Digital Commons Network^™

Arsenic Inhibits Dna Mismatch Repair By Promoting Egfr Expression And Pcna Phosphorylation, Dan Tong, Janice Ortega, Christine Kim, Jian Huang, Liya Gu, Guo-Min Li

Toxicology and Cancer Biology Faculty Publications

Both genotoxic and non-genotoxic chemicals can act as carcinogens. However, while genotoxic compounds lead directly to mutations that promote unregulated cell growth, the mechanism by which non-genotoxic carcinogens lead to cellular transformation is poorly understood. Using a model non-genotoxic carcinogen, arsenic, we show here that exposure to arsenic inhibits mismatch repair (MMR) in human cells, possibly through its ability to stimulate epidermal growth factor receptor (EGFR)-dependent tyrosine phosphorylation of proliferating cellular nuclear antigen (PCNA). HeLa cells exposed to exogenous arsenic demonstrate a dose- and time-dependent increase in the levels of EGFR and tyrosine 211-phosphorylated PCNA. Cell extracts derived from arsenic-treated …

Integrative Medical Approaches To Allergic Rhinitis, Benjamin F. Asher, Michael Seidman, William D. Reddy, Folashade S. Omole

Otolaryngology Articles

PURPOSE OF REVIEW: Complementary and integrative medicine (CIM), formerly known as alternative medicine, is now part of the mainstream management for patients with a host of medical issues. This current opinion focuses on the use of CIM, more specifically, the use of nutritional and herbal therapies and homeopathic medications for patients with allergic symptoms.

RECENT FINDINGS: The literature review revealed that naturally occurring substances when compared with placebo more often than not resulted in significant improvement of the allergic rhinitis symptoms.

SUMMARY: Despite encouraging results, additional studies with greater rigor are needed.

Long Non-Coding Rna Malat1 Regulates Hyperglycaemia Induced Inflammatory Process In The Endothelial Cells., Prasanth Puthanveetil, Shali Chen, Biao Feng, Anirudh Gautam, Subrata Chakrabarti

Pathology Publications

To examine whether the long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is altered in the endothelial cells in response to glucose and the significance of such alteration. We incubated human umbilical vein endothelial cells with media containing various glucose levels. We found an increase in MALAT1 expression peaking after 12 hrs of incubation in high glucose. This increase was associated with parallel increase in serum amyloid antigen 3 (SAA3), an inflammatory ligand and target of MALAT1 and was further accompanied by increase in mRNAs and proteins of inflammatory mediators, tumour necrosis factor alpha (TNF-α) and interleukin …

Fusion Analysis Of Functional Mri Data For Classification Of Individuals Based On Patterns Of Activation., Mahdi Ramezani, Purang Abolmaesumi, Kris Marble, Heather Trang, Ingrid Johnsrude

Brain and Mind Institute Researchers' Publications

Classification of individuals based on patterns of brain activity observed in functional MRI contrasts may be helpful for diagnosis of neurological disorders. Prior work for classification based on these patterns have primarily focused on using a single contrast, which does not take advantage of complementary information that may be available in multiple contrasts. Where multiple contrasts are used, the objective has been only to identify the joint, distinct brain activity patterns that differ between groups of subjects; not to use the information to classify individuals. Here, we use joint Independent Component Analysis (jICA) within a Support Vector Machine (SVM) classification …

Transaction Cost Analysis Of In-Clinic Versus Telehealth Consultations For Chronic Pain: Preliminary Evidence For Rapid And Affordable Access To Interdisciplinary Collaborative Consultation, Brian R. Theodore, Jan Whittington, Cara Towle, David J. Tauben, Barbara Endicott-Popovsky, Alex Cahana, Ardith Z. Doorenbos

Project ECHO Bibliography

OBJECTIVES: With ever increasing mandates to reduce costs and increase the quality of pain management, health care institutions are faced with the challenge of adopting innovative technologies and shifting workflows to provide value-based care. Transaction cost economic analysis can provide comparative evaluation of the consequences of these changes in the delivery of care. The aim of this study was to establish proof-of-concept using transaction cost analysis to examine chronic pain management in-clinic and through telehealth.

