In Mexico, the genetic mechanisms underlying childhood obesity are poorly known. We evaluated the effect of loci, known to be associated with childhood body mass index (BMI) in Europeans, in Mexican ...children from different ethnic groups. We performed linear and logistic analyses of BMI and obesity, respectively, in Mestizos and Amerindians (Seris, Yaquis and Nahuatl speakers) from Northern (
= 369) and Central Mexico (
= 8545). We used linear models to understand the effect of degree of Amerindian ancestry (AMA) and genetic risk score (GRS) on BMI z-score. Northern Mexican Mestizos showed the highest overweight-obesity prevalence (47.4%), followed by Seri (36.2%) and Central Mexican (31.5%) children. Eleven loci (
/rs543874,
/rs12429545/rs9568856,
/rs9939609,
/rs6567160,
/rs13130484,
/rs7132908,
/rs944990,
/rs3829849,
/rs13387838,
/rs9299) were associated with BMI and seven (
/rs543874,
/rs12429545/rs9568856,
/rs9939609,
/rs6567160,
rs13130484,
/rs3829849) were associated with obesity in Central Mexican children. One SNP was associated with obesity in Northern Mexicans and Yaquis (
/rs543874). We found higher BMI z-score at higher GRS (β = 0.11,
= 0.2 × 10
) and at lower AMA (β = -0.05,
= 6.8 × 10
). The GRS interacts with AMA to increase BMI (β = 0.03,
= 6.08 × 10
). High genetic BMI susceptibility increase the risk of higher BMI, including in Amerindian children.
Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery ...efforts are based on data from populations of European ancestry
. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific
. Additionally, effect sizes and their derived risk prediction scores derived in one population may not accurately extrapolate to other populations
. Here we demonstrate the value of diverse, multi-ethnic participants in large-scale genomic studies. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioural phenotypes in 49,839 non-European individuals. Using strategies tailored for analysis of multi-ethnic and admixed populations, we describe a framework for analysing diverse populations, identify 27 novel loci and 38 secondary signals at known loci, as well as replicate 1,444 GWAS catalogue associations across these traits. Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications. In the United States-where minority populations have a disproportionately higher burden of chronic conditions
-the lack of representation of diverse populations in genetic research will result in inequitable access to precision medicine for those with the highest burden of disease. We strongly advocate for continued, large genome-wide efforts in diverse populations to maximize genetic discovery and reduce health disparities.
Ultraviolet (UV) light and incompletely understood genetic and epigenetic variations determine skin color. Here we describe an UV- and microphthalmia-associated transcription factor ...(MITF)-independent mechanism of skin pigmentation. Targeting the mitochondrial redox-regulating enzyme nicotinamide nucleotide transhydrogenase (NNT) resulted in cellular redox changes that affect tyrosinase degradation. These changes regulate melanosome maturation and, consequently, eumelanin levels and pigmentation. Topical application of small-molecule inhibitors yielded skin darkening in human skin, and mice with decreased NNT function displayed increased pigmentation. Additionally, genetic modification of NNT in zebrafish alters melanocytic pigmentation. Analysis of four diverse human cohorts revealed significant associations of skin color, tanning, and sun protection use with various single-nucleotide polymorphisms within NNT. NNT levels were independent of UVB irradiation and redox modulation. Individuals with postinflammatory hyperpigmentation or lentigines displayed decreased skin NNT levels, suggesting an NNT-driven, redox-dependent pigmentation mechanism that can be targeted with NNT-modifying topical drugs for medical and cosmetic purposes.
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•Identification of a redox-dependent skin pigmentation mechanism•Modification of NNT affects ubiquitin-proteasome-mediated tyrosinase degradation•Alteration of NNT levels affects skin pigmentation through melanosome maturation•Human NNT SNPs are associated with skin pigmentation, tanning, and use of sun protection
Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial redox-regulating enzyme that mediates pigmentation via a UVB- and MITF-independent mechanism.
