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Articles 151 - 180 of 838
Full-Text Articles in Biology
Regulation Of Neuronal Cell-Type-Specific Transcription By Non-Cg Methylation And Mecp2, James Russell Moore
Regulation Of Neuronal Cell-Type-Specific Transcription By Non-Cg Methylation And Mecp2, James Russell Moore
Arts & Sciences Graduate Student Theses and Dissertations
Modulation of gene expression is fundamental to the exceptional complexity and diversity of cells in the nervous system. Within that last decade, evidence has emerged that neurons utilize unique forms of DNA methylation to regulate transcriptional programs, with multiple types of neurons displaying high levels of cytosine methylation in a non-CG context compared to non-neural cells. This non-CG methylation primarily occurs at CA dinucleotides (mCA) and is read out by methyl-CpG binding protein 2 (MeCP2). Inactivation of MeCP2 results in Rett Syndrome (RTT), a severe neurodevelopmental disorder, while overexpression of MeCP2 results in MeCP2 duplication syndrome, an autism spectrum disorder. …
Identification And Characterization Of Ube3a Gain Of Function Variants As A Driver Of Neurodevelopmental Disease, Kellan Phoebe Weston
Identification And Characterization Of Ube3a Gain Of Function Variants As A Driver Of Neurodevelopmental Disease, Kellan Phoebe Weston
Arts & Sciences Graduate Student Theses and Dissertations
UBE3A is a HECT (homologous to E6AP-Terminus) domain E3 ubiquitin ligase that targets substrate proteins for polyubiquitination and subsequent degradation through the ubiquitin-proteasome pathway. The UBE3A gene is of unique interest for its gene dosage-dependent effect in the developing brain: deletion of the maternal copy of UBE3A causes a severe intellectual disability known as Angelman syndrome; meanwhile, duplication or triplication of the genomic region containing UBE3A is linked to a prevalent syndromic form of autism known as Dup15q syndrome. However, little is known about the effects of missense variants which cause a single amino acid change in the resulting UBE3A …
Investigating The Involvement Of Gabaergic Interneurons And A Gene Therapy Strategy For Epilepsy In Cln2 Disease, Keigo Takahashi
Investigating The Involvement Of Gabaergic Interneurons And A Gene Therapy Strategy For Epilepsy In Cln2 Disease, Keigo Takahashi
Arts & Sciences Graduate Student Theses and Dissertations
The neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative lysosomal storage disorders affecting children and young adults. CLN2 disease, or classic late infantile neuronal ceroid lipofuscinosis, is one of the most common forms of NCL and is caused by a deficiency of tripeptidyl peptidase 1 (TPP1). Although an FDA-approved enzyme replacement therapy for CLN2 disease now exists, a poor understanding of pathophysiology has hampered the development of more effective and persistent therapy. While Cln2R207X/R207X knock-in mice which carry one of the most common pathogenic mutations in human patients were developed in 2017, this genetically accurate mouse model for CLN2 …
Dual Modes Of Dopamine Underly Distinct Facets Of Impulsive Actions, Tzvia Pinkhasov
Dual Modes Of Dopamine Underly Distinct Facets Of Impulsive Actions, Tzvia Pinkhasov
Arts & Sciences Graduate Student Theses and Dissertations
During the pursuit of basic needs, animals sometimes fail to suppress actions that are maladaptive and counterproductive to their survival. In humans, these actions are often called impulsive because they can incur negative consequences. Impulsivity is ubiquitous across psychiatric disorders and related to debilitating outcomes such as substance abuse, crime and suicidality. Despite its risks, a lack of a neural mechanism understanding of impulsive actions impedes the development of effective treatments.In this dissertation, I set out to bridge the knowledge gained from the parallel fields of neuropsychopharmacology, experimental psychology, and systems neuroscience to uncover neural mechanisms of impulsive actions. Clinicians …
Integrating Dna Methylation And 3d-Genome Architecture To Identify Functional Regulatory Sequences In Idh-Mutant Aml, Elisabeth Wilson
Integrating Dna Methylation And 3d-Genome Architecture To Identify Functional Regulatory Sequences In Idh-Mutant Aml, Elisabeth Wilson
Arts & Sciences Graduate Student Theses and Dissertations
Acute myeloid leukemia (AML) is a genetically and phenotypically heterogeneous disease. Recurrent mutations in genes involved in epigenetic pathways are common in AML and are thought to contribute to this variability by disrupting epigenetic patterns relative to normal hematopoietic cells. The most well-studied epigenetic modification in AML is DNA methylation. Although methods for studying DNA methylation have improved significantly in the past decade, the landscape of methylation changes in AML and how they relate to chromatin architecture and gene regulation is still not fully understood. This thesis is focused on the DNA methylation phenotype of IDH1 or IDH2 mutations in …
Neuroepigenetic Mechanisms Of Brain Development: From Technology To Biological Insights, Allen Yen
Neuroepigenetic Mechanisms Of Brain Development: From Technology To Biological Insights, Allen Yen
Arts & Sciences Graduate Student Theses and Dissertations
Each cell in the brain has the same genomic sequence, yet they can have vastly different phenotypes and function. This diversity is a result of complex genetic and signaling pathways, and knowing how these are regulated is key to understanding physiological development and how pathogenic dysfunctions arise. Genomic methods such as chromatin immunoprecipitation followed by sequencing (ChIP-seq) and assay for transposase-accessible chromatin with sequencing (ATAC-seq) have played pivotal roles in dissecting these processes. However, a key limitation is that the cells are destroyed upon observation of their molecular states, which preclude our ability to correlate historical epigenetic information with future …
Understanding Gene Regulation By Non-Cg Dna Methylation And Mecp2 At Cellular Resolution In The Brain, Mati Nemera
Understanding Gene Regulation By Non-Cg Dna Methylation And Mecp2 At Cellular Resolution In The Brain, Mati Nemera
Arts & Sciences Graduate Student Theses and Dissertations
The mammalian brain features a variety of cell types with distinct functions and properties. This cellular diversity is maintained by epigenomic regulation of gene expression. Neurons in particular express long genes and are uniquely enriched for non-CG methylation, especially methylation at CA dinucleotides (mCA). MeCP2, whose mutation results in Rett syndrome, regulates gene expression by binding to mCA. However, the function of this mCA-MeCP2 pathway in the regulation of fine-tuned neuronal gene expression programs has not been investigated. Here, we provide evidence that mCA-MeCP2 pathway plays a role in the maintenance of neuron type-specific gene expression programs at a high …
Dimerization Of The Fluoride Channel Fluc In Membranes, Melanie Ernst
Dimerization Of The Fluoride Channel Fluc In Membranes, Melanie Ernst
Arts & Sciences Graduate Student Theses and Dissertations
Many ion channels are multi-subunit complexes where oligomerization is an obligatory requirement for function as the binding axis forms the charged permeation pathway. However, the mechanisms of assembly within the membrane are largely unknown. Are ion channel complexes thermodynamically stable, and do they participate in dynamic equilibrium oligomerization reactions in membranes? If so, what are the molecular factors governing these reactions? In this thesis, I present several key advances in the study of ion channel oligomerization in membranes through quantitative studies of the dimerization equilibrium reaction of the inverted topology, homodimeric fluoride channel Fluc in lipid bilayers. Chapter 1 provides …
Investigating Tumor-Stroma Interactions During Ovarian Cancer Metastasis, Angela Marie Schab
Investigating Tumor-Stroma Interactions During Ovarian Cancer Metastasis, Angela Marie Schab
Arts & Sciences Graduate Student Theses and Dissertations
The majority of ovarian cancer patients have metastatic disease throughout the peritoneal cavity at the time of diagnosis, at which point the five-year survival is only around 30%. However, no effective therapy exists to prevent or treat ovarian cancer metastasis. To implant into the peritoneal cavity, ovarian cancer cells must attach to the mesothelial cell layer-a monolayer of cells that surrounds all organs of the peritoneal cavity- clear the mesothelial cell layer and invade into the underlying stroma, which hosts fibroblasts and extracellular matrix (ECM). The tumor microenvironment (TME) plays an important role in supporting metastasis and thus is a …
Determining The Role Of Ddr2 In Acquired Chemo-Resistance In Ovarian Cancer, Alyssa Oplt
Determining The Role Of Ddr2 In Acquired Chemo-Resistance In Ovarian Cancer, Alyssa Oplt
Arts & Sciences Graduate Student Theses and Dissertations
Ovarian cancer is the 5th leading cause of cancer death in women with a 5-year survival rate around 30%. Up to 80% of ovarian cancer patients experience disease recurrence and the majority of those cases are resistant to treatment. Therefore, there is a need to understand the mechanisms of chemo-resistance in order to create new therapies and increase patient survival. To accomplish this, I first developed novel, chemo-resistant, syngeneic mouse ovarian cancer cell lines by serial passaging ovarian cancer cells through mice and treating with increasing doses of chemotherapy. These cell lines fill a need in the field for matched …
Dissecting The Role Of Chromatin Remodeling In Direct Lineage Reprogramming, Kunal Jindal
Dissecting The Role Of Chromatin Remodeling In Direct Lineage Reprogramming, Kunal Jindal
Arts & Sciences Graduate Student Theses and Dissertations
Direct reprogramming, the direct forced conversion of one somatic cell type to another has widespread applications in regenerative medicine. Owing to its highly complex nature, discovery and validation of new factors for direct reprogramming is challenging and many current protocols suffer from low conversion efficiency, failing to create mature cell types comparable to their in vivo counterparts. Recent advances in single-cell have coupled cell ancestry and transcriptomic state measurement in single-cell RNA sequencing (scRNA-seq) assays. In reprogramming and development, these have allowed mapping lineage specific transcriptional changes both before and during cell fate specification. These methods work by encoding lineage …
Development And Structure Of Spinal Interneuron Connectivity In Larval Zebrafish, Saul Bello Rojas
Development And Structure Of Spinal Interneuron Connectivity In Larval Zebrafish, Saul Bello Rojas
Arts & Sciences Graduate Student Theses and Dissertations
In vertebrates, spinal interneurons are essential for the initiation and propagation of locomotor activity with each class of interneurons serving its own unique role. Ipsilateral interneurons function to control locomotor speed; whereas, commissural interneurons aid in left – right alternation. To date, most studies have been aimed at studying the impact of each individual class of interneurons onto motor neurons. However, not much work has revolved around studying interneuron – interneuron connectivity among the various cardinal classes. Furthermore, it remains unknown how the connectivity of interneurons changes along their entire axonal reach. This thesis aims to address the developmental patterns …
Inferring Function From Form: Subcortical Projection Cell Types In Rat Orbitofrontal Cortex, Suelynn Ren
Inferring Function From Form: Subcortical Projection Cell Types In Rat Orbitofrontal Cortex, Suelynn Ren
Arts & Sciences Graduate Student Theses and Dissertations
Frontal cortex supports sophisticated behaviors by controlling phylogenetically older subcortical brain regions. Within the deep layers of cortex, subcortically projecting pyramidal neurons integrate local and long-range inputs along the entire depth of the cortical column. How subcortically projecting neurons might be fractionated into cell types and how their unique features constrain top-down communication is unknown. In this dissertation, I first established the output circuit architecture of subcortically projecting neurons in rat orbitofrontal cortex at a cellular resolution. I found that subcortically projecting neurons preferentially innervated a single target, demonstrating a one-neuron-one-target projection logic. Such target-defined projection neurons were molecularly distinct …
Mechanisms Of Rod Photoreceptor Metabolism And Function In Health And Disease, Tae Jun Lee
Mechanisms Of Rod Photoreceptor Metabolism And Function In Health And Disease, Tae Jun Lee
Arts & Sciences Graduate Student Theses and Dissertations
Over 250 million people globally live with visual acuity loss or blindness as an estimated 7 million people suffer from visual acuity loss in the United States. People in the United States value vision over memory, hearing, or speech and consider losing vision to be among the top four worst outcome to happen to them. The economic cost of major vision problems is estimated to increase to 373 billion dollars by the year 2050. Among the irreparable causes of vision loss, retinal degeneration stands as a chief contributor to catastrophic eye disease. The retina is a neurosensory tissue located in …
Germinal Center Persistence Diversifies B Cell Responses To Vaccination, Katherine Marie Mcintire
Germinal Center Persistence Diversifies B Cell Responses To Vaccination, Katherine Marie Mcintire
Arts & Sciences Graduate Student Theses and Dissertations
Vaccination is the best defense against infection, but highly variable and evolving pathogens like influenza virus pose a significant immunological challenge for vaccine design. An ideal influenza virus vaccine should elicit a durable and broadly cross-reactive antibody response. However, the development of cross-reactive antibodies is hindered by the high degree of antigenic variation among influenza viruses, particularly in the surface glycoprotein hemagglutinin (HA), which is the main target of vaccine-induced responses. Successful vaccination works by driving the differentiation of antigen-specific B cells into short-lived, antibody-secreting plasmablasts (PBs) and long-lived populations of memory B cells (MBCs) and bone marrow plasma cells …
Investigating The Role Of Circular Rnas In Metastatic Colorectal Cancer Progression, Sidi Zhao