METHODS: Participating health care providers were asked to identify and describe two comparable completed transactions for patients with chronic pain: one consultation between patient and …

Genome-Wide Association Study And Admixture Mapping Reveal New Loci Associated With Total Ige Levels In Latinos, Maria Pino-Yanes, Christopher R. Gignoux, Joshua M. Galanter, Albert M. Levin, Catarina D. Campbell, Celeste Eng, Scott Huntsman, Katherine K. Nishimura, Pierre-Antoine Gourraud, Kiana Mohajeri, Brian O'Roak, Donglei Hu, Rasika A. Mathias, Elizabeth A. Nguyen, Lindsey A. Roth, Badri Padhukasahasram, Andres Moreno-Estrada, Karla Sandoval, Cheryl A. Winkler, Fred Lurmann, Adam Davis, Harold J. Farber, Kelley Meade, Pedro C. Avila, Denise Serebrisky, Rocio Chapela, Jean G. Ford, Michael A. Lenoir, Shannon M. Thyne, Emerita Brigino-Buenaventura, Luisa N. Borrell, William Rodriguez-Cintron, Saunak Sen, Rajesh Kumar, Jose R. Rodriguez-Santana, Carlos D. Bustamante, Fernando D. Martinez, Benjamin A. Raby, Scott T. Weiss, Dan L. Nicolae, Carole Ober, Deborah A. Meyers, Eugene R. Bleecker, Steven J. Mack, Ryan D. Hernandez, Evan E. Eichler, Kathleen C. Barnes, Keoki L. Williams, Dara G. Torgerson, Esteban G. Burchard

Center for Health Policy and Health Services Research Articles

BACKGROUND: IgE is a key mediator of allergic inflammation, and its levels are frequently increased in patients with allergic disorders.

OBJECTIVE: We sought to identify genetic variants associated with IgE levels in Latinos.

METHODS: We performed a genome-wide association study and admixture mapping of total IgE levels in 3334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1564 European Americans, and 3187 African Americans from independent studies.

RESULTS: We confirmed associations of 6 genes identified by means of previous genome-wide association studies and identified a novel genome-wide significant association of …

Quantifying Unnecessary Normal Tissue Complication Risks Due To Suboptimal Planning: A Secondary Study Of Rtog 0126., Kevin L. Moore, Rachel Schmidt, Vitali Moiseenko, Lindsey A. Olsen, Jun Tan, Ying Xiao, James Galvin, Stephanie Pugh, Michael J Seider, Adam P. Dicker, Walter Bosch, Jeff Michalski, Sasa Mutic

Department of Radiation Oncology Faculty Papers

PURPOSE: The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol.

METHODS AND MATERIALS: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative …

Spatial Heterogeneity, Host Movement And Mosquito-Borne Disease Transmission, Miguel A. Acevedo, Olivia Prosper, Kenneth Lopiano, Nick Ruktanonchai, T. Trevor Caughlin, Maia Martcheva, Craig W. Osenberg, David L. Smith

Dartmouth Scholarship

Mosquito-borne diseases are a global health priority disproportionately affecting low-income populations in tropical and sub-tropical countries. These pathogens live in mosquitoes and hosts that interact in spatially heterogeneous environments where hosts move between regions of varying transmission intensity. Although there is increasing interest in the implications of spatial processes for mosquito-borne disease dynamics, most of our understanding derives from models that assume spatially homogeneous transmission. Spatial variation in contact rates can influence transmission and the risk of epidemics, yet the interaction between spatial heterogeneity and movement of hosts remains relatively unexplored. Here we explore, analytically and through numerical simulations, how …

Integrated Psychological Care In Head And Neck Cancer: Views From Health Care Providers, Patients, And Supports, Michelle T. Jesse, Michael Ryan, Anne Eshelman, Tamer Ghanem, Amy M. Williams, Lisa R. Miller-Matero, Kathleen Yaremchuk

Otolaryngology Articles

OBJECTIVES/HYPOTHESIS: An evaluation by head-and-neck cancer (HNC) staff, patients, and patient support feedback regarding integrated psychological care and perceived benefit based on patient characteristics.

STUDY DESIGN: Cross-sectional survey of HNC staff, patients, and their primary supports; and retrospective chart review of psychiatric characteristics of HNC patients.

