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AbstractIn 2004 the Netherlands Twin Register (NTR) started a large scale biological sample collection in twin families to create a resource for genetic studies on health, lifestyle and personality. Between January 2004 and July 2008, adult participants from NTR research projects were invited into the study. During a home visit between 7:00 and 10:00 am, fasting blood and morning urine samples were collected. Fertile women were bled on day 2–4 of the menstrual cycle, or in their pill-free week. Biological samples were collected for DNA isolation, gene expression studies, creation of cell lines and for biomarker assessment. At the time of blood sampling, additional phenotypic information concerning health, medication use, body composition and smoking was collected. Of the participants contacted, 69% participated. Blood and urine samples were collected in 9,530 participants (63% female, average age 44.4 (SD 15.5) years) from 3,477 families. Lipid profile, glucose, insulin, HbA1c, haematology, CRP, fibrinogen, liver enzymes and creatinine have been assessed. Longitudinal survey data on health, personality and lifestyle are currently available for 90% of all participants. Genome-wide SNP data are available for 3,524 participants, with additional genotyping ongoing. The NTR biobank, combined with the extensive phenotypic information available within the NTR, provides a valuable resource for the study of genetic determinants of individual differences in mental and physical health. It offers opportunities for DNA-based and gene expression studies as well as for future metabolomic and proteomic projects.

[Background] The G1-to-S transition of the cell cycle in the yeast Saccharomyces cerevisiae involves an extensive transcriptional program driven by transcription factors SBF (Swi4-Swi6) and MBF (Mbp1-Swi6). Activation of these factors ultimately depends on the G1 cyclin Cln3. ; [Results] To determine the transcriptional targets of Cln3 and their dependence on SBF or MBF, we first have used DNA microarrays to interrogate gene expression upon Cln3 overexpression in synchronized cultures of strains lacking components of SBF and/or MBF. Secondly, we have integrated this expression dataset together with other heterogeneous data sources into a single probabilistic model based on Bayesian statistics. Our analysis has produced more than 200 transcription factor-target assignments, validated by ChIP assays and by functional enrichment. Our predictions show higher internal coherence and predictive power than previous classifications. Our results support a model whereby SBF and MBF may be differentially activated by Cln3. ; [Conclusions] Integration of heterogeneous genome-wide datasets is key to building accurate transcriptional networks. By such integration, we provide here a reliable transcriptional network at the G1-to-S transition in the budding yeast cell cycle. Our results suggest that to improve the reliability of predictions we need to feed our models with more informative experimental data. ; This work was funded by the Ministerio de Ciencia e Innovación of Spain (Consolider-Ingenio 2010), and the European Union (FEDER). FF and NC are researchers of the Ramón y Cajal program. ; Peer Reviewed

AbstractThe aim of this study was to examine whether maximal walking speed, maximal isometric muscle strength, leg extensor power and lower leg muscle cross-sectional area (CSA) shared a genetic effect in common. In addition, we wanted to identify the chromosomal areas linked to maximal walking speed and these muscle characteristics and also investigate whether maximal walking speed and these three skeletal muscle characteristics are regulated by the same chromosomal areas. We studied 217 monozygotic (MZ) and dizygotic (DZ) female twin pairs aged 66 to 75 years in the Finnish Twin Study on Aging study. The DZ pairs (94) were genotyped for 397 microsatellite markers in 22 autosomes and X-chromosome. Genetic modeling showed that, muscle CSA, strength, power and walking speed shared a genetic effect in common which accounted for 7% of the variation in CSA, 51% in strength, 37% in power and 35% in walking speed. The results of an explorative multipoint linkage analysis suggested that the highest LOD score found for each phenotype was 2.41 for walking speed on chromosome 13q22.1, 2.14 for strength on chromosome 15q14, 2.84 for power on chromosome 8q24.23, and 2.93 for muscle CSA on chromosome 20q13.31. Also a suggestive LOD score, 2.68, for muscle CSA was found on chromosome 9q34.3. The chromosomal areas of a suggestive linkage for strength and power partly overlapped LOD scores higher than 1.0 being seen for these phenotypes on chromosome 15. The present study was the first genome-wide linkage analysis to be conducted for these multifactorial and clinically important phenotypes underlying functional independence in older women.

