Genotype plus genotype by-environment interaction biplot and genetic diversity analyses on multi-environment trials data of yield and technological traits of cotton cultivars / Biplot de genótipo mais interação genótipo por ambiente e diversidade genética em dados de produtividade e qualidade de fibras em cultivares de algodão provenientes de ensaios multi-ambientes

Understanding the genetic diversity and overcoming genotype-by-environment interaction issues is an essential step in breeding programs that aims to improve the performance of desirable traits. This study estimated genetic diversity and applied genotype + genotype-by-environment (GGE) biplot analyses in cotton genotypes. Twelve genotypes were evaluated for fiber yield, fiber length, fiber strength, and micronaire. Estimation of variance components and genetic parameters was made through restricted maximum likelihood and the prediction of genotypic values was made through best linear unbiased prediction. The modified Tocher and principal component analysis (PCA) methods, were used to quantify genetic diversity among genotypes. GGE biplot was performed to find the best genotypes regarding adaptability and stability. The Tocher technique and PCA allowed for the formation of clusters of similar genotypes based on a multivariate framework. The GGE biplot indicated that the genotypes IMACV 690 and IMA08 WS were highly adaptable and stable for the main traits in cotton. The cross between the genotype IMACV 690 and IMA08 WS is the most recommended to increase the performance of the main traits in cotton crops.

Compreender a diversidade genética e contornar os problemas causados pela interação genótipos por ambientes é uma etapa importante em programas de melhoramento. Este estudo teve como objetivo estimar a diversidade genética e aplicar a metodologia de biplot genótipo + genótipo por ambiente (GGE biplot) em doze genótipos de algodão avaliados quanto ao rendimento da fibra, comprimento da fibra, resistência da fibra e micronaire. A estimativa dos componentes de variância e dos parâmetros genéticos foi feita através do método da máxima verossimilhança restrita e a predição dos valores genotípicos por meio da melhor predição linear não enviesada. Os métodos de Tocher modificado e análise de componentes principais (PCA) foram utilizados para quantificar a diversidade genética entre os genótipos. O método GGE biplot foi conduzido para encontrar os melhores genótipos em relação à adaptabilidade e estabilidade. As técnicas de Tocher e PCA permitiram a formação de clusters de genótipos semelhantes com base em uma estrutura multivariada. O GGE biplot indicou que os genótipos IMACV 690 e IMA08 WS foram altamente adaptáveis e estáveis para as principais características do algodão. O cruzamento dentre os genótipos IMACV 690 e IMA08 WS é o mais recomendado para aumentar o desempenho das principais características na cultura do algodão.

Craniometric geographical variation in Hylaeamys megacephalus populations / Variação geográfica craniométrica em populações de Hylaeamys megacephalus

Hylaeamys megacephalus (G. Fisher, 1814) presents great genetic diversity and wide geographical distribution, and occurs in both the Amazon and Cerrado biomes. Because of its generalist aspect, this species tolerates different eating habits and habitats. It occurs in flooded and dry areas and is predominantly terrestrial, which allows greater gene flow between populations even over long distances. Studies that seek a better understanding of morphological variations resulting from differences imposed by the environment throughout this species' distribution are still lacking. This study aimed to analyze the differences between H. megacephalus populations based on craniometry, investigating whether the environment has an influence on morphology. We analyzed a total of 142 specimens from three scientific mammal collections: National Museum, "Universidade Federal do Rio de Janeiro" (MN-UFRJ); "Laboratório de Biologia e Parasitologia de Mamíferos Reservatórios Silvestres", "Instituto Oswaldo Cruz", "Fundação Oswaldo Cruz"(LBCE-Fiocruz); and "Laboratório de Biodiversidade", "Universidade Federal de Goiás", "Regional Jataí" (LZE-UFG), and took 20 craniometric measurements. Craniometry was explored using unweighted pair group method with arithmetic mean (UPGMA), canonical variate analysis, and principal component analysis (PCA). The results led us to conclude that there are three craniometric groups of H. megacephalus with a tendency to differentiate as a result of geographical influences.(AU)

