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Β-Hydroxy-Β-Methylbutyrate Supplementation Promotes Antitumor Immunity In An Obesity Responsive Mouse Model Of Pancreatic Ductal Adenocarcinoma, Michael F. Coleman, Kristyn A. Liu, Alexander J. Pfeil, Suhas K. Etigunta, Xiaohu Tang, Salvador Fabela, Et. Al. Dec 2021

Β-Hydroxy-Β-Methylbutyrate Supplementation Promotes Antitumor Immunity In An Obesity Responsive Mouse Model Of Pancreatic Ductal Adenocarcinoma, Michael F. Coleman, Kristyn A. Liu, Alexander J. Pfeil, Suhas K. Etigunta, Xiaohu Tang, Salvador Fabela, Et. Al.

Michigan Tech Publications, Part 1

Pancreatic cancer (PDAC) is a deadly disease, exacerbated by obesity, which lacks effective therapeutic interventions. Most PDAC has a limited response to immune- and chemotherapy. Treating PDAC is made additionally challenging by the rapid emergence of muscle wasting and cachexia, which predict poor response to several therapies. We have found that dietary supplementation with β-hydroxy-β-methylbutyrate promotes immunosurveillance in PDAC tumors and protects muscle. This dietary supplement has the potential to be an important adjuvant in PDAC therapy, opening the doors to immunotherapy response.


Analysis Of Spore Shape Determination In Streptomyces, Ning Sun Dec 2021

Analysis Of Spore Shape Determination In Streptomyces, Ning Sun

Electronic Theses and Dissertations

Streptomycetes are Gram-positive, soil-dwelling bacteria that possess a complex life cycle with the alternation of vegetative mycelium, aerial mycelium, and spores. Streptomyces. coelicolor spore maturation is a complex process that involves spore shape metamorphosis from cylindrical pre-spores into ellipsoid spores, but the details of this process have remained enigmatic. Previously, our lab identified a novel gene ssdA that might play a role in spore shape determination using a transposon-based insertion mutagenesis in S. coelicolor. In this study, I isolated a S. coelicolor ssdA-null mutant that showed increased colony hydrophobicity and misshapen spores in sizes and shapes, confirming the …


Development Of A Muc16-Targeted Near-Infrared Antibody Probe For Fluorescence-Guided Surgery Of Pancreatic Cancer, Madeline T. Olson Dec 2021

Development Of A Muc16-Targeted Near-Infrared Antibody Probe For Fluorescence-Guided Surgery Of Pancreatic Cancer, Madeline T. Olson

Theses & Dissertations

Pancreatic cancer (PDAC) is an extremely lethal disease with an overall survival rate of 10%. Surgery remains the only potentially curative treatment option, but resections are complicated by infiltrative disease, proximity of critical vasculature, peritumoral inflammation, and dense stroma. Surgeons are limited to tactile and visual cues to differentiate cancerous tissue from normal tissue. Furthermore, translating preoperative images to the intraoperative setting poses additional challenges for tumor detection, and can result in undetected and unresected lesions. Thus, PDAC has high rates of incomplete resections, and subsequently, disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to improve intraoperative detection …


Joint Management Of Upland & Aquatic Habitat For The California Red-Legged Frog & California Tiger Salamander, Kyle E. Verblaauw Dec 2021

Joint Management Of Upland & Aquatic Habitat For The California Red-Legged Frog & California Tiger Salamander, Kyle E. Verblaauw

Master's Projects and Capstones

As federally and state protected amphibians, the California tiger salamander (Ambystoma californiense) and the California red-legged frog (Rana draytonii) are recipients of ample management focus. Both species face a variety of threats, including habitat loss and alteration, introduction of non-native species, spread of disease, and effects of climate change. While management plans for the California tiger salamander and California red-legged frog exist, they frequently do not consider both species in tandem and often contain multiple shortcomings. This document aims to address the shortfalls of current management by providing practical recommendations for jointly managing the upland and …


