Molecular phylogenetics of soricid shrews (Mammalia) based on mitochondrial cytochrome b gene sequences: with special reference to the Soricinae

Molecular phylogeny of soricid shrews (Soricidae, Eulipotyphla, Mammalia) based on 1140 bp mitochondrial cytochrome b gene (cytb) sequences was inferred by the maximum likelihood (ML) method. All 13 genera of extant Soricinae and two genera of Crocidurinae were included in the analyses. Anourosorex was phylogenetically distant from the main groupings within Soricinae and Crocidurinae in the ML tree. Thus, it could not be determined to which subfamily Anourosorex should be assigned: Soricinae, Crocidurinae or a new subfamily. Soricinae (excluding Anourosorex) should be divided into four tribes: Neomyini, Notiosoricini, Soricini and Blarinini. However, monophyly of Blarinini was not robust in the present data set. Also, branching orders among tribes of Soricinae and those among genera of Neomyini could not be determined because of insufficient phylogenetic information of the cytb sequences. For water shrews of Neomyini (Chimarrogale, Nectogale and Neomys), monophyly of Neomys and the Chimarrogale-Nectogale group could not be verified, which implies the possibility of multiple origins for the semi-aquatic mode of living among taxa within Neomyini. Episoriculus may contain several separate genera. Blarinella was included in Blarinini not Soricini, based on the cytb sequences, but the confidence level was rather low; hence more phylogenetic information is needed to determine its phylogenetic position. Furthermore, some specific problems of taxonomy of soricid shrews were clarified, for example phylogeny of local populations of Notiosorex crawfordi, Chimarrogale himalayica and Crocidura attenuata.

EADock: docking of small molecules into protein active sites with a multiobjective evolutionary optimization.

In recent years, protein-ligand docking has become a powerful tool for drug development. Although several approaches suitable for high throughput screening are available, there is a need for methods able to identify binding modes with high accuracy. This accuracy is essential to reliably compute the binding free energy of the ligand. Such methods are needed when the binding mode of lead compounds is not determined experimentally but is needed for structure-based lead optimization. We present here a new docking software, called EADock, that aims at this goal. It uses an hybrid evolutionary algorithm with two fitness functions, in combination with a sophisticated management of the diversity. EADock is interfaced with the CHARMM package for energy calculations and coordinate handling. A validation was carried out on 37 crystallized protein-ligand complexes featuring 11 different proteins. The search space was defined as a sphere of 15 A around the center of mass of the ligand position in the crystal structure, and on the contrary to other benchmarks, our algorithm was fed with optimized ligand positions up to 10 A root mean square deviation (RMSD) from the crystal structure, excluding the latter. This validation illustrates the efficiency of our sampling strategy, as correct binding modes, defined by a RMSD to the crystal structure lower than 2 A, were identified and ranked first for 68% of the complexes. The success rate increases to 78% when considering the five best ranked clusters, and 92% when all clusters present in the last generation are taken into account. Most failures could be explained by the presence of crystal contacts in the experimental structure. Finally, the ability of EADock to accurately predict binding modes on a real application was illustrated by the successful docking of the RGD cyclic pentapeptide on the alphaVbeta3 integrin, starting far away from the binding pocket.

Is the function of the serratus anterior muscle disturbed following division during a standard thoracotomy?

In a prospective study the functional results after dissection or preservation of the serratus anterior muscle in the postero-lateral standard thoracotomy were evaluated. In 14 patients of our clinic with dissection and suture and in 14 patients with preservation of the serratus muscle the muscle function was assessed and compared preoperatively, within the first two post-operative weeks, and three months after the operation by the same physiotherapists. The two groups were blinded in regard to age, original disease, and mode of intervention. We compared the wing position of the scapula in the sitting position and the positioning of the scapula at fixation of the shoulder joint in the sitting and in the supine position. Using a four-grade function assessment scheme, both groups obtained the same functional results. There was no seroma in either group. After 2.8 (2.5 to 3.0) years all the surviving patients described symmetric functional conditions. We therefore conclude that in order to achieve a better view of the operative field the serratus muscle may be dissected close to the origin if it is then readapted.

