Medicine and Health Sciences Commons^™

A Selective Impairment Of Perception Of Sound Motion Direction In Peripheral Space: A Case Study., Lore Thaler, Joseph Paciocco, Mark Daley, Gabriella D Lesniak, David W Purcell, J Alexander Fraser, Gordon N Dutton, Stephanie Rossit, Melvyn A Goodale, Jody C Culham

Brain and Mind Institute Researchers' Publications

It is still an open question if the auditory system, similar to the visual system, processes auditory motion independently from other aspects of spatial hearing, such as static location. Here, we report psychophysical data from a patient (female, 42 and 44 years old at the time of two testing sessions), who suffered a bilateral occipital infarction over 12 years earlier, and who has extensive damage in the occipital lobe bilaterally, extending into inferior posterior temporal cortex bilaterally and into right parietal cortex. We measured the patient's spatial hearing ability to discriminate static location, detect motion and perceive motion direction in …

In-Silico Identification Of Prognostically Inversely Correlated Mirnas And Mrnas (Pic’S) In Multiple Cancers, Chirayu Pankaj Goswami, Zi-Xuan Wang

Department of Pathology, Anatomy, and Cell Biology Posters

Despite numerous methods available to identify potential mRNA targets for miRNAs, prognostic relationship of these molecules in diseases like cancers where deregulation of gene expression is a major pathogenic factor, has not yet been emphasized. We performed in-silico identification of prognostically inversely correlated miRNA - mRNA pairs (PIC’s) in multiple cancers using expression data from The Cancer Genome Atlas. Partners in a PIC show inverse correlation of expression and opposite hazard implication. Using a three step approach, we identified a total of 1,253,443 PIC’s from 23 cancer types, several of which have previously been shown to have a predicted or …

Genetic Susceptibility Loci Of Idiopathic Interstitial Pneumonia Do Not Represent Risk For Systemic Sclerosis: A Case Control Study In Caucasian Patients, Minghua Wu, Shervin Assassi, Gloria A. Salazar, Claudia Pedroza, Olga Y. Gorlova, Wei V. Chen, Julio Charles, Miranda L. Taing, Kelley Liao, Fredrick M. Wigley

Dartmouth Scholarship

Background: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) has phenotypic similarities to lung involvement in idiopathic interstitial pneumonia (IIP). We aimed to assess whether genetic susceptibility loci recently identified in the large IIP genome-wide association studies (GWASs) were also risk loci for SSc overall or severity of ILD in SSc. Methods: A total of 2571 SSc patients and 4500 healthy controls were investigated from the US discovery GWAS and additional US replication cohorts. Thirteen IIP-related selected single nucleotide polymorphisms (SNPs) were genotyped and analyzed for their association with SSc. Results: We found an association of SSc with the SNP rs6793295 …

Non-Alcoholic Fatty Liver Disease Induces Signs Of Alzheimer’S Disease (Ad) In Wild-Type Mice And Accelerates Pathological Signs Of Ad In An Ad Model, Do-Geun Kim, Antje Krenz, Leon E. Toussaint, Kirk J. Maurer

Dartmouth Scholarship

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease afflicting about one third of the world's population and 30 % of the US population. It is induced by consumption of high-lipid diets and is characterized by liver inflammation and subsequent liver pathology. Obesity and consumption of a high-fat diet are known to increase the risk of Alzheimer's disease (AD). Here, we investigated NAFLD-induced liver inflammation in the pathogenesis of AD.