Steroid Receptor-Coregulator Transcriptional Complexes: New Insights From Cryoem, Ping Yi, Xinzhe Yu, Zhao Wang, Bert W O'Malley Dec 2021

Steroid Receptor-Coregulator Transcriptional Complexes: New Insights From Cryoem, Ping Yi, Xinzhe Yu, Zhao Wang, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid receptors activate gene transcription through recruitment of a number of coregulators to facilitate histone modification, chromatin remodeling, and general transcription machinery stabilization. Understanding the structures of full-length steroid receptor and coregulatory complexes has been difficult due to their large molecular sizes and dynamic structural conformations. Recent developments in cryo-electron microscopy (cryoEM) technology and proteomics have advanced the structural studies of steroid receptor complexes. Here, we will review the insights we learned from cryoEM studies of the estrogen and androgen receptor transcriptional complexes. Despite similar domain organizations, the two receptors have different coregulator interaction modes. The cryoEM structures now have …


Characterization Of Landfill Leachate For Enhanced Metal Recovery, Hanna Fulford, Amisha Shah, Inez Hua, Nadezhda Zyaykina, Lori Hoagland, Alejandro Rodriguez Sanchez, Umut Bicim Dec 2021

Characterization Of Landfill Leachate For Enhanced Metal Recovery, Hanna Fulford, Amisha Shah, Inez Hua, Nadezhda Zyaykina, Lori Hoagland, Alejandro Rodriguez Sanchez, Umut Bicim

Discovery Undergraduate Interdisciplinary Research Internship

Landfills contain a trove of valuable materials, such as critical, precious, and rare earth metals, that are integral to the United State’s economy and national security. The leachate that filters through landfills picks up these materials, which allows for the possibility of recovery. For this research, samples will be analyzed from landfills throughout the Midwestern United States to provide a baseline on water quality constituents, elements present, and microbial activity. Preliminary data for this study was acquired by analyzing samples of landfill leachate from a landfill in northern Indiana. pH readings indicate that the leachate is slightly basic. It also …


Rapid Source To Sink Transition In A Mixed-Conifer Forest Following Stand-Replacing Fire, Ryan Matthew Schulze Dec 2021

Rapid Source To Sink Transition In A Mixed-Conifer Forest Following Stand-Replacing Fire, Ryan Matthew Schulze

Biology ETDs

Mixed-conifer forests play an important role in the Southwestern USA’s regional carbon cycle by sequestering and storing large amounts of atmospheric carbon onto the landscape. Despite this, little is known about how large, stand-replacing fire alters ecosystem carbon sink-source dynamics. In this study, we used eddy covariance to quantify how stand-replacing fire altered forest sink strength, and the sensitivity of carbon uptake to soil and atmospheric drought in a mixed-conifer forest located in The Valles Caldera National Preserve, NM. We found that the post-burn ecosystem returned to an annual net sink of carbon in the year immediately following the fire, …


Restoring Polyhyrdoxybutyrate (Phb) Depolymerase Expression In A Bald Mutant Of Streptomyces Sp. Sfb5a, Youmna Moawad Dec 2021

Restoring Polyhyrdoxybutyrate (Phb) Depolymerase Expression In A Bald Mutant Of Streptomyces Sp. Sfb5a, Youmna Moawad

Honors Projects

Polyhydroxybutyrate (PHB) is a biodegradable, plastic-like polymer produced by some bacteria and degraded by others. The filamentous bacterium Streptomyces sp. SFB5A degrades PHB for growth using an extracellular PHB depolymerase, encoded by the phaZ gene. A morphological mutant of this bacterium, bld4, cannot form aerial filaments and cannot produce PHB depolymerase, despite having the phaZ gene. The inability to synthesize PHB depolymerase may be due to a mutation in a gene encoding one of its transcriptional regulators. A gene (lrp) coding for a potential transcriptional regulator is located 2,700 base pairs upstream from phaZ. Our goal …


