In vitro ovicidal and larvicidal activity of a hydroalcoholic extract and its fractions from Cyrtocarpa procera fruits on Haemonchus contortus.

This study describes the in vitro anthelmintic effect of a hydroalcoholic extract (HA-E) and its fractions from Cyrtocarpa procera fruits against Haemonchus contortus eggs and infective larvae. The HA-E was subjected to bipartition using ethyl acetate, which resulted in an aqueous fraction (Aq-F) and an organic fraction (EtOAc-F). The HA-E and both fractions were tested using the egg hatching inhibition assay (EHIA) and the larval mortality test (LMT). Fractionation of the EtOAc-F was achieved using different chromatographic processes, i.e., open glass column and HPLC analysis. Fractionation of the EtOAc-F gave 18 subfractions (C1R1-C1R18), and those that showed the highest yields (C1R15, C1R16, C1R17 and C1R18) were subjected to anthelmintic assays. The HA-E and the EtOAc-F displayed 100% egg hatching inhibition at 3 and 1 mg/mL, respectively, whereas Aq-F exhibited 92.57% EHI at 3 mg/mL. All subfractions tested showed ovicidal effect. Regarding the larval mortality test, HA-E and EtOAc-F exhibited a larvicidal effect higher than 50% at 50 and 30 mg/mL, respectively. The subfractions that showed the highest larval mortality against H. contortus were C1R15 and C1R17, with larval mortalities of 53.57% and 60.23% at 10 mg/mL, respectively. Chemical analysis of these bioactive subfractions (C1R15 and C1R17) revealed the presence of gallic acid, protocatechuic acid, and ellagic acid. This study shows evidence about the ovicidal and larvicidal properties of C. procera fruits that could make these plant products to be considered as a natural potential anthelmintic agents for controlling haemonchosis in goats and sheep.

Association between BMI z-score and body composition indexes with blood pressure and grip strength in school-age children: a cross-sectional study.

Childhood obesity is linked to diverse health outcomes, including elevated blood pressure (EBP). Emerging evidence showed that excess fat mass (FM) may have a deleterious impact on blood pressure even in normal-weight children. The primary objective of this study was to assess the association between body weight status by BMI z-score and body composition parameters by conventional bioelectrical impedance analysis (BIA) and bioelectrical impedance vector analysis (BIVA). Also, we aimed to explore the performance of BMI z-score, %FM, and FM index (FMI) in discriminating EBP in a sample of school-age Mexican children. Children were classified as having normal weight, overweight or obesity according to WHO criteria for BMI z-score. FMI was considered high when above 75th percentile, and fat free mass index (FFMI) was considered low when below 25th percentile of the reference population. Body composition was also classified according to the BIVA method and EBP was determined when systolic and/or diastolic blood pressure ≥ 90th percentile. BMI z-score groups were compared by Student´s t-test or the Mann-Whitney U test, or by the chi-square test or Fisher exact test. Receiving operating characteristic (ROC) analysis was performed. 61 children were included (52.5% boys, median age 9.8 (25th, 75th percentiles: 8.5, 11.0)) years. High FMI was observed in 32.3% of children with normal weight. Low FFMI was present in 93.5% of children with normal weight and 53.3% of those with overweight/obesity. According to BIVA, 58.1% and 43.3% of children with normal weight and overweight/obesity were classified as having cachexia. All the three adiposity indicators showed significant areas under the ROC curve (AURC) greater than 0.775 for EBP, with the largest one displayed for FM% (0.794). Hight FMI and low FFMI are common in children with normal weight. Identifying deficiency of FFM might be limited by using solely BMI indicators. Cachexia by BIVA was present in a high proportion of children with either normal weight or overweight/obesity. Both BMI z-score and FM (% and FMI) performed well at discriminating EBP, with a numerically greater AURC observed for FM%. Body composition in pediatric population is relevant for identifying body composition abnormalities at early age.

Differential DNA Methylation from Autistic Children Enriches Evidence for Genes Associated with ASD and New Candidate Genes.

The etiology of Autism Spectrum Disorders (ASD) is a result of the interaction between genes and the environment. The study of epigenetic factors that affect gene expression, such as DNA methylation, has become an important area of research in ASD. In recent years, there has been an increasing body of evidence pointing to epigenetic mechanisms that influence brain development, as in the case of ASD, when gene methylation dysregulation is present. Our analysis revealed 853 differentially methylated CpG in ASD patients, affecting 509 genes across the genome. Enrichment analysis showed five related diseases, including autistic disorder and mental disorders, which are particularly significant. In this work, we identified 64 genes that were previously reported in the SFARI gene database, classified according to their impact index. Additionally, we identified new genes that have not been previously reported as candidates with differences in the methylation patterns of Mexican children with ASD.

Modulation of the autophagy-lysosomal pathway and endoplasmic reticulum stress by ketone bodies in experimental models of stroke.

Ischemic stroke is a leading cause of disability worldwide. There is no simple treatment to alleviate ischemic brain injury, as thrombolytic therapy is applicable within a narrow time window. During the last years, the ketogenic diet (KD) and the exogenous administration of the ketone body ß-hydroxybutyrate (BHB) have been proposed as therapeutic tools for acute neurological disorders and both can reduce ischemic brain injury. However, the mechanisms involved are not completely clear. We have previously shown that the D enantiomer of BHB stimulates the autophagic flux in cultured neurons exposed to glucose deprivation (GD) and in the brain of hypoglycemic rats. Here, we have investigated the effect of the systemic administration of D-BHB, followed by its continuous infusion after middle cerebral artery occlusion (MCAO), on the autophagy-lysosomal pathway and the activation of the unfolded protein response (UPR). Results show for the first time that the protective effect of BHB against MCAO injury is enantiomer selective as only D-BHB, the physiologic enantiomer of BHB, significantly reduced brain injury. D-BHB treatment prevented the cleavage of the lysosomal membrane protein LAMP2 and stimulated the autophagic flux in the ischemic core and the penumbra. In addition, D-BHB notably reduced the activation of the PERK/eIF2α/ATF4 pathway of the UPR and inhibited IRE1α phosphorylation. L-BHB showed no significant effect relative to ischemic animals. In cortical cultures under GD, D-BHB prevented LAMP2 cleavage and decreased lysosomal number. It also abated the activation of the PERK/eIF2α/ATF4 pathway, partially sustained protein synthesis, and reduced pIRE1α. In contrast, L-BHB showed no significant effects. Results suggest that protection elicited by D-BHB treatment post-ischemia prevents lysosomal rupture allowing functional autophagy, preventing the loss of proteostasis and UPR activation.

The ARG8m Reporter for the Study of Yeast Mitochondrial Translation.

Mitochondrial translation is an intricate process involving both general and mRNA-specific factors. In addition, in the yeast Saccharomyces cerevisiae, translation of mitochondrial mRNAs is coupled to assembly of nascent polypeptides into the membrane. ARG8m is a reporter gene widely used to study the mechanisms of yeast mitochondrial translation. This reporter is a recodified gene that uses the mitochondrial genetic code and is inserted at the desired locus in the mitochondrial genome. After deletion of the endogenous nuclear gene, this reporter produces Arg8, an enzyme necessary for arginine biosynthesis. Since Arg8 is a soluble protein with no relation to oxidative phosphorylation, it is a reliable reporter to study mitochondrial mRNAs translation and dissect translation form assembly processes. In this chapter, we explain how to insert the ARG8m reporter in the desired spot in the mitochondrial DNA, how to analyze Arg8 synthesis inside mitochondria, and how to follow steady-state levels of the protein. We also explain how to use it to find spontaneous suppressors of translation defects.

The cytochrome b carboxyl terminal region is necessary for mitochondrial complex III assembly.

Mitochondrial bc 1 complex from yeast has 10 subunits, but only cytochrome b (Cytb) subunit is encoded in the mitochondrial genome. Cytb has eight transmembrane helices containing two hemes b for electron transfer. Cbp3 and Cbp6 assist Cytb synthesis, and together with Cbp4 induce Cytb hemylation. Subunits Qcr7/Qcr8 participate in the first steps of assembly, and lack of Qcr7 reduces Cytb synthesis through an assembly-feedback mechanism involving Cbp3/Cbp6. Because Qcr7 resides near the Cytb carboxyl region, we wondered whether this region is important for Cytb synthesis/assembly. Although deletion of the Cytb C-region did not abrogate Cytb synthesis, the assembly-feedback regulation was lost, so Cytb synthesis was normal even if Qcr7 was missing. Mutants lacking the Cytb C-terminus were non-respiratory because of the absence of fully assembled bc 1 complex. By performing complexome profiling, we showed the existence of aberrant early-stage subassemblies in the mutant. In this work, we demonstrate that the C-terminal region of Cytb is critical for regulation of Cytb synthesis and bc 1 complex assembly.

Single nucleotide variants in microRNA biosynthesis genes in Mexican individuals.

