Digital Commons Network^™

The Role Of Dendritic Cell Subsets And Innate Immunity In The Pathogenesis Of Type 1 Diabetes And Other Autoimmune Diseases, Jeffrey D. Price, Kristin V. Tarbell

Nebraska Center for Virology: Faculty Publications

Dendritic cells (DCs) are key antigen-presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, there are four main subsets identified in both mouse and human: conventional cDC1 and cDC2, plasmacytoid DCs, and monocyte-derived DCs. In this review, we will discuss the role of these subsets in …

Evidence Of Distinctive Structural Alterations That Differentiate Adhd Boys With And Without A Comorbid Reading Disability, Dhruman Dilip Goradia

Wayne State University Dissertations

Attention deficit hyperactivity disorder (ADHD) and reading disability (RD) are neurodevelopmental disorders that often co-occur. Children with ADHD and co-occurring RD (ADHD/+RD) tend to show greater cognitive deficits than children with ADHD alone (ADHD/-RD). However, the extents to which comorbid RD impact structural alteration in children with ADHD have never been investigated. The overall goal of this study was to assess structural alterations in the subcortical, cortical and white matter that may differentiate ADHD/-RD from ADHD/+RD. The general hypothesis was that ADHD/+RD would show extensive alterations in regions implicated in ADHD than ADHD/-RD as well as show additional abnormalities in …

Neural Alterations Influencing Skilled Reading In Adhd: A Task-Based Fmri Study, Brianne Mohl

Wayne State University Dissertations

Attention-Deficit/Hyperactivity Disorder (ADHD) is a heterogeneous, neurodevelopmental disorder which co-occurs often with Reading Disability (RD). ADHD with and without RD consistently have higher inattentive ratings compared with typically developing controls, with co-occurring ADHD and RD (ADHD/+RD) also demonstrating impaired phonological processing. Accordingly, inattention has been associated with greater phonological impairment, though neither the neural correlates of the co-occurring disorders nor the association are well understood from a functional neuroimaging perspective. The goal was to assess to what extent ADHD/+RD differ from ADHD without RD (ADHD/-RD) and typically developing controls (TDC) in functional activation of attention- and reading-related areas during various …

Concentration-Dependent Diversification Effects Of Free Cholesterol Loading On Macrophage Viability And Polarization, Xiaoyang Xu, Aolin Zhang, Ningjun Li, Pin-Lan Li, Fan Zhang

Pharmacology and Toxicology Publications

Background/Aims: The accumulation of free cholesterol in atherosclerotic lesions has been well documented in both animals and humans. In studying the relevance of free cholesterol buildup in atherosclerosis, contradictory results have been generated, indicating that free cholesterol produces both pro- and anti-atherosclerosis effects in macrophages. This inconsistency might stem from the examination of only select concentrations of free cholesterol. In the present study, we sought to investigate the implication of excess free cholesterol loading in the pathophysiology of atherosclerosis across a broad concentration range from (in µg/ml) 0 to 60. Methods:Macrophage viability was determined by measuring formazan formation and …

Transcriptional Pathways Associated With Skeletal Muscle Changes After Spinal Cord Injury And Treadmill Locomotor Training., Celine Baligand, Yi-Wen Chen, Fan Ye, Sachchida Nand Pandey, San-Huei Lai, Min Liu, Krista Vandenborne

Genomics and Precision Medicine Faculty Publications

The genetic and molecular events associated with changes in muscle mass and function after SCI and after the implementation of candidate therapeutic approaches are still not completely known. The overall objective of this study was to identify key molecular pathways activated with muscle remodeling after SCI and locomotor training. We implemented treadmill training in a well-characterized rat model of moderate SCI and performed genome wide expression profiling on soleus muscles at multiple time points: 3, 8, and 14 days after SCI. We found that the activity of the protein ubiquitination and mitochondrial function related pathways was altered with SCI and …

Neuroscience, Mindreading, And The Courts: The Example Of Pain, Henry T. Greely

Journal of Health Care Law and Policy

No abstract provided.

