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Isochores are long genome segments homogeneous in G+C. Here, we describe an algorithm (IsoFinder) running on the web (http://bioinfo2.ugr.es/IsoF/isofinder.html) able to predict isochores at the sequence level. We move a sliding pointer from left to right along the DNA sequence. At each position of the pointer, we compute the mean G+C values to the left and to the right of the pointer. We then determine the position of the pointer for which the difference between left and right mean values (as measured by the t-statistic) reaches its maximum. Next, we determine the statistical significance of this potential cutting point, after filtering out short-scale heterogeneities below 3 kb by applying a coarse-graining technique. Finally, the program checks whether this significance exceeds a probability threshold. If so, the sequence is cut at this point into two subsequences; otherwise, the sequence remains undivided. The procedure continues recursively for each of the two resulting subsequences created by each cut. This leads to the decomposition of a chromosome sequence into long homogeneous genome regions (LHGRs) with well-defined mean G+C contents, each significantly different from the G+C contents of the adjacent LHGRs. Most LHGRs can be identified with Bernardi's isochores, given their correlation with biological features such as gene density, SINE and LINE (short, long interspersed repetitive elements) densities, recombination rate or single nucleotide polymorphism variability. The resulting isochore maps are available at our web site (http://bioinfo2.ugr.es/isochores/), and also at the UCSC Genome Browser (http://genome.cse.ucsc.edu/). ; This work was supported by the Spanish Government (Grants Nos. BIO2002-04014-C03-01 and 02) and Plan Andaluz de Investigación (CVI-162). M.H. acknowledges a predoctoral grant from the University of Granada (Spain).

IN 2001 the government produced the first ever National strategy for sexual health and HIV.1 The strategy called for a broader role for general practice in the promotion of better sexual health. Surveys undertaken in the United Kingdom (UK) in recent years suggest that more people have more sexual partners than ever before. This has been associated with a rise in sexually transmitted infections (STIs). Screening and testing for Chlamydia trachomatis have become more widespread in the UK.

The concept of plant intelligence has been advanced by Trewavas as a potentially useful framework to guide those seeking to understand plant growth and development. In this short critique, the validity of this concept is critically assessed. Central to this critique is the proposition that the concept of the individual, to which intelligence and behaviour are intimately linked, cannot usefully be applied to plants. It is argued that the adaptive responses of plants are best appreciated if the importance of the autonomy of the individual organs is acknowledged. Although Trewavas does acknowledge the autonomy of organs by describing an individual plant as being 'a democratic confederation', that terminology implies a complexity to the interaction between organs which would demand a cogitative ability beyond that actually demonstrated in plants. It may be more appropriate to consider a plant as operating normally as a simple economic federation of many specialized economies (organs and cells). Occasionally, there can be a dramatic, and sometimes complex, reshaping of the economic balances, with the result that the fate of some or many of the individual cells will change. However, such major changes in growth and development are driven by a few simple events in an individual organ and cells. These driving events are more akin to small local revolutions in individual states than they are to democratic decisions in a sophisticated confederation.

Racialization has become one of the central concepts in the study of race and racism. It is widely used in both theoretical and empirical studies of racial situations. There has been a proliferation of texts that use this notion in quite diverse ways. It is used broadly to refer to ways of thinking about race as well as to institutional processes that give expression to forms of ethno-racial categorization. An important issue in the work of writers such as Robert Miles, for example, concerns the ways in which the construction of race is shaped historically and how the usage of that idea forms a basis for exclusionary practices. The concept therefore refers both to cultural or political processes or situations where race is invoked as an explanation, as well as to specific ideological practices in which race is deployed. It is evident, however, that despite the increasing popularity of the concept of racialization there has been relatively little critical analysis exploring its theoretical and empirical usages. It is with this underlying concern in mind that Racialization: Studies in Theory and Practice brings together leading international scholars in the field of race and ethnicity in order to explore both the utility of the concept and its limitations.

