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Peripheral artery disease (PAD) and non-compressible artery disease (NCAD) constitute predictors of subclinical atherosclerosis easily assessed through the ankle brachial index (ABI). Although both diseases show substantial genetic influences, few genetic association studies have focused on the ABI and PAD, and none have focused on NCAD. To overcome these limitations, we assessed the role of several candidate genes on the ABI, both in its continuous distribution and in the clinical manifestations associated to its extreme values: PAD and NCAD. We examined 13 candidate genomic regions in 1606 participants from the ARTPER study, a prospective population-based cohort, with the ABI assessed through ultrasonography. Association analyses were conducted independently for individuals with PAD (ABI < 0.9) or with NCAD (ABI > 1.4) vs. healthy participants. After including potential covariates and correction for multiple testing, minor alleles in the genetic markers rs10757278 and rs1333049, both in the 9p21.3 region, were significantly associated with a decreased risk of NCAD. Associations with the ABI showed limited support to these results. No significant associations were detected for PAD. The locus 9p21.3 constitutes the first genetic locus associated with NCAD, an assessment of subclinical atherosclerosis feasible for implementation in primary healthcare settings that has been systematically neglected from genetic studies.

Under the EU Air Quality Directive (AQD) 2008/50/EC member states are required to undertake routine monitoring of PM 2.5 composition at background stations. The AQD states for PM 2.5 speciation this should include at least: nitrate NO 3 - , sulfate SO 4 2 - , chloride (Cl - ), ammonium (NH4 + ), sodium (Na + ), potassium (K + ), magnesium (Mg 2+ ), calcium (Ca 2+ ), elemental carbon (EC) and organic carbon (OC). Until 2017, it was the responsibility of each country to determine the methodology used to report the composition for the inorganic components of PM 2.5 . In August 2017 a European standard method of measurement of PM 2.5 inorganic chemical components ( NO 3 - , SO 4 2 - , Cl - , NH 4 + , Na + , K + , Mg 2+ , Ca 2+ ) as deposited on filters (EN16913:2017) was published. From August 2019 this then became the European standard method. This filter method is labour-intensive and provides limited time resolution and is prone to losses of volatile compounds. There is therefore increasing interest in the use of alternative automated methods. For example, the UK reports hourly PM 2.5 chemical composition using the Monitor for AeRosols and Gases in Ambient air (MARGA, Metrohm, NL). This study is a pre-assessment review of available data to demonstrate if or to what extent equivalence is possible using either the MARGA or other available automatic methods, including the Aerosol Chemical Speciation Monitor (ACSM, Aerodyne Research Inc. US) and the Ambient Ion Monitor (AIM, URG, US). To demonstrate equivalence three objectives were to be met. The first two objectives focused on data capture and were met by all three instruments. The third objective was to have less than a 50% expanded uncertainty compared to the reference method for each species. Analysis of this objective was carried out using existing paired datasets available from different regions around the world. It was found that the MARGA (2006-2019 model) had the potential to demonstrate equivalence for all species in the standard, though it was only through a combination of case studies that it passed uncertainty criteria. The ACSM has the potential to demonstrate equivalence for NH 4 + , SO 4 2 - and in some conditions NO 3 - , but did not for Cl - due to its inability to quantify refractory aerosol such as sea salt. The AIM has the potential for NH 4 + , NO 3 - , SO 4 2 - , Cl - and Mg 2+ . Future investigations are required to determine if the AIM could be optimised to meet the expanded uncertainty criterion for Na + , K + and Ca 2+ . The recommendation is that a second stage to demonstrate equivalence is required which would include both laboratory and field studies of the three candidate methods and any other technologies identified with the potential to report the required species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Schizophrenia (SZ) is a complex disorder with a highly polygenic inheritance. It can be conceived as the extreme expression of a continuum of traits that are present in the general population often broadly referred to as schizotypy. However, it is still poorly understood how these traits overlap genetically with the disorder. We investigated whether polygenic risk for SZ is associated with these disorder-related phenotypes (schizotypy, psychotic-like experiences, and subclinical psychopathology) in a sample of 253 non-clinically identified participants. Polygenic risk scores (PRSs) were constructed based on the latest SZ genome-wide association study using the PRS-CS method. Their association with self-report and interview measures of SZ-related traits was tested. No association with either schizotypy or psychotic-like experiences was found. However, we identified a significant association with the Motor Change subscale of the Comprehensive Assessment of At-Risk Mental States (CAARMS) interview. Our results indicate that the genetic overlap of SZ with schizotypy and psychotic-like experiences is less robust than previously hypothesized. The relationship between high PRS for SZ and motor abnormalities could reflect neurodevelopmental processes associated with psychosis proneness and SZ., (© 2023. The Author(s).)

Source apportionment (SA) techniques allocate the measured ambient pollutants with their potential source origin; thus, they are a powerful tool for designing air pollution mitigation strategies. Positive Matrix Factorization (PMF) is one of the most widely used SA approaches, and its multi-time resolution (MTR) methodology, which enables mixing different instrument data in their original time resolution, was the focus of this study. One year of co-located measurements in Barcelona, Spain, of non-refractory submicronic particulate matter (NR-PM 1 ), black carbon (BC) and metals were obtained by a Q-ACSM (Aerodyne Research Inc.), an aethalometer (Aerosol d.o.o.) and fine offline quartz-fibre filters, respectively. These data were combined in a MTR PMF analysis preserving the high time resolution (30 min for the NR-PM 1 and BC, and 24 h every 4th day for the offline samples). The MTR-PMF outcomes were assessed varying the time resolution of the high-resolution data subset and exploring the error weightings of both subsets. The time resolution assessment revealed that averaging the high-resolution data was disadvantageous in terms of model residuals and environmental interpretability. The MTR-PMF resolved eight PM 1 sources: ammonium sulphate + heavy oil combustion (25%), ammonium nitrate + ammonium chloride (17%), aged secondary organic aerosol (SOA) (16%), traffic (14%), biomass burning (9%), fresh SOA (8%), cooking-like organic aerosol (5%), and industry (4%). The MTR-PMF technique identified two more sources relative to the 24 h base case data subset using the same species and four more with respect to the pseudo-conventional approach mimicking offline PMF, indicating that the combination of both high and low TR data is significantly beneficial for SA. Besides the higher number of sources, the MTR-PMF technique has enabled some sources disentanglement compared to the pseudo-conventional and base case PMF as well as the characterisation of their intra-day patterns., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Animal behavior plays a critical role in the delivery of ecosystem services, yet the study of animal behavior and ecosystem services rarely intersect. The study of behavior-mediated ecosystem services should be prioritized, focusing on the conditions that allow these critical behaviors to persist and adapt to global change., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Post-stroke cognitive and emotional complications are frequent in the chronic stages of stroke and have important implications for the functionality and quality of life of those affected and their caregivers. Strategies such as mindfulness meditation, physical exercise (PE), or computerized cognitive training (CCT) may benefit stroke patients by impacting neuroplasticity and brain health., Materials and Methods: One hundred and forty-one chronic stroke patients are randomly allocated to receive mindfulness-based stress reduction + CCT ( n = 47), multicomponent PE program + CCT ( n = 47), or CCT alone ( n = 47). Interventions consist of 12-week home-based programs five days per week. Before and after the interventions, we collect data from cognitive, psychological, and physical tests, blood and stool samples, and structural and functional brain scans., Results: The effects of the interventions on cognitive and emotional outcomes will be described in intention-to-treat and per-protocol analyses. We will also explore potential mediators and moderators, such as genetic, molecular, brain, demographic, and clinical factors in our per-protocol sample., Discussion: The MindFit Project is a randomized clinical trial that aims to assess the impact of mindfulness and PE combined with CCT on chronic stroke patients' cognitive and emotional wellbeing. Furthermore, our design takes a multimodal biopsychosocial approach that will generate new knowledge at multiple levels of evidence, from molecular bases to behavioral changes., Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04759950., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bermudo-Gallaguet, Ariza, Dacosta-Aguayo, Agudelo, Camins-Vila, Boldó, Carrera, Vidal, Ferrer-Uris, Busquets, Via, Pera, Cáceres, Gomis, García-Molina, Tormos, Arrabé, Diez, Durà Mata, Torán-Monserrat, Soriano-Raya, Domènech, Perera-Lluna, Erickson and Mataró.)

