Medicine and Health Sciences Commons^™

Role Of Nono-Histone Interaction In Tnfα-Suppressed Prolyl-4-Hydroxylase Α1, Cheng Zhang, Ming-Xiang Zhang, Ying H Shen, Jared K Burks, Xiao-Nan Li, Scott A Lemaire, Koichi Yoshimura, Hiroki Aoki, Masunori Matsuzaki, Feng-Shuang An, David A Engler, Risë K Matsunami, Joseph S Coselli, Yun Zhang, Xing Li Wang

Faculty, Staff and Student Publications

Inflammation is a key process in cardiovascular diseases. The extracellular matrix (ECM) of the vasculature is a major target of inflammatory cytokines, and TNFalpha regulates ECM metabolism by affecting collagen production. In this study, we have examined the pathways mediating TNFalpha-induced suppression of prolyl-4 hydroxylase alpha1 (P4Halpha1), the rate-limiting isoform of P4H responsible for procollagen hydroxylation, maturation, and organization. Using human aortic smooth muscle cells, we found that TNFalpha activated the MKK4-JNK1 pathway, which induced histone (H) 4 lysine 12 acetylation within the TNFalpha response element in the P4Halpha1 promoter. The acetylated-H4 then recruited a transcription factor, NonO, which, in …

Structures And Functions Of The Normal And Injured Human Olfactory Epithelium, Jonathan P Schuermann, Jianwen Jiang, Jorge Cuellar, Oscar Llorca, Liping Wang, Luis E Gimenez, Suping Jin, Alexander B Taylor, Borries Demeler, Kevin A Morano, P John Hart, Jose M Valpuesta, Eileen M Lafer, Rui Sousa

Faculty, Staff and Student Publications

Hsp70s mediate protein folding, translocation, and macromolecular complex remodeling reactions. Their activities are regulated by proteins that exchange ADP for ATP from the nucleotide-binding domain (NBD) of the Hsp70. These nucleotide exchange factors (NEFs) include the Hsp110s, which are themselves members of the Hsp70 family. We report the structure of an Hsp110:Hsc70 nucleotide exchange complex. The complex is characterized by extensive protein:protein interactions and symmetric bridging interactions between the nucleotides bound in each partner protein's NBD. An electropositive pore allows nucleotides to enter and exit the complex. The role of nucleotides in complex formation and dissociation, and the effects of …

Correction: Molecular Subsets In The Gene Expression Signatures Of Scleroderma Skin, Ausra Milano, Sarah A. Pendergrass, Jennifer L. Sargent, Lacy K. George, Timothy H. Mccalmont, M. Kari Connolly, Michael L. Whitfield

Dartmouth Scholarship

Background: Scleroderma is a clinically heterogeneous disease with a complex phenotype. The disease is characterized by vascular dysfunction, tissue fibrosis, internal organ dysfunction, and immune dysfunction resulting in autoantibody production. Methodology and Findings: We analyzed the genome-wide patterns of gene expression with DNA microarrays in skin biopsies from distinct scleroderma subsets including 17 patients with systemic sclerosis (SSc) with diffuse scleroderma (dSSc), 7 patients with SSc with limited scleroderma (lSSc), 3 patients with morphea, and 6 healthy controls. 61 skin biopsies were analyzed in a total of 75 microarray hybridizations. Analysis by hierarchical clustering demonstrates nearly identical patterns of gene …

Freesurfer-Initiated Fully-Automated Subcortical Brain Segmentation In Mri Using Large Deformation Diffeomorphic Metric Mapping., Ali R Khan, Lei Wang, Mirza Faisal Beg

Brain and Mind Institute Researchers' Publications

Fully-automated brain segmentation methods have not been widely adopted for clinical use because of issues related to reliability, accuracy, and limitations of delineation protocol. By combining the probabilistic-based FreeSurfer (FS) method with the Large Deformation Diffeomorphic Metric Mapping (LDDMM)-based label-propagation method, we are able to increase reliability and accuracy, and allow for flexibility in template choice. Our method uses the automated FreeSurfer subcortical labeling to provide a coarse-to-fine introduction of information in the LDDMM template-based segmentation resulting in a fully-automated subcortical brain segmentation method (FS+LDDMM). One major advantage of the FS+LDDMM-based approach is that the automatically generated segmentations generated are …

A Pooled Analysis Of Two Placebo-Controlled Trials Of Desvenlafaxine In Major Depressive Disorder., Daniel Z Lieberman, Stuart A Montgomery, Karen A Tourian, Claudine Brisard, Gregory Rosas, Krishna Padmanabhan, Jean-Michel Germain, Bruno Pitrosky

Psychiatry and Behavioral Sciences Faculty Publications

The efficacy, safety, and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) were evaluated in two similarly designed, phase 3, randomized, double-blind, placebo-controlled, venlafaxine-extended-release-referenced, flexible-dose studies of outpatients with a primary diagnosis of major depressive disorder. Owing to a high placebo response, the individual studies were underpowered. Therefore, a post-hoc pooled analysis was performed (desvenlafaxine and placebo data were pooled; venlafaxine extended release data were not, owing to different flexible-dose regimens in the two studies). The primary outcome measure was the change from baseline on the 17-item Hamilton Rating Scale for Depression; the Clinical Global Impressions-Improvement item score was a secondary …

Pathways To Change: The Effect Of A Web Application On Treatment Interest., Daniel Z Lieberman, Suena H Massey

Psychiatry and Behavioral Sciences Faculty Publications

Most individuals with drinking problems do not receive treatment, generally because they do not perceive the need for it. It is difficult to access this population of problem drinkers in order to encourage treatment-seeking. A Web-based program was written, designed to increase motivation for change. The program guided non-treatment-seekers through a multi-stage assessment and provided them with feedback. The level of interest in treatment was measured pre-and post-intervention. Compared to baseline, after the intervention, significantly more individuals rated themselves "very interested" in participating in some form of traditional treatment (19% vs. 28%), and their focus on a specific modality increased.

Medical Students: Abuse Of Psychoactive Substances And Sexuality Aspects, Kepler Alencar Mendes Carvalho, Maria José Carvalho Sant'anna, Verônica Coates, Hatim A. Omar

Pediatrics Faculty Publications

University students aged 17 to 24 years of age are prone to many risk factors.

OBJECTIVES: Identify risk factors related to exploring sexuality and characteristics of consumption of psychoactive substances in students attending medical school.

METHODS: 465 Medical students from Santa Casa of São Paulo Faculty of Medical Sciences (FCMSCSP) were prospectively and transversely evaluated during 2005. An anonymous, semi-structured, self-filling questionnaire was used. The average age of the students was 21.5 years, 43% females. 76.2% preferred alcohol, and 11.1% tobacco consumption; chloroethane (lança-perfume) consumption occurred in 22.6% and 15.3% consumption of other types of illicit drugs, with marijuana as …

Medical Supervision Of Young Female Athletes Training In Complex Coordinational Sports, Irina Schevchenko, Viktor V. Abramov, Paul T Gibson, Hatim A. Omar

Pediatrics Faculty Publications

This article proposes simple medical criteria that can be used by trainers and others for effective medical supervision of young female athletes.

METHODS: The cross-sectional, age-stratified study compared girls 10-17 years of age involved in intensive training in gymnastic floor exercises, trampoline, or badminton. Each sport and/or control group was represented by 40-45 girls. Data included medical history, morphometric variables and observation of biological development.

RESULTS: Gymnasts started training earliest (approximately 5-years-old) and trained most intensely (18-20 h/wk), followed by trampolinists and then badmintonists. Height, weight, body mass index, and % body fat were reduced in athletes, with gymnasts showing …

Killing Of Human Melanoma Cells Induced By Activation Of Class I Interferon-Regulated Signaling Pathways Via Mda-7/Il-24, Suhendan Ekmekcioglu, John B Mumm, Malini Udtha, Sunil Chada, Elizabeth A Grimm

Faculty, Staff and Student Publications

Restoration of the tumor-suppression function by gene transfer of the melanoma differentiation-associated gene 7 (MDA7)/interleukin 24 (IL-24) successfully induces apoptosis in melanoma tumors in vivo. To address the molecular mechanisms involved, we previously revealed that MDA7/IL-24 treatment of melanoma cells down-regulates interferon regulatory factor (IRF)-1 expression and concomitantly up-regulates IRF-2 expression, which competes with the activity of IRF-1 and reverses the induction of IRF-1-regulated inducible nitric oxide synthase (iNOS). Interferons (IFNs) influence melanoma cell survival by modulating apoptosis. A class I IFN (IFN-alpha) has been approved for the treatment of advanced melanoma with some limited success. A class II IFN …

Functional Status, Heart Rate, And Rhythm Abnormalities In 521 Fontan Patients 6 To 18 Years Of Age., Andrew D. Blaufox, Lynn A. Sleeper, David J. Bradley, Roger E. Breitbart, Allan Hordof, Ronald J. Kanter, Elizabeth A. Stephenson, Mario Stylianou, Victoria L. Vetter, J Philip Saul, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Our objective was to determine the relationship between functional outcome and abnormalities of heart rate and rhythm after the Fontan operation.

METHODS: The National Heart, Lung, and Blood Institute Pediatric Heart Network conducted a cross-sectional analysis of patients who had undergone a Fontan procedure at the 7 network centers. Analysis was based on 521 patients with an electrocardiogram (n = 509) and/or bicycle exercise test (n = 404). The Child Health Questionnaire parent report and the oxygen consumption at the anaerobic threshold were used as markers of functional outcome.

RESULTS: Various Fontan procedures had been performed: intracardiac lateral tunnel …

Pcr-Based Assay Using Occult Blood Detection Cards For Detection Of Diarrheagenic Escherichia Coli In Specimens From Us Travelers To Mexico With Acute Diarrhea, Kevin A Grimes, Jamal A Mohamed, Herbert L Dupont, Ranjit S Padda, Zhi-Dong Jiang, Jose Flores, Jaime Belkind-Gerson, Francisco G Martinez-Sandoval, Pablo C Okhuysen

Faculty, Staff and Student Publications

Large field studies of travelers' diarrhea for multiple destinations are limited by the need to perform stool cultures on site in a timely manner. A method for the collection, transport, and storage of fecal specimens that does not require immediate processing and refrigeration and that is stable for months would be advantageous. This study was designed to determine if enterotoxigenic Escherichia coli (ETEC) and enteroaggregative E. coli (EAEC) DNA could be identified from cards that were processed for the evaluation of fecal occult blood. U.S. students traveling to Mexico during 2005 to 2007 were monitored for the occurrence of diarrheal …

The Temporal Relationship Between The Coronavirus Disease 2019 (Covid-19) Pandemic And Preterm Birth, Harold E Bedell, Mahalakshmi Ramamurthy, Saumil S Patel, Shobana Subramaniam, Lan-Phuong Vu-Yu, Jianliang Tong

Faculty, Staff and Student Publications

Despite rapid to-and-fro motion of the retinal image that results from their incessant involuntary eye movements, persons with infantile nystagmus (IN) rarely report the perception of motion smear. We performed two experiments to determine if the reduction of perceived motion smear in persons with IN is associated with an increase in the speed of the temporal impulse response. In Experiment 1, increment thresholds were determined for pairs of successively presented flashes of a long horizontal line, presented on a 65-cd/m2 background field. The stimulus-onset asynchrony (SOA) between the first and second flash varied from 5.9 to 234 ms. In experiment …

Obesity And Cardiac Metabolism In Women, Heinrich Taegtmeyer, Mohamed F Algahim

Faculty, Staff and Student Publications

No abstract provided.

Generalized Fuzzy Clustering For Segmentation Of Multi-Spectral Magnetic Resonance Images, Renjie He, Sushmita Datta, Balasrinivasa Rao Sajja, Ponnada A Narayana

Faculty, Staff and Student Publications

An integrated approach for multi-spectral segmentation of MR images is presented. This method is based on the fuzzy c-means (FCM) and includes bias field correction and contextual constraints over spatial intensity distribution and accounts for the non-spherical cluster's shape in the feature space. The bias field is modeled as a linear combination of smooth polynomial basis functions for fast computation in the clustering iterations. Regularization terms for the neighborhood continuity of intensity are added into the FCM cost functions. To reduce the computational complexity, the contextual regularizations are separated from the clustering iterations. Since the feature space is not isotropic, …

Beta3 Integrin Haplotype Influences Gene Regulation And Plasma Von Willebrand Factor Activity, Katie E. Payne, Paul F. Bray, Peter J. Grant, Angela M. Carter

