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Articles 211 - 240 of 838
Full-Text Articles in Biology
Tafopathies Result From Derangements In Transcriptional Regulation Of Metabolism, Jamison Maxwell Leid
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
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
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
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
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
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 …
A Thesis On The Human Genetic Basis Of Severe Pneumococcal Infection In Papua New Guinea, Emma Catherine Walker
A Thesis On The Human Genetic Basis Of Severe Pneumococcal Infection In Papua New Guinea, Emma Catherine Walker
Arts & Sciences Graduate Student Theses and Dissertations
Pneumonia remains a major cause of childhood mortality, especially in under-resourced communities. The profound morbidity of pediatric pneumonia in Papua New Guinea (PNG) compels innovative approaches to ameliorate disease. While the high incidence of pneumonia has been ascribed to environmental factors, we here identify a heritable allele increasing risk of severe pneumonia. In a pilot study, whole exome sequencing reveals a single nucleotide variant (SNV) in coenzyme Q6 (COQ6), a mitochondrial enzyme essential for ubiquinone biosynthesis. Significant association of SNV homozygosity with pneumonia replicates in an independently recruited cohort (p=0.036). Mice homozygous for the murine variant exhibit increased mortality after …
Investigating The Effects Of Opioid Exposure And Withdrawal On Endogenous Opioid Peptide Systems, Neuroimmune Interactions, And Striatal Neuron Activity, Marwa Mikati
Arts & Sciences Graduate Student Theses and Dissertations
Endogenous opioid peptides and their receptors perform critical roles in reward, aversion, and drug exposure processes. Both the peptides and the receptors perform distinct roles in modulating behavior depending on the brain region and stimulus in question. It has long been a challenge to study opioid peptides specifically because they are structurally similar to each other and occur at very low concentrations. Therefore, understanding their roles in stress, drug exposure, and drug withdrawal has presented difficulty for researchers over the years. To address this difficulty, I helped develop a method for the detection of enkephalins, a class of opioid peptides, …
Automated Processing Of Metabolomics Data For Population-Scale Studies, Ethan Stancliffe
Automated Processing Of Metabolomics Data For Population-Scale Studies, Ethan Stancliffe
Arts & Sciences Graduate Student Theses and Dissertations
The growth of untargeted metabolomic profiling technology has prompted the upstart of many large cohort studies. Metabolomics serves as an informative complement to other more established ‘omics (e.g., genomics, transcriptomics, proteomics). As a younger discipline, however, experimental and computational workflows are non-standardized and at times inadequate for large-scale studies. Two primary limitations in analysis of untargeted metabolomics data are 1) the poor performance and scalability of the algorithms applied to detect metabolite signals from the raw LC/MS data and 2) inefficient and arduous metabolite identification, which is the process of determining the biochemical structures that correspond to the detected LC/MS …
Function Of Deubiquitinase Mysm1 In Attenuation Of Dna Damage Responses, Brendan Mathias
Function Of Deubiquitinase Mysm1 In Attenuation Of Dna Damage Responses, Brendan Mathias
Arts & Sciences Graduate Student Theses and Dissertations
MYSM1 deficiency has been identified in patients with B cell lymphopenia, hypogammaglobulinemia, primary immune deficiency and bone marrow failure. MYSM1 is a known deubiquitinase that acts on histone H2A to promote gene expression. MYSM1 also functions in cellular responses to DNA injury and patients with loss of MYSM1 have increased sensitivity to DNA damaging agents. The specific role and function of MYSM1 in DNA damage responses has yet to be determined. Here, I have shown that MYSM1 does not mediate generation or repair of DSBs, but rather acts to attenuate and terminate DNA damage signaling after repair. Loss of MYSM1 …
Investigation Of Metabolic And Molecular Pathways That Promote Gastric Parietal Cell Regeneration, Mahliyah Lenore Adkins-Threats
Investigation Of Metabolic And Molecular Pathways That Promote Gastric Parietal Cell Regeneration, Mahliyah Lenore Adkins-Threats
