Digital Commons Network^™

Fear Conditioning And Extinction In Youth With Obsessive-Compulsive Disorder, Joseph F. Mcguire, Scott P. Orr, Monica S. Wu, Adam B. Lewin, Brent J. Small, Vicky Phares, Tanya K. Murphy, Sabine Wilhelm, Daniel S. Pine, Daniel Geller, Eric A. Storch

Psychology Faculty Publications

BACKGROUND: Fear acquisition and extinction are central constructs in the cognitive-behavioral model of obsessive-compulsive disorder (OCD), which underlies exposure-based cognitive-behavioral therapy (CBT). Youth with OCD may have impairments in fear acquisition and extinction that carry treatment implications. We examined these processes using a differential conditioning procedure.

METHODS: Forty-one youth (19 OCD, 22 community comparisons) completed a battery of clinical interviews, rating scales, and a differential conditioning task that included habituation, acquisition, and extinction phases. Skin conductance response (SCR) served as the primary dependent measure.

RESULTS: During habituation, no difference between groups was observed. During acquisition, differential fear conditioning was observed …

Extracorporeal Membrane Oxygenation (Ecmo) For Severe Toxicological Exposures: Review Of The Toxicology Investigators Consortium (Toxic)., G S. Wang, R Levitan, T J. Wiegand, Jennifer Lowry, R F. Schult, S Yin, Toxicology Investigators Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Although there have been many developments related to specific strategies for treating patients after poisoning exposures, the mainstay of therapy remains symptomatic and supportive care. One of the most aggressive supportive modalities is extracorporeal membrane oxygenation (ECMO). Our goal was to describe the use of ECMO for toxicological exposures reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC). We performed a retrospective review of the ACMT ToxIC Registry from January 1, 2010 to December 31, 2013. Inclusion criteria included patients aged 0 to 89 years, evaluated between January 2010 through December 2013, and received ECMO for …

Retigabine Holds Kv7 Channels Open And Stabilizes The Resting Potential, Aaron Corbin-Leftwich, Sayeed M. Mossadeq, Junghoon Ha, Iwona Ruchala, Audrey Han Ngoc Le, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The anticonvulsant Retigabine is a KV7 channel agonist used to treat hyperexcitability disorders in humans. Retigabine shifts the voltage dependence for activation of the heteromeric KV7.2/KV7.3 channel to more negative potentials, thus facilitating activation. Although the molecular mechanism underlying Retigabine's action remains unknown, previous studies have identified the pore region of KV7 channels as the drug's target. This suggested that the Retigabine-induced shift in voltage dependence likely derives from the stabilization of the pore domain in an open (conducting) conformation. Testing this idea, we show that the heteromeric KV7.2/KV7.3 channel has at least two open states, which we named O1 …

Cddo-Me Redirects Activation Of Breast Tumor Associated Macrophages, Michael S. Ball, Emilie P. Shipman, Hyunjung Kim, Karen T. Liby, Patricia A. Pioli

Dartmouth Scholarship

Tumor-associated macrophages can account for up to 50% of the tumor mass in breast cancer patients and high TAM density is associated with poor clinical prognosis. Because TAMs enhance tumor growth, development, and metastatic potential, redirection of TAM activation may have significant therapeutic benefit. Our studies in primary human macrophages and murine breast TAMs suggest that the synthetic oleanane triterpenoid CDDO-methyl ester (CDDO-Me) reprograms the activation profile of TAMs from tumor-promoting to tumor-inhibiting. We show that CDDO-Me treatment inhibits expression of IL-10 and VEGF in stimulated human M2 macrophages and TAMs but increases expression of TNF-α and IL-6. Surface expression …

Genomic Characterization Of Patient-Derived Xenograft Models Established From Fine Needle Aspirate Biopsies Of A Primary Pancreatic Ductal Adenocarcinoma And From Patient-Matched Metastatic Sites, Robert J. Allaway, Dawn A. Fischer, Francine B. De Abreu, Timothy B. Gardner, Stuart R. Gordon, Richard J. Barth, Thomas A. Colacchio, Matthew Wood, Balint Z. Kacsoh, Stephanie J. Bouley