Background: MicroRNAs (miRNAs) are important regulators in a variety of biological processes, and their dysregulation is associated with multiple human diseases. Single nucleotide variants (SNVs) in genes involved in the processing of microRNAs may alter miRNA regulation and could present high allele heterogeneity in populations from different ethnic groups. Thus, the aim of this study was to genotype 15 SNVs in eight genes involved in the miRNA processing pathway in Mexican individuals and compare their frequencies across 21 populations from five continental groups. Methods: Genomic DNA was obtained from 399 healthy Mexican individuals. SNVs in AGO2 (rs2293939 and rs4961280), DGCR8 (rs720012), DICER (rs3742330 and rs13078), DROSHA (rs10719 and rs6877842), GEMIN3 (rs197388 and rs197414), GEMIN4 (rs7813, rs2740349, and rs4968104), TNRC6B (rs9611280), and XP05 (rs11077 and rs34324334) were genotyped using TaqMan probes. The minor allele frequency of each SNV was compared to those reported in the 1,000 Genomes database using chi-squared. Sankey plot was created in the SankeyMATIC package to visualize the frequency range of each variant in the different countries analyzed. Results: In Mexican individuals, all 15 SNVs were found in Hardy-Weinberg equilibrium, with frequencies ranging from 0.04 to 0.45. The SNVs rs4961280, rs2740349, rs34324334, and rs720012 in Mexican individuals had the highest minor allele frequencies worldwide, whereas the minor allele frequencies of rs197388, rs10719, rs197414, and rs1107 were among the lowest in Mexican individuals. The variants had high allele heterogeneity among the sub-continental populations, ranging from monomorphic, as was the case for rs9611280 and rs34324334 in African groups, to >0.50, which was the case for variants rs11077 and rs10719 in most of the populations. Importantly, the variants rs197388, rs720012, and rs197414 had FST values > 0.18, indicating a directional selective process. Finally, the SNVs rs13078 and rs10719 significantly correlated with both latitude and longitude. Conclusion: These data indicate the presence of high allelic heterogeneity in the worldwide distribution of the frequency of SNVs located in components of the miRNA processing pathway, which could modify the genetic susceptibility associated with human diseases in populations with different ancestry.

Evaluation of essential fatty acids in lactating sow diets on sow reproductive performance, colostrum and milk composition, and piglet survivability.

Mixed parity sows (n = 3,451; PIC, Hendersonville, TN; parities 2 through 9) and their litters were used to evaluate the effects of essential fatty acid (EFA) intake on sow reproductive performance, piglet growth and survivability, and colostrum and milk composition. Our hypothesis, like observed in earlier research, was that increasing linoleic acid (LA) and α-linolenic acid (ALA) would improve sow and litter performance. At approximately day 112 of gestation, sows were randomly assigned within parity groups to 1 of 4 corn-soybean meal-wheat-based lactation diets that contained 0.5 (Control) or 3% choice white grease (CWG), 3% soybean oil (SO), or a combination of 3% soybean oil and 2% choice white grease (Combination). Thus, sows were provided diets with low LA and ALA in diets with CWG or high LA and ALA in diets that included soybean oil. Sows received their assigned EFA treatments until weaning and were then fed a common gestation and lactation diet in the subsequent reproductive cycle. Average daily feed intake during the lactation period increased (P < 0.05) for sows fed the Combination and CWG diets compared with sows fed the Control or SO diet. However, daily LA and ALA intakes of sows fed the Combination and SO diets were still greater (P < 0.05) than those of sows fed 0.5 or 3% CWG. Overall, sows consuming high EFA from the Combination or SO diets produced litters with heavier (P < 0.05) piglet weaning weights and greater (P < 0.05) litter ADG when compared with litters from sows fed diets with CWG that provided low EFA. Despite advantages in growth performance, there was no impact of sow EFA intake on piglet survivability (P > 0.10). Additionally, lactation diet EFA composition did not influence sow colostrum or milk dry matter, crude protein, or crude fat content (P > 0.10). However, LA and ALA content in colostrum and milk increased (P < 0.05) in response to elevated dietary EFA from SO. There was no evidence for differences (P > 0.10) in subsequent sow reproductive or litter performance due to previous lactation EFA intake. In conclusion, increased LA and ALA intake provided by soybean oil during lactation increased overall litter growth and pig weaning weights, reduced sow ADFI, but did not affect piglet survivability or subsequent performance of sows.

Supplemental fat sources are an effective and widely accepted strategy to increase energy density of sow lactation diets that can also provide essential fatty acids such as linoleic acid (LA) and α-linolenic acid (ALA). Currently, the effects of supplemental LA and ALA provided shortly before farrowing on colostrum and milk composition are not fully understood. Additionally, the influence of elevated LA and ALA provided in sow lactation diets on litter growth and survivability responses has not been extensively evaluated. Therefore, this trial was conducted to evaluate the effects of fat sources providing low and high LA and ALA intake on sow performance, litter growth and survivability, colostrum and milk composition, and subsequent reproductive performance. Overall, sows consuming diets with high LA and ALA provided by soybean oil produced litters with heavier piglet weaning weights and greater litter average daily gain when compared with sows consuming diets with low LA and ALA content. Increasing LA and ALA by added soybean oil also increased their content in colostrum and milk. However, there was no influence of sow LA and ALA intake on litter survivability or subsequent reproductive performance of sows.

A dietary pattern high in full-fat dairy and sweetened beverages is associated with glycated hemoglobin and weight in Mexican patients with type-2 diabetes.

INTRODUCTION: Objective: the aim of this study was to identify dietary patterns in a sample of patients with type-2 diabetes, and to evaluate their association with markers of metabolic control. Methods: a cross-sectional study in 395 patients with type-2 diabetes in primary care was conducted. Fasting blood levels of glycated hemoglobin (A1c), glucose, total cholesterol, low- (LDL-c) and high-density lipoprotein cholesterol (HDL-c), and triglycerides were measured. Waist circumference, body mass index (BMI), and blood pressure were evaluated. Dietary intake was assessed by a food frequency questionnaire, and dietary patterns were derived by cluster analysis. Three dietary patterns were identified: 'fruits and vegetables', 'dairy and sweetened beverages', and 'diverse with alcohol'. Results: an association between the 'dairy and sweetened beverages' dietary pattern and A1c levels was identified (ß = 0.61; 95 % CI: 0.09, 1.12, p = 0.021), considering the 'fruits and vegetables' dietary pattern as the reference group. We also observed a trend towards an adjusted increased risk of A1c ≥ 7 % (odds ratio [OR]: 1.56; 95 % CI: 0.92, 2.64; p = 0.099) and an increased risk of BMI ≥ 25 kg/m2 (OR: 2.62, 95 % CI: 1.20, 5.71, p = 0.015) among patients in the 'dairy and sweetened beverages' dietary pattern as compared to the reference group. Conclusions: a dietary pattern characterized by a high intake of full-fat dairy and sweetened beverages was associated with higher A1c levels and increased risk of high glucose and BMI when compared to a dietary pattern with a higher consumption of fruits and vegetables.

INTRODUCCIÓN: Objetivo: el objetivo de este estudio fue identificar los patrones dietéticos de una muestra de pacientes con diabetes de tipo 2 y evaluar su asociación con los marcadores de control metabólico. Métodos: se realizó un estudio transversal de 395 pacientes con diabetes de tipo 2 en atención primaria. Se estimaron los niveles de hemoglobina glicosilada (A1c), glucosa, colesterol total, colesterol de lipoproteínas de baja (LDL-c) y alta densidad (HDL-c), y triglicéridos en ayunas. Se evaluaron el perímetro de la cintura, el índice de masa corporal (IMC) y la presión arterial. La ingesta dietética se evaluó mediante un cuestionario de frecuencia de alimentos y los patrones dietéticos se obtuvieron mediante un análisis de conglomerados. Se identificaron tres patrones dietéticos: "frutas y verduras", "lácteos y bebidas azucaradas" y "diversos con alcohol". Resultados: se identificó una asociación entre el patrón dietético de "productos lácteos y bebidas azucaradas" y los niveles de A1c (ß = 0,61; IC del 95 %: 0,09, 1,12, p = 0,021), considerando el patrón dietético de "frutas y verduras" como grupo de referencia. También se observó una tendencia a un mayor riesgo ajustado de A1c ≥ 7 % (odds ratio [OR]: 1,56; IC del 95 %: 0,92, 2,64; p = 0,099) y un mayor riesgo de IMC ≥ 25 kg/m2 (OR: 2,62; IC del 95 %: 1,20, 5,71, p = 0,015) entre los pacientes del patrón "lácteos y bebidas azucaradas" en comparación con el grupo de referencia. Conclusiones: el patrón dietético caracterizado por un alto consumo de lácteos y bebidas azucaradas se asoció con niveles más altos de A1c y un mayor riesgo de elevación de la glucosa y el IMC, en comparación con un patrón dietético con mayor consumo de frutas y verduras.

Adherence to the DASH dietary pattern is associated with blood pressure and anthropometric indicators in Mexican adults.