Organic aerosol (OA) is a key component of total submicron particulate matter (PM 1 ), and comprehensive knowledge of OA sources across Europe is crucial to mitigate PM 1 levels. Europe has a well-established air quality research infrastructure from which yearlong datasets using 21 aerosol chemical speciation monitors (ACSMs) and 1 aerosol mass spectrometer (AMS) were gathered during 2013-2019. It includes 9 non-urban and 13 urban sites. This study developed a state-of-the-art source apportionment protocol to analyse long-term OA mass spectrum data by applying the most advanced source apportionment strategies (i.e., rolling PMF, ME-2, and bootstrap). This harmonised protocol was followed strictly for all 22 datasets, making the source apportionment results more comparable. In addition, it enables quantification of the most common OA components such as hydrocarbon-like OA (HOA), biomass burning OA (BBOA), cooking-like OA (COA), more oxidised-oxygenated OA (MO-OOA), and less oxidised-oxygenated OA (LO-OOA). Other components such as coal combustion OA (CCOA), solid fuel OA (SFOA: mainly mixture of coal and peat combustion), cigarette smoke OA (CSOA), sea salt (mostly inorganic but part of the OA mass spectrum), coffee OA, and ship industry OA could also be separated at a few specific sites. Oxygenated OA (OOA) components make up most of the submicron OA mass (average = 71.1%, range from 43.7 to 100%). Solid fuel combustion-related OA components (i.e., BBOA, CCOA, and SFOA) are still considerable with in total 16.0% yearly contribution to the OA, yet mainly during winter months (21.4%). Overall, this comprehensive protocol works effectively across all sites governed by different sources and generates robust and consistent source apportionment results. Our work presents a comprehensive overview of OA sources in Europe with a unique combination of high time resolution (30-240 min) and long-term data coverage (9-36 months), providing essential information to improve/validate air quality, health impact, and climate models., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A natural range separation of the Coulomb hole into two components, one of them being predominant at long interelectronic separations (h c I ) and the other at short distances (h c II ), is exhaustively analyzed throughout various examples that put forward the most relevant features of this approach and how they can be used to develop efficient ways to capture electron correlation. We show that h c I , which only depends on the first-order reduced density matrix, can be used to identify molecules with a predominant nondynamic correlation regime and differentiate between two types of nondynamic correlation, types A and B. Through the asymptotic properties of the hole components, we explain how h c I can retrieve the long-range part of electron correlation. We perform an exhaustive analysis of the hydrogen molecule in a minimal basis set, dissecting the hole contributions into spin components. We also analyze the simplest molecule presenting a dispersion interaction and how h c II helps identify it. The study of several atoms in different spin states reveals that the Coulomb hole components distinguish correlation regimes that are not apparent from the entire hole. The results of this work hold out the promise to aid in developing new electronic structure methods that efficiently capture electron correlation.

Behavioral interventions have shown promising neuroprotective effects, but the cascade of molecular, brain and behavioral changes involved in these benefits remains poorly understood. Projecte Moviment is a 12-week (5 days per week-45 min per day) multi-domain, single-blind, proof-of-concept randomized controlled trial examining the cognitive effect and underlying mechanisms of an aerobic exercise (AE), computerized cognitive training (CCT) and a combined (COMB) groups compared to a waitlist control group. Adherence was > 80% for 82/109 participants recruited (62% female; age = 58.38 ± 5.47). In this study we report intervention-related changes in plasma biomarkers (BDNF, TNF-α, HGF, ICAM-1, SDF1-α) and structural-MRI (brain volume) and how they related to changes in physical activity and individual variables (age and sex) and their potential role as mediators in the cognitive changes. Our results show that although there were no significant changes in molecular biomarker concentrations in any intervention group, changes in ICAM-1 and SDF1-α were negatively associated with changes in physical activity outcomes in AE and COMB groups. Brain volume changes were found in the CCT showing a significant increase in precuneus volume. Sex moderated the brain volume change in the AE and COMB groups, suggesting that men may benefit more than women. Changes in molecular biomarkers and brain volumes did not significantly mediate the cognitive-related benefits found previously for any group. This study shows crucial initial molecular and brain volume changes related to lifestyle interventions at early stages and highlights the value of examining activity parameters, individual difference characteristics and using a multi-level analysis approach to address these questions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Castells-Sánchez, Roig-Coll, Dacosta-Aguayo, Lamonja-Vicente, Torán-Monserrat, Pera, García-Molina, Tormos, Montero-Alía, Heras-Tébar, Soriano-Raya, Cáceres, Domènech, Via, Erickson and Mataró.)

