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2019

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Conformational Dynamics Of The Nuclear Pore Complex Studied With Coarse-Grained Modelling And Polarized Light Microscopy, Joan Pulupa Jan 2019

Conformational Dynamics Of The Nuclear Pore Complex Studied With Coarse-Grained Modelling And Polarized Light Microscopy, Joan Pulupa

Student Theses and Dissertations

In my thesis work, I explored the organization and dynamics of the nuclear pore complex (NPC) through coarse-grained modelling and polarized-total internal reflection fluorescence (pol-TIRF) microscopy. The NPC is a large (~120 MDa in humans) macromolecular assembly that controls the flow of molecules into and out of the nucleus. The NPC is a key regulator of intracellular trafficking, nuclear organization, and gene expression. The study of this cellular gatekeeper is hampered by its size and complexity, as well as the difficulty of measuring protein dynamics in vivo. Although various models for how cargo translocates the NPC have been proposed, the …

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Functional Organization Of Molecular Memories In The Crispr-Cas Immune System, Jon Mcginn Jan 2019

Functional Organization Of Molecular Memories In The Crispr-Cas Immune System, Jon Mcginn

Student Theses and Dissertations

CRISPR-Cas systems endow bacteria and archaea with adaptive immunity against foreign genetic threats, like phages and plasmids. These immune systems are comprised of CRISPR-associated (Cas) protein effectors and DNA-based storage of immunological memories in the CRISPR array. The CRISPR array is a series of direct repeats intercalated by variable spacer sequences (~30bp) of foreign origin. Upon infection, spacers are excised from the foreign genome and integrated into the array. The array is then transcribed and parsed into individual CRISPR RNAs, each containing a single spacer sequence, which are used by Cas nucleases to identify foreign nucleic acids for destruction. Thus, …

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In Vitro, In Vivo, And In Silico Studies Of Reticulospinal Circuits And Generalized Arousal, Adele Bubnys Jan 2019

In Vitro, In Vivo, And In Silico Studies Of Reticulospinal Circuits And Generalized Arousal, Adele Bubnys

Student Theses and Dissertations

Generalized arousal (GA) is a fundamental force in the nervous system that alerts an individual to abrupt changes in its environment. A state of high GA is operationally defined by increases in an animal's a.) locomotor output, b.) responsiveness to sensory stimuli, and c.) emotional reactivity. Previous studies have identified the nucleus gigantocellularis (NGC), a small group of large-bodied neurons in the hindbrain reticular formation, as a potential neuronal substrate for GA. These neurons are responsive to a wide range of sensory modalities and have diverse projections that target both forebrain areas and motor effectors directly within the spinal cord, …

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Molecular Characterization Of Novel Mutations In Fanconi Anemia Patients, Kimberly Rickman Jan 2019

Molecular Characterization Of Novel Mutations In Fanconi Anemia Patients, Kimberly Rickman

Student Theses and Dissertations

Fanconi anemia (FA) is a rare disorder that is characterized by bone marrow failure in the first decade of life, developmental abnormalities, and predisposition to malignancies. The majority of patients have mutations in one of the 22 known FA genes, while a small number of patients have not been assigned to a complementation group. FA proteins are required for the proper repair of DNA interstrand crosslinks (ICL), a deleterious type of DNA damage that covalently binds DNA strands. We have used Whole Exome Sequencing (WES) in conjunction with cell-based assays to determine disease-causing mutations in a subset of patients enrolled …

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A Stress-Induced Trna Depletion Response Mediates Codon-Based Translational Repression And Growth Suppression, Doowon Huh Jan 2019

A Stress-Induced Trna Depletion Response Mediates Codon-Based Translational Repression And Growth Suppression, Doowon Huh

Student Theses and Dissertations

Eukaryotic transfer RNAs (tRNAs) can become fragmented upon various cellular stresses, generating tRNA-derived RNA fragments (tRFs). Though this process has been observed for numerous cellular stresses and in many species ranging from plant cells to yeast and human cells, it is still poorly characterized and understood. Such tRNA fragmentation has previously been thought to affect a small fraction of the tRNA pool and was thus presumed to not affect the role of tRNAs in translation. We report that in human cells, oxidative stress can rapidly generate tRFs derived from tyrosyl tRNAGUA—resulting in a significant depletion of the precursor tRNA molecule …

