Communally breeding Bechstein's bats have a stable social system that is independent from the postglacial history and location of the populations.

Investigating macro-geographical genetic structures of animal populations is crucial to reconstruct population histories and to identify significant units for conservation. This approach may also provide information about the intraspecific flexibility of social systems. We investigated the history and current structure of a large number of populations in the communally breeding Bechstein's bat (Myotis bechsteinii). Our aim was to understand which factors shape the species' social system over a large ecological and geographical range. Using sequence data from one coding and one noncoding mitochondrial DNA region, we identified the Balkan Peninsula as the main and probably only glacial refugium of the species in Europe. Sequence data also suggest the presence of a cryptic taxon in the Caucasus and Anatolia. In a second step, we used seven autosomal and two mitochondrial microsatellite loci to compare population structures inside and outside of the Balkan glacial refugium. Central European and Balkan populations both were more strongly differentiated for mitochondrial DNA than for nuclear DNA, had higher genetic diversities and lower levels of relatedness at swarming (mating) sites than in maternity (breeding) colonies, and showed more differentiation between colonies than between swarming sites. All these suggest that populations are shaped by strong female philopatry, male dispersal, and outbreeding throughout their European range. We conclude that Bechstein's bats have a stable social system that is independent from the postglacial history and location of the populations. Our findings have implications for the understanding of the benefits of sociality in female Bechstein's bats and for the conservation of this endangered species.

CD4+ T cell count recovery in HIV type 1-infected patients is independent of class of antiretroviral therapy.

BACKGROUND: In recent years, treatment options for human immunodeficiency virus type 1 (HIV-1) infection have changed from nonboosted protease inhibitors (PIs) to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) and boosted PI-based antiretroviral drug regimens, but the impact on immunological recovery remains uncertain. METHODS: During January 1996 through December 2004 [corrected] all patients in the Swiss HIV Cohort were included if they received the first combination antiretroviral therapy (cART) and had known baseline CD4(+) T cell counts and HIV-1 RNA values (n = 3293). For follow-up, we used the Swiss HIV Cohort Study database update of May 2007 [corrected] The mean (+/-SD) duration of follow-up was 26.8 +/- 20.5 months. The follow-up time was limited to the duration of the first cART. CD4(+) T cell recovery was analyzed in 3 different treatment groups: nonboosted PI, NNRTI, or boosted PI. The end point was the absolute increase of CD4(+) T cell count in the 3 treatment groups after the initiation of cART. RESULTS: Two thousand five hundred ninety individuals (78.7%) initiated a nonboosted-PI regimen, 452 (13.7%) initiated an NNRTI regimen, and 251 (7.6%) initiated a boosted-PI regimen. Absolute CD4(+) T cell count increases at 48 months were as follows: in the nonboosted-PI group, from 210 to 520 cells/muL; in the NNRTI group, from 220 to 475 cells/muL; and in the boosted-PI group, from 168 to 511 cells/muL. In a multivariate analysis, the treatment group did not affect the response of CD4(+) T cells; however, increased age, pretreatment with nucleoside reverse-transcriptase inhibitors, serological tests positive for hepatitis C virus, Centers for Disease Control and Prevention stage C infection, lower baseline CD4(+) T cell count, and lower baseline HIV-1 RNA level were risk factors for smaller increases in CD4(+) T cell count. CONCLUSION: CD4(+) T cell recovery was similar in patients receiving nonboosted PI-, NNRTI-, and boosted PI-based cART.

Evolution of ascariasis in humans and pigs: a multi-disciplinary approach

The nematode parasite Ascaris lumbricoides infects the digestive tracts of over 1.4 billion people worldwide, and its sister species, Ascaris suum, has infected a countless number of domesticated and feral pigs. It is generally thought that the putative ancestor to these worms infected either humans or pigs, but with the advent of domestication, they had ample opportunity to jump to a new host and subsequently specialize and evolve into a new species. While nuclear DNA markers decisively separate the two populations, mitochondrial sequences reveal that three major haplotypes are found in A. suum and in A. lumbricoides, indicating either occasional hybridization, causing introgression of gene trees, or retention of polymorphism dating back to the original ancestral species. This article provides an illustration of the combined contribution of parasitology, archaeoparasitology, genetics and paleogenetics to the history of ascariasis. We specifically investigate the molecular history of ascariasis in humans by sequencing DNA from the eggs of Ascaris found among ancient archeological remains. The findings of this paleogenetic survey will explain whether the three mitochondrial haplotypes result from recent hybridization and introgression, due to intensive human-pig interaction, or whether their co-occurrence predates pig husbandry, perhaps dating back to the common ancestor. We hope to show how human-pig interaction has shaped the recent evolutionary history of this disease, perhaps revealing the identity of the ancestral host.

