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In 1970, the seventh pandemic of cholera (7 P) reached both Africa and Europe. Between 1970 and 2011, several European countries reported cholera outbreaks of a few to more than 2,000 cases. We report here a whole-genome analysis of 1,324 7 P V. cholerae El Tor (7 PET) isolates, including 172 from autochthonous sporadic or outbreak cholera cases occurring between 1970 and 2011 in Europe, providing insight into the spatial and temporal spread of this pathogen across Europe. In this work, we show that the 7 PET lineage was introduced at least eight times into two main regions: Eastern and Southern Europe. Greater recurrence of the disease was observed in Eastern Europe, where it persisted until 2011. It was introduced into this region from Southern Asia, often circulating regionally in the countries bordering the Black Sea, and in the Middle East before reaching Eastern Africa on several occasions. In Southern Europe, the disease was mostly seen in individual countries during the 1970s and was imported from North and West Africa, except in 1994, when cholera was imported into Albania and Italy from the Black Sea region. These results shed light on the geographic course of cholera during the seventh pandemic and highlight the role of humans in its global dissemination., Since 1970, several cholera outbreaks caused by the “seventh pandemic” (7PET) lineage have been reported in Europe. Here, the authors demonstrate that the outbreaks were caused by repeated introductions of 7PET into Europe, rather than local environmental sources.

International audience

Objectives The Central African Republic (CAR), a site of recurrent disease emergence, developed a noteworthy epidemiological surveillance system from the colonial period, but its health measures have remained among the world’s lowest. To understand this disparity between surveillance and public health, we examined selected moments in its history of surveillance and changing relations with public health structures. Methods We conducted archival research in CAR and French archives and 18 semi-structured interviews with key researchers working in CAR. Results We find long-term continuities in privileging surveillance over the health system and population health, making the CAR a ‘‘hotspot’’ for emerging diseases and a ‘‘blind spot’’ of primary health care. From the colonial period, the country attracted considerable support for surveillance, without concomitant investment in public health system. Political disputes and financial constraints have obscured real primary care needs on the ground. Conclusions As both a hotspot and a blind spot for global health, the CAR signals the need to reorient health interventions to address the long-term health of Central African people.

International audience; Taste is essential for the interaction of animals with their food and has co-evolved with diet. Humans have peopled a large range of environments and present a wide range of diets, but little is known about the diversity and evolution of human taste perception. We measured taste recognition thresholds across populations differing in lifestyles (hunter gatherers and farmers from Central Africa, nomad herders, and farmers from Central Asia). We also generated genome-wide genotype data and performed association studies and selection scans in order to link the phenotypic variation in taste sensitivity with genetic variation. We found that hunter gatherers have lower overall sensitivity as well as lower sensitivity to quinine and fructose than their farming neighbors. In parallel, there is strong population divergence in genes associated with tongue morphogenesis and genes involved in the transduction pathway of taste signals in the African populations. We find signals of recent selection in bitter taste-receptor genes for all four populations. Enrichment analysis on association scans for the various tastes confirmed already documented associations and revealed novel GO terms that are good candidates for being involved in taste perception. Our framework permitted us to gain insight into the genetic basis of taste sensitivity variation across populations and lifestyles.

International audience

Background: Transmission of many viruses occurs by direct transmission during a close contact between two hosts, or by an indirect transmission through the environment. Several and often interconnected factors, both abiotic and biotic, determine the persistence of these viruses released in the environment, which can last from a few seconds to several years. Moreover, viruses in the environment are able to travel short to very long distances, especially in the air or in water. Summary: Although well described now, the role of these environments as intermediaries or as reservoirs in virus transmission has been extensively studied and debated in the last century. The majority of these discoveries, such as the pioneer work on bacteria transmission, the progressive discoveries of viruses, as well as the persistence of the influenza virus in the air varying along with droplet sizes, or the role of water in the transmission of poliovirus, have contributed to the improvement of public health. Recent outbreaks of human coronavirus, influenza virus, and Ebola virus have also demonstrated the contemporaneity of these research studies and the need to study virus persistence in the environment. Key Messages: In this review, we discuss historical discoveries that contributed to describe biotic and abiotic factors determining viral persistence in the environment.

International audience; Widespread administration of oral poliovirus vaccine (OPV) has decreased global incidence of poliomyelitis by ≈99.9%. However, the emergence of vaccine-derived polioviruses (VDPVs) is threatening polio-eradication program. Primary immunodeficiency (PID) patients are at higher risks of vaccine-associated paralytic poliomyelitis (VAPP) and prolonged excretion of immunodeficiency-associated VDPV (iVDPV). We searched Embase, Medline, Science direct, Scopus, Web of Science, and CDC and WHO databases by 30 September 2016, for all reports of iVDPV cases. Patient-level data were extracted form eligible studies. Data on immunization coverage and income-level of countries were extracted from WHO/UNICEF and the WORLD BANK databases, respectively. We assessed bivariate associations between immunological, clinical, and virological parameters, and exploited multivariable modeling to identify independent determinants of poliovirus evolution and patients' outcomes. Study protocol was registered with PROSPERO (CRD42016052931). 4329 duplicate-removed titles were screened. A total of 107 iVDPV cases were identified from 68 eligible articles. The majority of cases were from higher income countries with high polio-immunization coverage. 74 (69.81%) patients developed VAPP. Combined immunodeficiency patients showed lower rates of VAPP (p \textless .001) and infection clearance (p = .02), compared to humoral immunodeficiency patients. The rate of poliovirus genomic evolution was higher at early stages of replication, decreasing over time until reaching a steady state. Independent of replication duration, higher extent (p = .04) and rates (p = .03) of genome divergence contributed to a less likelihood of virus clearance. PID type (p \textless .001), VAPP occurrence (p = .008), and income-level of country (p = .04) independently influenced patients' survival. With the use of OPV, new iVDPVs will emerge independent of the rate of immunization coverage. Inherent features of PIDs contribute to the clinical course of iVDPV infection and virus evolution. This finding could shed further light on poliomyelitis pathogenesis and iVDPV evolution pattern. It also has implications for public health, the polio eradication effort and the development of effective antiviral interventions.

Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems are well-known acquired immunity systems that are widespread in archaea and bacteria. The RNA-guided nucleases from CRISPR-Cas systems are currently regarded as the most reliable tools for genome editing and engineering. The first hint of their existence came in 1987, when an unusual repetitive DNA sequence, which subsequently was defined as a CRISPR, was discovered in the Escherichia coli genome during an analysis of genes involved in phosphate metabolism. Similar sequence patterns were then reported in a range of other bacteria as well as in halophilic archaea, suggesting an important role for such evolutionarily conserved clusters of repeated sequences. A critical step toward functional characterization of the CRISPR-Cas systems was the recognition of a link between CRISPRs and the associated Cas proteins, which were initially hypothesized to be involved in DNA repair in hyperthermophilic archaea. Comparative genomics, structural biology, and advanced biochemistry could then work hand in hand, not only culminating in the explosion of genome editing tools based on CRISPR-Cas9 and other class II CRISPR-Cas systems but also providing insights into the origin and evolution of this system from mobile genetic elements denoted casposons. To celebrate the 30th anniversary of the discovery of CRISPR, this minireview briefly discusses the fascinating history of CRISPR-Cas systems, from the original observation of an enigmatic sequence in E. coli to genome editing in humans.

Summary Background Ampicillin, the first semi-synthetic penicillin active against Enterobacteriaceae, was released onto the market in 1961. The first outbreaks of disease caused by ampicillin-resistant strains of Salmonella enterica serotype Typhimurium were identified in the UK in 1962 and 1964. We aimed to date the emergence of this resistance in historical isolates of S enterica serotype Typhimurium. Methods In this retrospective, whole-genome sequencing study, we analysed 288 S enterica serotype Typhimurium isolates collected between 1911 and 1969 from 31 countries on four continents and from various sources including human beings, animals, feed, and food. All isolates were tested for antimicrobial drug susceptibility with the disc diffusion method, and isolates shown to be resistant to ampicillin underwent resistance-transfer experiments. To provide insights into population structure and mechanisms of ampicillin resistance, we did whole-genome sequencing on a subset of 225 isolates, selected to maximise source, spatiotemporal, and genetic diversity. Findings 11 (4%) of 288 isolates were resistant to ampicillin because of acquisition of various β lactamase genes, including bla TEM-1 , carried by various plasmids, including the virulence plasmid of S enterica serotype Typhimurium. These 11 isolates were from three phylogenomic groups. One isolate producing TEM-1 β lactamase was isolated in France in 1959 and two isolates producing TEM-1 β lactamase were isolated in Tunisia in 1960, before ampicillin went on sale. The vectors for ampicillin resistance were different from those reported in the strains responsible for the outbreaks in the UK in the 1960s. Interpretation The association between antibiotic use and selection of resistance determinants is not as direct as often presumed. Our results suggest that the non-clinical use of narrow-spectrum penicillins (eg, benzylpenicillin) might have favoured the diffusion of plasmids carrying the bla TEM-1 gene in S enterica serotype Typhimurium in the late 1950s. Funding Institut Pasteur, Sante publique France, the French Government's Investissement d'Avenir programme, the Fondation Le Roch-Les Mousquetaires.

International audience

International audience; Morphine derived from Papaver somniferum is commonly used as an analgesic compound for pain relief. It is now accepted that endogenous morphine, structurally identical to vegetal morphine-alkaloid, is synthesized by mammalian cells from dopamine. Morphine binds mu opioid receptor and induces antinociceptive effects. However, the exact role of these compounds is a matter of debate although different links with infection, sepsis, inflammation, as well as major neurological pathologies (Parkinson's disease, schizophrenia) have been proposed. The present review describes endogenous morphine and morphine derivative discovery, synthesis, localization and potential implications in physiological and pathological processes.

International audience; We mark the 50th anniversary of the International Committee on Taxonomy of Viruses (ICTV) by presenting a brief history of the organization since its foundation, showing how it has adapted to advancements in our knowledge of virus diversity and the methods used to characterize it. We also outline recent developments, supported by a grant from the Wellcome Trust (UK), that are facilitating substantial changes in the operations of the ICTV and promoting dialogue with the virology community. These developments will generate improved online resources, including a freely available and regularly updated ICTV Virus Taxonomy Report. They also include a series of meetings between the ICTV and the broader community focused on some of the major challenges facing virus taxonomy, with the outcomes helping to inform the future policy and practice of the ICTV.

International audience; This review describes the historical emergence of the concept of bone marrow mesenchymal stem cells (MSCs), summarizing data on Wolf and Trentin's hematopoietic inductive microenvironment; Dexter's hematopoiesis-supportive stromal cells; Friedenstein's osteogenic cells; and Pittenger's trilineal osteoblastic, chondrocytic, and adipocytic precursors; to finally introduce the specific bone marrow mesenchymal stem cells with differentiation potential to four lineages (mesenchymal and vascular smooth muscle lineages), and stromal and immunomodulatory capacities. Two points are the object of detailed discussion. The first point envisions the stem cell attributes (multipotentiality, self-renewal, tissue regeneration, population heterogeneity, plasticity, and lineage priming) compared with that of the paradigmatic hematopoietic stem cell. In the second point, we discuss the possible existence of bone marrow cells with greater differentiation potential, eventually pluripotential cells. The latter point raises the issues of cell fusion, reprogramming, or selection under nonstandardized conditions of rare populations of neuroectodermal origin, or of cells that had undergone mesenchymal-to-epithelial transition. In the last section, we review data on MSC senescence and possible malignant transformation secondary to extensive culture, gene transfer of telomerase, or mutations such as leading to Ewing's sarcoma. The set of data leads to the conclusion that bone marrow MSCs constitute a specific adult tissue stem cell population. The multiple characteristics of this stem cell type account for the versatility of the mechanisms of injured tissue repair. Although MSC administration may be extremely useful in a number of clinical applications, their transplantation is not without risks that must not be overlooked when developing cell therapy protocols.

International audience; Indications for nerve biopsy have decreased during the last 20 years. For the most part, this is a result of progress in the application of molecular biologic diagnostic testing for genetic peripheral neuropathies (PNs) and the increasing use of skin biopsy. The latter is primarily used to evaluate small-fiber PN, although it rarely discloses the specific etiology of a PN. Nerve biopsies are usually performed on either the sural or the superficial peroneal nerve, the latter in combination with removal of portions of the peroneus brevis muscle. The definite diagnosis of vasculitic lesions can be readily established on small paraffin-embedded nerve biopsy samples, although in some cases, the characteristic lesions are only apparent in muscle specimens. Other nerve specimens are routinely fixed in buffered glutaraldehyde and prepared for semithin sections and electron microscopy; frozen specimens are used for immunofluorescence studies. Electron microscopy is of great value in some cases of chronic inflammatory demyelinating polyneuropathies, monoclonal gammopathy, and storage diseases. Because more than 30 genes may be involved in genetic PNs, analysis of nerve lesions can direct the search for mutations in specific genes. Electron microscopy immunocytochemistry is mandatory in some cases of monoclonal dysglobulinemia. Thus, nerve biopsy is still of value in specific circumstances when it is performed by trained physicians and examined in a laboratory with expertise in nerve pathology.

