Enhancement of the influenza A hemagglutinin (HA)-mediated cell-cell fusion and virus entry by the viral neuraminidase (NA).

International audienceBACKGROUND: The major role of the neuraminidase (NA) protein of influenza A virus is related to its sialidase activity, which disrupts the interaction between the envelope hemagglutinin (HA) protein and the sialic acid receptors expressed at the surface of infected cells. This enzymatic activity is known to promote the release and spread of progeny viral particles following their production by infected cells, but a potential role of NA in earlier steps of the viral life cycle has never been clearly demonstrated. In this study we have examined the impact of NA expression on influenza HA-mediated viral membrane fusion and virion infectivity. METHODOLOGY/PRINCIPAL FINDINGS: The role of NA in the early stages of influenza virus replication was examined using a cell-cell fusion assay that mimics HA-mediated membrane fusion, and a virion infectivity assay using HIV-based pseudoparticles expressing influenza HA and/or NA proteins. In the cell-cell fusion assay, which bypasses the endocytocytosis step that is characteristic of influenza virus entry, we found that in proper HA maturation conditions, NA clearly enhanced fusion in a dose-dependent manner. Similarly, expression of NA at the surface of pseudoparticles significantly enhanced virion infectivity. Further experiments using exogenous soluble NA revealed that the most likely mechanism for enhancement of fusion and infectivity by NA was related to desialylation of virion-expressed HA. CONCLUSION/SIGNIFICANCE: The NA protein of influenza A virus is not only required for virion release and spread but also plays a critical role in virion infectivity and HA-mediated membrane fusion

Sex-Specific Associations of Genetically Predicted Circulating Lp(a) (Lipoprotein(a)) and Hepatic LPA Gene Expression Levels With Cardiovascular Outcomes: Mendelian Randomization and Observational Analyses.

BACKGROUND: Elevated Lp(a) (Lipoprotein(a)) levels are associated with coronary artery disease (CAD), ischemic stroke (IS), and calcific aortic valve stenosis (CAVS). Studies investigating the association between Lp(a) levels and these diseases in women have yielded inconsistent results. METHODS: To investigate the association of Lp(a) with sex-specific cardiovascular outcomes, we determined the association between genetically predicted Lp(a) levels (using 27 single nucleotide polymorphisms at the LPA locus) and hepatic LPA expression (using 80 single nucleotide polymorphisms at the LPA locus associated with LPA mRNA expression in liver samples from the Genotype-Tissue Expression dataset) on CAD, IS, and CAVS using individual participant data from the UK Biobank: 408 403 participants of European ancestry (37 102, 4283, and 2574 with prevalent CAD, IS, and CAVS, respectively). The long-term association between Lp(a) levels and incident CAD, IS, and CAVS was also investigated in European Prospective Investigation into Cancer and Nutrition-Norfolk: 18 721 participants (3964, 846, and 424 with incident CAD, IS, and CAVS, respectively). RESULTS: Genetically predicted plasma Lp(a) levels were positively and similarly associated with prevalent and incident CAD and CAVS in men and women. Genetically predicted plasma Lp(a) levels were associated with prevalent and incident IS when we studied men and women pooled together, and in men only. Genetically predicted LPA expression levels were associated with prevalent CAD and CAVS in men and women but not with IS. CONCLUSIONS: Genetically predicted blood Lp(a) and hepatic LPA gene expression as well as serum Lp(a) levels predict the risk of CAD and CAVS in men and in women. Whether RNA interference therapies aiming at lowering Lp(a) levels could be useful in reducing cardiovascular disease risk in both men and women with high Lp(a) levels needs to be determined in large-scale cardiovascular outcomes trials

