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T Cells Expressing Allograft Inflammatory Factor 1 Display Increased Chemotaxis And Induce A Profibrotic Phenotype In Normal Fibroblasts In Vitro, Francesco Del Galdo M.D., Ph.D., Sergio A. Jimenez M.D.

Department of Dermatology and Cutaneous Biology Faculty Papers

Objective. Allograft inflammatory factor 1 (AIF-1) was first identified in rat cardiac allografts undergoing chronic rejection. The vasculopathy of chronic allograft rejection is strikingly similar to that seen in patients with systemic sclerosis (SSc). We previously demonstrated AIF-1 expression in inflammatory cells infiltrating skin and lungs from SSc patients, but its role in SSc pathogenesis is unknown. The present study was undertaken to investigate the effects of AIF-1 on T cell migration and production of cytokines capable of modulating normal dermal fibroblast functions.

Methods. Stably transfected Jurkat T cells expressing 2 AIF-1 splicing variants were prepared, and their migration toward …

A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets Of Subtype B And C Hiv-1 Primary Viruses, Hua-Xin Liao, Laura L. Sutherland, Shi-Mao Xia, Mary E. Brock, Richard M. Scearce, Stacie Vanleeuwen, S. Munir Alam, Mildred Mcadams, Eric A. Weaver, Zenaido T. Camacho, Ben-Jiang Ma, Yingying Li, Julie M. Decker, Gary J. Nabel, David C. Montefiori, Beatrice H. Hahn, Bette T. Korber, Feng Gao, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

HIV-1 subtype C is the most common HIV-1 group M subtype in Africa and many parts of Asia. However, to date HIV-1 vaccine candidate immunogens have not induced potent and broadly neutralizing antibodies against subtype C primary isolates. We have used a centralized gene strategy to address HIV-1 diversity, and generated a group M consensus envelope gene with shortened consensus variable loops (CON-S) for comparative studies with wildtype (WT) Env immunogens. Our results indicate that the consensus HIV-1 group M CON-S Env elicited cross-subtype neutralizing antibodies of similar or greater breadth and titer than the WT Envs tested, indicating the …

The Neural Correlates Of Non-Spatial Working Memory In Velocardiofacial Syndrome (22q11.2 Deletion Syndrome), Wendy R. Kates, Beth R. Krauss, Nuria Abdulsabur, Dierdre Colgan, Kevin M. Antshel, Anne Marie Higgins, Robert J. Shprintzen

Communication Disorders Faculty Publications

Velocardiofacial syndrome (VCFS), also known as 22q11.2 deletion syndrome, is a neurogenetic disorder that is associated with both learning disabilities and a consistent neuropsychological phenotype, including deficits in executive function, visuospatial perception, and working memory. Anatomic imaging studies have identified significant volumetric reductions in the parietal lobe of individuals with VCFS, but several studies have reported that the frontal lobe is relatively preserved. We used functional magnetic resonance imaging to investigate the neural correlates of non-spatial working memory in 17 youths with VCFS, 10 of their unaffected siblings, and 10 community controls (with the same proportion of learning disabilities as …

Selective Repression Of Retinoic Acid Target Genes By Rip140 During Induced Tumor Cell Differentiation Of Pluripotent Human Embryonal Carcinoma Cells, Kelly C. Heim, Kristina A. White, Dexin Deng, Craig R. Tomlinson, Jason Moore, Sarah Freemantle, Michael Spinella

Dartmouth Scholarship

The use of retinoids as anti-cancer agents has been limited due to resistance and low efficacy. The dynamics of nuclear receptor coregulation are incompletely understood. Cell-and context-specific activities of nuclear receptors may be in part due to distinct coregulator complexes recruited to distinct subsets of target genes. RIP140 (also called NRIP1) is a ligand-dependent corepressor that is inducible with retinoic acid (RA). We had previously shown that RIP140 limits RA induced tumor cell differentiation of embryonal carcinoma; the pluriopotent stem cells of testicular germ cell tumors. This implies that RIP140 represses key genes required for RA-mediated tumor cell differentiation. Identification …

