Identifying synonymous regulatory elements in vertebrate genomes

Synonymous gene regulation, defined by regulatory elements driving shared temporal and/or spatial aspects of gene expression, is most probably predicated on genomic elements that contain similar modules of certain transcription factor binding sites (TFBS). We have developed a method to scan vertebrate genomes for evolutionary conserved modules of TFBS in a predefined configuration, and created a tool, named SynoR that identifies synonymous regulatory elements (SREs) in vertebrate genomes. SynoR performs de novo identification of SREs utilizing known patterns of TFBS in active regulatory elements (REs) as seeds for genome scans. Layers of multiple-species conservation allow the use of differential phylogenetic sequence conservation filters in search of SREs and the results are displayed such as to provide an extensive annotation of the genes containing the detected REs. Gene Ontology categories are utilized to further functionally classify the identified genes, and integrated GNF Expression Atlas 2 data allow the cataloging of tissue-specificities of the predicted SREs. SynoR is publicly available at

An <i>in vivo cis</i>-Regulatory Screen at the Type 2 Diabetes Associated <i>TCF7L2</i> Locus Identifies Multiple Tissue-Specific Enhancers

Genome-wide association studies (GWAS) have repeatedly shown an association between non-coding variants in the TCF7L2 locus and risk for type 2 diabetes (T2D), implicating a role for cis-regulatory variation within this locus in disease etiology. Supporting this hypothesis, we previously localized complex regulatory activity to the TCF7L2 T2D-associated interval using an in vivo bacterial artificial chromosome (BAC) enhancer-trapping reporter strategy. To follow-up on this broad initial survey of the TCF7L2 regulatory landscape, we performed a fine-mapping enhancer scan using in vivo mouse transgenic reporter assays. We functionally interrogated approximately 50% of the sequences within the T2D-associated interval, utilizing sequence conservation within this 92-kb interval to determine the regulatory potential of all evolutionary conserved sequences that exhibited conservation to the non-eutherian mammal opossum. Included in this study was a detailed functional interrogation of sequences spanning both protective and risk alleles of single nucleotide polymorphism (SNP) rs7903146, which has exhibited allele-specific enhancer function in pancreatic beta cells. Using these assays, we identified nine segments regulating various aspects of the TCF7L2 expression profile and that constitute nearly 70% of the sequences tested. These results highlight the regulatory complexity of this interval and support the notion that a TCF7L2 cis-regulatory disruption leads to T2D predisposition.</p

Tbx20 Is Required in Mid-Gestation Cardiomyocytes and Plays a Central Role in Atrial Development.

RationaleMutations in the transcription factor TBX20 (T-box 20) are associated with congenital heart disease. Germline ablation of Tbx20 results in abnormal heart development and embryonic lethality by embryonic day 9.5. Because Tbx20 is expressed in multiple cell lineages required for myocardial development, including pharyngeal endoderm, cardiogenic mesoderm, endocardium, and myocardium, the cell type-specific requirement for TBX20 in early myocardial development remains to be explored.ObjectiveHere, we investigated roles of TBX20 in midgestation cardiomyocytes for heart development.Methods and resultsAblation of Tbx20 from developing cardiomyocytes using a doxycycline inducible cTnTCre transgene led to embryonic lethality. The circumference of developing ventricular and atrial chambers, and in particular that of prospective left atrium, was significantly reduced in Tbx20 conditional knockout mutants. Cell cycle analysis demonstrated reduced proliferation of Tbx20 mutant cardiomyocytes and their arrest at the G1-S phase transition. Genome-wide transcriptome analysis of mutant cardiomyocytes revealed differential expression of multiple genes critical for cell cycle regulation. Moreover, atrial and ventricular gene programs seemed to be aberrantly regulated. Putative direct TBX20 targets were identified using TBX20 ChIP-Seq (chromatin immunoprecipitation with high throughput sequencing) from embryonic heart and included key cell cycle genes and atrial and ventricular specific genes. Notably, TBX20 bound a conserved enhancer for a gene key to atrial development and identity, COUP-TFII/Nr2f2 (chicken ovalbumin upstream promoter transcription factor 2/nuclear receptor subfamily 2, group F, member 2). This enhancer interacted with the NR2F2 promoter in human cardiomyocytes and conferred atrial specific gene expression in a transgenic mouse in a TBX20-dependent manner.ConclusionsMyocardial TBX20 directly regulates a subset of genes required for fetal cardiomyocyte proliferation, including those required for the G1-S transition. TBX20 also directly downregulates progenitor-specific genes and, in addition to regulating genes that specify chamber versus nonchamber myocardium, directly activates genes required for establishment or maintenance of atrial and ventricular identity. TBX20 plays a previously unappreciated key role in atrial development through direct regulation of an evolutionarily conserved COUPT-FII enhancer

