Divergent selection in a Mediterranean pine on local spatial scales

1. The effects of selection on an organism's genome are hard to detect on small spatial scales, as gene flow can swamp signatures of local adaptation. Therefore, most genome scans to detect signatures of environmental selection are performed on large spatial scales; however, divergent selection on the local scale (e.g. between contrasting soil conditions) has also been demonstrated, in particular for herbaceous plants. 2. Here, we hypothesised that in topographically complex landscapes, microenvironment variability is strong enough to leave a selective footprint in the genomes of long-lived organisms. To test this, we investigated paired south- versus north-facing Pinus pinaster stands on the local scale, with trees growing in close vicinity (≤820 m distance between paired south- and north-facing stands), in a Mediterranean mountain area. While trees on north-facing slopes experience less radiation, trees on south-facing slopes suffer from especially harsh conditions, particularly during the dry summer season. 3. Two outlier analyses consistently revealed five putatively adaptive loci (out of 4034), in candidate genes two of which encoded non-synonymous substitutions. Additionally, one locus showed consistent allele frequency differences in all three stand pairs indicating divergent selection despite high gene flow on the local scale. Permutation tests demonstrated that our findings were robust. 4. Functional annotation of these candidate genes revealed biological functions related to abiotic stress response, such as water availability, in other plant species. 5. Synthesis. Our study highlights how divergent selection in heterogeneous microenvironments shapes and maintains the functional genetic variation within populations of long-lived forest tree species, being the first to focus on adaptive genetic divergence between south- and north-facing slopes within continuous forest stands. This is especially relevant in the current context of climate change, as this variation is at the base of plant population responses to future climate.European Commission http://dx.doi.org/10.13039/501100000780European Science Foundation http://dx.doi.org/10.13039/501100000782Spanish Ministry of Science and Innovation http://dx.doi.org/10.13039/501100004837University of BrodeauxPeer Reviewe

Egg consumption and dyslipidemia in a Mediterranean cohort

Introduction and objectives: Our aim was to prospectively evaluate the association between egg consumption and dyslipidemia in a Mediterranean cohort. Methods: We followed-up 13,104 Spanish university graduates for a mean period of 8 years. Dietary habits at baseline were assessed using a validated semi-quantitative 136-item food-frequency questionnaire. Self-reported blood concentrations of total cholesterol, high-density lipoproteins cholesterol (HDL-c) and triglycerides were evaluated according to categories of egg consumption after 6 and 8 years of follow-up. We also assessed the association between baseline egg consumption and the incidence of hypercholesterolemia, low HDL-c concentrations and hypertriglyceridemia during follow-up. Results: We observed a significant inverse association for intermediate levels of egg consumption (2 to 4 eggs/week vs. less than 1 egg/week) and hypertriglyceridemia with OR = 0.71 (95% confidence interval [CI]: 0.54 to 0.93, p < 0.05) in the multivariable-adjusted model. Using HDL-c values after 8-year follow-up, we found an association between higher egg consumption and lower HDL-c levels (p for trend = 0.02) with an adjusted difference of –4.01 mg/dl (-7.42 to -0.61) for > 4 vs. < 1 egg/week. Lower means of triglycerides were found in each of the three upper categories of egg consumption compared to the lowest category (< 1 egg/week) with significant results for some of these categories both after 6 and 8 year follow-up. Conclusions: Our data do not support that higher egg consumption was associated with abnormal blood levels of total cholesterol or triglycerides; an inverse association with HDL-c as a quantitative variable was found only in one of our analyses.Introducción y objetivos: evaluar prospectivamente la asociación entre el consumo de huevo y el riesgo de dislipidemia en una cohorte mediterránea. Métodos: se siguieron 13.104 graduados universitarios españoles durante un periodo medio de 8 años. La dieta se evaluó al inicio utilizando un cuestionario semicuantitativo de frecuencia de consumo de alimentos repetidamente validado. Las concentraciones sanguíneas de colesterol total, lipoproteínas de alta densidad (HDL-c) y triglicéridos autorreferidas fueron evaluadas según categorías de consumo de huevo tras 6 y 8 años de seguimiento. También se evaluó la asociación entre el consumo basal de huevo y la incidencia de hipercolesterolemia, concentraciones bajas de HDL-c e hipertrigliceridemia durante el seguimiento. Resultados: se observó una asociación entre los niveles intermedios de consumo de huevo (2-4 unidades/semana frente a < 1 unidad/semana) y menor riesgo de hipertrigliceridemia con OR = 0,71 (intervalo de confianza del 95% [IC]: 0,54 a 0,93, p < 0,05) en el modelo más ajustado. Tras 8 años de seguimiento, encontramos una asociación entre un mayor consumo de huevo y menores niveles de HDL-c (p tendencia lineal = 0,02) con una diferencia ajustada de -4,01 mg/dl (-7,42 a -0,61) para > 4 vs. < 1 unidad/semana. Se encontraron menores concentraciones de triglicéridos en las tres categorías superiores de consumo de huevo en comparación con la inferior con resultados significativos para algunas de estas categorías después de 6 y 8 años de seguimiento. Conclusiones: un mayor consumo de huevo no se asoció con niveles anormales de colesterol total o triglicéridos; se encontró una asociación inversa con HDL-c como variable cuantitativa solo en uno de nuestros análisis

