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https://www.readbyqxmd.com/read/28447391/transcriptional-response-of-escherichia-coli-to-ammonia-and-glucose-fluctuations
#1
Joana Danica Simen, Michael Löffler, Günter Jäger, Karin Schäferhoff, Andreas Freund, Jakob Matthes, Jan Müller, Ralf Takors
In large-scale production processes, metabolic control is typically achieved by limited supply of essential nutrients such as glucose or ammonia. With increasing bioreactor dimensions, microbial producers such as Escherichia coli are exposed to changing substrate availabilities due to limited mixing. In turn, cells sense and respond to these dynamic conditions leading to frequent activation of their regulatory programmes. Previously, we characterized short- and long-term strategies of cells to adapt to glucose fluctuations...
April 26, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28443625/genome-wide-meta-analysis-of-241-258-adults-accounting-for-smoking-behaviour-identifies-novel-loci-for-obesity-traits
#2
Anne E Justice, Thomas W Winkler, Mary F Feitosa, Misa Graff, Virginia A Fisher, Kristin Young, Llilda Barata, Xuan Deng, Jacek Czajkowski, David Hadley, Julius S Ngwa, Tarunveer S Ahluwalia, Audrey Y Chu, Nancy L Heard-Costa, Elise Lim, Jeremiah Perez, John D Eicher, Zoltán Kutalik, Luting Xue, Anubha Mahajan, Frida Renström, Joseph Wu, Qibin Qi, Shafqat Ahmad, Tamuno Alfred, Najaf Amin, Lawrence F Bielak, Amelie Bonnefond, Jennifer Bragg, Gemma Cadby, Martina Chittani, Scott Coggeshall, Tanguy Corre, Nese Direk, Joel Eriksson, Krista Fischer, Mathias Gorski, Marie Neergaard Harder, Momoko Horikoshi, Tao Huang, Jennifer E Huffman, Anne U Jackson, Johanne Marie Justesen, Stavroula Kanoni, Leena Kinnunen, Marcus E Kleber, Pirjo Komulainen, Meena Kumari, Unhee Lim, Jian'an Luan, Leo-Pekka Lyytikäinen, Massimo Mangino, Ani Manichaikul, Jonathan Marten, Rita P S Middelberg, Martina Müller-Nurasyid, Pau Navarro, Louis Pérusse, Natalia Pervjakova, Cinzia Sarti, Albert Vernon Smith, Jennifer A Smith, Alena Stančáková, Rona J Strawbridge, Heather M Stringham, Yun Ju Sung, Toshiko Tanaka, Alexander Teumer, Stella Trompet, Sander W van der Laan, Peter J van der Most, Jana V Van Vliet-Ostaptchouk, Sailaja L Vedantam, Niek Verweij, Jacqueline M Vink, Veronique Vitart, Ying Wu, Loic Yengo, Weihua Zhang, Jing Hua Zhao, Martina E Zimmermann, Niha Zubair, Gonçalo R Abecasis, Linda S Adair, Saima Afaq, Uzma Afzal, Stephan J L Bakker, Traci M Bartz, John Beilby, Richard N Bergman, Sven Bergmann, Reiner Biffar, John Blangero, Eric Boerwinkle, Lori L Bonnycastle, Erwin Bottinger, Daniele Braga, Brendan M Buckley, Steve Buyske, Harry Campbell, John C Chambers, Francis S Collins, Joanne E Curran, Gert J de Borst, Anton J M de Craen, Eco J C de Geus, George Dedoussis, Graciela E Delgado, Hester M den Ruijter, Gudny Eiriksdottir, Anna L Eriksson, Tõnu Esko, Jessica D Faul, Ian Ford, Terrence Forrester, Karl Gertow, Bruna Gigante, Nicola Glorioso, Jian Gong, Harald Grallert, Tanja B Grammer, Niels Grarup, Saskia Haitjema, Göran Hallmans, Anders Hamsten, Torben Hansen, Tamara B Harris, Catharina A Hartman, Maija Hassinen, Nicholas D Hastie, Andrew C Heath, Dena