Alan closing his departing speech at LMCB in 2006 by featuring his lab. Image by Ione Karney. ![][1] Alan Hall died of a heart attack during his regular Sunday morning jog on May 3rd in New York City, where he had lived with his wife Eileen. Alan's untimely and unexpected death happened just a couple of weeks before his 63rd birthday, which he would undoubtedly have celebrated with his two children and two young grandchildren. Before joining the Sloane Kettering Institute as chair of the cell biology program in 2006, most of Alan's career was spent in the UK. After graduating from Oxford, he stayed in town to start his PhD with Jeremy Knowles, but he received his first exposure to US science quite unintentionally when Jeremy announced he was relocating to Harvard after two months. Over his four years in Harvard, Alan perfected his training in biochemistry. He then did a two‐year postdoc with Charles Weissmann (University of Zurich) where he developed his molecular biology skills and helped clone interferon. It was only after joining the Institute of … [1]: /embed/graphic-1.gif

International audience; The ratio between the body circumference at the waist and the hips (or WHR) is a secondary sexual trait that is unique to humans and is well known to influence men's mate preferences. Because a woman's WHR also provides information about her age, health and fertility, men's preference concerning this physical feature may possibly be a cognitive adaptation selected in the human lineage. However, it is unclear whether the preferred WHR in western countries reflects a universal ideal, as geographic variation in non-western areas has been found, and discordances about its temporal consistency remain in the literature. We analyzed the WHR of women considered as ideally beautiful who were depicted in western artworks from 500 BCE to the present. These vestiges of the past feminine ideal were then compared to more recent symbols of beauty: Playboy models and winners of several Miss pageants from 1920 to 2014. We found that the ideal WHR has changed over time in western societies: it was constant during almost a millennium in antiquity (from 500 BCE to 400 CE) and has decreased from the 15th century to the present. Then, based on Playboy models and Miss pageants winners, this decrease appears to slow down or even reverse during the second half of the 20th century. The universality of an ideal WHR is thus challenged, and historical changes in western societies could have caused these variations in men's preferences. The potential adaptive explanations for these results are discussed.

International audience

International audience; We performed a geographical analysis of cancer mortality in the communes surrounding an industrial mining complex (Salsigne, France) where suspicious levels of pollution due to arsenic were measured. Compared with that observed in a control area, we showed a significant excess of mortality due to all cancer types (ratio of standard mortality ratios (ratio of SMRs)=1.1), lung cancer (ratio of SMRs=1.8), pharynx cancer (ratio of SMRs=2.1) in the whole population, and due to digestive system cancer (ratio of SMRs=1.3) among women. The results were similar after controlling for the occupation distribution in the populations. Excluding mining complex workers deaths from the deaths in the studied populations did not modify the pattern of our results. We concluded that the excess of cancer deaths could not be exclusively due to potential professional exposures among the workers of the mining complex and are probably explained by environmental contamination.

International audience; Until fairly recently, mentally ill mothers were separated from their new-borns because of the potential danger to the baby. Over the past 50 years, however, we have learned more about the perinatal period, with the development of child psychiatry and interest in maternal postpartum disorders. This knowledge has led psychiatric departments to develop new ways to provide care without separating mentally ill mothers from their babies. Joint full-time admissions began in Great Britain in 1948. The first Mother-Baby Unit (MBU) in France opened in 1979 and in Belgium in 1990. In 2003, there are 17 MBUs in France and 3 in Belgium. From 1995 to 1998, Odile Cazas and Nine Glangeaud, working with a group of child and adult psychiatrists and psychologists, adapted the English Marcé Checklist to the French and Belgian health and child protective systems and added items useful for research.

International audience

International audience; In 1984, the Met receptor and its ligand, the HGF/SF, were discovered thanks to their ability to induce cell transformation and proliferation. Thirty years of research highlighted their crucial role in the development and homeostasis of various structures, including many epithelial organs. This period also allowed unraveling the structural basis of their interaction and their complex signaling network. In parallel, Met was shown to be deregulated and associated with a poor prognosis in many cancers. Met involvement in resistance to current therapies is also being deciphered. Based on these data, pharmaceutical companies developed a variety of Met inhibitors, some of which are evaluated in phase III clinical trials. In this review, we trace the exemplary track record of research on Met receptor, which allowed moving from bench to bedside through the development of therapies targeting its activity. Many questions still remain unanswered such as the involvement of Met in several processes of development, the mechanisms involving Met in resistance to current therapies or the likely emergence of resistances to Met-targeted therapies.; En 1984, le récepteur à activité tyrosine kinase Met et son ligand l’HGF (hepatocyte growth factor)/SF (scatter factor) sont découverts grâce à leur aptitude à induire la transformation et la prolifération cellulaires. Trois décennies ont permis de mettre en évidence leur rôle fondamental dans le déve­loppement et l’homéostasie de nombreuses structures, notamment des organes épithéliaux. Cette même période a permis de décrypter les bases structurales de leur interaction, ainsi qu’un réseau de signalisation complexe. Parallèlement, l’implication de la dérégulation de Met dans la tumorigenèse, supposée dès sa découverte, a été démontrée ; elle est associée à un mauvais pronostic dans de nombreux cancers. Le rôle de cette dérégulation dans des phénomènes de résistance aux thérapies actuelles commence également à être déchiffré. Sur la base de ces données, des compagnies pharmaceutiques ont développé une grande diversité d’inhibiteurs ciblant l’HGF/SF ou le récepteur Met, dont certains sont actuellement évalués dans des essais cliniques de phase III. Nous proposons dans cette revue de retracer le parcours exemplaire des recherches sur le récepteur Met, qui auront permis en trente ans de passer de la découverte fondamentale d’un oncogène au développement de thérapies ciblant son action. Cependant, de nombreuses questions restent en suspens. Par exemple, l’implication de Met dans plusieurs étapes du développement reste à préciser, de même que les mécanismes faisant de ce récepteur un facteur de résistance aux traitements actuels ou le développement probable de résistances aux thérapies ciblant sa propre activité.

International audience; Preliminary results of an empirical study of human experimentation practices are presented and contrasted with those of a survey conducted a hundred years ago when clinical research, although tolerated, was culturally deviant. Now that biomedical research is both authorized and controlled, its actors (sponsors, committees, investigators, subjects) come out with heterogeneous rationalities, and they appear to be engaged in a transactional process of negotiating their rationales with one another. In the European context "protective" of subjects, surprisingly the subjects we interviewed (and especially patient-subjects) were creative and revealed an aptitude for integrating experimental medicine into common culture.

