Digital Commons Network^™

Respiratory Sinus Arrhythmia Reactivity To A Sad Film Predicts Depression Symptom Improvement And Symptomatic Trajectory, Vanessa Panaite, Alexandra Cowden Hindash, Lauren M. Bylsma, Brent J. Small, Kristen Salomon, Johnathan Rottenberg

Psychology Faculty Publications

Respiratory sinus arrhythmia (RSA) reactivity, an index of cardiac vagal tone, has been linked to self-regulation and the severity and course of depression (Rottenberg, 2007). Although initial data supports the proposition that RSA withdrawal during a sad film is a specific predictor of depression course (Fraguas, 2007; Rottenberg, 2005), the robustness and specificity of this finding are unclear. To provide a stronger test, RSA reactivity to three emotion films (happy, sad, fear) and to a more robust stressor, a speech task, were examined in currently depressed individuals (n = 37), who were assessed for their degree of symptomatic improvement over …

Cardiovascular Pharmacokinetics, Pharmacodynamics, And Pharmacogenomics For The Clinical Practitioner, Anna T. Sleder, James Kalus, David Lanfear

Cardiology Articles

Current clinical cardiovascular practice requires a clinician to have a strong foundation in multiple aspects of pharmacology. Modern cardiovascular regimens are complex, and optimal management, application of evolving guidelines, and adoption of new therapies build off a more basic understanding of pharmacokinetics and pharmacodynamics. In addition, it is likely time to add a third pillar into this discussion, the expanding field of pharmacogenomics referring to the genetic influences on drug response. This field has increasing applications in medicine and clearly holds significant promise for cardiovascular disease management. Awareness of pharmacogenomic advances and the fundamentals of pharmacokinetics and pharmacodynamics can help …

Neighborhood-Level Poverty At Menarche And Prepregnancy Obesity In African-American Women, Andrea E. Cassidy-Bushrow, Rosalind M. Peters, Charlotte Burmeister, Lawrence F. Bielak, Dayna A. Johnson

Public Health Sciences Articles

Introduction: Menarche is a critical time point in a woman's reproductive system development; exposures at menarche may influence maternal health. Living in a poorer neighborhood is associated with adult obesity; however, little is known if neighborhood factors at menarche are associated with prepregnancy obesity.

Methods: We examined the association of neighborhood-level poverty at menarche with prepregnancy body mass index category in 144 pregnant African-American women. Address at menarche was geocoded to census tract (closest to year of menarche); neighborhood-level poverty was defined as the proportion of residents living under the federal poverty level. Cumulative logistic regression was used to examine …

Repositioning Of Drugs Using Open-Access Data Portal Dtome: A Test Case With Probenecid (Review), Mohammad U. Ahmed, Dylan J. Bennett, Tze-Chen Hsieh, Barbara B. Doonan, Saba Ahmed, Joseph M. Wu

NYMC Faculty Publications

The one gene-one enzyme hypothesis, first introduced by Beadle and Tatum in the 1940s and based on their genetic analysis and observation of phenotype changes in Neurospora crassa challenged by various experimental conditions, has witnessed significant advances in recent decades. Much of our understanding of the association between genes and their phenotype expression has benefited from the completion of the human genome project, and has shown continual transformation guided by the effort directed at the annotation and characterization of human genes. Similarly, the idea of one drug‑one primary disease indication that traditionally has been the benchmark for the labeling and …

Follicular Lymphoma Tregs Have A Distinct Transcription Profile Impacting Their Migration And Retention In The Malignant Lymph Node, Hristina Nedelkovska, Alexander F. Rosenberg, Shannon P. Hilchey, Ollivier Hyrien, W. Richard Burack, Sally A. Quataert, Christina M. Baker, Mitra Azadniv, Stephen L. Welle, Stephen M. Ansell, Minsoo Kim, Steven H. Bernstein

