Adiponectin Prevents Diabetic Premature Senescence of Endothelial Progenitor Cells and Promotes Endothelial Repair by Suppressing the p38 MAP Kinase/p16INK4A Signaling Pathway

OBJECTIVE - A reduced number of circulating endothelial progenitor cells (EPCs) are casually associated with the cardiovascular complication of diabetes. Adiponectin exerts multiple protective effects against cardiovascular disease, independent of its insulin-sensitizing activity. The objective of this study was to investigate whether adiponectin plays a role in modulating the bioavailability of circulating EPCs and endothelial repair. RESEARCH DESIGN AND METHODS - Adiponectin knockout mice were crossed with db+/- mice to produce db/db diabetic mice without adiponectin. Circulating number of EPCs were analyzed by flow cytometry. Reendothelialization was evaluated by staining with Evans blue after wire-induced carotid injury. RESULTS - In adiponectin knockout mice, the number of circulating EPCs decreased in an age-dependent manner compared with the wild-type controls, and this difference was reversed by the chronic infusion of recombinant adiponectin. In db/db diabetic mice, the lack of adiponectin aggravated the hyperglycemia-induced decrease in circulating EPCs and also diminished the stimulatory effects of the PPARγ agonist rosiglitazone on EPC production and reendothelialization. In EPCs isolated from both human peripheral blood and mouse bone marrow, treatment with adiponectin prevented high glucose-induced premature senescence. At the molecular level, adiponectin decreased high glucose-induced accumulation of intracellular reactive oxygen species and consequently suppressed activation of p38 MAP kinase (MAPK) and expression of the senescence marker p16INK4A. CONCLUSIONS - Adiponectin prevents EPC senescence by inhibiting the ROS/p38 MAPK/p16 INK4A signaling cascade. The protective effects of adiponectin against diabetes vascular complications are attributed in part to its ability to counteract hyperglycemia-mediated decrease in the number of circulating EPCs. © 2010 by the American Diabetes Association.published_or_final_versio

Diversidade e Estrutura Genéticas de Bryconamericus aff. Iheringii (Characiformes: Characidae) na Área de Influência do Reservatório da Itaipu

Trabalho de Conclusão de Curso apresentado ao Instituto Latino-Americano de Ciências da Vida e Natureza da Universidade Federal da Integração Latino-Americana, como requisito parcial à obtenção do título de Bacharel em Ciências Biológicas – Ecologia e Biodiversidade.A diversidade genética é necessária para que as populações evoluam e se adaptem às mudanças ambientais, e comumente, está distribuída em um padrão dentro e entre populações que é referido como estrutura genética. O isolamento e a existência de poucos caminhos migratórios entre águas doces implicam na estruturação genética, principalmente, para peixes que possuem baixa mobilidade. Peixes de pequeno porte (≤ 15 cm de comprimento), que habitam riachos, representam, no mínimo 50% de toda a ictiofauna sul-americana e apresentam um alto grau de endemismo, devido, em parte, à sua baixa capacidade de deslocamento. Neste contexto, o presente trabalho objetivou avaliar a diversidade e a estrutura genéticas do caracídeo Bryconamericus aff. iheringii na área de influência do reservatório da Itaipu Binacional. Para isto, foram analisados 47 espécimes, 23 coletados em riachos da margem direita (Paraguai) e 24 coletados em riachos da margem esquerda (Brasil) do reservatório da Itaipu. Para acessar sua diversidade genética, foi empregado o marcador molecular D-loop, sendo estimado o número de haplótipos, os índices de diversidade haplotípica e nucleotídica e o nível de estruturação entre as diferentes amostras. B. aff. iheringii apresentou níveis de diversidade genética dentro do padrão relatado para a espécie, com moderados (amostras do Paraguai) a altos (amostras do Brasil) níveis de diversidade, o que se deve, sobretudo, ao fato de que quase todos os riachos paraguaios analisados são de uma única microbacia, enquanto os riachos brasileiros são de quatro microbacias diferentes. As populações não parecem ter respondido a eventos drásticos recentes, pois mesmo as presentes em regiões sob a pressão de atividades agrícolas, mostram variações no DNA mitocondrial. Foram encontrados altos níveis de estruturação genética entre o conjunto de amostras paraguaio e brasileiro e entre as microbacias dentro de cada país, o que se deve, principalmente, aos processos de colonização destas drenagens, os quais possivelmente envolvem fundadores com diferentes linhagens haplotípicas. Além disso, parece plausível que o rio Paraná (reservatório da Itaipu) funciona como uma barreira ao fluxo gênico entre as diferentes margens e entre suas microbacias. Deste modo, a identificação de linhagens é de grande importância, pois a manutenção da diversidade genética de uma espécie depende de sua preservação. Considerando a importância de estudos genético-populacionais para a conservação de espécies, espera-se que este trabalho possa servir como base para futuros estudos mais amplos com peixes de riachos

Restoring the imaging quality of circular transducer array-based PACT using synthetic aperture focusing technique integrated with 2nd-derivative-based back projection scheme

Circular-array-based photoacoustic computed tomography (CA-PACT) is a promising imaging tool owing to its broad acoustic detection coverage and fidelity. However, CA-PACT suffers from poor image quality outside the focal zone along both elevational and lateral dimensions. To address this challenge, we proposed a novel reconstruction strategy by integrating the synthetic aperture focusing technique (SAFT) with the 2nd derivative-based back projection (2nd D-BP) algorithm to restore the image quality outside the focal zone along both the elevational and lateral axes. The proposed solution is a two-phase reconstruction scheme. In the first phase, with the assistance of an acoustic lens, we designed a circular array-based SAFT algorithm to restore the resolution and SNR along the elevational axis. The acoustic lens pushes the boundary of the upper limit of the SAFT scheme to achieve enhanced elevational resolution. In the second phase, we proposed a 2nd D-BP scheme to improve the lateral resolution and suppress noises in 3D imaging results. The 2nd D-BP strategy enhances the image quality along the lateral dimension by up-converting the high spatial frequencies of the object’s absorption pattern. We validated the effectiveness of the proposed strategy using both phantoms and in vivo human experiments. The experimental results demonstrated superior image quality (7-fold enhancement in elevational resolution, 3-fold enhancement in lateral resolution, and an 11-dB increase in SNR). This strategy provides a new paradigm in the PACT system as it significantly enhances the spatial resolution and imaging contrast in both the elevational and lateral dimensions while maintaining a large focal zone

Cancer gene mutations in congenital pulmonary airway malformation patients

Background Newborns affected with congenital pulmonary airway malformations (CPAMs) may present with severe respiratory distress or remain asymptomatic. While surgical resection is the definitive treatment for symptomatic CPAMs, prophylactic elective surgery may be recommended for asymptomatic CPAMs owing to the risk of tumour development. However, the implementation of prophylactic surgery is quite controversial on the grounds that more evidence linking CPAMs and cancer is needed. The large gap in knowledge of CPAM pathogenesis results in uncertainties and controversies in disease management. As developmental genes control postnatal cell growth and contribute to cancer development, we hypothesised that CPAMs may be underlain by germline mutations in genes governing airways development. Methods Sequencing of the exome of 19 patients and their unaffected parents. Results A more than expected number of mutations in cancer genes (false discovery rate q-value <5.01×10−5) was observed. The co-occurrence, in the same patient, of damaging variants in genes encoding interacting proteins is intriguing, the most striking being thyroglobulin (TG) and its receptor, megalin (LRP2). Both genes are highly relevant in lung development and cancer. Conclusions The overall excess of mutations in cancer genes may account for the reported association of CPAMs with carcinomas and provide some evidence to argue for prophylactic surgery by some surgeons

Congenital lung malformations

Congenital lung malformations (CLMs) are rare developmental anomalies of the lung, including congenital pulmonary airway malformations (CPAM), bronchopulmonary sequestration, congenital lobar overinflation, bronchogenic cyst and isolated congenital bronchial atresia. CLMs occur in 4 out of 10,000 live births. Postnatal presentation ranges from an asymptomatic infant to respiratory failure. CLMs are typically diagnosed with antenatal ultrasonography and confirmed by chest CT angiography in the first few months of life. Although surgical treatment is the gold standard for symptomatic CLMs, a consensus on asymptomatic cases has not been reached. Resection, either thoracoscopically or through thoracotomy, minimizes the risk of local morbidity, including recurrent infections and pneumothorax, and avoids the risk of malignancies that have been associated with CPAM, bronchopulmonary sequestration and bronchogenic cyst. However, some surgeons suggest expectant management as the incidence of adverse outcomes, including malignancy, remains unknown. In either case, a planned follow-up and a proper transition to adult care are needed. The biological mechanisms through which some CLMs may trigger malignant transformation are under investigation. KRAS has already been confirmed to be somatically mutated in CPAM and other genetic susceptibilities linked to tumour development have been explored. By summarizing current progress in CLM diagnosis, management and molecular understanding we hope to highlight open questions that require urgent attention.</p