mechanism of action and interactions with drug molecules. The level of populations studies individual species of bacteria that are resistant to specific antibiotics. The next higher scale, of microbiomes, examines many species …


Uncovering The Determinants Of Compositionally Distinct, Coexisting Biomolecular Condensates, Andrew Zijia Lin Nov 2023

Uncovering The Determinants Of Compositionally Distinct, Coexisting Biomolecular Condensates, Andrew Zijia Lin

Arts & Sciences Graduate Student Theses and Dissertations

Biomolecular condensates form via the phase transitions of proteins and nucleic acids. What is unclear is how unique condensates achieve compositional specificity. Of particular interest is the ability of distinct condensates to have shared and distinct components. This is readily apparent in the multinucleate filamentous fungi Ashbya gossypii, where condensates share a common cytoplasm. In Ashbya, the RNA-binding protein Whi3 forms condensates with CLN3, BNI1, and SPA2. These RNAs are responsible for initiating the cell cycle, forming actin cables, and directing polarized cell growth respectively. However in vivo observations have shown that certain Whi3-RNA condensates are capable of mixing while …


T-Bet And Eomes Are Required For Mature Nk Cell Homeostasis And Function, Pamela Wong Nov 2023

T-Bet And Eomes Are Required For Mature Nk Cell Homeostasis And Function, Pamela Wong

Arts & Sciences Graduate Student Theses and Dissertations

Natural Killer (NK) cells are innate lymphocytes known for their role in recognizing and killing virus-infected or tumor cells without prior sensitization. NK cells express a variety of inhibitory and activating receptors that control their effector functions. Once activated by target cells, cytokines, or activating receptor ligation, NK cells are capable of potent IFN-γ secretion in addition to direct cytotoxicity mediated by perforin and granzymes. Because of their anti-tumor function, NK cells are currently utilized in promising immunotherapy approaches. NK cells develop in the bone marrow and arise from the common lymphoid progenitor, which also gives rise to T, B, …


Trna Methyltransferases Mediate Acinetobacter Baumannii Pathobiology, Jenna Mcguffey Nov 2023

Trna Methyltransferases Mediate Acinetobacter Baumannii Pathobiology, Jenna Mcguffey

Arts & Sciences Graduate Student Theses and Dissertations

Bacterial pathogens commonly encounter hostile conditions, including disinfectants, antimicrobials, and the host immune system. To be successful, they must adapt through dynamic and complex regulatory mechanisms, such as post-transcriptional modifications on a variety of molecules, including tRNA. In recent years, this tRNA “epitranscriptome” has been increasingly appreciated as an under-researched mechanism for bacterial stress responses. These modifications can impact the translation efficiency of a cohort of stress response factors whose transcripts are enriched for the corresponding codons. However, the variety and roles of tRNA modification enzymes in human pathogens is still largely unknown. The Gram-negative pathogen Acinetobacter baumannii is currently …


Shining A Light Through A Multiomic Lens On Germline Variants: Patterns And Functional Implications Across Cancer Types, Fernanda Martins Rodrigues Nov 2023

Shining A Light Through A Multiomic Lens On Germline Variants: Patterns And Functional Implications Across Cancer Types, Fernanda Martins Rodrigues

Arts & Sciences Graduate Student Theses and Dissertations

The landscape of cancer research has undergone a profound transformation, transcending traditional tissue-centric viewpoints to embrace a more intricate understanding of cellular origins and molecular drivers. It has become evident that genes and variants implicated in specific cancers extend their influence across a spectrum of cancer types. Our prior work, encompassing an >10K cases from The Cancer Genome Atlas (TCGA) and more than >1K pediatric cases, illuminated the intricate web of germline predisposition variants and genes spanning 33 cancer types. These findings not only contributed to the refinement of guidelines for rare germline variant detection but also enriched the clinical …


