HiCRes: a computational method to estimate and predict the genomic resolution of Hi-C libraries.

Three-dimensional (3D) conformation of the chromatin is crucial to stringently regulate gene expression patterns and DNA replication in a cell-type specific manner. Hi-C is a key technique for measuring 3D chromatin interactions genome wide. Estimating and predicting the resolution of a library is an essential step in any Hi-C experimental design. Here, we present the mathematical concepts to estimate the resolution of a dataset and predict whether deeper sequencing would enhance the resolution. We have developed HiCRes, a docker pipeline, by applying these concepts to several Hi-C libraries.

[Association between educational level and suspicion of cognitive imparirment in Chilean older people]. / Asociación entre nivel educacional y sospecha de deterioro cognitivo en personas mayores chilenas: resultados de la Encuesta Nacional de Salud 2016-2017.

BACKGROUND: A low education level has been associated with cognitive impairment in older adults. AIM: To determine the association between educational attainment and suspicion of cognitive imparirment in older Chilean population. MATERIAL AND METHODS: Data from 2,005 adults aged ≥ 60 years assessed during 2016-2017 Chilean National Health Survey were included. Education was self-reported and categorized as primary: ≤ 8 years; secondary: 9 to 12 years and beyond secondary: > 12 years. suspicion of cognitive imparirment was assessed with the Mini-Mental questionnaire. RESULTS: Men and women with low education attainment had a higher prevalence of cognitive impairment (33% [95% confidence intervals (CI): 24; 41] and 27% [95% CI: 21; 33], respectively). Men who reported less schooling (≤ 8 years) were more likely to be at risk of suspicion of cognitive imparirment (Odds ratio (OR): 4.53 [95% CI: 1.10, 18.62]) compared to their peers. Women showed a substantially higher magnitude of association than men. The probability of suspicion of cognitive imparirment increased 9-times (OR: 9.96 [95% CI: 1.24; 79.6]) for 9-12 years and 18-times for ≤ 8 years of education (OR: 18.8 [95% CI: 2.42; 146.1]) compared to women with higher education. CONCLUSIONS: Older adults with low education attainment had an increased likelihood of developing suspicion of cognitive imparirment. However, the risk differs by sex, being higher in women than men.

[Older people in Chile: the new social, economic and health challenge for the 21st century]. / Personas mayores en Chile: el nuevo desafío social, económico y sanitario del Siglo XXI.

Ageing will be one of the most significant social transformations of the 21st century worldwide. In the last 40 years, Chile has tripled its older adult population. As a result, by 2050 the country will have the highest proportion of older adults in Latin America. This remarkable growth reinforces the need to identify their current situation and to revise what is the society doing to maintain older people as active members. In this context, this narrative revision aimed to describe the sociodemographic, epidemiologic and sociocultural profile of the older Chilean adults. Besides, programs and public policies focused on the improvement of their quality of life were identified.

[Prevalence of low hand grip strength in Chilean older adults. Findings from the national health survey 2016-2017]. / Prevalencia de debilidad muscular en personas mayores chilenas: resultados de la Encuesta Nacional de Salud 2016-2017.

BACKGROUND: Handgrip strength is an indicator of frailty in older people. AIM: To determine the prevalence of low handgrip strength in older Chilean adults. MATERIAL AND METHODS: A cross-sectional analysis of 244 individuals aged 60 years or more, participating in the 2016-2017 Chilean National Health Survey, was carried out. Handgrip strength was evaluated by a hand dynamometer and low grip strength was determined as a grip strength ≤ 15 kg and ≤ 27 kg for women and men, respectively. RESULTS: Twenty nine percent of participants had low grip strength. The average grip strength among 60-year-old men and women was 34.7 and 22.1 kg, respectively. These figures decreased to 28.8 kg and 17.2 kg among 90-year-old men and women, respectively. The prevalence of low grip strength in men and women aged 60 years was 18%. In 90-year-old men and women, these figures increased to 79% and 56.3%, respectively. CONCLUSIONS: The prevalence of low grip strength increased substantially with age.

Long-term quality of life in octogenarians and nonagenarians with nonvalvular atrial fibrillation following WATCHMAN™ device implantation.