Department of Medicine Faculty Papers

The Leu33Pro polymorphism of the gene encoding beta(3) integrin (ITGB3) is associated with acute coronary syndromes and influences platelet aggregation. Three common promoter polymorphisms have also been identified. The aims of this study were to (1) investigate the influence of the ITGB3 -400C/A, -425A/C and -468G/A promoter polymorphisms on reporter gene expression and nuclear protein binding and (2) determine genotype and haplotype associations with platelet alpha(IIb)beta(3) receptor density. Promoter haplotypes were introduced into an ITGB3 promoter-pGL3 construct by site directed mutagenesis and luciferase reporter gene expression analysed in HEL and HMEC-1 cells. Binding of nuclear proteins was assessed by electrophoretic …

Enterotoxin Preconditioning Restores Calcium-Sensing Receptor-Mediated Cytostasis In Colon Cancer Cells, Giovanni Mario Pitari, Jieru E. Lin, Fawad J. Shah, Wilhelm J. Lubbe, David Zuzga, Peng Li, Stephanie Schulz, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Guanylyl cyclase C (GCC), the receptor for diarrheagenic bacterial heat-stable enterotoxins (STs), inhibits colorectal cancer cell proliferation by co-opting Ca(2+) as the intracellular messenger. Similarly, extracellular Ca(2+) (Ca(2+)(o)) opposes proliferation and induces terminal differentiation in intestinal epithelial cells. In that context, human colon cancer cells develop a phenotype characterized by insensitivity to cytostasis imposed by Ca(2+)(o). Here, preconditioning with ST, mediated by GCC signaling through cyclic nucleotide-gated channels, restored Ca(2+)(o)-dependent cytostasis, reflecting posttranscriptional regulation of calcium-sensing receptors (CaRs). ST-induced GCC signaling deployed CaRs to the surface of human colon cancer cells, whereas elimination of GCC signaling in mice nearly abolished …

Role Played By Serum, A Biological Cue, In The Adherence Of Enterococcus Faecalis To Extracellular Matrix Proteins, Collagen, Fibrinogen, And Fibronectin, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

BACKGROUND: Most previous studies have found that Enterococcus faecalis isolates do not show significant adherence to fibronectin and fibrinogen.

METHODS: The influence of various conditions on E. faecalis adherence to extracellular matrix (ECM) proteins was evaluated using a radiolabeled-cell adherence assay.

RESULTS: Among the conditions studied, growth in 40% horse serum (a biological cue with potential clinical relevance) elicited adherence of all 46 E. faecalis strains tested to fibronectin and fibrinogen but not to elastin; adherence levels were independent of strain source, and adherence was eliminated by treating cells with trypsin. As previously reported, serum also elicited adherence to collagen. …

Blood Utilization In Children Managed Non-Operatively For Blunt Solid Organ Injury., Scott J. Keckler, Kuojen Tsao, Susan W. Sharp, G W. Holcomb Iii, Daniel J. Ostlie, Shawn D. St Peter

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Blood product utilization is an important issue in health care, given the frequent shortages in hospitals and the societal burden required to maintain the supply. Therefore, we retrospectively audited our blunt spleen/liver trauma experience to determine the percentage of cross-matched blood that was transfused to see whether more stringent typing criteria should be applied.

METHODS: A retrospective analysis of a recent 7-year experience with nonoperative management in patients with blunt spleen or liver injury was performed. Demographics, packed red blood cells prepared by cross-match, and transfusions were measured. Unmatched, O-type blood given in the trauma bay was excluded. Patients …

Management Of Pediatric Acute Appendicitis In The Computed Tomographic Era., Kuojen Tsao, Shawn D. St Peter, Patricia A. Valusek, Troy L. Spilde, Scott J. Keckler, Abhilash Nair, Daniel J. Ostlie, G W. Holcomb Iii

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND/PURPOSE: The treatment options for complicated appendicitis in children continue to evolve. Optimal management of complicated appendicitis relies on an accurate preoperative diagnosis. We examined the accuracy of our preoperative diagnosis including computed tomography (CT) and the influence on the management of children with perforated and nonperforated appendicitis.

METHODS: Following IRB approval, a 6-year review of all patients that underwent an appendectomy for suspected appendicitis was performed. Treatments included immediate operations and initial nonoperative management (antibiotic therapy +/- percutaneous drainage of abscess). Appendicitis was confirmed by histological examination.