Morfologia da deposição de trombos murais: trajeto da luz residual em aneurismas de aorta abdominal infra-renal

PURPOSE: To assess the most frequent deposition site of mural thrombi in infrarenal abdominal aorta aneurisms, as well as the route of the residual lumen. METHODS: Assessment of CT scan images from 100 patients presenting asymptomatic abdominal aorta aneurism, and followed at HC-FMRP-USP. RESULTS: In 53% of the cases the mural thrombus was deposited on the anterior wall; from these, in 22%, the residual lumen described a predominantly right sided route; in 22%, a left sided route; on the mid line in 5%; and crossing over the mid line in 1%. In 23%, the deposition of thrombi was concentric. In 11% it occured on the posterior wall; from these, in 5%, the route of the residual anterior lumen was predominantly right sided; in 5%, left sided; and crossed over the mid line in 1%. In 13% complex morfological deposition patterns were found. CONCLUSION: Mural thrombi formation was predominantly found on the anterior wall of the aneurismatic mass, with the route of the residual lumen projecting towards the posterior wall.OBJETIVOS: Avaliar o local mais freqüente de deposição do trombo mural em aneurismas de aorta abdominal infrarenal, bem como o trajeto da luz residual. MÉTODOS: Avaliação de tomografias de 100 pacientes do HC-FMRP-USP apresentando aneurisma de aorta abdominal assintomático. RESULTADOS: O trombo mural se deposita na parede anterior em 53% dos casos, sendo que a luz residual posterior descreveu um trajeto predominantemente à direita em 22% dos casos, à esquerda em 22%, na linha mediana em 5% e cruzando da direita para a esquerda em 4%. 23% dos casos apresentaram deposição concêntrica do trombo e 11% apresentaram deposição na parede posterior, sendo o trajeto da luz residual anterior predominante a direita em 5% dos casos, a esquerda em 5% e cruzando a linha mediana em 1%. Padrões morfológicos complexos de deposição do trombo foram encontrados em 13% dos casos. CONCLUSÃO: A formação do trombo mural predominou na parede anterior da massa aneurismática, com o trajeto da luz residual se projetando para a parede posterior.FAEP

La calidad de vida de las madres de niños trabajadores en las calles de São Paulo, Brasil

The present study evaluated the perceived quality of life of the mothers of street children and investigated the association with their history of childhood violence, the occurrence of current domestic violence, their current mental states and that of their children, and family functioning. the applied instruments were as follows: Strengths and Difficulties Questionnaire, WorldSAFECore Questionnaire, Instrument for the Assessment of Quality of Life of the WHO, Global Assessment of Relational Functioning Scale, Childhood Trauma Questionnaire and a socio-demographic questionnaire. the sample of convenience consisted of 79 low-income mothers who raised their children alone, and most of whom had a positive screening for mental illness. the multiple regression analysis showed that the perception of quality of life of these women was associated with the presence of psychopathology either in themselves or their children and family dysfunction. Thus any program aimed at improving the quality of life of such mothers should consider addressing their mental problems as well as those of their children, besides offering educational and psychotherapeutic approaches to these families to improve the social environment.Universidade Federal de São Paulo, Dept Psiquiatria, BR-04038020 São Paulo, SP, BrazilUniv São Paulo, Inst Matemat & Estat, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psiquiatria, BR-04038020 São Paulo, SP, BrazilWeb of Scienc