The genetic code provides the translation table necessary to transform the information contained in DNA into the language of proteins. In this table, a correspondence between each codon and each amino acid is established: tRNA is the main adaptor that links the two. Although the genetic code is nearly universal, several variants of this code have been described in a wide range of nuclear and organellar systems, especially in metazoan mitochondria. These variants are generally found by searching for conserved positions that consistently code for a specific alternative amino acid in a new species. We have devised an accurate computational method to automate these comparisons, and have tested it with 626 metazoan mitochondrial genomes. Our results indicate that several arthropods have a new genetic code and translate the codon AGG as lysine instead of serine (as in the invertebrate mitochondrial genetic code) or arginine (as in the standard genetic code). We have investigated the evolution of the genetic code in the arthropods and found several events of parallel evolution in which the AGG codon was reassigned between serine and lysine. Our analyses also revealed correlated evolution between the arthropod genetic codes and the tRNA-Lys/-Ser, which show specific point mutations at the anticodons. These rather simple mutations, together with a low usage of the AGG codon, might explain the recurrence of the AGG reassignments. ; This work was supported by a research grant from the Fundación BBVA (Spain). DP is also supported by the Ramón y Cajal programme of the Spanish Government. ; Peer reviewed

Alternative splicing plays an essential role in many cellular processes and bears major relevance in the understanding of multiple diseases, including cancer. High-throughput RNA sequencing allows genome-wide analyses of splicing across multiple conditions. However, the increasing number of available data sets represents a major challenge in terms of computation time and storage requirements. We describe SUPPA, a computational tool to calculate relative inclusion values of alternative splicing events, exploiting fast transcript quantification. SUPPA accuracy is comparable and sometimes superior to standard methods using simulated as well as real RNA-sequencing data compared with experimentally validated events. We assess the variability in terms of the choice of annotation and provide evidence that using complete transcripts rather than more transcripts per gene provides better estimates. Moreover, SUPPA coupled with de novo transcript reconstruction methods does not achieve accuracies as high as using quantification of known transcripts, but remains comparable to existing methods. Finally, we show that SUPPA is more than 1000 times faster than standard methods. Coupled with fast transcript quantification, SUPPA provides inclusion values at a much higher speed than existing methods without compromising accuracy, thereby facilitating the systematic splicing analysis of large data sets with limited computational resources. The software is implemented in Python 2.7 and is available under the MIT license at https://bitbucket.org/regulatorygenomicsupf/suppa. ; This work was supported by the Spanish Government (BIO2011-23920, CSD2009-00080), the Sandra Ibarra Foundation for Cancer (FSI-2013), and partially by the Spanish National Institute of Bioinformatics (INB)

INTRODUCTION: During military service, many household costs for both married and single service personnel are subsidised, and transition can leave veterans unprepared for the financial demands of civilian life. Armed Forces organisations such as Sailor, Soldier, Air Force Association (SSAFA) play a central role in understanding the financial challenges that UK veterans face and provide an insight into the financial hardship experienced by veterans. The aim of this study was to use SSAFA beneficiary data as a proxy to identify the nature of financial benefit, the spatial distribution of financial hardship in the Scottish SSAFA beneficiary community and explore factors that might predict where those recipients are located. METHODS: Using an anonymised data set of Scottish SSAFA financial beneficiaries between 2014 and 2019, this study used a geographical methodology to identify the geospatial distribution of SSAFA benefit recipients and exploratory regression analysis to explore factors to explain where SSAFA beneficiaries are located. RESULTS: Over half of benefit applicants (n=10 735) were concentrated in only 50 postcode districts, showing evidence of a clustered pattern, and modelling demonstrates association with area-level deprivation. The findings highlight strong association between older injured veterans and need for SSAFA beneficiary assistance. CONCLUSION: The findings demonstrate that beneficiaries were statistically clustered into areas of high deprivation, experiencing similar challenges to that of the wider population in these areas. Military service injury or disability was strongly associated with areas of high SSAFA benefit use and in those areas high unemployment was also a significant factor to consider.

Introduction: During military service, many household costs for both married and single service personnel are subsidised, and transition can leave veterans unprepared for the financial demands of civilian life. Armed Forces organisations such as Sailor, Soldier, Air Force Association (SSAFA) play a central role in understanding the financial challenges that UK veterans face and provide an insight into the financial hardship experienced by veterans. The aim of this study was to use SSAFA beneficiary data as a proxy to identify the nature of financial benefit, the spatial distribution of financial hardship in the Scottish SSAFA beneficiary community and explore factors that might predict where those recipients are located. Methods: Using an anonymised dataset of Scottish SSAFA financial beneficiaries between 2014 and 2019, this study used a geographical methodology to identify the geospatial distribution of SSAFA benefit recipients and exploratory regression analysis to explore factors to explain where SSAFA beneficiaries are located. Results: Over half of benefit applicants (n= 10,735) were concentrated in only 50 postcode districts, showing evidence of a clustered pattern, and modelling demonstrates association with area level deprivation. The findings highlight strong association between older injured veterans and need for SSAFA beneficiary assistance. Conclusion: The findings demonstrate that beneficiaries were statistically clustered into areas of high deprivation, experiencing similar challenges to that of the wider population in these areas. Military service injury or disability was strongly associated with areas of high SSAFA benefit use and in those areas high unemployment was also a significant factor to consider.

Background: As the global incidence of end-stage organ failure increases, the gap between organ donors and recipients continues to widen. This study was conducted to determine the association between organ donation awareness and organ donation willingness among students of a Saudi university.Design and methods: This analytical cross-sectional study was conducted in King Faisal University, Al-Ahsa, Saudi Arabia. Multi-stage stratified random sampling was used to select the required 723 sample size. Estimation of proportion of students who were aware about organ donation and those who were willing to donate their organs was performed using EpiInfo© Version 7. Association between organ donation awareness and willingness was determined using multivariate logistic regression.Results: Nearly 98% of the participants were aware that organ donation saves lives (95% CI: 96.27%-98.53%); 84.09% were aware that Islam allows organ donation (95% CI: 81.25%-86.58%); 64.87% were aware that organ donation is successfully done in Saudi Arabia (95% CI: 61.32%-68.26%); 32.64% were aware that the government gives incentives to the family of an organ donor (95% CI: 29.32%-36.14%). Over half (56.71%) of the students (95% CI: 53.07 - 60.28%) expressed willingness to donate their organs. Positive association was found between awareness on the position of Islam on organ donation (OR=2.7023, p<0.0001) and awareness of that organ donation can be successfully performed in Saudi Arabia (OR=1.9447, p=0.0001).Conclusions: Awareness that Islam allows organ donation and awareness that organ donation is successfully done in Saudi Arabia increased the students' willingness to donate.

Transregionalization has already become a powerful trend in world politics. States and regional associations employ transregional initiatives to realize their own and collective interests. This new level of international interaction embraces a wide range of actors and fosters interconnectedness based on geographical proximity but shared functional preferences. Given the opposition between isolationism and disintegration, there is a problem of the relation between transregionalization and globalization. If the processes are unidirectional, then transregionalization is a stage of globalization. If they contradict each other, transregionalization facilitates the creation of new dividing lines.Considering several cases of megaprojects, especially in the Asia-Pacific, the article substantiates the typology of transregionalization, emphasizing its cooperative (inclusive and aimed at global integration) and competitive form (mostly exclusive and impossible to converge with other projects). The author stresses that strengthening functional ties makes transregionalization an adaptive version of globalization driven by common interests and shared views of future global development paths. Intensification of transregional relations is likely to stimulate globalization and integration practices and the participation of state and nonstate actors in global governance.In today's world politics, transregionalization exists mainly in the form of projects and initiatives. This signifies both difficulties in reaching consensus on further cooperation and conservative states' policy towards participating in such large-scale associations. However, the very emergence of transregional associations with varying degrees of convergence and institutionalization, promoting specific institutional and economic development and cooperation patterns, strengthens multipolarity of the international system.

