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1. The Preliminary Analysis of Cave Lion Cubs Panthera spelaea (Goldfuss, 1810) from the Permafrost of Siberia

Author

Gennady G. Boeskorov, Valery V. Plotnikov, Albert V. Protopopov, Gennady F. Baryshnikov, Philippe Fosse, Love Dalén, David W. G. Stanton, Innokenty S. Pavlov, Naoki Suzuki, and Alexey N. Tikhonov

Subjects
cave lion, Panthera spelaea, cubs, morphological description, radiocarbon dating, Siberia, Human evolution, GN281-289, Stratigraphy, QE640-699
Abstract

A preliminary description is presented of the well-preserved frozen mummies of two cubs of the extinct cave lion Panthera spelaea (finds of 2017–2018, Semyuelyakh River, Yakutia, eastern Siberia, Russia). The fossil lion cubs were found in close proximity, but they do not belong to the same litter, since their radiocarbon ages differ: the female (named ‘Sparta’) was dated to 27,962 ± 109 uncal years BP, and the male (named ‘Boris’) was dated to 43,448 ± 389 uncal years BP. The lion cubs have similar individual ages, 1–2 months. The general tone of the colour of the fur coat of Sparta is greyish to light brown, whereas, in Boris, the fur is generally lighter, greyish yellowish. It is, therefore, possible that light colouration prevailed with age in cave lions and was adaptive for northern snow-covered landscapes. The article discusses the results of computed tomography of cubs of the cave lion, the possible reasons for their death, and the peculiarities of their existence in the Siberian Arctic.

Published
2021
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2. Tafonomía y arqueozoología comparadas de algunos yacimientos de los Pirineos franceses y de Cantabria

Author

Jérôme Quiles and Philippe Fosse

Subjects
Pirineos, fauna, tafonomía, arqueozoología, Auxiliary sciences of history, Archaeology, CC1-960
Abstract

El Pirineo francés y Cantabria presentan analogías en las muestras paleontológicas, tanto a nivel biocronológico como antropozoologico. Por eso, estas dos regiones -que contienen abundantes yacimientos pleistocenos-, presentan un modelo de ocupación y de explotación de zonas de montañas comparable, con ocupaciones humanas principalmente posteriores al Eemiense y generalmente implantadas en contexto ursino. A partir del Paleolítico Superior Medio una explotación más diversificada de recursos animales (caza selectiva, actividades industriales y artisticas) parece más evidente. Se presenta aqui un esquema general de procesos de ocupación del Pirineo francés con comparaciones inter-regionales con numerosos elementos de reflexión arqueozoológicos y tafonómicos.

Published
2005

4. Bison and Aurochs, Emblematic Figures of the Upper Paleolithic in Southwestern Europe

Author

Carole Fritz, Jean-Philip Brugal, Philippe Fosse, Gilles Tosello, Maison des Sciences de l'Homme et de la Société de Toulouse (MSHS-T), Centre National de la Recherche Scientifique (CNRS)-Université de Toulouse (UT), Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire méditerranéen de préhistoire Europe-Afrique (LAMPEA), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC)

Subjects
[SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, bison, Paleontology, palaeolithic art, aurochs
Abstract

The large bovids, bison and aurochs, both feature in Paleolithic archaeofauna and art, particularly in Southwestern Eu- rope during the Late Upper Pleistocene. We present a brief taxonomic and morphological description of the bovid spe- cies present at that time, as well as their biogeographical distribution. We then compare this distribution data with their presence in cave and portable art from this period and describe and interpret their depictions according to a number of themes. Our knowledge of the anatomical traits and ecology of these species allows us to better identify and interpret their representation in cave art and portable art made by hunter-gatherer societies. Several examples of Paleolithic art are given, illustrating the relationship between biological context and socio-economic value, and allowing us to under- stand the particular and highly symbolic nature of the relationship between humans and bovids. Beyond subsistence, Paleolithic representations clearly demonstrate a mythological dimension.

Published
2022

5. Retroviral nucleocapsid proteins and DNA strand transfers

Author

Brigitte René, Olivier Mauffret, Philippe Fosse, Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), and École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Base pair, Review, Biochemistry, Genome, lcsh:Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Retrovirus, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, lcsh:QD415-436, ComputingMilieux_MISCELLANEOUS, Zinc finger, Nucleocapsid protein, biology, RNA, HIV, Reverse transcription, Strand transfer, biology.organism_classification, Reverse transcriptase, 3. Good health, Cell biology, 030104 developmental biology, chemistry, Nucleic acid, DNA
Abstract

An infectious retroviral particle contains 1000–1500 molecules of the nucleocapsid protein (NC) that cover the diploid RNA genome. NC is a small zinc finger protein that possesses nucleic acid chaperone activity that enables NC to rearrange DNA and RNA molecules into the most thermodynamically stable structures usually those containing the maximum number of base pairs. Thanks to the chaperone activity, NC plays an essential role in reverse transcription of the retroviral genome by facilitating the strand transfer reactions of this process. In addition, these reactions are involved in recombination events that can generate multiple drug resistance mutations in the presence of anti-HIV-1 drugs. The strand transfer reactions rely on base pairing of folded DNA/RNA structures. The molecular mechanisms responsible for NC-mediated strand transfer reactions are presented and discussed in this review. Antiretroviral strategies targeting the NC-mediated strand transfer events are also discussed., Highlights • DNA strand transfers are essential steps of reverse transcription in retroviruses. • DNA strand transfers rely on base pairing of structured nucleic acids. • In vitro studies identified NC as an actor who facilitates DNA strand transfers. • NC increases the rate of transfers, thanks to its nucleic acid chaperone activity. • The nucleic acid-NC complexes are potential targets for antiretroviral therapy.

Published
2018

6. SurLym trial: study protocol for a multicentre pragmatic randomised controlled trial on the added value of reconstructive lymphatic surgery to decongestive lymphatic therapy for the treatment of lymphoedema

Author

Nele Devoogdt, Lode Godderis, Sarah Thomis, Beate Bechter-Hugl, Inge Fourneau, Steffen Fieuws, Geert Maleux, Daniel Devos, Thierry Deltombe, Tessa De Vrieze, An-Kathleen Heroes, Katarina Segers, Jacqueline Frippiat, Maxime Servaes, Aline Berners, Philippe Fosseprez, Bruno Krug, Francoise Kayser, Ana Falticeanu, Caren Randon, Chris Monten, Koen Van Landuyt, Bernard De Pypere, Liesl Degraeve, Tina Decorte, Mieke De Schryver, Vickie Van Besien, Sinikka Suominen, Jaume Masia Ayala, and Gemma Pons

Subjects
Medicine
Abstract

Introduction Lymphoedema is a chronic condition caused by lymphatic insufficiency. It leads to swelling of the limb/midline region and an increased risk of infection. Lymphoedema is often associated with mental and physical problems limiting quality of life. The first choice of treatment is a conservative treatment, consisting of exercises, skin care, lymph drainage and compression. Reconstructive lymphatic surgery is also often performed, that is, lymphovenous anastomoses, lymph node transfer or a combination. However, robust evidence on the effectiveness of reconstructive lymphatic surgery is missing. Therefore, the objective of this trial is to investigate the added value of reconstructive lymphatic surgery to the conservative treatment in patients with lymphoedema.Methods and analysis A multicentre randomised controlled and pragmatic trial was started in March 2022 in three Belgian university hospitals. 90 patients with arm lymphoedema and 90 patients with leg lymphoedema will be included. All patients are randomised between conservative treatment alone (control group) or conservative treatment with reconstructive lymphatic surgery (intervention group). Assessments are performed at baseline and at 1, 3, 6, 12, 18, 24 and 36 months. The primary outcome is lymphoedema-specific quality of life at 18 months. Key secondary outcomes are limb volume and duration of wearing the compression garment at 18 months. The approach of reconstructive lymphatic surgery is based on presurgical investigations including clinical examination, lymphofluoroscopy, lymphoscintigraphy, lymph MRI or CT angiography (if needed). All patients receive conservative treatment during 36 months, which is applied by the patient’s own physical therapist and by the patient self. From months 7 to 12, the hours a day of wearing the compression garment are gradually decreased.Ethics and dissemination The study has been approved by the ethical committees of University Hospitals Leuven, Ghent University Hospital and CHU UCL Namur. Results will be disseminated via peer-reviewed journals and presentations.Trial registration number NCT05064176

Published
2024
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7. The lynxes (Lynx pardinus/spelaeus, Lynx lynx) from the Middle Pleistocene to the Holocene in southern France : a paleontological and taphonomical overview

Author

Philippe Fosse, Jean Philippe Brugal, Evelyne Crégut‐bonnoure, Jean-Baptiste FOURVEL, Stéphane Madelaine, Laboratoire méditerranéen de préhistoire Europe-Afrique (LAMPEA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), and Fosse, Philippe

Subjects
[SHS] Humanities and Social Sciences, ComputingMilieux_MISCELLANEOUS, [SHS]Humanities and Social Sciences
Abstract

International audience

Published
2021

8. Salvage anastomosis in free PAP-flap breast reconstruction: What about free flap neovascularization?

Author

Michaël Hepp, Aline Berners, Christine Deconinck, Genevieve Pirson, Maxime Servaes, and Philippe Fosseprez

Subjects
Free flap, Autonomy, Vascular pedicle, Revascularization, PAP flap, Microsurgery, Surgery, RD1-811
Abstract

Since the emergence of microsurgery in reconstructive surgery, free flaps have become a key tool in the management of patients with breast cancer. One such flap is the profunda artery perforator (PAP) flap. To date, there is no scientific consensus on whether voluminous free flaps remain dependent on their vascular pedicle throughout their lifespan. Therefore, the pedicle should always be carefully protected during revision surgery. In this article, we review the case of a middle-aged woman who suffered a pedicle transection needing re-anastomosis during revision surgery six months after free-flap breast reconstruction. A 52-year-old woman who noticed a firm nodule in her right breast and armpit was referred to our department for surgical management. The Caucasian woman presented with no significant medical history or symptoms at the first consultation. Ultrasound-guided biopsy confirmed an invasive grade III lobular carcinoma. Following staging, the patient underwent neoadjuvant chemotherapy before a right mastectomy with a complete homolateral axillary lymph node dissection and postoperative radiotherapy. One year after completing radiotherapy, free flap reconstruction with a PAP flap was performed, and six months later, revision surgery was required to enhance the volume of the reconstructed breast with a tissue expander and later an implant. Unfortunately, pedicle transection occurred during revision surgery, causing complete devascularization of the flap, which was confirmed by intraoperative Indocyanine Green imaging. The authors elected to perform salvage re-anastomosis during the surgery. In keeping with the author’s 23-year experience with free flaps, the vascular pedicle should always be preserved in voluminous free flaps, as neovascularization alone may not ensure whole flap survival. The authors suggest always attempting re-anastomosis if vessels are compromised during revision surgery.

Published
2023
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9. Quaternary cliff-dwelling bovids (Capra, Rupicapra, Hemitragus, Ovis): site’s typology and taphonomic remarks

Author

philippe Fosse, Jean-Philip Brugal, Jean-Baptiste Fourvel, Stéphane Madelaine, Laboratoire méditerranéen de préhistoire Europe-Afrique (LAMPEA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), and Fosse, Philippe

Subjects
[SHS] Humanities and Social Sciences, ComputingMilieux_MISCELLANEOUS, [SHS]Humanities and Social Sciences
Abstract

International audience

Published
2020

10. Herbivores et carnivores pléistocènes en France : bilan général récent bibliographique, des gisements et de la taxinomie

Author

Jean-Baptiste Fourvel, Pierre Magniez, Philippe Fosse, Jean-Luc Guadelli, Alain Argant, Roman Croitor, Myriam Boudadi-Maligne, Philippe Fernandez, Antigone Uzunidis, Bruno Labe, Evelyne Crégut-Bonnoure, Jean-Philip Brugal, Laboratoire méditerranéen de préhistoire Europe-Afrique (LAMPEA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Muséum Requien, and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)

Subjects
Rupicaprines, Felidae, Bibliography, Rhinocérotidés Bovidés, Fauna, Équidés, Rhinocerotidae, 01 natural sciences, Rupicaprinés, Hyenidae, Mustélidés, ComputingMilieux_MISCELLANEOUS, Bibliographie, Ursidés, biology, Ecology, Gisements, Antilopinés, Antilopines, Pleistocene, Geography, Sites, Carnivores, Taxonomy (biology), France, [SDU.STU.PG]Sciences of the Universe [physics]/Earth Sciences/Paleontology, Ursidae, 010506 paleontology, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Mustelidae, Félidés, Bovinés, Bovidae, Bovines, Hyénidés, Canidés, Taxinomie, Pléistocène, 0105 earth and related environmental sciences, Canidae, Taxonomy, Herbivore, Paleontology, Equidae, 15. Life on land, Caprinés, biology.organism_classification, Caprines, Taxon, Proboscidiens, Cervidés, Quaternary, Herbivores
Abstract

International audience; This contribution presents a general account and summary of the research carried out over the past decades on the Quaternary faunas of France. This country is located in the center of Western Europe, and presents distinct topographical features and very varied climatic influences. This paper is the result of collaborative work between French teams and different researchers specialized in the paleontology of large mammals. Over a hundred paleontological or archaeological sites are mentioned in this review, which covers a broad chronological period, ranging from the Early (including the end of Pliocene/Gelasien) and Middle Pleistocene to the Late Pleistocene. One of the aims of this work is to present studies of the main families or subfamilies of herbivores (Equidae, Rhinocerotidae, Bovidae [Bovines, Caprines, Antilopines, and Rupicaprines], Cervidae, Proboscid) and carnivores (Canidae, Ursidae, Mustelidae, Hyenidae, Felidae). It is not exhaustive at the generic and specific level, but details on the taxonomic status, evolutionary levels and biochronological importance of the most important taxa are given alongside an extensive and up-to-date bibliography of French works.; Cette contribution expose un bilan général et synthétique des recherches menées ces dernières décades en France sur les faunes Quaternaires de ce pays situé au centre de l’Europe de l’Ouest, avec une topographie et des influences climatiques très variées. Cet article est le résultat d’un travail collectif entre différents spécialistes et équipes françaises en Paléontologie des grands mammifères. Près d’une centaine de gisements, paléontologiques ou archéologiques sont concernés et couvrent une large période, depuis la fin du Pliocène, le Pléistocène inférieur et moyen jusqu’au Pléistocène supérieur. Un des buts du travail est de présenter les études réalisées sur les principales familles ou sous-familles d’herbivores (Équidés, Rhinocérotidés Bovidés [Bovinés, Caprinés, Antilopinés, Rupicaprinés] Cervidés, Proboscidiens) et de carnivores (Canidés, Ursidés, Mustélidés, Hyénidés, Félidés). Sans être exhaustif au niveau générique et spécifique, des précisions sur le statut taxonomique, les degrés évolutifs et l’importance biochronologique des taxons sont présentées, accompagnées d’une bibliographie abondante et à jour des travaux français.

Published
2019

11. Rationally Designed Peptides as Efficient Inhibitors of Nucleic Acid Chaperone Activity of HIV-1 Nucleocapsid Protein

Author

Beata Basta, Philippe Fosse, Jean-Luc Darlix, Nicolas Humbert, Volodymyr V. Shvadchak, Stefano Ciaco, Sarwat Zgheib, Olivier Mauffret, Eleonore Real, Ouerdia Maskri, Yves Mély, May C. Morris, Johannes P. M. Langedijk, Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), Centre de recherches de biochimie macromoléculaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-IFR122-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Bioimagerie et Pathologie (LBP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Bioimagerie et Pathologies (LBP), Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), and Université de Toulouse (UT)-Université de Toulouse (UT)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Models, Molecular, 0301 basic medicine, Anti-HIV Agents, Drug Evaluation, Preclinical, HIV Infections, Peptide, gag Gene Products, Human Immunodeficiency Virus, Biochemistry, Conserved sequence, 03 medical and health sciences, Nucleic Acids, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, 030102 biochemistry & molecular biology, biology, Small molecule, In vitro, 3. Good health, Amino acid, 030104 developmental biology, chemistry, Viral replication, Drug Design, Chaperone (protein), HIV-1, Nucleic acid, biology.protein, Peptides, HeLa Cells
Abstract

Due to its essential roles in the viral replication cycle and to its highly conserved sequence, the nucleocapsid protein (NCp7) of the human immunodeficiency virus type 1 is a target of choice for inhibiting replication of the virus. Most NCp7 inhibitors identified so far are small molecules. A small number of short peptides also act as NCp7 inhibitors by competing with its nucleic acid (NA) binding and chaperone activities but exhibit antiviral activity only at relatively high concentrations. In this work, in order to obtain more potent NCp7 competitors, we designed a library of longer peptides (10-17 amino acids) whose sequences include most of the NCp7 structural determinants responsible for its specific NA binding and destabilizing activities. Using an in vitro assay, the most active peptide (pE) was found to inhibit the NCp7 destabilizing activity, with a 50% inhibitory concentration in the nanomolar range, by competing with NCp7 for binding to its NA substrates. Formulated with a cell-penetrating peptide (CPP), pE was found to accumulate into HeLa cells, with low cytotoxicity. However, either formulated with a CPP or overexpressed in cells, pE did not show any antiviral activity. In vitro competition experiments revealed that its poor antiviral activity may be partly due to its sequestration by cellular RNAs. The selected peptide pE therefore appears to be a useful tool for investigating NCp7 properties and functions in vitro, but further work will be needed to design pE-derived peptides with antiviral activity.

Published
2018

12. Structural and Dynamical Impact of a Universal Fluorescent Nucleoside Analogue Inserted Into a DNA Duplex

Author

Nelly Morellet, Loussiné Zargarian, Olivier Mauffret, Yves Mély, Brigitte René, Nicolas Barthes, Krishna Gavvala, Alain Burger, Akli Ben Imeddourene, Benoît Y. Michel, Philippe Fosse, Cyril A. Kenfack, Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UM3)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Siemens Industry Software SAS [Roanne], Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie des Molécules Bioactives et des Armes, Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Université Paul-Valéry - Montpellier 3 (UPVM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), 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 de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université Paul-Valéry - Montpellier 3 (UPVM)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Université Nice Sophia Antipolis (1965 - 2019) (UNS)

Subjects
Base pair, [SDV]Life Sciences [q-bio], Stacking, Molecular Dynamics Simulation, 010402 general chemistry, 01 natural sciences, Fluorescence, chemistry.chemical_compound, Materials Chemistry, medicine, A-DNA, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Physical and Theoretical Chemistry, ComputingMilieux_MISCELLANEOUS, Nucleoside analogue, 010405 organic chemistry, DNA, 3. Good health, 0104 chemical sciences, Surfaces, Coatings and Films, Biochemistry, chemistry, Duplex (building), Chromones, Biophysics, Nucleic Acid Conformation, Nucleoside, medicine.drug
Abstract

Recently, a 3-hydroxychromone based nucleoside 3HCnt has been developed as a highly environment-sensitive nucleoside surrogate to investigate protein-DNA interactions. When it is incorporated in DNA, the probe is up to 50-fold brighter than 2-aminopurine, the reference fluorescent nucleoside. Although the insertion of 3HCnt in DNA was previously shown to not alter the overall DNA structure, the possibility of the probe inducing local effects cannot be ruled out. Hence, a systematic structural and dynamic study is required to unveil the 3HCnt's limitations and to properly interpret the data obtained with this universal probe. Here, we investigated by NMR a 12-mer duplex, in which a central adenine was replaced by 3HCnt. The chemical shifts variations and nOe contacts revealed that the 3HCnt is well inserted in the DNA double helix with extensive stacking interactions with the neighbor base pairs. These observations are in excellent agreement with the steady-state and time-resolved fluorescence properties indicating that the 3HCnt fluorophore is protected from the solvent and does not exhibit rotational motion. The 3HCnt insertion in DNA is accompanied by the extrusion of the opposite nucleobase from the double helix. Molecular dynamics simulations using NMR-restraints demonstrated that 3HCnt fluorophore exhibits only translational dynamics. Taken together, our data showed an excellent intercalation of 3HCnt in the DNA double helix, which is accompanied by localized perturbations. This confirms 3HCnt as a highly promising tool for nucleic acid labeling and sensing.

Published
2017

13. Dynamic interactions of the HIV-1 Tat with nucleic acids are critical for Tat activity in reverse transcription

Author

Christian Boudier, Julien Godet, Françoise Chaminade, Philippe Fosse, Nicolas Humbert, Yves Mély, Hugues de Rocquigny, Yingying Chen, Olivier Mauffret, Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))

Subjects
[SDV]Life Sciences [q-bio], Response element, Protein domain, Molecular Sequence Data, Oligonucleotides, Plasma protein binding, Biology, Transactivation, Transcription (biology), Genetics, Amino Acid Sequence, Molecular Biology, ComputingMilieux_MISCELLANEOUS, HIV Long Terminal Repeat, Base Sequence, Oligonucleotide, Reverse Transcription, 3. Good health, Cell biology, Protein Structure, Tertiary, Biochemistry, Nucleic acid, HIV-1, Nucleic Acid Conformation, tat Gene Products, Human Immunodeficiency Virus, Peptides, Protein Binding
Abstract

The HIV-1 transactivator of transcription (Tat) protein is thought to stimulate reverse transcription (RTion). The Tat protein and, more specifically, its (44–61) domain were recently shown to promote the annealing of complementary DNA sequences representing the HIV-1 transactivation response element TAR, named dTAR and cTAR, that plays a key role in RTion. Moreover, the kinetic mechanism of the basic Tat(44–61) peptide in this annealing further revealed that this peptide constitutes a representative nucleic acid annealer. To further understand the structure–activity relationships of this highly conserved domain, we investigated by electrophoresis and fluorescence approaches the binding and annealing properties of various Tat(44–61) mutants. Our data showed that the Tyr47 and basic residues of the Tat(44–61) domain were instrumental for binding to cTAR through stacking and electrostatic interactions, respectively, and promoting its annealing with dTAR. Furthermore, the annealing efficiency of the mutants clearly correlates with their ability to rapidly associate and dissociate the complementary oligonucleotides and to promote RTion. Thus, transient and dynamic nucleic acid interactions likely constitute a key mechanistic component of annealers and the role of Tat in the late steps of RTion. Finally, our data suggest that Lys50 and Lys51 acetylation regulates Tat activity in RTion.

Published
2013

14. Insights into the mechanisms of RNA secondary structure destabilization by the HIV-1 nucleocapsid protein

Author

Nelly Morellet, Loussiné Zargarian, Brigitte René, Ouerdia Maskri, Yves Mély, Philippe Fosse, Carine Tisné, Olivier Mauffret, Dona Sleiman, Anissa Belfetmi, Ewen Lescop, Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie et pharmacologie appliquée (LBPA), and Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)

Subjects
0301 basic medicine, RNA Stability, Low protein, Base pair, [SDV]Life Sciences [q-bio], Molecular Sequence Data, nucleic acid dynamics, imino protons, Biology, Response Elements, gag Gene Products, Human Immunodeficiency Virus, Article, Nucleic acid secondary structure, 03 medical and health sciences, NMR spectroscopy, HIV-1 nucleocapsid protein, Nucleotide, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Base Sequence, Inverted Repeat Sequences, RNA, kinetic model, Nuclear magnetic resonance spectroscopy, Virology, 3. Good health, Kinetics, 030104 developmental biology, chemistry, HIV-1, Biophysics, Nucleic acid, Nucleic Acid Conformation, RNA, Viral, Protein Binding
Abstract

The mature HIV-1 nucleocapsid protein NCp7 (NC) plays a key role in reverse transcription facilitating the two obligatory strand transfers. Several properties contribute to its efficient chaperon activity: preferential binding to single-stranded regions, nucleic acid aggregation, helix destabilization, and rapid dissociation from nucleic acids. However, little is known about the relationships between these different properties, which are complicated by the ability of the protein to recognize particular HIV-1 stem–loops, such as SL1, SL2, and SL3, with high affinity and without destabilizing them. These latter properties are important in the context of genome packaging, during which NC is part of the Gag precursor. We used NMR to investigate destabilization of the full-length TAR (trans activating response element) RNA by NC, which is involved in the first strand transfer step of reverse transcription. NC was used at a low protein:nucleotide (nt) ratio of 1:59 in these experiments. NMR data for the imino protons of TAR identified most of the base pairs destabilized by NC. These base pairs were adjacent to the loops in the upper part of the TAR hairpin rather than randomly distributed. Gel retardation assays showed that conversion from the initial TAR–cTAR complex to the fully annealed form occurred much more slowly at the 1:59 ratio than at the higher ratios classically used. Nevertheless, NC significantly accelerated the formation of the initial complex at a ratio of 1:59.

Published
2016

15. Structural insights into the HIV-1 minus-strand strong-stop DNA

Author

Yingying Chen, Brigitte René, Ouerdia Maskri, Yves Mély, Jessica Benkaroun, Olivier Mauffret, Julien Godet, Françoise Chaminade, Philippe Fosse, Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))

Subjects
Models, Molecular, 0301 basic medicine, Protein Conformation, Base pair, viruses, [SDV]Life Sciences [q-bio], DNA, Recombinant, DNA, Single-Stranded, Electrophoretic Mobility Shift Assay, DNA and Chromosomes, Biology, gag Gene Products, Human Immunodeficiency Virus, Biochemistry, 03 medical and health sciences, Nucleic acid thermodynamics, chemistry.chemical_compound, Protein structure, Protein–DNA interaction, Nucleic acid structure, Binding site, Molecular Biology, Protein secondary structure, Phylogeny, ComputingMilieux_MISCELLANEOUS, Binding Sites, 030102 biochemistry & molecular biology, Nucleic Acid Hybridization, Cell Biology, Nucleocapsid Proteins, Molecular biology, 3. Good health, Molecular Weight, Kinetics, 030104 developmental biology, chemistry, DNA, Viral, Mutation, Codon, Terminator, HIV-1, Biophysics, Nucleic Acid Conformation, RNA, Viral, DNA
Abstract

International audience; An essential step of human immunodeficiency virus type 1 (HIV-1) reverse transcription is the first strand transfer that requires base pairing of the R region at the 3-end of the genomic RNA with the complementary r region at the 3-end of minus-strand strong-stop DNA (ssDNA). HIV-1 nucleocapsid protein (NC) facilitates this annealing process. Determination of the ssDNA structure is needed to understand the molecular basis of NC-mediated genomic RNA-ssDNA annealing. For this purpose, we investigated ssDNA using structural probes (nucleases and potassium permanganate). This study is the first to determine the secondary structure of the full-length HIV-1 ssDNA in the absence or presence of NC. The probing data and phylogenetic analysis support the folding of ssDNA into three stem-loop structures and the presence of four high-affinity binding sites for NC. Our results support a model for the NC-mediated annealing process in which the preferential binding of NC to four sites triggers unfolding of the three-dimensional structure of ssDNA, thus facilitating interaction of the r sequence of ssDNA with the R sequence of the genomic RNA. In addition, using gel retardation assays and ssDNA mutants, we show that the NC-mediated annealing process does not rely on a single pathway (zipper intermediate or kissing complex).