Evolution des transferts interhospitaliers au départ d'un centre hospitalier universitaire suisse [Trends in interhospital transfers from a Swiss university hospital center].

OBJECTIVE: Research on interhospital transfers provides a basis for describing and quantifying patient flow and its evolution over time, offering an insight into hospital organization and management and hospital overcrowding. The purpose of this study was to conduct a qualitative and quantitative analysis of patient flow and to examine trends over an eight-year period. METHODS: A retrospective descriptive study of interhospital transfers was conducted between 2003 and 2011 based on an analysis of demographic, medical and operational characteristics. Ambulance transfers and transfers requiring physician assistance were analyzed separately. RESULTS: The number of interhospital transfers increased significantly over the study period,from 4,026 in 2003 to 6,481 in 2011 (+60.9%). The number of ambulance transfers increased by almost 300% (616 in 2003 compared to 2,460 in 2011). Most of the transfers (98%) were to hospitals located less than 75 km from the university hospital (median: 24 km, 5-44). In 2011, 24% of all transfers were to psychiatric institutions. 26% of all transfer cases were direct transfers from the emergency department. An increasing number of transfers required physician assistance. 18% of these patients required ventilatory support, whole 9.8% required vasoactive drugs. 11.6% of these transfers were due to hospital overcrowding. Conclusion: The study shows that there has been a significant increase in interhospital transfers. This increase is related to hospital overcrowding and to the network-based systems governing patient care strategies.

Biased gene conversion and GC-content evolution in the coding sequences of reptiles and vertebrates.

Mammalian and avian genomes are characterized by a substantial spatial heterogeneity of GC-content, which is often interpreted as reflecting the effect of local GC-biased gene conversion (gBGC), a meiotic repair bias that favors G and C over A and T alleles in high-recombining genomic regions. Surprisingly, the first fully sequenced nonavian sauropsid (i.e., reptile), the green anole Anolis carolinensis, revealed a highly homogeneous genomic GC-content landscape, suggesting the possibility that gBGC might not be at work in this lineage. Here, we analyze GC-content evolution at third-codon positions (GC3) in 44 vertebrates species, including eight newly sequenced transcriptomes, with a specific focus on nonavian sauropsids. We report that reptiles, including the green anole, have a genome-wide distribution of GC3 similar to that of mammals and birds, and we infer a strong GC3-heterogeneity to be already present in the tetrapod ancestor. We further show that the dynamic of coding sequence GC-content is largely governed by karyotypic features in vertebrates, notably in the green anole, in agreement with the gBGC hypothesis. The discrepancy between third-codon positions and noncoding DNA regarding GC-content dynamics in the green anole could not be explained by the activity of transposable elements or selection on codon usage. This analysis highlights the unique value of third-codon positions as an insertion/deletion-free marker of nucleotide substitution biases that ultimately affect the evolution of proteins.

Modelling the mechanical aspects of the curing process of magneto-sensitive elastomeric materials

In this paper, a phenomenologically motivated magneto-mechanically coupled finite strain elastic framework for simulating the curing process of polymers in the presence of a magnetic load is proposed. This approach is in line with previous works by Hossain and co-workers on finite strain curing modelling framework for the purely mechanical polymer curing (Hossain et al., 2009b). The proposed thermodynamically consistent approach is independent of any particular free energy function that may be used for the fully-cured magneto-sensitive polymer modelling, i.e. any phenomenological or micromechanical-inspired free energy can be inserted into the main modelling framework. For the fabrication of magneto-sensitive polymers, micron-size ferromagnetic particles are mixed with the liquid matrix material in the uncured stage. The particles align in a preferred direction with the application of a magnetic field during the curing process. The polymer curing process is a complex (visco) elastic process that transforms a fluid to a solid with time. Such transformation process is modelled by an appropriate constitutive relation which takes into account the temporal evolution of the material parameters appearing in a particular energy function. For demonstration in this work, a frequently used energy function is chosen, i.e. the classical Mooney-Rivlin free energy enhanced by coupling terms. Several representative numerical examples are demonstrated that prove the capability of our approach to correctly capture common features in polymers undergoing curing processes in the presence of a magneto-mechanical coupled load.

Cutting edge: an essential role for Notch-1 in the development of both thymus-independent and -dependent T cells in the gut.

