The genetics of speciation: Insights from Fisher's geometric model.

Research in speciation genetics has uncovered many robust patterns in intrinsic reproductive isolation, and fitness landscape models have been useful in interpreting these patterns. Here, we examine fitness landscapes based on Fisher's geometric model. Such landscapes are analogous to models of optimizing selection acting on quantitative traits, and have been widely used to study adaptation and the distribution of mutational effects. We show that, with a few modifications, Fisher's model can generate all of the major findings of introgression studies (including "speciation genes" with strong deleterious effects, complex epistasis and asymmetry), and the major patterns in overall hybrid fitnesses (including Haldane's Rule, the speciation clock, heterosis, hybrid breakdown, and male-female asymmetry in the F1). We compare our approach to alternative modeling frameworks that assign fitnesses to genotypes by identifying combinations of incompatible alleles. In some cases, the predictions are importantly different. For example, Fisher's model can explain conflicting empirical results about the rate at which incompatibilities accumulate with genetic divergence. In other cases, the predictions are identical. For example, the quality of reproductive isolation is little affected by the manner in which populations diverge.Agence Nationale de la Recherche (HYSEA project, ANR-12-BSV7- 0011)This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/evo.1296

An economic evaluation of irbesartan in the treatment of patients with type 2 diabetes, hypertension and nephropathy: cost-effectiveness of Irbesartan in Diabetic Nephropathy Trial (IDNT) in the Belgian and French settings

Background. In the Irbesartan in Diabetic Nephropathy Trial (IDNT), treatment with irbesartan demonstrated 23 and 20% reductions in the combined endpoint of doubling of serum creatinine (DSC), end-stage renal disease (ESRD) or death in patients with hypertension, type 2 diabetes and overt nephropathy compared with amlodipine and control, respectively. A simulation model was developed to project long-term cost consequences of the IDNT in Belgium and France. Methods. A Markov model simulated progression from nephropathy to DSC, ESRD and death in patients with hypertension, type 2 diabetes and overt nephropathy. Treatment-specific probabilities were derived from IDNT. Country-specific ESRD-related data were retrieved from published sources. Delay in onset of ESRD, life expectancy and mean lifetime costs were calculated for patients with a baseline age of 59 years. Future costs were discounted at 3% per annum (p.a.), and clinical benefits were discounted at 0 and 3% p.a.. Extensive sensitivity analyses were performed. Results. Onset of ESRD was delayed with irbesartan by 1.41 and 1.35 years vs amlodipine and control, respectively. When a 10-year time horizon was considered, delay in ESRD onset led to anticipated improvements in life expectancy of 0.13 years vs amlodipine and 0.26 years vs control. Irbesartan was associated with cost savings of €14 949 and €9205/patient in Belgium, and €20 128 and €13 337 in France, vs amlodipine and control, respectively. The results were robust under a wide range of plausible assumptions. Conclusions. Treating patients with hypertension, type 2 diabetes and overt nephropathy using irbesartan was both cost- and life-saving compared with amlodipine and contro

Cost-effectiveness of irbesartan in diabetic nephropathy: a systematic review of published studies

Background. To review published studies on the cost-effectiveness of the use of irbesartan for treatment of advance overt nephropathy in patients with type 2 diabetes and hypertension. Methods. Articles were identified based on a search of the PubMed databases using the keywords ‘irbesartan', ‘ESRD', ‘cost-effectiveness', ‘nephropathy' and ‘costs', and by personal communication with the authors. Only studies published in the last 10 years were included. All costs data from the cost-effectiveness studies were inflated to 2003 Euros using published governmental conversion tables. Results. Seven published studies were identified, spanning the following country settings: the US, Belgium and France, Germany, Hungary, Italy, Spain, and the UK. In each, the same pharmacoeconomic model was adapted using country-specific data to project and evaluate the clinical and cost outcomes of the treatment arms of the Irbesartan in Diabetic Nephropathy Trial (IDNT) (irbesartan, amlodipine or standard blood pressure control). Mean time to onset of ESRD was 8.23 years for irbesartan, 6.82 years for amlodipine and 6.88 years for the control (values were the same for Belgium, France, Germany, Hungary, Italy and Spain as transition probabilities for progression to ESRD were all derived from the IDNT). Mean cumulative incidence of ESRD was 36% with irbesartan, 49% with amlodipine and 45% with control treatment. Treatment with irbesartan was projected to improve life expectancy compared to both amlodipine and control in all seven published studies. Analysis of total lifetime costs showed that irbesartan treatment was cost saving compared to the other two treatment regimens, due to the associated reduction in ESRD cases. Cost savings with irbesartan became evident very early; after 2-3 years of treatment in most settings. Conclusions. Modelling studies based on the IDNT published to date suggest that irbesartan treatment in patients with type 2 diabetes, hypertension and advanced nephropathy is both life- and cost-saving compared to amlodipine or contro