Published
2016

16. Structural and dynamic characterization of the upper part of the HIV-1 cTAR DNA hairpin

Author

Philippe Fosse, Ali Bazzi, Igor Kanevsky, Olivier Mauffret, Jonathan Boynard, Loussiné Zargarian, and Françoise Chaminade

Subjects
Models, Molecular, DNA, Complementary, viruses, Molecular Sequence Data, Human immunodeficiency virus (HIV), Biology, medicine.disease_cause, Strand transfer, chemistry.chemical_compound, Structural Biology, Genetics, medicine, Dna hairpin, Nuclear Magnetic Resonance, Biomolecular, HIV Long Terminal Repeat, Carbon Isotopes, Base Sequence, RNA, Phosphorus Isotopes, Internal loop, Molecular biology, Reverse transcriptase, chemistry, DNA, Viral, Mutation, Biophysics, HIV-1, Nucleic Acid Conformation, DNA
Abstract

First strand transfer is essential for HIV-1 reverse transcription. During this step, the TAR RNA hairpin anneals to the cTAR DNA hairpin; this annealing reaction is promoted by the nucleocapsid protein and involves an initial loop-loop interaction between the apical loops of TAR and cTAR. Using NMR and probing methods, we investigated the structural and dynamic properties of the top half of the cTAR DNA (mini-cTAR). We show that the upper stem located between the apical and the internal loops is stable, but that the lower stem of mini-cTAR is unstable. The residues of the internal loop undergo slow motions at the NMR time-scale that are consistent with conformational exchange phenomena. In contrast, residues of the apical loop undergo fast motions. The lower stem is destabilized by the slow interconversion processes in the internal loop, and thus the internal loop is responsible for asymmetric destabilization of mini-cTAR. These findings are consistent with the functions of cTAR in first strand transfer: its apical loop is suitably exposed to interact with the apical loop of TAR RNA and its lower stem is significantly destabilized to facilitate the subsequent action of the nucleocapsid protein which promotes the annealing reaction.

Published
2009

17. Large mammals of Fouvent-Saint-Andoche (Haute-Saône, France): a glimpse into a Late Pleistocene hyena den

Author

Jean-Baptiste Fourvel, Philippe Fosse, Pierre-Olivier Antoine, Philippe Fernandez, Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire méditerranéen de préhistoire Europe-Afrique (LAMPEA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, and École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Felidae, 010506 paleontology, Vulpes, Carnivora, Zoology, Context (language use), Rhinocerotidae, Meles, 010502 geochemistry & geophysics, Crocuta crocuta, 01 natural sciences, Proboscidea, [SHS]Humanities and Social Sciences, Mustelidae, Animalia, Chordata, Perissodactyla, ComputingMilieux_MISCELLANEOUS, Taxonomy, Canidae, Artiodactyla, 0105 earth and related environmental sciences, Elephantidae, Cervidae, biology, Ecology, Megaloceros, Paleontology, Geology, Biodiversity, Equidae, 15. Life on land, biology.organism_classification, Equus, Mustela eversmanii, [SHS.ENVIR]Humanities and Social Sciences/Environmental studies, Mammalia, Bovidae, Hyaenidae, Mammal, Ursidae
Abstract

International audience; The paleontological site of Fouvent-Saint-Andoche (Fouvent-le-Bas, Haute-Saône, France) is a large bone accumulation in a karstic context known since the early nineteenth century. This article focuses on the analysis of 14977 remains from both the historical collection (excavations in 1842) and the material of the recent excavations (1989–1992). A faunal list of 18/19 large mammal species has been established: 12 carnivores (Crocuta crocuta spelaea (Goldfüss, 1832), Panthera (Leo) spelaea (Goldfüss, 1810), Ursus spelaeus Rosenmüller & Heinroth, 1794, Canis lupus Linnaeus, 1758, Vulpes vulpes Linnaeus, 1758, cf. Alopex, Gulo gulo Linnaeus, 1758, Meles meles Linnaeus, 1758, Martes sp., Mustela eversmanii Lesson, 1827, Mustela sp.) and seven/eight ungulates (Mammuthus primigenius Blumenbach, 1799, Coelodonta antiquitatis (Blumenbach, 1799), Megaloceros giganteus Blumenbach, 1799, Cervus elaphus Linnaeus, 1758, Rangifer tarandus (Linnaeus, 1758), Equus germanicus Nehring, 1884, Bos primigenius Bojanus, 1827 and/or Bison priscus Bojanus, 1827). The palaeontological analysis allows us to characterize the evolutionary stage related to each species and to comment their biochronological significance. The detailed study of particular species, such as C. c. spelaea, E. germanicus, or C. antiquitatis improves our knowledge on species associations and their implication in Late Pleistocene hyena dens.

Published
2015

18. Spotted, striped or brown? Taphonomic studies at dens of extant hyaenas in eastern and southern Africa

Author

Graham Avery, Jean-Baptiste Fourvel, Philippe Fosse, Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS), and Iziko South African Museum, Cape Town

Subjects
Ungulate, Kleptoparasitism, Osteology, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Ecology, media_common.quotation_subject, Foraging, 15. Life on land, Biology, biology.organism_classification, Crocuta crocuta, Competition (biology), Predation, 13. Climate action, Hyaena, ComputingMilieux_MISCELLANEOUS, Earth-Surface Processes, media_common
Abstract

An article from the special issue "Eastern African Quaternary Research Association 4th conference" comprising six articles (plus the introduction). This special issue emerged from the PAGES supported meeting: ‘Eastern African Quaternary Climate Change and Variability: A View from the Highlands’ held in Nanyuki Kenya from 23 27 July 2013. ABSTRACT: We compare taphonomically relevant aspects of 6 bone accumulations produced by extant spotted hyaenas Crocuta crocuta striped hyaenas Hyaena hyaena and brown hyaenas Parahyaena brunnea) from eastern and southern Africa (Republic of Djibouti and Namibia) and published accounts. We highlight similarities and differences in the bone cracking/consumption and bone collecting habits of each hyaena species with a view to revealing criteria that might be used to distinguish these species. Four parameters are described: i) the prey taken and preferences ii) the skeletal part distribution iii) the long bone fragmentation iv) the tooth mark diversity and frequency. Information from hyaena ecology and the ungulate remains recovered from each bone accumulation reveals differences (or a lack thereof) related to environment anthropogenic pressure and ethology. Spotted hyaena hunting strategy and clan size suggest a low degree of inter group competition but high levels of intra group on carcass competition; fewer osteological remains are brought back to dens. In contrast striped and brown hyaenas are primarily scavengers (removing carcass remnants) and produce significant accumulations of bones at their dens. These differences are likely to be related mainly to inter specific competition and serve to reduce interaction with other carnivores and to limit kleptoparasitism; the composition of accumulations at dens is determined by food availability and foraging behaviour to a greater or lesser degree. Modern analogues are essential baseline tools for elucidating characteristics that might distinguish each species. The development of neo taphonomic models is the first step towards comparison and greater understanding of the palaeo ethology of extinct Pleistocene hyaenids.

Published
2015

19. A brown hyaena bone accumulation in the Uniab River coastal fan, Skeleton Coast Park, Namibia and taphonomic implications

Author

Graham Avery, Philippe Fosse, Jean-Baptiste FOURVEL, Jean-François Tournepiche, Rudi Loutit, Margaret Avery, Steve Braine, Iziko South African Museum, Cape Town, Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), INQUA - Human and Biosphere project #1402, and Fourvel, Jean-Baptiste

Subjects
[SDV.EE]Life Sciences [q-bio]/Ecology, environment, [SDV.EE] Life Sciences [q-bio]/Ecology, environment, [SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

20. Extant African and Extinct European Hyenas: Taphonomical characterization of their bone accumulations

Author

Philippe Fosse, Jean-Baptiste FOURVEL, Jean-Philip Brugal, Graham Avery, Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire méditerranéen de préhistoire Europe-Afrique (LAMPEA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Iziko South African Museum, Cape Town, INQUA - Human and Biosphere project #1402, Fourvel, Jean-Baptiste, École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), and Université de Toulouse (UT)-Université de Toulouse (UT)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

21. Dynamics of linker residues modulate the nucleic acid binding properties of the HIV-1 nucleocapsid protein zinc fingers

Author

Xiaoqian Xu, Yves Mély, Nelly Morellet, Loussiné Zargarian, Olivier Mauffret, Carine Tisné, Philippe Fosse, Brigitte René, Pierre Barraud, Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université Paris Descartes - Paris 5 (UPD5) - Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Models, Molecular, Viral Diseases, Biochemistry, Nucleocapsids, Physical Chemistry, chemistry.chemical_compound, Immunodeficiency Viruses, [CHIM] Chemical Sciences, Macromolecular Structure Analysis, Medicine and Health Sciences, Zinc finger, 0303 health sciences, Multidisciplinary, Physics, Protein dynamics, 030302 biochemistry & molecular biology, Magnetism, Zinc Fingers, Nucleocapsid Proteins, Condensed Matter Physics, 3. Good health, Chemistry, Infectious Diseases, Medical Microbiology, Viral Pathogens, Physical Sciences, Medicine, Research Article, Protein Structure, Rotation, Nuclear Magnetic Resonance, Science, Viral Structure, Microbiology, 03 medical and health sciences, Virology, [CHIM]Chemical Sciences, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Microbial Pathogens, Molecular Biology, 030304 developmental biology, LIM domain, Biology and Life Sciences, Proteins, Computational Biology, HIV, RNA, Nucleic Acid Strand, DNA, Chemical Properties, chemistry, HIV-1, Nucleic acid, Biophysics, Linker
Abstract