INTRODUCTION: Background: adherence to Dietary Approach to Stop Hypertension (DASH) has demonstrated to be effective in lowering blood pressure and other cardiovascular risk markers in different populations, but has never been evaluated in the Mexican population. Objective: to assess adherence to the DASH dietary pattern by using an adapted DASH adequacy index (DASH-AI), and to evaluate its association with cardiovascular risk markers in an adult Mexican population. Methods: we conducted a cross-sectional analysis of data of 1,490 adults aged 20-50 years. Diet was assessed with a Food Frequency Questionnaire and sodium intake by 24-hour urinary sodium excretion; the DASH-AI score was calculated based on the DASH nutrient targets. Multivariable linear and logistic regression analyses were performed to estimate the association between the DASH-AI score and cardiovascular risk markers (body mass index [BMI], waist circumferences, systolic (SBP) and diastolic blood pressure (DBP), glucose, triglycerides, total cholesterol, and high- and low-density lipoproteins). Results: we observed an association of the DASH-AI score with BMI, WC and DBP in the linear (BMI, : -0.55, 95 % CI: -0.77, -0.33; WC, : -1.66, 95 % CI: -2.19, -1.13; DBP, : -0.65, 95 % CI: -1.07, -0.24), and logistic (BMI > 25 kg/m2, OR: 0.82, 95 % CI: 0.74, 0.93; elevated WC, OR: 0.72, 95 % CI: 0.64, 0.81; DBP, OR: 0.83, 95 % CI: 0.72, 0 .95) models. Conclusion: compliance to the DASH-style diet was inversely associated with BMI, WC and DBP in this Mexican population. Promoting adherence to this dietary pattern in the context of Mexican diet is needed to improve cardiovascular health in this population.

INTRODUCCIÓN: Antecedentes: la adherencia al patrón de alimentación DASH ha mostrado ser eficaz para reducir la presión arterial y los marcadores de riesgo cardiovascular en diferentes poblaciones, pero nunca en la mexicana. Objetivo: evaluar la adherencia al patrón de alimentación DASH mediante un índice adapatado a los lineamientos DASH (DASH-AI) y evaluar su asociación con marcadores de riesgo. Métodos: análisis transversal de datos de 1490 adultos de entre 20 y 50 años de edad. La ingesta dietética se evaluó utilizando un cuestionario de frecuencia de consumo de alimentos y el sodio a través de la excresión urinaria en 24 horas; la puntuación DASH-AI se calculó de acuerdo con la adherencia a las recomendaciones DASH. Se realizaron modelos logísticos y lineales para estimar la asociación entre el puntaje DASH-AI y los marcadores de riesgo cardiovascular (índice de masa corporal [IMC], circunferencia de cintura (CC), presión arterial sistólica (PAS) y diastólica (PAD), glucosa, triglicéridos, colesterol total, lipoproteínas de alta y baja densidad). Resultados: observamos una asociación del DASH-AI con el IMC, la CC y la PAD en los modelos lineales (IMC : -0,55, IC del 95 %: -0,77, -0,33; CC : -1,66, IC del 95 %: -2,19, -1,33; PAD, : -0,65, IC del 95 %: -1,07, -0,24) y logístico (IMC > 25 kg/m2, OR: 0,82, IC del 95 %: 0,74, 0,93; CC elevado, OR: 0,72; IC del 95 %: 0,64, 0,81; PAD, OR: 0,83, IC del 95 %: 0,72, 0,95). Conclusión: la adherencia a la dieta DASH se asoció inversamente con el IMC, la CC y la PAD en la población estudiada. Es necesario promover la adherencia a este patrón dietético para mejorar la salud cardiovascular.

MRX8, the conserved mitochondrial YihA GTPase family member, is required for de novo Cox1 synthesis at suboptimal temperatures in Saccharomyces cerevisiae.

The synthesis of Cox1, the conserved catalytic-core subunit of Complex IV, a multisubunit machinery of the mitochondrial oxidative phosphorylation (OXPHOS) system under environmental stress, has not been sufficiently addressed. In this study, we show that the putative YihA superfamily GTPase, Mrx8, is a bona fide mitochondrial protein required for Cox1 translation initiation and elongation during suboptimal growth condition at 16°C. Mrx8 was found in a complex with mitochondrial ribosomes, consistent with a role in protein synthesis. Cells expressing mutant Mrx8 predicted to be defective in guanine nucleotide binding and hydrolysis were compromised for robust cellular respiration. We show that the requirement of Pet309 and Mss51 for cellular respiration is not bypassed by overexpression of Mrx8 and vice versa. Consistently the ribosomal association of Mss51 is independent of Mrx8. Significantly, we find that GTPBP8, the human orthologue, complements the loss of cellular respiration in Δmrx8 cells and GTPBP8 localizes to the mitochondria in mammalian cells. This strongly suggests a universal role of the MRX8 family of proteins in regulating mitochondrial function.

IRE1α RIDD activity induced under ER stress drives neuronal death by the degradation of 14-3-3 θ mRNA in cortical neurons during glucose deprivation.