Methods: WT and APP-Tg mice were fed with a standard diet (SD) or a high-fat diet (HFD) for 2, 5 months, or 1 year to induce NAFLD. Another …

Metabolomics Workbench: An International Repository For Metabolomics Data And Metadata, Metabolite Standards, Protocols, Tutorials And Training, And Analysis Tools, Manish Sud, Eoin Fahy, Dawn Cotter, Kenan Azam, Ilango Vadivelu, Charles Burant, Arthur Edison, Oliver Fiehn, Richard M. Higashi, K. Sreekumaran Nair, Susan Sumner, Shankar Subramaniam

Toxicology and Cancer Biology Faculty Publications

The Metabolomics Workbench, available at www.metabolomicsworkbench.org, is a public repository for metabolomics metadata and experimental data spanning various species and experimental platforms, metabolite standards, metabolite structures, protocols, tutorials, and training material and other educational resources. It provides a computational platform to integrate, analyze, track, deposit and disseminate large volumes of heterogeneous data from a wide variety of metabolomics studies including mass spectrometry (MS) and nuclear magnetic resonance spectrometry (NMR) data spanning over 20 different species covering all the major taxonomic categories including humans and other mammals, plants, insects, invertebrates and microorganisms. Additionally, a number of protocols are provided for …

Week Of January 4, 2016, New York Medical College

InTouch

• Katharine Yamulla is Named Director of the Clinical Skills and Simulation Center
• SOM Bids Farewell to Montgomery Douglas, M.D.
• Department of Microbiology and Immunology Hosts Research Forum
• Class of 2018 Helps Spread Holiday Cheer
• NYMC Welcomes Orange-Ulster BOCES Health Occupations Students of America

Time-Course Analysis Of Brain Regional Expression Network Responses To Chronic Intermittent Ethanol And Withdrawal: Implications For Mechanisms Underlying Excessive Ethanol Consumption, Maren L. Smith, Marcelo F. Lopez, Kellie Archer, Aaron R. Wolen, Howard C. Becker, Michael F. Miles

Pharmacology and Toxicology Publications

Long lasting abusive consumption, dependence, and withdrawal are characteristic features of alcohol use disorders (AUD). Mechanistically, persistent changes in gene expression are hypothesized to contribute to brain adaptations leading to ethanol toxicity and AUD. We employed repeated chronic intermittent ethanol (CIE) exposure by vapor chamber as a mouse model to simulate the cycles of ethanol exposure and withdrawal commonly seen with AUD. This model has been shown to induce progressive ethanol consumption in rodents. Brain CIE-responsive expression networks were identified by microarray analysis across five regions of the mesolimbic dopamine system and extended amygdala with tissue harvested from 0-hours to …

The Frequency And Outcome Of Lupus Nephritis: Results From An International Inception Cohort Study, J. G. Hanly, A. G. O'Keeffe, L. Su, M. B. Urowitz, J. Romero-Diaz, C. Gordon, S. C. Bae, E. M. Ginzler, C. Aranow, V. Farewell, +35 Additional Authors

Journal Articles

OBJECTIVE: To determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort. METHODS: Patients in the Systemic Lupus International Collaborating Clinics inception cohort (

The Reliability And Validity Of Functional Brain Connectivity Compared To A Self-Reported Measure Of Pain, Ali Alsouhibani

Maria Dittman Library Research Competition: Student Award Winners

Pain is a multidimensional perception that is complex in nature. It is a unitary construct that includes overlapping domains such as intensity, affect, quality, and frequency. These domains do not reflect the amount of tissue damage. It reflects the end result of the perception of pain in which multiple biopsychosocial factors are involved (Gatchel et al., 2007). Multiple self-reported measures have been used in an attempt to capture most factors that may influence pain such as psychological factors. However, there is no one scale that can be used to characterize pain as a whole with all its factors. Furthermore, physical …

A Competitive Random Sequential Adsorption Model For Immunoassay Activity, Dana Mackey, Eilis Kelly, Robert Nooney

Conference papers

Immunoassays rely on highly specific reactions between antibodies and antigens and are used in biomedical diagnostics applications to detect biomarkers for a variety of diseases. Antibody immobilization to solid interfaces through random adsorption is a widely used technique but has the disadvantage of severely reducing the antigen binding activity and, consequently, the assay performance. This paper proposes a simple mathematical framework, based on the theory known as competitive random sequential adsorption (CRSA), for describing how the activity of immobilized antibodies depends on their orientation and packing density and generalizes a previous model by introducing the antibody aspect ratio as an …

