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Creation Of An Immunodeficient Hla-Transgenic Mouse (Humamice) And Functional Validation Of Human Immunity After Transfer Of Hla-Matched Human Cells, Yang Zeng, Bingrun Liu, Marie-Therese Rubio, Xinyue Wang, David M. Ojcius, Ruoping Tang, Antoine Durrbach, Zhitao Ru, Yusen Zhou, Yu-Chun Lone

All Dugoni School of Dentistry Faculty Articles

Research on human immunology has been hindered by the lack of optimal small animal models, given that the protective immune responses of human and non-human species show significant differences. However, due to ethical constraints[1] and the high cost of clinical trials, it is urgent to improve the current animal models that can mimic faithfully human physiology, particularly the human immune system (HIS). HIS mice had been generated recently by engrafting human hematopoietic stem cells (hHSCs) or human peripheral mononuclear cells (hPBMCs) into highly immuno-deficient mice such as NSG, NOG or NRG mice. However, a major experimental drawback for studies using …

Week Of April 10, 2017, New York Medical College

InTouch

• New York Medical College and Westchester Medical Center Enter Into Long-Term Academic Affiliation Agreement
• NYMedTalks Explores Crossroads of Health Care and Technology
• Chancellor Halperin Addresses NYMC Community at Town Hall Meeting
• SOM P2P Committee Recognizes Role Models at NYMC
• NYMC Receives Full Accreditation From AAALAC

The Use Of Rhyme, Rhythm, And Melody As A Form Of Repetition Priming To Aid In Encoding, Storage, And Retrieval Of Semantic Memories In Alzheimer’S Patients, Faiz Plastikwala

Virginias Collegiate Honors Council Conference

Treating Alzheimer’s disease, especially through non-pharmaceutical means, has become increasingly important over the past few decades. I examined the use of melody, rhyme, and rhythm as encoding mechanisms to aid in the retrieval of long term semantic information by juxtaposing previous experiments in the field. Melody, rhyme, and rhythm provide an organizational structure to facilitate the encoding of information. Specifically, chunking, the grouping of smaller units into larger ‘chunks’, helps facilitate long term encoding in patients, and is the byproduct of the organizational structure of a text. A major drawback of using these devices is the loss in the depth …

Unfair Competition Governs The Interaction Of Pcpi-17 With Myosin Phosphatase (Pp1-Mypt1)., Joshua J. Filter, Byron C. Williams, Masumi Eto, David Shalloway, Michael L. Goldberg

Department of Molecular Physiology and Biophysics Faculty Papers

The small phosphoprotein pCPI-17 inhibits myosin light-chain phosphatase (MLCP). Current models postulate that during muscle relaxation, phosphatases other than MLCP dephosphorylate and inactivate pCPI-17 to restore MLCP activity. We show here that such hypotheses are insufficient to account for the observed rapidity of pCPI-17 inactivation in mammalian smooth muscles. Instead, MLCP itself is the critical enzyme for pCPI-17 dephosphorylation. We call the mutual sequestration mechanism through which pCPI-17 and MLCP interact inhibition by unfair competition: MLCP protects pCPI-17 from other phosphatases, while pCPI-17 blocks other substrates from MLCP's active site. MLCP dephosphorylates pCPI-17 at a slow rate that is, nonetheless, …

Validation Of The Pre-B Cell Receptor As A Therapeutic Target In B Cell Precursor Acute Lymphoblastic Leukemia, Michael Frank Erasmus

Biomedical Sciences ETDs

This dissertation is built upon the fundamental idea that the pre-B cell receptor (pre-BCR) is important to leukemia cell survival and a logical therapeutic target in B cell precursor acute lymphoblastic leukemia (BCP-ALL). The pre-BCR is expressed early at a specific stage during B cell development where it plays a central role in survival of healthy B lymphocytes. This receptor is composed of the membrane heavy chain (mIgμ) associated with surrogate light chain components, 5 and VpreB. Through the use of advanced imaging modalities, in particular two-color single particle tracking (SPT), we showed that pre-BCRs formed transient, homotypic interactions. These …

