26 results on '"St Jude Children's Research Hospital"'
Search Results
2. Role of pharmacogenomics and pharmacodynamics in the treatment of acute lymphoblastic leukaemia
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Pui, Ching-Hon, Relling, Mary V, and Evans, William E
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- 2002
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3. Interaction of Group A Streptococci with Human Plasmin(ogen) under Physiological Conditions
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D'Costa, Sybil S. and Boyle, Michael D.P.
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- 2000
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4. Developmental Regulation of Zbu1, a DNA-Binding Member of the SWI2/SNF2 Family
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Gong, Xiaohua, Kaushal, Sunjay, Ceccarelli, Elena, Bogdanova, Natalia, Neville, Craig, Nguyen, Tom, Clark, Hilary, Khatib, Ziad A., Valentine, Marcus, Look, A.Thomas, and Rosenthal, Nadia
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- 1997
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5. Clinical utility of nuclear imaging in the evaluation of pediatric adrenal neoplasms
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Fargette, Christelle, Shulkin, Barry, Jha, Abhishek, Pacak, Karel, Taïeb, David, Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), St Jude Children's Research Hospital, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Service de médecine nucléaire [Marseille], and Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)
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nuclear imaging ,neuroblastoma ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Cancer Research ,PET ,adrenal ,pediatric neoplams ,Oncology ,[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging ,cushing ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,pheochromocytoma - Abstract
Adrenal neoplasms rarely occur in children. They can be diagnosed in the presence of endocrine, metabolic or neurological problems, an abdominal mass, more rarely an adrenal incidentaloma, or in the context of an adrenal mass discovered in the evaluation of childhood cancer including hematologic malignancy. According to standard medical practice, pediatric malignancies are almost always evaluated by 18F-fluorodeoxyglucose positron emission tomography with computed tomography ([18F]FDG PET/CT). Nuclear imaging using specific radiotracers is also an important tool for diagnosing and staging neuroblastoma, pheochromocytoma, hormone hypersecretion, or indeterminate adrenal masses. The Hippocratic oath “primum non nocere” encourages limitation of radiation in children per the ALARA concept (as low as reasonably achievable) but should not lead to the under-use of nuclear imaging because of the potential risk of inaccurate diagnosis or underestimation of the extent of disease. As in adults, nuclear imaging in children should be performed in conjunction with hormone evaluation and morphological imaging.
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- 2023
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6. Pathogenic bacteria target NEDD8-conjugated cullins to hijack host-cell signaling pathways
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Jean-Philippe Nougayrède, C. Erec Stebbins, Ascel Samba-Louaka, Eric Oswald, Brenda A. Schulman, Claude Watrin, David M. Duda, Grégory Jubelin, Yun Hsu, Marie Penary, Rika Nobe, Frédéric Taieb, Unité de Microbiologie (MIC), Institut National de la Recherche Agronomique (INRA), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Department of Structural Biology, Howard Hughes Medical Institute (HHMI)-St Jude Children's Research Hospital, Rockefeller University [New York], Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), St Jude Children's Research Hospital, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), taieb, frederic, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CHU Toulouse [Toulouse]
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Infectious Diseases/Gastrointestinal Infections ,Cell ,Cell Biology/Cell Growth and Division ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,[SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,NEDD8 ,Cell Biology/Cell Signaling ,Infectious Diseases/Bacterial Infections ,sécrétion ,Ubiquitin ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,invertébré ,Microbiology/Parasitology ,Biology (General) ,Host cell nucleus ,Cells, Cultured ,Escherichia coli Infections ,0303 health sciences ,ubiquitine ,biology ,Escherichia coli Proteins ,030302 biochemistry & molecular biology ,Cell Cycle ,Microbiology and Parasitology ,Intracellular Signaling Peptides and Proteins ,in vitro ,Cell cycle ,Microbiologie et Parasitologie ,3. Good health ,Cell biology ,Ubiquitin ligase ,Protein Transport ,medicine.anatomical_structure ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Biochemistry ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Signal transduction ,escherichia coli ,bactérie pathogène ,Cyclin-Dependent Kinase Inhibitor p27 ,Signal Transduction ,Research Article ,Infectious Diseases/Tropical and Travel-Associated Diseases ,Cyclin-Dependent Kinase Inhibitor p21 ,NEDD8 Protein ,QH301-705.5 ,Immunology ,Blotting, Western ,Microbiology ,03 medical and health sciences ,Virology ,Two-Hybrid System Techniques ,Genetics ,medicine ,[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Animals ,Humans ,Immunoprecipitation ,[SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health ,Ubiquitins ,Molecular Biology ,Actin ,030304 developmental biology ,Cell Nucleus ,[SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health ,SKP Cullin F-Box Protein Ligases ,Ubiquitination ,[SDV.EE.IEO] Life Sciences [q-bio]/Ecology, environment/Symbiosis ,RC581-607 ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,vertébré ,Actins ,Rats ,biology.protein ,Parasitology ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Immunologic diseases. Allergy ,[SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis - Abstract
The cycle inhibiting factors (Cif), produced by pathogenic bacteria isolated from vertebrates and invertebrates, belong to a family of molecules called cyclomodulins that interfere with the eukaryotic cell cycle. Cif blocks the cell cycle at both the G1/S and G2/M transitions by inducing the stabilization of cyclin-dependent kinase inhibitors p21waf1 and p27kip1. Using yeast two-hybrid screens, we identified the ubiquitin-like protein NEDD8 as a target of Cif. Cif co-compartmentalized with NEDD8 in the host cell nucleus and induced accumulation of NEDD8-conjugated cullins. This accumulation occurred early after cell infection and correlated with that of p21 and p27. Co-immunoprecipitation revealed that Cif interacted with cullin-RING ubiquitin ligase complexes (CRLs) through binding with the neddylated forms of cullins 1, 2, 3, 4A and 4B subunits of CRL. Using an in vitro ubiquitylation assay, we demonstrate that Cif directly inhibits the neddylated CUL1-associated ubiquitin ligase activity. Consistent with this inhibition and the interaction of Cif with several neddylated cullins, we further observed that Cif modulates the cellular half-lives of various CRL targets, which might contribute to the pathogenic potential of diverse bacteria., Author Summary Among the arsenal of virulence factors used by bacterial pathogens to infect and manipulate their hosts, cyclomodulins are a growing family of bacterial toxins that interfere with the eukaryotic cell-cycle. Cif is one of these cyclomodulins produced by both mammalian and invertebrate pathogenic bacteria. Cif blocks the host cell cycle by inducing the accumulation of two regulators of cell cycle progression: the cyclin-dependent kinase inhibitors p21 and p27. To decipher the mode of action of Cif, we performed yeast two-hybrid screenings. We show that Cif binds to NEDD8 and induce accumulation of neddylated cullins early after infection. Cullins are scaffold components of cullin-RING ubiquitin ligases (CRLs), which ubiquitinate proteins and target them for degradation by the 26S proteasome. We demonstrate that Cif directly inhibits the ubiquitin ligase activity of these CRLs and consequently the targeting of p21 and p27 for ubiquitin-dependent degradation. Targeting at NEDD8 represents a novel strategy for modulation of host cell functions by bacterial pathogens. By inhibiting the most prominent class of ubiquitin-ligases, Cif controls the stability of a cohort of key regulators and impinge on not only cell cycle progression but also on many cellular and biological processes such as immunity, development, transcription, and cell signaling.
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- 2010
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7. Human domination of the global water cycle absent from depictions and perceptions
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David Ellison, Tamara Kolbe, Stefan Krause, Madeline Buhman, Benjamin W. Abbott, Sayedeh Sara Sayedi, Jean Marçais, Lafe Conner, Amanda Huebner, David M. Hannah, Camille Minaudo, Rebecca J. Frei, Stephen Plont, Kathryn D. Henderson, Gilles Pinay, Sen Gu, F. S. Chapin, Ovidiu Ursache, Sarah E. Godsey, Melissa C. Chapin, Jay P. Zarnetske, Tyler Hampton, Kevin Bishop, Brigham Young University (BYU), Department of Earth Sciences, Uppsala University, Uppsala University, GéoHydrosystèmes COntinentaux (GéHCO EA6293), Université de Tours, School of Geography, Earth and Environmental Sciences [Birmingham], University of Birmingham [Birmingham], Department of Pathology, St Jude Children's Research Hospital, Virginia Polytechnic Institute and State University [Blacksburg], Géosciences Rennes (GR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique du Globe de Paris (IPGP), Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Swedish University of Agricultural Sciences (SLU), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Department of Earth Sciences - Palaeobiology [Uppsala], Université de Tours (UT), Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-IPG PARIS-Institut national des sciences de l'Univers (INSU - CNRS), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), and Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS)
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Water resources ,010504 meteorology & atmospheric sciences ,Natural resource economics ,river ,0207 environmental engineering ,Climate change ,security ,02 engineering and technology ,insights ,decline ,01 natural sciences ,Water scarcity ,Hydrology (agriculture) ,framework ,[SDU.STU.HY]Sciences of the Universe [physics]/Earth Sciences/Hydrology ,Water cycle ,020701 environmental engineering ,science ,0105 earth and related environmental sciences ,Ecology ,Moisture recycling ,footprint ,15. Life on land ,protection ,6. Clean water ,Environmental sciences ,Water security ,quality ,13. Climate action ,General Earth and Planetary Sciences ,Hydrology ,Climate sciences ,Water use - Abstract
[Departement_IRSTEA]Eaux [ADD1_IRSTEA]Systèmes aquatiques soumis à des pressions multiples; International audience; Human water use, climate change and land conversion have created a water crisis for billions of individuals and many ecosystems worldwide. Global water stocks and fluxes are estimated empirically and with computer models, but this information is conveyed to policymakers and researchers through water cycle diagrams. Here we compiled a synthesis of the global water cycle, which we compared with 464 water cycle diagrams from around the world. Although human freshwater appropriation now equals half of global river discharge, only 15% of the water cycle diagrams depicted human interaction with water. Only 2% of the diagrams showed climate change or water pollution—two of the central causes of the global water crisis—which effectively conveys a false sense of water security. A single catchment was depicted in 95% of the diagrams, which precludes the representation of teleconnections such as ocean–land interactions and continental moisture recycling. These inaccuracies correspond with specific dimensions of water mismanagement, which suggest that flaws in water diagrams reflect and reinforce the misunderstanding of global hydrology by policymakers, researchers and the public. Correct depictions of the water cycle will not solve the global water crisis, but reconceiving this symbol is an important step towards equitable water governance, sustainable development and planetary thinking in the Anthropocene.
