Genetic analysis for mastitis resistance and milk somatic cell score in French Lacaune dairy sheep

Genetic analysis for mastitis resistance was studied from two data sets. Firstly, risk factors for different mastitis traits, i.e. culling due to clinical or chronic mastitis and subclinical mastitis predicted from somatic cell count (SCC), were explored using data from 957 first lactation Lacaune ewes of an experimental INRA flock composed of two divergent lines for milk yield. Secondly, genetic parameters for SCC were estimated from 5 272 first lactation Lacaune ewes recorded among 38 flocks, using an animal model. In the experimental flock, the frequency of culling due to clinical mastitis (5%) was lower than that of subclinical mastitis (10%) predicted from SCC. Predicted subclinical mastitis was unfavourably associated with the milk yield level. Such an antagonism was not detected for clinical mastitis, which could result, to some extent, from its low frequency or from the limited amount of data. In practice, however, selection for mastitis resistance could be limited in a first approach to selection against subclinical mastitis using SCC. The heritability estimate of SCC was 0.15 for the lactation mean trait and varied from 0.04 to 0.12 from the first to the fifth test-day. The genetic correlation between lactation SCC and milk yield was slightly positive (0.15) but showed a strong evolution during lactation, i.e. from favourable (-0.48) to antagonistic (0.27). On a lactation basis, our results suggest that selection for mastitis resistance based on SCC is feasible. Patterns for genetic parameters within first lactation, however, require further confirmation and investigation

Joint use of static and dynamic software verification techniques: a cross-domain view in safety critical system industries

International audienceHow different are the approaches to combining formal methods (FM) and testing in the safety standards of the automotive, aeronautic, nuclear, process, railway and space industries? This is the question addressed in this paper by a cross-domain group of experts involved in the revision committees of ISO 26262, DO-178C, IEC 60880, IEC 61508, EN 50128 and ECSS-Q-ST-8OC. First we review some commonalities and differences regarding application of formal methods in theaforementioned standards. Are they mandatory or recommended only? What kind of properties are they advised to be applied to? What is specified in the different standards regarding coverage (both functional and structural) if testing and formal methods are used jointly?We also account for the return on experience of the group members in the six industrial domains regarding state of the art practice of joint use of formal methods and testing. Where did formal methods actually prove to outperform testing? Then we discuss verification coverage, and more specifically the role of structural coverage. Does structural coverage play the same role in all the standards? Is it specific to testing and irrelevant for formal methods? What verification terminationcriteria is applicable in case FM-test mix? We conclude on some prospective views on how software safety standards may evolve to maximize the benefits of joint use of dynamic (testing) and static (FM) verification methods