Arts & Sciences Graduate Student Theses and Dissertations
The stomach contains gastric epithelial cells, including acid-pumping parietal cells (PCs), that are constantly renewed throughout life from a multipotent stem cell to maintain a balance between producing and protecting from the acid and enzymes needed to kill pathogens and initiate digestion. Despite this dynamic renewal, disorders of the gastric epithelium occur and are one of the most common etiologies of human diseases ranging from simple heartburn to reflux, peptic ulcers and gastric cancer. PCs are characterized by elaborate plasma membrane foldings and vesicles that house their proton pumps and an abundance of mitochondria needed to power secretion of that …
Investigating Novel Neoantigen Sources For Personalized Cancer Vaccines, Megan Richters
Investigating Novel Neoantigen Sources For Personalized Cancer Vaccines, Megan Richters
Arts & Sciences Graduate Student Theses and Dissertations
The adaptive immune system has inherent antitumor properties that are capable of inducing tumor-specific cell death. CD8+ and CD4+ T cells, two immune cell types critical to this process, recognize antigens bound by class I and II major histocompatibility complexes on the cell surface, respectively. After antigen recognition, T cells can signal growth arrest and cell death to tumor cells displaying the antigen. Neoantigens, or tumor-specific peptides, are targeted by cancer immunotherapies to induce T cell-mediated degradation. Treatments such as personalized vaccines and immune checkpoint blockade thus provide a unique avenue to selectively recognize and destroy tumor cells while keeping …
Mass Spectrometry-Based Discovery Of Tumor Antigens For Cancer Immunotherapy, Wei Meng
Mass Spectrometry-Based Discovery Of Tumor Antigens For Cancer Immunotherapy, Wei Meng
Arts & Sciences Graduate Student Theses and Dissertations
The immune system plays an essential role in cancer evolution and cancer treatment. One of the major mechanisms of immune-mediated tumor rejection is the recognition of tumor antigens by T cells. Upon recognition of tumor antigens, naïve T cells become activated and subsequently infiltrate inside the tumor. Since the early discovery of tumor-specific T cells, many efforts have elucidated the molecular nature of their cognate antigens. It is now established that MHC-I and MHC-II restricted peptides are critical to generate CD8+ and CD4+ antigen-specific T cells that can recognize tumor-derived antigens. Two main categories of these antigens are those originating …
The Role Of Phenylacetic Acid (Paa) Catabolism In Acinetobacter Physiology, Anna Josephine Hooppaw
The Role Of Phenylacetic Acid (Paa) Catabolism In Acinetobacter Physiology, Anna Josephine Hooppaw
Arts & Sciences Graduate Student Theses and Dissertations
Microorganisms are constantly challenged by stressful environments and have evolved mechanisms to adapt to or counteract these threats. The Gram-negative pathogen Acinetobacter baumannii is thought to rely on a “persist and resist” strategy that facilitates its remarkable ability to survive in a variety of harsh conditions, giving it the capacity to cause life-threatening infections. Currently, over 60% of the global A. baumannii clinical isolates are multidrug resistant (MDR), leading the World Health Organization and the Centers for Disease Control and Prevention to categorize this pathogen as a top priority for the research and development of new antimicrobial therapies. Understanding the …
Distinct Roles For Ltα3 And Ltα1Β2 Produced By B Cells Contribute To Their Multi-Faceted Impact On Ileitis, Emma Claire Erlich
Distinct Roles For Ltα3 And Ltα1Β2 Produced By B Cells Contribute To Their Multi-Faceted Impact On Ileitis, Emma Claire Erlich
Arts & Sciences Graduate Student Theses and Dissertations
Crohn’s disease, one of the most common forms of inflammatory bowel disease, is marked by local intestinal inflammation. However, pathology in CD patients is not strictly limited to the gastrointestinal system, and almost 50% of CD patients exhibit extraintestinal manifestations of disease. Many, though not all, of these systemic pathologies are linked to intestinal inflammation and, thus, resolution of local gastrointestinal disease also ameliorates systemic disease. How the connection between local and systemic inflammation is mediated is not well understand, nor is why only some patients exhibit these extraintestinal manifestations of disease. Blocking dissemination of inflammatory signals generated in the …