Lemon essential oil (LEO) emulsions were prepared using mesquite gum (MG) - chia mucilage (CM) mixtures (90-10 and 80-20 MG-CM weight ratios) and MG as control sample, LEO emulsions were thenspray ...dried for obtaining the respective microcapsules.LEO emulsions were analyzed by mean droplet size and apparent viscosity, while microcapsules were characterized through mean particle size, morphology, volatile oil retention (≤51.5%), encapsulation efficiency (≥96.9%), as well asoxidation and release kinetics of LEO. TheLEO oxidation kinetics showed that 90–10 and 80–20MG-CM microcapsules displayed maximum peroxide values of 91.6 and 90.5 meq hydroperoxides kg−1 of oil, respectively, without significant differences between them (p > .05).MG-CM microcapsules provided better protection to LEO against oxidation than those formed with MG; where the oxidation kinetics were well adjusted to zero-order (r2 ≥ 0.94).The LEO release kinetics from microcapsules were carried out at differentpH (2.5 and 6.5) and temperature (37 °C and 65 °C) and four mathematical models (zero-order, first-order, Higuchi and Peppas) were used to evaluate the experimental data; the release kinetics indicated that the 80-20 MG-CM microcapsules had a longer delay in LEO release rate, followed by 90-10 MG-CM and MG microcapsules, hence, CM addition in MG-CM microcapsules contributed to delay the LEO release rate. This work clearly demonstrates that use of a relatively small amount of CM mixed with MGimproves oxidative stability and delays the release rate of encapsulated LEO regarding MG microcapsules, therefore, MG-CM mixtures are interesting additives systems suitable for being applied in food industry.
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•Mesquite gum (MG) - Chia mucilage (CM) mixtures were used to encapsulate lemon oil.•MG-CM emulsions had larger droplet size and higher viscosity than MG emulsions.•MG-CM microcapsules had better oil oxidative stability at 35 °C than MG microcapsules.•MG-CM microcapsules had slower oil release rates than MG microcapsules.•MG-CM microcapsules had better functional characteristics than MG microcapsules.
Growing evidence shows a hypercoagulable state in obstructive sleep apnea (OSA) that could be a risk factor for thromboembolic disease.
We aimed to elucidate mechanisms involved in the procoagulant ...profile observed in patients with OSA and to investigate the potential utility of global tests in its characterization.
Thirty-eight patients with severe OSA without previous history of thrombosis and nineteen healthy age- and sex-matched controls were included. Kinetic of clot formation was determined using rotational thromboelastometry. Haemostatic capacity of plasma and microparticles was determined by Calibrated Automated Thrombinography. Platelet surface receptors, activation markers and formation of platelet/leukocytes aggregates were analyzed by flow cytometry.
Thromboelastometry showed a procoagulant state in patients with OSA that did not seem to be related to a basal activation of platelets but by the increased existence of platelet/leukocyte aggregates. Patients with OSA presented many signs of endothelial damage such as increased plasma levels of E-selectin and cfDNA and enhanced thrombin generation due to the presence of microparticles rich in tissue-factor, which is related to OSA severity.
OSA induces an enhancement in the dynamics of clot formation which appears to be caused by at least two pathological mechanisms. First, a greater formation of platelet-leukocyte aggregates; secondly, endothelial damage which provokes a greater procoagulant potential due to the increase in tissue factor-rich microparticles. Moreover, this study has identified thromboelastometry and thrombin generation assay as useful tools to evaluate the prothrombotic state in these patients.
