Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Grey (Halichoerus grypus) and harbour seals (Phoca vitulina) are sympatric seal species, but they display distinct strategies of habitat use and connectivity between haulout sites. The distribution patterns and variations in relative abundance of both species were investigated along the French coast of the English Channel, at the southern limit of their range where seal numbers are increasing. Regular censuses conducted at all main haulout sites in mainland France showed significant seasonal variations at most sites, with more harbour seals counted during summer (breeding and moulting seasons), and more grey seals during summer only in the eastern English Channel. Trends in maximum haulout numbers at haulout sites showed a significant increase over the last five years, ranging from 9.7 to 30.9% per year for harbour seals, and from 5.8% (in the western English Channel) to 49.2% (in the eastern English Channel) per year for grey seals. These rates of increase in grey seal numbers are not linked to local pup production and most probably result from seal movements from the southwest British Isles and the North Sea, respectively. Aerial surveys conducted across the English Channel showed that most seal observations at sea were concentrated in the north-eastern English Channel. Telemetry showed that the 28 harbour seals tracked remained highly coastal, within a radius of 100 km from their haulout sites, and did not move to other known colonies. Grey seals moved much greater distances, reaching up to 1200 km from their capture site. More than half of the 45 grey seals tracked crossed the English Channel, especially during the breeding season, moving to known colonies in the southwest British Isles and the North Sea. Combining individual tracks and long-term surveys of the seal populations allowed a better understanding of the dynamics of these populations and their connectivity at a larger regional scale. The findings provide direct information for the management of grey and harbour seals within the frame of the Marine Strategy Framework Directive, and highlight focus areas where potential interactions between the two species should be monitored.
ISSN: 0967-0645

hal-01509674
https://hal.archives-ouvertes.fr/hal-01509674
DOI : 10.1016/j.dsr2.2017.04.004

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The scleractinian coral Pocillopora damicornis type β is known to present a mixed reproduction mode: through sexual reproduction, new genotypes are created, while asexual reproduction insures their propagation. In order to investigate the relative proportion of each reproduction mode in P. damicornis type β populations from Reunion Island, Indian Ocean, clonal propagation along the west coast was assessed through four sampling sites with increasing geographical distance between sites. Coral colonies were sampled either exhaustively, randomly or haphazardly within each site, and genotypic diversity was assessed using 13 microsatellite loci over a total of 510 P. damicornis type β determined a posteriori from their mtDNA haplotype (a 840 bp sequenced fragment of the Open Reading Frame). Overall, 47% of all the sampled colonies presented the same multi-locus genotype (MLG), a superclone, suggesting that asexual propagation is extremely important in Reunion Island. Within each site, numerous MLGs were shared by several colonies, suggesting local clonal propagation through fragmentation. Moreover, some of these MLGs were found to be shared among several sites located 40 km apart. While asexual reproduction by fragmentation seems unlikely over long distances, our results suggest a production of parthenogenetic larvae. Despite shared MLGs, two differentiated clusters were enclosed among populations of the west coast of Reunion Island, revealing the necessity to set up appropriate managing strategies at a local scale.
ISSN: 1932-6203

hal-01450078
http://hal.univ-reunion.fr/hal-01450078
DOI : 10.1371/journal.pone.0169692

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Few studies have been undertaken to assess the possible effects of bisphenol A (BPA) on the reproductive hormone balance in animals or humans with often contradictory results. We investigated possible direct endocrine disruption by BPA of the fetal testes of 2 rat strains (14.5-17.5 days post-coitum) and humans (8-12 gestational weeks) and under different culture conditions. BPA concentrations of 10-8M and 10-5M for 72h reduced testosterone production by the Sprague-Dawley fetal rat testes, while only 10-5M suppressed it in the Wistar strain. The suppressive effects at 10-5M were seen as early as 24h and 48h in both strains. BPA at 10-7-10-5M for 72h suppressed the levels of fetal rat Leydig cell insulin-like factor 3 (INSL3). BPA exposure at 10-8M, 10-7M, and 10-5M for 72h inhibited testosterone production in fetal human testes. For the lowest doses, the effects observed occurred only when no gonadotrophin was added to the culture media and were associated with a poorly preserved testicular morphology. We concluded that (i) BPA can display anti-androgenic effects both in rat and human fetal testes; (ii) it is essential to ascertain that the divergent effects of endocrine disruptors between species in vitro do not result from the culture conditions used, and/or the rodent strain selected; (iii) the optimization of each in vitro assay for a given species should be a major objective rather than the search of an hypothetical trans-species consensual model-system, as the organization of the testis is intrinsically different between mammalian species; (iv) due to the uncertainty existing on the internal exposure of the human fetal testis to BPA, and the insufficient number of epidemiological studies on the endocrine disruptive effects of BPA, caution should be taken in the extrapolation of our present results to the human reproductive health after fetal exposure to BPA.
ISSN: 1932-6203