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- 2019
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8. Molecular Characterization of Closely Related H6N2 Avian Influenza Viruses Isolated from Turkey, Egypt, and Uganda
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Mercan, Yavuz, Atim, Gladys, Kayed, Ahmed E., Azbazdar, M. Ekin, Kandeil, Ahmed, Ali, Mohamed A., Rubrum, Adam, McKenzie, Pamela, Webby, Richard J., Erima, Bernard, Wabwire-Mangen, Fred, Ukuli, Qouilazoni A., Tugume, Titus, Byarugaba, Denis K., Kayali, Ghazi, Ducatez, Mariette F., Koçer, Zeynep A., Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Makerere University [Kampala, Ouganda] (MAK), Walter Reed Project, National Research Centre - NRC (EGYPT), St Jude Children's Research Hospital, The University of Texas Health Science Center at Houston (UTHealth), Human Link, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and The part of this study that was performed in Turkey was funded by Izmir Biomedicine and Genome Center. The Egyptian and Ugandan parts of the study was funded by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, under contract number HHSN272201400006C.
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migratory birds ,Turkey ,molecular markers ,[SDV]Life Sciences [q-bio] ,viruses ,lcsh:QR1-502 ,Animals, Wild ,Genome, Viral ,avian influenza virus ,lcsh:Microbiology ,Poultry ,Article ,Influenza A virus ,Influenza in Birds ,Animals ,Humans ,Animal Migration ,Egypt ,Uganda ,reassortment ,waterfowl ,Chickens ,Phylogeny ,Reassortant Viruses - Abstract
International audience; Genetic analysis of circulating avian influenza viruses (AIVs) in wild birds at different geographical regions during the same period could improve our knowledge about virus transmission dynamics in natural hosts, virus evolution as well as zoonotic potential. Here, we report the genetic and molecular characterization of H6N2 influenza viruses isolated from migratory birds in Turkey, Egypt, and Uganda during 2017–2018. The Egyptian and Turkish isolates were genetically closer to each other than they were to the virus isolated from Uganda. Our results also suggest that multiple reassortment events were involved in the genesis of the isolated viruses. All viruses contained molecular markers previously associated with increased replication and/or pathogenicity in mammals. The results of this study indicate that H6N2 viruses carried by migratory birds on the West Asian/East African and Mediterranean/Black Sea flyways have the potential to transmit to mammals including humans. Additionally, adaptation markers in these viruses indicate the potential risk for poultry, which also increases the possibility of human exposure to these viruses.
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- 2021
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9. The phenotypic spectrum of germline YARS2 variants
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Lee Hilliard, Joëlle Rudinger-Thirion, Alexander J. Rennings, Magali Frugier, Richard J. Roodenburg, Lisa G. Riley, Leonor Arenillas, David P. Steensma, Josep Fita-Torró, Elie Bechara, Mark D. Fleming, Sylvia S. Bottomley, Gregory A. Hale, Janet L. Kwiatkowski, Rienk Y. J. Tamminga, Ronghao Zhou, Dean R. Campagna, Joel Kaplan, Miguel R. Abboud, Matthew M. Heeney, Colin A. Sieff, Nicolaas Schaap, Rasha Ahmed, John Christodoulou, Dorine W. Swinkels, Gerwin Huls, Mayka Sanchez, Tjitske Kleefstra, Roula Farah, Annet Simons, Stem Cell Aging Leukemia and Lymphoma (SALL), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Genetic Metabolic Disorders Research Unit, Westmead Hospital [Sydney]-Kids Research Institute, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), St Jude Children's Research Hospital, 849 Department of Human Genetics, Radboud University Medical Center [Nijmegen], Balamand University Medical School, and Westmead Hospital [Sydney]
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0301 basic medicine ,Anemia ,[SDV]Life Sciences [q-bio] ,Anèmia ,TRANSFER-RNA SYNTHETASE ,Biology ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,Germline mutation ,Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience [Radboudumc 7] ,Sideroblastic anemia ,Mitochondrial myopathy ,medicine ,Missense mutation ,HETEROGENEITY ,Allele ,MUTATION ,Exome sequencing ,ComputingMilieux_MISCELLANEOUS ,Genetics ,IDENTIFICATION ,Cancer development and immune defence RIHS: Radboud Institute for Health Sciences [Radboudumc 2] ,Hematology ,medicine.disease ,Renal disorders RIMLS: Radboud Institute for Molecular Life Sciences [Radboudumc 11] ,3. Good health ,Fenotip ,Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Mitochondrial diseases RIMLS: Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,030104 developmental biology ,Lactic acidosis - Abstract
YARS2 variants have previously been described in patients with myopathy, lactic acidosis and sideroblastic anemia 2 (MLASA2). YARS2 encodes the mitochondrial tyrosyl-tRNA synthetase, which is responsible for conjugating tyrosine to its cognate mt-tRNA for mitochondrial protein synthesis. Here we describe 14 individuals from 11 families presenting with sideroblastic anemia and YARS2 variants that we identified using a sideroblastic anemia gene panel or exome sequencing. The phenotype of these patients ranged from MLASA to isolated congenital sideroblastic anemia. As in previous cases, inter- and intra-familial phenotypic variability was observed, however, this report includes the first cases with isolated sideroblastic anemia and patients with biallelic YARS2 variants that have no clinically ascertainable phenotype. We identified ten novel YARS2 variants and three previously reported variants. In vitro amino-acylation assays of five novel missense variants showed that three had less effect on the catalytic activity of YARS2 than the most commonly reported variant, p.(Phe52Leu), associated with MLASA2, which may explain the milder phenotypes in patients with these variants. However, the other two missense variants had a more severe effect on YARS2 catalytic efficiency. Several patients carried the common YARS2 c.572 G>T, p.(Gly191Val) variant (minor allele frequency =0.1259) in trans with a rare deleterious YARS2 variant. We have previously shown that the p.(Gly191Val) variant reduces YARS2 catalytic activity. Consequently, we suggest that biallelic YARS2 variants, including severe loss-of-function alleles in trans of the common p.(Gly191Val) variant, should be considered as a cause of isolated congenital sideroblastic anemia, as well as the MLASA syndromic phenotype. This research was funded by grants from Instituto de Salud Carlos III (ISCIII) PI14/01867, PI16/02024 and PI17/00701, TRASCAN (EPICA), CIBERONC (CB16/12/00489; Co-finance with FEDER funds), RTICC (RD12/0036/0068) and Departamento de Salud del Gobierno de Navarra 40/2016. N.M. is supported by a FEHH-Celgene research grant, M.P. was supported by a Sara Borrell fellowship CD12/00540 and RO was supported by Ministerio de Ciencia, Innovación y Universidades of Spain, Subprograma de Formación de Profesorado Universitario (FPU) award number FPU14/04331.
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- 2018
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10. Serological Surveillance of Influenza D Virus in Ruminants and Swine in West and East Africa, 2017–2020
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Koffi Dogno, Idrissa Nonmon Sanogo, Richard J. Webby, Mariette F. Ducatez, Komlan Adjabli, Emmanuel Couacy-Hymann, Fred Wabwire-Mangen, Titus Tugume, Casimir K. Kouakou, Denis K. Byarugaba, Qouilazoni A. Ukuli, Gladys Atim, Fidélia Djegui, Pamela McKenzie, Wolali Go-Maro, Komla Batawui, Rachidatou Adjin, Ghazi Kayali, Bernard Erima, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Segou, Faculté d’Agronomie et de Médecine Animale, Université de Ségou (FAMA-US), Laboratoire National d'Appui au Développement Agricole (LANADA), Laboratoire Central Vétérinaire de Lomé, Laboratoire de Diagnostic Vétérinaire et de Sérosurveillance (LADISERO), Makerere University [Kampala, Ouganda] (MAK), Walter Reed Project, LANADA Central Laboratory for Animal Diseases, Partenaires INRAE, University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), Human Link, St Jude Children's Research Hospital, and This study was founded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (CEIRS contract no. HHSN272201400006C). I.N.S. is supported by a PhD scholarship of the French Embassy in Mali.
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Male ,medicine.medical_specialty ,Veterinary medicine ,030231 tropical medicine ,Cattle Diseases ,serology ,Biology ,Microbiology ,Virus ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Orthomyxoviridae Infections ,Seroepidemiologic Studies ,Virology ,Epidemiology ,medicine ,East africa ,Animals ,small ruminants ,influenza D virus ,030304 developmental biology ,Swine Diseases ,0303 health sciences ,[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,Hemagglutination assay ,Brief Report ,swine ,Ruminants ,Africa, Eastern ,Serum samples ,QR1-502 ,3. Good health ,Africa, Western ,Infectious Diseases ,cattle ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Africa ,Female ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,epidemiology ,Thogotovirus - Abstract
This study was approved by the St. Jude Children’s Research Hospital Institutional Animal Care and Use Committee (Amended IACUC Approval # 546-100491-07/17; expires 4/5/23).; International audience; Influenza D virus (IDV) was first isolated in 2011 in Oklahoma, USA from pigs presenting with influenza-like symptoms. IDV is known to mainly circulate in ruminants, especially cattle. In Africa, there is limited information on the epidemiology of IDV, although the virus has likely circulated in the region since 2012. In the present study, we investigated the seropositivity of IDV among domestic ruminants and swine in West and East Africa from 2017 to 2020. Serum samples were analyzed using the hemagglutination inhibition (HI) assay. Our study demonstrated that IDV is still circulating in Africa, with variations in seropositivity among countries and species. The highest seropositivity was detected in cattle (3.9 to 20.9%). Our data highlights a need for extensive surveillance of IDV in Africa in order to better understand the epidemiology of the virus in the region.