In this work, time-series analyses of the chemical composition and source contributions of PM 2.5 from an urban background station in Barcelona (BCN) and a rural background station in Montseny (MSY) in northeastern Spain from 2009 to 2018 were investigated and compared. A multisite positive matrix factorization analysis was used to compare the source contributions between the two stations, while the trends for both the chemical species and source contributions were studied using the Theil-Sen trend estimator. Between 2009 and 2018, both stations showed a statistically significant decrease in PM 2.5 concentrations, which was driven by the downward trends of levels of chemical species and anthropogenic source contributions, mainly from heavy oil combustion, mixed combustion, industry, and secondary sulfate. These source contributions showed a continuous decrease over the study period, signifying the continuing success of mitigation strategies, although the trends of heavy oil combustion and secondary sulfate have flattened since 2016. Secondary nitrate also followed a significant decreasing trend in BCN, while secondary organic aerosols (SOA) very slightly decreased in MSY. The observed decreasing trends, in combination with the absence of a trend for the organic aerosols (OA) at both stations, resulted in an increase in the relative proportion of OA in PM 2.5 by 12% in BCN and 9% in MSY, mostly from SOA, which increased by 7% in BCN and 4% in MSY. Thus, at the end of the study period, OA accounted for 40% and 50% of the annual mean PM 2.5 at BCN and MSY, respectively. This might have relevant implications for air quality policies aiming at abating PM 2.5 in the study region and for possible changes in toxicity of PM 2.5 due to marked changes in composition and source apportionment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain., Methods: We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders. We describe how we have tackled methodological issues surrounding genetic meta-analysis of EEG features. We discuss the importance of harmonizing EEG signal processing, cleaning, and feature extraction. Finally, we explain our selection of EEG features currently being investigated, including the temporal dynamics of oscillations and the connectivity network based on synchronization of oscillations., Results: We present data that show how to perform systematic quality control and evaluate how choices in reference electrode and montage affect individual differences in EEG parameters., Conclusion: The long list of potential challenges to our large-scale meta-analytic approach requires extensive effort and organization between participating cohorts; however, our perspective shows that these challenges are surmountable. Our perspective argues that elucidating the genetic of EEG oscillatory activity is a worthwhile effort in order to elucidate the pathway from gene to disease liability., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Although exercise is known to have a neuroprotective effect in aging, the mediators underlying the exercise-cognition association remain poorly understood. In this paper we aimed to study the molecular, brain, and behavioral changes related to physical activity and their potential role as mediators. Methods: We obtained demographic, physical activity outcomes [sportive physical activity and cardiorespiratory fitness (CRF)], plasma biomarkers (TNF-α, ICAM-1, HGF, SDF1-α, and BDNF), structural-MRI (brain volume areas), psychological and sleep health (mood, depressive and distress symptoms, and sleep quality), and multi-domain cognitive data from 115 adults aged 50-70 years. We conducted linear regression models and mediation analyses stratifying results by sex in a final sample of 104 individuals [65 women (age = 56.75 ± 4.96) and 39 men (age = 58.59 ± 5.86)]. Results: Women engaging in greater amounts of exercising showed lower TNF-α levels and greater dorsolateral prefrontal cortex and temporal lobe volumes. Men engaging in greater amounts of exercise showed greater temporal lobe volumes. CRF levels were not related to any of the analyzed outcomes in women but in men higher CRF was associated with lower TNF-α, HGF and ventricle volumes, greater volume of temporal and parietal lobes and fewer depressive symptoms and better mood. In men, reduced TNF-α and HGF levels mediated brain and cognitive CRF-related benefits. Conclusion: Our results show that exercise is a promising approach for influencing inflammation and brain volume and also contributes to ongoing discussions about the physiological mediators for the association between CRF and cognition in men., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Castells-Sánchez, Roig-Coll, Dacosta-Aguayo, Lamonja-Vicente, Sawicka, Torán-Monserrat, Pera, Montero-Alía, Heras-Tebar, Domènech, Via, Erickson and Mataró.)

Apolipoprotein E (APOE) has an important role in the multiple trajectories of cognitive aging. However, environmental variables and other genes mediate the impact of APOE on cognition. Our main objective was to analyze the effect of APOE genotype on cognition and its interactions and relationships with sex, age, lipid profile, C-reactive protein, and Brain-derived neurotrophic factor (BDNF) genotype in a sample of 648 healthy participants over 50 years of age with a comprehensive neuropsychological assessment. Our results showed that APOE ε2 carriers performed better in the Verbal Memory (p = .002) and Fluency Domains (p = .001). When we studied the effect of sex, we observed that the beneficial effect of APOE ε2 on the normalized values of these cognitive domains occurred only in females (β = 0.735; 95% confidence interval, 0.396-1.074; p = 3.167·10-5 and β = 0.568; 95% confidence interval, 0.276-0.861; p = 1.853·10-4, respectively). Similarly, the sex-specific effects of APOE ε2 were further observed on lipidic and inflammation biomarkers. In the whole sample, APOE ε2 carriers showed significantly lower levels of total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein. These differences were found only among females. Furthermore, total cholesterol and low-density lipoprotein cholesterol mediated the protective effect of APOE ε2 on cognition in the whole sample and total cholesterol in females, providing candidate physiological mechanisms for the observed genetic effects. Our results show that the neuroprotective role of APOE ε2 in cognition varies with sex and that the lipidic profile partially mediates this protection. Age-related cognitive and functional decline is a continuous biological process with different cognitive trajectories (1). Complex interactions between heritability, environmental influence, and cognitive functions in aging have been highlighted (2). In particular, genetic differences explain around 15%-25% of the variance in life expectancy (3). Therefore, the identification of susceptibility genes and their biological effects on cognitive aging is required to establish interindividual differences in this process and promote early personalized interventions to delay cognitive decline and minimize the financial burden of aging in the health care system., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: We aimed to study subclinical non-invasive vascular markers as predictors of incident long-term cognitive impairment in a longitudinal population-based study., Methods: The Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) study is a population-based study that included a random sample of 933 Caucasian subjects (mean age 66 years, 64% male) with a moderate-high vascular risk and without history of stroke or dementia. Subclinical carotid and intracranial stenosis was assessed at baseline visit by cervical and transcranial color-coded duplex (TCCD) and confirmed by magnetic resonance angiography. Cervico-cerebral stenosis (CCS) was defined as the presence of extra and/or intracranial stenosis >50%. Baseline middle cerebral artery pulsatility index (MCA-PI) was measured bilaterally by TCCD, and mean PI of both sides was considered for analyses. Subjects were followed-up to determine incident long-term cognitive impairment (mild cognitive impairment or dementia)., Results: After a median of 7.16 [6.91-7.75] years of follow-up, 91 subjects (9.7%) developed cognitive impairment, 27 of them mild cognitive impairment, and 64 dementia. Incidence of cognitive impairment was significantly higher among subjects with subclinical CCS (21.4% versus 9% in those without CCS) and among those with mean MCA-PI>1 (13.5% versus 7.4% in those with MCA-PI<1). In multivariate Cox regression analyses, both CCS and MCA-PI>1 were independently associated with incident cognitive impairment with HR of 2.07 [1.11-3.88] and 1.58 [1.02-2.46], respectively., Conclusions: Subclinical cervico-cerebral stenosis and higher MCA-PI are non-invasive neurosonological markers of incident long-term cognitive impairment in our population., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lockdown measures came into force in Spain from March 14th, two weeks after the start of the SARS-CoV-2 epidemic, to reduce the epidemic curve. Our study aims to describe changes in air pollution levels during the lockdown measures in the city of Barcelona (NE Spain), by studying the time evolution of atmospheric pollutants recorded at the urban background and traffic air quality monitoring stations. After two weeks of lockdown, urban air pollution markedly decreased but with substantial differences among pollutants. The most significant reduction was estimated for BC and NO2 (-45 to -51%), pollutants mainly related to traffic emissions. A lower reduction was observed for PM10 (-28 to -31.0%). By contrast, O 3 levels increased (+33 to +57% of the 8 h daily maxima), probably due to lower titration of O 3 by NO and the decrease of NOx in a VOC-limited environment. Relevant differences in the meteorology of these two periods were also evidenced. The low reduction for PM10 is probably related to a significant regional contribution and the prevailing secondary origin of fine aerosols, but an in-depth evaluation has to be carried out to interpret this lower decrease. There is no defined trend for the low SO 2 levels, probably due to the preferential reduction in emissions from the least polluting ships. A reduction of most pollutants to minimal concentrations are expected for the forthcoming weeks because of the more restrictive actions implemented for a total lockdown, which entered into force on March 30th. There are still open questions on why PM10 levels were much less reduced than BC and NO 2 and on what is the proportion of the abatement of pollution directly related to the lockdown, without meteorological interferences., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Age-related health, brain, and cognitive impairment is a great challenge in current society. Cognitive training, aerobic exercise and their combination have been shown to benefit health, brain, cognition and psychological status in healthy older adults. Inconsistent results across studies may be related to several variables. We need to better identify cognitive changes, individual variables that may predict the effect of these interventions, and changes in structural and functional brain outcomes as well as physiological molecular correlates that may be mediating these effects. Projecte Moviment is a multi-domain randomized trial examining the effect of these interventions applied 5 days per week for 3 months compared to a passive control group. The aim of this paper is to describe the sample, procedures and planned analyses., Methods: One hundred and forty healthy physically inactive older adults will be randomly assigned to computerized cognitive training (CCT), aerobic exercise (AE), combined training (COMB), or a control group. The intervention consists of a 3 month home-based program 5 days per week in sessions of 45 min. Data from cognitive, physical, and psychological tests, cardiovascular risk factors, structural and functional brain scans, and blood samples will be obtained before and after the intervention., Results: Effects of the interventions on cognitive outcomes will be described in intention-to-treat and per protocol analyses. We will also analyze potential genetic, demographic, brain, and physiological molecular correlates that may predict the effects of intervention, as well as the association between cognitive effects and changes in these variables using the per protocol sample., Discussion: Projecte Moviment is a multi-domain intervention trial based on prior evidence that aims to understand the effects of CCT, AE, and COMB on cognitive and psychological outcomes compared to a passive control group, and to determine related biological correlates and predictors of the intervention effects. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03123900.