ALTIMETRY ASSESSMENT OF ASTER GDEM v2 AND SRTM v3 DIGITAL ELEVATION MODELS: A CASE STUDY IN URBAN AREA OF BELO HORIZONTE, MG, BRAZIL

This work is an altimetry evaluation study involving Digital Elevation Models ASTER GDEM version 2 and SRTM version 3. Both models are readily available free of charge, however as they are built from different remote sensing methods it is also expected that they present different data qualities. LIDAR data with 25 cm vertical accuracy were used as reference for assessment validation. The evaluation study, carried out in urbanized area, investigated the distribution of the residuals and the relationship between the observed errors with land slopeclasses. Remote sensing principles, quantitative statistical methods and the Cartographic Accuracy Standard of Digital Mapping Products (PEC-PCD) were considered. The results indicated strong positive linear correlation and the existence of a functional relationship between the evaluated models and the reference model. Residuals between -4.36 m and 3.11 m grouped 47.7% of samples corresponding to ASTER GDEM and 63.7% of samples corresponding to SRTM. In both evaluated models, Root Mean Square Error values increased with increasing of land slope. Considering 1: 50,000 mapping scale the PEC-PCD classification indicated class B standard for SRTM and class C for ASTER GDEM. In all analyzes, SRTM presented smaller altimetry errors compared to ASTER GDEM, except in areas with steep relief

A relevância da pesquisa científica e produção acadêmica no ensino superior dos cursos de engenharia/ The relevance of scientific research and academic production in higher education engineering courses

O enfoque do presente artigo é a relevância de estudos científicos e pesquisas, assim como produções acadêmicas no ensino superior, mais precisamente nos cursos de engenharia. Debater essa questão educacional, tomando como referência o docente e a instituição de ensino superior, se torna necessária, uma vez que tal assunto é enxergado como indicador de qualidade na formação profissional. Em busca de atingir os objetivos propostos, foi realizada uma revisão bibliográfica sobre a pesquisa no meio acadêmico e seus desdobramentos. Além de definir conceitos relacionados à pesquisa, atrela sua prática ao estudo em sala de aula, e deixando clara a sua importância para o futuro profissional de engenharia. Por fim, é possível concluir que a pesquisa cientifica é uma prática que além de beneficiar a vida profissional do engenheiro, também agrega valores pessoais

Dietary macronutrient composition impacts gene regulation in adipose tissue

Diet is a key lifestyle component that influences metabolic health through several factors, including total energy intake and macronutrient composition. While the impact of caloric intake on gene expression and physiological phenomena in various tissues is well described, the influence of dietary macronutrient composition on these parameters is less well studied. Here, we use the Nutritional Geometry framework to investigate the role of macronutrient composition on metabolic function and gene regulation in adipose tissue. Using ten isocaloric diets that vary systematically in their proportion of energy from fat, protein, and carbohydrates, we find that gene expression and splicing are highly responsive to macronutrient composition, with distinct sets of genes regulated by different macronutrient interactions. Specifically, the expression of many genes associated with Bardet-Biedl syndrome is responsive to dietary fat content. Splicing and expression changes occur in largely separate gene sets, highlighting distinct mechanisms by which dietary composition influences the transcriptome and emphasizing the importance of considering splicing changes to more fully capture the gene regulation response to environmental changes such as diet. Our study provides insight into the gene regulation plasticity of adipose tissue in response to macronutrient composition, beyond the already well-characterized response to caloric intake