In 1984, the Met receptor and its ligand, the HGF/SF, were discovered thanks to their ability to induce cell transformation and proliferation. Thirty years of research highlighted their crucial role in the development and homeostasis of various structures, including many epithelial organs. This period also allowed unraveling the structural basis of their interaction and their complex signaling network. In parallel, Met was shown to be deregulated and associated with a poor prognosis in many cancers. Met involvement in resistance to current therapies is also being deciphered. Based on these data, pharmaceutical companies developed a variety of Met inhibitors, some of which are evaluated in phase III clinical trials. In this review, we trace the exemplary track record of research on Met receptor, which allowed moving from bench to bedside through the development of therapies targeting its activity. Many questions still remain unanswered such as the involvement of Met in several processes of development, the mechanisms involving Met in resistance to current therapies or the likely emergence of resistances to Met-targeted therapies., En 1984, le récepteur à activité tyrosine kinase Met et son ligand l’HGF (hepatocyte growth factor)/SF (scatter factor) sont découverts grâce à leur aptitude à induire la transformation et la prolifération cellulaires. Trois décennies ont permis de mettre en évidence leur rôle fondamental dans le déve­loppement et l’homéostasie de nombreuses structures, notamment des organes épithéliaux. Cette même période a permis de décrypter les bases structurales de leur interaction, ainsi qu’un réseau de signalisation complexe. Parallèlement, l’implication de la dérégulation de Met dans la tumorigenèse, supposée dès sa découverte, a été démontrée ; elle est associée à un mauvais pronostic dans de nombreux cancers. Le rôle de cette dérégulation dans des phénomènes de résistance aux thérapies actuelles commence également à être déchiffré. Sur la base de ces données, des compagnies pharmaceutiques ont développé une grande diversité d’inhibiteurs ciblant l’HGF/SF ou le récepteur Met, dont certains sont actuellement évalués dans des essais cliniques de phase III. Nous proposons dans cette revue de retracer le parcours exemplaire des recherches sur le récepteur Met, qui auront permis en trente ans de passer de la découverte fondamentale d’un oncogène au développement de thérapies ciblant son action. Cependant, de nombreuses questions restent en suspens. Par exemple, l’implication de Met dans plusieurs étapes du développement reste à préciser, de même que les mécanismes faisant de ce récepteur un facteur de résistance aux traitements actuels ou le développement probable de résistances aux thérapies ciblant sa propre activité.

International audience; The novelist Henry James shared with his brother William, the author of the Principles of Psychology, a deep interest in the ways in which personal identity is built through one's history and experiences. At the end of his life, Henry James suffered a vascular stroke in the right hemisphere and developed a striking identity delusion. He dictated in a perfectly clear and coherent manner two letters as if they were written by Napoleon Bonaparte. He also showed signs of reduplicative paramnesia. Negative symptoms resulting from right hemisphere damage may disrupt the feelings of "warmth and intimacy and immediacy" and the "resemblance among the parts of a continuum of feelings (especially bodily feelings)", which are the foundation of personal identity according to William James. On the other hand, a left hemisphere receiving inadequate input from the damaged right hemisphere may produce positive symptoms such as delusional, confabulatory narratives. Other fragments dictated during Henry James's final disease reveal some form of insight, if partial and disintegrated, into his condition. Thus, even when consciousness is impaired by brain damage, something of its deep nature may persist, as attested by the literary characteristics of the last fragments of the Master.

The aim of this study is the analysis of the historical complexities associated with cancer registries in Spain. After the acceptance of the International Classification of Diseases in 1900, the first cancer incidence survey was in 1902. Following the inteernational initiative by the German Central Committee for Canceer Research (DZK), the Instituto Rubio conducted a census of all cancer patients undeer medical tretment. Spain attended the meeting in Berlin where the International Association for Cancer Research was founded (1908), and the Inteernational Union Against Cancer (IUAC) constitutional congress was held in Madrid (1933). Nonetheless, Spanish was absent from the first cancer registries conference (Copenhagen, September 1946), and from the WHO committe to support cancer registry programming (1950). As a result, contemporary history of Spanish cancer registries starts as late as 1960 in Zaragoza, particularly through the establishment of a Latin language speaking countries registries team., Este estudio tiene como objetivo analizar las complejidades históricas de los registros de cáncer en España. Tras la aceptación en 1900 de la primera clasificación internacional de enfermedades, se produjo en 1902 el primer estudio de incidencia del cáncer. A causa de la iniciativa internacional del Comité Central Alemán para la Investigación sobre el Cáncer (DZK), el Instituto Rubio realizó un censo de todos los pacientes bajo tratamiento médico. España participó en la fundación en Berlín de la International Association for Cancer Research (1908) y el congreso constituyente de la Unión Internacional Contra el Cáncer (UICC) se reunió en 1933 en Madrid, pero no asistió a la primera conferencia de registros de cáncer (Copenhague, septiembre de 1946), ni al comité de programación del registro de cáncer de la OMS (1950). Como resultado, la historia contemporánea del registro de cáncer español empieza en Zaragoza en 1960. La evolución de las técnicas epidemiológicas permite afirmar que España, pionera en los registros hospitalarios, se convirtió al sistema de registros poblacionales tardíamente, en particular gracias a la instauración de un equipo de los registros latinos en el que Zaragoza jugó un papel importante., La présente étude a pour objectif l'analyse des situations historiques complexes du registre des cancers en Espagne. Une fois acceptée en 1900 la première classification internationale des maladies, en 1902 s'est effectuée la première étude d'incidence du cancer. Le partenariat international du Comité central allemand pour la recherche sur le cancer (DZK) a mis en disposition le Instituto Rubio d'élaborer un recensement de tous les patients sous traitement médical. L'Espagne a participé à la fondation à Berlin de l'association internationale de la recherche sur le cancer (1908) et le Congrès constituant de l'Union internationale contre le cancer (UICC) s'est tenu à Madrid en 1933, mais n'a participé à la première conférence des registres des cancers (Copenhague, septembre 1946), ni au comité de programmation du registre de cancer de l'OMS (1950). En conséquence, l'histoire contemporaine du registre de cancer espagnol commence en 1960 à Zaragoza. L'évolution des techniques épidémiologiques permet d'affirmer que l'Espagne, pionnière dans le domaine des registres des hôpitaux, ne s'est convertie au système des registres basés sur la population que tardivement, par le biais notamment de la mise en place d'une équipe des registres latins où Zaragoza a joué un rôle important.

International audience; First published in 1909 in La Cellule, F. A. Janssens's "The chiasmatype theory. A new interpretation of the maturation divisions" proved controversial and was for several decades resisted by many geneticists and cytologists. In this month's Perspectives, Koszul et al. revisit Janssens's findings and the surrounding controversies. Here, translated for the first time in English, GENETICS republishes the original Janssens's article. The article is presented as closely as possible to the original publication's format and style.(2) GENETICS wishes to thank Romain Koszul and Denise Zickler for their labors in presenting the scientific community with this new translation.

International audience; Cultural exchanges and interactions between France and Argentina are not restricted to tango, exile stories, sports or fiction literature. Indeed, scientific interactions represent one of the most active areas of collaboration between the two countries. This Special Issue of the Journal of Physiology (Paris) includes some of the papers presented at the First Franco-Argentinean Symposium in Neurosciences, which was held in Buenos Aires in November, 2010. This was the first joint meeting of the Sociedad Argentina de Investigación en Neurociencias (SAN) and the Société des Neurosciences Française (SNF), and brought together many Argentinean neuroscientists as well as French guest speakers.