METHODS: HNC staff, patients (who were evaluated by the integrated psychologist), and their primary supports were given questionnaires on their perception of benefit of including a psychologist in the evaluation and treatment of HNC patients. Also, a retrospective chart review on patients who were psychiatrically evaluated by the psychologist on sociodemographics and psychiatric characteristics. …

Preclinical Characterization Of Duoc-01, A Cell Therapy Product Derived From Banked Umbilical Cord Blood For Use As An Adjuvant To Umbilical Cord Blood Transplantation For Treatment Of Inherited Metabolic Diseases., Joanne Kurtzberg, Susan Buntz, Tracy Gentry, Pamela Noeldner, April Ozamiz, Benjamin Rusche, Robert W. Storms, Amy Wollish, David A Wenger, Andrew E. Balber

Department of Neurology Faculty Papers

BACKGROUND AIMS: Cord blood (CB) transplantation slows neurodegeneration during certain inherited metabolic diseases. However, the number of donor cells in the brain of patients does not appear to be sufficient to provide benefit until several months after transplant. We developed the cell product DUOC-01 to provide therapeutic effects in the early post-transplant period.

METHODS: DUOC-01 cultures initiated from banked CB units were characterized by use of time-lapse photomicroscopy during the 21-day manufacturing process. Antigen expression was measured by means of flow cytometry and immunocytochemistry; transcripts for cytokines and enzymes by quantitative real-time polymerase chain reaction; activities of lysosomal enzymes by …

Mind The Gap: A Novel Care Transitions Curriculum For Hospitalists And Residents, Anita Vanka, Grace Farris, Jonathan Bortinger, Grace Huang, Melissa L P Mattison

Project ECHO Bibliography

No abstract provided.

Iarc Monographs: 40 Years Of Evaluating Carcinogenic Hazards To Humans, Neil E. Pearce, Aaron Blair, Paolo Vineis, Wolfgang Ahrens, Aage Andersom, Josep M. Anto, Bruce K. Armstrong, Andrea A. Baccarelli, Frederick A. Beland, Amy Berrington, Pier Alberto Bertazzi, Linda S. Birnbaum, Ross C. Brownson, John R. Bucher, Kenneth P. Cantor, Elisabeth Cardis, John W. Cherrie, David C. Christiani, Pierluigi Cocco, David Coggon, Pietro Comba, Paul A. Demers, John M. Dement, Jeroen Douwes, Ellen A. Eisen, Lawrence S. Engel, Richard A. Fenske, Lora E. Fleming, Tony Fletcher, Elizabeth Fontham, Francesco Forastiere, Rainer Frentzel-Beyme, Lin Fritschi, Michel Gerin, Marcel Goldberg, Philippe Grandjean, Tom K. Grimsrud, Per Gustavsson, Andy Haines, Patricia Hartge, Johnni Hansen, Michael Hauptmann, Dick Heederik, Kari Hemminki, Denis Hemon, Irva Hertz-Picciotto, Jane A. Hoppin, James Huff, Bengt Jarvholm, Daehee Kang, Margaret R. Karagas

Dartmouth Scholarship

Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.

Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process …

New Functions For Alpha-Catenins In Health And Disease: From Cancer To Heart Regeneration., Alexia Vite, Jifen Li, Glenn L. Radice

Center for Translational Medicine Faculty Papers

Strong cell-cell adhesion mediated by adherens junctions is dependent on anchoring the transmembrane cadherin molecule to the underlying actin cytoskeleton. To do this, the cadherin cytoplasmic domain interacts with catenin proteins, which include α-catenin that binds directly to filamentous actin. Originally thought to be a static structure, the connection between the cadherin/catenin adhesion complex and the actin cytoskeleton is now considered to be dynamic and responsive to both intercellular and intracellular signals. Alpha-catenins are mechanosensing proteins that undergo conformational change in response to cytoskeletal tension thus modifying the linkage between the cadherin and the actin cytoskeleton. There are three α-catenin …

Understanding Nucleus Pulposus Cell Phenotype: A Prerequisite For Stem Cell Based Therapies To Treat Intervertebral Disc Degeneration., Hyowon Choi, Zariel I. Johnson, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Intervertebral disc (IVD) degeneration and associated low back pain (LBP) remains a major burden to our society without significant improvements in treatment strategies or patient's quality of life. While the recent cell-transplantation studies for treatment of degenerative disc disease have shown promising results, to better gauge the success and functional outcomes of these therapies, it is crucial to understand if transplanted cells give rise to healthy nucleus pulposus (NP) tissue. NP cell phenotype is unique and is defined by expression of a characteristic set of markers that reflect specialized physiology and function. This review summarizes phenotypic markers that mirror the …

Prophylactic Methylprednisolone To Reduce Inflammation And Improve Outcomes From One Lung Ventilation In Children: A Randomized Clinical Trial., Mary C. Theroux, Alicia Olivant Fisher, Maria E. Rodriguez, Robert P. Brislin, Kirk W. Reichard, Suken A. Shah, Matt Mccoy, Melinda Brown, Kirk W. Dabney, William G. Mackenzie, Douglas A. Katz, Thomas H. Shaffer

Department of Anesthesiology Faculty Papers

BACKGROUND: One lung ventilation (OLV) results in inflammatory and mechanical injury, leading to intraoperative and postoperative complications in children. No interventions have been studied in children to minimize such injury.