Suppression Of Peroxisomal Enzyme Activities And Cytochrome P450 4a Isozyme Expression By Congeneric Polybrominated And Polychlorinated Biphenyls, Larry W. Robertson, Isabelle Berberian, Tim Borges, Li-Chuan Chen, Ching K. Chow, Howard P. Glauert, Johannes G. Filser, Helmut Thomas

Toxicology and Cancer Biology Faculty Publications

The purpose of this study was to determine the effects of PCBs and PBBs on peroxisome proliferator-activated receptor-alpha-(PPARalpha-) associated enzyme activities or protein levels. Male Sprague-Dawley rats were administered a single IP injection (150 mu mol/kg) of either 3,3',4,4'-tetrabromobiphenyl, 3,3',4,4'-tetrachlorobiphenyl, 3,3',5,5'-tetrabromobiphenyl, 2',3,3',4,5-pentachlorobiphenyl, 3,3',4,4',5-pentachlorobiphenyl, 2,2',3,3',5,5'-hexachlorobiphenyl, or 3,3',4,4',5,5'-hexabromobiphenyl in corn oil (10 ml/kg). One week later, the activities of catalase, peroxisomal fatty acyl-CoA oxidase, and peroxisomal beta-oxidation as well as cytochrome P450 4A (CYP4A) protein content were determined in subcellular liver fractions. None of the peroxisomal enzyme activities were significantly increased by any of the halogenated biphenyl congeners tested. Except for minor …

Mir-29 Regulates Mcl-1 Protein Expression And Apoptosis., Justin L. Mott, Shogo Kobayashi, Steven F. Bronk, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

Cellular expression of Mcl-1, an anti-apoptotic Bcl-2 family member, is tightly regulated. Recently, Bcl-2 expression was shown to be regulated by microRNAs, small endogenous RNA molecules that regulate protein expression through sequence-specific interaction with messenger RNA. By analogy, we reasoned that Mcl-1 expression may also be regulated by microRNAs. We chose human immortalized, but non-malignant, H69 cholangiocyte and malignant KMCH cholangiocarcinoma cell lines for these studies, because Mcl-1 is dysregulated in cells with the malignant phenotype. By in silico analysis, we identified a putative target site in the Mcl-1 mRNA for the mir-29 family, and found that mir-29b was highly …

A Role For The Forebrain In Mediating Time-Of-Day Differences In Glucocorticoid Counterregulatory Responses To Hypoglycemia In Rats, Lori Gorton, Arshad Khan, Maryann Bohland, Graciela Sanchez-Watts, Casey Donovan, Alan Watts

Selected Works Temporary Series

No abstract provided.

A Role For The Forebrain In Mediating Time-Of-Day Differences In Glucocorticoid Counterregulatory Responses To Hypoglycemia In Rats, Gorton, Arshad Khan, Maryann Bohland, Graciela Sanchez-Watts, Casey Donovan, Alan Watts

Departmental Papers (Biology)

No abstract provided.

Uniaxial Stretch-Induced Regulation Of Mitogen-Activated Protein Kinase, Akt And P70s6 Kinase In The Ageing Fischer 344 × Brown Norway Rat Aorta, Kevin M. Rice, Devashish H. Desai, Deborah L. Preston, Paulette S. Wehner, Eric R. Blough

MIIR Faculty Research

The effects of ageing on the cardiovascular system contribute to substantial alterations in cellular morphology and function. The variables regulating these changes are unknown; however, one set of signalling molecules that may be of particular importance in mediating numerous cellular responses, including control of cell growth, differentiation and adaptation, are the proteins associated with the mitogen-activated protein kinase (MAPK) signalling systems. The MAPKs, in conjunction with the p70 S6k signalling cascade, have emerged as critical components for regulating numerous mechanotransduction-related cellular responses. Here we investigate the ability of uniaxial stretch to activate the MAPK and p70 S6k pathways in adult …

Recent Advances In Cancer Stem/Progenitor Cell Research: Therapeutic Implications For Overcoming Resistance To The Most Aggressive Cancers., M. Mimeault, Ralph Hauke, Parmender P. Mehta, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers. This review summarizes recent advances in our understanding of the cellular origin and molecular mechanisms at the basis of cancer initiation and progression as well as the heterogeneity of cancers arising from the malignant transformation of adult stem/progenitor cells. We describe the critical functions provided by several growth factor cascades, including epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF) receptor (KIT), hedgehog and Wnt/beta-catenin signalling pathways that …

The Influence Of Ambient Lighting Levels On Postural Sway In Healthy Children Ages 9 To 11, Yvette Blanchard, Rebecca Mcveigh, Megan Graham, Melissa Cadet, Kabulo Mwilambwe, Christi Scott

All PTHMS Faculty Publications

The purpose of this study was to determine whether postural sway in healthy children varied in different levels of ambient lighting. Twelve boys and 26 girls with a mean age of 118 months stood on a force platform under three conditions: eyes closed, eyes opened in regular light (200 lx) and eyes opened in dim light (3 lx). Analysis of variance and pairwise comparisons revealed significantly more postural sway with the eyes closed condition compared to the regular and dim light conditions but no differences between the regular and dim light conditions. While our results on postural sway during the …

Utility Of Mri In Assessment Of Pituitary Iron Overload, Abdul Mueed Zafar, Lubna Zuberi, Ameer Hamza Khan, Humera Ahsan

Medical College Documents

Beta thalassemia is highly prevalent in Pakistan with a carrier rate of 5-8%. The main complication of beta thalassemia major is iron overload, especially in reticuloendothelial system, heart, joints and endocrine glands. Pituitary siderosis leads to hypogonadotropic hypogonadism and growth hormone deficiency. Measures of plasma ferritin levels and hepatic iron level are used for assessing body iron overload but these are limited for various reasons particularly in case of pituitary siderosis. Magnetic Resonance Imaging (MRI) is a reliable, non invasive and easily available utility for assessing tissue siderosis. We assessed a 20 year old female beta thalassemic diagnosed with hypogonadotropic …

The Effect Of Caffeine And Ethanol On Flatworm Regeneration., Erica Leighanne Collins

Electronic Theses and Dissertations

Flatworms, or planarian, have a high potential for regeneration and have been used as a model to investigate regeneration and stem cell biology for over a century. Chemicals, temperature, and seasonal factors can influence planarian regeneration. Caffeine and ethanol are two widely used drugs and their effect on flatworm regeneration was evaluated in this experiment. Non-toxic levels of caffeine, a stimulant, and ethanol, a depressant, were determined. The tails of the flatworms were removed and the regeneration stage was analyzed every 3 days for 15 days to see the effect of these drugs alone and in combination on regeneration. For …

Human Collagen Krox Up-Regulates Type I Collagen Expression In Normal And Scleroderma Fibroblasts Through Interaction With Sp1 And Sp3 Transcription Factors., Magdalini Kypriotou, Gallic Beauchef, Christos Chadjichristos, Russell Widom, Emmanuelle Renard, Sergio A. Jimenez, Joseph Korn, François-Xavier Maquart, Thierry Oddos, Otto Von Stetten, Jean-Pierre Pujol, Philippe Galéra

Department of Medicine Faculty Papers

Despite several investigations, the transcriptional mechanisms that regulate the expression of both type I collagen genes (COL1A1 and COL1A2) in either physiological or pathological situations, such as scleroderma, are not completely known. We have investigated the role of hc-Krox transcription factor on type I collagen expression by human dermal fibroblasts. hc-Krox exerted a stimulating effect on type I collagen protein synthesis and enhanced the corresponding mRNA steady-state levels of COL1A1 and COL1A2 in foreskin fibroblasts (FF), adult normal fibroblasts (ANF), and scleroderma fibroblasts (SF). Forced hc-Krox expression was found to up-regulate COL1A1 transcription through a -112/-61-bp sequence in FF, ANF, …

