A multiple-outgroup approach to resolving division-level phylogenetic relationships using 16S rDNA data

The 16S rRNA gene (16S rDNA) is currently the most widely used gene for estimating the evolutionary history of prokaryotes, To date, there are more than 30 000 16S rDNA sequences available from the core databases, GenBank, EMBL and DDBJ, This great number may cause a dilemma when composing datasets for phylogenetic analysis, since the choice and number of reference organisms are known to affect the resulting tree topology. A group of sequences appearing monophyletic in one dataset may not be so in another. This can be especially problematic when establishing the relationships of distantly related sequences at the division (phylum) level. In this study, a multiple-outgroup approach to resolving division-level phylogenetic relationships is suggested using 16S rDNA data. The approach is illustrated by two case studies concerning the monophyly of two recently proposed bacterial divisions, OP9 and OP10.

Globalisation and sustainability: environmental Kuznets curve and the WTO

Economic globalisation is seen by many as a driving force for global economic growth. Yet opinion is divided about the benefits of this process, as highlighted by the WTO meeting in Seattle in late 1999. Proponents of economic globalisation view it as a positive force for environmental improvement and as a major factor increasing the likelihood of sustainable development through its likely boost to global investment. These proponents mostly appeal to analysis based on the environmental Kuznets curve (EKC) to support their views about environmental improvement. But EKC-analysis has significant deficiencies. Furthermore, it is impossible to be confident that the process of economic globalisation will result in sustainable development, if 'weak conditions' only are satisfied. 'Strong conditions' probably need to be satisfied to achieve sustainable development, and given current global institutional arrangements, these are likely to be violated by the economic globalisation process. Global political action seems to be needed-to avert a deterioration in the global environment and to prevent unsustainability of development. This exposition demonstrates the limitations of EKC-analysis, identifies positive and negative effects of economic globalisation on pollution levels, and highlights connections between globalisation and the debate about whether strong or weak conditions are required for sustainable development. The article concludes with a short discussion of the position of WTO in relation to trade and the environment and the seemingly de facto endorsement of WTO of weak conditions for sustainable development. It suggests that WTO's relative neglect of environmental concerns is no longer politically tenable and needs to be reassessed in the light of recent developments in economic analysis. The skew of economic growth, e.g. in favour of developing countries, is shown to be extremely important from a global environmental perspective. (C) 2001 Elsevier Science B.V. All rights reserved.

Time of treatment influences the appearance of drug-resistant parasites in Plasmodium falciparum infections

A deterministic mathematical model which predicts the probability of developing a new drug-resistant parasite population within the human host is reported, The model incorporates the host's specific antibody response to PfEMP1, and also investigates the influence of chemotherapy on the probability of developing a viable drug-resistant parasite population within the host. Results indicate that early, treatment, and a high antibody threshold coupled with a long lag time between antibody stimulation and activity, are risk factors which increase the likelihood of developing a viable drug-resistant parasite population. High parasite mutation rates and fast PfEMP1 var gene switching are also identified as risk factors. The model output allows the relative importance of the various risk factors as well as the relationships between them to be established, thereby increasing the understanding of the conditions which favour the development of a new drug-resistant parasite population.

A zero-augmented gamma mixed model for longitudinal data with many zeros

In many occupational safety interventions, the objective is to reduce the injury incidence as well as the mean claims cost once injury has occurred. The claims cost data within a period typically contain a large proportion of zero observations (no claim). The distribution thus comprises a point mass at 0 mixed with a non-degenerate parametric component. Essentially, the likelihood function can be factorized into two orthogonal components. These two components relate respectively to the effect of covariates on the incidence of claims and the magnitude of claims, given that claims are made. Furthermore, the longitudinal nature of the intervention inherently imposes some correlation among the observations. This paper introduces a zero-augmented gamma random effects model for analysing longitudinal data with many zeros. Adopting the generalized linear mixed model (GLMM) approach reduces the original problem to the fitting of two independent GLMMs. The method is applied to evaluate the effectiveness of a workplace risk assessment teams program, trialled within the cleaning services of a Western Australian public hospital.