Investigating The Role Of Circular Rnas In Metastatic Colorectal Cancer Progression, Sidi Zhao
Arts & Sciences Graduate Student Theses and Dissertations
Colorectal cancer (CRC) is the most common gastrointestinal malignancy and a leading cause of cancer deaths in the U.S.A. More than half of CRC patients develop metastatic disease (mCRC) with a 13% average 5-year survival rate. Despite advances in our understanding of primary CRC oncogenesis and biology, the mechanisms of tumor metastasis remain poorly characterized. To date, CRC research has primarily focused on the dysregulation of protein-coding genes to identify oncogenes and tumor suppressors as potential diagnostic and therapeutic targets, thereby under-representing the critical role of many classes of non-coding RNAs (ncRNAs). One emerging class of ncRNAs, circular RNAs (circRNAs), …
Dihydroceramide Desaturase Governs Endoplasmic Reticulum And Lipid Droplet Homeostasis To Promote Glial Function In The Nervous System, Yuqing Zhu
Arts & Sciences Graduate Student Theses and Dissertations
Dihydroceramide desaturase converts dihydroceramides to ceramides in the final step of de novo ceramide biosynthesis. Reduction of dihydroceramide desaturase DEGS1 function in humans leads to hypomyelinating leukodystrophy-18, but the etiology of this disease remains unclear. Using mutants from a forward genetic screen, we discovered that infertile crescent (ifc), the sole Drosophila dihydroceramide desaturase, governs central nervous system development and morphology. ifc is primarily expressed in glia and acts cell-autonomously in glia to control glial morphology and function during nervous system development. Loss of ifc leads to severe glial defects, particularly in cortex glia, including endoplasmic reticulum expansion, glial swelling, compromised …
Interleukin-1Α And Leukemia Inhibitory Factor Promote Cancer-Induced Extramedullary Hematopoiesis, Derek Arthur George Barisas
Interleukin-1Α And Leukemia Inhibitory Factor Promote Cancer-Induced Extramedullary Hematopoiesis, Derek Arthur George Barisas
Arts & Sciences Graduate Student Theses and Dissertations
Hematopoiesis, the formation of blood and immune cells from stem and progenitor cells, is a central biological process that alters in response to the organismal state. Many cytokines that accompany diseases have an impact on the rate, cellular output, and underlying mechanisms of hematopoiesis. Deepening our understanding of the alterations to hematopoiesis that occur with disease may offer therapeutics that normalize hematopoiesis and promote health. One component of hematopoiesis that is often overlooked are the non-hematopoietic cells of the stem cell niche that have crucial roles in affecting the parameters of hematopoiesis. While progress in understanding the hematopoietic stem cell …
Characterizing The Causal Role Of Svep1 In Human Disease, Jared S. Elenbaas
Characterizing The Causal Role Of Svep1 In Human Disease, Jared S. Elenbaas
Arts & Sciences Graduate Student Theses and Dissertations
Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is a poorly understood, putative extracellular matrix protein. Several human traits and diseases are associated with SVEP1, including coronary artery disease, hypertension, type 2 diabetes, glaucoma, dementia, longevity, and platelet reactivity. This dissertation establishes a causal link between SVEP1 and human disease using Mendelian randomization and mouse models. It also provides insights into the disease mechanisms of the protein, including a novel interaction between SVEP1 and the orphan receptor Platelet endothelial aggregation receptor 1. The relevance of this interaction to platelet biology and its potential role in …
Mechanisms Of Electrical Substrate Reprogramming After Cardiac Radiotherapy, David Meng Zhang
Mechanisms Of Electrical Substrate Reprogramming After Cardiac Radiotherapy, David Meng Zhang
Arts & Sciences Graduate Student Theses and Dissertations
Ventricular tachycardia (VT) is frequently associated with morbidity in patients with heart disease and can lead to sudden cardiac death, which accounts for over 350,000 deaths per year and nearly half of all cardiovascular-related deaths in the United States. Despite its status as a major public health concern, arrhythmia management strategies are severely limited in safety and efficacy. Standards-of-care include defibrillators, anti-arrhythmic drugs, and/or ablations. Implantable cardioverter defibrillators improve survival in at-risk populations but severely reduce quality-of-life and increase risks of further-declining ventricular function. Pharmacologic interventions are limited in efficacy and have dozens of off-target effects which are major sources …
Stromal Reprogramming By Fak Inhibition Overcomes Radiation Resistance To Allow For Immune Priming And Response To Checkpoint Blockade, Varintra Lander
