11 research outputs found
Genome sequencing reveals Zika virus diversity and spread in the Americas
Although the recent Zika virus (ZIKV) epidemic in the Americas and its link to birth defects have attracted a great deal of attention, much remains unknown about ZIKV disease epidemiology and ZIKV evolution, in part owing to a lack of genomic data. Here we address this gap in knowledge by using multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analysed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental United States. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of surveillance of viral infections. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those that might be relevant to the effectiveness of diagnostic tests
Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa
West Africa is currently witnessing the most extensive Ebola virus (EBOV) outbreak so far recorded. Until now, there have been 27,013 reported cases and 11,134 deaths. The origin of the virus is thought to have been a zoonotic transmission from a bat to a two-year-old boy in December 2013 (ref. 2). From this index case the virus was spread by human-to-human contact throughout Guinea, Sierra Leone and Liberia. However, the origin of the particular virus in each country and time of transmission is not known and currently relies on epidemiological analysis, which may be unreliable owing to the difficulties of obtaining patient information. Here we trace the genetic evolution of EBOV in the current outbreak that has resulted in multiple lineages. Deep sequencing of 179 patient samples processed by the European Mobile Laboratory, the first diagnostics unit to be deployed to the epicentre of the outbreak in Guinea, reveals an epidemiological and evolutionary history of the epidemic from March 2014 to January 2015. Analysis of EBOV genome evolution has also benefited from a similar sequencing effort of patient samples from Sierra Leone. Our results confirm that the EBOV from Guinea moved into Sierra Leone, most likely in April or early May. The viruses of the Guinea/Sierra Leone lineage mixed around June/July 2014. Viral sequences covering August, September and October 2014 indicate that this lineage evolved independently within Guinea. These data can be used in conjunction with epidemiological information to test retrospectively the effectiveness of control measures, and provides an unprecedented window into the evolution of an ongoing viral haemorrhagic fever outbreak.status: publishe
Le DĂ©fi magique, volume 2
La magie avait tendance Ă ĂȘtre considĂ©rĂ©e jusqu'Ă ces derniĂšres annĂ©es comme une entreprise individuelle et un phĂ©nomĂšne rĂ©siduel sans avenir. Or, ce que l'on constate aujourd'hui, c'est non seulement un regain d'intĂ©rĂȘt pour l'occultisme, le satanisme et la sorcellerie, mais aussi la formation de mouvement magiques organisĂ©s Ă l'Ă©chelle nationale et internationale, qui constituent un dĂ©fi pour nos sociĂ©tĂ©s modernes, rationalistes et scientifiques. Au-delĂ du sensationnalisme et des polĂ©miques, des universitaires et des acteurs dans le domaine religieux apportent dans ce volume des Ă©claircissements et des prĂ©cisions sur plusieurs arguments controversĂ©s : le dĂ©bat sur le satanisme criminel aux Etats-Unis et ailleurs ; le regain d'intĂ©rĂȘt pour l'exorcisme constatĂ© dans plusieurs Eglises chrĂ©tiennes ; la permanence de la sorcellerie populaire et les diffĂ©rences avec la nĂ©o-sorcellerie bourgeoise, dite âwicaâ ; les rĂ©actions des Eglises, de la presse, des tribunaux au retour de l'occulte ; les influences multiples du satanisme sur la littĂ©rature et sur l'art ; les rapprochements qui peuvent ĂȘtre Ă©tablis dans l'interprĂ©tation du mal et dans la vision du diable entre certaines traditions religieuses (judĂ©ochrĂ©tienne, indienne, japonaise), ou entre les traditions religieuses et la psychanalyse ou la psychiatrie
Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency
International audienceWe report two children, born from consanguineous parents, who presented with early-onset refractory epilepsy associated with psychomotor delay, failure to thrive, blindness and deafness. Polarographic and spectrophotometric analyses in fibroblasts and liver revealed a respiratory chain (RC) dysfunction. Surprisingly, we identified a homozygous nonsense mutation in the GM3 synthase gene by using exome sequencing. GM3 synthase catalyzes the formation of GM3 ganglioside from lactosylceramide, which is the first step in the synthesis of complex ganglioside species. Mass spectrometry analysis revealed that the complete absence of GM3 ganglioside and its biosynthetic derivatives was associated with an upregulation of the alternative globoside pathway in fibroblasts. The accumulation of Gb3 and Gb4 globosides likely has a role in RC dysfunction and in the decrease of mitochondrial membrane potential leading to apoptosis, which we observed in fibroblasts. We show for the first time that GM3 synthase deficiency, responsible for early-onset epilepsy syndrome, leads to a secondary RC dysfunction. Our study highlights the role of secondary mitochondrial disorders that can interfere with the diagnosis and the evolution of other metabolic diseases.European Journal of Human Genetics advance online publication, 19 September 2012; doi:10.1038/ejhg.2012.202.</p
Survival and Morbidity of Preterm Children Born at 22 Through 34 Weeksâ Gestation in France in 2011
International audienceImportance Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. Objectives To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeksâ gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. Design, Setting, and Participants The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeksâ gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. Main Outcomes and Measures Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). Results A total of 0.7% of infants born before 24 weeksâ gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (Pâ<â.001) at 25 through 29 weeks and 6% (Pâ<â.001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. Conclusions and Relevance The substantial improvement in survival in France for newborns born at 25 through 31 weeksâ gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard