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1. Towards a European health research and innovation cloud (HRIC)

Author

F. M. Aarestrup, A. Albeyatti, W. J. Armitage, C. Auffray, L. Augello, R. Balling, N. Benhabiles, G. Bertolini, J. G. Bjaalie, M. Black, N. Blomberg, P. Bogaert, M. Bubak, B. Claerhout, L. Clarke, B. De Meulder, G. D’Errico, A. Di Meglio, N. Forgo, C. Gans-Combe, A. E. Gray, I. Gut, A. Gyllenberg, G. Hemmrich-Stanisak, L. Hjorth, Y. Ioannidis, S. Jarmalaite, A. Kel, F. Kherif, J. O. Korbel, C. Larue, M. Laszlo, A. Maas, L. Magalhaes, I. Manneh-Vangramberen, E. Morley-Fletcher, C. Ohmann, P. Oksvold, N. P. Oxtoby, I. Perseil, V. Pezoulas, O. Riess, H. Riper, J. Roca, P. Rosenstiel, P. Sabatier, F. Sanz, M. Tayeb, G. Thomassen, J. Van Bussel, M. Van den Bulcke, and H. Van Oyen

Subjects
Medicine, Genetics, QH426-470
Abstract

Abstract The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe.

Published
2020
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2. PIONEER: European Commission Innovative Medicines Initiative funded BD4BO (Big data for better outcome) project on prostate cancer

Author

S. Evans Axelsson, T. Abbott, L. Fullwood, M.I. Omar, M. Cavelaars, A. Asiimwe, M. Roobol, M.J. Ribal, C. Auffray, Z. Devecseri, E.J. Smith, M. Van Hemelrijck, S. MacLennan, D. Horgan, C. Reich, B. De Meulder, D. Lancet, C. Bangma, A. Briganti, D. Tilki, H. Van Poppel, M.P. Wirth, J. N’Dow, and A. Bjartell

Subjects
Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2020
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3. Blood Gene Expression Predicts Bronchiolitis Obliterans Syndrome

Author

Richard Danger, Pierre-Joseph Royer, Damien Reboulleau, Eugénie Durand, Jennifer Loy, Adrien Tissot, Philippe Lacoste, Antoine Roux, Martine Reynaud-Gaubert, Carine Gomez, Romain Kessler, Sacha Mussot, Claire Dromer, Olivier Brugière, Jean-François Mornex, Romain Guillemain, Marcel Dahan, Christiane Knoop, Karine Botturi, Aurore Foureau, Christophe Pison, Angela Koutsokera, Laurent P. Nicod, Sophie Brouard, Antoine Magnan, The COLT and SysCLAD Consortia, J. Jougon, J.-F. Velly, H. Rozé, E. Blanchard, C. Dromer, M. Antoine, M. Cappello, R. Souilamas, M. Ruiz, Y. Sokolow, F. Vanden Eynden, G. Van Nooten, L. Barvais, J. Berré, S. Brimioulle, D. De Backer, J. Créteur, E. Engelman, I. Huybrechts, B. Ickx, T. J. C. Preiser, T. Tuna, L. Van Obberghe, N. Vancutsem, J.-L. Vincent, P. De Vuyst, I. Etienne, F. Féry, F. Jacobs, C. Knoop, J. L. Vachiéry, P. Van den Borne, I. Wellemans, G. Amand, L. Collignon, M. Giroux, E. Arnaud-Crozat, V. Bach, P.-Y. Brichon, P. Chaffanjon, O. Chavanon, A. de Lambert, J. P. Fleury, S. Guigard, K. Hireche, A. Pirvu, P. Porcu, R. Hacini, P. Albaladejo, C. Allègre, A. Bataillard, D. Bedague, E. Briot, M. Casez-Brasseur, D. Colas, G. Dessertaine, M. Durand, G. Francony, A. Hebrard, M. R. Marino, B. Oummahan, D. Protar, D. Rehm, S. Robin, M. Rossi-Blancher, P. Bedouch, A. Boignard, H. Bouvaist, A. Briault, B. Camara, S. Chanoine, M. Dubuc, S. Lantuéjoul, S. Quétant, J. Maurizi, P. Pavèse, C. Pison, C. Saint-Raymond, N. Wion, C. Chérion, R. Grima, O. Jegaden, J.-M. Maury, F. Tronc, C. Flamens, S. Paulus, J. F. Mornex, F. Philit, A. Senechal, J.-C. Glérant, S. Turquier, D. Gamondes, L. Chalabresse, F. Thivolet-Bejui, C. Barnel, C. Dubois, A. Tiberghien, F. Le Pimpec-Barthes, A. Bel, P. Mordant, P. Achouh, V. Boussaud, R. Guillemain, D. Méléard, M. O. Bricourt, B. Cholley, V. Pezella, M. Adda, M. Badier, F. Bregeon, B. Coltey, X. B. D’Journo, S. Dizier, C. Doddoli, N. Dufeu, H. Dutau, J. M. Forel, J. Y. Gaubert, C. Gomez, M. Leone, A. Nieves, B. Orsini, L. Papazian, L. C. Picard, M. Reynaud-Gaubert, A. Roch, J. M. Rolain, E. Sampol, V. Secq, P. Thomas, D. Trousse, M. Yahyaoui, O. Baron, P. Lacoste, C. Perigaud, J. C. Roussel, I. Danner, A. Haloun, A. Magnan, A. Tissot, T. Lepoivre, M. Treilhaud, K. Botturi-Cavaillès, S. Brouard, R. Danger, J. Loy, M. Morisset, M. Pain, S. Pares, D. Reboulleau, P. J. Royer, E. Durand, A. Foureau, Ph. Dartevelle, D. Fabre, E. Fadel, O. Mercier, S. Mussot, F. Stephan, P. Viard, J. Cerrina, P. Dorfmuller, S. Feuillet, M. Ghigna, Ph. Hervén, F. Le Roy Ladurie, J. Le Pavec, V. Thomas de Montpreville, L. Lamrani, Y. Castier, P. Cerceau, F. Francis, G. Lesèche, N. Allou, P. Augustin, S. Boudinet, M. Desmard, G. Dufour, P. Montravers, O. Brugière, G. Dauriat, G. Jébrak, H. Mal, A. Marceau, A.-C. Métivier, G. Thabut, B. Ait Ilalne, P. Falcoz, G. Massard, N. Santelmo, G. Ajob, O. Collange, O. Helms, J. Hentz, A. Roche, B. Bakouboula, T. Degot, A. Dory, S. Hirschi, S. Ohlmann-Caillard, L. Kessler, R. Kessler, A. Schuller, K. Bennedif, S. Vargas, P. Bonnette, A. Chapelier, P. Puyo, E. Sage, J. Bresson, V. Caille, C. Cerf, J. Devaquet, V. Dumans-Nizard, M. L. Felten, M. Fischler, A. G. Si Larbi, M. Leguen, L. Ley, N. Liu, G. Trebbia, S. De Miranda, B. Douvry, F. Gonin, D. Grenet, A. M. Hamid, H. Neveu, F. Parquin, C. Picard, A. Roux, M. Stern, F. Bouillioud, P. Cahen, M. Colombat, C. Dautricourt, M. Delahousse, B. D’Urso, J. Gravisse, A. Guth, S. Hillaire, P. Honderlick, M. Lequintrec, E. Longchampt, F. Mellot, A. Scherrer, L. Temagoult, L. Tricot, M. Vasse, C. Veyrie, L. Zemoura, J. Berjaud, L. Brouchet, M. Dahan, F. Le Balle, O. Mathe, H. Benahoua, A. Didier, A. L. Goin, M. Murris, L. Crognier, O. Fourcade, T. Krueger, H. B. Ris, M. Gonzalez, J.-D. Aubert, L. P. Nicod, B. J. Marsland, T. C. Berutto, T. Rochat, P. Soccal, Ph. Jolliet, A. Koutsokera, C. Marcucci, O. Manuel, E. Bernasconi, M. Chollet, F. Gronchi, C. Courbon, Zurich S. Hillinger, I. Inci, P. Kestenholz, W. Weder, R. Schuepbach, M. Zalunardo, C. Benden, U. Buergi, L. C. Huber, B. Isenring, M. M. Schuurmans, A. Gaspert, D. Holzmann, N. Müller, C. Schmid, B. Vrugt, T. Rechsteiner, A. Fritz, D. Maier, K. Desplanche, D. Koubi, F. Ernst, T. Paprotka, M. Schmitt, B. Wahl, J.-P. Boissel, G. Olivera-Botello, C. Trocmé, B. Toussaint, S. Bourgoin-Voillard, M. Séve, M. Benmerad, V. Siroux, R. Slama, C. Auffray, D. Charron, and J. Pellet

Subjects
lung transplantation, bronchiolitis obliterans syndrome, gene expression, biomarkers, blood, Immunologic diseases. Allergy, RC581-607
Abstract

Bronchiolitis obliterans syndrome (BOS), the main manifestation of chronic lung allograft dysfunction, leads to poor long-term survival after lung transplantation. Identifying predictors of BOS is essential to prevent the progression of dysfunction before irreversible damage occurs. By using a large set of 107 samples from lung recipients, we performed microarray gene expression profiling of whole blood to identify early biomarkers of BOS, including samples from 49 patients with stable function for at least 3 years, 32 samples collected at least 6 months before BOS diagnosis (prediction group), and 26 samples at or after BOS diagnosis (diagnosis group). An independent set from 25 lung recipients was used for validation by quantitative PCR (13 stables, 11 in the prediction group, and 8 in the diagnosis group). We identified 50 transcripts differentially expressed between stable and BOS recipients. Three genes, namely POU class 2 associating factor 1 (POU2AF1), T-cell leukemia/lymphoma protein 1A (TCL1A), and B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and 0.78 respectively. These genes allow stratification based on BOS risk (log-rank test p

Published
2018
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4. Automatic Quantitation of Hybridization Signals on cDNA Arrays

Author

F. Tahi, B. Achddou, C. Decraene, O. Alibert, H. Guiot, C. Auffray, and G. Piétu

Subjects
Biology (General), QH301-705.5
Abstract

Large-scale hybridization of simple or complex cDNA probes to cDNA clones arrayed on high-density filters is a method frequently used to determine systematically the expression profiles of thousands of genes. Hybridization signal intensities, which reflect the level of transcription of the corresponding genes, are captured on phosphor screens with an imaging system. We describe a high-throughput system, Xdots-Reader, that performs automatic detection and quantitation of each signal on hundreds of images. Reproducibility of spot detection and quantitation within filters and between filters has been assessed in analysis of more than 8 50 000 hybridization signals on 436 filters. The automatic analysis success was greater than 97%, with 424 of the 436 tested filters fully analyzed without any human intervention. XdotsReaderis available from the Software Library at www.BioTechniques. com or at http://www.lami.univ-evry. fr/~tahi/XDotsReader. It runs on SUN workstations under UNIX (SunOS or Solaris) and on PC under LINUX. No particular hardware is required, and the software is compatible with any other software. It supports the main standard image formats.

Published
2002
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5. Identification of oropharyngeal microbiome-driven asthma and wheezing clusters in children

Author

M I Abdel-Aziz, J Thorsen, S Hashimoto, S J H Vijverberg, A H Neerincx, P Brinkman, W V Aalderen, J Stokholm, M Roggenbuck-Wedemeyer, N H Vissing, M S Mortensen, A D Brejnrod, L J Fleming, C S Murray, S J Fowler, U Frey, A Bush, F Singer, G Hedlin, B Nordlund, D E Shaw, K F Chung, I M Adcock, R Djukanovic, C Auffray, A T Bansal, A R Sousa, S S Wagers, B L Chawes, K Bønnelykke, S J Sørensen, A D Kraneveld, P J Sterk, G Roberts, H Bisgaard, and A H Maitland-Van Der Zee

Published
2022

6. Medication Adherence in Patients With Severe Asthma Prescribed Oral Corticosteroids in the U-BIOPRED Cohort

Author

P. J. Sterk, John H. Riley, Thomas Sandström, Anna Selby, Laurie Pahus, C. Auffray, Ioannis Pandis, Julie Corfield, R. Djukanovic, K. Sun, Massimo Caruso, Jørgen Vestbo, Matthew J. Loza, Andrew J. Simpson, Dominic Burg, I.M. Adcock, S. Bates, Scott Wagers, Ana R. Sousa, J. Corfield, Ariane H. Wagener, René Lutter, Barbro Dahlén, Ratko Djukanovic, G. Praticò, I. Pandis, N. Mores, G. Hedlin, Navin Rao, I. Horváth, Alexander Mazein, B. De Meulder, Richard G. Knowles, John-Olof Thörngren, Wolfgang Seibold, P H Howarth, Victoria M. Goss, Cristina Gómez, Clare S. Murray, Paul Brinkman, Ildiko Horvath, Anthony D. Postle, M. Caruso, Martina Gahlemann, M. Puig Valls, F.K. Chung, P. Montuschi, Dominick E. Shaw, Kai Sun, Aruna T. Bansal, Fahad Alahmadi, Amphun Chaiboonchoe, Graham Roberts, Kian Fan Chung, Yike Guo, H. Ahmed, Thomas Geiser, Klaus Bønnelykke, M. Miralpeix, Simone Hashimoto, Diane Lefaudeux, S.S. Wagers, D. Erzen, B. Thornton, Florian Singer, Louise Fleming, Stephen J. Fowler, Neil Fitch, P. Bakke, Craig E. Wheelock, Nadja Hawwa Vissing, Tim Higenbottam, Jamie Matthews, F. Singer, S.E. Dahlén, Sarah Masefield, Roelinde Middelveld, Jens M. Hohlfeld, Anthony V. D'Amico, Paul Skipp, W.M.C. van Aalderen, Alan J. Knox, Sven-Erik Dahlén, Andrew Bush, A.T. Bansal, Pieter-Paul Hekking, Joost Brandsma, Stewart Bates, L.J. Fleming, Norbert Krug, N. Krug, Magnus Ericsson, J. Riley, P. Powel, Jacek Musiał, Amanda Roberts, Peter J. Sterk, Ian M. Adcock, Pascal Chanez, Cecile T.J. Holweg, F. Baribaud, Stelios Pavlidis, Veit J. Erpenbeck, Z. Weiszhart, C.E. Wheelock, Ralf Sigmund, James P.R. Schofield, Alexander Manta, Andrea Meiser, Susan J. Wilson, Jeanette Bigler, G. Roberts, M. van Geest, Hans Bisgaard, Urs Frey, Michael Boedigheimer, Per Bakke, Chris Compton, Enrica Bucchioni, Paolo Montuschi, David Myles, E.H.D. Bel, Anna James, Elena Formaggio, Anthony Rowe, Dominic E. Shaw, J. Haughney, P. Chanez, A.R. Sousa, S.J. Fowler, K. Fichtner, B. Dahlèn, Publica, Commission of the European Communities, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pulmonology, AII - Inflammatory diseases, and Paediatric Pulmonology

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, urinary corticosteroids, Prescription Drugs, Settore BIO/14 - FARMACOLOGIA, medicine.drug_class, [SDV]Life Sciences [q-bio], Urinary system, Respiratory System, Administration, Oral, 610 Medicine & health, Critical Care and Intensive Care Medicine, Hospital Anxiety and Depression Scale, Medication Adherence, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Interquartile range, Internal medicine, Surveys and Questionnaires, Administration, Inhalation, Medicine, Humans, 030212 general & internal medicine, adherence, Glucocorticoids, ComputingMilieux_MISCELLANEOUS, U-BIOPRED Study Group, Asthma, Dose-Response Relationship, Drug, business.industry, 1103 Clinical Sciences, Middle Aged, asthma, medicine.disease, 030228 respiratory system, Cohort, Prednisolone, Quality of Life, Corticosteroid, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

Background: Although estimates of suboptimal adherence to oral corticosteroids in asthma range from 30% to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to be particularly high. Research Questions: What is the prevalence of suboptimal adherence detected by self-reporting and direct measures? Is suboptimal adherence associated with disease activity? Study Design and Methods: Data were included from individuals with severe asthma taking part in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study and prescribed daily oral corticosteroids. Participants completed the Medication Adherence Report Scale, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid chromatography-mass spectrometry. Results: Data from 166 participants were included in this study: mean (SD) age, 54.2 (± 11.9) years; FEV 1, 65.1% (± 20.5%) predicted; female, 58%; 37% completing the Medication Adherence Report Scale reported suboptimal adherence; and 43% with urinary corticosteroid data did not have detectable prednisolone or metabolites in their urine. Good adherence by both methods was detected in 49 of the 142 (35%) of participants in whom both methods were performed; adherence detection did not match between methods in 53%. Self-reported high adherers had better asthma control and quality of life, whereas directly measured high adherers had lower blood eosinophil levels. Interpretation: Low adherence is a common problem in severe asthma, whether measured directly or self-reported. We report poor agreement between the two methods, suggesting some disassociation between self-assessment of medication adherence and regular oral corticosteroid use, which suggests that each approach may provide complementary information in clinical practice.