The correlation part of the pair density is separated into two components, one of them being predominant at short electronic ranges and the other at long ranges. The analysis of the intracular part of these components permits to classify molecular systems according to the prevailing correlation: dynamic or nondynamic. The study of the long-range asymptotics reveals the key component of the pair density that is responsible for the description of London dispersion forces and a universal decay with the interelectronic distance. The natural range-separation, the identification of the dispersion forces, and the kind of predominant correlation type that arise from this analysis are expected to be important assets in the development of new electronic structure methods in wave function, density, and reduced density-matrix functional theories.

Background: Single lung transplantation (SLT) and double lung transplantation (DLT) are associated with differences in morbidity and mortality, although the effects of transplant type on patient-reported outcomes are not widely reported and conclusions have differed. Previous studies compared mean health-related quality of life (HRQOL) scores but did not evaluate potentially different temporal trajectories in the context of longitudinal follow-up. To address this uncertainty, this study was designed to evaluate longitudinal HRQOL after SLT and DLT with the hypothesis that temporal trajectories differ between SLT and DLT., Methods: Patients transplanted at a single institution were eligible to be surveyed at 1 month, 3 months, 6 months, and then annually after transplant using the Short Form 36 Health Survey, with longitudinal physical component summary (PCS) and mental component summary (MCS) scores as the primary outcomes. Multivariable mixed-effects models were used to evaluate the effects of transplant type and time posttransplant on longitudinal PCS and MCS after adjusting age, diagnosis, rejection, Lung Allocation Score quartile, and intubation duration. Time by transplant type interaction effects were used to test whether the temporal trajectories of HRQOL differ between SLT and DLT recipients. HRQOL scores were referenced to general population norms (range, 40 to 60; mean, 50 ± 10) using accepted standards for a minimally important difference (½ SD, 5 points)., Results: Postoperative surveys (n = 345) were analyzed for 136 patients (52% male, 23% SLT, age 52 ± 13 years, LAS 42 ± 12, follow-up 37 ± 29 months [range, 0.6 to 133]) who underwent lung transplantation between 2005 and 2016. After adjusting for model covariates, overall posttransplant PCS scores have a significant downward trajectory (p = 0.015) whereas MCS scores remain stable (p = 0.593), with both averaging within general population norms. The time by transplant type interaction effect (p = 0.002), however, indicate that posttransplant PCS scores of SLT recipients decline at a rate of 2.4 points per year over the total observation period compared to DLT. At approximately 60 months, the PCS scores of SLT recipients, but not DLT recipients, fall below general population norms., Conclusions: The trajectory of physical HRQOL in patients receiving SLT declines over time compared with DLT, indicating that, in the longer term, SLT recipients are more likely to have physical HRQOL scores that fall substantively below general population norms. Physical HRQOL after 5 years may be a consideration for lung allocation and patient counseling regarding expectations when recommending SLT or DLT., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A systematic study of the performance of several density functional methodologies to study spin-crossover (SCO) on first row transition metal complexes is reported. All functionals have been tested against several mononuclear systems containing first row transition metal complexes and exhibiting spin-crossover. Among the tested functionals, the hybrid meta-GGA functional TPSSh with a triple-ζ basis set including polarization functions on all atoms provides the best results across different metals and oxidation states, and its performance in both predicting the correct ground state and the right energy window for SCO to occur is quite satisfactory. The effect of some additional contributions, such as zero-point energies, relativistic effects, and intramolecular dispersion interactions, has been analyzed. The reported strategy thus expands the use of the TPSSh functional to other metals and oxidation states other than Fe II , making it the method of choice to study SCO in first row transition metal complexes. Additionally, the presented results validate the potential use of the TPSSh functional for virtual screening of new molecules with SCO, or its use in the study of the electronic structure of such systems.

The chemical formation process has been studied from relaxation holes, Δh(u), resulting from the difference between the radial intracule density and the nonrelaxed counterpart, which is obtained from atomic radial intracule densities and the pair density constructed from the overlap of the atomic densities. Δh(u) plots show that the internal reorganization of electron pairs prior to bond formation and the covalent bond formation from electrons in separate atoms are completely recognizable processes from the shape of the relaxation hole, Δh(u). The magnitude of Δh(u), the shape of Δh(u) ∀ u < R eq , and the distance between the minimum and the maximum in Δh(u) provide further information about the nature of the chemical bond formed. A computational affordable approach to calculate the radial intracule density from approximate pair densities has been also suggested, paving the way to study electron-pair distributions in larger systems.

The energy usually serves as a yardstick in assessing the performance of approximate methods in computational chemistry. After all, these methods are mostly used for the calculation of the electronic energy of chemical systems. However, computational methods should be also aimed at reproducing other properties, such strategy leading to more robust approximations with a wider range of applicability. In this study, we suggest a battery of ten tests with the aim to analyze density matrix functional approximations (DMFAs), including several properties that the exact functional should satisfy. The tests are performed on a model system with varying electron correlation, carrying a very small computational effort. Our results not only put forward a complete and exhaustive benchmark test for DMFAs, currently lacking, but also reveal serious deficiencies of existing approximations that lead to important clues in the construction of more robust DMFAs.

Introduction: Differences in the prevalence of dementia among populations and in the effect of apolipoprotein E (APOE) on the emergence of Alzheimer disease (AD), which is the main type of dementia, have been reported., Methods: This study estimated the ancestry of a group of individuals with late-onset Alzheimer disease (LOAD) (N=280) and established whether there were any differences when compared with a control group (N=357) in a sample of the Colombian population., Results: When the analyses were adjusted for known risk factors such as age, sex, presence of APOE[Latin Small Letter Open E]4, socioeconomic status, educational attainment, and place of birth, African ancestry was associated with an increased LOAD risk (odds ratio: 1.55; 95% confidence interval, 1.09-2.03; P=0.029), whereas Native American ancestry was associated with lower risk (odds ratio: 0.75; 95% confidence interval, 0.61-0.98; P=0.046), for every 10% increase in ancestry. In addition, there were significant differences in the proportion of Native American ancestry between carriers and noncarriers of the APOE[Latin Small Letter Open E]4 allele (Mann-Whitney U test, P=0.047), with noncarriers having higher mean Native American ancestry when compared with carriers., Conclusions: Our results are consistent with the presence of variants of African origin in the genome of the Colombian population and different from APOE[Latin Small Letter Open E]4 that represents a risk factor for the development of LOAD, whereas variants of Native American origin may be conferring protection. However, unknown environmental factors or epigenetic differences among continental groups could also explain the observed associations.

Attention capture by potentially relevant environmental stimuli is critical for human survival, yet it varies considerably among individuals. A large series of studies has suggested that attention capture may depend on the cognitive balance between maintenance and manipulation of mental representations and the flexible switch between goal-directed representations and potentially relevant stimuli outside the focus of attention; a balance that seems modulated by a prefrontostriatal dopamine pathway. Here, we examined inter-individual differences in the cognitive control of attention through studying the effects of two single nucleotide polymorphisms regulating dopamine at the prefrontal cortex and the striatum (i.e., COMTMet108/158Val and ANKK1/DRD2TaqIA) on stimulus-driven attention capture. Healthy adult participants (N = 40) were assigned to different groups according to the combination of the polymorphisms COMTMet108/158Val and ANKK1/DRD2TaqIA, and were instructed to perform on a well-established distraction protocol. Performance in individuals with a balance between prefrontal dopamine display and striatal receptor density was slowed down by the occurrence of unexpected distracting events, while those with a rather unbalanced dopamine activity were able maintain task performance with no time delay, yet at the expense of a slightly lower accuracy. This advantage, associated to their distinct genetic profiles, was paralleled by an electrophysiological mechanism of phase-resetting of gamma neural oscillation to the novel, distracting events. Taken together, the current results suggest that the epistatic interaction between COMTVal108/158Met and ANKK1/DRD2 TaqIa genetic polymorphisms lies at the basis of stimulus-driven attention capture.

Objective: The association of variants in CLU, CR1, PICALM, BIN1, ABCA7, and CD33 genes with late-onset Alzheimer's disease (LOAD) was evaluated and confirmed through genome-wide association study. However, it is unknown whether these associations can be replicated in admixed populations., Methods: The association of 14 single-nucleotide polymorphisms in those genes was evaluated in 280 LOAD cases and 357 controls from the Colombian population., Results: In a multivariate analysis using age, gender, APOE∊4 status, and admixture covariates, significant associations were obtained ( P < .05) for variants in BIN1 (rs744373, odds ratio [OR]: 1.42), CLU (rs11136000, OR: 0.66), PICALM (rs541458, OR: 0.69), ABCA7 (rs3764650, OR: 1.7), and CD33 (rs3865444, OR: 1.12). Likewise, a significant interaction effect was observed between CLU and CR1 variants with APOE., Conclusion: This study replicated the associations previously reported in populations of European ancestry and shows that APOE variants have a regulatory role on the effect that variants in other loci have on LOAD, reflecting the importance of gene-gene interactions in the etiology of neurodegenerative diseases.

Objectives: The population analysis of cardiovascular risk and non-risk genetic variation can help to identify adaptive or random demographic processes that shaped coronary incidence variation across geography., Material and Methods: In this study, 114 single nucleotide polymorphisms and 17 tandem repeat polymorphisms from Nitric Oxide Synthases (NOS) regions were analyzed in 1686 individuals from 35 populations from Europe, North Africa, and the Middle East. NOS genes encode for key enzymes on nitric oxide availability, which is involved in several cardiovascular processes. These genetic variations were used to test for selection and to infer the population structure of NOS regions. Moreover, we tested whether the variation in the incidence of coronary events and in the levels of classical risk factors in 11 of these European populations could be explained by the population structure estimates., Results: Our results supported, first, the absence of clear signs of selection for NOS genetic variants associated with cardiovascular diseases, and second, the presence of a continuous genetic pattern of variation across European and North African populations without a Mediterranean barrier for gene flow. Finally, population structure estimates from NOS regions are closely correlated with coronary event rates and classical risk parameters (explaining 39-98%) among European populations., Conclusion: Our results reinforce the hypothesis that genetic bases of cardiovascular diseases and associated complex phenotypes could be geographically shaped by random demographic processes., (© 2016 Wiley Periodicals, Inc.)

A flourishing line of evidence has highlighted the encoding of speech sounds in the subcortical auditory system as being shaped by acoustic, linguistic, and musical experience and training. And while the heritability of auditory speech as well as nonspeech processing has been suggested, the genetic determinants of subcortical speech processing have not yet been uncovered. Here, we postulated that the serotonin transporter-linked polymorphic region (5-HTTLPR), a common functional polymorphism located in the promoter region of the serotonin transporter gene (SLC6A4), is implicated in speech encoding in the human subcortical auditory pathway. Serotonin has been shown as essential for modulating the brain response to sound both cortically and subcortically, yet the genetic factors regulating this modulation regarding speech sounds have not been disclosed. We recorded the frequency following response, a biomarker of the neural tracking of speech sounds in the subcortical auditory pathway, and cortical evoked potentials in 58 participants elicited to the syllable /ba/, which was presented >2000 times. Participants with low serotonin transporter expression had higher signal-to-noise ratios as well as a higher pitch strength representation of the periodic part of the syllable than participants with medium to high expression, possibly by tuning synaptic activity to the stimulus features and hence a more efficient suppression of noise. These results imply the 5-HTTLPR in subcortical auditory speech encoding and add an important, genetically determined layer to the factors shaping the human subcortical response to speech sounds., Significance Statement: The accurate encoding of speech sounds in the subcortical auditory nervous system is of paramount relevance for human communication, and it has been shown to be altered in different disorders of speech and auditory processing. Importantly, this encoding is plastic and can therefore be enhanced by language and music experience. Whether genetic factors play a role in speech encoding at the subcortical level remains unresolved. Here we show that a common polymorphism in the serotonin transporter gene relates to an accurate and robust neural tracking of speech stimuli in the subcortical auditory pathway. This indicates that serotonin transporter expression, eventually in combination with other polymorphisms, delimits the extent to which lifetime experience shapes the subcortical encoding of speech., (Copyright © 2016 the authors 0270-6474/16/3610782-09$15.00/0.)

Background: In recent years, several genomic regions have been robustly associated with coronary artery disease (CAD) in different genome-wide association studies (GWASs) conducted mainly in people of European descent. These kinds of data are lacking in African populations, even though heart diseases are a major cause of premature death and disability., Methods: Here, 384 single nucleotide polymorphisms (SNPs) in the top four CAD risk regions (1p13, 1q41, 9p21, and 10q11) were genotyped in 274 case-control samples from Morocco and Tunisia, with the aim of analyzing for the first time if the associations found in European populations were transferable to North Africans., Results: The results indicate that, as in Europe, these four genetic regions are also important for CAD risk in North Africa. However, the individual SNPs associated with CAD in Africa are different from those identified in Europe in most cases (1p13, 1q41, and 9p21). Moreover, the seven risk variants identified in North Africans are efficient in discriminating between cases and controls in North African populations, but not in European populations., Conclusions: This study indicates a disparity in markers associated to CAD susceptibility between North Africans and Europeans that may be related to population differences in the chromosomal architecture of these risk regions.