Whereas most T cells arise in the thymus, a distinct lineage of extrathymically derived T cells is present in the gut mucosa. The developmental origin of extrathymic T cells is poorly understood. We show here that Notch-1, a transmembrane receptor involved in T cell fate specification of bipotential T/B precursors in the thymus, is absolutely required for the development of extrathymic (as well as thymus-derived) mature T cells in the intestinal epithelium. In the absence of Notch-1, CD117(+) T cell precursors are relatively more abundant in the gut than the thymus, whereas immature B cells accumulate in the thymus but not the gut. Collectively, these data demonstrate that Notch-1 is essential for both thymic and extrathymic T cell fate specification and further suggest that bipotential T/B precursors that do not receive a Notch-1 signal adopt a B cell fate in the thymus but become developmentally arrested in the gut.

Evolution de l'intensité moyenne et de la fréquence des précipitations en Suisse de 1900 à 2009

Les précipitations moyennes et les nombres de jours de pluie par saison et par an ont été analysés pour 151 séries de mesures pluviométriques en Suisse de 1900 à 2009. Ces analyses révèlent que les précipitations moyennes ont augmenté durant le 20ème siècle pour toutes les saisons, sauf en été. Cette hausse est la plus marquée en hiver, surtout dans le Nord des Alpes et en Valais. Les nombres de jours de pluie ont également augmenté en hiver, mais moins fortement que les précipitations moyennes, alors qu'ils tendent à diminuer très légèrement durant les autres saisons. On en déduit que l'intensité moyenne des précipitations s'est accrue en Suisse durant le 20ème siècle en toutes saisons.

Developmental and Anatomical Constraints on Vertebrate Genome Evolution

Pendant ma thèse de doctorat, j'ai utilisé des espèces modèles, comme la souris et le poisson-zèbre, pour étudier les facteurs qui affectent l'évolution des gènes et leur expression. Plus précisément, j'ai montré que l'anatomie et le développement sont des facteurs clés à prendre en compte, car ils influencent la vitesse d'évolution de la séquence des gènes, l'impact sur eux de mutations (i.e. la délétion du gène est-elle létale ?), et leur tendance à se dupliquer. Où et quand il est exprimé impose à un gène certaines contraintes ou au contraire lui donne des opportunités d'évoluer. J'ai pu comparer ces tendances aux modèles classiques d'évolution de la morphologie, que l'on pensait auparavant refléter directement les contraintes s'appliquant sur le génome. Nous avons montré que les contraintes entre ces deux niveaux d'organisation ne peuvent pas être transférées simplement : il n'y a pas de lien direct entre la conservation du génotype et celle de phénotypes comme la morphologie. Ce travail a été possible grâce au développement d'outils bioinformatiques. Notamment, j'ai travaillé sur le développement de la base de données Bgee, qui a pour but de comparer l'expression des gènes entre différentes espèces de manière automatique et à large échelle. Cela implique une formalisation de l'anatomie, du développement et de concepts liés à l'homologie grâce à l'utilisation d'ontologies. Une intégration cohérente de données d'expression hétérogènes (puces à ADN, marqueurs de séquence exprimée, hybridations in situ) a aussi été nécessaire. Cette base de données est mise à jour régulièrement et disponible librement. Elle devrait contribuer à étendre les possibilités de comparaison de l'expression des gènes entre espèces pour des études d'évo-devo (évolution du développement) et de génomique. During my PhD, I used model species of vertebrates, such as mouse and zebrafish, to study factors affecting the evolution of genes and their expression. More precisely I have shown that anatomy and development are key factors to take into account, influencing the rate of gene sequence evolution, the impact of mutations (i.e. is the deletion of a gene lethal?), and the propensity of a gene to duplicate. Where and when genes are expressed imposes constraints, or on the contrary leaves them some opportunity to evolve. We analyzed these patterns in relation to classical models of morphological evolution in vertebrates, which were previously thought to directly reflect constraints on the genomes. We showed that the patterns of evolution at these two levels of organization do not translate smoothly: there is no direct link between the conservation of genotype and phenotypes such as morphology. This work was made possible by the development of bioinformatics tools. Notably, I worked on the development of the database Bgee, which aims at comparing gene expression between different species in an automated and large-scale way. This involves the formalization of anatomy, development, and concepts related to homology, through the use of ontologies. A coherent integration of heterogeneous expression data (microarray, expressed sequence tags, in situ hybridizations) is also required. This database is regularly updated and freely available. It should contribute to extend the possibilities for comparison of gene expression between species in evo-devo and genomics studies.