Dartmouth Scholarship

N-of-1 trials target actionable mutations, yet such approaches do not test genomically-informed therapies in patient tumor models prior to patient treatment. To address this, we developed patient-derived xenograft (PDX) models from fine needle aspiration (FNA) biopsies (FNA-PDX) obtained from primary pancreatic ductal adenocarcinoma (PDAC) at the time of diagnosis. Here, we characterize PDX models established from one primary and two metastatic sites of one patient. We identified an activating KRAS G12R mutation among other mutations in these models. In explant cells derived from these PDX tumor models with a KRAS G12R mutation, treatment with inhibitors of CDKs (including CDK9) reduced …

Role Of Deubiquitinating Enzymes In Dna Repair, Younghoon Kee, Tony T. Huang

Molecular Biosciences Faculty Publications

Both proteolytic and nonproteolytic functions of ubiquitination are essential regulatory mechanisms for promoting DNA repair and the DNA damage response in mammalian cells. Deubiquitinating enzymes (DUBs) have emerged as key players in the maintenance of genome stability. In this minireview, we discuss the recent findings on human DUBs that participate in genome maintenance, with a focus on the role of DUBs in the modulation of DNA repair and DNA damage signaling.

Differential Expression Of Pancreatic Protein And Chemosensing Receptor Mrnas In Nkcc1-Null Intestine, Emily M. Bradford, Kanimozhi Vairamani, Gary E. Shull

Internal Medicine Faculty Publications

AIM: To investigate the intestinal functions of the NKCC1 Na⁺-K⁺-2Cl cotransporter (SLC12a2 gene), differential mRNA expression changes in NKCC1-null intestine were analyzed.

METHODS: Microarray analysis of mRNA from intestines of adult wild-type mice and gene-targeted NKCC1-null mice (n = 6 of each genotype) was performed to identify patterns of differential gene expression changes. Differential expression patterns were further examined by Gene Ontology analysis using the online Gorilla program, and expression changes of selected genes were verified using northern blot analysis and quantitative real time-polymerase chain reaction. Histological staining and immunofluorescence were performed …

The Two-Component System Cpxra Negatively Regulates The Locus Of Enterocyte Effacement Of Enterohemorrhagic Escherichia Coli Involving Σ32 And Lon Protease, Miguel A. De La Cruz, Jason K. Morgan, Miguel A. Ares, Jorge A. Yáñez-Santos, James T. Riordan, Jorge A. Girón

Molecular Biosciences Faculty Publications

Enterohemorrhagic Escherichia coli (EHEC) is a significant cause of serious human gastrointestinal disease worldwide. EHEC strains contain a pathogenicity island called the locus of enterocyte effacement (LEE), which encodes virulence factors responsible for damaging the gut mucosa. The Cpx envelope stress response of E. coli is controlled by a two-component system (TCS) consisting of a sensor histidine kinase (CpxA) and a cytoplasmic response regulator (CpxR). In this study, we investigated the role of CpxRA in the expression of LEE-encoded virulence factors of EHEC. We found that a mutation in cpxA significantly affected adherence of EHEC to human epithelial cells. Analysis …

Sensory Plasticity In Human Motor Learning., David J Ostry, Paul L Gribble

Brain and Mind Institute Researchers' Publications

There is accumulating evidence from behavioral, neurophysiological, and neuroimaging studies that the acquisition of motor skills involves both perceptual and motor learning. Perceptual learning alters movements, motor learning, and motor networks of the brain. Motor learning changes perceptual function and the sensory circuits of the brain. Here, we review studies of both human limb movement and speech that indicate that plasticity in sensory and motor systems is reciprocally linked. Taken together, this points to an approach to motor learning in which perceptual learning and sensory plasticity have a fundamental role.