Com grande diversidade genética e distribuição geográfica, Hylaeamys megacephalus (G. Fisher, 1814) ocorre tanto na Amazônia quanto no Cerrado. Visto seu aspecto generalista, esta espécie tolera diversos hábitos alimentares e habitats, ocorrendo em áreas inundadas ou não, sendo predominantemente terrestre, permitindo maior fluxo de genes entre as populações, mesmo em longas distâncias. Apresenta ampla distribuição, e carece de estudos que busquem um melhor entendimento sobre as variações morfológicas resultantes das diferenças impostas pelo meio ao longo de sua distribuição. O estudo teve como objetivo, analisar as diferenças entre as populações de H. megacephalus, com base na craniometria investigando se o ambiente interfere na morfologia. Analisamos um total de 142 espécimes oriundos de coleções científicas de mamíferos, do Museu Nacional, Universidade Federal do Rio de Janeiro (MN-UFRJ), Laboratório de Biologia e Parasitologia de Mamíferos Reservatórios Silvestres, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (LBCE-Fiocruz) e Laboratório de Biodiversidade, Universidade Federal de Goiás, Regional Jataí, nos quais foram tomadas 20 medidas craniométricas. A craniometria foi explorada nas análises estatísticas de agrupamento de pares não ponderados com médias aritméticas (UPGMA), variação canônica e análise dos Componentes Principais (PCA). Os resultados encontrados nos levaram a concluir a existência de três grupos craniométricos da espécie de H. megacephalus com tendência a se diferenciarem, por influências geográficas.(AU)

Relationships of rice yield and quality based on genotype by trait (GT) biplot

ABSTRACT An experiment was conducted to examine the influencing characters on rice by using 64 rice genotypes, including four local landraces, four released cultivars and 56 mutant lines (M5) derived from these genotypes, with application of the genotype by trait (GT) biplot methodology. The first two principal components (PC1 and PC2) accounted for 46.6% of total variation in 64 genotypes. The polygon view of GT biplot suggested seven sections for 64 genotypes. The vertex G38 had good amounts of grain yield, panicle length, hundred grain weight, internodes length, plant height and fertility percentage. Generally based on vector view it was demonstrated that the selection of high grain yield would be performed via thousand grain weight, panicle weight and number of filled grain per panicle. These traits should be considered simultaneously as effective selection criteria evolving high yielding rice genotypes because of their large contribution to grain yield. The genotypes G2, G4 and G7 could be considered for the developing of desirable progenies in the selection strategy of rice improvement programs. This study revealed GT biplot can graphically display the interrelationships among traits. In conclusion, it is recommended the use of GGE biplot to identify superior genotypes for simultaneous improvement of several traits.

Association between serotonin 2C receptor gene (HTR2C) polymorphisms and psychopathological symptoms in children and adolescents

Serotonin 2C receptors (5HT2C) are involved in serotonin-driven dynamic equilibrium adjustments responsible for homeostatic stability in brain structures that modulate behavior and emotions. Single nucleotide polymorphisms (SNPs) from the serotonin 2C receptor gene (HTR2C) have been associated with several neurological and mental disorders, including abnormalities in cognitive and emotional processes. The aim of this study was to evaluate the association between the rs6318 SNP of the HTR2C gene and behavioral characteristics exhibited by children and adolescents based on the Child Behavior Checklist (CBCL/6-18) inventory. Eighty-five psychiatric outpatients between 8 and 18 years of age underwent genotyping of the rs6318 SNP. The CBCL/6-18 scale was administered to their caregivers. The chi-squared test was used to assess differences in the frequency of C and G alleles of the rs6318 SNP relative to the grouped CBCL/6-18 scores; significance level was 5%. The presence of the G allele of rs6318 was found to be associated with characteristics of aggressive behavior and social problems, and aggressive behavior was found to be associated with heterozygosis in females. These findings contribute to the identification of mental and behavioral phenotypes associated with gene expression.