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Oxytocin, Dopamine, And The Neuromodulation Of Mating Behavior In C. Elegans, Meghan Aileen Lockard Jan 2019

Oxytocin, Dopamine, And The Neuromodulation Of Mating Behavior In C. Elegans, Meghan Aileen Lockard

Student Theses and Dissertations

In the four modalities of analysis that Tinbergen describes: mechanistic, ontological, functional, and phylogenetic, I look at both the "how" and the "why" of oxytocin as a releaser of reproductive behavior. To do so, I take the wide view across 600 million years of metazoan evolution, focusing on the oxytocin-mediated mating behavior and physiology of the often-overlooked invertebrates. By looking to these simpler animals with both smaller, paired-down nervous systems and more diverse sets of mating strategies, I elucidate some of the basic and general principles of the oxytocin circuit (Chapter I). In Chapter II, I give a survey of …

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Molecular Mechanisms Underlying Stress-Induced Glia Remodeling In The Nematode C. Elegans, In Hae Lee Jan 2019

Molecular Mechanisms Underlying Stress-Induced Glia Remodeling In The Nematode C. Elegans, In Hae Lee

Student Theses and Dissertations

Animals can adapt to long-term environmental changes by modifying their behavior, which can be accompanied by structural alterations of the nervous system. Such alterations are common in sensory organs, composed of sensory neurons and glia, which initially detect environmental stress. The molecular mechanisms driving cell shape remodeling following environmental stress and the effects of such remodeling on animal survival are not well understood. C. elegans is an excellent model in which to study neuronal and glial cell remodeling. Under normal growth conditions, the sensory receptive endings of the bilateral AWC sensory neurons, which respond to volatile odorants, are individually ensheathed …

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Multimodal Strategies Of Host-Seeking Mosquitoes, Molly Zhen Liu Jan 2019

Multimodal Strategies Of Host-Seeking Mosquitoes, Molly Zhen Liu

Student Theses and Dissertations

Mosquitoes use multiple sensory modalities, including olfaction, thermosensation, and vision, to hunt human hosts and obtain a blood-meal for egg production. Any individual sensory cue is an incomplete signal of a human host, and so a mosquito must integrate multimodal sensory information before committing to approaching and biting a person. Mosquito host-seeking behavior is thus a particularly fruitful model for studying multimodal integration because of its robustness, intricacy, and public health importance. Using tethered and free flight assays, we have teased apart responses to attractive visual and thermal cues in female Aedes aegypti, the yellow fever mosquito, uncovering their contributions …

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Gpcr Activation Of The G Protein-Gated Inward-Rectifier Potassium Channel, Kouki Touhara Jan 2019

Gpcr Activation Of The G Protein-Gated Inward-Rectifier Potassium Channel, Kouki Touhara

Student Theses and Dissertations

Heart rate is tightly regulated by the combined effects of the sympathetic and parasympathetic branches of the autonomic nervous system. These two branches control heart rate by stimulating different G protein-coupled receptors (GPCRs), which in turn activate ion channels that modify the electrical properties of cardiac pacemaker cells. Sympathetic stimulation accelerates heart rate through activation of beta-adrenergic receptors (βARs), which open excitatory ion channels through the stimulatory G protein (Gαs) pathway. Parasympathetic stimulation slows heart rate through activation of the muscarinic acetylcholine receptor M2 (M2Rs), which inhibits the effect of sympathetic stimulation through the inhibitory G protein (Gαi) pathway. M2Rs …

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Chemical Biology, Biochemical And Structural Studies Of Mdn1, An Aaa Protein Required For Ribosome Biogenesis, Zhen Chen Jan 2019

Chemical Biology, Biochemical And Structural Studies Of Mdn1, An Aaa Protein Required For Ribosome Biogenesis, Zhen Chen

