Generalized conjugate priors for Bayesian analysis of risk and survival regressions

Conjugate priors for Bayesian analyses of relative risks can be quite restrictive, because their shape depends on their location. By introducing a separate location parameter, however, these priors generalize to allow modeling of a broad range of prior opinions, while still preserving the computational simplicity of conjugate analyses. The present article illustrates the resulting generalized conjugate analyses using examples from case-control studies of the association of residential wire codes and magnetic fields with childhood leukemia.     

Overview of techniques to account for confounding due to population stratification and cryptic relatedness in genomic data association analyses

Population-based genomic association analyses are more powerful than within-family analyses. However, population stratification (unknown or ignored origin of individuals from multiple source populations) and cryptic relatedness (unknown or ignored covariance between individuals because of their relatedness) are confounding factors in population-based genomic association analyses, which inflate the false-positive rate. As a consequence, false association signals may arise in genomic data association analyses for reasons other than true association between the tested genomic factor (marker genotype, gene or protein expression) and the study phenotype. It is therefore important to correct or account for these confounders in population-based genomic data association analyses. The common correction techniques for population stratification and cryptic relatedness problems are presented here in the phenotype–marker association analysis context, and comments on their suitability for other types of genomic association analyses (for example, phenotype–expression association) are also provided. Even though many of these techniques have originally been developed in the context of human genetics, most of them are also applicable to model organisms and breeding populations.     

Calcium channel auxiliary subunits

Many channels and carriers associate with auxiliary subunits which modify their activities and facilitate biogenesis. Advances in genome sequencing as well as biochemical, molecular genetic, and physiological experimentation have allowed for the discovery of many transport auxiliary subunits. Recent interests in the pharmacology of the calcium auxiliary subunits prompted a large amount of effort in deciphering their specific role in the conductance of calcium ions. In this review, we evaluate the functions of the 'extra' subunits of the voltage-gated calcium channels in animals as an example of auxiliary subunits of transporters in general. We discuss the functional data available for each of these subunits, present phylogenetic analyses, and discuss their potential evolutionary origins. Our analyses also reveal novel homologues of these subunits which might be of interest to the community.     

Bacterial adaptation to life in association with plants - A proteomic perspective from culture to in situ conditions

Diverse bacterial taxa that live in association with plants affect plant health and development. This is most evident for those bacteria that undergo a symbiotic association with plants or infect the plants as pathogens. Proteome analyses have contributed significantly toward a deeper understanding of the molecular mechanisms underlying the development of these associations. They were applied to obtain a general overview of the protein composition of these bacteria, but more so to study effects of plant signaling molecules on the cytosolic proteome composition or metabolic adaptations upon plant colonization. Proteomic analyses are particularly useful for the identification of secreted proteins, which are indispensable to manipulate a host plant. Recent advances in the field of proteome analyses have initiated a new research area, the analysis of more complex microbial communities. Such studies are just at their beginning but hold great potential for the future to elucidate not only the interactions between bacteria and their host plants, but also of bacteria-bacteria interactions between different bacterial taxa when living in association with plants. These include not only the symbiotic and pathogenic bacteria, but also the commensal bacteria that are consistently found in association with plants and whose functions remain currently largely uncovered.     

Complexities and uncertainties of neuronal network function

The nervous system generates behaviours through the activity in groups of neurons assembled into networks. Understanding these networks is thus essential to our understanding of nervous system function. Understanding a network requires information on its component cells, their interactions and their functional properties. Few networks come close to providing complete information on these aspects. However, even if complete information were available it would still only provide limited insight into network function. This is because the functional and structural properties of a network are not fixed but are plastic and can change over time. The number of interacting network components, their (variable) functional properties, and various plasticity mechanisms endows networks with considerable flexibility, but these features inevitably complicate network analyses. This review will initially discuss the general approaches and problems of network analyses. It will then examine the success of these analyses in a model spinal cord locomotor network in the lamprey, to determine to what extent in this relatively simple vertebrate system it is possible to claim detailed understanding of network function and plasticity.     