Interactive effects of genotype x environment on the live weight of GIFT Nile tilapias

ABSTRACT In this paper, the existence of a genotype x environment interaction for the average daily weight in GIFT Nile tilapia (Oreochromis niloticus) in different regions in the state of Paraná (Brazil) was analyzed. The heritability results were high in the uni-characteristic analysis: 0.71, 0.72 and 0.67 for the cities of Palotina (PL), Floriano (FL) and Diamond North (DN), respectively. Genetic correlations estimated in bivariate analyzes were weak with values between 0.12 for PL-FL, 0.06 for PL and 0.23 for DN-FL-DN. The Spearman correlation values were low, which indicated a change in ranking in the selection of animals in different environments in the study. There was heterogeneity in the phenotypic variance among the three regions and heterogeneity in the residual variance between PL and DN. The direct genetic gain was greater for the region with a DN value gain of 198.24 g/generation, followed by FL (98.73 g/generation) and finally PL (98.73 g/generation). The indirect genetic gains were lower than 0.37 and greater than 0.02 g/generation. The evidence of the genotype x environment interaction was verified, which indicated the phenotypic heterogeneity of the variances among the three regions, weak genetic correlation and modified rankings in the different environments.

Behçet's disease: review with emphasis on dermatological aspects

Abstract: Behçet's disease is a systemic vasculitis characterized by attacks of acute inflammation, which can affect almost every vascularized area of the body. There is a close correlation between the geographical distribution of HLA-B51 and its prevalence. In the etiopathogenesis there are indications of genetic susceptibility associated with environmental influence. Among the involved genes are those that encompass innate and adaptive immunities. Polymorphisms and epistatic interactions in several genes are described, as well as the presence of imbalance lineage between HLA-B51 and A (MICA). Herpes simplex and Streptococcus sanguinis may be important extrinsic factors. An increase of Th1 response and of IL-21 is observed. The production of IL-21 is positively related to Th17 cells and negatively to T-regs. The mucocutaneous manifestations are Behcet´s disease markers, and their earlier onset indicates a worse prognosis. Recurrent oral ulcers have varied sizes and arrangements, genital ulcers are recurrent, leaving scars, skin lesions are multivaried, and pathergy, although not so frequent, is important for the diagnosis. There are numerous attempts to validate indexes that can evaluate the disease activity and among them the Mucocutaneous Activity Index. This is a specific score that can help with therapeutic decisions and to reduce morbidity, but still lacks validation. The clinical manifestations of other organs are described as well as treatment options.

Paraoxonase 1 (PON1) Q192R genotypes and their interaction with smoking strongly increase atherogenicity and the Framingham risk score

ABSTRACT Objective Paraoxonase 1 (PON1) polymorphisms are associated with an increased susceptibility to cardiovascular disease. PON1 Q192R polymorphism (rs662) partially determine PON1 hydrolytic activity and protect against oxidation of LDL and HDL. This study aimed to delineate the association of PON1 status (functional 192 genotype and plasma activity levels) and atherogenicity in urbans residents aged 40 years or more. Materials and methods Anthropometric data, lipid profiles, the atherogenic index of the plasma (AIP) and Framingham score risk were measured. Three kinetic assays were conducted to assay PON1 status using phenylacetate and 4-(chloromethyl)phenyl acetate as substrates. Results Smoking per se did not significantly impact the AIP but the interaction PON1 genotype by smoking significantly increased the AIP. In subjects with the RR genotype smoking increased the AIP index from (estimated mean ± SEM) -0.038 ± 0.039 to 0.224 ± 0.094. The QR genotype increased the Framingham risk index by around 1.3 points. Smoking by RR genotype carriers significantly increased the Framingham risk score (17.23 ± 2.04) as compared to smoking (13.00 ± 1.06) and non-smoking (7.79 ± 0.70) by QQ+QR genotype carriers. The interaction RR genotype by smoking was a more important predictor (odds ratio = 7.90) of an increased Framingham risk score (> 20) than smoking per se (odds ratio = 2.73). The interaction smoking by RR genotype carriers significantly increased triglycerides and lowered HDL cholesterol. Conclusion Smoking per se has no (AIP) or a mild (Framingham risk score) effect on atherogenicity, while the interaction smoking by PON1 RR genotype has a clinically highly significant impact on atherogenicity.