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- 2021
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11. Risk Mapping of Influenza D Virus Occurrence in Ruminants and Swine in Togo Using a Spatial Multicriteria Decision Analysis Approach
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Fusade-Boyer, Maxime, Pato, Pidemnéwé S., Komlan, Mathias, Dogno, Koffi, Batawui, Komla, Go-Maro, Emilie, McKenzie, Pamela, Guinat, Claire, Sécula, Aurélie, Paul, Mathilde, Webby, Richard J., Tran, Annelise, Waret-Szkuta, Agnès, Ducatez, Mariette, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire Central Vétérinaire de Lomé, St Jude Children's Research Hospital, Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and This study was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (CEIRS contract no. HHSN272201400006C). M.F.B. is supported by a PhD scholarship of the French Ministry of Research and Higher Education.
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[SDV.SA]Life Sciences [q-bio]/Agricultural sciences ,Ruminant ,Swine ,[SDV]Life Sciences [q-bio] ,lcsh:QR1-502 ,L73 - Maladies des animaux ,Risque ,influenza D virus ,Togo ,risk mapping ,spatial MCDA ,Antibodies, Viral ,Influenzavirus ,Article ,lcsh:Microbiology ,Decision Support Techniques ,Porcin ,Orthomyxoviridae Infections ,Risk Factors ,Animals ,Surveillance épidémiologique ,Spatial Analysis ,[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,Cartographie ,influenza d virus ,togo ,spatial mcda ,Distribution spatiale ,Ruminants ,Hemagglutination Inhibition Tests ,Epidemiological Monitoring ,Cattle ,U30 - Méthodes de recherche ,système d'aide à la décision ,Thogotovirus - Abstract
International audience; Influenza D virus (IDV) has been identified in several continents, with serological evidence for the virus in Africa. In order to improve the sensitivity and cost-benefit of IDV surveillance in Togo, risk maps were drawn using a spatial multicriteria decision analysis (MCDA) and experts' opinion to evaluate the relevance of sampling areas used so far. Areas at highest risk of IDV occurrence were the main cattle markets. The maps were evaluated with previous field surveillance data collected in Togo between 2017 and 2019: 1216 sera from cattle, small ruminants, and swine were screened for antibodies to IDV by hemagglutination inhibition (HI) assays. While further samples collections are needed to validate the maps, the risk maps resulting from the spatial MCDA approach generated here highlight several priority areas for IDV circulation assessment.
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- 2020
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12. Diversity of Dromedary Camel Coronavirus HKU23 in African Camels Revealed Multiple Recombination Events among Closely Related Betacoronaviruses of the Subgenus Embecovirus
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S A Kuranga, Ray T.Y. So, Patrick C. Y. Woo, Jamiu O Oladipo, Gelagay Aylet, Malik Peiris, Mo-Sheung Cheng, Ouafaa Fassi-Fihri, Véronique Chevalier, Ranawaka A.P.M. Perera, Eve Miguel, François Roger, Ronald L.W. Ko, Ziqi Zhou, Daniel K.W. Chu, Richard J. Webby, Leo L.M. Poon, University of Hong Kong, 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]), University of Ilorin, Université Hassan II [Casablanca] (UH2MC), Pan African Veterinary Vaccine Center, Partenaires INRAE, Kasetsart University (KU), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), St Jude Children's Research Hospital, NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [HHSN272201400006C], Health and Medical Research Fund, Food and Health Bureau, Government of the Hong Kong Special Administrative Region, and Theme-based Research Scheme, University Grant Committee, Hong Kong [T11/707/15]
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viruses ,L73 - Maladies des animaux ,phylogeny ,medicine.disease_cause ,Genetic recombination ,Coronavirinae ,Zoonoses ,genomic features [EN] ,Clade ,Coronavirus ,Recombination, Genetic ,Genetics ,0303 health sciences ,[SDV.BA]Life Sciences [q-bio]/Animal biology ,virus diseases ,dromedary camels ,Morocco ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Middle East Respiratory Syndrome Coronavirus ,Rabbits ,Coronavirus Infections ,Recombination ,endocrine system ,Camelus ,Genotype ,Middle East respiratory syndrome coronavirus ,coronaviruses ,Dromadaire ,Immunology ,Nigeria ,Genome, Viral ,Biology ,Microbiology ,génomique ,Evolution, Molecular ,Betacoronavirus ,Open Reading Frames ,03 medical and health sciences ,Phylogenetics ,Virology ,evolution ,medicine ,Animals ,Transmission des maladies ,030304 developmental biology ,[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,Hemagglutinin esterase ,030306 microbiology ,Genetic Variation ,betacoronaviruses ,L10 - Génétique et amélioration des animaux ,biology.organism_classification ,Antibodies, Neutralizing ,recombination ,Genetic Diversity and Evolution ,Insect Science ,Ethiopia - Abstract
Genetic recombination is often demonstrated in coronaviruses and can result in host range expansion or alteration in tissue tropism. Here, we showed interspecies events of recombination of an endemic dromedary camel coronavirus, HKU23, with other clade A betacoronaviruses. Our results supported the possibility that the zoonotic pathogen MERS-CoV, which also cocirculates in the same camel species, may have undergone similar recombination events facilitating its emergence or may do so in its future evolution., Genetic recombination has frequently been observed in coronaviruses. Here, we sequenced multiple complete genomes of dromedary camel coronavirus HKU23 (DcCoV-HKU23) from Nigeria, Morocco, and Ethiopia and identified several genomic positions indicative of cross-species virus recombination events among other betacoronaviruses of the subgenus Embecovirus (clade A beta-CoVs). Recombinant fragments of a rabbit coronavirus (RbCoV-HKU14) were identified at the hemagglutinin esterase gene position. Homolog fragments of a rodent CoV were also observed at 8.9-kDa open reading frame 4a at the 3′ end of the spike gene. The patterns of recombination differed geographically across the African region, highlighting a mosaic structure of DcCoV-HKU23 genomes circulating in dromedaries. Our results highlighted active recombination of coronaviruses circulating in dromedaries and are also relevant to the emergence and evolution of other betacoronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV). IMPORTANCE Genetic recombination is often demonstrated in coronaviruses and can result in host range expansion or alteration in tissue tropism. Here, we showed interspecies events of recombination of an endemic dromedary camel coronavirus, HKU23, with other clade A betacoronaviruses. Our results supported the possibility that the zoonotic pathogen MERS-CoV, which also cocirculates in the same camel species, may have undergone similar recombination events facilitating its emergence or may do so in its future evolution.
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- 2019
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13. System-Wide Modulation of HECT E3 Ligases with Selective Ubiquitin Variant Probes
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Emmanuel Lemichez, Brenda A. Schulman, Zhenyue Hao, Sachdev S. Sidhu, Nan Li, Ryan Murchie, Wei Zhang, Maria A. Sartori, Kuen-Phon Wu, Jason Moffat, John R. Walker, Avinash Persaud, Yi Sheng, Alban Ordureau, Jicheng Hu, Chong Jiang, Manjeet Mukherjee, Kevin R. Brown, Yufeng Tong, Yanjun Li, Junjie Chen, Anne Doye, Peter Y. Mercredi, Daniela Rotin, Hari B. Kamadurai, J. Wade Harper, Donnelly Center Cellular and Biomolecular Research [Univ. Toronto], University of Toronto, St Jude Children's Research Hospital, Department of Cell Biology, Harvard Medical School [Boston] (HMS), Program in Cell Biology [Toronto], The Hospital for sick children [Toronto] (SickKids)-Department of Biochemistry [University of Toronto], University of Toronto-University of Toronto, Structural Genomics Consortium, The University of Texas M.D. Anderson Cancer Center [Houston], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of York [York, UK], Campbell Family Institute for Breast Cancer Research, University Health Network, Department of Pharmacology and Toxicology [Toronto], Department of Molecular Genetics [Toronto], The Donnelly Centre for Cellular and Biomolecular Research [Toronto, ON, Canada] (CCBR), J.W.H. was supported by NIH (R37NS083524 and GM095567). A.O. was supported by an Edward R. and Anne G. Lefler Center postdoctoral fellowship. J.W.H. is a consultant for Millennium: the Takada Oncology Company and Biogen. D.R. holds a Canada Research Chair (Tier 1 in Biochemistry and Signal Transduction) and was supported by CIHR (MOP#130422). B.A.S. is an investigator of the Howard Hughes Medical Institute (HHMI) and was supported by ALSAC, NIH R37GM065930 and P30CA021765. NECAT and APS were supported by NIH P41 GM103403 and DOE Contract DE-AC02-06CH11357. W.Z. was supported by a CIHR postdoctoral fellowship. S.S.S. and J.M. were supported by CIHR (MOP#111149 and 136956). The Structural Genomics Consortium (SGC) is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada, Innovative Medicines Initiative (EU/EFPIA) (ULTRA-DD grant no. 115766), Janssen, Merck & Co., Novartis Pharma AG, Ontario Ministry of Economic Development and Innovation, Pfizer, São Paulo Research Foundation-FAPESP, Takeda, and the Wellcome Trust., and We thank members of the Sidhu and Schulman groups for helpful comments. We thank Andrew Vorobyov, Eva Chou, Yogesh Hooda, Jun Gu, and Aiping Dong for technical assistance. We are indebted to Pankaj Garg, Andreas Ernst, Abiodun Ogunjimi, Clare Jeon, Satra Nim, Frank Sicheri, and Hongrui Wang for reagents and advice.
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Models, Molecular ,0301 basic medicine ,Subfamily ,[SDV]Life Sciences [q-bio] ,MESH: Catalytic Domain ,NEDD4 ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,MESH: Ubiquitin/chemistry ,MESH: Ubiquitin/metabolism ,Madin Darby Canine Kidney Cells ,MESH: Dogs ,Ubiquitin ,Cell Movement ,Catalytic Domain ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,MESH: Animals ,MESH: Cell Movement ,chemistry.chemical_classification ,MESH: Organoids/metabolism ,biology ,MESH: Ubiquitin-Protein Ligases/chemistry ,Cell migration ,Cell biology ,MESH: Ubiquitin/genetics ,Organoids ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,MESH: Models, Molecular ,MESH: HCT116 Cells ,Ubiquitin-Protein Ligases ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,macromolecular substances ,Cell Line ,03 medical and health sciences ,Dogs ,Peptide Library ,Animals ,Humans ,Molecular Biology ,NEDD4L ,DNA ligase ,MESH: Humans ,MESH: Organoids/cytology ,MESH: Madin Darby Canine Kidney Cells ,MESH: Ubiquitin-Protein Ligases/metabolism ,Cell Biology ,HCT116 Cells ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,MESH: Cell Line ,030104 developmental biology ,chemistry ,biology.protein ,MESH: Peptide Library ,Genetic screen - Abstract
Comment in : A Billion Ubiquitin Variants to Probe and Modulate the UPS. [Mol Cell. 2016]; International audience; HECT-family E3 ligases ubiquitinate protein substrates to control virtually every eukaryotic process and are misregulated in numerous diseases. Nonetheless, understanding of HECT E3s is limited by a paucity of selective and potent modulators. To overcome this challenge, we systematically developed ubiquitin variants (UbVs) that inhibit or activate HECT E3s. Structural analysis of 6 HECT-UbV complexes revealed UbV inhibitors hijacking the E2-binding site and activators occupying a ubiquitin-binding exosite. Furthermore, UbVs unearthed distinct regulation mechanisms among NEDD4 subfamily HECTs and proved useful for modulating therapeutically relevant targets of HECT E3s in cells and intestinal organoids, and in a genetic screen that identified a role for NEDD4L in regulating cell migration. Our work demonstrates versatility of UbVs for modulating activity across an E3 family, defines mechanisms and provides a toolkit for probing functions of HECT E3s, and establishes a general strategy for systematic development of modulators targeting families of signaling proteins.
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- 2016
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14. New Insights Into the Role of Cav2 Protein Family in Calcium Flux Deregulation in Fmr1-KO Neurons
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Castagnola, Sara, Delhaye, Sébastien, Folci, Alessandra, Paquet, Agnès, Brau, Frédéric, Duprat, Fabrice, Jarjat, Marielle, Grossi, Mauro, Béal, Méline, Martin, Stéphane, Mantegazza, Massimo, Bardoni, Barbara, Maurin, Thomas, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Laboratoire International Associé 'Neogenex' (LIA Neogenex), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-St Jude Children's Research Hospital-Hôpital Pequeño Principe, Martin, Stephane, Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
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congenital, hereditary, and neonatal diseases and abnormalities ,ratiometric calcium imaging ,calcium homeostasis ,[SDV]Life Sciences [q-bio] ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,nervous system diseases ,[SDV] Life Sciences [q-bio] ,Cellular and Molecular Neuroscience ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Molecular Biology ,Neuroscience ,Original Research ,Cacna1a ,Cav2.1 ,Fragile X syndrome - Abstract
International audience; Fragile X syndrome (FXS), the most common form of inherited intellectual disability (ID) and a leading cause of autism, results from the loss of expression of the Fmr1 gene which encodes the RNA-binding protein Fragile X Mental Retardation Protein (FMRP). Among the thousands mRNA targets of FMRP, numerous encode regulators of ion homeostasis. It has also been described that FMRP directly interacts with Ca2+ channels modulating their activity. Collectively these findings suggest that FMRP plays critical roles in Ca2+ homeostasis during nervous system development. We carried out a functional analysis of Ca2+ regulation using a calcium imaging approach in Fmr1-KO cultured neurons and we show that these cells display impaired steady state Ca2+ concentration and an altered entry of Ca2+ after KCl-triggered depolarization. Consistent with these data, we show that the protein product of the Cacna1a gene, the pore-forming subunit of the Cav2.1 channel, is less expressed at the plasma membrane of Fmr1-KO neurons compared to wild-type (WT). Thus, our findings point out the critical role that Cav2.1 plays in the altered Ca2+ flux in Fmr1-KO neurons, impacting Ca2+ homeostasis of these cells. Remarkably, we highlight a new phenotype of cultured Fmr1-KO neurons that can be considered a novel cellular biomarker and is amenable to small molecule screening and identification of new drugs to treat FXS.
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- 2018
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15. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs
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Tom Mikkelsen, Rogier Versteeg, Christelle Dufour, Jens Schittenhelm, Umut H. Toprak, Eleonora Aronica, Sariah Allen, Stefan M. Pfister, Arie Perry, Dominique Figarella-Branger, David T.W. Jones, Stephan Wolf, Irene Slavc, Christian Mawrin, Pieter Wesseling, Nada Jabado, Cynthia Cowdrey, David W. Ellison, Andreas von Deimling, Jörg Felsberg, Michael A. Grotzer, Pascale Varlet, Michael C. Frühwald, Volker Hovestadt, Timothy E. Van Meter, Gnanaprakash Balasubramanian, V. Peter Collins, Wolfram Scheurlen, Christian Hagel, Volkmar Hans, Johannes Gojo, Irina Leis, Michael D. Taylor, Catherine Keohane, Marco Prinz, Rachid Drissi, Maria Łastowska, Istvan Vajtai, Anne Jouvet, Sonika Dahiya, Marietta Wolter, Matthias Schlesner, Till Milde, Chris Jones, Pascal Johann, Kristian W. Pajtler, Anna Maria Buccoliero, Marina Ryzhova, David Scheie, Kenneth Aldape, Matija Snuderl, Martin Ebinger, Bret C. Mobley, Sebastian Brabetz, Joanna J. Phillips, Tarek Shalaby, Silvia Hofer, Christian Koelsche, Christel Herold-Mende, Barbara C. Worst, Martin U. Schuhmann, Jüri Reimand, Walter Berger, Stephan Frank, Diana Carvalho, Daniela Lötsch, Christof M. Kramm, Amar Gajjar, David Capper, Peter van Sluis, Ivo Buchhalter, Christine Haberler, Katja von Hoff, Stefan Rutkowski, Roland Eils, Martin Hasselblatt, Ulrich Schüller, Maryam Fouladi, Jochen Rößler, Guido Reifenberger, Brent A. Orr, Andrew S. Moore, Alan Mackay, Marc Remke, André O. von Bueren, Felix Sahm, Jan Koster, Karel Zitterbart, Dominik Sturm, Paul A. Northcott, Peter Lichter, Matthias A. Karajannis, Stefan Holm, Martin Sill, Wiesława Grajkowska, Stéphanie Puget, Felice Giangaspero, Marcel Kool, Reinhard Schneppenheim, Lynn Ann Forrester, Mariarita Santi, Torsten Pietsch, Camelia M. Monoranu, Richard Volckmann, Iris Fried, Matthew Schniederjan, Andrey Korshunov, Elke Pfaff, Rainer Grobholz, Jacques Grill, Pathology, CCA - Cancer biology, Heidelberg University Hospital [Heidelberg], St Jude Children's Research Hospital, Department of Neuropathology, Institute of Pathology, NN Burdenko Neurosurgical Institute (NNBNI), University of Toronto, The Institute of Cancer Research, Royal Cancer Hospital, University of California [San Francisco] (UC San Francisco), University of California (UC), Children's Hospital Medical Center, Children's Hospital Medical Center Cincinnatri, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), The Children's Memorial Health Institute, Cnopf’sche Kinderklinik, Universität Bonn = University of Bonn, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Medizinische Universität Wien = Medical University of Vienna, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Karolinska Institutet [Stockholm], Luzerner Kantonsspital, University of Freiburg [Freiburg], Cork University Hospital, Hadassah Hebrew University Medical Center [Jerusalem], Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Vanderbilt University [Nashville], Children’s Healthcare of Atlanta, Children’s Hospital of Philadelphia (CHOP ), Università degli Studi di Firenze = University of Florence (UniFI), Washington University in Saint Louis (WUSTL), University Medical Center Göttingen (UMG), Klinikum Augsburg, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Radboud University Medical Center [Nijmegen], Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Tübingen University Hospital [Germany], University Hospital Basel [Basel], Hirslanden Medical Center, University Hospital Berne, Medical Center Bielefeld, Masaryk University [Brno] (MUNI), Department of Pathology, University of Cambridge [UK] (CAM), University of Amsterdam [Amsterdam] (UvA), Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, Institut Gustave Roussy (IGR), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), University hospital of Zurich [Zurich], Virginia Commonwealth University (VCU), Biocenter University of Würzburg = Biozentrum der Universität Würzburg, Julius-Maximilians-Universität Würzburg (JMU), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), VU University Medical Center [Amsterdam], Henry Ford Hospital, The University of Texas M.D. Anderson Cancer Center [Houston], University of Queensland [Brisbane], McGill University = Université McGill [Montréal, Canada], Cellular and Computational Neuroscience (SILS, FNWI), University of California [San Francisco] (UCSF), University of California, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], University of Bonn, Otto-von-Guericke University [Magdeburg] (OVGU), Anna Meyer Children's Hospital and University of Florence, Freiburg University Medical Center, Masaryk University and University Hospital Brno, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), ANS - Cellular & Molecular Mechanisms, APH - Amsterdam Public Health, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, Oncogenomics, and Other departments
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Pathology ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Astroblastoma ,Neuroectodermal Tumors ,Repressor Proteins / genetics ,CNS-PNETs ,Biochemistry ,Central Nervous System Neoplasms ,0302 clinical medicine ,Neuroectodermal Tumors / diagnosis ,Central Nervous System Neoplasms / classification ,Central Nervous System Neoplasms / genetics ,Non-U.S. Gov't ,Child ,Tumor Suppressor Proteins / genetics ,Central Nervous System Neoplasms / pathology ,Research Support, Non-U.S. Gov't ,food and beverages ,Forkhead Transcription Factors ,genetics and molecular biology ,neuroectodermal tumors ,central nervous system ,3. Good health ,Gene Expression Regulation, Neoplastic ,Neuroepithelial cell ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Sarcoma ,Signal Transduction ,tumor ,Repressor Proteins / chemistry ,medicine.medical_specialty ,Molecular Sequence Data ,Central nervous system ,Brain tumor ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Neuroectodermal Tumors / genetics ,Neuroectodermal Tumors / pathology ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,Biology ,Research Support ,General Biochemistry, Genetics and Molecular Biology ,N.I.H ,03 medical and health sciences ,Research Support, N.I.H., Extramural ,Forkhead Transcription Factors / genetics ,Proto-Oncogene Proteins ,Neuroblastoma ,Journal Article ,medicine ,Humans ,Amino Acid Sequence ,Neuroectodermal Tumors / classification ,Proto-Oncogene Proteins / genetics ,Medulloblastoma ,Biochemistry, Genetics and Molecular Biology(all) ,Tumor Suppressor Proteins ,Gene Expression Profiling ,Extramural ,DNA Methylation ,medicine.disease ,Proto-Oncogene Proteins / chemistry ,Repressor Proteins ,Gene expression profiling ,Immunology ,Trans-Activators ,Central Nervous System Neoplasms / diagnosis ,ddc:004 ,030217 neurology & neurosurgery ,Genetics and Molecular Biology(all) - Abstract
Item does not contain fulltext Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.
