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1. 2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales

Author

Kuhn, Jens H, Adkins, Scott, Agwanda, Bernard R, Al Kubrusli, Rim, Alkhovsky, Sergey V, Amarasinghe, Gaya K, Avšič-Županc, Tatjana, Ayllón, María A, Bahl, Justin, Balkema-Buschmann, Anne, Ballinger, Matthew J, Basler, Christopher F, Bavari, Sina, Beer, Martin, Bejerman, Nicolas, Bennett, Andrew J, Bente, Dennis A, Bergeron, Éric, Bird, Brian H, Blair, Carol D, Blasdell, Kim R, Blystad, Dag-Ragnar, Bojko, Jamie, Borth, Wayne B, Bradfute, Steven, Breyta, Rachel, Briese, Thomas, Brown, Paul A, Brown, Judith K, Buchholz, Ursula J, Buchmeier, Michael J, Bukreyev, Alexander, Burt, Felicity, Büttner, Carmen, Calisher, Charles H, Cao, Mengji, Casas, Inmaculada, Chandran, Kartik, Charrel, Rémi N, Cheng, Qi, Chiaki, Yuya, Chiapello, Marco, Choi, Il-Ryong, Ciuffo, Marina, Clegg, J Christopher S, Crozier, Ian, Dal Bó, Elena, de la Torre, Juan Carlos, de Lamballerie, Xavier, de Swart, Rik L, Debat, Humberto, Dheilly, Nolwenn M, Di Cicco, Emiliano, Di Paola, Nicholas, Di Serio, Francesco, Dietzgen, Ralf G, Digiaro, Michele, Dolnik, Olga, Drebot, Michael A, Drexler, J Felix, Dundon, William G, Duprex, W Paul, Dürrwald, Ralf, Dye, John M, Easton, Andrew J, Ebihara, Hideki, Elbeaino, Toufic, Ergünay, Koray, Ferguson, Hugh W, Fooks, Anthony R, Forgia, Marco, Formenty, Pierre B H, Fránová, Jana, Freitas-Astúa, Juliana, Fu, Jingjing, Fürl, Stephanie, Gago-Zachert, Selma, Gāo, George Fú, García, María Laura, García-Sastre, Adolfo, Garrison, Aura R, Gaskin, Thomas, Gonzalez, Jean-Paul J, Griffiths, Anthony, Goldberg, Tony L, Groschup, Martin H, Günther, Stephan, Hall, Roy A, Hammond, John, Han, Tong, Hepojoki, Jussi, Hewson, Roger, Hong, Jiang, Hong, Ni, Hongo, Seiji, Horie, Masayuki, Hu, John S, Hu, Tao, Hughes, Holly R, Hüttner, Florian, Hyndman, Timothy H, Ilyas, M, Jalkanen, Risto, Jiāng, Dàohóng, Jonson, Gilda B, Junglen, Sandra, Kadono, Fujio, Kaukinen, Karia H, Kawate, Michael, Klempa, Boris, Klingström, Jonas, Kobinger, Gary, Koloniuk, Igor, Kondō, Hideki, Koonin, Eugene V, Krupovic, Mart, Kubota, Kenji, Kurath, Gael, Laenen, Lies, Lambert, Amy J, Langevin, Stanley L, Lee, Benhur, Lefkowitz, Elliot J, Leroy, Eric M, Li, Shaorong, Li, Longhui, Lǐ, Jiànróng, Liu, Huazhen, Lukashevich, Igor S, Maes, Piet, de Souza, William Marciel, Marklewitz, Marco, Marshall, Sergio H, Marzano, Shin-Yi L, Massart, Sebastien, McCauley, John W, Melzer, Michael, Mielke-Ehret, Nicole, Miller, Kristina M, Ming, Tobi J, Mirazimi, Ali, Mordecai, Gideon J, Mühlbach, Hans-Peter, Mühlberger, Elke, Naidu, Rayapati, Natsuaki, Tomohide, Navarro, José A, Netesov, Sergey V, Neumann, Gabriele, Nowotny, Norbert, Nunes, Márcio R T, Olmedo-Velarde, Alejandro, Palacios, Gustavo, Pallás, Vicente, Pályi, Bernadett, Papa, Anna, Paraskevopoulou, Sofia, Park, Adam C, Parrish, Colin R, Patterson, David A, Pauvolid-Corrêa, Alex, Pawęska, Janusz T, Payne, Susan, Peracchio, Carlotta, Pérez, Daniel R, Postler, Thomas S, Qi, Liying, Radoshitzky, Sheli R, Resende, Renato O, Reyes, Carina A, Rima, Bertus K, Luna, Gabriel Robles, Romanowski, Víctor, Rota, Paul, Rubbenstroth, Dennis, Rubino, Luisa, Runstadler, Jonathan A, Sabanadzovic, Sead, Sall, Amadou Alpha, Salvato, Maria S, Sang, Rosemary, Sasaya, Takahide, Schulze, Angela D, Schwemmle, Martin, Shi, Mang, Shí, Xiǎohóng, Shí, Zhènglì, Shimomoto, Yoshifumi, Shirako, Yukio, Siddell, Stuart G, Simmonds, Peter, Sironi, Manuela, Smagghe, Guy, Smither, Sophie, Song, Jin-Won, Spann, Kirsten, Spengler, Jessica R, Stenglein, Mark D, Stone, David M, Sugano, Jari, Suttle, Curtis A, Tabata, Amy, Takada, Ayato, Takeuchi, Shigeharu, Tchouassi, David P, Teffer, Amy, Tesh, Robert B, Thornburg, Natalie J, Tomitaka, Yasuhiro, Tomonaga, Keizō, Tordo, Noël, Torto, Baldwyn, Towner, Jonathan S, Tsuda, Shinya, Tu, Changchun, Turina, Massimo, Tzanetakis, Ioannis E, Uchida, Janice, Usugi, Tomio, Vaira, Anna Maria, Vallino, Marta, van den Hoogen, Bernadette, Varsani, Arvind, Vasilakis, Nikos, Verbeek, Martin, von Bargen, Susanne, Wada, Jiro, Wahl, Victoria, Walker, Peter J, Wang, Lin-Fa, Wang, Guoping, Wang, Yanxiang, Wang, Yaqin, Waqas, Muhammad, Wèi, Tàiyún, Wen, Shaohua, Whitfield, Anna E, Williams, John V, Wolf, Yuri I, Wu, Jiangxiang, Xu, Lei, Yanagisawa, Hironobu, Yang, Caixia, Yang, Zuokun, Zerbini, F Murilo, Zhai, Lifeng, Zhang, Yong-Zhen, Zhang, Song, Zhang, Jinguo, Zhang, Zhe, Zhou, Xueping, Kuhn, Jens H., Agwanda, Bernard R., Alkhovsky, Sergey V., Amarasinghe, Gaya K., Ayllón, María A., Ballinger, Matthew J., Basler, Christopher F., Bennett, Andrew J., Bente, Dennis A., Bird, Brian H., Blair, Carol D., Blasdell, Kim R., Borth, Wayne B., Brown, Paul A., Brown, Judith K., Buchholz, Ursula J., Buchmeier, Michael J., Calisher, Charles H., Charrel, Rémi N., Clegg, J. Christopher S., de Swart, Rik L., Dheilly, Nolwenn M., Dietzgen, Ralf G., Drebot, Michael A., Drexler, J. Felix, Dundon, William G., Duprex, W. Paul, Dye, John M., Easton, Andrew J., Ferguson, Hugh W., Fooks, Anthony R., Formenty, Pierre B. H., Garrison, Aura R., Gonzalez, Jean-Paul J., Goldberg, Tony L., Groschup, Martin H., Hall, Roy A., Hu, John S., Hughes, Holly R., Hyndman, Timothy H., Ilyas, M., Jonson, Gilda B., Kaukinen, Karia H., Koonin, Eugene V., Lambert, Amy J., Langevin, Stanley L., Lefkowitz, Elliot J., Leroy, Eric M., Lukashevich, Igor S., Marshall, Sergio H., Marzano, Shin-Yi L., McCauley, John W., Miller, Kristina M., Ming, Tobi J., Mordecai, Gideon J., Navarro, José A., Netesov, Sergey V., Nunes, Márcio R. T., Park, Adam C., Parrish, Colin R., Patterson, David A., Pawęska, Janusz T., Pérez, Daniel R., Postler, Thomas S., Radoshitzky, Sheli R., Resende, Renato O., Reyes, Carina A., Rima, Bertus K., Runstadler, Jonathan A., Salvato, Maria S., Schulze, Angela D., Siddell, Stuart G., Spengler, Jessica R., Stenglein, Mark D., Stone, David M., Suttle, Curtis A., Tchouassi, David P., Tesh, Robert B., Thornburg, Natalie J., Towner, Jonathan S., Tzanetakis, Ioannis E., Walker, Peter J., Whitfield, Anna E., Williams, John V., Wolf, Yuri I., Zerbini, F. Murilo, NIH - National Institute of Allergy and Infectious Diseases (NIAID) (Estados Unidos), NIH - National Cancer Institute (NCI) (Estados Unidos), National Institutes of Health (Estados Unidos), United States Department of Agriculture. National Institute of Food and Agriculture, Cancer Research UK (Reino Unido), Medical Research Council (Reino Unido), Wellcome Trust, Mississippi State University (Estados Unidos), Battelle National Biodefense Institute, National Biodefense Analysis and Countermeasures Center, Tunnell Government Services (Estados Unidos), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), U.S. Horticultural Research Laboratory ( Fort Pierce, USA), United States Department of Agriculture (USDA), Jomo Kenyatta University of Agriculture and Technology (JKUAT), National Museums of Kenya, Humboldt University Of Berlin, Ministry of Health and Social Development of Russian Federation [Moscow], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), University of Ljubljana, Universidad Politécnica de Madrid (UPM), University of Georgia [USA], Institute of Novel and Emerging Infectious Diseases (INNT), Friedrich-Loeffler-Institut (FLI), Laboratoire de Ploufragan-Plouzané-Niort [ANSES], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virologie UMR1161 (VIRO), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Virologie des archées - Archaeal Virology, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Stratégies antivirales, Institut Pasteur [Paris] (IP), Centre collaborateur de l'OMS Arbovirus et Fièvres Hémorragiques virales - Stratégies antivirales (CC-OMS), NIAID under Contract No. HHSN272201800013C, NCI, NIH under Contract No. 75N91019D00024, NIH contract HHSN272201000040I/HHSN27200004/D04 and grant R24AI120942, US Department of Agriculture, Hatch Project 1021494, Cancer Research UK (FC001030), UK Medical Research Council (FC001030), Wellcome Trust (FC001030), Integrated Research Facility at Fort Detrick (IRF-Frederick), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), ARS, Medical School, University of Ljubljana, École nationale vétérinaire d'Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Virology