Stromal Reprogramming By Fak Inhibition Overcomes Radiation Resistance To Allow For Immune Priming And Response To Checkpoint Blockade, Varintra Lander
Arts & Sciences Graduate Student Theses and Dissertations
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal malignancies. While immune checkpoint blockade (ICB) is effective in many solid cancers, it has not been effective in PDAC. Furthermore, clinical trials combining ICB with standard of care chemo- or radio-therapy (RT), which should be able to prime anti-tumor immunity and unlock ICB, have not been overwhelmingly successful. Thus, understanding the effect of RT on PDAC tumor immunity is critical to plan better combination treatment strategies for this highly recalcitrant cancer. To elucidate if RT can prime antigen specific T cell responses, we first looked at human PDAC resections. In …
A Test Of The Pioneer Factor Hypothesis For Silent Gene Activation, Jeffrey Hansen
A Test Of The Pioneer Factor Hypothesis For Silent Gene Activation, Jeffrey Hansen
Arts & Sciences Graduate Student Theses and Dissertations
Transcription factors (TFs) activate silent genes by binding to and opening heterochromatic instances of their motifs. While we rely on this process for cellular reprogramming, we have an incomplete understanding of which TFs are capable of recognizing inaccessible instance of their motifs and what parameters are important for this activity. My thesis work aimed to address these two questions. The leading model for silent gene activation is the pioneer factor hypothesis (PFH). The PFH states that pioneer factors (PFs) are qualitatively unique TFs that can bind to and open DNA and subsequently recruit non-pioneer factors (nonPFs) to activate expression. We …
Applications Of Bioinformatics For Exploring The Genomic Landscape Of Cancer And Characterizing Treatment Response For Precision Oncology, Sharon Freshour
Applications Of Bioinformatics For Exploring The Genomic Landscape Of Cancer And Characterizing Treatment Response For Precision Oncology, Sharon Freshour
Arts & Sciences Graduate Student Theses and Dissertations
While the integration of next-generation sequencing and bioinformatics into cancer research has been immeasurably useful for advancing the field, there are still many gaps in understanding the genomic landscape of cancer due to the complexity of cancer development and evolution. Likewise, there are still many challenges for identifying and applying effective therapeutics for cancer treatment. Thus, there remains a need to continue characterizing the genomic landscape of cancer, to explore the evolution of cancer, and to understand how tumors respond to treatment. The projects described in this dissertation cover several applications of next-generation sequencing, bioinformatic analysis, and database resources for …
The Macrophage Autophagy-Lysosome System In Atherosclerosis Pathogenesis, Astrid Carolina Rodriguez Velez
The Macrophage Autophagy-Lysosome System In Atherosclerosis Pathogenesis, Astrid Carolina Rodriguez Velez
Arts & Sciences Graduate Student Theses and Dissertations
Cardiovascular diseases, particularly atherosclerosis, pose significant health concerns, necessitating a comprehensive understanding of underlying mechanisms for effective therapeutic interventions. In this dissertation, I studied diverse topics, ranging from dietary impacts to intracellular processes, shedding light on novel avenues for atherosclerosis research. It is divided in 4 core projects. In Chapter 2) I studied how dietary protein drives atherosclerosis and lesion complexity. We found that protein ingestion acutely elevates amino acid levels in blood and atherosclerotic plaques, stimulating macrophage mTOR signaling. This is causal in plaque progression as the effects are abrogated in macrophage-specific Raptor-null mice. Mechanistically, we find amino acids …
Investigation Of The Deubiquitinating Enzyme Usp7 In The Brain, Hao Chen
Investigation Of The Deubiquitinating Enzyme Usp7 In The Brain, Hao Chen
Arts & Sciences Graduate Student Theses and Dissertations
The development of the nervous system relies on precise control of protein ubiquitination and degradation. Consequently, imbalance in the ubiquitin signaling network is believed to have significant implications for neurological disorders. Recent research has not only detailed the various functions of different ubiquitin ligases in neural development, but has also disclosed the role of deubiquitinating enzyme as an additional regulatory dimension in the ubiquitin signaling network. Specifically, deletion or mutation of the deubiquitinating enzyme USP7 causes the Hao-Fountain syndrome, characterized by developmental delay, intellectual disability, autism, and aggressive behavior. Although USP7 has been studied in proliferating cells in the context …