Genetic Loci Associated With Renal Function Measures And Chronic Kidney Disease In Children: The Pediatric Investigation For Genetic Factors Linked With Renal Progression Consortium., Matthias Wuttke, Craig S. Wong, Elke Wühl, Daniel Epting, Li Luo, Anselm Hoppmann, Anke Doyon, Yong Li, Gkdgen Consortium, Betül Sözeri, Daniela Thurn, Martin Helmstädter, Tobias B. Huber, Tom D. Blydt-Hansen, Albrecht Kramer-Zucker, Otto Mehls, Anette Melk, Uwe Querfeld, Susan L. Furth, Bradley A. Warady, Franz Schaefer, Anna Köttgen

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Chronic kidney disease (CKD) in children is characterized by rapid progression and a high incidence of end-stage renal disease and therefore constitutes an important health problem. While unbiased genetic screens have identified common risk variants influencing renal function and CKD in adults, the presence and identity of such variants in pediatric CKD are unknown.

METHODS: The international Pediatric Investigation for Genetic Factors Linked with Renal Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) and Cardiovascular …

Endosteal Biologic Augmentation For Surgical Fixation Of Displaced Femoral Neck Fractures, Lionel E Lazaro, Jacqueline F Birnbaum, Nadja A Farshad-Amacker, David L Helfet, Hollis G Potter, Dean G Lorich

Faculty, Staff and Student Publications

OBJECTIVES: To report outcomes of a cohort with displaced femoral neck fractures (FNFs) treated with a length/angle-stable construct augmented with an endosteal fibular allograft serving as a biologic dowel.

DESIGN: Prospective.

SETTING: Level I Trauma Center.

PATIENTS: The study group consists of 27 patients with isolated FNF surgically treated by a single surgeon.

INTERVENTION: Open reduction of the femoral neck, fixed with a length- and angle-stable construct of 2 fully threaded cannulated screws augmented with an endosteal fibular allograft serving as a biologic dowel.

MAIN OUTCOME MEASUREMENTS: Clinical and radiographic outcomes of the fixation construct and the viability of both …

The Mosaic Mitral Valve Bioprosthesis: A Long-Term Clinical And Hemodynamic Follow-Up, Michele Celiento, Stefania Blasi, Andrea De Martino, Stefano Pratali, Aldo D Milano, Uberto Bortolotti

The Texas Heart Institute Journal

We reviewed the cases of 100 patients (mean age, 73 ± 10 yr; 64 men) who had mitral valve replacement with a Medtronic Mosaic porcine bioprosthesis from 1995 through 2011. The mean New York Heart Association (NYHA) class was 3 ± 0.7, and 52 patients were in atrial fibrillation. Prosthetic sizes were chiefly 27 mm (50 patients) and 29 mm (40 patients). Follow-up ended in December 2012 and is 97% complete, with a cumulative duration of 611 patient-years (mean duration, 6 ± 4.6 yr; maximum, 17.7 yr). The early mortality rate was 10% (6% in elective patients); late deaths occurred …

Predator Diet And Trophic Position Modified With Altered Habitat Morphology, Alexander Tewfik, Susan S. Bell, Kevin S. Mccann, Kristina Morrow

Integrative Biology Faculty and Staff Publications

Empirical patterns that emerge from an examination of food webs over gradients of environmental variation can help to predict the implications of anthropogenic disturbance on ecosystems. This “dynamic food web approach” is rarely applied at the coastal margin where aquatic and terrestrial systems are coupled and human development activities are often concentrated. We propose a simple model of ghost crab (Ocypode quadrata) feeding that predicts changing dominant prey (Emerita talpoida, Talorchestia sp., Donax variablis) along a gradient of beach morphology and test this model using a suite of 16 beaches along the Florida, USA coast. …

Identification Of Novel Cyclic Lipopeptides From A Positional Scanning Combinatorial Library With Enhanced Antibacterial And Antibiofilm Activities, Nina Bionda, Renee M. Fleeman, César De La Fuente-Núñez, Maria C. Rodriguez, Fany Reffuveille, Lindsey N. Shaw, Irena Pastar, Stephen C Davis, Robert E W Hancock, Predrag Cudic