Preparing The Periphery For A Subsequent Behavior: Motor Neuronal Activity During Biting Generates Little Force But Prepares A Retractor Muscle To Generate Larger Forces During Swallowing In Aplysia, Hui Lu, Jeffrey M. Mcmanus, Miranda J. Cullins, Hillel J. Chiel

Faculty Scholarship

Some behaviors occur in obligatory sequence, such as reaching before grasping an object. Can the earlier behavior serve to prepare the musculature for the later behavior? If it does, what is the underlying neural mechanism of the preparation? To address this question, we examined two feeding behaviors in the marine mollusk Aplysia californica, one of which must precede the second: biting and swallowing. Biting is an attempt to grasp food. When that attempt is successful, the animal immediately switches to swallowing to ingest food. The main muscle responsible for pulling food into the buccal cavity during swallowing is the I3 …

Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance In High Fat-Fed Mice, Michelle B. Trevino, David Mazur-Hart, Yui Machida, Timothy King, Joseph Nadler, Elena V. Galkina, Arjun Poddar, Sucharita Dutta, Yumi Imai

Mathematics & Statistics Faculty Publications

Perilipin 5 (PLIN5) is a lipid droplet (LD) protein highly expressed in oxidative tissues, including the fasted liver. However, its expression also increases in nonalcoholic fatty liver. To determine whether PLIN5 regulates metabolic phenotypes of hepatosteatosis under nutritional excess, liver targeted overexpression of PLIN5 was achieved using adenoviral vector (Ad-PLIN5) in male C57BL/6J mice fed high-fat diet. Mice treated with adenovirus expressing green fluorescent protein (GFP) (Ad-GFP) served as control. Ad-PLIN5 livers increased LD in the liver section, and liquid chromatography with tandem mass spectrometry revealed increases in lipid classes associated with LD, including triacylglycerol, cholesterol ester, and phospholipid classes, …

Panel 2: “Excess” Pain, Hyperalgesia, And The Variability Of Subjective Experience, Amanda Pustilnik, David Seminowicz, Stephen Rigg, Joel Greenspan, Morris Hoffman, Adam Kolber, Michael Pardo

Journal of Health Care Law and Policy

No abstract provided.

Panel 3: Chronic Pain, “Psychogenic” Pain, And Emotion, David Seminowicz, Amanda Pustilnik, M. Kaylie Gioioso, Jennifer Chandler, Robert Dinerstein, Jennifer A. Haythornthwaite, Tor D. Wager

Journal of Health Care Law and Policy

No abstract provided.

Panel 4: Translational Expectations And Issues: Making It Work In Practice, Amanda Pustilnik, David Seminowicz, M. Kaylie Gioioso, Martha Farah, Nancy Gertner, Stacey Tovino

Journal of Health Care Law and Policy

No abstract provided.

Improved Accuracy Of Surgical Pathology Accessioning, Coding, And Billing Practices After Self-Evaluation, Allison F. Goldberg, Md

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

INTRODUCTION

Accurate accessioning, coding, and billing of specimens are vital, but often disregarded, aspects of a surgical pathologist’s job. This study had two aims related to those aspects. First, to evaluate the quality of our systems based practices in order to identify areas for improvement. Second, to assess if changes made based on our self-evaluation improved accuracy.

Analysis Of Patient Results Distributions To Reevaluate A Reference Range Change For Calcium, After A Change In Assay Reagents On The Roche Cobas C500 Analyzer, Upasana Joneja, Md, Laura J. Mccloskey, Md, Douglas F. Stickle, Md

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Introduction:

A change in reagents for calcium (Ca) on the Roche Cobas c500 used in our laboratory analyzer took place in 2013. The previous reference range (8.5-10.5 mg/dL) was replaced with that from the manufacturer's study (8.6-10.0 mg/dL), based on correlation of results between the new and old assays. As a matter of quality assurance, we undertook a post-assay-change reevaluation of the reference range change, using a method based on that of Bhattacharya [1]. In short, the method relies on the assumption that the reference range is a normal distribution, which assumption enables this distribution to be isolated mathematically from …

A Novel Codon-Optimized Siv Gag-Pol Immunogen For Genebased Vaccination, Catherine M. Crosby, Eric A. Weaver, Reeti Khare, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is its gag-pol protein that bears many epitopes to drive multivalent immune T cell responses. While gag-pol is an attractive antigen, it is only translated after a frame shift between gag and pol with the effect that gag and pol are expressed at an approximate 10/1 ratio. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells …

Decoding Nf1 Intragenic Copy-Number Changes, Meng-Chang Hsiao

All ETDs from UAB

Genomic rearrangements may cause both Mendelian and complex disorders. Currently, several major mechanisms causing genomic rearrangements have been proposed such as non-allelic homologous recombination (NAHR), non-homologous end joining (NHEJ), fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR). However, to what extent these mechanisms contribute to gene-specific pathogenic copy-number changes (CNCs) remains understudied. Furthermore, only few studies resolved these pathogenic alterations at the nucleotide-level. Accordingly, our aim was to explore which mechanisms contribute to a large, unique set of locus-specific non-recurrent genomic rearrangements causing the genetic neurocutaneous disorder neurofibromatosis type 1 (NF1). Through breakpoint-spanning PCR as well as …

Energy Metabolism Of Platelets During Activation, Oxidative Stress And Storage, Saranya Ravi

All ETDs from UAB

The principal function of platelets is to regulate hemostasis, and dysfunction of platelet aggregation or activation can lead to either excessive thrombotic or hemorrhagic complications. It has been shown that the ability to generate ATP and exposure to oxidative stress can affect platelet thrombotic potential. While platelet metabolism has been extensively studied, the importance of substrate availability and metabolic plasticity in regulating aggregation under physiological or pathological conditions is not well understood. In this dissertation, we examined the reliance of platelets on different metabolic substrates, the importance of ATP production for aggregation in response to thrombin stimulation, metabolic stress following …

Role Of Vapb/Als8 Signaling Through Lar Receptor, Jessica Lindsey Winek Schultz

All ETDs from UAB

In humans, a P56S point mutation in the VAPB/ALS8 MSP domain is associated with amyotrophic lateral sclerosis (ALS) and late-onset spinal muscular atrophy (SMA). The N-terminal MSP domain is cleaved from the C-terminus, and secreted through an unknown, nonconventional manner. The P56S mutation inhibits secretion of the MSP domain. We use Caenorhabditis elegans to study live secretion of VPR-1, as well as to understand vMSP receptor signaling in muscle and gonad. To study the secretion mechanism of VPR-1 we created a transgenic line of C. elegans with a fluorescently tagged VPR-1. Using this model, we were able to visualize live …

Bracing Of The Trunk And Neck Has A Differential Effect On Head Control During Gait, S. Morrison, D. M. Russell, K. Kelleran, M. L. Walker

Rehabilitation Sciences Faculty Publications

During gait, the trunk and neck are believed to play an important role in dissipating the transmission of forces from the ground to the head. This attenuation process is important to ensure head control is maintained. The aim of the present study was to assess the impact of externally restricting the motion of the trunk and/or neck segments on acceleration patterns of the upper body and head and related trunk muscle activity. Twelve healthy adults performed three walking trials on a flat, straight 65-m walkway, under four different bracing conditions: 1) control-no brace; 2) neck-braced; 3) trunk-braced; and 4) neck-trunk …

High-Definition Tdcs Of Noun And Verb Retrieval In Naming And Lexical Decision, Svetlana Malyutina, Dirk B. Den Ouden

Communication Sciences and Disorders Faculty Articles and Research

High-definition transcranial direct current stimulation (HD-tDCS) is a novel brain stimulation method that has high potential for use in language therapy for speakers with aphasia, due to its safety and focality. This study aimed to obtain foundational data on using HD-tDCS to modulate language processing in healthy speakers. Participants received stimulation either of left Broca’s area or of angular gyrus (20 minutes of anodal, cathodal and sham stimulation on separate days), followed by naming and lexical decision tasks with single-word verb and noun stimuli. We found that cathodal stimulation over both Broca’s area and left angular gyrus increased naming speed …

Understanding The Function Of Dyrk1a Through Characterization Of Its Interacting Proteins, Varsha Ananthapadmanabhan