Low Molecular Weight Protein Tyrosine Phosphatase (Lmw-Ptp) And Its Possible Physiological Functions Of Redox Signaling In The Eye Lens, Kuiyi Xing, Ashraf Raza, Stefan Lofgren, M. Rohan Fernando, Ye-Shih Ho, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Low molecular weight protein tyrosine phosphatase (LMW-PTP) was cloned from human lens epithelial B3 cells (HLE B3) and the recombinant enzyme was purified to homogeneity. The pure enzyme reacted positively with anti-LMW-PTP antibody, displayed tyrosine-specific phosphatase activity and was extremely sensitive to H2O2. The inactivated LMW-PTP could be regenerated by thioltransferase (TTase)/GSH system as demonstrated by both activity assay and by mass spectrometry (MS). The MS study also showed that an intramolecular disulfide bond was formed between C13 and C18 at the active site, and was reduced by the TTase/GSH system. The putative role of LMW-PTP in regulating platelet derived …

Assays Of Vacuole Fusion Resolve The Stages Of Docking, Lipid Mixing, And Content Mixing, Youngsoo Jun, William Wickner

Dartmouth Scholarship

Membrane fusion entails organelle docking and subsequent mixing of membrane bilayers and luminal compartments. We now present an in vitro assay of fusion, using yeast vacuoles bearing domains of either Fos or Jun fused to complementary halves of beta-lactamase. Upon fusion, these proteins associate to yield beta-lactamase activity. This assay complements the standard fusion assay (activation of pro-Pho8p in protease-deficient vacuoles by proteases from pho8Delta vacuoles). Both the beta-lactamase and pro-Pho8p activation assays of fusion show the same long kinetic delay between SNARE pairing and luminal compartment mixing. Lipid-mixing occurs rapidly after SNARE pairing but well before aqueous compartment mixing. …

All-Trans Retinoic Acid Mediates Enhanced T Reg Cell Growth, Differentiation, And Gut Homing In The Face Of High Levels Of Co-Stimulation, Micah J. Benson, Karina Pino-Lagos, Mario Rosemblatt, Randolph J. Noelle

Dartmouth Scholarship

We demonstrate that all-trans retinoic acid (RA) induces FoxP3(+) adaptive T regulatory cells (A-Tregs) to acquire a gut-homing phenotype (alpha 4 beta 7(+) CC chemokine receptor 9(+)) and the capacity to home to the lamina propria of the small intestine. Under conditions that favor the differentiation of A-Tregs (transforming growth factor-beta1 and interleukin 2) in vitro, the inclusion of RA induces nearly all activated CD4(+) T cells to express FoxP3 and greatly increases the accumulation of these cells. In the absence of RA, A-Treg differentiation is abruptly impaired by proficient antigen presenting cells or through direct co-stimulation. In the presence …

Human Muc4 Mucin Induces Ultra-Structural Changes And Tumorigenicity In Pancreatic Cancer Cells., N. Moniaux, P. Chaturvedi, G. C. Varshney, Jane L. Meza, J. F. Rodriguez-Sierra, J-P Aubert, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

MUC4 is a type-1 transmembrane glycoprotein and is overexpressed in many carcinomas. It is a heterodimeric protein of 930 kDa, composed of a mucin-type subunit, MUC4alpha, and a membrane-bound growth factor-like subunit, MUC4beta. MUC4 mRNA contains unique 5' and 3' coding sequences along with a large variable number of tandem repeat (VNTR) domain of 7-19 kb. A direct association of MUC4 overexpression has been established with the degree of invasiveness and poor prognosis of pancreatic cancer. To understand the precise role of MUC4 in pancreatic cancer, we engineered a MUC4 complementary DNA construct, mini-MUC4, whose deduced protein (320 kDa) is …

A Serratia Marcescens Oxyr Homolog Mediates Surface Attachment And Biofilm Formation, Robert M. Q. Shanks, Nicholas A. Stella, Eric J. Kalivoda, Megan R. Doe

