Genomics reveals the role of admixture in the evolution of structure among sperm whale populations within the Mediterranean Sea

In oceanic ecosystems, the nature of barriers to gene flow and the processes by which populations may become isolated are different from the terrestrial environment, and less well understood. In this study we investigate a highly mobile species (the sperm whale, Physeter macrocephalus) that is genetically differentiated between an open North Atlantic population and the populations in the Mediterranean Sea. We apply high-resolution single nucleotide polymorphism (SNP) analysis to study the nature of barriers to gene flow in this system, assessing the putative boundary into the Mediterranean (Strait of Gibraltar and Alboran Sea region), and including novel analyses on structuring among sperm whale populations within the Mediterranean basin. Our data support a recent founding of the Mediterranean population, around the time of the last glacial maximum, and show concerted historical demographic profiles in both the Atlantic and the Mediterranean. In each region there is evidence for a population decline around the time of the founder event. The largest decline was seen within the Mediterranean Sea where effective population size is substantially lower (especially in the eastern basin). While differentiation is strongest at the Atlantic/Mediterranean boundary, there is also weaker but significant differentiation between the eastern and western basins of the Mediterranean Sea. We propose, however, that the mechanisms are different. While post-founding gene flow was reduced between the Mediterranean and Atlantic populations, within the Mediterranean an important factor differentiating the basins is probably a greater degree of admixture between the western basin and the North Atlantic and some level of isolation between the western and eastern Mediterranean basins. Subdivision within the Mediterranean Sea exacerbates conservation concerns and will require consideration of what distinct impacts may affect populations in the two basins

Recombination between Polioviruses and Co-Circulating Coxsackie A Viruses: Role in the Emergence of Pathogenic Vaccine-Derived Polioviruses

Ten outbreaks of poliomyelitis caused by pathogenic circulating vaccine-derived polioviruses (cVDPVs) have recently been reported in different regions of the world. Two of these outbreaks occurred in Madagascar. Most cVDPVs were recombinants of mutated poliovaccine strains and other unidentified enteroviruses of species C. We previously reported that a type 2 cVDPV isolated during an outbreak in Madagascar was co-circulating with coxsackieviruses A17 (CA17) and that sequences in the 3′ half of the cVDPV and CA17 genomes were related. The goal of this study was to investigate whether these CA17 isolates can act as recombination partners of poliovirus and subsequently to evaluate the major effects of recombination events on the phenotype of the recombinants. We first cloned the infectious cDNA of a Madagascar CA17 isolate. We then generated recombinant constructs combining the genetic material of this CA17 isolate with that of the type 2 vaccine strain and that of the type 2 cVDPV. Our results showed that poliovirus/CA17 recombinants are viable. The recombinant in which the 3′ half of the vaccine strain genome had been replaced by that of the CA17 genome yielded larger plaques and was less temperature sensitive than its parental strains. The virus in which the 3′ portion of the cVDPV genome was replaced by the 3′ half of the CA17 genome was almost as neurovirulent as the cVDPV in transgenic mice expressing the poliovirus cellular receptor gene. The co-circulation in children and genetic recombination of viruses, differing in their pathogenicity for humans and in certain other biological properties such as receptor usage, can lead to the generation of pathogenic recombinants, thus constituting an interesting model of viral evolution and emergence

Étude des grands mammifères marins en Méditerranée pour mieux adapter les politiques de conservation

