Familiality and SNP heritability of age at onset and episodicity in major depressive disorder.

BACKGROUND: Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability). METHOD: For investigating familiality, we used 691 families with 2-5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software. RESULTS: Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity. CONCLUSIONS: AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.

Spatial variation in the temporal change of male and female melanic ornamentation in the barn owl.

Because the magnitude of selection can vary between sexes and in space and time, sexually antagonistic selection is difficult to demonstrate. In a Swiss population of barn owls (Tyto alba), a heritable eumelanic colour trait (size of black spots on ventral feathers) was positively selected with respect to yearling survival only in females. It remains unclear whether the absence of negative selection in males is typical in this species. To tackle this issue indirectly, we measured the size of black spots in 1733 skin specimens collected by museums from 1816 to 2001 in seven European countries and in the Middle-East. The temporal change in spot size was sex- and country-specific. In males, spots became smaller particularly in three countries (Middle-East, Italy and Switzerland). In females, the size of spots increased significantly in two countries (UK and Spain) and decreased in two others (Germany and Switzerland). Because migration and phenotypic plasticity cannot explain these results, selection is the most likely cause. The weaker temporal change in spot size in females than males may be because of the combined effect of strong genetic correlation between the sexes and stronger negative selection in males than positive selection in females. We thus suggest that in the barn owl, spot size (or genetically correlated traits) is sexually antagonistically selected and that its pattern of selection may account for the maintenance of its variation and sexual dimorphism.

Effect of External Noise Correlation in Optical Coherence Resonance

Coherence resonance occurring in semiconductor lasers with optical feedback is studied via the Lang-Kobayashi model with external nonwhite noise in the pumping current. The temporal correlation and the amplitude of the noise have a highly relevant influence in the system, leading to an optimal coherent response for suitable values of both the noise amplitude and correlation time. This phenomenon is quantitatively characterized by means of several statistical measures.

Congenital disorder of glycosylation type Id (CDG Id) : phenotypic, biochemical and molecular characterization of a new patient

Rapport de synthèseLes troubles de la glycosylation (Congenital Disorders of Glycosylation, CDG) regroupent une famille de maladies multi-systémiques héréditaires causées par des défauts dans la synthèse de glycoconjugés. La glycosylation est une réaction enzymatique consistant à lier de façon covalente un glucide à une chaîne peptidique ou une protéine. Il existe deux types de glycosylation. La N-gjycosylation est l'addition de glucides aux chaînes peptidiques en croissance dès leur entrée dans la lumière du réticulum endoplasmique. Elle s'effectue sur les futures glycoprotéines membranaires et conduit à des chaînes de sucres courtes et ramifiées. La O-glycosylation est l'addition de glucides au niveau des résidus hydroxylés des acides aminés sérine et thréonine des chaînes peptidiques déjà présentes dans la lumière de l'appareil de Golgi. Elle est, dans la plupart des cas, effectuée sur îes protéoglycanes et conduit à des chaînes de sucres longues et non ramifiées. La classification des CDG repose sur le niveau de l'étape limitante de la glycosylation. Les CDG de type 1, plus fréquents, regroupent les déficits enzymatiques se situant en amont du transfert de Poligosaccharide sur la chaîne peptidique. Les CDG de type 2 regroupent ceux ayant lieu en aval de ce transfert. Parmi les nombreux différents sous-types de CDG, le CDG de type ld est causé par une anomalie de la mannosyltransferase, enzyme codée par le gène ALG3 (chromosome 3q27). Jusqu'à ce jour, six patients atteints de CDG ld ont été reportés dans la littérature. Notre travail a permis de décrire un septième patient et d'affiner les caractéristiques cliniques, biologiques, neuroradiologiques et moléculaires du CDG ld. Notre patient est notamment porteur d'une nouvelle mutation de type missense sur le gène ALG3. Tous les patients atteints de CDG ld présentent une encéphalopathie progressive avec microcéphalie, retard psychomoteur sévère et épilepsie. Une ostéopénie marquée est présente chez certains patients. Elle est parfois sous diagnostiquée et révélée uniquement lors de fracture pathologique. Les patients atteints de CDG ld présentent également des traits dysmorphiques typiques, mais aucune atteinte multi-systémique ou anomalie biologique spécifique n'est retrouvée telle que dans les autres types de CDG. Le dépistage biochimique des troubles de la glycosylation se fait par une analyse simple et peu coûteuse qui est l'analyse de la transferrine sérique par isoelectrofocusing ou par électrophorèse capillaire. Un tel dépistage devrait être effectué chez tout patient présentant une encéphalopathie d'origine indéterminée, et cela même en l'absence d'atteinte multi- systémique. Notre travail a été publié sous forme d'article de type « short report », peer-reviewed, dans le Journal of Inherited Metabolic Diseases. Le Journal est une révue spécialisée du domaine des erreirs innées du métabolisme. S'agissant d'un seul patient rapporté, l'article ne montre que très synthétiquement le travail effectué, Pour cette raison un complément à l'article avec matériel, méthodes et résultats figure ci-après et concerne la partie de recherche moléculaire de notre travail. La doctorante a non seulement encadré personnellement le patient au niveau clinique et biochimique, mais a plus particulièrement mis au point l'analyse moléculaire du gène ALG3 dans le laboratoire de Pédiatrie Moléculaire pour la première fois ; cela a impliqué l'étude du gène, le choix des oligonucleotides et l'optimisation des réactions d'amplification et séquençage.