Frecuencia de comidas fuera de casa y calidad de hidratos de carbono y de grasas en el proyecto SUN

Objetivo: Investigar la asociación entre la frecuencia de comidas fuera de casa (CFC) con a) la calidad de hidratos de carbono y b) la calidad de grasas. Materiales y métodos: Se evaluaron 19.371 participantes de la cohorte SUN que completaron un cuestionario basal de frecuencia de consumo de alimentos previamente validado. Se utilizaron los índices de calidad de hidratos de carbono (ICHC) en una escala de 4 a 20 y de grasas (ICG) en una escala de 0,62 a 5,92. En ambos casos, a mayor puntuación mayor calidad. Se utilizó la regresión lineal múltiple para determinar la asociación entre la frecuencia de CFC (4 categorías) y la puntuación de ambos índices, y la regresión logística para medir la asociación entre la frecuencia de CFC y un bajo ICHC o ICG (<percentil 25). Resultados: Los participantes mostraron una media de ICHC e ICG de 11,3 (DE 3,2) y 1,7 (DE 0,5), respectivamente. Una mayor frecuencia de CFC (≥ 2 veces / semana) se asoció con un menor ICHC (ß: -0,29, IC 95%: -0,41 a -0,17, p <0,001), y con un menor ICG (ß: -0,02, IC 95%: -0,03 a -0,001, p <0,03). Los participantes con CFC ≥ 2 veces/semana tuvieron mayor riesgo de peor ICHC (OR: 1,31, IC 95%: 1,17-1,46, p <0,001), pero no de peor ICG (OR: 0,93 IC 95%: 0,83-1,03, p 0,194). Conclusiones: Hacer con mayor frecuencia CFC se asoció con una peor calidad de grasas en la dieta y especialmente con peor calidad de hidratos de carbono. Estos resultados destacan la importancia de la educación nutricional dirigida a los consumidores de CFC.Objective: To investigate the association between eating- away-from-home (EAFH) and a) the quality of dietary carbohydrate intake and b) the quality of fat intake. Material and methods: We assessed 19,371 participants in the SUN cohort who completed a validated baseline food frequency questionnaire. Quality indices of carbohydrate (CQI) and fat (FQI) were used. Multiple regression models were fitted to determine the association between the frequency of EAFH (4 categories) and both indices. Logistic regression analysis was used to assess the association between the frequency of EAFH and low CQI or FQI (<25th percentile). Results: Participants showed an average CQI and FQI of 11,3 (SD 3,2) and 1,7 (SD 0,5), respectively. A higher frequency of EAFH (≥ 2 times/week) was associated with a poorer CQI and a poorer FQI. For CQI, the adjusted mean difference was -0,29, 95%CI: -0,41, -0,17 (p for trend <0,001), and for FQI it was -0,02, 95%CI: -0,03, -0,001 (p for trend 0,03). Participants with a highest frequency (≥ 2 times/week) of EAFH had higher adjusted risk of a poorer CQI, (adjusted OR 1,31, 95%CI 1,17, 1,46, p for trend <0,001), but this habit (EAFH) was unrelated to FQI (adjusted OR 0,93, 95%CI: 0,83, 1,03, p for trend 0,194). Key findings: A higher frequency of EAFH was associated with a poorer quality of dietary fat, and particularly, dietary carbohohydrate. These findings highlight the importance of nutritional education addressed to consumers who frequently do out-of-home meals