The fin whale, Balaenoptera physalus, is the largest mysticete in the Mediterranean Sea. Its Mediterranean population is considered as resident and distinct from that of the Atlantic. This species is threatened by human activities and scientific knowledge on this species is limited. This thesis has improved our collective understanding of fin whale demographics and life history traits (current and effective size, population structure, parentage links, demographic history) and will help to protect the species. Using newly developed microsatellite markers and photo-identification data, we estimated the population size at 1,300 individuals and the effective size between 400 and 500 individuals. Furthermore, we identified a decrease (by 3.6) in effective size which began 260,000 years ago. Over the course of this thesis, other important discoveries were made, including the finding that the Mediterranean population lacks a genetic structure, and is a population composed of large families. Further, and for the first time ever in whales, full-siblings were discovered within these families. The results of this thesis not only contribute to enhancing our general knowledge for the fin whale, but will be used to define further conservation measures to protect this vulnerable species and other cetaceans present in the Mediterranean and beyond.Le Rorqual commun, Balaenoptera physalus, est le plus grand mysticète présent en Méditerranée. Sa population Méditerranéenne est considérée comme résidente et distincte de celle présente dans l'Atlantique. Cette espèce est largement menacée par les activités anthropiques et les connaissances sur cette population sont limitée. Ce travail de thèse a permis d'augmenter les connaissances (taille réelle et efficace, structure de la population, liens de parenté, histoire démographique) afin de pouvoir protéger au mieux l'espèce. Les différentes analyses réalisées sur des marqueurs microsatellites nouvellement développés ainsi que sur des données de photo-identification ont permis d'estimer la taille réelle de la population à 1 300 individus et la taille efficace entre 400 et 500 individus. De plus, nous avons identifié une forte diminution (par un facteur de 3.6) de la taille de la population depuis 260 000 ans. Au cours de cette thèse, d'autres éléments importants ont été mis en évidence, la population Méditerranéenne ne présente pas de structure génétique et est composée de quelques grandes familles. Au sein de ces familles, des pleins frères et sœurs ont été découverts, ce qui est une première chez les cétacés. L'ensemble des résultats obtenus au cours de cette thèse augmente les connaissances que l'on a sur cette espèce et sur cette population. Ils seront utiles dans la mise en place de futures mesures de conservation dans le but de protéger cette espèce vulnérable mais aussi les autres cétacés présents dans la zone

Axon guidance of regenerating retinal ganglion cells into the suprachiasmatic nucleus