International audience; Exposure to radiation is one of the main concerns for space exploration by humans. By focusing deliberately on the works performed on human cells, we endeavored to review, decade by decade, the technological developments and conceptual advances of space radiation biology. Despite considerable efforts, the cancer and the toxicity risks remain to be quantified: 1) the nature and the frequency of secondary heavy ions need to be better characterized in order to estimate their contribution to the dose and to the final biological response; 2) the diversity of radiation history of each astronaut and the impact of individual susceptibility make very difficult any epidemiological analysis for estimating hazards specifically due to space radiation exposure. 3) Cytogenetic data undoubtedly revealed that space radiation exposure produce significant damage in cells. However, our knowledge of the basic mechanisms specific to low-dose, to repeated doses and to adaptive response is still poor. The application of new radiobiological techniques, like immunofluorescence, and the use of human tissue models different from blood, like skin fibroblasts, may help in clarifying all the above items.

International audience; Rabies is a fatal disease transmitted by infected animals by bite, scratch, licking on broken skin or contamination of mucosis by saliva. The regimen of post-exposure prophylaxis for people not previously vaccinated, that is currently recommended by WHO, consists of a combination of wound cleaning, active immunization and passive immunization when the exposure is of category 3. Most of the products available on the market, in particular human rabies immunoglobulins, highly purified equine rabies immunoglobulins and the derived F(ab')(2) fragments, are now characterized by high potency and safety. Although the interest of passive anti-rabies immunization was first demonstrated in the first half of the 20th century, there is still an inadequate supply of these products to the target populations mostly in developing countries. Therefore, it is urgent to set-up training and information actions for healthcare personnel on the need to use passive immunotherapy and the lack of adverse effects of the related products. For the future, we hope that a scale up of production and a lower price will improve the accessibility to these products. The development of new products based on monoclonal antibodies and molecular biology, and which may be cheaper, is promising.

International audience; This review describes the historical emergence of the concept of bone marrow mesenchymal stem cells (MSCs), summarizing data on Wolf and Trentin's hematopoietic inductive microenvironment; Dexter's hematopoiesis-supportive stromal cells; Friedenstein's osteogenic cells; and Pittenger's trilineal osteoblastic, chondrocytic, and adipocytic precursors; to finally introduce the specific bone marrow mesenchymal stem cells with differentiation potential to four lineages (mesenchymal and vascular smooth muscle lineages), and stromal and immunomodulatory capacities. Two points are the object of detailed discussion. The first point envisions the stem cell attributes (multipotentiality, self-renewal, tissue regeneration, population heterogeneity, plasticity, and lineage priming) compared with that of the paradigmatic hematopoietic stem cell. In the second point, we discuss the possible existence of bone marrow cells with greater differentiation potential, eventually pluripotential cells. The latter point raises the issues of cell fusion, reprogramming, or selection under nonstandardized conditions of rare populations of neuroectodermal origin, or of cells that had undergone mesenchymal-to-epithelial transition. In the last section, we review data on MSC senescence and possible malignant transformation secondary to extensive culture, gene transfer of telomerase, or mutations such as leading to Ewing's sarcoma. The set of data leads to the conclusion that bone marrow MSCs constitute a specific adult tissue stem cell population. The multiple characteristics of this stem cell type account for the versatility of the mechanisms of injured tissue repair. Although MSC administration may be extremely useful in a number of clinical applications, their transplantation is not without risks that must not be overlooked when developing cell therapy protocols.

International audience; This review describes the historical emergence of the concept of bone marrow mesenchymal stem cells (MSCs), summarizing data on Wolf and Trentin's hematopoietic inductive microenvironment; Dexter's hematopoiesis-supportive stromal cells; Friedenstein's osteogenic cells; and Pittenger's trilineal osteoblastic, chondrocytic, and adipocytic precursors; to finally introduce the specific bone marrow mesenchymal stem cells with differentiation potential to four lineages (mesenchymal and vascular smooth muscle lineages), and stromal and immunomodulatory capacities. Two points are the object of detailed discussion. The first point envisions the stem cell attributes (multipotentiality, self-renewal, tissue regeneration, population heterogeneity, plasticity, and lineage priming) compared with that of the paradigmatic hematopoietic stem cell. In the second point, we discuss the possible existence of bone marrow cells with greater differentiation potential, eventually pluripotential cells. The latter point raises the issues of cell fusion, reprogramming, or selection under nonstandardized conditions of rare populations of neuroectodermal origin, or of cells that had undergone mesenchymal-to-epithelial transition. In the last section, we review data on MSC senescence and possible malignant transformation secondary to extensive culture, gene transfer of telomerase, or mutations such as leading to Ewing's sarcoma. The set of data leads to the conclusion that bone marrow MSCs constitute a specific adult tissue stem cell population. The multiple characteristics of this stem cell type account for the versatility of the mechanisms of injured tissue repair. Although MSC administration may be extremely useful in a number of clinical applications, their transplantation is not without risks that must not be overlooked when developing cell therapy protocols.

Susceptibility to antibiotics of 4,816 clinical L. monocytogenes strains isolated since 1926 was studied, and the temporal evolution of susceptibility to antibiotics was analyzed through several decades. The mechanisms of resistance in each resistant strain were studied. The prevalence of resistant strains was estimated at 1.27% among isolates from humans. Resistance to tetracyclines+ and fluoroquinolones was more common and has recently emerged. Although acquired resistance in clinical L. monocytogenes did not implicate clinically relevant antibiotics, the possibility of resistance gene transfers, the description of the first clinical isolate with high-level resistance to trimethoprim, and the recent increase in penicillin MICs up to 2 μg/ml reinforce the need for microbiological surveillance.