Diversification rates and phenotypic evolution in venomous snakes (Elapidae)

Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.The relationship between rates of diversification and of body size change (a common proxy for phenotypic evolution) was investigated across Elapidae, the largest radiation of highly venomous snakes. Time-calibrated phylogenetic trees for 175 species of elapids (more than 50% of known taxa) were constructed using seven mitochondrial and nuclear genes. Analyses using these trees revealed no evidence for a link between speciation rates and changes in body size. Two clades (Hydrophis, Micrurus) show anomalously high rates of diversification within Elapidae, yet exhibit rates of body size evolution almost identical to the general elapid ‘background’ rate. Although correlations between speciation rates and rates of body size change exist in certain groups (e.g. ray-finned fishes, passerine birds), the two processes appear to be uncoupled in elapid snakes. There is also no detectable shift in diversification dynamics associated with the colonization of Australasia, which is surprising given that elapids appear to be the first clade of venomous snakes to reach the continent

The Pseudoautosomal Regions of the U/V Sex Chromosomes of the Brown Alga Ectocarpus Exhibit Unusual Features

International audienceThe recombining regions of sex chromosomes (pseudoautosomal regions, PARs) are predicted to exhibit unusual features due to their being genetically linked to the nonrecombining, sex-determining region. This phenomenon is expected to occur in both diploid (XY, ZW) and haploid (UV) sexual systems, with slightly different consequences for UV sexual systems because of the absence of masking during the haploid phase (when sex is expressed) and because there is no homozygous sex in these systems. Despite a considerable amount of theoretical work on PAR genetics and evolution, these genomic regions have remained poorly characterized empirically. We show here that although the PARs of the U/V sex chromosomes of the brown alga Ectocarpus recombine at a similar rate to autosomal regions of the genome, they exhibit many genomic features typical of nonrecombining regions. The PARs were enriched in clusters of genes that are preferentially, and often exclusively, expressed during the sporophyte generation of the life cycle, and many of these genes appear to have evolved since the Ectocarpales diverged from other brown algal lineages. A modeling-based approach was used to investigate possible evolutionary mechanisms underlying this enrichment in sporophyte-biased genes. Our results are consistent with the evolution of the PAR in haploid systems being influenced by differential selection pressures in males and females acting on alleles that are advantageous during the sporophyte generation of the life cycle

Bronchopulmonary Dysplasia

Hospitalizations for respiratory syncytial virus bronchioliti

Cross-sectional study of morbidity, morbidity-associated factors and cost of treatment in Ngaoundere, Cameroon, with implications for health policy in developing countries and development assistance policy

BACKGROUND: In a population-based epidemiological study in Ngaoundere, Cameroon, we studied cross-sectional child morbidity and the cost of necessary investigation and treatment. METHODS: Three teams of two to three health workers visited haphazardly selected households in all major housing quarters. We asked permission to enter for a health survey. Children with cough, fever or weight loss as well as sick adults were offered free-of-charge local hospital examination and treatment. RESULTS: From 177 households with 1777 persons, 51 (2.9%) persons were referred. Thirty-five of them had an undiagnosed disease threatening individual health and in many cases also public health. Seven were hospitalised, including three adults with tuberculosis. Malnutrition was diagnosed in nine small children. Four patients had AIDS, seven had malaria. Average total cost for ambulant patients was 15 USD, for hospitalised patients 110 USD. In the households, almost half of the women 16–50 years of age had no schooling. Two per cent of women and nine per cent of men were daily smokers. Coughing children were more likely than non-coughing children to live in a household with at least one smoker (OR = 3.58, 95% CI 1.72 to 7.46), and they generally lived in more poor households (P = 0.018). Twelve of 16 children with weight loss were referred from households with a high poverty score. CONCLUSIONS: Adult smoking and poverty affect children's health. The cost of hospitalisation or long-lasting therapy is beyond the means of most ordinary families. Diseases with severe consequences for public health, like tuberculosis, AIDS and malaria should have national programs with free, decentralised examination and treatment. Access to generic drugs is important. A major educational effort is needed to improve public health