The analysis of human population variation is an area of considerable interest in the forensic, medical genetics and anthropological fields. Several forensic single nucleotide polymorphism (SNP) assays provide ancestry-informative genotypes in sensitive tests designed to work with limited DNA samples, including a 34-SNP multiplex differentiating African, European and East Asian ancestries. Although assays capable of differentiating Oceanian ancestry at a global scale have become available, this study describes markers compiled specifically for differentiation of Oceanian populations. A sensitive multiplex assay, termed Pacifiplex, was developed and optimized in a small-scale test applicable to forensic analyses. The Pacifiplex assay comprises 29 ancestry-informative marker SNPs (AIM-SNPs) selected to complement the 34-plex test, that in a combined set distinguish Africans, Europeans, East Asians and Oceanians. Nine Pacific region study populations were genotyped with both SNP assays, then compared to four reference population groups from the HGDP-CEPH human diversity panel. STRUCTURE analyses estimated population cluster membership proportions that aligned with the patterns of variation suggested for each study population's currently inferred demographic histories. Aboriginal Taiwanese and Philippine samples indicated high East Asian ancestry components, Papua New Guinean and Aboriginal Australians samples were predominantly Oceanian, while other populations displayed cluster patterns explained by the distribution of divergence amongst Melanesians, Polynesians and Micronesians. Genotype data from Pacifiplex and 34-plex tests is particularly well suited to analysis of Australian Aboriginal populations and when combined with Y and mitochondrial DNA variation will provide a powerful set of markers for ancestry inference applied to modern Australian demographic profiles. On a broader geographic scale, Pacifiplex adds highly informative data for inferring the ancestry of individuals from Oceanian populations. The sensitivity of Pacifiplex enabled successful genotyping of population samples from 50-year-old serum samples obtained from several Oceanian regions that would otherwise be unlikely to produce useful population data. This indicates tests primarily developed for forensic ancestry analysis also provide an important contribution to studies of populations where useful samples are in limited supply., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Coronary artery disease (CAD) is a complex disease and the leading cause of death in the world. Populations of different ancestry do not always share the same risk markers. Natural selective processes may be the cause of some of the population differences detected for specific risk mutations., Objective: In this study, 384 single nucleotide polymorphisms (SNPs) located in four genomic regions associated with CAD (1p13, 1q41, 9p21 and 10q11) are analysed in a set of 19 populations from Europe, Middle East and North Africa and also in Asian and African samples from the 1000 Genomes Project. The aim of this survey is to explore for the first time whether the genetic variability in these genomic regions is better explained by demography or by natural selection., Results: The results indicate significant differences in the structure of genetic variation and in the LD patterns among populations that probably explain the population disparities found in markers of susceptibility to CAD., Conclusions: The results are consistent with potential signature of positive selection in the 9p21 region and of balancing selection in the 9p21 and 10q11. Specifically, in Europe three CAD risk markers in the 9p21 region (rs9632884, rs1537371 and rs1333042) show consistent signals of positive selection. The results of this study are consistent with a potential selective role of CAD in the configuration of genetic diversity in current human populations.

Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide., (Copyright © 2014, American Association for the Advancement of Science.)

Chromosome counts and karyotypes of two species of Chrysolaena H. Robinson 1988 are presented in this paper. Mitotic analysis revealed that both taxa have x=10, a basic chromosome number considered characteristic of the genus. The chromosome number and the karyotype of Chrysolaena cristobaliana are reported for the first time, as well as a new cytotype and the karyotype of Chrysolaena sceptrum. Chrysolaena cristobaliana showed heptaploid cytotype with 2n=7x=70 and a karyotype composed of 46 m + 24 sm chromosomes. On the other hand, Chrysolaena sceptrum presented tetraploid cytotype with 2n=4x=40 and a karyotype with 30 m + 10 sm chromosomes. Accessory chromosomes were observed in cells of both species. The chromosome analysis showed that these species differ in the chromosome number and the total chromosome length, although they showed similar chromosome morphology and asymmetry indexes. The results support the use of chromosome data in taxonomic treatments of the American members of the tribe Vernonieae.

Coronary artery disease (CAD) mortality and morbidity is present in the European continent in a four-fold gradient across populations, from the South (Spain and France) with the lowest CAD mortality, towards the North (Finland and UK). This observed gradient has not been fully explained by classical or single genetic risk factors, resulting in some cases in the so called Southern European or Mediterranean paradox. Here we approached population genetic risk estimates using genetic risk scores (GRS) constructed with single nucleotide polymorphisms (SNP) from nitric oxide synthases (NOS) genes. These SNPs appeared to be associated with myocardial infarction (MI) in 2165 cases and 2153 controls. The GRSs were computed in 34 general European populations. Although the contribution of these GRS was lower than 1% between cases and controls, the mean GRS per population was positively correlated with coronary incidence explaining 65-85% of the variation among populations (67% in women and 86% in men). This large contribution to CAD incidence variation among populations might be a result of colinearity with several other common genetic and environmental factors. These results are not consistent with the cardiovascular Mediterranean paradox for genetics and support a CAD genetic architecture mainly based on combinations of common genetic polymorphisms. Population genetic risk scores is a promising approach in public health interventions to develop lifestyle programs and prevent intermediate risk factors in certain subpopulations with specific genetic predisposition.

Jordan, located in the Levant region, is an area crucial for the investigation of human migration between Africa and Eurasia. However, the genetic history of Jordanians has yet to be clarified, including the origin of the Bedouins today resident in Jordan. Here, we provide new genetic data on autosomal independent markers in two Jordanian population samples (Bedouins and the general population) to begin to examine the genetic diversity inside this country and to provide new information about the genetic position of these populations in the context of the Mediterranean and Middle East area. The markers analyzed were 18 Alu polymorphic insertions characterized by their identity by descent, known ancestral state (lack of insertion), and apparent selective neutrality. The results indicate significant genetic diffferences between Bedouins and general Jordanians (p = 0.038). Whereas Bedouins show a close genetic proximity to North Africans, general Jordanians appear genetically more similar to other Middle East populations. In general, these data are consistent with the hypothesis that Bedouins had an important role in the peopling of Jordan and constitute the original substrate of the current population. However, migration into Jordan in recent years likely has contributed to the diversity among current Jordanian population groups., (Copyright © 2014 Wayne State University Press, Detroit, Michigan 48201-1309.)

Researchers have identified thousands of loci involved in complex traits and drug response. However, in most cases they only explain a small proportion of the heritability of the trait. Among different strategies conducted to identify this 'missing heritability', here we illustrate the importance of complex gene-environment interactions using findings regarding the role of leukotrienes on the bronchodilator response to albuterol in Latino asthmatics. Patients managing their asthma with leukotriene-modifying medication presented higher increases in the bronchodilator response to albuterol. Moreover, interactions between genes responsible for leukotriene production were associated with a decreased risk of asthma. Combining genetic and pharmacologic effects, leukotriene-modifying users carrying certain combinations of alleles presented higher improvements in lung function after bronchodilator administration. Genes and drugs act at different orders of interaction (from individual effects to gene-gene-drug-drug interactions) and population-specific effects have to be considered. These results may be extrapolated to other complex phenotypes.