Cannabinoid Receptor Interacting Protein Suppresses Agonist-Driven Cb1 Receptor Internalization And Regulates Receptor Replenishment In An Agonist-Biased Manner, Lawrence C. Blumes, Sandra Leone-Kabler, Deborah J. Luessen, Glenn S. Marrs, Erica Lyons, Caroline E. Bass, Rong Chen, Dana E. Selley, Allyn C. Howlett

Neurology Publications

Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that modulates CB1R signaling via G proteins, and CB1R down-regulation but not desensitization (Blume et al. [2015] Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In this study, we determined the involvement of CRIP1a in CB1R plasma membrane trafficking. To follow the effects of agonists and antagonists on cell surface CB(1)Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2, which endogenously expresses both CB1R and CRIP1a, and exhibits a well-characterized endocannabinoid signaling system. We developed stable CRIP1a-over-expressing and CRIP1a-siRNA-silenced knockdown …

Sestrin2 Is Induced By Glucose Starvation Via The Unfolded Protein Response And Protects Cells From Non-Canonical Necroptotic Cell Death, Boxiao Ding, Anita Parmigiani, Ajit S. Divakaruni, Kellie Archer, Anne N. Murphy, Andrei V. Budanov

Human and Molecular Genetics Publications

Sestrin2 is a member of a family of stress responsive proteins, which controls cell viability via antioxidant activity and regulation of the mammalian target of rapamycin protein kinase (mTOR). Sestrin2 is induced by different stress insults, which diminish ATP production and induce energetic stress in the cells. Glucose is a critical substrate for ATP production utilized via glycolysis and mitochondrial respiration as well as for glycosylation of newly synthesized proteins in the endoplasmic reticulum (ER) and Golgi. Thus, glucose starvation causes both energy deficiency and activation of ER stress followed by the unfolding protein response (UPR). Here, we show that …

Rnaseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation As A Major Abnormality In Als Spinal Cord, David G. Brohawn, Laura C. O'Brien, James P. Bennett

Human and Molecular Genetics Publications

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned >50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2 …

Krüppel-Like Transcription Factor Klf1 Is Required For Optimal Γ- And Β-Globin Expression In Human Fetal Erythroblasts, Divya Vinjamur, Yousef N. Alhashem, Safa Mohamad, Parth Amin, David C. Williams Jr., Joyce A. Lloyd

Human and Molecular Genetics Publications

In human adult erythroid cells, lower than normal levels of Krüppel-like transcription factor 1 (KLF1) are generally associated with decreased adult β- and increased fetal γ-globin gene expression. KLF1 also regulates BCL11A, a known repressor of adult γ-globin expression. In seeming contrast to the findings in adult cells, lower amounts of KLF1 correlate with both reduced embryonic and reduced fetal β-like globin mRNA in mouse embryonic erythroid cells. The role of KLF1 in primary human fetal erythroid cells, which express both γ- and β-globin mRNA, is less well understood. Therefore, we studied the role of KLF1 in ex vivo differentiated …

An Ultrasonographic Analysis Of The Structures Of The Subacromial Space, As They Relate To The Postures Of Upper String Musicians, Elliot V. Smithson

Theses, Dissertations and Capstones

Background: The leading source of general population shoulder pain is subacromial impingement syndrome (SAIS) which can contribute to rotator cuff disease (RCD). 1 It has been reported that up to 12% of musicians end their musical career due to musculoskeletal injury.2 SAIS is a common source of shoulder pain in the bowing arm of upper string musicians.3 However, the mechanisms leading to shoulder pain in upper string musicians are not well known.

Purpose: The purpose of this study was to characterize aspects of the subacromial space anatomy while in standard playing positions of upper string musicians, specifically measurements …

The Physiological And Clinical Importance Of Sodium Potassium Atpase In Cardiovascular Diseases, Yanling Yan, Joseph I. Shapiro Md

Biochemistry and Microbiology

The Na/K-ATPase has been extensively studied, but it is only recently that its role as a scaffolding and signaling protein has been identified. It has been identified that cardiotonic steroids (CTS) such as digitalis mediate signal transduction through the Na/K-ATPase in a process found to result in the generation of reactive oxygen species (ROS). As these ROS also appear capable of initiating this signal cascade, a feed forward amplification process has been postulated and subsequently implicated in some disease pathways including uremic cardiomyopathy.

Structure Of The Polyisoprenyl-Phosphate Glycosyltransferase Gtrb And Insights Into The Mechanism Of Catalysis, Chiara Ardiccioni, Oliver B. Clarke, David Tomasek, Habon A. Issa, Desiree C. Von Alpen, Heather L. Pond, M. Chiara Manzini, +11 Additional Authors

Pharmacology and Physiology Faculty Publications

The attachment of a sugar to a hydrophobic polyisoprenyl carrier is the first step for all extracellular glycosylation processes. The enzymes that perform these reactions, polyisoprenyl-glycosyltransferases (PI-GTs) include dolichol phosphate mannose synthase (DPMS), which generates the mannose donor for glycosylation in the endoplasmic reticulum. Here we report the 3.0Å resolution crystal structure of GtrB, a glucose-specific PI-GT from Synechocystis, showing a tetramer in which each protomer contributes two helices to a membrane-spanning bundle. The active site is 15 Å from the membrane, raising the question of how water-soluble and membrane-embedded substrates are brought into apposition for catalysis. A conserved …

Treatment Of Men For “Low Testosterone”: A Systematic Review, Samantha Huo, Anthony R. Scialli, Sean Mcgarvey, Elizabeth Hill, Buğra Tügertimur, Alycia Hogenmiller, Alessandra I. Hirsch, Adriane Fugh-Berman

Pharmacology and Physiology Faculty Publications

Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of “low testosterone” (low-T) for cardiovascular health, sexual function, muscle weakness or wasting, mood and behavior, and cognition. We performed a systematic review of 156 eligible randomized controlled trials in which testosterone was compared to placebo for one or more of these conditions. We included studies in bibliographic databases between January 1, 1950 and April 9, 2016, and excluded studies involving bodybuilding, contraceptive effectiveness, or treatment of any condition in women or children. Studies with multiple relevant endpoints were included in all relevant tables. Testosterone supplementation …

Brain Responses To Biological Motion Predict Treatment Outcome In Young Children With Autism, D. Yang, Kevin Pelphrey, D. Sukholdolsky, M. Crowley, E. Dayan, +6 Additional Authors

Pharmacology and Physiology Faculty Publications

Autism spectrum disorders (ASDs) are common yet complex neurodevelopmental disorders, characterized by social, communication and behavioral deficits. Behavioral interventions have shown favorable results—however, the promise of precision medicine in ASD is hampered by a lack of sensitive, objective neurobiological markers (neurobiomarkers) to identify subgroups of young children likely to respond to specific treatments. Such neurobiomarkers are essential because early childhood provides a sensitive window of opportunity for intervention, while unsuccessful intervention is costly to children, families and society. In young children with ASD, we show that functional magnetic resonance imaging-based stratification neurobiomarkers accurately predict responses to an evidence-based behavioral treatment—pivotal …

Sensory Hypo-Excitability In A Rat Model Of Fetal Development In Fragile X Syndrome, Julia Berzhanskaya, Marnie Phillips, Jing Shen, Matthew Colonnese