hal-01121759
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121759
PUBMED : 25706302
DOI : 10.1371/journal.pone.0117226

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: The aim of this systematic review was to evaluate and compare the pros and cons of using living donors or brain-dead donors in uterus transplantation programs, 2 years after the first worldwide live birth after uterus transplantation. METHODS: The Medline database and the Central Cochrane Library were used to locate uterine transplantation studies carried out in human or nonhuman primates. All types of articles (case reports, original studies, meta-analyses, reviews) in English or French were considered for inclusion. RESULTS: Overall, 92 articles were screened and 44 were retained for review. Proof of concept for human uterine transplantation was demonstrated in 2014 with a living donor. Compared with a brain-dead donor strategy, a living donor strategy offers greater possibilities for planning surgery and also decreases cold ischemia time, potentially translating into a higher success rate. However, this approach poses ethical problems, given that the donor is exposed to surgery risks but does not derive any direct benefit. A brain-dead donor strategy is more acceptable from an ethical viewpoint, but its feasibility is currently unproven, potentially owing to a lack of compatible donors, and is associated with a longer cold ischemia time and a potentially higher rejection rate. CONCLUSIONS: The systematic review demonstrates that uterine transplantation is a major surgical innovation for the treatment of absolute uterine factor infertility. Living and brain-dead donor strategies are not mutually exclusive and, in view of the current scarcity of uterine grafts and the anticipated future rise in demand, both will probably be necessary.
Transplantation

hal-01447062
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01447062
DOI : 10.1097/TP.0000000000001481
PUBMED : 27607535

Éditeur(s) : HAL CCSD
Résumé : International audience
Traffic air pollution is a major health problem and is recognized as an important risk factor for cardiovascular disease. Even so the role of particles-induced adverse health effects is well established, recent studies outlined the contribution of nitrogen dioxide (NO2) in these effects, in particular on the cardiovascular function. The main sources of this pollutant are oxidation catalysts used to reduce emissions of carbon monoxide and non-methane hydrocarbons from the exhaust of diesel engines and also to facilitate filter regeneration. However, the contribution of NO2 compared to other gaseous and particulate pollutants remains unknown. Consequently, the main objective of this study was to analyze the specific contributions of NO2 in the traffic-related air pollution-induced cardiovascular adverse effects. For this, Wistar rats were exposed for 3 weeks (3h/day, 5 days/week) to either a continuous flow of catalyzed diesel exhaust (DE), particle free or whole DE (particles concentration 2mg/m3), either to a continuous flow of NO2 used at a concentration identical to that measured in the exhaust line. The composition of the emission and the NO2 analyses were monitored on-line during the whole experiment. We evaluated cardiac function and biological effects after 16h recovery in clean air. DE or NO2 exposures induced a modest cardiac dysfunction characterized by an increase in left ventricular diameters and a decrease in fractional shortening. In the case of DE, the presence of particles did not worsen the impairment of cardiac function. In parallel to this effect, mitochondrial function was altered as illustrated by the reduction of the oxygen consumption and of the ATP production. Mitochondrial reactive oxygen species was increased only by the NO2 exposure. In conclusion, these results suggest that DE-induced cardiac dysfunction is due to, at least in part, to NO2 present in DE.
Archives of Cardiovascular Diseases Supplements
Toulouse, France

hal-01150495
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01150495
DOI : 10.1016/S1878-6480(15)30036-7