Theses and Dissertations

DYRK1A is a protein kinase encoded by a gene implicated in Down syndrome pathogenesis. Loss of DYRK1A could promote oncogenic transformation. However, the regulation and substrates of DYRK1A are not fully understood. MudPIT proteomic analysis revealed novel DYRK1A interacting proteins with poorly characterized or even unknown functions. Therefore, the aim of this thesis was to understand the function of DYRK1A through the characterization of its interacting proteins. To achieve this aim, we established stable cell lines expressing these proteins and confirmed the interactions between DYRK1A and seven candidate binding partners. Furthermore, we found that all novel DYRK1A-interacting proteins also bind …

An Association Study Between Adult Blood Pressure And Time To First Cardiovascular Disease, Yongjia Pu

Theses and Dissertations

BACKGROUND: Several studies have demonstrated the association between the time to hypertension event and multiple baseline measurements for adults, yet other survival cardiovascular disease (CVD) outcomes such as high cholesterol and heart attack have been somewhat less considered. The Fels Longitudinal Study (FLS) provides us an opportunity to connect adult blood pressure (BP) at certain ages to the time to first CVD outcomes. The availability of long-term serial BP measurements from FLS also potentially allows us to evaluate if the trend of the measured BP biomarkers over time predicts survival outcomes in adulthood through statistical modeling.

METHODS: When the reference …

Gene Expression And Alzheimer's Disease: Evaluation Of Gene Expression Patterns In Brain And Blood For An Alzheimer's Disease Mouse Model, Amanda Hazy

Senior Honors Theses

Previous studies have established a causative role for altered gene expression in development of Alzheimer’s disease (AD). These changes can be affected by methylation and miRNA regulation. In this study, expression of miRNA known to change methylation status in AD was assessed by qPCR. Genome-wide expression changes were determined by RNA-sequencing of mRNA from hippocampus and blood of control and AD mice. The qPCR data showed significantly increased expression of Mir 17 in AD, and sequencing data revealed 230 genes in hippocampus, 58 genes in blood, and 8 overlapping genes showing significant differential expression (p value ≤ 0.05). Expression data …

Comparison Of Helmet And Facial Mask During Noninvasiveventilation In Patients With Acute Exacerbation Of Chronic Obstructivepulmonary Disease: A Randomized Controlled Study, Özlem Çakir Gürbüz, Ali̇ Alagöz, Fatma Ulus, Mehtap Tunç, Şazi̇ye Şahi̇n

Turkish Journal of Medical Sciences

Background/aim: Noninvasive mechanical ventilation (NIMV) is an approach to prevent complications in acute respiratory failure. In this study we aimed to compare the efficacy of a full face mask and a helmet in chronic obstructive pulmonary disease (COPD). Materials and methods: Fifty patients were divided randomly into 2 groups as full face mask (Group F) and helmet (Group H). Demographic data, forced expiratory volume at 1 s (FEV1), additional disease, hemodynamic parameters, respiratory rate, APACHE II score, peripheral O2 saturation (SpO2), arterial blood gases (ABG), patient tolerance scale (PTS) score, and fraction of inspired oxygen (FiO2) were recorded. Parameters were …

Tau-Sh3 Interactions: Implications For Alzheimer's Disease, Jesse Nicholas Cochran

All ETDs from UAB

Alzheimer’s disease (AD) is the most common neurodegenerative disease and with Americans’ increasing longevity it is becoming an epidemic. There are currently no effective treatments for this disorder. Abnormalities of tau track more closely with cognitive decline than the most studied therapeutic target in AD, amyloid-beta, but the optimal strategy for targeting tau has not yet been identified. Based on considerable preclinical data from AD models, we hypothesize that interactions between tau and SH3 domain–containing proteins are pathogenic in AD. Genetically reducing either tau or tau interactants has beneficial effects relevant to AD. Here, we describe a drug screen for …

Defining The Role Of Trps1 In Phosphate Mediated Mineralization, Maria Kuzynski

All ETDs from UAB

Mineralization is a tightly controlled bi-phasic process that occurs when crystals of calcium and phosphate (Pi) are laid down within the extracellular matrix. However, the molecular networks regulating the initiation and progression of this process have not been well characterized. Pi, as one of the components of mineral crystals and a signaling molecule that regulates expression of mineralization-related genes, is essential to the mineralization process. In our studies, we discovered a novel function for Pi in this process: Pi is sufficient to induce secretion of matrix vesicles, which support the initiation of mineralization. Furthermore, we determined that this induction is …

