A step-by-step tutorial to use HierFstat to analyse populations hierarchically structured at multiple levels.

The populations of parasites and infectious agents are most of the time structured in complex hierarchy that lies beyond the classical nested design described by Wright's F-statistics (F(IS), F(ST) and F(IT)). In this note we propose a user-friendly step-by-step notice for using recent software (HierFstat) that computes and test fixation indices for any hierarchical structure. We add some tricks and tips for some special data kind (haploid, single locus), some other procedure (bootstrap over loci) and how to handle crossed factors.

Multi-receptor binding profile of clozapine and olanzapine: a structural study based on the new beta (2) adrenergic receptor template

Schizophrenia is a devastating mental disorder that has a largeimpact on the quality of life for those who are afflicted and isvery costly for families and society.[1] Although the etiology ofschizophrenia is still unknown and no cure has yet beenfound, it is treatable, and pharmacological therapy often producessatisfactory results. Among the various antipsychoticdrugs in use, clozapine is widely recognized as one ofthemost clinically effective agents, even if it elicits significant sideeffects such as metabolic disorders and agranulocytosis. Clozapineand the closely related compound olanzapine are goodexamples ofdrug s with a complex multi-receptor profile ;[2]they have affinities toward serotonin, dopamine, a adrenergic,muscarinic, and histamine receptors, among others.

Estimation of inelastic seismic material properties of a surgical sea-bed from multi-component marine seismic data

To date, state-of-the-art seismic material parameter estimates from multi-component sea-bed seismic data are based on the assumption that the sea-bed consists of a fully elastic half-space. In reality, however, the shallow sea-bed generally consists of soft, unconsolidated sediments that are characterized by strong to very strong seismic attenuation. To explore the potential implications, we apply a state-of-the-art elastic decomposition algorithm to synthetic data for a range of canonical sea-bed models consisting of a viscoelastic half-space of varying attenuation. We find that in the presence of strong seismic attenuation, as quantified by Q-values of 10 or less, significant errors arise in the conventional elastic estimation of seismic properties. Tests on synthetic data indicate that these errors can be largely avoided by accounting for the inherent attenuation of the seafloor when estimating the seismic parameters. This can be achieved by replacing the real-valued expressions for the elastic moduli in the governing equations in the parameter estimation by their complex-valued viscoelastic equivalents. The practical application of our parameter procedure yields realistic estimates of the elastic seismic material properties of the shallow sea-bed, while the corresponding Q-estimates seem to be biased towards too low values, particularly for S-waves. Given that the estimation of inelastic material parameters is notoriously difficult, particularly in the immediate vicinity of the sea-bed, this is expected to be of interest and importance for civil and ocean engineering purposes.

Comparative gene finding in chicken indicates that we are closing in on the set of multi-exonic widely-expressed human genes

The recent availability of the chicken genome sequence poses the question of whether there are human protein-coding genes conserved in chicken that are currently not included in the human gene catalog. Here, we show, using comparative gene finding followed by experimental verification of exon pairs by RT–PCR, that the addition to the multi-exonic subset of this catalog could be as little as 0.2%, suggesting that we may be closing in on the human gene set. Our protocol, however, has two shortcomings: (i) the bioinformatic screening of the predicted genes, applied to filter out false positives, cannot handle intronless genes; and (ii) the experimental verification could fail to identify expression at a specific developmental time. This highlights the importance of developing methods that could provide a reliable estimate of the number of these two types of genes.

Analysis of the multi-copy gene family FAM90A as a copy number variant in different ethnic backgrounds

Copy number variants contribute extensively to inter-individual genomic differences, but little is known about their inter-population variability and diversity. In a previous study (Bosch et al., 2007; 16:2572-2582), we reported that the primate-specific gene family FAM90A, which accounts for as many as 25 members in the human reference assembly, has expanded the number of FAM90A clusters across the hominoid lineage. Here we examined the copy number variability of FAM90A genes in 260 HapMap samples of European, African, and Asian ancestry, and showed significant inter-population differences (p<0.0001). Based on the recent study of Stranger et al. (2007; 315:848-853), we also explored the correlation between copy number variability and expression levels of the FAM90A gene family. Despite the high genomic variability, we found a low correlation between FAM90A copy number and expression levels, which could be due to the action of independent trans-acting factors. Our results show that FAM90A is highly variable in copy number between individuals and between populations. However, this variability has little impact on gene expression levels, thus highlighting the importance of genomic variability for genes located in regions containing segmental duplications.

Capacity-achieving input covariance for single-user multi-antenna channels

We characterize the capacity-achieving input covariance for multi-antenna channels known instantaneously at the receiver and in distribution at the transmitter. Our characterization, valid for arbitrary numbers of antennas, encompasses both the eigenvectors and the eigenvalues. The eigenvectors are found for zero-mean channels with arbitrary fading profiles and a wide range of correlation and keyhole structures. For the eigenvalues, in turn, we present necessary and sufficient conditions as well as an iterative algorithm that exhibits remarkable properties: universal applicability, robustness and rapid convergence. In addition, we identify channel structures for which an isotropic input achieves capacity.

Analyse de modèles murins adultes de régénération cardiaque

Résumé Le mammifère adulte possède des capacités de régénération tissulaire beaucoup plus limitées que celles des mammifères à l'âge foetal, ou d'autres vertébrés adultes comme les amphibiens urodèles et anuriens. Le mode de réparation tissulaire généralement utilisé par le mammifère adulte est la cicatrisation. Celle-ci suit un déroulement physio-pathologique très reproductible, qui a été le mieux décrit dans la peau, mais est également applicable à d'autres tissus comme le coeur en cas d'infarctus. Toutefois, le coeur de mammifère adulte semble posséder un certain potentiel régénérateur, bien qu'insuffisant pour réparer une lésion d'infarctus; en particulier, il contient des populations de cellules exprimant des marqueurs de surface des cellules souches hématopoiétiques comme l'antigène de cellules souches (stem cell antigen; Sca-1) ou le récepteur pour le facteur de cellules souches (stem cell factor; SCF), c-kit. Le comportement de ces cellules ressemble à de nombreux égards à celui de cellules souches adultes résidentes. D'autre part, un modèle mammifère adulte de régénération tissulaire, la souris NIRL, a été décrit ,récemment ; si cette souris répare. l'infarctus ischémique du ventricule gauche par cicatrisation, elle est par contre capable de régénérer complètement le myocarde après cryoinfarctus du ventricule droit, sans former la moindre cicatrice. Le but de cette thèse a été l'exploration par différentes approches des potentiels régénérateurs cardiaques après infarctus chez le mammifère adulte. La première approche choisie a été l'étude de la régénération myocardique chez la souris MRL. Il s'agissait de comprendre pourquoi la souris MRL régénère le coeur après cryoinfarctus du ventricule droit, et pas après infarctus ischémique du ventricule gauche, ainsi que d'élucider les mécanismes à la base de la régénération cardiaque chez cette souris. En utilisant le protocole original d'infarctus cryogénique du ventricule droit, nous n'avons pas observé de régénération cardiaque chez la souris MRL, qui a réparé l'infarctus par cicatrisation.- Nous avons ensuite modifié la sévérité du stimulus cryogénique, la localisation de la lésion cardiaque, et le type de lésion lui-même (infarctus ischémique induit par ligature coronarienne). En théorie, ces aspects expérimentaux sont les principaux facteurs pouvant influencer la réparation tissulaire. En utilisant cinq protocoles expérimentaux différents, nous n'avons pas observé de régénération cardiaque chez la souris MRL. Nous avons également analysé la prolifération cellulaire dans trois régions différentes du coeur à 15 et 40 jours après infarctus, et n'avons pas observé de différence entre la souris MRL et la souris contrôle C57B1/6. Quant à la composition en collagène de la cicatrice, elle est la même chez les deux souches de souris. Nos résultats ne peuvent donc pas confirmer la validité de ce modèle marin de régénération cardiaque récemment publié. Nous nous sommes alors tournés vers une deuxième approche d'étude du potentiel régénérateur du coeur de mammifère adulte, celle des cellules souches adultes résidentes. Nous avons isolé et purifié la population de cellules cardiaques qui expriment le marqueur de surface Sca-1 ;nous les avons maintenues en cultures pendant plusieurs dizaines de passages, et les avons ré-injectées dans le myocarde. Cette deuxième approche .ouvre la voie à l'étude de cellules souches cardiaques adultes candidates, ainsi qu'à la thérapie cellulaire de l'infarctus du myocarde. Summary Adult mammals possess limited tissue regeneration capacities as compared to foetal mammals or other adult vertebrates such as anurian and urodele amphibians. Usually, adult mammals heal tissues by scarring. The process of scarring is characterized by physiopathological events which have been best studied in skin; but which also occur in other organs like the heart. Nevertheless, the adult mammalian heart seems to possess a certain regenerative potential, though insufficient to efficiently repair infarct lesions. It indeed contains cell populations expressing haematopoietic stem cell surface markers such as Scat or c-kit. These cells behave in many ways like resident adult. stem cells. On the other hand; an adult mammalian model of tissue regeneration, the MRL mouse, has been recently described; although this mouse repairs an ischemic infarct of the left ventricle by scarring, it is able of fully regenerating a cryoinfarction of the right ventricle without scanning . The goal of this thesis was to explore the regenerative potential of the adult mammalian heart after infarction by using different approaches. A first approach was to study the myocardial regeneration in the MRL mouse. It was about understanding why this mouse regenerates a right ventricular cryoinfarction and not an ischemic infarction of the left ventricle, as well as elucidating the mechanisms underlying myocardial regeneration in this model. By using the original protocol of right ventricular cryoinfarction, we did not observe any heart regeneration in the MRL mouse, which healed the infarct by scarring. We then modified the intensity of the cryogenic stimulus, the site of lesion, and -the type of lesion itself (ischemic infarction by coronary artery ligation). In theory, these experimental aspects are the main factors likely to influence tissue repair. Although. we used five different protocols, we did not observe any regeneration in the MRL mouse. We also analysed cell proliferation in three different regions of the heart, at 15 and 40 days after infarction, and did not see any difference between the MRL and C57B1/6 mouse. Collagen content of the scar was shown to be the same in both strains. Our results cannot confirm the validity of this recently published model. We then chose another way to study the adult mammalian heart regenerative potential, by taking the adult resident stem cells approach. We isolated and purified a cardiac cell population expressing the Sca-1 surface marker; we kept these cells in culture for over 30 passages, and re-injected them into the myocardium. This second approach opens the way to candidate adult cardiac stem cell study, as well as cell therapy.