Neuromyelitis Optica Spectrum Disorder (NMOSD) is a demyelinating autoimmune disease of the central nervous system, more prevalent in individuals of non-European ancestry. Few studies have analyzed ...genetic risk factors in NMOSD, and HLA class II gene variation has been associated NMOSD risk in various populations including Mexicans. Thymopoietin (
TMPO
) has not been tested as a candidate gene for NMOSD or other autoimmune disease, however, experimental evidence suggests this gene may be involved in negative selection of autoreactive T cells and autoimmunity. We thus investigated whether the missense
TMPO
variant rs17028450 (Arg630Cys, frequent in Latin America) is associated with NMOSD, and whether this variant shows an interaction with HLA-class II rs9272219, previously associated with NMOSD risk. A total of 119 Mexican NMOSD patients, 1208 controls and 357 Native Mexican individuals were included. The HLA rs9272219 “T” risk allele frequency ranged from 21 to 68%, while the rs17028450 “T” minor allele frequency was as high as 18% in Native Mexican groups. Both rs9272219 and rs17028450 were significantly associated with NMOSD risk under additive models (
OR
= 2.48;
p
= 8 × 10
–10
and
OR
= 1.59;
p
= 0.0075, respectively), and a significant interaction between both variants was identified with logistic regression models (
p
= 0.048). Individuals bearing both risk alleles had an estimated 3.9-fold increased risk of NMOSD. To our knowledge, this is the first study reporting an association of
TMPO
gene variation with an autoimmune disorder and the interaction of specific susceptibility gene variants, that may contribute to the genetic architecture of NMOSD in admixed Latin American populations.
This study describes and classifies a case of multiple malformations in an unborn blue shark Prionace glauca fetus, which was extracted from a gravid female captured during a research campaign ...addressed to the biological study of sharks in northern and central Chile. The analyzed specimen shows tetrophthalmia with unilateral synophthalmia, anomaly characterized by the existence of 4 ocular globes, two of which are partially fused. In addition, the axial skeleton of the fetus shows thoracic lordosis and helical torsion in the abdominal-caudal portion. This is the first world report of tetrophthalmia with unilateral synophthalmia in chondrichthyans.
Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disease characterized by progressive cerebellar ataxia and macular degeneration causing progressive blindness. It accounts for 1 to ...11.6 % of spinocerebellar ataxias (SCAs) cases worldwide and for 7.4 % of SCA7 cases in Mexico. We identified a cluster of SCA7 families who resided in a circumscribed area of Veracruz and investigated whether the high incidence of the disease in this region was due to a founder effect. A total of 181 individuals from 20 families were studied. Four microsatellite markers and one SNP flanking the
ATNX7
gene were genotyped and the ancestral origin and local ancestry analysis of the SCA7 mutation were evaluated. Ninety individuals from 19 families had the SCA7 mutation; all were found to share a common haplotype, suggesting that the mutation in these families originated from a common ancestor. Ancestral origin and local ancestry analysis of SCA7 showed that the chromosomal segment containing the mutation was of European origin. We here present evidence strongly suggesting that the high frequency of SCA7 in Veracruz is due to a founder effect and that the mutation is most likely of European origin with greatest resemblance to the Finnish population.
el texto que se presenta aquí sistematiza las experiencias del proyecto “Diplomatura virtual en prevención de problemáticas psicosociales en el ámbito universitario con énfasis en adicciones”, ...auspiciado por el Centro Coordinador de la Investigación de la Federación Internacional de Universidades Católicas –FIUC-, en el que participaron las Universidades: Universidad Católica Luis Amigó (Colombia) a partir del reconocimiento como universidad que otorgó el Ministerio de Educación Nacional a la institución, el 10 de noviembre de 2016; Católica de Honduras Nuestra Señora Reina de la Paz; Católica de Costa Rica y Católica de Chile Cardenal Silva Henríquez. En la primera parte del texto se da cuenta del proyecto, sus antecedentes, objetivos, metodología y actividades; una reseña sobre las instituciones participantes y una reflexión sobre los problemas psicosociales de los universitarios hoy. En la segunda parte, se presentan los resultados de las pesquisas desarrolladas por cada una de la Universidades participantes, para dar cuenta de las problemáticas psicosociales que más afectan a sus propias comunidades educativas y del programa de prevención diseñado para intervenir dichos problemas.
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