Altered protein homeostasis is associated with neurodegenerative diseases and acute brain injury induced under energy depletion conditions such as ischemia. The accumulation of damaged or unfolded proteins triggers the unfolded protein response (UPR), which can act as a homeostatic response or lead to cell death. However, the factors involved in turning and adaptive response into a cell death mechanism are still not well understood. Several mechanisms leading to brain injury induced by severe hypoglycemia have been described but the contribution of the UPR has been poorly studied. Cell responses triggered during both the hypoglycemia and the glucose reinfusion periods can contribute to neuronal death. Therefore, we have investigated the activation dynamics of the PERK and the IRE1α branches of the UPR and their contribution to neuronal death in a model of glucose deprivation (GD) and glucose reintroduction (GR) in cortical neurons. Results show a rapid activation of the PERK/p-eIF2α/ATF4 pathway leading to protein synthesis inhibition during GD, which contributes to neuronal adaptation, however, sustained blockade of protein synthesis during GR promotes neuronal death. On the other hand, IRE1α activation occurs early during GD due to its interaction with BAK/BAX, while ASK1 is recruited to IRE1α activation complex during GR promoting the nuclear translocation of JNK and the upregulation of Chop. Most importantly, results show that IRE1α RNase activity towards its splicing target Xbp1 mRNA occurs late after GR, precluding a homeostatic role. Instead, IRE1α activity during GR drives neuronal death by positively regulating ASK1/JNK activity through the degradation of 14-3-3 θ mRNA, a negative regulator of ASK and an adaptor protein highly expressed in brain, implicated in neuroprotection. Collectively, results describe a novel regulatory mechanism of cell death in neurons, triggered by the downregulation of 14-3-3 θ mRNA induced by the IRE1α branch of the UPR.

FOXP2 expression and gray matter density in the male brains of patients with schizophrenia.

Common genetic variants of FOXP2 may contribute to schizophrenia vulnerability, but controversial results have been reported for this proposal. Here we evaluated the potential impact of the common FOXP2 rs2396753 polymorphism in schizophrenia. It was previously reported to be part of a risk haplotype for this disease and to have significant effects on gray matter concentration in the patients. We undertook the first examination into whether rs2396753 affects the brain expression of FOXP2 and a replication study of earlier neuroimaging findings of the influence of this genetic variant on brain structure. FOXP2 expression levels were measured in postmortem prefrontal cortex samples of 84 male subjects (48 patients and 36 controls) from the CIBERSAM Brain and the Stanley Foundation Array Collections. High-resolution anatomical magnetic resonance imaging was performed on 79 male subjects (61 patients, 18 controls) using optimized voxel-based morphometry. We found differences in FOXP2 expression and brain morphometry depending on the rs2396753, relating low FOXP2 mRNA levels with reduction of gray matter density. We detected an interaction between rs2396753 and the clinical groups, showing that heterozygous patients for this polymorphism have gray matter density decrease and low FOXP2 expression comparing with the heterozygous controls. This study shows the importance of independent replication of neuroimaging genetic studies of FOXP2 as a candidate gene in schizophrenia. Furthermore, our results suggest that the FOXP2 rs2396753 affects mRNA levels, thus providing new knowledge about its significance as a potential susceptibility polymorphism in schizophrenia.

FOXP2 and language alterations in psychiatric pathology / FOXP2 and language alterations in psychiatric pathology

Abstract Background From the first reports of the linguist Noam Chomsky it has become clear that the development of language has an important genetic component. Several reports in families have shown the relationship between language disorders and genetic polymorphisms. The FOXP2 gene has been a fundamental piece for the understanding of language development. This gene codes for a transcription factor containing a forkhead domain of DNA binding and participates in the regulation of the expression of a large number of genes involved in the embryonic development of fundamental neuronal structures needed for the development of speech and language. Objective To present an updated view of the relationship between FOXP2 and language alterations in psychiatric pathology. Method Narrative review of information reported in databases on the recent advances supporting genetic participation in language disorders of psychiatric illness. Results Update of content related to FOXP2 and its participation in language alterations in psychiatric diseases. Discussion and conclusion Advances in the genetic study of language disorders in psychiatric pathology open up new avenues of investigation that allow us to explore how language emerged and how it evolved, as well as to carry out comparative studies on the structure and functioning of genes to approach the understanding of this complex characteristic that makes us human.

Resumen Antecedentes Desde los primeros reportes del lingüista Noam Chomsky ha quedado claro que el desarrollo del lenguaje tiene un importante componente genético. Diversos reportes en familias han mostrado la relación entre los trastornos del lenguaje y ciertos marcadores genéticos. El gen FOXP2 ha sido una pieza fundamental para entender el desarrollo del lenguaje. Se trata de un gen que codifica para un factor de transcripción con un dominio forkhead de unión al DNA y que participa en la regulación de la expresión de un gran número de genes durante el desarrollo embrionario de estructuras neuronales fundamentales para el desarrollo del habla y el lenguaje. Objetivo Presentar un panorama actualizado de la relación del gen FOXP2 en las alteraciones del lenguaje en la patología psiquiátrica. Método Revisión narrativa de la información reportada en diversas bases de datos sobre los recientes avances que soportan la participación genética en las alteraciones del lenguaje presentes en enfermedades psiquiátricas. Resultados Actualización del contenido relacionado con el gen FOXP2 y su participación en las alteraciones del lenguaje en las enfermedades psiquiátricas. Discusión y conclusión Los avances en el estudio genético de las alteraciones del lenguaje en la patología psiquiátrica abren nuevos caminos de investigación que permiten explorar cómo surgió y cómo ha evolucionado el lenguaje, así como para llevar a cabo estudios comparativos sobre la estructura y el funcionamiento de genes para aproximarse al entendimiento de esta compleja característica que nos hace humanos.