Hernandez, Lucia Hindorff, Lynne J Hocking, Mette Hollensted, Oddgeir L Holmen, Georg Homuth, Jouke Jan Hottenga, Jie Huang, Joseph Hung, Nina Hutri-Kähönen, Erik Ingelsson, Alan L James, John-Olov Jansson, Marjo-Riitta Jarvelin, Min A Jhun, Marit E Jørgensen, Markus Juonala, Mika Kähönen, Magnus Karlsson, Heikki A Koistinen, Ivana Kolcic, Genovefa Kolovou, Charles Kooperberg, Bernhard K Krämer, Johanna Kuusisto, Kirsti Kvaløy, Timo A Lakka, Claudia Langenberg, Lenore J Launer, Karin Leander, Nanette R Lee, Lars Lind, Cecilia M Lindgren, Allan Linneberg, Stephane Lobbens, Marie Loh, Mattias Lorentzon, Robert Luben, Gitta Lubke, Anja Ludolph-Donislawski, Sara Lupoli, Pamela A F Madden, Reija Männikkö, Pedro Marques-Vidal, Nicholas G Martin, Colin A McKenzie, Barbara McKnight, Dan Mellström, Cristina Menni, Grant W Montgomery, Aw Bill Musk, Narisu Narisu, Matthias Nauck, Ilja M Nolte, Albertine J Oldehinkel, Matthias Olden, Ken K Ong, Sandosh Padmanabhan, Patricia A Peyser, Charlotta Pisinger, David J Porteous, Olli T Raitakari, Tuomo Rankinen, D C Rao, Laura J Rasmussen-Torvik, Rajesh Rawal, Treva Rice, Paul M Ridker, Lynda M Rose, Stephanie A Bien, Igor Rudan, Serena Sanna, Mark A Sarzynski, Naveed Sattar, Kai Savonen, David Schlessinger, Salome Scholtens, Claudia Schurmann, Robert A Scott, Bengt Sennblad, Marten A Siemelink, Günther Silbernagel, P Eline Slagboom, Harold Snieder, Jan A Staessen, David J Stott, Morris A Swertz, Amy J Swift, Kent D Taylor, Bamidele O Tayo, Barbara Thorand, Dorothee Thuillier, Jaakko Tuomilehto, Andre G Uitterlinden, Liesbeth Vandenput, Marie-Claude Vohl, Henry Völzke, Judith M Vonk, Gérard Waeber, Melanie Waldenberger, R G J Westendorp, Sarah Wild, Gonneke Willemsen, Bruce H R Wolffenbuttel, Andrew Wong, Alan F Wright, Wei Zhao, M Carola Zillikens, Damiano Baldassarre, Beverley Balkau, Stefania Bandinelli, Carsten A Böger, Dorret I Boomsma, Claude Bouchard, Marcel Bruinenberg, Daniel I Chasman, Yii-DerIda Chen, Peter S Chines, Richard S Cooper, Francesco Cucca, Daniele Cusi, Ulf de Faire, Luigi Ferrucci, Paul W Franks, Philippe Froguel, Penny Gordon-Larsen, Hans-Jörgen Grabe, Vilmundur Gudnason, Christopher A Haiman, Caroline Hayward, Kristian Hveem, Andrew D Johnson, J Wouter Jukema, Sharon L R Kardia, Mika Kivimaki, Jaspal S Kooner, Diana Kuh, Markku Laakso, Terho Lehtimäki, Loic Le Marchand, Winfried März, Mark I McCarthy, Andres Metspalu, Andrew P Morris, Claes Ohlsson, Lyle J Palmer, Gerard Pasterkamp, Oluf Pedersen, Annette Peters, Ulrike Peters, Ozren Polasek, Bruce M Psaty, Lu Qi, Rainer Rauramaa, Blair H Smith, Thorkild I A Sørensen, Konstantin Strauch, Henning Tiemeier, Elena Tremoli, Pim van der Harst, Henrik Vestergaard, Peter Vollenweider, Nicholas J Wareham, David R Weir, John B Whitfield, James F Wilson, Jessica Tyrrell, Timothy M Frayling, Inês Barroso, Michael Boehnke, Panagiotis Deloukas, Caroline S Fox, Joel N Hirschhorn, David J Hunter, Tim D Spector, David P Strachan, Cornelia M van Duijn, Iris M Heid, Karen L Mohlke, Jonathan Marchini, Ruth J F Loos, Tuomas O Kilpeläinen, Ching-Ti Liu, Ingrid B Borecki, Kari E North, L Adrienne Cupples
Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits...