A Dynamic Duo: Investigating The Interactions Between Xanthomonas Citri Pv. Malvacearum And Pseudomonas Syringae, Taylor Harris
A Dynamic Duo: Investigating The Interactions Between Xanthomonas Citri Pv. Malvacearum And Pseudomonas Syringae, Taylor Harris
Arts & Sciences Graduate Student Theses and Dissertations
Bacterial pathogens threaten crop production worldwide, which highlights the need to understand plant and pathogen interactions. Studies on plant-pathogen interactions typically focus on a single host and pathogen. However, bacteria exist in complex microbial communities, not alone. There are few studies that examine the mechanisms behind multi-pathogen infections which renders a gap in our understanding of the subsequent implications on agriculture. In this dissertation, I use in vitro plate assays with RNA-sequencing and in planta assays to investigate the interactions between two cotton bacterial pathogens, Xanthomonas citri pv. malvaearum (Xcm) and Pseudomonas syringae (Ps). In vitro plate assays demonstrate that …
Tfeb Degradation Is Regulated By An Ikk/Β-Trcp2 Phosphorylation-Ubiquitination Cascade, Yan Xiong
Tfeb Degradation Is Regulated By An Ikk/Β-Trcp2 Phosphorylation-Ubiquitination Cascade, Yan Xiong
Arts & Sciences Graduate Student Theses and Dissertations
Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy that plays a key role in the regulation of cellular clearance pathways. TFEB is regulated via a complex array of post-translational modifications (PTMs), but the exact molecular mechanism that regulates TFEB stability has remained elusive. Here, we show that TFEB levels are critically regulated by a defined phosphorylation-ubiquitination cascade. A human kinome screen identifies IKK (inhibitor of κB kinase) as a TFEB modifier, and a combination of phosphorylation assays, mass spectrometry analyses, and site-specific mutagenesis unveils a previously unrecognized TFEB phospho-degron (423SPFPSLS429) as the target of IKK. …
Discerning The Roles Of Novel Glycosyltransferases In The Pathogenic Yeast Cryptococcus Neoformans, Liza Loza
Discerning The Roles Of Novel Glycosyltransferases In The Pathogenic Yeast Cryptococcus Neoformans, Liza Loza
Arts & Sciences Graduate Student Theses and Dissertations
Cryptococcus neoformans (Cn) is an opportunistic fungal pathogen responsible for over 112,000 deaths each year. This yeast is ubiquitous in the environment, where it is particularly associated with soil, trees, and bird excreta. When a susceptible host inhales infectious particles, Cn can proliferate in the lungs before disseminating to the brain to cause an often-fatal meningoencephalitis. Cryptococcosis primarily afflicts those living with uncontrolled HIV/AIDS, accounting for ~15% of AIDS-related mortality. The antifungals available to treat this devastating disease are few in number, toxic to patients, and largely inaccessible in resource-limited settings. The major virulence factor of Cn is its complex …
A Quantum Physics-Based Force Field For Biomolecular Simulation, Roseane Dos Reis Silva
A Quantum Physics-Based Force Field For Biomolecular Simulation, Roseane Dos Reis Silva
Arts & Sciences Graduate Student Theses and Dissertations
This dissertation explores the development of a physics-based force field meticulously tailored to guide molecular dynamics simulations of biomolecules. At its core, the Hydrogen-like Intermolecular Polarizable Potential (HIPPO) force field emerges as an apex of achievement, devised to refine the precision of short-range intermolecular interactions. HIPPO's inception marks a profound stride towards heightened realism in molecular simulations, anchored in Quantum Physics theory and fortified by state-of-the-art Quantum Chemistry calculations. This force field's efficacy is attested by its systematic application in constructing models featuring diverse organic molecules, from water to benzene, and those with motifs resembling proteins and nucleic acids. HIPPO …
Apolipoprotein E Adopts An Antiparallel Dimer In Discoidal Lipoproteins, Michael Ray Strickland
Apolipoprotein E Adopts An Antiparallel Dimer In Discoidal Lipoproteins, Michael Ray Strickland
Arts & Sciences Graduate Student Theses and Dissertations
Apolipoprotein E (ApoE) is the major lipoprotein in the central nervous system and forms high density lipoprotein (HDL) like lipoprotein. ApoE is primarily secreted by astrocytes in the central nervous system and is thought to play an important role in cholesterol and lipid transport. The APOE gene has three major alleles, APOE2, APOE3, and APOE4. These alleles encode for 3 common APOE protein isoforms, ApoE2, ApoE3, and ApoE4. APOE3 is most common isoform of APOE with the other two isoforms differing by the loss (ApoE4, Cys112Arg) or gain (ApoE2, Arg158Cys) of a cysteine residue. APOE4 is the largest risk factor …