OBJECTIVES: To assess the impact of WATCHMAN™ on quality of life (QoL) in octogenarians and nonagenarians. BACKGROUND: QoL after WATCHMAN™ device in the elderly remains unknown. METHODS: This is a prospective and retrospective cohort study of patients that underwent WATCHMAN™ implantation in a tertiary cardiovascular center from April 1, 2015 to September 27, 2017. The primary outcome was a prospective assessment of QoL via the SF-12v2 Health Survey (SF-12v2) in those aged ≥80 and ≥90 years. Secondary outcomes include major bleeding, stroke, vascular complications, pericardial effusion, device related thrombus (DRT), prolonged length of stay (LOS), acute kidney injury (AKI), and recurrent hospitalizations. RESULTS: This cohort of 151 patients included 48/151 (32%) females with a mean age of 80 ± 7.7 years. Mean CHA2 DS2 -VASc was 4.38 ± 1.36 and mean HAS-BLED was 3.27 ± 1.17. Octogenarians 65/81(80%) and nonagenarians 16/81(20%) comprised 81/151(54%) of patients (mean age 86 ± 4.3 years) from which 36/65 (55%) octogenarians and 10/16 (63%) nonagenarians completed SF-12v2 evaluation at 22 ± 10 and 30 ± 10-months. Octogenarians demonstrated enhanced physical component scores (PCS), and nonagenarians equal PCS versus the age-adjusted norm (45.43 ± 9.84 versus 38.68 ± 11.04, P = 0.0003, and 41.26 ± 12.36 versus 38.68 ± 11.04, P = 0.6463, respectively). The mental component scores (MCS) of octogenarians and nonagenarians remained comparable (51.80 ± 9.56 and 48.97 ± 9.92 versus 50.06 ± 10.94, respectively, P = 0.4659). No stroke, vascular complications, pericardial effusions, or readmissions related to WATCHMAN™ occurred. No difference among patients <80, ≥80, and ≥90 years was found in major bleeding events, DRT, prolonged LOS, or AKI (P = 0.0569, 0.116, 0.498, and 0.795, respectively). CONCLUSIONS: Octogenarians and nonagenarians experience favorable long-term QoL after WATCHMAN™, with acceptable bleeding risk and low incidence of procedure-related complications.

[Correlates of sedentary behaviors in Chile: evidence from the National Health Survey 2009-2010]. / Factores asociados a sedentarismo en Chile: evidencia de la Encuesta Nacional de Salud 2009-2010.

BACKGROUND: Sedentary behaviors are one of the major risk factors for cardiovascular diseases. AIM: To identify factors associated with high sedentary behaviors in the Chilean population. MATERIAL AND METHODS: We included 5,040 participants from the Chilean National Health Survey 2009-2010. Physical activity level and sedentary behavior (sitting time) were measured using the Global Physical Activity Questionnaire (GPAQ v2). Highly sedentary behaviors were determined as > 4 hours per day of sitting time. Logistic regression was used to identify correlates of highly sedentary behavior. RESULTS: Forty seven percent of the study population reported spending more than 4 hours per day sitting. The prevalence was higher in women. The main factors associated with high sedentary behavior were: high income levels (Odds ratio (OR):1.91 [95% Confidence intervals (CI:1.61-2.27]); being woman (OR:1.39 [95% CI:1.24-1.56]): having central obesity (OR:1.15 [95% CI:1.02-1.30]), being physically inactive (OR:2.35 [95% CI:2.06-2.68]), and living in an urban area (OR:1.92 [95% CI:1.63-2.26]). Other factors associates with high sedentary behavior were: being smoker, having a television set, computer and private car at their homes. Participants reporting a poor self-reported health and wellbeing and those with diabetes or metabolic syndrome were more likely to be highly sedentary. CONCLUSIONS: The main factors associated with high levels of sedentary behavior are socio-demographic issues, lifestyles and health status.

[Effects of a lower body weight or waist circumference on cardiovascular risk]. / Menor peso corporal, de índice de masa corporal y de perímetro de cintura se asocian a una disminución en factores de riesgo cardiovascular en población chilena: Findings from the Chilean health surveyç.

