Parental influences on pathogen resistance in brown trout embryos and effects of outcrossing within a river network.

Phenotypic plasticity can increase tolerance to heterogeneous environments but the elevations and slopes of reaction norms are often population specific. Disruption of locally adapted reaction norms through outcrossing can lower individual viability. Here, we sampled five genetically distinct populations of brown trout (Salmo trutta) from within a river network, crossed them in a full-factorial design, and challenged the embryos with the opportunistic pathogen Pseudomonas fluorescens. By virtue of our design, we were able to disentangle effects of genetic crossing distance from sire and dam effects on early life-history traits. While pathogen infection did not increase mortality, it was associated with delayed hatching of smaller larvae with reduced yolk sac reserves. We found no evidence of a relationship between genetic distance (W, FST) and the expression of early-life history traits. Moreover, hybrids did not differ in phenotypic means or reaction norms in comparison to offspring from within-population crosses. Heritable variation in early life-history traits was found to remain stable across the control and pathogen environments. Our findings show that outcrossing within a rather narrow geographical scale can have neutral effects on F1 hybrid viability at the embryonic stage, i.e. at a stage when environmental and genetic effects on phenotypes are usually large.

Applications of stochastic analysis in finance and statistical inference

First: A continuous-time version of Kyle's model (Kyle 1985), known as the Back's model (Back 1992), of asset pricing with asymmetric information, is studied. A larger class of price processes and of noise traders' processes are studied. The price process, as in Kyle's model, is allowed to depend on the path of the market order. The process of the noise traders' is an inhomogeneous Lévy process. Solutions are found by the Hamilton-Jacobi-Bellman equations. With the insider being risk-neutral, the price pressure is constant, and there is no equilibirium in the presence of jumps. If the insider is risk-averse, there is no equilibirium in the presence of either jumps or drifts. Also, it is analised when the release time is unknown. A general relation is established between the problem of finding an equilibrium and of enlargement of filtrations. Random announcement time is random is also considered. In such a case the market is not fully efficient and there exists equilibrium if the sensitivity of prices with respect to the global demand is time decreasing according with the distribution of the random time. Second: Power variations. it is considered, the asymptotic behavior of the power variation of processes of the form _integral_0^t u(s-)dS(s), where S_ is an alpha-stable process with index of stability 0&alpha&2 and the integral is an Itô integral. Stable convergence of corresponding fluctuations is established. These results provide statistical tools to infer the process u from discrete observations. Third: A bond market is studied where short rates r(t) evolve as an integral of g(t-s)sigma(s) with respect to W(ds), where g and sigma are deterministic and W is the stochastic Wiener measure. Processes of this type are particular cases of ambit processes. These processes are in general not of the semimartingale kind.

Positional scanning-synthetic peptide library-based analysis of self- and pathogen-derived peptide cross-reactivity with tumor-reactive Melan-A-specific CTL.

Synthetic combinatorial peptide libraries in positional scanning format (PS-SCL) have recently emerged as a useful tool for the analysis of T cell recognition. This includes identification of potentially cross-reactive sequences of self or pathogen origin that could be relevant for the understanding of TCR repertoire selection and maintenance, as well as of the cross-reactive potential of Ag-specific immune responses. In this study, we have analyzed the recognition of sequences retrieved by using a biometric analysis of the data generated by screening a PS-SCL with a tumor-reactive CTL clone specific for an immunodominant peptide from the melanocyte differentiation and tumor-associated Ag Melan-A. We found that 39% of the retrieved peptides were recognized by the CTL clone used for PS-SCL screening. The proportion of peptides recognized was higher among those with both high predicted affinity for the HLA-A2 molecule and high predicted stimulatory score. Interestingly, up to 94% of the retrieved peptides were cross-recognized by other Melan-A-specific CTL. Cross-recognition was at least partially focused, as some peptides were cross-recognized by the majority of CTL. Importantly, stimulation of PBMC from melanoma patients with the most frequently recognized peptides elicited the expansion of heterogeneous CD8(+) T cell populations, one fraction of which cross-recognized Melan-A. Together, these results underline the high predictive value of PS-SCL for the identification of sequences cross-recognized by Ag-specific T cells.

Genome-Wide Analysis of Salicylate and Dibenzofuran Metabolism in Sphingomonas Wittichii RW1.