There is great scientific and popular interest in understanding the genetic history of populations in the Americas. We wish to understand when different regions of the continent were inhabited, where settlers came from, and how current inhabitants relate genetically to earlier populations. Recent studies unraveled parts of the genetic history of the continent using genotyping arrays and uniparental markers. The 1000 Genomes Project provides a unique opportunity for improving our understanding of population genetic history by providing over a hundred sequenced low coverage genomes and exomes from Colombian (CLM), Mexican-American (MXL), and Puerto Rican (PUR) populations. Here, we explore the genomic contributions of African, European, and especially Native American ancestry to these populations. Estimated Native American ancestry is 48% in MXL, 25% in CLM, and 13% in PUR. Native American ancestry in PUR is most closely related to populations surrounding the Orinoco River basin, confirming the Southern American ancestry of the Taíno people of the Caribbean. We present new methods to estimate the allele frequencies in the Native American fraction of the populations, and model their distribution using a demographic model for three ancestral Native American populations. These ancestral populations likely split in close succession: the most likely scenario, based on a peopling of the Americas 16 thousand years ago (kya), supports that the MXL Ancestors split 12.2kya, with a subsequent split of the ancestors to CLM and PUR 11.7kya. The model also features effective populations of 62,000 in Mexico, 8,700 in Colombia, and 1,900 in Puerto Rico. Modeling Identity-by-descent (IBD) and ancestry tract length, we show that post-contact populations also differ markedly in their effective sizes and migration patterns, with Puerto Rico showing the smallest effective size and the earlier migration from Europe. Finally, we compare IBD and ancestry assignments to find evidence for relatedness among European founders to the three populations., Competing Interests: The authors have declared that no competing interests exist.

The APOE/C1/C4/C2 gene cluster presents high relevance in lipid metabolism and, therefore, has important epidemiological implications. Here, we study for the first time the variation patterns of 25 polymorphisms (10 short tandem repeats, STRs, and 15 single nucleotide polymorphismas, SNPs) in two native Andean samples from Bolivia (45 Aymaras and 45 Quechuas) as well as one European sample (n = 41) as external reference. We estimated diversity parameters, linkage disequilibrium patterns, population structure, and possible selective effects. In general, diversity was low and could be partly attributed to selection (probably due to its physiological importance), since the APOE/C1/C4/C2 region was highly conserved compared to the flanking genes in both Bolivians and Europeans. Moreover, the lower gene diversity in Bolivians compared to Europeans for some markers might indicate different demographic histories. Regarding the APOE isoforms, in addition to ɛ3 (94%) and ɛ4 (5%), isoform ɛ2 (1%) was also detected in Bolivians. In relation to previous hypotheses, our results support that genetic drift or founder effects rather than selection for increased cholesterol absorption are the main factors that have shaped the distribution of APOE isoforms observed in South America., (© 2012 The Authors Annals of Human Genetics © 2012 Blackwell Publishing Ltd/University College London.)

Background: This work describes, for the first time, the profile of Middle Atlas Berbers and Arabic-speaking central Moroccans for 15 autosomal STR loci widely used in forensic sciences., Aim: The main objectives were to determine the degree of heterogeneity among different Moroccan samples to identify geographic or linguistic patterns and to evaluate the usefulness of forensic STRs in anthropological studies., Subjects and Methods: Blood samples were collected from 71 Arabic-speakers and 75 Berbers from the regions of Doukkala (central-west coast) and Khenifra (Middle Atlas), respectively. The AmpFlSTR Identifier kit was used to genotype 15 autosomal STR in both samples., Results: Middle Atlas Berbers showed slightly higher genetic variation values compared to Arabic-speakers, both in the number of alleles and heterozygosity. In order to assess population relationships, data from Morocco, Algeria, Tunisia, Libya, Egypt, Kuwait, Qatar, Palestine, Syria, South-Spain and Turkey were included in the analysis. Within Morocco, genetic distances followed a clear geographic pattern. In the Arabic-speaking sample the genetic proportion of 'Arabian' admixture was estimated in 13%., Conclusion: The low value of admixture suggests that the Arabization of Morocco had a reduced demographic impact, which should be taken with caution because it is based on autosomal STRs with low inter-population variation levels.

Among US Latinas and Mexican women, those with higher European ancestry have increased risk of breast cancer. We combined an admixture mapping and genome-wide association mapping approach to search for genomic regions that may explain this observation. Latina women with breast cancer (n= 1497) and Latina controls (n= 1272) were genotyped using Affymetrix and Illumina arrays. We inferred locus-specific genetic ancestry and compared the ancestry between cases and controls. We also performed single nucleotide polymorphism (SNP) association analyses in regions of interest. Correction for multiple-hypothesis testing was conducted using permutations (P(corrected)). We identified one region where genetic ancestry was significantly associated with breast cancer risk: 6q25 [odds ratio (OR) per Indigenous American chromosome 0.75, 95% confidence interval (CI): 0.65-0.85, P= 1.1 × 10(-5), P(corrected)= 0.02]. A second region on 11p15 showed a trend towards association (OR per Indigenous American chromosome 0.77, 95% CI: 0.68-0.87, P= 4.3 × 10(-5), P(corrected)= 0.08). In both regions, breast cancer risk decreased with higher Indigenous American ancestry in concordance with observations made on global ancestry. The peak of the 6q25 signal includes the estrogen receptor 1 (ESR1) gene and 5' region, a locus previously implicated in breast cancer. Genome-wide association analysis found that a multi-SNP model explained the admixture signal in both regions. Our results confirm that the association between genetic ancestry and breast cancer risk in US Latinas is partly due to genetic differences between populations of European and Indigenous Americans origin. Fine-mapping within the 6q25 and possibly the 11p15 loci will lead to the discovery of the biologically functional variant/s behind this association.

Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R² > 0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region., Competing Interests: CB and EGB are on the Scientific Advisory Board of 23andme's project "Roots into the Future." 23andme is a Mountain View, CA, company that provides direct-to-consumer genetic products. CB is also on the SAB of Ancestry.com, a company in Provo, UT, that provides direct-to-consumer genetic products. Neither company played a part in the research described here or has a financial stake in the results. The remaining authors have declared that no competing interests exist.

The population of Argentina is the result of the intermixing between several groups, including Indigenous American, European and African populations. Despite the commonly held idea that the population of Argentina is of mostly European origin, multiple studies have shown that this process of admixture had an impact in the entire Argentine population. In the present study we characterized the distribution of Indigenous American, European and African ancestry among individuals from different regions of Argentina and evaluated the level of discrepancy between self-reported grandparental origin and genetic ancestry estimates. A set of 99 autosomal ancestry informative markers (AIMs) was genotyped in a sample of 441 Argentine individuals to estimate genetic ancestry. We used non-parametric tests to evaluate statistical significance. The average ancestry for the Argentine sample overall was 65% European (95%CI: 63-68%), 31% Indigenous American (28-33%) and 4% African (3-4%). We observed statistically significant differences in European ancestry across Argentine regions [Buenos Aires province (BA) 76%, 95%CI: 73-79%; Northeast (NEA) 54%, 95%CI: 49-58%; Northwest (NWA) 33%, 95%CI: 21-41%; South 54%, 95%CI: 49-59%; p<0.0001] as well as between the capital and immediate suburbs of Buenos Aires city compared to more distant suburbs [80% (95%CI: 75-86%) versus 68% (95%CI: 58-77%), p = 0.01]. European ancestry among individuals that declared all grandparents born in Europe was 91% (95%CI: 88-94%) compared to 54% (95%CI: 51-57%) among those with no European grandparents (p<0.001). Our results demonstrate the range of variation in genetic ancestry among Argentine individuals from different regions in the country, highlighting the importance of taking this variation into account in genetic association and admixture mapping studies in this population.

