Digital Commons Network^™

Conservation Of Inner Nuclear Membrane Targeting Sequences In Mammalian Pom121 And Yeast Heh2 Membrane Proteins., Annemarie Kralt, Noorjahan B Jagalur, Vincent Van Den Boom, Ravi K Lokareddy, Anton Steen, Gino Cingolani, Maarten Fornerod, Liesbeth M Veenhoff

Department of Biochemistry and Molecular Biology Faculty Papers

Endoplasmic reticulum-synthesized membrane proteins traffic through the nuclear pore complex (NPC) en route to the inner nuclear membrane (INM). Although many membrane proteins pass the NPC by simple diffusion, two yeast proteins, ScSrc1/ScHeh1 and ScHeh2, are actively imported. In these proteins, a nuclear localization signal (NLS) and an intrinsically disordered linker encode the sorting signal for recruiting the transport factors for FG-Nup and RanGTP-dependent transport through the NPC. Here we address whether a similar import mechanism applies in metazoans. We show that the (putative) NLSs of metazoan HsSun2, MmLem2, HsLBR, and HsLap2β are not sufficient to drive nuclear accumulation of …

Rna-Seq Analysis Of Differential Splice Junction Usage And Intron Retentions By Dexseq, Yafang Li, Xiayu Rao, William W. Mattox, Christopher I. Amos, Bin Liu

Dartmouth Scholarship

Alternative splicing is an important biological process in the generation of multiple functional transcripts from the same genomic sequences. Differential analysis of splice junctions (SJs) and intron retentions (IRs) is helpful in the detection of alternative splicing events. In this study, we conducted differential analysis of SJs and IRs by use of DEXSeq, a Bioconductor package originally designed for differential exon usage analysis in RNA-seq data analysis. We set up an analysis pipeline including mapping of RNA-seq reads, the preparation of count tables of SJs and IRs as the input files, and the differential analysis in DEXSeq. We analyzed the …

Gene Diversification Of An Emerging Pathogen: A Decade Of Mutation In A Novel Fish Viral Hemorrhagic Septicemia (Vhs) Substrain Since Its First Appearance In The Laurentian Great Lakes, Carol A. Stepien, Lindsey R. Pierce, Douglas W. Leaman, Megan D. Niner, Brian S. Shepherd

Biological Sciences Faculty Publications

Viral Hemorrhagic Septicemia virus (VHSv) is an RNA rhabdovirus, which causes one of the world's most serious fish diseases, infecting >80 freshwater and marine species across the Northern Hemisphere. A new, novel, and especially virulent substrain—VHSv-IVb—first appeared in the Laurentian Great Lakes about a decade ago, resulting in massive fish kills. It rapidly spread and has genetically diversified. This study analyzes temporal and spatial mutational patterns of VHSv-IVb across the Great Lakes for the novel non-virion (Nv) gene that is unique to this group of novirhabdoviruses, in relation to its glycoprotein (G), phosphoprotein (P), …

Investigation Of Behavioral And Cellular Changes In The Maternal Immune Activation Model Of Autism Spectrum Disorders, Shreya Roy

Theses & Dissertations

Maternal infection during pregnancy, which leads to maternal immune activation (MIA), is an environmental risk factor for autism spectrum disorders (ASD). MIA can be induced in mice and their offspring exhibit behaviors that model the core symptoms of ASD. One of the core behavioral symptoms in ASD patients is presence of increased repetitive behavior, which is modeled by an increase in marble burying in MIA mice. It has been shown that the deficits seen in MIA mice are associated with the dysregulation of cytokine levels in the developing brain, specifically an increase in pro-inflammatory cytokines. In this thesis, I tested …

New Paradigms In The Treatment Of Acute Complicated And Uncomplicated Type B Aortic Dissection, Eric S. Weiss

Journal of Patient-Centered Research and Reviews

The treatment of acute type B aortic dissection is a rapidly evolving field, due in a large part to the advent of thoracic endovascular aortic repair (TEVAR). This review will summarize the current literature on the management of both complicated and uncomplicated type B dissections, with special attention paid to emerging evidence supporting earlier aggressive treatment.

Vascular Medicine: A ‘Primary’ Specialty, Mark W. Mewissen

Journal of Patient-Centered Research and Reviews

N/A

Duration Estimates Within A Modality Are Integrated Sub-Optimally, Ming Bo Cai, David M. Eagleman

Faculty, Staff and Students Publications

Perceived duration can be influenced by various properties of sensory stimuli. For example, visual stimuli of higher temporal frequency are perceived to last longer than those of lower temporal frequency. How does the brain form a representation of duration when each of two simultaneously presented stimuli influences perceived duration in different way? To answer this question, we investigated the perceived duration of a pair of dynamic visual stimuli of different temporal frequencies in comparison to that of a single visual stimulus of either low or high temporal frequency. We found that the duration representation of simultaneously occurring visual stimuli is …

Application Of Β-Lactamase Reporter Fusions As An Indicator Of Effector Protein Secretion During Infections With The Obligate Intracellular Pathogen Chlamydia Trachomatis , Konrad E. Mueller, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chlamydia spp. utilize multiple secretion systems, including the type III secretion system (T3SS), to deploy host-interactive effector proteins into infected host cells. Elucidation of secreted proteins has traditionally required ectopic expression in a surrogate T3SS followed by immunolocalization of endogenous candidate effectors to confirm secretion by chlamydiae. The ability to transform Chlamydia and achieve stable expression of recombinant gene products has enabled a more direct assessment of secretion. We adapted TEM-1 β-lactamase as a reporter system for assessment of chlamydial protein secretion. We provide evidence that this system facilitates visualization of secretion in the context of infection. Specifically, our findings …

Does The Microbiota Play A Role In The Pathogenesis Of Autoimmune Diseases?, Mairi H. Mclean, Dario Dieguez, Lindsey M. Miller, Howard A. Young

United States Public Health Resources

The microbiota of the human metaorganism is not a mere bystander. These microbes have coevolved with us and are pivotal to normal development and homoeostasis. Dysbiosis of the GI microbiota is associated with many disease susceptibilities, including obesity, malignancy, liver disease and GI pathology such as IBD. It is clear that there is direct and indirect crosstalk between this microbial community and host immune response. However, the precise mechanism of this microbial influence in disease pathogenesis remains elusive and is now a major research focus. There is emerging literature on the role of the microbiota in the pathogenesis of autoimmune …

Tract-Based Spatial Statistics In Preterm-Born Neonates Predicts Cognitive And Motor Outcomes At 18 Months., E G Duerden, J Foong, V Chau, H Branson, K J Poskitt, R E Grunau, A Synnes, J G Zwicker, S P Miller

Brain and Mind Institute Researchers' Publications

BACKGROUND AND PURPOSE: Adverse neurodevelopmental outcome is common in children born preterm. Early sensitive predictors of neurodevelopmental outcome such as MR imaging are needed. Tract-based spatial statistics, a diffusion MR imaging analysis method, performed at term-equivalent age (40 weeks) is a promising predictor of neurodevelopmental outcomes in children born very preterm. We sought to determine the association of tract-based spatial statistics findings before term-equivalent age with neurodevelopmental outcome at 18-months corrected age.

MATERIALS AND METHODS: Of 180 neonates (born at 24-32-weeks' gestation) enrolled, 153 had DTI acquired early at 32 weeks' postmenstrual age and 105 had DTI acquired later at …

Optical Tracking System To Monitor Laparoscopic Training, William D. Rytlewski

Masters Theses

Laparoscopic Surgery, also known as Minimally Invasive Surgery, is a surgical technique where surgeons perform surgery through small incisions in the patient’s abdomen using a camera to monitor the movements of the instruments inside the patient. In order for the surgery to be performed, the surgeon must possess a unique set of skills obtained through training using a variety of techniques. Simulators are the preferred method of training for laparoscopic surgery since they provide medical residents with real world scenarios as well as a tremendous amount of feedback on what he/she did wrong or right. However, due to the high …

Synthesis And Flammability Testing Of Epoxy Functionalized Phosphorous-Based Flame Retardants, Vladimir Benin, Xuemei Cui, Alexander Morgan, Karl Seiwert

Chemistry Faculty Publications

Several potential new phosphorus-containing flame retardant molecules were evaluated for heat release reduction potential by incorporation of the molecules into a polyurethane, generated from methylene diphenyl diisocyanate and 1,3-propane diol. The heat release reduction potential of these substances was evaluated using the pyrolysis combustion flow calorimeter (PCFC). The polyurethanes were prepared in the presence of the potential flame retardants via solvent mixing and copolymerization methods to qualitatively evaluate their potential reactivity into the polyurethane prior to heat release testing. The functionality of the flame retardants was epoxide based that would potentially react with the diol during polyurethane synthesis. Flammability testing …

The Effect Of Sleep On Perceptual Learning And Memory Consolidation, Vanessa Claire Irsik

UNLV Theses, Dissertations, Professional Papers, and Capstones

An ability to segregate speech accurately is essential given that most auditory environments contain other overlapping conversations or environmental noise. While perceiving speech among background noise can be difficult in and of itself, those with hearing impairments can experience considerable difficulty. While training has been shown to benefit perceptual segregation of trained sounds, it is unclear how such training transfers to sounds not included in a training regimen. The current study aimed to address this question by training listeners on a portion of sounds during a vowel segregation task, and subsequently testing on both the trained sounds and untrained sounds. …

Improving Attenuation Correction In Hybrid Positron Emission To Mography, Hua Asher Ai

Dissertations and Theses (Open Access)

Hybrid positron emission tomography imaging techniques such as PET/CT and PET/MR have undergone significant developments over the last two decades and have played increasingly more important roles both in research and in the clinic. A unique advantage PET has over other clinical imaging modalities is its capability of accurate quantification. However, as the most critical component of PET quantification, attenuation correction in hybrid PET systems is challenged in several different aspects, including the spatial- temporal mismatch between the PET emission images and the associated attenuation images provided by the complementary modality, and the difficulty in bone identification in the MR-based …

Reduction Of Dose Calculation Errors For Patients With Metal Implants Receiving Photon Radiation Therapy, Jessie Huang-Vredevoogd

Dissertations and Theses (Open Access)

Many patients receiving external beam radiation therapy have metal implants that can affect their treatment, and these metal implants can degrade the accuracy of dose calculations. Dose calculation errors result from limitations of modern dose calculation algorithms in modeling metal/tissue interface effects. Metals also cause streak artifacts in the computed tomography (CT) images that are used for treatment planning, and these artifacts can also degrade dose calculation accuracy. Metal based-energy deposition kernels are a potential solution for the calculation errors associated with the limitations of the convolution/superposition (C/S) dose calculation method as they better model photon interactions and scatter in …

Methylation Of Egfr By Arginine Methyltransferase Prmt1 Enhances Egfr Signaling And Cetuximab Resistance, Hsin-Wei Liao

Dissertations and Theses (Open Access)

Protein modifications of epidermal growth factor receptor (EGFR) intracellular domain are well known regulators of EGFR functions whereas those of its extracellular domain remain relatively unexplored. Here, we report that methylation at R198 and R200 of EGFR extracellular domain by protein arginine methyltransferase 1 (PRMT1) upregulates its binding to EGF and subsequent receptor dimerization and signaling activation. Methylation-defective EGFR mutant reduced tumor growth in mouse orthotopic xenograft model. Importantly, increased EGFR methylation sustains its signaling activation and cell proliferation in the presence of therapeutic EGFR monoclonal antibody, cetuximab. EGFR methylation level also correlates with higher recurrence rate after cetuximab treatment …

Ankyrin-B And Mtor Complex 1 In The Regulation Of Electrical Activities In The Heart, Henry C. Wu, Henry C. Wu

Dissertations and Theses (Open Access)

The mammalian target of rapamycin complex 1 (mTORC1) activity is paramount in the regulation of electrical activities in the brain and the heart. In the brain, the tumor suppressor gene TSC2 encodes the protein product tuberin that interacts with hamartin to form a heterodimer Tuberous Sclerosis Complex (TSC) that regulates mTORC1. When TSC2 is disrupted, mTORC1 activity becomes dysregulated resulting in abnormal electrical activities in the brain manifesting in the form of epileptic seizures. In the heart, mTORC1 activity is triggered by a sustained increase in hemodynamic pressure causing the heart to electrically remodel. A likely candidate serving as the …

The Adaptive Change Of Hla-Drb1 Allele Frequencies Caused By Natural Selection In A Mongolian Population That Migrated To The South Of China, Hao Sun, Zhaoqing Yang, Keqin Lin, Shuyuan Liu, Kai Huang, Xiuyun Wang, Jiayou Chu, Xinyu Huang

Faculty Publications

Pathogen-driven balancing selection determines the richness of human leukocyte antigen (HLA) alleles. Changes in the pathogen spectrum may cause corresponding changes in HLA loci. Approximately 700 years ago, a Mongolian population moved from the north of China to the Yunnan region in the south of China. The pathogen spectrum in the south of China differs from that in the north. In this study, changes in the HLA genes in the Yunnan Mongolian population, as well as the underlying mechanism, were investigated. A sequence-based typing method (SBT) was used to genotype HLA-DRB1 in 470 individuals from two Mongolian populations and another …