Published
2021
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7. How Well do Polygenic Risk Scores Identify Men at High Risk for Prostate Cancer? Systematic Review and Meta-Analysis

Author

Aino Siltari, Ragnar Lönnerbro, Karl Pang, Kirill Shiranov, Alex Asiimwe, Susan Evans-Axelsson, Billy Franks, Amit Kiran, Teemu J. Murtola, Jack Schalken, Carl Steinbeisser, Anders Bjartell, Anssi Auvinen, J. N’Dow, E.J. Smith, R. Shepherd, M. Ribal, N. Mottet, L. Moris, M. Lardas, P-P. Willemse, G. Gandaglia, R. Campi, Rossella Nicoletti, M. Gacci, A. Briganti, M.M. Ratti, E. Alleva, L. Leardini, E.S. Sisca, R. Bangma, M. Roobol, S. Remmers, D. Tilki, T. Visakorpi, K. Talala, T. Tammela, M. van Hemelrijck, K. Bayer, S. Lejeune, S. Byrne, L. Fialho, P. Palaiologou B. De Meulder, C. Auffray, A. Hijazy, S. Power, N. Zounemat Kermani, K. van Bochove, M. Kalafati, M. Moinat, E. Voss, D. Horgan, L. Fullwood, M. Holtorf, D. Lancet, G. Bernstein, I. Omar, S. MacLennan, S. Maclennan, S. Tripathee, M. Wirth, M. Froehner, B. Brenner, A. Borkowetz, C. Thomas, F. Horn, K. Reiche, M. Kreux, A. Josefsson, D. Gasi Tandefekt, J. Hugosson, H. Huisman, J. Schalken, T. Hofmacher, P. Lindgren, E. Andersson, A. Fridhammar, J. Zong, J-E. Butler-Ransohoff, R. Herrera, M. Maass, P. Torremante, M.D. Voss, Z. Devecseri, T. Abbott, C. Dau, K. Papineni, R. Snijder, M. Lambrecht, R. Wolfinger, S. Rogiers, A. Servan, L. Antoni, K. Pacoe, P. Robinson, B. Jaton, D. Bakkard, H. Turunen, O. Kilkku, P. Pohjanjousi, O. Voima, L. Nevalaita, C. Reich, S. Araujo, E. Longden-Chapman, D. Burke, P. Agapow, S. Derkits, M. Licour, C. McCrea, S. Payne, A. Yong, L. Thompson, S. Le Mare, M Bussmann, and D. Kotik

Subjects
All institutes and research themes of the Radboud University Medical Center, Oncology, Urology, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15]
Abstract

Contains fulltext : 291547.pdf (Publisher’s version ) (Open Access) OBJECTIVES: Genome-wide association studies have revealed over 200 genetic susceptibility loci for prostate cancer (PCa). By combining them, polygenic risk scores (PRS) can be generated to predict risk of PCa. We summarize the published evidence and conduct meta-analyses of PRS as a predictor of PCa risk in Caucasian men. PATIENTS AND METHODS: Data were extracted from 59 studies, with 16 studies including 17 separate analyses used in the main meta-analysis with a total of 20,786 cases and 69,106 controls identified through a systematic search of ten databases. Random effects meta-analysis was used to obtain pooled estimates of area under the receiver-operating characteristic curve (AUC). Meta-regression was used to assess the impact of number of single-nucleotide polymorphisms (SNPs) incorporated in PRS on AUC. Heterogeneity is expressed as I(2) scores. Publication bias was evaluated using funnel plots and Egger tests. RESULTS: The ability of PRS to identify men with PCa was modest (pooled AUC 0.63, 95% CI 0.62-0.64) with moderate consistency (I(2) 64%). Combining PRS with clinical variables increased the pooled AUC to 0.74 (0.68-0.81). Meta-regression showed only negligible increase in AUC for adding incremental SNPs. Despite moderate heterogeneity, publication bias was not evident. CONCLUSION: Typically, PRS accuracy is comparable to PSA or family history with a pooled AUC value 0.63 indicating mediocre performance for PRS alone. 01 april 2023

Published
2023

8. Urinary Leukotriene E 4 and Prostaglandin D 2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type 2 Inflammation. A Clinical Observational Study

Author

Johan Kolmert, Cristina Gómez, David Balgoma, Marcus Sjödin, Johan Bood, Jon R. Konradsen, Magnus Ericsson, John-Olof Thörngren, Anna James, Maria Mikus, Ana R. Sousa, John H. Riley, Stewart Bates, Per S. Bakke, Ioannis Pandis, Massimo Caruso, Pascal Chanez, Stephen J. Fowler, Thomas Geiser, Peter Howarth, Ildikó Horváth, Norbert Krug, Paolo Montuschi, Marek Sanak, Annelie Behndig, Dominick E. Shaw, Richard G. Knowles, Cécile T. J. Holweg, Åsa M. Wheelock, Barbro Dahlén, Björn Nordlund, Kjell Alving, Gunilla Hedlin, Kian Fan Chung, Ian M. Adcock, Peter J. Sterk, Ratko Djukanovic, Sven-Erik Dahlén, Craig E. Wheelock, H. Ahmed, C. Auffray, A. T. Bansal, E. H. Bel, J. Bigler, B. Billing, F. Baribaud, H. Bisgaard, M. J. Boedigheimer, K. Bønnelykke, J. Brandsma, P. Brinkman, E. Bucchioni, D. Burg, A. Bush, A. Chaiboonchoe, C. H. Compton, J. Corfield, D. Cunoosamy, A. D’Amico, B. De Meulder, V. J. Erpenbeck, D. Erzen, K. Fichtner, N. Fitch, L. J. Fleming, E. Formaggio, U. Frey, M. Gahlemann, V. Goss, Y. Guo, S. Hashimoto, J. Haughney, P. W. Hekking, T. Higenbottam, J. M. Hohlfeld, A. J. Knox, N. Lazarinis, D. Lefaudeux, M. J. Loza, R. Lutter, A. Manta, S. Masefield, J. G. Matthews, A. Mazein, A. Meiser, R. J. M. Middelveld, M. Miralpeix, N. Mores, C. S. Murray, J. Musial, D. Myles, L. Pahus, S. Pavlidis, A. Postle, P. Powel, G. Praticò, M. PuigValls, N. Rao, A. Roberts, G. Roberts, A. Rowe, T. Sandström, J. P. R. Schofield, W. Seibold, A. Selby, R. Sigmund, F. Singer, P. J. Skipp, M. Smicker, K. Sun, B. Thornton, M. Uddin, W. M. van Aalderen, M. van Geest, J. Vestbo, N. H. Vissing, A. H. Wagener, S. S. Wagers, Z. Weiszhart, S. J. Wilson, J. Östling, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Male, Severe asthma, Metabolite, type 2 inflammation, Respiratory Medicine and Allergy, [SDV]Life Sciences [q-bio], Physiology, Omalizumab, Critical Care and Intensive Care Medicine, chemistry.chemical_compound, 0302 clinical medicine, 030212 general & internal medicine, Child, ComputingMilieux_MISCELLANEOUS, mass spectrometry, Lungmedicin och allergi, 2. Zero hunger, Leukotriene E4, Prostaglandin D2, Type 2 inflammation, Middle Aged, respiratory system, 3. Good health, medicine.anatomical_structure, Prednisolone, Female, lipids (amino acids, peptides, and proteins), medicine.drug, Pulmonary and Respiratory Medicine, Adult, severe asthma, Settore BIO/14 - FARMACOLOGIA, Urinary system, U-BIOPRED, Asthma and Allergy, 03 medical and health sciences, Correspondence, medicine, Humans, Asthma, Inflammation, Mass spectrometry, business.industry, Original Articles, Eosinophil, medicine.disease, respiratory tract diseases, urinary eicosanoid metabolites, 030228 respiratory system, chemistry, Diabetes Mellitus, Type 2, Exhaled nitric oxide, Prostaglandins, Urinary eicosanoid metabolites, business, Biomarkers
Abstract

Rationale: New approaches are needed to guide personalized treatment of asthma. Objectives: To test if urinary eicosanoid metabolites can direct asthma phenotyping. Methods: Urinary metabolites of prostaglandins (PGs), cysteinyl leukotrienes (CysLTs), and isoprostanes were quantified in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes) study including 86 adults with mild-to-moderate asthma (MMA), 411 with severe asthma (SA), and 100 healthy control participants. Validation was performed internally in 302 participants with SA followed up after 12-18 months and externally in 95 adolescents with asthma. Measurement and Main Results: Metabolite concentrations in healthy control participants were unrelated to age, body mass index, and sex, except for the PGE 2 pathway. Eicosanoid concentrations were generally greater in participants with MMA relative to healthy control participants, with further elevations in participants with SA. However, PGE 2 metabolite concentrations were either the same or lower in male nonsmokers with asthma than in healthy control participants. Metabolite concentrations were unchanged in those with asthma who adhered to oral corticosteroid treatment as documented by urinary prednisolone detection, whereas those with SA treated with omalizumab had lower concentrations of LTE 4 and the PGD 2 metabolite 2,3-dinor-11β-PGF 2α. High concentrations of LTE 4 and PGD 2 metabolites were associated with lower lung function and increased amounts of exhaled nitric oxide and eosinophil markers in blood, sputum, and urine in U-BIOPRED participants and in adolescents with asthma. These type 2 (T2) asthma associations were reproduced in the follow-up visit of the U-BIOPRED study and were found to be as sensitive to detect T2 inflammation as the established biomarkers. Conclusions: Monitoring of urinary eicosanoids can identify T2 asthma and introduces a new noninvasive approach for molecular phenotyping of adult and adolescent asthma.Clinical trial registered with www.clinicaltrials.gov (NCT01976767).

Published
2020
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9. PIONEER: European Commission Innovative Medicines Initiative funded BD4BO (Big data for better outcome) project on prostate cancer

Author

Emma Jane Smith, Thomas Abbott, H. Van Poppel, Marinel Cavelaars, C. Auffray, B. De Meulder, Steven MacLennan, Zsuzsanna Devecseri, Anders Bjartell, Alex Asiimwe, Manfred P. Wirth, Doron Lancet, Denis Horgan, C.H. Bangma, Monique J. Roobol, Louise Fullwood, A. Briganti, Muhammad Imran Omar, Derya Tilki, S. Evans Axelsson, Maria J. Ribal, M. Van Hemelrijck, Christian Reich, and James N’Dow

Subjects
medicine.medical_specialty, business.industry, Urology, Big data, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, lcsh:RC870-923, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Outcome (game theory), lcsh:RC254-282, Prostate cancer, Political science, Family medicine, medicine, European commission, business
Published
2020

10. Asthma similarities across ProAR (Brazil) and U-BIOPRED (Europe) adult cohorts of contrasting locations, ethnicity and socioeconomic status

Author

Ana R. Sousa, Anna Selby, Jeanette Bigler, Hans Bisgaard, J. Cunha, I.M. Adcock, A.C.C. Coelho, Ryan Santos Costa, Pieter-Paul Hekking, Louise Fleming, Kai Sun, Amphun Chaiboonchoe, C.V.N. Santana, P. Moura-Santos, Scott Wagers, Ratko Djukanovic, G.P. Pinheiro, G. Hedlin, J.V. de Jesus, Kian Fan Chung, Jacek Musiał, Thomas Geiser, F. Baribaud, Emília Maria Medeiros de Andrade Belitardo, L. Cardoso, Klaus Bønnelykke, Anthony D. Postle, P H Howarth, Adelmir Souza-Machado, Valmar Biao-Lima, Stephen J. Fowler, Craig E. Wheelock, Alvaro A. Cruz, Mauricio Lima Barreto, Maria Ilma Araujo, Massimo Caruso, Laurie Pahus, P. J. Cooper, Florian Singer, W.M.C. van Aalderen, Paulo Augusto Moreira Camargos, Wolfgang Seibold, Ildiko Horvath, René Lutter, P.C.A. Almeida, I. Pandis, Victoria M. Goss, Aruna T. Bansal, John H. Riley, M. Puig Valls, P. Powel, Amanda Roberts, Alexander Mazein, M. Miralpeix, I. Paixao-Araujo, B. De Meulder, Michael Boedigheimer, Isaac Suzart Gomes-Filho, Chris Compton, C. Auffray, Jamie Matthews, Diane Lefaudeux, Elena Formaggio, A.A. Cruz, L.M. Mello, Anthony V. D'Amico, A. Lima-Matos, J. Fernandes, P. J. Sterk, Clare S. Murray, Enrica Bucchioni, Andrea Meiser, D. Erzen, Roelinde Middelveld, M. van Geest, Jørgen Vestbo, Alan J. Knox, Graham Roberts, Norbert Krug, Stewart Bates, G. Santos-Lima, Maggie Davis, Stelios Pavlidis, Paul Skipp, Yike Guo, Ariane H. Wagener, E.V. Ponte, Jens M. Hohlfeld, A. Souza-Machado, M.A. Lessa, I.S. Muniz, C.S. Cruz, Nadja Hawwa Vissing, Neuza Maria Alcantara-Neves, Tim Higenbottam, Navin Rao, Dominic Burg, Sarah Masefield, Z. Weiszhart, Matthew J. Loza, J. Haughney, Simone Hashimoto, Per Bakke, B. Thornton, José Miguel Chatkin, Andrew Bush, SE Dahlen, Joost Brandsma, N. Mores, G. Praticò, Kathleen C. Barnes, Carolina Souza-Machado, Rafael Stelmach, V. Bião-Lima, Martina Gahlemann, Paolo Montuschi, T.M.O. Souza, V.S. Vasquez, Camila Alexandrina Figueiredo, P. Chanez, Eduardo Vieira Ponte, Neil Fitch, Anthony Rowe, Cecile T.J. Holweg, S.J. Wilson, K. Fichtner, Alexander Manta, Lidia Lins, Dominic E. Shaw, David Myles, Julie Corfield, B. Dahlén, Thomas Sandström, Peter J. Sterk, Ian M. Adcock, Ralf Sigmund, James P.R. Schofield, Urs Frey, Laura C. Rodrigues, Leila Denise Alves Ferreira Amorim, E.H.D. Bel, Anna James, R.A. Franco, Paula Cristina Andrade Almeida, Paul Brinkman, H. Ahmed, Veit J. Erpenbeck, Richard G. Knowles, National Institute for Health Research, Pulmonology, and AII - Inflammatory diseases

Subjects
Male, Cardiac & Cardiovascular Systems, BLOOD, Cross-sectional study, COUNT, Respiratory System, Ethnic group, Disease, Severity of Illness Index, Cohort Studies, 0302 clinical medicine, Quality of life, Forced Expiratory Volume, Disease management, Medicine, 030212 general & internal medicine, 610 Medicine & health, 1102 Cardiorespiratory Medicine and Haematology, Middle Aged, PREVALENCE, Europe, Phenotypes, Phenotype, INFECTIONS, Female, Life Sciences & Biomedicine, Brazil, Cohort study, Pulmonary and Respiratory Medicine, Adult, Cross sectional study, U-BIOPRED Study Groups, 03 medical and health sciences, FEV1/FVC ratio, ProAR Study Group, Humans, Socioeconomic status, Asthma, Science & Technology, business.industry, 1103 Clinical Sciences, medicine.disease, SPIROMETRY, REFERENCE VALUES, respiratory tract diseases, SEVERITY, Cross-Sectional Studies, 030228 respiratory system, Social Class, Cardiovascular System & Cardiology, Quality of Life, business, Biomarkers, Demography
Abstract

Background Asthma prevalence is 339 million globally. ‘Severe asthma’ (SA) comprises subjects with uncontrolled asthma despite proper management. Objectives To compare asthma from diverse ethnicities and environments. Methods A cross-sectional analysis of two adult cohorts, a Brazilian (ProAR) and a European (U-BIOPRED). U-BIOPRED comprised of 311 non-smoking with Severe Asthma (SAn), 110 smokers or ex-smokers with SA (SAs) and 88 mild to moderate asthmatics (MMA) while ProAR included 544 SA and 452 MMA. Although these projects were independent, there were similarities in objectives and methodology, with ProAR adopting operating procedures of U-BIOPRED. Results Among SA subjects, age, weight, proportion of former smokers and FEV1 pre-bronchodilator were similar. The proportion of SA with a positive skin prick tests (SPT) to aeroallergens, the scores of sino-nasal symptoms and quality of life were comparable. In addition, blood eosinophil counts (EOS) and the % of subjects with EOS > 300 cells/μl were not different. The Europeans with SA however, were more severe with a greater proportion of continuous oral corticosteroids (OCS), worse symptoms and more frequent exacerbations. FEV1/FVC pre- and post-bronchodilator were lower among the Europeans. The MMA cohorts were less comparable in control and treatment, but similar in the proportion of allergic rhinitis, gastroesophageal reflux disease and EOS >3%. Conclusions ProAR and U-BIOPRED cohorts, with varying severity, ethnicity and environment have similarities, which provide the basis for global external validation of asthma phenotypes. This should stimulate collaboration between asthma consortia with the aim of understanding SA, which will lead to better management.

