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151. Evidence for carry-over effects of predator exposure on pathogen transmission potential

Author

Thierry Lefèvre, Koudraogo B. Yameogo, Kounbobr Roch Dabiré, Frédéric Simard, Olivier Roux, Abdoulaye Diabaté, Benjamin Roche, Amélie Vantaux, Institut de Recherche en Sciences de la Santé (IRSS), CNRST, Diversity, ecology, evolution & Adaptation of arthropod vectors (MIVEGEC-DEEVA), Evolution des Systèmes Vectoriels (ESV), 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])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-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])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Institut de Recherche pour le Développement (IRD [France-Nord])-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Sorbonne Université (SU), Transmission-Interactions-Adaptations hôtes/vecteurs/pathogènes (MIVEGEC-TRIAD), O.R. received financial support through a post-doctoral fellowship from the IRD. Experimental infections were supported by the ANR grant no. 11-PDOC-006-01., and We thank the Associate Editor Dr Pejman Rohani and two anonymous reviewers for their valuable comments that greatly improved the manuscript. We thank Boubacar Nikiema for the RFLP-PCR, Jean Bazié and Raymond Hien for technical help with dissections and Andrea Yockey-Dejean for proofreading the paper.

Subjects
Male, life history, [SDV]Life Sciences [q-bio], Predation, Food chain, MESH: Malaria, Falciparum/transmission, MESH: Animals, Malaria, Falciparum, Life history, Predator, Pathogen, Research Articles, General Environmental Science, media_common, Ecology, Transmission potential, Longevity, General Medicine, Anopheles coluzzii, 3. Good health, carry-over effects, MESH: Larva/growth & development, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Anopheles/physiology, MESH: Longevity, Larva, Female, General Agricultural and Biological Sciences, Food Chain, media_common.quotation_subject, Plasmodium falciparum, MESH: Insect Vectors, Biology, General Biochemistry, Genetics and Molecular Biology, Competition (biology), MESH: Predatory Behavior, Heteroptera, MESH: Plasmodium falciparum/growth & development, Anopheles, parasitic diseases, Animals, Humans, MESH: Food Chain, host-parasite and predator-prey, MESH: Humans, General Immunology and Microbiology, fungi, MESH: Anopheles/growth & development, MESH: Heteroptera/physiology, MESH: Fertility, interactions, host–parasite and predator–prey interactions, MESH: Male, Insect Vectors, non-consumptive effects, MESH: Larva/physiology, Fertility, Predatory Behavior, MESH: Female
Abstract

Accumulating evidence indicates that species interactions such as competition and predation can indirectly alter interactions with other community members, including parasites. For example, presence of predators can induce behavioural defences in the prey, resulting in a change in susceptibility to parasites. Such predator-induced phenotypic changes may be especially pervasive in prey with discrete larval and adult stages, for which exposure to predators during larval development can have strong carry-over effects on adult phenotypes. To the best of our knowledge, no study to date has examined possible carry-over effects of predator exposure on pathogen transmission. We addressed this question using a natural food web consisting of the human malaria parasite Plasmodium falciparum , the mosquito vector Anopheles coluzzii and a backswimmer, an aquatic predator of mosquito larvae. Although predator exposure did not significantly alter mosquito susceptibility to P. falciparum , it incurred strong fitness costs on other key mosquito life-history traits, including larval development, adult size, fecundity and longevity. Using an epidemiological model, we show that larval predator exposure should overall significantly decrease malaria transmission. These results highlight the importance of taking into account the effect of environmental stressors on disease ecology and epidemiology.

Published
2015

152. Risk of brain tumours in relation to estimated RF dose from mobile phones: results from five Interphone countries

Author

Lynne D. Richardson, Elisabeth Cardis, Martine Vrijheid, Alistair Woodward, Graham G. Giles, Rodrigo Villegas, Jordi Figuerola, Marie-Élise Parent, Daniel Krewski, Bruce K. Armstrong, Martine Hours, Julianne Brown, Avital Jarus-Hakak, L. Montestruq, Louise Nadon, Angela Chetrit, Chen Hoffmann, Siegal Sadetzki, Mary L. McBride, Joseph D. Bowman, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Sydney School of Public Health, The University of Sydney, Engineering and Physical Hazards Branch, National Institute for Occupational Safety and Health, Cancer Epidemiology Centre, Cancer Council Victoria, Centre for MEGA Epidemiology, University of Melbourne-School of Population Health, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), McLaughlin Centre for Population Health Risk Assessment, University of Ottawa [Ottawa], BC Cancer Research Centre, BC Cancer Agency (BCCRC), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Cancer and Radiation Epidemiology Unit, Chaim Sheba Medical Center-Gertner Institute, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], School of Population Health, University of Auckland [Auckland], Department of Diagnostic Imaging, Chaim Sheba Medical Center, Department of Population health, Hospital Research Centre-University of Montreal, Funding for the Interphone Study was provided by the European Fifth Framework Program, 'Quality of Life and Management of Living Resources' (contract QLK4-CT-1999901563), the International Union against Cancer (UICC). The UICC received funds for this purpose from the Mobile Manufacturers' Forum and GSM Association. Provision of funds to the Interphone Study investigators via the UICC was governed by agreements that guaranteed Interphone's complete scientific independence. The terms of these agreements are publicly available at http://www.iarc.fr/en/research-groups/RAD/RCAd.html Specific additional funds were provided for the development and analysis of the radio frequency exposure gradient and by the Fondation Santé et Radiofréquences, France and the Bundesamt fuer Strahlenschutz, Germany. The Australian centre was supported by the National Health and Medical Research Council (EME grant 219129), and BKA was supported by the University of Sydney Medical Foundation Program Grant and Julianne Brown by an Australian Postgraduate Award. The Cancer Council NSW and the Cancer Council Victoria provided most of the infrastructure for the project in Australia. The Canada-Montréal data collection was funded by a grant from the Canadian Institutes of Health Research (project MOP-42525). Additionally, Dr Siemiatycki's research team was partly funded by the Canada Research Chair programme and by the Guzzo-CRS Chair in Environment and Cancer. Dr. Parent had salary support from the Fonds de recherche en santé du Québec. The other Canadian centres were supported by a universityeindustry partnership grant from the Canadian Institutes of Health Research (CIHR), the latter including partial support from the Canadian Wireless Telecommunications Association. The CIHR universityeindustry partnerships program also includes provisions that ensure complete scientific independence of the investigators. DK is the NSERC/SSHRC/McLaughlin Chair in Population Health Risk Assessment at the University of Ottawa. Additional funding for the study in France was provided by l'Association pour la Recherche sur le Cancer (ARC) (contract 5142) and three network operators (Orange, SFR, Bouygues Télécom). The funds provided by the operators represented 5% of the total cost of the French study and were governed by contracts guaranteeing the complete scientific independence of the investigators. In New Zealand, funding was provided by the Health Research Council, Hawkes Bay Medical Research Foundation and the Cancer Society of New Zealand. The findings and conclusions in this paper have not been formally disseminated by the National Institute for Occupational Safety and Health and should not be construed to represent any agency determination or policy.