Halting The Hallmarks: A Cellular Automaton Model Of Early Cancer Growth Inhibition, Jenna Butler, Frances Mackay, Colin Denniston, Mark Daley

Brain and Mind Institute Researchers' Publications

Cancer treatment is a fragmented and varied process, as ‘‘cancer’’ is really hundreds of different diseases. The ‘‘hallmarks of cancer’’ proposed by Hanahan and Weinberg (Cell 100(1):57–70, 2000) are a framework for viewing cancer within a common set of underlying principles—ten properties that are common to almost all cancers, allowing them to grow uncontrollably and ravage the body. We used a cellular automaton model of tumour growth paired with lattice Boltzmann methods modelling oxygen flow to simulate combination drugs targeted at knocking out pairs of hallmarks. We found that knocking out some pairs of cancer-enabling hallmarks did not prevent tumour …

Regulated Phosphorylation Of The K-Cl Cotransporter Kcc3 Is A Molecular Switch Of Intracellular Potassium Content And Cell Volume Homeostasis, Norma C. Adragna, Nagendra B. Ravilla, Peter K. Lauf, Gulnaz Begum, Arjun R. Khanna, Dandan Sun, Kristopher K. Kahle

Pharmacology and Toxicology Faculty Publications

The defense of cell volume against excessive shrinkage or swelling is a requirement for cell function and organismal survival. Cell swelling triggers a coordinated homeostatic response termed regulatory volume decrease (RVD), resulting in K+ and Cl− efflux via activation of K+ channels, volume-regulated anion channels (VRACs), and the K+-Cl− cotransporters, including KCC3. Here, we show genetic alanine (Ala) substitution at threonines (Thr) 991 and 1048 in the KCC3a isoform carboxyl-terminus, preventing inhibitory phosphorylation at these sites, not only significantly up-regulates KCC3a activity up to 25-fold in normally inhibitory isotonic conditions, but is also accompanied by reversal of activity of the …

Mir-21 In Extracellular Vesicles Leads To Neurotoxicity Via Tlr7 Signaling In Siv Neurological Disease., Sowmya V. Yelamanchili, Benjamin G. Lamberty, Deborah A. Rennard, Brenda M. Morsey, Colleen G. Hochfelder, Brittney M. Meays, Efrat Levy, Howard S. Fox

Journal Articles: Pharmacology & Experimental Neuroscience

Recent studies have found that extracellular vesicles (EVs) play an important role in normal and disease processes. In the present study, we isolated and characterized EVs from the brains of rhesus macaques, both with and without simian immunodeficiency virus (SIV) induced central nervous system (CNS) disease. Small RNA sequencing revealed increased miR-21 levels in EVs from SIV encephalitic (SIVE) brains. In situ hybridization revealed increased miR-21 expression in neurons and macrophage/microglial cells/nodules during SIV induced CNS disease. In vitro culture of macrophages revealed that miR-21 is released into EVs and is neurotoxic when compared to EVs derived from miR-21-/- knockout …

Bacterially-Based Immune Challenges And Trauma Elicit Terminal Investment In Male Aedes Aegypti, Molly K. Schumacher

Theses and Dissertations

Investment in life history traits such as immune function and reproduction is constrained by finite available resources. A cost-of-immunity trade-off may occur in response to infection when resources are diverted away from reproductive effort and into an immune response. Alternatively, an infected individual may enhance reproductive effort to maximize terminal reproductive success in response to the survival threat inherent to infection (terminal investment). We measured male Aedes aegypti reproductive behavior following inoculations with: living bacteria; killed bacteria as an immune elicitor; and a sham control. Mating competitiveness relative to naïve males was also determined through a binary mate choice experiment …

Neurocysticercosis, Abigail Hill

Nursing Student Class Projects (Formerly MSN)

Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system in humans and is the most serious clinical manifestation of cysticercosis. NCC is caused by the ingestion of the larval form of the pork tapeworm Taenia solium. NCC is endemic in low income developing countries where pigs are commonly raised, including the countries of Central America, South America, and parts of Africa and Asia. (Naddaf, Seeger, & Stafstrom, 2014). The parasite Taenia solium encysts in the brain and can express a broad range of symptoms including seizures, headache, hydrocephalus, encephalitis, stroke and mental health and …

Diabetic Ketoacidosis, Mario Bianconi

Nursing Student Class Projects (Formerly MSN)