Het wonder van de wortelknobbelaaltjes: de unieke moleculaire interacties tussen een obligate parasiet en haar waardplanten

Wortelknobbelaaltjes (Meloidogyne spp.) behoren tot de meest geavanceerde parasieten onder de ziekteverwekkers van planten. Ze onderscheiden zich van veel obligaat biotrofe pathogenen door hun brede waardplantenreeks. Eenmaal gevestigd in het wortelstelsel onttrekken ze vervolgens gedurende enkele weken voedingsstoffen aan de plant via speciaal daarvoor aangelegde voedingsstructuren - de reuzecellen. Ze kunnen zich al naar gelang de omstandigheden dat vereisen, op allerlei manieren voortplanten.De laatste jaren zijn door de toepassing van moleculaire technieken een aantal bijzondere ontdekkingen gedaan die betrekking hebben op deze aanpassingen. Ingegaan wordt op de ontwikkelingen met nadruk op de genen, die betrokken zijn bij de parasitaire levensstijl van de nematod

RACE-OC Project: Rotation and variability in the open cluster M11 (NGC6705)

Rotation and magnetic activity are intimately linked in main-sequence stars of G or later spectral types. The presence and level of magnetic activity depend on stellar rotation, and rotation itself is strongly influenced by strength and topology of the magnetic fields. Open clusters represent especially useful targets to investigate the rotation/activity/age connection. The open cluster M11 has been studied as a part of the RACE-OC project (Rotation and ACtivity Evolution in Open Clusters), which is aimed at exploring the evolution of rotation and magnetic activity in the late-type members of open clusters with different ages. Photometric observations of the open cluster M11 were carried out in June 2004 using LOAO 1m telescope. The rotation periods of the cluster members are determined by Fourier analysis of photometric data time series. We further investigated the relations between the surface activity, characterized by the light curve amplitude, and rotation. We have discovered a total of 75 periodic variables in the M11 FoV, of which 38 are candidate cluster members. Specifically, among cluster members we discovered 6 early-type, 2 eclipsing binaries and 30 bona-fide single periodic late-type variables. Considering the rotation periods of 16 G-type members of the almost coeval 200-Myr M34 cluster, we could determine the rotation period distribution from a more numerous sample of 46 single G stars at an age of about 200-230 Myr and determine a median rotation period P=4.8d. A comparison with the younger M35 cluster (~150 Myr) and with the older M37 cluster (~550 Myr) shows that G stars rotate slower than younger M35 stars and faster than older M37 stars. The measured variation of the median rotation period is consistent with the scenario of rotational braking of main-sequence spotted stars as they age.Comment: Accepted by Astronomy and Astrophysics on Dec 15, 200

Altruism can proliferate through group/kin selection despite high random gene flow

The ways in which natural selection can allow the proliferation of cooperative behavior have long been seen as a central problem in evolutionary biology. Most of the literature has focused on interactions between pairs of individuals and on linear public goods games. This emphasis led to the conclusion that even modest levels of migration would pose a serious problem to the spread of altruism in group structured populations. Here we challenge this conclusion, by analyzing evolution in a framework which allows for complex group interactions and random migration among groups. We conclude that contingent forms of strong altruism can spread when rare under realistic group sizes and levels of migration. Our analysis combines group-centric and gene-centric perspectives, allows for arbitrary strength of selection, and leads to extensions of Hamilton's rule for the spread of altruistic alleles, applicable under broad conditions.Comment: 5 pages, 2 figures. Supplementary material with 50 pages and 26 figure