Published
2019

11. Metagenomic Analysis of Sputum in the U-Biopred Cohort Shows Reduced Diversity in Asthmatics

Author

A. Versi, S. Bates, J.H. Riley, S. Pavlidis, R. Djukanovic, P.J. Sterk, A. Bansal, A.R. Sousa, D. Shaw, S. Fowler, S.S. Wagers, G. Roberts, C. Auffray, S.-E.K. Dahlen, F. Baribaud, K.F. Chung, I.M. Adcock, P. Howarth, and null U-BIOPRED Study group

Subjects
Metagenomics, media_common.quotation_subject, Cohort, Immunology, medicine, Sputum, medicine.symptom, Biology, Diversity (politics), media_common
Published
2019
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12. Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Author

Zala Jevnikar, Jörgen Östling, Elisabeth Ax, Jenny Calvén, Kristofer Thörn, Elisabeth Israelsson, Lisa Öberg, Akul Singhania, Laurie C.K. Lau, Susan J. Wilson, Jonathan A. Ward, Anoop Chauhan, Ana R. Sousa, Bertrand De Meulder, Matthew J. Loza, Frédéric Baribaud, Peter J. Sterk, Kian Fan Chung, Kai Sun, Yike Guo, Ian M. Adcock, Debbie Payne, Barbro Dahlen, Pascal Chanez, Dominick E. Shaw, Norbert Krug, Jens M. Hohlfeld, Thomas Sandström, Ratko Djukanovic, Anna James, Timothy S.C. Hinks, Peter H. Howarth, Outi Vaarala, Marleen van Geest, Henric Olsson, I.M. Adcock, H. Ahmed, C. Auffray, P. Bakke, A.T. Bansal, F. Baribaud, S. Bates, E.H. Bel, J. Bigler, H. Bisgaard, M.J. Boedigheimer, K. Bønnelykke, J. Brandsma, P. Brinkman, E. Bucchioni, D. Burg, A. Bush, M. Caruso, A. Chaiboonchoe, P. Chanez, F.K. Chung, C.H. Compton, J. Corfield, A. D'Amico, S.E. Dahlen, B. De Meulder, R. Djukanovic, V.J. Erpenbeck, D. Erzen, K. Fichtner, N. Fitch, L.J. Fleming, E. Formaggio, S.J. Fowler, U. Frey, M. Gahlemann, T. Geiser, V. Goss, Y. Guo, S. Hashimoto, J. Haughney, G. Hedlin, P.W. Hekking, T. Higenbottam, J.M. Hohlfeld, C. Holweg, I. Horváth, A.J. James, R. Knowles, A.J. Knox, N. Krug, D. Lefaudeux, M.J. Loza, A. Manta, J.G. Matthews, A. Mazein, A. Meiser, R.J.M. Middelveld, M. Miralpeix, P. Montuschi, N. Mores, C.S. Murray, J. Musial, D. Myles, L. Pahus, I. Pandis, S. Pavlidis, A. Postle, P. Powel, G. Praticò, N. Rao, J. Riley, A. Roberts, G. Roberts, A. Rowe, T. Sandström, J.P.R. Schofield, W. Seibold, A. Selby, D.E. Shaw, R. Sigmund, F. Singer, P.J. Skipp, A.R. Sousa, P.J. Sterk, K. Sun, B. Thornton, W.M. van Aalderen, M. van Geest, J. Vestbo, N.H. Vissing, A.H. Wagener, S.S. Wagers, Z. Weiszhart, C.E. Wheelock, S.J. Wilson, Publica, HUS Children and Adolescents, Commission of the European Communities, Pulmonology, AII - Inflammatory diseases, and Paediatric Pulmonology

Subjects
Male, 0301 basic medicine, MMP3, Allergy, MATRIX METALLOPROTEINASES, Respiratory Medicine and Allergy, Eepithelial integrity, airway inflammation, Systemic inflammation, DISEASE, Cohort Studies, transcriptomics, 0302 clinical medicine, Receptors, Immunology and Allergy, Lung, Macrophage inflammatory protein, Cells, Cultured, Lungmedicin och allergi, remodeling, Toll-like receptor, Cultured, CHITINASE-LIKE PROTEIN, 3. Good health, Phenotype, TARGET, medicine.anatomical_structure, 1107 Immunology, Airway Remodeling, eosinophils, medicine.symptom, Life Sciences & Biomedicine, hierarchical clustering, Signal Transduction, Adult, Settore BIO/14 - FARMACOLOGIA, Immunology, lung epithelium, 03 medical and health sciences, HYPERRESPONSIVENESS, Respiratory Hypersensitivity, medicine, Humans, Hierarchical Clustering, Inflammation, Science & Technology, Innate immune system, exacerbation frequency, Interleukin-6, business.industry, Sputum, Epithelial Cells, Gene signature, Receptors, Interleukin-6, DYSFUNCTION, Asthma, respiratory tract diseases, Eosinophils, Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes study group, Cross-Sectional Studies, SEVERITY, 030104 developmental biology, Gene Expression Regulation, 030228 respiratory system, INTERLEUKIN-6 RECEPTOR, BARRIER FUNCTION, 3121 General medicine, internal medicine and other clinical medicine, CELLS, epithelial integrity, IL-6 signaling, Exacerbation frequency, Transcriptome, business, Biomarkers
Abstract

BackgroundAlthough several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear.ObjectiveWe sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients.MethodsAn IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS–specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens.ResultsActivation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS–high asthma with increased epithelial expression of IL-6TS–inducible genes in the absence of systemic inflammation. The IL-6TS–high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1β, IL-8, and IL-1β.ConclusionsLocal lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.

Published
2019
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13. IL-17-high asthma with features of a psoriasis immunophenotype

Author

Jörgen Östling, Marleen van Geest, James P.R. Schofield, Zala Jevnikar, Susan Wilson, Jonathan Ward, Rene Lutter, Dominick E. Shaw, Per S. Bakke, Massimo Caruso, Sven-Erik Dahlen, Stephen J. Fowler, Ildikó Horváth, Norbert Krug, Paolo Montuschi, Marek Sanak, Thomas Sandström, Kai Sun, Ioannis Pandis, Charles Auffray, Ana R. Sousa, Yike Guo, Ian M. Adcock, Peter Howarth, Kian Fan Chung, Jeanette Bigler, Peter J. Sterk, Paul J. Skipp, Ratko Djukanović, Outi Vaarala, I.M. Adcock, H. Ahmed, C. Auffray, P. Bakke, A.T. Bansal, F. Baribaud, S. Bates, E.H. Bel, J. Bigler, H. Bisgaard, M.J. Boedigheimer, K. Bønnelykke, J. Brandsma, P. Brinkman, E. Bucchioni, D. Burg, A. Bush, M. Caruso, A. Chaiboonchoe, P. Chanez, K.F. Chung, C.H. Compton, J. Corfield, A. D'Amico, S.E. Dahlen, B. De Meulder, R. Djukanovic, V.J. Erpenbeck, D. Erzen, K. Fichtner, N. Fitch, L.J. Fleming, E. Formaggio, S.J. Fowler, U. Frey, M. Gahlemann, T. Geiser, Y. Guo, S. Hashimoto, J. Haughney, G. Hedlin, P.W. Hekking, T. Higenbottam, J.M. Hohlfeld, C. Holweg, I. Horváth, P. Howarth, A.J. James, R. Knowles, A.J. Knox, N. Krug, D. Lefaudeux, M.J. Loza, R. Lutter, A. Manta, S. Masefield, A. Mazein, A. Meiser, R.J.M. Middelveld, M. Miralpeix, P. Montuschi, N. Mores, C.S. Murray, J. Musial, D. Myles, L. Pahus, I. Pandis, S. Pavlidis, P. Powell, G. Praticò, M. Puig N. Rao, J. Riley, A. Roberts, G. Roberts, A. Rowe, T. Sandström, W. Seibold, A. Selby, D.E. Shaw, R. Sigmund, F. Singer, P.J. Skipp, A.R. Sousa, P.J. Sterk, K. Sun, B. Thornton, W.M. van Aalderen, M. van Geest, J. Vestbo, N.H. Vissing, A.H. Wagener, S.S. Wagers, Z. Weiszhart, C.E. Wheelock, S.J. Wilson, Antonios Aliprantis, David Allen, Kjell Alving, P. Badorrek, David Balgoma, S. Ballereau, Clair Barber, Manohara Kanangana Batuwitage, A. Bautmans, A. Bedding, A.F. Behndig, Jorge Beleta, A. Berglind, A. Berton, Grazyna Bochenek, Armin Braun, D. Campagna, Leon Carayannopoulos, C. Casaulta, Romanas Chaleckis, B. Dahlén, imothy Davison, Jorge De Alba, Inge De Lepeleire, Tamara Dekker, Ingrid Delin, P. Dennison, Annemiek Dijkhuis, Paul Dodson, Aleksandra Draper, K. Dyson, Jessica Edwards, L. El Hadjam, Rosalia Emma, Magnus Ericsson, C. Faulenbach, Breda Flood, G. Galffy, Hector Gallart, D. Garissi, J. Gent, M. Gerhardsson de Verdier, D. Gibeon, Cristina Gomez, Kerry Gove, Neil Gozzard, E. Guillmant-Farry, E. Henriksson, Lorraine Hewitt, U. Hoda, Richard Hu, Sile Hu, X. Hu, E. Jeyasingham, K. Johnson, N. Jullian, Juliette Kamphuis, Erika J. Kennington, Dyson Kerry, G. Kerry, M. Klüglich, Hugo Knobel, Johan Kolmert, J.R. Konradsen, Maxim Kots, Kosmas Kretsos, L. Krueger, Scott Kuo, Maciej Kupczyk, Bart Lambrecht, A.-S. Lantz, Christopher Larminie, L.X. Larsson, P. Latzin, N. Lazarinis, N. Lemonnier, Saeeda Lone-Latif, L.A. Lowe, Alexander Manta, Lisa Marouzet, Jane Martin, Caroline Mathon, L. McEvoy, Sally Meah, A. Menzies-Gow, Leanne Metcalf, Maria Mikus, Philip Monk, Shama Naz, K. Nething, Ben Nicholas, U. Nihlén, Peter Nilsson, R. Niven, B. Nordlund, S. Nsubuga, Antonio Pacino, Susanna Palkonen, J. Pellet, Giorgio Pennazza, Anne Petrén, Sandy Pink, C. Pison, Anthony Postle, Malayka Rahman-Amin, Lara Ravanetti, Emma Ray, Stacey Reinke, Leanne Reynolds, K. Riemann, Martine Robberechts, J.P. Rocha, C. Rossios, Kirsty Russell, Michael Rutgers, G. Santini, Marco Santoninco, M. Saqi, Corinna Schoelch, S. Scott, N. Sehgal, Marcus Sjödin, Barbara Smids, Caroline Smith, Jessica Smith, Katherine M. Smith, P. Söderman, A. Sogbessan, F. Spycher, Doroteya Staykova, S. Stephan, J. Stokholm, K. Strandberg, M. Sunther, M. Szentkereszty, L. Tamasi, K. Tariq, John-Olof Thörngren, Jonathan Thorsen, S. Valente, Marianne van de Pol, C.M. van Drunen, Jonathan Van Eyll, Jenny Versnel, Anton Vink, C. von Garnier, A. Vyas, Frans Wald, Samantha Walker, Kristiane Wetzel, Coen Wiegman, Siân Williams, Xian Yang, Elizabeth Yeyasingham, W. Yu Amgen, W. Zetterquist, Z. Zolkipli, A.H. Zwinderman, Publica, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Pulmonology, AII - Inflammatory diseases, Experimental Immunology, Ear, Nose and Throat, Epidemiology and Data Science, APH - Methodology, and Commission of the European Communities

Subjects
0301 basic medicine, Male, URINARY-EXCRETION, Allergy, Neutrophils, Inflammatory bowel disease, Cohort Studies, DOUBLE-BLIND, 0302 clinical medicine, Immunology and Allergy, POPULATION, Interleukin-13, Interleukin-17, psoriasis, BRODALUMAB, Up-Regulation, IL-17, Phenotype, 1107 Immunology, Biomarker (medicine), Female, Interleukin 17, medicine.symptom, Life Sciences & Biomedicine, ENDOTYPES, Signal Transduction, EXPRESSION, Adult, Settore BIO/14 - FARMACOLOGIA, Immunology, PHENOTYPES, Bronchi, 03 medical and health sciences, INFLAMMATION, Psoriasis, medicine, Humans, Interleukin 8, Asthma, U-BIOPRED Study Group, Science & Technology, business.industry, Gene Expression Profiling, biomarkers, Epithelial Cells, asthma, bronchial brushings, medicine.disease, bronchial biopsies, Neutrophilia, 030104 developmental biology, 030228 respiratory system, EXACERBATION, CELLS, Sputum, business, Transcriptome, Biomarkers
Abstract

Background The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required. Objective We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. Methods Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes. Results Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin. Conclusion The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.