Relación entre factores genéticos y medioambientales y la hipercolesterolemia en niños / Relationship between genetic and environmental factors and hypercholesterolemia in children

Introducción. La hipercolesterolemia infantil aumentó en las últimas décadas. Conocer los factores ambientales y genéticos que influyen sobre ella permitiría establecer pautas de pesquisa más adecuadas. Objetivos. Analizar si existe asociación entre factores genéticos y ambientales y la hipercolesterolemia en niños. Evaluar las cualidades predictivas de las variables que muestren asociación con la hipercolesterolemia. Material y métodos. Estudio observacional, analítico, transversal. Población: alumnos de todas las escuelas de Jovita. Edad: > 6 y < 12 años. Se midió la colesterolemia total. Mediante encuestas a los padres, se evaluó la historia clínica familiar (HCF) y el nivel socioeconómico (NSE). Se registró el peso y la talla para determinar el estado nutricional. Por medio de una encuesta al niño, se identificó el nivel de actividad física y los hábitos dietéticos. Se evaluó la asociación mediante el cálculo de OR (p < 0,05). Se efectuaron pruebas diagnósticas sobre las variables para predecir hipercolesterolemia. Resultados. Se incluyeron382 alumnos. La media de colesterolemia fue de 168 mg/dl. Un 13,4% presentaron hipercolesterolemia. El sedentarismo fue del 22,8%, y la obesidad, del 10,5%. La HCF positiva, el NSE alto-mediano y la obesidad se asociaron con hipercolesterolemia (OR 2,10; 2,10 y 2,05, respectivamente). No se encontró asociación entre actividad física e ingesta de grasas y colesterol e hipercolesterolemia. La HCF positiva y el NSE alto-mediano mostraron sensibilidad (75% y 88%) para predecir hipercolesterolemia. La hipercolesterolemia de ambos padres en relación con la hipercolesterolemia del hijo mostró un OR 9,59, sensibilidad de 73%, especificidad de 71%, valor predictivo positivo de 57% y negativo de 83%. Conclusiones. La HCF positiva, el NSE alto-mediano y la obesidad se asociaron con hipercolesterolemia en el niño. La hipercolesterolemia en ambos padres presentó una asociación con la de los niños y mostró un buen potencial como factor predictor y criterio de pesquisa.

Introduction. Pediatric hypercholesterolemia has increased over the past decades. Knowing the environmental and genetic factors that have an impact on it would allow establishing more adequate screening guidelines. Objectives. To determine if there is an association between genetic and environmental factors and hypercholesterolemia in children. To assess the predictive qualities of outcome measures associated with hypercholesterolemia. Material and methods. Observational, analytical, cross-sectional study. Population: students from all schools located in Jovita. Age: > 6 and < 12 years old. The total cholesterol level was measured. A survey was administered to parents to assess their family medical history (FMH) and socioeconomic level (SEL). Weight and height were recorded to establish nutritional status. A survey was administered to children to identify their level of physical activity and their eating habits. The association was assessed by estimating the OR value (p < 0.05). Diagnostic tests were done to establish outcome measures that predict hypercholesterolemia. Results. Three hundred and eighty-two students were included. Their mean cholesterol level was 168 mg/dL, and 13.4% had hypercholesterolemia. A sedentary lifestyle was observed in 22.8%, and obesity, in 10.5%. A positive FMH, a high/ middle SEL, and obesity were associated with hypercholesterolemia (OR: 2.10, 2.10 and 2.05, respectively). No association was found between physical activity and fat/cholesterol intake and hypercholesterolemia. A positive FMH and a high/middle SEL were sensitive enough (75% and 88%) to predict hypercholesterolemia. The presence of hypercholesterolemia inboth parents in relation to hypercholesterolemia in their child showed an OR of 9.59, a sensitivity of 73%, a specificity of 71%, a positive predictive value of 57%, and a negative predictive value of 83%. Conclusions. A positive FMH, a high/ middle SEL, and obesity were associated with hypercholesterolemia in children. The presence of hypercholesterolemia in both parents was associated with hypercholesterolemia in their child and showed itself to be a great potential predictor and screening criterion.

Genetic and Environmental Effects on the Abdominal Aortic Diameter Development / Efeitos Genéticos e Ambientais no Desenvolvimento do Diâmetro da Aorta Abdominal

Abstract Background: Configuration of the abdominal aorta is related to healthy aging and a variety of disorders. Objectives: We aimed to assess heritable and environmental effects on the abdominal aortic diameter. Methods: 114 adult (69 monozygotic, 45 same-sex dizygotic) twin pairs (mean age 43.6 ± 16.3 years) underwent abdominal ultrasound with Esaote MyLab 70X ultrasound machine to visualize the abdominal aorta below the level of the origin of the renal arteries and 1-3 cm above the bifurcation. Results: Age- and sex-adjusted heritability of the abdominal aortic diameter below the level of the origin of the renal arteries was 40% [95% confidence interval (CI), 14 to 67%] and 55% above the aortic bifurcation (95% CI, 45 to 70%). None of the aortic diameters showed common environmental effects, but unshared environmental effects were responsible for 60% and 45% of the traits, respectively. Conclusions: Our analysis documents the moderate heritability and its segment-specific difference of the abdominal aortic diameter. The moderate part of variance was explained by unshared environmental components, emphasizing the importance of lifestyle factors in primary prevention. Further studies in this field may guide future gene-mapping efforts and investigate specific lifestyle factors to prevent abdominal aortic dilatation and its complications.

Resumo Fundamento: A configuração da aorta abdominal relaciona-se com o envelhecimento saudável e uma série de distúrbios. Objetivos: Avaliar efeitos herdáveis e ambientais no diâmetro da aorta abdominal. Métodos: 114 pares de gêmeos adultos (69 monozigóticos e 45 dizigóticos do mesmo sexo), com idade média de 43,6 ± 16,3 anos, foram submetidos a ultrassonografia abdominal com o aparelho Esaote MyLab 70X para visualização da aorta abdominal abaixo da origem das artérias renais e 1-3 cm acima da bifurcação aórtica. Resultados: A herdabilidade ajustada para idade e sexo do diâmetro da aorta abdominal abaixo da origem das artérias renais foi 40% [intervalo de confiança (IC) 95%, 14 – 67%] e acima da bifurcação, 55% (IC 95%, 45 – 70%). Nenhum dos diâmetros aórticos apresentou efeitos ambientais comuns, mas os efeitos ambientais não compartilhados foram responsáveis por 60% e 45% dos traços, respectivamente. Conclusões: Nossa análise mostrou herdabilidade moderada e diferença do diâmetro da aorta abdominal com especificidade de segmento. A parte moderada da variância foi explicada pelo componente ambiental não compartilhado, enfatizando a importância do estilo de vida na prevenção primária. Estudos adicionais nesse campo poderão guiar futuros esforços de mapeamento genético e investigar fatores específicos de estilo de vida para prevenir dilatação da aorta abdominal e suas complicações.

A determinação biológica dos transtornos mentais: uma discussão a partir de teses neurocientíficas recentes / La determinación biológica de los trastornos mentales: una discusión a partir de tesis neurocientíficas recientes / Biological determination of mental disorders: a discussion based on recent hypotheses from neuroscience

Resumo: A compreensão dos processos de formação dos transtornos mentais vem se mostrando desafiadora desde a fundação do campo psiquiátrico. O desenvolvimento das neurociências proporcionou novo fôlego à expectativa de encontrar estritamente no funcionamento biológico a explicação para o surgimento dos transtornos mentais. No entanto, tal objetivo não vem sendo alcançado com a esperada facilidade, de modo que novas hipóteses começam a se destacar nas pesquisas neurocientíficas. Neste artigo, identificamos as noções de epigenética, neurodesenvolvimento e plasticidade como os principais indicativos de um novo modo de compreender a biologia dos fenômenos mentais. A complexidade genética, o papel formativo do ambiente e as variações que caracterizam a vulnerabilidade implicam importantes modificações nas principais teses sobre a determinação biológica dos transtornos mentais, sugerindo uma reconfiguração dos limites entre o "social" e o "biológico" nas pesquisas em neurociências.