BACKGROUND: Overall and central obesity are important risk factors for cardiovascular disease. AIM: To investigate the association of body weight, body mass index (BMI) and waist circumference (WC) with cardiovascular risk factors in Chile. MATERIAL AND METHODS: We included 5,157 participants from the National Health Survey 2009-2010. Prevalence of type 2 diabetes, hypertension, metabolic syndrome and dyslipidemia (high total cholesterol and triglyceride levels and low HDL-cholesterol) were defined using international recommendations. BMI and WC were measured using standardized protocols. RESULTS: A five percent lower body weight, BMI and WC were associated with a significant reduction in cardiovascular risk factors. For each 5% reduction in body weight, the risk for hypertension decreased by 8 and 9% in women and men respectively. Similar risk reductions were observed for diabetes (9 and 11% respectively), metabolic syndrome (23 and 30% respectively), low HDL cholesterol (13 and 13% respectively), high triglyceride levels (16 and 18% respectively) and total cholesterol (8 and 10% respectively). Similar findings were observed for BMI and WC. CONCLUSIONS: Lower body weight, BMI or WC are associated with important reductions in cardiovascular risk factors. A 5% reduction in these adiposity markers could be a perfectly feasible goal for lifestyle interventions.

[Association of active commuting with obesity: findings from the Chilean National Health Survey 2009-2010]. / Mayores niveles de transporte activo se asocian a un menor nivel de adiposidad y menor riesgo de obesidad: resultados de la Encuesta Nacional de Salud 2009-2010.

BACKGROUND: Active commuting is associated with a lower risk for obesity in developed countries. AIM: To investigate the association between active commuting and obesity risk in Chile. MATERIAL AND METHODS: Active commuting was measured using the Global Physical Activity Questionnaire (GPAQ v2) in 5,293 participants from the Chilean National Health Survey 2009-2010. Body mass index (BMI) and waist circumference (WC) were the study outcomes. The association between active commuting and obesity was investigated using linear and logistic regression analysis. RESULTS: Thirty four percent of responders [95% confidence intervals (CI): 32.6-35.1] were passive commuters. Active commuters had a lower BMI and WC than their passive counterparts. Thirty minutes increment in active commuting were associated with a -0.20 kg.m-2 lower BMI [95% CI: -0.33 to -0.07, p < 0.01] and a -076 cm lower WC [95% CI: -1.08 to -0.43, p < 0.01]. The odds of having a BMI > 25 kg.m-2 was 0.93 [95% CI: 0.88 to 0.98, p = 0.01] per every 30 minutes' increment in active commuting, whereas the odds for central obesity was 0.87 [95% CI: 0.82 to 0.92, p < 0.01]. CONCLUSIONS: Active commuting is associated with a lower adiposity and lower risk for obesity in Chilean adults.

Co-activator candidate interactions for orphan nuclear receptor NR2E1.

BACKGROUND: NR2E1 (Tlx) is an orphan nuclear receptor that regulates the maintenance and self-renewal of neural stem cells, and promotes tumourigenesis. Nr2e1-null mice exhibit reduced cortical and limbic structures and pronounced retinal dystrophy. NR2E1 functions mainly as a repressor of gene transcription in association with the co-repressors atrophin-1, LSD1, HDAC and BCL11A. Recent evidence suggests that NR2E1 also acts as an activator of gene transcription. However, co-activator complexes that interact with NR2E1 have not yet been identified. In order to find potential novel co-regulators for NR2E1, we used a microarray assay for real-time analysis of co-regulator-nuclear receptor interaction (MARCoNI) that contains peptides representing interaction motifs from potential co-regulatory proteins, including known co-activator nuclear receptor box sequences (LxxLL motif). RESULTS: We found that NR2E1 binds strongly to an atrophin-1 peptide (Atro box) used as positive control and to 19 other peptides that constitute candidate NR2E1 partners. Two of these proteins, p300 and androgen receptor (AR), were further validated by reciprocal pull-down assays. The specificity of NR2E1 binding to peptides in the array was evaluated using two single amino acid variants, R274G and R276Q, which disrupted the majority of the binding interactions observed with wild-type NR2E1. The decreased binding affinity of these variants to co-regulators was further validated by pull-down assays using atrophin1 as bait. Despite the high conservation of arginine 274 in vertebrates, its reduced interactions with co-regulators were not significant in vivo as determined by retinal phenotype analysis in single-copy Nr2e1-null mice carrying the variant R274G. CONCLUSIONS: We showed that MARCoNI is a specific assay to test interactions of NR2E1 with candidate co-regulators. In this way, we unveiled 19 potential co-regulator partners for NR2E1, including eight co-activators. All the candidates here identified need to be further validated using in vitro and in vivo models. This assay was sensitive to point mutations in NR2E1 ligand binding domain making it useful to identify mutations and/or small molecules that alter binding of NR2E1 to protein partners.