Les neurones matures du système nerveux central (SNC) sont incapables de régénérer. De ce fait toute lésion du SNC conduit à des pertes irréversibles des fonctions motrices, sensitives et/ou cognitives. Ainsi, comprendre les mécanismes sous-jacents de la régénération axonale constitue l’un des plus grands défis en Neurobiologie. En plus d’un environnement réfractaire à la repousse axonale, les neurones du SNC perdent leur capacité de croissance une fois mature et après la lésion. Ainsi, moduler les capacités intrinsèques des neurones matures ouvre une nouvelle voie de recherche très prometteuse pour réparer le SNC endommagé. En utilisant le modèle du nerf optique, nous avons démontré que l’activation simultanée des voies de signalisation mTOR, JAK/STAT et c-myc dans les cellules ganglionnaires de la rétine (CGR) permet une repousse axonale robuste à longue distance chez la souris : depuis l’œil jusqu’au cerveau. Cependant, ces axones en cours de régénération présentent de nombreux défauts de projections faisant obstacle à la formation des circuits nerveux. En effet, ces défauts de projections représentent des axones perdus qui n’atteindront jamais leurs cibles et qui peuvent même conduire, dans le pire des cas, à la formation de circuits aberrants et compromettre le retour des fonctions. La question principale de ma thèse est de savoir s’il est possible de modifier la trajectoire des axones en cours de régénération et de les conduire vers leurs cibles originales. En effet, le guidage axonal est un mécanisme qui permet la formation des circuits nerveux lors du développement chez l’embryon. Or, nous ne savons pas si les axones matures sont capables de répondre à leur environnement ou d’intégrer les signaux de guidage. De plus, la topographie d’expression des facteurs de guidage dans le système nerveux mature est peu connue. Pour répondre à ces questions, j’ai choisi comme modèle d’étude la cible la plus proche des CGR : le noyau Suprachiasmatique (NSC). Ce noyau, situé dans l’hypothalamus antérieur juste au-dessus du chiasma optique, est innervé par une population spécifique de CGR : les CGRip qui expriment le photopigment mélanopsine et qui sont intrinsèquement sensibles à la lumière. De manière intéressante, dans notre modèle de régénération, les axones qui régénèrent évitent le NSC alors que les CGRip survivent très bien suite à une lésion du nerf optique. Grâce à un criblage par candidats, nous avons identifié des facteurs de guidage répulsifs dans le NSC mature et leurs récepteurs dans les CGR adultes. En utilisant des cultures ex-vivo d’explant de rétines et de SCN adultes ou des cellules COS exprimant nos molécules d’intérêt, nous avons confirmé leur effet répulsif sur les CGR matures. In vivo, nous avons montré que la délétion des récepteurs de ces facteurs de guidage dans les CGR, permettait d’augmenter considérablement le nombre d’axones entrant dans le NSC. Pour finir, nous avons étudié la fonctionnalité du circuit nerveux nouvellement formé. L’ensemble de ces travaux a permis de montrer que le guidage axonal dans un contexte de régénération est une étape clé pour la formation de nouveaux circuits nerveux chez l’adulte.Central nervous system (CNS) impairment leads to irreversible loss of sensitive, motor and/or cognitive functions, as mature neurons do not regenerate. Thus, understanding the detailed mechanisms of axonal growth and repair remains one of the greatest challenges in Neurobiology. Besides the inhibitory role of the CNS environment on axon regeneration, neurons from the CNS lose their ability to regrow their axons during development and after an injury. Thus, the modulation of intrinsic capabilities of matures neurons open up new ways to repair damaged CNS. By using the mouse visual system, we showed that the simultaneous activation of mTOR, JAK/STAT and c-myc pathways, within the retinal ganglion cells (RGC), induces unprecedented extent of regeneration, from the eye to the brain, and provides an exciting avenue for functional studies and therapeutic strategies. However, our results also exacerbate axon guidance defects hindering nervous circuits formation. Indeed, mis-projecting axons not only miss their targets but they could evenutally form aberrant circuits counteracting any attempt for functional recovery. Thus, the main question of my thesis is to determine whether it is possible to modify regenerating axons trajectory to drive them towards their original targets. Indeed, axon guidance is a process involved during nervous circuits formation in the embryo. However, we do not know whether matures neurons are able to respond to their environment or to integrate guidance factors signaling. Moreover, the expression pattern of guidance cues in the adult nervous system is poorly known. To address these exciting questions, I chose as a proof of concept to focus on the first target encountered by regenerative RGC: the Suprachiasmatic nuclei (SCN). These brain nuclei are located in the anterior part of the hypothalamus just above the optic chiasm. They are innervated by a specific RGC subpopulation: ipRGC which express a photopigment the melanopsin and that are intrinsically sensitive to the light. Interestingly, we observed that regenerating axons avoid the SCN in our model even if ipRGC are surviving after optic nerve crush. After a candidates screening, we identified repulsive guidance cues expressed by mature SCN and their receptors within RGC. By using co-cultures of adult retinal explant with adult SCN explants or COS cells expressing our guidance cues of interest, we confirmed their repulsive effect on mature RGC axons. In vivo, we showed that receptors modulation of these repulsive guidance cues within RGC allows to increase greatly the number of regenerative axons into the SCN. Finally, we assessed the functionality of this new neuronal circuit. All together these results point out that axon guidance mechanism is a key step for the formation of new neuronal circuit in adult during regeneration

Characterization of 25 new microsatellite markers for the fin whale (Balaenoptera physalus) and cross-species amplification in other cetaceans

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Correction: Tissue factor pathway inhibitor for prediction of placenta-mediated adverse pregnancy outcomes in high-risk women: AngioPred study.

[This corrects the article DOI: 10.1371/journal.pone.0173596.]

Genetic evidence for plastic reproductive philopatry and matrotrophy in blacktip reef sharks (Carcharhinus melanopterus) of the Moorea Island (French Polynesia)

Abstract The exploitation of sharks and the degradation of their habitats elevate the urgency to understand the factors that influence offspring survival and ultimately shark reproductive success. We monitored and sampled blacktip reef sharks (Carcharhinus melanopterus) in nursery habitats of Moorea Island (French Polynesia), to improve knowledge on shark reproductive behavior and biology. We sampled fin clips and morphometrics from 230 young-of-the-year sharks and used microsatellite DNA markers to process parentage analysis to study the reproductive philopatric behavior in female sharks and the matrotrophy within litters. These traits are driving the success of the local replenishment influencing selection through birth site and maternal reserves transmitted to pups. Parentage analysis revealed that some female sharks changed their parturition areas (inter-seasonally) while other female sharks came back to the same site for parturition, providing evidence for a plastic philopatric behavior. Morphometrics showed that there was no significant relationship between body condition indices and nursery locations. However, similarities and differences in body condition were observed between individuals sharing the same mother, indicating that resource allocation within some shark litters might be unbalanced. Our findings further our understanding of the reproductive biology and behavior that shape shark populations with the aim to introduce these parameters into future conservation strategies