Population Ecology Of The Queensnake (Regina Septemvittata) In An Urban Creek, 2008 To 2019, Rachel Beiler, R. Elliot Miller, Norman Reichenbach Dec 2021

Population Ecology Of The Queensnake (Regina Septemvittata) In An Urban Creek, 2008 To 2019, Rachel Beiler, R. Elliot Miller, Norman Reichenbach

Faculty Publications and Presentations

Habitat fragmentation is a common result of urbanization and species living in these fragments are at risk of extirpation. We conducted a 12-y (2008–2019) capture-mark-recapture study on snakes living in a 593-m section of Rock Castle Creek flowing through an urban area in central Virginia, USA. Our study site was occupied primarily by Queensnakes (Regina septemvittata). We used data from 168 individual Queensnakes to examine several aspects of their population ecology including survival rates (0.52), reproductive effort (21.3% juvenile to adult ratio), growth rates (68% and 30.6% increase for 1 to 2 y-old and 2 to 3+ y-old snakes, respectively), …


Exploring The Biofilm Of Candida Auris As It Relates To Persistence In Clinical Setting And Susceptibility To Antimicrobials, Bethany Butts Dec 2021

Exploring The Biofilm Of Candida Auris As It Relates To Persistence In Clinical Setting And Susceptibility To Antimicrobials, Bethany Butts

Master of Science in Integrative Biology Theses

The rapid rise of drug-resistant pathogens is a global health concern. Known pathogens are acquiring resistance to many commonly used drugs, while new drug-resistant pathogens are emerging. These resistant pathogens are responsible for many healthcare-associated infections (HAI) [1, 2]. Candida auris is among these emerging drug-resistant pathogens, first described in 2009. The CDC labels C. auris at the highest level of global public health threat [3,4]. Effective methods of decolonization and control of the organisms have yet to be established, as it is resistant to many agents used for microbial control. Recent research has found that C. auris has the …


Flavonoids Reduce Lipid Peroxides And Increase Glutathione Levels In Pooled Human Liver Microsomes (Hlms), William Yaw Boadi, Camille Stevenson, Dontrez Johnson, Mohamed Adel Mohamed Dec 2021

Flavonoids Reduce Lipid Peroxides And Increase Glutathione Levels In Pooled Human Liver Microsomes (Hlms), William Yaw Boadi, Camille Stevenson, Dontrez Johnson, Mohamed Adel Mohamed

Chemistry Faculty Research

The effects of each of the flavonoids; genistein (G), quercetin (Q) and kaempferol (K) at several doses on lipid peroxides (LP) and reduced glutathione (GSH) in pooled human liver microsomes (HLMs) were investigated following the oxidative damage for 4, 6, 18 and 24 hr. HLMs (1 mg/ml) were exposed to each of the above flavonoids at 0, 5, 10, 15, 20 or 25 μM and incubated for the respective times as previously stated. Our hypothesis was that HLMs exposed to the flavonoids for the respective exposure times can decrease LP and increase GSH in HLMs to better cope with the …


Measuring Science Teachers' Emotional Experiences With Evolution Using Real World Scenarios, William Lee Romine, Rutuja Mahajan, Amber Todd Dec 2021

Measuring Science Teachers' Emotional Experiences With Evolution Using Real World Scenarios, William Lee Romine, Rutuja Mahajan, Amber Todd

Biological Sciences Faculty Publications

Low acceptance of evolution remains an obstacle to quality biology instruction. We develop and utilize a novel assessment which measures emotional experience in light of real-world evolution education scenarios. We presented 296 science teachers 4 pro-evolution and 8 anti-evolution scenarios and asked them to rate their levels of joy, anger, sadness, fear, disgust, shame, and guilt elicited by that scenario on an ordinal 5-point scale. We used exploratory factor analysis to extract the most important dimensions in the teachers’ responses, Rasch analysis to explore the validity of the extracted subscales, and stepwise regression to find the most important factors driving …