Resumen: La comprensión de los procesos de formación de los trastornos mentales ha representado un desafio desde que nació el campo de la psiquiatria. El desarrollo de las neurociencias proporcionó un nuevo aliento a la expectativa de encontrar, estrictamente en el funcionamiento biológico, la explicación para el surgimiento de los trastornos mentales. No obstante, tal objetivo no se alcanza con la esperada facilidad, de modo que nuevas hipótesis comienzan a destacarse en las investigaciones neurocientíficas. En este artículo, identificamos las nociones de epigenética, neurodesarrollo y plasticidad como los principales indicativos de un nuevo modo de comprender la biología de los fenómenos mentales. La complejidad genética, el papel formativo del ambiente y las variaciones que caracterizan la vulnerabilidad implican importantes modificaciones en las principales tesis sobre la determinación biológica de los trastornos mentales, sugiriendo una reconfiguración de los límites entre lo "social" y lo "biológico" en las investigaciones en neurociencias.

Abstract: Understanding the processes involved in the development of mental disorders has proven challenging ever since psychiatry was founded as a field. Neuroscience has provided new expectations that an explanation will be found for the development of mental disorders based on biological functioning alone. However, such a goal has not been that easy to achieve, and new hypotheses have begun to appear in neuroscience research. In this article we identify epigenetics, neurodevelopment, and plasticity as the principal avenues for a new understanding of the biology of mental phenomena. Genetic complexity, the environment's formative role, and variations in vulnerability involve important changes in the principal hypotheses on biological determination of mental disorders, suggesting a reconfiguration of the limits between the "social" and the "biological" in neuroscience research.

Genetic and environmental influence on thyroid gland volume and thickness of thyroid isthmus: a twin study

Objectives Decreased thyroid volume has been related to increased prevalence of thyroid cancer. Subjects and methods One hundred and fourteen Hungarian adult twin pairs (69 monozygotic, 45 dizygotic) with or without known thyroid disorders underwent thyroid ultrasound. Thickness of the thyroid isthmus was measured at the thickest portion of the gland in the midline using electronic calipers at the time of scanning. Volume of the thyroid lobe was computed according to the following formula: thyroid height*width*depth*correction factor (0.63). Results Age-, sex-, body mass index- and smoking-adjusted heritability of the thickness of thyroid isthmus was 50% (95% confidence interval [CI], 35 to 66%). Neither left nor right thyroid volume showed additive genetic effects, but shared environments were 68% (95% CI, 48 to 80%) and 79% (95% CI, 72 to 87%), respectively. Magnitudes of monozygotic and dizygotic co-twin correlations were not substantially impacted by the correction of covariates of body mass index and smoking. Unshared environmental effects showed a moderate influence on dependent parameters (24-50%). Conclusions Our analysis support that familial factors are important for thyroid measures in a general twin population. A larger sample size is needed to show whether this is because of common environmental (e.g. intrauterine effects, regional nutrition habits, iodine supply) or genetic effects.

The key role of 99mTc-MIBI SPECT/CT in the diagnosis of parathyroid adenoma: a case report

The concomitant occurrence of primary hyperparathyroidism (PHPT) due to parathyroid adenoma and papillary thyroid carcinoma (PTC) is not common. The co-occurrence of parathyroid tumors and thyroid diseases can lead to misdiagnosis owing to mutual interference of imaging in the early period of disease. The most commonly used imaging techniques for the preoperative localization of parathyroid and thyroid adenomas are technetium-99m sestamibi (99mTc-MIBI) scintigraphy and ultrasonography of the neck. Recently, 99mTc-MIBI single-photon emission computed tomography associated with computed tomography scintigraphy (SPECT/CT) has been used to detect PHPT, and its diagnostic value is being evaluated. Herein, we report a patient with an unusual co-occurrence of parathyroid adenoma and multiple thyroid diseases, including papillary thyroid carcinoma, thyroid adenoma and lymphocytic thyroiditis, which were localized with 99mTc-MIBI SPECT/CT and confirmed surgically. We suggest that 99mTc-MIBI SPECT/CT can play an important role in the diagnosis of parathyroid and thyroid lesions. Arch Endocrinol Metab. 2015;59(3):265-9.

Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.