A mixture model-based approach to the clustering of microarray expression data

Motivation: This paper introduces the software EMMIX-GENE that has been developed for the specific purpose of a model-based approach to the clustering of microarray expression data, in particular, of tissue samples on a very large number of genes. The latter is a nonstandard problem in parametric cluster analysis because the dimension of the feature space (the number of genes) is typically much greater than the number of tissues. A feasible approach is provided by first selecting a subset of the genes relevant for the clustering of the tissue samples by fitting mixtures of t distributions to rank the genes in order of increasing size of the likelihood ratio statistic for the test of one versus two components in the mixture model. The imposition of a threshold on the likelihood ratio statistic used in conjunction with a threshold on the size of a cluster allows the selection of a relevant set of genes. However, even this reduced set of genes will usually be too large for a normal mixture model to be fitted directly to the tissues, and so the use of mixtures of factor analyzers is exploited to reduce effectively the dimension of the feature space of genes. Results: The usefulness of the EMMIX-GENE approach for the clustering of tissue samples is demonstrated on two well-known data sets on colon and leukaemia tissues. For both data sets, relevant subsets of the genes are able to be selected that reveal interesting clusterings of the tissues that are either consistent with the external classification of the tissues or with background and biological knowledge of these sets.

Genetic Covariation between Serum {gamma}-Glutamyltransferase Activity and Cardiovascular Risk Factors

Background: Several studies have shown that variation in serum gamma-glutamyltransferase (GGT) in the population is associated with risk of death or development of cardiovascular disease, type 2 diabetes, stroke, or hypertension. This association is only partly explained by associations between GGT and recognized risk factors. Our aim was to estimate the relative importance of genetic and environmental sources of variation in GGT as well as genetic and environmental sources of covariation between GGT and other liver enzymes and markers of cardiovascular risk in adult twin pairs. Methods: We recruited 1134 men and 2241 women through the Australian Twin Registry. Data were collected through mailed questionnaires, telephone interviews, and by analysis of blood samples. Sources of variation in GGT, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and of covariation between GGT and cardiovascular risk factors were assessed by maximum-likelihood model-fitting. Results: Serum GGT, ALT, and AST were affected by additive genetic and nonshared environmental factors, with heritabilities estimated at 0.52, 0.48, and 0.32, respectively. One-half of the genetic variance in GGT was shared with ALT, AST, or both. There were highly significant correlations between GGT and body mass index; serum lipids, lipoproteins, glucose, and insulin; and blood pressure. These correlations were more attributable to genes that affect both GGT and known cardiovascular risk factors than to environmental factors. Conclusions: Variation in serum enzymes that reflect liver function showed significant genetic effects, and there was evidence that both genetic and environmental factors that affect these enzymes can also affect cardiovascular risk. (C) 2002 American Association for Clinical Chemistry.

Gene-Environment Interaction Effects on Behavioral Variation and Risk of Complex Disorders: The Example of Alcoholism and Other Psychiatric Disorders

There have been few replicated examples of genotype x environment interaction effects on behavioral variation or risk of psychiatric disorder. We review some of the factors that have made detection of genotype x environment interaction effects difficult, and show how genotype x shared environment interaction (GxSE) effects are commonly confounded with genetic parameters in data from twin pairs reared together. Historic data on twin pairs reared apart can in principle be used to estimate such GxSE effects, but have rarely been used for this purpose. We illustrate this using previously published data from the Swedish Adoption Twin Study of Aging (SATSA), which suggest that GxSE effects could account for as much as 25% of the total variance in risk of becoming a regular smoker. Since few separated twin pairs will be available for study in the future, we also consider methods for modifying variance components linkage analysis to allow for environmental interactions with linked loci.

Geographical variation in the penetrance of CDKN2A mutations for melanoma

Background: Germline mutations in the CDKN2A gene, which encodes two proteins (p16INK4A and p14ARF), are the most common cause of inherited susceptibility to melanoma. We examined the penetrance of such mutations using data from eight groups from Europe, Australia and the United States that are part of The Melanoma Genetics Consortium Methods: We analyzed 80 families with documented CDKN2A mutations and multiple cases of cutaneous melanoma. We modeled penetrance for melanoma using a logistic regression model incorporating survival analysis. Hypothesis testing was based on likelihood ratio tests. Covariates included gender, alterations in p14APF protein, and population melanoma incidence rates. All statistical tests were two-sided. Results: The 80 analyzed families contained 402 melanoma patients, 320 of whom were tested for mutations and 291 were mutation carriers. We also tested 713 unaffected family members for mutations and 194 were carriers. Overall, CDKN2A mutation penetrance was estimated to be 0.30 (95% confidence interval (CI) = 0.12 to 0.62) by age 50 years and 0.67 (95% CI = 0.31 to 0.96) by age 80 years. Penetrance was not statistically significantly modified by gender or by whether the CDKN2A mutation altered p14ARF protein. However, there was a statistically significant effect of residing in a location with a high population incidence rate of melanoma (P = .003). By age 50 years CDKN2A mutation penetrance reached 0.13 in Europe, 0.50 in the United States, and 0.32 in Australia; by age 80 years it was 0.58 in Europe, 0.76 in the United States, and 0.91 in Australia. Conclusions: This study, which gives the most informed estimates of CDKN2A mutation penetrance available, indicates that the penetrance varies with melanoma population incidence rates. Thus, the same factors that affect population incidence of melanoma may also mediate CDKN2A penetrance.

Atom lasers, coherent states, and coherence. I. Physically realizable ensembles of pure states

A laser, be it an optical laser or an atom laser, is an open quantum system that produces a coherent beam of bosons (photons or atoms, respectively). Far above threshold, the stationary state rho(ss) of the laser mode is a mixture of coherent-field states with random phase, or, equivalently, a Poissonian mixture of number states. This paper answers the question: can descriptions such as these, of rho(ss) as a stationary ensemble of pure states, be physically realized? Here physical realization is as defined previously by us [H. M. Wiseman and J. A. Vaccaro, Phys. Lett. A 250, 241 (1998)]: an ensemble of pure states for a particular system can be physically realized if, without changing the dynamics of the system, an experimenter can (in principle) know at any time that the system is in one of the pure-state members of the ensemble. Such knowledge can be obtained by monitoring the baths to which the system is coupled, provided that coupling is describable by a Markovian master equation. Using a family of master equations for the (atom) laser, we solve for the physically realizable (PR) ensembles. We find that for any finite self-energy chi of the bosons in the laser mode, the coherent-state ensemble is not PR; the closest one can come to it is an ensemble of squeezed states. This is particularly relevant for atom lasers, where the self-energy arising from elastic collisions is expected to be large. By contrast, the number-state ensemble is always PR. As the self-energy chi increases, the states in the PR ensemble closest to the coherent-state ensemble become increasingly squeezed. Nevertheless, there are values of chi for which states with well-defined coherent amplitudes are PR, even though the atom laser is not coherent (in the sense of having a Bose-degenerate output). We discuss the physical significance of this anomaly in terms of conditional coherence (and hence conditional Bose degeneracy).

The ethics of germ line gene manipulation - A five dimensional debate

Contributors to the debate surrounding the ethics of germ line gene manipulation have by and large concentrated their efforts on discussions of the potential risks that are associated with the use of this technology. Many international advisory committees have ruled out the acceptability of germ line gene manipulation at least for the time being. The purpose of this work is to generate much needed discussion on the many other ethical issues concerning the implementation of not only germ line gene manipulation but also other related biotechnologies. In this paper I systematically investigate and analyse the most salient issues put forward by proponents and opponents alike. I argue that if germ line manipulation proves to be a safe and effective procedure, then the principle of beneficence imposes on the medical profession a moral duty to pursue the technology.