April 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28441415/pax7-remodels-the-chromatin-landscape-in-skeletal-muscle-stem-cells
#3
Karin C Lilja, Nan Zhang, Alessandro Magli, Volkan Gunduz, Christopher J Bowman, Robert W Arpke, Radbod Darabi, Michael Kyba, Rita Perlingeiro, Brian D Dynlacht
Pluripotent stem cells (PSC) hold great promise for the treatment of human skeletal muscle diseases. However, it remains challenging to convert PSC to skeletal muscle cells, and the mechanisms by which the master regulatory transcription factor, Pax7, promotes muscle stem (satellite) cell identity are not yet understood. We have taken advantage of PSC-derived skeletal muscle precursor cells (iPax7), wherein the induced expression of Pax7 robustly initiates the muscle program and enables the in vitro generation of precursors that seed the satellite cell compartment upon transplantation...
2017: PloS One
https://www.readbyqxmd.com/read/28434096/benefits-and-risks-of-a-percutaneous-endoscopic-gastrostomy-peg-for-decompression-in-patients-with-malignant-gastrointestinal-obstruction
#4
Anne Dittrich, Barbara Schubert, Michael Kramer, Felicitas Lenz, Karin Kast, Ulrich Schuler, Markus K Schuler
PURPOSE: Gastrointestinal obstruction presents many burdens for patients with end-stage abdominal cancer, such as nausea and vomiting. Few detailed data on the efficacy of a percutaneous endoscopic gastrostomy (PEG) for decompression exists. This retrospective cohort study investigates the quantity of symptom relief realized with PEG and the corresponding complications. METHODS: Chart reviews of 75 patients with malignant gastrointestinal obstruction, who received a PEG for decompression, were performed...
April 22, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28431484/who-5-well-being-index-as-screening-instrument-for-psychological-comorbidity-in-patients-with-temporomandibular-disorder
#5
Fadi Ismail, Karin Lange, Marit Gillig, Katarzyna Zinken, Lena Schwabe, Meike Stiesch, Michael Eisenburger
OBJECTIVES: The aim of the study was to compare the WHO-Five Well-Being Index (WHO-5) with the Oral Health Impact Profile-49 (OHIP-49) questionnaire as screening tools to detect psychological comorbidity in TMDs. METHODS: A TMD group (92 patients, 42.8 ± 17.1 yrs) and a control group (90 patients of the Department of Prosthetic Dentistry, 38.9 ± 10.1 yrs) completed the WHO-5 and the OHIP-49 questionnaire. RESULTS: The patients with TMD reported significantly greater OHIP-49 sum scores than controls (47...
April 21, 2017: Cranio: the Journal of Craniomandibular Practice
https://www.readbyqxmd.com/read/28426741/as3mt-mediated-tolerance-to-arsenic-evolved-by-multiple-independent-horizontal-gene-transfers-from-bacteria-to-eukaryotes
#6
Michael Palmgren, Karin Engström, Björn M Hallström, Karin Wahlberg, Dan Ariel Søndergaard, Torbjörn Säll, Marie Vahter, Karin Broberg
Organisms have evolved the ability to tolerate toxic substances in their environments, often by producing metabolic enzymes that efficiently detoxify the toxicant. Inorganic arsenic is one of the most toxic and carcinogenic substances in the environment, but many organisms, including humans, metabolise inorganic arsenic to less toxic metabolites. This multistep process produces mono-, di-, and trimethylated arsenic metabolites, which the organism excretes. In humans, arsenite methyltransferase (AS3MT) appears to be the main metabolic enzyme that methylates arsenic...
2017: PloS One
https://www.readbyqxmd.com/read/28425591/reflective-functioning-and-personality-organization-associations-with-negative-maternal-behaviors
#7
Karin Ensink, Marie-Eve Rousseau, Marko Biberdzic, Michaël Bégin, Lina Normandin
The aim of this study was to examine whether mothers who manifest insensitive and disconnected behaviors in interaction with their infants differ in terms of maternal reflective functioning (RF), personality organization, and histories of abuse. A total of 86 mother-infant dyads, 28 of them with histories of abuse, participated in the study. RF was assessed with the Adult Attachment Interview (C. George, N. Kaplan, & M. Main, 1985), and personality organization was assessed with the self-report Inventory of Personality Organization (M...