Published
2019
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15. Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung

Author

Stéphane Mouraux, Eric Bernasconi, Céline Pattaroni, Angela Koutsokera, John-David Aubert, Johanna Claustre, Christophe Pison, Pierre-Joseph Royer, Antoine Magnan, Romain Kessler, Christian Benden, Paola M. Soccal, Benjamin J. Marsland, Laurent P. Nicod, J. Jougon, J.-F. Velly, H. Rozé, E. Blanchard, C. Dromer, M. Antoine, M. Cappello, M. Ruiz, Y. Sokolow, F. Vanden Eynden, G. Van Nooten, L. Barvais, J. Berré, S. Brimioulle, D. De Backer, J. Créteur, E. Engelman, I. Huybrechts, B. Ickx, T.J.C. Preiser, T. Tuna, L. Van Obberghe, N. Vancutsem, J.-L. Vincent, P. De Vuyst, I. Etienne, F. Féry, F. Jacobs, C. Knoop, J.L. Vachiéry, P. Van den Borne, I. Wellemans, G. Amand, L. Collignon, M. Giroux, D. Angelescu, O. Chavanon, R. Hacini, A. Pirvu, P. Porcu, P. Albaladejo, C. Allègre, A. Bataillard, D. Bedague, E. Briot, M. Casez-Brasseur, D. Colas, G. Dessertaine, M. Durand, G. Francony, A. Hebrard, M.R. Marino, B. Oummahan, D. Protar, D. Rehm, S. Robin, M. Rossi-Blancher, C. Augier, P. Bedouch, A. Boignard, H. Bouvaist, A. Briault, B. Camara, J. Claustre, S. Chanoine, M. Dubuc, S. Quétant, J. Maurizi, P. Pavèse, C. Pison, C. Saint-Raymond, N. Wion, C. Chérion, R. Grima, O. Jegaden, J.-M. Maury, F. Tronc, C. Flamens, S. Paulus, J.-F. Mornex, F. Philit, A. Senechal, J.-C. Glérant, S. Turquier, D. Gamondes, L. Chalabresse, F. Thivolet-Bejui, C. Barnel, C. Dubois, A. Tiberghien, F. Le Pimpec-Barthes, A. Bel, P. Mordant, P. Achouh, V. Boussaud, R. Guillemain, D. Méléard, M.O. Bricourt, B. Cholley, V. Pezella, G. Brioude, X.B. D'Journo, C. Doddoli, P. Thomas, D. Trousse, S. Dizier, M. Leone, L. Papazian, F. Bregeon, A. Basire, B. Coltey, N. Dufeu, H. Dutau, S. Garcia, J.Y. Gaubert, C. Gomez, S. Laroumagne, A. Nieves, L.C. Picard, M. Reynaud-Gaubert, V. Secq, G. Mouton, O. Baron, P. Lacoste, C. Perigaud, J.C. Roussel, I. Danner, A. Haloun, A. Magnan, A. Tissot, T. Lepoivre, M. Treilhaud, K. Botturi-Cavaillès, S. Brouard, R. Danger, J. Loy, M. Morisset, M. Pain, S. Pares, D. Reboulleau, P.-J. Royer, D. Fabre, E. Fadel, O. Mercier, S. Mussot, F. Stephan, P. Viard, J. Cerrina, P. Dorfmuller, S.M. Ghigna, Ph. Hervén, F. Le Roy Ladurie, J. Le Pavec, V. Thomas de Montpreville, L. Lamrani, Y. Castier, P. Cerceau, P. Augustin, S. Jean-Baptiste, S. Boudinet, P. Montravers, O. Brugière, G. Dauriat, G. Jébrak, H. Mal, A. Marceau, A.-C. Métivier, G. Thabut, E. Lhuillier, C. Dupin, V. Bunel, P. Falcoz, G. Massard, N. Santelmo, G. Ajob, O. Collange, O. Helms, J. Hentz, A. Roche, B. Bakouboula, T. Degot, A. Dory, S. Hirschi, S. Ohlmann-Caillard, L. Kessler, R. Kessler, A. Schuller, K. Bennedif, S. Vargas, J. Stauder, S. Ali-Azouaou, P. Bonnette, A. Chapelier, P. Puyo, E. Sage, J. Bresson, V. Caille, C. Cerf, J. Devaquet, V. Dumans-Nizard, M.-L. Felten, M. Fischler, A.-G. Si Larbi, M. Leguen, L. Ley, N. Liu, G. Trebbia, S. De Miranda, B. Douvry, F. Gonin, D. Grenet, A.M. Hamid, H. Neveu, F. Parquin, C. Picard, A. Roux, M. Stern, F. Bouillioud, P. Cahen, M. Colombat, C. Dautricourt, M. Delahousse, B. D'Urso, J. Gravisse, A. Guth, S. Hillaire, P. Honderlick, M. Lequintrec, E. Longchampt, F. Mellot, A. Scherrer, L. Temagoult, L. Tricot, M. Vasse, C. Veyrie, L. Zemoura, J. Berjaud, L. Brouchet, M. Dahan, F.O. Mathe, H. Benahoua, M. DaCosta, I. Serres, V. Merlet-Dupuy, M. Grigoli, A. Didier, M. Murris, L. Crognier, O. Fourcade, T. Krueger, H.B. Ris, M. Gonzalez, Ph. Jolliet, C. Marcucci, M. Chollet, F. Gronchi, C. Courbon, C. Berutto, O. Manuel, A. Koutsokera, J.-D. Aubert, L.P. Nicod, S. Mouraux, E. Bernasconi, C. Pattaroni, B.J. Marsland, P.M. Soccal, T. Rochat, L.M. Lücker, S. Hillinger, I. Inci, W. Weder, R. Schuepbach, M. Zalunardo, C. Benden, M.M. Schuurmans, A. Gaspert, D. Holzmann, N. Müller, C. Schmid, B. Vrugt, A. Fritz, D. Maier, K. Deplanche, D. Koubi, F. Ernst, T. Paprotka, M. Schmitt, B. Wahl, J.-P. Boissel, G. Olivera-Botello, C. Trocmé, B. Toussaint, S. Bourgoin-Voillard, M. Sève, M. Benmerad, V. Siroux, R. Slama, C. Auffray, D. Charron, D. Lefaudeux, J. Pellet, Division of Pulmonary Medicine, Medical University Vienna, Clinique Universitaire de Pneumologie, Pôle Thorax et Vaisseaux, Centre Hospitalier Universitaire de Grenoble, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Pneumologie, Nouvel Hôpital Civil Strasbourg, Division Pulmonary Medicine, University hospital of Zurich [Zurich], Geneva University Hospital (HUG), Rochat, Thierry, and Licker, Marc

Subjects
0301 basic medicine, Male, THP-DM, THP1-derived macrophages, Microbiota/immunology, Anabolism, Fibroblasts/immunology/pathology, [SDV]Life Sciences [q-bio], Bacteria/classification/immunology, Matrix metalloproteinase, SPP1, Secreted phosphoprotein 1, Immunology and Allergy, Lung, Lung/immunology/microbiology/pathology, ddc:616, medicine.diagnostic_test, Microbiota, Airway remodeling, respiratory system, Middle Aged, 3. Good health, Extracellular Matrix, macrophages, rRNA, Ribosomal RNA, Extracellular Matrix/immunology/pathology, Female, PDGFD, Platelet-derived growth factor D, THBS1, Thrombospondin 1, Lung Transplantation, Signal Transduction, Airway Remodeling/immunology, CFU, Colony-forming unit, Adult, BAL, Bronchoalveolar lavage, Immunology, COPD, Chronic obstructive pulmonary disease, MMP, Matrix metallopeptidase, Biology, Macrophages/immunology/pathology, KEGG, Kyoto Encyclopedia of Genes and Genomes, CHI3L1, Article, Proinflammatory cytokine, 03 medical and health sciences, CLAD, Chronic lung allograft dysfunction, fibroblasts, Thrombospondin 1, GO, Gene Ontology, medicine, microbiota, Humans, IGF, Insulin-like growth factor, Thrombospondin, Signal Transduction/immunology, Matrix, Bacteria, Catabolism, Macrophages, IQR, Interquartile range, Fibroblasts, matrix, respiratory tract diseases, 030104 developmental biology, Bronchoalveolar lavage, CHI3L1, Chitinase 3-like 1, SysCLAD, System prediction of Chronic Lung Allograft Dysfunction, KO, KEGG ortholog
Abstract

Background Homeostatic turnover of the extracellular matrix conditions the structure and function of the healthy lung. In lung transplantation, long-term management remains limited by chronic lung allograft dysfunction, an umbrella term used for a heterogeneous entity ultimately associated with pathological airway and/or parenchyma remodeling. Objective This study assessed whether the local cross-talk between the pulmonary microbiota and host cells is a key determinant in the control of lower airway remodeling posttransplantation. Methods Microbiota DNA and host total RNA were isolated from 189 bronchoalveolar lavages obtained from 116 patients post lung transplantation. Expression of a set of 11 genes encoding either matrix components or factors involved in matrix synthesis or degradation (anabolic and catabolic remodeling, respectively) was quantified by real-time quantitative PCR. Microbiota composition was characterized using 16S ribosomal RNA gene sequencing and culture. Results We identified 4 host gene expression profiles, among which catabolic remodeling, associated with high expression of metallopeptidase-7, -9, and -12, diverged from anabolic remodeling linked to maximal thrombospondin and platelet-derived growth factor D expression. While catabolic remodeling aligned with a microbiota dominated by proinflammatory bacteria (eg, Staphylococcus, Pseudomonas, and Corynebacterium), anabolic remodeling was linked to typical members of the healthy steady state (eg, Prevotella, Streptococcus, and Veillonella). Mechanistic assays provided direct evidence that these bacteria can impact host macrophage-fibroblast activation and matrix deposition. Conclusions Host-microbes interplay potentially determines remodeling activities in the transplanted lung, highlighting new therapeutic opportunities to ultimately improve long-term lung transplant outcome., Graphical abstract

Published
2018
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16. Pathway discovery using transcriptomic profiles in adult-onset severe asthma

Author

Pieter-Paul Hekking, Matt J. Loza, Stelios Pavlidis, Bertrand de Meulder, Diane Lefaudeux, Fred Baribaud, Charles Auffray, Ariane H. Wagener, Paul Brinkman, Rene Lutter, Aruna T. Bansal, Ana R. Sousa, Steve A. Bates, Yannis Pandis, Louise J. Fleming, Dominique E. Shaw, Stephen J. Fowler, Y. Guo, Andrea Meiser, Kai Sun, Julie Corfield, Peter H. Howarth, Elisabeth H. Bel, Ian M. Adcock, Kian Fan Chung, Ratko Djukanovic, Peter J. Sterk, I.M. Adcock, H. Ahmed, C. Auffray, P. Bakke, A.T. Bansal, F. Baribaud, S. Bates, E.H. Bel, J. Bigler, H. Bisgaard, M.J. Boedigheimer, K. Bønnelykke, J. Brandsma, P. Brinkman, E. Bucchioni, D. Burg, A. Bush, M. Caruso, A. Chaiboonchoe, P. Chanez, F.K. Chung, C.H. Compton, J. Corfield, A. D'Amico, S.E. Dahlen, B. De Meulder, R. Djukanovic, V.J. Erpenbeck, D. Erzen, K. Fichtner, N. Fitch, L.J. Fleming, E. Formaggio, S.J. Fowler, U. Frey, M. Gahlemann, T. Geiser, S. Hashimoto, J. Haughney, G. Hedlin, P.W. Hekking, T. Higenbottam, J.M. Hohlfeld, C. Holweg, I. Horváth, P. Howarth, A.J. James, R. Knowles, N. Krug, D. Lefaudeux, M.J. Loza, R. Lutter, A. Manta, S. Masefield, J.G. Matthews, A. Mazein, A. Meiser, R.J.M. Middelveld, M. Miralpeix, N. Mores, C.S. Murray, J. Musial, D. Myles, L. Pahus, I. Pandis, S. Pavlidis, P. Powel, G. Praticò, M Puig Valls, N. Rao, J. Riley, A. Roberts, G. Roberts, A. Rowe, T. Sandström, W. Seibold, A. Selby, D.E. Shaw, R. Sigmund, F. Singer, P.J. Skipp, A.R. Sousa, P.J. Sterk, K. Sun, B. Thornton, W.M. van Aalderen, M. van Geest, J. Vestbo, N.H. Vissing, A.H. Wagener, S.S. Wagers, Z. Weiszhart, C.E. Wheelock, S.J. Wilson, Publica, Pulmonology, AII - Inflammatory diseases, Graduate School, AII - Amsterdam institute for Infection and Immunity, ARD - Amsterdam Reproduction and Development, Medical Research Council (MRC), and Pediatric surgery

Subjects
0301 basic medicine, Male, Allergy, Severe asthma, ILC3, mast cells, Disease, Eosinophil, Severity of Illness Index, transcriptomics, 0302 clinical medicine, Eosinophilic, Immunology and Allergy, Medicine, Age of Onset, Oligonucleotide Array Sequence Analysis, mechanisms, Innate lymphoid cell, Adult-onset asthma, eosinophils, gene set variation analysis, phenotyping, severe asthma, Middle Aged, Phenotype, Asthma Control Questionnaire, 1107 Immunology, Female, medicine.symptom, Adult, Genetic Markers, Immunology, mechanism, macromolecular substances, Lung injury, 03 medical and health sciences, Humans, adult-onset asthma, Asthma, U-BIOPRED Study Group, business.industry, Gene Expression Profiling, medicine.disease, respiratory tract diseases, 030104 developmental biology, Cross-Sectional Studies, 030228 respiratory system, Sputum, business, Transcriptome, mast cell
Abstract

Background: Adult-onset severe asthma is characterized by highly symptomatic disease despite high-intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease is needed for the development of targeted treatments. Gene set variation analysis is a statistical technique used to identify gene profiles in heterogeneous samples. Objective: We sought to identify gene profiles associated with adult-onset severe asthma. Methods: This was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at age ≥18 years) as compared with childhood-onset severe asthma (

Published
2018
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17. Molecular evidence of Group 1 innate lymphoid cell activation in the U-BIOPRED cohort

Author

Stelios Pavlidis, Fan Chung, Uruj Hoda, Yike Guo, Ana R. Sousa, Ratko Djukanovic, Kai Sun, Julie Corfield, Frédéric Baribaud, Anthony Rowe, Peter J. Sterk, Ian M. Adcock, Matt Loza, Christos Rossios, and C. Auffray

Subjects
0301 basic medicine, business.industry, Innate lymphoid cell, Inflammation, Inflammasome, medicine.disease, M2 Macrophage, respiratory tract diseases, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030228 respiratory system, Immunology, medicine, Macrophage, Sputum, Tumor necrosis factor alpha, medicine.symptom, business, Asthma, medicine.drug
Abstract

Background: The Group 1 innate lymphoid cell (Gp 1 ILC), which includes ILC1 and natural killer (NK) cells, express T-bet and IFNγ, and are cytotoxic. Their role in asthma is unclear. Aim: Explore the enrichment of ILC1, ILC2, ILC3 and NK activation signatures in asthmatic transcriptomic samples. Methods: U-BIOPRED participants were classified as moderate to severe asthma eosinophilic, neutrophilic, mixed and paucigranulocytic, based on sputum cell counts, and healthy. We applied Gene Set Variation Analysis to sputum, nasal, bronchial brush and bronchial biopsies using published signatures [Bjorklund et al. Nat Immunol 2016,17:451-60]. Results: ILC1 but not ILC2 or ILC3 ES were higher in non-smoking severe sputum, particularly in neutrophilic and mixed patients. This phenotype has been associated with inflammasome, IFNγ and TNF activation [Kuo at al. Eur Respir J.2017, 49, in press]. In eosinophilic asthma, ILC1 ES was lower, ILC2 higher and ILC3 similar across groups (Fig1A). ILC1 and NK ES correlated with M1 macrophage signature in all compartments (Fig1B). ILC2 ES correlated with M2 macrophage signature, except in nasal brush. Conclusion: A neutrophilic severe asthma phenotype has been characterized by Group 1 ILC activation, associated with inflammasome, IFNγ, and TNF, which may reflect an antimicrobial response and contribute to chronic inflammation and remodelling in severe asthma.

Published
2017
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18. Developmental Stability in House Mice Heterozygous for Single Robertsonian Fusions

Author

Pierre Fontanillas, J. Catalan, J. Britton-Davidian, and J.-C. Auffray

Subjects
Male, Heterozygote, Down syndrome, Centromere, Chromosome Disorders, Chromosomal translocation, medicine.disease_cause, Translocation, Genetic, House mouse, Fluctuating asymmetry, Loss of heterozygosity, Mice, Chromosomal Abnormality, Genetics, medicine, Animals, Molecular Biology, Crosses, Genetic, In Situ Hybridization, Fluorescence, Genetics (clinical), Chromosome Aberrations, Mutation, Models, Genetic, biology, Mosaicism, biology.organism_classification, medicine.disease, Chromosome Banding, Female, House mice, Tooth, Biotechnology
Abstract

Fluctuating asymmetry (FA) of tooth traits has been reported to be increased in Down syndrome patients as well as hybrids between chromosomal races of the house mouse differing in several Robertsonian (Rb) fusions. Developmental stability, assessed by FA, is thus thought to be impaired by spontaneous chromosomal abnormality or by chromosomal heterozygosity. Although the effect of a single fusion on developmental stability could theoretically be expected, it has never been documented. Crosses involving two chromosomal races of the house mouse diverging for one Rb fusion were performed to assess developmental stability in parental homozygous races as well as in their hybrids. Moreover, the occurrence of a spontaneous chromosomal mutation (WART type-b) allowed us to study the instantaneous effect of such a translocation on developmental stability. No difference in fluctuating asymmetry levels was detected among the groups considered in this study. This result suggested that a single stable or spontaneous balanced structural rearrangement did not inherently disturb developmental stability. In addition, the differential effect on developmental stability of one versus many heterozygous Rb fusions highlights the role of their quantitative accumulation in the disruption of coadaptation in chromosomal hybrids.

