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Genome-Wide Transcriptomic And Proteomic Analyses Of Bollworm-Infested Developing Cotton Bolls Revealed The Genes And Pathways Involved In The Insect Pest Defence Mechanism, Saravanan Kumar, Kanakachari Mogilicherla, Dhandapani Gurusamy, Krishan Kumar, Prabhakaran Narayanasamy, Padmalatha Kethireddy Venkata, Amolkumar Solanke, Savita Gamanagatti, Vamadevaiah Hiremath, Ishwarappa S. Katageri, Sadhu Leelavathi, Polumetla Ananda Kumar, Vanga Siva Reddy Jan 2016

Genome-Wide Transcriptomic And Proteomic Analyses Of Bollworm-Infested Developing Cotton Bolls Revealed The Genes And Pathways Involved In The Insect Pest Defence Mechanism, Saravanan Kumar, Kanakachari Mogilicherla, Dhandapani Gurusamy, Krishan Kumar, Prabhakaran Narayanasamy, Padmalatha Kethireddy Venkata, Amolkumar Solanke, Savita Gamanagatti, Vamadevaiah Hiremath, Ishwarappa S. Katageri, Sadhu Leelavathi, Polumetla Ananda Kumar, Vanga Siva Reddy

Entomology Faculty Publications

Cotton bollworm, Helicoverpa armigera, is a major insect pest that feeds on cotton bolls causing extensive damage leading to crop and productivity loss. In spite of such a major impact, cotton plant response to bollworm infection is yet to be witnessed. In this context, we have studied the genome-wide response of cotton bolls infested with bollworm using transcriptomic and proteomic approaches. Further, we have validated this data using semi-quantitative real-time PCR. Comparative analyses have revealed that 39% of the transcriptome and 35% of the proteome were differentially regulated during bollworm infestation. Around 36% of significantly regulated transcripts and 45% …


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 Jan 2016

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 rag2E450fs (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 …


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 Jan 2016

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 Jan 2016

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 Jan 2016

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 Jan 2016

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 …


Analyzing Clustered Data: Why And How To Account For Multiple Observations Nested Within A Study Participant?, Erika L. Moen, Catherine J. Fricano-Kugler, Bryan W. Luikart, A. James O’Malley Jan 2016

Analyzing Clustered Data: Why And How To Account For Multiple Observations Nested Within A Study Participant?, Erika L. Moen, Catherine J. Fricano-Kugler, Bryan W. Luikart, A. James O’Malley

Dartmouth Scholarship

A conventional study design among medical and biological experimentalists involves col- lecting multiple measurements from a study subject. For example, experiments utilizing mouse models in neuroscience often involve collecting multiple neuron measurements per mouse to increase the number of observations without requiring a large number of mice. This leads to a form of statistical dependence referred to as clustering. Inappropriate analy- ses of clustered data have resulted in several recent critiques of neuroscience research that suggest the bar for statistical analyses within the field is set too low. We compare naïve ana- lytical approaches to marginal, fixed-effect, and mixed-effect models …


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 Jan 2016

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 Jan 2016

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 Jan 2016

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 Jan 2016

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 …


Dc Beadm1™: Towards An Optimal Transcatheter Hepatic Tumour Therapy., Andrew L Lewis, Matthew R Dreher, Vincent O'Byrne, David Grey, Marcus Caine, Anthony Dunn, Yiqing Tang, Brenda Hall, Kirk D Fowers, Carmen Gacchina Johnson, Karun V. Sharma, Bradford J Wood Jan 2016

Dc Beadm1™: Towards An Optimal Transcatheter Hepatic Tumour Therapy., Andrew L Lewis, Matthew R Dreher, Vincent O'Byrne, David Grey, Marcus Caine, Anthony Dunn, Yiqing Tang, Brenda Hall, Kirk D Fowers, Carmen Gacchina Johnson, Karun V. Sharma, Bradford J Wood

Pediatrics Faculty Publications

Clinical use of DC Bead™ loaded with doxorubicin (DEBDOX™) or irinotecan (DEBIRI™), for the treatment of primary and secondary tumours of the liver respectively, is showing great promise. Recently there has been a tendency to select smaller bead size ranges to treat tumours in an effort to allow more drug dose to be administered, improve tumoural penetration and resultant drug delivery and tumour coverage. Herein we describe the development and performance characterisation of a new DC Bead size range (DC BeadM1 (TM), 70-150 μm) capable of an increased bead delivery in the distal vasculature, corresponding to greater tumour coverage and …


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 Jan 2016

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 …


West African Anopheles Gambiae Mosquitoes Harbor A Taxonomically Diverse Virome Including New Insect-Specific Flaviviruses, Mononegaviruses, And Totiviruses, Joseph R. Fauver, Nathan D. Grubaugh, Benjamin J. Krajacich, James Weger-Lucarelli, Steven M. Lakin, Lawrence S. Fakoli, Fatorma K. Bolay, Joseph W. Diclaro, Kounbobr Roch Dabiré, Brian D. Foy, Doug E. Brackney, Gregory D. Ebel, Mark D. Stenglein Jan 2016

West African Anopheles Gambiae Mosquitoes Harbor A Taxonomically Diverse Virome Including New Insect-Specific Flaviviruses, Mononegaviruses, And Totiviruses, Joseph R. Fauver, Nathan D. Grubaugh, Benjamin J. Krajacich, James Weger-Lucarelli, Steven M. Lakin, Lawrence S. Fakoli, Fatorma K. Bolay, Joseph W. Diclaro, Kounbobr Roch Dabiré, Brian D. Foy, Doug E. Brackney, Gregory D. Ebel, Mark D. Stenglein

Journal Articles: Epidemiology

Anopheles gambiae are a major vector of malaria in sub-Saharan Africa. Viruses that naturally infect these mosquitoes may impact their physiology and ability to transmit pathogens. We therefore used metagenomics sequencing to search for viruses in adult Anopheles mosquitoes collected from Liberia, Senegal, and Burkina Faso. We identified a number of virus and virus-like sequences from mosquito midgut contents, including 14 coding-complete genome segments and 26 partial sequences. The coding-complete sequences define new viruses in the order Mononegavirales, and the families Flaviviridae, and Totiviridae. The identification of a flavivirus infecting Anopheles mosquitoes broadens our understanding of the evolution and host …


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 Jan 2016

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.


A Moral Argument For Veganism, Dan Hooley, Nathan Nobis Jan 2016

A Moral Argument For Veganism, Dan Hooley, Nathan Nobis

Human Health Collection

In this essay, we argue for dietary veganism. Our case has two steps. First, we argue that, in most circumstances, it is morally wrong to raise animals to produce meat, dairy products, most eggs (a possible exception we discuss is eggs from pet chickens) and most other animal food products. Turning animals into food, and using them for their byproducts, causes serious harms to animals that are morally unjustified: that is, the reasons given to justify causing these kinds of harms – goods or alleged goods that result from animal farming and slaughter – are inadequate to justify the bad …


Cardiac Mitochondrial Respiratory Dysfunction And Tissue Damage In Chronic Hyperglycemia Correlate With Reduced Aldehyde Dehydrogenase-2 Activity, Vishal R. Mali, Guodong Pan, Mandar Deshpande, Rajarajan A. Thandavarayan, Jiang Xu, Xiao-Ping Yang, Suresh S. Palaniyandi Jan 2016

Cardiac Mitochondrial Respiratory Dysfunction And Tissue Damage In Chronic Hyperglycemia Correlate With Reduced Aldehyde Dehydrogenase-2 Activity, Vishal R. Mali, Guodong Pan, Mandar Deshpande, Rajarajan A. Thandavarayan, Jiang Xu, Xiao-Ping Yang, Suresh S. Palaniyandi

Hypertension and Vascular Research Articles

Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial isozyme of the heart involved in the metabolism of toxic aldehydes produced from oxidative stress. We hypothesized that hyperglycemia-mediated decrease in ALDH2 activity may impair mitochondrial respiration and ultimately result in cardiac damage. A single dose (65 mg/kg; i.p.) streptozotocin injection to rats resulted in hyperglycemia with blood glucose levels of 443 ± 9 mg/dl versus 121 ± 7 mg/dl in control animals, p<0.0001, N = 7-11. After 6 months of diabetes mellitus (DM) induction, the rats were sacrificed after recording the functionality of their hearts. Increase in the cardiomyocyte cross sectional area (446 ± 32 μm2 Vs 221 ± 10 μm2; p<0.0001) indicated cardiac hypertrophy in DM rats. Both diastolic and systolic dysfunctions were observed with DM rats compared to controls. Most importantly, myocardial ALDH2 activity and levels were reduced, and immunostaining for 4HNE protein adducts was increased in DM hearts compared to controls. The mitochondrial oxygen consumption rate (OCR), an index of mitochondrial respiration, was decreased in mitochondria isolated from DM hearts compared to controls (p<0.0001). Furthermore, the rate of mitochondrial respiration and the increase in carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)-induced maximal respiration were also decreased with chronic hyperglycemia. Chronic hyperglycemia reduced mitochondrial OXPHOS proteins. Reduced ALDH2 activity was correlated with mitochondrial dysfunction, pathological remodeling and cardiac dysfunction, respectively. Our results suggest that chronic hyperglycemia reduces ALDH2 activity, leading to mitochondrial respiratory dysfunction and consequently cardiac damage and dysfunction.