Socio-demographic patterns of physical activity and sedentary behaviour in Chile: results from the National Health Survey 2009-2010.

BACKGROUND: Surveillance of physical activity (PA) is essential for the development of health promotion initiatives. The aim of the present study was to examine the prevalence of PA and sedentary behaviour with respect to socio-demographic factors in Chile. METHODS: A representative sample of 5434 adults aged ≥15 years (59% women) who participated in the Chilean National Health Survey (2009-2010) were included. Socio-demographic data (age, sex, environment, education level, income level and smoking status) were collected for all participants. PA levels were assessed using the Global Physical Activity Questionnaire. RESULTS: 19.8% [95% CI: 18.1-21.6] of the Chilean population did not meet PA recommendations (≥600 MET min week(-1)). The prevalence of physical inactivity was higher in participants aged ≥65 years, compared with the youngest age groups and was higher in women than in men. However, it was lower for participants with high, compared with low, education or income levels. The overall prevalence of sedentary risk behaviour (spending >4 h sitting per day) was 35.9% [95% CI: 33.7-38.2]. CONCLUSION: Physical inactivity correlates strongly with socio-demographic factors such as age, gender and educational level. Results identify social and economic groups to which future public health interventions should be aimed to increase PA in the Chilean population.

Combined serial analysis of gene expression and transcription factor binding site prediction identifies novel-candidate-target genes of Nr2e1 in neocortex development.

BACKGROUND: Nr2e1 (nuclear receptor subfamily 2, group e, member 1) encodes a transcription factor important in neocortex development. Previous work has shown that nuclear receptors can have hundreds of target genes, and bind more than 300 co-interacting proteins. However, recognition of the critical role of Nr2e1 in neural stem cells and neocortex development is relatively recent, thus the molecular mechanisms involved for this nuclear receptor are only beginning to be understood. Serial analysis of gene expression (SAGE), has given researchers both qualitative and quantitative information pertaining to biological processes. Thus, in this work, six LongSAGE mouse libraries were generated from laser microdissected tissue samples of dorsal VZ/SVZ (ventricular zone and subventricular zone) from the telencephalon of wild-type (Wt) and Nr2e1-null embryos at the critical development ages E13.5, E15.5, and E17.5. We then used a novel approach, implementing multiple computational methods followed by biological validation to further our understanding of Nr2e1 in neocortex development. RESULTS: In this work, we have generated a list of 1279 genes that are differentially expressed in response to altered Nr2e1 expression during in vivo neocortex development. We have refined this list to 64 candidate direct-targets of NR2E1. Our data suggested distinct roles for Nr2e1 during different neocortex developmental stages. Most importantly, our results suggest a possible novel pathway by which Nr2e1 regulates neurogenesis, which includes Lhx2 as one of the candidate direct-target genes, and SOX9 as a co-interactor. CONCLUSIONS: In conclusion, we have provided new candidate interacting partners and numerous well-developed testable hypotheses for understanding the pathways by which Nr2e1 functions to regulate neocortex development.

Modelling human regulatory variation in mouse: finding the function in genome-wide association studies and whole-genome sequencing.

An increasing body of literature from genome-wide association studies and human whole-genome sequencing highlights the identification of large numbers of candidate regulatory variants of potential therapeutic interest in numerous diseases. Our relatively poor understanding of the functions of non-coding genomic sequence, and the slow and laborious process of experimental validation of the functional significance of human regulatory variants, limits our ability to fully benefit from this information in our efforts to comprehend human disease. Humanized mouse models (HuMMs), in which human genes are introduced into the mouse, suggest an approach to this problem. In the past, HuMMs have been used successfully to study human disease variants; e.g., the complex genetic condition arising from Down syndrome, common monogenic disorders such as Huntington disease and ß-thalassemia, and cancer susceptibility genes such as BRCA1. In this commentary, we highlight a novel method for high-throughput single-copy site-specific generation of HuMMs entitled High-throughput Human Genes on the X Chromosome (HuGX). This method can be applied to most human genes for which a bacterial artificial chromosome (BAC) construct can be derived and a mouse-null allele exists. This strategy comprises (1) the use of recombineering technology to create a human variant-harbouring BAC, (2) knock-in of this BAC into the mouse genome using Hprt docking technology, and (3) allele comparison by interspecies complementation. We demonstrate the throughput of the HuGX method by generating a series of seven different alleles for the human NR2E1 gene at Hprt. In future challenges, we consider the current limitations of experimental approaches and call for a concerted effort by the genetics community, for both human and mouse, to solve the challenge of the functional analysis of human regulatory variation.

QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration.

DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and >8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 methylation quantitative trait loci and 12,505 expression quantitative trait loci) and 13,747 DNA methylation loci affecting gene expression, with over one-third specific to the retina. Methylation and expression quantitative trait loci show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration. Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of macular degeneration pathology by genotype-environment interaction in retina.

QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration.

DNA methylation (DNAm) provides a crucial epigenetic mark linking genetic variations to environmental influence. We analyzed array-based DNAm profiles of 160 human retinas with co-measured RNA-seq and > 8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 mQTLs and 12,505 eQTLs) and 13,747 eQTMs (DNAm loci affecting gene expression), with over one-third specific to the retina. mQTLs and eQTMs show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration (AMD). Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of AMD pathology by genotype-environment interaction in retina.

Absence of NR2E1 mutations in patients with aniridia.

PURPOSE: Nuclear receptor 2E1 (NR2E1) is a transcription factor with many roles during eye development and thus may be responsible for the occurrence of certain congenital eye disorders in humans. To test this hypothesis, we screened NR2E1 for candidate mutations in patients with aniridia and other congenital ocular malformations (anterior segment dysgenesis, congenital optic nerve malformation, and microphthalmia). METHODS: The NR2E1 coding region, 5' and 3' untranslated regions (UTRs), exon flanking regions including consensus splice sites, and six evolutionarily conserved non-coding candidate regulatory regions were analyzed by sequencing 58 probands with aniridia of whom 42 were negative for PAX6 mutations. Nineteen probands with anterior segment dysgenesis, one proband with optic nerve malformation, and two probands with microphthalmia were also sequenced. The control population comprised 376 healthy individuals. All sequences were analyzed against the GenBank sequence AL078596.8 for NR2E1. In addition, the coding region and flanking intronic sequences of FOXE3, FOXC1, PITX2, CYP1B1, PAX6, and B3GALTL were sequenced in one patient and his relatives. RESULTS: Sequencing analysis showed 17 NR2E1 variants including two novel rare non-coding variants (g.-1507G>A, g.14258C>T), and one novel rare coding variant (p.Arg274Gly). The latter was present in a male diagnosed with Peters' anomaly who subsequently was found to have a known causative mutation for Peters' plus syndrome in B3GALTL (c.660+1G>A). In addition, the NR2E1 novel rare variant Arg274Gly was present in the unaffected mother of the patient but absent in 746 control chromosomes. CONCLUSIONS: We eliminated a major role for NR2E1 regulatory and coding mutations in aniridia and found a novel rare coding variant in NR2E1. In addition, we found no coding region variation in the control population for NR2E1, which further supports its previously reported high level of conservation and low genetic diversity. Future NR2E1 studies in ocular disease groups such as those involving retinal and optic nerve abnormalities should be undertaken to determine whether NR2E1 plays a role in these conditions.

Sustainability of Cocoa (Theobroma cacao) Cultivation in the Mining District of Ponce Enríquez: A Trace Metal Approach.

Historically, cocoa (Theobroma cacao) has been one of Ecuador's most important export crops. In the Ponce Enriquez district, artisanal and small gold mining (ASGM), and quarrying account for 42% of economic activities, while agriculture and livestock farming account for 30%, making the analysis of their synergy and interaction key to understanding the long term viability of the different activities. In this study, we evaluated the concentration of potentially toxic metals in different parts of the cocoa plant and fruit, in relation to mining activities within the area. Gold extraction generates pollution, including potentially toxic metals such as mercury (Hg), cadmium (Cd), arsenic (As), copper (Cu), lead (Pb) and zinc (Zn). In order to understand the mobility of these metals within the cocoa plant and fruit, the analysis was conducted separately for leaves, pod, husk and cocoa bean. Concentrations of the target metals in the different plant parts and soil were measured using ICP-MS, and the mobility and risk factors were calculated using the transfer factor (TF) and the risk ratio (HQ). The results suggest that Zn, Cd and Cu are indeed moving from the soil to cocoa leaves and beans. Furthermore, the results show that the concentrations of toxic metals in the different parts of the cocoa fruit and plant, particularly in the cocoa bean, which is used for chocolate manufacture, are not higher than those regulated by FAO food standards, as is the case of Cd, which is limited to 0.2 mg Cd/kg and in the samples analyzed does not exceed this limit. Even though the concentration of these metals does not exceed the safety standard, the presence of these potentially hazardous metals, and the fact they are absorbed by this important local crop, are worrying for the long-term sustainability of cocoa cultivation in the area. Therefore, it is fundamental to monitor the local environment, understanding the distribution of heavy metal pollution, and work with the local authorities in landscape management to minimize the exposure of crops to ASGM pollution.