Bosque: integrated phylogenetic analysis software

Phylogenetic analyses today involve dealing with computer files in different formats and often several computer programs. Although some widely used applications have integrated important functionalities for such analyses, they still work with local resources only: input/output files (users have to manage them) and local computing (users have sometimes to leave their programs, on their desktop computers, running for extended periods of time). To address these problems we have developed 'Bosque', a multi-platform client-server software that performs standard phylogenetic tasks either locally or remotely on servers, and integrates the results on a local relational database. Bosque performs sequence alignments and graphical visualization and editing of trees, thus providing a powerful environment that integrates all the steps of phylogenetic analyses. AVAILABILITY: http://bosque.udec.cl     

Multilocus definition of MHC haplotypes in pedigreed cynomolgus macaques (Macaca fascicularis)

Cynomolgus macaques (Macaca fascicularis) are used widely in biomedical research, and the genetics of their MHC (Mhc-Mafa) has become the focus of considerable attention in recent years. The cohort of Indonesian pedigreed macaques that we present here was typed for Mafa-A, -B, and -DR, by sequencing, as described in earlier studies. Additionally, the DRB region of these animals was characterised by microsatellite analyses. In this study, full-length sequencing of Mafa-DPA/B and -DQA/B in these animals was performed. A total of 75 different alleles were observed; 22 of which have not previously been reported, plus 18 extended exon 2 alleles that were already known. Furthermore, two microsatellites, D6S2854 and D6S2859, were used to characterise the complex Mafa-A region. Sequencing and segregation analyses revealed that the length patterns of these microsatellites are unique for each Mafa-A haplotype. In this work, we present a pedigreed colony of approximately 120 cynomolgus macaques; all of which are typed for the most significant polymorphic MHC class I and class II markers. Offspring of these pedigreed animals are easily characterised for their MHC by microsatellite analyses on the Mafa-A and -DRB regions, which makes the cumbersome sequencing analyses redundant.     

A mechanical perspective on foliage leaf form and function

The mechanical behaviour of large foliage leaves in response to static and dynamic mechanical forces is reviewed in the context of a few basic engineering principles and illustrated in terms of species drawn from a variety of vascular plant lineages. When loaded under their own weight or subjected to externally applied forces, petioles simultaneously bend and twist, and thus mechanically operate as cantilevered beams. The stresses that develop in petioles reach their maximum intensities either at their surface or very near their centroid axes, where they are accommodated either by living and hydrostatic tissues (parenchyma and collenchyma) or dead and stiff tissues (sclerenchyma and vascular fibres) depending on the size of the leaf and the species from which it is drawn. Allometric analyses of diverse species indicate size-dependent variations in petiole length, transverse shape, geometry and stiffness that accord well with those required to maintain a uniform tip-deflection for leaves with laminae differing in mass. When dynamically loaded, the laminae of many broad-leaved species fold and curl into streamlined objects, thereby reducing the drag forces that they experience and transmit to their subtending petioles and stems. From a mechanical perspective, the laminae of these species operate as stress-skin panels that distribute point loads more or less equally over their entire surface. Although comparatively little is known about the mechanical structure and behaviour of foliage leaves, new advances in engineering theory and computer analyses reveal these organs to be far more complex than previously thought. For example, finite-element analyses of the base of palm leaves reveal that stresses are decreased when these structures are composed of anisotropic as opposed to isotropic materials (tissues).     

Insight into the physiological functions of PDGF through genetic studies in mice

Genetic analyses in mice have contributed significantly to the understanding of the physiological functions of platelet-derived growth factors (PDGFs) and their receptors. Phenotypic analyses of gene knockouts of PDGF-A, PDGF-B, PDGF alpha-receptors (PDGFRalpha) and beta-receptors (PDGFRbeta) have shown that these ligands and receptors play major roles during embryonic development. Conditional and subtle mutations in the same genes and analysis of chimeric mice have provided additional information about the roles of these genes in postnatal development. Transgenic over-expression studies have also demonstrated that PDGF ligands are capable of inducing pathological cell proliferation in a number of different organs. The present review summarizes these findings and discusses their implications for mammalian development and disease.     

The impact of fossils and taxon sampling on ancient molecular dating analyses

The number and complexity of molecular dating studies has increased over the past decade. Along with a broadening acceptance of their utility has come significant controversy over the methods and models that are appropriate, as well as the accuracy of the estimates yielded by molecular clock analyses. Radically different age estimates have been published for the same divergences from analyses of different datasets with different fossil constraints obtained with different methods, and the underlying explanation for these differences is often unclear. Here we utilize two previously published datasets to examine the effect of fossil calibrations and taxon sampling on the age estimates for two deep eukaryote divergences in an attempt to discern the relative impact of these factors. Penalized likelihood, non-parametric rate smoothing, and Bayesian methods were utilized to generate age estimates for the origin of the Metazoa from a 7-gene dataset and for the divergence of Eukaryotes from a 129-gene dataset. From these analyses, it is clear that the fossil calibrations chosen and the method for applying constraints to these nodes have a large impact on age estimates, while the degree of taxon sampling within a dataset is less important in terms of the resulting age estimates. Concerns and recommendations for addressing these two factors when initiating a dating analysis are discussed.     