Dartmouth Scholarship

OxyR is a conserved bacterial transcription factor with a regulatory role in oxidative stress response. From a genetic screen for genes that modulate biofilm formation in the opportunistic pathogen Serratia marcescens, mutations in an oxyR homolog and predicted fimbria structural genes were identified. S. marcescens oxyR mutants were severely impaired in biofilm formation, in contrast to the hyperbiofilm phenotype exhibited by oxyR mutants of Escherichia coli and Burkholderia pseudomallei. Further analysis revealed that OxyR plays a role in the primary attachment of cells to a surface. Similar to what is observed in other bacterial species, S. marcescens OxyR …

P27 Expression In Endothelin-1 Stimulated Mitogenesis, Joseph Kiriu

Masters Theses & Specialist Projects

Bovine corneal endothelial cells (BCECs) have been shown in our lab to synthesize and secrete endothelin-1 (ET-1). The endothelin-1 binds ETA receptors, this elevates intracellular calcium, stimulate DNA replication and cell division. This investigation explores ET-l's role as a mitogenic factor in corneal endothelial cells and addresses whether mitogenic activity is mediated through the cyclin dependent kinase inhibitor p27. BCEC were isolated from bovine eyes and grown in DMEM-10% serum in a 5% C02, 37° C incubator. Confluent cultures of BCEC were incubated for 24 hours with lOOnM Endothelin-1, luM BQ123 and BQ123 +100nM Endothelin-1 and some left untreated. Total …

Some Barriers To Development In Cameroon, Kenya And Swaziland, Matthew Moore

Masters Theses & Specialist Projects

In the study of development, researchers attempt to identify and measure the independent variables believed to influence economic growth and social development indicators in countries throughout the world. These researchers employ quantitative cross-national research methods, also known as the variable-oriented approach, while others may pursue a more case-oriented approach and examine a handful of countries employing a historical-comparative method. Education is a variable that has been identified in both of these research traditions to be positively related to the development of a country. However, when the effects of education on development are examined cross-nationally, it is clear that the countries …

The Whitehead Link On The Cubic Lattice, Elizabeth Haynes

Masters Theses & Specialist Projects

The cubic lattice is a graph in Â3 where the vertices are points with integer coordinates and edges are unit length line segments parallel to the x-, y-, or z-axis. A step is a line segment that connects one vertex to a neighboring vertex one unit away in the x-, y-, or z-direction. This thesis will show that the Whitehead Link needs at least 34 steps to be embedded on the cubic lattice.

Human Mst But Not Mt Responds To Tactile Stimulation, Michael S. Beauchamp, Nafi E. Yasar, Neel Kishan, Tony Ro

Publications and Research

Previous reports of tactile responses in human visual area MT/V5 have used complex stimuli, such as a brush stroking the arm. These complex moving stimuli are likely to induce imagery of visual motion, which is known to be a powerful activator of MT. The area described as “MT” in previous reports consists of at least two distinct cortical areas, MT and MST. Using functional magnetic resonance imaging, we separately localized human MT and MST and measured their response to vibrotactile stimuli unlikely to induce imagery of visual motion. Strong vibrotactile responses were observed in MST but not in MT. Vibrotactile …

A Second Large Plasmid Encodes Conjugative Transfer And Antimicrobial Resistance In O119:H2 And Some Typical O111 Enteropathogenic Escherichia Coli Strains, Adaobi I. Nwaneshiudu, Tania Mucci, Derek J. Pickard, Iruka N. Okeke

Student Papers, Posters & Projects

A novel and functional conjugative transfer system identified in O119:H2 enteropathogenic Escherichia coli (EPEC) strain MB80 by subtractive hybridization is encoded on a large multidrug resistance plasmid, distinct from the well-described EPEC adherence factor (EAF) plasmid. Variants of the MB80 conjugative resistance plasmid were identified in other EPEC strains, including the prototypical O111:NM strain B171, from which the EAF plasmid has been sequenced. This separate large plasmid and the selective advantage that it confers in the antibiotic era have been overlooked because it comigrates with the virulence plasmid on conventional gels.