High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci.

Chromatin organization and enhancer-promoter contacts establish unique spatiotemporal gene expression patterns in distinct cell types. Non-coding genetic variants can influence cellular phenotypes by modifying higher-order transcriptional hubs and consequently gene expression. To elucidate genomic regulation in human retina, we mapped chromatin contacts at high resolution and integrated with super-enhancers (SEs), histone marks, binding of CTCF and select transcription factors. We show that topologically associated domains (TADs) with central SEs exhibit stronger insulation and augmented contact with retinal genes relative to TADs with edge SEs. Merging genome-wide expression quantitative trait loci (eQTLs) with topology map reveals physical links between 100 eQTLs and corresponding eGenes associated with retinal neurodegeneration. Additionally, we uncover candidate genes for susceptibility variants linked to age-related macular degeneration and glaucoma. Our study of high-resolution genomic architecture of human retina provides insights into genetic control of tissue-specific functions, suggests paradigms for missing heritability, and enables the dissection of common blinding disease phenotypes.

Artisanal and Small Gold Mining and Petroleum Production as Potential Sources of Heavy Metal Contamination in Ecuador: A Call to Action.

Mining and petroleum production are the source of many elements and base materials fundamental for our modern way of life. The flip side of these keystone industries is the environmental degradation they can cause if not properly managed. Metallic mining and petroleum production can contaminate the local ecosystem with sediments, chemicals used in the industrial processes and heavy metals, part of the metallic ore or oil reservoir. The objective of this project was to analyze the spatial distribution of the presence of different potentially hazardous elements that make up the metallic deposits and oil reservoirs in Ecuador, focused mainly on artisanal and small-scale gold mining (ASGM) districts. Additionally, we were interested in analyzing this information under the local political and administrative contexts which are key to determining how likely it is that mismanagement of the local mineral deposits and petroleum exploitation projects will end up causing environmental degradation. An extensive and intensive literature search was conducted for information on the presence and concentration of 19 potentially harmful elements. We analyzed data on 11 metallic deposits throughout Ecuador and a major oilfield in the Ecuadorian Amazon basin. We used geographic information systems to analyze the spatial distribution of these reservoirs and their mineral compositions. The results indicated a widespread distribution and high concentration of elements potentially harmful for human health, such as mercury, cadmium and arsenic, throughout the metallic deposits in Ecuador. This is particularly true for long-exploited ASGM districts, such as Ponce-Enríquez, Portovelo-Zaruma and Nambija. This study highlights the importance of understanding geological diversity and its potential risks to better protect the biological diversity and public health of its inhabitants. Furthermore, we consider our work not as a call to stop ASGM mining nor petroleum production, but on the contrary as a strong call to plan every mining and petroleum production project considering these risks. Moreover, our work is a call to action by the local government and authorities to stop corruption and fulfill their duties overseeing the activities of mining and petroleum companies, stopping illegal mining, helping ASGM communities to improve their environmental standards, finding alternative income sources and protecting the local environment.

Aging of the Retina: Molecular and Metabolic Turbulences and Potential Interventions.

Multifaceted and divergent manifestations across tissues and cell types have curtailed advances in deciphering the cellular events that accompany advanced age and contribute to morbidities and mortalities. Increase in human lifespan during the past century has heightened awareness of the need to prevent age-associated frailty of neuronal and sensory systems to allow a healthy and productive life. In this review, we discuss molecular and physiological attributes of aging of the retina, with a goal of understanding age-related impairment of visual function. We highlight the epigenome-metabolism nexus and proteostasis as key contributors to retinal aging and discuss lifestyle changes as potential modulators of retinal function. Finally, we deliberate promising intervention strategies for promoting healthy aging of the retina for improved vision.