The I507-Atc→Att Silent Codon Change Contributes To The Misfolding Of ∆F508 Cftr, Vedrana Bali

All ETDs from UAB

Synonymous codon changes (SCCs) do not alter the amino acid sequence of proteins, but may significantly change the phenotype. The frequency of synonymous codons is species- and gene-specific, described as codon usage bias (CUB). Over the past 50 years, research has shown that SCCs affect protein biogenesis, development of human disorders and the function of recombinant proteins developed for therapeutic applications. However, the molecular mechanisms by which SCCs alter the function of gene products are not completely understood. In Chapter 2 we summarize present knowledge in this field. The most common cause of cystic fibrosis (CF) is the deletion of …

Exploiting Novel Interactions With Parp1 In Dna Repair Proficient Human Breast Cancers, Jennifer Anne Stanley

All ETDs from UAB

Breast cancer remains the most frequently diagnosed cancer amongst women worldwide. Despite advances in treatment, patients with more aggressive basal-like and HER2-positive cancer experience high rates of recurrence and necessitate novel therapeutic approaches. A class of inhibitors targeted against poly (ADP-ribose) polymerases (PARP), important DNA repair proteins, are effective in cancers with a defective DNA repair response. As such, extensive preclinical and clinical research has examined their efficacy in these cancers. Although this data is promising, it is only applicable to a lim-ited patient population. The main goal of this dissertation is to expand the utility of these well-tolerated drugs …

Does Pharmacogenetics Play A Role In The Treatment Of Type Ii Diabetes Mellitus?, Lucas N. Vanemelen

Physician Assistant Scholarly Project Posters

• Type 2 diabetes mellitus (T2DM) is a disease commonly presented in the family practice setting. Current therapies include one or multiple medications. Until recently, providers have used algorithms and medical expertise to control T2DM.

• Pharmacogenomics is a branch of pharmacology dealing with genetic variation on a medication response in an individual patient to discover medication compatibility, efficacy or toxicity.

• Analysis of genetic factors are still being discovered; however, this growing field may change the way medications are being prescribed for diabetes. This analysis investigated if pharmacogenetics is a useful tool for prescribing diabetic medications to T2DM patients. …

Surgical Management Of Pulmonary Aspergilloma: Clinical Experience With 77 Cases, Koray Aydoğdu, Funda İncekara, Mehmet Furkan Şahi̇n, Seli̇m Şaki̇r Erkmen Gülhan, Göktürk Findik, Abdullah İrfan Taştepe, Sadi̇ Kaya

Turkish Journal of Medical Sciences

Background/aim: This retrospective study evaluated the clinical presentation, underlying lung disease, surgical indications, technique, treatment outcomes, and postoperative complications of pulmonary aspergilloma. Materials and methods: We evaluated 77 patients who underwent pulmonary resection of an aspergilloma at Atatürk Chest Diseases and Thoracic Surgery Research and Training Hospital between January 2000 and December 2013. The initial operations were 4 pneumonectomies, 24 lobectomies, 9 lobectomy plus myoplasties, 10 segmental resections, and 30 wedge resections. Six reoperations were carried out to deal with postoperative complications: 1 myoplasty, 2 completion lobectomies plus myoplasties, 2 myoplasties with rib resections, and 1 completion lobectomy. Results: The …

Burnout In Caregivers Of Patients With Schizophrenia, Ahmet Kokurcan, Ayşe Gül Yilmaz Özpolat, Ali̇ Kemal Göğüş

Turkish Journal of Medical Sciences

Background/aim: To evaluate the burnout of schizophrenia patients' caregivers and to determine the possible relationships between sociodemographic characteristics, symptomatology, perceived social support, and the burnout profile of the caregivers. Materials and methods: Subjects included in the study are 76 schizophrenia patients, diagnosed according to DSM-IV-TR criteria, and their caregivers. A sociodemographic form, the Scale for the Assessment of Positive Symptoms, and the Scale for the Assessment of Negative Symptoms were applied to evaluate the severity of the symptoms. The Maslach Burnout Inventory for Caregivers and the Multidimensional Scale of Perceived Social Support were applied to the caregivers of the patients. …