Subjects
Oncology, Male, epidemiological study, MESH: Neoplasms, Radiation-Induced, Neoplasms, Radiation-Induced, Radio Waves, non-ionising radiation, MESH: Logistic Models, MESH: Meningioma, MESH: Radio Waves, MESH: Electromagnetic Fields, MESH: Glioma, 0302 clinical medicine, MESH: New Zealand, MESH: Risk Factors, Mobile phones, 030212 general & internal medicine, MESH: Middle Aged, ionising radiation, Brain Neoplasms, MESH: Israel, risk assessment, Brain, MESH: Case-Control Studies, RF exposure assessment, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, Original Article, epidemiology, Female, physics, Algorithms, electromagnetic fields, medicine.medical_specialty, MESH: Radiation Dosage, Rf exposure, MESH: Australia, MESH: Algorithms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Radiation Dosage, Meningioma, 03 medical and health sciences, MESH: Canada, Glioma, Internal medicine, medicine, cancer, Humans, MESH: Humans, business.industry, MESH: Time Factors, Public Health, Environmental and Occupational Health, Case-control study, MESH: Adult, Odds ratio, medicine.disease, MESH: Meningeal Neoplasms, hygiene/occupational hygiene, MESH: Male, MESH: Odds Ratio, Surgery, nervous system diseases, MESH: France, Increased risk, Multicenter study, MESH: Cellular Phone, business, MESH: Female, Cell Phone
Abstract

International audience; OBJECTIVES: The objective of this study was to examine the associations of brain tumours with radio frequency (RF) fields from mobile phones. METHODS: Patients with brain tumour from the Australian, Canadian, French, Israeli and New Zealand components of the Interphone Study, whose tumours were localised by neuroradiologists, were analysed. Controls were matched on age, sex and region and allocated the 'tumour location' of their matched case. Analyses included 553 glioma and 676 meningioma cases and 1762 and 1911 controls, respectively. RF dose was estimated as total cumulative specific energy (TCSE; J/kg) absorbed at the tumour's estimated centre taking into account multiple RF exposure determinants. RESULTS: ORs with ever having been a regular mobile phone user were 0.93 (95% CI 0.73 to 1.18) for glioma and 0.80 (95% CI 0.66 to 0.96) for meningioma. ORs for glioma were below 1 in the first four quintiles of TCSE but above 1 in the highest quintile, 1.35 (95% CI 0.96 to 1.90). The OR increased with increasing TCSE 7+ years before diagnosis (p-trend 0.01; OR 1.91, 95% CI 1.05 to 3.47 in the highest quintile). A complementary analysis in which 44 glioma and 135 meningioma cases in the most exposed area of the brain were compared with gliomas and meningiomas located elsewhere in the brain showed increased ORs for tumours in the most exposed part of the brain in those with 10+ years of mobile phone use (OR 2.80, 95% CI 1.13 to 6.94 for glioma). Patterns for meningioma were similar, but ORs were lower, many below 1.0. CONCLUSIONS: There were suggestions of an increased risk of glioma in long-term mobile phone users with high RF exposure and of similar, but apparently much smaller, increases in meningioma risk. The uncertainty of these results requires that they be replicated before a causal interpretation can be made.

Published
2011

153. p53 regulates epithelial–mesenchymal transition through microRNAs targeting ZEB1 and ZEB2

Author

Young-Jun Jeon, Flavia Pichiorri, Angelo Veronese, Pascal Pineau, Anne Dejean, Tae Jin Lee, Hansjuerg Alder, Agnès Marchio, Stefano Volinia, Taewan Kim, Jeff Palatini, Chang Gong Liu, Sung Suk Suh, Carlo M. Croce, Comprehensive Cancer Center [Colombus], Ohio State University [Columbus] (OSU), Molecular, Cellular, and Developmental Biology Program [Columbus] (MCDB), Organisation Nucléaire et Oncogenèse, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was funded by National Cancer Institute grant RC2 CA148302., We thank Dr. B. Vogelstein for p53+/+ and p53−/− RKO cells, Dr. Gustavo Leone for p53+/+ and p53−/− MEFs, Dr. Gregory J. Goodall for pCIneo-hRL-ZEB1/2 constructs, and Dr. Anders H. Lund for pcDNA3-Zeb2-HA constructs. We also thank Dr. Kay Huebner (The Ohio State University), Dr. Thomas D. Schmittgen (The Ohio State University), and Susan Lutz for careful editing of this paper, and Sharon Palko and Dorothee Wernicke-Jameson for the administrative support., Pineau, Pascal, and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: Zinc Finger E-box-Binding Homeobox 1, genetics/metabolism, biosynthesis/genetics, Metastasis, genetics/metabolism/pathology, 0302 clinical medicine, MESH: Liver Neoplasms, Immunology and Allergy, genetics, RNA, Neoplasm, Neoplasm Metastasis, MESH: Carcinoma, Hepatocellular, MESH: Tumor Suppressor Protein p53, 0303 health sciences, digestive, oral, and skin physiology, Liver Neoplasms, Hep G2 Cells, MESH: Gene Expression Regulation, Neoplastic, MESH: Transcription Factors, Gene Expression Regulation, Neoplastic, MESH: Repressor Proteins, 030220 oncology & carcinogenesis, embryonic structures, Female, Transcriptional Activation, Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, Immunology, Repressor, MESH: Hep G2 Cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, MESH: Gene Expression Profiling, [SDV.CAN] Life Sciences [q-bio]/Cancer, microRNA, MESH: Homeodomain Proteins, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Epithelial–mesenchymal transition, Transcription factor, Zinc Finger E-box Binding Homeobox 2, 030304 developmental biology, MESH: Zinc Finger E-box Binding Homeobox 2, Homeodomain Proteins, Neoplastic, MESH: Humans, Gene Expression Profiling, Carcinoma, Brief Definitive Report, Zinc Finger E-box-Binding Homeobox 1, Hepatocellular, Cell Biology, HCCS, medicine.disease, MESH: RNA, Neoplasm, MESH: Neoplasm Metastasis, MESH: Male, Repressor Proteins, Gene expression profiling, MicroRNAs, MESH: Epithelial-Mesenchymal Transition, Gene Expression Regulation, Tumor progression, Cancer research, RNA, Neoplasm, MESH: Transcriptional Activation, genetics/metabolism/pathology, Epithelial-Mesenchymal Transition, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Hep G2 Cells, Homeodomain Proteins, biosynthesis/genetics, Humans, Liver Neoplasms, genetics/metabolism/pathology, Male, MicroRNAs, genetics/metabolism, Neoplasm Metastasis, RNA, genetics/metabolism, Repressor Proteins, biosynthesis/genetics, Transcription Factors, biosynthesis/genetics, Transcriptional Activation, genetics, Tumor Suppressor Protein p53, Tumor Suppressor Protein p53, MESH: Female, MESH: MicroRNAs, 030215 immunology, Transcription Factors
Abstract

