Digital Commons Network^™

Human Cytomegalovirus-Encoded Pul7 Is A Novel Ceacam1-Like Molecule Responsible For Promotion Of Angiogenesis., Jason D. Macmaniman, Andrew Meuser, Sara Botto, Patricia P. Smith, Fenyong Liu, Michael A. Jarvis, Jay A. Nelson, Patrizia Caposio

School of Biomedical Sciences

UNLABELLED: Persistent human cytomegalovirus (HCMV) infection has been linked to several diseases, including atherosclerosis, transplant vascular sclerosis (TVS), restenosis, and glioblastoma. We have previously shown that factors secreted from HCMV-infected cells induce angiogenesis and that this process is due, at least in part, to increased secretion of interleukin-6 (IL-6). In order to identify the HCMV gene(s) responsible for angiogenesis promotion, we constructed a large panel of replication-competent HCMV recombinants. One HCMV recombinant deleted for UL1 to UL10 was unable to induce secretion of factors necessary for angiogenesis. Fine mapping using additional HCMV recombinants identified UL7 as a viral gene required …

A Case Of Cutaneous Larva Migrans Presenting In A Pregnant Patient., Kasie Kudrewicz, Kylee N Crittenden, Alison Himes

Women’s Health Articles

Cutaneous larva migrans (CLM) is a pruritic dermatitis caused by migration of the animal hookworm larvae into the epidermis. We present a case of CLM in a 31-year-old pregnant woman. The treatment of CLM relies on antihelminthic agents, such as thiabendazole, albendazole, and ivermectin. This case was interesting in that the standard treatment options previously mentioned were contraindicated owing to the patient's pregnancy. Cryotherapy with liquid nitrogen resulted in complete resolution of her lesion and symptoms.

Successful Mdr-Tb Treatment Regimens Including Amikacin Are Associated With High Rates Of Hearing Loss, Chawangwa Modongo, Rafal S. Sobota, Boikobo Kesenogile, Ronald Ncube

Dartmouth Scholarship

Aminoglycosides are a critical component of multidrug-resistant tuberculosis (MDR-TB) treatment but data on their efficacy and adverse effects in Botswana is scarce. We determined the effect of amikacin on treatment outcomes and development of hearing loss in MDR-TB patients. Patients started on MDR-TB treatment between 2006 and 2012 were included. Multivariate analysis was used to determine the effect of amikacin on treatment outcomes and development of hearing loss.

Self-Reported Memory Complaints: Implications From A Longitudinal Cohort With Autopsies, Richard J. Kryscio, Erin L. Abner, Gregory E. Cooper, David W. Fardo, Greg A. Jicha, Peter T. Nelson, Charles D. Smith, Linda J. Van Eldik, Lijie Wan, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE: We assessed salience of subjective memory complaints (SMCs) by older individuals as a predictor of subsequent cognitive impairment while accounting for risk factors and eventual neuropathologies.

METHODS: Subjects (n = 531) enrolled while cognitively intact at the University of Kentucky were asked annually if they perceived changes in memory since their last visit. A multistate model estimated when transition to impairment occurred while adjusting for intervening death. Risk factors affecting the timing and probability of an impairment were identified. The association between SMCs and Alzheimer-type neuropathology was assessed from autopsies (n = 243).

RESULTS: SMCs were …

Musculoskeletal Safety Outcomes Of Patients Receiving Daptomycin With Hmg-Coa Reductase Inhibitors, Christopher M. Bland, P Brandon Bookstaver, Z Kevin Lu, Brianne L. Dunn, Kathey Fulton Rumley

Faculty Publications

Daptomycin, a cyclic lipopeptide antibiotic, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are commonly administered in the inpatient setting and are associated with creatine phosphokinase (CPK) elevations, myalgias, and muscle weakness. Safety data for coadministration of daptomycin with statins are limited. To determine the safety of coadministration of daptomycin with statin therapy, a multicenter, retrospective, observational study was performed at 13 institutions in the Southeastern United States. Forty-nine adult patients receiving statins concurrently with daptomycin were compared with 171 patients receiving daptomycin without statin therapy. Detailed information, including treatment indication and duration, infecting pathogen, baseline and subsequent CPK levels, and …