Published
2017

19. T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED

Author

René Lutter, Peter J. Sterk, Ian M. Adcock, Chih-Hsi Scott Kuo, Julie Corfield, Stelios Pavlidis, F. Baribaud, Ratko Djukanovic, Iaonnis Pandis, Yike Guo, Anthony Rowe, Ana C. A. Sousa, C. Auffray, Kian Fan Chung, Matthew J. Loza, AII - Inflammatory diseases, Pulmonology, AII - Amsterdam institute for Infection and Immunity, Other departments, National Institute for Health Research, Commission of the European Communities, and Medical Research Council (MRC)

Subjects
0301 basic medicine, Male, AIRWAY INFLAMMATION, CCR3, Respiratory System, DISEASE, NLRP3 INFLAMMASOME, SUBTYPES, Leukocyte Count, 0302 clinical medicine, Adrenal Cortex Hormones, Forced Expiratory Volume, 11 Medical and Health Sciences, GENE-EXPRESSION, Interleukin-13, Innate lymphoid cell, Middle Aged, U-BIOPRED Study Group, medicine.anatomical_structure, C-Reactive Protein, Phenotype, Area Under Curve, Female, medicine.symptom, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, Adult, INNATE LYMPHOID-CELLS, NEUTROPHILIC ASTHMA, Biology, Nitric Oxide, 03 medical and health sciences, Immune system, Th2 Cells, medicine, Humans, Asthma, Aged, Science & Technology, Sputum, Eosinophil, medicine.disease, Neutrophilia, United Kingdom, respiratory tract diseases, Eosinophils, 030104 developmental biology, 030228 respiratory system, DISCOVERY, Case-Control Studies, Immunology, Exhaled nitric oxide, Transcriptome, Biomarkers
Abstract

Asthma is characterised by heterogeneous clinical phenotypes. Our objective was to determine molecular phenotypes of asthma by analysing sputum cell transcriptomics from 104 moderate-to-severe asthmatic subjects and 16 nonasthmatic subjects.After filtering on the differentially expressed genes between eosinophil- and noneosinophil-associated sputum inflammation, we used unbiased hierarchical clustering on 508 differentially expressed genes and gene set variation analysis of specific gene sets.We defined three transcriptome-associated clusters (TACs): TAC1 (characterised by immune receptors IL33R, CCR3 and TSLPR), TAC2 (characterised by interferon-, tumour necrosis factor-α- and inflammasome-associated genes) and TAC3 (characterised by genes of metabolic pathways, ubiquitination and mitochondrial function). TAC1 showed the highest enrichment of gene signatures for interleukin-13/T-helper cell type 2 (Th2) and innate lymphoid cell type 2. TAC1 had the highest sputum eosinophilia and exhaled nitric oxide fraction, and was restricted to severe asthma with oral corticosteroid dependency, frequent exacerbations and severe airflow obstruction. TAC2 showed the highest sputum neutrophilia, serum C-reactive protein levels and prevalence of eczema. TAC3 had normal to moderately high sputum eosinophils and better preserved forced expiratory volume in 1 s. Gene–protein coexpression networks from TAC1 and TAC2 extended this molecular classification.We defined one Th2-high eosinophilic phenotype TAC1, and two non-Th2 phenotypes TAC2 and TAC3, characterised by inflammasome-associated and metabolic/mitochondrial pathways, respectively.

Published
2017

20. Specific gene expression signature associated with development of autoimmune type-I diabetes using whole-blood microarray analysis

Author

Fanny Turrel-Davin, C Auffray, Malick Paye, N. Bendelac, Bruno Mougin, Q Xu, Fabien Petit, Alexandre Pachot, A Hot, M. Nicolino, Frédéric Reynier, and Charles Thivolet

Subjects
Male, Adolescent, Immunology, Biology, Bioinformatics, Autoimmune Process, Diabetes mellitus, Gene expression, Genetics, medicine, Cluster Analysis, Humans, Gene Regulatory Networks, Child, Gene, Genetics (clinical), Oligonucleotide Array Sequence Analysis, Whole blood, Reverse Transcriptase Polymerase Chain Reaction, Microarray analysis techniques, Gene Expression Profiling, medicine.disease, Major gene, Gene expression profiling, Diabetes Mellitus, Type 1, Female
Abstract

Understanding the pathogenesis of type-I diabetes (T1D) is hindered in humans by the long autoimmune process occurring before clinical onset and by the difficulty to study the pancreas directly. Alternatively, exploring body fluids and particularly peripheral blood can provide some insights. Indeed, circulating cells can function as 'sentinels', with subtle changes in gene expression occurring in association with disease. Therefore, we investigated the gene expression profiles of circulating blood cells using Affymetrix microarrays. Whole-blood samples from 20 first-degree relatives of T1D children with autoimmune diabetes-related antibodies, 19 children immediately after the onset of clinical T1D and 20 age- and sex-matched healthy controls were collected in PAXgene tubes. A global gene expression analysis with MDS approach allowed the discrimination of pre-diabetic subjects, diabetic patients and healthy controls. Univariate statistical analysis highlighted 107 distinct genes differently expressed between these three groups. Two major gene expression profiles were characterized, including type-I IFN-regulated genes and genes associated with biosynthesis and oxidative phosphorylation. Our results showed the presence of early functional modifications associated with T1D, which could help to understand the disease and suggest possible avenues for therapeutic interventions.

Published
2010
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21. Restriction fragment length polymorphism analysis of major histocompatibility complex class II genes from inbred chicken lines

Author

Arne W. Nordskog, Y X Xu, Carol M. Warner, Susan J. Lamont, Y. Bourlet, C. Auffray, and B M Gerndt

Subjects
Genetics, Polymorphism, Genetic, Genes, MHC Class II, Haplotype, General Medicine, Biology, HindIII, Major histocompatibility complex, Molecular biology, Restriction enzyme, B vitamins, Terminal restriction fragment length polymorphism, symbols.namesake, Haplotypes, biology.protein, Mendelian inheritance, symbols, Animals, Animal Science and Zoology, Restriction fragment length polymorphism, Chickens, Polymorphism, Restriction Fragment Length
Abstract

High molecular weight DNA was extracted from sperm from chickens of 14 inbred lines. The DNA was digested with each of four restriction enzymes (Pvu II, Hind III, Bgl II, and Bam HI), electrophoresed for 18 or 45 h, blotted onto nitrocellulose, and hybridized to a chicken major histocompatibility complex (MHC, B complex) class II beta-chain probe (beta 2-exon specific). Restriction fragment length polymorphisms (RFLPs) were found with each of the restriction enzymes used. Birds with the same B haplotype always showed the same RFLP pattern; however, some birds of different B haplotypes also shared the same RFLP pattern. To test for the Mendelian inheritance of the RFLP patterns, the F2 progeny of an informative cross were analysed. The RFLP patterns corresponded with the serologically determined B haplotypes of the F2 birds, thereby showing the Mendelian inheritance of the polymorphic bands.

Published
2009
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22. LATE-BREAKING ABSTRACT: Transcriptomic fingerprinting in severe adult-onset asthma shows type2-high and inflammatory-cell gene signatures in the U-BIOPRED cohort

Author

F. Baribaud, Julie Corfield, K.F. Chung, B. De Meulder, Stelios Pavlidis, Aruna T. Bansal, C. Auffray, Ana R. Sousa, Ratko. Djukanovic, I.M. Adcock, P. J. Sterk, Ariane H. Wagener, Matthew J. Loza, E.H.D. Bel, and P.P. Hekking

Subjects
Transcriptome, business.industry, Adult onset asthma, Cohort, Inflammatory cell, Medicine, business, Bioinformatics, Gene
Published
2015
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23. Integration of chicken cytogenetic and genetic maps: 18 new polymorphic markers isolated from BAC and PAC clones

Author

Jean-Philippe Vit, A. Pouzadoux, V. Fillon, M. Morisson, J. Gellin, Frédérique Pitel, Alain Vignal, C. Auffray, R. Zoorob, and R. Berge

Subjects
Genetic Markers, Genetic Linkage, Biology, Cytogenetics, Gene mapping, Genetics, medicine, Animals, Cloning, Molecular, In Situ Hybridization, Fluorescence, Polymorphism, Single-Stranded Conformational, DNA Primers, Genomic Library, Bacterial artificial chromosome, Polymorphism, Genetic, Base Sequence, medicine.diagnostic_test, Chromosome Mapping, Chromosome, General Medicine, Chromosome 3, Genetic marker, Microchromosome, Microsatellite, Animal Science and Zoology, Chickens, Microsatellite Repeats, Fluorescence in situ hybridization
Abstract

As an approach to integrate the chicken genetic and cytogenetic maps, bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC) clones were localized by fluorescence in situ hybridization (FISH) on chromosomes and by genetic mapping on the East Lansing and Compton reference families. Some of the clones used in this study were previously selected for the presence of potentially polymorphic (CA)n repeats and a microsatellite marker was developed when possible for genetic mapping. For other clones, a single strand conformational polymorphism (SSCP) was developed and used for this purpose. Between the two approaches, 18 markers linking the cytogenetic and genetic maps, seven on macrochromosomes and 11 on microchromosomes, were generated. Our results enabled the assignment and orientation of a linkage group to chromosome 3, together with the assignment of linkage groups to eight different microchromosomes, a fraction of the genome lacking mapping data and for which the degree of coverage by the genetic map was not well estimated previously.

Published
1998
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24. [Untitled]

Author

Mireille Morisson, Alain Vignal, R. Zoorob, M. Douaire, Valerie Fillon, C. Auffray, and Joël Gellin

Subjects
medicine.diagnostic_test, Gene mapping, Evolutionary biology, Genetic marker, Hybridization probe, Gene density, Genetics, medicine, Microchromosome, Microsatellite, Biology, Genome, Fluorescence in situ hybridization
Abstract

A feature of avian karyotypes is the presence of microchromosomes. As a typical avian genome, the chicken karyotype (2n = 78) consists of nine pairs of macrochromosomes, including the W and Z sexual chromosomes, and 30 pairs of indistinguishable microchromosomes usually ordered arbitrarily by decreasing size. Despite their reduced size, microchromosomes represent one-third of the genome and have a high gene density. So as to provide a tool to identify them, we developed a set of large insert-containing clones to be used as tags in two-colour fluorescence in situ hybridization experiments. Seventeen clones, six of which contain a microsatellite sequence and two others the fatty acid synthase gene or genes from the major histocompatibility complex, all presenting a strong hybridization signal, were selected for this purpose and enabled us to identify 16 different microchromosomes. The ability to recognize individual microchromosomes will be of great value for cytogenetic gene mapping, assignation of linkage groups from genetic maps and other studies on avian genome structure.

Published
1998
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25. Contents, Vol. 77, 1997

Author

A. Botta, K. Rojas, P. Zaragoza, X.-X. Zhang, M. Pritchard, B.P. Chowdhary, J.P. Park, J.L. Kissil, A. Rocchi, T.K. Watanabe, T. Siddque, N.P. Mertvetsov, W. Engel, A.A. Bosma, C. Rodellar, A. Arai, F. Shimizu, B. Hoebee, K.N. Sastry, R. Houlgatte, P.A. Voûte, N. Guo, U.W. Kenkare, J.-J. Cassiman, J. Guimera, W.R. Harrison, M.Z. Limongi, G. Mirza, A. Fratello, C.H. van Os, T. Ikeuchi, M. Chaffanet, T. Goldammer, M. Mannens, D. Grady, D. Wells, V. Romano, O. Miura, As. Ricco, M. Schwerin, M. Gersh, M.L. Filipenko, S.A. Wilcox, H. Levéziel, S.J. O’Brien, G.F.M. Merkx, C.C. Morton, G. Hardiman, R. Marzella, S. Hirosawa, T.J. Robinson, K.B.M. Reid, C. Elduque, A.S. Hewson, P.M.T. Deen, J.A. Squire, J.A.M. Graves, L. Vatteroni, E. Viegas-Péquignot, K. Yamamoto, M. Carter, L. Frönicke, N.V. Vorobieva, J. Overhauser, N. Ceratto, N.A. de Haan, M. Suzuki, T. Kozaki, M.S. Aly, B. Redeker, S. van Beersum, P.M. Borodin, F.F.B. Elder, A. Kimchi, A.S. Graphodatsky, B. Beatty, J.A. McMahon, M. de Meulemeester, J.B. Searle, I.V. Koroleva, W.Y. Hung, Y. Kuga, M. Jeanpierre, N. Sakuragawa, S. Feo, C. Auffray, M. Ogawa, M. Rocchi, M.P. Hande, C.K. Ullrich, J. Widmer, A. Ponce de León, F.O. Fackelmayer, S. Weremowicz, A. Pizzuti, K. Ohsugi, S. Okuno, R.J.M. Bindels, L.D. Matyakhina, A.P. McMahon, R. Leube, Y. Yang, A. Pandita, M. Lachtermacher, A. Tanzariello, B. Dallapiccola, M.A. Ferguson-Smith, A. Musio, A.F. Davies, D. Patterson, N. Lynch, Y. Nakamura, G. Rainaldi, M. Steenman, S.-T. Lee, H. Hayes, P.C.M. O’Brien, G.G. Karpova, C.H.M. Mellink, E. Jenkins, J.H. Xia, M. Schepens, A.T. Natarajan, B.-L. Lim, R. Meneveri, W.G. Nash, J. Kissing, M. Stacey, T. Fujiwara, M. Schmid, L.A. Witters, C. Zijlstra, L. Viggiano, F. Yang, M. Nagata, W. Bie, H. Scherthan, H. Murer, B. Ghebrehiwet, A. Westerveld, S. Kurata, H.N. Seuánez, M. Lovett, K.-H. Lee, R. Godbout, H.G. Brunner, J.M. Varley, P. Thygesen, R. Slater, S. Ishikawa, S.D. Pack, E. Takahashi, O.V. Cheryaukene, C. Bendixen, F. Ugolini, M. Matsumoto, R.M. Brunner, A. Risch, D. Birnbaum, Y. Takei, C.H. Fan, L.A. James, E.M. Ladenburger, P. Laurent, G. von Beust, T.K. Mohandas, H. Kobayashi, E. Burt, K. Wiesmeijer, M. Kai, A. Baldini, P. Eydoux, F.C. Canavez, F. Pelliccia, A. Geurts van Kessel, Déborah Bourc'his, S.-H. Park, S. Sebastian, C. Dobkin, R. Stanyon, R.A. Kastelein, L. Langbein, R. Toder, K. Okui, O.L. Serov, N. Matas, M.R. Koehler, R. Moyzis, J.F. Bazan, M.A. van Kuijck, A. Simons, P. Miniou, Y. Yokoyama, D. Molina Gomes, L. Xu, M.A.M. Moreira, H. Kim, E. Sim, J. Ragoussis, F. Saito-Ohara, M. Kool, N. Miyasaka, T. Katagiri, P. Bosco, X. Estivill, N. Archidiacono, G. Novelli, R. Knippers, P. Maccarone, J. Wienberg, M.-J. Pébusque, H.S. Tenenhouse, M. Nadal, W. Schwaeble, H. Hameister, H. van Bokhoven, T. Takahashi, E.I.B. Peerschke, V. Jurecic, X.-L. Yao, Y. Hey, P. Riegman, S.N. Malchenko, H.X. Deng, A.B. Spurdle, and N. Hoggard

Subjects
Botany, Genetics, Zoology, Biology, Molecular Biology, Genetics (clinical)
Published
1997
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26. Relative warp analysis of skull shape across the hybrid zone of the house mouse ( Mus musculus ) in Denmark

Author

J.‐C. Auffray, C. Latieule, Barbara Dod, and Paul Alibert

Subjects
education.field_of_study, biology, Population, Introgression, Cline (biology), Anatomy, Subspecies, biology.organism_classification, House mouse, Skull, Hybrid zone, medicine.anatomical_structure, Evolutionary biology, medicine, Animal Science and Zoology, education, Ecology, Evolution, Behavior and Systematics, Hybrid
Abstract

The changes in skull shape that occur in the hybrid zone between the two European subspecies of the house mouse (Mus musculus musculus and M. m. domesticus) were studied by relative warp analyses. Landmarks observed on the ventral view of the skulls of 269 mice sampled in 18 localities in Denmark were analysed. Each population was also characterized by a hybrid index estimated from allozymic data. Although no clear pattern of within-population variability of shape could be established across the hybrid zone, the shape changes among the 18 populations were found to be correlated with the allozymic introgression but not with geographical location. Finally, the cline obtained for skull shape seems to be steeper than that corresponding to the average allozyme hybrid index which suggests that skull development could be slightly perturbed in hybrids.