April 20, 2017: Infant Mental Health Journal
https://www.readbyqxmd.com/read/28416579/inflammatory-stimuli-induce-acyl-coa-thioesterase-7-and-remodeling-of-phospholipids-containing-unsaturated-long-%C3%A2-c20-acyl-chains-in-macrophages
#8
Valerie Z Wall, Shelley Barnhart, Farah Kramer, Jenny E Kanter, Anuradha Vivekanandan-Giri, Subramaniam Pennathur, Chiara Bolego, Jessica M Ellis, Miguel A Gijón, Michael J Wolfgang, Karin E Bornfeldt
Acyl-CoA thioesterase 7 (ACOT7) is an intracellular enzyme that converts acyl-CoAs to free fatty acids. ACOT7 is induced by lipopolysaccharide (LPS), thus we investigated downstream effects of LPS-induced induction of ACOT7 and its role in inflammatory settings in myeloid cells. Enzymatic thioesterase activity assays in wildtype and ACOT7-deficient macrophage lysates indicated that endogenous ACOT7 contributes a significant fraction of total acyl-CoA thioesterase activity towards C20:4-CoA, C20:5-CoA and C22:6-CoA, but contributes little activity towards shorter acyl-CoA species...
April 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28414429/sublethal-lead-exposure-alters-movement-behavior-in-free-ranging-golden-eagles
#9
Frauke Ecke, Navinder J Singh, Jon M Arnemo, Anders Bignert, Björn Helander, Åsa M M Berglund, Hans Borg, Caroline Bröjer, Karin Holm, Michael Lanzone, Tricia Miller, Åke Nordström, Jannikke Räikkönen, Ilia Rodushkin, Erik Ågren, Birger Hörnfeldt
Lead poisoning of animals due to ingestion of fragments from lead-based ammunition in carcasses and offal of shot wildlife is acknowledged globally and raises great concerns about potential behavioral effects leading to increased mortality risks. Lead levels in blood were correlated with progress of the moose hunting season. Based on analyses of tracking data, we found that even sublethal lead concentrations in blood (25 ppb, wet weight), can likely negatively affect movement behavior (flight height and movement rate) of free-ranging scavenging Golden Eagles (Aquila chrysaetos)...
April 26, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28412516/switching-between-nitrogen-and-glucose-limitation-unraveling-transcriptional-dynamics-in-escherichia-coli
#10
Michael Löffler, Joana Danica Simen, Jan Müller, Günter Jäger, Salaheddine Laghrami, Karin Schäferhoff, Andreas Freund, Ralf Takors, Ralf Takors
Transcriptional control under nitrogen and carbon-limitation conditions have been well analyzed for Escherichia coli. However, the transcriptional dynamics that underlie the shift in regulatory programs from nitrogen to carbon limitation is not well studied. In the present study, cells were cultivated at steady state under nitrogen (ammonia)-limited conditions then shifted to carbon (glucose) limitation to monitor changes in transcriptional dynamics. Nitrogen limitation was found to be dominated by sigma 54 (RpoN) and sigma 38 (RpoS), whereas the "housekeeping" sigma factor 70 (RpoD) and sigma 38 regulate cellular status under glucose limitation...
April 12, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28407399/abnormal-rab11-rab8-vesicles-cluster-in-enterocytes-of-patients-with-microvillus-inclusion-disease
#11
Georg F Vogel, Andreas R Janecke, Iris M Krainer, Karin Gutleben, Barbara Witting, Sally G Mitton, Sahar Mansour, Antje Ballauff, Joseph T Roland, Amy C Engevik, Ernest Cutz, Thomas Müller, James R Goldenring, Lukas A Huber, Michael W Hess
Microvillus Inclusion Disease (MVID) is a congenital enteropathy characterized by accumulation of vesiculo-tubular endomembranes in the subapical cytoplasm of enterocytes, historically termed "secretory granules". However, neither their identity nor pathophysiological significance is well defined. Using immunoelectron microscopy and tomography we studied biopsies from MVID patients (3x Myosin 5b mutations, 1x Syntaxin3 mutation) and compared them to controls and genome-edited CaCo2 cell models, harboring relevant mutations...