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
This study aimed to identify factors associated with virological response (VR) to raltegravir (RAL)-containing regimens in 468 treatment-experienced but integrase inhibitor-naive HIV-1 patients receiving a RAL-containing regimen. VR was defined at Month 6 (M6) as HIV-1 RNA viral load (VL) <50 copies/mL. The impacts on VR of baseline integrase mutations, VL, CD4 count, genotypic sensitivity score for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the number of new antiretrovirals used for the first time associated with RAL were investigated. For patients with VL >50 copies/mL at M6, integrase mutations selected were characterised. Median baseline VL was 4.2 log(10)copies/mL (IQR 3.3-4.9 log(10) copies/mL) and CD4 count was 219 cells/mm(3) (IQR 96-368 cells/mm(3)). At M6, 71% of patients were responders. In multivariate analysis, baseline VL and CD4 count and ≥ 2 new antiretrovirals among darunavir, etravirine, maraviroc and enfuvirtide were associated with VR to RAL. Neither HIV-1 subtype nor baseline integrase polymorphisms were associated with VR to RAL. Among 63 failing patients at M6, selection of ≥ 1 change in the integrase gene was observed in 49 (77.8%), and 27/63 (42.9%) were considered as RAL-associated resistance mutations. Factors independently associated with the occurrence of ≥ 1 RAL-associated resistance mutation were VL at failure >3 log(10) and having no new drugs associated with RAL. RAL showed great potency in treatment-experienced patients. The number of new drugs associated with RAL was an important factor associated with VR. HIV-1 subtype and baseline integrase polymorphisms do not influence the RAL VR.
ISSN: 0924-8579

hal-00875083
https://hal.archives-ouvertes.fr/hal-00875083
DOI : 10.1016/j.ijantimicag.2013.02.016
PUBMED : 23562640

Éditeur(s) : HAL CCSD
Résumé : International audience
Background Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. Methods We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. Results We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. Conclusions We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. Trial registration numbers NCT01746121 and NCT02397824
Journal of Medical Genetics

hal-01272929
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01272929
DOI : 10.1136/jmedgenet-2015-103302
PUBMED : 26502894

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Cnidarian-dinoflagellate symbiosis disruption and subsequent bleaching are major concerns, especially regarding their ecological consequences on coral reefs and temperate coralligenous communities. Cnidarian bleaching is caused by a variety of environmental stressors, such as elevated seawater temperature associated with global climate change, and by pollutants, such as herbicides and metals. Several cellular events have been described to explain symbiosis dysfunction and bleaching. Excess or damaged Symbiodinium symbionts are removed through a variety of mechanisms, including exocytosis, apoptosis, necrosis and autophagy. However, few studies have compared in the same species the relative involvement of these mechanisms, according to the stress inducing the bleaching. In this study, we used two different treatments —temperature and menthol— to induce bleaching in the sea anemone Anemonia viridis. By monitoring the ultrastructural tissue modifications, in control specimens we observed a basal rate of in situ symbiont digestion —or symbiophagy— induced by starvation. Symbiophagy was strongly induced in menthol-treated specimens and was the main cellular process of bleaching, whereas apoptosis and necrosis predominated in hyperthermal-induced bleaching. These results suggested a host effect through autophagy in menthol-treated specimens. These observations also suggested that symbiont removal may result from reengagement of the phagosomal maturation process in the host. These overall data demonstrate that several Symbiodinium cell removal mechanisms coexist and that stressors can activate one or more of these pathways, depending on the stress type, intensity or duration.
ISSN: 0334-5114

