bluuebunny/crossref_metadata_2025 huggingface dataset:
Ancestral sequence reconstruction as a tool to understand natural history and guide synthetic biology: realizing and extending the vision of Zuckerkandl and Pauling
Authors: Gaucher Eric A.
Published: September 2008

The perspective on natural history and medicine by Emile Zuckerkandl combined with the chemical expertise of Linus Pauling generated many novel ideas concerning molecular evolution. These included generating multiple sequence alignments, determining phylogenetic relationships based on sequence data, formulating the molecular clock hypothesis, and the proposal to resurrect ancestral sequences based on information contained within extant sequences, inter alia. Although the field of ancestral sequence reconstruction is still burgeoning, the concepts guiding the field are embraced by today's community more so than when originally proposed by Zuckerkandl and Pauling. This chapter presents a view of the field of ancestral sequence reconstruction, including recognition that genes are dynamic fossils in that they record ancient events while still adapting to new environments. It concludes with a discussion of the potential of combining ancestral sequence space and synthetic biology to expand protein functionality for directed evolution studies.
Estimating the history of mutations on a phylogeny
Authors: Bollback Jonathan P. , Gardner Paul P. , Nielsen Rasmus
Published: September 2008

Evolution has left its signature on the molecules and morphology of living organisms. Ancestral reconstruction offers an excellent tool for understanding the process of evolution using comparative information. Methods for ancestral reconstruction have generally focused on reconstructing the ancestral states at the internal nodes of a phylogeny. Often, we are not interested in particular nodes of the phylogeny but the whole history of a character. This chapter focuses on a Bayesian method for estimating these histories, or mutational paths, on phylogenies. Mutational path methods differ most notably from other approaches in their ability to estimate not only the ancestral states at the internal nodes of a phylogeny, but also the order and timing of mutational changes across the phylogeny. The chapter provides a concise introduction to the statistical tools needed for sampling mutational paths on a phylogeny.
Using ancestral sequence inference to determine the trend of functional divergence after gene duplication
Authors: Gu Xun , Zheng Ying , Huang Yong , Xu Dongping
Published: September 2008

This chapter presents a new approach to functional divergence analysis with the combination of ancestral sequence inference, using the family of animal G-protein subunits as an example. Using the method, the evolutionary trends of two types of functional divergence of amino acid residues after gene duplication are traced. These pieces of evolutionary information are useful for making testable hypotheses about functional divergence between protein subfamilies, such as subtypes of G-protein subunits, which can be verified by further experimentation.
Expression
Authors: Schroeder Mark
Published: September 2008

This chapter explores how the notion of expression should be understood within an expressivist theory. It is first argued that the key attractions of expressivism can be understood without any understanding of expression, in the process illustrating an argumentative technique important for expressivism: the Basic Expressivist Maneuver. The embedding problem is introduced, and used to show that expressivists need to treat sentential connectives as operating on mental states, rather than on propositions or truth values. This conclusion, along with other problems, is then used to dismiss common accounts of the expression relation in favour of the interpretation of expressivism as a kind of assertability semantics. And this, in turn, is used to draw the conclusion that ordinary descriptive sentences must inherit their truth conditions from the mental states that they express.
Composition and Logic
Authors: Schroeder Mark
Published: September 2008

This chapter shows that once we have accepted the solution to the negation problem from Chapter 4, this leads immediately to solutions to analogous problems about conjunction and disjunction, and in fact to a constructive semantics for a very simple normative language with the expressive power of propositional logic. The semantics for this simple language is outlined, and inconsistency, entailment, and validity are defined. It is proven, given very simple assumptions, that the semantics yields the correct results about which sentences are inconsistent with which. Logical inconsistency is distinguished from ordinary inconsistency and given a precise definition, and it is shown why Geach's original moral modus ponens argument is logically valid. Finally, a loose end about the inconsistency of ‘murdering is wrong’ and ‘not murdering is wrong’ is set aside.
Descriptive Language and Belief
Authors: Schroeder Mark
Published: September 2008

This chapter takes up the project of analyzing ordinary descriptive belief in terms of the attitude of being for. A first-pass account, according to which believing p is being for proceeding as if p, is developed and dismissed on the basis of the new negation problem: negated descriptive sentences don't turn out to express the right beliefs in order to receive the right truth conditions. This is replaced by the proposal that belief is a biforcated attitude, consisting in two states of being for: being for proceeding as if p, and being for not proceeding as if p. It is shown that this treatment glosses the new negation problem up to the notion of commitment-equivalence. Finally, it is argued that the biforcated attitude analysis of belief is not ad hoc and has other interesting applications, particularly in elucidating the concept of disbelief.
Making Social Sciences More Scientific
Authors: Taagepera Rein
Published: September 2008