BACKGROUND: Despite the fact that the overwhelming majority of mental health services are delivered in outpatient settings, the effect of changes in non-hospital-based mental health care on increased suicide rates is largely unknown. This study examines the association between changes in community mental health center (CMHC) supply and suicide mortality in the United States. METHODS: Retrospective analysis was performed using data from National Mental Health Services Survey (N-MHSS) and the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research (WONDER) (2014–2017). Population-weighted multiple linear regressions were used to examine within-state associations between CMHCs per capita and suicide mortality. Models controlled for state-level characteristics (i.e., number of hospital psychiatric units per capita, number of mental health professionals per capita, age, race, and percent low-income), year and state. RESULTS: From 2014 to 2017, the number of CMHCs decreased by 14% nationally (from 3406 to 2920). Suicide increased by 9.7% (from 15.4 to 16.9 per 100,000) in the same time period. We find a small but negative association between the number of CMHCs and suicide deaths (− 0.52, 95% CI − 1.08 to 0.03; p = 0.066). Declines in the number of CMHCs from 2014 to 2017 may be associated with approximately 6% of the national increase in suicide, representing 263 additional suicide deaths. CONCLUSIONS: State governments should avoid the declining number of CMHCs and the services these facilities provide, which may be an important component of suicide prevention efforts.

Purpose: To identify how child health status differs by mother's educational attainment for the overall US population and by race/ethnicity and to assess whether these disparities have changed from 2000 to 2017. Design: Repeated cross-sectional data from the 2000-2017 National Health Interview Survey (NHIS). Setting: United States. Participants: Children aged 1 to 17 years from a nationally representative sample of the noninstitutionalized US population (N = 199 427). Measures: Reported child health status, mother's educational attainment, child's race/ethnicity, and control variables were measured using the NHIS. Analysis: Using logistic regression models, we assessed the relationship between maternal education and child health. Missing data were imputed. Results: Children whose mothers had less than a high school education (odds ratio [OR] = 3.84, 95% confidence interval [CI]: 3.62-4.07), high school diploma or equivalent (OR = 2.57, 95% CI: 2.44-2.70), or some college (OR = 1.90, 95% CI: 1.80-2.00) had worse reported health status compared to children whose mothers graduated college. These associations were strongest among non-Hispanic white children, with significantly ( P < .05) smaller associations observed for non-Hispanic black, Mexican origin, and other Hispanic children. The associations were smaller but persisted with inclusion of controls. From 2000 to 2017, child health disparities slightly narrowed or remained stagnant among white, non-Hispanic black, and other Hispanic children but widened for Mexican origin children ( P < .05). Conclusion: Maternal education disparities in child health are wide and have persisted.

A better understanding of the solution chemistry of the lanthanide (Ln) salts in water would have wide ranging implications in materials processing, waste management, element tracing, medicine and many more fields. This is particularly true for minerals processing, given governmental concerns about lanthanide security of supply and the drive to identify environmentally sustainable processing routes. Despite much effort, even in simple systems, the mechanisms and thermodynamics of Ln(III) association with small anions remain unclear. In the present study, molecular dynamics (MD), using a newly developed force field, provide new insights into LnCl(3)(aq) solutions. The force field accurately reproduces the structure and dynamics of Nd(3+), Gd(3+) and Er(3+) in water when compared to calculations using density functional theory (DFT). Adaptive‐bias MD simulations show that the mechanisms for ion pairing change from dissociative to associative exchange depending upon cation size. Thermodynamics of association reveal that whereas ion pairing is favourable, the equilibrium distribution of species at low concentration is dominated by weakly bound solvent‐shared and solvent‐separated ion pairs, rather than contact ion pairs, reconciling a number of contrasting observations of Ln(III)–Cl association in the literature. In addition, we show that the thermodynamic stabilities of a range of inner sphere and outer sphere [Formula: see text] coordination complexes are comparable and that the kinetics of anion binding to cations may control solution speciation distributions beyond ion pairs. The techniques adopted in this work provide a framework with which to investigate more complex solution chemistries of cations in water.