Student Theses and Dissertations

Cellular proteins are synthesized by ribosomes, which are ~3 MDa macromolecular complexes comprised of four ribosomal RNAs and ~80 ribosomal proteins in yeast. The biogenesis of such complicated ribonucleoprotein complexes is a highly regulated, multistep process requiring a plethora of more than 200 unique assembly factors. Energy-harnessing enzymes, such as ATPases and GTPases, are needed to remodel the precursors of ribosomes at fast time scales. Mdn1 is an essential dynein-like AAA protein (ATPases Associated with various Activities) that releases specific assembly factors from the precursors of 60S subunit of ribosomes. However, Mdn1's unusually large size (~5000 amino acids in a …

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Sensory Coding And Olfactory Integration In Caenorhabditis Elegans, May Dobosiewicz Jan 2019

Sensory Coding And Olfactory Integration In Caenorhabditis Elegans, May Dobosiewicz

Student Theses and Dissertations

Animals must sense their external environments to guide meaningful behavior. The nematode Caenorhabditis elegans, for example, uses volatile cues to navigate toward food from a distance. How does an animal integrate the olfactory information from its environment? Here, I ask how multiple sensory neurons drive and shape one interneuron's activity. C. elegans senses several odors, including the bacterial metabolite diacetyl, using the AWA sensory neurons. AWA forms chemical and electrical synapses onto several interconnected interneurons, which contribute to chemotaxis toward attractive odors like diacetyl. One AWA target is the interneuron AIA, which is connected to AWA via a putative electrical …

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Spontaneity And Precision In The Drosophila Central Nervous System, Bennett Ferris Jan 2019

Spontaneity And Precision In The Drosophila Central Nervous System, Bennett Ferris

Student Theses and Dissertations

Many organisms that can locomote change their navigational strategies depending upon behavioral context. During foraging or exploration, for instance, many animals navigate by interspersing straight runs with turns whose direction and frequency may originate, at least at times, from largely stochastic processes. Conversely, during goal-directed navigation, animals may use stored heading and distance signals to travel efficiently to a desired location. This thesis explores the circuitry underlying these disparate navigational strategies in Drosophila. I first show that normal synaptic transmission in a genetically specified population of neurons is necessary for one to observe an appreciable rate of spontaneous flight turns …

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Modeling Alzheimer's Disease Using Crispr/Cas9 Gene Editing And Induced Pluripotent Stem Cells Reveals Conserved Cellular Mechanisms, Dylan Kwart Jan 2019

Modeling Alzheimer's Disease Using Crispr/Cas9 Gene Editing And Induced Pluripotent Stem Cells Reveals Conserved Cellular Mechanisms, Dylan Kwart

Student Theses and Dissertations

Alzheimer's disease (AD) is the most common cause of dementia worldwide and a leading cause of death in the United States. Rare cases of autosomal dominant familial AD (fAD) result from genetic mutations in three key genes: amyloid precursor protein (APP), and two APP processing-related genes (presenilin-1 (PSEN1), and presenilin-2 (PSEN2)), supporting the theory that altered APP metabolism is a central cause of AD. However, which product of APP metabolism is causal remains a matter of investigation. A probable source of this lack of understanding stems from the poor disease model systems that have been utilized in the field for …

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Distinct Populations Of Layer 5b Pyramidal Neurons In The Primary Motor Cortex, Maria V. Moya Jan 2019

Distinct Populations Of Layer 5b Pyramidal Neurons In The Primary Motor Cortex, Maria V. Moya

Student Theses and Dissertations

The ability of motor cortex to plan, execute, and refine different movements depends on the coordinated activity of many neurons found across its laminar structure. Layer 5b (L5b), a deep cortical layer that drives output signals from the cortex, contains excitatory pyramidal neurons that innervate many subcortical areas of the brain. In the motor cortex, L5b is thicker and contains more pyramidal neurons than L5b of other cortical areas. Electrophysiological, anatomical, and RNA-Seq profiling of neurons in the motor cortex suggests there are diverse pyramidal neuron types within L5b. However, the precise identities of these distinct populations and their defining …

