Archéologie d’un parasite du cheval

Oxyuris equi, l’oxyure du cheval, est un vers parasite spécifique des équidés régulièrement mis en évidence lors des études paléoparasitologiques. Nous proposons ici une synthèse originale entre les mentions de ce parasite connues dans la bibliographie et les textes anciens, avec des données inédites issues de nos recherches en paléoparasitologie. Cette compilation des données montre que la plus ancienne observation de l’oxyure du cheval date du milieu du Ier millénaire avant notre ère en Asie centrale, et du second âge du Fer en Europe de l’Ouest. Les mouvements de populations au moment de la conquête romaine, les échanges commerciaux et l’avancée des troupes à travers l’Empire romain ont pu contribuer à diffuser le parasite en Europe de l’Ouest. Il apparaît également que l’oxyure du cheval n’est pas détecté sur le continent américain avant l’époque contemporaine. Le rôle des migrations européennes autour du xve siècle est discuté pour expliquer l’observation tardive d’Oxyuris equi sur le continent américain. L’absence d’observation de ce parasite avant l’âge du Fer en Eurasie peut également s’expliquer par son écologie, un échantillonnage non favorable, voire la relative rareté des restes de chevaux sur les sites archéologiques.The intestinal pinworm Oxyuris equi is a parasite that specifically affects horses and that is regularly picked up in parasitological analyses. Here we give an overview combining references to these parasites in the literature and in ancient sources with hitherto unpublished results from our own palaeo-parasitological studies. This reveals that the earliest case of horse pinworm dates to the middle of the first millennium BC in central Asia, and to the Later Iron Age in western Europe. Population movements at the time of the Roman conquest, trade and exchange, and the movement of troops within the Roman empire may have contributed to the spread of this parasite in western Europe. It seems that the horse pinworm does not appear in America before the modern period. The role European emigration around the fifteenth century may have played in the late introduction of Oxyuris equi on the American continent is also discussed. The absence of evidence for pinworms before the Iron Age in Eurasia may perhaps be explained by its ecology, by unfavourable sampling conditions, or even by the rarity of finds of horses on archaeological sites.Oxyuris equi, la oxiuriasis equina, es una enfermedad parasitaria propia de los équidos transmitida por un gusano de la cual se encuentran regularmente evidencias a través de estudios paleoparasitológicos. En el presente texto se propone una síntesis original de las menciones de dicho parásito encontradas en la bibliografía y los textos antiguos, además de datos inéditos recabados durante nuestras investigaciones en paleoparasitología. El acerbo de datos muestra que las observaciones más antiguas de la oxiuriasis equina remontan a mediados del primer milenio antes de nuestra era en Asia central y a la Segunda Edad del Hierro en Europa occidental. Los desplazamientos de población durante la conquista romana, así como los intercambios comerciales y el avance de las tropas a través del Imperio romano, pudieron contribuir a la difusión de este parásito en Europa occidental. Se observa además que no existen rastros de oxiuriasis equina en el continente americano antes del período contemporáneo. Con el fin de explicar la observación tardía de Oxyuris equi en dicho continente, se discute el papel desempeñado por las migraciones europeas alrededor del siglo XV. Por lo demás, el hecho de que no se hayan encontrado rastros del parásito antes de la Edad del Hierro en Eurasia puede deberse a su ecología, a muestrarios poco favorables, e incluso a la presencia relativamente escasa de restos de caballos en los sitios arqueológicos

A dual drug regimen synergistically blocks human parainfluenza virus infection.

International audienceHuman parainfluenza type-3 virus (hPIV-3) is one of the principal aetiological agents of acute respiratory illness in infants worldwide and also shows high disease severity in the elderly and immunocompromised, but neither therapies nor vaccines are available to treat or prevent infection, respectively. Using a multidisciplinary approach we report herein that the approved drug suramin acts as a non-competitive in vitro inhibitor of the hPIV-3 haemagglutinin-neuraminidase (HN). Furthermore, the drug inhibits viral replication in mammalian epithelial cells with an IC50 of 30 μM, when applied post-adsorption. Significantly, we show in cell-based drug-combination studies using virus infection blockade assays, that suramin acts synergistically with the anti-influenza virus drug zanamivir. Our data suggests that lower concentrations of both drugs can be used to yield high levels of inhibition. Finally, using NMR spectroscopy and in silico docking simulations we confirmed that suramin binds HN simultaneously with zanamivir. This binding event occurs most likely in the vicinity of the protein primary binding site, resulting in an enhancement of the inhibitory potential of the N-acetylneuraminic acid-based inhibitor. This study offers a potentially exciting avenue for the treatment of parainfluenza infection by a combinatorial repurposing approach of well-established approved drugs

A novel function of the key nitrogen-fixation activator NifA in beta-rhizobia: Repression of bacterial auxin synthesis during symbiosis