Published
1996
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27. Integration of Transcript and Genetic Maps of Chromosome 16 at Near-1-Mb Resolution: Demonstration of a 'Hot Spot' for Recombination at 16p12

Author

D.F. CALLEN, S.A. LANE, H. KOZMAN, G. KREMMIDIOTIS, S.A. WHITMORE, M. LOWENSTEIN, N.A. DOGGETT, N. KENMOCHI, D.C. PAGE, D.R. MAGLOTT, W.C. NIERMAN, K. MURAKAWA, R. BERRY, J.M. SIKELA, R. HOULGATTE, C. AUFFRAY, and G.R. SUTHERLAND

Subjects
Genetic Markers, Databases, Factual, Transcription, Genetic, Molecular Sequence Data, Hybrid Cells, Biology, Polymerase Chain Reaction, Genetic recombination, Cell Fusion, Mice, Chromosome 16, Gene mapping, Human Genome Project, Genetics, Animals, Humans, Gene, DNA Primers, Recombination, Genetic, Base Sequence, Gene map, Breakpoint, Chromosome Mapping, Genetic marker, Chromosome Deletion, Chromosome 22, Chromosomes, Human, Pair 16
Abstract

A single mapping resource, a mouse/human somatic cell panel with average distance between breakpoints of 1.2 Mb and a potential resolution of 1 Mb, has been utilized to integrate the genetic map and a transcript map of human chromosome 16. This map includes 141 genetic markers and 200 genes and transcripts. The localization of four genes (CHEL3, TK2, TRG1, and MMP9) reported to map to chromosome 16 could not be confirmed, and for three of these localizations to other human chromosomes are reported. A correlation between genetic and physical distance over a region estimated to be 23 Mb on the short arm of chromosome 16 identified an interval demonstrating a greatly increased rate of recombination where, in females, 1 cM is equivalent to a physical distance of 100 kb.

Published
1995
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28. Adaptation and plasticity in insular evolution of the house mouse mandible

Author

J-C. Auffray, Sabrina Renaud, Ecologie et évolution des populations, Département écologie évolutive [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0106 biological sciences, Morphometrics, 0303 health sciences, Phenotypic plasticity, education.field_of_study, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Shape change, biology, Ecology, Population, biology.organism_classification, 010603 evolutionary biology, 01 natural sciences, House mouse, 03 medical and health sciences, Genetics, Animal Science and Zoology, House mice, Adaptation, education, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology
Abstract

Morphometric methods allow the quantification of directions of phenotypic changes and their statistical comparison in a morphometric space. We applied this approach to investigate several candidate factors to explain changes in mandible shape occurring in house mice (Mus musculus domesticus, Mammalia, Rodentia) in Corsica and a nearby islet. The role of niche widening and of the concomitant change in diet was evaluated by comparing the micro-evolutionary insular change to the macro-evolutionary difference between omnivorous and herbivorous rodents. Phenotypic plasticity, which may contribute to rapid insular evolution, was assessed by breeding laboratory mice on hard versus soft food. The related change in mandible shape was compared with differences between continental and insular populations. The role of allometry was evaluated by assessing shape change related to size within the continental population and comparing this direction of change with differences on islands. Finally, evolution may be facilitated along the direction of the greatest phenotypic variance. This hypothesis was tested by computing in wild populations vectors corresponding to this direction and by comparing these vectors with those corresponding to estimates of shape changes related to plasticity, micro- and macro-evolutionary processes. In Corsica, the congruence in directions of macro- and micro-evolutionary phenotypic vectors (Corsican/continental mice versus omnivorous/herbivorous rodents) supports the hypothesis of adaptation in mandible shape evolution. By contrast, on the islet, phenotypic divergence follows directions of plastic response to food consistency as well as within-population allometry. Thus, results suggest differences in the relative importance of processes which may influence rodent mandibular shape depending on the size of the islands they colonized. Faster evolution and plasticity may be more evident in small and often ephemeral populations living on small islands, whereas micro-evolutionary processes may have enough time and genetic variability to progressively ‘align’ with macro-evolutionary trends in large populations from big islands. Resume Les methodes morphometriques permettent de quantifier des directions de changements phenotypiques et de les comparer statistiquement. Cette approche a ete appliquee pour evaluer plusieurs facteurs explicatifs des differences de forme de la mandibule observees chez des populations de souris domestiques (Mus musculus domesticus) de Corse, de Sardaigne et d’un ilot voisin de la Corse. Le role de l’elargissement de la niche et du changement alimentaire concomitant a ete teste en comparant le changement insulaire (echelle micro-evolutive) a celui observe entre mandibules de rongeurs omnivores et herbivores (echelle macro-evolutive). La plasticite phenotypique pourrait egalement contribuer a l’acceleration des changements evolutifs sur les iles. Le changement mandibulaire associe a eteevalue en elevant des souris de laboratoire avec deux nourritures de consistance differente, en granules ou gelifiee. La composante allometrique de la variation de forme a eteevaluee sur des populations continentales. Enfin, l’evolution phenotypique peut etre facilitee le long des directions de plus grande variance. Cette hypothese a ete testee en evaluant ces directions dans les differentes populations sauvages et en les comparant aux directions des changements plastiques, allometriques, micro- et macro-evolutifs. La congruence des directions micro- et macro-evolutives observee dans le cas de la differentiation continent – Corse, continent – Sardaigne et omnivores – herbivores, corrobore le role de l’adaptation dans le changement de forme de la mandibule chez les souris corses et sardes. La divergence de la population de l’ilot, en revanche, correspond aux directions de changement allometrique et de remodelage osseux en reponse a la consistance de nourriture. Ces resultats montrent l’interet de comparer quantitativement des directions de changement phenotypique pour analyser les causes complexes de differenciation des populations naturelles. Ils suggerent en outre que differents processus agissent sur des iles de taille contrastee, possiblement a des pas de temps differents : plus long sur les grandes iles comme la Corse, et plus rapides, impliquant une reponse plastique, sur de petits ilots.

Published
2010
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29. Contents Vol. 92, 2001

Author

L. Iannuzzi, C. Broccardo, Y. Mao, J.J.M. van Groningen, W.D. Phillips, J. Wang, J. Rathjen, T. Krieg, D.S. Gallagher, F. Sangiuolo, P. Lichter, M. Wilbrink, P.D. Rathjen, N.W. Richards, K.-M. Debatin, Y. Matsuda, A. Vaiman, K.J. Portbury, P. Perelman, F. Bourgeois, X. Huang, D.L. Gumucio, I. Jentsch, S.S. Bhattacharya, Q. Jiang, K. Ying, I. Matera, A. Rösen-Wolff, C. Mas, K. Ogura, J. Koch, S. Kiuru-Kuhlefelt, C. Auffray, P. Denèfle, R. Allikmets, M. Miettinen, S. Schmutz, M.P. Hildebrand, I. Arnould, C. Prades, R. Sauer, C. Sapienza, R.B. Voyle, F. Yang, M. Gahr, L.J. Coignet, A. Kuroiwa, C.G. Scheuerpflug, N. Serdukova, W.O. Bauer, L.M. Gulluyan, B. Brewer, M. Simonneau, J. Fanburg-Smith, A.S. Graphodatsky, I. Kola, C. Stover, M. Sancandi, J. Dai, W. El-Rifai, Y. Obara, M. Bozzali, M.-D. Devignes, E. Reichenberger, A.G. Marneros, T. Otoguro, B.R. Olsen, A. Botta, C. Drögemüller, A. Mincheva, W. Schwaeble, W. Wang, F. Jakob, S-I. Kawada, L. Naudin, B. Jordan, T. Isobe, M.R. Speicher, G. Palumbo, L. Granjon, S. Knuutila, C. Chelala, A. Bulfone, K. Engel, A. Hoffmann, E. Kater-Baats, H. Kuiper, R. Ravazzolo, G. Gradl, S. Fojo, Z. Zhou, M. Schmid, N. Serakıncı, D. Di Berardino, J. Rubes, I. Ceccherini, K. Matsumoto, B. Dallapiccola, K. Tsuchiya, J.M. Moalic, M.A. Lee-Kirsch, S. Galiègue-Zouitina, G. Merkx, S. Thomas, M.A.J. Weterman, V.T. Volobouev, M. Dean, M. Stumm, G. Novelli, F. Guimiot, N. Tommerup, M. Fredholm, A. Baldini, V. Jurecic, N.B. Atkin, W. Zhao, C. Hansen, W. Nie, G.P. Di Meo, I. Gustavsson, M. van Rooijen, S. Cirera, A.T. Remaley, J. Osorio, S. Imbeaud, R. Cinti, F. Amati, R.-D. Wegner, E. Conti, S. Murray, A. Geurts van Kessel, A. Pizzuti, C.M. Owczarek, K. Friis Henriksen, S. Halford, C. Lafargue, R. Tang, C.Y. Gregory-Evans, S. Cui, C.P. Popescu, P.J. Hertzog, T. Leeb, T. Ogura, P.E. Schaner, M. Kuro-o, Diederik R.H. de Bruijn, S. Shulenin, P. Wieacker, W. Rens, N.A. Jenkins, B. Pedersen, M. Fava, H.R. Treutlein, C. Roumier, M. Berloco, F. Pardo-Manuel de Villena, M. Rosier, P.C.M. O’Brien, N.D. Ebenezer, L. Kutschke, D. Fukushi, E.P. Cribiu, A. Ratti, G. Beck, O. Distl, M.-F. Luciani, S.E. Antonarakis, M. Eleveld, Y. Huang, R.M. Hope, J. Kere, J.A. Kennell, Y. Xie, B.S. Milne, M.A. Ferguson-Smith, S. Neubauer, J. Womack, R. Zoorob, H. Hayes, A. Eggen, N.G. Copeland, B. Levacher, Y.-A. Lee, B. Sicard, M. Bak, S.X. Liang, D.J. Gilbert, G. Stranzinger, E. Paditz, H. Mehenni, R. Wieser, G. Chimini, M.G. Mattei, L.M. Schriml, S. Keindorff, I. Nanda, and M. Shichiri

Subjects
Botany, Genetics, Biology, Molecular Biology, Genetics (clinical)
Published
2000
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30. Mapping of the genetically independent chicken major histocompatibility complexes B@ and RFP-Y@ to the same microchromosome by two-color fluorescent in situ hybridization

Author

C. Auffray, Martine Yerle, Valerie Fillon, Alain Vignal, and R. Zoorob

Subjects
Genetics, biology, In situ hybridization, Major histocompatibility complex, Molecular biology, Fluorescence, Gene mapping, Microchromosome, biology.protein, Molecular Biology, Gene, Genetics (clinical), Major histocompatibility
Abstract

The chicken MHC is organized in two genetically independent gene complexes B@and RFP-Y®. Previous studies have shown the localization of the B@complex on a small microchromosome. By using two-color fluorescent in situ hybridization, we demonstrate the localization of the RFP-Y@ complex to the same chromosome. A recombination hot spot between the two loci might account for their independent segregation.

Published
1996
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31. Assignment of the chicken NOV gene (alias CCN3) to chromosome 2q34--q36: Conserved and compared synteny between avian, mouse and human

Author

P, Coullin, C L, Li, L, Ziercher, C, Auffray, A, Bernheim, R, Zoorob, and B, Perbal

Subjects
Chromosomes, Artificial, Bacterial, Connective Tissue Growth Factor, Chromosome Mapping, Wilms Tumor, Chromosome Banding, Immediate-Early Proteins, Mice, Nephroblastoma Overexpressed Protein, Species Specificity, Animals, Humans, Intercellular Signaling Peptides and Proteins, Chickens, In Situ Hybridization, Fluorescence
Published
2002

32. Molecular studies on the colonization of the Madeiran archipelago by house mice

Author

I, Gündüz, J C, Auffray, J, Britton-Davidian, J, Catalan, G, Ganem, M G, Ramalhinho, M L, Mathias, and J B, Searle

Subjects
Europe, Evolution, Molecular, Mice, Haplotypes, Portugal, Molecular Sequence Data, Animals, Genetic Variation, DNA, Mitochondrial, Phylogeny
Abstract

To study the colonization history of the house mouse (Mus musculus domesticus) on the Madeiran archipelago, complete mitochondrial D-loop sequences were obtained for 44 individuals from Madeira, Porto Santo and Ilhas Desertas. Altogether, 19 D-loop haplotypes were identified which formed part of a single clade in a phylogeny incorporating haplotypes from elsewhere in the range of M. m. domesticus, indicating that the Madeiras were colonized from a single source. Similarities between the sequences found in the Madeiras and those in Scandinavia and northern Germany suggest that northern Europe was the source area, and there is the intriguing possibility that the Vikings may have accidentally brought house mice to the archipelago. However, there is no record of Vikings visiting the Madeiras; on historical grounds, Portugal is the most likely source area for Madeiran mice and further molecular data from Portugal are needed to rule out that possibility.

Published
2001

33. Spontaneous occurrence of a Robertsonian fusion involving chromosome 19 by single whole-arm reciprocal translocation (WART) in wild-derived house mice

Author

J, Catalan, J C, Auffray, F, Pellestor, and J, Britton-Davidian

Subjects
Male, Mice, Mosaicism, Centromere, Mutation, Animals, Female, DNA, Ribosomal, Crosses, Genetic, In Situ Hybridization, Fluorescence, Translocation, Genetic, Chromosome Banding
Abstract

Chromosomal races of the house mouse (Mus musculus domesticus) bear Robertsonian (Rb) fusions, which consist of centric translocations between two non-homologous acrocentric chromosomes. The high level of diversity of these fusions in house mice is generated by de-novo formation of Rb fusions and subsequent whole-arm reciprocal exchanges (WARTs). This paper describes the spontaneous occurrence of a new Rb fusion, Rb(4.19), in progeny of wild-derived house mice segregating for Rb(4.12). The chromosomal mutation was traced to a female which exhibited germline and somatic mosaicism indicating an early embryonic origin of the mutation. FISH analysis of centromerically-located ribosomal genes suggested that no modification was observed on chromosomes 12 and 19 prior to or following the occurrence of Rb(4.19). Distribution of telomeric sequences showed that both Rb fusions lacked telomeres in their centromeric regions. It is argued that this spontaneous mutation most likely originated by single whole-arm reciprocal translocation (WART) between Rb(4.12) and an acrocentric chromosome 19, resulting in Rb(4.19) and a neo-acrocentric chromosome 12. Sequences required for centromeric function and proximal telomeres would have been transferred to the neo-chromosome 12 from chromosome 19 during the translocation. The existence of such WARTs which generate derived acrocentric chromosomes has several implications for chromosomal evolution in house mice.

