Migration and horizontal gene transfer divide microbial genomes into multiple niches.

Horizontal gene transfer is central to microbial evolution, because it enables genetic regions to spread horizontally through diverse communities. However, how gene transfer exerts such a strong effect is not understood. Here we develop an eco-evolutionary model and show how genetic transfer, even when rare, can transform the evolution and ecology of microbes. We recapitulate existing models, which suggest that asexual reproduction will overpower horizontal transfer and greatly limit its effects. We then show that allowing immigration completely changes these predictions. With migration, the rates and impacts of horizontal transfer are greatly increased, and transfer is most frequent for loci under positive natural selection. Our analysis explains how ecologically important loci can sweep through competing strains and species. In this way, microbial genomes can evolve to become ecologically diverse where different genomic regions encode for partially overlapping, but distinct, ecologies. Under these conditions ecological species do not exist, because genes, not species, inhabit niches.

Temporal Patterns of Alcohol Consumption and Alcohol-Related Road Accidents in Young Swiss Men: Seasonal, Weekday and Public Holiday Effects.

AIMS: To assess seasonal, weekday, and public holiday effects on alcohol-related road accidents and drinking diaries among young Swiss men. METHODS: Federal road accident data (35,485 accidents) from Switzerland and drinking diary data from a large cohort of young Swiss men (11,930 subjects) were analysed for temporal effects by calendar week, weekday and public holiday (Christmas, New Years, National Day). Alcohol-related accidents were analysed using rate ratios for observed versus expected numbers of accidents and proportions of alcohol-related accidents relative to the total number. Drinking diaries were analysed for the proportion of drinkers, median number of drinks consumed, and the 90th percentile's number of drinks consumed. RESULTS: Several parallel peaks were identified in alcohol-related accidents and drinking diaries. These included increases on Fridays and Saturdays, with Saturday drinking extending until early Sunday morning, an increase during the summer on workdays but not weekends, an increase at the end of the year, and increases on public holidays and the evening before. CONCLUSIONS: Our results suggest specific time-windows that are associated with increases in drinking and alcohol-related harm. Established prevention measures should be enforced during these time-windows to reduce associated peaks.

Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain.

In a classic model of mammalian brain formation, precursors of principal glutamatergic neurons migrate radially along radial glia fibers whereas GABAergic interneuron precursors migrate tangentially. These migration modes have significant implications for brain function. Here we used clonal lineage tracing of active radial glia-like neural stem cells in the adult mouse dentate gyrus and made the surprising discovery that proliferating neuronal precursors of glutamatergic granule neurons exhibit significant tangential migration along blood vessels, followed by limited radial migration. Genetic birthdating and morphological and molecular analyses pinpointed the neuroblast stage as the main developmental window when tangential migration occurs. We also developed a partial "whole-mount" dentate gyrus preparation and observed a dense plexus of capillaries, with which only neuroblasts, among the entire population of progenitors, are directly associated. Together, these results provide insight into neuronal migration in the adult mammalian nervous system.

Evidence for daily and weekly rhythmicity but not lunar or seasonal rhythmicity of physical activity in a large cohort of individuals from five different countries.

Background Biological rhythmicity has been extensively studied in animals for many decades. Although temporal patterns of physical activity have been identified in humans, no large-scale, multi-national study has been published, and no comparison has been attempted of the ubiquity of activity rhythms at different time scales (such as daily, weekly, monthly, and annual). Methods Using individually worn actigraphy devices, physical activity of 2,328 individuals from five different countries (adults of African descent from Ghana, South Africa, Jamaica, Seychelles, and the United States) was measured for seven consecutive days at different times of the year. Results Analysis for rhythmic patterns identified daily rhythmicity of physical activity in all five of the represented nationalities. Weekly rhythmicity was found in some, but not all, of the nationalities. No significant evidence of lunar rhythmicity or seasonal rhythmicity was found in any of the groups. Conclusions These findings extend previous small-scale observations of daily rhythmicity to a large cohort of individuals from around the world. The findings also confirm the existence of modest weekly rhythmicity but not lunar or seasonal rhythmicity in human activity. These differences in rhythm strength have implications for the management of health hazards of rhythm misalignment. Key Messages Analysis of the pattern of physical activity of 2,328 individuals from five countries revealed strong daily rhythmicity in all five countries, moderate weekly rhythmicity in some countries, and no lunar rhythmicity or seasonal rhythmicity in any of the countries.

NLRP12 is a neutrophil-specific, negative regulator of in vitro cell migration but does not modulate LPS- or infection-induced NF-κB or ERK signalling.

NOD-like receptors (NLR) are a family of cytosolic pattern recognition receptors that include many key drivers of innate immune responses. NLRP12 is an emerging member of the NLR family that is closely related to the well-known inflammasome scaffold, NLRP3. Since its discovery, various functions have been proposed for NLRP12, including the positive regulation of dendritic cell (DC) and neutrophil migration and the inhibition of NF-κB and ERK signalling in DC and macrophages. We show here that NLRP12 is poorly expressed in murine macrophages and DC, but is strongly expressed in neutrophils. Using myeloid cells from WT and Nlrp12(-/)(-) mice, we show that, contrary to previous reports, NLRP12 does not suppress LPS- or infection-induced NF-κB or ERK activation in myeloid cells, and is not required for DC migration in vitro. Surprisingly, we found that Nlrp12 deficiency caused increased rather than decreased neutrophil migration towards the chemokine CXCL1 and the neutrophil parasite Leishmania major, revealing NLRP12 as a negative regulator of directed neutrophil migration under these conditions.

Health Migration Policies and Ethical Controversies: the Case of African Nurses in the UK

The United Kingdom (UK) for last few decades has been faced with a growing need for health personnel and has therefore attracted professionals, particularly overseas nurses. The country has been characterised by a historical migration policy favourable to the recruitment of foreign health staff. However, in the context of deep shortage and high level of diseases and health system weakness, the international health professional recruitment from Sub Saharan Africa has created unprecedented ethical controversies which have pushed the UK to the centre of discussions because of its liberal policies towards international recruitment that have been considered as aggressive. While the 'brain drain' controversy is well known, less attention has been devoted to the specific international health migration controversy and the pivotal role of the UK in the diffusion of ethical code of practice. Using mainly the perspective of the policy analysis of controversy (Roe 1994) and the analysis of discourses (de Haas 2008), our paper comes back respectively to the nature of the controversy and the pivotal role of the UK. It also analyses how the implementation of UK ethical policies - Code of Practice, banned countries list of recruitment, restrictive immigration policies - have been considered as inefficient and unethical in their contents and their targets.

High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates.

The vulnerability to infection of newborns is associated with a limited ability to mount efficient immune responses. High concentrations of adenosine and prostaglandins in the fetal and neonatal circulation hamper the antimicrobial responses of newborn immune cells. However, the existence of mechanisms counterbalancing neonatal immunosuppression has not been investigated. Remarkably, circulating levels of macrophage migration inhibitory factor (MIF), a proinflammatory immunoregulatory cytokine expressed constitutively, were 10-fold higher in newborns than in children and adults. Newborn monocytes expressed high levels of MIF and released MIF upon stimulation with Escherichia coli and group B Streptococcus, the leading pathogens of early-onset neonatal sepsis. Inhibition of MIF activity or MIF expression reduced microbial product-induced phosphorylation of p38 and ERK1/2 mitogen-activated protein kinases and secretion of cytokines. Recombinant MIF used at newborn, but not adult, concentrations counterregulated adenosine and prostaglandin E2-mediated inhibition of ERK1/2 activation and TNF production in newborn monocytes exposed to E. coli. In agreement with the concept that once infection is established high levels of MIF are detrimental to the host, treatment with a small molecule inhibitor of MIF reduced systemic inflammatory response, bacterial proliferation, and mortality of septic newborn mice. Altogether, these data provide a mechanistic explanation for how newborns may cope with an immunosuppressive environment to maintain a certain threshold of innate defenses. However, the same defense mechanisms may be at the expense of the host in conditions of severe infection, suggesting that MIF could represent a potential attractive target for immune-modulating adjunctive therapies for neonatal sepsis.