Rhizobia fix nitrogen within root nodules of host plants where nitrogenase expression is strictly controlled by its key regulator NifA. We recently discovered that in nodules infected by the beta-rhizobial strain Paraburkholderia phymatum STM815, NifA controls expression of two bacterial auxin synthesis genes. Both the iaaM and iaaH transcripts, as well as the metabolites indole-acetamide (IAM) and indole-3-acetic acid (IAA) showed increased abundance in nodules occupied by a nifA mutant compared to wild-type nodules. Here, we document the structural changes that a P. phymatum nifA mutant induces in common bean (Phaseolus vulgaris) nodules, eventually leading to hypernodulation. To investigate the role of the P. phymatum iaaMH genes during symbiosis, we monitored their expression in presence and absence of NifA over different stages of the symbiosis. The iaaMH genes were found to be under negative control of NifA in all symbiotic stages. While a P. phymatum iaaMH mutant produced the same number of nodules and nitrogenase activity as the wild-type strain, the nifA mutant produced more nodules than the wild-type that clustered into regularly-patterned root zones. Mutation of the iaaMH genes in a nifA mutant background reduced the presence of these nodule clusters on the root. We further show that the P. phymatum iaaMH genes are located in a region of the symbiotic plasmid with a significantly lower GC content and exhibit high similarity to two genes of the IAM pathway often used by bacterial phytopathogens to deploy IAA as a virulence factor. Overall, our data suggest that the increased abundance of rhizobial auxin in the non-fixing nifA mutant strain enables greater root infection rates and a role for bacterial auxin production in the control of early stage symbiotic interactions

Comparaison de méthodes dévaluation d'efforts par mesures PIV

International audienceDans ce papier, nous mettons en œuvre et comparons deux méthodes de calcul d’efforts s’appliquant sur une structure immergée dans un écoulement, à partir de données PIV stéréo. Les formulations se basent sur un bilan global de quantité de mouvement moyenné en temps. Une de ces méthodes permet, dans le cadre aérodynamique, de distinguer les contributions de traînée induite et de traînée de profil à partir de mesures du sillage uniquement. Les prédictions de traînée utilisant des données PIV stéréo et sonde 5-trous sont comparées à des mesures directes faites par balance. Ces comparaisons montrent que l’approche globale alimentée par des données PIV est effectivement viable, et qu’elle peut être utilisée pour décrire et étudier les phénomènes physiques à l’origine de la traînée

Interdisciplinarity and infectious diseases : an Ebola case study

International audienceHigh-profile epidemics such as Ebola, avian influenza, and severe acute respiratory syndrome (SARS) repeatedly thrust infectious diseases into the limelight. Because the emergence of dis-eases involves so many factors, the need for interdisciplinary approaches to studying emerging infections, particularly those originating from animals (i.e., zoonoses), is frequently discussed. However, effective integration across disciplines is challenging in practice. Ecological ideas, for example, are rarely considered in biomedical research, while insights from biomedicine are often neglected in ecological studies of infectious diseases. One practical reason for this is that researchers in these fields focus on vastly different scales of biological organization, which are difficult to bridge both intellectually and methodologically. Nevertheless, integration across biological scales is increasingly needed for solving the complex problems zoonotic diseases pose to human and animal well-being. Motivated by current events, we use Ebola virusas a case study to highlight fundamental questions about zoonoses that can be addressed by integrating insights and approaches across scales

Automatic reconstruction of urban wastewater and stormwater networks based on uncertain manhole cover locations

International audienceAccurate maps of sewer and stormwater networks in cities are mandatory for an integrated management of water resources. However, in many countries this information is unavailable or inaccurate. A new two-fold mapping method is put forward. The first step consists in using imageprocessing techniques to detect buried network surface elements such as manhole covers on very high resolution aerial imagery. The second step consists in connecting them automatically using a tree-shaped graph constrained by industry rules. The method is tested on Prades-le-Lez, Southern France. The shape and topology of the reconstructed network are compared to the actual ones.The impact of the detected objects’ density is also assessed

Global variability in seawater Mg:Ca and Sr:Ca ratios in the modern ocean

Seawater Mg:Ca and Sr:Ca ratios are biogeochemical parameters reflecting the Earth–ocean–atmosphere dynamic exchange of elements. The ratios’ dependence on the environment and organisms' biology facilitates their application in marine sciences. Here, we present a measured single-laboratory dataset, combined with previous data, to test the assumption of limited seawater Mg:Ca and Sr:Ca variability across marine environments globally. High variability was found in open-ocean upwelling and polar regions, shelves/neritic and river-influenced areas, where seawater Mg:Ca and Sr:Ca ratios range from ∼4.40 to 6.40 mmol:mol and ∼6.95 to 9.80 mmol:mol, respectively. Open-ocean seawater Mg:Ca is semiconservative (∼4.90 to 5.30 mol:mol), while Sr:Ca is more variable and nonconservative (∼7.70 to 8.80 mmol:mol); both ratios are nonconservative in coastal seas. Further, the Ca, Mg, and Sr elemental fluxes are connected to large total alkalinity deviations from International Association for the Physical Sciences of the Oceans (IAPSO) standard values. Because there is significant modern seawater Mg:Ca and Sr:Ca ratios variability across marine environments we cannot absolutely assume that fossil archives using taxa-specific proxies reflect true global seawater chemistry but rather taxa- and process-specific ecosystem variations, reflecting regional conditions. This variability could reconcile secular seawater Mg:Ca and Sr:Ca ratio reconstructions using different taxa and techniques by assuming an error of 1 to 1.50 mol:mol, and 1 to 1.90 mmol:mol, respectively. The modern ratios’ variability is similar to the reconstructed rise over 20 Ma (Neogene Period), nurturing the question of seminonconservative behavior of Ca, Mg, and Sr over modern Earth geological history with an overlooked environmental effect

Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers

Amyloid-beta 42 (A beta 42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for A beta 42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple A beta 42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.Peer reviewe

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease