Using gene-network landscape to dissect genotype effects of TCF7L2 genetic variant on diabetes and cardiovascular risk

Vaquero AR, Ferreira NE, Omae SV, Rodrigues MV, Teixeira SK, Krieger JE, Pereira AC. Using gene-network landscape to dissect genotype effects of TCF7L2 genetic variant on diabetes and cardiovascular risk. Physiol Genomics 44: 903-914, 2012. First published August 7, 2012; doi:10.1152/physiolgenomics.00030.2012.-The single nucleotide polymorphism (SNP) within the TCF7L2 gene, rs7903146, is, to date, the most significant genetic marker associated with Type 2 diabetes mellitus (T2DM) risk. Nonetheless, its functional role in disease pathology is poorly understood. The aim of the present study was to investigate, in vascular smooth muscle cells from 92 patients undergoing aortocoronary bypass surgery, the contribution of this SNP in T2DM using expression levels and expression correlation comparison approaches, which were visually represented as gene interaction networks. Initially, the expression levels of 41 genes (seven TCF7L2 splice forms and 40 other T2DM relevant genes) were compared between rs7903146 wild-type (CC) and T2DM-risk (CT + TT) genotype groups. Next, we compared the expression correlation patterns of these 41 genes between groups to observe if the relationships between genes were different. Five TCF7L2 splice forms and nine genes showed significant expression differences between groups. RXR alpha gene was pinpointed as showing the most different expression correlation pattern with other genes. Therefore, T2DM risk alleles appear to be influencing TCF7L2 splice form's expression in vascular smooth muscle cells, and RXR alpha gene is pointed out as a treatment target candidate for risk reduction in individuals with high risk of developing T2DM, especially individuals harboring TCF7L2 risk genotypes.

OPTIMUM RATIO OF CALCIUM AND BORON IN THE NUTRIENT SOLUTION OR IN CASTOR BEAN SHOOT FOR FRUIT YIELD AND SEED OIL CONTENT

Calcium (Ca) and boron (B) have been reported as the major macro-and micronutrient required for castor bean plant yield. The objective of this study was to determine the Ca: B ratios (in the growth media and plant tissue) for fruit yield and shoot dry weight of the castor bean (Ricinus communis L.), grown in a nutrient solution, and to evaluate Ca and B supply on concentration and total uptake of Ca, potassium (K), magnesium (Mg), and B, as well on the seed oil content. The treatments were arranged in a 3 x 3 factorial fashion, consisting of three rates of Ca (40, 80, and 160 mg L-1) and three of B (0.32, 0.96, and 1.60 mg L-1). Calcium and B rates increased the shoot and root dry weight and fruit yield at a Ca: B ratio in the nutrient solution of 166 and 100, respectively. Symptoms of B deficiency were observed in plants supplied with 0.32 mg B L-1, regardless of the Ca concentration in the nutrient solution. Plants which showed visual symptoms of Ca deficiency cultivated with 40 mg Ca L-1 presented concentration of Ca in plant tissue up to 10 g kg(-1). The concentration and total Ca and B uptake increased with the rates of them. Notwithstanding, the shoot Ca accumulation was improved by B rates. In addition, there were no decreases in K and Mg uptake due to Ca rates. Furthermore, addition of 80 mg L-1 of Ca and 1.60 mg L-1 of B in the growth media increased the seed oil content. The Ca: B ratio in the diagnostic leaf associated with the highest plant dry weight (shoot and root) and fruit yield, was 500 (16 to 20 g kg(-1) of Ca, and for 30 to 40 mg kg(-1) of B).