Migration et compétence sanitaire : constats et exemple de l'Hôpital de l'enfance à Lausanne

[...] L'objectif de ce travail est d'exposer les notions de "compétence sanitaire" (Health Literacy) et d' "autonomisation" (Empowerment) dans un contexte de prise en charge pédiatrique des enfants de migrants. Nous sommes convaincus que ces deux concepts émergeants dans le domaine de la santé et appliqués au contexte migratoire constituent, sur les plans économiques et de management, des éléments qui peuvent mener à terme à : i) une réduction mesurable des coûts de la santé et ii) une porte d'entrée efficace dans un processus d'intégration - dont l'importance est reconnue sur le plan économique - des migrants dans leur pays d'accueil. Tout au long de ce travail, il apparaîtra comme évident que des données propres à la prise en charge sanitaire pédiatrique des enfants de migrants font actuellement souvent défaut, a fortiori l'application des concepts de compétence sanitaire et d'autonomisation pour cette part de la société. Nous le percevons comme une opportunité de mettre en place les conditions cadres pour combler ce vide. Nous poserons tout d'abord le cadre de ce mémoire au travers de la présentation des concepts de compétence sanitaire et d'autonomisation, en mettant en avant leurs aspects économiques dans les systèmes de santé actuels, en particulier en Suisse. Nous présenterons dans les chapitres 2 et 3 d'une part des données concernant l'état de santé de la population migrante en Suisse et d'autre part la stratégie mise en place au niveau fédéral dans le domaine " migration et santé 2008-2013 ". Le chapitre 4 nous permettra de présenter un "case study" que nous avons intégré à notre travail afin d'apporter des éléments plus concrets aux notions théoriques abordées dans ce mémoire. Nous avons choisi de nous concentrer sur l'Hôpital de l'Enfance de Lausanne (HEL) parce que l'HEL nous semble présenter un cas de structure hospitalière qui fait un effort remarquable de prise en charge médico-psycho-sociale des enfants de migrants. Le chapitre 5, en conclusion, aura pour objectif principal de soutenir que l'inclusion d'une dimension de management/gestion de la santé (représenté ici par l'autonomisation et la compétence sanitaire) introduirait une valeur ajoutée remarquable à l'effort constructif consenti sur le plan médico-social décrit au chapitre précédent. [Auteure, p. 4-5]

Essays on the Economics of Conflict and Migration

Les conflits civils sont des événements dramatiques qui poussent les individus hors de leurs pays d'origine. Mais si l'émigration était elle-même une force pacificatrice? Dans les deux premiers chapitres, je me suis intéressée à l'impact de l'émigration sur l'incidence des conflits civils dans les pays d'origine. Tout d'abord, je construis un modèle théorique d'équilibre général, dans lequel le niveau de conflit d'équilibre est déterminé par la ratio de combattants dans l'économie. Dans ce modèle, l'émigration décourage les conflits en réduisant les gains d'une rébellion, tout en augmentant le coût d'opportunité des combats. La principale prédiction du modèle est que le conflit diminue avec le niveau du salaire étranger net des coûts de migration. Dans le deuxième chapitre, je teste cette prédiction empiriquement. En utilisant une variable instrumentale, je démontre que l'émigration vers les pays développés diminue l'incidence de guerres civiles dans les pays d'origine. Ces résultats prouvent qu'en ouvrant leurs frontières, les pays d'accueil pourraient contribuer à sauver des vies, aussi bien celles des migrants que celles des habitants restés dans leur pays. De plus, les conflits civils tendent à détruire des sociétés en traumatisant les personnes touchées, augmentant ainsi le risque des conflits futurs. Afin de mieux comprendre ce cercle vicieux et de pouvoir y remédier, le troisième chapitre détermine si les enfants ayant vécu la guerre ont une tendance à être plus violent que des co-nationaux nés après la guerre. L'analyse se concentre sur les demandeurs d'asile en Suisse : Cette population est intéressante puisque l'allocation des demandeurs d'asile entre cantons est aléatoire, ce qui prévient le choix d'un canton avec un taux de criminalité plus élevé. Les résultats démontrent un effet de traumatisme causé par la guerre augmentant ainsi le risque de criminalité dans la vie adulte. Cependant, l'analyse de politiques publiques montre que la mise en place de politiques judicieuses permet d'éviter les conséquences de l'exposition à la guerre. En particulier, en offrant aux nouveaux arrivants l'accès au marché de travail ainsi que des perspectives à long-terme, la Suisse peut éliminer complètement l'effet du traumatisme sur la criminalité.