Pharmacology and Physiology Faculty Publications

Fragile X syndrome (FXS) is characterized by sensory hyper-sensitivity, and animal models suggest that neuronal hyper-excitability contributes to this phenotype. To understand how sensory dysfunction develops in FXS, we used the rat model (FMR-KO) to quantify the maturation of cortical visual responses from the onset of responsiveness prior to eye-opening, through age equivalents of human juveniles. Rather than hyper-excitability, visual responses before eye-opening had reduced spike rates and an absence of early gamma oscillations, a marker for normal thalamic function at this age. Despite early hypo-excitability, the developmental trajectory of visual responses in FMR-KO rats was normal, and showed the …

Rnai-Mediated Gene Knockdown By Microinjection In The Model Entomopathogenic Nematode Heterorhabditis Bacteriophora., Ramesh Ratnappan, Jonathan Vadnal, Melissa Keaney, Ioannis Eleftherianos, Damien O'Halloran, John M. Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Parasitic nematodes threaten the health of humans and livestock and cause a major financial and socioeconomic burden to modern society. Given the widespread distribution of diseases caused by parasitic nematodes there is an urgent need to develop tools that will elucidate the genetic complexity of host-parasite interactions. Heterorhabditis bacteriophora is a parasitic nematode that allows simultaneous monitoring of nematode infection processes and host immune function, and offers potential as a tractable model for parasitic nematode infections. However, molecular tools to investigate these processes are required prior to its widespread acceptance as a robust model organism. In this paper we …

Identification And Spontaneous Immune Targeting Of An Endogenous Retrovirus K Envelope Protein In The Indian Rhesus Macaque Model Of Human Disease., Helen L Wu, Enrique J Léon, Lyle T Wallace, Francesca A Nimiyongskul, Matthew B Buechler, Laura P Newman, Philip A Castrovinci, R Paul Johnson, Robert J Gifford, R. Brad Jones, Jonah B Sacha

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections that have invaded the germ line of both humans and non-human primates. Most ERVs are functionally crippled by deletions, mutations, and hypermethylation, leading to the view that they are inert genomic fossils. However, some ERVs can produce mRNA transcripts, functional viral proteins, and even non-infectious virus particles during certain developmental and pathological processes. While there have been reports of ERV-specific immunity associated with ERV activity in humans, adaptive immune responses to ERV-encoded gene products remain poorly defined and have not been investigated in the physiologically relevant non-human primate model of …

Cold Atmospheric Plasma Inhibits Hiv-1 Replication In Macrophages By Targeting Both The Virus And The Cells., Olga Volotskova, Larisa Dubrovsky, Michael Keidar, Michael Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Cold atmospheric plasma (CAP) is a specific type of partially ionized gas that is less than 104°F at the point of application. It was recently shown that CAP can be used for decontamination and sterilization, as well as anti-cancer treatment. Here, we investigated the effects of CAP on HIV-1 replication in monocyte-derived macrophages (MDM). We demonstrate that pre-treatment of MDM with CAP reduced levels of CD4 and CCR5, inhibiting virus-cell fusion, viral reverse transcription and integration. In addition, CAP pre-treatment affected cellular factors required for post-entry events, as replication of VSV-G-pseudotyped HIV-1, which by-passes HIV receptor-mediated fusion at the plasma …

Fusion, 2016, George Washington University, William H. Beaumont Medical Research Honor Society

Fusion

No abstract provided.

Stability Of Metabolic Factor Before And After Bariatric Surgery, Brandon Davis, Joseph Indelicato

The School of Health Sciences Publications and Research

No abstract provided.

The Effects Of Allergies And Anaphylaxis On The Body And Mind: A Survey Of Opinions And Knowledge On These Disorders, Kathryn E. O'Brien

Honors Program: Student Scholarship & Creative Works

Despite common knowledge, allergies and anaphylaxis are considered disabilities. As such, these disorders affect the daily lives of those who have them, including one's mental health. In this paper, all the nuances of allergies and anaphylaxis will be discussed as the etiology and scientific aspects of allergies, anaphylaxis, and hypersensitivity are distinguished from one another. Furthermore, the findings are reported from two surveys; an assessment of how well educated and prepared teachers are for students with allergies and whether other students with food allergies have had similar experiences to the author's and those described in research by other studies concerning …