Chapitre 1. La grotte

La grotte de Pergouset a été découverte en février 1964 par J.‑G. Astruc, C. Brillant, G. et M.‑T. Maury, C. Milhas et l’abbé Terret, tous membres du Groupe spéléologique du Quercy. Elle a fait l’objet d’une étude pluridisciplinaire qui a duré dix années, dont les résultats sont publiés ici. La grotte s’ouvre sur les berges du Lot, sur la commune de Saint‑Géry (Lot). Elle est formée d’un conduit unique et très étroit, long de 190 m, se terminant par une chatière conduisant à un petit cours d’eau souterrain. Elle constitue la galerie supérieure et le trop‑plein de ce ruisseau. Les secteurs ornés de gravures pariétales sont de petites salles dans lesquelles on peut se tenir assis. La partie profonde est par contre plus vaste. Une série de 16 sondages a permis d’étudier le remplissage de la cavité. Les sédiments sont principalement argilo‑limoneux et souvent finement feuilletés. Ils ont été déposés par la rivière souterraine et par le Lot. Ils sont épais de plusieurs mètres à l’entrée et de 1 à 2,50 m dans les galeries profondes où se trouvent les gravures. La cavité est régulièrement inondée en hiver par les crues du Lot : elle le fut également tout au long du passé et même dès le Paléolithique. Les sondages, complétés par des nettoyages du bas des parois couvert de limon d’inondation, n’ont révélé aucune gravure pariétale ensevelie sous le remplissage. Dans la zone d’entrée, les sondages ont permis de mettre en évidence l’importance de l’occupation médiévale, en relation probable avec une exploitation des ressources de la rivière (pêcherie). Aucun niveau paléolithique n’a été mis au jour. Les quelques menus charbons trouvés lors des fouilles dans les zones ornées de gravures (salle II) sont d’époque récente, probablement médiévale. Ils semblent avoir été introduits par les eaux du Lot, lors d’une crue exceptionnelle. Les zones intérieures explorées par les autres sondages se sont avérées archéologiquement stériles. Le seul indice possible de présence paléolithique au pied de la paroi ornée a été découvert dans la salle IV. Il s’agit d’un charbon de bois situé sur une corniche rocheuse et qui était recouvert par 5 cm de limon ; il a été daté de 32 850 ans ± 520 BP (Gif A96675) mais ne semble pas avoir de relation avec les gravures dont l’ensemble est très probablement magdalénien. La fréquentation paléolithique de la grotte lors de la production des gravures a dû être discrète et peu prolongée puisqu’aucun vestige n’a été mis au jour dans les sédiments malgré une recherche systématique incluant même des examens microscopiques. Les études géologique (J.‑G. Astruc), sédimentologique (C. Ferrier) pollinique (F. Diot), anthracologique (J.‑L. Vernet), ichtyologique (O. Le Gall) ainsi que l’étude anthropologique de restes humains découverts dans l’entrée (M. Escola) ont apporté des informations qui complètent les données des sondages et permettent de comprendre l’évolution du site ainsi que son utilisation par l’homme au cours du temps. En tenant compte de la localisation générale des gravures au‑dessus des niveaux d’inondation visibles dans les différents secteurs de la grotte et en s’appuyant également sur les résultats des sondages et de toutes les analyses scientifiques, l’ensemble du travail réalisé permet d’affirmer qu’au moment de l’exécution des gravures, le sol de la grotte était à peu près au niveau où il se trouve aujourd’hui. Presque toutes les gravures sont situées à l’emplacement et à la hauteur où un graveur les placerait aujourd’hui. L’ancienneté de la grande majorité du remplissage, sa stabilité actuelle et sa stérilité archéologique sont donc acquises. Même en acceptant l’existence hypothétique d’un dépôt récent de quelques centimètres dans divers secteurs de la galerie, la permanence topographique des lieux est établie. En réponse à la question qui se posait dès le début des recherches dans la grotte, il est maintenant possible d’affirmer que Pergouset fut bien au Paléolithique une cavité étroite, à peu près aussi étroite qu’aujourd’hui, renfermant un sanctuaire difficile d’accès.The cave of Pergouset was discovered in February 1964 by J.‑G. Astruc, C. Brillant, G. & M.‑T. Maury, C. Milhas and the abbé Terret, all members of the Quercy Spelaeological Group. It has now been the subject of a ten‑year multidisciplinary study, the results of which are presented in this monograph. Located on the bank of the River Lot, in the commune of Saint‑Géry (Lot), it comprises a single, very narrow passage, 190 m long, which ends in a crawlway leading to a small underground watercourse. This constitutes the upper gallery and overflow of this subterranean stream. The areas decorated with parietal engravings are small chambers in which one can only sit. The deep part, on the other hand, is more spacious. A series of sixteen test‑pits have made it possible to study the cave’s fill. The sediments are mostly clay and silt, often finely laminated, which were laid down by the underground river and the Lot. They are several metres thick at the entrance, and 1 to 2.5 m thick in the deep galleries where the engravings are located. The cave is regularly inundated in winter when the Lot floods: the same phenomenon occurred throughout the past, and even in the Palaeolithic. The test‑pits, together with cleaning of the bottom of the walls covered by flood silts, have not revealed a single parietal engraving buried beneath the fill. In the entrance zone, the test‑pits brought to light the importance of the medieval occupation, probably related to exploitation of the river’s resources (fisheries). No palaeolithic layer was discovered. The few small bits of charcoal produced by excavations in the zones decorated with engravings (chamber II) date to a recent period, probably medieval. They seem to have been brought in by the waters of the Lot during an exceptional flood. The interior zones explored by the other test‑pits proved to be archaeologically sterile. The only possible evidence of a palaeolithic presence at the base of the decorated wall was discovered in chamber IV. It was a piece of wood charcoal that lay on a rocky ledge and was covered by five centimetres of silt; it has been dated to 32,850 ± 520 BP (Gif A96675), but does not seem to have any relationship with the engravings, all of which are very probably magdalenian. Palaeolithic visits to the cave at the time when the engravings were produced must have been unobtrusive and of short duration, since no evidence has been found in the sediments despite a systematic search, including microscopic examinations. Geological (J.