Theory for correlation functions of processes driven by external colored noise

We study steady-state correlation functions of nonlinear stochastic processes driven by external colored noise. We present a methodology that provides explicit expressions of correlation functions approximating simultaneously short- and long-time regimes. The non-Markov nature is reduced to an effective Markovian formulation, and the nonlinearities are treated systematically by means of double expansions in high and low frequencies. We also derive some exact expressions for the coefficients of these expansions for arbitrary noise by means of a generalization of projection-operator techniques.

Intensity correlation functions of dye lasers: Comparison of colored-gain-noise and colored-loss-noise models

The intensity correlation functions C(t) for the colored-gain-noise model of dye lasers are analyzed and compared with those for the loss-noise model. For correlation times ¿ larger than the deterministic relaxation time td, we show with the use of the adiabatic approximation that C(t) values coincide for both models. For small correlation times we use a method that provides explicit expressions of non-Markovian correlation functions, approximating simultaneously short- and long-time behaviors. Comparison with numerical simulations shows excellent results simultaneously for short- and long-time regimes. It is found that, when the correlation time of the noise increases, differences between the gain- and loss-noise models tend to disappear. The decay of C(t) for both models can be described by a time scale that approaches the deterministic relaxation time. However, in contrast with the loss-noise model, a secondary time scale remains for large times for the gain-noise model, which could allow one to distinguish between both models.

Mineralogy of the clay fraction of alfisols in two slope curvatures: IV - spatial correlation with physical properties

Although the influence of clay mineralogy on soil physical properties has been widely studied, spatial relationships between these features in Alfisols have rarely been examined. The purpose of this work was to relate the clay minerals and physical properties of an Alfisol of sandstone origin in two slope curvatures. The crystallographic properties such as mean crystallite size (MCS) and width at half height (WHH) of hematite, goethite, kaolinite and gibbsite; contents of hematite and goethite; aluminium substitution (AS) and specific surface area (SSA) of hematite and goethite; the goethite/(goethite+hematite) and kaolinite/(kaolinite+gibbsite) ratios; and the citrate/bicarbonate/dithionite extractable Fe (Fe d) were correlated with the soil physical properties through Pearson correlation coefficients and cross-semivariograms. The correlations found between aluminium substitution in goethite and the soil physical properties suggest that the degree of crystallinity of this mineral influences soil properties used as soil quality indicators. Thus, goethite with a high aluminium substitution resulted in large aggregate sizes and a high porosity, and also in a low bulk density and soil penetration resistance. The presence of highly crystalline gibbsite resulted in a high density and micropore content, as well as in smaller aggregates. Interpretation of the cross-semivariogram and classification of landscape compartments in terms of the spatial dependence pattern for the relief-dependent physical and mineralogical properties of the soil proved an effective supplementary method for assessing Pearson correlations between the soil physical and mineralogical properties.

