Digital Commons Network^™

Fibroblast Growth Factor 23 (Fgf23) Levels, Phosphate Intake And Its Association With Indices Of Renal Handling Of Phosphate In Healthy Volunteers, Noreen Abbas, Aysha Habib Khan, Farooq Ghani, Imran Siddiqui

Department of Pathology and Laboratory Medicine

FGF23 is a novel phosphaturic hormone; we aimed to assess the FGF23 levels and its association with dietary phosphate intake and indices of renal handling of phosphate in this study. Prospective study was conducted in which dietary phosphate intake was assessed by food frequency questionnaire (FFQ) along with blood and spot urine samples were collected after overnight fast for determining serum phosphate, FGF23, fractional excretion of phosphate (FePO4 ) and tubular maximum for phosphate (TmP/GFR). FGF23 (C-Term) was measured by a sandwich ELISA. The mean dietary phosphate intake of eighty healthy adults (mean age of 29 ± 5 years) was …

Week Of January 19, 2016, New York Medical College

InTouch

• SOM Hosts Children's Health Translational Science Institute Workshop
• Renowned Exercise Scientist Set To Speak at 19th Annual Medical Student Research Forum
• AOA History of Medicine Lecture Is Set for February 2
• Micro Mentee is Named an Intel Science Talent Search Semifinalist
• From the Collection of Edward C. Halperin, M.D., M.A.
• Join Mill Etienne, M.D. '02, M.P.H., at Local Event on Brain Health Awareness

Overexpression Of Pd2 Leads To Increased Tumorigenicity And Metastasis In Pancreatic Ductal Adenocarcinoma., Arokia Priyanka Vaz, Shonali Deb, Satyanarayana Rachagani, Parama Dey, Sakthivel Muniyan, Imayavaramban Lakshmanan, Saswati Karmakar, Lynette M. Smith, Sonny L. Johansson, Subodh M. Lele, M Ouellette, Moorthy P. Ponnusamy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Pancreatic differentiation 2 (PD2), an important subunit of the human PAF complex, was identified after differential screening analysis of 19q13 amplicon, and its overexpression induces oncogenic transformation of NIH3T3 cells, hence raising the possibility of a role for PD2 in tumorigenesis and metastasis. To test this hypothesis, we analyzed here the functional role and clinical significance of PD2 in pancreatic ductal adenocarcinoma (PDAC) and its pathogenesis. Using immunohistochemical analysis, we found that PD2 is detected in the acini but not in the ducts in the normal pancreas. In human PDAC specimens, PD2 was instead primarily detected in the ducts (12/48 …

Vaccines And The Looming Threat Of Syphilis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

During the past several decades, syphilis has increased in the US and explosively so in China and Russia.While most current cases can be cured by penicillin or second line antibiotics, strains of the syphilis spirochete (Treponema pallidum) resistant to the latter have emerged.And the potential of strains to acquire resistance to penicillin via plasmids has recently been recognized.The 36 million-plus undertreated cases of syphilis in the world represent metaphorically a vast global 37°C incubator allowing exchange of antibiotic resistant genes among the human-borne bacteria and theoretically permitting the emergence of penicillin resistant strains.None has yet been identified but …

The Pseudorabies Virus Protein, Pul56, Enhances Virus Dissemination And Virulence But Is Dispensable For Axonal Transport, Gina R. Daniel, Patricia J. Sollars, Gary E. Pickard, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

Neurotropic herpesviruses exit the peripheral nervous system and return to exposed body surfaces following reactivation from latency. The pUS9 protein is a critical viral effector of the anterograde axonal transport that underlies this process. We recently reported that while pUS9 increases the frequency of sorting of newly assembled pseudorabies virus particles to axons from the neural soma during egress, subsequent axonal transport of individual virus particles occurs with wild-type kinetics in the absence of the protein. Here, we examine the role of a related pseudorabies virus protein, pUL56, during neuronal infection. The findings indicate that pUL56 is a virulence factor …

Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response To Pulmonary Tuberculosis In A Rabbit Model, Selvakumar Subbian, Liana Tsenova, Jennifer Holloway, Blas Peixoto, Paul O'Brien, Veronique Dartois, Vikram Khetani, Jerome B. Zeldis, Gilla Kaplan

Publications and Research

Objectives: Adjunctive host-directed therapy is emerging as a new potential approach to improve the outcome of conventional antimicrobial treatment for tuberculosis (TB).We tested the ability of a phosphodiesterase-4 inhibitor (PDE4i) CC-11050, co-administered with the first-line anti-TB drug isoniazid (INH), to accelerate bacillary killing and reduce chronic inflammation in the lungs of rabbits with experimental Mycobacterium tuberculosis (Mtb) infection.

Methods: A rabbit model of pulmonary TB that recapitulates the pathologic manifestations seen in humans was used. Rabbits were infected with virulent Mtb by aerosol exposure and treated for eight weeks with INH with orwithout CC-11050, starting at fourweeks post infection. The …

Characterization Of Rna Helicase Csha And Its Role In Protecting Mrnas And Small Rnas Of Staphylococcus Aureus Strain Newman, Samin Kim, Anna-Rita Corvaglia, Stefano Léo, Ambrose Cheung, Patrice Francois

Dartmouth Scholarship

The toxin MazF_sa in Staphylococcus aureus is a sequence-specific endoribonuclease that cleaves the majority of the mRNAs in vivo but spares many essential mRNAs (e.g., secY mRNA) and, surprisingly, an mRNA encoding a regulatory protein (i.e., sarA mRNA). We hypothesize that some mRNAs may be protected by RNA-binding protein(s) from degradation by MazF_sa. Using heparin-Sepharose-enriched fractions that hybridized to sarA mRNA on Northwestern blots, we identified among multiple proteins the DEAD box RNA helicase CshA (NWMN_1985 or SA1885) by mass spectroscopy. Purified CshA exhibits typical RNA helicase activities, as exemplified by RNA-dependent ATPase activity and unwinding of …

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 …

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

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 …

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 …

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 …

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 …

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 …

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 …

Cytoplasmic Myosin-Exposed Apoptotic Cells Appear With Caspase-3 Activation And Enhance Cll Cell Viability, X. Cui, L. Zhang, A. R. Magli, R. Catera, X. J. Yan, D. O. Griffin, T. L. Rothstein, J. Barrientos, J. E. Kolitz, S. L. Allen, K. R. Rai, N. Chiorazzi, C. C. Chu

Journal Articles

The degree of chronic lymphocytic leukemia (CLL) B-cell antigen receptor (BCR) binding to myosin-exposed apoptotic cells (MEACs) correlates with worse patient outcomes, suggesting a link to disease activity. Therefore, we studied MEAC formation and the effects of MEAC binding on CLL cells. In cell line studies, both intrinsic (spontaneous or camptothecin-induced) and extrinsic (FasL- or anti-Fas-induced) apoptosis created a high percent of MEACs over time in a process associated with caspase-3 activation, leading to cytoplasmic myosin cleavage and trafficking to cell membranes. The involvement of common apoptosis pathways suggests that most cells can produce MEACs and indeed CLL cells themselves …

Elevated 1-Hour Plasma Glucose Levels Are Associated With Dysglycemia, Impaired Beta-Cell Function, And Insulin Sensitivity: A Pilot Study From A Real World Health Care Setting, R. Jagannathan, M. A. Sevick, H. Li, D. Fink, R. Dankner, A. Chetrit, J. Roth, M. Bergman

Journal Articles

No abstract provided.