VEGFR2 Translocates to the Nucleus to Regulate Its Own Transcription

Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) is the major mediator of the angiogenic effects of VEGF. In addition to its well known role as a membrane receptor that activates multiple signaling pathways, VEGFR2 also has a nuclear localization. However, what VEGFR2 does in the nucleus is still unknown. In the present report we show that, in endothelial cells, nuclear VEGFR2 interacts with several nuclear proteins, including the Sp1, a transcription factor that has been implicated in the regulation of genes needed for angiogenesis. By in vivo chromatin immunoprecipitation (ChIP) assays, we found that VEGFR2 binds to the Sp1-responsive region of the VEGFR2 proximal promoter. These results were confirmed by EMSA assays, using the same region of the VEGFR2 promoter. Importantly, we show that the VEGFR2 DNA binding is directly linked to the transcriptional activation of the VEGFR2 promoter. By reporter assays, we found that the region between -300/-116 relative to the transcription start site is essential to confer VEGFR2-dependent transcriptional activity. It was previously described that nuclear translocation of the VEGFR2 is dependent on its activation by VEGF. In agreement, we observed that the binding of VEGFR2 to DNA requires VEGF activation, being blocked by Bevacizumab and Sunitinib, two anti-angiogenic agents that inhibit VEGFR2 activation. Our findings demonstrate a new mechanism by which VEGFR2 activates its own promoter that could be involved in amplifying the angiogenic response

Genetic polymorphisms at the leptin receptor gene in three beef cattle breeds

The genetic diversity of a single nucleotide polymorphism (SNP) at the exon 20 (T945M) of the leptin receptor gene (LEPR) and of three short tandem repeats (STRs BM7225, BMS694, and BMS2145) linked to LEPR was investigated in three beef cattle herds (Brangus Ibagé, Charolais, and Aberdeen Angus). A cheap and effective new method to analyze the T945M polymorphism in cattle populations was developed and the possible role of these polymorphisms in reproduction and weight gain of postpartum cows was evaluated. High levels of genetic diversity were observed with the average heterozygosity of STRs ranging from 0.71 to 0.81. No significant association was detected between LEPR markers and reproductive parameters or daily weight gain. These negative results suggest that the LEPR gene polymorphisms, at least those herein described, do not influence postpartum cows production

Suplementação de novilhos nelore em pastejo de Brachiaria brizantha com diferentes níveis e fontes de concentrado Supplementation of Nellore grazing steers with different sources and concentrate levels

O objetivo deste trabalho foi avaliar o ganho médio diário (GMD) de novilhos em pastejo de B.brizantha cv. Marandu, suplementados com três tipos de suplementos, no período de julho a dezembro, em dois níveis de fornecimento. Foram utilizados 54 novilhos Nelore (nove por tratamento) com idade aproximada de 20 meses e peso vivo inicial de 370 kg. Os suplementos utilizados foram: suplemento rico em amido (AMI), rico em óleo (OLE) e suplemento composto de amido+óleo (A+O). Os suplementos foram fornecidos em níveis de 0,7 e 1,4% do peso vivo. A disponibilidade de lâminas verdes do capim-braquiária foi de 5,12 kg de MS/100 kg de PV. Os suplementos e níveis influenciaram o ganho médio diário (GMD). Nos dois níveis de fornecimento, o suplemento A+O promoveu o melhor desempenho. No menor nível de fornecimento (0,7% PV), os suplementos com AMI e OLE não diferiram entre si, mas ambos diferiram do suplemento A+O. Para este nível de fornecimento, o GMD foi 0,46; 0,44 e 0,57 kg para os tratamentos AMI, OLE e A+O, respectivamente. Resultados semelhantes foram observados no nível de fornecimento de 1,4% do PV. Neste caso, o suplemento A+O foi superior ao AMI e OLE, que não diferiram entre si. O GMD foi 0,58 kg para AMI, 0,61 kg para OLE e 0,72 kg para A+O. A suplementação com concentrados compostos pela mistura de alimentos ricos em amido (milho) e óleo (caroço de algodão) proporcionou melhor desempenho dos animais em comparação aos suplementados separadamente com as respectivas fontes, independentemente do nível de suplementação. O maior nível de suplementação (1,4% do PV) apresentou eficiência econômica inferior, quando comparada à do menor nível (0,7% do PV).<br>This work was carried out to study the daily average gain (DAG) of steers grazing Brachiaria brizantha cv. Marandu, supplemented, from July to December, with two levels of three different supplements. Fifty-four Nellore steers (9 for each treatment) aged approximately 20 months and initial average live weight of 370 kg were used. The experimental treatments were: AMI - supplement rich in starch (based on corn), OLE - supplement rich in fat (based on whole cottonseed) and A+O - supplement combination (based on mixture of AMI and OLE). All supplements were offered in .7 and 1.4% of liveweight (LW). The green blade availability was 5.12 kg DM/100 kg LW. Treatments and levels influenced DAG. In both levels of supplementation, the combination of feeds promoted higher performance. The lowest level (.7% LW) AMI and OLE was not different, and both were different from A+O. DAG was .44, .46, and .57 kg for AMI, OLE and A+O respectively. Similar results were registered on the higher level (1.4% LW) of supplementation. In this level A+O showed better performance than AMI and OLE that was not different. DAG was .58 kg for AMI, .61 kg for OLE and .72 kg for A+O. The supplementation with concentrates composed by the mixture of rich feeds in starch (corn) and oil (cotton seed) provided higher performance of the animals, that when supplemented separately with the respective sources, independently of the supplementation level. The higher supplementation level (1.4% of LW) showed lower economical efficiency, when compared to the smallest level (.7% PV)