Human Plcg2 Haploinsufficiency Results In A Novel Immunodeficiency, Joshua Brandon Alinger Dec 2021

Human Plcg2 Haploinsufficiency Results In A Novel Immunodeficiency, Joshua Brandon Alinger

Arts & Sciences Graduate Student Theses and Dissertations

NK cells are critical for the recognition and lysis of herpesvirus-infected cells. Patients with NK cell immunodeficiency may suffer from unusually severe and/or recurrent herpesvirus infections; however, the genetic cause is frequently unknown. PLCG2 encodes a signaling protein in NK cell and B cell receptor signaling, in which dominant-negative or gain-of-function mutations may cause cold urticaria, antibody deficiency, or autoinflammation. However, loss-of-function mutations and PLCG2 haploinsufficiency have never been reported in human disease. We examined 2 families with autosomal dominant NK cell immunodeficiency with dual high-dimensional techniques, mass cytometry and whole-exome sequencing, to identify the cause of disease. We identified …


On The Challenges And Rewards Of Analyzing Molecular Dynamics At The Terabyte And Millisecond Scale, Justin Roy Porter Dec 2021

On The Challenges And Rewards Of Analyzing Molecular Dynamics At The Terabyte And Millisecond Scale, Justin Roy Porter

Arts & Sciences Graduate Student Theses and Dissertations

Molecular Dynamics (MD) and Markov state models (MSMs) are powerful tools for estimating and concisely representing the conformational ensemble accessible to biological macromolecules, particularly proteins. Conformational ensembles are of special importance biological function, both in health and disease, because biology derives from molecules’ entire conformational distribution rather than any single structure. Consequently, MD is poised to become a powerful tool for personalized medicine and for the study of molecular sequence-function relationships generally. However, because of their hyperdimensionality and size, just generating MD datasets and Markov state models (MSMs) that represent biologically relevant molecules is a substantive technical challenge. Then, even …


Influence Of Focal Activity On Macroscale Brain Dynamics In Health And Disease, Zachary Pollack Rosenthal Dec 2021

Influence Of Focal Activity On Macroscale Brain Dynamics In Health And Disease, Zachary Pollack Rosenthal

Arts & Sciences Graduate Student Theses and Dissertations

Macroscopic recordings of brain activity (e.g. fMRI, EEG) are a sensitive biomarker of the neural networks supporting neurocognitive function. However, it remains largely unclear what mechanisms mediate changes in macroscale networks after focal brain injuries like stroke, seizure, and TBI. Recently, optical neuroimaging in animal models has emerged as a powerful tool to begin addressing these questions. Using widefield imaging of cortical calcium dynamics in mice, this dissertation investigates the mechanisms by which focal disruptions in activity alter brain-wide functional dynamics. In two chapters, I demonstrate 1) that focal sensory stimulation elicits state-dependent, global slow waves propagating from primary somatosensory …


Regulation Of Metabolic Stress By The Snhg3 Locus, Arthur Curtis Sletten Dec 2021

Regulation Of Metabolic Stress By The Snhg3 Locus, Arthur Curtis Sletten

Arts & Sciences Graduate Student Theses and Dissertations

Dyslipidemia and lipotoxicity are pathologic signatures of the metabolic syndrome and type 2 diabetes. Excess lipid causes cell dysfunction and induces cell death through pleiotropic mechanisms that link to oxidative stress. However, pathways that regulate the response to metabolic stress are not fully understood. To identify novel genes involved in metabolic stress, our group performed an unbiased forward genetic screen for lipotoxicity resistance. My studies focused on characterizing one of the mutant cell lines isolated from this screen, in which promoter trap mutagenesis disrupted one allele of the small nucleolar RNA hosting gene 3 (Snhg3). I demonstrate that diminished expression …


Role Of Interferon Receptors In Sting-Associated Autoinflammatory Disease In Mice, William Alexander Stinson Dec 2021