By transactivating expression of miRNAs that repress expression of the ZEB1 and ZEB2 transcription factors, p53 inhibits the epithelial–mesenchymal transition., p53 suppresses tumor progression and metastasis. Epithelial–mesenchymal transition (EMT) is a key process in tumor progression and metastasis. The transcription factors ZEB1 and ZEB2 promote EMT. Here, we show that p53 suppresses EMT by repressing expression of ZEB1 and ZEB2. By profiling 92 primary hepatocellular carcinomas (HCCs) and 9 HCC cell lines, we found that p53 up-regulates microRNAs (miRNAs), including miR-200 and miR-192 family members. The miR-200 family members transactivated by p53 then repress ZEB1/2 expression. p53-regulated miR-192 family members also repress ZEB2 expression. Inhibition or overexpression of the miRNAs affects p53-regulated EMT by altering ZEB1 and ZEB2 expression. Our findings indicate that p53 can regulate EMT, and that p53-regulated miRNAs are critical mediators of p53-regulated EMT.

Published
2011

154. A computational framework for gene regulatory network inference that combines multiple methods and datasets

Author

Philipp Antczak, Anna Stincone, Sarah Durant, Francesco Falciani, Andreas Bikfalvi, Rita Gupta, Roy Bicknell, School of Biosciences, University of Birmingham [Birmingham], Institute of Biomedical Research, Mecanismes Moleculaires de l'Angiogenese, Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), The work described in this paper was funded by the CRUK grant C8504/A9488 and partially funded by the BBSRC grant BBC5151041. AS is a recipient of a Darwin Trust PhD fellowship and PA is a recipient of a BBSRC PhD studentship., BMC, Ed., and Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: Hydrogen-Ion Concentration, Time Factors, Gene regulatory network, Inference, Multiple methods, computer.software_genre, 0302 clinical medicine, Structural Biology, Gene regulatory network inference, Neoplasms, MESH: Gene Silencing, MESH: Neoplasms, Gene Regulatory Networks, MESH: Stress, Physiological, lcsh:QH301-705.5, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Gene Regulatory Networks, Genetics, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Escherichia coli, Applied Mathematics, Systems Biology, Methodology Article, Hydrogen-Ion Concentration, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer Science Applications, Modeling and Simulation, MESH: Systems Biology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Reverse engineering, MESH: Cell Line, Tumor, Systems biology, Biology, Machine learning, Models, Biological, 03 medical and health sciences, Stress, Physiological, Modelling and Simulation, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Cell Line, Tumor, Escherichia coli, Humans, Gene Silencing, Molecular Biology, 030304 developmental biology, MESH: Humans, business.industry, MESH: Time Factors, Ode, MESH: Models, Biological, lcsh:Biology (General), Time course, Artificial intelligence, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, computer, 030217 neurology & neurosurgery
Abstract

Background Reverse engineering in systems biology entails inference of gene regulatory networks from observational data. This data typically include gene expression measurements of wild type and mutant cells in response to a given stimulus. It has been shown that when more than one type of experiment is used in the network inference process the accuracy is higher. Therefore the development of generally applicable and effective methodologies that embed multiple sources of information in a single computational framework is a worthwhile objective. Results This paper presents a new method for network inference, which uses multi-objective optimisation (MOO) to integrate multiple inference methods and experiments. We illustrate the potential of the methodology by combining ODE and correlation-based network inference procedures as well as time course and gene inactivation experiments. Here we show that our methodology is effective for a wide spectrum of data sets and method integration strategies. Conclusions The approach we present in this paper is flexible and can be used in any scenario that benefits from integration of multiple sources of information and modelling procedures in the inference process. Moreover, the application of this method to two case studies representative of bacteria and vertebrate systems has shown potential in identifying key regulators of important biological processes.

Published
2011

155. Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murine model of peritoneal carcinomatosis

Author

Patrick Rat, Hervé Tixier, François Radais, Delphine Delroeux, François Ghiringhelli, Sylvain Ladoire, Olivier Facy, Pablo Ortega-Deballon, Bruno Chauffert, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Chirurgie Digestive [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), This paper was supported by grants from the French National League against Cancer (Committees of Saône et Loire, Nièvre, and Côte d'Or)., BMC, Ed., Service de chirurgie digestive et cancérologie, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service de chirurgie digestive [Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Service d'oncologie médicale, and CHU Amiens-Picardie