The Role Of Nogo-A During Development Of The Chick Central Nervous System, Shelly A. Caltharp

Loma Linda University Electronic Theses, Dissertations & Projects

Nogo-A is a potent inhibitor of axon regeneration that is expressed by myelin forming oligodendrocytes of the adult central nervous system (CNS). However, neuronal expression of Nogo-A during development suggests an additional role. Little is known about the putative functions of Nogo-A during embryonic development. To examine its potential role we isolated and analyzed the Nogo-A sequence in the chick, we localized its mRNA expression pattern and cell-specific distribution during key phases of cortical development, and studied regulation of its expression during phases that showed promise of function based on expression patterns.

Our results revealed five previously undescribed Nogo-A specific …

Molecular Basis Of Resistance To Muramidase And Cationic Antimicrobial Peptide Activity Of Lysozyme In Staphylococci, Silvia Herbert, Agnieszka Bera, Christiane Nerz, Dirk Kraus, Andreas Peschel, Christiane Goerke, Michael Meehl, Ambrose Cheung, Friedrich Gotz

Dartmouth Scholarship

It has been shown recently that modification of peptidoglycan by O-acetylation renders pathogenic staphylococci resistant to the muramidase activity of lysozyme. Here, we show that a Staphylococcus aureus double mutant defective in O-acetyltransferase A (OatA), and the glycopeptide resistance-associated two-component system, GraRS, is much more sensitive to lysozyme than S. aureus with the oatA mutation alone. The graRS single mutant was resistant to the muramidase activity of lysozyme, but was sensitive to cationic antimicrobial peptides (CAMPs) such as the human lysozyme-derived peptide ₁₀₇R-A-W-V-A-W-R-N-R₁₁₅ (LP9), polymyxin B, or gallidermin. A comparative transcriptome analysis of wild …

Poor Knowledge--Predictor Of Nonadherence To Universal Precautions For Blood Borne Pathogens At First Level Care Facilities In Pakistan, Naveed Z. Janjua, Mahreen Razaq, Subhash Chandir, Shafquat Rozi, Bushra Mahmood

Community Health Sciences

Background: We conducted an assessment of knowledge about blood borne pathogens (BBP) and use of universal precautions at first level care facilities (FLCF) in two districts of Pakistan.Methods: We conducted a cross-sectional survey and selected three different types of FLCFs ; public, general practitioners and unqualified practitioners through stratified random sampling technique. At each facility, we interviewed a prescriber, a dispenser, and a housekeeper for knowledge of BBPs transmission and preventive practices, risk perception, and use of universal precautions. We performed multiple linear regression to assess the effect of knowledge score (11 items) on the practice of universal precautions score …

American Academy Of Allergy, Asthma & Immunology Work Group Report: Allergy Diagnosis In Clinical Practice, Dana V. Wallace, Sami L. Bahna, Stan Goldstein, Robert G. Hamilton, John R. Cohn

Department of Medicine Faculty Papers

No abstract provided.

Catecholaminergic Control Of Mitogen-Activated Protein Kinase Signaling In Paraventricular Neuroendocrine Neurons In Vivo And In Vitro: A Proposed Role During Glycemic Challenges, Arshad Khan, Todd Ponzio, Graciela Sanchez-Watts, B. Stanley, Glenn Hatton, Alan Watts

Selected Works Temporary Series

No abstract provided.

Phenotypic Alterations In Type Ii Alveolar Epithelial Cells In Cd4+ T Cell Mediated Lung Inflammation, Marcus Gereke, Lothar Gröbe, Silvia Prettin, Michael Kasper, Stefanie Deppenmeier, Achim D. Gruber, Richard I. Enelow, Jan Buer, Dunja Bruder

Dartmouth Scholarship

Although the contribution of alveolar type II epithelial cell (AEC II) activities in various aspects of respiratory immune regulation has become increasingly appreciated, our understanding of the contribution of AEC II transcriptosome in immunopathologic lung injury remains poorly understood. We have previously established a mouse model for chronic T cell-mediated pulmonary inflammation in which influenza hemagglutinin (HA) is expressed as a transgene in AEC II, in mice expressing a transgenic T cell receptor specific for a class II-restricted epitope of HA. Pulmonary inflammation in these mice occurs as a result of CD4+ T cell recognition of alveolar antigen. This model …