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Elucidation Of The Functional Architecture Of The Early Pre-Ribosomal Processing Machinery In Yeast, Mirjam Hunziker Jan 2019

Elucidation Of The Functional Architecture Of The Early Pre-Ribosomal Processing Machinery In Yeast, Mirjam Hunziker

Student Theses and Dissertations

Ribosomes carry out one of the most fundamental functions of life - the translation of genetic information into functional proteins. The pivotal role of the ribosome in the cell is reflected in its immensely complicated and energy-consuming assembly pathway. The maturation of a eukaryotic ribosome involves more than 200 non-ribosomal factors and the activity of all three RNA polymerases. In yeast, ribosome biogenesis starts with the transcription of the 35S pre-ribosomal RNA in the nucleolus. This large RNA molecule contains three of the four ribosomal RNAs separated by several internal and external transcribed spacer regions. The 5' external transcribed spacer …

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Regulation Of Protein Degradation By Adp-Ribosylation, Yetis Gultekin Jan 2019

Regulation Of Protein Degradation By Adp-Ribosylation, Yetis Gultekin

Student Theses and Dissertations

Protein quality control is essential for cellular homeostasis. The Ubiquitin-Proteasome System (UPS) is responsible for the regulated breakdown of intracellular proteins. All proteins are not degraded at the same rate in the cell. For instance, global protein turnover rates in mammals change with an average time between 1-2 days. On the other hand, a handful of proteins such as myelin exhibits limited turnover for months or even years. The UPS recycles most of the short-lived proteins in a time range from minutes to days depending on their localization and post-translational modifications. The post-translational modification, poly-ADPribosylation has an estimated half-life of …

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Substrate Identification Of An Oncogenic Kinase: Elucidating The Pathogenesis Of A Rare Liver Cancer, Melissa Jarmel Jan 2019

Substrate Identification Of An Oncogenic Kinase: Elucidating The Pathogenesis Of A Rare Liver Cancer, Melissa Jarmel

Student Theses and Dissertations

Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer with limited treatment options. This cancer primarily affects adolescents and young adults. Our lab has identified a new fusion gene in this cancer called DNAJB1-PRKACA that results from a break and re-fusion in chromosome 19. This chimeric gene results in a fusion kinase that acts as the driver of this cancer. While we have shown that the kinase activity of the fusion protein is essential for transformation, it is not currently known whether the oncogenic kinase that results from this fusion event, DNAJB1- PRKACA, phosphorylates the same substrates as PRKACA, the …

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The Skin Remembers: Epigenetic Memories Of Inflammation Past, Samantha B. Larsen Jan 2019

The Skin Remembers: Epigenetic Memories Of Inflammation Past, Samantha B. Larsen

Student Theses and Dissertations

As one of the body's largest environmental interfaces, the skin is routinely exposed to a myriad of inflammatory stimuli. It functions as a barrier acting as the first line of defense against pathogens, while simultaneously protecting the organism from dehydration. Maintaining an intact barrier is therefore paramount to organismal survival, and the foremost torchbearers of this task are skin epithelial stem cells (EpSCs). EpSCs reside in the basal layer of the skin, survive long-term, and are capable of both self-renewing and differentiating into multiple skin lineages. To efficaciously maintain the barrier, EpSCs must be able to sense and respond to …

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Burnout Levels Of Teachers Within A Selected School District In Minnesota, Adam Whirley Jan 2019

Burnout Levels Of Teachers Within A Selected School District In Minnesota, Adam Whirley

All Graduate Theses, Dissertations, and Other Capstone Projects

The purpose of this study was to identify feelings of burnout within a selected school district in Minnesota and to identify contributing demographic factors. For this study, a random school district in Minnesota was chosen to be surveyed. By identifying feelings of burnout and demographic factors associated with these feelings, appropriate mental health interventions will be developed and implemented within school districts and the workplace. By implementing these interventions there will be a reduction in occupational burnout and stronger mental health among employees. The study showed a significance relationship between 9-12(High School) teachers and higher levels of burnout when compared …