Lipoprotein-associated phospholipase A2 activity, genetics and calcific aortic valve stenosis in humans.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has been shown to predict calcific aortic valve stenosis (CAVS) outcomes. Our objective was to test the association between plasma Lp-PLA2 activity and genetically elevated Lp-PLA2 mass/activity with CAVS in humans. METHODS AND RESULTS: Lp-PLA2 activity was measured in 890 patients undergoing cardiac surgery, including 476 patients undergoing aortic valve replacement for CAVS and 414 control patients undergoing coronary artery bypass grafting. After multivariable adjustment, Lp-PLA2 activity was positively associated with the presence of CAVS (OR=1.21 (95% CI 1.04 to 1.41) per SD increment). We selected four single nucleotide polymorphisms (SNPs) at the PLA2G7 locus associated with either Lp-PLA2 mass or activity (rs7756935, rs1421368, rs1805017 and rs4498351). Genetic association studies were performed in eight cohorts: Quebec-CAVS (1009 cases/1017 controls), UK Biobank (1350 cases/349 043 controls), European Prospective Investigation into Cancer and Nutrition-Norfolk (504 cases/20 307 controls), Genetic Epidemiology Research on Aging (3469 cases/51 723 controls), Malmö Diet and Cancer Study (682 cases/5963 controls) and three French cohorts (3123 cases/6532 controls), totalling 10 137 CAVS cases and 434 585 controls. A fixed-effect meta-analysis using the inverse-variance weighted method revealed that none of the four SNPs was associated with CAVS (OR=0.99 (95% CI 0.96 to 1.02, p=0.55) for rs7756935, 0.97 (95% CI 0.93 to 1.01, p=0.11) for rs1421368, 1.00 (95% CI 1.00 to 1.01, p=0.29) for rs1805017, and 1.00 (95% CI 0.97 to 1.04, p=0.87) for rs4498351). CONCLUSIONS: Higher Lp-PLA2 activity is significantly associated with the presence of CAVS and might represent a biomarker of CAVS in patients with heart disease. Results of our genetic association study suggest that Lp-PLA2 is however unlikely to represent a causal risk factor or therapeutic target for CAVS

Genetic Variation in LPA, Calcific Aortic Valve Stenosis in Patients Undergoing Cardiac Surgery, and Familial Risk of Aortic Valve Microcalcification.

IMPORTANCE: Genetic variants at the LPA locus are associated with both calcific aortic valve stenosis (CAVS) and coronary artery disease (CAD). Whether these variants are associated with CAVS in patients with CAD vs those without CAD is unknown. OBJECTIVE: To study the associations of LPA variants with CAVS in a cohort of patients undergoing heart surgery and LPA with CAVS in patients with CAD vs those without CAD and to determine whether first-degree relatives of patients with CAVS and high lipoprotein(a) (Lp[a]) levels showed evidence of aortic valve microcalcification. DESIGN, SETTING, AND PARTICIPANTS: This genetic association study included patients undergoing cardiac surgery from the Genome-Wide Association Study on Calcific Aortic Valve Stenosis in Quebec (QUEBEC-CAVS) study and patients with CAD, patients without CAD, and control participants from 6 genetic association studies: the UK Biobank, the European Prospective Investigation of Cancer (EPIC)-Norfolk, and Genetic Epidemiology Research on Aging (GERA) studies and 3 French cohorts. In addition, a family study included first-degree relatives of patients with CAVS. Data were collected from January 1993 to September 2018, and analysis was completed from September 2017 to September 2018. EXPOSURES: Case-control studies. MAIN OUTCOMES AND MEASURES: Presence of CAVS according to a weighted genetic risk score based on 3 common Lp(a)-raising variants and aortic valve microcalcification, defined as the mean tissue to background ratio of 1.25 or more, measured by fluorine 18-labeled sodium fluoride positron emission tomography/computed tomography. RESULTS: This study included 1009 individuals undergoing cardiac surgery and 1017 control participants in the QUEBEC-CAVS cohort; 3258 individuals with CAVS and CAD, 41 100 controls with CAD, 2069 individuals with CAVS without CAD, and 380 075 control participants without CAD in the UK Biobank, EPIC-Norfolk, and GERA studies and 3 French cohorts combined; and 33 first-degree relatives of 17 patients with CAVS and high Lp(a) levels (≥60 mg/dL) and 23 control participants with normal Lp(a) levels (<60 mg/dL). In the QUEBEC-CAVS study, each SD increase of the genetic risk score was associated with a higher risk of CAVS (odds ratio [OR], 1.35 [95% CI, 1.10-1.66]; P = .003). Each SD increase of the genetic risk score was associated with a higher risk of CAVS in patients with CAD (OR, 1.30 [95% CI, 1.20-1.42]; P < .001) and without CAD (OR, 1.33 [95% CI, 1.14-1.55]; P < .001). The percentage of individuals with a tissue to background ratio of 1.25 or more or CAVS was higher in first-degree relatives of patients with CAVS and high Lp(a) (16 of 33 [49%]) than control participants (3 of 23 [13%]; P = .006). CONCLUSIONS AND RELEVANCE: In this study, a genetically elevated Lp(a) level was associated with CAVS independently of the presence of CAD. These findings support further research on the potential usefulness of Lp(a) cascade screening in CAVS