Myeloid Derived Hypoxia Inducible Factor 1-Alpha Is Required For Protection Against Pulmonary Aspergillus Fumigatus Infection, Kelly M. Shepardson, Anupam Jhingran, Alayna Caffrey, Joshua J. Obar, Benjamin T. Suratt, Brent L. Berwin, Tobias M. Hohl, Robert A. Cramer

Dartmouth Scholarship

Hypoxia inducible factor 1α (HIF1α) is the mammalian transcriptional factor that controls metabolism, survival, and innate immunity in response to inflammation and low oxygen. Previous work established that generation of hypoxic microenvironments occurs within the lung during infection with the human fungal pathogen Aspergillus fumigatus. Here we demonstrate that A. fumigatus stabilizes HIF1α protein early after pulmonary challenge that is inhibited by treatment of mice with the steroid triamcinolone. Utilizing myeloid deficient HIF1α mice, we observed that HIF1α is required for survival and fungal clearance early following pulmonary challenge with A. fumigatus. Unlike previously reported research with bacterial …

Life History And Demographic Drivers Of Reservoir Competence For Three Tick-Borne Zoonotic Pathogens, Richard S. Ostfeld, Taal Levi, Anna E. Jolles, Lynn B. Martin, Parviez R. Hosseini, Felicia Keesing

Integrative Biology Faculty and Staff Publications

Animal and plant species differ dramatically in their quality as hosts for multi-host pathogens, but the causes of this variation are poorly understood. A group of small mammals, including small rodents and shrews, are among the most competent natural reservoirs for three tick-borne zoonotic pathogens, Borrelia burgdorferi, Babesia microti, and Anaplasma phagocytophilum, in eastern North America. For a group of nine commonly-infected mammals spanning >2 orders of magnitude in body mass, we asked whether life history features or surrogates for (unknown) encounter rates with ticks, predicted reservoir competence for each pathogen. Life history features associated with a fast pace …

Assessing Climate Variability Effects On Dengue Incidence In San Juan, Puerto Rico, Pablo Méndez-Lázaro, Frank E. Muller-Karger, Daniel Otis, Matthew J Mccarthy, Marisol Peña-Orellana

Marine Science Faculty Publications

We test the hypothesis that climate and environmental conditions are becoming favorable for dengue transmission in San Juan, Puerto Rico. Sea Level Pressure (SLP), Mean Sea Level (MSL), Wind, Sea Surface Temperature (SST), Air Surface Temperature (AST), Rainfall, and confirmed dengue cases were analyzed. We evaluated the dengue incidence and environmental data with Principal Component Analysis, Pearson correlation coefficient, Mann-Kendall trend test and logistic regressions. Results indicated that dry days are increasing and wet days are decreasing. MSL is increasing, posing higher risk of dengue as the perimeter of the San Juan Bay estuary expands and shorelines move inland. Warming …

Diagnosis-Specific Readmission Risk Prediction Using Electronic Health Data: A Retrospective Cohort Study, Courtney Hebert, Chaitanya Shivade, Randi Foraker, Jared Wasserman, Caryn Roth, Hagop Mekhjan, Stanley Lemeshow, Peter Embi

Dartmouth Scholarship

Background: Readmissions after hospital discharge are a common occurrence and are costly for both hospitals and patients. Previous attempts to create universal risk prediction models for readmission have not met with success. In this study we leveraged a comprehensive electronic health record to create readmission-risk models that were institution- and patient- specific in an attempt to improve our ability to predict readmission. Methods: This is a retrospective cohort study performed at a large midwestern tertiary care medical center. All patients with a primary discharge diagnosis of congestive heart failure, acute myocardial infarction or pneumonia over a two-year time period were …

Rules And Values: A Coordinated Regulatory And Educational Approach To The Public Health Crises Of Chronic Pain And Addiction, Joanna G. Katzman, George D. Comerci, Michael Landen, Larry Loring, Steven M. Jenkusky, Sanjeev Arora, Summers Kalishman, Lisa Marr, Chris Camarata, Daniel Duhigg, Jennifer Dillow, Eugene Koshkin, Denise E. Taylor, Cynthia M A Geppert

Project ECHO Bibliography

Chronic pain and opioid addiction are 2 pressing public health problems, and prescribing clinicians often lack the skills necessary to manage these conditions. Our study sought to address the benefits of a coalition of an academic medical center pain faculty and government agencies in addressing the high unintentional overdose death rates in New Mexico. New Mexico's 2012-2013 mandated chronic pain and addiction education programs studied more than 1000 clinicians. Positive changes were noted in precourse and postcourse surveys of knowledge, self-efficacy, and attitudes. Controlled substance dispensing data from the New Mexico Board of Pharmacy also demonstrated safer prescribing. The total …

Expanding The Scope And Relevance Of Health Interventions: Moving Beyond Clinical Trials And Behavior Change Models, Khary K. Rigg, Hilary H. Cook, John W. Murphy

Mental Health Law & Policy Faculty Publications

An overemphasis on clinical trials and behavior change models has narrowed the knowledge base that can be used to design interventions. The overarching point is that the process of overanalyzing variables is impeding the process of gaining insight into the everyday experiences that shape how people define health and seek treatment. This claim is especially important to health decision-making and behavior change because subtle interpretations often influence the decisions that people make. This manuscript provides a critique of traditional approaches to developing health interventions, and theoretically justifies what and why changes are warranted. The limited scope of these models is …

Host Species Restriction Of Middle East Respiratory Syndrome Coronavirus Through Its Receptor, Dipeptidyl Peptidase 4, Neeltje Van Doremalen, Kerri L. Miazgowicz, Shauna Milne-Price, Trenton Bushmaker, Shelly Robertson, Dana Scott, Joerg Kinne, Jason S. Mclellan

Dartmouth Scholarship

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and …

A Global Compendium Of Human Dengue Virus Occurrence, Jane P. Messina, Oliver J Brady, David M. Pigott, John S. Brownstein, Anne Hoen, Simon Hay

Dartmouth Scholarship

A global geographic database of human dengue virus occurrence was produced to generate a global risk map and associated burden estimates1. Herein we present the database, which comprises occurrence data linked to point or polygon locations, derived from peer-reviewed literature and case reports as well as informal online sources. Entries date from 1960 to 2012. We describe all data collection processes in full, as well as geo-positioning, database management and quality-control procedures. This is the most comprehensive database of confirmed human dengue infection to-date, consisting of 8,309 geo-positioned occurrences in total.

Interventions To Improve Delivery Of Isoniazid Preventive Therapy: An Overview Of Systematic Reviews, Lisa V. Adams, Elizabeth A. Talbot, Karen Odato, Heather Blunt, Karen R. Steingart

Dartmouth Scholarship

Background:

Uptake of isoniazid preventive therapy (IPT) to prevent tuberculosis has been poor, particularly in the highest risk populations. Interventions to improve IPT delivery could promote implementation. The large number of existing systematic reviews on treatment adherence has made drawing conclusions a challenge. To provide decision makers with the evidence they need, we performed an overview of systematic reviews to compare different organizational interventions to improve IPT delivery as measured by treatment completion among those at highest risk for the development of TB disease, namely child contacts or HIV-infected individuals.

Methods:

We searched the Cochrane Database of Systematic Reviews, the …

Performance Of The Oraquick Hcv Rapid Antibody Test For Screening Exposed Patients In A Hepatitis C Outbreak Investigation, Fengxiang Gao, Elizabeth A. Talbot, Carol H. Loring, Jill J. Power, Jodie Dionne-Odom

Dartmouth Scholarship

During a nosocomial hepatitis C outbreak, emergency public clinics employed the OraQuick HCV rapid antibody test on site, and all results were verified by a standard enzyme immunoassay (EIA). Of 1,157 persons, 1,149 (99.3%) exhibited concordant results between the two tests (16 positive, 1,133 negative). The sensitivity, specificity, positive predictive value, and negative predictive value were 94.1%, 99.5%, 72.7%, and 99.9%, respectively. OraQuick performed well as a screening test during an outbreak investigation and could be integrated into future hepatitis C virus (HCV) outbreak testing algorithms.

A Dna Microarray-Based Assay To Detect Dual Infection With Two Dengue Virus Serotypes, Alvaro Diaz-Badillo, María De Lourdes Muñoz, Gerardo Pérez-Ramírez, Victor Altuzar, Juan Burgueño, Julio G. Mendoza-Alvarez, Jorge P. Martínez-Muñoz, Alejandro Cisneros, Joel Navarrete-Espinosa, Feliciano Sanchez-Sinencio

School of Medicine Publications

Here; we have described and tested a microarray based-method for the screening of dengue virus (DENV) serotypes. This DNA microarray assay is specific and sensitive and can detect dual infections with two dengue virus serotypes and single-serotype infections. Other methodologies may underestimate samples containing more than one serotype. This technology can be used to discriminate between the four DENV serotypes. Single-stranded DNA targets were covalently attached to glass slides and hybridised with specific labelled probes. DENV isolates and dengue samples were used to evaluate microarray performance. Our results demonstrate that the probes hybridized specifically to DENV serotypes; with no detection …

Integrated Assessment Of Predicted Mhc Binding And Cross-Conservation With Self Reveals Patterns Of Viral Camouflage, Lu He, Anne S. De Groot, Andres H. Gutierrez, William D. Martin, Lenny Moise, Chris Bailey-Kellogg

Dartmouth Scholarship

Immune recognition of foreign proteins by T cells hinges on the formation of a ternary complex sandwiching a constituent peptide of the protein between a major histocompatibility complex (MHC) molecule and a T cell receptor (TCR). Viruses have evolved means of "camouflaging" themselves, avoiding immune recognition by reducing the MHC and/or TCR binding of their constituent peptides. Computer-driven T cell epitope mapping tools have been used to evaluate the degree to which articular viruses have used this means of avoiding immune response, but most such analyses focus on MHC-facing ‘agretopes'. Here we set out a new means of evaluating the …

Gene And Protein Sequence Optimization For High-Level Production Of Fully Active And Aglycosylated Lysostaphin In Pichia Pastoris, Hongliang Zhao, Kristina Blazanovic, Yoonjoo Choi, Chris Bailey-Kellogg, Karl E. Griswold

Dartmouth Scholarship

Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant Staphylococcus aureus (MRSA). However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. The first barrier can …

The Spectrum Of Eye Disease In Hospitalized Adults Living With Hiv, 1995-2010., Christopher Miller, William Short, Md, Mph, Lorena Perez-Povis, Josephine Lontok, Christopher Fecarotta, Mengdan Liu, Jocelyn Sendecki, Katherine Belden

Department of Medicine Faculty Papers

Eye disease is a well-documented complication of HIV infection. Opportunistic infections generally comprised the majority of pre-antiretroviral therapy (ART) eye complications. With the introduction of ART, opportunistic infections diminished. However, early ART regimens were cumbersome regarding side effects and pill burden, making patient compliance difficult. Newer ART regimens are better tolerated and consist of fewer pills, theoretically making compliance easier and therapy more effective. The aim of this chart review study is to examine eye disease epidemiology in HIV patients as ART has evolved. We reviewed 222 admissions at Thomas Jefferson University Hospitals for 188 patients. These cases were divided …

Acute Cranial Neuropathies Heralding Neurosyphilis In Human Immunodeficiency Virus-Infected Patient., Saeed Alqahtani

Neurology Faculty Publications

No abstract provided.

Baseline Natural Killer And T Cell Populations Correlation With Virologic Outcome After Regimen Simplification To Atazanavir/Ritonavir Alone (Actg 5201)., John E Mckinnon, Robbie B Mailliard, Susan Swindells, Timothy J Wilkin, Luann Borowski, Jillian M Roper, + 5 More

Medicine Faculty Publications

OBJECTIVES: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification.

METHODS: Thirty-four participants with virologic suppression ≥ 48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient …

Day-To-Day Fluctuation Of Point-Of-Care Circulating Cathodic Antigen Test Scores And Faecal Egg Counts In Children Infected With Schistosoma Mansoni In Ethiopia, Abraham Degarege, Mengistu Legesse, Girmay Medhin, Tilahun Teklehaymanot, Berhanu Erko

Journal Articles: Epidemiology

BACKGROUND: Determining the variation of circulating cathodic antigen (CCA) in urine and egg counts variation in stool between days in Schistosoma mansoni (S. mansoni) infected individuals is vital to decide whether or not to rely on a single-sample test for diagnosis of Schistosomiasis. In this study, the magnitude of day-to-day variation in urine-CCA test scores and in faecal egg counts was evaluated in school children in Ethiopia.

METHODS: A total of 620 school children (age 8 to 12 years) were examined for S. mansoni infection using double Kato-Katz and single urine-CCA cassette methods (batch 32727) on three consecutive days.

RESULTS: …

Broad And Direct Interaction Between Tlr And Siglec Families Of Pattern Recognition Receptors And Its Regulation By Neu1., Guo-Yun Chen, Nicholas K. Brown, Wei Wu, Zahra Khedri, Hai Yu, Xi Chen, Diantha Van De Vlekkert, Alessandra D'Azzo, Pan Zheng, Yang Liu

Pediatrics Faculty Publications

Both pathogen- and tissue damage-associated molecular patterns induce inflammation through toll-like receptors (TLRs), while sialic acid-binding immunoglobulin superfamily lectin receptors (Siglecs) provide negative regulation. Here we report extensive and direct interactions between these pattern recognition receptors. The promiscuous TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F. Mouse Siglec-G did not show appreciable binding to any TLRs tested. Correspondingly, Siglece deletion enhanced dendritic cell responses to all microbial TLR ligands tested, while Siglecg deletion did not affect the responses to these ligands. TLR4 activation triggers Neu1 translocation to cell surface to disrupt TLR4:Siglec-E interaction. Conversely, sialidase inhibitor Neu5Gc2en prevented TLR4 ligand-induced …

Hiv Testing Implementation In Two Urban Cities: Practice, Policy, And Perceived Barriers., Camden J Hallmark, Jennifer Skillicorn, Thomas P Giordano, Jessica A Davila, Marlene Mcneese, Nestor Rocha, Avemaria Smith, Stacey Cooper, Amanda D. Castel

Epidemiology Faculty Publications

BACKGROUND: Although funding has supported the scale up of routine, opt-out HIV testing in the US, variance in implementation mechanisms and barriers in high-burden jurisdictions remains unknown.

METHODS: We conducted a survey of health care organizations in Washington, DC and Houston/Harris County to determine number of HIV tests completed in 2011, policy and practices associated with HIV testing, funding mechanisms, and reported barriers to testing in each jurisdiction and to compare results between jurisdictions.

RESULTS: In 2012, 43 Houston and 35 DC HIV-testing organizations participated in the survey. Participants represented 85% of Department of Health-supported testers in DC and 90% …

Plagiarism Of Ideas. Benjamin Rush And Charles Caldwell--A Student-Mentor Dispute, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Strong Relationship Between Oral Dose And Tenofovir Hair Levels In A Randomized Trial: Hair As A Potential Adherence Measure For Pre-Exposure Prophylaxis (Prep)., Albert Y. Liu, Qiyun Yang, Yong Huang, Peter Bacchetti, Peter L. Anderson, Chengshi Jin, Kathy Goggin, Kristefer Stojanovski, Robert Grant, Susan P. Buchbinder, Ruth M. Greenblatt, Monica Gandhi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pre-exposure prophylaxis (PrEP) trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults.