Variant in CAPN10 gene and environmental factors show evidence of association with excess weight among young people in a Colombian population / Una variante del gen CAPN10 y los factores ambientales muestran asociación con el exceso de peso en jóvenes colombianos.

Introduction : Obesity results from interaction between genetic and environmental risk factors. Objective: To evaluate the effect of three gene variants and environmental factors on obesity and overweight in young people aged 10 to 18 years in a Colombian population. Materials and methods: A total of 424 subjects were selected and separated into three groups for a cross-sectional study; 100 obese and 112 overweight subjects were matched with 212 normal-weight controls. Associations were evaluated between excess weight and three genetic polymorphisms ( UCP3- rs1800849, FTO -rs17817449, and CAPN10 -rs3842570), as well as the family history, the time spent watching television and playing video games, and the diet. Results: A family history of obesity, the time spent watching television and playing video games, the lack of breastfeeding, a low consumption of cereals, legumes, fruits, vegetables, and a high consumption of fast foods were characteristics typically found in obese individuals compared to controls. A significant association between genotype I/I (SNP19 of CAPN10 ) and excess weight was found even with an active lifestyle. In addition, significant associations between the C/C genotype of the UCP3 gene and the G/G and T/T genotypes of the FTO gene and excess weight were found only in young sedentary individuals. Conclusions: In this population, inadequate diet and sedentary lifestyle increased the risk of excess weight. Genotype I/I of SNP19 in CAPN10 was significantly associated with excess weight. In contrast, FTO and UCP3 variants exhibited effects only in sedentary environments.

Introducción. La obesidad resulta de la interacción entre factores de riesgo genéticos y ambientales. Objetivo. Evaluar el efecto de tres variantes genéticas y factores ambientales en el exceso de peso en jóvenes de 10 a 18 años de Medellín, Colombia. Materiales y métodos. Se hizo un estudio transversal en 424 jóvenes divididos en tres grupos: 100 obesos, 112 jóvenes con sobrepeso, y, pareados con ellos, 212 jóvenes con peso adecuado, que conformaron el grupo de control. Se evaluó la asociación entre tres polimorfismos genéticos ( UCP3 -rs1800849, FTO -rs17817449 y CAPN10 -rs3842570) y el exceso de peso, así como su interacción con antecedentes familiares de enfermedad, el tiempo dedicado a ver televisión y a jugar videojuegos y el consumo de alimentos. Resultados. Los antecedentes familiares de obesidad, la dedicación de más de dos horas al día a ver televisión y jugar videojuegos, la falta de lactancia materna, el bajo consumo de cereales, legumbres, frutas y verduras y el gran consumo de comidas rápidas fueron más frecuentes entre los obesos que en los controles. Se observó una asociación significativa entre el genotipo I/I (SNP19 del CAPN10 ) y el exceso de peso, incluso en los jóvenes que llevaban una vida activa. Además, se encontró una asociación significativa entre los genotipos C/C del UCP3 y G/G y T/T del FTO y el exceso de peso, pero solo en los jóvenes sedentarios. Conclusiones. En esta población, la alimentación inadecuada y el sedentarismo aumentaron el riesgo de exceso de peso. El genotipo I/I de SNP19 del CAPN10 se asoció significativamente con el exceso de peso. Algunas variantes del FTO y el UCP3 mostraron tener efecto solo en jóvenes sedentarios.

Association between interleukin-6 polymorphism in the -174 G/C region and hearing loss in the elderly with a history of occupational noise exposure / Associação entre interleucina-6 polimorfismo na região de -174 G/C e perda auditiva em idosos com história de exposição ao ruído ocupacional

INTRODUCTION: The biological processes involved in noise-induced hearing loss (NIHL) are still unclear. The involvement of inflammation in this condition has been suggested. OBJECTIVE: To investigate the association between interleukin - 6 (IL-6) polymorphism and susceptibility to NIHL. METHODS: This was a cross-sectional study with a sample of 191 independent elderly individuals aged > 60 years of age. Information on exposure to occupational noise was obtained by interviews. Audiological evaluation was performed using pure tone audiometry and genotyped through PCR by restriction fragment length polymorphism - PCR-RFLP. Data were analyzed using the Chi-square test and the Odds ratio (OR), with the significance level set at 5%. RESULTS: Among elderly with hearing loss (78.0%), 18.8% had a history of exposure to occupational noise. There was a statistically significant association between the genotype frequencies of the IL-6 -174 and NIHL. The elderly with the CC genotype were less likely to have hearing loss due to occupational noise exposure when compared to those carrying the GG genotype (OR = 0.0124; 95% CI 0.0023-0.0671; p < 0.001). CONCLUSION: This study suggests there is an association of polymorphisms in the IL- 6 gene at position - G174C with susceptibility to noise-induced hearing loss. .