The origins and spread of domestic horses from the Western Eurasian steppes

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: All collapsed and paired-end sequence data for samples sequenced in this study are available in compressed fastq format through the European Nucleotide Archive under accession number PRJEB44430, together with rescaled and trimmed bam sequence alignments against both the nuclear and mitochondrial horse reference genomes. Previously published ancient data used in this study are available under accession numbers PRJEB7537, PRJEB10098, PRJEB10854, PRJEB22390 and PRJEB31613, and detailed in Supplementary Table 1. The genomes of ten modern horses, publicly available, were also accessed as indicated in their corresponding original publications57,61,85-87.NOTE: see the published version available via the DOI in this record for the full list of authorsDomestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 BC. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture

L'étude des hypoplasies linéaires de l'émail et la caractérisation de l'élevage porcin au Moyen Âge sur les sites de Boves (Somme) et de Vincennes (Val-de-Marne)

Die auf dem Skelett sichtbaren Pathologien und die Zähne sind von der Gesundheit und den Lebensbedingungendes Tieresabhängig. Eine Form der Missbildung der Zähne (lineare Zahnschmelzhypoplasie LEH) entspricht einer punktuell unzureichenden Entwicklung des Zahnemails während der Bildung der Krone. Diese Anomalie zeichnet sich durch Linien oder Rillen an der Oberfläche der Zahnkrone aus. Die Untersuchung dieser Linien ermöglicht es, chronologische Modelle von physiologischen Stressphasen zu rekonstruieren, die das Tier während seiner Entwicklungsphase durchlebt hat und die oft mit einer Verschlechterung der Ernahrung zusammenhängen. Die ersten Ergebnisse von den Burgkomplexen von Boves (8. - 14. Jahrhundert) und Vincennes (14. Jahrhundert) lassen vermuten, dass die in Bezug auf Anzahl und Art unterschiedlichen Linien mit den Umwelt- und Haltungsbedingungen zwischen dem 8. und dem 14. Jahrhundert in Zusammenhang zu bringen sind. Die Beobachtung der Frequenzen linearer Zahnschmelzhypoplasie erlaubt es, mehrere Standorte oder unterschiedliche Phasen eines Standortes miteinander zu vergleichen. Der Vergleich mehrerer Perioden des gleichen Ortes miteinander erlaubt es auch zu verstehen, aus welchen Gründen sich die Zuchtbedingungen im Laufe der Zeit verändern können.Pathologies which may appear on the bones or teeth of an animal are related to its health and its living conditions. A dental malformation known as linear enamel hypoplasia (LEH) is caused by temporary insufficiencies in the build-up of the enamel as the crown develops. This anomaly is characterised by the appearance of lines or ridges on the surface of the crown. The study of these lines makes it possible to propose chronological models of periods of physiological stress occurring during the animal's development, and can often be related to a deterioration in diet. The first results obtained from the castle sites of Boves (eighth century - fourteenth century) and Vincennes (fourteenth century) suggest that variations in the number and aspect of the lines observed on the teeth of pigs may be related to environmental conditions and livestock farming practices current between the eighth and the fourteenth centuries. Thanks to the observation of LEH occurrence, comparisons may be established between different sites, or different phases of one particular site. The possibility of comparing several periods on the same site also provides an opportunity to research the incidents or conditions in the livestock raising process that may have determined these variations.Les pathologies visibles sur le squelette et les dents présentent des relations avec la santé et les conditions de vie de l'animal. Une malformation dentaire (hypoplasie linéaire de l'émail ou LEH) correspond à des insuffisances ponctuelles du développement en épaisseur de l'émail au cours de la formation de la couronne. Cette anomalie se caractérise par la présence de lignes ou des rainures à la surface de la couronne de la dent. L'étude de ces lignes permet de construire des modèles chronologiques de phases de stress physiologiques, intervenues durant la période de développement de l'animal, souvent à mettre en relation avec une dégradation du régime alimentaire. Les premiers résultats obtenus sur les sites castraux de Boves (VIIIe-XIVe s.) et de Vincennes (XIVe s.) tendraient à indiquer l'existence de variation dans les quantités et les qualités des lignes observées sur les dents de porcs en relation avec les conditions environnementales et les pratiques d'élevage entre les VIIIe et XIVe siècles. L'observation des fréquences en LEH permet de comparer entre eux différents sites ou phases d'un même site. Le fait de pouvoir comparer plusieurs périodes d'un même site permet aussi de chercher les motifs de variation qui peuvent intervenir au cours du temps dans les conditions d'élevage.Clavel Benoît, Sicard Sébastien. L'étude des hypoplasies linéaires de l'émail et la caractérisation de l'élevage porcin au Moyen Âge sur les sites de Boves (Somme) et de Vincennes (Val-de-Marne). In: Revue archéologique de Picardie, n°3-4, 2007. pp. 143-156