Thujone Inhibits The Function Of Α7-Nicotinic Acetylcholine Receptors And Impairs Nicotine-Induced Memory Enhancement In One-Trial Passive Avoidance Paradigm, Ahmed Sultan, Keun-Hang Susan Yang, Dmytro Isaev, Eslam El Nebrisi, Nurulain Syed, Nadia Khan, Christopher F. Howarth, Bassem Sadek, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α7 subunit of the human nicotinic acetylcholine (α7 nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100 μM)-induced currents with an IC50 value of 24.7 μM. The effect of thujone was not dependent on the membrane potential and did not involve Ca2+-dependent Cl- channels expressed endogenously in oocytes. Inhibition by thujone was not reversed by increasing ACh concentrations. Moreover, specific binding of [125I] -bungarotoxin was not altered by thujone. Further experiments in SH-EP1 …

G Protein-Coupled Receptor Kinase-2 (Grk-2) Regulates Serotonin Metabolism Through The Monoamine Oxidase Amx-2 In Caenorhabditis Elegans., Jianjun Wang, Jiansong Luo, Dipendra K. Aryal, William C. Wetsel, Richard Nass, Jeffrey L. Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

G protein-coupled receptors (GPCRs) regulate many animal behaviors. GPCR signaling is mediated by agonist-promoted interactions of GPCRs with heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. To further elucidate the role of GRKs in regulating GPCR-mediated behaviors, we utilized the genetic model system Caenorhabditis elegans Our studies demonstrate that grk-2 loss-of-function strains are egg laying-defective and contain low levels of serotonin (5-HT) and high levels of the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA). The egg laying defect could be rescued by the expression of wild type but not by catalytically inactive grk-2 or by the selective expression of grk-2 in …

Receptor-Associated Protein (Rap) Models In Vivo Reelin Haploinsufficiency: Implications In Schizophrenia, Jamileh Ahmed

USF Tampa Graduate Theses and Dissertations

The “two-hit” schizophrenia hypothesis suggests genetic and environmental abnormalities interrupt early CNS function. This increases vulnerability of a “second hit” and schizophrenia onset. Chronic stress and decreased Reelin signaling are reportedly associated with schizophrenia. Heterozygous Reeler Mice (HRM) show a 50% reduction in Reelin and display major schizophrenia phenotypes. Receptor-Associated Protein (RAP) blocks ligand-association to Reelin receptor Apolipoprotein E receptor 2 (ApoER2). In this study, we sought to replicate major heterozygous reeler mouse (HRM) phenotypes using in vivo RAP studies to establish an experimental in vitro model. Using an in vitro model, we investigated the effects of chronic stress and …

Production Of Putative Enhanced Oral Cholera Vaccine Strains That Express Toxin-Coregulated Pilus, Caitlyn A. Hauke, Ronald K. Taylor

Dartmouth Scholarship

The use of whole cell killed (WCK) oral cholera vaccines is an important strategy for cholera prevention in endemic areas. To overcome current vaccine limitations, we engineered strains of V. cholerae to be non-toxigenic and to express the protective protein colonization factor, toxin-coregulated pilus (TCP), under scale-up conditions potentially amenable to vaccine production. Two V. cholerae clinical strains were selected and their cholera toxin genes deleted. The tcp operon was placed under control of a rhamnose-inducible promoter. Production and stability of TCP were assessed under various conditions. The strains lack detectable cholera toxin production. The addition of 0.1% …

Plasma Cross-Gestational Sphingolipidomic Analyses Reveal Potential First Trimester Biomarkers Of Preeclampsia, Aneta Dobierzewska, Sony Soman, Sebastian E Illanes, Andrew J. Morris

Saha Cardiovascular Research Center Faculty Publications

Introduction

Preeclampsia (PE) is a gestational disorder, manifested in the second half of pregnancy by maternal hypertension, proteinuria and generalized edema. PE is a major cause of maternal and fetal morbidity and mortality, accounting for nearly 40% of all premature births worldwide. Bioactive sphingolipids are emerging as key molecules involved in etiopathogenesis of PE, characterized by maternal angiogenic imbalance and symptoms of metabolic syndrome. The aim of this study was to compare the cross-gestational profile of circulating bioactive sphingolipids in maternal plasma from preeclamptic (PE) versus normotensive control (CTL) subjects with the goal of identifying sphingolipids as candidate first trimester …

Acetaminophen Associated Neurotoxicity And Its Relevance To Neurodevelopmental Disorders, Seol-Hee Kim

USF Tampa Graduate Theses and Dissertations

Autism is a lifelong neurodevelopmental disorder. The etiology of autism still remains unclear due to the heterogeneous and complex nature of the disorder, however synergistic actions between genetic components and environmental factors have been suggested. Acetaminophen (APAP) is one of the most popular over-the-counter drugs that possess antipyretic and analgesic effects. It is considered a relatively safe and effective within therapeutic doses. Recently, early exposure to APAP has been suggested to be one of the underlying cause of autism. Children are often prescribed APAP to lessen fever or irritability after vaccination during the first year, and APAP may adversely affect …