International audience; Microbeam radiation therapy (MRT) uses highly collimated, quasi-parallel arrays of X-ray microbeams of 50-600keV, produced by third generation synchrotron sources, such as the European Synchrotron Radiation Facility (ESRF), in France. The main advantages of highly brilliant synchrotron sources are an extremely high dose rate and very small beam divergence. High dose rates are necessary to deliver therapeutic doses in microscopic volumes, to avoid spreading of the microbeams by cardiosynchronous movement of the tissues. The minimal beam divergence results in the advantage of steeper dose gradients delivered to a tumor target, thus achieving a higher dose deposition in the target volume in fractions of seconds, with a sharper penumbra than that produced in conventional radiotherapy. MRT research over the past 20 years has yielded many results from preclinical trials based on different animal models, including mice, rats, piglets and rabbits. Typically, MRT uses arrays of narrow ( approximately 25-100 microm wide) microplanar beams separated by wider (100-400 microm centre-to-centre) microplanar spaces. The height of these microbeams typically varies from 1 to 100 mm, depending on the target and the desired preselected field size to be irradiated. Peak entrance doses of several hundreds of Gy are surprisingly well tolerated by normal tissues, up to approximately 2 yr after irradiation, and at the same time show a preferential damage of malignant tumor tissues; these effects of MRT have now been extensively studied over nearly two decades. More recently, some biological in vivo effects of synchrotron X-ray beams in the millimeter range (0.68-0.95 mm, centre-to-centre distances 1.2-4 mm), which may differ to some extent from those of microscopic beams, have been followed up to approximately 7 months after irradiation. Comparisons between broad-beam irradiation and MRT indicate a higher tumor control for the same sparing of normal tissue in the latter, even if a substantial fraction of tumor cells are not receiving a radiotoxic level of radiation. The hypothesis of a selective radiovulnerability of the tumor vasculature versus normal blood vessels by MRT, and of the cellular and molecular mechanisms involved remains under investigation. The paper highlights the history of MRT including salient biological findings after microbeam irradiation with emphasis on the vascular components and the tolerance of the central nervous system. Details on experimental and theoretical dosimetry of microbeams, core issues and possible therapeutic applications of MRT are presented.

Between 1942 and 1956, Jacques Monod, Nobel Prize winner in Physiology/Medicine, contributed a number of papers to the Annales de l' Institut Pasteur, the ancestor of the journal "Research in Microbiology". Circumstances that led him to publish in the "Annales" are recalled here. Entre 1942 et 1956, Jacques Monod, Prix Nobel de physiologie et de médecine a rédigé de nombreux articles dans les Annales de l'Institut Pasteur, ancêtre du journal "Research in Microbiology". Les circonstances qui l'ont amené à publier dans les "Annales" sont rappelées ici.

Malaria is the most widespread deadly parasitic disease, affecting 500 million individuals and causing the death of 1–2 million children under 5 years of age and, among adults, mainly prima gravida...

International audience; Rabies is a fatal disease transmitted by infected animals by bite, scratch, licking on broken skin or contamination of mucosis by saliva. The regimen of post-exposure prophylaxis for people not previously vaccinated, that is currently recommended by WHO, consists of a combination of wound cleaning, active immunization and passive immunization when the exposure is of category 3. Most of the products available on the market, in particular human rabies immunoglobulins, highly purified equine rabies immunoglobulins and the derived F(ab')(2) fragments, are now characterized by high potency and safety. Although the interest of passive anti-rabies immunization was first demonstrated in the first half of the 20th century, there is still an inadequate supply of these products to the target populations mostly in developing countries. Therefore, it is urgent to set-up training and information actions for healthcare personnel on the need to use passive immunotherapy and the lack of adverse effects of the related products. For the future, we hope that a scale up of production and a lower price will improve the accessibility to these products. The development of new products based on monoclonal antibodies and molecular biology, and which may be cheaper, is promising.

Background: Our aim was to validate the use of historical events as tools for estimating the age of people ≧65 years in Cotonou (Benin). Methods: The survey was conducted in Cotonou, the economic capital of Benin. We included people aged ≧65 years, with at least a primary education level and an administrative document certifying their date of birth. The historical events were the solar eclipse of 1946 covering the national territory and the date of independence (1st August 1960) of Dahomey (Benin). Agreement between estimated and actual age was assessed by the intraclass correlation coefficient and the Bland and Altman graphical representation. Results: We included 112 subjects. The intraclass correlation coefficient between actual and estimated age by the use of historical landmarks was 0.87 (95% CI = 0.81–0.91), i.e. an excellent concordance. The graph of Bland and Altman did not demonstrate any systematic error of estimation. Conclusion: The development of similar tools in other parts of Africa and developing countries may improve the quality of information collected in epidemiological studies and thereby enhance the accuracy of the results of studies conducted on age-related disorders such as dementia.

http://www.architalbiol.org/aib/article/view/14859/20830969; International audience; Ten years have now passed since the discovery of quiescent neural stem cells within the mammalian retina. Beside the fascinating aspect of stem cell biology in basic science, these cells have also offered hope for the treatment of incurable retinal diseases. The field has thus rapidly evolved, fluctuating between major advances and recurring doubts. In this review, we will retrace the efforts of scientists during this last decade to characterize these cells and to use them in regenerative medicine. We will also highlight advances made in animal models capable of stem cell-mediated retinal regeneration.

A l'occasion du centenaire du bulletin scientifique "Les Archives de l'Institut Pasteur de Tunis'' et pour commémorer ses cent années de publications, nous publions cet article qui retrace sommairement les travaux de Charles Nicolle et de ses collaborateurs.

International audience; Since the 1960s, deep brain stimulation and spinal cord stimulation at low frequency (30 Hz) have been used to treat intractable pain of various origins. For this purpose, specific hardware have been designed, including deep brain electrodes, extensions, and implantable programmable generators (IPGs). In the meantime, movement disorders, and particularly parkinsonian and essential tremors, were treated by electrolytic or mechanic lesions in various targets of the basal ganglia, particularly in the thalamus and in the internal pallidum. The advent in the 1960s of levodopa, as well as the side effects and complications of ablative surgery (e.g., thalamotomy and pallidotomy), has sent functional neurosurgery of movement disorders to oblivion. In 1987, the serendipitous discovery of the effect of high-frequency stimulation (HFS), mimicking lesions, allowed the revival of the surgery of movement disorders by stimulation of the thalamus, which treated tremors with limited morbidity, and adaptable and reversible results. The stability along time of these effects allowed extending it to new targets suggested by basic research in monkeys. The HFS of the subthalamic nucleus (STN) has profoundly challenged the practice of functional surgery as the effect on the triad of dopaminergic symptoms was very significant, allowing to decrease the drug dosage and therefore a decrease of their complications, the levodopa-induced dyskinesias. In the meantime, based on the results of previous basic research in various fields, HFS has been progressively extended to potentially treat epilepsy and, more recently, psychiatric disorders, such as obsessive-compulsive disorders, Gilles de la Tourette tics, and severe depression. Similarly, suggested by the observation of changes in PET scan, applications have been extended to cluster headaches by stimulation of the posterior hypothalamus and even more recently, to obesity and drug addiction. In the field of movement disorders, it has become clear that STN stimulation is not efficient on the nondopaminergic symptoms such as freezing of gait. Based on experimental data obtained in MPTP-treated parkinsonian monkeys, the pedunculopontine nucleus has been used as a new target, and as suggested by the animal research results, its use indeed improves walking and stability when stimulation is performed at low frequency (25 Hz). The concept of simultaneous stimulation of multiple targets eventually at low or high frequency, and that of several electrodes in one target, is being accepted to increase the efficiency. This leads to and is being facilitated by the development of new hardware (multiple-channel IPGs, specific electrodes, rechargeable batteries). Still additional efforts are needed at the level of the stimulation paradigm and in the waveform. The recent development of nanotechnologies allows the design of totally new systems expanding the field of deep brain stimulation. These new techniques will make it possible to not only inhibit or excite deep brain structures to alleviate abnormal symptoms but also open the field for the use of recording cortical activities to drive neuroprostheses through brain-computer interfaces. The new field of compensation of deficits will then become part of the field of functional neurosurgery.