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- 2016
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16. Size effect of anaerobic granular sludge on biogas production: A micro scale study
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Souhila Poncin, Huai-Zhi Li, Jian E. Zuo, Zhong Liang Zhang, Kai Jun Wang, Zhi Ping Cao, Zohaib Ur Rehman Afridi, Jing Wu, State Key Joint Lab Environm Simulat & Pollut Con, Tsinghua University [Beijing] (THU), Laboratoire Réactions et Génie des Procédés (LRGP), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Developmental Neurobiology, St Jude Children's Research Hospital, and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)
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Environmental Engineering ,Bioengineering ,02 engineering and technology ,010501 environmental sciences ,01 natural sciences ,7. Clean energy ,Bioreactors ,Biogas ,Bioenergy ,Bioreactor ,[SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering ,Anaerobiosis ,Particle Size ,Porosity ,Waste Management and Disposal ,ComputingMilieux_MISCELLANEOUS ,0105 earth and related environmental sciences ,Biogas production ,Chromatography ,Sewage ,[SDE.IE]Environmental Sciences/Environmental Engineering ,Renewable Energy, Sustainability and the Environment ,Chemistry ,Granule (cell biology) ,General Medicine ,021001 nanoscience & nanotechnology ,6. Clean water ,Chemical engineering ,Biofuels ,Particle size ,0210 nano-technology ,Anaerobic exercise - Abstract
This study investigated the influence of anaerobic granular sludge size on its bioactivity at COD concentration of 1000, 3000 and 6000 mg/L. Based on size, granules were categorized as large (3-3.5 mm), medium (1.5-2 mm) and small (0.5-1 mm). A positive relationship was obtained between granule size and biogas production rate. For instance, at COD 6000 mg/L, large granules had highest biogas production rate of 0.031 m(3)/kgVSS/d while medium and small granules had 0.016 and 0.006 m(3)/kgVSS/d respectively. The results were reaffirmed by applying modified Fick's law of diffusion. Diffusion rates of substrate for large, medium and small granules were 1.67×10(-3), 6.1×10(-4)and 1.8×10(-4) mg/s respectively at that COD. Large granules were highly bio-active due to their internal structure, i.e. big pore size, high porosity and short diffusion distance as compared to medium and small granules, thus large granules could improve the performance of reactor.
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- 2016
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17. Germline Variants in Phosphodiesterase Genes and Genetic Predisposition to Pediatric Adrenocortical Tumors
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Jérôme Bertherat, Carlos Rodriguez-Galindo, Fabio R. Faucz, Gerard P. Zambetti, Enzo Lalli, Gang Wu, Luana Zampieron Paza, Raul C. Ribeiro, Constantine A. Stratakis, Elizabeth S. Fernandes, Bonald C. Figueiredo, Emilia M. Pinto, St Jude Children's Research Hospital, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Pelé Pequeno Príncipe Research Institute [Curitiba, Brazil], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'endocrinologie et maladies métaboliques (Hôpital Cochin), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de référence des maladies rares de la surrénale ( CHU Cochin [AP-HP]), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Faculdades Pequeno Príncipe [Curitiba, Brazil], Centro de Genética Molecular e Pesquisa do Câncer em Crianças [Curitiba, Brazil] (CEGEMPAC), Instituto de Pesquisa Pelé Pequeno Principe, Federal University of Paraná [Curitiba, Brazil], This research was funded by the American Lebanese Syrian Associated Charities (ALSAC)., CHU Cochin [AP-HP], Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Lalli, Enzo, Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
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0301 basic medicine ,Cancer Research ,11p ,[SDV]Life Sciences [q-bio] ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,medicine.disease_cause ,lcsh:RC254-282 ,Article ,Germline ,Loss of heterozygosity ,03 medical and health sciences ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,medicine ,Adrenocortical carcinoma ,TP53 ,Gene ,Exome sequencing ,Phosphodiesterase ,tp53 ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Uniparental disomy ,3. Good health ,[SDV] Life Sciences [q-bio] ,030104 developmental biology ,Oncology ,adrenocortical tumor ,030220 oncology & carcinogenesis ,Cancer research ,Carcinogenesis ,phosphodiesterase ,cAMP pathway - Abstract
Phosphodiesterases (PDEs) form a superfamily of enzymes that catalyze the hydrolysis of cyclic nucleotides adenosine 3&prime, 5&prime, cyclic monophosphate (cAMP) and guanosine 3&prime, cyclic monophosphate (cGMP) to their inactive 5&prime, monophosphates. cAMP plays a critical role as a second messenger in endocrine tissues, and activation of cAMP signaling has been reported in endocrine tumors. Germline variants in PDEs have been associated with benign cortisol-secreting adrenocortical adenomas and testicular germ cell cancer but not adrenocortical carcinoma. We performed whole genome sequencing (WGS) and whole exome sequencing (WES) of paired blood and tumor samples from 37 pediatric adrenocortical tumors (ACTs). Germline inactivating variants in PDEs were observed in 9 of 37 (24%) patients. Tumor DNA analysis revealed loss of heterozygosity, with maintenance of the mutated allele in all cases. Our results suggest that germline variants in PDEs and other regulators of the cAMP-signaling pathway may contribute to pediatric adrenocortical tumorigenesis, perhaps by cooperating with germline hypomorphic mutant TP53 alleles and uniparental disomy of chromosome 11p15 (Beckwith&ndash, Wiedemann syndrome).
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- 2020
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18. Active Surveillance for Influenza A Virus among Swine, Midwestern United States, 2009–2011
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Marie R. Culhane, Mariette F. Ducatez, James Lowe, Cesar Corzo, Richard J. Webby, Evelyn Stigger-Rosser, Kevin Juleen, University of Minnesota [Twin Cities] (UMN), University of Minnesota System, St Jude Children's Research Hospital, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Carthage Veterinary Services, and Partenaires INRAE
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Epidemiology ,viruses ,lcsh:Medicine ,medicine.disease_cause ,Public health surveillance ,Influenza A virus ,Medicine ,Public Health Surveillance ,Swine Diseases ,Animal biology ,0303 health sciences ,education.field_of_study ,[SDV.BA]Life Sciences [q-bio]/Animal biology ,Microbiology and Parasitology ,virus diseases ,Agriculture ,Microbiologie et Parasitologie ,3. Good health ,Santé publique et épidémiologie ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Infectious Diseases ,surveillance ,Seasons ,midwestern United States ,Microbiology (medical) ,Population ,Médecine humaine et pathologie ,History, 21st Century ,Virus ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Orthomyxoviridae Infections ,Influenza ,monitoring ,swine ,Biologie animale ,Animals ,lcsh:RC109-216 ,education ,Pig farms ,030304 developmental biology ,030306 microbiology ,business.industry ,Research ,lcsh:R ,Influenza a ,Virology ,Influenza A virus subtype H5N1 ,Epidemiological surveillance ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Human health and pathology ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Veterinary diagnostic laboratories identify and characterize influenza A viruses primarily through passive surveillance. However, additional surveillance programs are needed. To meet this need, an active surveillance program was conducted at pig farms throughout the midwestern United States. From June 2009 through December 2011, nasal swab samples were collected monthly from among 540 groups of growing pigs and tested for influenza A virus by real-time reverse transcription PCR. Of 16,170 samples, 746 were positive for influenza A virus; of these, 18.0% were subtype H1N1, 16.0% H1N2, 7.6% H3N2, and 14.5% (H1N1)pdm09. An influenza (H3N2) and (H1N1)pdm09 virus were identified simultaneously in 8 groups. This active influenza A virus surveillance program provided quality data and increased the understanding of the current situation of circulating viruses in the midwestern US pig population.