Biology

We have previously shown that regulatory T cells (Tregs) infiltrating follicular lymphoma lymph nodes are quantitatively and qualitatively different than those infiltrating normal and reactive nodes. To gain insight into how such Treg populations differ, we performed RNA sequence (RNAseq) analyses on flow sorted Tregs from all three sources. We identify several molecules that could contribute to the observed increased suppressive capacity of follicular lymphoma nodal tregs, including upregulation of CTLA-4, IL-10, and GITR, all confirmed by protein expression. In addition, we identify, and confirm functionally, a novel mechanism by which Tregs target to and accumulate within a human tumor …

Dysfunctional Epileptic Neuronal Circuits And Dysmorphic Dendritic Spines Are Mitigated By Platelet-Activating Factor Receptor Antagonism, Alberto E. Musto, Robert F. Rosencrans, Chelsey P. Walker, Surjyadipta Bhattacharjee, Chittalsinh M. Raulji, Ludmila Belayev, Zhide Fang, William C. Gordon, Nicolas G. Bazan

Journal Articles: Pediatrics

Temporal lobe epilepsy or limbic epilepsy lacks effective therapies due to a void in understanding the cellular and molecular mechanisms that set in motion aberrant neuronal network formations during the course of limbic epileptogenesis (LE). Here we show in in vivo rodent models of LE that the phospholipid mediator platelet-activating factor (PAF) increases in LE and that PAF receptor (PAF-r) ablation mitigates its progression. Synthetic PAF-r antagonists, when administered intraperitoneally in LE, re-establish hippocampal dendritic spine density and prevent formation of dysmorphic dendritic spines. Concomitantly, hippocampal interictal spikes, aberrant oscillations, and neuronal hyper-excitability, evaluated 15-16 weeks after LE using multi-array …

Effect Of Vitamins C And E On Endothelial Function In Type 1 Diabetes Mellitus, Rachel-Marie Cazeau, Hong Huang, John A. Bauer, Robert P. Hoffman

Pediatrics Faculty Publications

Background/Objectives. Endothelial dysfunction due to hyperglycemia-induced oxidative damage is an important predictor of future cardiovascular risk in patients with type 1 diabetes mellitus (T1DM) and is present in adolescent T1DM. We hypothesized that combined treatment with the antioxidant vitamins C and E might improve endothelial function (EF) and other biochemical risk factors in adolescents with T1DM. Subjects/Methods. Open-label antioxidant supplementation was given for six weeks with endpoint measurements collected at baseline and study completion. Endpoints measured included EF and plasma measurements of biochemical endothelial risk. Results. Two males and 7 females were studied. Mean age was 12.9 ± 0.9 yrs; …

Allergic Diseases And Internalizing Behaviors In Early Childhood., Maya K. Nanda, Grace K. Lemasters, Linda Levin, Marc E. Rothenberg, Amal H. Assa'ad, Nicholas Newman, David Bernstein, Gurjit Khurana-Hershey, James E. Lockey, Patrick H. Ryan

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: The relationship between allergic diseases and internalizing disorders has not been well characterized with regard to multiple allergic diseases or longitudinal study. The objective of this study was to examine the association between multiple allergic diseases in early childhood with validated measures of internalizing disorders in the school-age years.

METHODS: Children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study underwent skin testing and examinations at ages 1, 2, 3, 4, and 7 years. At age 7, parents completed the Behavior Assessment System for Children, Second Edition (BASC-2), a validated measure of childhood behavior and emotion. …

Dog Walking Among Adolescents: Correlates And Contribution To Physical Activity., Jessa K. Engelberg, Jordan A. Carlson, Terry L. Conway, Kelli L. Cain, Brian E. Saelens, Karen Glanz, Lawrence D. Frank, James F. Sallis

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: To assess the association of dog walking with adolescents' moderate-to-vigorous physical activity (MVPA) and body mass index (BMI), and identify correlates of dog walking.