Exploring Therapeutic Approaches For Marfan Syndrome Associated Aortic Aneurysm, Mitra Esfandiarei

Science Seminar Series

Esfandiearei will be discussing her research on understanding the underlying mechanisms contributing to the progression of aortic aneurysm in Marfan syndrome and the protective effects that exercise may have on the disease process in both laboratory animal models and human patients. Her research has been supported by the Canadian Institutes of Health Research (CIHR), Rare Diseases Foundation, and the Marfan Foundation.

Neuropeptide Modulation Of The Large Conductance Potassium (Bk) Channel In The Auditory System: Therapeutic Implications For Age-Related Hearing Loss, Ellliott James Brecht

USF Tampa Graduate Theses and Dissertations

The auditory temporal processing deficits associated with age-dependent hearing decline have been increasingly attributed to issues beyond peripheral hearing loss. Age-related hearing loss (ARHL), also known as presbycusis, is linked with changes in the expression of both excitatory and inhibitory neurotransmitters in the central auditory system. There are also age-related changes in the expression and function of the ion channels which mediate action potential firing. The slow, Ca²⁺ activated, K⁺ channels of the BK-type are essential in controlling both neurotransmitter release and neural communication via alteration of action potential durations, firing frequency, and neural adaptation. There are many …

Week Of April 3, 2017, New York Medical College

InTouch

• Department of Biochemistry and Molecular Biology Hosts Fulbright Scholar to Study Effect of Neuropeptides on Stress Disorders
• SHSP and StuHE Ready for National Public Health Week
• NYMC Hosts Inaugural A cappella Invitational

Stem Cell Derived Osteoprogenitors And Their Role In Bone Repair Using Morphogenic Activators, George Washington Brownridge Iii, Sylvanna Islas, Angelina Miller, Warren Hoeffler

Student Research Posters

Bone constantly cycles through a dynamic process of breakdown and remodeling. Osteoblasts are the specialized mesenchymal stem cells that have a major role in bone formation and the remodeling process whereas their counterpart osteoclasts, handle bone resorption. Embryonic stem cells can be partially differentiated into Progenitor cells, and we worked with #18, a candidate for being an osteoprogenitor that has the potential to respond to morphogenic activators. In the case of bone remodeling, TGF-β 2, BMP-2 and an abundance of CA++ have been shown to be potential activators of differentiation into osteoblasts. Eight different trials were conducted with the cells …

Rapid And Rigorous Il-17a Production By A Distinct Subpopulation Of Effector Memory T Lymphocytes Constitutes A Novel Mechanism Of Toxic Shock Syndrome Immunopathology, Peter A. Szabo, Ankur Goswami, Delfina M. Mazzuca, Kyoungok Kim, David B. O'Gorman, David A. Hess, Ian D. Welch, Howard A. Young, Bhagirath Singh, John K. Mccormick, S. M.Mansour Haeryfar

United States Public Health Resources

Toxic shock syndrome (TSS) is caused by staphylococcal and streptococcal superantigens (SAgs) that provoke a swift hyperinflammatory response typified by a cytokine storm. The precipitous decline in the host's clinical status and the lack of targeted therapies for TSS emphasize the need to identify key players of the storm's initial wave. Using a humanized mouse model of TSS and human cells, we herein demonstrate that SAgs elicit in vitro and in vivo IL-17A responses within hours. SAg-triggered human IL-17A production was characterized by remarkably high mRNA stability for this cytokine. A distinct subpopulation of CD4+ effector memory T (TEM) cells …

Csf Protein Changes Associated With Hippocampal Sclerosis Risk Gene Variants Highlight Impact Of Grn/Pgrn, David W. Fardo, Yuriko Katsumata, John S. K. Kauwe, Yuetiva Deming, Oscar Harari, Carlos Cruchaga, Alzheimer’S Disease Neuroimaging Initiative, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Objective—Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs).

Methods—Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes.

Results—The GRN risk …

Outcomes After Diagnosis Of Mild Cognitive Impairment In A Large Autopsy Series, Erin L. Abner, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Daniela C. Moga, Eseosa T. Ighodaro, Gregory A. Jicha, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Randall L. Woltjer, Julie A. Schneider, Nigel J. Cairns, David A. Bennett, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).

METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

RESULTS: Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical …

Overcoming Hurdles To Development Of A Vaccine Against Pneumocystis Jirovecii, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Development of Pneumocystis pneumonia (PCP) is a common problem among immunosuppressed individuals. There are windows of opportunity in which vaccination would be beneficial, but to date, no vaccines have made it to clinical trials. Significant hurdles to vaccine development include host range specificity, making it difficult to translate from animal models to humans. Discovery of cross-reactive epitopes is critical to moving vaccine candidates from preclinical animal studies to clinical trials.

Table Of Contents

Journal of the South Carolina Academy of Science

No abstract provided.

Antitumor Activity Of Selected Derivatives Of Pyrazole- Benzenesulfonamides From Dilithiated C(Α), N-Phenylhydrazones And Lithiated Methyl 2-(Aminosulfonyl)Benzoate, N. Dwight Camper [Deceased], James M. Gum, Darby E. Lyles, William T. Pennington, Charles F. Beam, Clyde R. Metz

Journal of the South Carolina Academy of Science

Several pyrazole-benzenesulfonamides were subjected to biological evaluation involving tumor formation on potato discs caused by Agrobacterium tumefaciens. This assay led to some excellent and promising initial results with three of the pyrazole compounds showing increased tumor inhibition when compared to a recognized standard, camptothecin. The select pyrazole-benzenesulfonamides were prepared by condensation-cyclization of several dilithiated C(α),N-phenylhydrazones with lithiated methyl 2-aminosulfonyl-benzoate.

A Comparative Study Of Three Different Types Of Stem Cells For Treatment Of Rat Spinal Cord Injury, Jiri Ruzicka, L Machova-Urdzikova, John Gillick, T Amemori, N Romanyuk, K Karova, K Zaviskova, J Dubisova, S Kubinova, Raj Murali, E Sykova, Meena Jhanwar-Uniyal, P Jendelova

NYMC Faculty Publications

Three different sources of human stem cells-bone marrow-derived mesenchymal stem cells (BM-MSCs), neural progenitors (NPs) derived from immortalized spinal fetal cell line (SPC-01), and induced pluripotent stem cells (iPSCs)-were compared in the treatment of a balloon-induced spinal cord compression lesion in rats. One week after lesioning, the rats received either BM-MSCs (intrathecally) or NPs (SPC-01 cells or iPSC-NPs, both intraspinally), or saline. The rats were assessed for their locomotor skills (BBB, flat beam test, and rotarod). Morphometric analyses of spared white and gray matter, axonal sprouting, and glial scar formation, as well as qPCR and Luminex assay, were conducted to …

Fine-Mapping The Mhc Locus In Juvenile Idiopathic Arthritis (Jia) Reveals Genetic Heterogeneity Corresponding To Distinct Adult Inflammatory Arthritic Diseases., A Hinks, J Bowes, J Cobb, H C. Ainsworth, M C. Marion, M E. Comeau, M Sudman, B Han, Juvenile Arthritis Consortium For Immunochip, Mara L. Becker, J F. Bohnsack, P I W De Bakker, J P. Haas, M Hazen, D J. Lovell, P A. Nigrovic, E Nordal, M Punnaro, A M. Rosenberg, M Rygg, S L. Smith, C A. Wise, V Videm, L R. Wedderburn, A Yarwood, R S M Yeung, S Prahalad, C D. Langefeld, S Raychaudhuri, S D. Thompson, W Thomson

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides.

METHODS: Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. …

Genomic Contraindications For Heart Transplantation., Danton S. Char, Gabriel Lázaro-Muñoz, Aliessa Barnes, David Magnus, Michael J. Deem, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

Genome sequencing raises new ethical challenges. Decoding the genome produces new forms of diagnostic and prognostic information; however, the information is often difficult to interpret. The connection between most genetic variants and their phenotypic manifestations is not understood. This scenario is particularly true for disorders that are not associated with an autosomal genetic variant. The analytic uncertainty is compounded by moral uncertainty about how, exactly, the results of genomic testing should influence clinical decisions. In this Ethics Rounds, we present a case in which genomic findings seemed to play a role in deciding whether a patient was to be listed …

Regulation Of System Xc-By The Neuropeptide Pacap: Implications For Glutamate Transmission In Drug Addiction, Linghai Kong

Dissertations (1934 -)