Subjects
Phylum, Identification, Alpharhabdovirinae, Strains, Field-collected mosquitos, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Article, MESH: Viruses, ICTV, 03 medical and health sciences, Biointeractions and Plant Health, MESH: Mononegavirales, Taxonomy of Viruses, Virology, Life Science, Humans, Crepuscuviridae, Myriaviridae, ComputingMilieux_MISCELLANEOUS, Taxonomy, 030304 developmental biology, Bunyavirales, 2. Zero hunger, 0303 health sciences, Virome, 030306 microbiology, Borne virus-infectons, Betarhabdovirinae, Rhabdovirus, General Medicine, Taxonomía de Virus, Merida virus, 3. Good health, Negarnaviricota, Aliusviridae, Triniti-virus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Viruses, Queensland, Mononegavirales, Hantavirus
Abstract

In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV. Instituto de Patología Vegetal Fil: Kuhn, Jens H. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Integrated Research Facility at Fort Detrick; Estados Unidos Fil: Adkins, Scott. United States Department of Agriculture. Agricultural Research Service. US Horticultural Research Laboratory; Estados Unidos Fil: Agwanda, Bernard R. National Museums of Kenya. Zoology Department; Kenia Fil: Agwanda, Bernard R. Jomo Kenyatta University of Agriculture & Technology; Kenia Fil: Kubrusli, Rim Al. Humboldt-Universität zu Berlin. Faculty of Life Sciences. Division Phytomedicine; Alemania Fil: Alkhovsky, Sergey V. D.I. Ivanovsky Institute of Virology of N.F. Gamaleya National Center on Epidemiology and Microbiology of Ministry of Health of Russian Federation; Rusia Fil: Amarasinghe, Gaya K. Washington University School of Medicine. Department of Pathology and Immunology; Estados Unidos Fil: Avšič-Županc, Tatjana. University of Ljubljana. Faculty of Medicine; Eslovenia Fil: Ayllón, María A. Universidad Politécnica de Madrid—Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria. Campus de Montegancedo. Centro de Biotecnología y Genómica de Plantas; España Fil: Ayllón, María A. Universidad Politécnica de Madrid. Escuela Técnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas. Departamento de Biotecnología-Biología Vegetal; España Fil: Bahl, Justin. University of Georgia. Center for Ecology of Infectious Diseases, Department of Infectious Diseases, Department of Epidemiology and Biostatistics, Insitute of Bioinformatics; Estados Unidos Fil: Balkema-Buschmann, Anne. Institute of Novel and Emerging Infectious Diseases. Friedrich-Loeffler-Institut. Federal Research Institute for Animal Health; Alemania Fil: Bejerman, Nicolas Esteban. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; Argentina Fil: Bejerman, Nicolas Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Fitopatología y Modelización Agrícola (UFyMA); Argentina Fil: Debat, Humberto Julio. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; Argentina Fil: Debat, Humberto Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Fitopatología y Modelización Agrícola (UFyMA); Argentina Fil: Zhou, Xueping. Chinese Academy of Agricultural Sciences. Institute of Plant Protection. State Key Laboratory for Biology of Plant Diseases and Insect Pests; China

Published
2021
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2. Thrombotic microangiopathy, DIC-syndrome and COVID-19: link with pregnancy prothrombotic state

Author

Viktoriya Bitsadze, Jamilya Khizroeva, N. A. Makatsariya, A. D. Makatsariya, Elvira Grandone, M. V. Tretyakova, T. Mashkova, Jean-Christophe Gris, V. I. Tsibizova, Ismail Elalamy, E. V. Slukhanchuk, Sechenov First Moscow State Medical University, Petrovsky National Research Centre of Surgery, National Medical Research Center for Obstetrics, Gynecology and Perinatology [Moscow, Russia], Ministry of Health and Social Development of Russian Federation [Moscow], Almazov National Medical Research Centre (St. Petersburg), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS)

Subjects
0301 basic medicine, medicine.medical_specialty, Thrombotic microangiopathy, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030204 cardiovascular system & hematology, medicine.disease_cause, Complement system activation, Pathogenesis, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Von Willebrand factor, COVID-19 and coagulopathy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pregnancy, Obstetrics and Gynaecology, DIC-syndrome, medicine, Humans, Pediatrics, Perinatology, and Child Health, Intensive care medicine, Pathological, Coronavirus, Disseminated intravascular coagulation, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Prothrombotic state in pregnancy, biology, business.industry, SARS-CoV-2, Thrombotic Microangiopathies, Obstetrics and Gynecology, COVID-19, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Disseminated Intravascular Coagulation, medicine.disease, 3. Good health, Systemic inflammatory response syndrome, Dacarbazine, 030104 developmental biology, Pediatrics, Perinatology and Child Health, biology.protein, Female, business, Thrombotic microangiopathy and COVID-19
Abstract

International audience; For last months, humanity has faced a formidable unknown enemy, which is presented as a new coronavirus infection. Despite the fact that the causative agents of new diseases appear at a certain frequency and that the virus SARS-CoV-2 has certain common properties with its predecessors, at the moment we are dealing with a new unknown pathogenesis of the development of severe complications in patients with risk factors. A final understanding of pathological process mechanisms is the goal of the scientific community. Summarizing research data from different countries, it became obvious that in severe cases of viral infection, we are dealing with a combination of the systemic inflammatory response syndrome, disseminated intravascular coagulation and thrombotic microangiopathy (TMA). Thrombotic microangiopathy is represented by a group of different conditions in which thrombocytopenia, hemolytic anemia, and multiple organ failure occur. The article reflects the main types of TMA, pathogenesis and principles of therapy. The main participants in the process are described in detail, including the von Willebrand factor and ADAMTS-13. Based on the knowledge available, as well as new data obtained from patients with COVID-19, we proposed possible models for the implementation of conditions such as sepsis, TMA, and DIC in patients with severe new coronavirus infection. Through a deeper understanding of pathogenesis, it will be possible to develop more effective diagnosis and therapy.