RESULTS: One thousand seventy-eight patients underwent appendectomy for suspected appendicitis. Preoperative CT …

Clinical Features And Management Of Autoimmune Hepatitis, Edward L. Krawitt

Dartmouth Scholarship

Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology which can progress to cirrhosis. Its clinical manifestations are highly variable and sometimes follow a fluctuating course. Diagnosis is based on characteristic histologic, clinical, biochemical and serological findings. Anti-inflammatory/immunosuppressive treatment frequently induces remission but long-term maintenance therapy is often required. Liver transplantation is generally successful in patients with decompensated cirrhosis unresponsive to or intolerant of medical therapy.

Spatiotemporal Postural Control Deficits Are Present In Those With Chronic Ankle Instability, Patrick O. Mckeon, Jay Hertel

Physical Therapy Faculty Publications

BACKGROUND: Postural control deficits have been purported to be a potential contributing factor in chronic ankle instability (CAI). Summary forceplate measures such as center of pressure velocity and area have not consistently detected postural control deficits associated with CAI. A novel measurement technique derived from the dynamical systems theory of motor control known as Time-to-boundary (TTB) has shown promise in detecting deficits in postural control related to chronic ankle instability (CAI). In a previous study, TTB deficits were detected in a sample of females with CAI. The purpose of this study was to examine postural control in sample of males …

Effects Of Acute Ethyl Alcohol Consumption On A Psychophysical Measure Of Lateral Inhibition In Human Vision., Kevin D Johnston, Brian Timney

Brain and Mind Institute Researchers' Publications

Acute consumption of ethyl alcohol affects a variety of visual functions. However, there have been few systematic attempts to investigate the neural mechanisms underlying these effects. Here, we employed the Westheimer paradigm to investigate the hypothesis that alcohol reduces lateral inhibition within human "perceptive fields", the psychophysical analogue of physiological receptive fields. Westheimer functions obtained under alcohol and no-alcohol conditions at photopic, mesopic, and scotopic levels of adaptation showed changes consistent with an alcohol-induced decrease in lateral inhibition. We conclude that this decrease in lateral inhibition may be responsible for some of the changes in visual perception that result from …

Nerve Growth Factor Regulation Of Cyclin D1 In Pc12 Cells Through A P21ras Extracellular Signal-Regulated Kinase Pathway Requires Cooperative Interactions Between Sp1 And Nuclear Factor-Kappab., Francesco Marampon, Mathew C Casimiro, Maofu Fu, Michael J Powell, Vladimir M Popov, Jaime Lindsay, Bianca M Zani, Carmela Ciccarelli, Genichi Watanabe, Richard J Lee, Richard G Pestell

Department of Cancer Biology Faculty Papers

The PC12 pheochromocytoma cell line responds to nerve growth factor (NGF) by exiting from the cell cycle and differentiating to induce extending neurites. Cyclin D1 is an important regulator of G1/S phase cell cycle progression, and it is known to play a role in myocyte differentiation in cultured cells. Herein, NGF induced cyclin D1 promoter, mRNA, and protein expression via the p21(RAS) pathway. Antisense- or small interfering RNA to cyclin D1 abolished NGF-mediated neurite outgrowth, demonstrating the essential role of cyclin D1 in NGF-mediated differentiation. Expression vectors encoding mutants of the Ras/mitogen-activated protein kinase pathway, and chemical inhibitors, demonstrated NGF …

Primary Care Physicians And Insulin Initiation: Multiple Barriers, Lack Of Knowledge Or Both?, Serge Jabbour, Md, Facp, Face

Department of Medicine Faculty Papers

Primary care physicians (PCPs) provide diabetes care for 82% of patients with type 2 diabetes (1). Many patients with type 2 diabetes will eventually need insulin. The UKPDS (2) showed that ß-cell failure is progressive. From 50% of normal ß-cell function present at diagnosis, there is a steady decline with almost complete loss of ß-cell mass within 10-15 years, even earlier in some patients. On average, as many as 40-80% of patients with type 2 diabetes will need insulin within 10 years after diagnosis (1,2). These statistics can vary between patients and depending on the different agents used after the …

Usefulness Of Baseline Lipids And C-Reactive Protein In Women Receiving Menopausal Hormone Therapy As Predictors Of Treatment-Related Coronary Events., Paul Bray, Joseph C Larson, Andrea Z Lacroix, Joann Manson, Marian C Limacher, Jacques E Rossouw, Norman L Lasser, William E Lawson, Marcia L Stefanick, Robert D Langer, Karen L Margolis