Exome Screening To Identify Loss-Of-Function Mutations In The Rhesus Macaque For Development Of Preclinical Models Of Human Disease, Adam Cornish, Robert M. Gibbs, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Exome sequencing has been utilized to identify genetic variants associated with disease in humans. Identification of loss-of-function mutations with exome sequencing in rhesus macaques (Macaca mulatta) could lead to valuable animal models of genetic disease. Attempts have been made to identify variants in rhesus macaques by aligning exome data against the rheMac2 draft genome. However, such efforts have been impaired due to the incompleteness and annotation errors associated with rheMac2. We wished to determine whether aligning exome reads against our new, improved rhesus genome, MacaM, could be used to identify high impact, loss-of-function mutations in rhesus macaques that would …

Microvascular Endothelial Cells-Derived Microvesicles Imply In Ischemic Stroke By Modulating Astrocyte And Blood Brain Barrier Function And Cerebral Blood Flow, Qunwen Pan, Caixia He, Hua Liu, Xiaorong Liao, Bingyan Dai, Yanfang Chen, Yi Yang, Bin Zhao, Ji C. Bihl, Xiaotang Ma

Pharmacology and Toxicology Faculty Publications

Background

Endothelial cell (EC) released microvesicles (EMVs) can affect various target cells by transferring carried genetic information. Astrocytes are the main components of the blood brain barrier (BBB) structure in the brain and participate in regulating BBB integrity and blood flow. The interactions between ECs and astrocytes are essential for BBB integrity in homeostasis and pathological conditions. Here, we studied the effects of human brain microvascular ECs released EMVs on astrocyte functions. Additionally, we investigated the effects of EMVs treated astrocytes on regulating BBB function and cerebral ischemic damage.

Results

EMVs prepared from ECs cultured in normal condition (n-EMVs) or …

Analysis Of Igm Antibody Production And Repertoire In A Mouse Model Of Sjogren's Syndrome, J. M. Kramer, N. E. Holodick, T. C. Vizconde, I. Raman, M. Yan, Q. Z. Li, D. P. Gaile, T. L. Rothstein

Journal Articles

This study tested the hypothesis that B cells from salivary tissue are distinct in terms of proliferative capacity, immunoglobulin M secretion, repertoire, and autoantibody enrichment in Sjogren's syndrome. We sorted purified B cells from the spleen, cervical lymph nodes, and submandibular glands of a primary Sjogren's syndrome mouse model (Id3-/-). Enzyme-linked immunospot and proliferation assays were performed with stimulated B cells. We single-cell sorted B cells from the spleen, cervical lymph nodes, and submandibular gland tissue from Sjogren's syndrome mice and sequenced immunoglobulin M heavy-chain variable regions. Finally, autoantigen arrays were performed using immunoglobulin M derived from sera, cervical lymph …

Btk Inhibition Results In Impaired Cxcr4 Chemokine Receptor Surface Expression, Signaling And Function In Chronic Lymphocytic Leukemia, S. S. Chen, B. Y. Chang, S. Chang, T. Tong, S. Ham, B. Sherry, J. A. Burger, K. R. Rai, N. Chiorazzi

Journal Articles

Bruton's tyrosine kinase (BTK) is involved in the regulation of B-cell growth, migration and adhesion. The importance of BTK in cell trafficking is emphasized by the clonal contraction proceeded by lymphocytosis typical for the enzyme inhibitor, ibrutinib, in B-cell malignancies, including chronic lymphocytic leukemia (CLL). Here, we investigated BTK regulation of leukemic B-cell trafficking in a mouse model of aggressive TCL1 CLL-like disease. Inhibiting BTK by ibrutinib reduced surface membrane (sm) levels of CXCR4 but not CXCR5, CD49d and other adhesion/homing receptors. Decreased smCXCR4 levels resulted from blocking receptor signal transduction, which in turn aborted cycling from and to the …