Among the most important changes that it was hoped would flow from the 1989 Children Act were, first, a reduction in delays in care proceedings, since this was recognized to be harmful to children and, second, a shift away from the use of compulsion towards working in partnership. In this article, Bridget McKeigue and Chris Beckett demonstrate that, in both respects, the Act has not only failed to deliver, but has been followed by rapid change in the opposite direction to the one hoped for. However, many commentators, both within and outside of government, continue to speak of the Act as if it had been a success. The article considers a series of characteristic rhetorical manoeuvres, which seem to allow the Act's failings to be passed over in much of this discourse. They conclude that progress is more likely to be made if the Act's failure to deliver is frankly confronted.

PMCID: PMC443556.-- Final edited version available at: http://dx.doi.org/10.1093/nar/gnh088 ; Many studies have tried to identify specific nucleotide sequences in the quasispecies of hepatitis C virus (HCV) that determine resistance or sensitivity to interferon (IFN) therapy, unfortunately without conclusive results. Although viral proteins represent the most evident phenotype of the virus, genomic RNA sequences determine secondary and tertiary structures which are also part of the viral phenotype and can be involved in important biological roles. In this work, a method of RNA structure analysis has been developed based on the hybridization of labelled HCV transcripts to microarrays of complementary DNA oligonucleotides. Hybridizations were carried out at non-denaturing conditions, using appropriate temperature and buffer composition to allow binding to the immobilized probes of the RNA transcript without disturbing its secondary/tertiary structural motifs. Oligonucleotides printed onto the microarray covered the entire 5' non-coding region (5'NCR), the first three-quarters of the core region, the E2–NS2 junction and the first 400 nt of the NS3 region. We document the use of this methodology to analyse the structural degree of a large region of HCV genomic RNA in two genotypes associated with different responses to IFN treatment. The results reported here show different structural degree along the genome regions analysed, and differential hybridization patterns for distinct genotypes in NS2 and NS3 HCV regions. ; M.M. was supported in part by grants DITTO-HCV QLK2-2000-0836 from the European Commission FP5 and Red Nacional de Gastroenterología y Hepatología (C03/02). The work in Hospital Vall d'Hebron was supported in part by grants SAF2000/0183 and PROFIT (FIT-010000-2003-51) from the Ministerio de Ciencia y Tecnología. The work at CAB was supported by the European Union, Instituto Nacional de Técnica Aerospacial, Ministerio de Ciencia y Tecnología and Comunidad de Madrid. ; Peer reviewed

10 páginas, 4 figuras, 3 tablas.-- El PDF es la versión post-print. ; [Background and aims]: Mediterranean woody plants have a wide variety of phenological strategies. Some authors have classified the Mediterranean phanaerophytes into two broad phenological categories: phenophase-verlappers (that overlap resource-demanding activities in a short period of the year) and phenophase-sequencers (that protract resource-demanding activities throughout the year). In this work the impact of both phenological strategies on leaf nutrient accumulation and retranslocation dynamics at the level of leaves and branches was evaluated. Phenophase-overlappers were expected to accumulate nutrients in leaves throughout most of the year and withdraw them efficiently in a short period. Phenophase-sequencers were expected to withdraw nutrients progressively throughout the year, without long accumulation periods. [Methods]: To test this hypothesis, variations in phenology and leaf NPK in the crown of a phenophase-overlapper Cistus laurifolius and a phenophase-sequencer Bupleurum fruticosum were monitored monthly during 2 years. [Key Results]: Changes in nutrient concentration at the leaf level were not clearly related with the different phenologies. Nitrogen and phosphorous resorption efficiencies were lower in the phenophase-overlapper, and accumulation–retranslocation seasonality was similar in both species. Changes in the branch nutrient pool agreed with the hypothesis that the phenophase-overlapper accumulated nutrients from summer until the bud burst of the following spring, recovering a large nutrient pool during massive leaf shedding. The phenophase-sequencer did not accumulate nutrients from autumn until early spring, achieving lower nutrient recovery during spring leaf shedding. [Conclusions]: It is concluded that phenological demands influence branch nutrient cycling. This effect is easier to detect by assessing changes in the branch nutrient pool rather than changes in the leaf nutrient concentration. ; This study was supported by the "Comisión Interministerial de Ciencia y Tecnología" (Spanish government) project REN 2000-0163-P4-05, REN2002-02635/GLO and the Thematic Network GLOBIMED (REN 2001-4841-E/GLO); and 2) the "Gobierno de Aragón" project P-024/2001 and financial support to R. M. ; Peer reviewed