According to “Statistics About Diabetes” (2014), in 2012, 29.1 million Americans, or 9.3% of the population, had diabetes. Additionally, of the 29.1 million, 21 million of the population were diagnosed, and 8.1 million were undiagnosed. With such a high prevalence, it is imperative that the hospital nurse is aware not only how to treat diabetes, but also how to look for complications of diabetes. One of the severe complications of diabetes is Diabetic Ketoacidosis, or DKA. DKA occurs as a result of prolonged untreated diabetes. It is the result of the body not being able to produce, or use, insulin …

Neurological, Nutritional And Cognitive Effects Of Environmental Lead Exposure In Infants And Children, Melissa Bianchi

Nursing Student Class Projects (Formerly MSN)

Environmental lead exposure is a pertinent public health risk that affects our rural population in Wyandot County, Ohio. Children exposed to lead hazards through toys, home remodeling and contaminated soil and water are at a greater risk for developing neurological, cognitive and behavioral issues than are children not exposed to lead (Cecil et al., 2011). Wyandot County parents are not adequately educated on the risks and consequences of elevated blood lead levels in their children. As a child advocate and director of the Women, Infant and Children program for Wyandot County there is an obligation to educate and inform parents …

Chagas Disease: Immigrating Into The United States, Angela Metzger

Nursing Student Class Projects (Formerly MSN)

Chagas Disease is starting to make a profound entrance into our communities within the United States. The influx of the immigrant population is the principal cause of the accumulation in the number of reported cases. (Center for Disease Control and Prevention, 2014). The Trypanosoma cruzi is a parasite that causes Chagas disease. The triatomine blood sucking insect enjoys the mucosal membranes of their pray, both humans and animals. The most common regions of the penetrating bite are the conjunctiva of the eye or around the mouth. It is through the feces of the vector entering the inoculation site that initiates …

Thrombotic Thrombocytopenia Purpura, Ann Oliva

Nursing Student Class Projects (Formerly MSN)

Patients with Thrombotic Thrombocytopenia Purpura, or TTP, are often times seen in the emergency department and subsequently admitted to the inpatient or the critical care unit. The problems that TTP patients can present with vary greatly and astute nursing assessment plus knowledge of the pathophysiology behind the diagnosis is vital to deliver excellent nursing care. Thrombotic Thrombocytopenia Purpura or TTP is a rare but potentially fatal condition that occurs as result of decreased levels of ADAMTS-13, a cleaving protease for von Willebrand factor (vWF), which causes platelet aggregation and microvascular thrombi and subsequent end-organ damage, along with thrombocytopenia, hemolytic anemia, …

Malignant Hyperthermia: A Clinical Crisis, Eric Reing

Nursing Student Class Projects (Formerly MSN)

Malignant hyperthermia, though uncommon, is a serious and life threatening condition. Malignant hyperthermia is an autosomal dominant disorder that affects skeletal muscle. It can be caused by various general anesthetic agents like succinylcholine and several inhaled anesthetics. Malignant hyperthermia is a relevant topic to certified registered nurse anesthetists due to the potentially fatal result if not recognized and treated promptly. In understanding the pathophysiology, risk factors, signs and symptoms, epidemiology, and current treatments the health care provider can help to prevent complications due to this disorder (Nagelhout, 2014).

Tuberculosis, Lindsay Mackey

Nursing Student Class Projects (Formerly MSN)

Tuberculosis (TB) is an infectious bacterial disease caused by Mycobacterium tuberculosis and mostly affects the lungs and sometimes other organs such as the kidneys, spine, and brain (Center for Disease Control and Prevention, 2015). In 2013, the CDC (2015) estimated that approximately 9 million people were infected with Mycobacterium tuberculosis worldwide and approximately 1.5 million deaths were a result of TB. Tuberculosis is an airborne infection which can be spread through the air from an infected individuals cough, sneeze, or speech. Individuals infected with TB can either have latent or active stage. Latent TB is when an individual becomes infected …

Dermatitis Herpetiformis, Rachel Wolf

Nursing Student Class Projects (Formerly MSN)

The main sign that accompanies DH is the eruption of intensely pruritic papulovesical lesions that typically present bilaterally on the elbows, knees, buttocks, neck, and scalp (Criado et al., 2012). They may appear on the upper back, abdomen, groin, and face as well. The lesions are small blisters that resemble those that are caused by the herpes simplex virus. By the time a patient seeks evaluation by a care provider, the lesions have often been scratched so much as to cause erosions, excoriation, and or crusted papules (Junkins-Hopkins, 2010). The surrounding area may have erythema and or urticarial plaques. Patients …