Bayesian estimation of ancestral character states on phylogenies

Biologists frequently attempt to infer the character states at ancestral nodes of a phylogeny from the distribution of traits observed in contemporary organisms. Because phylogenies are normally inferences from data, it is desirable to account for the uncertainty in estimates of the tree and its branch lengths when making inferences about ancestral states or other comparative parameters. Here we present a general Bayesian approach for testing comparative hypotheses across statistically justified samples of phylogenies, focusing on the specific issue of reconstructing ancestral states. The method uses Markov chain Monte Carlo techniques for sampling phylogenetic trees and for investigating the parameters of a statistical model of trait evolution. We describe how to combine information about the uncertainty of the phylogeny with uncertainty in the estimate of the ancestral state. Our approach does not constrain the sample of trees only to those that contain the ancestral node or nodes of interest, and we show how to reconstruct ancestral states of uncertain nodes using a most-recent-common-ancestor approach. We illustrate the methods with data on ribonuclease evolution in the Artiodactyla. Software implementing the methods ( BayesMultiState) is available from the authors.

A phylogenetic mixture model for detecting pattern-heterogeneity in gene sequence or character-state data

We describe a general likelihood-based 'mixture model' for inferring phylogenetic trees from gene-sequence or other character-state data. The model accommodates cases in which different sites in the alignment evolve in qualitatively distinct ways, but does not require prior knowledge of these patterns or partitioning of the data. We call this qualitative variability in the pattern of evolution across sites "pattern-heterogeneity" to distinguish it from both a homogenous process of evolution and from one characterized principally by differences in rates of evolution. We present studies to show that the model correctly retrieves the signals of pattern-heterogeneity from simulated gene-sequence data, and we apply the method to protein-coding genes and to a ribosomal 12S data set. The mixture model outperforms conventional partitioning in both these data sets. We implement the mixture model such that it can simultaneously detect rate- and pattern-heterogeneity. The model simplifies to a homogeneous model or a rate- variability model as special cases, and therefore always performs at least as well as these two approaches, and often considerably improves upon them. We make the model available within a Bayesian Markov-chain Monte Carlo framework for phylogenetic inference, as an easy-to-use computer program.

Hypothesis about mechanisms through which nicotine might exert its effect on the interdependence of inflammation and gut barrier function in ulcerative colitis

Ulcerative colitis (UC) is characterized by impairment of the epithelial barrier and the formation of ulcer-type lesions, which result in local leaks and generalized alterations of mucosal tight junctions. Ultimately, this results in increased basal permeability. Although disruption of the epithelial barrier in the gut is a hallmark of inflammatory bowel disease and intestinal infections, it remains unclear whether barrier breakdown is an initiating event of UC or rather a consequence of an underlying inflammation, evidenced by increased production of proinflammatory cytokines. UC is less common in smokers, suggesting that the nicotine in cigarettes may ameliorate disease severity. The mechanism behind this therapeutic effect is still not fully understood, and indeed it remains unclear if nicotine is the true protective agent in cigarettes. Nicotine is metabolized in the body into a variety of metabolites and can also be degraded to form various breakdown products. It is possible these metabolites or degradation products may be the true protective or curative agents. A greater understanding of the pharmacodynamics and kinetics of nicotine in relation to the immune system and enhanced knowledge of out permeability defects in UC are required to establish the exact protective nature of nicotine and its metabolites in UC. This review suggests possible hypotheses for the protective mechanism of nicotine in UC, highlighting the relationship between gut permeability and inflammation, and indicates where in the pathogenesis of the disease nicotine may mediate its effect.

Modelling the interdependence between the stoichiometry of receptor oligomerization and ligand binding for a coexisting dimer/tetramer receptor system

Many G protein-coupled receptors have been shown to exist as oligomers, but the oligomerization state and the effects of this on receptor function are unclear. For some G protein-coupled receptors, in ligand binding assays, different radioligands provide different maximal binding capacities. Here we have developed mathematical models for co-expressed dimeric and tetrameric species of receptors. We have considered models where the dimers and tetramers are in equilibrium and where they do not interconvert and we have also considered the potential influence of the ligands on the degree of oligomerization. By analogy with agonist efficacy, we have considered ligands that promote, inhibit or have no effect on oligomerization. Cell surface receptor expression and the intrinsic capacity of receptors to oligomerize are quantitative parameters of the equations. The models can account for differences in the maximal binding capacities of radioligands in different preparations of receptors and provide a conceptual framework for simulation and data fitting in complex oligomeric receptor situations.

Simultaneous bridge-localized and mixed-valence character in diruthenium radical cations featuring diethynylaromatic bridging ligands

A series of bimetallic ruthenium complexes [{Ru(dppe)Cp*}2(μ-C≡CArC≡C)] featuring diethynylaromatic bridging ligands (Ar = 1,4-phenylene, 1,4-naphthylene, 9,10-anthrylene) have been prepared and some representative molecular structures determined. A combination of UV–vis–NIR and IR spectroelectrochemical methods and density functional theory (DFT) have been used to demonstrate that one-electron oxidation of compounds [{Ru(dppe)Cp*}2(μ-C≡CArC≡C)](HC≡CArC≡CH = 1,4-diethynylbenzene; 1,4-diethynyl-2,5-dimethoxybenzene; 1,4-diethynylnaphthalene; 9,10-diethynylanthracene) yields solutions containing radical cations that exhibit characteristics of both oxidation of the diethynylaromatic portion of the bridge, and a mixed-valence state. The simultaneous population of bridge-oxidized and mixed-valence states is likely related to a number of factors, including orientation of the plane of the aromatic portion of the bridging ligand with respect to the metal d-orbitals of appropriate π-symmetry.

Self, role and character: developing a professional identity as a drama teacher

The paper reports on research into what may have influenced trainees on four post-graduate teacher training courses in England to become specialist drama teachers rather than pursue careers in the world of professional entertainment. In doing so it raises questions regarding the value of considering teaching as a performing art. The paper goes on to explore how drama trainees regard an understanding of performance, and an ability to both use and demonstrate performance techniques, as integral to their role as subject specialists. The subsequent discussion examines how a drama teacher’s professional identity may be seen as being made up of the three inter-connected elements, self, role and character. Thus, while all teaching may be considered to involve some elements of performativity , this paper suggests that, for the drama specialist, an understanding of what constitutes ‘performance’ has a particular importance. One conclusion drawn from the research is that recognising the place of performance in their practice may result in experienced teachers of drama regarding themselves as artists whose art is teaching drama; another is that recognising the different ways in which adopting a role may involve performance could be of value to all teachers and teacher educators.