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Video Gaming As A Gendered Pursuit, Jenna M. Drenten, Robert L. Harrison, Nicholas J. Pendarvis Jan 2019

Video Gaming As A Gendered Pursuit, Jenna M. Drenten, Robert L. Harrison, Nicholas J. Pendarvis

School of Business: Faculty Publications and Other Works

As video game technology has evolved, so too has the gendered nature of the video gaming subculture. This chapter characterizes the broad cultural context of gaming and the shifting social patterns of gendered game play. By reviewing existing research at the intersection of gender, gaming, and consumption, we identify three primary research opportunities to build upon existing research: understanding consumers’ lived experiences in the gendered gaming subculture, exploring the gendered gaming marketplace (e.g., shopping, advertising), and investigating the systemic, structural, and cultural underpinnings of gaming. Existing research in the field is not exhaustive nor complete; rather, opportunities for research identify …

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Equally Strange Fruit: Catholic Health Care And The Appropriation Of Residential Segregation, Cory D. Mitchell, M. Therese Lysaught Jan 2019

Equally Strange Fruit: Catholic Health Care And The Appropriation Of Residential Segregation, Cory D. Mitchell, M. Therese Lysaught

Institute of Pastoral Studies: Faculty Publications and Other Works

FROM THE EARLIEST BEGINNINGS OF CHRISTIAN history and from the moment the Ursuline Sisters opened the first Catholic hospital in the United States in 1728, charity toward the poor and marginalized has been the chief identifying characteristic of Catholic health care.3 Again and again, small groups of in-trepid nuns sought out the poorest communities, set up hospitals, in-novated on reimbursement methods, raised donations, lived in solidarity with and dedicated their lives to caring for the health needs of the poor, needs often exacerbated by extraordinarily difficult living conditions.4

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Secrets Of The Deep: Defining Privacy Underwater, Annie Brett Jan 2019

Secrets Of The Deep: Defining Privacy Underwater, Annie Brett

Missouri Law Review

No abstract provided.

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Medicine@Yale June/July 2019 Volume 15, Issue 2, Yale School Of Medicine Office Of Communications Jan 2019

Medicine@Yale June/July 2019 Volume 15, Issue 2, Yale School Of Medicine Office Of Communications

Medicine@Yale - development newsletter

Medicine@Yale : advancing biomedical science, education and health care was a print and online newsletter which published news about academics, research and philanthropy for alumni, donors, faculty, students and the general public. It was initially published 6 times a year and then changed to a quarterly schedule. The first issue came out June/Jul. 2005. The final issue was published in May/June 2022, vol. 17, issue 1. Published by Yale School of Medicine, Office of Communications.

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Targeting Hunk To Suppress Autophagy: A Novel Target For Her2+ Breast Cancer, Joelle Nieves Zambrano Jan 2019

Targeting Hunk To Suppress Autophagy: A Novel Target For Her2+ Breast Cancer, Joelle Nieves Zambrano

MUSC Theses and Dissertations

Despite the availability of targeted therapeutics, the development of resistance to HER2 inhibitors represents a significant barrier to the treatment of HER2+ breast cancers. To enhance the efficacy of these inhibitors, identifying novel molecular targets which facilitate tumorigenesis and resistance is essential. HUNK (Hormonally Upregulated Neu-associated Kinase) is a protein kinase which has been shown to promote HER2+ mammary tumorigenesis in a kinase-dependent fashion. Previous studies also indicate HUNK upregulates autophagy in a HER2+ breast cancer model that is resistant to HER2 inhibitors, though the mechanism for this regulation currently remains unknown. We have recently identified staurosporine (STU) as a …

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Role Of Bdnf In The Ability Of Exercise To Attenuate Dependence-Related Escalated Alcohol Drinking In C57bl/6j Mice, Matthew Gustav Solomon Jan 2019

Role Of Bdnf In The Ability Of Exercise To Attenuate Dependence-Related Escalated Alcohol Drinking In C57bl/6j Mice, Matthew Gustav Solomon