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 Jan 2016

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 Jan 2016

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), …


Endocidal Regulation Of Secondary Metabolites In The Producing Organisms, Shiyou Li, Ping Wang, Wei Yuan, Zushang Su, Steven H. Bullard Jan 2016

Endocidal Regulation Of Secondary Metabolites In The Producing Organisms, Shiyou Li, Ping Wang, Wei Yuan, Zushang Su, Steven H. Bullard

Faculty Publications

Secondary metabolites are defined as organic compounds that are not directly involved in the normal growth, development, and reproduction of an organism. They are widely believed to be responsible for interactions between the producing organism and its environment, with the producer avoiding their toxicities. In our experiments, however, none of the randomly selected 44 species representing different groups of plants and insects can avoid autotoxicity by its endogenous metabolites once made available. We coined the term endocides (endogenous biocides) to describe such metabolites that can poison or inhibit the parent via induced biosynthesis or external applications. Dosage-dependent endocides can selectively …


Aristotle's Clivus Naturae, John Thorp Jan 2016

Aristotle's Clivus Naturae, John Thorp

Philosophy Presentations

It is usually thought that Aristotle's understanding of the soul sees it has having four distinct parts, cumulatively arranged, resulting in a kind of scala or ladder: all living things have the nutritive and reproductive soul; animals have, in addition, the sensitive soul, and most of them also the locomotive soul; only humans have all these plus the intellective soul. This ladder-like picture emerges from his theoretical work de Anima. In his more empirical studies, though, the discreteness of these levels is softened, and the image is more that of a clivus or slope, rather than a scala or ladder …


Microglia And Neurons In The Hippocampus Of Migratory Sandpipers., C G Diniz, N G M Magalhães, A A Sousa, C Santos Filho, D G Diniz, C M Lima, M A Oliveira, D C Paulo, P D C Pereira, D F Sherry, C W Picanço-Diniz Jan 2016

Microglia And Neurons In The Hippocampus Of Migratory Sandpipers., C G Diniz, N G M Magalhães, A A Sousa, C Santos Filho, D G Diniz, C M Lima, M A Oliveira, D C Paulo, P D C Pereira, D F Sherry, C W Picanço-Diniz

Brain and Mind Institute Researchers' Publications

The semipalmated sandpiper Calidris pusilla and the spotted sandpiper Actitis macularia are long- and short-distance migrants, respectively. C. pusilla breeds in the sub-arctic and mid-arctic tundra of Canada and Alaska and winters on the north and east coasts of South America. A. macularia breeds in a broad distribution across most of North America from the treeline to the southern United States. It winters in the southern United States, and Central and South America. The autumn migration route of C. pusilla includes a non-stop flight over the Atlantic Ocean, whereas autumn route of A. macularia is largely over land. Because of …


Context-Dependent Egr1 Expression In The Avian Hippocampus., Stephanie L Grella, Mélanie F Guigueno, David J White, David F Sherry, Diano F Marrone Jan 2016

Context-Dependent Egr1 Expression In The Avian Hippocampus., Stephanie L Grella, Mélanie F Guigueno, David J White, David F Sherry, Diano F Marrone

Brain and Mind Institute Researchers' Publications

In mammals, episodic memory and spatial cognition involve context-specific recruitment of unique ensembles in the hippocampal formation (HF). Despite their capacity for sophisticated spatial (e.g., for migration) and episodic-like (e.g., for food-caching) memory, the mechanisms underlying contextual representation in birds is not well understood. Here we demonstrate environment-specific Egr1 expression as male brown-headed cowbirds (Molothrus ater) navigate environments for food reward, showing that the avian HF, like its mammalian counterpart, recruits distinct neuronal ensembles to represent different contexts.