Society needs more from social sciences than they have delivered. One reason for falling short is that social science methods have depended excessively on regression and other statistical approaches, neglecting logical model building. Science is not only about the empirical “What is?” but also very much about the conceptual “How should it be on logical grounds?” Statistical approaches are essentially descriptive, while quantitatively formulated logical models are predictive in an explanatory way. This book contrasts the predominance of statistics in today's social sciences with predominance of quantitatively predictive logical models in physics. It shows how to construct predictive models and gives social science examples. Only secondary school mathematics is often needed, plus willingness to simplify reality outrageously. The book also shows how to use and report basic statistical analysis in more informative ways, including emphasis on symmetric regression.
11 Beyond Constraint‐Based Models: Communication Channels and Growth Rates
Authors: Taagepera Rein
Published: September 2008

The number of communication channels may well turn out to be a major building block in constructing quantitatively predictive logical models in social sciences. This number does determine representative assembly sizes and mean durations of cabinets. Some physical and social processes involve minimization or maximization of some quantities. Models for various processes can be formulated as differential equations, especially those that express rates of change in time, space, etc. Quantities that are conserved during changes play an important role in physics and might do so in social sciences.
16 Converting from Descriptive Analysis to Predictive Models
Authors: Taagepera Rein
Published: September 2008

The results of existing statistical analysis can sometimes be used to estimate the parameters in quantitatively predictive logical models. This is important, because it expands the value of previously published work in social sciences. Inferring logical model parameters in this way, however, may require more involved mathematics than direct testing.
18 Beyond Regression: The Need for Predictive Models
Authors: Taagepera Rein
Published: September 2008

Society needs more from social sciences than they have delivered, and this book offers openings. To the society at large, quantitative social scientists presently seem no better at prediction than qualitative historians, philosophers, and journalists — they just look more boring. computers could be a boon to social sciences, but they have turned out a curse in disguise, by enabling people with insufficient understanding of scientific process to use canned computer programs and grind out reams of numbers parading as “results,” to be printed — and hardly ever used again. One may discard this book on the basis of errors of detail, but the problems it points out will still be there. Unless corrected, they will lead to a Ptolemaic dead end.
6 Political Leadership in the European Commission: The Santer and Prodi Commissions, 1995–2005
Authors: Cini Michelle
Published: September 2008

Expectations of the Commission's ability to provide leadership derived from its treaty functions, the cultivated spillover from them, and the Hallstein and Delors presidencies. Its functions of agenda-setting and policy initiation have given it political influence. President Santer sought to do less in this area and concentrate on the Commission's neglected administrative role. This low-profile, introverted focus on managerial reform left the preparation of enlargement and the Euro to others. Santer's enforced resignation was followed by President Prodi's completion of major East European enlargement and the changeover to the Euro. He was ineffective in enforcing the Stability and Growth Pact, and in his forlorn attempt at federalist treaty reform when the EU was moving increasingly towards intergovernmentalism. Increased intervention by the Council of Ministers and Parliament has confined the Commission to the management of policy networks rather than political leadership.
8 Franco‐German Relations: From Active to Reactive Cooperation
Authors: Cole Alistair
Published: September 2008

Neither the centrality nor cohesion of Franco-German EU potential leadership should be assumed. However, the EU has great institutional, symbolic, economic and political resources enabling it to initiate increased integration and formulate acceptable compromises to others. The Common Agricultural Policy was an enduring bilateral bargain. Any pretence of a hegemonic Franco-German directorate receded under the leadership of Chirac and Schröder, Sarkozy and Merkel. Disagreements over enlargement and constitutional provisions in particular have increased other bilateral and multilateral relationships in a larger EU. Where Franco-German agreement exists on intergovernmental matters they can block changes or enforce issues relating to the Stability and Growth Pact sanctions on which Germany had insisted. On foreign and defence policy (e.g., over Iraq), Germany has moved closer to France than the USA, while both Merkel and Sarkozy promoted a minimal substitute for the constitutional reform fiasco. Their leadership capacity is no longer what it used to be.
10 Leaderless Enlargement? The Difficult Reform of the New Pan‐European Political System
Authors: Magone José M.
Published: September 2008

Far from EU enlargement and deepening being contradictory, the addition of new members to the EU led to new policies such as the redistributive regional policy structural funds consequent on the southward expansion of the 1980s. They became second only to the Common Agricultural Policy in expenditure. Northern enlargement encouraged environmental, social, and employment policies, while Central and Eastern enlargement was based on democratic and anti-corruption conditionality. Members who favoured enlargement were Britain, the Scandinavian countries, and Germany, while the others were either reticent or hostile, notably France towards Turkish accession. Enlargement was on elite-led process, popular hostility contributing to the rejection of the constitutional referendum in France and the Netherlands. Enlargement has necessitated institutional and financial adjustments, increasing problems of convergence and of leadership.
13 The European Parliament: Leadership and ‘Followership’
Authors: Judge David , Earnshaw David
Published: September 2008

