The Life Span Determinant p66Shc Localizes to Mitochondria Where It Associates with Mitochondrial Heat Shock Protein 70 and Regulates Trans-membrane Potential

P66Shc regulates life span in mammals and is a critical component of the apoptotic response to oxidative stress. It functions as a downstream target of the tumor suppressor p53 and is indispensable for the ability of oxidative stress-activated p53 to induce apoptosis. The molecular mechanisms underlying the apoptogenic effect of p66Shc are unknown. Here we report the following three findings. (i) The apoptosome can be properly activated in vitro in the absence of p66Shc only if purified cytochrome c is supplied. (ii) Cytochrome c release after oxidative signals is impaired in the absence of p66Shc. (iii) p66Shc induces the collapse of the mitochondrial trans-membrane potential after oxidative stress. Furthermore, we showed that a fraction of cytosolic p66Shc localizes within mitochondria where it forms a complex with mitochondrial Hsp70. Treatment of cells with ultraviolet radiation induced the dissociation of this complex and the release of monomeric p66Shc. We propose that p66Shc regulates the mitochondrial pathway of apoptosis by inducing mitochondrial damage after dissociation from an inhibitory protein complex. Genetic and biochemical evidence suggests that mitochondria regulate life span through their effects on the energetic metabolism (mitochondrial theory of aging). Our data suggest that mitochondrial regulation of apoptosis might also contribute to life span determination

Do lixo à reciclagem: Ressignificando saberes e fazeres

Nowadays, we live a development model focused in an exasperated individualism, consumerism, in waste, and social inequality. These situations have been demanding answers from society and public gestors, not only technical, but mainly, human. This paper presents the extensionists experience by academics of psychology at Centro Universitário Metodista – IPA in a solid waste triage unit, in Porto Alegre/RS, developed through informal insertion and the community group.Atualmente, vivemos um modelo de desenvolvimento focado no individualismo exacerbado, no consumismo, no desperdício e na desigualdade social. Essas situações têm exigido da sociedade e dos gestores públicos respostas não apenas técnicas, mas, principalmente, humanas. Este trabalho apresenta a experiência extensionista dos acadêmicos do curso de Psicologia do Centro Universitário Metodista - IPA em uma Unidade de Triagem de resíduos sólidos em Porto Alegre (RS), desenvolvida mediante inserções informais e do Grupo Comunitário

Do lixo à reciclagem: Ressignificando saberes e fazeres

Nowadays, we live a development model focused in an exasperated individualism, consumerism, in waste, and social inequality. These situations have been demanding answers from society and public gestors, not only technical, but mainly, human. This paper presents the extensionists experience by academics of psychology at Centro Universitário Metodista – IPA in a solid waste triage unit, in Porto Alegre/RS, developed through informal insertion and the community group.Atualmente, vivemos um modelo de desenvolvimento focado no individualismo exacerbado, no consumismo, no desperdício e na desigualdade social. Essas situações têm exigido da sociedade e dos gestores públicos respostas não apenas técnicas, mas, principalmente, humanas. Este trabalho apresenta a experiência extensionista dos acadêmicos do curso de Psicologia do Centro Universitário Metodista - IPA em uma Unidade de Triagem de resíduos sólidos em Porto Alegre (RS), desenvolvida mediante inserções informais e do Grupo Comunitário

A three-dimensional electronic report of the venous echo color-Doppler of the lower limbs: MEVeC®”

Background: The reports of ultrasound evaluation of lower limb veins are difficult to understand by general practitioners (GPs) and physicians who are not specialized. We developed software for a three-dimensional (3D) electronic report of venous hemodynamic mapping (MEVeC®) in order to represent lower limb venous vasculature in a 3D way. The aim of the study is to compare the novel 3D report with the standard report. Methods: Thirty subjects (medical students and GPs) evaluated a standard report and a novel 3D report of the lower limb veins of a prespecified patient. The cases were randomly and blindly taken from an archive of 100 cases. GPs and students answered a questionnaire made up of 13 questions that were structured in order to investigate the readability and comprehension of the two reports. A score ranging from 0 to 10 (0= not understandable; 10= full comprehension) was attributed to each report for each question according to the readability of the venous scheme proposed. Results: The scores from each question of the questionnaire were compared. The 3D report (MEVeC®) obtained higher scores than those from the evaluation of the standard report (P<0.0001). Each question revealed the superiority of the 3D report (MEVeC®) as compared with the standard report of the ultrasound evaluation of lower limbs. When dividing the scores according to percentiles, the 3D report (MEVeC®) still continued to show more readability than the standard report in a statistically significant way (P<0.0001). Conclusion: The new 3D report (MEVeC®) concerning ultrasound evaluation of lower limb veins is more reproducible than the standard report when evaluated by medical physicians not specialized in the evaluation of the vein tree of lower limbs

Biomarkers of Response to Low-Dose Aspirin in Familial Adenomatous Polyposis Patients

Background: The results of Aspirin prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP) are controversial. Methods: We conducted a biomarker-based clinical study in eight FAP patients treated with enteric-coated low-dose Aspirin (100 mg daily for three months) to explore whether the drug targets mainly platelet cyclooxygenase (COX)-1 or affects extraplatelet cellular sources expressing COX-isozymes and/or off-target effects in colorectal adenomas. Results: In FAP patients, low-dose Aspirin-acetylated platelet COX-1 at Serine529 (>70%) was associated with an almost complete inhibition of platelet thromboxane (TX) B2 generation ex vivo (serum TXB2). However, enhanced residual urinary 11-dehydro-TXB2 and urinary PGEM, primary metabolites of TXA2 and prostaglandin (PG)E2, respectively, were detected in association with incomplete acetylation of COX-1 in normal colorectal biopsies and adenomas. Proteomics of adenomas showed that Aspirin significantly modulated only eight proteins. The upregulation of vimentin and downregulation of HBB (hemoglobin subunit beta) distinguished two groups with high vs. low residual 11-dehydro-TXB2 levels, possibly identifying the nonresponders and responders to Aspirin. Conclusions: Although low-dose Aspirin appropriately inhibited the platelet, persistently high systemic TXA2 and PGE2 biosynthesis were found, plausibly for a marginal inhibitory effect on prostanoid biosynthesis in the colorectum. Novel chemotherapeutic strategies in FAP can involve blocking the effects of TXA2 and PGE2 signaling with receptor antagonists