METHODS/DESIGN: Participants were 12-17year-olds (n=925) from the Baltimore, MD and Seattle, WA regions. Differences in accelerometer-assessed minutes/day of MVPA and self-reported BMI (percentile) were compared among adolescents (1) without a dog (n=441) and those with a dog who (2) did (≥1days/week, n=300) or (3) did not (n=184) walk it. Correlates of (1) dog walking (any vs. none) among adolescents with dogs (n=484), and (2) days/week of dog walking among dog walkers (n=300) were investigated. Potential …

Biological Markers For Pulpal Inflammation: A Systematic Review., Dan-Krister Rechenberg, Johnah C. Galicia, Ove A. Peters

All Dugoni School of Dentistry Faculty Articles

BACKGROUND AND OBJECTIVE: Pulpitis is mainly caused by an opportunistic infection of the pulp space with commensal oral microorganisms. Depending on the state of inflammation, different treatment regimes are currently advocated. Predictable vital pulp therapy depends on accurate determination of the pulpal status that will allow repair to occur. The role of several players of the host response in pulpitis is well documented: cytokines, proteases, inflammatory mediators, growth factors, antimicrobial peptides and others contribute to pulpal defense mechanisms; these factors may serve as biomarkers that indicate the status of the pulp. Therefore, the aim of this systematic review was to …

Two-Arm Randomized Pilot Intervention Trial To Decrease Sitting Time And Increase Sit-To-Stand Transitions In Working And Non-Working Older Adults., Jacqueline Kerr, Michelle Takemoto, Khalisa Bolling, Andrew Atkin, Jordan A. Carlson, Dori Rosenberg, Katie Crist, Suneeta Godbole, Brittany Lewars, Claudia Pena, Gina Merchant

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Excessive sitting has been linked to poor health. It is unknown whether reducing total sitting time or increasing brief sit-to-stand transitions is more beneficial. We conducted a randomized pilot study to assess whether it is feasible for working and non-working older adults to reduce these two different behavioral targets.

METHODS: Thirty adults (15 workers and 15 non-workers) age 50-70 years were randomized to one of two conditions (a 2-hour reduction in daily sitting or accumulating 30 additional brief sit-to-stand transitions per day). Sitting time, standing time, sit-to-stand transitions and stepping were assessed by a thigh worn inclinometer (activPAL). Participants …

Contraceptive Provision To Adolescent Females Prescribed Teratogenic Medications., Stephani L. Stancil, Melissa K. Miller, Holley Briggs, Daryl Lynch, Kathy Goggin, Gregory Kearns

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Rates of adult women receiving contraceptive provision when simultaneously prescribed a known teratogen are alarmingly low. The prevalence of this behavior among pediatric providers and their adolescent patients is unknown. The objective of this study was to describe pediatric provider behaviors for prescribing teratogens concurrently with counseling, referral, and/or prescribing of contraception (collectively called contraceptive provision) in the adolescent population.

METHODS: A retrospective review was conducted examining visits in 2008-2012 by adolescents aged 14 to 25 years in which a known teratogen (US Food and Drug Administration pregnancy risk category D or X) was prescribed. The electronic …

Stress Granules And Rna Processing Bodies Are Novel Autoantibody Targets In Systemic Sclerosis, Michael E. Johnson, Andrew V. Grassetti, Jaclyn N. Taroni, Shawn M. Lyons, Devin Schweppe, Jessica K. Gordon, Robert F. Speira, Robert Lafyatis, Paul J. Anderson, Scott A. Gerber, Michael L. Whitfield

Dartmouth Scholarship

Autoantibody profiles represent important patient stratification markers in systemic sclerosis (SSc). Here, we performed serum-immunoprecipitations with patient antibodies followed by mass spectrometry (LC-MS/MS) to obtain an unbiased view of all possible autoantibody targets and their associated molecular complexes recognized by SSc.

Identification And Use Of Frailty Indicators From Text To Examine Associations With Clinical Outcomes Among Patients With Heart Failure., Yijun Shao, April F Mohanty, Ali Ahmed, Charlene R Weir, Bruce E Bray, Rashmee U Shah, Douglas Redd, Qing Zeng-Treitler

Clinical Research and Leadership Faculty Publications

Frailty is an important health outcomes indicator and valuable for guiding healthcare decisions in older adults, but is rarely collected in a quantitative, systematic fashion in routine healthcare. Using a cohort of 12,000 Veterans with heart failure, we investigated the feasibility of topic modeling to identify frailty topics in clinical notes. Topics were generated through unsupervised learning and then manually reviewed by an expert. A total of 53 frailty topics were identified from 100,000 notes. We further examined associations of frailty with age-, sex-, and Charlson Comorbidity Index-adjusted 1-year hospitalizations and mortality (composite outcome) using logistic regression. Frailty (≤ 4 …

The Challenge Of Analyzing The Results Of Next-Generation Sequencing In Children., Isabelle Thiffault, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

In recent years, next-generation sequencing technologies have revolutionized approaches to genetic studies. Whole-exome or whole-genome sequencing allows diagnoses in many patients who have complex phenotypes and unusual clinical presentations. As genomic and exomic testing expands in both the research and clinical settings, pediatricians will need to understand the technology of next-generation sequencing and the complexity of interpreting genomic variants relevant to patient phenotypic features. This article briefly explains the technology by which genomes are sequenced and discusses some of the complexity related to interpreting genomic variants. We conclude with some thoughts on the clinical applications of such testing.

Early Adverse Experiences And Health: The Transition To College, Kelly B. Filipkowski, Kristin E. Heron, Joshua M. Smyth

Psychology Faculty Publications

Objective: This study cross-sectionally and prospectively examined the impact of adversity experienced prior to college on the health and well-being of students adjusting to their first college semester. Methods: Two-hundred sixteen (216) first-year students completed measures of adverse life experiences, perceived stress, physical symptoms, and health-related behaviors during the first 2 weeks of college entry and again at the end of the first semester. Results: Reported adversity prior to college predicted greater perceived stress and physical symptoms at college entry and an increase in physical symptoms over the semester; perceived stress mediated the prospective changes. Early adversity …

Palmitate-Induced Changes In Energy Demand Cause Reallocation Of Atp Supply In Rat And Human Skeletal Muscle Cells., Raid B. Nisr, Charles Affourtit

School of Biomedical Sciences

Mitochondrial dysfunction has been associated with obesity-related muscle insulin resistance, but the causality of this association is controversial. The notion that mitochondrial oxidative capacity may be insufficient to deal appropriately with excessive nutrient loads is for example disputed. Effective mitochondrial capacity is indirectly, but largely determined by ATP-consuming processes because skeletal muscle energy metabolism is mostly controlled by ATP demand. Probing the bioenergetics of rat and human myoblasts in real time we show here that the saturated fatty acid palmitate lowers the rate and coupling efficiency of oxidative phosphorylation under conditions it causes insulin resistance. Stearate affects the bioenergetic parameters …

Changes In The Eeg Amplitude As A Biomarker For Early Detection Of Alzheimer's Disease., Ali H. Al-Nuaimi, Emmanuel Jammeh, Lingfen Sun, Emmanuel Ifeachor

School of Engineering, Computing and Mathematics

The rapid increase in the number of older people with Alzheimer's disease (AD) and other forms of dementia represents one of the major challenges to the health and social care systems. Early detection of AD makes it possible for patients to access appropriate services and to benefit from new treatments and therapies, as and when they become available. The onset of AD starts many years before the clinical symptoms become clear. A biomarker that can measure the brain changes in this period would be useful for early diagnosis of AD. Potentially, the electroencephalogram (EEG) can play a valuable role in …

Endothelial Cells Expressing Endothelial And Mesenchymal Cell Gene Products In Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease., Fabian A. Mendoza, Sonsoles Piera-Velazquez, John L. Farber, Carol Feghali-Bostwick, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT).