‑G. Astruc), sedimentological (C. Ferrier), palynological (F. Diot), anthracological (J.‑L. Vernet) and ichthyological (O. Le Gall) studies, as well as the anthropological analysis of the human remains discovered in the entrance (M. Escola) have contributed a variety of information that completes the data from the test‑pits and makes it possible to understand the site’s evolution as well as its utilisation by people through time. If one takes into account the general location of the engravings above the flood levels visible in the cave’s different sectors, and also the results of the test‑pits and all the scientific analyses, then ail of the work carried out enables one to claim that, at the time when the engravings were made, the cave floor was more or less at today’s level. Almost all the engravings are placed in locations and at the height where an engraver would put them today. So the antiquity of most of the fill, its present stability and its archaeological sterility are definite facts. Even if one accepts the hypothetical existence of a recent deposit of a few centimetres in various sectors of the gallery, the cave’s topographic permanence is now well established. In answer to the question that our research posed from the start, it is now possible to affirm that Pergouset in the Palaeolithic was indeed a narrow cave, more or less as narrow as today, that contained a sanctuary which was difficult to reach.En febrero de 1964, J.‑G. Astruc, C. Brillant, G. y M.‑T. Maury, C. Milhas y el abate Terret, todos ellos miembros del Grupo Espeleológico de Quercy, descubrieron la gruta de Pergouset. Ésta, durante diez años fue objeto de un estudio monográfico pluridisciplinar, cuyos resultados se publican aqui. Abierta sobre las riberas del río Lot, en el término municipal de Saint‑Géry (Lot), está formada por un único y muy estrecho conducto de 190m de longitud terminado por una gatera que conduce a un pequeño arroyo subterráneo. La gruta constituye la galería superior y el desagüe de ese arroyo subterráneo. Los sectores decorados con grabados parietales son salas pequeñas en las que una persona puede mantenerse sentada. La parte profunda es más amplia. Una serie de dieciséis sondeos permitió estudiar el relleno de la cavidad. Los sedimentos, depositados por la corriente subterránea y por el Lot, son principalmente arcillo‑limosos, a menudo con finas laminaciones. Su espesor alcanza varios metros en la entrada y oscilan entre 1 y 2.50m en las galerías profundas, en las que se localizan los grabados. La cavidad se inunda regularmente en invierno por las crecidas del Lot ; lo mismo ocurrió en tiempos remotos, incluso en el Paleolítico. Completados con limpiezas de las partes bajas de las paredes cubiertas por limos de inundación, los sondeos no sacaron a la luz grabado parietal alguno que hubiera sido tapado por el relleno. En la zona de entrada, los sondeos pusieron de relieve la importancia de la ocupación medieval, relacionada con una explotación de los recursos ribereños (pesqueria). Ningún nivel paleolítico ha sido descubierto. Algunos diminutos carbones recuperados durante las excavaciones en las zonas decoradas con grabados (sala II) son de época reciente, probablemente medieval. Puede que hayan sido introducidos allí por las aguas del Lot, con ocasión de una crecida excepcional. Las zonas interiores, exploradas con otros sondeos, se han revelado arqueológicamente estériles. El único índice posible de una presencia paleolítica se descubrió en la sala IV al pie de la pared decorada. Se trata de un carbón de madera recubierto por cinco centímetros de limo que se hallaba en una cornisa rocosa. Se dato en 32850 años ± 520 BP (Gif A 96675), pero no parece tener relación con los grabados, cuyo conjunto es muy probablemente magdaleniense. Durante la realización de los grabados, la frecuencia de entrada en la gruta debió de ser discreta y poco prolongada, puesto que ningún vestigio ha sido descubierto en los sedimentos, pese a una búsqueda sistemática, incluso con estudios microscópicos. Los estudios geológico (J.‑G Astruc), sedimentológico (C. Ferrier), polinico (F. Diot), antracologico (J.‑L. Vernet) e ictiológico (O. Le Gall), así como el estudio antropológico de los restos humanos descubiertos en la entrada (M. Escola) han proporcionado informaciones variadas que complementan los datos de los sondeos y permiten comprender la evolución del sitio, así como su utilización por el hombre a lo largo del tiempo. Teniendo en cuenta la localización general de los grabados por encima de los niveles de inundación, visibles en los diferentes sectores de la gruta, y apoyándose igualmente en los resultados de los sondeos y demás análisis científicos, el conjunto del trabajo realizado permite afirmar que cuando se hicieron los grabados el suelo de la cueva estaba poco más o menos al nivel en que se encuentra hoy. Casi todos los grabados se sitúan en el emplazamiento y a la altura en los que hoy día los colocaría un grabador. Por lo tanto podemos considerar como datos reconocidos la antigüedad de la mayoría del relleno, su estabilidad y su esterilidad arqueológica. Incluso aún cuando aceptemos la existencia de un depósito de algunos centimètres de espesor en diversos sectores de la galeria, queda establecida la permanencia topográfica de los lugares. Ahora es posible afirmar que la gruta de Pergouset fue, ya desde el Paleolitico, una cavidad estrecha, poco más o menos como lo es hoy, que encerraba un santuario de dificil acceso

Response to Treatment and Disease Progression Linked to CD4+ T Cell Surface CC Chemokine Receptor 5 Density in Human Immunodeficiency Virus Type 1 Vertical Infection

The factors governing interindividual variability in disease progression among children vertically infected with human immunodeficiency virus type 1 (HIV-1) remain unclear. Because it has recently been shown in infected adults that the density of CC chemokine receptor 5 (CCR5) molecules at the surface of nonactivated (human leukocyte antigen [HLA]-DR-) CD4+ T cells correlates with disease progression, the same correlation was sought in children. HLA-DR-CD4+ T cell surface CCR5 density was constant over time and correlated with the bioclinical stage and with the CD4 cell slope observed before antiretroviral treatment. In addition, CCR5 density was negatively correlated with the intensity of the decrease in viremia during antiretroviral therapy and was positively correlated with CD4 cell slope since birth. These results are compatible with the hypothesis that CCR5 density is a key factor governing disease progression in pediatric HIV-1 infection and, thereby, an indicator of prognosis. Moreover, they suggest that therapies aimed at reducing CCR5 accessibility should slow down HIV disease evolution in childre

A validation study of loci associated with mastitis resistance in two French dairy sheep breeds

The identification of loci associated with resistance to mastitis or of the causative mutations may be helpful in breeding programs for dairy sheep as it is for cattle worldwide. Seven genomic regions that control milk somatic cell counts, an indirect indicator of udder infection, have already been identified in sheep (Spanish Churra, French Lacaune and Italian Sardinian-Lacaune backcross populations). In this study, we used a 960 custom-designed ovine single nucleotide polymorphism (SNP) chip in Lacaune and Manech Tete Rousse dairy sheep to validate these seven genomic regions associated with mastitis. The most significant SNP (rs868996547) on Ovis aries chromosome (OAR) 3 was a previously described mutation in the suppressor of cytokine signalling 2 (SOCS2) gene. An antagonist effect of this causal candidate between health and growth in Lacaune sheep was confirmed. Effects of the mutation on the infectious status of the udder, i.e. increases in milk somatic cell counts and bacteria shedding, were also identified. This SNP was not present in the data available on Manech Tete Rousse. Three other regions associated with mastitis were also confirmed on OAR16 (Manech Tete Rousse), 19 (Lacaune) and 2 (both breeds). For the OAR2 region, we validated previously detected SNPs in several other breeds (Sarda, Churra, and Chios). For significant SNPs in the four mastitis regions, the effect varied from 0.24 to 0.67 phenotypic standard deviation of the traits. Two of the mastitis quantitative trait loci (QTL) regions (OAR2 and 16) that we validated here were also associated in opposite ways with milk production traits in both populations. These results indicate, at least in part, a genomic basis for the trade-off between milk production and mastitis resistance. Four of the seven mastitis QTL regions that were previously identified in independent populations, were confirmed in this study, which demonstrates partial sharing of mastitis-related genetic mechanisms between different distant dairy sheep populations

Evolution conjointe depuis les années 1990 des systèmes d'élevage dans le Rayon de Roquefort en lien avec le potentiel laitier de la brebis Lacaune

National audienc

Bilan et perspectives de la gestion de la variabilité génétique des ovins laitiers en France

Management of genetic diversity is a major concern in animal breeding, especially as genomic selection starting in French dairy sheep will reduce generation interval and increase genetic progress. Hence, it appeared important to assess the evolution of genetic diversity over the last decades using pedigree information to better monitor the breeding schemes. The results obtained in the Lacaune (LL) and Ref-Faced Manech breed (MTR) are satisfying: respectively + 0.29 and + 0.42 % of inbreeding increase per generation over 2000-2009, even though it is still possible to better balance elite families in MTR. On the contrary, results from Basco-Bearnaise (BB) and Black-Faced Manech breeds (MTN) underline a less efficient management of genetic diversity: respectively + 0.74 and + 1.02 % of inbreeding increase per generation over 2000-2009. This situation results from the too small number of sires of ram families (PAB) compared to the number allowed by the size of the nucleus of selection BB and MTN. This is a consequence of an imbalanced use of PAB families due to the very short duration of the AI period (fresh semen) and the lower AI fertility in these two breeds. Studies were carried out with the managers of breeding societies. This was done in order to increase the number of PAB families and to provide at each step of selection, the indicators of genetic variability allowing a more balanced management of these PAB families. Corse breed pedigrees are not extensive enough to allow a relevant pedigree analysis. Studies are on-going in these five breeds to assess genetic variability based on SNP (Single Nucleotid Polymorphism) from the 18,500 genotypes available with genomic selection

On the importance of diffusion management for local breeds selection

International audienc