Can the European Parliament (EP) provide a democratic leadership link with citizen followers? Because there is no EU government, the EU cannot be authorized by and accountable to the EP which has had to exercise leadership in three other ways. First, it acted as a visionary constitutional entrepreneur in preparing the draft Treaty of European Union and the abortive Constitutional Treaty. Second, the EP has held the Commission to account and influenced and legitimized its agenda through prior authorization. Third, the EP has contributed to policy leadership, notably in environment, water policy, and biotechnology. Nevertheless, the EP's past and likely future leadership role derives from the fact that as the only directly elected supranational institution, it can offer the prospect of participative followership.
15 Collective Leadership in Leaderless Europe: A Sceptical View
Authors: Dimitrakopoulos Dionyssis G.
Published: September 2008

Collective leadership is about choosing priorities and resolving conflicts by a group of actors through compromise. However, it weakens clarity, speed, and uniformity of decisions and blurs responsibility. Nevertheless, it is how the EU is meant to operate through the Commission, the Council of Ministers, and the European Council. The Commission acts collegially and both councils avoid voting, seeking consensus, as does the European Parliament. System preservation is as important as problem solving, but it was an integrated way of achieving a single market and currency. The future prospects for effective collective leadership look bleak without shared material interests, e.g., budgetary negotiations, or ideology, such as controversial neo-liberal policy, or a clear institutional leadership, weakened by enlargement.
The Role of Structure in Plato's Mereological Writings
Authors: Koslicki Kathrin
Published: September 2008

The methodological and ontological considerations that arose in connection with Kit Fine's theory of embodiments provide motivation to search for an alternative approach which preserves the neo-Aristotelian spirit of Fine's account while avoiding its troubling features. Since the kind of theory of composition for which we are aiming has its historical origins in Aristotle, and, as it turns out in Plato as well, the next two chapters examine some of the rich and rewarding writings of these two ancient authors on parts and wholes, turning first to Plato's mereological writings and Verity Harte's recent insightful readings of them (especially in her Plato on Parts and Wholes: The Metaphysics of Structure); Aristotle's treatment of parts and wholes will be the subject of the following chapter.
7 Early Works (before 403)
Authors: Houghton H. A. G.
Published: September 2008

An analysis of Augustine's works written before 403 shows that his primary citations of John in all cases follow an Old Latin text-type. This is particularly notable in De diuersis quaestionibus 64 and De trinitate 1; the latter is based on a different biblical codex from the rest of the work. Readings unique to Augustine, several of which form part of his mental text, are already in evidence in this early period. In Contra Faustum and Contra Adimantum, Augustine reproduces distinctive features from the text of his opponents; this is also true of his work against Petilianus the Donatist.
8 Middle Period (403 to 419)
Authors: Houghton H. A. G.
Published: September 2008

The chapter begins with an analysis of De consensu euangelistarum, showing that it is based on a Vulgate text-type even though Old Latin forms are found in citations out of the gospel sequence. The long primary citation of John 3 in De peccatorum meritis is also clearly Vulgate. In works against the Donatists Parmenianus and Gaudentius, as well as an anonymous Arian sermon, Augustine again shows himself to be influenced by the biblical text of his opponents. In De baptismo, his use of Cyprian's sententia episcoporum leads to the appearance of Old Latin readings.
9 Later Works (after 419)
Authors: Houghton H. A. G.
Published: September 2008

The analysis of the citations of John in Augustine's works composed after 419 reveals the increasing influence of the Vulgate. In secondary citations the Old Latin forms typical of his mental text are replaced by examples which match the Vulgate. Nonetheless, there are still examples of his customary text, including some unique readings, and in De dono perseuerantiae from 429 Augustine appears to be relying on an Old Latin exemplar for a four-verse citation from John 12. The two works against Maximinus show the similarity of the Arian's text to Codex Monacensis. Augustine's collection of biblical testimonia, the Speculum quis ignorat, has had its original form of text replaced with the Vulgate by a later editor.
3 When does deliberation begin?
Authors: Goodin Robert E. , Niemeyer Simon J.
Published: September 2008

Political deliberation involves both internal reflection and public discussion. The former might be far more important than implied by deliberative democrats' heavy emphasis the discursive component. Analysis of the deliberations of a citizen's jury on an Australian environmental issue shows jurors' attitudes changing more in response to the ‘informational’ phase of the jury proceedings involving a large degree of ‘deliberation within’ than during the formal ‘discussion’ phase. Various ways can be imagined for evoking internal reflection of that sort, even in mass political settings.
4 Talking politics: perils and promise
Authors: Goodin Robert E.
Published: September 2008

In its recent ‘deliberative’ turn, democratic theory has forgotten a conventional wisdom, once widely appreciated, that there is much in politics that is better not discussed. This chapter catalogues what topics might be deemed ‘politically undiscussable’, and why, as a first step toward showing how and to what extent talking about such matters might help or hinder their resolution. One important way discussion helps is by information-pooling helping to establish the truth of the matter. Even where that is not a viable aspiration, discussion might nonetheless serve a ‘premise-revealing’ function, showing one another that we are reasonable agents and in that way helping to desensitize contentious issues.
6 First talk, then vote
Authors: Goodin Robert E.
Published: September 2008