METHODS: Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed …

Identification Of A Novel Gene On 10q221 Causing Autosomal Dominant Retinitis Pigmentosa (Adrp), Stephen P Daiger, Lori S Sullivan, Sara J Bowne, Daniel C Koboldt, Susan H Blanton, Dianna K Wheaton, Cheryl E Avery, Elizabeth D Cadena, Robert K Koenekoop, Robert S Fulton, Richard K Wilson, George M Weinstock, Richard A Lewis, David G Birch

Faculty, Staff and Students Publications

Whole-genome linkage mapping identified a region on chromosome 10q21.3-q22.1 with a maximum LOD score of 3.0 at 0 % recombination in a six-generation family with autosomal dominant retinitis pigmentosa (adRP). All known adRP genes and X-linked RP genes were excluded in the family by a combination of methods. Whole-exome next-generation sequencing revealed a missense mutation in hexokinase 1, HK1 c.2539G > A, p.Glu847Lys, tracking with disease in all affected family members. One severely-affected male is homozygous for this region by linkage analysis and has two copies of the mutation. No other potential mutations were detected in the linkage region nor were …

Ethnic Differences In Maternal Adipokines During Normal Pregnancy, Xinhua Chen, Theresa O Scholl

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Two adipokines (adiponectin and resistin) have opposite relations with insulin resistance and inflammation. Our major focus was to determine whether there were detectable ethnic differences in maternal adipokines during pregnancy. We also explored the correlation of the adipokines with maternal glucose homeostasis, blood pressure and anthropometric parameters. Pregnant women (n = 1634) were from a large prospective cohort study in Camden NJ (African-American 36.8%; Hispanic 47.6%; Caucasian 15.6%). Serum adiponectin and resistin were measured at entry (week 16.8) and the 3rd trimester (week 30.7) using the Luminex xMapTechnology. Significant differences were observed among ethnic groups, controlling for confounding variables. African …

Are Immune Modulating Single Nucleotide Polymorphisms Associated With Necrotizing Enterocolitis?, Ashanti L Franklin, Mariam Said, Clint D Cappiello, Heather Gordish-Dressman, Zohreh Tatari-Calderone, Stanislav Vukmanovic, Khodayar Rais-Bahrami, Naomi L C Luban, Joseph M Devaney, Anthony D Sandler

Genomics and Precision Medicine Faculty Publications

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48-29.39), and over …

Selective Vip Receptor Agonists Facilitate Immune Transformation For Dopaminergic Neuroprotection In Mptp-Intoxicated Mice., Katherine E. Olson, Lisa M. Kosloski-Bilek, Kristi M. Anderson, Breha J. Diggs, Barbara E. Clark, John M. Gledhill, Scott J. Shandler, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

UNLABELLED: Vasoactive intestinal peptide (VIP) mediates a broad range of biological responses by activating two related receptors, VIP receptor 1 and 2 (VIPR1 and VIPR2). Although the use of native VIP facilitates neuroprotection, clinical application of the hormone is limited due to VIP's rapid metabolism and inability to distinguish between VIPR1 and VIPR2 receptors. In addition, activation of both receptors by therapeutics may increase adverse secondary toxicities. Therefore, we developed metabolically stable and receptor-selective agonists for VIPR1 and VIPR2 to improve pharmacokinetic and pharmacodynamic therapeutic end points. Selective agonists were investigated for their abilities to protect mice against MPTP-induced neurodegeneration …

Leveraging Global Gene Expression Patterns To Predict Expression Of Unmeasured Genes, James Rudd, René A. Zelaya, Eugene Demidenko, Ellen L. Goode, Casey S. Greene S. Greene, Jennifer A. Doherty

Dartmouth Scholarship

BackgroundLarge collections of paraffin-embedded tissue represent a rich resource to test hypotheses based on gene expression patterns; however, measurement of genome-wide expression is cost-prohibitive on a large scale. Using the known expression correlation structure within a given disease type (in this case, high grade serous ovarian cancer; HGSC), we sought to identify reduced sets of directly measured (DM) genes which could accurately predict the expression of a maximized number of unmeasured genes.