Uncovering The Genetic Basis Underlying The Pseudomonas Syringae Pv. Tomato Strain Dc3000’S Response To Iaa And Its Role In Regulating Ptodc3000 Biology, Joshua Michael Brian Johnson Nov 2023

Uncovering The Genetic Basis Underlying The Pseudomonas Syringae Pv. Tomato Strain Dc3000’S Response To Iaa And Its Role In Regulating Ptodc3000 Biology, Joshua Michael Brian Johnson

Arts & Sciences Graduate Student Theses and Dissertations

Indole-3-acetic acid (IAA) is a molecule ubiquitous to the environment and is known to be produced across all three domains of life. It is most well-known for its role as an important plant hormone (an auxin) and until recently, its roles in other organisms have not been explored. It is well established that bacteria, and pathogens in particular, need to sense and respond to environmental signals. One model organism for studying plant pathogen interactions that is known to both produce and respond to IAA is Pseudomonas syringae pv. tomato strain DC3000 (PtoDC3000). Many plant metabolites have been explored as potential …


Examining The Role Of Microglia In Diabetic Retinopathy: Phenotypes, Mechanisms, And Therapies, Charles W. Pfeifer Oct 2023

Examining The Role Of Microglia In Diabetic Retinopathy: Phenotypes, Mechanisms, And Therapies, Charles W. Pfeifer

Arts & Sciences Graduate Student Theses and Dissertations

Retinal microglia activation and function is a pivotal component of ocular disease pathology, but their involvement in diabetic retinopathy, a complex neurovascular complication of diabetes, remains unclear. The purpose of this thesis work is to thoroughly examine features of microglia activation in DR, identify mechanistic underpinnings of their contributions to neuroinflammatory features of disease pathogenesis, and assess immunotherapeutic targeting of microglia as a potential approach to treating early-stage DR. Here, we show that chronic hyperglycemia elicits morphological, ultrastructural, and transcriptional changes in retinal microglia during early-stage DR while other elements of the retinal neurovascular unit remain unperturbed. Through chronic ablation …


Evaluating The Utility Of S100a8/A9 As A Non-Invasive Biomarker, Leah Mellett Oct 2023

Evaluating The Utility Of S100a8/A9 As A Non-Invasive Biomarker, Leah Mellett

Arts & Sciences Graduate Student Theses and Dissertations

Biomarkers, a portmanteau of “biological markers”, are clinically relevant observations that can accurately and reproducibly indicate or predict patient outcomes. These objective measurements have vast clinical utility as they can aid clinicians with diagnoses, provide information about patient prognoses, and monitor changes in patient health statuses. While the discovery of several biomarkers are attributed to differential expression or concentration of genes or proteins within blood samples, biomarkers can be alternatively found in other bodily fluids or tissues depending on the associated condition. Recently, advances in urine proteomics have allowed for the identification of urine biomarkers that may eliminate the drawbacks …


On The Origin Of Aids: Card8’S Role In Pathogenesis And Cure, Kolin Clark Oct 2023

On The Origin Of Aids: Card8’S Role In Pathogenesis And Cure, Kolin Clark

Arts & Sciences Graduate Student Theses and Dissertations

HIV infection remains a major global health burden with 1.7 million new acquisitions and 770,000 deaths in 2018 alone. While these numbers are declining due to antiretroviral therapy, only a handful of individuals have achieved complete remission from HIV. With the advent of antiretroviral therapy, HIV has turned a death sentence into a chronic, manageable condition. However, current antiretroviral therapies have only been studied on their ability to block infection and have not been able to clear the viral reservoir. Additionally, HIV cure strategies often rely upon sensing of highly variable epitopes such as the HIV envelope and have not …


A Thesis On Phosphatidylserine As A Key Signaling Moiety During Adipocyte Differentiation, Brady Jeffrey Barron Oct 2023

A Thesis On Phosphatidylserine As A Key Signaling Moiety During Adipocyte Differentiation, Brady Jeffrey Barron