OBJECTIVE: We hypothesized that a single 2-mg·kg(-1) dose of methylprednisolone given 45-60 min prior to lung collapse would minimize injury from OLV and improve physiological stability.

METHODS: Twenty-eight children scheduled to undergo OLV were randomly assigned to receive 2 mg·kg(-1) methylprednisolone (MP) or normal saline (placebo group) prior to OLV. Anesthetic management was standardized, and data were collected for physiological stability (bronchospasm, respiratory resistance, and compliance). Plasma was assayed for …

Computational Modeling Analysis Of Mitochondrial Superoxide Production Under Varying Substrate Conditions And Upon Inhibition Of Different Segments Of The Electron Transport Chain., Nikolai I. Markevich, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A computational mechanistic model of superoxide (O2•-) formation in the mitochondrial electron transport chain (ETC) was developed to facilitate the quantitative analysis of factors controlling mitochondrial O2•- production and assist in the interpretation of experimental studies. The model takes into account all individual electron transfer reactions in Complexes I and III. The model accounts for multiple, often seemingly contradictory observations on the effects of ΔΨ and ΔpH, and for the effects of multiple substrate and inhibitor conditions, including differential effects of Complex III inhibitors antimycin A, myxothiazol and stigmatellin. Simulation results confirm that, in addition to O2•- formation in Complex …

Magnetic Resonance Imaging In Pediatric Pulmonary Hypertension, Ayhan Pektas, Rana Olgunturk, Ayhan Cevik, Semiha Terlemez, Emre Kacar, Yusuf Ali Oner

The Texas Heart Institute Journal

The present study aims to determine the efficacy and reliability of cardiovascular magnetic resonance imaging in establishing the diagnosis and prognosis of pulmonary hypertension in children.

This is a retrospective comparison of 25 children with pulmonary hypertension and a control group comprising 19 healthy children. The diagnosis of pulmonary hypertension was made when the mean pulmonary artery pressure was ≥25 mmHg by catheter angiography.

The children with pulmonary hypertension had significantly lower body mass indices than did the healthy children (P=0.048). In addition, the children with pulmonary hypertension had significantly larger main pulmonary artery diameters and ascending aortic diameters (both …

Is Autologous Or Heterologous Pericardium Better For Valvuloplasty? A Comparative Study Of Calcification Propensity, Arthur W Bracey

The Texas Heart Institute Journal

No abstract provided.

Target-Specific Oral Anticoagulants: Should We Switch From Warfarin?, Payam Safavi-Naeini, Mohammad Saeed

The Texas Heart Institute Journal

No abstract provided.

Identification Of Novel Genes That Regulate Androgen Receptor Signaling And Growth Of Androgen-Deprived Prostate Cancer Cells, Elina Levina, Hao Ji, Mengqiang Chen, Mirza Baig, David Oliver, Patrice Ohouo, Chang-Uk Lim, Garry Schools, Steven Carmack, Ye Ding, Eugenia Broude, Igor Roninson, Ralph Buttyan, Michael Shtutman

Faculty Publications

Prostate cancer progression to castration refractory disease is associated with anomalous transcriptional activity of the androgen receptor (AR) in an androgen-depleted milieu. To identify novel gene products whose downregulation transactivates AR in prostate cancer cells, we performed a screen of enzymatically-generated shRNA lenti-libraries selecting for transduced LNCaP cells with elevated expression of a fluorescent reporter gene under the control of an AR-responsive promoter. The shRNAs present in selected populations were analyzed using high-throughput sequencing to identify target genes. Highly enriched gene targets were then validated with siRNAs against selected genes, testing first for increased expression of luciferase from an AR-responsive …

Effects Of Individualized Centrifugation Training On Orthostatic Tolerance In Men And Women, Nandu Goswami, Joyce Evans, Stefan Schneider, Melanie Von Der Wiesche, Edwin Mulder, Andreas Rössler, Helmut Hinghofer-Szalkay, Andrew P. Blaber

Biomedical Engineering Faculty Publications

AIMS: Exposure to artificial gravity (AG) at different G loads and durations on human centrifuges has been shown to improve orthostatic tolerance in men. However, the effects on women and of an individual-specific AG training protocol on tolerance are not known.