Deliberative democrats offer ‘talk as a decision procedure’. This chapter argues that it is a good ‘discovery procedure’, particularly because of the way it expands the agenda; but talk is a flawed ‘decision procedure’ because ‘path dependency’ can render its outcomes indeterminate or arbitrary. A risk of path dependency is inevitable, insofar as talk is a serial process with dynamic updating, as deliberative democrats want it to be. The best way to capture the benefits of ‘talk as a discovery procedure’, while avoiding the risks of ‘talk as a decision procedure’, is to adopt the rule: ‘first talk, then vote’.
7 Who counts?
Authors: Goodin Robert E.
Published: September 2008

Constituting the demos — deciding who gets a say, or a vote — is the first task of any democracy, but it is a topic on which democratic theory has surprisingly little to offer. ‘Enfranchising all affected interests’ is a good start. When unpacked, however, it turns out that the most defensible version of that rule requires us to extend membership in the demos to every interest that would probably be affected by any possible decision arising out of any possible agenda. Given the broad scope of the ‘possible’, that means we ought, in principle, include just about everyone worldwide in the same demos.
Women‐Friendly Policies
Authors: Kenworthy Lane
Published: September 2008

This chapter examines the impact of ‘women-friendly’ policies — funding or provision of childcare, paid maternity/home care leaves, public employment, promotion of part-time work, tax systems that do not penalize a second earner in a household, and antidiscrimination and affirmative action policies — on women's employment. It also considers the relationship between female employment levels and household income inequality.
Government Benefits
Authors: Kenworthy Lane
Published: September 2008

This chapter begins by examining the relationship between government benefits and inequality and between benefits and employment. It uses a new approach to measuring comparative benefit generosity, the outlines a policy package that can potentially provide generous benefits to working-age individuals and households who need them without creating excessive employment disincentives. The package features generous transfers to those unable to work due to involuntary job loss, sickness, disability, or family responsibilities. However, benefits provided on a temporary basis should be of relatively short duration, and eligibility criteria for those provided on a permanent basis should be fairly strict. In exchange for this strictness, extensive support should be provided for those entering or returning to the work force, in the form of training, job placement, public employment, and childcare. A key component of the benefit package is an employment-conditional earnings subsidy.
MeltDB: a software platform for the analysis and integration of metabolomics experiment data
Authors: Neuweger Heiko , Albaum Stefan P. , Dondrup Michael , Persicke Marcus , Watt Tony , Niehaus Karsten , Stoye Jens , Goesmann Alexander
Published: September 2008

Motivation: The recent advances in metabolomics have created the potential to measure the levels of hundreds of metabolites which are the end products of cellular regulatory processes. The automation of the sample acquisition and subsequent analysis in high-throughput instruments that are capable of measuring metabolites is posing a challenge on the necessary systematic storage and computational processing of the experimental datasets. Whereas a multitude of specialized software systems for individual instruments and preprocessing methods exists, there is clearly a need for a free and platform-independent system that allows the standardized and integrated storage and analysis of data obtained from metabolomics experiments. Currently there exists no such system that on the one hand supports preprocessing of raw datasets but also allows to visualize and integrate the results of higher level statistical analyses within a functional genomics context.

Results: To facilitate the systematic storage, analysis and integration of metabolomics experiments, we have implemented MeltDB, a web-based software platform for the analysis and annotation of datasets from metabolomics experiments. MeltDB supports open file formats (netCDF, mzXML, mzDATA) and facilitates the integration and evaluation of existing preprocessing methods. The system provides researchers with means to consistently describe and store their experimental datasets. Comprehensive analysis and visualization features of metabolomics datasets are offered to the community through a web-based user interface. The system covers the process from raw data to the visualization of results in a knowledge-based background and is integrated into the context of existing software platforms of genomics and transcriptomics at Bielefeld University. We demonstrate the potential of MeltDB by means of a sample experiment where we dissect the influence of three different carbon sources on the gram-negative bacterium Xanthomonas campestris pv. campestris on the level of measured metabolites. Experimental data are stored, analyzed and annotated within MeltDB and accessible via the public MeltDB web server.

Availability: The system is publicly available at http://meltdb.cebitec.uni-bielefeld.de.