Obesity and diabetes are increasing in prevalence worldwide. Despite excessive dietary consumption, obese individuals have high rates of micronutrient deficiencies. Deficiencies of specific vitamins and minerals that play important roles in glucose metabolism and insulin signaling pathways may contribute to the development of diabetes in the obese population. This paper reviews the current evidence supporting this hypothesis.

Background: Although Mexicans and Puerto Ricans are jointly classified as "Hispanic/Latino," there are significant differences in asthma prevalence, severity, and mortality between the 2 groups. We sought to examine the possibility that population-specific genetic risks contribute to this disparity., Objectives: More than 100 candidate genes have been associated with asthma and replicated in an independent population, and 7 genome-wide association studies in asthma have been performed. We compared the pattern of replication of these associations in Puerto Ricans and Mexicans., Methods: We genotyped Mexican and Puerto Rican trios using an Affymetrix 6.0 GeneChip and used a family-based analysis to test for genetic associations in 124 genes previously associated with asthma., Results: We identified 32 single nucleotide polymorphisms (SNPs) in 17 genes associated with asthma in at least 1 of the 2 populations. Twenty-two of these SNPs in 11 genes were significantly associated with asthma in the combined population and showed no significant heterogeneity of association, whereas 5 SNPs were associated in only 1 population and showed statistically significant heterogeneity. In a gene-based approach 2 additional genes were associated with asthma in the combined population, and 3 additional genes displayed ethnic-specific associations with heterogeneity., Conclusions: Our results show that only a minority of genetic association studies replicate in our population of Mexican and Puerto Rican asthmatic subjects. Among SNPs that were successfully replicated, most showed no significant heterogeneity across populations. However, we identified several population-specific genetic associations., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Contemporary genetic variation among Latin Americans human groups reflects population migrations shaped by complex historical, social and economic factors. Consequently, admixture patterns may vary by geographic regions ranging from countries to neighborhoods. We examined the geographic variation of admixture across the island of Puerto Rico and the degree to which it could be explained by historic and social events. We analyzed a census-based sample of 642 Puerto Rican individuals that were genotyped for 93 ancestry informative markers (AIMs) to estimate African, European and Native American ancestry. Socioeconomic status (SES) data and geographic location were obtained for each individual. There was significant geographic variation of ancestry across the island. In particular, African ancestry demonstrated a decreasing East to West gradient that was partially explained by historical factors linked to the colonial sugar plantation system. SES also demonstrated a parallel decreasing cline from East to West. However, at a local level, SES and African ancestry were negatively correlated. European ancestry was strongly negatively correlated with African ancestry and therefore showed patterns complementary to African ancestry. By contrast, Native American ancestry showed little variation across the island and across individuals and appears to have played little social role historically. The observed geographic distributions of SES and genetic variation relate to historical social events and mating patterns, and have substantial implications for the design of studies in the recently admixed Puerto Rican population. More generally, our results demonstrate the importance of incorporating social and geographic data with genetics when studying contemporary admixed populations.

Background: Understanding the effects of interactions between multiple genes and asthma medications may aid in the understanding of the heterogeneous response to asthma therapies., Objective: To identify modulating effects of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A(4) hydrolase (LTA4H) gene polymorphisms on the drug-drug interaction between leukotriene modifiers and albuterol in Mexicans and Puerto Ricans., Methods: In a cross-sectional study of 293 Mexicans and 356 Puerto Ricans with asthma, ALOX5AP and LTA4H genes were sequenced, and interactions between gene polymorphisms and bronchodilator responsiveness to albuterol were compared between leukotriene modifier users and nonusers., Results: In heterozygotes and homozygotes for the minor allele at LTA4H single nucleotide polymorphism (SNP) rs2540491 and heterozygotes for the major allele at LTA4H SNP rs2540487, leukotriene modifier use was associated with a clinically significant increase in percent change in FEV(1) after albuterol administration of 7.10% (P = .002), 10.06% (P = .001), and 10.03% (P < .001), respectively. Presence of the major allele at ALOX5AP SNP rs10507391 or the minor allele at ALOX5AP SNP rs9551963 augmented this response. When stratified by ethnicity, these findings held true for Puerto Ricans but not Mexicans., Conclusion: LTA4H and ALOX5AP gene polymorphisms modify the augmentation of bronchodilator responsiveness by leukotriene modifiers in Puerto Ricans but not Mexicans with asthma., (Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Leukotrienes play an important role in allergic and inflammatory diseases, but reports on the involvement of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A(4) hydrolase (LTA4H) in asthma have been inconclusive., Objective: To determine whether polymorphisms in ALOX5AP and LTA4H genes are risk factors for asthma in two different Latino groups: Mexicans and Puerto Ricans., Methods: The LTA4H gene was sequenced in individuals from both groups to identify novel polymorphisms. Single-nucleotide polymorphisms (SNPs) in the ALOX5AP and LTA4H genes were analysed for associations with asthma and asthma-related phenotypes in 687 parent-child trios of Mexican and Puerto Rican origin., Results: In LTA4H, five previously unknown polymorphisms were identified. Two SNPs within LTA4H (rs17525488 and rs2540493) were protective for asthma in Latinos (P=0.007 and 0.05, respectively). Among the Mexican patients, LTA4H polymorphisms were associated with baseline lung function and IgE levels. For ALOX5AP, the minor allele at SNP rs10507391 was associated with protection from asthma (odds ratio=0.78, P=0.02) and baseline lung function (P=0.018) in Puerto Ricans. A gene-gene interaction was identified between LTA4H (rs17525488) and ALOX5AP (rs10507391), (P=0.003, in the combined sample)., Conclusion: Our results support the role of LTA4H and ALOX5AP variants as risk factors for asthma in Latino populations.

The variation of 18 Alu polymorphisms and 3 linked STRs was determined in 1,831 individuals from 15 Mediterranean populations to analyze the relationships between human groups in this geographical region and provide a complementary perspective to information from studies based on uniparental markers. Patterns of population diversity revealed by the two kinds of markers examined were different from one another, likely in relation to their different mutation rates. Therefore, while the Alu biallelic variation underlies general heterogeneity throughout the whole Mediterranean region, the combined use of Alu and STR points to a considerable genetic differentiation between the two Mediterranean shores, presumably strengthened by a considerable sub-Saharan African genetic contribution in North Africa (around 13% calculated from Alu markers). Gene flow analysis confirms the permeability of the Sahara to human passage along with the existence of trans-Mediterranean interchanges. Two specific Alu/STR combinations-CD4 110(-) and DM 107(-)-detected in all North African samples, the Iberian Peninsula, Greece, Turkey, and some Mediterranean islands suggest an ancient genetic background of current Mediterranean peoples.