Individual reproductive success and effective population size in the greater white-toothed shrew Crocidura russula.

In order to investigate the determinants of effective population size in the socially monogamous Crocidura russula, the reproductive output of 44 individuals was estimated through genetic assignment methods. The individual variance in breeding success turned out to be surprisingly high, mostly because the males were markedly less monogamous than expected from previous behavioural data. Males paired simultaneously with up to four females and polygynous males had significantly more offspring than monogamous ones. The variance in female reproductive success also exceeded that of a Poisson distribution (though to a lesser extent), partly because females paired with multiply mated males weaned significantly more offspring. Polyandry also occurred occasionally, but only sequentially (i.e. without multiple paternity of litters). Estimates of the effective to census size ratio were ca. 0.60, which excluded the mating system as a potential explanation for the high genetic variance found in this shrew's populations. Our data suggest that gene flow from the neighbourhood (up to one-third of the total recruitment) is the most likely cause of the high levels of genetic diversity observed in this shrew's subpopulations.

Assessing ageing of individual T lymphocytes: Mission impossible?

Effector T lymphocytes are the progeny of a limited number of antigen- specific precursor cells and it has been estimated that clonotypic human T cells may expand million fold on their way reaching high cell numbers that are sufficient for immune protection. Moreover, memory T cell responses are characterized by repetitive expansion of antigen-specific T cell clonotypes, and limitations in the proliferative capacity could lead to immune senescence. Because telomeres progressively shorten as a function of cell division, telomere length is a powerful indicator of the replicative in vivo history of human T lymphocytes. In this review, we summarize observations made over the last decade on telomere length dynamics of well-defined T cell populations derived from healthy donors and patients with infectious disease or cancer. We focus on T cell differentiation, T cell ageing, and natural and vaccine induced immune responses. We also discuss the scientific evidence for in vivo replicative senescence of antigen-specific T cells, and evaluate the available methods for measuring telomere lengths and telomerase activity, and their potential and limitations to increase our understanding of T cell physiology. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

Functional architecture of olfactory ionotropic glutamate receptors.

Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate chemical communication between neurons at synapses. A variant iGluR subfamily, the Ionotropic Receptors (IRs), was recently proposed to detect environmental volatile chemicals in olfactory cilia. Here, we elucidate how these peripheral chemosensors have evolved mechanistically from their iGluR ancestors. Using a Drosophila model, we demonstrate that IRs act in combinations of up to three subunits, comprising individual odor-specific receptors and one or two broadly expressed coreceptors. Heteromeric IR complex formation is necessary and sufficient for trafficking to cilia and mediating odor-evoked electrophysiological responses in vivo and in vitro. IRs display heterogeneous ion conduction specificities related to their variable pore sequences, and divergent ligand-binding domains function in odor recognition and cilia localization. Our results provide insights into the conserved and distinct architecture of these olfactory and synaptic ion channels and offer perspectives into the use of IRs as genetically encoded chemical sensors. VIDEO ABSTRACT:

Predicting clinical scores from magnetic resonance scans in Alzheimer's disease.

Machine learning and pattern recognition methods have been used to diagnose Alzheimer's disease (AD) and mild cognitive impairment (MCI) from individual MRI scans. Another application of such methods is to predict clinical scores from individual scans. Using relevance vector regression (RVR), we predicted individuals' performances on established tests from their MRI T1 weighted image in two independent data sets. From Mayo Clinic, 73 probable AD patients and 91 cognitively normal (CN) controls completed the Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), and Auditory Verbal Learning Test (AVLT) within 3months of their scan. Baseline MRI's from the Alzheimer's disease Neuroimaging Initiative (ADNI) comprised the other data set; 113 AD, 351 MCI, and 122 CN subjects completed the MMSE and Alzheimer's Disease Assessment Scale-Cognitive subtest (ADAS-cog) and 39 AD, 92 MCI, and 32 CN ADNI subjects completed MMSE, ADAS-cog, and AVLT. Predicted and actual clinical scores were highly correlated for the MMSE, DRS, and ADAS-cog tests (P<0.0001). Training with one data set and testing with another demonstrated stability between data sets. DRS, MMSE, and ADAS-Cog correlated better than AVLT with whole brain grey matter changes associated with AD. This result underscores their utility for screening and tracking disease. RVR offers a novel way to measure interactions between structural changes and neuropsychological tests beyond that of univariate methods. In clinical practice, we envision using RVR to aid in diagnosis and predict clinical outcome.

Stereospecific recognition of pyochelin and enantio-pyochelin by the PchR proteins in fluorescent pseudomonads.

The siderophore pyochelin of Pseudomonas aeruginosa promotes growth under iron limitation and induces the expression of its biosynthesis genes via the transcriptional AraC/XylS-type regulator PchR. Pseudomonas fluorescens strain CHA0 makes the optical antipode of pyochelin termed enantio-pyochelin, which also promotes growth and induces the expression of its biosynthesis genes when iron is scarce. Growth promotion and signalling by pyochelin and enantio-pyochelin are highly stereospecific and are known to involve the pyochelin and enantio-pyochelin outer-membrane receptors FptA and FetA, respectively. Here we show that stereospecificity in signalling is also based on the stereospecificity of the homologous PchR proteins of P. aeruginosa and P. fluorescens towards their respective siderophore effectors. We found that PchR functioned in the heterologous species only if supplied with its native ligand and that the FptA and FetA receptors enhanced the efficiency of signalling. By constructing and expressing hybrid and truncated PchR regulators we showed that the weakly conserved N-terminal domain of PchR is responsible for siderophore specificity. Thus, both uptake and transcriptional regulation confer stereospecificity to pyochelin and enantio-pyochelin biosynthesis.

Influence of clients' personality and individual characteristics on the effectiveness of a career counselling intervention

Clients' personality traits and individual characteristics, such as age, gender, reason for seeking counselling, and further compounding problems in their personal or academic lives, may pose risk factors that render career decision making difficult and may also impact the overall effectiveness of a career counselling intervention. Neuroticism and conscien- tiousness as well as clients' age and gender directly affected clients' satisfaction with life and certain aspects of their career indecision scores before participating in our short-term career counselling intervention. Career counsellors can use personality and career-specific and career-non-specific instruments to tailor career counselling interventions to meet clients' individual needs.

Designing phase III or IV trials for vaccines: choosing between individual or cluster randomised trial designs.

The choice of design between individual randomisation, cluster or pseudo-cluster randomisation is often made difficult. Clear methodological guidelines have been given for trials in general practice, but not for vaccine trials. This article proposes a decisional flow-chart to choose the most adapted design for evaluating the effectiveness of a vaccine in large-scale studies. Six criteria have been identified: importance of herd immunity or herd protection, ability to delimit epidemiological units, homogeneity of transmission probability across sub-populations, population's acceptability of randomisation, availability of logistical resources, and estimated sample size. This easy to use decisional method could help sponsors, trial steering committees and ethical committees adopt the most suitable design.

Characterization of olive oil by carbon isotope analysis of individual fatty acids: Implications for authentication

The fatty acids of olive oils of distinct quality grade from the most important European Union (EU) producer countries were chemically and isotopically characterized. The analytical approach utilized combined capillary column gas chromatography-mass spectrometry (GC/MS) and the novel technique of compound-specific isotope analysis (CSIA) through gas chromatography coupled to a stable isotope ratio mass spectrometer (IRMS) via a combustion (C) interface (GC/C/IRMS). This approach provides further insights into the control of the purity and geographical origin of oils sold as cold-pressed extra virgin olive oil with certified origin appellation. The results indicate that substantial enrichment in heavy carbon isotope (C-13) of the bulk oil and of individual fatty acids are related to (1) a thermally induced degradation due to deodorization or steam washing of the olive oils and (2) the potential blend with refined olive oil or other vegetable oils. The interpretation of the data is based on principal component analysis of the fatty acids concentrations and isotopic data (delta(13)C(oil), delta(13)C(16:0), delta(13)C(18:1)) and on the delta(13)C(16:0) vs delta(13)C(18:1) covariations. The differences in the delta(13)C values of palmitic and oleic acids are discussed in terms of biosynthesis of these acids in the plant tissue and admixture of distinct oils.

Meta-analysis of gene-level associations for rare variants based on single-variant statistics.

Meta-analysis of genome-wide association studies (GWASs) has led to the discoveries of many common variants associated with complex human diseases. There is a growing recognition that identifying "causal" rare variants also requires large-scale meta-analysis. The fact that association tests with rare variants are performed at the gene level rather than at the variant level poses unprecedented challenges in the meta-analysis. First, different studies may adopt different gene-level tests, so the results are not compatible. Second, gene-level tests require multivariate statistics (i.e., components of the test statistic and their covariance matrix), which are difficult to obtain. To overcome these challenges, we propose to perform gene-level tests for rare variants by combining the results of single-variant analysis (i.e., p values of association tests and effect estimates) from participating studies. This simple strategy is possible because of an insight that multivariate statistics can be recovered from single-variant statistics, together with the correlation matrix of the single-variant test statistics, which can be estimated from one of the participating studies or from a publicly available database. We show both theoretically and numerically that the proposed meta-analysis approach provides accurate control of the type I error and is as powerful as joint analysis of individual participant data. This approach accommodates any disease phenotype and any study design and produces all commonly used gene-level tests. An application to the GWAS summary results of the Genetic Investigation of ANthropometric Traits (GIANT) consortium reveals rare and low-frequency variants associated with human height. The relevant software is freely available.

The hematology laboratory in blood doping (bd): 2014 update on the athlete biological passport (APB)

Introduction: Blood doping (BD) is the use of Erythropoietic Stimulating Agents (ESAs) and/or transfusion to increase aerobic performance in athletes. Direct toxicologic techniques are insufficient to unmask sophisticated doping protocols. The Hematological module of the ABP (World Anti-Doping Agency), associates decision support technology and expert assessment to indirectly detect BD hematological effects. Methods: The ABP module is based on blood parameters, under strict pre-analytical and analytical rules for collection, storage and transport at 2-12°C, internal and external QC. Accuracy, reproducibility and interlaboratory harmonization fulfill forensic standard. Blood samples are collected in competition and out-ofcompetition. Primary parameters for longitudinal monitoring are: - hemoglobin (HGB); - reticulocyte percentage (RET); - OFF score, indicator of suppressed erythropoiesis, calculated as [HGB(g/L) * 60-√RET%]. Statistical calculation predicts individual expected limits by probabilistic inference. Secondary parameters are RBC, HCT, MCHC-MCH-MCV-RDW-IFR. ABP profiles flagged as atypical are review by experts in hematology, pharmacology, sports medicine or physiology, and classified as: - normal - suspect (to target) - likely due to BD - likely due to pathology. Results: Thousands of athletes worldwide are currently monitored. Since 2010, at least 35 athletes have been sanctioned and others are prosecuted on the sole basis of abnormal ABP, with a 240% increase of positivity to direct tests for ESA, thanks to improved targeting of suspicious athletes (WADA data). Specific doping scenarios have been identified by the Experts (Table and Figure). Figure. Typical HGB and RET profiles in two highly suspicious athletes. A. Sample 2: simultaneous increases in HGB and RET (likely ESA stimulation) in a male. B. Samples 3, 6 and 7: "OFF" picture, with high HGB and low RET in a female. Sample 10: normal HGB and increased RET (ESA or blood withdrawal). Conclusions: ABP is a powerful tool for indirect doping detection, based on the recognition of specific, unphysiological changes triggered by blood doping. The effect of factors of heterogeneity, such as sex and altitude, must also be considered. Schumacher YO, et al. Drug Test Anal 2012, 4:846-853. Sottas PE, et al. Clin Chem 2011, 57:969-976.

Co-evolution between sociality and dispersal: The role of synergistic cooperative benefits.

Explaining the evolution of sociality is challenging because social individuals face disadvantages that must be balanced by intrinsic benefits of living in a group. One potential route towards the evolution of sociality may emerge from the avoidance of dispersal, which can be risky in some environments. Although early studies found that local competition may cancel the benefits of cooperation in viscous populations, subsequent studies have identified conditions, such as the presence of kin recognition or specific demographic conditions, under which altruism will still spread. Most of these studies assume that the costs of cooperating outweigh the direct benefits (strong altruism). In nature, however, many organisms gain synergistic benefits from group living, which may counterbalance even costly altruistic behaviours. Here, we use an individual based model to investigate how dispersal and social behaviour co-evolve when social behaviours result in synergistic benefits that counterbalance the relative cost of altruism to a greater extent than assumed in previous models. When the cost of cooperation is high, selection for sociality responds strongly to the cost of dispersal. In particular, cooperation can begin to spread in a population when higher cooperation levels become correlated with lower dispersal tendencies within individuals. In contrast, less costly social behaviours are less sensitive to the cost of dispersal. In line with previous studies, we find that mechanisms of global population control also affect this relationship: when whole patches (groups) go extinct each generation, selection favours a relatively high dispersal propensity, and social behaviours evolve only when they are not very costly. If random individuals within groups experience mortality each generation to maintain a global carrying capacity, on the other hand, social behaviours spread and dispersal is reduced, even when the latter is not costly.

Recognition judgments and the performance of the recognition heuristic depend on the size of the reference class

In a series of three experiments, participants made inferences about which one of a pair of two objects scored higher on a criterion. The first experiment was designed to contrast the prediction of Probabilistic Mental Model theory (Gigerenzer, Hoffrage, & Kleinbölting, 1991) concerning sampling procedure with the hard-easy effect. The experiment failed to support the theory's prediction that a particular pair of randomly sampled item sets would differ in percentage correct; but the observation that German participants performed practically as well on comparisons between U.S. cities (many of which they did not even recognize) than on comparisons between German cities (about which they knew much more) ultimately led to the formulation of the recognition heuristic. Experiment 2 was a second, this time successful, attempt to unconfound item difficulty and sampling procedure. In Experiment 3, participants' knowledge and recognition of each city was elicited, and how often this could be used to make an inference was manipulated. Choices were consistent with the recognition heuristic in about 80% of the cases when it discriminated and people had no additional knowledge about the recognized city (and in about 90% when they had such knowledge). The frequency with which the heuristic could be used affected the percentage correct, mean confidence, and overconfidence as predicted. The size of the reference class, which was also manipulated, modified these effects in meaningful and theoretically important ways.

Altruism, dispersal, and phenotype-matching kin recognition.

We investigate the coevolution between philopatry and altruism in island-model populations when kin recognition occurs through phenotype matching. In saturated environments, a good discrimination ability is a necessary prerequisite for the emergence of sociality. Discrimination decreases not only with the average phenotypic similarity between immigrants and residents (i.e., with environmental homogeneity and past gene flow) but also with the sampling variance of similarity distributions (a negative function of the number of traits sampled). Whether discrimination should rely on genetically or environmentally determined traits depends on the apportionment of phenotypic variance and, in particular, on the relative values of e (the among-group component of environmental variance) and r (the among-group component of genetic variance, which also measures relatedness among group members). If r exceeds e, highly heritable cues do better. Discrimination and altruism, however, remain low unless philopatry is enforced by ecological constraints. If e exceeds r, by contrast, nonheritable traits do better. High e values improve discrimination drastically and thus have the potential to drive sociality, even in the absence of ecological constraints. The emergence of sociality thus can be facilitated by enhancing e, which we argue is the main purpose of cue standardization within groups, as observed in many social insects, birds, and mammals, including humans.