hal-01546908
http://hal.upmc.fr/hal-01546908
DOI : 10.1007/s13199-016-0406-y

Éditeur(s) : HAL CCSD Pôle de Recherche pour l'Organisation et la diffusion de l'Information Géographique
Résumé : International audience
The Amazon has recently experienced a dramatic decline in deforestation coupled with economic development. However, this process is uneven. While large and medium-sized producers are intensifying and diversifying their production systems in the already cleared areas, thus apparently abandoning expansion strategies at the moment, family farming remains aloof from this decoupling between production and deforestation. In this article, the commitments of public authorities and sectors, their effects on deforestation and inequalities of adaptation are analyzed at the scale of the Legal Amazon and in a municipality considered as a model because involved in a Município Verde initiative: Paragominas, in the Eastern Amazon.
L’Amazonie a amorcé depuis quelques années une baisse de la déforestation couplée à un développement économique. Le processus est cependant inégal. Si les grands et moyens producteurs font évoluer leurs systèmes de production vers l’intensification et la diversification dans les espaces déjà ouverts, délaissant en apparence les stratégies d’expansion, l’agriculture familiale reste à l’écart du découplage entre production et déforestation. Dans cet article, les engagements des pouvoirs publics et des filières, leurs effets en matière de déforestation et les inégalités d’adaptation sont analysés à l’échelle de l’Amazonie Légale et à celle d’une municipalité considérée comme un modèle car à l’initiative d’une démarche de Município Verde : Paragominas, en Amazonie orientale.
ISSN: 1963-1197

halshs-01609039
https://halshs.archives-ouvertes.fr/halshs-01609039
DOI : 10.4000/echogeo.15035

Éditeur(s) : HAL CCSD
Résumé : International audience
Recent studies have shown that accounting for intraspecific trait variation (ITV) may better address major questions in community ecology. However, a general picture of the relative extent of ITV compared to interspecific trait variation in plant communities is still missing. Here, weconducted a meta-analysis of the relative extent of ITV within and among plant communities worldwide, using a data set encompassing 629 communities (plots) and 36 functional traits. Overall, ITV accounted for 25% of the total trait variation within communities and 32% of the totaltrait variation among communities on average. The relative extent of ITV tended to be greater for whole-plant (e.g. plant height) vs. organ-level traits and for leaf chemical (e.g. leaf N and P concentration) vs. leaf morphological (e.g. leaf area and thickness) traits. The relative amount of ITV decreased with increasing species richness and spatial extent, but did not vary with plant growth form or climate. These results highlight global patterns in the relative importance of ITV in plant communities, providing practical guidelines for when researchers should include ITV in trait-based community and ecosystem studies.
Ecology Letters

hal-01237101
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237101
DOI : 10.1111/ele.12508
PUBMED : 26415616

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The symbiotic interaction between cnidarians, such as corals and sea anemones, and the unicellular algae Symbiodinium is regulated by yet poorly understood cellular mechanisms, despite the ecological importance of coral reefs. These mechanisms, including host-symbiont recognition and metabolic exchange, control symbiosis stability under normal conditions, but also lead to symbiosis breakdown (bleaching) during stress. This study describes the repertoire of the sterol-trafficking proteins Niemann-Pick type C (NPC1 and NPC2) in the symbiotic sea anemone Anemonia viridis. We found one NPC1 gene in contrast to the two genes (NPC1 and NPC1L1) present in vertebrate genomes. While only one NPC2 gene is present in many metazoans, this gene has been duplicated in cnidarians, and we detected four NPC2 genes in A. viridis. However, only one gene (AvNPC2-d) was upregulated in symbiotic relative to aposymbiotic sea anemones and displayed higher expression in the gastrodermis (symbiont-containing tissue) than in the epidermis. We performed immunolabelling experiments on tentacle cross sections and demonstrated that the AvNPC2-d protein was closely associated with symbiosomes. In addition, AvNPC1 and AvNPC2-d gene expression was strongly downregulated during stress. These data suggest that AvNPC2-d is involved in both the stability and dysfunction of cnidarian-dinoflagellate symbioses.
ISSN: 0962-1083

hal-01546166
https://hal.archives-ouvertes.fr/hal-01546166
DOI : 10.1111/mec.12876