Contact:  hneuwege@cebitec.uni-bielefeld.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
An Extract of Antrodia camphorata Mycelia Attenuates the Progression of Nephritis in Systemic Lupus Erythematosus‐Prone NZB/W F1 Mice
Authors: Chang Jia-Ming , Lee Yi-Ru , Hung Le-Mei , Liu Sheng-Yung , Kuo Mao-Tien , Wen Wu-Che , Chen Peini
Published: September 2008

Antrodia camphorata is used in folk medicine for the treatment of inflammation syndromes and liver‐related diseases in Taiwan. The goal of this study was to evaluate the efficacy of the mycelial extract of A. camphorata (ACE) for the treatment of systemic lupus erythematosus (SLE) in SLE‐prone NZB/W F1 mice. After antibodies against double‐stranded DNA appeared in NZB/W mice, the mice were orally administered varying dosages of ACE (100, 200 and 400 mg kg−1) for 5 consecutive days per week for 12 weeks via gavage. To assess the efficacy of ACE, we measured SLE‐associated biochemical and histopathological biomarkers levels of blood urine nitrogen (BUN), blood creatinine, urine protein and urine creatinine and thickness of the kidney glomerular basement membrane by staining with periodic acid‐Schiff. Antroquinonol, an active component of ACE, was investigated for anti‐inflammation activity in lipopolysaccharide‐induced RAW 267.4 cells. ACE at 400 mg kg−1 significantly suppressed urine protein and serum BUN levels and decreased the thickness of the kidney glomerular basement membrane. Antroquinonol significantly inhibited the production of tumor necrosis factor‐α and interleukin‐1β by 75 and 78%, respectively. In conclusion, ACE reduced urine protein and creatinine levels and suppressed the thickening of the kidney glomerular basement membrane, suggesting that ACE protects the kidney from immunological damage resulting from autoimmune disease.
First Report of Colletotrichum dematium on Pongamia pinnata in India
Authors: Vinay B. R. , Sudisha J. , Sunayana N. , Lokesh S. , Govindappa M. , Kumar T. Vasanth
Published: September 2008

Karanj or Indian beech (Pongamia pinnata) is a multipurpose tree grown in many parts of Karnataka. In several nurseries, a high proportion of seedlings of this tree exhibited chlorotic spots on the leaves. Acervuli of Colletotrichum dematium (Pers.) Grove were found on the adaxial surfaces at the region of chlorosis. The fungus was isolated and used to complete Koch's postulates. This is the first confirmed report of anthracnose caused by C. dematium on P. pinnata in India.

Accepted for publication 12 June 2008. Published 2 September 2008.
An age-structured model to evaluate the potential of novel malaria-control interventions: a case study of fungal biopesticide sprays
Authors: Hancock P.A , Thomas M.B , Godfray H.C.J
Published: September 2008

It has recently been proposed that mosquito vectors of human diseases, particularly malaria, may be controlled by spraying with fungal biopesticides that increase the rate of adult mortality. Though fungal pathogens do not cause instantaneous mortality, they can kill mosquitoes before they are old enough to transmit disease. A model is developed (i) to explore the potential for fungal entomopathogens to reduce significantly infectious mosquito populations, (ii) to assess the relative value of the many different fungal strains that might be used, and (iii) to help guide the tactical design of vector-control programmes. The model follows the dynamics of different classes of adult mosquitoes with the risk of mortality due to the fungus being assumed to be a function of time since infection (modelled using the Weibull distribution). It is shown that substantial reductions in mosquito numbers are feasible for realistic assumptions about mosquito, fungus and malaria biology and moderate to low daily fungal infection probability. The choice of optimal fungal strain and spraying regime is shown to depend on local mosquito and malaria biology. Fungal pathogens may also influence the ability of mosquitoes to transmit malaria and such effects are shown to further reduce vectorial capacity.
A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs
Authors: Gould Fred , Huang Yunxin , Legros Mathieu , Lloyd Alun L
Published: September 2008

A number of genetic mechanisms have been suggested for driving anti-pathogen genes into natural populations. Each of these mechanisms requires complex genetic engineering, and most are theoretically expected to permanently spread throughout the target species' geographical range. In the near term, risk issues and technical limits of molecular methods could delay the development and use of these mechanisms. We propose a gene-drive mechanism that can be self-limiting over time and space, and is simpler to build. This mechanism involves one gene that codes for toxicity (killer) and a second that confers immunity to the toxic effects (rescue). We use population-genetic models to explore cases with one or two independent insertions of the killer gene and one insertion of the rescue gene. We vary the dominance and penetrance of gene action, as well as the magnitude of fitness costs. Even with the fitness costs of 10 per cent for each gene, the proportion of mosquitoes expected to transmit the pathogen decreases below 5 per cent for over 40 generations after one 2 : 1 release (engineered : wild) or after four 1 : 2 releases. Both the killer and rescue genes will be lost from the population over time, if the rescue construct has any associated fitness cost. Molecular approaches for constructing strains are discussed.
Assessment of the role of sutures in a lizard skull: a computer modelling study
Authors: Moazen Mehran , Curtis Neil , O'Higgins Paul , Jones Marc E.H , Evans Susan E , Fagan Michael J
Published: September 2008