The Synergistic Roles Of Cholecystokinin B And Dopamine D5 Receptors On The Regulation Of Renal Sodium Excretion., Xiaoliang Jiang, Wei Chen, Xing Liu, Zihao Wang, Yunpeng Liu, Robin A Felder, John J Gildea, Pedro A. Jose, Chuan Qin, Zhiwei Yang Jan 2016

The Synergistic Roles Of Cholecystokinin B And Dopamine D5 Receptors On The Regulation Of Renal Sodium Excretion., Xiaoliang Jiang, Wei Chen, Xing Liu, Zihao Wang, Yunpeng Liu, Robin A Felder, John J Gildea, Pedro A. Jose, Chuan Qin, Zhiwei Yang

Medicine Faculty Publications

Renal dopamine D1-like receptors (D1R and D5R) and the gastrin receptor (CCKBR) are involved in the maintenance of sodium homeostasis. The D1R has been found to interact synergistically with CCKBR in renal proximal tubule (RPT) cells to promote natriuresis and diuresis. D5R, which has a higher affinity for dopamine than D1R, has some constitutive activity. Hence, we sought to investigate the interaction between D5R and CCKBR in the regulation of renal sodium excretion. In present study, we found D5R and CCKBR increase each other's expression in a concentration- and time-dependent manner in the HK-2 cell, the specificity of which was …


How The Bending Kinematics Of Swimming Lampreys Build Negative Pressure Fields For Suction Thrust, Brad J. Gemmell, Stephanie M. Fogerson, John H. Costello, Jennifer R. Morgan, John O. Dabiri, Sean P. Colin Jan 2016

How The Bending Kinematics Of Swimming Lampreys Build Negative Pressure Fields For Suction Thrust, Brad J. Gemmell, Stephanie M. Fogerson, John H. Costello, Jennifer R. Morgan, John O. Dabiri, Sean P. Colin

Integrative Biology Faculty and Staff Publications

Swimming animals commonly bend their bodies to generate thrust. For undulating animals such as eels and lampreys, their bodies bend in the form of waves that travel from head to tail. These kinematics accelerate the flow of adjacent fluids, which alters the pressure field in a manner that generates thrust. We used a comparative approach to evaluate the cause-and-effect relationships in this process by quantifying the hydrodynamic effects of body kinematics at the body-fluid interface of the lamprey, Petromyzon marinus, during steady-state swimming. We compared the kinematics and hydrodynamics of healthy control lampreys to lampreys whose spinal cord had been …


The Pros And Cons Of Ecological Risk Assessment Based On Data From Different Levels Of Biological Organization, Jason R. Rohr, Christopher J. Salice, Roger M. Nisbet Jan 2016

The Pros And Cons Of Ecological Risk Assessment Based On Data From Different Levels Of Biological Organization, Jason R. Rohr, Christopher J. Salice, Roger M. Nisbet

Integrative Biology Faculty and Staff Publications

Ecological risk assessment (ERA) is the process used to evaluate the safety of manufactured chemicals to the environment. Here we review the pros and cons of ERA across levels of biological organization, including suborganismal (e.g., biomarkers), individual, population, community, ecosystem and landscapes levels. Our review revealed that level of biological organization is often related negatively with ease at assessing cause-effect relationships, ease of high-throughput screening of large numbers of chemicals (it is especially easier for suborganismal endpoints), and uncertainty of the ERA because low levels of biological organization tend to have a large distance between their measurement (what is quantified) …


Maporal Hantavirus Causes Mild Pathology In Deer Mice (Peromyscus Maniculatus), Amanda Mcguire, Kaitlyn Miedema, Joseph R. Fauver, Amber Rico, Tawfik Aboellail, Sandra L. Quackenbush, Ann Hawkinson, Tony Schountz Jan 2016

Maporal Hantavirus Causes Mild Pathology In Deer Mice (Peromyscus Maniculatus), Amanda Mcguire, Kaitlyn Miedema, Joseph R. Fauver, Amber Rico, Tawfik Aboellail, Sandra L. Quackenbush, Ann Hawkinson, Tony Schountz