International audience; The HIV-1 nucleocapsid protein (NC) is a small basic protein containing two zinc fingers (ZF) separated by a short linker. It is involved in several steps of the replication cycle and acts as a nucleic acid chaperone protein in facilitating nucleic acid strand transfers occurring during reverse transcription. Recent analysis of three-dimensional structures of NC-nucleic acids complexes established a new property: the unpaired guanines targeted by NC are more often inserted in the C-terminal zinc finger (ZF2) than in the N-terminal zinc finger (ZF1). Although previous NMR dynamic studies were performed with NC, the dynamic behavior of the linker residues connecting the two ZF domains remains unclear. This prompted us to investigate the dynamic behavior of the linker residues. Here, we collected 15 N NMR relaxation data and used for the first time data at several fields to probe the protein dynamics. The analysis at two fields allows us to detect a slow motion occurring between the two domains around a hinge located in the linker at the G35 position. However, the amplitude of motion appears limited in our conditions. In addition, we showed that the neighboring linker residues R29, A30, P31, R32, K33 displayed restricted motion and numerous contacts with residues of ZF1. Our results are fully consistent with a model in which the ZF1-linker contacts prevent the ZF1 domain to interact with unpaired guanines, whereas the ZF2 domain is more accessible and competent to interact with unpaired guanines. In contrast, ZF1 with its large hydrophobic plateau is able to destabilize the double-stranded regions adjacent to the guanines bound by ZF2. The linker residues and the internal dynamics of NC regulate therefore the different functions of the two zinc fingers that are required for an optimal chaperone activity.

Published
2014

22. Characterization of bear remains consumption by Pleistocene large carnivores (Felidae, Hyaenidae, Canidae)

Author

Evelyne Crégut-Bonnoure, Philippe Fosse, Jean-François Tournepiche, Ludovic Slimak, Jean-Philip Brugal, Jean-Baptiste Fourvel, Slimak, Ludovic, Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Museum Requien, Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), and Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, biology, Ecology, Panthera onca, 15. Life on land, Ursus thibetanus, biology.organism_classification, Crocuta crocuta, Canis, Hyena, biology.animal, Carnivore, Ursus, Ursus deningeri, ComputingMilieux_MISCELLANEOUS, Earth-Surface Processes
Abstract

Numerous palaeontological sites containing bear hibernation levels are developed in Europe during the Quaternary. These particular assemblages allowed researchers to study Ursidae evolution, in particular Pleistocene species, and characterize extinct species behavior. These sites are not the only ones which contain bear remains. Large carnivore dens (in particular hyena dens), largely represented in Europe during the Late Pleistocene, include frequently consumed bear remains in their bone accumulations. Bear presence in these bone accumulations is discussed here. Through the observation of age estimations, skeletal part representation and bear bone morphology resulting of carnivore consumption (fragmentation and tooth marks), this study tries to discuss bear as potential prey for the other large predators. Six French assemblages, covering Middle and Late Pleistocene and representing three different types of samples, are presented: 1 – Four hyena dens: Eemian den of Peyre ( Ursus cf. spelaeus n = 11), Artenac level 10, at the beginning of Late Pleistocene ( U. cf. spelaeus n = 63) and wurmian assemblages from Fouvent ( U. spelaeus n = 17) and Conives ( U. spelaeus n = 6). 2 – An archaeological site alternating human and carnivore occupations named Grand Abri aux Puces which includes three bear species ( U. cf. spelaeus n = 11, Ursus arctos n = 52 and Ursus thibetanus n = 2) consumed by two potential predators (wolf and hyena). 3 – Artenac I and II (>500 ka) considered as bear hibernation levels ( Ursus deningeri n = 918) hunted/scavenging by large felid ( Panthera onca gombaszoegensis ). This analysis allows us to define and characterize bear consumption ( U. deningeri , U. spelaeus , U. arctos , U. thibetanus ) by three large carnivores ( P. onca gombaszoegensis , Crocuta crocuta spelaea , Canis lupus ).

Published
2014

23. Woolly mammoths (Mammuthus primigenius) in southern France during the Late Palaeolithic: a geo-chronological assessment based on the palaeontological, rock art and portable art records

Author

Philippe Fosse, Carole Fritz, Évelyne Cregut‑bonnoure, Guillaume Fleury, Jean-Baptiste FOURVEL, Stéphane Madelaine, Georges Sauvet, Fourvel, Jean-Baptiste, Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Museum Requien, Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Musée National de Préhistoire, Ministère de la Culture et de la Communication (MCC), Maison des Sciences de l'Homme et de la Société de Toulouse (MSHS-T), Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées, and Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

24. Gastric erosion on artiodactyl acropodials eaten by large carnivores and vultures: a taphonomic comparison

Author

Philippe Fosse, Montserrat Esteban-Nadal, Graham Avery, D Vigne, J., Patrice Méniel, Pierre Magniez, Stéphane Madelaine, Jean-Baptiste FOURVEL, Jean-Philip Brugal, Jean-François Tournepiche, Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS), Universitat Rovira i Virgili, Iziko South African Museum, Cape Town, Archéozoologie, archéobotanique : sociétés, pratiques et environnements (AASPE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Archéologie, Terre, Histoire, Sociétés [Dijon] (ARTeHiS), Ministère de la Culture et de la Communication (MCC)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Histoire naturelle de l'Homme préhistorique (HNHP), Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Musée National de Préhistoire, Ministère de la Culture et de la Communication (MCC), Laboratoire méditerranéen de préhistoire Europe-Afrique (LAMPEA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Fourvel, Jean-Baptiste, École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), and Université de Toulouse (UT)-Université de Toulouse (UT)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2012

25. Consumption of ungulate long bones by Pleistocene hyenas : a comparative study

Author

Jean-Baptiste FOURVEL, Philippe Fosse, Jean-François Tournepiche, Evelyne Crégut-Bonnoure, Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), and PACEA, UMR5199

Subjects
[SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, préhistoire, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2012

26. Bone modification by modern wolf (Canis lupus) : a taphonomic study from their natural feeding places

Author

Philippe Fosse, Nuria Selva, Adam Wajrak, Jean-Baptiste FOURVEL, Stéphane Madelaine, Montserrat Esteban-Nadal, José Yravedra, Jean-Philip Brugal, Audrey Prucca, Gary Haynes, Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS), Adam Mickiewicz University in Poznań (UAM), Musée National de Préhistoire, Ministère de la Culture et de la Communication (MCC), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Universitat Rovira i Virgili, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Laboratoire méditerranéen de préhistoire Europe-Afrique (LAMPEA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), University of Nevada [Reno], PACEA, UMR5199, École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)

Subjects
WOLF, [SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, préhistoire, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, BONE DESTRUCTIONS, SCATS, ComputingMilieux_MISCELLANEOUS, TAPHONOMY
Abstract

International audience

Published
2012

27. Structural insights into the cTAR DNA recognition by the HIV-1 nucleocapsid protein: role of sugar deoxyriboses in the binding polarity of NC

Author

Christian Boudier, Olivier Mauffret, Loussiné Zargarian, Brigitte René, Yves Mély, Françoise Chaminade, Philippe Fosse, Ali Bazzi, Hughes De Rocquigny, Département Micro-Ondes (MO), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))

Subjects
Models, Molecular, Guanine, Molecular Sequence Data, Electrophoretic Mobility Shift Assay, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, gag Gene Products, Human Immunodeficiency Virus, Nucleobase, 03 medical and health sciences, chemistry.chemical_compound, Structural Biology, Ribose, Genetics, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Nuclear Magnetic Resonance, Biomolecular, ComputingMilieux_MISCELLANEOUS, HIV Long Terminal Repeat, 030304 developmental biology, 0303 health sciences, Deoxyribose, 030302 biochemistry & molecular biology, RNA, 3. Good health, Thymine, chemistry, Biochemistry, DNA, Viral, Nucleic acid, Biophysics, Hydrophobic and Hydrophilic Interactions, DNA, Protein Binding
Abstract

International audience; An essential step of the reverse transcription of the HIV-1 genome is the first strand transfer that requires the annealing of the TAR RNA hairpin to the cTAR DNA hairpin. HIV-1 nucleocapsid protein (NC) plays a crucial role by facilitating annealing of the complementary hairpins. Using nuclear magnetic resonance and gel retardation assays, we investigated the interaction between NC and the top half of the cTAR DNA (mini-cTAR). We show that NC(11-55) binds the TGG sequence in the lower stem that is destabilized by the adjacent internal loop. The 5 0 thymine interacts with residues of the N-terminal zinc knuckle and the 3 0 guanine is inserted in the hydrophobic plateau of the C-terminal zinc knuckle. The TGG sequence is preferred relative to the apical and internal loops containing unpaired guanines. Investigation of the DNA-protein contacts shows the major role of hydrophobic interactions involving nucleobases and deoxyribose sugars. A similar network of hydrophobic contacts is observed in the published NC:DNA complexes, whereas NC contacts ribose differently in NC:RNA complexes. We propose that the binding polarity of NC is related to these contacts that could be responsible for the preferential binding to single-stranded nucleic acids.