This article presents a comparative study of public perceptions of food risk across 25 European member states. A secondary data analysis is conducted on a Eurobarometer survey fielded to nationally representative samples in 2005. The survey included closed questions as well as free associations to map risk perceptions. Taking a quantitative approach, we find that people in a majority of European countries express similar levels of concern about food risks. However, outside this majority a North‐South divide is evident, with the Northern countries worrying less than the Southern countries. Multilevel modeling shows that cross‐national differences in individual respondents' level of worry are in part attributable to shared country effects and to generalized risk sensitivity about a range of personal risks. On the underlying structure of food risk concerns, factor analysis points to three dimensions described by groupings of risks related to adulteration and contamination, health effects, and production and hygiene. A qualitative analysis of respondents' free associations about problems and risks with food identifies three major themes that are consistent with the quantitative results. However, the free associations also point toward greater cross‐national diversity and to striking variations in the range and importance of food risks. Overall, the picture is of a public that frames food risks in a wider context of beliefs about the links between diet and health. We conclude with some implications for research on food risk perceptions in particular and risk perception studies in general.

This paper investigates the spatial structure of employment in the Jakarta Metropolitan Area (JMA), with reference to the concept of the Southeast Asian extended metropolitan region (EMR). A combination of factor analysis and local Getis-Ord (Gi*) hot-spot analysis is used to identify clusters of employment in the region, including those of the urban and agriculture sectors. Spatial statistical analysis is further used to probe the spatial association of identified employment clusters with their surroundings on several dimensions, including the spatial association between the central business district (CBD) in Jakarta city on employment density in the region, the spatial impacts of urban expansion on population growth and the degree of urban-rural interaction. The degree of spatial interaction for the whole JMA is measured by the patterns of commuting trips destined to the various employment clusters. Results reveal the strong role of the urban core of Jakarta, and the regional CBD, as the centre for mixed job sectors such as retail, wholesale, services and finance. Manufacturing and local government services, on the other hand, form corridors radiating out of the urban core, reaching out to the agriculture zones in the fringes. Strong associations between the urban expansion corridors and population growth, and urban-rural mix, are revealed particularly in the eastern and western parts of JMA. Metropolitan wide commuting patterns are focussed on the urban core of Jakarta and the CBD, while relatively local commuting patterns are shown to be prevalent for the employment corridors.

This paper examines the ideological asymmetry hypothesis with respect tothe interface between legitimizing ideologies and psychological attachment to one's ethnic group. The ideological asymmetry hypothesis suggests that hierarchy‐enhancing legitimizing ideologies should be positively associated with ingroup attachment among high‐status groups, but that among low‐status groups these associations should be either less positive in magnitude (isotropic asymmetry) relative to high‐status groups or negative in direction (anisotropic asymmetry). The opposite pattern should be found with respect to the interface between hierarchy‐attenuating legitimizing ideologies and ingroup attachment: Among high‐status groups these associations should be negative, but among low‐status groups these associations should be either less negative in magnitude (isotropic asymmetry) relative to high‐status groups or positive in direction (anisotropic asymmetry). The presence of isotropic versus anisotropic asymmetry is hypothesized to depend on the degree of disparity in status between the groups being compared: Wider status gaps should tend toward anisotropic asymmetries. The relationships between legitimizing ideologies and ingroup attachment were compared for (1) relatively high‐status ethnic groups (European and Asian Americans) versus relatively low‐status ethnic groups (Latinos and African Americans) in the United States, (2) the higher‐status Jewish ethnic group (Ashkenazim) versus the lower‐status Jewish ethnic group (Mizrachim) in Israel, and (3) the high‐status Israeli Jews versus the low‐status Israeli Arabs. The data were largely consistent with the ideological asymmetry hypothesis. The implications of these findings are discussed within the theoretical frameworks of social dominance theory and other approaches to intergroup relations.