Published
2000

34. The SysCLAD- Systems Prediction of Chronic Lung Allograft Dysfunction Study: Aims, Strategy and First Data

Author

Sacha Mussot, Michel Seve, J.-D. Aubert, Ronald C. Kessler, Claire Dromer, G. Oliveira, M. Dahan, Marc Stern, C. Auffray, J.-P. Boissel, D. Maier, K. Deplanche, Sophie Brouard, V. Boussaud, Adrien Tissot, Annette Boehler, Laurent P. Nicod, C. Knopp, Martine Reynaud-Gaubert, Antoine Magnan, Gabriel Thabut, B. Marshland, J.-F. Mornex, D. Koubi, C. Pison, and K. Botturi

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.medical_treatment, Bronchiolitis obliterans, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Lung transplantation, 030304 developmental biology, Whole blood, 0303 health sciences, Transplantation, COPD, Bronchiectasis, Lung, business.industry, medicine.disease, 3. Good health, medicine.anatomical_structure, Cohort, Immunology, Surgery, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract

Purpose The SysCLAD study is an European Union-funded project under the FP-7 to predict CLAD signature by year-1 post lung transplantation (LT) before any decline in lung function. CLAD and its subtypes Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome represent the actual limitation resulting in a high morbi-mortality and costs. Specific aims of SysCLAD are identification of CLAD biomarkers, a better understanding of CLAD mechanisms and a predictive and personalized signature of CLAD. Methods and Materials Built upon a cohort of LT recipients already transplanted and recruited since September 2009 in 14 LT centres, SysCLAD signature will be based on a mathematical model developed through a systems medicine approach integrating clinical and biological data collected within the first year post LT in 2 steps, using calibration and validation samples within LT cohort. Clinical data include donors and recipients characteristics and post LT clinical events; biological data donors and recipients HLA, whole blood transcriptomics, BAL and blood proteomics at months 6 and 12, together with once miRNA, BAL microbiote and recipient genetic polymorphisms analysis at month 6. Results By November 2012, 820 LT candidates of whom 652 received a LT; indications were by digressive order CF, COPD/emphysema, IPF, PH, bronchiectasis and others; LT recipients were 42.7 ± 15.2 yrs old, 320 received a double LT; 2-years survival was 76%. In SysCLAD biobank, they are by year-1 post LT to predict besides “clinicome”: 1 152 TBB, 7 537 PBMC aliquots, 2362 BAL, 1311 blood samples for transcriptomics Paxgene®, 12 903 plasma and 11 008 sera aliquots. Conclusions CLAD tool is expected by early personalized interventions to improve morbi-mortality and increase the cost-effectiveness of LT. Funds from PHRC 2008 and Vaincre La Mucoviscidose within the 11 French lung Transplantation centres to launch Cohort in Lung Transplantation (COLT)-ClinicalTrials.gov Identifier: NCT00980967, Programme transplantation 2008, PRTP-13, and #HEALTH-F5-2012-305457, a FP-7 call.

Published
2013
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35. A gene map of the human genome

Author

G D, Schuler, M S, Boguski, E A, Stewart, L D, Stein, G, Gyapay, K, Rice, R E, White, P, Rodriguez-Tomé, A, Aggarwal, E, Bajorek, S, Bentolila, B B, Birren, A, Butler, A B, Castle, N, Chiannilkulchai, A, Chu, C, Clee, S, Cowles, P J, Day, T, Dibling, N, Drouot, I, Dunham, S, Duprat, C, East, C, Edwards, J B, Fan, N, Fang, C, Fizames, C, Garrett, L, Green, D, Hadley, M, Harris, P, Harrison, S, Brady, A, Hicks, E, Holloway, L, Hui, S, Hussain, C, Louis-Dit-Sully, J, Ma, A, MacGilvery, C, Mader, A, Maratukulam, T C, Matise, K B, McKusick, J, Morissette, A, Mungall, D, Muselet, H C, Nusbaum, D C, Page, A, Peck, S, Perkins, M, Piercy, F, Qin, J, Quackenbush, S, Ranby, T, Reif, S, Rozen, C, Sanders, X, She, J, Silva, D K, Slonim, C, Soderlund, W L, Sun, P, Tabar, T, Thangarajah, N, Vega-Czarny, D, Vollrath, S, Voyticky, T, Wilmer, X, Wu, M D, Adams, C, Auffray, N A, Walter, R, Brandon, A, Dehejia, P N, Goodfellow, R, Houlgatte, J R, Hudson, S E, Ide, K R, Iorio, W Y, Lee, N, Seki, T, Nagase, K, Ishikawa, N, Nomura, C, Phillips, M H, Polymeropoulos, M, Sandusky, K, Schmitt, R, Berry, K, Swanson, R, Torres, J C, Venter, J M, Sikela, J S, Beckmann, J, Weissenbach, R M, Myers, D R, Cox, M R, James, D, Bentley, P, Deloukas, E S, Lander, and T J, Hudson

Subjects
Genetic Markers, DNA, Complementary, Base Sequence, Databases, Factual, Genome, Human, Chromosome Mapping, Gene Expression, Cell Line, Computer Communication Networks, Multigene Family, Sequence Homology, Nucleic Acid, Human Genome Project, Animals, Humans, Amino Acid Sequence, RNA, Messenger, Chromosomes, Artificial, Yeast, Sequence Tagged Sites
Abstract

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Published
1996

36. Molecular basis of T lymphocyte CD4 antigen functions

Author

M, Gaubin, M, Autiero, R, Houlgatte, S, Basmaciogullari, C, Auffray, and D, Piatier-Tonneau

Subjects
Models, Molecular, Binding Sites, CD4 Antigens, HIV-1, Histocompatibility Antigens Class II, Humans, HIV Envelope Protein gp120
Abstract

The T cell surface antigen CD4 plays a pivotal role in the MHC class II-restricted response of specific T lymphocytes and serves as the major receptor of human immunodeficiency viruses (HIV). Recent studies have shown the high complexity of CD4 functions in physiological and pathological conditions. We report here a short review of recent developments in the field and discuss the structural features which regulate the functions mediated by the CD4 coreceptor in mature T lymphocytes.

Published
1996

37. House mouse ancestor from late Pliocene Siwalik sediments of India

Author

R, Patnaik, J C, Auffray, J J, Jaeger, and A, Sahni

Subjects
Muridae, Geologic Sediments, Fossils, Animals, India, Biological Evolution
Abstract

A well preserved mouse skull has been recovered from a pedogenically modified mudstone layer (c. 2 millions years (MY) old) of Pinjor Formation (Upper Siwaliks) exposed east of Chandigarh, India. Comparison of the present skull with those of the extant species of the subgenus Mus reveals its closer relationship towards the house mouse Mus musculus lineage. The present fossil evidence is very much in line with the molecular, allozymic and ecological proposals for the time and place of origin of the subgenus Mus.

Published
1996

38. Human lymphocyte cDNA ordered library analyzed by 2D gel electrophoresis. 3. Analysis of individual clones

Author

G, Béhar, C, Coleclough, R, Houlgatte, C, Auffray, and I, Lefkovits

Subjects
DNA, Complementary, Base Sequence, Molecular Sequence Data, Humans, Electrophoresis, Gel, Two-Dimensional, Pilot Projects, Lymphocytes, Clone Cells, Gene Library
Abstract

We pursued the goal of obtaining global information on cDNA libraries from lymphocytes by combining data on the genes with data on the expressed proteins. Ordered libraries enabled us to establish the properties of the clones by direct retrieval of individual clones from the matrix (in our system a 24 x 16 x 12 array). We have picked-upon inspection of radiofluorographs obtained from the pools of the library--39 clones and performed a 2D gel analysis on the cell free expressed clonal products and have established also their partial nucleotide sequences. Details on two such clones are reported; clone CEM1001 is a new gene, while clone CEM1002 is a gene for human elongation factor 1-beta.

Published
1995

39. Human lymphocyte cDNA ordered library analyzed by 2D gel electrophoresis. 1. Pooling strategy and matching of gel patterns

Author

I, Lefkovits, J R, Frey, L, Kuhn, J R, Kettman, G, Béhar, C, Auffray, J P, Hoffmann, and C, Coleclough

Subjects
Genomic Library, DNA, Complementary, Leukemia, Databases, Factual, Image Processing, Computer-Assisted, Tumor Cells, Cultured, Humans, Electrophoresis, Gel, Two-Dimensional, Lymphocytes
Abstract

We have analyzed an ordered library of 4,608 cDNA clones from the CEM human leukemic cell line. The aim was to facilitate gene retrieval, to enable immediate access to cDNA clones and to provide information on the protein expression of the individual clones in a 2D gel readout. The matrix array of 24 x 16 x 12, each position of which contained lambda jacII phage from one plaque, enabled us to establish pools of clones along the three axes (24 pools of complexity 192 cloned entities, 16 pools of complexity 288 and 12 pools of complexity 384). The total cDNA complexity is here reduced to such a level that spots which in more complex gels served as landmark spots are not present in each pool, and thus cannot serve as landmarks anymore. The image analysis of such gels and especially the matching of spots is not reliable under these circumstances. In order to achieve reliable matching, additional samples were created, such that pools were co-electrophoresed according to a special concatenation scheme; these samples then contained over-lapping elements (e.g., pools 1 + 2 + 3 and 3 + 4 + 5 have at least those spots in common, which originate from pool 3). This approach turned out to be feasible and we have completed the matching of one half of the ordered library. Already from the present stage of analysis we have obtained valuable information on the cDNA library and on the distribution of clones in this library.

Published
1995

40. HLA class II antigens and the HIV envelope glycoprotein gp120 bind to the same face of CD4

Author

R, Houlgatte, P, Scarmato, S, el Marhomy, M, Martin, M, Ostankovitch, S, Lafosse, A, Vervisch, C, Auffray, and D, Platier-Tonneau

Subjects
Models, Molecular, Binding Sites, Protein Conformation, Molecular Sequence Data, Histocompatibility Antigens Class II, Antibodies, Monoclonal, HIV Envelope Protein gp120, Cell Line, Epitopes, HLA Antigens, Mutagenesis, CD4 Antigens, Animals, Humans, Amino Acid Sequence
Abstract

Although the HIV gp120 binding site of CD4 is well characterized, its interaction site with HLA class II molecules is still controversial. Sixty-seven mutations within the four extracellular domains of CD4 were examined for their effects on cell surface expression and conformational changes and for adhesion of HLA class II-expressing B lymphocytes and HIV gp120 binding to CD4-transfected COS cells. Mutations within the gp120 binding site affected both assays similarly, indicating that the two sites fully overlap. A few additional substitutions of residues mapping on the same face of domains 1 and 2 induced decreased rosette formation. Molecular modeling studies indicated that this is likely to be the consequence of conformational changes induced by the mutations. Thus, CD4 appears to interact with HLA class II molecules mainly through the HIV gp120 binding site and possibly through a second minor interaction site mapping on the same face of the molecule.

Published
1994

41. Werner Schmid, 1930–2002

Author

Z. Liu, H. Starke, C.L. Li, A. Rupprecht, S.L. Ewart, L. Fröhlich, R. Tomasini, D. Gallagher, N. Gmachl, N. Ghaffari-Tabrizi, N.A. Jenkins, T. Leeb, M. Grosz, S. Izraeli, H. Akutsu, C. Steinlein, I. Eisenberg, C. Drögemüller, M. Satoh, W. Engel, I.M. Adham, D.J. Gilbert, K. Ying, H.P. Klinger, Y. Ma, N. Coleman, J. Nowak, T. Yagi, R.L. Prueitt, A. Bernheim, N.B. Atkin, H. Kikuchi, R. Tang, M. Bina, L. Ziercher, T. Osada, N. Dusetti, J. Taylor, E. Antoniou, E.I. Pares-Matos, C. Knorr, D.R. Beier, A. Kuechler, H. Chen, T. Haaf, Y. Mao, W. Feichtinger, D.B. Zimonjic, A. Heller, S.K. Swanson, D.K. Griffin, P. Quignon, B. Bjerkehagen, M. Muenke, M. Shibazaki, N.G. Copeland, H. Kuiper, J.C. Phillips, G. Cao, E. Nacheva, L.A. Azizi Samir, H.-U.G. Weier, M.-G. Mattei, M. Wills-Karp, H. Hochner, D.C. Shing, T.P. Yang, H. Cheng, R. Shamsadin, A.M. Simckes, E. Roessler, D.M. Shubitowski, K. Mrasek, R. Fries, B. Lanske, I. Artner, M.-J. Pébusque, S. Kollers, C.A. Morley-Jacob, A. Dutra, S. Mitrani-Rosenbaum, N. Kleiter, R.A. White, P. Coullin, F. Micci, I. Roberts, A.R. Zinn, N.C. Popescu, S. Heim, R. Yanagimachi, F. Galibert, A. Weise, A. Srisodsai, C. Auffray, S.C. Harvey, B. Brenig, I. Kirsch, X. Ni, Selena Davis, C. Ji, C.L. Keck-Waggoner, B. Perbal, Z.H. Shan, J. Young, Y. Xie, B. Hong, T. Niimi, H. Kaiser, S. Fukushige, D.J. Penman, L.A.P. Carrasco, R.I. Barnes, W.H. Brooks, N.R. Bromage, J. Masabanda, J.-L. Iovanna, G.A. Rohrer, O. Distl, S.G. Rak, M. Schmid, Y. Shiratori, K. Kratochwil, M. Sadeh, H. Kusakabe, U. Claussen, M. Jiang, M.R. Teixeira, Z. Argov, T. Liehr, R. Zoorob, W.H. Reeves, J. Womack, J.D. Karkera, S. Kimura, J.-C. Dagorn, and L. Guo

Subjects
Psychoanalysis, Genetics, Biology, Molecular Biology, Genetics (clinical)
Published
2002
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42. Evolution ostéométrique de Rattus rattus et de Mus musculus domesticus sur de petites îles: comparaison de populations médiévales et actuelles des îles Lavezzi (Corse) et de Corse

Author

G. Cheylan, J.-D. Vigne, J.-C. Auffray, and L. Granjon

Subjects
Geography, Animal Science and Zoology, Biological evolution, Humanities, Ecology, Evolution, Behavior and Systematics
Abstract

Pres de 2 500 restes osseux et dentaires de Rattus rattus et de Mus musculus domesticus ont ete decouverts dans des couches archeologiques datees du XIV e et du XVII e siecle sur l'ile Lavezzi (Bouches de Bonifacio, Bonifacio, Corse-du-Sud). L'analyse taphonomique montre qu'ils sont principalement issus de pelotes de rejection de chouette effraie (Tyto alba). La comparaison osteometrique des rats subfossiles avec ceux de populations actuelles de Corse (Bonifacio) et de l'ile Lavezzi, peu differentes l'une de l'autre, montre que les mâchoires, rangees dentaires et os longs etaient plus grands dans la population medievale

Published
1993
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43. Subject Index Vol. 92, 2001