Published
2020
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3. Probing Mitotic CENP-E Kinesin with the Tethered Cargo Motion Assay and Laser Tweezers

Author

Don W. Cleveland, Alexei L. Drobyshev, Vadim Mustyatsa, Ekaterina L. Grishchuk, Nikita Gudimchuk, Ekaterina V. Tarasovetc, Benjamin Vitre, Fazly I. Ataullakhanov, Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, University of California [San Diego] (UC San Diego), University of California-University of California-Ludwig Institute for Cancer Research - Department of Cellular and Molecular Medicine, National Research Center for Haematology [Moscow], and Ministry of Health and Social Development of Russian Federation [Moscow]

Subjects
0301 basic medicine, Optical Tweezers, 1.1 Normal biological development and functioning, Movement, [SDV]Life Sciences [q-bio], Biophysics, Kinesins, Mitosis, Bioengineering, 03 medical and health sciences, 0302 clinical medicine, Microtubule, Underpinning research, Chromosome Segregation, Molecular motor, Molecular Machines, Motors, and Nanoscale Biophysics, ComputingMilieux_MISCELLANEOUS, Physics, [PHYS]Physics [physics], Tethering, Kinetochore, Biological Sciences, Spindle apparatus, Biomechanical Phenomena, 030104 developmental biology, Optical tweezers, Physical Sciences, Chemical Sciences, Kinesin, Generic health relevance, 030217 neurology & neurosurgery
Abstract

Coiled-coil stalks of various kinesins differ significantly in predicted length and structure; this is an adaption that helps these motors carry out their specialized functions. However, little is known about the dynamic stalk configuration in moving motors. To gain insight into the conformational properties of the transporting motors, we developed a theoretical model to predict Brownian motion of a microbead tethered to the tail of a single, freely walking molecule. This approach, which we call the tethered cargo motion (TCM) assay, provides an accurate measure of the mechanical properties of motor-cargo tethering, verified using kinesin-1 conjugated to a microbead via DNA links in vitro. Applying the TCM assay to the mitotic kinesin CENP-E unexpectedly revealed that when walking along a microtubule track, this highly elongated molecule with a contour length of 230 nm formed a 20-nm-long tether. The stalk of a walking CENP-E could not be extended fully by application of sideways force with optical tweezers (up to 4 pN), implying that CENP-E carries its cargo in a compact configuration. Assisting force applied along the microtubule track accelerates CENP-E walking, but this increase does not depend on the presence of the CENP-E stalk. Our results suggest that the unusually large stalk of CENP-E has little role in regulating its function as a transporter. The adjustable stalk configuration may represent a regulatory mechanism for controlling the physical reach between kinetochore-bound CENP-E and spindle microtubules, or it may assist localizing various kinetochore regulators in the immediate vicinity of the kinetochore-embedded microtubule ends. The TCM assay and underlying theoretical framework will provide a general guide for determining the dynamic configurations of various molecular motors moving along their tracks, freely or under force.

Published
2018
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4. Facile one-pot synthesis of copper hexacyanoferrate nanoparticle functionalised silica monoliths for the selective entrapment of 137Cs

Author

Micheàl Moloney, Yves Barré, Alexey Tokarev, Jérémy Causse, Agnès Grandjean, Johann Ravaux, Nanomatériaux pour l'Energie et le Recyclage (LNER), Institut de Chimie Séparative de Marcoule (ICSM - UMR 5257), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), National Research Center for Haematology [Moscow], Ministry of Health and Social Development of Russian Federation [Moscow], Etude de la Matière en Mode Environnemental (L2ME), Laboratoire des Procédés Supercritiques et de Décontamination, Commisariat de l'Energie Atomique, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Oxide minerals, Materials science, Aqueous solution, Renewable Energy, Sustainability and the Environment, Inorganic chemistry, One-pot synthesis, Nanoparticle, chemistry.chemical_element, Sorption, [CHIM.MATE]Chemical Sciences/Material chemistry, 02 engineering and technology, General Chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, Copper, 0104 chemical sciences, chemistry.chemical_compound, Colloid, chemistry, General Materials Science, Ferricyanide, 0210 nano-technology, ComputingMilieux_MISCELLANEOUS, Nuclear chemistry
Abstract

In this study, hexacyanoferrate nanoparticle (NP) functionalised silica monoliths were used to selectively remove Cs+ from aqueous solutions which also contained large concentrations of Na+. Various NP loading levels were examined from 0.2 wt% up to 5.1 wt% producing different 133Cs and 137Cs sorption results.

Published
2014
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5. Procoagulant Platelets Form an α-Granule Protein-covered 'Cap' on Their Surface That Promotes Their Attachment to Aggregates

Author

Yana N. Kotova, Anastasia A. Abaeva, Mikhail A. Panteleev, Alena O. Yakimenko, Marie-Christine Alessi, Alan T. Nurden, Nadezhda A. Podoplelova, Hervé Chambost, Vladimir N. Kolyadko, Sergey I. Obydennyy, Matthias Canault, Fazoil I. Ataullakhanov, Aleksei V. Mazurov, Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plasma Theory Department, Institute for Nuclear Research, Laboratoire d'hématologie biologique [Hôpital de la Timone - Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), National Research Center for Haematology [Moscow], Ministry of Health and Social Development of Russian Federation [Moscow], Russian Foundation for Basic Research 11-04-00303 12-04-00438 12-04-31401 12-04-31788 12-04-32246 12-04-31873 12-04-33055 13-04-00401, Russian Academy of Sciences Presidium Basic Research Program 'Molecular and Cellular Biology', Russian Academy of Sciences Presidium Basic Research Program 'Basic Science for Medicine', Russian Academy of Sciences Presidium Basic Research Program 'Molecular Mechanisms of Physiologic Functions', and Russian Federation SP-2274.2012.4

Subjects
Platelet Aggregation, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], 030204 cardiovascular system & hematology, Fibrinogen, Biochemistry, Polymerization, STIMULATED PLATELETS, 0302 clinical medicine, Thrombasthenia, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Platelet, GLYCOPROTEIN-IIB-IIIA, INTEGRIN ALPHA(IIB)BETA(3), THROMBUS FORMATION, GLANZMANN THROMBASTHENIA, ADHERENT PLATELETS, COATED-PLATELETS, FACTOR-XIIIA, FIBRINOGEN, SUBPOPULATIONS, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Microscopy, Confocal, biology, Chemistry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Flow Cytometry, GPRP, 3. Good health, Female, Oligopeptides, medicine.drug, Blood Platelets, Blotting, Western, Integrin, Phosphatidylserines, Fibrin, 03 medical and health sciences, medicine, Humans, Thrombospondins, Blood Coagulation, Molecular Biology, 030304 developmental biology, Thrombospondin, Transglutaminases, Thrombosis, Cell Biology, Molecular biology, biology.protein, Biophysics
Abstract

International audience; Strongly activated "coated" platelets are characterized by increased phosphatidylserine (PS) surface expression, alpha-granule protein retention, and lack of active integrin alpha(IIb)beta(3). To study how they are incorporated into thrombi despite a lack of free activated integrin, we investigated the structure, function, and formation of the alpha-granule protein "coat." Confocal microscopy revealed that fibrin(ogen) and thrombospondin colocalized as "cap," a single patch on the PS-positive platelet surface. In aggregates, the cap was located at the point of attachment of the PS-positive platelets. Without fibrin(ogen) retention, their ability to be incorporated in aggregates was drastically reduced. The surface fibrin(ogen) was strongly decreased in the presence of a fibrin polymerization inhibitor GPRP and also in platelets from a patient with dysfibrinogenemia and a fibrinogen polymerization defect. In contrast, a fibrinogen-clotting protease ancistron increased the amount of fibrin(ogen) and thrombospondin on the surface of the PS-positive platelets stimulated with collagen-related peptide. Transglutaminases are also involved in fibrin( ogen) retention. However, platelets from patients with factor XIII deficiency had normal retention, and a pan-transglutaminase inhibitor T101 had only a modest inhibitory effect. Fibrin( ogen) retention was normal in Bernard-Soulier syndrome and kindlin-3 deficiency, but not in Glanzmann thrombasthenia lacking the platelet pool of fibrinogen and alpha(IIb)beta(3). These data show that the fibrin(ogen)-covered cap, predominantly formed as a result of fibrin polymerization, is a critical mechanism that allows coated (or rather "capped") platelets to become incorporated into thrombi despite their lack of active integrins.

Published
2013
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6. Segregation of Flowing Blood: Mathematical Description

Author

A Tokarev, Grigory Panasenko, Fazoil I. Ataullakhanov, Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), National Research Center for Haematology [Moscow], and Ministry of Health and Social Development of Russian Federation [Moscow]

Subjects
Blood clotting, Applied Mathematics, 0206 medical engineering, 02 engineering and technology, Radial distribution, Blood flow, Biology, 020601 biomedical engineering, 01 natural sciences, 010305 fluids & plasmas, Rheology, Modeling and Simulation, 0103 physical sciences, Immunology, Biophysics, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Platelet, Blood corpuscles, ComputingMilieux_MISCELLANEOUS, circulatory and respiratory physiology
Abstract

Blood rheology is completely determined by its major corpuscles which are erythro- cytes, or red blood cells (RBCs). That is why understanding and correct mathematical description of RBCs behavior in blood is a critical step in modelling the blood dynamics. Various phenom- ena provided by RBCs such as aggregation, deformation, shear-induced diffusion and non-uniform radial distribution affect the passage of blood through the vessels. Hence, they have to be taken into account while modelling the blood dynamics. Other important blood corpuscles are platelets, which are crucial for blood clotting. RBCs strongly affect the platelet transport in blood expelling them to the vessel walls and increasing their dispersion, which has to be considered in models of clotting. In this article we give a brief review of basic modern approaches in mathematical descrip- tion of these phenomena, discuss their applicability to real flow conditions and propose further pathways for developing the theory of blood flow.