The history of the rise and diffusion of the merit principle in American government is common lore to students of public administration and political science. Several descriptive accounts notwithstanding, scholars have ignored an intriguing puzzle vis-à-vis state merit adoptions: Why did some states adopt merit systems early in the twentieth century while other states followed suit decades later, and then only when they were forced to do so by the federal government? When we analyze state merit adoptions that occurred between 1900 and 1939 we find nationwide and state-specific demographic, economic, structural, and political factors—for example, growth in patronage constituencies; the use of the Australian ballot; political party competition; dwindling patronage resources post-Pendleton; and the onset of the Great Depression—that shifted politicians' preferences for the merit principle rather than patronage. Our research thus breaks sharply with the extant literature by emphasizing the political undercurrents of merit ...

This article discusses the language that is used by children and family social workers when talking about their work, and specifically the metaphors that such language draws upon. The question of the relationship between language and reality that has been raised by postmodernist theory is considered, but it is argued that it remains sensible to see language as 'a reflection of reality', however partial. Drawing on ideas about metaphor from other disciplines, it is suggested that by identifying the sources of metaphors used in spoken language it is possible to gain insights into underlying mental concepts. Metaphors in the language of social work are found to come from several sources, including medicine, business and industry, but attention is drawn here in particular to terms with military connotations, implying underlying conceptual metaphors that equate social work with war. The implications of this are discussed.

The United States today dominates the globe and many regional geographical sub-systems in an unprecedented way, maintaining a hegemonic order that is in no way similar to the 'anarchy' assumed in realist analyses. The global system today is not simply unipolar; it is a hegemonic system that is increasingly globalised, in which the basic concepts of realism (anarchy, self-help and power-balancing) provide little guidance or understanding in explaining state behaviour. This essay describes the US hegemonic system, analyses the roles of China and Japan within that system, and examines how the Bush administration's plans for missile defence might transform that system. There are critical implications from this analysis for realist interpretations of international politics.

The United States today dominates the globe and many regional geographical sub-systems in an unprecedented way, maintaining a hegemonic order that is in no way similar to the 'anarchy' assumed in realist analyses. The global system today is not simply unipolar; it is a hegemonic system that is increasingly globalised, in which the basic concepts of realism (anarchy, self-help and power-balancing) provide little guidance or understanding in explaining state behaviour. This essay describes the US hegemonic system, analyses the roles of China and Japan within that system, and examines how the Bush administration's plans for missile defence might transform that system. There are critical implications from this analysis for realist interpretations of international politics.

Background Many studies have shown the health burden of a sedentary lifestyle. The main goal of this study was to determine the prevalence of sedentary lifestyles in the 15 Member States of the European Union (EU) and to identify the main correlates of a sedentary lifestyle. Methods Nationally representative samples (n ≈ 1000 subjects in each country; >15 years) completed a questionnaire concerning attitudes to physical activity, body weight, and health; in total 15 239 subjects. Sedentary people were defined in two ways: (1) those expending less than 10% of their leisure time expenditure in activities involving ≥4 metabolic equivalents (MET). (2) Those who did not practice any leisure-time physical activity and who also were above the median in the number of hours spent sitting down during leisure time. Logistic regression models were fitted to analyse the association between sedentary lifestyles and gender, age, body mass index (BMI), educational level, weight change in the last 6 months, and marital and smoking status. Results Percentages of sedentary lifestyles across European countries ranged between 43.3% (Sweden) and 87.8% (Portugal) according to the first definition. According to both definitions, a lower prevalence of sedentary lifestyle was found in Northern countries (especially Scandinavian countries) as compared with Mediterranean countries, whereas the prevalence was higher among older, obese, less educated, widowed/divorced individuals, and current smokers. Similar relative differences between countries and socio-demographic groups were found independently of the method used to define a sedentary lifestyle. Conclusion Prevalence of sedentary lifestyle in the EU is high, especially among inhabitants of some Mediterranean countries, obese subjects, less-educated people, and current smokers. This high prevalence involves important public health burdens and preventive strategies are urgently needed.