Roles Of Type I Interferon Signaling In Drug Resistant Mycobacterium Tuberculosis Infection, Suhas Bobba
Roles Of Type I Interferon Signaling In Drug Resistant Mycobacterium Tuberculosis Infection, Suhas Bobba
Arts & Sciences Graduate Student Theses and Dissertations
Tuberculosis (TB) is a global health threat, with 10 million people developing active TB disease and a million deaths attributed to TB annually. Emergence of drug resistance in Mycobacterium tuberculosis (Mtb), the causative agent of TB, has led to half a million cases of drug resistant (DR) TB annually. Further, clinical reports suggest dysregulation and suppression of immune responses in DR TB patients as compared with DS TB patients. However, we do not understand how acquisition of drug resistance-conferring mutations can drive broad and systemic differences in immune responses of DR TB patients. We found that rpoB-H445Y a specific DR …
The Sperm-Specific K+ Channel Slo3, A Regulator Of Human Fertility And New Target For Contraception, Maximilian Daniel Lyon
The Sperm-Specific K+ Channel Slo3, A Regulator Of Human Fertility And New Target For Contraception, Maximilian Daniel Lyon
Arts & Sciences Graduate Student Theses and Dissertations
Sperm from mammalian species are incapable of fertilization at the point of ejaculation. Several maturation steps must take place in the female genital tract that give the sperm the capacity to fertilize, which are collectively called capacitation. The mechanisms behind and interactions between these steps appear to rapidly evolve between species. One of these steps is a hyperpolarization of the membrane to a more negative potential. Human sperm hyperpolarize during capacitation, however the processes that regulate and are regulated by this hyperpolarization remain unclear. This is due in part to discrepancies between what is known about hyperpolarization in other species, …
Mechanisms Of Immunopathology And Protection In Genital Herpes Simplex Virus 2 Infection, Ying Shiang Lim
Mechanisms Of Immunopathology And Protection In Genital Herpes Simplex Virus 2 Infection, Ying Shiang Lim
Arts & Sciences Graduate Student Theses and Dissertations
Genital Herpes Simplex Virus-2 (HSV-2) infections is a highly prevalent and incurable sexually transmitted disease. Upon infection at the primary genital mucosa, HSV-2 localizes to the sensory ganglia to establish chronic latency. Symptomatic and asymptomatic recurrences can then occur episodically to promote viral transmissions. Painful genital and peri-genital lesions can be formed, increasing the risk for secondary HIV-1 acquisition by three times. Despite being a serious public health risk with severe physiological and psycho-sociological impacts, there are currently no cures or FDA-approved vaccines for this chronic infection. Thus, it is imperative to understand how the immune system interacts with HSV-2 …
Investigating How Sterol Transport Affects Survival Of The Pathogenic Fungus Cryptococcus Neoformans In Host-Like Conditions, Hau Lam Choy
Investigating How Sterol Transport Affects Survival Of The Pathogenic Fungus Cryptococcus Neoformans In Host-Like Conditions, Hau Lam Choy
Arts & Sciences Graduate Student Theses and Dissertations
Cryptococcus neoformans is an opportunistic fungal pathogen that has an enormous impact on global health and is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. With a mortality rate of 10-75%, cryptococcal meningitis results in over 100,000 deaths per year, comprising 18% of all AIDS-related deaths worldwide. These numbers emphasize the need to understand the basic biology and pathogenesis of this fungus. During infection, spores or desiccated yeast cells are inhaled, resulting in primary pulmonary infection. In immunocompetent hosts, these infections are asymptomatic and are either quickly cleared or remain latent. In immunocompromised patients, …
Ca2+ Dynamics And Genome Protection, Lingzhen Kong
Ca2+ Dynamics And Genome Protection, Lingzhen Kong
Arts & Sciences Graduate Student Theses and Dissertations
DNA replication is a fundamental process and defects in replication can cause genetic mutations and instability and various human diseases including cancer. The progression of replication forks can be challenged by both intrinsic and environmental factors, such as DNA lesions, secondary structure, insufficient nucleotides, collision with the transcription apparatus, radiation, or cancer drugs. These challenges necessitate robust mechanisms to protect the fork structure in the event of replication stress. Tumor suppressors like BRCA1, BRCA2, and FANC can protect fork structure by controlling nucleases that can attack stalled replication forks, which otherwise can cause fork collapse and DNA damage. In addition …