Published
2011
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7. Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial

Author

Hervé, Bachelez, Peter C M, van de Kerkhof, Robert, Strohal, Alexey, Kubanov, Fernando, Valenzuela, Joo-Heung, Lee, Vladimir, Yakusevich, Sergio, Chimenti, Jocelyne, Papacharalambous, James, Proulx, Pankaj, Gupta, Huaming, Tan, Margaret, Tawadrous, Hernan, Valdez, Robert, Wolk, Robert, Burd, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Radboud University Medical Center [Nijmegen], Federal Academic Teaching Hospital (FATH - FELDKIRCH), Federal Academic Teaching Hospital, State Research Center of Dermatology and Venerology (SRCDV - MOSCOU), Ministry of Health and Social Development of Russian Federation [Moscow], Department of Dermatology (Dep Dermato - SANTIAGO), University of Chile Clinical Hospital, Probity Medical Research, Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, Soloviev's Clinical Hospital for Urgent Medical Care, Soloviev's Clinical Hospital, Department of Dermatology (Dermato - ROME), University of Rome, Pfizer, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Dermatology, and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

Subjects
Male, [SDV]Life Sciences [q-bio], Receptors, Tumor Necrosis Factor, Etanercept, MESH: Dose-Response Relationship, Drug, 030207 dermatology & venereal diseases, 0302 clinical medicine, Piperidines, Medicine, MESH: Protein Kinase Inhibitors, MESH: Double-Blind Method, Janus kinase inhibitor, MESH: Treatment Outcome, MESH: Immunoglobulin G, 0303 health sciences, MESH: Psoriasis, MESH: Middle Aged, Anti-Inflammatory Agents, Non-Steroidal, General Medicine, Middle Aged, MESH: Anti-Inflammatory Agents, Non-Steroidal, 3. Good health, Treatment Outcome, MESH: Piperidines, Rheumatoid arthritis, MESH: Pyrroles, Female, medicine.drug, Adult, medicine.medical_specialty, MESH: Drug Administration Schedule, Placebo, Drug Administration Schedule, 03 medical and health sciences, Double-Blind Method, Psoriasis Area and Severity Index, Psoriasis, Internal medicine, Humans, Pyrroles, Adverse effect, Protein Kinase Inhibitors, 030304 developmental biology, Tofacitinib, MESH: Humans, Dose-Response Relationship, Drug, business.industry, MESH: Chronic Disease, MESH: Etanercept, MESH: Adult, medicine.disease, MESH: Receptors, Tumor Necrosis Factor, MESH: Male, Surgery, Pyrimidines, Immunoglobulin G, MESH: Pyrimidines, Chronic Disease, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract

Item does not contain fulltext BACKGROUND: New therapeutic options are needed for patients with psoriasis. Tofacitinib, an oral Janus kinase inhibitor, is being investigated as a treatment for moderate-to-severe chronic plaque psoriasis. In this study, we aimed to compare two tofacitinib doses with high-dose etanercept or placebo in this patient population. METHODS: In this phase 3, randomised, multicentre, double-dummy, placebo-controlled, 12-week, non-inferiority trial, adult patients with chronic stable plaque psoriasis (for >/=12 months) who were candidates for systemic or phototherapy and had a Psoriasis Area and Severity Index (PASI) score of 12 or higher and a Physician's Global Assessment (PGA) of moderate or severe, and had failed to respond to, had a contraindication to, or were intolerant to at least one conventional systemic therapy, were enrolled from 122 investigational dermatology centres worldwide. Eligible patients were randomly assigned in a 3:3:3:1 ratio to receive tofacitinib 5 mg or 10 mg twice daily at about 12 h intervals, etanercept 50 mg subcutaneously twice weekly at about 3-4 day intervals, or placebo. Randomisation was done by a computer-generated randomisation schedule, and all patients and study personnel were masked to treatment assignment. The co-primary endpoints were the proportion of patients at week 12 with at least a 75% reduction in the PASI score from baseline (PASI75 response) and the proportion of patients achieving a PGA score of "clear" or "almost clear" (PGA response), analysed in the full analysis set (all patients who were randomised and received at least one dose of study drug). This study is registered with ClinicalTrials.gov, number NCT01241591. FINDINGS: Between Nov 29, 2010, and Sept 13, 2012, we enrolled 1106 eligible adult patients with chronic plaque psoriasis and randomly assigned them to the four treatment groups (330 to tofacitinib 5 mg twice daily, 332 to tofacitinib 10 mg twice daily, 336 to etanercept 50 mg twice weekly, and 108 to placebo). Of these patients, 1101 actually received their assigned study medication (329 in the tofactinib 5 mg group, 330 in the tofacitinib 10 mg group, 335 in the etanercept group, and 107 in the placebo group). At week 12, PASI75 responses were recorded in 130 (39.5%) of 329 patients in the tofacitinib 5 mg group, 210 (63.6%) of 330 in the tofacitinib 10 mg group, 197 (58.8%) of 335 in the etanercept group, and six (5.6%) of 107 in the placebo group. A PGA response was achieved by 155 (47.1%) of 329 patients in the tofacitinib 5 mg group, 225 (68.2%) of 330 in the tofacitinib 10 mg group, 222 (66.3%) of 335 in the etanercept group, and 16 (15.0%) of 107 in the placebo group. The rate of adverse events was similar across the four groups, with serious adverse events occurring in seven (2%) of 329 patients in the tofacitinib 5 mg group, five (2%) of 330 in the tofacitinib 10 mg group, seven (2%) of 335 in the etanercept group, and two (2%) of 107 in the placebo group. Three (1%) of 329 patients in the tofacitinib 5 mg group, ten (3%) of 330 in the tofacitinib 10 mg group, 11 (3%) of 335 in the etanercept group, and four (4%) of 107 patients in the placebo group discontinued their assigned treatment because of adverse events. INTERPRETATION: In patients with moderate-to-severe plaque psoriasis, the 10 mg twice daily dose of tofacitinib was non-inferior to etanercept 50 mg twice weekly and was superior to placebo, but the 5 mg twice daily dose did not show non-inferiority to etanercept 50 mg twice weekly. The adverse event rates over 12 weeks were similar for tofacitinib and etanercept. This study indicates that in the future tofacitinib could provide a convenient and well-tolerated therapeutic option for patients with moderate-to-severe plaque psoriasis. FUNDING: Pfizer Inc.

Published
2015

8. Modelling of platelet–fibrin clot formation in flow with a DPD–PDE method

Author

Alen Tosenberger, Vitaly Volpert, Alexei Tokarev, Fazly I. Ataullakhanov, Mikhail A. Panteleev, Nikolai Bessonov, Multi-scale modelling of cell dynamics : application to hematopoiesis (DRACULA), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Modélisation mathématique, calcul scientifique (MMCS), Institut Camille Jordan [Villeurbanne] (ICJ), National Research Center for Haematology [Moscow], Ministry of Health and Social Development of Russian Federation [Moscow], Institute of Mechanical Engineering Problems [St. Petersburg] (IPME), Russian Academy of Sciences [Moscow] (RAS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan (ICJ), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Institut Camille Jordan (ICJ), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Blood Platelets, 0301 basic medicine, Platelet Aggregation, Nanotechnology, Models, Biological, Fibrin, 03 medical and health sciences, Platelet Adhesiveness, Platelet adhesiveness, Animals, Humans, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Platelet, Blood Coagulation, Hemostasis, biology, Chemistry, Applied Mathematics, Dissipative particle dynamics, Computational Biology, Mathematical Concepts, Agricultural and Biological Sciences (miscellaneous), Shear rate, 030104 developmental biology, Coagulation, Modeling and Simulation, Hemorheology, biology.protein, Biophysics
Abstract

International audience; The paper is devoted to mathematical modelling of clot growth in bloodflow. Great complexity of the hemostatic system dictates the need of usage of themathematical models to understand its functioning in the normal and especially inpathological situations. In this work we investigate the interaction of blood flow,platelet aggregation and plasma coagulation. We develop a hybrid DPD–PDE modelwhere dissipative particle dynamics (DPD) is used to model plasma flow and platelets,while the regulatory network of plasma coagulation is described by a system of partialdifferential equations. Modelling results confirm the potency of the scenario of clotgrowth where at the first stage of clot formation platelets form an aggregate due toweak inter-platelet connections and then due to their activation. This enables the formationof the fibrin net in the centre of the platelet aggregate where the flow velocity issignificantly reduced. The fibrin net reinforces the clot and allows its further growth.When the clot becomes sufficiently large, it stops growing due to the narrowed vesseland the increase of flow shear rate at the surface of the clot. Its outer part is detachedby the flow revealing the inner part covered by fibrin. This fibrin cap does not allownew platelets to attach at the high shear rate, and the clot stops growing. Dependenceof the final clot size on wall shear rate and on other parameters is studied.

Published
2015
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9. Somatic changes in primary liver cancer in Russia: A pilot study

Author

Kalinina, Olga, Marchio, Agnès, Urbanskii, Aleksandr, Tarkova, Aleksandra, Rebbani, Khadija, Granov, Dmitri, Dejean, Anne, Generalov, Mikhail, Pineau, Pascal, Laboratory of Molecular Microbiology [St. Petersburg], Institut Pasteur de Saint-Pétersbourg, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Almazov National Medical Research Centre (St. Petersburg), Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Central Research Institute of Roentgenology and Radiology [Moscow], Ministry of Health and Social Development of Russian Federation [Moscow], Laboratoire des Hépatites Virales [Casablanca, Maroc] (LHV), Institut Pasteur du Maroc, This work, part of the ACIP 2006/(Action Concertée InterPasteurienne), was funded by the Division International at the Institut Pasteur and the French National League against Cancer., We thank Kathleen Victoir and Marc Jouan for their support. We are greatly indebted to Camille Baron for her invaluable help in setting-up the protocol and Case Report Form., We are grateful to Christiane Bouchier and Catherine Gouyette from the Plateforme Génomique #1 (PF1) from the Institut Pasteur for their help. We thank Professor Benoît Terris for helpful discussion., and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
primary liver cancer, MESH: Hepatitis B, Chronic, MESH: beta Catenin, MESH: Genes, p53, MESH: Comorbidity, [SDV.CAN]Life Sciences [q-bio]/Cancer, Environment, MESH: PTEN Phosphohydrolase, Chromosomes, MESH: Chromosomal Instability, MESH: Aged, 80 and over, MESH: Liver Neoplasms, MESH: Risk Factors, MESH: Axin Protein, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], HCC, MESH: Carcinoma, Hepatocellular, MESH: Cohort Studies, MESH: Point Mutation, MESH: Loss of Heterozygosity, MESH: Aged, MESH: Proto-Oncogene Proteins B-raf, MESH: Humans, MESH: Middle Aged, MESH: Russia, MESH: NF-E2-Related Factor 2, MESH: Aflatoxin B1, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Oncogenes, hepatocellular carcinoma, MESH: Pilot Projects, MESH: Cholangiocarcinoma, MESH: Monosomy, MESH: Male, MESH: Hepatitis C, Chronic, MESH: Genes, ras, Tumour suppressors, MESH: Young Adult, Viruses, PLC, MESH: Chromosomes, Human, Pair 18, Liver cancer, MESH: Female
Abstract

International audience; Primary liver cancer (PLC) is a major public health concern worldwide, ranking third among the causes of death from cancer. Molecular pathogenesis of PLC is known to be especially sensitive to ethno-environmental variations that modulate mutation spectra in tumours. Despite a high prevalence of chronic liver diseases, the molecular epidemiology of PLC is still poorly known in Russia. To characterize the major genetic features of liver tumours in Russian populations, we conducted a pilot study on 34 PLC cases (28 hepatocellular, two cholangiocellular, and four mixed cases) among patients attending the Radiology and Roentgenology Hospital in Saint Petersburg. Point mutations were searched in 9 genes that are commonly altered in PLC, viz. TP53, CTNNB1, AXIN1, H/K/N-RAS, BRAF, PTEN, and NFE2L2. The genes TP53 and AXIN1 were mutated in 16% and 10% of the cases, respectively, whereas mutations of β-catenin were present in only 7% of samples, an unusual situation for Europe but common in East Asia. No R249S mutation indicative of exposure to aflatoxin B1 was detected in TP53. A single case harboured an NFE2L2 mutation. The loss of chromosome 18q was associated with early onset of tumours (mean 50 vs 62yrs, p=0.0252) and with the patient's place of birth in Caucasus or Siberia. A lack of any risk factor was noted in 47% of the patients, whereas only 23% of the patients were infected either by hepatitis virus B or C. An extension of the present cohort as well as further molecular studies are now warranted in order to understand the processes governing liver carcinogenesis affecting Russian populations.

Published
2013
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10. Modelling of thrombus growth and growth stop in flow by the method of dissipative particle dynamics

Author

Vitaly Volpert, A Tokarev, Fazly I. Ataullakhanov, Mikhail A. Panteleev, N. Bessonov, Alen Tosenberger, Multi-scale modelling of cell dynamics : application to hematopoiesis (DRACULA), Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), National Research Center for Haematology [Moscow], Ministry of Health and Social Development of Russian Federation [Moscow], Lomonosov Moscow State University (MSU), Institute of Mechanical Engineering Problems [St. Petersburg] (IPME), Russian Academy of Sciences [Moscow] (RAS), ANR-10-BLAN-0107,Bimod,Modèles hybrides pour les populations de cellules. Application à la modélisation et au traitement du cancer(2010), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan (ICJ), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0303 health sciences, Numerical Analysis, Materials science, biology, Platelet adhesion, 0206 medical engineering, Flow (psychology), Dissipative particle dynamics, 02 engineering and technology, medicine.disease, 020601 biomedical engineering, Fibrin, 03 medical and health sciences, Thrombin, Modeling and Simulation, Growth arrest, medicine, biology.protein, Biophysics, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Platelet, Statistical physics, Thrombus, 030304 developmental biology, medicine.drug
Abstract

International audience; Platelet aggregation at the site of the vascular injury leads to the formation of a hemostatic plug covering the injury site, or a thrombus in the pathological case. The mechanisms that control clot growth or lead to growth arrest are not yet completely understood. In order to study these mechanisms theoretically, we use the Dissipative Particle Dynamics method, which allows us to model individual platelets in the flow and in the clot. The model takes into account different stages of the platelet adhesion process. First, a platelet is captured reversibly by the aggregate, then it is activated and adheres firmly, becoming a part of its core.We suggest that the core of the clot is composed of platelets unable to attach new platelets from the flow due to their activation by thrombin and/or wrapping by the fibrin mesh. The simulations are in a good agreement with the experimental results [9]. Modelling shows that stopping the growth of a hemostatic plug (and thrombus) may result from its exterior part being removed by the flow and exposed its non-adhesive core to the flow.

Published
2012
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11. Continuous Mathematical Model of Platelet Thrombus Formation in Blood Flow

Author

Fazoil I. Ataullakhanov, A. A. Butylin, I. Sirakov, Emmanuil E. Shnol, Vitaly Volpert, A Tokarev, Grigory Panasenko, National Research Center for Haematology [Moscow], Ministry of Health and Social Development of Russian Federation [Moscow], Université Jean Monnet [Saint-Étienne] (UJM), Multi-scale modelling of cell dynamics : application to hematopoiesis (DRACULA), Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institute of Mathematical Problems in Biology (IMPB RAS), Russian Academy of Sciences [Moscow] (RAS), Faculty of Physics [MSU, Moscow], Lomonosov Moscow State University (MSU), Center for Theoretical Problems of Physicochemical Pharmacology, Université Jean Monnet - Saint-Étienne (UJM), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Camille Jordan (ICJ), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0303 health sciences, Numerical Analysis, Work (thermodynamics), Materials science, Mathematical model, Flow (psychology), Nanotechnology, Blood flow, Mechanics, Adhesion, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Modeling and Simulation, medicine, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Platelet, Thrombus, 030304 developmental biology, Blood vessel
Abstract

International audience; An injury of a blood vessel requires quick repairing of the wound in order to prevent a loss of blood. This is done by the hemostatic system. The key point of its work is the formation of an aggregate from special blood elements, namely, platelets. The construction of a mathematical model of the formation of a thrombocyte aggregate with an adequate representation of its physical, chemical, and biological processes is an extremely complicated problem. A large size of platelets compared to that of molecules, strong inhomogeneity of their distribution across the blood flow, high shear velocities, the moving boundary of the aggregate, the interdependence of its growth and the blood flux hamper the construction of closed mathematical models convenient for biologists. We propose a new PDE-based model of a thrombocyte aggregate formation. In this model, the movement of its boundary due to the adhesion and detachment of platelets is determined by the level set method. The model takes into account the distribution inhomogeneity of erythrocytes and platelets across the blood flow, the invertible adhesion of platelets, their activation, secretion, and aggregation. The calculation results are in accordance with the experimental data concerning the kinetics of the ADP-evoked growth of a thrombus in vivo for different flow velocities.

Published
2012
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12. Finite platelet size could be responsible for the platelet margination effect

Author

Tokarev, Alexey, Butylin, A., Ermakova, E.A., Shnol, E.E., Panasenko, Grigory, Ataullakhanov, Fazly, Panasenko, Grigory, National Research Center for Haematology [Moscow], Ministry of Health and Social Development of Russian Federation [Moscow], Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], [MATH.MATH-AP] Mathematics [math]/Analysis of PDEs [math.AP]
Abstract

International audience; Blood flows through vessels as a segregated suspension. Erythrocytes distribute closer to the vessel axis, whereas platelets accumulate near vessel walls. Directed platelet migration to the vessel walls promotes their hemostatic function. The mechanisms underlying this migration remain poorly understood, although various hypotheses have been proposed to explain this phenomenon (e.g., the available volume model and the drift-flux model). To study this issue, we constructed a mathematical model that predicts the platelet distribution profile across the flow in the presence of erythrocytes. This model considers platelet and erythrocyte dimensions and assumes an even platelet distribution between erythrocytes. The model predictions agree with available experimental data for near-wall layer margination using platelets and platelet-modeling particles and the lateral migration rate for these particles. Our analysis shows that the strong expulsion of the platelets from the core to the periphery of the blood vessel may mainly arise from the finite size of the platelets, which impedes their positioning in between the densely packed erythrocytes in the core. This result provides what we believe is a new insight into the rheological control of platelet hemostasis by erythrocytes.

Published
2011

13. International study of factors affecting human chromosome translocations

Author

Alan Edwards, L. Gayle Littlefield, Nori Nakamura, Günther Stephan, Ursula Oestreicher, E. Janet Tawn, Mimako Nakano, Ernst Schmid, Radim J. Sram, Ruth A. Kleinerman, Firouz Darroudi, Caroline A. Whitehouse, Michael Hauptmann, Alice J. Sigurdson, Vorobtsova Ie, David H. Blakey, James D. Tucker, Joan F. Barquinero, Olena Beskid, Gordon K. Livingston, Laurence Roy, L. Michelle Bennett, P. Voisin, Yoshiaki Kodama, Lee C. Yong, Mina Ha, Isamu Hayata, Manfred Bauchinger, Chunyan Wang, Hai Won Chung, Carita Lindholm, Parveen Bhatti, Wei Zhang, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Dankook University, Division of Cancer Epidemiology and Genetics, National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Department of Bioinformatics and Statistics, Netherlands Cancer Institute, University of Central Lancashire [Preston] (UCLAN), Radiation and Nuclear Safety Authority [Helsinki] (STUK), Radiation Effects Research Foundation, Central Research Institute of Roentgenology and Radiology [Moscow], Ministry of Health and Social Development of Russian Federation [Moscow], Bundesamt für Strahlenschutz (BfS), National Institute for Occupational Safety and Health [Cincinnati] (NIOSH), Centers for Disease Control and Prevention (CDC), GSF – National Research Centre for Environment and Health, Seoul National University [Seoul] (SNU), Leiden University Medical Centre [Leyde, Pays-Bas], Leiden University, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Universitat Autònoma de Barcelona (UAB), National Institute of Radiological Sciences (NIRS), National Institute for Radiological Protection (NIRP), Center for Cancer Research, Oak Ridge Associated Universities (ORAU), National Radiological Protection Board (NRPB), and Wayne State University [Detroit]

Subjects
Male, mutation rate, Health, Toxicology and Mutagenesis, International Cooperation, [SDV]Life Sciences [q-bio], cigarette smoking, Chromosomal translocation, Translocation, Genetic, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, newborn, Risk Factors, Ethnicity, gender, 80 and over, Child, In Situ Hybridization, Fluorescence, In Situ Hybridization, Genetics, Aged, 80 and over, medicine.diagnostic_test, adult, Smoking, article, Age Factors, Middle Aged, 3. Good health, Europe, aged, female, priority journal, 030220 oncology & carcinogenesis, Cord blood, Child, Preschool, Asia, Adolescent, Translocation, Ethnic Groups, In situ hybridization, Biology, Fluorescence, Chromosome Painting, 03 medical and health sciences, Sex Factors, Genetic, medicine, Humans, controlled study, human, Preschool, fluorescence in situ hybridization, Chromosome translocations, Background frequency, Controls, Fluorescence in situ hybridization, aging, Infant, Newborn, Chromosome, Infant, major clinical study, Peripheral blood, confidence interval, Peripheral blood lymphocyte, North America, linear regression analysis, Poisson distribution, umbilical cord blood, chromosome damage, chromosome translocation, peripheral lymphocyte
Abstract

Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from 16 laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages versus a linear relationship (p < 0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR) = 1.19, 95% confidence interval (CI), 1.09-1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p < 0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes. © 2008 Elsevier B.V. All rights reserved.

Published
2008
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14. Guided Self-rehabilitation Contracts Combined With AbobotulinumtoxinA in Adults With Spastic Paresis.

Author

Gracies JM, Francisco GE, Jech R, Khatkova S, Rios CD, and Maisonobe P

Subjects
Adult, Botulinum Toxins, Type A, Humans, Paresis, Prospective Studies, Treatment Outcome, Muscle Spasticity drug therapy, Quality of Life
Abstract

Background and Purpose: Guided self-rehabilitation contracts (GSCs) are a diary-based rehabilitation strategy, wherein specific muscles are identified for prescription of high-load, home self-stretching techniques. We assessed the effect of GSCs combined with simultaneous upper limb (UL) and lower limb (LL) abobotulinumtoxinA injections on composite active range of motion (CXA) in adults with chronic spastic paresis., Methods: This was an international, prospective, single-arm, open-label study (ENGAGE, NCT02969356). Personalized GSCs were monitored by phone every other week, alongside 2 consecutive abobotulinumtoxinA injections (1500 U) across UL and LL, over 6 to 9 months. Primary outcomes were responder rates (CXA improvement ≥35° [UL] or ≥5° [LL]) at week 6 cycle 2. Secondary outcomes were active function (UL: Modified Frenchay Scale [MFS]; LL: 10-m barefoot maximal walking speed [WS]) and quality of life (12-item Short Form Health Survey, SF-12)., Results: Of the 153 treated participants, 136 had primary endpoint data; 72.1% (95% confidence interval [CI], 64.0-78.9) were responders. Mean (SD) CXA changes from baseline to last study visit were +49.3° (63.4) for UL and +20.1° (27.6) for LL. Mean (95% CI) changes from baseline to week 12 cycle 2 were +0.55 (0.43-0.66) in MFS, +0.12 m/s (0.09-0.15) for WS, and +4.0 (2.8-5.2) for SF-12 physical scores. In the safety population (n = 157), 49.7% of participants reported treatment-emergent adverse events (AEs); 12.1% reported 25 serious AEs., Discussion and Conclusions: GSC combined with simultaneous UL and LL abobotulinumtoxinA injections led to improvements in CXA and function in both limbs, and quality-of-life physical scores. These results suggest the beneficial effect of combined GSC and abobotulinumtoxinA therapy in the management of spastic paresis.Video Abstract available for more insight from the authors (see the Supplementary Video, available at: http://links.lww.com/JNPT/A346)., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc.)

Published
2021
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15. Efficacy and Safety of AbobotulinumtoxinA (Dysport) for the Treatment of Hemiparesis in Adults With Upper Limb Spasticity Previously Treated With Botulinum Toxin: Subanalysis From a Phase 3 Randomized Controlled Trial.

Author

Marciniak C, McAllister P, Walker H, Brashear A, Edgley S, Deltombe T, Khatkova S, Banach M, Gul F, Vilain C, Picaut P, Grandoulier AS, and Gracies JM

Subjects
Acetylcholine Release Inhibitors administration & dosage, Adolescent, Adult, Aged, Aged, 80 and over, Double-Blind Method, Female, Humans, Injections, Intramuscular, Male, Middle Aged, Muscle Spasticity etiology, Muscle Spasticity physiopathology, Neuromuscular Agents administration & dosage, Paresis complications, Paresis physiopathology, Prospective Studies, Treatment Outcome, Upper Extremity, Young Adult, Botulinum Toxins, Type A administration & dosage, Muscle Spasticity drug therapy, Paresis economics
Abstract

Objective: To assess the efficacy and safety of abobotulinumtoxinA in adults with upper limb spasticity previously treated with botulinum toxin A (BoNT-A)., Design: A post hoc analysis from a Phase 3, prospective, double-blind, randomized, placebo-controlled study (NCT01313299)., Setting: A total of 34 neurology or rehabilitation clinics in 9 countries., Participants: Adults aged 18-80 years with hemiparesis, ≥6 months after stroke or traumatic brain injury. This analysis focused on a subgroup of subjects with previous onabotulinumtoxinA or incobotulinumtoxinA treatment (n = 105 of 243 in the total trial population) in the affected limb. The mean age was 52 years, and 62% were male., Intervention: Study subjects were randomized 1:1:1 to receive a single injection session with abobotulinumtoxinA 500 or 1000 U or with placebo in the most hypertonic muscle group among the elbow, wrist, or finger flexors (primary target muscle group [PTMG]), and ≥2 additional muscle groups from the upper limb., Main Outcome Measurements: Efficacy and safety measures were assessed, including muscle tone (Modified Ashworth Scale [MAS] in the PTMG), Physician Global Assessment (PGA), perceived function, spasticity, active movement, and treatment-emergent adverse events., Results: At week 4, more subjects had ≥1 grade improvement in MAS for the PTMG with abobotulinumtoxinA versus placebo (abobotulinumtoxinA 500 U, 81.1%; abobotulinumtoxinA 1000 U, 75.0%; placebo, 25.0%). PGA scores ≥1 were achieved by 75.7% and 87.5% of abobotulinumtoxinA 500 and 1000 U subjects versus 41.7% with placebo. Perceived function (Disability Assessment Scale), spasticity angle (Tardieu Scale), and active movement were also improved with abobotulinumtoxinA. There were no treatment-related deaths or serious adverse events., Conclusions: The efficacy and safety of abobotulinumtoxinA in subjects previously treated with BoNT-A were consistent with those in the total trial population. Hence, abobotulinumtoxinA is a treatment option in these patients, and no difference in initial dosing appears to be required compared to that in individuals not treated previously., Level of Evidence: III., (Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Published
2017
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16. Safety and efficacy of abobotulinumtoxinA for hemiparesis in adults with upper limb spasticity after stroke or traumatic brain injury: a double-blind randomised controlled trial.

Author

Gracies JM, Brashear A, Jech R, McAllister P, Banach M, Valkovic P, Walker H, Marciniak C, Deltombe T, Skoromets A, Khatkova S, Edgley S, Gul F, Catus F, De Fer BB, Vilain C, and Picaut P

Subjects
Acetylcholine Release Inhibitors administration & dosage, Acetylcholine Release Inhibitors adverse effects, Adult, Botulinum Toxins, Type A administration & dosage, Botulinum Toxins, Type A adverse effects, Double-Blind Method, Female, Humans, Injections, Intramuscular, Male, Middle Aged, Muscle Spasticity etiology, Paresis etiology, Treatment Outcome, Acetylcholine Release Inhibitors pharmacology, Botulinum Toxins, Type A pharmacology, Brain Injuries complications, Muscle Spasticity drug therapy, Paresis drug therapy, Stroke complications, Upper Extremity physiopathology
Abstract

Background: Resistance from antagonistic muscle groups might be a crucial factor reducing function in chronic hemiparesis. The resistance due to spastic co-contraction might be reduced by botulinum toxin injections. We assessed the effects of abobotulinumtoxinA injection in the upper limb muscles on muscle tone, spasticity, active movement, and function., Methods: In this randomised, placebo-controlled, double-blind study, we enrolled adults (aged 18-80 years) at least 6 months after stroke or brain trauma from 34 neurology or rehabilitation clinics in Europe and the USA. Eligible participants were randomly allocated in a 1:1:1 ratio with a computer-generated list to receive a single injection session of abobotulinumtoxinA 500 U or 1000 U or placebo into the most hypertonic muscle group among the elbow, wrist, or finger flexors (primary target muscle group [PTMG]), and into at least two additional muscle groups from the elbow, wrist, or finger flexors or shoulder extensors. Patients and investigators were masked to treatment allocation. The primary endpoint was the change in muscle tone (Modified Ashworth Scale [MAS]) in the PTMG from baseline to 4 weeks. Secondary endpoints were Physician Global Assessment (PGA) at week 4 and change from baseline to 4 weeks in the perceived function (Disability Assessment Scale [DAS]) in the principal target of treatment, selected by the patient together with physician from four functional domains (dressing, hygiene, limb position, and pain). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01313299., Findings: 243 patients were randomly allocated to placebo (n=81), abobotulinumtoxinA 500 U (n=81), or abobotulinumtoxinA 1000 U (n=81). Mean change in MAS score from baseline at week 4 in the PTMG was -0·3 (SD 0·6) in the placebo group (n=79), -1·2 (1·0) in the abobotulinumtoxinA 500 U group (n=80; difference -0·9, 95% CI -1·2 to -0·6; p<0·0001 vs placebo), and -1·4 (1·1) in the abobotulinumtoxinA 1000 U group (n=79; -1·1, -1·4 to -0·8; p<0·0001 vs placebo). Mean PGA score at week 4 was 0·6 (SD 1·0) in the placebo group (n=78), 1·4 (1·1) in the abobotulinumtoxinA 500 U group (n=80; p=0·0003 vs placebo), and 1·8 (1·1) in the abobotulinumtoxinA 1000 U group (n=78; p<0·0001 vs placebo). Mean change from baseline at week 4 in DAS score for the principal target of treatment was -0·5 (0·7) in the placebo group (n=79), -0·7 (0·8) in the abobotulinumtoxinA 500 U group (n=80; p=0·2560 vs placebo), and -0·7 (0·7) in the abobotulinumtoxinA 1000 U group (n=78; p=0·0772 vs placebo). Three serious adverse events occurred in each group and none were treatment related; two resulted in death (from pulmonary oedema in the placebo group and a pre-existing unspecified cardiovascular disorder in the abobotulinumtoxinA 500 U group). Adverse events that were thought to be treatment related occurred in two (2%), six (7%), and seven (9%) patients in the placebo, abobotulinumtoxinA 500 U, and abobotulinumtoxinA 1000 U groups, respectively. The most common treatment-related adverse event was mild muscle weakness. All adverse events were mild or moderate., Interpretation: AbobotulinumtoxinA at doses of 500 U or 1000 U injected into upper limb muscles provided tone reduction and clinical benefit in hemiparesis. Future research into the treatment of spastic paresis with botulinum toxin should use active movement and function as primary outcome measures., Funding: Ipsen., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Published
2015
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17. Non-thermal argon plasma is bactericidal for the intracellular bacterial pathogen Chlamydia trachomatis.

Author

Ermolaeva SA, Sysolyatina EV, Kolkova NI, Bortsov P, Tuhvatulin AI, Vasiliev MM, Mukhachev AY, Petrov OF, Tetsuji S, Naroditsky BS, Morfill GE, Fortov VE, Grigoriev AI, Zigangirova NA, and Gintsburg AL

Subjects
Animals, Bacterial Load, Fibroblasts microbiology, Mice, Anti-Bacterial Agents pharmacology, Argon pharmacology, Chlamydia trachomatis drug effects, Microbial Viability drug effects, Plasma Gases pharmacology
Abstract

Non-thermal plasma (NTP) is a flow of partially ionized argon gas at an ambient macroscopic temperature and is microbicidal for bacteria, viruses and fungi. Viability of the Gram-negative obligate intracellular bacterial parasite Chlamydia trachomatis and its host cells was investigated after NTP treatment. NTP treatment of C. trachomatis extracellular elementary bodies (EBs) diminished the concentration of infectious bacteria by a factor of 9×10(4), as established by the parallel infection of murine fibroblast McCoy cells with treated and control EBs. NTP treatment of infected McCoy cells caused disruption of membrane-restricted vacuoles (inclusions), where C. trachomatis intracellular reticulate bodies (RBs) multiply, and a 2×10(6)-fold reduction in the concentration of infectious bacteria. When the samples were covered with magnesium fluoride glass to obstruct plasma particles and UV rays alone were applied, the bactericidal effect was reduced 1.4×10(1)-fold and 5×10(4)-fold for EBs and RBs, respectively. NTP treatment caused the viability of host McCoy cells to diminish by 19%. Therefore, the results obtained demonstrated that (i) both extracellular and intracellular forms of C. trachomatis are sensitive to NTP treatment; (ii) the reduction in concentration of infectious bacteria after NTP treatment of infected cells is superior to the reduction in viability of host cells; and (iii) the effect of NTP on intracellular bacteria does not depend on UV rays.

Published
2012
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18. Markers of transmembrane and energy exchange in cells of terminal placental villi in spontaneous and induced pregnancy.

Author

Alexandrova NV, Dubova EA, Baev OR, Shchegolev AI, and Sukhikh GT

Subjects
Adult, Annexin A3 metabolism, Apoferritins metabolism, Female, Humans, Immunohistochemistry, Male, Pregnancy, Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins metabolism, Chorionic Villi metabolism, Placenta metabolism
Abstract

We performed a comparative morphological study of the placentas in spontaneous and induced pregnancy. Immunohistochemical analysis revealed pronounced decrease in the expression of markers of transmembrane (α-SNAP 23, annexin 3) and energy (ferritin light chain, ATP5J) in placental terminal villi.

Published
2012
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19. Contamination of cell cultures with bovine viral diarrhea virus (BVDV).