Sutures form an integral part of the functioning skull, but their role has long been debated among vertebrate morphologists and palaeontologists. Furthermore, the relationship between typical skull sutures, and those involved in cranial kinesis, is poorly understood. In a series of computational modelling studies, complex loading conditions obtained through multibody dynamics analysis were imposed on a finite element model of the skull ofUromastyx hardwickii, an akinetic herbivorous lizard. A finite element analysis (FEA) of a skull with no sutures revealed higher patterns of strain in regions where cranial sutures are located in the skull. From these findings, FEAs were performed on skulls with sutures (individual and groups of sutures) to investigate their role and function more thoroughly. Our results showed that individual sutures relieved strain locally, but only at the expense of elevated strain in other regions of the skull. These findings provide an insight into the behaviour of sutures and show how they are adapted to work together to distribute strain around the skull. Premature fusion of one suture could therefore lead to increased abnormal loading on other regions of the skull causing irregular bone growth and deformities. This detailed investigation also revealed that the frontal–parietal suture of theUromastyxskull played a substantial role in relieving strain compared with the other sutures. This raises questions about the original role of mesokinesis in squamate evolution.
Stochastic spread ofWolbachia
Authors: Jansen Vincent A.A , Turelli Michael , Godfray H. Charles J
Published: September 2008

Wolbachiaare very common, maternally transmitted endosymbionts of insects. They often spread by a mechanism termed cytoplasmic incompatibility (CI) that involves reduced egg hatch whenWolbachia-free ova are fertilized by sperm fromWolbachia-infected males. Because the progeny ofWolbachia-infected females generally do not suffer CI-induced mortality, infected females are often at a reproductive advantage in polymorphic populations. Deterministic models show thatWolbachiathat impose no costs on their hosts and have perfect maternal transmission will spread from arbitrarily low frequencies (though initially very slowly); otherwise, there will be a threshold frequency below whichWolbachiafrequencies decline to extinction and above which they increase to fixation or a high stable equilibrium. Stochastic theory was used to calculate the probability of fixation in populations of different size for arbitrary current frequencies ofWolbachia, with special attention paid to the case of spread after the arrival of a single infected female. Exact results are given based on a Moran process that assumes a specific demographic model, and approximate results are obtained using the more general Wright–Fisher theory. A new analytical approximation for the probability of fixation is derived, which performs well for small population sizes. The significance of stochastic effects in the natural spread ofWolbachiaand their relevance to the use ofWolbachiaas a drive mechanism in vector and pest management are discussed.
Temperature-dependent sex-biased embryo mortality in a bird
Authors: Eiby Yvonne A , Wilmer Jessica Worthington , Booth David T
Published: September 2008

Sex ratios have important evolutionary consequences and are often biased by environmental factors. The effect of developmental temperature on offspring sex ratios has been widely documented across a diverse range of taxa but has rarely been investigated in birds and mammals. However, recent field observations and artificial incubation experiments have demonstrated that the hatching sex ratio of a megapode, the Australian brush-turkey (
Alectura lathami
), varied with incubation temperature; more females hatched at high incubation temperatures and more males hatched at low temperatures. Here, we investigated the causes of this temperature-dependent sex-biasing system. Molecular sexing of chicks and embryos confirmed that male embryo mortality was greater at high temperatures while female embryo mortality is greater at low temperatures, with mortality in both sexes similar at intermediate incubation temperatures. Temperature-dependent sex-biased embryo mortality represents a novel mechanism of altering sex ratios in birds. This novel mechanism, coupled with the unique breeding biology of the brush-turkey, offers a potentially unparalleled opportunity in which to investigate sex allocation theory in birds.
Genome size and wing parameters in passerine birds
Authors: Andrews Chandler B , Mackenzie Stuart A , Gregory T. Ryan
Published: September 2008

Despite their status as the most speciose group of terrestrial vertebrates, birds exhibit the smallest and least variable genome sizes among tetrapods. It has been suggested that this is because powered flight imposes metabolic constraints on cell size, and thus on genome size. This notion has been supported by analyses of genome size and cell size versus resting metabolic rate and other parameters across birds, but most previous studies suffer from one or more limitations that have left the question open. The present study provides new insights into this issue through an examination of newly measured genome sizes, nucleus and cell sizes, body masses and wing parameters for 74 species of birds in the order Passeriformes. A positive relationship was found between genome size and nucleus/cell size, as well as between genome size and wing loading index, which is interpreted as an indicator of adaptations for efficient flight. This represents the single largest dataset presented for birds to date, and is the first to analyse a distinctly flight-related parameter along with genome size using phylogenetic comparative analyses. The results lend additional support to the hypothesis that the small genomes of birds are indeed related in some manner to flight, though the mechanistic and historical bases for this association remain an interesting area of investigation.
Cryptic diversity, molecular phylogeny and biogeography of the rock- and leaf litter-dwelling land snails of Belau (Republic of Palau, Oceania)
Authors: Rundell Rebecca J
Published: September 2008

The endemic diplommatinid land snails (Caenogastropoda: Mollusca) of Belau (Republic of Palau, Micronesia) are an exceptionally diverse group of largely undescribed species distributed among rock and leaf litter habitats on most of Belau's 586 islands. Diplommatinid shell morphology (e.g. shell sculpture) reflects habitat type. In this study, I analysed a subset of the 90 diplommatinid species representing a broad geographical spread of islands in order to reveal the species' phylogenetic relationships and biogeography within the Belau archipelago. Diplommatinid species from the islands of Yap, Pohnpei, Kosrae and Guam are also included in the analysis. One nuclear (28S rRNA) and two mitochondrial (16S rRNA, COI) gene regions comprising 1906 bp were used for phylogenetic reconstruction. Results show that (i) the Belau Diplommatinidae are not monophyletic, as Guam and Yap species should be included as part of the radiation, (ii) Pohnpei and Kosrae species are highly divergent from Belau diplommatinids, (iii) there is little evidence forin situradiation within individual Belau islands, (iv) spined and heavily calcified rock-dwelling species form a well-supported clade, and (v) Belau diplommatinid genera are in need of revision.
Management actions are required to improve the viability of the rare grassland herb Carlina biebersteinii
Authors: Ramula Satu , Puhakainen Lauri , Suhonen Jukka , Vallius Elisa
Published: September 2008

Small population size of many rare or endangered plant species makes a quantitative assessment of population status challenging because of the lack of detailed demographic data on different life‐history stages. However, an urgent assessment is often required to start possible management actions. We performed a count‐based population viability analysis (PVA) using discontinuous time series to quantitatively assess the viability of a rare, monocarpic, grassland herb Carlina biebersteinii Bernh. ex Hornem. (synonyms: C. vulgaris L. ssp. longifolia, C. vulgaris L. ssp. stricta) and examined demographic and environmental factors contributing to its viability. Based on 12 abundance counts of eight C. biebersteinii populations in Finland, we found that seven out of the eight population sizes declined during the observation period, and that annual population growth rates were slightly synchronised among the populations. Synchrony in annual population growth rates declined with increasing geographic distances among the populations, while fluctuations in the number of flowering plants were unrelated to geographic distances among the populations. According to stochastic simulations, the risk of losing all flowering individuals during the next 20 years will be high for unmanaged populations. To prevent the populations from gradually declining, our results suggest that summer grazing or removal of woody vegetation is required to increase habitat openness and consequently, to improve fecundity and seedling recruitment.
Randomized controlled trial of motivational interviewing compared with drug information and advice for early intervention among young cannabis users
Authors: McCambridge Jim , Slym Renee L. , Strang John
Published: September 2008

Aim  To test the effectiveness of motivational interviewing (MI) in comparison with drug information and advice in opportunistically securing reductions in drug‐related risk among young cannabis users not seeking help.

Design  Randomized controlled trial.

Setting  Eleven London Further Education colleges.

Participants  A total of 326 students aged 16–19 years who smoked cannabis weekly or more frequently.

Interventions  Participants were randomized to a single‐session intervention of MI or drug information and advice‐giving.

Measurements  Cannabis use, cigarette smoking and alcohol consumption and harm outcomes were assessed after both 3 and 6 months.

Findings  No differences were found between MI and drug information and advice, although MI fidelity was not high. There were wide‐ranging individual practitioner effects on observed outcomes and a practitioner–intervention interaction was detected in relation to cannabis cessation after 3 months. Change over time was more pronounced for cannabis use than for other drug use.

Conclusions  Further study of the nature and consequences of MI fidelity, and individual practitioner effects more generally, is needed. Advice may be an effective brief intervention with young cannabis users in its own right and should be evaluated further in trials.
The role of PilZ domain proteins in the virulence of Xanthomonas campestris pv. campestris
Authors: MCCARTHY YVONNE , RYAN ROBERT P. , O'DONOVAN KAREN , HE YONG‐QIANG , JIANG BO‐LE , FENG JIA‐XUN , TANG JI‐LIANG , DOW J. MAXWELL
Published: September 2008

Cyclic di‐GMP [(bis‐(3′–5′)‐cyclic di‐guanosine monophosphate)] is an almost ubiquitous second messenger in bacteria that is implicated in the regulation of a range of functions that include developmental transitions, aggregative behaviour, adhesion, biofilm formation and virulence. Comparatively little is known about the mechanism(s) by which cyclic di‐GMP exerts these various regulatory effects. PilZ has been identified as a cyclic di‐GMP binding protein domain; proteins with this domain are involved in regulation of specific cellular processes, including the virulence of animal pathogens. Here we have examined the role of PilZ domain proteins in virulence and the regulation of virulence factor synthesis in Xanthomonas campestris pv. campestris (Xcc), the causal agent of black rot of crucifers. The Xcc genome encodes four proteins (XC0965, XC2249, XC2317 and XC3221) that have a PilZ domain. Mutation of XC0965, XC2249 and XC3221 led to a significant reduction of virulence in Chinese radish. Mutation of XC2249 and XC3221 led to a reduction in motility whereas mutation of XC2249 and XC0965 affected extracellular enzyme production. All mutant strains were unaffected in biofilm formation in vitro. The reduction of virulence following mutation of XC3221 could not be wholly attributed to an effect on motility as mutation of pilA, which abolishes motility, has a lesser effect on virulence.
Co‐administration of proton pump inhibitors delays elimination of plasma methotrexate in high‐dose methotrexate therapy
Authors: Suzuki Kunihiro , Doki Kosuke , Homma Masato , Tamaki Hirofumi , Hori Satoko , Ohtani Hisakazu , Sawada Yasufumi , Kohda Yukinao
Published: September 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Co‐administration of proton pump inhibitors (PPIs) increases plasma methotrexate (MTX) concentration in cancer patients receiving high‐dose MTX (HDMTX) therapy.