Author

N.W. Richards, M. Gahr, L.J. Coignet, G. Novelli, C. Hansen, D.L. Gumucio, A. Geurts van Kessel, N. Tommerup, L.M. Gulluyan, N. Serakıncı, M. Sancandi, K. Friis Henriksen, B. Dallapiccola, N.A. Jenkins, M. Shichiri, G.P. Di Meo, I. Gustavsson, B.R. Olsen, S.X. Liang, L. Kutschke, J.M. Moalic, G. Beck, A. Baldini, P. Wieacker, D.J. Gilbert, R.-D. Wegner, F. Sangiuolo, W.D. Phillips, J. Fanburg-Smith, A.S. Graphodatsky, C.P. Popescu, M. Kuro-o, G. Stranzinger, J.A. Kennell, M. Schmid, E. Paditz, Y. Obara, H. Kuiper, W. El-Rifai, Y. Xie, J. Wang, S. Shulenin, A.T. Remaley, S. Thomas, K. Ogura, A. Botta, J. Koch, K. Tsuchiya, B.S. Milne, P.D. Rathjen, C. Broccardo, A. Bulfone, C. Drögemüller, S-I. Kawada, S. Knuutila, J.J.M. van Groningen, J. Rathjen, T. Isobe, G. Palumbo, M. Fava, H.R. Treutlein, M.A. Ferguson-Smith, S. Fojo, L. Iannuzzi, P. Denèfle, C. Roumier, M. Wilbrink, K. Engel, T. Krieg, K.-M. Debatin, G. Merkx, G. Chimini, I. Ceccherini, Y. Mao, F. Pardo-Manuel de Villena, M. Rosier, F. Yang, N.D. Ebenezer, M.G. Mattei, P.C.M. O’Brien, M. Miettinen, A. Mincheva, W. Schwaeble, D.S. Gallagher, R. Sauer, D. Fukushi, S. Galiègue-Zouitina, Y. Matsuda, B. Pedersen, M. Berloco, A. Kuroiwa, S. Cirera, E.P. Cribiu, S. Imbeaud, Z. Zhou, F. Amati, C. Sapienza, Diederik R.H. de Bruijn, M.A.J. Weterman, A. Ratti, W. Wang, B. Brewer, V. Jurecic, C. Mas, K. Matsumoto, C.G. Scheuerpflug, N. Serdukova, V.T. Volobouev, A. Vaiman, M. Simonneau, S. Neubauer, J. Womack, C. Auffray, M.-D. Devignes, M.A. Lee-Kirsch, F. Jakob, K.J. Portbury, R. Allikmets, H. Mehenni, T. Ogura, R. Cinti, O. Distl, W. Zhao, M.-F. Luciani, S.E. Antonarakis, E. Conti, L. Granjon, L. Naudin, M.R. Speicher, R.B. Voyle, C.M. Owczarek, Y.-A. Lee, F. Guimiot, R. Zoorob, H. Hayes, S. Schmutz, L.M. Schriml, J. Dai, C. Chelala, E. Kater-Baats, P.J. Hertzog, P.E. Schaner, J. Kere, B. Sicard, A.G. Marneros, I. Arnould, S. Keindorff, E. Reichenberger, P. Perelman, F. Bourgeois, P. Lichter, R.M. Hope, I. Nanda, M. Eleveld, R. Tang, C.Y. Gregory-Evans, S. Cui, W. Nie, Y. Huang, A. Hoffmann, M. Fredholm, C. Prades, M.P. Hildebrand, B. Jordan, D. Di Berardino, M. Bak, I. Jentsch, J. Rubes, A. Rösen-Wolff, S. Kiuru-Kuhlefelt, M. Dean, T. Otoguro, S. Halford, C. Lafargue, R. Ravazzolo, M. Bozzali, W.O. Bauer, G. Gradl, S.S. Bhattacharya, Q. Jiang, S. Murray, M. van Rooijen, K. Ying, J. Osorio, X. Huang, M. Stumm, I. Matera, T. Leeb, W. Rens, N.B. Atkin, A. Eggen, I. Kola, C. Stover, A. Pizzuti, R. Wieser, N.G. Copeland, and B. Levacher

Subjects
Genetics, Index (economics), Subject (documents), Social science, Biology, Molecular Biology, Genetics (clinical)
Published
2001
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44. [Acute poisoning by insecticides with anticholinesterase activity. Evaluation of the efficacy of a cholinesterase reactivator, pralidoxime]

Author

G, Duval, J M, Rakouer, D, Tillant, J C, Auffray, J, Nigond, and G, Deluvallee

Subjects
Cholinesterase Reactivators, Insecticides, Pralidoxime Compounds, Poisoning, Humans, Cholinesterase Inhibitors
Abstract

Pralidoxime is the most frequently used antidote in anticholinesterase insecticide poisoning, owing to its cholinesterase reactivating action. The efficiency of Pralidoxime has been retrospectively evaluated by comparing two groups of 31 patients, the first one treated by Pralidoxime in the most commonly used doses (1200mg/24H), the second one untreated. Age, sex and nature of poison were taken in consideration to make a matched distribution in both groups. The clinical and biological initial features were nearly the same in both groups; the other therapeutic measures were the same. There was no statistical difference between the both groups for evolutive criteria such as that mortality, duration of artificial ventilation, intubation, atropine administration, decrease in plasma cholinesterase. The results pleading against the use of Pralidoxime, at least at this dose, in anticholinesterase insecticide poisoning, warrant confirmation by prospective randomized studies. The efficiency of Pralidoxime warrants confirmation firstly in the course of poisonings by some clearly identified insecticides, to which pralidoxime is supposed to be the most effective, cater used in high doses, as recommended by some authors.

Published
1991

45. Immunohistochemical localisation of nerve growth factor in a subpopulation of chick spinal ganglion neurons

Author

Robert A. Rush, Robert W. Williams, C. Auffray, A. Keller, and J. Vahaviolos

Subjects
Central nervous system, Population, Molecular Sequence Data, Enzyme-Linked Immunosorbent Assay, Chick Embryo, Biology, Cellular and Molecular Neuroscience, Ganglia, Spinal, medicine, Animals, Amino Acid Sequence, Nerve Growth Factors, education, Peptide sequence, Neurons, education.field_of_study, Spinal cord, Immunohistochemistry, Ganglion, Cell biology, Nerve growth factor, medicine.anatomical_structure, nervous system, Spinal Cord, Cell culture, Neuroscience
Abstract

We have previously isolated and sequenced the chicken nerve growth factor (NGF) gene and now, from the deduced amino acid sequence, selected and produced peptides suitable for use as antigens. Anti-sera raised against these peptides inhibit the biological activity of a partially purified preparation of native chicken NGF and, when used in immunocytochemical studies, allow the visualisation of sensory neurons accumulating endogenous NGF. Immunoreactive cells form a distinct population of small neurons which may correspond to the well-described neurons generated in the dorsomedial area of spinal ganglia. We conclude that two subpopulations of neurons exist within dorsal root ganglia, whose requirements for, and use of, NGF may be quite distinct.

Published
1990

46. Subject Index, Vol. 77, 1997

Author

A.S. Graphodatsky, G. Hardiman, J.A. Squire, L. Frönicke, P. Bosco, N. Ceratto, S. van Beersum, J.A.M. Graves, H.N. Seuánez, X. Estivill, N. Archidiacono, G. Novelli, G.G. Karpova, C.H.M. Mellink, E. Jenkins, M. Stacey, T. Fujiwara, M. Lovett, R. Knippers, R. Moyzis, M. Jeanpierre, P. Maccarone, J. Wienberg, M. Rocchi, C. Bendixen, S. Weremowicz, B.P. Chowdhary, Y. Yang, A. Pandita, M. Lachtermacher, N. Matas, K.-H. Lee, N. Miyasaka, T. Katagiri, F. Pelliccia, M.-J. Pébusque, R. Godbout, M. Gersh, R. Leube, F. Ugolini, M. Kai, S.-T. Lee, O. Miura, H.G. Brunner, O.V. Cheryaukene, K. Ohsugi, A. Tanzariello, M.A. Ferguson-Smith, A. Geurts van Kessel, P.C.M. O’Brien, W.G. Nash, A. Baldini, T.J. Robinson, M. Matsumoto, A. Pizzuti, Y. Nakamura, M. Mannens, V. Romano, A. Musio, J. Widmer, Déborah Bourc'his, A. Botta, K. Rojas, M.Z. Limongi, L.A. James, A.F. Davies, M. de Meulemeester, R.M. Brunner, C.H. van Os, J.H. Xia, T.K. Watanabe, E.M. Ladenburger, S.-H. Park, C. Rodellar, M. Pritchard, J.L. Kissil, A.S. Hewson, A. Arai, K.N. Sastry, P.M.T. Deen, P. Eydoux, J.A. McMahon, F.C. Canavez, L. Langbein, R. Toder, G. von Beust, M. Schmid, R. Houlgatte, T. Takahashi, P.A. Voûte, N.V. Vorobieva, J. Overhauser, R. Stanyon, E.I.B. Peerschke, K. Yamamoto, J.P. Park, T.K. Mohandas, S. Feo, C. Zijlstra, N.P. Mertvetsov, M. Steenman, U.W. Kenkare, S.A. Wilcox, J. Guimera, P. Zaragoza, N.A. de Haan, W.Y. Hung, J. Ragoussis, D. Birnbaum, M. Ogawa, H. Kobayashi, W. Engel, F. Shimizu, B. Hoebee, B. Ghebrehiwet, T. Ikeuchi, M. Chaffanet, W.R. Harrison, T. Goldammer, S. Ishikawa, E. Burt, K. Wiesmeijer, V. Jurecic, S.D. Pack, M.R. Koehler, B. Beatty, M. Nagata, E. Takahashi, J.F. Bazan, N. Lynch, M. Schwerin, Y. Yokoyama, G. Mirza, A. Fratello, D. Grady, D. Molina Gomes, F. Saito-Ohara, N. Hoggard, C. Dobkin, H. Scherthan, H. van Bokhoven, L.D. Matyakhina, R. Meneveri, A.P. McMahon, H. Murer, R. Marzella, K. Okui, J. Kissing, A. Risch, J.M. Varley, X.-L. Yao, M. Carter, X.-X. Zhang, H.S. Tenenhouse, S. Kurata, O.L. Serov, P.M. Borodin, M. Nadal, M.L. Filipenko, A. Rocchi, M. Kool, W. Schwaeble, H. Hayes, Y. Takei, H. Levéziel, S.J. O’Brien, P. Thygesen, C.H. Fan, H.X. Deng, M. Suzuki, H. Hameister, G.F.M. Merkx, R. Slater, P. Laurent, S. Sebastian, B. Redeker, R.A. Kastelein, E. Viegas-Péquignot, M.A. van Kuijck, L. Xu, M.A.M. Moreira, T. Kozaki, C.C. Morton, M.S. Aly, I.V. Koroleva, H. Kim, E. Sim, A. Ponce de León, A.B. Spurdle, A. Kimchi, A. Simons, G. Rainaldi, Y. Hey, P. Miniou, D. Wells, F.F.B. Elder, P. Riegman, D. Patterson, M. Schepens, S.N. Malchenko, L.A. Witters, L. Viggiano, S. Hirosawa, F. Yang, K.B.M. Reid, C. Elduque, C. Auffray, A.A. Bosma, N. Guo, J.-J. Cassiman, F.O. Fackelmayer, R.J.M. Bindels, A.T. Natarajan, B.-L. Lim, J.B. Searle, As. Ricco, N. Sakuragawa, L. Vatteroni, M.P. Hande, C.K. Ullrich, S. Okuno, T. Siddque, W. Bie, A. Westerveld, Y. Kuga, and B. Dallapiccola

Subjects
Index (economics), Statistics, Genetics, Subject (documents), Biology, Molecular Biology, Genetics (clinical)
Published
1997
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47. Brief Gene Mapping Reports A / B / C / D / E / F / G

Author

Y. Mao, M. Grosz, S. Izraeli, J.D. Karkera, S. Kimura, I.M. Adham, A.R. Zinn, Y. Ma, T. Yagi, T. Haaf, S. Mitrani-Rosenbaum, N. Coleman, N. Ghaffari-Tabrizi, J. Taylor, J. Nowak, A. Srisodsai, W. Feichtinger, J.-L. Iovanna, C.L. Li, A. Rupprecht, N.A. Jenkins, P. Coullin, M. Muenke, Selena Davis, C. Ji, D.B. Zimonjic, A. Heller, J. Masabanda, J.-C. Dagorn, Y. Xie, B. Hong, H. Kuiper, R.I. Barnes, W.H. Brooks, A.M. Simckes, T. Leeb, D.J. Gilbert, I. Eisenberg, D.M. Shubitowski, R. Fries, B. Lanske, R. Zoorob, G. Cao, W.H. Reeves, M. Satoh, E. Roessler, S.G. Rak, W. Engel, H. Akutsu, L. Guo, H. Kusakabe, S.K. Swanson, D.R. Beier, K. Mrasek, N. Dusetti, M. Shibazaki, C. Steinlein, L. Fröhlich, S.L. Ewart, H. Starke, S. Kollers, C.A. Morley-Jacob, B. Bjerkehagen, N. Kleiter, R.A. White, T.P. Yang, T. Niimi, L.A.P. Carrasco, H. Kikuchi, A. Weise, M. Jiang, R. Tomasini, M.R. Teixeira, L.A. Azizi Samir, C. Auffray, A. Kuechler, H. Cheng, S. Heim, H.-U.G. Weier, M.-J. Pébusque, Z. Liu, S.C. Harvey, D. Gallagher, J.C. Phillips, F. Micci, H. Hochner, N. Gmachl, X. Ni, M.-G. Mattei, A. Dutra, E. Nacheva, C. Drögemüller, R.L. Prueitt, J. Womack, Z.H. Shan, N.C. Popescu, R. Tang, H. Kaiser, G.A. Rohrer, N.G. Copeland, O. Distl, N.R. Bromage, M. Schmid, A. Bernheim, K. Kratochwil, F. Galibert, M. Bina, R. Shamsadin, B. Brenig, Y. Shiratori, E. Antoniou, H. Chen, R. Yanagimachi, M. Sadeh, S. Fukushige, U. Claussen, I. Kirsch, N.B. Atkin, B. Perbal, C.L. Keck-Waggoner, H.P. Klinger, T. Osada, E.I. Pares-Matos, J. Young, C. Knorr, D.J. Penman, K. Ying, L. Ziercher, P. Quignon, M. Wills-Karp, I. Artner, I. Roberts, D.K. Griffin, T. Liehr, D.C. Shing, and Z. Argov

Subjects
Genetics, Gene mapping, Biology, Molecular Biology, Genetics (clinical)
Published
2002
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48. Correction for Debat et al. , Independence between developmental stability and canalization in the skull of the house mouse

Author

J.-C. Auffray, Paul Alibert, Emmanuel Paradis, Vincent Debat, and Patrice David

Subjects
General Immunology and Microbiology, biology, media_common.quotation_subject, Stability (learning theory), General Medicine, biology.organism_classification, General Biochemistry, Genetics and Molecular Biology, Genealogy, House mouse, Independence, Developmental psychology, Skull, medicine.anatomical_structure, medicine, General Agricultural and Biological Sciences, Psychology, General Environmental Science, media_common
Abstract

Correction for ‘Independence between developmental stability and canalization in the skull of the house mouse’ by V. Debat, P. Alibert, P. David, E. Paradis and J.-C. Auffray (Proc. R. Soc. Lond. B 267 , 423–430. (doi: 10.1098/rspb.2000.1017)). There were multiple errors in the values in table 1 (p. 426). A corrected version of this table is presented below. Consequences on F -tests are also presented.

Published
2001
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49. Special Notice to Contributors

Author

L.V. Monteagudo, A. Geurts van Kessel, C.L. Bevins, A.M. Lawler, W.S. Modi, I. Janssen, M. Wilbrink, C. Zijlstra, F. Tihy, Y. Miura, C. Rosenberg, G. Stetten, B.T. Lamb, F. Darroudi, A. Vignal, E. van den Berg, M.C. Yoshida, J. Gnarra, G. Diamond, W. Li, F. Martin, A. Ido, C. Auffray, D.A. Lawrence, C.A. Werner, W.-J Song, N.A. de Haan, J.R. Cypser, M.V. Arruga, P. de Boer, G.P. Di Meo, M.A.J. Weterman, R. Zoorob, M. Baudis, S. Joos, P. Slijepcevic, D.M. Kurnit, W.M. Linehan, C.H.M. Mellink, U.S.R. Bergerheim, J.D. Gearhart, N. Flavin, A.K. Voltz, V. Fillon, I. Craig, A.A. Bosma, M. Rogers, C. Li, S. Ennis, H.A.P. Janssen, S.V. Ivanov, N. Lemieux, S.E. Fisher, M.L. Van Keuren, H.S. Tenenhouse, D. Ma, W. Barendse, D.R. Rosen, D.S. Gallagher, M. Bentz, M.J. Merino, M. Yerle, H.A. Drabkin, L. Granjon, L. lannuzzi, A.C. Walsh, J.H. de Jong, H. Murer, G. Arkesteijn, Y. Akao, T. Tamaoki, C.H. Kos, B. Zbar, Y. Xiao, J.E. Womack, A.T. Natarajan, A. Heriz, V. Volobouev, Y. Matsuda, P. Lichter, R.M. Gemmill, K. Yamada, and A.G.J. Kuipers

Subjects
Notice, Genetics, Engineering ethics, Biology, Bioinformatics, Molecular Biology, Genetics (clinical)
Published
1996
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