Journal Articles: Epidemiology

Rodent-borne hantaviruses can cause two human diseases with many pathological similarities: hantavirus cardiopulmonary syndrome (HCPS) in the western hemisphere and hemorrhagic fever with renal syndrome in the eastern hemisphere. Each virus is hosted by specific reservoir species without conspicuous disease. HCPS-causing hantaviruses require animal biosafety level-4 (ABSL-4) containment, which substantially limits experimental research of interactions between the viruses and their reservoir hosts. Maporal virus (MAPV) is a South American hantavirus not known to cause disease in humans, thus it can be manipulated under ABSL-3 conditions. The aim of this study was to develop an ABSL-3 hantavirus infection model using the …


Plasmodium Falciparum Infection Status Among Children With Schistosoma In Sub-Saharan Africa: A Systematic Review And Meta-Analysis, Abraham Degarege, Dawit Degarege, Emir Veledar, Berhanu Erko, Mathieu Nacher, Consuelo M. Beck-Sague, Purnima Madhivanan Jan 2016

Plasmodium Falciparum Infection Status Among Children With Schistosoma In Sub-Saharan Africa: A Systematic Review And Meta-Analysis, Abraham Degarege, Dawit Degarege, Emir Veledar, Berhanu Erko, Mathieu Nacher, Consuelo M. Beck-Sague, Purnima Madhivanan

Journal Articles: Epidemiology

BACKGROUND: It has been suggested that Schistosoma infection may be associated with Plasmodium falciparum infection or related reduction in haemoglobin level, but the nature of this interaction remains unclear. This systematic review synthesized evidence on the relationship of S. haematobium or S. mansoni infection with the occurrence of P. falciparum malaria, Plasmodium density and related reduction in haemoglobin level among children in sub-Saharan Africa (SSA).

METHODOLOGY/PRINCIPAL FINDINGS: A systematic review in according with PRISMA guidelines was conducted. All published articles available in PubMed, Embase, Cochrane library and CINAHL databases before May 20, 2015 were searched without any limits. Two reviewers …


It Is All About (U)Biquitin: Role Of Altered Ubiquitin-Proteasome System And Uchl1 In Alzheimer Disease, Antonella Tramutola, Fabio Di Domenico, Eugenio Barone, Marzia Perluigi, D. Allan Butterfield Jan 2016

It Is All About (U)Biquitin: Role Of Altered Ubiquitin-Proteasome System And Uchl1 In Alzheimer Disease, Antonella Tramutola, Fabio Di Domenico, Eugenio Barone, Marzia Perluigi, D. Allan Butterfield

Chemistry Faculty Publications

Free radical-mediated damage to macromolecules and the resulting oxidative modification of different cellular components are a common feature of aging, and this process becomes much more pronounced in age-associated pathologies, including Alzheimer disease (AD). In particular, proteins are particularly sensitive to oxidative stress-induced damage and these irreversible modifications lead to the alteration of protein structure and function. In order to maintain cell homeostasis, these oxidized/damaged proteins have to be removed in order to prevent their toxic accumulation. It is generally accepted that the age-related accumulation of “aberrant” proteins results from both the increased occurrence of damage and the decreased efficiency …


Modulatory Action By The Serotonergic System: Behavior And Neurophysiology In Drosophila Melanogaster, Zana R Majeed, Esraa Abdeljaber, Robin Soveland, Kristin Cornwell, Aubrey Bankemper, Felicitas Koch, Robin L. Cooper Jan 2016

Modulatory Action By The Serotonergic System: Behavior And Neurophysiology In Drosophila Melanogaster, Zana R Majeed, Esraa Abdeljaber, Robin Soveland, Kristin Cornwell, Aubrey Bankemper, Felicitas Koch, Robin L. Cooper

Biology Faculty Publications

Serotonin modulates various physiological processes and behaviors. This study investigates the role of 5-HT in locomotion and feeding behaviors as well as in modulation of sensory-motor circuits. The 5-HT biosynthesis was dysregulated by feeding Drosophila larvae 5-HT, a 5-HT precursor, or an inhibitor of tryptophan hydroxylase during early stages of development. The effects of feeding fluoxetine, a selective serotonin reuptake inhibitor, during early second instars were also examined. 5-HT receptor subtypes were manipulated using RNA interference mediated knockdown and 5-HT receptor insertional mutations. Moreover, synaptic transmission at 5-HT neurons was blocked or enhanced in both larvae and adult flies. The …