Brazilian urban population genetic structure reveals a high degree of admixture

Advances in genotyping technologies have contributed to a better understanding of human population genetic structure and improved the analysis of association studies. To analyze patterns of human genetic variation in Brazil, we used SNP data from 1129 individuals - 138 from the urban population of Sao Paulo, Brazil, and 991 from 11 populations of the HapMap Project. Principal components analysis was performed on the SNPs common to these populations, to identify the composition and the number of SNPs needed to capture the genetic variation of them. Both admixture and local ancestry inference were performed in individuals of the Brazilian sample. Individuals from the Brazilian sample fell between Europeans, Mexicans, and Africans. Brazilians are suggested to have the highest internal genetic variation of sampled populations. Our results indicate, as expected, that the Brazilian sample analyzed descend from Amerindians, African, and/or European ancestors, but intermarriage between individuals of different ethnic origin had an important role in generating the broad genetic variation observed in the present-day population. The data support the notion that the Brazilian population, due to its high degree of admixture, can provide a valuable resource for strategies aiming at using admixture as a tool for mapping complex traits in humans. European Journal of Human Genetics (2012) 20, 111-116; doi:10.1038/ejhg.2011.144; published online 24 August 2011

Strategic environmental assessment in tourism planning - Extent of application and quality of documentation

Strategic environmental assessment (SEA) has been applied throughout the world in different sectors and in various ways. This paper reports on results of a PhD research on SEA applied to tourism development planning, reflecting the situation in mid-2010. First, the extent of tourism specific SEA application world-wide is established. Then, based on a review of the quality of 10 selected SEA reports, good practice, as well as challenges, trends and opportunities for tourism specific SEA are identified. Shortcomings of SEA in tourism planning are established and implications for future research are outlined. (C) 2012 Elsevier Inc. All rights reserved.

Heparin Increases HLA-G Levels in Primary Antiphospholipid Syndrome

Objectives. The aim of this study was to investigate the HLA-G serum levels in Primary Antiphospholipid Syndrome (PAPS) patients, its impact on clinical and laboratory findings, and heparin treatment. Methods. Forty-four PAPS patients were age and gender matched with 43 controls. HLA-G serum levels were measured using an enzyme-linked immunosorbent assay (ELISA). Results. An increase in soluble HLA-G levels was found in patients compared to controls (3.35 (0 22.9) versus 1.1 (0 14), P = 0.017). There were no significant differences in HLA-G levels between patients with and without obstetric events, arterial thrombosis, venous thrombosis, or stroke. Sixty-six percent of patients were being treated with heparin. Interestingly, patients treated with heparin had higher HLA-G levels than ones who were not treated with this medication (5 (0-22.9) versus 1.8 (0-16) ng/mL, P = 0.038). Furthermore, patients on heparin who experienced obstetric events had a trend to increased HLA-G levels compared to patients who were not on heparin and did not have obstetric events (5.8 (0-22.9) versus 2 (0-15.2) ng/mL, P = 0.05). Conclusion. This is the first study to demonstrate that serum HLA-G levels are increased in APS patients. We also demonstrated that heparin increases HLA-G levels and may increase tolerance towards autoantigens.

Genetic diversity of Stryphnodendron adstringens (Mart.) Coville determined by AFLP molecular markers

Bark extracts of Stryphnodendron adstringens (Mart) Coville a Leguminosae species, well known in Brazil as barbatimao, are popularly used as healing agent. The objective of this work was to determine the genetic diversity of S. adstringens populations and to correlate genetic distances to the production of tannins. S. adstringens accessions from populations found in Cerrado regions in the states of Goias, Minas Gerais and Sao Paulo were analyzed using the AFLP (Amplified Fragment Length Polymorphism) technique. A total of 236 polymorphic bands were scored and higher proportion of genetic diversity was found inter populations (70.9%), rather than intra populations (29.1%). F-ST value was found to be significantly greater than zero (0.2906), demonstrating the complex genetic structure of S. adstringens populations. Accessions collected in Cristalina, GO, showed higher percentage of polymorphic loci (87.3%) and the highest genetic diversity. The lowest genetic variability was detected among accessions from the population growing in Caldas Novas, GO. The genetic distance among populations was estimated using the Unweighted Pair Group Method with Arithmetic Mean (UPGMA), which grouped populations into 3 clusters. Moreover, chemotypes with tannin concentration above 40% showed higher genetic similarity. AFLP analysis proved to be an efficient gene mapping technique to determine the genetic diversity among remaining populations of S. adstringens. Obtained results may be employed to implement further strategies for the conservation of this medicinal plant. (C) 2011 Elsevier Ltd. All rights reserved.

Thioredoxin interacting protein (TXNIP) rs7212 polymorphism is associated with arterial stiffness in the Brazilian general population

Thioredoxin interacting protein plays a pivotal role in several important processes of cardiovascular homeostasis by functioning as a biological sensor for biomechanical and oxidative stress. However, the effects of genetic variants in the modulation of arterial stiffness are unknown. In this scenario, the present study evaluated the relationship between the TXNIP rs7212 polymorphism and arterial stiffness. In the overall sample and in the diabetic group, individuals carrying CG + GG genotypes had higher PWV values compared with CC genotype group ( 10.0 vs 9.8 ms(-1), P = 0.03; 12.3 vs 11.2 ms(-1), P = 0.01; respectively). Our findings indicated that the G allele may contribute to increased arterial stiffness in the Brazilian general population and suggest a possible interaction with diabetes.

Vascular leiomyoma in the oral cavity

The aim of this study was to examine a case report of vascular leiomyoma located in the oral mucosa of the oral cavity. Vascular leiomyoma is a benign tumor arising from smooth muscle. One factor that makes vascular leiomyomas in the oral cavity rare is that there is little smooth muscle in the mouth. The most common histological subtype in the oral cavity is the vascular subtype. The greatest difficulty in histological diagnosis of this entity is the similarity in morphology with other malignancies, particularly of neural or fibroblastic lineage. Wide surgical resection is the only treatment reported in the literature with good results. The recurrence rate is very low if complete resection is achieved. The study of rare or unusual lesions is very important for the clinical diagnosis of vascular leiomyoma

Influence of technique and manipulation on self-adhesive resin cements used to cement intraradicular posts

Statement of problem: Resin cements are widely used to cement intraradicular posts, but bond strength is significantly influenced by the technique and material used for cementation. Purpose: The purpose of this study was to evaluate the bond strength of 3 self-adhesive cements used to cement intraradicular glass fiber posts. The cements all required different application and handling techniques. Material and Methods: Forty-five human maxillary canines were selected and randomly divided into 3 groups n= 15 by drawing lots: Group BIS – Biscem, Group BRE – Breeze, and Group MAX – Maxcem. Each group was divided into 3 subgroups according to application and handling techniques: Sub-group A – Automix/Point tip applicator, Sub-group L – Handmix/Lentulo, and Sub-group C – Handmix/Centrix. Cementation of the posts was performed according to the manufacturers’ instructions. The push-out test was performed with a crosshead speed of 0.5 mm/min, and bond strength was expressed in megapascals. The results were evaluated by 2-way ANOVA and the all pairwise multiple comparison procedures (Tukey test) (?=.05). Results: Breeze cement showed the highest average for the subgroups A, L, and C when compared to the Biscem cement and Maxcem Elite (P<.05). Statistically significant differences among the subgroups were only observed for Biscem. Conclusions: This study shows that application and handling techniques may influence the bond strength of different self-adhesive cements when used for intraradicular post cementation.

A negative screen for mutations in calstabin 1 and 2 genes in patients with dilated cardiomyopathy

Background Calstabins 1 and 2 bind to Ryanodine receptors regulating muscle excitation-contraction coupling. Mutations in Ryanodine receptors affecting their interaction with calstabins lead to different cardiac pathologies. Animal studies suggest the involvement of calstabins with dilated cardiomyopathy. Results We tested the hypothesis that calstabins mutations may cause dilated cardiomyopathy in humans screening 186 patients with idiopathic dilated cardiomyopathy for genetic alterations in calstabins 1 and 2 genes (FKBP12 and FKBP12.6). No missense variant was found. Five no-coding variations were found but not related to the disease. Conclusions These data corroborate other studies suggesting that mutations in FKBP12 and FKBP12.6 genes are not commonly related to cardiac diseases.