MUSC Theses and Dissertations

Alcohol use disorder (AUD) continues to be a burden to society. Currently, few efficacious treatments exist. In addition to behavioral therapy and support groups (e.g. Alcoholics Anonymous), there are only three FDA approved pharmacotherapies. The lack of treatment options for alcohol addiction denotes the need to discover and develop new strategies and pharmacological targets to improve abstinence, prevent relapse, and inhibit the development of alcohol addiction. Chronic alcohol exposure reduces brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC). Reductions of BDNF in the mPFC drive alcohol-dependent drinking in mice and conversely, elevating BDNF in this region blocks alcohol …

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Evolution Of The Zhx Transcription Factor Family And Analysis Of Zhx2 Target Genes Cyp2a4 And Cyp2a5 In Mouse Liver, Alexandra Nichole Nail Jan 2019

Evolution Of The Zhx Transcription Factor Family And Analysis Of Zhx2 Target Genes Cyp2a4 And Cyp2a5 In Mouse Liver, Alexandra Nichole Nail

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

The liver is the largest internal organ and performs a wide variety of functions to maintain organismal homeostasis. While some liver functions are carried out by all hepatocytes, other functions are restricted to certain populations of hepatocytes within the liver. This phenomenon, called zonal gene regulation or liver zonation, controls may metabolic processes within the liver including ammonia detoxification; glucose homeostasis; bile acid and glutamine synthesis; and metabolism of xenobiotics, lipids, and amino acids. The liver also expresses many genes in a developmental or sex-biased manner. Some genes are expressed at higher levels early or late in development, or alternatively, …

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2019 Commencement Program, Morehead State University. Registrar's Office. Jan 2019

2019 Commencement Program, Morehead State University. Registrar's Office.

Morehead State Commencement Programs

2019 commencement programs of Morehead State University.

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Water Pollution In Old Towns Affecting The Environment And Ecological Restoration, Zou Hang, Muhammad Aqeel Ashraf, Yung Tse Hung Jan 2019

Water Pollution In Old Towns Affecting The Environment And Ecological Restoration, Zou Hang, Muhammad Aqeel Ashraf, Yung Tse Hung

Civil and Environmental Engineering Faculty Publications

© 2019 Technoscience Publications. All rights reserved. In order to solve the problem that the traditional activated sludge method is not effective in recovering the ecological process of water pollution in urban areas, the membrane bioreactor-based sewage treatment process was studied experimentally. Two flat-plate ultrafiltration membranes were used to form the ultrafilter tank in the experimental device sampled, and the processes of nitrate cycle and sludge cycle were adopted. Ozonation and granular activated carbon filtration were adopted to treat the micropollutants. After repeated experiments in 17 experimental cycles, the obtained experimental data were analysed, and it was found that under …

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Metabolic Cost Calculations Of Gait Using Musculoskeletal Energy Models, A Comparison Study, Anne D. Koelewijn, Dieter Heinrich, Antonie J. Van Den Bogert Jan 2019

Metabolic Cost Calculations Of Gait Using Musculoskeletal Energy Models, A Comparison Study, Anne D. Koelewijn, Dieter Heinrich, Antonie J. Van Den Bogert

Mechanical Engineering Faculty Publications

This paper compares predictions of metabolic energy expenditure in gait using seven metabolic energy expenditure models to assess their correlation with experimental data. Ground reaction forces, marker data, and pulmonary gas exchange data were recorded for six walking trials at combinations of two speeds, 0.8 m/s and 1.3 m/s, and three inclines, -8% (downhill), level, and 8% (uphill). The metabolic cost, calculated with the metabolic energy models was compared to the metabolic cost from the pulmonary gas exchange rates. A repeated measures correlation showed that all models correlated well with experimental data, with correlations of at least 0.9. The model …

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Conflicts Of Interest In Medicine: Should We Contract, Conserve, Or Expand The Traditional Definition And Scope Of Regulation?, Marc A. Rodwin Jan 2019

Conflicts Of Interest In Medicine: Should We Contract, Conserve, Or Expand The Traditional Definition And Scope Of Regulation?, Marc A. Rodwin

Journal of Health Care Law and Policy

No abstract provided.

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