International audience; The Bordeaux Neuroscience Institute brings together all the disciplines that constitute the clinical and experimental neurosciences. Outside of the Paris region, the Institute represents the largest community of researchers working on the nervous system. The aim of this brief historical piece is to describe how neuroscientists in Bordeaux are the heirs to a long neuropsychiatric tradition established by pioneers of national and international renown. This tradition has been maintained, without interruption, through many generations. The careers and scientific work of these great neurologists and psychiatrists are briefly evoked, and particularly those of A. Pitres, E. Régis and E. Azam in the 19th century; and, in the 20th century, J. Abadie, H. Verger and R. Cruchet. The determining influence of P Delmas-Marsalet (1898-1977), Professor of Neuropsychiatry, on the development of modern neurosciences in Bordeaux is recalled through his work, his teachings, and his numerous students.

Twenty-five years after the publication of the first report on gene transfer in vitro in cultured cells by the means of electric pulse delivery, reversible cell electroporation for gene transfer and gene therapy (DNA electrotransfer) is at a crossroad in its development. Present knowledge on the effects of cell exposure to appropriate electric field pulses, particularly at the level of the cell membrane, is reported here as an introduction to the large range of applications described in this book. The importance of the models of electric field distribution in tissues and of the correct choice of electrodes and applied voltages is highlighted. The mechanisms involved in DNA electrotransfer, which include cell electropermeabilization and DNA electrophoresis, are also surveyed. The feasibility of electric pulse for gene transfer in humans is discussed taking into account that electric pulse delivery is already regularly used for localized drug delivery in the treatment of cutaneous and subcutaneous solid tumors by electrochemotherapy. Because recent technological developments have made DNA electrotransfer more efficient and safer, this nonviral gene therapy approach is now ready to reach the clinical stage. A good understanding of DNA electrotransfer principles and a respect for safe procedures will be key elements for the successful future transition of DNA electrotransfer to the clinics.

ERMA; International audience; If we observe the evolution of the Alzheimer's disease of a premature entorhinal stage at an evolved stage of the neocortex, the succession of the confusions of the simple mnesic complaint in the aphasia, praxia, gnosia, visual, psychological and comportemental difficulties testify of the extension of the lesions in the neocortical structures. This neocortical regression seems to take the inverse road of the phylo- and ontogenetic evolution, where this hegemonic neocerebral cortex - which had grown again on the borders of the archeocortical and paleocortical barbarian empire - sees itself dispossessed of its conquests and gives free rein to these ancestral structures. We could compare the Alzheimer's disease with the fall of the neocortical empire at the age of nonsense.

Ángeles Alvariño (1916–2005), who belonged to the second generation of Spanish female oceanographers, started out professionally as a researcher with the Instituto Español de Oceanografía (IEO), Madrid, where she had her early papers published in the 1950s. She covered in these papers different geographical areas, focusing mostly on plankton and on marine fisheries. During her stay at IEO she enjoyed scholarships in England and U.S.A. She later furthered in the latter country her professional career at such other prestigious research centres as Scripps Institution of Oceanography (1958-1969) and Southwest Research Center (1970-1987), both in California. Until her retirement in 1987 she directed her researches towards biological oceanography, becoming a worldwide expert in different groups of marine zooplankton, as regards both their taxonomic aspects and their application to fisheries. She described 22 new plankton species and had close to one hundred papers published in reputable Spanish, American and Latin American journals. She was also concerned with the history of Spanish scientific expeditions, on which she published a book in 2003. An analysis made on Thomson's-Wok platform shows the impact that this lady is having in international bibliography, with an average annual 8.8 citations in the analysed period (1964-2008). The overall recorded 387 citations (excluding self-citations) are distributed over different aspects regarding plankton predator species as they affect finfish eggs and larvae., Ángeles Alvariño González (1916–2005), perteneciente a la 2ª generación de oceanógra-fas españolas, inició su carrera investigadora en el Instituto Español de Oceanografía (IEO), en cuyas publicaciones de los años cincuenta aparecieron sus primeros trabajos. Abarcando éstos diferentes áreas geográficas, se centraron mayoritariamente en el plancton y en las pesquerías. Durante su estancia en el IEO disfrutó de becas en Inglaterra y en los EE.UU. Continuaría en ese último país su carrera profesional, trabajando en otros prestigiosos centros de investigación en California, Scripps Institution of Oceanography (1958–69) y Southwest Fisheries Center (1970–87). Hasta su jubilación en 1987 dirigió sus investigaciones hacia la oceanografía biológica, y se convirtió en experta mundial de diferentes grupos del zooplancton marino, tanto en sus aspectos taxonómicos, como biogeográficos y de aplicación a las pesquerías. Describió 22 nuevas especies planctónicas y publicó cerca de un centenar de artículos en reputadas revistas españolas, norteamericanas y sudamericanas; así como monografías y capítulos de libros. También se interesó por las históricas expediciones científicas españolas, sobre las que publicó un libro en 2003. El análisis realizado sobre la plataforma Thomson-Wok muestra el importante impacto de Alvariño en la bibliografía internacional, con una media de 8,8 citas anuales para el período analizado (1964–2008). Las 387 citas contabilizadas (excluyendo las autocitas) se reparten en diferentes aspectos relacionados con las especies predadoras del plancton y su incidencia sobre los huevos y larvas de peces., Ángeles Alvariño (1916–2005), issue de la seconde génération de femmes océanographes espagnoles, a débuté professionnellement comme chercheuse auprès de l'Instituto Español de Oceanografía (IEO), Madrid, où ses premiers articles scientifiques ont été publiés au début des années 50. Ces articles ont couvert différentes régions géographiques, en mettant principalement l'accent sur le plancton et les stocks de poisson. Pendant son temps au IEO, elle a bénéficié de bourses d'études en Angleterre et aux États-Unis. Plus tard, elle a fait progresser sa carrière profesionnelle dans d'autres centres de recherche prestigieux comme Scripps Institution of Oceanography (1958-1969) et Southwest Research Center (1970-1987), basés en Californie. Ayant pris sa retraite en 1987, sa recherche a été orientée vers l'océanographie biologique, jusqu'à en devenir une experte mondiale en divers groupes de zooplancton marin, concernant leurs aspects taxonomiques et pour ce qui est de leur application dans le domaine de la pêche. Elle a décrit 22 nouvelles espèces de plancton et a publié près de 100 articles dans des journaux renommés espagnols, américains et latinoaméricains. Abordant l'histoire des expéditions scientifiques espagnoles, elle a fait paraître dans cet esprit, en 2003, un livre. À la lumière d'une analyse sur l'impact auquel cette femme est confrontée dans la bibliographie internationale, effectuée sur la plateforme Web of Knowledge de Thomson au long de la période analysée (1964-2008), sa citation annuelle moyenne a été de 8.8. Ses 387 citations globales (auto-citations non comprises), sont réparties sur différents aspects des espèces de prédateurs du plancton puisqu'elles peuvent avoir des répercussions sur les poissons à nageoires et les larves.

International audience; Nowadays, catatonia is no more considered as a subtype of schizophrenia. Catatonia seems more frequently associated to mood disorders as well as general medical conditions. It is sometimes difficult to associate formally a medical etiology to this syndrome. But we found, in the literature, three groups of associated general medical conditions: neurological disorders, drug induced and toxic induced conditions, metabolic conditions. We present a prospective study of 12 clinical cases of catatonia due to general medical conditions we realized in the Consultation-Liaison Psychiatry Department of the University Hospital of LILLE (France) during a period of 5 months. We find coherent data with the literature. However, our results suggest that if medical conditions precipitate the catatonia syndrome, they are rarely its only etiology. We think that if somatic factors are co-morbid with psychiatric conditions they do not necessarily predominate as the target of treatment. The treatment of the catatonia must be a priority and remain symptomatic, to allow in parallel the specific treatment for the somatic disorder or the psychiatric disorder.

International audience; Hepatitis C virus (HCV) infection in Cameroon is characterized by widespread seropositivity and great virus genetic diversity (3 genotypes and over 10 subtypes). A total of 244 HCV NS5B sequences of 382-405 bp long (95 type 1, 58 type 2, and 91 type 4) were phylogenetically analyzed to estimate the history of the HCV epidemic in Cameroon. The newly developed Bayesian coalescent approach was used to infer the history of each HCV type. The estimated dates of the most recent common ancestors (MRCA) for genotypes 1 (1500; 95% confidence interval (95% CI): 1300-1650) and 4 (1500; 95% CI: 1350-1700) were in the same range, while the date for genotype 2 MRCA (1600; 95% CI: 1400-1750) was slightly more recent. The mean genetic distance between HCV genotype 1 sequences was greater than that of HCV type 4 sequences, itself greater than that of HCV type 2 sequences. The initial infected populations of all three genotypes did not grow until recently, when they grew exponentially. The growth rate has now begun to slow, with a less steep exponential growth curve. The period of exponential growth of all the three genotypes was between 1920 and 1960. These results (i) confirm that HCV genotypes 1 and 4 have produced long-term endemics, (ii) suggest that genotype 2 was introduced into Cameroon more recently, and (iii) indicate that the exponential spread of the three genotypes between 1920 and 1960 coincided with the mass campaign against trypanosomiasis and mass vaccinations in Cameroon.

International audience; Rigidity is commonly defined as a resistance to passive movement. In Parkinson's disease (PD), two types of rigidity are classically recognized which may coexist, "leadpipe " and "cogwheel". Charcot was the first to investigate parkinsonian rigidity during the second half of the nineteenth century, whereas Negro and Moyer described cogwheel rigidity at the beginning of the twentieth century. Jules Froment, a French neurologist from Lyon, contributed to the study of parkinsonian rigidity during the 1920s. He investigated rigidity of the wrist at rest in a sitting position as well as in stable and unstable standing postures, both clinically and with physiological recordings using a myograph. With Gardère, Froment described enhanced resistance to passive movements of a limb about a joint that can be detected specifically when there is a voluntary action of another contralateral body part. This has been designated in the literature as the "Froment's maneuver " and the activation or facilitation test. In addition, Froment showed that parkinsonian rigidity diminishes, vanishes, or enhances depending on the static posture of the body. He proposed that in PD "maintenance stabilization " of the body is impaired and that "reactive stabilization " becomes the operative mode of muscular tone control. He considered "rigidification " as compensatory against the forces of gravity. Froment also demonstrated that parkinsonian rigidity increases during the Romberg test, gaze deviation, and oriented attention. In their number, breadth, and originality, Froment's contributions to the study of parkinsonian rigidity remain currently relevant to clinical and neurophysiological issues of PD.

International audience; The definition of the epileptogenic zone, as proposed by Talairach and Bancaud, is an ictal electro-clinical definition based on the results of stereotactic intracerebral EEG (SEEG) recordings. It takes into account not only the anatomical location of the "site of the beginning and of the primary organization" of the epileptic discharge, but also how this discharge gives rise to the accompanying clinical symptoms. This definition is different from the North American view since, for the French authors, the epileptogenic zone is not synonymous with what can be called the "what-to-remove area". In fact, it is above all a conceptual definition which emphazises the importance of studying the spatio-temporal dynamics of seizure discharges, and not only their starting point.

International audience; BACKGROUND: Recent studies have demonstrated magnetic resonance (MR) capabilities in evaluating renal morphology and function in patients with urinary obstruction. The objective of this report is to support the introduction of dynamic MR renography on any MR equipment. METHODS: A custom-made device of vials filled with different concentrations of gadolinium was studied by combinations of T1-weighted gradient-echo sequences and coils. We compared the capabilities of two coils (phased array vs. standard body), the properties of dynamic sequences, and the effects of increasing concentrations of gadolinium on signal intensity. In a second section, we designed MR urography plug-ins of Image J (DICOM image software) for the analysis of dynamic studies. RESULTS: Optimized gradient-echo sequences acquired with a phased array body coil produced acceptable quality images with a linear relation between signal intensity and the lowest concentrations of gadolinium. In vitro measurements showed loss of linearity above 8 mmol/L. CONCLUSION: Theoretical calculation and data from the literature suggest that the gadolinium dose to the patient should not exceed one-fourth of the usual one (0.025 mmol/kg). Postprocessing using Image J software and the specifically designed plug-ins was validated. The collection of plug-ins is now available on the Internet.

International audience; Starting from Garcia's definition, the historical evolution of the notion of vocal registers from then until now is considered. Even though much research has been carried out on vocal registers since then, the notion of registers is still confused in the singing voice community, and defined in many different ways. While some authors consider a vocal register as a totally laryngeal event, others define it in terms of overall voice quality similarities. This confusion is reflected in the multiplicity of labellings, and it lies in the difficulty of identifying and specifying the mechanisms distinguished by these terms. The concept of laryngeal mechanism is then introduced, on the basis of laryngeal transition phenomena detected by means of electroglottography. It helps to specify at least the laryngeal nature of a given singing voice register. On this basis, the main physiological, acoustic, and perceptual characteristics of the most common singing voice registers are surveyed.