METHODS: We examined the effects of 90 minutes of AG vs. 90 minutes of supine rest on the orthostatic tolerance limit (OTL), using head up tilt and lower body negative pressure until presyncope of 7 men and 5 women. Subjects were placed in the centrifuge nacelle while instrumented and after one-hour they underwent either: 1) AG exposure …

Macrophage Migration Inhibitory Factor Mediates Par-Induced Bladder Pain., Dimitrios E. Kouzoukas, Katherine L. Meyer-Siegler, Fei Ma, Karin N. Westlund, David E. Hunt, Pedro L. Vera

Physiology Faculty Publications

INTRODUCTION: Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is constitutively expressed in urothelial cells that also express protease-activated receptors (PAR). Urothelial PAR1 receptors were shown to mediate bladder inflammation. We showed that PAR1 and PAR4 activator, thrombin, also mediates urothelial MIF release. We hypothesized that stimulation of urothelial PAR1 or PAR4 receptors elicits release of urothelial MIF that acts on MIF receptors in the urothelium to mediate bladder inflammation and pain. Thus, we examined the effect of activation of specific bladder PAR receptors on MIF release, bladder pain, micturition and histological changes.

METHODS: MIF release was measured …

Pseudomonas Aeruginosa Reduces Vx-809 Stimulated F508del-Cftr Chloride Secretion By Airway Epithelial Cells, Bruce A. Stanton, Bonita Coutermarsh, Roxanna Barnaby, Deborah Hogan

Dartmouth Scholarship

Background:

P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and …

Successful Implementation Of A Packed Red Blood Cell And Fresh Frozen Plasma Transfusion Protocol In The Surgical Intensive Care Unit, Benjamin E. Szpila, Tezcan Ozrazgat-Baslanti, Jianyi Zhang, Jennifer Lanz, Ruth Davis, Annette Rebel, Erin Vanzant, Lori F. Gentile, Alex G. Cuenca, Darwin N. Ang, Huazhi Liu, Lawrence Lottenberg, Peggy Marker, Marc Zumberg, Azra Bihorac, Frederick A. Moore, Scott Brakenridge, Philip A. Efron

Anesthesiology Faculty Publications

BACKGROUND: Blood product transfusions are associated with increased morbidity and mortality. The purpose of this study was to determine if implementation of a restrictive protocol for packed red blood cell (PRBC) and fresh frozen plasma (FFP) transfusion safely reduces blood product utilization and costs in a surgical intensive care unit (SICU).

STUDY DESIGN: We performed a retrospective, historical control analysis comparing before (PRE) and after (POST) implementation of a restrictive PRBC/FFP transfusion protocol for SICU patients. Univariate analysis was utilized to compare patient demographics and blood product transfusion totals between the PRE and POST cohorts. Multivariate logistic regression …

Ventilation Heterogeneity In Ex-Smokers Without Airflow Limitation., Damien Pike, Miranda Kirby, Fumin Guo, David G Mccormack, Grace Parraga

Medical Biophysics Publications

RATIONALE AND OBJECTIVES: Hyperpolarized (3)He magnetic resonance imaging (MRI) ventilation abnormalities are visible in ex-smokers without airflow limitation, but the clinical relevance of this is not well-understood. Our objective was to phenotype healthy ex-smokers with normal and abnormally elevated ventilation defect percent (VDP).

MATERIALS AND METHODS: Sixty ex-smokers without airflow limitation provided written informed consent to (3)He MRI, computed tomography (CT), and pulmonary function tests in a single visit. (3)He MRI VDP and apparent diffusion coefficients (ADCs) were measured for whole-lung and each lung lobe as were CT measurements of emphysema (relative area [RA] with attenuation ≤-950 HU, RA950) and …

Antibacterial Activity Of Native California Medicinal Plant Extracts Isolated From Rhamnus Californica And Umbellularia Californica., Maria G. Carranza, Mary B. Sevigny, Debashree Banerjee, Lacie Fox-Cubley

Natural Sciences and Mathematics | Faculty Scholarship

BACKGROUND: Antimicrobial resistance (AMR) is a major threat to global public health. Medicinal plants have long been used as remedies for infectious diseases by native cultures around the world and have the potential for providing effective treatments for antibiotic-resistant infections. Rhamnus californica (Rhamnaceae) and Umbellularia californica (Lauraceae) are two indigenous California plant species historically used by Native Americans to treat skin, respiratory and gastrointestinal infections. This study aimed to assess the in vitro antimicrobial activity of methanolic extracts of leaves and bark of R. and U. californica against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive and Gram-negative bacteria.