Cardeza Foundation for Hematologic Research

Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women's Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen …

Resource Utilization And Outcomes From Percutaneous Drainage And Interval Appendectomy For Perforated Appendicitis With Abscess., Scott J. Keckler, Kuojen Tsao, Susan W. Sharp, Daniel J. Ostlie, G W. Holcomb Iii, Shawn D. St Peter

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Given the perceived technical demands of laparoscopic appendectomy and the expected postoperative morbidity in patients with a well-defined abscess, initial percutaneous drainage has become an attractive option in this patient population. This strategy allows for a laparoscopic appendectomy to be performed in an elective manner at the convenience of the surgeon. However, the medical burden on the patient and on the quality of patient outcomes has not been described in the literature. Therefore, we audited our experience with initial percutaneous drainage followed by laparoscopic interval appendectomy to evaluate the need for a prospective trial.

METHODS: After institutional review board …

Single Daily Dosing Ceftriaxone And Metronidazole Vs Standard Triple Antibiotic Regimen For Perforated Appendicitis In Children: A Prospective Randomized Trial., Shawn D. St Peter, Kuojen Tsao, Troy L. Spilde, G W. Holcomb Iii, Susan W. Sharp, J Patrick Murphy, Charles L. Snyder, Ronald J. Sharp, Walter S. Andrews, Daniel J. Ostlie

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Appendicitis is the most common emergency condition in children. Historically, a 3-drug regimen consisting of ampicillin, gentamicin, and clindamycin (AGC) has been used postoperatively for perforated appendicitis. A retrospective review at our institution has found single day dosing of ceftriaxone and metronidazole (CM) to be a more simple and cost-effective antibiotic strategy. Therefore, we performed a prospective, randomized trial to compare efficacy and cost-effectiveness of these 2 regimens.

METHODS: After internal review board approval (IRB no. 04 12-149), children found to have perforated appendicitis at appendectomy were randomized to either once daily dosing of CM (2 total doses per …

A New Model For Hemoglobin Ingestion And Transport By The Human Malaria Parasite Plasmodium Falciparum., Michelle D Lazarus, Timothy G Schneider, Theodore F Taraschi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The current model for hemoglobin ingestion and transport by intraerythrocytic Plasmodium falciparum malaria parasites shares similarities with endocytosis. However, the model is largely hypothetical, and the mechanisms responsible for the ingestion and transport of host cell hemoglobin to the lysosome-like food vacuole (FV) of the parasite are poorly understood. Because actin dynamics play key roles in vesicle formation and transport in endocytosis, we used the actin-perturbing agents jasplakinolide and cytochalasin D to investigate the role of parasite actin in hemoglobin ingestion and transport to the FV. In addition, we tested the current hemoglobin trafficking model through extensive analysis of serial …

Rtr1 Is The Saccharomyces Cerevisiae Homolog Of A Novel Family Of Rna Polymerase Ii-Binding Proteins, Patrick A Gibney, Thomas Fries, Susanne M Bailer, Kevin A Morano

Faculty, Staff and Student Publications

Cells must rapidly sense and respond to a wide variety of potentially cytotoxic external stressors to survive in a constantly changing environment. In a search for novel genes required for stress tolerance in Saccharomyces cerevisiae, we identified the uncharacterized open reading frame YER139C as a gene required for growth at 37 degrees C in the presence of the heat shock mimetic formamide. YER139C encodes the closest yeast homolog of the human RPAP2 protein, recently identified as a novel RNA polymerase II (RNAPII)-associated factor. Multiple lines of evidence support a role for this gene family in transcription, prompting us to rename …

Neuromyelitis Optica Pathogenesis And Aquaporin 4, David J. Graber, Michael Levy, Douglas Kerr, William F. Wade

Dartmouth Scholarship

Neuromyelitis optica (NMO) is a severe, debilitating human disease that predominantly features immunopathology in the optic nerves and the spinal cord. An IgG1 autoantibody (NMO-IgG) that binds aquaporin 4 (AQP4) has been identified in the sera of a significant number of NMO patients, as well as in patients with two related neurologic conditions, bilateral optic neuritis (ON), and longitudinal extensive transverse myelitis (LETM), that are generally considered to lie within the NMO spectrum of diseases. NMO-IgG is not the only autoantibody found in NMO patient sera, but the correlation of pathology in central nervous system (CNS) with tissues that normally …