• There is controversy as to whether or not co‐administration of PPIs affects plasma MTX elimination in HDMTX therapy.

• Inhibitory activity of PPIs on breast cancer resistance protein (BCRP) is a possible mechanism for the drug interaction between MTX and PPIs.

WHAT THIS STUDY ADDS

• Co‐administration of a PPI (omeprazole, lansoprazole, or rabeprazole) was more frequently observed in the delayed MTX elimination group than in the normal MTX elimination group.

• Multiple logistic regression analysis with adjustment for significant covariates revealed that PPI co‐administration was a significant risk factor for delayed plasma MTX elimination.

• The half‐maximal inhibitory concentration of each PPI in inhibiting BCRP function was much higher than the therapeutic unbound concentration in the plasma.

AIM

To assess whether or not co‐administration of proton pump inhibitors (PPIs) is a risk factor for delayed elimination of plasma methotrexate (MTX) in high‐dose MTX (HDMTX) therapy for malignant diseases.

METHODS

To assess the effects of PPI co‐administration on elimination of plasma MTX, we examined plasma MTX concentration data on 171 cycles of HDMTX therapy performed in 74 patients. We performed multiple logistic regression analysis to evaluate PPI co‐administration as a risk factor. Inhibitory potencies of omeprazole, lansoprazole, rabeprazole and pantoprazole on MTX transport via breast cancer resistance protein (BCRP, ABCG2) were also investigated in an in vitro study using membrane vesicles expressing human BCRP.

RESULTS

We identified co‐administration of PPIs as a risk factor for delayed elimination (odds ratio 2.65, 95% confidence interval 1.03, 6.82) as well as renal and liver dysfunction. All four PPIs inhibited BCRP‐mediated transport of MTX, with half‐maximal inhibitory concentrations of 5.5–17.6 µM – considerably higher than the unbound plasma concentrations of the PPIs.

CONCLUSIONS

Our results support previous findings suggesting that PPI co‐administration is associated with delayed elimination of plasma MTX in patients with HDMTX therapy. This drug interaction, however, cannot be explained solely by the inhibitory effects of PPIs on BCRP‐mediated MTX transport.
Asthma and allergic symptoms in relation to house dust endotoxin: Phase Two of the International Study on Asthma and Allergies in Childhood (ISAAC II)
Authors: Gehring U. , Strikwold M. , Schram‐Bijkerk D. , Weinmayr G. , Genuneit J. , Nagel G. , Wickens K. , Siebers R. , Crane J. , Doekes G. , Di Domenicantonio R. , Nilsson L. , Priftanji A. , Sandin A. , El‐Sharif N. , Strachan D. , Van Hage M. , Von Mutius E. , Brunekreef B. ,   and the ISAAC Phase Two Study Group
Published: September 2008

Background
Several studies have consistently reported inverse associations between exposure to endotoxin in house dust and atopy. With regard to the association between house dust endotoxin and asthma, the results are inconsistent.

Objectives
To study the association between house dust endotoxin levels and respiratory symptoms and atopy in populations from largely different countries.

Methods
Data were collected within the International Study on Asthma and Allergies in Childhood Phase Two, a multi‐centre cross‐sectional study of 840 children aged 9–12 years from six centres in the five countries of Albania, Italy, New Zealand, Sweden and the United Kingdom. Living room floor dust was collected and analysed for endotoxin. Health end‐points and demographics were assessed by standardized questionnaires. Atopy was assessed by measurements of allergen‐specific IgE against a panel of inhalant allergens. Associations between house dust endotoxin and health outcomes were analysed by logistic regression. Odds ratios (ORs) were presented for an overall interquartile range increase in exposure.

Results
Many associations between house dust endotoxin in living room floor dust and health outcomes varied between countries. Combined across countries, endotoxin levels were inversely associated with asthma ever [adjusted OR (95% confidence interval (CI)) 0.53 (0.29–0.96) for endotoxin levels per m2 of living room floor] and current wheeze [adjusted OR (95% CI) 0.77 (0.64–0.93) for endotoxin levels per gram of living room floor dust]. There were inverse associations between endotoxin concentrations and atopy, which were statistically significant in unadjusted analyses, but not after adjustment for gender, parental allergies, cat and house dust mite allergens. No associations were found with dust quantity and between endotoxin exposure and hayfever.

Conclusion
These findings suggest an inverse association between endotoxin levels in living room floor dust and asthma in children.