Drug addiction is a chronic brain disorder characterized by heightened relapse susceptibility. Drug-induced aberrant glutamate signaling in corticostriatal circuitry contributes to behaviors in virtually every preclinical model of drug seeking and correlates with drug craving in human. Here, we propose that glutamate signaling is a product of integrated activity between neurons and astrocytes, such that disruptions within astrocytes can stem from abnormal neuronal signaling (e.g., altered corticostriatal firing) and be the source of additional disruptions in other neuronal circuits. The astrocytic mechanism studied in these experiments is system xc- (Sxc) since drug-induced changes to this non-vesicular glutamate release mechanism contribute …

A Review Of The Role Of Interleukin-6 On Disease Progression In Epithelial Ovarian Cancer, Urmimala Chaudhuri

Browse all Theses and Dissertations

Ovarian cancer is one of the most harmful gynecological cancers and has one of the highest mortality rates. As ovarian cancer progresses, the patient has changes to the immune system and energy metabolism with symptoms being weight loss, nausea, and fatigue. Changes to the immune system include overexpression of proinflammatory cytokines. One such cytokine is Interleukin-6 (IL-6), which is a useful prognostic marker to measure disease progression. IL-6 is thought to promote cancer cell proliferation by upregulating apoptosis inhibitory proteins. IL-6 also plays a role in ascites formation. While tumors may initially respond to chemotherapy treatment, most patients will have …

Fast Genome-Wide Qtl Association Mapping On Pedigree And Population Data, Hua Zhou, John Blangero, Thomas D. Dyer, Kei-Hang K. Chan, Kenneth Lange, Eric M. Sobel

School of Medicine Publications

Since most analysis software for genome-wide association studies (GWAS) currently exploit only unrelated individuals, there is a need for efficient applications that can handle general pedigree data or mixtures of both population and pedigree data. Even datasets thought to consist of only unrelated individuals may include cryptic relationships that can lead to false positives if not discovered and controlled for. In addition, family designs possess compelling advantages. They are better equipped to detect rare variants, control for population stratification, and facilitate the study of parent-of-origin effects. Pedigrees selected for extreme trait values often segregate a single gene with strong effect. …

Short-Term Bilateral Adrenalectomy: Biochemical And Morphological Alterations In The Rat Hippocampus, Ahlam Said Abi Issa

Theses

Several studies showed the effects of glucocorticoid hormones on the hippocampus. It has been reported that the chronic administration of high dose glucocorticoids (GC) results in the degeneration of pyramidal neurons. However, bilateral adrenalectomy has been shown to damage the hippocampal neurons. Although the effects of long-term adrenalectomy have been studied extensively, there are few publications on the effects of short-term bilateral adrenalectomy (ADX). We aimed to investigate the effects of ADX on levels of pro-inflammatory cytokines interleukin-1β (IL-1β), interkeukin-6 (IL-6) and tumor necrosis factor-α (TNF-α); levels of growth factors, response of microglia and astrocytes to neuronal death, and oxidative …

Melatonin Modulates Inflammatory Response And Suppresses Burn-Induced Apoptotic Injury, Ganka Bekyarova, Milena Atanasova, Maria Tzaneva, Anelia Dimitrova

Journal of Mind and Medical Sciences

Introduction: Melatonin, the principal secretory product of the pineal gland, has antioxidant functions as a potent antioxidant and free radical scavenger. Objectives of the present study were to investigate the effect of melatonin against inflammatory response, burn-induced oxidative damage and apoptotic changes of rat liver. Methods: Melatonin (10 mg /kg, i.p.) was applied immediately after 30% of total body surface area (TBSA) burns on male Wistar rats. The level of malondialdehyde (MDA) as a marker of an oxidative stress was quantified by thiobarbituric method. Hepatic TNFα and IL-10 as inflammatory markers were assayed by ELISA. Using light immunоchistochemistry …

Natural Killer (Nk) Cells And Their Involvement In Different Types Of Cancer. Current Status Of Clinical Research, Isadora Zaharescu, Adina D. Moldovan, Cristiana Tanase

Journal of Mind and Medical Sciences

Natural killer cells are the main agents of innate immunity. Since 1970, various studies have repeatedly confirmed their involvement in decreasing local tumor growth and also decreasing the risk of metastasis, due to their cytotoxic effects and also through the release of immunostimulatory cytokines such as IFN-gamma. In the 1990s, several studies demonstrated the existence of certain inhibiting and stimulating receptors of these cells, leading to the concept of “induced self”, thus explaining why tumors with MHC-1 are destroyed and autologous cells without it are saved out. Recognition and destruction of tumor cells by the NK cells are the result …