Chromosomal gene movements reflect the recent origin and biology of therian sex chromosomes

Mammalian sex chromosomes stem from ancestral autosomes and have substantially differentiated. It was shown that X-linked genes have generated duplicate intronless gene copies (retrogenes) on autosomes due to this differentiation. However, the precise driving forces for this out-of-X gene "movement" and its evolutionary onset are not known. Based on expression analyses of male germ-cell populations, we here substantiate and extend the hypothesis that autosomal retrogenes functionally compensate for the silencing of their X-linked housekeeping parental genes during, but also after, male meiotic sex chromosome inactivation (MSCI). Thus, sexually antagonistic forces have not played a major role for the selective fixation of X-derived gene copies in mammals. Our dating analyses reveal that although retrogenes were produced ever since the common mammalian ancestor, selectively driven retrogene export from the X only started later, on the placental mammal (eutherian) and marsupial (metatherian) lineages, respectively. Together, these observations suggest that chromosome-wide MSCI emerged close to the eutherian-marsupial split approximately 180 million years ago. Given that MSCI probably reflects the spread of the recombination barrier between the X and Y, crucial for their differentiation, our data imply that these chromosomes became more widely differentiated only late in the therian ancestor, well after the divergence of the monotreme lineage. Thus, our study also provides strong independent support for the recent notion that our sex chromosomes emerged, not in the common ancestor of all mammals, but rather in the therian ancestor, and therefore are much younger than previously thought

The evolution of sex determination

Sexual reproduction is a fundamental aspect of life. Sex-determination mechanisms are responsible for the sexual fate and development of sexual characteristics in an organism, be it a unicellular alga, a plant, or an animal. Surprisingly, sex-determination mechanisms are not evolutionarily conserved but are bewilderingly diverse and appear to have had rapid turnover rates during evolution. Evolutionary biologists continue to seek a solution to this conundrum. What drives the surprising dynamics of such a fundamental process that always leads to the same outcome: two sex types, male and female? The answer is complex but the ongoing genomic revolution has already greatly increased our knowledge of sex-determination systems and sex chromosomes in recent years. This novel book presents and synthesizes our current understanding, and clearly shows that sex-determination evolution will remain a dynamic field of future research. The Evolution of Sex Determination is an advanced, research level text suitable for graduate students and researchers in genetics, developmental biology, and evolution.

Evolution of vitellogenin genes: comparative analysis of the nucleotide sequences downstream of the transcription initiation site of four Xenopus laevis and one chicken gene.

Electron microscopic analysis of heteroduplexes between the most distantly related Xenopus vitellogenin genes (A genes X B genes) has revealed the distribution of homologous regions that have been preferentially conserved after the duplication events that gave rise to the multigene family in Xenopus laevis. DNA sequence analysis was limited to the region downstream of the transcription initiation site of the Xenopus genes A1, B1 and B2 and a comparison with the Xenopus A2 and the major chicken vitellogenin gene is presented. Within the coding regions of the first three exons, nucleotide substitutions resulting in amino acid changes accumulate at a rate similar to that observed in globin genes. This suggests that the duplication event which led to the formation of the A and B ancestral genes in Xenopus laevis occurred about 150 million years ago. Homologous exons of the A1-A2 and B1-B2 gene pairs, which formed about 30 million years ago, show a quite similar sequence divergence. In contrast, A1-A2 homologous introns seem to have evolved much faster than their B1-B2 counterparts.

Accepting Methadone: The Evolution of an Institutional Decision

This is a study of organisational decision making among senior civil servants in the Department of Health (DOH) in relation to the acceptance of methadone maintenance as a valid treatment modality for opiate misuse in Ireland. A qualitative strategy was adopted with an emergent design and grounded theory perspective. The data was collected using a naturalistic mode of inquiry and comprised of documentary analysis and semi-structured interviews. The aspects of decision making chosen for the study were: 1. Identifying the actors involved considering the heretofore dominant 'corporation sole' culture of the Irish public administration. 2. Identifying two (out of the myriad) processes involved in decision making. 3. Identifying what theoretical model(s) of decision making most closely approximates to this case. The findings were as follows: 1. Actors involved at all levels of the decision making could be identified, albeit with some difficulty. This as a result of the strategic management initiative. Previously, it may not have been possible. Stages or phases could not, in this case, be readily identified though limitations of this study may prove significant. 2. Both the processes selected in decision-making in this case were confirmed. Personal and professional support provided by peers and seniors is crucial to decision making. Decision making does occur within networks: these tend to be those that are formally appointed rather than informal ones. 3. The model closest to that of this case was that of incremental decision making within network settings.This resource was contributed by The National Documentation Centre on Drug Use.