Published
2011

28. New evidence for Upper Palaeolithic small domestic dogs in South-Western Europe

Author

Philippe Fosse, Maud Pionnier-Capitan, Jean-Georges Ferrié, Pierre Bodu, Michel Garcià, Guy Célérier, Jean-Denis Vigne, Céline Bemilli, Archéozoologie, archéobotanique : sociétés, pratiques et environnements (AASPE), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Ctr Archeol Grand Quevilly, Partenaires INRAE, Université Paris Ouest Nanterre la Défense, Université Sciences et Technologies - Bordeaux 1, and Université Toulouse Le Mirail (Toulouse 2) (UTM)

Subjects
010506 paleontology, Archeology, Dog (Canis familiaris), Azilian, Taphonomy, [SDV]Life Sciences [q-bio], 01 natural sciences, Domestication, REMAINS, 0601 history and archaeology, Glacial period, Magdalenian, Mesolithic, 0105 earth and related environmental sciences, SITES, Epipaleolithic, 060102 archaeology, Dhole (Cuter alpinus), 06 humanities and the arts, Archaeology, Wolf (Canis lupus), Geography, Late Glacial, EAST, Upper Paleolithic, France
Abstract

International audience; Osteoarchaeology and genetics agree that the earliest dog domestications took place during the Upper Palaeolithic. However, they partially disagree about the process of domestication. The former indicated multiple origins, when some of the results of the latter suggested that dogs mainly came from a Chinese centre of domestication. In this study, we describe and discuss new evidence for Late Glacial small dogs in the South-West (Pont d'Ambon and Montespan) and North of France (Le Closeau). Special attention was paid to the possibility of miss-identification between small early dogs and dholes (Cuon alpinus), a middle-sized Canidae, the size of which can be similar to early small dogs. Detailed analyses of the archaeological contexts alongside that of taphonomy, morphoscopy, morphometry and pathology, identified 49 small canid remains from the three sites. They allowed us to exclude the presence of dholes and to conclude that they were all small Upper Paleolithic dogs. These, together with other more sparse discoveries, confirmed the presence of Western European Upper Paleolithic Small (WEUPS) dogs from, at least, the Middle Magdalenian to the end of the Epipaleolithic (i.e. 15,000-11,500 cal BP). As they are contemporaneous with the much larger Russian Upper Paleolithic dogs, they plea for several Euro-Asian origins for Late Palaeolithic dogs. (C) 2011 Elsevier Ltd. All rights reserved.

Published
2011

29. The cave lion (P. spelaea) in karstic setting : a survey from (recent) paleontological and rock art discoveries in southern France and northern Spain

Author

Philippe Fosse, Duranthon Francis, Jean-Baptiste Fourvel, Stéphane Madelaine, Guillaume Fleury, Pedro Castaños, Arriza Villaluenga Martinez, Carole Fritz, Gilles Tosello, Marc Azéma, Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS), Muséum d'Histoire Naturelle de Toulouse, Musée National de Préhistoire, Ministère de la Culture et de la Communication (MCC), and Fourvel, Jean-Baptiste

Subjects
[SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2010

30. Norepinephrine weaning in septic shock patients by closed loop control based on fuzzy logic

Author

Frédéric Lapostolle, Yves Cohen, Carole Marbeuf-Gueye, Christophe Clec’h, Stephen W. Borron, François Vincent, Jean-Philippe Fosse, Frédéric Adnet, Mehdi Merouani, Bruno Guignard, Eric Vicaut, Philippe Karoubi, Samu 93, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Anesthésie et de Réanimation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Service de Réanimation Médico-Chirurgicale [Avicenne], Department of Surgery (Emergency Medicine), The University of Texas Health Science Center at Houston (UTHealth), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche Clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Fernand-Widal, Laboratoire de Biophysique Moléculaire Cellulaire et Tissulaire (BIOMOCETI), Université Paris 13 (UP13)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), and Vesin, Aurélien

Subjects
Adult, Male, medicine.medical_specialty, Mean arterial pressure, medicine.medical_treatment, Critical Care and Intensive Care Medicine, Fuzzy logic, Norepinephrine (medication), 03 medical and health sciences, Norepinephrine, 0302 clinical medicine, Fuzzy Logic, Interquartile range, medicine, Weaning, Humans, Vasoconstrictor Agents, 030212 general & internal medicine, Infusions, Intravenous, Decision Making, Computer-Assisted, Aged, Mechanical ventilation, Septic shock, business.industry, Research, 030208 emergency & critical care medicine, Middle Aged, medicine.disease, Shock, Septic, 3. Good health, Surgery, Intensive Care Units, Withholding Treatment, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Shock (circulatory), Anesthesia, Commentary, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, medicine.symptom, business, medicine.drug
Abstract

International audience; ABSTRACT: INTRODUCTION: The rate of weaning of vasopressors drugs is usually an empirical choice made by the treating in critically ill patients. We applied fuzzy logic principles to modify intravenous norepinephrine (noradrenaline) infusion rates during norepinephrine infusion in septic patients in order to reduce the duration of shock. METHODS: Septic patients were randomly assigned to norepinephrine infused either at the clinician's discretion (control group) or under closed-loop control based on fuzzy logic (fuzzy group). The infusion rate changed automatically after analysis of mean arterial pressure in the fuzzy group. The primary end-point was time to cessation of norepinephrine. The secondary end-points were 28-day survival, total amount of norepinephine infused and duration of mechanical ventilation. RESULTS: Nineteen patients were randomly assigned to fuzzy group and 20 to control group. Weaning of norepinephrine was achieved in 18 of the 20 control patients and in all 19 fuzzy group patients. Median (interquartile range) duration of shock was significantly shorter in the fuzzy group than in the control group (28.5 [20.5 to 42] hours versus 57.5 [43.7 to 117.5] hours; P < 0.0001). There was no significant difference in duration of mechanical ventilation or survival at 28 days between the two groups. The median (interquartile range) total amount of norepinephrine infused during shock was significantly lower in the fuzzy group than in the control group (0.6 [0.2 to 1.0] mug/kg versus 1.4 [0.6 to 2.7] mug/kg; P < 0.01). CONCLUSIONS: Our study has shown a reduction in norepinephrine weaning duration in septic patients enrolled in the fuzzy group. We attribute this reduction to fuzzy control of norepinephrine infusion. TRIAL REGISTRATION: Trial registration: Clinicaltrials.gov NCT00763906.

Published
2008

31. Are daily routine chest radiographs useful in critically ill, mechanically ventilated patients? A randomized study

Author

Christophe Clec’h, Yves Cohen, Frédéric Gonzalez, Jean-Philippe Fosse, Aïcha Hamdi, Lilia Hamza, Philippe Karoubi, François Vincent, Paul Simon, Service de Réanimation Médico-Chirurgicale [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), and Vesin, Aurélien

Subjects
Male, MESH: Chi-Square Distribution, medicine.medical_treatment, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Surveys and Questionnaires, Prospective Studies, MESH: Respiration, Artificial, Prospective cohort study, MESH: Middle Aged, Middle Aged, Prognosis, Intensive care unit, 3. Good health, MESH: Critical Illness, Female, Radiography, Thoracic, medicine.medical_specialty, Critical Care, Critical Illness, MESH: Prognosis, 03 medical and health sciences, Anesthesiology, Intensive care, medicine, Humans, MESH: Intensive Care, Medical prescription, Intensive care medicine, MESH: Diagnostic Tests, Routine, Mechanical ventilation, Chi-Square Distribution, MESH: Humans, business.industry, Diagnostic Tests, Routine, MESH: Questionnaires, MESH: Radiography, Thoracic, Respiration, Artificial, MESH: Male, MESH: Prospective Studies, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Emergency medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Chi-squared distribution, MESH: Female
Abstract

International audience; OBJECTIVE: Whether chest radiographs (CXRs) in mechanically ventilated patients should be routinely obtained or only when an abnormality is anticipated remains debated. We aimed to compare the diagnostic, therapeutic and outcome efficacy of a restrictive prescription of CXRs with that of a routine prescription, focusing on delayed diagnoses and treatments potentially related to the restrictive prescription. DESIGN: Randomized controlled trial. SETTING: Intensive care unit of the Avicenne Teaching Hospital, Bobigny, France. PATIENTS AND PARTICIPANTS: All consecutive patients mechanically ventilated for > or = 48h between January and June 2006. INTERVENTIONS: Patients were randomly assigned to have daily routine CXRs (routine prescription group) or clinically indicated CXRs (restrictive prescription group). MEASUREMENTS AND RESULTS: For each CXR, a questionnaire was completed addressing the reason for the CXR, the new findings, and any subsequent therapeutic intervention. The endpoints were the rates of new findings, the rates of new findings that prompted therapeutic intervention, the rate of delayed diagnoses, and mortality. Eighty-four patients were included in the routine prescription group and 81 in the restrictive prescription group. The rates of new findings and the rates of new findings that prompted therapeutic intervention in the restrictive prescription group and in the routine prescription group were 66% vs. 7.2% (p < 0.0001), and 56.4% vs. 5.5% (p < 0.0001) respectively. The rate of delayed diagnoses in the restrictive prescription group was 0.7%. Mortality was similar. CONCLUSIONS: Restrictive use of CXRs in mechanically ventilated patients was associated with better diagnostic and therapeutic efficacies without impairing outcome.

Published
2008

32. Specific interactions between HIV-1 nucleocapsid protein and the TAR element

Author

Abdeladim Moumen, Matteo Negroni, Igor Kanevsky, Philippe Fosse, Jean-Luc Darlix, Robert J. Gorelick, Damien Ficheux, Françoise Chaminade, Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Régulation Enzymatique des Activités Cellulaires, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), AIDS Vaccine Program, NCI at Frederick, Biologie des Interactions Cellulaires (BIC), Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Untranslated region, Mutant, MESH: Reverse Transcription, MESH: DNA Replication, MESH: Amino Acid Sequence, MESH: Base Sequence, Virus Replication, Genome, gag Gene Products, Human Immunodeficiency Virus, MESH: HIV-1, chemistry.chemical_compound, Structural Biology, MESH: Capsid Proteins, Zinc finger, chemistry.chemical_classification, 0303 health sciences, MESH: HIV Long Terminal Repeat, MESH: Peptides, 030302 biochemistry & molecular biology, Zinc Fingers, MESH: gag Gene Products, Human Immunodeficiency Virus, 3. Good health, MESH: Nucleic Acid Conformation, MESH: DNA, Single-Stranded, MESH: Gene Products, gag, MESH: RNA, Viral, RNA, Viral, DNA Replication, MESH: Mutation, Molecular Sequence Data, DNA, Single-Stranded, Gene Products, gag, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 03 medical and health sciences, Viral Proteins, Humans, MESH: Zinc Fingers, Amino Acid Sequence, Molecular Biology, 030304 developmental biology, HIV Long Terminal Repeat, MESH: Molecular Sequence Data, MESH: Humans, Base Sequence, MESH: Virus Replication, RNA, Reverse Transcription, Molecular biology, MESH: Viral Proteins, Reverse transcriptase, MESH: DNA, Viral, Enzyme, chemistry, DNA, Viral, Mutation, HIV-1, Nucleic Acid Conformation, Capsid Proteins, Peptides, DNA
Abstract

During retroviral reverse transcription, the minus-strand strong-stop DNA (ss-cDNA) is transferred to the 3' end of the genomic RNA and this requires the repeat (R) sequences present at both ends of the genome. In vitro, the human immunodeficiency virus type 1 (HIV-1) R sequence can promote DNA strand transfer when present in ectopic internal positions. Using HIV-1 model systems, the R sequences and nucleocapsid protein (NC) were found to be key determinants of ss-cDNA transfer. To gain insights into specific interactions between HIV-1 NC and RNA and the influence of NC on R folding, we investigated the secondary structures of R in two natural contexts, namely at the 5' or 3' end of RNAs representing the terminal regions of the genome, and in two ectopic internal positions that also support efficient minus-strand transfer. To investigate the roles of NC zinc fingers and flanking basic domains in the NC/RNA interactions, we used NC mutants. Analyses of the viral RNA/NC complexes by chemical and enzymatic probings, and gel retardation assays were performed under conditions allowing ss-cDNA transfer by reverse transcriptase. We report that NC binds the TAR apical loop specifically in the four genetic contexts without changing the folding of the TAR hairpin and R region significantly, and this requires the NC zinc fingers. In addition, we show that efficient annealing of cTAR DNA to the 3' R relies on sequence complementarities between TAR and cTAR terminal loops. These findings suggest that the TAR apical loop in the acceptor RNA is the initiation site for the annealing reaction that is chaperoned by NC during the minus-strand transfer.

Published
2005

33. The use of bone as fuel during the Palaeolithic, experimental study of bone combustible properties.: Proceedings of the 9th Conference of the International Council of Archaeozoology, Durham, August 2002

Author

Isabelle Théry-Parisot, Sandrine Costamagno, Jean-Philip Brugal, Philippe Fosse, Raphaële Guilbert, Economies, sociétés et environnements préhistoriques (ESEP), Centre National de la Recherche Scientifique (CNRS)-Université de Provence - Aix-Marseille 1-Université Joseph Fourier - Grenoble 1 (UJF), Centre d'Études Préhistoire, Antiquité, Moyen-Age (CEPAM), 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), Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), Ministère de la Culture et de la Communication (MCC)-École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS), Laboratoire méditerranéen de préhistoire Europe-Afrique (LAMPEA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), J. Mulville and A. Outram (Editors), Université Nice Sophia Antipolis (1965 - 2019) (UNS), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), and Leglise, Nicolas

Subjects
structure de combustion, [SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, archéologie expérimentale, ossements animaux, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Préhistoire, Os brûlé, habitat, experiments, Paléolithique, foyer, Burned bones, expérimentation, fuel, combustible, combustion
Abstract

Burnt bone, mostly spongy bone, is found on many archaeological sites. An experimental study of the combustion properties of bone shows that the spongy parts, mainly distal, are more combustible than the more compact bone. The combustion of these parts is characterised by the production of high and durable flames, and the absence of a calcination phase. The use of bone for combustion is therefore reserved for hearths, whose function is related to the resulting flames (convective and radiant heat). For these functions, bone is more suitable than wood. The discussion relates to the motivation behind using bone for fuel in the specific context of the Palaeolithic. The assumption that the management of fuels strongly correlated with the length of site occupation and site function seems increasingly probable.

Published
2005

34. In vitro characterization of a base pairing interaction between the primer binding site and the minimal packaging signal of avian leukosis virus genomic RNA

Author

Philippe Fosse, Natalya Vasilenko, Hélène Dumay‐Odelot, Igor Kanevsky, Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), and Fosse, Philippe

Subjects
MESH: Base Sequence, MESH: Alpharetrovirus, Ribonuclease T1, MESH: Phylogeny, Base Pairing, Conserved Sequence, Phylogeny, 0303 health sciences, MESH: Conserved Sequence, 030302 biochemistry & molecular biology, Articles, 3. Good health, Cell biology, MESH: Mutagenesis, Site-Directed, MESH: RNA, Viral, Transfer RNA, RNA, Viral, MESH: 5' Untranslated Regions, MESH: Genome, Viral, Dimerization, Primer binding site, MESH: Virus Assembly, MESH: Ribonuclease T1, Base pair, Molecular Sequence Data, MESH: Base Pairing, Genome, Viral, Regulatory Sequences, Ribonucleic Acid, Biology, Alpharetrovirus, Terminal loop, 03 medical and health sciences, MESH: RNA, Genetics, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Binding site, 030304 developmental biology, Binding Sites, MESH: Molecular Sequence Data, Base Sequence, Virus Assembly, MESH: Regulatory Sequences, Ribonucleic Acid, RNA, Molecular biology, Reverse transcriptase, MESH: Binding Sites, MESH: Dimerization, Mutagenesis, Site-Directed, 5' Untranslated Regions, Pseudoknot
Abstract

International audience; The 5' leader region of avian sarcoma-leukosis viruses (ASLVs) folds into a series of RNA secondary structures which are involved in key steps in the viral replication cycle such as reverse transcription, dimerization and packaging of genomic RNA. The O3 stem and three stem-loops (O3SLa, O3SLb and O3SLc) form the minimal packaging signal that is located downstream of the primer binding site (PBS). The U5-PBS region contributes to packaging via a mechanism that remains unknown. In this in vitro study, we have investigated the possibility of interactions between the R-U5-PBS region and the minimal packaging signal using chemical and enzymatic probing, antisense oligonucleotides and site-directed mutagenesis. We have identified a base pairing interaction between the PBS sequence and the terminal loop of O3SLa. It was found that the PBS/O3SLa interaction was intramolecular since it occurred not only in dimeric RNA but also in monomeric RNA. This interaction probably corresponds to a pseudoknot interaction. The PBS/O3SLa interaction may be formed in vivo since the sequences are highly conserved in ASLV strains. The PBS/O3SLa interaction may regulate the processes of primer tRNA annealing, packaging and initiation of Gag translation through its involvement in leader tertiary structure. Interestingly, we found that in other retroviruses the PBS sequence can also base pair with a terminal loop of the stem-loops involved in RNA packaging.