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- 2013
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19. Multiple Reassortment between Pandemic (H1N1) 2009 and Endemic Influenza Viruses in Pigs, United States
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Kevin Juleen, Jeri-Carol Crumpton, Daniel Darnell, Ashley Webb, Ben M. Hause, Marie Gramer, Richard J. Webby, James Lowe, David Q.-H. Wang, Adam Rubrum, Cesar Corzo, Evelyn Stigger-Rosser, Christy Brockwell-Staats, Mariette F. Ducatez, Randy R. Simonson, St Jude Children's Research Hospital, Newport Laboratories, Partenaires INRAE, University of Minnesota [Twin Cities] (UMN), University of Minnesota System, and Carthage Veterinary Services
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Male ,Endemic Diseases ,Epidemiology ,animal diseases ,viruses ,Reassortment ,Sus scrofa ,lcsh:Medicine ,Influenza A Virus, H1N1 Subtype ,Genotype ,Pandemic ,Cells, Cultured ,Phylogeny ,Animal biology ,0303 health sciences ,pigs United States ,Transmission (medicine) ,[SDV.BA]Life Sciences [q-bio]/Animal biology ,Microbiology and Parasitology ,Microbiologie et Parasitologie ,3. Good health ,Santé publique et épidémiologie ,Infectious Diseases ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,reassortant ,endemic ,influenza ,Reassortant Viruses ,Microbiology (medical) ,Biology ,H5N1 genetic structure ,Virus ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Orthomyxoviridae Infections ,Influenza, Human ,Biologie animale ,Animals ,Humans ,lcsh:RC109-216 ,Pandemics ,030304 developmental biology ,multiple reassortment ,swine influenza ,030306 microbiology ,Research ,pandemic ,lcsh:R ,Ferrets ,Sequence Analysis, DNA ,Virology ,United States ,zoonoses ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie - Abstract
TOC Summary: Viruses belonging to these novel genotypes are indistinguishable phenotypically from endemic swine viruses., As a result of human-to-pig transmission, pandemic influenza A (H1N1) 2009 virus was detected in pigs soon after it emerged in humans. In the United States, this transmission was quickly followed by multiple reassortment between the pandemic virus and endemic swine viruses. Nine reassortant viruses representing 7 genotypes were detected in commercial pig farms in the United States. Field observations suggested that the newly described reassortant viruses did not differ substantially from pandemic (H1N1) 2009 or endemic strains in their ability to cause disease. Comparable growth properties of reassortant and endemic viruses in vitro supported these observations; similarly, a representative reassortant virus replicated in ferrets to the same extent as did pandemic (H1N1) 2009 and endemic swine virus. These novel reassortant viruses highlight the increasing complexity of influenza viruses within pig populations and the frequency at which viral diversification occurs in this ecologically important viral reservoir.
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- 2011
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20. Putative amino acid determinants of the emergence of the 2009 influenza A (H1N1) virus in the human population
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Thomas P. Fabrizio, Sun-Woo Yoon, Richard J. Webby, Mariette F. Ducatez, Daphna Meroz, Tomer Hertz, Nir Ben-Tal, Tel Aviv University [Tel Aviv], Department of Infectious Diseases, St Jude Children's Research Hospital, Fred Hutchinson Cancer Research Center, and Partenaires INRAE
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Erythrocytes ,Swine ,Population ,Virulence ,Biology ,H5N1 genetic structure ,Virus ,Antigenic drift ,Mice ,Influenza A Virus, H1N1 Subtype ,Species Specificity ,Antigen ,Immunity ,Biologie animale ,Influenza, Human ,Animals ,Humans ,Amino Acids ,education ,Animal biology ,education.field_of_study ,Multidisciplinary ,Strain (chemistry) ,[SDV.BA]Life Sciences [q-bio]/Animal biology ,Microbiology and Parasitology ,Biological Sciences ,Virology ,Microbiologie et Parasitologie ,Santé publique et épidémiologie ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie - Abstract
The emergence of the unique H1N1 influenza A virus in 2009 resulted in a pandemic that has spread to over 200 countries. The constellation of molecular factors leading to the emergence of this strain is still unclear. Using a computational approach, we identified molecular determinants that may discriminate the hemagglutinin protein of the 2009 human pandemic H1N1 (pH1N1) strain from that of other H1N1 strains. As expected, positions discriminating the pH1N1 from seasonal human strains were located in or near known H1N1 antigenic sites, thus camouflaging the pH1N1 strain from immune recognition. For example, the alteration S145K (an antigenic position) was found as a characteristic of the pH1N1 strain. We also detected positions in the hemagglutinin protein differentiating classical swine viruses from pH1N1. These positions were mostly located in and around the receptor-binding pocket, possibly influencing binding affinity to the human cell. Such alterations may be liable in part for the virus’s efficient infection and adaptation to humans. For instance, 133 A and 149 were identified as discriminative positions. Significantly, we showed that the substitutions R133 A K and R149K, predicted to be pH1N1 characteristics, each altered virus binding to erythrocytes and conferred virulence to A/swine/NC/18161/02 in mice, reinforcing the computational findings. Our findings provide a structural explanation for the deficient immunity of humans to the pH1N1 strain. Moreover, our analysis points to unique molecular factors that may have facilitated the emergence of this swine variant in humans, in contrast to other swine variants that failed.
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- 2011
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21. Changes to the dynamic nature of hemagglutinin and the emergence of the 2009 pandemic H1N1 influenza virus
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James C. Paulson, Noam Chen, Sun-Woo Yoon, Tomer Hertz, Richard J. Webby, Robert G. Webster, Subrata Barman, Nir Ben-Tal, Mariette F. Ducatez, Turkan Haliloglu, Thomas P. Fabrizio, Ryan McBride, Charles J. Russell, Department of Infectious Diseases, St Jude Children's Research Hospital, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Tel Aviv University [Tel Aviv], Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Department of Chemical Physiology, The Scripps Research Institute, Boǧaziçi üniversitesi = Boğaziçi University [Istanbul], Fred Hutchinson Cancer Research Center, Partenaires INRAE, National Institute of Allergy and Infectious Diseases (NIAID), Centers of Excellence for Influenza Research and Surveillance (CEIRS) [HHSN266200700005C], Cancer Center core grant [CA21765], ALSAC, Ministry of Science and Technology, Israel, TUBITAK project [110T088], NATO's Emerging Security Challenges Division of Science for Peace and Security Programme (SPS Project) [G4622], NIAID grant [AI058113], KRIBB Initiative program [KGM4691511], and Boğaziçi University [Istanbul]
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Swine ,[SDV]Life Sciences [q-bio] ,viruses ,Hemagglutinin (influenza) ,Hemagglutinin Glycoproteins, Influenza Virus ,Arginine ,Virus Replication ,Airborne transmission ,H5N1 genetic structure ,Article ,Virus ,Antigenic drift ,Microbiology ,Influenza A Virus, H1N1 Subtype ,Orthomyxoviridae Infections ,Influenza, Human ,Pandemic ,Animals ,Humans ,Multidisciplinary ,biology ,Lysine ,Ferrets ,Virology ,3. Good health ,Amino Acid Substitution ,Viral replication ,biology.protein ,Receptors, Virus ,Neuraminidase - Abstract
The virologic factors that limit the transmission of swine influenza viruses between humans are unresolved. While it has been shown that acquisition of the neuraminidase (NA) and matrix (M) gene segments from a Eurasian-lineage swine virus was required for airborne transmission of the 2009 pandemic H1N1 virus (H1N1pdm09), we show here that an arginine to lysine change in the hemagglutinin (HA) was also necessary. This change at position 149 was distal to the receptor binding site but affected virus-receptor affinity and HA dynamics, allowing the virus to replicate more efficiently in nasal turbinate epithelium and subsequently transmit between ferrets. Receptor affinity should be considered as a factor limiting swine virus spread in humans.
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- 2015
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22. Regulation of Legionella Phagosome Maturation and Infection through Flagellin and Host Ipaf
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Amer, Amal, Franchi, Luigi, Kanneganti, Thirumala-Devi, Body-Malapel, Mathilde, Ozören, Nesrin, Brady, Graham, Meshinchi, Sasha, Jagirdar, Rajesh, Gewirtz, Andrew, Akira, Shizuo, Nuñez, Gabriel, Özören, Nesrin, School of Biochemistry and Immunology, St Jude Children's Research Hospital, Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Department of Host Defense, Osaka University [Osaka], University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], and University of Michigan System-University of Michigan System
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Legionella ,[SDV]Life Sciences [q-bio] ,Bone Marrow Cells ,Endoplasmic Reticulum ,Biochemistry ,Legionella pneumophila ,Microbiology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,NLRC4 ,Nod1 Signaling Adaptor Protein ,Phagosomes ,NLR Family, Pyrin Domain-Containing 3 Protein ,Phagosome maturation ,Animals ,Secretion ,Molecular Biology ,Adaptor Proteins, Signal Transducing ,030304 developmental biology ,Phagosome ,Mice, Knockout ,0303 health sciences ,biology ,Macrophages ,Calcium-Binding Proteins ,Caspase 1 ,Cell Biology ,bacterial infections and mycoses ,biology.organism_classification ,respiratory tract diseases ,Enzyme Activation ,Gene Expression Regulation ,TLR5 ,biology.protein ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,bacteria ,Apoptosis Regulatory Proteins ,Carrier Proteins ,Flagellin ,030215 immunology - Abstract
International audience; Legionella pneumophila is an intracellular bacterium that causes an acute form of pneumonia called Legionnaires' disease. After infection of human macrophages, the Legionella-containing phagosome (LCP) avoids fusion with the lysosome allowing intracellular replication of the bacterium. In macrophages derived from most mouse strains, the LCP is delivered to the lysosome resulting in Legionella degradation and restricted bacterial growth. Mouse macrophages lacking the NLR protein Ipaf or its downstream effector caspase-1 are permissive to intracellular Legionella replication. However, the mechanism by which Ipaf restricts Legionella replication is not well understood. Here we demonstrate that the presence of flagellin and a competent type IV secretion system are critical for Legionella to activate caspase-1 in macrophages. Activation of caspase-1 in response to Legionella infection also required host Ipaf, but not TLR5. In the absence of Ipaf or caspase-1 activation, the LCP acquired endoplasmic reticulum-derived vesicles, avoided fusion with the lysosome, and allowed Legionella replication. Accordingly a Legionella mutant lacking flagellin did not activate caspase-1, avoided degradation, and replicated in wild-type macrophages. The regulation of phagosome maturation by Ipaf occurred within 2 h after infection and was independent of macrophage cell death. In vivo studies confirmed that flagellin and Ipaf play an important role in the control of Legionella clearance. These results reveal that Ipaf restricts Legionella replication through the regulation of phagosome maturation, providing a novel function for NLR proteins in host defense against an intracellular bacterium.