On-axis joint transform correlation based on a four-level power spectrum

We propose a method to obtain a single centered correlation with use of a joint transform correlator. We analyze the required setup to carry out the whole process optically, and we also present experimental results.

Optical correlation by use of partial phase-only modulation with VGA liquid-crystal displays

The development of liquid-crystal panels for use in commercial equipment has been aimed at improving the pixel resolution and the display efficiency. These improvements have led to a reduction in the thickness of such devices, among other outcomes, that involves a loss in phase modulation. We propose a modification of the classical phase-only filter to permit displays in VGA liquid-crystal panels with a constant amplitude modulation and less than a 2¿(PI) phase modulation. The method was tested experimentally in an optical setup.

Effects of thresholding level variation in fringe binarization of multiobject joint transform correlation

It is possible to improve the fringe binarization method of joint transform correlation by choosing a suitable threshold level.

Application of fuzzy-rule-based postprocessing to correlation methods in pattern recognition

One of the most important problems in optical pattern recognition by correlation is the appearance of sidelobes in the correlation plane, which causes false alarms. We present a method that eliminate sidelobes of up to a given height if certain conditions are satisfied. The method can be applied to any generalized synthetic discriminant function filter and is capable of rejecting lateral peaks that are even higher than the central correlation. Satisfactory results were obtained in both computer simulations and optical implementation.

Correlation postprocessing-based method for the detection of de focused images

We present a method to detect patterns in defocused scenes by means of a joint transform correlator. We describe analytically the correlation plane, and we also introduce an original procedure to recognize the target by postprocessing the correlation plane. The performance of the methodology when the defocused images are corrupted by additive noise is also considered.

SPATIAL CORRELATION BETWEEN PHYSICAL PROPERTIES OF SOIL AND WEEDS IN TWO MANAGEMENT SYSTEMS

The spatial correlation between soil properties and weeds is relevant in agronomic and environmental terms. The analysis of this correlation is crucial for the interpretation of its meaning, for influencing factors such as dispersal mechanisms, seed production and survival, and the range of influence of soil management techniques. This study aimed to evaluate the spatial correlation between the physical properties of soil and weeds in no-tillage (NT) and conventional tillage (CT) systems. The following physical properties of soil and weeds were analyzed: soil bulk density, macroporosity, microporosity, total porosity, aeration capacity of soil matrix, soil water content at field capacity, weed shoot biomass, weed density, Commelina benghalensis density, and Bidens pilosa density. Generally, the ranges of the spatial correlations were higher in NT than in CT. The cross-variograms showed that many variables have a structure of combined spatial variation and can therefore be mapped from one another by co-kriging. This combined variation also allows inferences about the physical and biological meanings of the study variables. Results also showed that soil management systems influence the spatial dependence structure significantly.

Finite-size effects in nonequilibrium correlation functions

We have shown that finite-size effects in the correlation functions away from equilibrium may be introduced through dimensionless numbers: the Nusselt numbers, accounting for both the nature of the boundaries and the size of the system. From an analysis based on fluctuating hydrodynamics, we conclude that the mean-square fluctuations satisfy scaling laws, since they depend only on the dimensionless numbers in addition to reduced variables. We focus on the case of diffusion modes and describe some physical situations in which finite-size effects may be relevant.

Self and cross-velocity correlation functions and diffusion coefficients in liquids: a molecular dynamics study of binary mixtures of soft spheres

Molecular dynamics simulation is applied to the study of the diffusion properties in binary liquid mixtures made up of soft-sphere particles with different sizes and masses. Self- and distinct velocity correlation functions and related diffusion coefficients have been calculated. Special attention has been paid to the dynamic cross correlations which have been computed through recently introduced relative mean molecular velocity correlation functions which are independent on the reference frame. The differences between the distinct velocity correlations and diffusion coefficients in different reference frames (mass-fixed, number-fixed, and solvent-fixed) are discussed.