Molecular Biosciences Faculty Publications

Treating bacterial infections can be difficult due to innate or acquired resistance mechanisms, and the formation of biofilms. Cyclic lipopeptides derived from fusaricidin/LI-F natural products represent particularly attractive candidates for the development of new antibacterial and antibiofilm agents, with the potential to meet the challenge of bacterial resistance to antibiotics. A positional-scanning combinatorial approach was used to identify the amino acid residues responsible for driving antibacterial activity, and increase the potency of these cyclic lipopeptides. Screening against the antibiotic resistant ESKAPE pathogens revealed the importance of hydrophobic as well as positively charged amino acid residues for activity of this class …

Gap Junction Mediated Mirna Intercellular Transfer And Gene Regulation: A Novel Mechanism For Intercellular Genetic Communication, Liang Zong, Yan Zhu, Ruqiang Liang, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Intercellular genetic communication is an essential requirement for coordination of cell proliferation and differentiation and has an important role in many cellular processes. Gap junction channels possess large pore allowing passage of ions and small molecules between cells. MicroRNAs (miRNAs) are small regulatory RNAs that can regulate gene expression broadly. Here, we report that miRNAs can pass through gap junction channels in a connexin-dependent manner. Connexin43 (Cx43) had higher permeability, whereas Cx30 showed little permeability to miRNAs. In the tested connexin cell lines, the permeability to miRNAs demonstrated: Cx43 > Cx26/30 > Cx26 > Cx31 > Cx30 = Cx-null. However, consistent with a uniform …

Imaging Tumour Cell Heterogeneity Following Cell Transplantation Into Optically Clear Immune-Deficient Zebrafish, Qin Tang, John C. Moore, Myron S. Ignatius, Inês M. Tenente, Madeline N. Hayes, Elaine G. Garcia, Nora Torres Yordán, Caitlin Bourque, Shuning He, Jessica S. Blackburn, A. Thomas Look, Yariv Houvras, David M. Langenau

Molecular and Cellular Biochemistry Faculty Publications

Cancers contain a wide diversity of cell types that are defined by differentiation states, genetic mutations and altered epigenetic programmes that impart functional diversity to individual cells. Elevated tumour cell heterogeneity is linked with progression, therapy resistance and relapse. Yet, imaging of tumour cell heterogeneity and the hallmarks of cancer has been a technical and biological challenge. Here we develop optically clear immune-compromised rag2^E450fs (casper) zebrafish for optimized cell transplantation and direct visualization of fluorescently labelled cancer cells at single-cell resolution. Tumour engraftment permits dynamic imaging of neovascularization, niche partitioning of tumour-propagating cells in embryonal rhabdomyosarcoma, emergence of clonal …

Mir494 Reduces Renal Cancer Cell Survival Coinciding With Increased Lipid Droplets And Mitochondrial Changes, Punashi Dutta, Edward Haller, Arielle Sharp, Meera Nanjundan

Molecular Biosciences Faculty Publications

Background: miRNAs can regulate cellular survival in various cancer cell types. Recent evidence implicates the formation of lipid droplets as a hallmark event during apoptotic cell death response. It is presently unknown whether MIR494, located at 14q32 which is deleted in renal cancers, reduces cell survival in renal cancer cells and if this process is accompanied by changes in the number of lipid droplets.

Methods: 769-P renal carcinoma cells were utilized for this study. Control or MIR494 mimic was expressed in these cells following which cell viability (via crystal violet) and apoptotic cell numbers (via Annexin V/PI staining) were …

H2ax Deficiency Is Associated With Erythroid Dysplasia And Compromised Haematopoietic Stem Cell Function, Baobing Zhao, Timothy L. Tan, Yang Mei, Jing Yang, Yiting Yu, Amit Verma, Ying Liang, Juehua Gao, Peng Ji