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND:Sickle cell anaemia (SCA) is a severe hereditary haemoglobinopathy characterised by haemorheological abnormalities, which play a role in the occurrence of several acute and chronic clinical complications. While βS -haplotypes and alpha-thalassaemia modulate SCA clinical severity, their effects on blood rheology have been incompletely described. The aim of this study was to test the effects of these genetic modifiers on the haemorheological properties and clinical complication of children with SCA.PROCEDURE:Steady-state haemorheological profile, biological parameters, βS -haplotypes, alpha-globin status, vaso-occlusive crisis (VOC) and acute chest syndrome frequencies were analysed in 128 children (aged 5 to 18 years) with SCA.RESULTS:Patients with alpha-thalassaemia showed increased red blood cell (RBC) deformability and aggregation compared to those without. Median VOC rate was higher in patients with homozygous alpha-thalassaemia compared to those with a normal alpha genotype. Conversely, the haemorheological profile and clinical complications were not influenced by the βS -haplotypes in our study.CONCLUSION:Our results demonstrate that alpha-thalassaemia is associated with higher risk for VOC events in children with SCA, which may be due in part to its effects on RBC deformability and aggregation.
ISSN: 1545-5009

hal-01668317
https://hal.univ-antilles.fr/hal-01668317
DOI : 10.1002/pbc.26455
PUBMED : 28097791

Éditeur(s) : HAL CCSD Endocrine Society
Résumé : International audience
: Context:Masculinization depends on the fetal testis. Exposure of the human fetus during pregnancy to paracetamol or/and to other mild-analgesics is associated with an increased risk of cryptorchidism.Objective:We aimed at determining whether mild analgesics disrupted the morphology and endocrine function of the human testis.Design:We used an in vitro system based on the culture of human fetal testes exposed or not to paracetamol, its metabolite AM404, aspirin, indomethacin, ketoconazole at 10(-4) M to 10(-7) M.Setting:The study was conducted at the University of Rennes I.Patients/Participants:Human fetal testes were from pregnant women following induced abortion, between 7 and 12 weeks of gestation (GW).Main Outcome Measures:Testosterone (radioimmunoassay: RIA), Anti-Müllerian Hormone (AMH; ELISA), insulin-like factor 3 (INSL3; RIA), prostaglandin D2 and E2 (PGD2 and PGE2, respectively; ELISA), were assayed in the media. Testicular cells were counted using histology and image analysis. The possible nuclear receptor-mediated activities of the analgesics were investigated using reporter cell lines expressing estrogen (ERs), androgen (AR) and peroxysome proliferator-activated γ ( PPARγ) receptors.Results:Indomethacin and aspirin stimulated testosterone production, particularly by the younger testes (8-9 GW vs 10-12 GW). Paracetamol, AM404 and ketoconazole decreased INSL3 levels. Aspirin stimulated, whereas ketoconazole inhibited AMH production. PGE2 levels were inhibited by paracetamol, and aspirin in the 7-12 GW testes, and by indomethacin but only in 7-9.86 GW old testes. The inhibitory trends seen for PGD2 were not statistically significant.Conclusions:Analgesics at concentrations relevant to human exposure cause endocrine disturbances in the fetal testis. We suggest that the fetal human testis displays slight critical age windows for sensitivity to direct exposure to aspirin, indomethacin and paracetamol. The analgesic-induced inhibition of INSL3 may be the mechanism by which analgesics increase the risk of cryptorchidism. Greater caution is required concerning consumption of analgesics during pregnancy.
ISSN: 0021-972X

inserm-00876125
http://www.hal.inserm.fr/inserm-00876125
DOI : 10.1210/jc.2013-2531
PUBMED : 24030937

Éditeur(s) : HAL CCSD Landes Bioscience
Résumé : International audience
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Autophagy

hal-00735751
https://hal.archives-ouvertes.fr/hal-00735751
PUBMED : 22966490

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial cells from systemic lupus erythematosus (SLE) patients expressed CD95L and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigration across the endothelial barrier at the expense of T regulatory cells. T cell migration relied on a direct interaction between the CD95 domain called calcium-inducing domain (CID) and the Src homology 3 domain of phospholipase C gamma 1. Th17 cells stimulated with cl-CD95L produced sphingosine-1-phosphate (S1P), which promoted endothelial transmigration by activating the S1P receptor 3. We generated a cell-penetrating CID peptide that prevented Th17 cell transmigration and alleviated clinical symptoms in lupus mice. Therefore, neutralizing the CD95 non-apoptotic signaling pathway could be an attractive therapeutic approach for SLE treatment.
ISSN: 1074-7613

hal-01359568
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359568
DOI : 10.1016/j.immuni.2016.06.028
PUBMED : 27438772