On positive solutions of nonlinear elliptic equations involving concave and critical nonlinearities

We study the existence of nonnegative solutions of elliptic equations involving concave and critical Sobolev nonlinearities. Applying various variational principles we obtain the existence of at least two nonnegative solutions.

Reconciling paleodistribution models and comparative phylogeography in the Wet Tropics rainforest land snail Gnarosophia bellendenkerensis (Brazier 1875)

Comparative phylogeography has proved useful for investigating biological responses to past climate change and is strongest when combined with extrinsic hypotheses derived from the fossil record or geology. However, the rarity of species with sufficient, spatially explicit fossil evidence restricts the application of this method. Here, we develop an alternative approach in which spatial models of predicted species distributions under serial paleoclimates are compared with a molecular phylogeography, in this case for a snail endemic to the rainforests of North Queensland, Australia. We also compare the phylogeography of the snail to those from several endemic vertebrates and use consilience across all of these approaches to enhance biogeographical inference for this rainforest fauna. The snail mtDNA phylogeography is consistent with predictions from paleoclimate modeling in relation to the location and size of climatic refugia through the late Pleistocene-Holocene and broad patterns of extinction and recolonization. There is general agreement between quantitative estimates of population expansion from sequence data (using likelihood and coalescent methods) vs. distributional modeling. The snail phylogeography represents a composite of both common and idiosyncratic patterns seen among vertebrates, reflecting the geographically finer scale of persistence and subdivision in the snail. In general, this multifaceted approach, combining spatially explicit paleoclimatological models and comparative phylogeography, provides a powerful approach to locating historical refugia and understanding species' responses to them.

Mapping intertidal habitats and an evaluation of their conservation status in Queensland, Australia

The goal of biodiversity conservation has been described as the conservation of diversity at three levels: ecosystem, species and genetic diversity. Developing a representative system of marine protected areas (MPAs) is considered an effective way to achieve this goal in the marine environment. In the absence of detailed information relating to biological distributions there has been increasing use of biodiversity surrogates to determine MPA priorities at regional levels. The development of biodiversity surrogates at fine scales (i.e. habitats) will have an increasingly important role in the identification of sites that will contribute to a representative system of MPAs. This is because it will increase the likelihood that the system will adequately achieve biodiversity objectives by ensuring protection of a greater range of habitats and species. This article provides an explanation of an intertidal shoreline habitat surrogate used to describe 24,216km of Queensland's coastline. The protective status of intertidal habitats was evaluated to assist with designing a representative system of intertidal MPAs. (C) 2002 Elsevier Science Ltd. All rights reserved.

Combining the analyses of introgressive hybridisation and linkage mapping to investigate the genetic architecture of population divergence in the lake whitefish (Coregonus clupeaformis, Mitchill)

Adaptation and reproductive isolation, the engines of biological diversity, are still elusive when discussing the genetic bases of speciation. Namely, the number of genes and magnitude of selection acting positively or negatively on genomic traits implicated in speciation is contentious. Here, we describe the first steps of an ongoing research program aimed at understanding the genetic bases of population divergence and reproductive isolation in the lake whitefish (Coregonus clupeaformis). A preliminary linkage map originating from a hybrid cross between dwarf and normal ecotypes is presented, whereby some of the segregating AFLP markers were found to be conserved among natural populations. Maximum-likelihood was used to estimate hybrid indices from non-diagnostic markers at 998 AFLP loci. This allowed identification of the most likely candidate loci that have been under the influence of selection during the natural hybridisation of whitefish originating from different glacial races. As some of these loci could be identified on the linkage map, the possibility that selection of traits in natural populations may eventually be correlated to specific chromosomal regions was demonstrated. The future prospects and potential of these approaches to elucidate the genetic bases of adaptation and reproductive isolation among sympatric ecotypes of lake whitefish is discussed.