Arts & Sciences Graduate Student Theses and Dissertations

The adipose tissue is composed of specialized energy storage cells called adipocytes. In white adipose tissue, when committed precursor cells (preadipocytes), receive specific cues, the preadipocytes differentiate into mature adipocytes via an adipogenic gene program promoted by transcription factors such as PPAR. Phosphatidylserine (PS) is a phospholipid asymmetrically maintained on the inner leaflet of the plasma membrane in healthy cells. PS flipping to the outer leaflet is a well-known hallmark of cell death, such as apoptosis. Here, while exploring the interplay between PS exposure and adipose tissue homeostasis, we made a surprising discovery in that non apoptotic PS exposure occurs …


Genetic And Pharmacological Factors Control Aging In Caenorhabditis Elegans., Brian Mcnally Egan Oct 2023

Genetic And Pharmacological Factors Control Aging In Caenorhabditis Elegans., Brian Mcnally Egan

Arts & Sciences Graduate Student Theses and Dissertations

Aging is a time-dependent decline in organismal structure and function that ultimately results in death. Aging occurs in nearly all metazoan organisms, and is a major risk factor for many human diseases including cancer, diabetes, hypertension, heart disease, and Alzheimer’s Disease. The genetic pathways and mechanistic factors that underly the aging process are poorly understood. Control of aging in the nematode C. elegans can be accomplished via modulation of gene activity by genetic knockdown or by the introduction of inhibitory pharmaceutical compounds. While many such interventions have been described in the literature, understanding the underlying mechanisms that control aging remains …


Charting The Landscape Of Ventral Stream Neural Code On Generative Image Manifolds, Binxu Wang Sep 2023

Charting The Landscape Of Ventral Stream Neural Code On Generative Image Manifolds, Binxu Wang

Arts & Sciences Graduate Student Theses and Dissertations

The natural world features high-dimensional retinal inputs to the visual system. In contrast, to study vision in the lab, only sparsely sampled image sets are used. Given this immense natural image manifold, what is a principled way to sample and understand the neural representations on it? In this thesis, we frame the neural coding question in a geometric way. Neural tuning can be conceptualized as a landscape on the natural image manifold, and generative models such as GANs provide a concrete instantiation of the manifolds. We hypothesized that the maximally activating images or peaks on these landscapes are critical for …


Role Of Copyback Viral Genomes In Activating Cellular Stress Responses During Pneumovirus And Paramyxovirus Infection, Lavinia Jose Gonzalez Aparicio Sep 2023

Role Of Copyback Viral Genomes In Activating Cellular Stress Responses During Pneumovirus And Paramyxovirus Infection, Lavinia Jose Gonzalez Aparicio

Arts & Sciences Graduate Student Theses and Dissertations

The interactions that occur between a virus and the infected cell determine the success of an infection. During negative-sense single-stranded RNA virus infections, copyback viral genomes (cbVGs) drive key virus-host interactions by activating the Mitochondrial Antiviral Signaling (MAVS) pathway that induces antiviral immunity and leads to reduced levels of virus replication. Whether cbVGs induce other cellular pathways and how these relate to their immunostimulatory activity is unknown. Here we show that cbVGs also induce a cellular stress response during pneumovirus and paramyxovirus infections. cbVGs activate the cellular stress response through Protein Kinase R (PKR) signaling, triggering translation inhibition and stress …


Combining Simulations And Single Molecule Spectroscopy To Understand Sars-Cov-2 Nucleocapsid Protein-Rna Interactions, Jhullian Jamille Alston Sep 2023

Combining Simulations And Single Molecule Spectroscopy To Understand Sars-Cov-2 Nucleocapsid Protein-Rna Interactions, Jhullian Jamille Alston