METHODS: Methanolic …

Disease-Related Microglia Heterogeneity In The Hippocampus Of Alzheimer's Disease, Dementia With Lewy Bodies, And Hippocampal Sclerosis Of Aging, Adam D. Bachstetter, Linda J. Van Eldik, Frederick A. Schmitt, Janna H. Neltner, Eseosa T. Ighodaro, Scott J. Webster, Ela Patel, Erin L. Abner, Richard J. Kryscio, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Introduction: Neuropathological, genetic, and biochemical studies have provided support for the hypothesis that microglia participate in Alzheimer's disease (AD) pathogenesis. Despite the extensive characterization of AD microglia, there are still many unanswered questions, and little is known about microglial morphology in other common forms of age-related dementia: particularly, dementia with Lewy bodies (DLB) and hippocampal sclerosis of aging (HS-Aging). In addition, no prior studies have attempted to compare and contrast the microglia morphology in the hippocampus of various neurodegenerative conditions.

Results: Here we studied cases with pathologically-confirmed AD (n = 7), HS-Aging (n = 7), AD + HS-aging …

Human Dna Exonuclease Trex1 Is Also An Exoribonuclease That Acts On Single-Stranded Rna, Fenghua Yuan, Tanmay Dutta, Ling Wang, Lei Song, Liya Gu, Liangyue Qian, Anaid Benitez, Shunbin Ning, Arun Malhotra, Murray P. Deutscher, Yanbin Zhang

Toxicology and Cancer Biology Faculty Publications

3' repair exonuclease 1 (TREX1) is a known DNA exonuclease involved in autoimmune disorders and the antiviral response. In this work, we show that TREX1 is also a RNA exonuclease. Purified TREX1 displays robust exoribonuclease activity that degrades single-stranded, but not double-stranded, RNA. TREX1-D200N, an Aicardi-Goutieres syndrome disease-causing mutant, is defective in degrading RNA. TREX1 activity is strongly inhibited by a stretch of pyrimidine residues as is a bacterial homolog, RNase T. Kinetic measurements indicate that the apparent K_m of TREX1 for RNA is higher than that for DNA. Like RNase T, human TREX1 is active in degrading native …

Genetic Heterogeneity Of Pseudoxanthoma Elasticum: The Chinese Signature Profile Of Abcc6 And Enpp1 Mutations., Liang Jin, Qiujie Jiang, Zhengsheng Wu, Changxia Shao, Yong Zhou, Luting Yang, Jouni Uitto, Gang Wang

Department of Dermatology and Cutaneous Biology Faculty Papers

Pseudoxanthoma elasticum (PXE), an autosomal recessive disorder characterized by ectopic mineralization, is caused by mutations in the ABCC6 gene. We examined clinically 29 Chinese PXE patients from unrelated families, so far the largest cohort of Asian PXE patients. In a subset of 22 patients, we sequenced ABCC6 and another candidate gene, ENPP1, and conducted pathogenicity analyses for each variant. We identified a total of 17 distinct mutations in ABCC6, 15 of them being, to our knowledge, previously unreported, including 5 frameshift and 10 missense variants. In addition, a missense mutation in combination with a recurrent nonsense mutation in ENPP1 was …

Optimization Of Image Reconstruction For Magnetic Resonance Imaging–Guided Near-Infrared Diffuse Optical Spectroscopy In Breast, Yan Zhao, Michael A. Mastanduno, Shudong Jiang, Fadi Ei-Ghussein, Jiang Gui, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

An optimized approach to nonlinear iterative reconstruction of magnetic resonance imaging (MRI)–guided near-infrared spectral tomography (NIRST) images was developed using an L-curve-based algorithm for the choice of regularization parameter. This approach was applied to clinical exam data to maximize the reconstructed values differentiating malignant and benign lesions. MRI/NIRST data from 25 patients with abnormal breast readings (BI-RADS category 4-5) were analyzed using this optimal regularization methodology, and the results showed enhanced p values and area under the curve (AUC) for the task of differentiating malignant from benign lesions. Of the four absorption parameters and two scatter parameters, the most significant …