METHODS: A …

Development Of A Prototype Lateral Flow Immunoassay (Lfi) For The Rapid Diagnosis Of Melioidosis., Raymond L. Houghton, Dana E. Reed, Mark A. Hubbard, Michael J. Dillon, Hongjing Chen, Bart J. Currie, Mark Mayo, Derek S. Sarovich, Vanessa Theobald, Direk Limmathurotsakul, Gumphol Wongsuvan, Narisara Chantratita, Sharon J. Peacock, Alex R. Hoffmaster, Brea Duval, Paul J. Brett, Mary N. Burtnick, David P. Aucoin

Peninsula Medical School

Burkholderia pseudomallei is a soil-dwelling bacterium and the causative agent of melioidosis. Isolation of B. pseudomallei from clinical samples is the "gold standard" for the diagnosis of melioidosis; results can take 3-7 days to produce. Alternatively, antibody-based tests have low specificity due to a high percentage of seropositive individuals in endemic areas. There is a clear need to develop a rapid point-of-care antigen detection assay for the diagnosis of melioidosis. Previously, we employed In vivo Microbial Antigen Discovery (InMAD) to identify potential B. pseudomallei diagnostic biomarkers. The B. pseudomallei capsular polysaccharide (CPS) and numerous protein antigens were identified as potential …

Galleria Mellonella Infection Model Demonstrates High Lethality Of St69 And St127 Uropathogenic E. Coli., Majed F. Alghoribi, Tarek M. Gibreel, Andrew R. Dodgson, Scott A. Beatson, Mathew Upton

School of Biomedical Sciences

Galleria mellonella larvae are an alternative in vivo model for investigating bacterial pathogenicity. Here, we examined the pathogenicity of 71 isolates from five leading uropathogenic E. coli (UPEC) lineages using G. mellonella larvae. Larvae were challenged with a range of inoculum doses to determine the 50% lethal dose (LD50) and for analysis of survival outcome using Kaplan-Meier plots. Virulence was correlated with carriage of a panel of 29 virulence factors (VF). Larvae inoculated with ST69 and ST127 isolates (10(4) colony-forming units/larvae) showed significantly higher mortality rates than those infected with ST73, ST95 and ST131 isolates, killing 50% of the larvae …

The Complete Genome Sequence Of Escherichia Coli Ec958: A High Quality Reference Sequence For The Globally Disseminated Multidrug Resistant E. Coli O25b:H4-St131 Clone., Brian M. Forde, Zakour Nl Ben, Mitchell Stanton-Cook, Minh Duy Phan, Makrina Totsika, Kate M. Peters, Kok Gan Chan, Mark A. Schembri, Mathew Upton, Scott A. Beatson

School of Biomedical Sciences

Escherichia coli ST131 is now recognised as a leading contributor to urinary tract and bloodstream infections in both community and clinical settings. Here we present the complete, annotated genome of E. coli EC958, which was isolated from the urine of a patient presenting with a urinary tract infection in the Northwest region of England and represents the most well characterised ST131 strain. Sequencing was carried out using the Pacific Biosciences platform, which provided sufficient depth and read-length to produce a complete genome without the need for other technologies. The discovery of spurious contigs within the assembly that correspond to site-specific …

Divergent Antibody Subclass And Specificity Profiles But Not Protective Hla-B Alleles Are Associated With Variable Antibody Effector Function Among Hiv-1 Controllers, Jennifer I. Lai, Anna F. Licht, Anne-Sophie Dugast, Todd Suscovich, Ickwon Choi, Chris Bailey-Kellogg, Galit Alter, Margaret E. Ackerman

Dartmouth Scholarship

Understanding the coordination between humoral and cellular immune responses may be the key to developing protective vaccines, and because genetic studies of long-term HIV-1 nonprogressors have associated specific HLA-B alleles with spontaneous control of viral replication, this subject group presents an opportunity to investigate relationships between arms of the adaptive immune system. Given evidence suggesting that cellular immunity may play a role in viral suppression, we sought to determine whether and how the humoral immune response might vary among controllers. Significantly, Fc-mediated antibody effector functions have likewise been associated with durable viral control. In this study, we compared the effector …