No association of HLA-DRB1 and TNF alleles in Mexican patients with autoimmune hepatitis.

HLA-DRB1 alleles has been found implicated in susceptibility to autoimmune hepatitis (AIH) in populations from different genetic backgrounds. In Mexicans, HLA-DRB1*04:04 is recognized as a risk allele for AIH but, to date, there is no high-resolution data supporting this association. Also, the association of other nonclassical HLA genes, such as TNF-LTA locus, have not, to our knowledge, been evaluated in this population. The association of HLA-DRB1 alleles determined by sequence-based typing and two polymorphisms in the TNF locus with AIH in a sample of Mexican patients was evaluated. Fifty-six patients from Guadalajara, Mexico, diagnosed with AIH and 115 age-gender matched healthy volunteer blood donors, were genotyped for HLA-DRB1 by the sequencing exon 2 and for TNFA-308G>A and LTA + 252A>G polymorphisms. Increased frequencies of both HLA-DRB1*04:04:01 and *16:02:01:01 alleles (OR = 2.91; 95% CI = 1.08-7.84) and the haplotype (DRB1-TNFA-LTA) *04:04:01-G-A (OR = 5.33; 95% CI = 1.32-21.49) were observed in AIH patients. However, after corrections for multiple comparisons, associations were not significant. In conclusion, our study does not support the association of HLA-DRB1*04:04:01 with the susceptibility to AIH in Mexican population. More studies including patients from other Mexican regions and considering other genetic, immunological, and environmental factors should be performed.

Interleukin-1 Alpha Polymorphisms Are Associated With Body Mass Index in Male But Not in Female Adolescents.

BACKGROUND: The Interleukin (IL)-1 family of cytokines plays a key role in the inflammatory response. Genes coding for IL-1α, IL-1ß, and IL-1Ra are located together as a block gene known as the IL-1 cluster. This genomic region shows wide nucleotide variability, and some polymorphisms have been widely studied and associated with features related to the metabolic syndrome. METHODS: Eight polymorphisms within three genes of the IL-1 cluster, including IL1A (rs3783553, rs17561, and rs1800587), IL1B (rs1143634, rs1143627, and rs16944) and IL1RN (rs419598 and rs2234663) were genotyped in 460 Mexican adolescents. Genotype and haplotype frequencies are reported, as well as the linkage disequilibrium analysis. Genetic associations with some anthropometric and metabolic traits were evaluated. RESULTS: Allele frequencies were similar to those found in other populations, and genotype proportions were according to the Hardy-Weinberg equilibrium. Seven haplotypes were observed at frequencies ≥5%. Of the entire cluster, only the rs17561-rs1800587 and rs1143627-rs16944 pairs showed highest and significant linkage disequilibrium values. An haplotype of IL1A, rs17561T-rs1800587T, was significantly associated with increase in body mass index in males (p <0.008), whereas IL1B and IL1RN variants showed associations with insulin, and hs-CRP (p <0.05). CONCLUSIONS: Some MetS parameters seem to be influenced by variations in the IL-1 gene cluster in Mexican adolescents. These variations may confer risk for metabolic alterations from early ages, and and these risks may be different when variables such as sex are considered. Strategies leading to generate protective behaviors could be designed to take into account specific variations in the IL-1 gene cluster and biological conditions such as sex.

Conservation and Variability of the AUG Initiation Codon Context in Eukaryotes.

Selection of the translation initiation site (TIS) is a crucial step during translation. In the 1980s Marylin Kozak performed key studies on vertebrate mRNAs to characterize the optimal TIS consensus sequence, the Kozak motif. Within this motif, conservation of nucleotides in crucial positions, namely a purine at -3 and a G at +4 (where the A of the AUG is numbered +1), is essential for TIS recognition. Ever since its characterization the Kozak motif has been regarded as the optimal sequence to initiate translation in all eukaryotes. We revisit here published in silico data on TIS consensus sequences, as well as experimental studies from diverse eukaryotic lineages, and propose that, while the -3A/G position is universally conserved, the remaining variability of the consensus sequences enables their classification as optimal, strong, and moderate TIS sequences.

The mitoribosome-specific protein mS38 is preferentially required for synthesis of cytochrome c oxidase subunits.