Importance de l'environnement cellulaire pour la réplication du virus de l'immunodéficience humaine

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Facteurs liés à l'observance de patients épileptiques selon deux interventions, hospitalière et communautaire, en République démocratique populaire Lao

Avec une prévalence de 7.7/1000, l'épilepsie est encore une condition négligée en RDP Lao. Un programme d'accès au traitement de l'épilepsie a ainsi été lancé en 2008 et nous avons voulu étudier les facteurs associés à l'observance au traitement antiépileptique en menant une enquête sur 99 patients ayant été confronté à deux interventions différents : une hospitalière et une communautaire. Résultats : Un taux d'observance évalué à 38.38% (42.86% pour le groupe d'intervention communautaire et 34% pour le groupe d'intervention communautaire). 3 facteurs liés à une bonne observance : diminution du nombre de crises depuis la mise sous traitement (p=0.002), recours à la prise en charge en Thaïlande (p=0.012) et bonnes connaissances des patients sur les traitements antiépileptiques (p=0.004). 3 facteurs liés à une mauvaise observance; être un adulte (p=0.024), avoir un ressenti négatif à cause de la maladie (p=0.005) et être préoccupé par le traitement antiépileptique (p=0.003).TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Electromagnetic characterization of PCB cards for mobile phones

International audienceIn this article we focus on the EMC characterization of PCB cards for mobile phones especially the filtering part in order to position the best way the components on the routing. To be precise, all the electrical characteristics of the cabling including the inductive couplings have to be taken into consideration. To achieve this modeling, the PEEC method (partial element equivalent circuit) has been used to obtain an electrical equivalent circuit of the connections of the PCB structure. This model takes into account all the parasitic elements. A study of the transfer function of the filter can be obtained and Spice-like simulations can give the waveforms of current and voltage in time domain. Moreover, solving the circuit equations on the global electrical model, the current distribution in the PCB tracks can be drawn and “hot” points can then been identified. Several configurations of a PCB card for mobile phone have been studied according the value of some geometrical parameters or the position of passive component on the PCB

Induction of Ucp2 expression in brain phagocytes and neurons following murine toxoplasmosis: An essential role of IFN-γ and an association with negative energy balance

A model of murine toxoplasmosis was used to study cellular and temporal expression of uncoupling protein-2 (Ucp2) in the brain. In situ hybridization indicated that Ucp2 was located in neurons. Nuclei structures involved in energy balance, in particular the nucleus of the solitary tract (NST), was shown to have a positive association between negative energy balance and Ucp2 levels. Infection-induced Ucp2 expression colocalized mainly with microglial cells, but also with infiltrating macrophages and neutrophils in the brain, which was evident from day 9 post-infection. Using cytokine knockout mice we demonstrate that microglial Ucp2 induction in the brain was largely dependant on interferon-γ, but not interleukin-6 or tumour-necrosis-factor-α in response to infection. In summary, this study shows that Ucp2 is regulated in a different manner in neurons than in microglia/phagocytes following infection. Our study indicates that an association exists between negative energy balance and neuronal Ucp2 levels in the NST, in particular