La perception des paysages et des agro-systèmes antiques de la moyenne vallée de l'Hérault. Apports des biomarqueurs à l'archéologie préventive

International audienceArchaeological and palaeoenvironmental data obtained during rescue work, prior to the construction of the A75 motorway between Pézenas and Béziers, have been assembled in an attempt to piece together the history of the landscape and rural economy, in the Languedoc region. During Antiquity, data obtained, point to the existence of a system of small to medium rural domains dedicated to the production of food crops (viticulture, arboriculture, and cereals) and underline the interaction between man and natural resources.Une réflexion sur les paysages et l'économie rurale antiques en Languedoc est proposée à partir des données archéologiques et paléoenvironnementales acquises lors des fouilles préventives de l'A75, entre Pézenas et Béziers (Hérault). Les recherches effectuées mettent en évidence un réseau de petits à moyens établissements ruraux, ainsi que leurs productions. Les pratiques agricoles et l'exploitation des ressources naturelles y sont également renseignées

Serum D-dimer is not predictive of placenta-mediated complications in pregnancy at high risk: The multicentric prospective cohort AngioPred study

Background: The theory that D-dimer level might has a predictive or diagnostic role in preeclampsia needs to be explored. Aim of the study was to evaluate the association between serum D-dimer level and the occurrence of placentamediated complications (PMC) in a pregnant population at high risk. Methods: A prospective multicenter cohort study including 200 pregnant women was conducted. Results: Serum D-dimer increases throughout pregnancy, with the highest levels at the end of gestation. Serum D-dimer level was similar for women with PMC and with no complication. Serum D-dimer level was not different in women with preeclampsia versus uncomplicated women. Serum D-dimer level was not different in women with early or late preeclampsia versus uncomplicated women. Conclusion: This result suggests that serum D-dimer level was not predictive of the PMC occurrence. This corroborates the fact that the origin of PMC based more on immunity than in hemostasis

Relationship between plasma tissue Factor Pathway Inhibitor (TFPI) levels, thrombin generation and clinical risk of bleeding in patients with severe haemophilia A or B

International audienceAbstract Introduction Bleeding severity in severe haemophilic patients, with low thrombin generation (TG) capacity, can vary widely between patients, possibly reflecting differences in tissue factor pathway inhibitor (TFPI) level. Aim To compare free TFPI (fTFPI) levels in patients with severe haemophilia A (sHA) and severe haemophilia B (sHB) and to investigate in these patients as a whole the relationships between bleeding and TG potential, between TG potential and fTFPI level and between fTFPI level and bleeding tendency. Methods Data on bleeding episodes retrospectively recorded during follow‐up visits over 5–10 years were collected and used to calculate the annualised joint bleeding rate (AJBR). fTFPI levels and basal TG parameters were determined in platelet‐poor plasma (PPP) and platelet‐rich plasma (PRP) using calibrated automated tomography (CAT). Results Mean fTFPI levels did not differ significantly between sHA ( n = 34) and sHB ( n = 19) patients. Mean values of endogenous thrombin potential (ETP) and thrombin peak (peak) in PPP and PRP were two‐fold higher when fTFPI levels < 9.4 versus > 14.3 ng/mL. In patients treated on demand, ETP and peak in PRP were doubled when AJBR was , AJBR being halved in patients with a low fTFPI level (9.4 ng/mL). In patients on factor prophylaxis, no association was found between TG parameters and either fTFPI level or AJBR. Conclusion In patients treated on demand, bleeding tendency was influenced by fTFPI levels, which in turn affected basal TG potential. In patients on prophylaxis, bleeding tendency is probably determined primarily by the intensity of this treatment