Arts & Sciences Graduate Student Theses and Dissertations

Disordered protein regions play crucial roles in various cellular functions, exhibiting high heterogeneity and sampling an ensemble of conformations distinct from folded domains. However, our understanding of their behavior and contributions to protein-protein and protein-nucleic acid interactions remains limited. This dissertation focuses on investigating the interactions between disordered regions and RNA, as well as folded regions of proteins, utilizing computational modeling and single-molecule fluorescence spectroscopy. The SARS-CoV-2 Nucleocapsid (N) protein serves as a model system to address broader questions concerning disordered protein behavior and N protein-mediated RNA genome packaging. I employed coarse-grained molecular dynamic simulations to characterize the cooperative binding …


Investigating The Role Of Dcia During The Cell Cycle In Mycobacterium, Helen Catherine Blaine Sep 2023

Investigating The Role Of Dcia During The Cell Cycle In Mycobacterium, Helen Catherine Blaine

Arts & Sciences Graduate Student Theses and Dissertations

The mycobacterial family contains many human pathogens, including Mycobacterium tuberculosis, Mycobacterium abcessus, and Mycobacterium leprae. Mycobacterium tuberculosis, the causative agent of the disease tuberculosis (TB), is a major public health problem. The emergence of increasing numbers of antibiotic resistant cases of TB has led to a push for novel drug development. A popular target for antibiotic development is DNA replication, as this is an essential process in bacterial cell development. Further understanding of the DNA replication process in mycobacteria will be key to drug development efforts. The process of DNA replication has been well studied in Escherichia coli and Bacillus …


Dfcp1 Regulates Lipid Droplet Catabolism In An Ntpase-Dependent Manner, Victoria Anne Ismail Sep 2023

Dfcp1 Regulates Lipid Droplet Catabolism In An Ntpase-Dependent Manner, Victoria Anne Ismail

Arts & Sciences Graduate Student Theses and Dissertations

Lipid Droplets (LDs) are lipid storage organelles that can be readily tapped to resupply cells with energy or lipid building blocks, and, therefore, play a central role in cellular metabolism. It has emerged that Double FYVE Domain Containing Protein 1 (DFCP1), which has routinely been used as a marker for early autophagy, is an LD-associated protein and is implicated in establishing contacts between the endoplasmic reticulum (ER) and LDs, but little is known about DFCP1’s function or how it influences either autophagy or LD metabolism. Here, we show that DFCP1 contains a novel NTPase domain that regulates its assembly onto …


The Role Of Gardnerella In Bacterial Vaginosis And Facilitating Colonization By Neisseria Gonorrhoeae, Sydney Rose Morrill Sep 2023

The Role Of Gardnerella In Bacterial Vaginosis And Facilitating Colonization By Neisseria Gonorrhoeae, Sydney Rose Morrill

Arts & Sciences Graduate Student Theses and Dissertations

Bacterial vaginosis (BV) is a condition of vaginal flora that affects about 1/3 of reproductive age women. The optimal vaginal microbiome is thought to be one dominated by Lactobacillus species. In the BV-positive microbiome, this lactobacillus-dominance is replaced by an outgrowth of diverse anaerobic bacteria. BV has been clinically linked to a number of negative health outcomes, including preterm birth, infertility, cervical dysplasia, and an increased risk of sexually-transmitted infections (STIs) such as gonorrhea. The underlying cause(s) of BV have been debated in the literature for over half a century. In 1955, it was first reported that a bacterium now …


Drives Blunted By Time: The Effects Of Aging On Motivational Behaviors And Responses To Social Isolation In Mice, Hanyue Lei Sep 2023

Drives Blunted By Time: The Effects Of Aging On Motivational Behaviors And Responses To Social Isolation In Mice, Hanyue Lei

Arts & Sciences Graduate Student Theses and Dissertations

Mental health in the elderly is an escalating social problem as the world population ages rapidly. Older adults are more susceptible to stressors like social isolation, which is a common risk factor for many mental disorders and health issues. However, how aging affects specific mental functions like motivational drive and stress responses, as well as the underlying neurobiological mechanisms, remains largely unstudied. We comprehensively examined behavioral phenotypes in both young and aged mice under the normal grouped-housing condition versus chronic social isolation treatment. The results suggested that natural aging and social isolation both impaired motivational behaviors and induce depressive- and …


Physiological Heterogeneity And Pain-Associated Plasticity In Human Sensory Neurons, Jiwon Yi Sep 2023

Physiological Heterogeneity And Pain-Associated Plasticity In Human Sensory Neurons, Jiwon Yi

Arts & Sciences Graduate Student Theses and Dissertations

Despite the widespread prevalence of chronic pain and extensive drug development efforts, non-opioid pharmacotherapeutic options for severe and chronic pain are limited. Nociceptors in the dorsal root ganglia (DRG) are peripheral sensors of noxious stimuli that play an integral role in pain transmission. Neuroplasticity in the periphery, such as hyperexcitability and spontaneous activity of sensory neurons following inflammation or injury, plays a central role in the pathogenesis of both acute and chronic pain. As such, a detailed understanding of the mechanisms associated with peripheral sensitization may reveal novel therapeutic targets of pain. An increasing number of studies have shown that …


Heterogeneity Of Human Tissue-Resident Lymphocytes, Natalia Jaeger Sep 2023

Heterogeneity Of Human Tissue-Resident Lymphocytes, Natalia Jaeger

Arts & Sciences Graduate Student Theses and Dissertations

The immune system plays a critical role in maintaining tissue homeostasis and defending against pathogens. Recent discoveries have highlighted the significance of tissue-resident memory T cells (TRM) and Innate Lymphoid Cells (ILCs) in tissue immunity. TRM exhibit memory-like properties, persist long-term in various tissues, and express markers such as CD69, CD103, and transcription factors like Hobit and Blimp-1. Similarly, ILCs, considered the innate counterparts of T cells, are abundant at barrier organs and mucosal sites, sharing similar markers and transcriptional factors with TRM, and rapidly responding to insults. Unraveling the heterogeneity and function of tissue-resident lymphocytes is crucial for understanding …


Tafopathies Result From Derangements In Transcriptional Regulation Of Metabolism, Jamison Maxwell Leid Sep 2023

Tafopathies Result From Derangements In Transcriptional Regulation Of Metabolism, Jamison Maxwell Leid

Arts & Sciences Graduate Student Theses and Dissertations

Cardiogenesis and the maintenance of cardiac physiology necessitate dynamic and carefully coordinated transcription programs. Studies in a many systems – both in vitro and in vivo – have elucidated critical signaling pathways, including Bmp, Fgf, Wnt, and Notch that induce a cardiogenic transcription program, thereby driving cardiac specification and differentiation. Recently, studies have discovered additional regulation at the epigenetic level that contributes to the tight temporal and spatial control of cardiac gene expression during development. Because transcriptional regulation is essential to cardiogenesis, changes in transcriptional regulation result in developmental defects, including but not limited to CHDs, the leading inborn cause …


Il-15 And Ifn-G Regulation In Murine Nk Cells, Maria Cimpean Sep 2023

Il-15 And Ifn-G Regulation In Murine Nk Cells, Maria Cimpean

Arts & Sciences Graduate Student Theses and Dissertations

Natural killer (NK) cells are innate lymphoid cells that play important roles in antiviral and antitumor responses through their cytotoxicity mechanisms and the ability to modulate immune responses through production of cytokines such as IFN-g. NK cells are able to execute these responses rapidly and without prior sensitization due to their germline-encoded receptors. Recent work in the field of immunometabolism has highlighted the impact that changes in cellular metabolism can have on immune cell function, including NK cell effector functions. Our lab has previously reported activation-specific metabolic requirements for IFN-g production by resting murine NK cells in vitro, which IL-15 …