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- 2006
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23. Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia
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Stephen Pavletic, Robert Peter Gale, Mukta Arora, Vikas Gupta, Haydar Frangoul, Dan Wang, Jon J. van Rood, Pierre Tiberghien, Gregory A. Hale, Philip L. McCarthy, John T. Horan, Luis Isola, Joerg Halter, Richard T. Maziarz, Mark R. Litzow, Vijay Reddy, Olle Ringdén, Theresa Hahn, Mei-Jie Zhang, Claudio Anasetti, Roswell Park Cancer Institute [Buffalo], Medical College of Wisconsin, University of Minnesota System, Mayo Clinic, Vanderbilt University [Nashville], St Jude Children's Research Hospital, Department of Pharmacology, Emory University [Atlanta, GA], Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Oregon Health and Science University [Portland] (OHSU), Leiden University Medical Center (LUMC), Princess Margaret Hospital, University of Toronto, University Hospital Basel [Basel], Florida Hospital Cancer Institute, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Karolinska University Hospital [Stockholm], Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Saas, Philippe
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Male ,Cancer Research ,Time Factors ,Graft vs Host Disease ,MESH: Peripheral Blood Stem Cell Transplantation ,MESH: Risk Assessment ,Severity of Illness Index ,0302 clinical medicine ,MESH: Risk Factors ,HLA Antigens ,Risk Factors ,Living Donors ,Cumulative incidence ,MESH: Bone Marrow Transplantation ,MESH: HLA Antigens ,MESH: Treatment Outcome ,Bone Marrow Transplantation ,MESH: Living Donors ,Leukemia ,Histocompatibility Testing ,Myeloid leukemia ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,3. Good health ,MESH: Reproducibility of Results ,Europe ,Leukemia, Myeloid, Acute ,surgical procedures, operative ,Treatment Outcome ,Oncology ,MESH: Young Adult ,030220 oncology & carcinogenesis ,Acute Disease ,MESH: Acute Disease ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,MESH: Leukemia, Myeloid, Acute ,medicine.drug ,Adult ,medicine.medical_specialty ,Canada ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Cyclophosphamide ,Adolescent ,MESH: Graft vs Host Disease ,MESH: Histocompatibility Testing ,Risk Assessment ,03 medical and health sciences ,Myelogenous ,Young Adult ,MESH: Canada ,Internal medicine ,Acute lymphocytic leukemia ,MESH: Severity of Illness Index ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,MESH: Leukemia ,medicine ,MESH: United States ,Humans ,Risk factor ,Retrospective Studies ,MESH: Adolescent ,MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Peripheral Blood Stem Cell Transplantation ,MESH: Humans ,business.industry ,Siblings ,MESH: Time Factors ,Reproducibility of Results ,MESH: Retrospective Studies ,MESH: Adult ,medicine.disease ,MESH: Male ,United States ,MESH: Siblings ,Graft-versus-host disease ,MESH: Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Immunology ,MESH: Europe ,business ,MESH: Female ,030215 immunology - Abstract
Purpose Acute graft-versus-host disease (GVHD) causes substantial morbidity and mortality after human leukocyte antigen (HLA)-identical sibling transplants. No large registry studies of acute GVHD risk factors have been reported in two decades. Risk factors may have changed in this interval as transplant-related techniques have evolved. Patients and Methods Acute GVHD risk factors were analyzed in 1,960 adults after HLA-identical sibling myeloablative transplant for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myeloid leukemia (CML) reported by 226 centers worldwide to the Center for International Blood and Marrow Transplant Research from 1995 to 2002. Outcome was measured as time from transplant to onset of grade 2 to 4 acute GVHD, with death without acute GVHD as a competing risk. Results Cumulative incidence of grade 2 to 4 acute GVHD was 35% (95% CI, 33% to 37%). In multivariable analyses, factors significantly associated with grade 2 to 4 acute GVHD were cyclophosphamide + total-body irradiation versus busulfan + cyclophosphamide (relative risk [RR] = 1.4; P < .0001), blood cell versus bone marrow grafts in patients age 18 to 39 years (RR = 1.43; P = .0023), recipient age 40 and older versus age 18 to 39 years receiving bone marrow grafts (RR = 1.44; P = .0005), CML versus AML/ALL (RR = 1.35; P = .0003), white/Black versus Asian/Hispanic race (RR = 1.54; P = .0003), Karnofsky performance score less than 90 versus 90 to 100 (RR = 1.27; P = .014), and recipient/donor cytomegalovirus-seronegative versus either positive (RR = 1.20; P = .04). Stratification by disease showed the same significant predictors of grade 2 to 4 acute GVHD for CML; however, KPS and cytomegalovirus serostatus were not significant predictors for AML/ALL. Conclusion This analysis confirmed several previously reported risk factors for grade 2 to 4 acute GVHD. However, several new factors were identified whereas others are no longer significant. These new data may facilitate individualized risk estimates and raise several interesting biologic questions.
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- 2008
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24. Specific Immunoassays for Placental Alkaline Phosphatase As a Tumor Marker
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Raul C. Ribeiro, Mara Albonei Dudeque Pianovski, João Carlos Minozzo, Dodie L. Arnold, Giovanna Assis Rodrigues, Bonald C. Figueiredo, Patrícia Zancanella, Juliana F. Moura, Enzo Lalli, Sérvio Túlio Stinghen, Luis G. Callefe, Centro de Genética Molecular e Pesquisa do Câncer em Crianças (CEGEMPAC), Instituto de Pesquisa Pelé Pequeno Principe, Division of Pediatric Hematology and Oncology, Department of Pediatrics, Universidade Federal do Paraná (UFPR), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Meharry Medical College, CPPI, Center for Research and Production of Immunoglobulins, Department of Hematology and Oncology and International Outreach Program, St Jude Children's Research Hospital, IPPP, Research Institute Pelé Pequeno Príncipe, and Fundação Araucária-PR, CAPES-COFECUB. American Lebanese Syrian Associated Charities (ALSAC), NIH/NCMHD
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Article Subject ,Health, Toxicology and Mutagenesis ,lcsh:Biotechnology ,Phosphatase ,lcsh:Medicine ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Embryonal carcinoma ,03 medical and health sciences ,0302 clinical medicine ,Affinity chromatography ,lcsh:TP248.13-248.65 ,Genetics ,Medicine ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Molecular Biology ,030304 developmental biology ,Tumor marker ,0303 health sciences ,biology ,business.industry ,lcsh:R ,General Medicine ,medicine.disease ,Molecular biology ,Enzyme assay ,Placental alkaline phosphatase ,Polyclonal antibodies ,030220 oncology & carcinogenesis ,Immunology ,embryonic structures ,biology.protein ,cardiovascular system ,Molecular Medicine ,Antibody ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Biotechnology ,Research Article - Abstract
Human placental (hPLAP) and germ cell (PLAP-like) alkaline phosphatases are polymorphic and heat-stable enzymes. This study was designed to develop specific immunoassays for quantifying hPLAP and PLAP-like enzyme activity (EA) in sera of cancer patients, pregnant women, or smokers. Polyclonal sheep anti-hPLAP antibodies were purified by affinity chromatography with whole hPLAP protein (ICA-PLAP assay) or a synthetic peptide (aa 57–71) of hPLAP (ICA-PEP assay); the working range was0.1–11U/L and cutoff value was0.2U/L EA for nonsmokers. The intra- and interassay coefficients of variation were3.7%–6.5% (ICA-PLAP assay) and9.0%–9.9% (ICA-PEP assay). An insignificant cross-reactivity was noted for high levels of unheated intestinal alkaline phosphatase in ICA-PEP assay. A positive correlation between the regression of tumor size and EA was noted in a child with embryonal carcinoma. It can be concluded that ICA-PEP assay is more specific than ICA-PLAP, which is still useful to detect other PLAP/PLAP-like phenotypes.
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- 2006
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25. Role of the cytoplasmic pattern recognition receptor Nod2 in Coxiella burnetii infection
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J. L. Mege, Peter J. Murray, Marie Benoit, Christian Capo, Yassina Bechah, Benoit Desnues, Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), St Jude Children's Research Hospital, INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), and Desnues, Benoit
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Microbiology (medical) ,Chemokine ,[SDV]Life Sciences [q-bio] ,Nod2 Signaling Adaptor Protein ,Microbiology ,Mice ,03 medical and health sciences ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,NOD2 ,Phagosome maturation ,Animals ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,Innate immune system ,biology ,030306 microbiology ,Pattern recognition receptor ,General Medicine ,Coxiella burnetii ,biology.organism_classification ,bacterial infections and mycoses ,Virology ,3. Good health ,[SDV] Life Sciences [q-bio] ,Disease Models, Animal ,TLR2 ,Infectious Diseases ,Receptors, Pattern Recognition ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,biology.protein ,TLR4 ,bacteria ,Q Fever - Abstract
Q fever is caused by Coxiella burnetii, an obligate intracellular bacterium, which survives in an acidic vacuole and escapes killing by preventing phagosome maturation [1]. In acute Q fever, granuloma formation is dependent on migration of leucocytes through the vascular endothelium. During chronic Q fever, granulomas are lacking and monocytes do not migrate across the endothelium [1], suggesting that host resistance against C. burnetii requires innate immune components. Toll-like receptors (TLRs) are pattern recognition receptors important in C. burnetii recognition. Although TLR4 ⁄) and control mice have a similar pattern of tissue infection and clearance, granuloma formation and cytokine response are controlled, in part, by TLR4 [1]. TLR2 is also involved in granuloma formation but seems dispensable for bacterial clearance [2]. The obligate intracellular lifestyle of C. burnetii drew our attention to elucidate the contribution of another family of proteins implicated in microbial detection, the cytoplasmic nucleotide-binding oligomerization domain (Nod) proteins, and more specifically Nod2, in innate immunity to C. burnetii. Nod2 contains leucine-rich repeats similar to those found in TLRs and is thought to be responsible for recognition of peptidoglycans from Gram positive and Gram negative bacteria through direct or indirect interaction with muramyl dipeptide. Nod2 signalling contributes to inflammatory response via activation of the transcription factor NF-jB, which is necessary for clearing pathogens. The intracellular localisation of Nod2 and C. burnetii makes Nod2 a potential candidate for C. burnetii recognition through leaking into the cytoplasm of muramyl dipeptide-containing cell wall fragments. Bone marrow-derived macrophages (BMDM) from control and Nod2 ⁄) mice [3] were incubated with C. burnetii for 4 h and cultured for 12 days. Infection was measured by determining the number of C. burnetii DNA copies as previously described [2]. Uptake and survival of C. burnetii in BMDM did not depend on Nod2 as DNA copy number was similar in control and Nod2 ⁄) BMDM (data not shown). Next, we tested whether the production of cytokines ⁄ chemokines by C. burnetii-stimulated BMDM required Nod2. We assessed the expression of genes encoding pro-inflammatory (TNF) and immunoregulatory cytokines (IL-10). BMDM were stimulated for 8 h with C. burnetii and gene expression was monitored by quantitative RTPCR [2]. In Nod2 ⁄) BMDM, although TNF transcripts were induced, they were significantly reduced compared with control macrophages (Fig. 1a). This result agrees with other studies showing that TNF and IL-12p40 levels are reduced in the absence of Nod2 after stimulation with Mycobacterium tuberculosis [4]. Note that IL10 was not affected by the absence of Nod2 (Fig. 1a). IL-10 is known to interfere with macrophage activation by stimulating the replication of C. burnetii through decreasing TNF production and blocking phagosomal maturation [1]. IL-10 is also associated with the chronic evolution of Q fever [1]. The absence of IL-10 modulation observed in Nod2 ⁄) BMDM is consistent with these data, as we did not observe any increase in bacterial replication. We also measured the expression of RANTES and MCP-1, two chemokines modulated in response to C. burnetii [5]. RANTES expression was fourfold increased in Nod2 ⁄) BMDM whereas MCP-1 expression was decreased by 40% (Fig. 1a). It is likely that RANTES and MCP-1 play a role in Q fever pathophysiology, as their production is Corresponding author and reprint requests: B. Desnues, CNRS UMR 6236, Faculte de Medecine de la Timone, 27 Bd J. Moulin, 13385 Marseille Cedex 05, France. E-mail: benoit.desnues@univmed.fr
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- 2009
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26. A Unified Nomenclature and Amino Acid Numbering for Human PTEN
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Seong-Seng Tan, Ramon Parsons, Nicholas K. Tonks, Paolo Pinton, Nicolas Wolff, Vrushank Davé, Rafael Malagoli Rocha, Britta J. Eickholt, Seung-Rock Lee, Rudiger Woscholski, Suzanne J. Baker, Arne Gericke, Hong Wu, Frank B. Furnari, Rafael Pulido, Maria Magdalena Georgescu, Jeroen den Hertog, Mathias Lösche, Benjamin D. Hopkins, Bangyan L. Stiles, María Molina, Manuel S. Rodriguez, João T. Barata, Manuel Serrano, Xeujun Jiang, Arkaitz Carracedo, Prerna Malaney, Xavier Matias-Guiu, Peter N. Devreotes, Vuk Stambolic, Akira Suzuki, Ian D. Chin-Sang, Víctor J. Cid, Lloyd C. Trotman, Charis Eng, Alonzo H. Ross, Nick R. Leslie, Pier Paolo Pandolfi, Carmen Rivas, BioCruces Research Institute, University of the Basque Country [Bizkaia] (UPV/EHU)-Hospital Universitario Cruces = Cruces University Hospital, Ikerbasque - Basque Foundation for Science, St Jude Children's Research Hospital, Instituto de Medicina Molecular (iMM), Faculdade de Medicina [Lisboa], Universidade de Lisboa (ULISBOA)-Universidade de Lisboa (ULISBOA), CIC BioGUNE, CIC Spain, University of the Basque Country [Bizkaia] (UPV/EHU), Instituto Ramon y Cajal de Investigacion Sanitaria [Madrid, Spain] (IRYCIS), Universidad de Alcalá - University of Alcalá (UAH), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Queen's University [Kingston, Canada], H. Lee Moffitt Cancer Center and Research Institute, Morsani College of Medicine [Tampa, USA], University of South Florida [Tampa] (USF), Hubrecht Institute [Utrecht, Netherlands], University Medical Center [Utrecht]-Royal Netherlands Academy of Arts and Sciences (KNAW), Institute Biology Leiden (IBL), Universiteit Leiden [Leiden], Johns Hopkins University School of Medicine [Baltimore], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genomic Medicine Institute [Cleveland], Cleveland Clinic, School of medicine [Cleveland, USA], Case Western Reserve University [Cleveland], Ludwig Institute for Cancer Research, University of Texas Southwestern Medical Center [Dallas], Worcester Polytechnic Institute, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Memorial Sloane Kettering Cancer Center [New York], Chonnam National University Medical School [Gwangju, South Korea], Chonnam National University [Gwangju], Carnegie Mellon University [Pittsburgh] (CMU), National Institute of Standards and Technology [Gaithersburg] (NIST), Arnau de Vilanova University Hospital [Lleida, Spain], Biomedical Research Institute of Lleida [Spain] (IRBLleida), Universitat de Lleida, Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Università degli Studi di Ferrara (UniFE), Centro Nacional de Biotecnología [Madrid] (CNB-CSIC), Biocomputing Unit [Madrid], Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas [Barcelona, Spain] (CiMUS-US), Universidade de Santiago de Compostela [Spain] (USC ), Instituto de Investigaciones Sanitarias, A. C. Camargo Hospital [São Paulo], Inbiomed [Spain], University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Spanish National Cancer Research Center (CNIO), University of Toronto, Princess Margaret Hospital, University Health Network, School of Pharmacy [USC, Los Angeles], University of Southern California (USC), Graduate School of Medicine [Akita, Japan], Akita University, University of Melbourne, Cold Spring Harbor Laboratory (CSHL), Résonance Magnétique Nucléaire des Biomolécules, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Chemistry [Imperial College London], Imperial College London, University of California [Los Angeles] (UCLA), University of California, Peking University [Beijing], Heriot-Watt University [Edinburgh] (HWU), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU)-Hospital Universitario Cruces = Cruces University Hospital, Universidade de Lisboa = University of Lisbon (ULISBOA)-Universidade de Lisboa = University of Lisbon (ULISBOA), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Universiteit Leiden, Università degli Studi di Ferrara = University of Ferrara (UniFE), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of California (UC), Hubrecht Institute for Developmental Biology and Stem Cell Research, and Repositório da Universidade de Lisboa
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MESH: Databases, Protein ,MESH: Terminology as Topic ,MESH: Amino Acids ,MESH: Codon, Initiator ,[SDV]Life Sciences [q-bio] ,Phosphatase ,Codon, Initiator ,ComputingMilieux_LEGALASPECTSOFCOMPUTING ,MESH: Amino Acid Sequence ,Oncogenicity ,Biochemistry ,MESH: PTEN Phosphohydrolase ,Germline ,Article ,Terminology as Topic ,PTEN ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Amino Acid Sequence ,Amino Acids ,Databases, Protein ,Molecular Biology ,Gene ,Peptide sequence ,PI3K/AKT/mTOR pathway ,Genetics ,chemistry.chemical_classification ,MESH: Humans ,biology ,PTEN Phosphohydrolase ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Cell Biology ,3. Good health ,Amino acid ,ComputingMilieux_GENERAL ,chemistry ,Cancer research ,biology.protein - Abstract
© Copyright 2015 by the American Association for the Advancement of Science; all rights reserved., The tumor suppressor PTEN is a major brake for cell transformation, mainly due to its phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] phosphatase activity that directly counteracts the oncogenicity of phosphoinositide 3-kinase (PI3K). PTEN mutations are frequent in tumors and in the germ line of patients with tumor predisposition or with neurological or cognitive disorders, which makes the PTEN gene and protein a major focus of interest in current biomedical research. After almost two decades of intense investigation on the 403-residue-long PTEN protein, a previously uncharacterized form of PTEN has been discovered that contains 173 amino-terminal extra amino acids, as a result of an alternate translation initiation site. To facilitate research in the field and to avoid ambiguities in the naming and identification of PTEN amino acids from publications and databases, we propose here a unifying nomenclature and amino acid numbering for this longer form of PTEN.
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