Message-specific translational regulation mechanisms shape the biogenesis of multimeric oxidative phosphorylation (OXPHOS) enzyme in mitochondria from the yeast Saccharomyces cerevisiae. These mechanisms, driven mainly by the action of mRNA-specific translational activators, help to coordinate synthesis of OXPHOS catalytic subunits by the mitoribosomes with both the import of their nucleus-encoded partners and their assembly to form the holocomplexes. However, little is known regarding the role that the mitoribosome itself may play in mRNA-specific translational regulation. Here, we show that the mitoribosome small subunit protein Cox24/mS38, known to be necessary for mitoribosome-specific intersubunit bridge formation and 15S rRNA H44 stabilization, is required for efficient mitoribogenesis. Consequently, mS38 is necessary to sustain the overall mitochondrial protein synthesis rate, despite an adaptive ∼2-fold increase in mitoribosome abundance in mS38-deleted cells. Additionally, the absence of mS38 preferentially disturbs translation initiation of COX1, COX2, and COX3 mRNAs, without affecting the levels of mRNA-specific translational activators. We propose that mS38 confers the mitochondrial ribosome an intrinsic capacity of translational regulation, probably acquired during evolution from bacterial ribosomes to facilitate the translation of mitochondrial mRNAs, which lack typical anti-Shine-Dalgarno sequences.

Bread Consumption Is Associated with Elevated Blood Pressure among Adults Living in Mexico City⁻A Sub-Analysis of the Tlalpan 2020 Study.

Excessive dietary sodium is associated with elevated blood pressure (EBP). Bread products are identified as one of the main sources of daily sodium intake. The objective of this cross-sectional study was to evaluate the association between bread and others cereal products consumption with EBP. Frequency intake of a standard serving of bread and other cereal products was recorded and categorized as: ≤3 times/month or never (reference category group) and ≥ once/week. EBP was defined as systolic blood pressure (SBP) ≥120 mmHg and/or diastolic blood pressure (DBP) ≥80 mmHg. Raw and adjusted odds ratios (OR) for the association between consumption of the studied food products and blood pressure status were estimated. Overall, 2011 participants aged 37.3 ± 9.1 years old were included. In the models adjusted for relevant covariates, consumption of one piece of bolillo or telera (OR = 1.39; 95% CI = 1.01⁻1.89) ≥ once/week was associated with an increased risk of EBP, compared to the reference category. Also, participants consuming one bowl of high-fiber breakfast cereal once/week were less likely to have EBP (OR = 0.73; 95% CI = 0.53⁻0.98). Initiatives to reduce sodium levels in bread products such as bolillo and telera are needed in Mexico to help manage the cardiovascular risk at the population level.

Metabolic and genetic markers' associations with elevated levels of alanine aminotransferase in adolescents.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in adolescents, is a feature of metabolic syndrome (MetS). Obesity and insulin resistance (IR) are risk factors for NAFLD, as well as inflammation-related genetic markers. The relationship between metabolic or inflammation-related genetic markers and alanine aminotransferase (ALT) is not fully understood. We examined the relationship of MetS, metabolic and inflammation-related genetic markers with elevated ALT in adolescents. METHODS: A total of 674 adolescents participated in a cross-sectional study in Guadalajara, Mexico. Elevated ALT (>40 IU/L), a surrogate marker of NAFLD, and MetS (International Diabetes Federation definition) were evaluated. Obesity, IR, lipids, C-reactive protein (CRP) and genetic markers (TNFA-308G>A, CRP+1444C>T, IL1RN and IL6-597/-572/-174 haplotype) were evaluated. Multivariate logistic regression was performed. RESULTS: Elevated ALT was observed in 3% and 14.1% (total and obese, respectively) of the adolescents. Obesity (odds ratio [OR], 5.86; 95% confidence interval [95% CI], 1.16-25.89), insulin (OR, 8.51; 95% CI, 2.61-27.71), IR (OR, 9.10; 95% CI, 2.82-29.38), total cholesterol (TC) (OR, 3.67; 95% CI, 1.25-10.72), low-density lipoprotein-cholesterol (LDL-C) (OR, 3.06; 95% CI, 1.06-8.33), non-high-density lipoprotein-cholesterol (HDL-C) (OR, 3.88; 95% CI, 1.27-11.90) and IL1RN (OR, 4.64; 95% CI, 1.10-19.53) were associated with elevated ALT. Among males, ≥2 MetS criteria were associated with elevated ALT (OR, 4.22; 95% CI, 1.14-15.71). CONCLUSIONS: Obesity, insulin, IR, high TC, high LDL-C, high non-HDL-C and IL1RN polymorphism were associated with elevated ALT. Among males, ≥2 MetS criteria were associated with elevated ALT. There is an urgent need to reduce obesity and IR in adolescents to prevent NAFLD.