Alignment of the protein sequence of DNA-dependent DNA polymerases has allowed the definition of a new motif, lying adjacent to motif B in the direction of the N-terminus and therefore named pre-motif B. Both motifs are located in the fingers subdomain, shown to rotate towards the active site to form a dNTP-binding pocket in several DNA polymerases in which a closed ternary complex pol:DNA:dNTP has been solved. The functional significance of pre-motif B has been studied by site-directed mutagenesis of phi 29 DNA polymerase. The affinity for nucleotides of phi 29 DNA polymerase mutant residues Ile364 and Lys371 was strongly affected in DNA- and terminal protein-primed reactions. Additionally, mutations in Ile364 affected the DNA-binding capacity of phi 29 DNA polymerase. The results suggest that Lys371 of phi 29 DNA polymerase, highly conserved among families A and B, interacts with the phosphate groups of the incoming nucleotide. On the other hand, the role of residue Ile364 seems to be structural, being important for both DNA and dNTP binding. Pre-motif B must therefore play an important role in binding the incoming nucleotide. Interestingly, the roles of Lys371 and Ile364 were also shown to be important in reactions without template, suggesting that phi 29 DNA polymerase can achieve the closed conformation in the absence of a DNA template ; This investigation has been aided by research grant 2R01 GM27242-22 from the National Institutes of Health, by grant PB98-0645 from the Dirección General de Investigación Científica y Técnica, by grant ERBFMRX CT97 0125 from the European Union and by an institutional grant from Fundación Ramón Areces. V.T. was a post-doctoral fellow of the Comunidad Autónoma de Madrid. ; Peer reviewed

Phage phi 29 encodes a DNA-dependent DNA polymerase belonging to the eukaryotic-type (family B) subgroup of DNA polymerases that use a protein as the primer for initiation of DNA synthesis. In one of the most important motifs present in the 3'5' exonucleolytic domain of proofreading DNA polymerases, the ExoII motif, phi 29 DNA polymerase contains three amino acid residues, Y59, H61 and F69, which are highly conserved among most proofreading DNA polymerases. These residues have recently been shown to be involved in proper stabilization of the primer terminus at the 3'5' exonuclease active site. Here we investigate by means of site-directed mutagenesis the role of these three residues in reactions that are specific for DNA polymerases utilizing a protein-primed DNA replication mechanism. Mutations introduced at residues Y59, H61 and F69 severely affected the protein-primed replication capacity of phi 29 DNA polymerase. For four of the mutants, namely Y59L, H61L, H61R and F69S, interaction with the terminal protein was affected, leading to few initiation and transition products. These findings, together with the specific conservation of Y59, H61 and F69 among DNA polymerases belonging to the protein-primed subgroup, strongly suggest a functional role of these amino acid residues in the DNA polymerase–terminal protein interaction ; This investigation was aided by research grant 5R01 GM27242-22 from the National Institutes of Health, by grant PB98-0645 from the Dirección General de Investigacíon Científica y Técnica, by grant ERBFMX CT97 0125 from the European Union and by an institutional grant from Fundación Ramón Areces. R.E. was a post-doctoral fellow of the European Union ; Peer reviewed

Producción Científica ; This paper analyses the alcohol consumption patterns in Spanish drivers, the incidence of alcohol-related problems and attempts to ascertain whether, in the end, drivers with alcohol-related problems are considered fit or unfit to drive. In accordance with Spanish and European Union legislation, driving licences cannot be issued or renewed to people suffering from alcohol-related problems. A medical, psychological and eyesight evaluation was performed to test the driving fitness of 8043 drivers attending 25 Medical Driving Test Centres on a national scale. Among other things, information was collected on the patterns of alcohol consumption, the AUDIT and CAGE tests, the incidence of alcohol-related problems (DSM-IV criteria for abuse, dependence and alcohol-induced disorder), as well as an evaluation of their fitness to drive. In all, 60.3% of drivers drink alcohol on a regular basis; 7.3% of drivers scored ≥8 points in the AUDIT test, and 2% met criteria for DSM-IV alcohol abuse, dependence or induced disorder. Drivers with alcohol-related problems have been involved in traffic accidents (23.2%) and have infringed driving regulations (18.7%) more frequently (P < 0.0001) than those without alcohol-related problems. Of those with alcohol-related problems, 72.2% were considered fit to drive. The study reveals that alcohol consumption is common among drivers, that a significant number of drivers have alcohol-related problems, and that three in four of the latter were considered fit to drive