Biophysically-Informed Models Of Heterogeneity In Transcription Factor Activity, Kaiser Loell
Biophysically-Informed Models Of Heterogeneity In Transcription Factor Activity, Kaiser Loell
Arts & Sciences Graduate Student Theses and Dissertations
The activity of a transcription factor (TF) can be remarkably heterogeneous, both within andbetween cells. Between cells, molecular fluctuations drive stochastic differences in the activitiesof TFs. I will describe a project in which we have quantified how the different components of aTF (its activation domain, affinity for DNA, concentration, and cooperative interactions) influencestochastic fluctuations in TF activity. In addition to stochastic fluctuations between cells, withincells TFs can switch between activating and repressing activities depending on the cis-regulatorycontent of their target genes. I will describe a second project in which we have modelled howthe balance between homo- and heterotypic interactions determines …
Uvrd1 Helicase Of Mycobacterium Tuberculosis That Can Be Activated By Multiple Unique Mechanisms, Ankita Chadda
Uvrd1 Helicase Of Mycobacterium Tuberculosis That Can Be Activated By Multiple Unique Mechanisms, Ankita Chadda
Arts & Sciences Graduate Student Theses and Dissertations
Abstract Mycobacterium tuberculosis (Mtb) causes tuberculosis disease in humans and is one of the leading causes of death worldwide due to infectious agents. During infection, Mtb is exposed to reactive oxygen species and reactive nitrogen intermediates from the host immune response that causes DNA damage. UvrD-like helicases are involved in DNA repair and use energy from ATP hydrolysis to translocate on single stranded DNA (ssDNA) or unwind double-stranded DNA (dsDNA) to remove the damaged DNA strand. Previous studies on UvrD-like helicases have shown that they exist in a monomer-dimer equilibrium and unwind only as dimers in the absence of accessory …
Biotic Interactions And The Maintenance Of Biodiversity Across A Tropical Elevational Gradient, David Henderson
Biotic Interactions And The Maintenance Of Biodiversity Across A Tropical Elevational Gradient, David Henderson
Arts & Sciences Graduate Student Theses and Dissertations
A major goal of community ecology is to elucidate the processes that create patterns of biodiversity. Specifically, the discipline focuses on the processes that influence community assembly, diversity gradients, and/or species coexistence. Coexistence mechanisms have been traditionally thought of in terms of resource competition, whereby species are able to coexist by having different niche requirements, both biotic and abiotic, that maximize their fitness. Much of the previous work in this arena focused on the abiotic factors that influence species coexistence. However, many of the seminal ideas about the forces that drive abundance and coexistence patterns hypothesized that it was differences …
Cardiovascular Sars-Cov-2 Tropism And Immunopathology, Oleksandr Dmytrenko
Cardiovascular Sars-Cov-2 Tropism And Immunopathology, Oleksandr Dmytrenko
Arts & Sciences Graduate Student Theses and Dissertations
Coronavirus Disease 2019 (COVID-19) is caused by SARS-CoV-2, a member of beta-coronaviridae family. This single-stranded RNA virus is transmitted through a respiratory route, binds to a host receptor ACE2 and enters lung pneumocytes, causing fulminant pulmonary disease in a subset of patients. In addition to pulmonary disease, SARS-CoV-2 can also lead to extrapulmonary manifestations, affecting brain, kidneys, blood vessels and heart. Cardiac complications are common in COVID-19 patients with both mild and severe clinical courses. However, it remains unclear which cardiac cell types are susceptible to SARS-CoV-2 and what the consequences of their infection are. In this work, I identified …
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 Graduate Student 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 …
The Evolution Of Transposable Elements As Cis-Regulatory Elements In Mammals, Alan Y. Du
The Evolution Of Transposable Elements As Cis-Regulatory Elements In Mammals, Alan Y. Du
Arts & Sciences Graduate Student Theses and Dissertations