Sphingomonas wittichii RW1 is a bacterium isolated for its ability to degrade the xenobiotic compounds dibenzodioxin and dibenzofuran (DBF). A number of genes involved in DBF degradation have been previously characterized, such as the dxn cluster, dbfB, and the electron transfer components fdx1, fdx3, and redA2. Here we use a combination of whole genome transcriptome analysis and transposon library screening to characterize RW1 catabolic and other genes implicated in the reaction to or degradation of DBF. To detect differentially expressed genes upon exposure to DBF, we applied three different growth exposure experiments, using either short DBF exposures to actively growing cells or growing them with DBF as sole carbon and energy source. Genome-wide gene expression was examined using a custom-made microarray. In addition, proportional abundance determination of transposon insertions in RW1 libraries grown on salicylate or DBF by ultra-high throughput sequencing was used to infer genes whose interruption caused a fitness loss for growth on DBF. Expression patterns showed that batch and chemostat growth conditions, and short or long exposure of cells to DBF produced very different responses. Numerous other uncharacterized catabolic gene clusters putatively involved in aromatic compound metabolism increased expression in response to DBF. In addition, only very few transposon insertions completely abolished growth on DBF. Some of those (e.g., in dxnA1) were expected, whereas others (in a gene cluster for phenylacetate degradation) were not. Both transcriptomic data and transposon screening suggest operation of multiple redundant and parallel aromatic pathways, depending on DBF exposure. In addition, increased expression of other non-catabolic genes suggests that during initial exposure, S. wittichii RW1 perceives DBF as a stressor, whereas after longer exposure, the compound is recognized as a carbon source and metabolized using several pathways in parallel.

Large-scale analysis of orthologs and paralogs under covarion-like and constant-but-different models of amino acid evolution.

Functional divergence between homologous proteins is expected to affect amino acid sequences in two main ways, which can be considered as proxies of biochemical divergence: a "covarion-like" pattern of correlated changes in evolutionary rates, and switches in conserved residues ("conserved but different"). Although these patterns have been used in case studies, a large-scale analysis is needed to estimate their frequency and distribution. We use a phylogenomic framework of animal genes to answer three questions: 1) What is the prevalence of such patterns? 2) Can we link such patterns at the amino acid level with selection inferred at the codon level? 3) Are patterns different between paralogs and orthologs? We find that covarion-like patterns are more frequently detected than "constant but different," but that only the latter are correlated with signal for positive selection. Finally, there is no obvious difference in patterns between orthologs and paralogs.

CoDaPack. An Excel and Visual Basic based software of compositional data analysis. Current version and discussion form upcoming versions

In the eighties, John Aitchison (1986) developed a new methodological approach for the statistical analysis of compositional data. This new methodology was implemented in Basic routines grouped under the name CODA and later NEWCODA inMatlab (Aitchison, 1997). After that, several other authors have published extensions to this methodology: Marín-Fernández and others (2000), Barceló-Vidal and others (2001), Pawlowsky-Glahn and Egozcue (2001, 2002) and Egozcue and others (2003). (...)

Comparative analysis of human and mouse expression data illuminates tissue-specific evolutionary patterns of miRNAs.

MicroRNAs (miRNAs) constitute an important class of gene regulators. While models have been proposed to explain their appearance and expansion, the validation of these models has been difficult due to the lack of comparative studies. Here, we analyze miRNA evolutionary patterns in two mammals, human and mouse, in relation to the age of miRNA families. In this comparative framework, we confirm some predictions of previously advanced models of miRNA evolution, e.g. that miRNAs arise more frequently de novo than by duplication, or that the number of protein-coding gene targeted by miRNAs decreases with evolutionary time. We also corroborate that miRNAs display an increase in expression level with evolutionary time, however we show that this relation is largely tissue-dependent, and especially low in embryonic or nervous tissues. We identify a bias of tag-sequencing techniques regarding the assessment of breadth of expression, leading us, contrary to predictions, to find more tissue-specific expression of older miRNAs. Together, our results refine the models used so far to depict the evolution of miRNA genes. They underline the role of tissue-specific selective forces on the evolution of miRNAs, as well as the potential co-evolution patterns between miRNAs and the protein-coding genes they target.

An Inquiry into the use of illegal electoral practices and effects of political violence

This article investigates whether vote-buying and the instigation of violence in the disputed 2007 Kenyan elections were strategically motivated, and whether those affected by electoral violence changed their views towards ethno-politics and the use of violence. To answer these questions, a panel survey conducted before and after the elections is combined with external indicators of electoral violence. We find that political parties targeted vote-buying towards specific groups to weaken the support of their political rivals and to mobilize their own supporters. Furthermore, parties instigated violence strategically in areas where they were less likely to win. Although the victims of violence would prefer that parties are no longer allowed to organize in ethnic or religious lines, they are more likely to identify in ethnic terms, support the use of violence and avoid relying on the police to resolve disputes. The overall findings suggest an increased risk of electoral-violence reoccurring.

L'analyse des renvois régionaux et interrégionaux en pratique médicale ambulatoire. [Analysis of regional and interregional referrals in ambulatory medical practice].