Author

Uryvaev LV, Dedova AV, Dedova LV, Ionova KS, Parasjuk NA, Selivanova TK, Bunkova NI, Gushina EA, Grebennikova TV, and Podchernjaeva RJ

Subjects
Animals, Antibodies, Monoclonal immunology, Cats, Cattle, Cell Line, Diarrhea Viruses, Bovine Viral genetics, Diarrhea Viruses, Bovine Viral isolation & purification, Dogs, Fluorescent Antibody Technique, Indirect, Haplorhini, Humans, RNA, Viral genetics, Rabbits, Reverse Transcriptase Polymerase Chain Reaction, Sheep, Swine, Viral Envelope Proteins immunology, Diarrhea Viruses, Bovine Viral growth & development
Abstract

The incidence of contamination of cell strains used in biological and virological studies and of fetal calf sera (FCS) manufactured by Russian and foreign companies used for cell culturing with noncytocidal bovine viral diarrhea virus (BVDV; Pestivirus, Flaviviridae) was analyzed. The virus was detected by reverse transcription PCR and indirect immunofluorescence with monoclonal antibodies to BVDV virion envelope glycoprotein in 25% of 117 cell strains and 45% of 35 tested FCS lots. The virus multiplied and persisted in a wide spectrum of human cell strains and in monkey, swine, sheep, rabbit, dog, cat, and other animal cells. The levels of BVDV genome RNA in contaminated cell cultures reached 10(2)-10(3) g-eq/cell and in serum samples 10(3)-10(7) g-eq/ml. These facts necessitate testing of cells and FCS for BVDV reproduced in cells without signs of infection detectable by light microscopy. The molecular mechanisms of long-term virus persistence in cells without manifestation of cell destruction are unknown.

Published
2012
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20. Finite platelet size could be responsible for platelet margination effect.

Author

Tokarev AA, Butylin AA, Ermakova EA, Shnol EE, Panasenko GP, and Ataullakhanov FI

Subjects
Blood Circulation, Cell Size, Erythrocytes cytology, Hematocrit, Humans, Blood Platelets cytology, Cell Movement, Models, Biological
Abstract

Blood flows through vessels as a segregated suspension. Erythrocytes distribute closer to the vessel axis, whereas platelets accumulate near vessel walls. Directed platelet migration to the vessel walls promotes their hemostatic function. The mechanisms underlying this migration remain poorly understood, although various hypotheses have been proposed to explain this phenomenon (e.g., the available volume model and the drift-flux model). To study this issue, we constructed a mathematical model that predicts the platelet distribution profile across the flow in the presence of erythrocytes. This model considers platelet and erythrocyte dimensions and assumes an even platelet distribution between erythrocytes. The model predictions agree with available experimental data for near-wall layer margination using platelets and platelet-modeling particles and the lateral migration rate for these particles. Our analysis shows that the strong expulsion of the platelets from the core to the periphery of the blood vessel may mainly arise from the finite size of the platelets, which impedes their positioning in between the densely packed erythrocytes in the core. This result provides what we believe is a new insight into the rheological control of platelet hemostasis by erythrocytes., (Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Published
2011
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21. Morphometric characteristics of placental villi in pregnant women with diabetes.

Author

Dubova EA, Pavlov KA, Yesayan RM, Nagovitsyna MN, Tkacheva ON, Shestakova MV, and Shchegolev AI

Subjects
Adult, Case-Control Studies, Chorionic Villi blood supply, Diabetes Mellitus, Type 1 complications, Female, Humans, Pregnancy, Chorionic Villi pathology, Diabetes Mellitus, Type 1 pathology, Diabetes, Gestational pathology, Pregnancy in Diabetics pathology
Abstract

We conducted a comparative morphological study of placentas from women with gestational diabetes and diabetes mellitus. Morphometry of histological preparations revealed similar type of changes in the studied parameters of placental villi in diabetes mellitus and gestational diabetes. The maximum deviation of the studied parameters from the control was noted in type 1 diabetes mellitus.

Published
2011
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22. Mouse splenocyte blast transformation in the presence of plasma γ-globulin fraction proteins and their complexes with copper and zinc.

Author

Cheknev SB, Grigorjeva EA, Nikolaeva TN, and Pronin AV

Subjects
Animals, Concanavalin A pharmacology, Coordination Complexes blood, Mice, Mice, Inbred BALB C, Mitogens, Thymidine metabolism, Copper blood, Lymphocyte Activation drug effects, Spleen cytology, Zinc blood, gamma-Globulins metabolism
Abstract

Plasma γ-globulin fraction proteins, copper and zinc cations, and metal complexes formed by these cations and human serum γ-globulin induce blast transformation of splenocytes from BALB/c mice at a level comparable to that induced by concanavalin A. Zinc bound to γ-globulin reduces by 25% and copper in complex with this protein stimulates by 1.6 times its capacity to induce blast transformation. Combinations with concanavalin A reproduce the effects of γ-globulin-metal complex under conditions of mitogen induction. Incorporation of(3)H-thymidine in splenocytes incubated with combinations of γ-globulin-copper metalcomplex, copper cations, and control protein with concanavalin A was by 1.4, 1.3 (p<0.1), and 1.25 times higher (p<0.05), respectively, than after incubation with concanavalin A alone.

Published
2011
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23. Plasma content of cholesterol and glycerol alcohols depends on the number of fatty acid double bonds in lipoprotein lipid pool.

Author

Titov VN and Lisitsyn DM

Subjects
Breast Neoplasms blood, Child, Diabetes Mellitus blood, Humans, Hypercholesterolemia blood, Hyperlipidemias blood, Triglycerides blood, Cholesterol blood, Fatty Acids, Unsaturated analysis, Glycerol blood, Lipoproteins chemistry
Abstract

The number of the fatty acid double bonds (unsaturation degree) in the plasma lipid pool was evaluated by automated ozone titration. A positive relationship between the content of double bonds, cholesterol, and glycerol was detected. The higher was plasma cholesterol level, the more double bonds contained fatty acids. At cholesterol level of 0.8-18.9 mmol/liter the double bond/cholesterol ratio approached 4.0 and double bond/glycerol ratio was 1.3-1.5. The maximum content of double bonds was detected in LDL. It was hypothesized that the greater part of plasma cholesterol is esterified with arachidonic acid possessing 4 double bonds; three fatty acids are esterified with glycerol, which altogether have 1-3 double bonds. It seems that plasma cholesterol level indirectly but significantly reflects the level of essential polyenic fatty acids, while glycerol reflects the levels of saturated and unsaturated fatty acids. The role of cholesterol in the plasma consists in the participation in transfer of essential fatty acid in the nonpolar form and their absorption by cells. LDL are the main transmitters of essential polyenic fatty acids in the form of cholesterol esters.

Published
2006
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24. The breastfeeding support and promotion in Baby-Friendly Maternity Hospitals and Not-as-Yet Baby-Friendly Hospitals in Russia.

Author

Abolyan LV

Subjects
Adult, Case-Control Studies, Female, Guideline Adherence, Health Education methods, Health Education standards, Health Promotion, Humans, Infant, Infant, Newborn, Outcome Assessment, Health Care, Patient Education as Topic methods, Patient Education as Topic standards, Perinatal Care methods, Perinatal Care standards, Russia epidemiology, Time Factors, United Nations, World Health Organization, Breast Feeding epidemiology, Breast Feeding psychology, Breast Feeding statistics & numerical data, Health Knowledge, Attitudes, Practice, Hospitals, Maternity standards, Mothers psychology, Personnel, Hospital psychology, Social Support
Abstract

Objective: The objective was to evaluate implementation of the WHO/UNICEF "Ten Steps to Successful Breastfeeding" as defined by the Baby-Friendly Hospital Initiative in eight maternity hospitals in the Moscow region. Four maternity hospitals had been certified Baby- Friendly Hospitals (BFHs), the experimental group; and four maternity hospitals Not-as-Yet Baby Friendly, the control group (NBFHs)., Methods: Maternal interviews and infant breastfeeding rates were the primary outcomes of the study. In total, 741 healthy postpartum women from the experimental and control group were interviewed: 383 and 358, respectively. Interviews were conducted over 5 months, from May to July 2004. In addition, an assessment of levels and trends in breastfeeding for the period of 1998 to 2003 was made for the area served by the BFHs and the NBFHs., Findings: Analyses of the questionnaires completed by the mothers found a positive effect of BFH practice on a number of parameters, such as an increased rate of in-hospital exclusive breastfeeding, mothers' decisions concerning planned duration of breastfeeding, mothers' and babies' health, and maternal knowledge about the necessary measures in BFHs. Mothers appreciated baby-friendly changes, such as rooming-in, breastfeeding on baby's demand, and taking care of their babies by themselves. The successful initiation of breastfeeding in the BFHs was shown to favor the promotion of breastfeeding among 1-year-old babies in the experimental areas. However, there were some shortcomings in the BFHs: frequent use of labor anesthesia; insufficient placing of newborns on the mother's abdomen, rooming-in, and initiating breastfeeding immediately; and a short length of "skin-to-skin" contact (<30 minutes). The women in BFHs also observed the use of feeding bottles and dummies, and experienced some problems with breast health., Conclusions: BFH practices can increase breastfeeding rates as well as maternal satisfaction. However, shortcomings in the training and support for mothers, and limited help of the medical personnel were noted. It is recommended that BFHs pay attention to maintaining adherence to the criteria of the 10 steps of the Baby-Friendly Hospital Initiative. Since 2003 to control the implementation of the Baby Friendly Initiative principles and sustain the progress in the hospitals designated as Baby Friendly reassessment of maternity hospitals is held in Russia in conformity with the requirements of WHO and UNICEF.

Published
2006
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