Role Of Interferon Receptors In Sting-Associated Autoinflammatory Disease In Mice, William Alexander Stinson

Arts & Sciences Graduate Student Theses and Dissertations

Over the past decade, the cGAS-STING pathway has emerged as a principal component of innate DNA sensing. Its activation of type I interferon (IFN) elicits host immune activation and in the absence of cGAS or STING, mice are rendered critically susceptible to infection by viruses and bacteria. Breakdowns in the molecules that regulate this pathway can promote unrestrained cGAS-STING activation and the development of various forms of autoimmune disease. For instance, gain-of-function mutations in STING cause autoinflammatory lung disease in mice and STING-associated vasculopathy with onset in infancy (SAVI) in humans. However, our understanding of the mechanisms that underlie STING-dependent …


Genetic Risk Factors For Neurodevelopmental Disorders: Insights From Hipsc-Cerebral Organoids, Michelle L. Wegscheid Dec 2021

Genetic Risk Factors For Neurodevelopmental Disorders: Insights From Hipsc-Cerebral Organoids, Michelle L. Wegscheid

Arts & Sciences Graduate Student Theses and Dissertations

Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder (NDD) characterized by remarkable phenotypic variability, where affected children manifest a spectrum of central nervous system (CNS) abnormalities, including brain tumors, impairments in attention, behavior, learning disabilities, and an increased incidence of autism spectrum disorder (ASD). A significant barrier to the implementation of precision medicine strategies for children with NF1 is a lack of prognostic risk factors to guide clinical management. However, emerging population-based genotype-phenotype association studies have suggested that the germline NF1 gene mutation may represent one clinically actionable risk factor for NF1-associated neurodevelopmental abnormalities. As a critical step in …


Weedy Rice As A Model System For The Study Of Microevolutionary Interactions In Agricultural Contexts, Marshall Jon Wedger Dec 2021

Weedy Rice As A Model System For The Study Of Microevolutionary Interactions In Agricultural Contexts, Marshall Jon Wedger

Arts & Sciences Graduate Student Theses and Dissertations

Just under one-half of the global population relies on cultivated rice (Oryza sativa) astheir primary source of calories, making the optimization of rice agriculture immensely important. One of the primary constraints to rice agriculture is the de-domesticated (feral) form of rice known as ‘weedy rice’ that aggressively competes for space, soil nutrients, and light. Heavy infestation can reduce crop yields by as much as 80%. As a closely-related weedy descendant of cultivated rice, chemical control is difficult in rice fields, and physical weeding is labor intensive, time consuming, and largely ineffective due to early life-stage mimicry of the crop. Weedy …


Cancer Epigenome Reprogramming, Jennifer Ann Karlow Dec 2021

Cancer Epigenome Reprogramming, Jennifer Ann Karlow

Arts & Sciences Graduate Student Theses and Dissertations

The identification of recurrent genetic mutations in cancer and their functionalcharacterization has provided a strong foundation for our understanding of tumorigenesis. The more recent observation of recurrent and specific epigenetic changes also present in cancer has widened this view, now establishing cancer as a disease of both genetic and epigenetic misregulation. Enhancers, genomic regions primarily responsible for tissue-specific gene expression, have been shown to be frequent targets of both genetic and epigenetic abnormalities. The observation that DNA methylation within regulatory regions has traditionally correlated with reduced gene expression, coupled with the known role of enhancers in regulating tissuespecific gene expression, …


Developments In Proteomics, Trans-Splicing Technology And Endogenous Transcript Manipulation, Justin Alexander Melendez Dec 2021

Developments In Proteomics, Trans-Splicing Technology And Endogenous Transcript Manipulation, Justin Alexander Melendez