Toxicology and Cancer Biology Faculty Publications

Myelodysplastic syndromes (MDS) are clonal disorders of haematopoiesis characterised by dysplastic changes of major myeloid cell lines. However, the mechanisms underlying these dysplastic changes are poorly understood. Here, we used a genetically modified mouse model and human patient data to examine the physiological roles of H2AX in haematopoiesis and how the loss of H2AX contributes to dyserythropoiesis in MDS. H2AX knockout mice showed cell-autonomous anaemia and erythroid dysplasia, mimicking dyserythropoiesis in MDS. Also, dyserythropoiesis was increased in MDS patients with the deletion of chromosome 11q23, where H2AX is located. Although loss of H2AX did not affect the early stage of …

Obesity-Induced Colorectal Cancer Is Driven By Caloric Silencing Of The Guanylin-Gucy2c Paracrine Signaling Axis., Jieru E. Lin, Francheska Colon-Gonzalez, Erik S. Blomain, Gilbert W. Kim, Amanda Aing, Brian Stoecker, Justin Rock, Adam E. Snook, Tingting Zhan, Terry M. Hyslop, Michal Tomczak, Richard S. Blumberg, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Obesity is a well-known risk factor for colorectal cancer but precisely how it influences risks of malignancy remains unclear. During colon cancer development in humans or animals, attenuation of the colonic cell surface receptor guanylyl cyclase C (GUCY2C) that occurs due to loss of its paracrine hormone ligand guanylin contributes universally to malignant progression. In this study, we explored a link between obesity and GUCY2C silencing in colorectal cancer. Using genetically engineered mice on different diets, we found that diet-induced obesity caused a loss of guanylin expression in the colon with subsequent GUCY2C silencing, epithelial dysfunction, and tumorigenesis. Mechanistic investigations …

Effect Of Hydroxychloroquine And Characterization Of Autophagy In A Mouse Model Of Endometriosis, A. Ruiz, S. Rockfield, N. Taran, E. Haller, Robert Engelman, I Flores, P Panina-Bordignon, Meera Nanjundan

Molecular Biosciences Faculty Publications

In endometriosis, the increased survival potential of shed endometrial cells (which normally undergo anoikis) is suggested to promote lesion development. One mechanism that may alter anoikis is autophagy. Using an autophagic flux inhibitor hydroxychloroquine (HCQ), we identified that it reduces the in vitro survival capacity of human endometriotic and endometrial T-HESC cells. We also identified that HCQ could decrease lesion numbers and disrupt lesion histopathology, as well as increase the levels of peritoneal macrophages and the IP-10 (10 kDa interferon-γ-induced protein) chemokine in a mouse model of endometriosis. We noted that RNA levels of a subset of autophagic …

Targeting Wnt/Β-Catenin Pathway In Hepatocellular Carcinoma Treatment, Valery Vilchez, Lilia M. Turcios, Francesc Marti, Roberto Gedaly

Surgery Faculty Publications

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Liver cancer is generally related to hepatitis B or C infection and cirrhosis. Usually, patients with HCC are asymptomatic and are diagnosed at late stages when surgical treatment is no longer suitable. Limited treatment options for patients with advanced HCC are a major concern. Therefore, there is an urge for finding novel therapies to treat HCC. Liver cancer is highly heterogeneous and involved deregulation of several signaling pathways. Wnt/β-catenin pathway is frequently upregulated in HCC and it is implicated in maintenance of tumor initiating cells, drug …

Non-Alcoholic Fatty Liver Disease Induces Signs Of Alzheimer’S Disease (Ad) In Wild-Type Mice And Accelerates Pathological Signs Of Ad In An Ad Model, Do-Geun Kim, Antje Krenz, Leon E. Toussaint, Kirk J. Maurer

Dartmouth Scholarship

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease afflicting about one third of the world's population and 30 % of the US population. It is induced by consumption of high-lipid diets and is characterized by liver inflammation and subsequent liver pathology. Obesity and consumption of a high-fat diet are known to increase the risk of Alzheimer's disease (AD). Here, we investigated NAFLD-induced liver inflammation in the pathogenesis of AD.