Transposable elements (TEs) are mobile genetic elements that make up a large proportion of mammalian genomes. Although TEs are highly prevalent genomic sequences, they have been understudied as they were once labeled as “junk DNA.” Despite their initial status as simple genomic parasites, recent studies have implicated TEs as cis-regulatory elements, supplying promoters, enhancers, and boundary elements. Functional testing of regulatory activity, however, remains a significant bottleneck. Nonetheless, due to their repetitive nature, TEs provide a unique model to examine the evolution of cis-regulatory elements, which has traditionally been difficult to study due to lack of homology at the sequence …
Investigating Cassava Susceptibility To Xanthomonas Induced Bacterial Blight Using Disease Phenotyping And Genome Engineering Strategies, Kiona Rajene Elliott
Investigating Cassava Susceptibility To Xanthomonas Induced Bacterial Blight Using Disease Phenotyping And Genome Engineering Strategies, Kiona Rajene Elliott
Arts & Sciences Graduate Student Theses and Dissertations
In nature, plants regularly contend with bacterial, viral, and fungal pathogens, which employ strategies that promote pathogen fitness and subsequently elicit disease in the host. Xanthomonads are a group of bacterial phytopathogens that induce disease in an extensive range of host plants. Mechanisms underlying pathogen disease promotion have been understudied in food staple crops such as cassava. Cassava is a starchy root crop susceptible to cassava bacterial blight (CBB) a disease caused by the pathogen Xanthomonas phaseoli pv. manihotis (Xpm). Xpm and other bacterial pathogens use effector molecules to manipulate host genes that promote disease susceptibility. Xpm has specialized effector …
Context Dependence, Cheating, And Long-Term Conflict In Social Interactions, Trey Scott
Context Dependence, Cheating, And Long-Term Conflict In Social Interactions, Trey Scott
Arts & Sciences Graduate Student Theses and Dissertations
Social interactions are widespread in nature and can have important ecological and evolutionary consequences. Interactions are often categorized by who is benefited or harmed by the symbiosis. For example, if both sides benefit, the interaction is cooperative. If one side benefits at the expense of the other, it is an antagonism. The kind of interaction can have important evolutionary implications, but interactions rarely fit neatly into these interaction categories. Instead, interactions often involve elements of cooperation and conflict. My dissertation explores the consequences of interactions and how they can involve both cooperation and conflict using a range of experimental, genomic, …
Leveraging Protein Dynamics To Drug Filovirus Protein-Nucleic Acid Interactions Using Simulations And Experiments, Matthew Alberto Cruz
Leveraging Protein Dynamics To Drug Filovirus Protein-Nucleic Acid Interactions Using Simulations And Experiments, Matthew Alberto Cruz
Arts & Sciences Graduate Student Theses and Dissertations
Drug discovery targeting protein nucleic acid (PNI) and protein-protein interactions (PPI) remains a difficult task. How to identify druggable conformations and discover compounds binding to these conformations is an unsolved problem. Here, I describe how we apply computational and experimental approaches to probe the conformational landscape of a key immune antagonist protein from the Zaire ebolavirus. Viral Protein 35 (VP35) binds to the viral pathogen associated molecular pattern, double stranded RNA (dsRNA), and blocks activation of the interferon (IFN) response. Long time scale molecular dynamics simulations reveal that VP35 adopts an alternative conformation which opens a pocket absent in experimental …
Spike-Timing-Dependent Plasticity Alters Sensory Network Connectivity, Adalee Lube
Spike-Timing-Dependent Plasticity Alters Sensory Network Connectivity, Adalee Lube
Arts & Sciences Graduate Student Theses and Dissertations
A fundamental question in neuroscience is: how does a sensory system optimize detection of behaviorally relevant stimuli, when those stimuli and the sensory environment are constantly changing? Spike-timing-dependent plasticity (STDP), in which synapse strength changes based on the relative timing of pre- and post-synaptic spiking, has been implicated in changes in neuronal connectivity thought to underlie learning and memory. Synaptic strength changes caused by STDP have been shown in optic tectum, visual cortex, hippocampus, and other brain regions in vitro across many organisms like fish, frogs, and mice. Although it is possible that STDP mechanisms underlie changes in sensory neuron …