This article examines, in two Swiss cantons, the interdependence from a medical care point of view of various regions (health planning zones in one canton, political districts in the other). The volume and the destination of patient referrals prescribed by physicians in ambulatory practice are analyzed. The available data (on 1609 referrals) were gathered by the practitioners themselves, during a National Ambulatory Medical Care Survey type study in February-March 1981, in which 203 physicians participated. Several indicators are proposed (including an integration coefficient and an attraction coefficient for each zone); they show marked differences among the regions. This dynamic approach, based on the effective behavior of physicians, appears to be of major interest for health planning purposes (as compared with the frequent practice to use mainly parameters in relation with the availability of care services--the "supply"--numbers of professionals and/or health facilities).

Pseudogenes in the ENCODE regions: consensus annotation, analysis of transcription, and evolution

Arising from either retrotransposition or genomic duplication of functional genes, pseudogenes are “genomic fossils” valuable for exploring the dynamics and evolution of genes and genomes. Pseudogene identification is an important problem in computational genomics, and is also critical for obtaining an accurate picture of a genome’s structure and function. However, no consensus computational scheme for defining and detecting pseudogenes has been developed thus far. As part of the ENCyclopedia Of DNA Elements (ENCODE) project, we have compared several distinct pseudogene annotation strategies and found that different approaches and parameters often resulted in rather distinct sets of pseudogenes. We subsequently developed a consensus approach for annotating pseudogenes (derived from protein coding genes) in the ENCODE regions, resulting in 201 pseudogenes, two-thirds of which originated from retrotransposition. A survey of orthologs for these pseudogenes in 28 vertebrate genomes showed that a significant fraction (∼80%) of the processed pseudogenes are primate-specific sequences, highlighting the increasing retrotransposition activity in primates. Analysis of sequence conservation and variation also demonstrated that most pseudogenes evolve neutrally, and processed pseudogenes appear to have lost their coding potential immediately or soon after their emergence. In order to explore the functional implication of pseudogene prevalence, we have extensively examined the transcriptional activity of the ENCODE pseudogenes. We performed systematic series of pseudogene-specific RACE analyses. These, together with complementary evidence derived from tiling microarrays and high throughput sequencing, demonstrated that at least a fifth of the 201 pseudogenes are transcribed in one or more cell lines or tissues.

Analysis of epidermis- and mesophyll-specific transcript accumulation in powdery mildew-inoculated wheat leaves.

Powdery mildew is an important disease of wheat caused by the obligate biotrophic fungus Blumeria graminis f. sp. tritici. This pathogen invades exclusively epidermal cells after penetrating directly through the cell wall. Because powdery mildew colonizes exclusively epidermal cells, it is of importance not only to identify genes which are activated, but also to monitor tissue specificity of gene activation. Acquired resistance of wheat to powdery mildew can be induced by a previous inoculation with the non-host pathogen B. graminis f. sp. hordei, the causal agent of barley powdery mildew. The establishment of the resistant state is accompanied by the activation of genes. Here we report the tissue-specific cDNA-AFLP analysis and cloning of transcripts accumulating 6 and 24 h after the resistance-inducing inoculation with B. graminis f. sp. hordei. A total of 25,000 fragments estimated to represent about 17,000 transcripts were displayed. Out of these, 141 transcripts, were found to accumulate after Bgh inoculation using microarray hybridization analysis. Forty-four accumulated predominantly in the epidermis whereas 76 transcripts accumulated mostly in mesophyll tissue.

Profiles of drug users in Switzerland and effects of early-onset intensive use of alcohol, tobacco and cannabis on other illicit drug use.

QUESTIONS UNDER STUDY / PRINCIPLES: The main aim of this study was to investigate profiles of drug users, with a particular focus on illicit drugs other than cannabis, and to explore the effect of early-onset intensive use (drunkenness, daily smoking, high on cannabis) on profiles of illicit drug use. METHODS: Baseline data from a representative sample of 5,831 young Swiss men in the ongoing Cohort Study on Substance Use Risk Factors were used. Substance use (alcohol, tobacco, cannabis and 15 types of other illicit drug) and age of onset of intensive use were assessed. The Item Response Theory (IRT) and prevalence rates at different ages of onset were used to reveal different profiles of illicit drug use. RESULTS: In addition to cannabis, there were two profiles of other illicit drug use: (a) "softer" drug users (uppers, hallucinogens and inhaled drugs), among which ecstasy had the highest discriminatory potential (IRT slope = 4.68, standard error (SE) = 0.48; p <0.001); and (b) "harder" drug users (heroin, ketamine, gamma-hydroxybutyrate/gamma-hydroxylactone, research chemicals, crystal meth and spice), among which ketamine had the highest discriminatory potential (slope = 4.05; SE = 0.63; p <0.001). Onset of intensive use at the age of 12 years or younger also discriminated between these two profiles. CONCLUSION: Both the IRT model and the effect of onset of intensive use enabled two groups of illicit drugs to be identified. In particular, very early onset (at 12 years or younger) intensive use of any substance was a marker for later use of the second group of drugs.