Comparative genomic and phylogeographic analysis of Mycobacterium leprae.

Reductive evolution and massive pseudogene formation have shaped the 3.31-Mb genome of Mycobacterium leprae, an unculturable obligate pathogen that causes leprosy in humans. The complete genome sequence of M. leprae strain Br4923 from Brazil was obtained by conventional methods (6x coverage), and Illumina resequencing technology was used to obtain the sequences of strains Thai53 (38x coverage) and NHDP63 (46x coverage) from Thailand and the United States, respectively. Whole-genome comparisons with the previously sequenced TN strain from India revealed that the four strains share 99.995% sequence identity and differ only in 215 polymorphic sites, mainly SNPs, and by 5 pseudogenes. Sixteen interrelated SNP subtypes were defined by genotyping both extant and extinct strains of M. leprae from around the world. The 16 SNP subtypes showed a strong geographical association that reflects the migration patterns of early humans and trade routes, with the Silk Road linking Europe to China having contributed to the spread of leprosy.

Challenges to the implementation of behavioural survellance for HIV/STI in Europe

Background: Well-conducted behavioural surveillance (BS) is essential for policy planning and evaluation. Data should be comparable across countries. In 2008, the European Centre for Disease Prevention and Control (ECDC) began a programme to support Member States in the implementation of BS for Second Generation Surveillance. Methods: Data from a mapping exercise on current BS activities in EU/EFTA countries led to recommendations for establishing national BS systems and international coordination, and the definition of a set of core and transversal (UNGASS-Dublin compatible) indicators for BS in the general and eight specific populations. A toolkit for establishing BS has been developed and a BS needs-assessment survey has been launched in 30 countries. Tools for BS self-assessment and planning are currently being tested during interactive workshops with country representatives. Results: The mapping exercise revealed extreme diversity between countries. Around half had established a BS system, but this did not always correspond to the epidemiological situation. Challenges to implementation and harmonisation at all levels emerged from survey findings and workshop feedback. These include: absence of synergy between biological and behavioural surveillance and of actors having an overall view of all system elements; lack of awareness of the relevance of BS and of coordination between agencies; insufficient use of available data; financial constraints; poor sustainability, data quality and access to certain key populations; unfavourable legislative environments. Conclusions: There is widespread need in the region not only for technical support but also for BS advocacy: BS remains the neglected partner of second generation surveillance and requires increased political support and capacity-building in order to become effective. Dissemination of validated tools for BS, developed in interaction with country experts, proves feasible and acceptable.

Interruptions de grossesse dans le canton de Vaud en 2010

[Table des matières] 1. Résumé. 2. Introduction. 3. Méthodes. 4. Population. 5. Résultats. 5.1. Tendances (Taux de recours à l'interruption de grossesse - Rapport entre interruptions de grossesse et naissances vivantes). 5.2. Comparaison intercantonale. 5.3. Caractéristiques sociodémographiques des résidentes vaudoises ayant interrompu leur grossesse en 2010 (Age - Nationalité - Niveau de formation et activité principale - Etat civil et type de ménage). 5.4. Fécondité et recours antérieur à l'interruption de grossesse. 5.5. Caractéristiques de l'interruption de grossesse(Motif de l'IG - Age gestationnel - Lieu d'intervention - Type d'intervention). 6. Conclusions. 7. Bibliographie. 8. Annexes. A1. Emploi de la Mifépristone. Avis d'expert no 15. A2. Formulaire de déclaration.

Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance.

Calpain 3 is a member of the calpain family of calcium-dependent intracellular proteases. Thirteen years ago it was discovered that mutations in calpain 3 (CAPN3) result in an autosomal recessive and progressive form of limb girdle muscular dystrophy called limb girdle muscular dystrophy type 2A. While calpain 3 mRNA is expressed at high levels in muscle and appears to have some role in developmental processes, muscles of patients and mice lacking calpain 3 still form apparently normal muscle during prenatal development; thus, a functional calpain 3 protease is not mandatory for muscle to form in vivo but it is a pre-requisite for muscle to remain healthy. Despite intensive research in this field, the physiological substrates of the calpain 3 protein (hereafter referred to as CAPN3) and its alternatively spliced isoforms remain elusive. The existence of these multiple isoforms complicates the search for the physiological functions of CAPN3 and its pathophysiological role. In this review, we summarize the genetic and biochemical evidence that point to loss of function of the full-length isoform of CAPN3, also known as p94, as the pathogenic isoform. We also argue that its natural substrates must reside in its proximity within the sarcomere where it is stored in an inactive state anchored to titin. We further propose that CAPN3 has many attributes that make it ideally suited as a sensor of sarcomeric integrity and function, involved in its repair and maintenance. Loss of these CAPN3-mediated activities can explain the "progressive" development of muscular dystrophy.

Comparaison internationale des résultats des politiques de lutte contre le VIH/sida : rapport sur mandat de l'Instance d'évaluation de la politique de lutte contre le sida (France)

[Table des matières] 1. Introduction. 2. Epidémiologie. 2.1 Dynamique et structure de l'épidémie de sida. 2.2 L'infection à VIH. 2.3 Evolution des comportements dans les principales populations de référence. 2.4 Conclusions intermédiaires. 3. Les politiques nationales de lutte contre le sida. 3.1 Introduction. 3.2 Les politiques et leur traduction institutionnelle. 3.3 Aspects spécifiques des politiques de lutte contre le sida. 4. Conclusions générales. 5. Annexes. 6. Tableaux comparatifs.

Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance.

Calpain 3 is a member of the calpain family of calcium-dependent intracellular proteases. Thirteen years ago it was discovered that mutations in calpain 3 (CAPN3) result in an autosomal recessive and progressive form of limb girdle muscular dystrophy called limb girdle muscular dystrophy type 2A. While calpain 3 mRNA is expressed at high levels in muscle and appears to have some role in developmental processes, muscles of patients and mice lacking calpain 3 still form apparently normal muscle during prenatal development; thus, a functional calpain 3 protease is not mandatory for muscle to form in vivo but it is a pre-requisite for muscle to remain healthy. Despite intensive research in this field, the physiological substrates of the calpain 3 protein (hereafter referred to as CAPN3) and its alternatively spliced isoforms remain elusive. The existence of these multiple isoforms complicates the search for the physiological functions of CAPN3 and its pathophysiological role. In this review, we summarize the genetic and biochemical evidence that point to loss of function of the full-length isoform of CAPN3, also known as p94, as the pathogenic isoform. We also argue that its natural substrates must reside in its proximity within the sarcomere where it is stored in an inactive state anchored to titin. We further propose that CAPN3 has many attributes that make it ideally suited as a sensor of sarcomeric integrity and function, involved in its repair and maintenance. Loss of these CAPN3-mediated activities can explain the "progressive" development of muscular dystrophy.

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.

Prévention de la toxicomanie auprès des jeunes : le rôle de la police, des tribunaux et des juges des mineurs

[Table des matières] 1. Introduction. 2. Méthode. 3. Contexte juridique dans une perspective fédérale. 4. Présentation de deux exemples de collaboration à l'étranger. 5. Présentation des exemples. 6. Synthèse des modèles d'interventions. 7. Réponses aux questions d'évaluation. 8. Conclusions et recommandations. 9. Annexes.