Published
2003

35. Characterization of loose and tight dimer forms of avian leukosis virus RNA

Author

Emmanuelle Polge, Jacques Paoletti, Philippe Fosse, Jean-Luc Darlix, Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Dimer, RNA Stability, MESH: Base Sequence, Genome, chemistry.chemical_compound, Retrovirus, Structural Biology, MESH: Animals, Base Pairing, Genetics, 0303 health sciences, Avian Leukosis Virus, 030302 biochemistry & molecular biology, Temperature, MESH: RNA Stability, MESH: Temperature, 3. Good health, MESH: Nucleic Acid Conformation, MESH: RNA, Viral, RNA, Viral, Thermodynamics, MESH: Oligoribonucleotides, MESH: Thermodynamics, MESH: Genome, Viral, Dimerization, MESH: Mutation, MESH: Base Pairing, Genome, Viral, Biology, Virus, 03 medical and health sciences, MESH: Avian leukosis virus, Molecule, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, Binding Sites, Oligoribonucleotides, Base Sequence, RNA, biology.organism_classification, In vitro, chemistry, MESH: Binding Sites, MESH: Dimerization, Duplex (building), Mutation, Biophysics, Nucleic Acid Conformation
Abstract

International audience; Retroviral genomes consist of two identical RNA molecules joined non-covalently near their 5'-ends. Recently, we showed that an imperfect autocomplementary sequence, located in the L3 domain, plays an essential role in avian sarcoma-leukosis virus (ASLV) RNA dimerization in vitro. This sequence can adopt a stem-loop structure and is involved in ASLV replication. Here, we found that in the absence of nucleocapsid protein, RNA transcripts of avian leukosis virus (ALV) were able to form two types of dimers in vitro that differ in their stability: a loose dimer, formed at a physiological temperature, and a tight dimer, formed at a high temperature. A mutational analysis was performed to define the features of these dimers. The results of this analysis unambiguously confirm that the two L3 stem-loops interact directly in both types of dimers. A loop-loop interaction is the main linkage in the loose dimer. In contrast, in the tight dimer, the stem and the loop of the L3 hairpin form an extended duplex. Surprisingly, we also found that the dimerization properties defined for our ALV strain (type SR-A) differ from those found in other ASLV strains.

Published
2000

36. Comparative study of bone assemblages made by recent and Pleistocene Hyenids

Author

Jean-Philip Brugal, philippe Fosse, Jean-Luc Guadelli, Economies, sociétés et environnements préhistoriques (ESEP), Centre National de la Recherche Scientifique (CNRS)-Université de Provence - Aix-Marseille 1-Université Joseph Fourier - Grenoble 1 (UJF), Unite toulousaine d'archéologie et d'histoire (UTAH), Université Toulouse - Jean Jaurès (UT2J)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Commission on Prehistoric Bone Industry Nomenclature, Working Group n°1, Unspecialized Bone Industries, M. Patou-Mathis (dir), Université Joseph Fourier - Grenoble 1 (UJF)-Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Guadelli, Jean-Luc, and Commission on Prehistoric Bone Industry Nomenclature, Working Group n°1, Unspecialized Bone Industries, M. Patou-Mathis (dir)

Subjects
Hyaena den, [SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, Age (mortality) profile, Frequency of Ungulate skeletal parts, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Carnivore/Herbivore ratio, Stades d'usure des mandibules d'hyène, Composition of Ungulate assemblages, Structure de taille, Dégats osseux, Structure d'âge, Composition des ensembles d'Ongulés, Rapport Carnivore/Herbivore, Crocuta crocuta spelaea, Wear stage for hyenid mandibule, Bone damage, Repaire d'Hyènes, Size structure, Hyène tachetée des cavernes, Spotted cave hyaena, Fréquence des portions squelettiques
Abstract

The main goal of this study is to establish the characteristics of bone assemblages accumulated by hyenids, essentially fossil spotted cave-hyenas, found in many karsts from the European Pleistocene. A comparative approach is utilized which includes modern and fossil African hyenid accumulations. Most of the criteria used are discussed and methodological problems are noted. Preliminary results concerning the age structure of hyenid populations as well as the size of their prey are given., Le but de ce travail consiste à établir les principales caractéristiques des ensembles osseux accumulés par des hyénidés, en particulier par l'hyène tachetée des cavernes, trouvés dans de nombreux sites karstiques du Pléistocène européen. Une approche comparative large inclut les accumulations de différentes espèces d'hyènes fossiles et actuelles d'Afrique. Les différents critères utilisés sont discutés permettant de relever quelques problèmes d'ordre méthodologique. Les résultats préliminaires concernent entre autres les structures d'âge des populations d'hyènes fossiles ainsi que les structures de taille de leurs proies.

Published
1997

37. RNA Structural Requirements for Nucleocapsid Protein-Mediated Extended Dimer Formation

Author

Françoise Chaminade, Jean-Luc Darlix, and Philippe Fossé

Subjects
nucleocapsid protein, RNA dimerization, Rous sarcoma virus (RSV), HIV-1, retrovirus, RNA secondary structure, Microbiology, QR1-502
Abstract

Retroviruses package two copies of their genomic RNA (gRNA) as non-covalently linked dimers. Many studies suggest that the retroviral nucleocapsid protein (NC) plays an important role in gRNA dimerization. The upper part of the L3 RNA stem-loop in the 5′ leader of the avian leukosis virus (ALV) is converted to the extended dimer by ALV NC. The L3 hairpin contains three stems and two internal loops. To investigate the roles of internal loops and stems in the NC-mediated extended dimer formation, we performed site-directed mutagenesis, gel electrophoresis, and analysis of thermostability of dimeric RNAs. We showed that the internal loops are necessary for efficient extended dimer formation. Destabilization of the lower stem of L3 is necessary for RNA dimerization, although it is not involved in the linkage structure of the extended dimer. We found that NCs from ALV, human immunodeficiency virus type 1 (HIV-1), and Moloney murine leukemia virus (M-MuLV) cannot promote the formation of the extended dimer when the apical stem contains ten consecutive base pairs. Five base pairs correspond to the maximum length for efficient L3 dimerization induced by the three NCs. L3 dimerization was less efficient with M-MuLV NC than with ALV NC and HIV-1 NC.

Published
2022
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38. Dynamics of linker residues modulate the nucleic acid binding properties of the HIV-1 nucleocapsid protein zinc fingers.

Author

Loussiné Zargarian, Carine Tisné, Pierre Barraud, Xiaoqian Xu, Nelly Morellet, Brigitte René, Yves Mély, Philippe Fossé, and Olivier Mauffret

Subjects
Medicine, Science
Abstract

The HIV-1 nucleocapsid protein (NC) is a small basic protein containing two zinc fingers (ZF) separated by a short linker. It is involved in several steps of the replication cycle and acts as a nucleic acid chaperone protein in facilitating nucleic acid strand transfers occurring during reverse transcription. Recent analysis of three-dimensional structures of NC-nucleic acids complexes established a new property: the unpaired guanines targeted by NC are more often inserted in the C-terminal zinc finger (ZF2) than in the N-terminal zinc finger (ZF1). Although previous NMR dynamic studies were performed with NC, the dynamic behavior of the linker residues connecting the two ZF domains remains unclear. This prompted us to investigate the dynamic behavior of the linker residues. Here, we collected 15N NMR relaxation data and used for the first time data at several fields to probe the protein dynamics. The analysis at two fields allows us to detect a slow motion occurring between the two domains around a hinge located in the linker at the G35 position. However, the amplitude of motion appears limited in our conditions. In addition, we showed that the neighboring linker residues R29, A30, P31, R32, K33 displayed restricted motion and numerous contacts with residues of ZF1. Our results are fully consistent with a model in which the ZF1-linker contacts prevent the ZF1 domain to interact with unpaired guanines, whereas the ZF2 domain is more accessible and competent to interact with unpaired guanines. In contrast, ZF1 with its large hydrophobic plateau is able to destabilize the double-stranded regions adjacent to the guanines bound by ZF2. The linker residues and the internal dynamics of NC regulate therefore the different functions of the two zinc fingers that are required for an optimal chaperone activity.

Published
2014
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39. Intrinsic nucleic acid dynamics modulates HIV-1 nucleocapsid protein binding to its targets.

Author

Ali Bazzi, Loussiné Zargarian, Françoise Chaminade, Hugues De Rocquigny, Brigitte René, Yves Mély, Philippe Fossé, and Olivier Mauffret

Subjects
Medicine, Science
Abstract

HIV-1 nucleocapsid protein (NC) is involved in the rearrangement of nucleic acids occurring in key steps of reverse transcription. The protein, through its two zinc fingers, interacts preferentially with unpaired guanines in single-stranded sequences. In mini-cTAR stem-loop, which corresponds to the top half of the cDNA copy of the transactivation response element of the HIV-1 genome, NC was found to exhibit a clear preference for the TGG sequence at the bottom of mini-cTAR stem. To further understand how this site was selected among several potential binding sites containing unpaired guanines, we probed the intrinsic dynamics of mini-cTAR using (13)C relaxation measurements. Results of spin relaxation time measurements have been analyzed using the model-free formalism and completed by dispersion relaxation measurements. Our data indicate that the preferentially recognized guanine in the lower part of the stem is exempt of conformational exchange and highly mobile. In contrast, the unrecognized unpaired guanines of mini-cTAR are involved in conformational exchange, probably related to transient base-pairs. These findings support the notion that NC preferentially recognizes unpaired guanines exhibiting a high degree of mobility. The ability of NC to discriminate between close sequences through their dynamic properties contributes to understanding how NC recognizes specific sites within the HIV genome.

Published
2012
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