Methods: WT and APP-Tg mice were fed with a standard diet (SD) or a high-fat diet (HFD) for 2, 5 months, or 1 year to induce NAFLD. Another …

Metabolomics Workbench: An International Repository For Metabolomics Data And Metadata, Metabolite Standards, Protocols, Tutorials And Training, And Analysis Tools, Manish Sud, Eoin Fahy, Dawn Cotter, Kenan Azam, Ilango Vadivelu, Charles Burant, Arthur Edison, Oliver Fiehn, Richard M. Higashi, K. Sreekumaran Nair, Susan Sumner, Shankar Subramaniam

Toxicology and Cancer Biology Faculty Publications

The Metabolomics Workbench, available at www.metabolomicsworkbench.org, is a public repository for metabolomics metadata and experimental data spanning various species and experimental platforms, metabolite standards, metabolite structures, protocols, tutorials, and training material and other educational resources. It provides a computational platform to integrate, analyze, track, deposit and disseminate large volumes of heterogeneous data from a wide variety of metabolomics studies including mass spectrometry (MS) and nuclear magnetic resonance spectrometry (NMR) data spanning over 20 different species covering all the major taxonomic categories including humans and other mammals, plants, insects, invertebrates and microorganisms. Additionally, a number of protocols are provided for …

Serum Amyloid A Impairs The Antiinflammatory Properties Of Hdl, Chang Yeop Han, Chongren Tang, Myriam E. Guevara, Hao Wei, Tomasz Wietecha, Baohai Shao, Savitha Subramanian, Mohamed Omer, Shari Wang, Kevin D. O'Brien, Santica M. Marcovina, Thomas N. Wight, Tomas Vaisar, Maria C. De Beer, Frederick C. De Beer, William R. Osborne, Keith B. Elkon, Alan Chait

Physiology Faculty Publications

HDL from healthy humans and lean mice inhibits palmitate-induced adipocyte inflammation; however, the effect of the inflammatory state on the functional properties of HDL on adipocytes is unknown. Here, we found that HDL from mice injected with AgNO₃ fails to inhibit palmitate-induced inflammation and reduces cholesterol efflux from 3T3-L1 adipocytes. Moreover, HDL isolated from obese mice with moderate inflammation and humans with systemic lupus erythematosus had similar effects. Since serum amyloid A (SAA) concentrations in HDL increase with inflammation, we investigated whether elevated SAA is a causal factor in HDL dysfunction. HDL from AgNO₃-injected mice lacking Saa1.1 …

Integrative Analysis Of Breast Cancer Reveals Prognostic Haematopoietic Activity And Patient-Specific Immune Response Profiles, Frederick S. Varn, Erik H. Andrews, David W. Mullins, Chao Cheng

Dartmouth Scholarship

Transcriptional programmes active in haematopoietic cells enable a variety of functions including dedifferentiation, innate immunity and adaptive immunity. Understanding how these programmes function in the context of cancer can provide valuable insights into host immune response, cancer severity and potential therapy response. Here we present a method that uses the transcriptomes of over 200 murine haematopoietic cells, to infer the lineage-specific haematopoietic activity present in human breast tumours. Correlating this activity with patient survival and tumour purity reveals that the transcriptional programmes of many cell types influence patient prognosis and are found in environments of high lymphocytic infiltration. Collectively, these …

[Formula: See Text]Differences In Memory Functioning Between Children With Attention-Deficit/Hyperactivity Disorder And/Or Focal Epilepsy., Sylvia E Lee, Michelle Y Kibby, Morris J Cohen, Lisa Stanford, Yong Park, Suzanne Strickland

Publications

No abstract provided.

Exome Screening To Identify Loss-Of-Function Mutations In The Rhesus Macaque For Development Of Preclinical Models Of Human Disease, Adam Cornish, Robert M. Gibbs, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Exome sequencing has been utilized to identify genetic variants associated with disease in humans. Identification of loss-of-function mutations with exome sequencing in rhesus macaques (Macaca mulatta) could lead to valuable animal models of genetic disease. Attempts have been made to identify variants in rhesus macaques by aligning exome data against the rheMac2 draft genome. However, such efforts have been impaired due to the incompleteness and annotation errors associated with rheMac2. We wished to determine whether aligning exome reads against our new, improved rhesus genome, MacaM, could be used to identify high impact, loss-of-function mutations in rhesus macaques that would …

High Throughput Genomic Sequencing Of Bioaerosols In Broiler Chicken Production Facilities, Kate M. O’Brien, Michael S. Chimenti, Morgan Farnell, Tom Tabler, Thomas Bair, Joey Lynn Bray, Matthew W. Nonnenmann

Faculty Publications

Chronic inhalation exposure to agricultural dust promotes the development of chronic respiratory diseases among poultry workers. Poultry dust is composed of dander, chicken feed, litter bedding and microbes. However, the microbial composition and abundance has not been fully elucidated. Genomic DNA was extracted from settled dust and personal inhalable dust collected while performing litter sampling or mortality collection tasks. DNA libraries were sequenced using a paired-end sequencing-by-synthesis approach on an Illumina HiSeq 2500. Sequencing data showed that poultry dust is predominantly composed of bacteria (64–67%) with a small quantity of avian, human and feed DNA (< 2% of total reads). Staphylococcus sp. AL1, Salinicoccus carnicancri and Lactobacillus crispatus were the most abundant bacterial species in personal exposure samples of inhalable dust. Settled dust had a moderate relative abundance of these species as well as Staphylococcus lentus and Lactobacillus salivarius. There was a statistical difference between the microbial composition of aerosolized and settled dust. Unlike settled dust composition, aerosolized dust composition had little variance between samples. These data provide an extensive analysis of the microbial composition and relative abundance in personal inhalable poultry dust and settled poultry dust.

Upregulation Of Rgs2: A New Mechanism For Pirfenidone Amelioration Of Pulmonary Fibrosis, Yan Xie, Haihong Jiang, Qian Zhang, Suneet Mehrotra, Peter W. Abel, Myron L. Toews, Dennis W. Wolff, Stephen I. Rennard, Reynold A. Panettieri, Thomas B. Casale, Yaping Tu

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Pirfenidone was recently approved for treatment of idiopathic pulmonary fibrosis. However, the therapeutic dose of pirfenidone is very high, causing side effects that limit its doses and therapeutic effectiveness. Understanding the molecular mechanisms of action of pirfenidone could improve its safety and efficacy. Because activated fibroblasts are critical effector cells associated with the progression of fibrosis, this study investigated the genes that change expression rapidly in response to pirfenidone treatment of pulmonary fibroblasts and explored their contributions to the anti-fibrotic effects of pirfenidone.

METHODS: We used the GeneChip microarray to screen for genes that were rapidly up-regulated upon exposure …

Antagonism Of Triazolam Self-Administration In Rhesus Monkeys Responding Under A Progressive-Ratio Schedule: In Vivo Apparent Pa2 Analysis., Bradford D Fischer, Donna M Platt, Sundari K Rallapalli, Ojas A Namjoshi, James M Cook, James K Rowlett

Cooper Medical School of Rowan University Departmental Research

BACKGROUND: Conventional benzodiazepines bind non-selectively to GABAA receptors containing α1, α2, α3, and α5 subunits (α1GABAA, α2GABAA, α3GABAA, and α5GABAA receptors, respectively), and the role of these different GABAA receptor subtypes in the reinforcing effects of benzodiazepines has not been characterized fully. We used a pharmacological antagonist approach with available subtype-selective ligands to evaluate the role of GABAA receptor subtypes in the reinforcing effects of the non-selective conventional benzodiazepine, triazolam.

METHODS: Rhesus monkeys (n=4) were trained under a progressive-ratio schedule of intravenous midazolam delivery and dose-response functions were determined for triazolam, in the absence and presence of flumazenil (non-selective antagonist), …