Subjects
MESH : Hyperthermia, Induced, MESH : Rats, Inbred Strains, Cancer Research, Pathology, Pharmacology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Peritoneal Neoplasm, 0302 clinical medicine, MESH : Tumor Cells, Cultured, Tumor Cells, Cultured, Medicine, MESH: Peritoneal Neoplasms, MESH : Female, MESH: Animals, Peritoneal Neoplasms, Ovarian Neoplasms, MESH : Cell Survival, 0303 health sciences, MESH : Rats, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, MESH: Rats, Inbred Strains, 3. Good health, MESH : Antineoplastic Agents, MESH: Ovarian Neoplasms, Epinephrine, Oncology, MESH: Cell Survival, 030220 oncology & carcinogenesis, Female, medicine.drug, Hyperthermia, medicine.medical_specialty, MESH: Rats, Cell Survival, MESH: Epinephrine, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, MESH : Cisplatin, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH : Peritoneal Neoplasms, In vivo, Animals, Humans, MESH: Tumor Cells, Cultured, MESH: Hyperthermia, Induced, 030304 developmental biology, Cisplatin, MESH: Humans, MESH : Ovarian Neoplasms, business.industry, Research, MESH : Humans, Rats, Inbred Strains, Hyperthermia, Induced, medicine.disease, MESH : Disease Models, Animal, Rats, Disease Models, Animal, MESH: Cisplatin, Apoptosis, MESH : Epinephrine, Cancer cell, MESH: Antineoplastic Agents, MESH : Animals, MESH: Disease Models, Animal, business, Ovarian cancer, MESH: Female
Abstract

Background The best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis. Methods Four groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured in vivo (tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and in vitro (cytotoxicity on human ovarian cancer cells). Results In vitro, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. In vivo, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia. Conclusion Adrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.

Published
2011

156. Malaria risk in Corsica, former hot spot of malaria in France

Author

Gilbert Le Goff, Céline Toty, Hélène Barré, Daniel Couret, Nil Rahola, Didier Fontenille, Isabelle Larget-Thiery, Caractérisation et contrôle des populations de vecteurs, Institut de Recherche pour le Développement (IRD), Direction de la Solidarité et de la Santé de Corse et de Corse-du-Sud, Sciences pour l'environnement (SPE), Centre National de la Recherche Scientifique (CNRS)-Université Pascal Paoli (UPP), Centre de Production et Infection des Anophèles (plateforme) - Center for the Production and Infection of Anopheles (platform) (CEPIA), Institut Pasteur [Paris], The paper is catalogued by the EDEN Steering Committee as EDEN 232 http://www.eden-fp6project.net/., Université Pascal Paoli (UPP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Centre de Production et Infection des Anophèles (Plateforme) (CEPIA)

Subjects
Risk, Entomology, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Plasmodium vivax, Plasmodium falciparum, MESH: Malaria, Zoology, MESH: Insect Vectors, Biology, Plasmodium, Polymerase Chain Reaction, lcsh:Infectious and parasitic diseases, MESH: Anopheles, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Anopheles, parasitic diseases, medicine, Animals, Humans, MESH: Animals, lcsh:RC109-216, MESH: Plasmodium falciparum, 0303 health sciences, MESH: Humans, MESH: Risk, 030306 microbiology, Ecology, Research, Outbreak, MESH: Polymerase Chain Reaction, medicine.disease, biology.organism_classification, 3. Good health, Insect Vectors, Malaria, MESH: Plasmodium vivax, MESH: France, Infectious Diseases, Parasitology, France
Abstract

Background The prevalence of Plasmodium falciparum and Plasmodium vivax malaria was very high in Corsica just before the Second World War. The last outbreak was in 1972 and the most recent indigenous case was in 2006. Results Analysis of historical data shows that anopheline vectors were abundant. Recent surveys demonstrated that potential vectors are still present in Corsica, despite the likely disappearance of Anopheles sacharovi. Moreover, P. falciparum can develop experimentally into these mosquitoes, notably Anopheles labranchiae, which is locally abundant, and parasites are regularly introduced into the island. Discussion, Conclusions The presence of vectors, the introduction of parasites and the conducive climate raise questions about the possibility of malaria re-emerging and becoming re-established in Corsica. Analysis of historic and current parasitological and entomological data shows that the current theoretical risk of indigenous cases or malaria foci is negligible, particularly since there is very little contact between humans and Anopheles mosquitoes, Plasmodium carriers are reliably treated and there is a widespread vector control on the island.

Published
2010

157. Mucin CYS domains are ancient and highly conserved modules that evolved in concert

Author

Jean-Luc Desseyn, Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut de médecine predictive et de recherche thérapeutique (IMPRT), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille 2 - Faculté de Médecine, The author gratefully acknowledges Dr. V. Gouyer (INSERM U795 and EA3925, Lille, France) and Pr. F. Gottrand (EA3925, University of Lille, France) for their critical comments. The author is indebted to Dr. P. Amieux (University of Washington, Seattle, WA) for help in improving the style of the paper., Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Faculté de Médecine Henri Warembourg - Université de Lille, and Lille Inflammation Research International Center - U 995 [LIRIC]

Subjects
MESH: Sequence Analysis, DNA, Animals, Conserved Sequence, Cysteine, Evolution, Molecular, Exons, Humans, Mucins, Phylogeny, Protein Interaction Domains and Motifs, Sequence Alignment, Sequence Analysis, DNA, [SDV]Life Sciences [q-bio], CYS domain, Genome, MUC5B, Exon, 0302 clinical medicine, Gel-forming mucin, MESH: Animals, MESH: Phylogeny, Genetics, 0303 health sciences, Concerted evolution, MESH: Conserved Sequence, Biochemistry, Coding repeats, MESH: Sequence Alignment, Biology, Evolution, Molecular, 03 medical and health sciences, MESH: Evolution, Molecular, MESH: Mucins/genetics, Amino acid residue, Molecular Biology, Gene, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, MESH: Protein Interaction Domains and Motifs, MESH: Humans, MESH: Mucins/metabolism, Mucin, Sequence Analysis, DNA, MUC5AC, MESH: Cysteine/genetics, Mucus, MUC2, MESH: Exons, 030217 neurology & neurosurgery, Function (biology)
Abstract

International audience; Background : Many large secreted gel-forming mucins contain multiple copies of a "naked" cysteine-enriched domain (CYS domain) that interrupt or are adjacent to mucin domains (Ser/Thr/Pro regions). There is less similarity of homologous CYS sequences between species than there is across CYS repeats within species. These CYS domains are likely implicated in reversible mucin-mucin interactions that play a central role in mucus properties. Results : The use of multiple genome sequences in a comparative analysis of CYS sequences identified new mucins containing the CYS domain in various species. Furthermore, analysis showed that this domain is at least 650 million-year old and that CYS sequences evolved under strong selective pressure in concerted fashion in all species examined by two mechanisms that never coexist within a given gene: either multiplication of exons encoding CYS modules or successive intra-exonic duplications. Conclusion : The CYS sequences appear to have undergone concerted evolution with a high selective pressure to conserve cysteine and other amino acid residues. This domain is the best-conserved domain in secreted mucins pointing toward an important common function in many different organisms.

Published
2008

158. Direct activation of caspase 8 by the proapoptotic E2 protein of HPV18 independent of adaptor proteins

Author

Caroline Demeret, Françoise Thierry, Expression Génétique et Maladies (EGM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Pasteur Institute, CNRS, Association pour la Recherche sur le Cancer (ARC) and La Ligue Contre le Cancer., We thank Moshe Yaniv and Jonathan Weitzman for critical reading of the paper. We thank Richard Siegel, Marcus Peter, Visha Dixit and Richard Kitsis for providing expression plasmids., and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Cytoplasm, Death fold, Fas-Associated Death Domain Protein, Caspase 2, Caspase 3, Apoptosis, Biology, Caspase 8, Protein Structure, Secondary, Cell Line, 03 medical and health sciences, Viral Proteins, Humans, FADD, Molecular Biology, 030304 developmental biology, 0303 health sciences, NLRP1, 030302 biochemistry & molecular biology, Cell Biology, Oncogene Proteins, Viral, Cell biology, Enzyme Activation, Death-inducing signaling complex, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Caspase 10
Abstract

International audience; The self-activation of initiator caspases is dependent on their oligomerization driven by interaction with the death fold domains (DFD) of adaptor proteins. Here, we show that the E2 protein of human papillomavirus type 18 triggers apoptosis by assembling cytoplasmic filaments together with caspase 8, in which its efficient self-activation occurs. The E2 protein binds directly to the death effector domains (DED) of caspase 8 through non-DFD interaction. This interaction is independent of FADD, but it can cooperate with FADD homotypic binding to caspase 8 to induce its oligomerization; hence cell death, while it is antagonized by competitive binding of MC159 FLICE inhibitory protein. The amino-terminal domain of E2 contains a 27 amino-acid a-helix, which is necessary and sufficient to induce caspase oligomerization and cell death. Our results provide evidence for adaptor-independent oligomerization of caspase 8, mediated by non-DFD direct interactions with the HPV18 E2 protein, thus deciphering a new pathway for caspase 8 activation.

Published
2008

159. Characterization of Staphylococcus aureus strains associated with food poisoning outbreaks in France

Author

Jacques-Antoine Hennekinne, Annaëlle Kerouanton, L. Petit, C. Letertre, Anne Brisabois, O. Chesneau, M.L. De Buyser, Agence Française de Sécurité Sanitaire des Aliments (AFSSA), Agents antibactériens, Institut Pasteur [Paris], We acknowledge the technical assistance of Trinh Tam Dao, Marie-Odile Delbart, Muriel Marault, and Anne Morvan. We dedicate this paper to the memory of Névine El Solh who contributed to the phage-typing and who passed away in January 2005., and Institut Pasteur [Paris] (IP)

Subjects
Salmonella, Enterotoxin, MESH: Base Sequence, medicine.disease_cause, SmaI, Disease Outbreaks, MESH: Genotype, Enterotoxins, Genotype, MESH: Staphylococcus aureus, MESH: Enterotoxins, Cluster Analysis, MESH: Disease Outbreaks, MESH: Phylogeny, Phylogeny, 2. Zero hunger, 0303 health sciences, General Medicine, PFGE, 3. Good health, Electrophoresis, Gel, Pulsed-Field, Phenotype, MESH: Electrophoresis, Gel, Pulsed-Field, Staphylococcus aureus, MESH: Staphylococcal Food Poisoning, France, Staphylococcal Food Poisoning, Food Contamination, Biology, MESH: Phenotype, Microbiology, Food-poisoning, 03 medical and health sciences, medicine, Pulsed-field gel electrophoresis, Humans, MESH: Food Microbiology, 030304 developmental biology, MESH: Humans, Base Sequence, 030306 microbiology, Outbreak, MESH: Food Contamination, MESH: Cluster Analysis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: France, Food Microbiology, Food Science
Abstract

International audience; Enterotoxins produced by Staphylococcus aureus are responsible for staphylococcal food-poisoning outbreaks (SFPO). In France, SFPO are the second cause of food-borne diseases after Salmonella. However, very little is known about the strains involved. The objective of this study was to characterize the staphylococcal strains related to these SFPO through phenotypic and genotypic analyses. A total of 178 coagulase-positive staphylococcal isolates recovered from 31 SFPO (1981-2002) were screened through biotyping. Thirty-three strains representative of the different biotypes in each SFPO were further examined for SmaI macrorestriction-type, phage-type, resistance to various antimicrobial drugs, presence of staphylococcal enterotoxin (se) genes sea to sei, and production of enterotoxins SEA to SED. All these 33 strains were identified as S. aureus species: 27 were of human biotypes and six ovine or non-host-specific biotypes. Most (74.1%) strains reacted with group III phages. Eleven strains were resistant to at least two classes of antibiotics and among them, two were resistant to methicillin. Twenty-nine strains carried one or several of the eight se genes tested; the gene sea was most common (n=23), and often linked to sed (n=12) or seh (n=5). The novel se genes seg-i were in all cases associated with se genes sea to sed except for one strain which carried only seg and sei. Pulsed-Field Gel Electrophoresis (PFGE) of SmaI macrorestriction digests of the 33 strains discriminated 32 PFGE patterns grouped into nine biotype-specific clusters. All five strains carrying sea and seh were grouped together into the same sub-cluster. Three of the four se-gene-negative strains were in one PFGE cluster: all four should be tested for se genes not included in this study and, if negative, be further investigated for the presence of unidentified SEs.