A Human Stat3 Gof Variant Alters T Cell Function To Drive Skin Inflammation, Kelsey Adele Toth Aug 2023

A Human Stat3 Gof Variant Alters T Cell Function To Drive Skin Inflammation, Kelsey Adele Toth

Arts & Sciences Graduate Student Theses and Dissertations

Inborn errors of immunity (IEIs) are disorders caused by monogenic variants that lead to immune deficiency and dysregulation. Although rare, IEIs have shaped our understanding of how single genes function in the immune systems of both humans and mice. The identification of loss-of-function (LOF) and gain-of-function (GOF) variants in the highly conserved signal transducer and activator of transcription (STAT) family molecules have led to discoveries involving how STAT signaling affects immune cell development, differentiation, and the induction and regulation of immune responses. Germline GOF variants in STAT3 cause early-onset multi-organ autoimmunity and immune dysregulation. Patients with STAT3 GOF syndrome have …


Unraveling The Molecular Basis Of Zinc Cluster Transcription Factor Specificity: A Comprehensive Study Of Half-Site Promoter Binding Interactions And Their Role In Gene Expression Regulation, Pamela Samantha Recio Aug 2023

Unraveling The Molecular Basis Of Zinc Cluster Transcription Factor Specificity: A Comprehensive Study Of Half-Site Promoter Binding Interactions And Their Role In Gene Expression Regulation, Pamela Samantha Recio

Arts & Sciences Graduate Student Theses and Dissertations

The regulation of gene expression relies on the complex interplay of transcription factors (TFs) that interact with DNA to control gene activity. Despite extensive research efforts, accurately predicting crucial aspects of the transcriptional process, such as TF occupancy in vivo, remains a challenging task. Existing thermodynamic models of TF function often fall short in explaining experimental observations, suggesting the presence of undiscovered biological mechanisms. This dissertation aims to unravel the underlying principles governing the binding specificity of Zinc cluster TFs and is organized into two chapters. Chapter 1 offers a comprehensive overview of transcriptional regulation in yeast, highlighting current TF …


Effect Of Age At Injury On Neuroinflammatory Response, Microstructural Outcomes, And Function Following Traumatic Brain Injury, Sydney J. Oswalt Reitz Aug 2023

Effect Of Age At Injury On Neuroinflammatory Response, Microstructural Outcomes, And Function Following Traumatic Brain Injury, Sydney J. Oswalt Reitz

Arts & Sciences Graduate Student Theses and Dissertations

Traumatic brain injury (TBI) is a significant public health concern. Elderly individuals are more likely to be hospitalized and die from a TBI than younger victims, and experience worse outcomes along a series of clinical and functional endpoints. Studies exploring the mechanisms responsible for these outcome disparities are limited. As aging has been demonstrated to enhance baseline neuroinflammatory profile and is associated with synaptopathic neurodegenerative conditions linked to TBI, this thesis study sought to better characterize the relationship between aging-related neuroinflammation, microstructural—including synaptic—endpoints, and functional outcome following TBI. To this end, mice were subjected to diffuse and focal experimental brain …


Inter-Areal Communication In Posterior Parietal Cortex Supporting Eye-Hand And Bimanual Coordination, Jung Uk Kang Aug 2023

Inter-Areal Communication In Posterior Parietal Cortex Supporting Eye-Hand And Bimanual Coordination, Jung Uk Kang

Arts & Sciences Graduate Student Theses and Dissertations

Understanding inter-areal communication is crucial for systems neuroscience. Much of the processing in the brain involves communication between different areas. Sensory areas must send information to motor areas, and motor areas must communicate with each other if different body parts are to be coordinated. For example, coordinating movements of the two arms likely requires interactions between motor areas in the two hemispheres. We therefore hypothesize that bimanual and eye-hand coordination relies on interhemispheric communication, and the most direct path for information exchange between the two hemispheres is through the corpus callosum. By reversibly blocking the callosal pathways connecting the left …