The genetic analysis of tropic responses

An increasing number of studies on tropic responses includes the genetic analysis of mutants defective in these morphogenetic processes. This review collates the information and discusses the implications of this approach to such studies. The review is organized on a systematic basis because most genetic analyses are insufficiently complete for general principles to have emerged. The most advanced analyses are those of lower eukaryotes because of their haploidy and the ease with which they can be manipulated in vitro. The extensive studies of phototropism, gravitropism and autochemotropism in the fungus Phycomyces blakesleeanus and of phototropism, polarotropism and gravitropism in the moss Physcomitrella patens are reviewed. In comparison with these studies, the genetic analysis of tropic responses in particular species of flowering plants is more limited. However, comparative physiological and ultra-structural studies of individual mutant and wild-type strains have been performed for a number of species. These results are discussed with particular regard to their support for established hypotheses.     

Covariate and multinomial: Accounting for distance in movement in capture–recapture analyses

Many biological quantities cannot be measured directly but rather need to be estimated from models. Estimates from models are statistical objects with variance and, when derived simultaneously, covariance. It is well known that their variance–covariance (VC) matrix must be considered in subsequent analyses. Although it is always preferable to carry out the proposed analyses on the raw data themselves, a two‐step approach cannot always be avoided. This situation arises when the parameters of a multinomial must be regressed against a covariate. The Delta method is an appropriate and frequently recommended way of deriving variance approximations of transformed and correlated variables. Implementing the Delta method is not trivial, and there is a lack of a detailed information on the procedure in the literature for complex situations such as those involved in constraining the parameters of a multinomial distribution. This paper proposes a how‐to guide for calculating the correct VC matrices of dependant estimates involved in multinomial distributions and how to use them for testing the effects of covariates in post hoc analyses when the integration of these analyses directly into a model is not possible. For illustrative purpose, we focus on variables calculated in capture–recapture models, but the same procedure can be applied to all analyses dealing with correlated estimates with multinomial distribution and their variances and covariances.     

The use of otolith shape and chemistry to determine stock structure of Mediterranean horse mackerel Trachurus mediterraneus (Steindachner)

Otolith shape and chemistry of Mediterranean horse mackerel Trachurus mediterraneus were simultaneously used to assess the feasibility of using these natural tags to discriminate populations throughout the Black, Marmara, Aegean and eastern Mediterranean Seas. Otolith shape and chemistry analyses showed a similar pattern of differentiation between T. mediterraneus stocks, revealing a clear discreteness of the middle Black Sea (Sinop) and Aegean Sea (Izmir) samples. Otolith upper side length and width, and Na, K, Mg and Ba, were the morphological traits and trace elements, respectively, differing most among groups. Overall assignment of individuals into their original sample was high for both otolith shape and chemistry. Highest reclassification rate was observed for the south-middle Black Sea and Aegean Sea samples for both analyses. Hierarchical cluster analyses also supported high differentiation of the south-middle Black Sea and Aegean Sea samples for both analyses. Mantel's test revealed that the Euclidean distance both for otolith shape ( r =−0·0917, P > 0·05) and chemistry ( r =−0·1248, P > 0·05) between these populations were not significantly associated with their geographical distances.     

Expression of virus-encoded proteinases: functional and structural similarities with cellular enzymes.

Many viruses express their genome, or part of their genome, initially as a polyprotein precursor that undergoes proteolytic processing. Molecular genetic analyses of viral gene expression have revealed that many of these processing events are mediated by virus-encoded proteinases. Biochemical activity studies and structural analyses of these viral enzymes reveal that they have remarkable similarities to cellular proteinases. However, the viral proteinases have evolved unique features that permit them to function in a cellular environment. In this article, the current status of plant and animal virus proteinases is described along with their role in the viral replication cycle. The reactions catalyzed by viral proteinases are not simple enzyme-substrate interactions; rather, the processing steps are highly regulated, are coordinated with other viral processes, and frequently involve the participation of other factors.