Published
2007

160. Trends in self-reported past alcoholic beverage consumption and ethanol intake from 1950 to 1995 observed in eight European countries participating in the European Investigation into Cancer and Nutrition (EPIC)

Author

J. Linseisen, Françoise Clavel-Chapelon, Calogero Saieva, Heiner Boeing, Magritt Brustad, Aurelio Barricarte, Fabrizio Veglia, Matthias B. Schulze, P. H. M. Peeters, Nadia Slimani, C. Martínez Garcia, Göran Berglund, Ulrich Keil, Elio Riboli, Merethe Kumle, A. Papadimitrou, Kim Overvad, Pagona Lagiou, H. B. Bueno-De-Mesquita, Naomi E. Allen, Lars Weinehall, Kerstin Klipstein-Grobusch, Anne Tjønneland, Pietro Ferrari, Angela A. Mulligan, Vittorio Krogh, Anne C. M. Thiébaut, [Klipstein-Grobusch,K, Boeing,H, Schulze,MB] Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany. [Slimani,N, Ferrari,P, Riboli,E] Unit of Nutrition and Cancer, International Agency for Cancer Research, Lyon, France. [Krogh,V] Epidemiology Unit, National Cancer Institute, Milan, Italy. [Keil,U] Department of Epidemiology and Social Medicine, University of Münster, German. [Overvad,K] Department of Epidemiology, University of Aarhus, Denmark. [Tjønneland,A] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Clavel-Chapelon,F, Thiébaut,A] INSERM, E3N–EPIC Group, Institute Gustave Roussy, Villejuif, France. [Linseisen,J] Department of Clinical Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Lagiou,P, Papadimitrou,A] Department of Hygiene and Epidemiology, School of Medicine, University of Athens, Greece. [Saieva,C] Molecular and Nutritional Epidemiology Unit, CSPO, Scientific Institute of Tuscany, Florence, Italy. [Veglia,F] Institute for Scientific Interchange Foundation, Turin, Italy. [Bueno-de-Mesquita,HB] Department for Chronic Disease Epidemiology, National Institute for Public Health and Environmental Protection, Bilthoven, The Netherlands. [Peeters,PHM] Julius Center for General Practice and Patient Oriented Research, University of Utrecht, The Netherland. [Kumle,M, Brustad,M] Institute of Community Medicine, University of Tromsø, Norway. [Martínez García,C] Andalusian School of Public Health, Granada, Spain. [Barricarte,A] Department of Epidemiology, Institute of Public Health of Navarra, Spain. [Berglund,G] Department of Medicine, Lund University, Malmö, Sweden. [Weinehal,G] Epidemiology, Public Health and Clinical Medicine, Umea University, Sweden. [Mulligan,A] Department of Public Health and Primary Care, University of Cambridge, UK. [Allen,N] Cancer Research UK, Cancer Epidemiology Unit, University of Oxford, UK., The work described in this paper was carried out with financial support of the ‘Europe Against Cancer’ Programme of the European Commission (SANCO), Ligue contre le Cancer (France), Société 3M (France), Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM), Institute Gustave Roussy, German Cancer Aid, German Cancer Research Centre, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health, the Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, Cancer Research UK, Medical Research Council, UK, Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, Wellcome Trust, UK, Greek Ministry of Health, Greek Ministry of Education, Italian Association for Research on Cancer, Italian National Research Council, Dutch Ministry of Public Health,Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane, Sweden, Norwegian Cancer Society, and Norwegian Research Council. Partial support for the publication of this supplement was provided by the Centre de Recherche et d’Information Nutritionnelles (CERIN).

Subjects
Male, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], Medicine (miscellaneous), Wine, Distribución por Edad, Estudios Retrospectivos, EPIC, Consumo de Bebidas Alcohólicas, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Recuerdo Mental, Technology, Industry, Agriculture::Food and Beverages::Beverages::Alcoholic Beverages::Beer [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Population Surveillance [Medical Subject Headings], Medicine, Masculino, 24-Hour dietary recall, Nutrition and Dietetics, Adulto, Femenino, Vino, Beer, Geographicals::Geographic Locations::Europe [Medical Subject Headings], Time trends, European Prospective Investigation into Cancer and Nutrition, Humanos, Europe, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], Disciplines and Occupations::Social Sciences::Demography::Sex Distribution [Medical Subject Headings], Population Surveillance, Cerveza, Female, Distribución por Sexo, Adult, Alcohol Drinking, Estudios Transversales, Check Tags::Male [Medical Subject Headings], Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::Memory::Mental Recall [Medical Subject Headings], Spirits, Age Distribution, Environmental health, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Humans, Europa (Continente), ddc:610, Disciplines and Occupations::Social Sciences::Demography::Age Distribution [Medical Subject Headings], Sex Distribution, Retrospective Studies, Consumption (economics), Ethanol, business.industry, Public Health, Environmental and Occupational Health, Alcoholic beverage consumption, Vigilancia de la Población, Technology, Industry, Agriculture::Food and Beverages::Beverages::Alcoholic Beverages::Wine [Medical Subject Headings], EPIC study, Cross-Sectional Studies, Check Tags::Female [Medical Subject Headings], Mental Recall, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], Alcoholic beverages, Ethanol intake, business, Cross-sectional analyses
Abstract

Objective:To describe the trends of self-reported past consumption of alcoholic beverages and ethanol intake from 1950 to 1995 within the European Prospective Investigation into Cancer and Nutrition (EPIC).Design:Data on consumption of beer/cider, wine and liqueur/spirits were obtained retrospectively at age 20, 30 and 40 years to calculate average consumption and ethanol intake for the time periods 1950–1975 (at age 20), 1960–1985 (at age 30) and 1970–1995 (at age 40). Regression analysis was conducted with the time period data to assess trends in past alcoholic beverage consumption and ethanol intake with time.Setting:The EPIC project.Subjects:In total, 392 064 EPIC participants (275 249 women and 116 815 men) from 21 study centres in eight European countries.Results:Generally, increases in beer/cider consumption were observed for most EPIC centres for 1950–1975, 1960–1985 and 1970–1995. Trends in wine consumption differed according to geographical location: downward trends with time were observed for men in southern European EPIC centres, upward trends for those in middle/northern European study centres. For women, similar but less pronounced trends were observed. Because wine consumption was the major contributor to ethanol intake for both men and women in most study centres, time trends for ethanol intake showed a similar geographical pattern to that of wine consumption.Conclusion:The different trends in alcoholic beverage consumption and ethanol intake suggest that information depicting lifetime history of ethanol intake should be included in analyses of the relationship between ethanol and chronic diseases, particularly in multi-centre studies such as EPIC.

Published
2002

161. Human mucin gene MUC5B, the 10.7-kb large central exon encodes various alternate subdomains resulting in a super-repeat. Structural evidence for a 11p15.5 gene family

Author

J L, Desseyn, V, Guyonnet-Dupérat, N, Porchet, J P, Aubert, A, Laine, Biologie et Physiopathologie des Cellules Mucipares (u377), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Biochimie [Hopital Huriez, Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), This work was supported by 'La Ligue contre le Cancer,' 'l'Association de Recherche contre le Cancer,' and 'l'Association Française de Lutte contre la Mucoviscidose.' The costs of publication of this article were defrayed in part by the payment of page charges., The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) Z72496[GenBank] (HSMUC5BEX)., and Lille Inflammation Research International Center - U 995 [LIRIC]

Subjects
Base Sequence, Nucleic Acid, Amino Acid Sequence, Blotting, Southern, DNA, Exons, Humans, Molecular Sequence Data, Mucin-5B, Mucins, Peptide Mapping, Repetitive Sequences, Restriction Mapping, Sequence Alignment, [SDV]Life Sciences [q-bio], Blotting, Southern, Repetitive Sequences, Nucleic Acid
Abstract

The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.; International audience; Human mucin gene MUC5B is mapped clustered with MUC6, MUC2, and MUC5AC on chromosome 11p15.5. We report here the isolation of three overlapping genomic clones of human MUC5B spanning approximately 40 kilobases. We have determined their partial restriction maps and the intron-exon boundaries of the central region encoding a single open reading frame. This coding region has been completely sequenced. Its length is 10,713 base pairs, and it encodes a 3570-amino acid peptide. Nineteen subdomains have been individualized. Some subdomains show similarity to each other, creating larger composite repeat units that we have called super-repeats. Four super-repeats of 528 amino acid residues are thus observed within the central exon. Each comprises (i) a subdomain composed of 11 repeats of the irregular repeat of 29 amino acid residues, (ii) a unique conserved subdomain with no typical repeat, and (iii) a cysteine-rich subdomain. This latter subdomain has high sequence similarity to the cysteine-rich domains described in MUC2 and MUC5AC. Sequence data of these three genes, together with their clustered organization, lead us to suggest that they may be a part of a multigene family. The super-repeat present in MUC5B is the largest ever determined in mucin genes and the central exon of this gene is, by far, the largest reported for a vertebrate gene.

Published
1997

162. Influence of multiple APOE genetic variants on cognitive function in a cohort of older men – results from the Normative Aging Study

Author

David G. Cox, Jia Zhong, Marc G. Weisskopf, Elena Colicino, Marco Sanchez-Guerra, Joel Schwartz, Diddier Prada, Andrea A. Baccarelli, Lifang Hou, Melinda C. Power, Avron Spiro, Luis A. Herrera, Pantel S. Vokonas, Department of Environmental Health, Harvard School of Public Health, Unidad de Investigación Biomédica en Cáncer, Universidad Nacional Autónoma de México (UNAM)-Instituto Nacional de Cancerología – Instituto de Investigaciones Biomédicas, Department of Biomedical Informatics, Universidad Nacional Autónoma de México (UNAM), Department of Epidemiology, Department of Epidemiology [Baltimore], Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Department of Veterans Affairs, VA Boston Healthcare System, DP is financially supported by Consejo Nacional de Ciencia y Tecnología(CONACYT) and the Fundación México en Harvard from the program'Postdoctoral Fellowships in the Sciences at Harvard University: Mexico'.Thepresent work has been supported by a grant from the National Institute ofEnvironmental Health Sciences (NIEHS) (R01ES021733).MP is supported by a grant from the National Institute of Aging (NIA) (T32AG027668). AS was supported by a Senior Research Career Scientist award fromthe Clinical Science Research and Development Service for the US Departmentof Veterans Affairs. The US Department of Veterans Affairs (VA) Normative AgingStudy (NAS) is supported by the Cooperative Studies Program/ERIC, USDepartment of Veterans Affairs, and is a research component of theMassachusetts Veterans Epidemiology Research and Information Center(MAVERIC). Additional support to the VA Normative Aging Study was providedby the US Department of Agriculture, Agricultural Research Service (contract53-K06-510). The views expressed in this paper are those of the authors and donot necessarily represent the views of the US Department of Veterans Affairs., Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM)-Instituto Nacional de Cancerología – Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Taibi, Nadia

Subjects
Oncology, Apolipoprotein E, Gerontology, Adult, Male, medicine.medical_specialty, Aging, Genetic variants, Genotype, Cognitive decline, Neuropsychological Tests, Odds, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Apolipoproteins E, Cognition, Polymorphism (computer science), Internal medicine, medicine, Humans, MESH: APOE, Epsilon, Alleles, Haplotypes, Genotyping, 030304 developmental biology, Aged, Aged, 80 and over, 0303 health sciences, Polymorphism, Genetic, Haplotype, Middle Aged, Psychiatry and Mental health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Psychology, Cognition Disorders, 030217 neurology & neurosurgery, APOE, Research Article
Abstract

Background APOE is the biomarker with the greatest known influence on cognitive function; however, the effect of complex haplotypes involving polymorphisms rs449647, rs405509, rs440446, rs429358 and rs7412 has never been studied in older populations. Methods We evaluated APOE polymorphisms using multiplex PCR for genotyping and Mini-Mental State Examination (MMSE) to evaluate cognitive function in 819 individuals from VA Normative Aging Study. Results Combinatorial analysis of all polymorphisms and individual analysis of polymorphisms rs449647, rs405509, rs440446 and rs7412 did not show any association with cognitive performance. Polymorphism rs429358 was associated with better cognitive performance (odds of MMSE ≤ 25 = 0.63, 95% CI 0.42-0.95; p = 0.03) in the oldest subsample (5th quintile of age) (odds of MMSE ≤ 25 = 0.34; 95% CI 0.13-0.86; p = 0.02). APOE allele ε4 was also associated with better cognitive performance (odds of MMSE ≤ 25 = 0.61, 95% CI 0.40-0.94; p = 0.02), also in the oldest subsample (odds of MMSE ≤ 25 = 0.35, 95% CI 0.14-0.90; p = 0.03). Conclusions These results suggest a beneficial effect of polymorphism rs429358 in the oldest men. Electronic supplementary material The online version of this article (doi:10.1186/s12888-014-0223-x) contains supplementary material, which is available to authorized users.

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163. Isolation and sequencing of Dashli virus, a novel Sicilian-like virus in sandflies from Iran; genetic and phylogenetic evidence for the creation of one novel species within the Phlebovirus genus in the Phenuiviridae family

Author

Xavier de Lamballerie, E. Javadian, Cigdem Alkan, Nourina Rahbarian, Bulent Alten, Laurence Bichaud, Nazli Ayhan, Mehdi Badakhshan, Vahideh Moin Vaziri, Rémi N. Charrel, BUISINE, Soline, European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID, Biology and control of vector-borne infections in Europe - EDENEXT - - EC:FP7:HEALTH2011-01-01 - 2015-06-30 - 261504 - VALID, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Department of Parasitology and Mycology [Tehran, Iran] (School of Medicine), Shahid Beheshti University of Medical Sciences [Tehran, Iran], Department of Medical Entomology and Vector Control [Tehran, Iran] (School of Public Health), Tehran University of Medical Sciences-Institute of Public Health Research [Tehran, Iran], Cellular and Molecular Biology Research Center [Tehran, Iran] (SBU), Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Hacettepe University = Hacettepe Üniversitesi, Hôpital de la Timone [CHU - APHM] (TIMONE), This work was supported through funds received from EU grant FP7-261504 EDENext and this paper is catalogued by the EDENext Steering Committee (http://www.edenext.eu), the European Virus Archive goes Global (EVAg) project in the European Union's Horizon 2020 research and innovation programme under grant agreement No 653316 (http://global.european- virus-archive.com/). The present article partly was supported by Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (Grant No: 1573) The work of RNC was done under the frame of EurNegVec (TD1303) COST Action., European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), European Project: 261504,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EDENEXT(2011), and Shahid Beheshti University-Shahid Beheshti University

Subjects
0301 basic medicine, Male, Phlebovirus, RNA viruses, Fevers, Iran, Disease Vectors, Pathology and Laboratory Medicine, Database and Informatics Methods, Phlebotomus Fever, Bunyaviruses, Medicine and Health Sciences, Sandfly Fever Sicilian Virus, Phylogeny, Data Management, Genetics, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology, Phylogenetic tree, lcsh:Public aspects of medicine, Phylogenetic Analysis, Gene Pool, 3. Good health, Phylogenetics, Infectious Diseases, Medical Microbiology, Viral Pathogens, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Viruses, RNA, Viral, Female, Gene pool, Pathogens, Sequence Analysis, Research Article, Computer and Information Sciences, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Bioinformatics, Genome, Viral, Research and Analysis Methods, Microbiology, Virus, 03 medical and health sciences, Signs and Symptoms, Amino Acid Sequence Analysis, Diagnostic Medicine, Animals, Humans, Evolutionary Systematics, Microbial Pathogens, Taxonomy, Evolutionary Biology, Base Sequence, Population Biology, Sequence Analysis, RNA, Public Health, Environmental and Occupational Health, Organisms, Biology and Life Sciences, lcsh:RA1-1270, biology.organism_classification, Rift Valley fever virus, Sandfly, Insect Vectors, Sand Flies, Species Interactions, 030104 developmental biology, Microbial genetics, Psychodidae, Population Genetics
Abstract

Phlebotomine sandflies are vectors of phleboviruses that cause sandfly fever or meningitis with significant implications for public health. Although several strains of these viruses had been isolated in Iran in the late 1970's, there was no recent data about the present situation at the outset of this study. Entomological investigations performed in 2009 and 2011 in Iran collected 4,770 sandflies from 10 different regions. Based on morphological identification, they were sorted into 315 pools according to species, sex, trapping station and date of capture. A phlebovirus, provisionally named Dashli virus (DASHV), was isolated from one pool of Sergentomyia spp, and subsequently DASHV RNA was detected in a second pool of Phlebotomus papatasi. Genetic and phylogenetic analyses based on complete coding genomic sequences indicated that (i) DASHV is most closely related to the Iranian isolates of Sandfly fever Sicilian virus [SFSV], (ii) there is a common ancestor to DASHV, Sandfly fever Sicilian- (SFS) and SFS-like viruses isolated in Italy, India, Turkey, and Cyprus (lineage I), (iii) DASHV is more distantly related with Corfou and Toros viruses (lineage II) although common ancestry is supported with 100% bootstrap, (iii) lineage I can be subdivided into sublineage Ia including all SFSV, SFCV and SFTV except those isolated in Iran which forms sublineage Ib (DASHV). Accordingly, we suggest to approve Sandfly fever Sicilian virus species consisting of the all aforementioned viruses. Owing that most of these viruses have been identified in human patients with febrile illness, DASHV should be considered as a potential human pathogen in Iran., Author summary Phlebotomine sandflies are vectors of phleboviruses that cause sandfly fever or meningitis with significant implications for public health. Although several strains of these viruses had been isolated in Iran in the late 1970's, there was no recent data about the present situation at the outset of this study. Entomological investigations performed in 2009 and 2011 in Iran collected 4,770 sandflies from 10 different regions. A phlebovirus, provisionally named Dashli virus (DASHV), was isolated / detected in two pools. DASHV strain was isolated in cell culture and complete genome sequence was determined. Sequence analysis indicated that (i) DASHV is most closely related to the Iranian isolates of Sandfly fever Sicilian virus [SFSV], a virus that is known to cause self-resolutive incapacitating febrile illness in humans, (ii) there is a common ancestor to DASHV and all other variants of SFSV isolated in Italy, India, Turkey, and Cyprus (lineage I), (iii) DASHV is more distantly related with Corfou and Toros viruses (lineage II) although common ancestry is supported with 100% bootstrap, (iii) lineage I can be subdivided into sublineage Ia including all SFSV strains, whereas Iranian viruses are most closely related and should be individualized as DASHV (sublineage Ib). Although discovered first in the 1940's, SFSV is still listed as "tentative species" by the International Committee for Taxonomy of Viruses. Based on the results described in this study, we propose to approve Sandfly fever Sicilian virus species. Owing that most of these viruses have been identified in human patients with febrile illness, DASHV should be considered as a potential human pathogen in Iran.

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