The Visual Priming Of Motion-Defined 3d Objects, Xiong Jiang, Yang Jiang, Raja Parasuraman

Behavioral Science Faculty Publications

The perception of a stimulus can be influenced by previous perceptual experience, a phenomenon known as perceptual priming. However, there has been limited investigation on perceptual priming of shape perception of three-dimensional object structures defined by moving dots. Here we examined the perceptual priming of a 3D object shape defined purely by motion-in-depth cues (i.e., Shape-From-Motion, SFM) using a classic prime-target paradigm. The results from the first two experiments revealed a significant increase in accuracy when a "cloudy" SFM stimulus (whose object structure was difficult to recognize due to the presence of strong noise) was preceded by an unambiguous SFM …

Genetic Modification Of Human Mesenchymal Stem Cells Helps To Reduce Adiposity And Improve Glucose Tolerance In An Obese Diabetic Mouse Model., Sabyasachi Sen, Cleyton C Domingues, Carol Rouphael, Cyril Chou, Chul Kim, Nagendra Yadava

Medicine Faculty Publications

INTRODUCTION: Human mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into fat, muscle, bone and cartilage cells. Exposure of subcutaneous abdominal adipose tissue derived AD-MSCs to high glucose (HG) leads to superoxide accumulation and up-regulation of inflammatory molecules. Our aim was to inquire how HG exposure affects MSCs differentiation and whether the mechanism is reversible.

METHODS: We exposed human adipose tissue derived MSCs to HG (25 mM) and compared it to normal glucose (NG, 5.5 mM) exposed cells at 7, 10 and 14 days. We examined mitochondrial superoxide accumulation (Mitosox-Red), cellular oxygen consumption rate (OCR, Seahorse) and gene …

Linker Histone H1 And H3k56 Acetylation Are Antagonistic Regulators Of Nucleosome Dynamics, Morgan Bernier, Yi Luo, Kingsley C. Nwokelo, Michelle Goodwin, Sarah J. Dreher, Pei Zhang, Mark R. Parthun, Yvonne N. Fondufe-Mittendorf, Jennifer J. Ottesen, Michael G. Poirier

Molecular and Cellular Biochemistry Faculty Publications

H1 linker histones are highly abundant proteins that compact nucleosomes and chromatin to regulate DNA accessibility and transcription. However, the mechanisms that target H1 regulation to specific regions of eukaryotic genomes are unknown. Here we report fluorescence measurements of human H1 regulation of nucleosome dynamics and transcription factor (TF) binding within nucleosomes. H1 does not block TF binding, instead it suppresses nucleosome unwrapping to reduce DNA accessibility within H1-bound nucleosomes. We then investigated H1 regulation by H3K56 and H3K122 acetylation, two transcriptional activating histone post translational modifications (PTMs). Only H3K56 acetylation, which increases nucleosome unwrapping, abolishes H1.0 reduction of TF …

‘Much Clearer With Pictures’: Using Community-Based Participatory Research To Design And Test A Picture Option Grid For Underserved Patients With Breast Cancer, Marie-Anne Durand, Shama Alam, Stuart W. Grande, Glyn Elwyn

Dartmouth Scholarship

Women of low socioeconomic status (SES) diagnosed with early stage breast cancer experience decision-making, treatment and outcome disparities. Evidence suggests that decision aids can benefit underserved patients, when tailored to their needs. Our aim was to develop and test the usability, acceptability and accessibility of a pictorial encounter decision aid targeted at women of low SES diagnosed with early stage breast cancer.

Chronic Ethanol Exposure Enhances The Aggressiveness Of Breast Cancer: The Role Of P38Γ, Mei Xu, Siying Wang, Zhenhua Ren, Jacqueline A. Frank, Xiuwei H. Yang, Zhuo Zhang, Zun-Ji Ke, Xianglin Shi, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12–48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the …

Differential Impact Of Lpg-And Pg-Deficient Leishmania Major Mutants On The Immune Response Of Human Dendritic Cells, Michelle A. Favila, Nicholas S. Geraci, Asha Jayakumar, Suzanne Hickerson, Janet Mostrom, Salvatore J. Turco, Stephen M. Beverley, Mary Ann Mcdowell

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Leishmania major infection induces robust interleukin-12 (IL12) production in human dendritic cells (hDC), ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of Leishmania parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG) and other phosphoglycan-containing molecules (PGs), making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS) responsible for IL12 induction.

METHODOLOGY/PRINCIPAL FINDINGS: Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating L. major Friedlin V1 mutants defective in LPG alone, (FV1 lpg1-), or generally deficient for all PGs, (FV1 lpg2-). Infection with metacyclic, infective …