Possible metabolic interplay between quality of life and fecal microbiota in a presenior population: Preliminary results

Objectives: The number of people aged 60 y is increasing worldwide, so establishing a relationship between lifestyle and health-associated factors, such as gut microbiota in an older population, is important. This study aimed to characterize the gut microbiota of a presenior population, and analyze the association between some bacteria and quality of life with the Short Form (SF) 36 questionnaire. Methods: Participants were adult men and women ages 50 to 80 y (n = 74). In addition to the SF-36 question- naire, fecal samples were collected in cryotubes, and 16S RNA gene sequencing was performed to character- ize microbial features. Participants were classified into two groups according to SF-36 punctuation. Linear and logistic regression models were performed to assess the possible association between any bacterial bowl and SF-36 score. Receiver operating characteristics curves were fitted to define the relative diagnostic strength of different bacterial taxa for the correct determination of quality of life. Results: A positive relationship was established between SF-36 score and Actinobacteria (P = 0.0310; R = 0.2510) compared with Peptostreptococcaceae (P = 0.0259; R = 0.2589), which increased with decreasing quality of life. Logistic regressions models and receiver operating characteristics curves showed that the rela- tive abundance of Actinobacteria and Peptostreptococcaceae may be useful to predict quality of life in a prese- nior population (area under the curve: 0.71). Conclusions: Quality of life may be associated with the relative abundance of certain bacteria, especially Acti- nobacteria and Peptostreptococcaceae, which may have a specific effect on certain markers and health care, which is important to improve quality of life in older populations

Carbohydrate quality, weight change and incident obesity in a mediterranean cohort: the sun project

Background/ Objectives: To evaluate the association between the carbohydrate quality (CQI) and weight change or incident overweight/obesity (BMI≥25 kg/m2) in the “Seguimiento Universidad de Navarra (SUN)” cohort. Subjects/ Methods: 8 741 participants initially free of overweight/obesity were followed‐up for a median of 7.9 years. We evaluated at baseline the CQI following 4 criteria: dietary fibre intake, glycemic index (GI), whole grains/total grains ratio and solid carbohydrates/total carbohydrates ratio. Subjects were classified into quintiles according to CQI. Weight was recorded at baseline and updated every 2 years during follow‐up. Results: Increasing CQI of diet was not significantly associated with lower weight gain, although participants in the highest quintile had the lowest average crude weight gain (+211 g/year). We observed 1 862 incident cases of overweight/obesity during followup. CQI was significantly associated (p for trend 0.006) with lower risk of overweight/obesity: adjusted OR for the 4rd and 5th quintiles: 0.81 (95% CI 0.66 to 0.99), and 0.74 (95% CI 0.60 to 0.92), respectively. Conclusions: In this Mediterranean cohort, CQI showed a significant inverse association with the incidence of overweight/obesity, which highlights that carbohydrate intake guidelines related to obesity prevention should be focused in improving the CQI of the diet

Determinants of self-rated health perception in a sample of a physically active population: PLENUFAR VI study

The aim of this study was to investigate determinants of self-rated health (SRH) perception in Spanish adults. This cross-sectional study including data from 11,342 participants from the Spanish PLENUFAR VI study. SRH status was grouped in two categories ('good'/'poor') and the associations of socio-demographic characteristics, lifestyles, diet adequacy and chronic disease with SRH were assessed. After adjusting for relevant confounders, the risk ratios (RR) and (95% confidence intervals) for poor SRH were 1.05 (1.03-1.07) for each hour of increment of sitting, 1.56 (1.30-1.88) for short (>= 5 h vs. 7-8 h) sleep duration, 0.63 (0.55-0.72) for vigorous (vs. light) physical activity, 0.61 (0.50-0.74) for adequate (vs. non-adequate) diet. Activities like jogging [RR for each unit of increment in the METs-h/day = 0.87 (0.82-0.92)], gymnastics [0.87 (0.81-0.93)], biking [0.91 (0.85-0.98)], and track and field [0.94 (0.89-0.98)], were associated with better health perception. Normally weight participants with any chronic disease had lower probability to report poor SRH than overweight/obese participants with any chronic disease. Frequent consumption of bread (>2 servings/day) was associated with a lower adjusted mean of health perception scale, while higher consumption of vegetables and fruit or fish were associated with higher values, concerning good SRH. We can conclude that normal-weight participants even suffering a chronic disease had lower probability to report poor health perception than participants with overweight/obesity and a chronic disease especially for hypertension and diabetes. Activities like jogging, gymnastics, biking, and track and field, and a higher consumption of fruits, vegetables and fish, were associated with better health rated perception

Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea

Background Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. Methods Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. Results A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI) mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. Conclusions NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality

Prognostic factors of a lower CD4/CD8 ratio in long term viral suppression HIV infected children

Background Combination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution. Methods Perinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit. Results 146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5-6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 <1 with lower CD4 nadir and baseline CD4; older age at diagnosis and at cART initiation; and a previous exposure to mono-dual therapy. Multivariate analysis also revealed relationship between CD4/CD8 <1 and lower CD4 nadir (OR: 1.002, CI 95% 1.000-1.004) as well as previous exposure to mono-dual therapy (OR: 0.16, CI 95% 0.003-0.720). Conclusions CD4/CD8 > 1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1)

Mitochondria function associated genes contribute to Parkinson's Disease risk and later age at onset

Mitochondrial dysfunction has been implicated in the etiology of monogenic Parkinson’s disease (PD). Yet the role that mitochondrial processes play in the most common form of the disease; sporadic PD, is yet to be fully established. Here, we comprehensively assessed the role of mitochondrial function-associated genes in sporadic PD by leveraging improvements in the scale and analysis of PD GWAS data with recent advances in our understanding of the genetics of mitochondrial disease. We calculated a mitochondrial-specific polygenic risk score (PRS) and showed that cumulative small effect variants within both our primary and secondary gene lists are significantly associated with increased PD risk. We further reported that the PRS of the secondary mitochondrial gene list was significantly associated with later age at onset. Finally, to identify possible functional genomic associations we implemented Mendelian randomization, which showed that 14 of these mitochondrial functionassociated genes showed functional consequence associated with PD risk. Further analysis suggested that the 14 identified genes are not only involved in mitophagy, but implicate new mitochondrial processes. Our data suggests that therapeutics targeting mitochondrial bioenergetics and proteostasis pathways distinct from mitophagy could be beneficial to treating the early stage of PD

Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson's disease heritability

Parkinson’s disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability attributable to common variation does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set highly expressed in astrocytic, microglial, and oligodendrocyte subtypes, and in LoF-intolerant genes, which were found highly expressed in almost all tested cellular subtypes. Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes detectable across several cell types