Physiologie des sexués femelles de fourmis (Hymenoptera; Formicidae) en relation avec le mode de fondation

A study was undertaken to determine if there was a relation between the mode of colony founding in ants and the physiology of the new queens produced, in which mature gynes of 24 ant species were examined. Gynes of species utilizing independent colony founding had a far higher relative fat content (X±SD; 54±6%)(g fat/g dry weight) than gynes of species employing dependent colony founding(19±8%). Dimorphism between queens and workers was significantly higher in species employing independent colony founding. Thus independent colony founding not only results in production of queens with a relatively higher fat content and therefore with a higher energy content per g, but also results in the production of larger queens (in comparison with worker size). Of species employing independent colony founding, 80% were monogynous, whereas only 11% of the species employing dependent colony founding were monogynous. These results are discussed with regard to the social structure and life-history of ant species.

The evolution and consequences of sex-specific reproductive variance.

Natural selection favors alleles that increase the number of offspring produced by their carriers. But in a world that is inherently uncertain within generations, selection also favors alleles that reduce the variance in the number of offspring produced. If previous studies have established this principle, they have largely ignored fundamental aspects of sexual reproduction and therefore how selection on sex-specific reproductive variance operates. To study the evolution and consequences of sex-specific reproductive variance, we present a population-genetic model of phenotypic evolution in a dioecious population that incorporates previously neglected components of reproductive variance. First, we derive the probability of fixation for mutations that affect male and/or female reproductive phenotypes under sex-specific selection. We find that even in the simplest scenarios, the direction of selection is altered when reproductive variance is taken into account. In particular, previously unaccounted for covariances between the reproductive outputs of different individuals are expected to play a significant role in determining the direction of selection. Then, the probability of fixation is used to develop a stochastic model of joint male and female phenotypic evolution. We find that sex-specific reproductive variance can be responsible for changes in the course of long-term evolution. Finally, the model is applied to an example of parental-care evolution. Overall, our model allows for the evolutionary analysis of social traits in finite and dioecious populations, where interactions can occur within and between sexes under a realistic scenario of reproduction.

Molecular evidence of interhuman transmission in an outbreak of Pneumocystis jirovecii pneumonia among renal transplant recipients.

S. Gianella, L. Haeberli, B. Joos, B. Ledergerber, R.P. Wüthrich, R. Weber, H. Kuster, P.M. Hauser, T. Fehr, N.J. Mueller. Molecular evidence of interhuman transmission in an outbreak of Pneumocystis jirovecii pneumonia among renal transplant recipients. Transpl Infect Dis 2009. All rights reserved Abstract: Pneumocystis jirovecii pneumonia (PCP) remains an important cause of morbidity and mortality in immunocompromised individuals. The epidemiology and pathogenesis of this infection are poorly understood, and the exact mode of transmission remains unclear. Recent studies reported clusters of PCP among immunocompromised patients, raising the suspicion of interhuman transmission. An unexpected increase of the incidence of PCP cases in our nephrology outpatient clinic prompted us to conduct a detailed analysis. Genotyping of 7 available specimens obtained from renal transplant recipients was performed using multi-locus DNA sequence typing (MLST). Fragments of 4 variable regions of the P. jirovecii genome (ITS1, 26S, mt26S, beta-tubulin) were sequenced and compared with those of 4 independent control patients. MLST analysis revealed identical sequences of the 4 regions among all 7 renal allograft recipients with available samples, indicating an infection with the same P. jirovecii genotype. We observed that all but 1 of the 19 PCP-infected transplant recipients had at least 1 concomitant visit with another PCP-infected patient within a common waiting area. This study provides evidence that nosocomial transmission among immunocompromised patients may have occurred in our nephrology outpatient clinic. Our findings have epidemiological implications and suggest that prolonged chemoprophylaxis for PCP may be warranted in an era of more intense immunosuppression.

Additive effects of ectoparasites over reproductive attempts in the long-lived Alpine swift

1. Parasitism is a non-negligible cost of reproduction in wild organisms, and hosts are selected to partition resources optimally between current and future reproduction. While parents can compensate for the cost of parasitism by increasing their current reproductive investment, such change in resource allocation is expected to carry-over costs on future reproduction. 2. Life history theory predicts that because long-lived organisms have a high residual reproductive value, they should be more reluctant to increase parental effort in response to parasites. Also, when rearing successive infested broods, the cost of parasitism can cumulate over the years and hence be exacerbated by past infestations. 3. We tested these two predictions in the alpine swift Apus melba, a long-lived colonial bird that is infested intensely by the nest-based blood sucking louse-fly Crataerina melbae. For this purpose, we manipulated ectoparasite load over 3 consecutive years and measured reproductive parameters in successive breeding attempts of adults assigned randomly to 'parasitized' and 'deparasitized' treatments. 4. In current reproduction, fathers of experimentally parasitized broods produced a similar number of offspring as fathers from the deparasitized treatment, but the rearing period was prolonged by 4 days. Fathers that were assigned to the parasitized treatment in year x produced significantly fewer fledglings the following year x + 1 than those of the deparasitized treatment. The number of young produced by fathers in year x + 1 was correlated negatively with the number of days they cared for their brood in the previous year x. We also found a significant interaction between treatments performed over 2 successive years, with fathers of parasitized broods suffering a larger fitness loss if in the past they had already cared for a parasitized brood rather than for a deparasitized one. Similar effects of parasitism, although partly non-significant (0.05 < P-values > 0.10), were found in mothers. 5. Altogether, our results show that parasites can modify resource allocation between current and future reproduction in long-lived hosts, and that the cost of parasitism can cumulate over the years. It emphasizes the fact that effects of parasites can depend on past infestations and become apparent in future reproduction only.

General unknown screening procedure for the characterization of human drug metabolites: application to loratadine phase I metabolism.

This article describes the application of a recently developed general unknown screening (GUS) strategy based on LC coupled to a hybrid linear IT-triple quadrupole mass spectrometer (LC-MS/MS-LIT) for the simultaneous detection and identification of drug metabolites following in vitro incubation with human liver microsomes. The histamine H1 receptor antagonist loratadine was chosen as a model compound to demonstrate the interest of such approach, because of its previously described complex and extensive metabolism. Detection and mass spectral characterization were based on data-dependent acquisition, switching between a survey scan acquired in the ion-trapping Q3 scan mode with dynamic subtraction of background noise, and a dependent scan in the ion-trapping product ion scan mode of automatically selected parent ions. In addition, the MS(3) mode was used in a second step to confirm the structure of a few fragment ions. The sensitivity of the ion-trapping modes combined with the selectivity of the triple quadrupole modes allowed, with only one injection, the detection and identification of 17 phase I metabolites of loratadine. The GUS procedure used in this study may be applicable as a generic technique for the characterization of drug metabolites after in vitro incubation, as well as probably in vivo experiments.

Effects of season, sex and body size on the feeding ecology of turtle-headed seasnakes (Emydocephalus annulatus) on IndoPacific inshore coral reefs

In terrestrial snakes, many cases of intraspecific shifts in dietary habits as a function of predator sex and body size are driven by gape-limitation - and hence, are most common in species that feed on relatively large prey, and exhibit a wide body-size range. Our data on seasnakes reveal an alternative mechanism for intraspecific niche partitioning, based on sex-specific seasonal anorexia induced by reproductive activities. Turtle-headed seasnakes (Emydocephalus annulatus) on coral reefs in the New Caledonian Lagoon feed entirely on the eggs of demersal-spawning fishes. DNA sequence data (cytochrome b gene) on eggs that we palpated from stomachs of 37 snakes showed that despite this ontogenetic-stage specialization, the prey come from a taxonomically diverse array of species including damselfish (41% of samples, at least 5 species), blennies (41%, 4 species) and gobies (19%, 5 species). The composition of snake diets shifted seasonally (with damselfish dominating in winter but not summer), presumably reflecting seasonality of fish reproduction. That seasonal shift affects male and female snakes differently, because reproduction is incompatible with foraging. Adult female seasnakes ceased feeding when they became heavily distended with developing embryos in late summer, and males ceased feeding while they were mate-searching in winter. The sex divergence in foraging habits may be amplified by sexual size dimorphism; females grow larger than males, and larger snakes (of both sexes) feed more on damselfish (which often lay their eggs in exposed sites) than on blennies and gobies (whose eggs are hidden within narrow crevices). Specific features of reproductive biology of coral-reef fish (seasonality and nest type) have generated intraspecific niche partitioning in these seasnakes, by mechanisms different from those that apply to terrestrial snakes.

Risk Assessement of Herbicide Mixtures

Lake Geneva is one of the largest European lakes with a surface area of 580 km2. Its catchment area covers 7400 km2, of which approximately 20% is arable land. Monitoring campaigns have been carried out in 2004 and 2005 to determine the contamination of the lake by pesticides. The results highlight the widespread presence of herbicides in water, the measured concentrations for most substances remaining constant in 2004 and 2005. However, for some individual herbicides the concentrations increased drastically (e.g., the herbicide foramsulfuron). We assessed the environmental risk of the herbicides detected in the lake using water quality criteria recently determined for the Swiss environmental protection agency. Furthermore, we assessed the risk of herbicide mixtures, grouped based upon their mode of action. Generally, the risk estimated for all single substances is low, except for some sulfonylurea compounds. For these substances, the measured concentrations are higher than the predicted no-effect concentration. Impact on the flora of the lake can therefore not be excluded. When mixtures of pesticides with similar mode of action are taken into account, the risk remains lower than the mixture water quality criteria for all groups, but can reach as high as one third of this quality criteria. A further step would therefore be to assess the risk of the total pesticide mixture, including similar and dissimilar modes of action.

Effects of cognitive abilities on metapopulation connectivity

Connectivity among demes in a metapopulation depends on both the landscape's and the focal organism's properties (including its mobility and cognitive abilities). Using individual-based simulations, we contrast the consequences of three different cognitive strategies on several measures of metapopulation connectivity. Model animals search suitable habitat patches while dispersing through a model landscape made of cells varying in size, shape, attractiveness and friction. In the blind strategy, the next cell is chosen randomly among the adjacent ones. In the near-sighted strategy, the choice depends on the relative attractiveness of these adjacent cells. In the far-sighted strategy, animals may additionally target suitable patches that appear within their perceptual range. Simulations show that the blind strategy provides the best overall connectivity, and results in balanced dispersal. The near-sighted strategy traps animals into corridors that reduce the number of potential targets, thereby fragmenting metapopulations in several local clusters of demes, and inducing sink-source dynamics. This sort of local trapping is somewhat prevented in the far-sighted strategy. The colonization success of strategies depends highly on initial energy reserves: blind does best when energy is high, near-sighted wins at intermediate levels, and far-sighted outcompetes its rivals at low energy reserves. We also expect strong effects in terms of metapopulation genetics: the blind strategy generates a migrant-pool mode of dispersal that should erase local structures. By contrast, near- and far-sighted strategies generate a propagule-pool mode of dispersal and source-sink behavior that should boost structures (high genetic variance among- and low variance within local clusters of demes), particularly if metapopulation dynamics is also affected by extinction-colonization processes. Our results thus point to important effects of the cognitive ability of dispersers on the connectivity, dynamics and genetics of metapopulations.

Indications, perspectives et limites de la stimulation électrique épidurale en cas d'artériopathie périphérique ou coronarienne [Indications, limits and future of epidural spinal cord electrical stimulation for coronary and peripheral artery disease]

The electrical stimulation of the dorsal columns of the spinal cord exerts a dual analgesic and vasodilatory effect on ischemic tissues. It is increasingly considered a valuable method to treat severe and otherwise intractable coronary and peripheral artery disease. The quality of the results depends from both a strict selection of the patients by vascular specialists and the frequency and quality of the follow-up controls. However the indications, limits, mode of action and results of spinal cord stimulation are still poorly understood. This article, based on a personal experience of 164 implantations for peripheral and coronary artery disease, aims to draw attention to this technique and to provide information on recent and future developments.

Assessing the epidemiology and pattern of care of colorectal cancer in Valais, Switzerland

Background: The Valais's cancer registry (RVsT) of the Observatoire valaisan de le santé (OVS) and the department of oncology of Valais's Hospital conducted a study on the epidemiology and pattern of care of colorectal cancer in Valais. Colorectal cancer is the third cause of death by cancer in Switzerland with about 1600 deaths per year. It is the third most frequent cancer for males and the second most frequent for females in Valais. The number of new colorectal cancer cases (average per year) increased between 1989 and 2009 for males as well as for females in Valais. The number of colorectal cancer death cases (average per year) slightly increased between 1989 and 2009 for males as well as for females in Valais. Age-standardized rates of incidence were stable for males and females in Valais and in Switzerland between 1989 and 2009, while age-standardized rates of mortality decreased for males and females in Valais and Switzerland. Results: 774 cases were recorded (59% males). Median age at diagnosis was 70 years old. Most of cancers were invasive (79%) and the main localization was the colon (71%). The most frequent mode of detection was a consultation for non emergency symptoms (75%), but almost 10% of patients consulted in emergency. 82% of patients were treated within 30 days from diagnosis. 90% of the patients were treated by surgery alone or with combined treatment. The first treatment was surgery, including endoscopic resection in 86% of the cases. The treatment was different according to the localization and the stage of the cancer. Survival rate was 95% at 30 days and 79% at one year. The survival was dependent on the stage and the age at diagnosis. Cox model shows an association between mortality and age (better survival for young people) and between mortality and stage (better survival for the lower stages). Methods: RVsT collects information on all cancer cases since 1989 for people registered in the communes of Valais. RVsT has an authorization to collect non anonymized data. All new incident cancers are coded according to the International Classification of Diseases for Oncology (ICD-O-3) and the stages are coded according to the TNM classification. We studied all cases of in situ and invasive colorectal cancers diagnosed between 2006 and 2009 and registered routinely at the RVsT. We checked for data completeness and if necessary sent questionnaires to avoid missing data. A distance of 15 cm has been chosen to delimitate the colon (sigmoid) and the rectal cancers. We made an active follow-up for vital status to have a valid survival analysis. We analyzed the characteristics of the tumors according to age, sex, localization and stage with stata 9 software. Kaplan-Meier curves were generated and Cox model were fitted to analyze survival. Conclusion: The characteristics of patients and tumors and the one year survival were similar to those observed in Switzerland and some European countries. Patterns of care were close to those recommended in guidelines. Routine data recorded in a cancer registry can be used, not only to provide general statistics, but also to help clinicians assess local practices.

Integrating nuclear receptor mobility in models of gene regulation.

The mode of action of nuclear receptors in living cells is an actively investigated field but much remains hypothetical due to the lack, until recently, of methods allowing the assessment of molecular mechanisms in vivo. However, these last years, the development of fluorescence microscopy methods has allowed initiating the dissection of the molecular mechanisms underlying gene regulation by nuclear receptors directly in living cells or organisms. Following our analyses on peroxisome proliferator activated receptors (PPARs) in living cells, we discuss here the different models arising from the use of these tools, that attempt to link mobility, DNA binding or chromatin interaction, and transcriptional activity.

Systematic assessment of factors influencing preferences of crohn's disease patients in selecting an anti-tumor necrosis factor agent (CHOOSE TNF TRIAL).

BACKGROUND: Infliximab (IFX), adalimumab (ADA), and certolizumab pegol (CZP) have similar efficacy in induction and maintenance of clinical remission in Crohn's disease (CD). Given the comparable nature of these drugs, patient preferences may influence the choice of the product. We aimed to identify factors that may contribute to CD patients' decision in selecting one anti-tumor necrosis factor (TNF) agent over the others. METHODS: A prospective survey was performed among anti-TNF-naïve CD patients. Prior to completion of a questionnaire, patients were provided with a written description of the three anti-TNF agents, focusing on indications, mode of administration, side effects, and scientific evidence of efficacy and safety for each drug. RESULTS: One hundred patients (47 females, mean age 45 ± 16 years, range 19-81) with an ileal, colonic, or ileocolonic (33%, 40%, and 27%, respectively) disease location completed the questionnaire. Based on the information provided, 36% of patients preferred ADA, 28% CZP, and 25% IFX, whereas 11% were undecided. The patients' decision in selecting a specific anti-TNF drug was influenced by the following factors: ease of use (69%), time required for therapy (34%), time interval between application of the drug (31%), scientific evidence for efficacy (19%), and fear of syringes (10%). CONCLUSIONS: The majority of patients preferred anti-TNF medications that were administered by subcutaneous injection rather than by intravenous infusion. Ease of use and time required for therapy were two major factors influencing the patients' selection of a specific anti-TNF drug. Patients' individual preferences should be taken into account when prescribing anti-TNF drugs. (Inflamm Bowel Dis 2012).