April 13, 2017: Traffic
https://www.readbyqxmd.com/read/28405610/btk-specific-inhibition-blocks-pathogenic-plasma-cell-signatures-and-myeloid-cell-associated-damage-in-ifn%C3%AE-driven-lupus-nephritis
#12
Arna Katewa, Yugang Wang, Jason A Hackney, Tao Huang, Eric Suto, Nandhini Ramamoorthi, Cary D Austin, Meire Bremer, Jacob Zhi Chen, James J Crawford, Kevin S Currie, Peter Blomgren, Jason DeVoss, Julie A DiPaolo, Jonathan Hau, Adam Johnson, Justin Lesch, Laura E DeForge, Zhonghua Lin, Marya Liimatta, Joseph W Lubach, Sami McVay, Zora Modrusan, Allen Nguyen, Chungkee Poon, Jianyong Wang, Lichuan Liu, Wyne P Lee, Harvey Wong, Wendy B Young, Michael J Townsend, Karin Reif
Systemic lupus erythematosus (SLE) is often associated with exaggerated B cell activation promoting plasma cell generation, immune-complex deposition in the kidney, renal infiltration of myeloid cells, and glomerular nephritis. Type-I IFNs amplify these autoimmune processes and promote severe disease. Bruton's tyrosine kinase (Btk) inhibitors are considered novel therapies for SLE. We describe the characterization of a highly selective reversible Btk inhibitor, G-744. G-744 is efficacious, and superior to blocking BAFF and Syk, in ameliorating severe lupus nephritis in both spontaneous and IFNα-accelerated lupus in NZB/W_F1 mice in therapeutic regimens...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28397975/the-jak2-stat5-signaling-pathway-as-a-potential-therapeutic-target-in-canine-mastocytoma
#13
Alexandra Keller, Bettina Wingelhofer, Barbara Peter, Karin Bauer, Daniela Berger, Susanne Gamperl, Martin Reifinger, Sabine Cerny-Reiterer, Richard Moriggl, Michael Willmann, Peter Valent, Emir Hadzijusufovic
BACKGROUND: Mastocytoma are frequently diagnosed cutaneous neoplasms in dogs. In non-resectable mastocytoma patients, novel targeted drugs are often applied. The transcription factor STAT5 has been implicated in the survival of human neoplastic mast cells (MC). Our study evaluated the JAK2/STAT5 pathway as a novel target in canine mastocytoma. MATERIALS AND METHODS: We employed inhibitors of JAK2 (R763, TG101348, AZD1480, ruxolitinib) and STAT5 (pimozide, piceatannol) and evaluated their effects on 2 mastocytoma cell lines, C2 and NI-1...
April 11, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28391912/effects-of-atorvastatin-on-biomarkers-of-immune-activation-inflammation-and-lipids-in-virologically-suppressed-human-immunodeficiency-virus-1-infected-individuals-with-low-density-lipoprotein-cholesterol-130%C3%A2-mg-dl-aids-clinical-trials-group-study-a5275
#14
Daniel E Nixon, Ronald J Bosch, Ellen S Chan, Nicholas T Funderburg, Sally Hodder, Jordan E Lake, Michael M Lederman, Karin L Klingman, Judith A Aberg
BACKGROUND: Persistent immune activation and inflammation in virologically suppressed human immunodeficiency virus (HIV) infection are linked to excess cardiovascular risk. OBJECTIVE: To evaluate atorvastatin as a strategy to reduce cardiovascular risk. METHODS: A5275 was a multicenter, prospective, randomized, double-blind, placebo-controlled, cross-over pilot study of atorvastatin (10 mg/day for 4 weeks then 20 mg/day for 16 weeks) with a planned enrollment of 97 HIV-infected participants ≥18 years old, receiving boosted protease inhibitor-based antiretroviral therapy for ≥6 months, with plasma HIV-1 RNAs below limits of quantification ≥180 days, and fasting low-density lipoprotein (LDL) cholesterol ≥70 and <130 mg/dL...
January 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28387757/gfi1-downregulation-promotes-inflammation-linked-metastasis-of-colorectal-cancer
#15
Wenjing Xing, Yun Xiao, Xinliang Lu, Hongyan Zhu, Xiangchuan He, Wei Huang, Elsa S Lopez, Jerry Wong, Huanyu Ju, Linlu Tian, Fengmin Zhang, Hongwei Xu, Sheng Dian Wang, Xia Li, Michael Karin, Huan Ren
Inflammation is frequently associated with initiation, progression, and metastasis of colorectal cancer (CRC). Here, we unveil a CRC-specific metastatic programme that is triggered via the transcriptional repressor, GFI1. Using data from a large cohort of clinical samples including inflammatory bowel disease and CRC, and a cellular model of CRC progression mediated by cross-talk between the cancer cell and the inflammatory microenvironment, we identified GFI1 as a gating regulator responsible for a constitutively activated signalling circuit that renders CRC cells competent for metastatic spread...
April 7, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28386856/change-in-medical-student-attitudes-toward-patients-with-substance-use-disorders-after-course-exposure
#16
Makeida B Koyi, Archana Nelliot, Dean MacKinnon, Darius A Rastegar, Michael Fingerhood, Anika Alvanzo, Leonard Feldman, Karin J Neufeld
OBJECTIVE: Negative physician attitudes toward patients with substance use disorders (SUD) pose a significant barrier to treatment. This study tests the overall and intra-individual change in attitudes of second year medical students after exposure to a 15 hour SUD course. METHODS: Two cohorts of second year medical students (2014 and 2015) responded to an anonymous 13-item previously published survey exploring personal views regarding patients with SUD using a four-point Likert scale...
April 6, 2017: Academic Psychiatry
https://www.readbyqxmd.com/read/28373834/adolescents-with-developmental-dyscalculia-do-not-have-a-generalized-magnitude-deficit-processing-of-discrete-and-continuous-magnitudes
#17
Ursina McCaskey, Michael von Aster, Ruth O'Gorman Tuura, Karin Kucian
The link between number and space has been discussed in the literature for some time, resulting in the theory that number, space and time might be part of a generalized magnitude system. To date, several behavioral and neuroimaging findings support the notion of a generalized magnitude system, although contradictory results showing a partial overlap or separate magnitude systems are also found. The possible existence of a generalized magnitude processing area leads to the question how individuals with developmental dyscalculia (DD), known for deficits in numerical-arithmetical abilities, process magnitudes...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28371945/-linkage-between-promotion-of-employment-and-promotion-of-health-in-the-community-setting-results-of-the-pilot-project-of-the-federal-employment-agency-and-the-statutory-health-insurance
#18
Michael Bellwinkel, Karin Schreiner-Kürten, Kathrin Melzer
The Federal Employment Agency and the Statutory Health Insurance (GKV) have put the link between the promotion of employment and of health to the test by making a joint approach aiming to reach unemployed persons with preventive health services and to maintain or improve their employability. Specialist case workers (Integrationsfachkräfte) of the job centres conducted health consultations, motivating unemployed persons and raising their awareness of their own health as well as enabling them to access health promotion services of health insurance funds on a voluntary basis...
April 3, 2017: Das Gesundheitswesen
https://www.readbyqxmd.com/read/28370029/long-term-effects-of-systemic-gene-therapy-in-a-canine-model-of-myotubular-myopathy
#19
Matthew Elverman, Melissa A Goddard, David Mack, Jessica M Snyder, Michael W Lawlor, Hui Meng, Alan H Beggs, Ana Buj-Bello, Karine Poulard, Anthony P Marsh, Robert W Grange, Valerie E Kelly, Martin K Childers
INTRODUCTION: X-linked myotubular myopathy (XLMTM), a devastating pediatric disease caused by the absence of the protein myotubularin, results from mutations in the MTM1 gene. While there is no cure for XLMTM, we previously reported effects of MTM1 gene therapy using adeno-associated viral (AAV) vector on muscle weakness and pathology in MTM1-mutant dogs. Here, we followed 2 AAV-infused dogs over 4 years. METHODS: We evaluated gait, strength, respiration, neurological function, muscle pathology, AAV vector copy number (VCN), and transgene expression...
March 29, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28347762/an-in%C3%A2-vitro-approach-for-comparative-interspecies-metabolism-of-agrochemicals
#20
Paul M Whalley, Michael Bartels, Karin S Bentley, Marco Corvaro, Dorothee Funk, Matthew W Himmelstein, Birgit Neumann, Christian Strupp, Fagen Zhang, Jyotigna Mehta
The metabolism and elimination of a xenobiotic has a direct bearing on its potential to cause toxicity in an organism. The confidence with which data from safety studies can be extrapolated to humans depends, among other factors, upon knowing whether humans are systemically exposed to the same chemical entities (i.e. a parent compound and its metabolites) as the laboratory animals used to study toxicity. Ideally, to understand a metabolite in terms of safety, both the chemical structure and the systemic exposure would need to be determined...
March 24, 2017: Regulatory Toxicology and Pharmacology: RTP
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