Different approaches for dealing with rare variants in family-based genetic studies: application of a Genetic Analysis Workshop 17 problem

Rare variants are becoming the new candidates in the search for genetic variants that predispose individuals to a phenotype of interest. Their low prevalence in a population requires the development of dedicated detection and analytical methods. A family-based approach could greatly enhance their detection and interpretation because rare variants are nearly family specific. In this report, we test several distinct approaches for analyzing the information provided by rare and common variants and how they can be effectively used to pinpoint putative candidate genes for follow-up studies. The analyses were performed on the mini-exome data set provided by Genetic Analysis Workshop 17. Eight approaches were tested, four using the trait’s heritability estimates and four using QTDT models. These methods had their sensitivity, specificity, and positive and negative predictive values compared in light of the simulation parameters. Our results highlight important limitations of current methods to deal with rare and common variants, all methods presented a reduced specificity and, consequently, prone to false positive associations. Methods analyzing common variants information showed an enhanced sensibility when compared to rare variants methods. Furthermore, our limited knowledge of the use of biological databases for gene annotations, possibly for use as covariates in regression models, imposes a barrier to further research.

Software para estimativa do custo operacional de máquinas agrícolas - MAQCONTROL

A seleção e a otimização de sistemas mecanizados são os principais objetivos da mecanização racional. Não é suficiente uma compra adequada do maquinário agrícola se sua utilização não for controlada em aspectos operacionais e financeiros. Neste trabalho, é descrito o desenvolvimento de software para estimativa do custo operacional de máquinas agrícolas (MAQCONTROL), utilizando o ambiente de desenvolvimento Borland Delphi e o banco de dados Firebird. Os custos operacionais foram divididos em fixos e variáveis. Nos custos fixos, foram estimadas as despesas com depreciação, juros, alojamento e seguros. Nos custos variáveis, foi dada ênfase aos custos de manutenção como: óleos lubrificantes, filtros, pneus, graxa, combustível, pequenos reparos e troca de peças. Os resultados demonstraram a eficiência do software para os objetivos propostos. Assim, o MAQCONTROL pode ser uma importante ferramenta no processo de administração rural, pois reduz os custos da informação e agiliza a determinação precisa dos custos operacionais de máquinas agrícolas.

Adesão em saúde e psicoterapia: conceituação e aplicação na enurese noturna

Existem diversos estudos sobre preditores da não adesão, mas poucos mostram estratégias efetivas para lidar com esse problema. Uma revisão da literatura sobre desistência em psicoterapia mostrou que quase metade dos pacientes que ingressam num atendimento não o concluem. A medida na psicoterapia em geral é a de não adesão, ou desistência do tratamento; no presente trabalho serão apresentados dados relativos à adesão ao tratamento da enurese com alarme de urina. A taxa de desistência em um grupo de 61 crianças e adolescentes foi levantada considerando três condições: suas famílias não compareceram aos atendimentos, não responderam ao contato telefônico ou relataram ter abandonado os procedimentos. A desistência correspondeu a 19,6% da amostra e a idade do grupo dos desistentes era significativamente inferior, quando comparada à daqueles que aderiram ao tratamento. A já demonstrada associação entre a intolerância parental e a idade do filho explica os resultados e aponta para a necessidade de trabalho educativo intenso com os pais de adolescentes portadores de enurese.

Comensalidade e cuidado: meninas-jovens-mulheres órfãs no contexto de HIV/Aids

O "monopólio da cozinha", histórica e culturalmente, é atribuído às mulheres, mães. Para cuidar da família, elas elegem alimentos, compram, cozinham e os servem. Sustentam a comensalidade. Em contextos de HIV/Aids, onde há perda da mãe, as filhas tornam-se responsáveis por esses cuidados. O que pensam as meninas do papel de cuidadoras com o qual, prematuramente, deparam-se? O que dizem seus irmãos sobre isso? Realizamos entrevistas semidirigidas com 14 jovens órfãos. Os dados foram analisados pela proposta de Mills (2009). As jovens não demonstram insatisfação por executarem novas tarefas, mas deploram o fato de impedirem o estudo e a vida além-casa. Seus irmãos entendem a lida da cozinha como coisa de mulher e, por isso, dificilmente colaboram. Essas jovens necessitam de cuidados direcionados à situação vulnerável em que vivem. As políticas de Saúde Pública poderiam pleitear macroestruturas que atuassem sobre essa demanda.