INTRODUÇÃO: Os processos biológicos envolvidos na perda auditiva induzida por ruído (PAIR) ainda não estão claros. O envolvimento de processo inflamatório nesta condição tem sido sugerido. OBJETIVO: Investigar a associação entre o polimorfismo no gene da interleucina-6 (IL-6) e a suscetibilidade à PAIR. MÉTODO: Trata-se de estudo transversal com amostra de 191 idosos independentes acima de 60 anos de idade. Informações sobre a exposição ao ruído ocupacional foram obtidas por entrevistas. A avaliação audiológica foi realizada por meio de audiometria tonal liminar e a genotipagem pela técnica da PCR-RFLP. Os dados foram analisados usando-se o teste Qui-quadrado e a razão de chances (OR), com o nível de significância fixado em 5%. RESULTADOS: Entre os idosos com perda auditiva (78,0%), 18,8% apresentavam histórico de exposição ao ruído ocupacional. Houve associação estatisticamente significante entre as frequências genotípicas da IL-6 -174 e a PAIR. Os idosos portadores do genótipo CC foram menos propensos a apresentar perda auditiva por exposição ao ruído ocupacional quando comparados a aqueles portadores do genótipo GG (OR = 0,0124; 95% IC 0,0023-0,0671; p < 0,001). CONCLUSÃO: O presente estudo sugere a associação do polimorfismo no gene da IL-6 na posição -G174C com a suscetibilidade à perda auditiva induzida por ruído. .

Association among genetic predisposition, gut microbiota, and host immune response in the etiopathogenesis of inflammatory bowel disease

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.

Association study between the Taq1A (rs1800497) polymorphism and schizophrenia in a Brazilian sample / Estudo de associação entre o polimorfismo genético Taq1A (rs1800497) e esquizofrenia em uma amostra brasileira

Schizophrenia is a severe psychotic disorder with recurrent relapse and functional impairment. It results from a poorly understood gene-environment interaction. The Taq1A polymorphism (located in the gene cluster NTAD) is a likely candidate for schizophrenia. Its rs1800497 polymorphism was shown to be associated with DRD2 gene expression. Therefore the present work aims to investigate a possible association between schizophrenia and such polymorphism. The compared distribution of the alleles and genotypes of the studied polymorphism was investigated in a Brazilian sample of 235 patients and 834 controls. Genotypic frequencies were in Hardy-Weinberg equilibrium. There was a trend of allelic association between the Taq1A polymorphism (rs1800497) with schizophrenia in the studied sample. However no statistically differences were found between cases and controls when analyzed by gender or schizophrenia subtypes.

A esquizofrenia é um grave transtorno psicótico que apresenta frequentes recaídas e incapacitação progressiva. Resulta de uma interação gene-ambiente ainda pouco compreendida. O polimorfismo Taq1A (localizado no grupamento genético NTAD) é considerado um possível candidato para esquizofrenia. O polimorfismo genético rs1800497 foi associado com alteração da expressão do gene do DRD2. Assim, o presente trabalho objetivou investigar a possível associação de tal polimorfismo com esquizofrenia. A distribuição de seus alelos e genótipos foi investigada em uma amostra brasileira composta de 235 pacientes e 834 controles. As frequências genotípicas estavam em equilíbrio de Hardy-Weinberg. Houve uma tendência de associação alélica entre o polimorfismo Taq1A (rs1800497) e esquizofrenia na amostra estudada. No entanto, não houve diferenças estatisticamente significantes entre os grupos de casos e controles, quando analisados por gênero e subtipos da esquizofrenia.