Arts & Sciences Graduate Student Theses and Dissertations

Technological innovation drives scientific discovery, unlocks new avenues of research, and allows us to ask questions in ways that were previously unavailable. With each technological advance, our ability to perturb and explore biological systems has grown in ways previously unimagined. The theme of my thesis is the development of new technologies in biology. To this end, I have worked on three technologies that contribute to the areas of protein sequencing, RNA barcoding for trans-splicing and single-cell applications, and a new method for transcriptional knockdown. In my first project, digital analysis of proteins by end sequencing (DAPES), we set out to …


Defining The Epigenetic And Transcriptional Regulatory Mechanisms By Which Hrsv Ns1 Alters Host Transcriptional Response, Nina Rose Beri Dec 2021

Defining The Epigenetic And Transcriptional Regulatory Mechanisms By Which Hrsv Ns1 Alters Host Transcriptional Response, Nina Rose Beri

Arts & Sciences Graduate Student Theses and Dissertations

No abstract provided.


Influence Of Aging And Cerebrovascular Disease On Neuroimaging Measures Of Alzheimer Disease, Lauren Nicole Koenig Dec 2021

Influence Of Aging And Cerebrovascular Disease On Neuroimaging Measures Of Alzheimer Disease, Lauren Nicole Koenig

Arts & Sciences Graduate Student Theses and Dissertations

The overall goal of this dissertation is to gain a better understanding of how Alzheimer disease relates to normal aging and cerebrovascular disease to impact neuroimaging measures in a clinically meaningful way. Both aging and cerebrovascular disease are known to influence measures of Alzheimer disease, making it difficult to separate what changes are attributable specifically to Alzheimer disease. We hypothesize that a better understanding of these relationships will allow future studies to appropriately take these factors into account. In Chapters 2 and 3 we attempt to separate out the influences of normal aging and Alzheimer disease on measures of atrophy. …


Structural Variants Are A Major Source Of Gene Expression Differences In Humans And Often Affect Multiple Nearby Genes, Alexandra Jane Scott Dec 2021

Structural Variants Are A Major Source Of Gene Expression Differences In Humans And Often Affect Multiple Nearby Genes, Alexandra Jane Scott

Arts & Sciences Graduate Student Theses and Dissertations

Structural variants (SVs), including copy number variants (CNVs), balanced rearrangements, and mobile element insertions (MEIs), are an important source of diversity in the human genome but their functional effects are not well understood. SVs are technically difficult to detect and genotype1, and mapping is dependent on deep whole genome sequencing (WGS) which was, until recently, unaffordable for large cohorts. For these reasons SVs are not included in most genome-wide studies of functional variants, despite the fact that SVs are known causal agents in multiple clinical disorders2-16. However, recent advancements in high-throughput sequencing technologies that allow for widespread use of WGS, …


Regional Reprogramming And The Small Intestine: Analysis And Modeling Of Adaptive Regeneration Of The Epithelium, Sarah Elizabeth Waye Dec 2021

Regional Reprogramming And The Small Intestine: Analysis And Modeling Of Adaptive Regeneration Of The Epithelium, Sarah Elizabeth Waye

Arts & Sciences Graduate Student Theses and Dissertations

The small intestine in homeostasis is capable of regular regeneration, but in cases of massive injury like Short Bowel Syndrome, the innate human response often fails to fully compensate for the loss of nutrient absorptive surface area that accompanies bowel resection. Murine models display an active compensatory reaction deemed “adaptation” in which the surface area of the bowel is increased to accommodate nutrient absorptive needs. This observation has highlighted several gaps in knowledge regarding bowel adaptation. Firstly, what occurs on a molecular level in murine models during adaptation? Secondly, how can the findings in mice be applied to humans in …


Identification Of Multi-Tissue Protein Quantitative Trait Loci And Causal Inference Of Protein Effects In Neurological And Other Complex Human Diseases Via Mendelian Randomization, Chengran Yang Dec 2021

Identification Of Multi-Tissue Protein Quantitative Trait Loci And Causal Inference Of Protein Effects In Neurological And Other Complex Human Diseases Via Mendelian Randomization, Chengran Yang

Arts & Sciences Graduate Student Theses and Dissertations

Alzheimer disease (AD) is the most common neurodegenerative disease, affecting 6.2 million people mostly aged 65 years or older in the United States as of early 2021. AD has been widely studied and characterized worldwide, but there is still no effective treatment or cure. Even the latest FDA-approved treatment, Aducanumab, cannot stop decline or improve cognition. To develop a truly effective treatments, researchers keep discovering genetic and molecular mechanisms underlying the disease. Protein biomarkers are keys to bridge the mechanisms to disease. Here, I first used a high-throughput proteomic dataset from three tissues (CSF, plasma, and brain) with array-based genotype …


Deep Multi-Omics Investigations Elucidate Novel Oncogenesis Paradigms, Therapeutic Targets, And Mechanisms Of Treatment Resistance In Cancer, Daniel Cui Zhou Dec 2021

Deep Multi-Omics Investigations Elucidate Novel Oncogenesis Paradigms, Therapeutic Targets, And Mechanisms Of Treatment Resistance In Cancer, Daniel Cui Zhou

Arts & Sciences Graduate Student Theses and Dissertations

No abstract provided.


Deconvolving Genomic Regulatory Heterogeneity With Self-Reporting Transposons, Arnav Moudgil Dec 2021

Deconvolving Genomic Regulatory Heterogeneity With Self-Reporting Transposons, Arnav Moudgil

Arts & Sciences Graduate Student Theses and Dissertations

A cell’s identity is a function of the genes expressed in that cell, which are in turn regulated by transcription factors. Over the last decade, single-cell RNA sequencing (RNA-seq) has emerged as a powerful class of techniques to characterize cellular diversity in heterogeneous tissues. These methods barcode transcripts by their cell-of-origin and assign them to specific genes. The resulting high-dimensional data are further processed to reveal clusters of cells sharing transcriptional states. Annotating these clusters, based on either known or discovered marker genes, offers a glimpse into the dynamic composition of an organ or biological process. While single-cell RNA-seq excels …


Dissecting The Molecular Mechanism Of Familial Cardiomyopathies, Sarah Ruth Clippinger Schulte Dec 2021

Dissecting The Molecular Mechanism Of Familial Cardiomyopathies, Sarah Ruth Clippinger Schulte

Arts & Sciences Graduate Student Theses and Dissertations

Familial cardiomyopathies, including hypertrophic (HCM), restrictive (RCM) and dilated cardiomyopathy (DCM), are the leading cause of sudden cardiac death in young people. These diseases, which are characterized by altered cardiac contractility and remodeling of the heart, can lead to heart failure. These diseases are primarily caused by point mutations in sarcomeric proteins that generate or regulate heart contraction, such as troponin T. In the heart, the troponin complex together with tropomyosin lie along the actin filament and regulate myosin’s ability to bind actin and produce force. Here I show how mutations in troponin T affect contractility at the molecular level …


A Study On The Hormonal Regulation And Novel Role Of Na+ Leak Channel, Non-Selective (Nalcn) In Human Myometrial Smooth Muscle Cells, Chinwendu Amazu Dec 2021

A Study On The Hormonal Regulation And Novel Role Of Na+ Leak Channel, Non-Selective (Nalcn) In Human Myometrial Smooth Muscle Cells, Chinwendu Amazu

Arts & Sciences Graduate Student Theses and Dissertations

During pregnancy, the uterus transitions from a quiescent state to an excitable, highly contractile state to deliver the fetus. Two important contributors essential for this transition are progesterone (P4) and estrogen (E2), which promote quiescence or contraction, respectively, by acting on the myometrial smooth muscle cells (MSMCs). While these hormones regulate uterine contractions, it is unclear how they affect electrical activity of MSMCs, which underlies uterine contractile activity. Our lab recently identified Na+ leak channel, non-selective (NALCN) as a component of the leak current in human MSMCs and showed that mice lacking NALCN in the uterus have dysfunctional labor. In …