P66Shc signals to age

Oxygen metabolism is thought to impact on aging through the formation of reactive oxygen species (ROS) that are supposed to damage biological molecules. The study of p66Shc, a crucial regulator of ROS level involved in aging dysfunction, suggests that the incidence of degenerative disease and longevity are determined by a specific signaling function of ROS other than their unspecific damaging property

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

Os retratos de Maria Isabel e Maria Francisca de Bragança, de Nicolas-Antoine Taunay

Nicolas-Antoine Taunay, French landscape painter, produced also several portraits during his stay at the Rio de Janeiro Court. In this city, in 1816, he paints the queen Carlota Joaquina and all her daughters. In this group, two portraits have a very special way: the paintings still today catalogued as Maria Francisca and Maria Teresa, but probably being Maria Isabel and Maria Francisca de Assis - princesses that, in this year, left Brazil to marry the Spanish King Fernando VII, and his brother Carlos Maria Isidro de Bourbon. In this article, beyond to describe these portraits (and analyse the identities of the portrayed princesses), I analyse their functions in the Court society and the mains artists of this gender in Europe. I will discuss, as well, the hypothesis about the Taunay choices. In this sense, I will analyse the possible circulation of the typologies of portrait between Italy, Portugal, Spain and France, understanding these productions by Taunay and the functions occupied by these portraits in the political relations between Brazil and Europe.Nicolas-Antoine Taunay, pintor de paisagens francês, também realizou alguns retratos durante sua estadia na corte do Rio de Janeiro. Nessa cidade, em 1816, ele pinta a rainha Carlota Joaquina e todas as suas filhas. Nesse conjunto, dois retratos sobressaem-se de modo especial: os hoje ainda inventariados como de Maria Francisca e de Maria Teresa, mas que provavelmente são o de Maria Isabel e o de Maria Francisca de Assis - princesas que, nesse ano, deixavam o Brasil para casar-se, respectivamente, com Fernando VII, o rei espanhol, e com seu irmão Carlos Isidro de Bourbon. Neste artigo, além de descrevermos os retratos (e analisarmos a questão da identidade das princesas retratadas), abordamos suas funções na sociedade das cortes e os principais artistas do gênero na Europa. Discutimos, também, as hipóteses que permeiam as escolhas de Taunay para sua execução. Nesse sentido, tratamos da possível circulação de tipologias entre Itália, Portugal, Espanha e França, buscando entender a forma como Taunay os realizou e as funções que doravante tais retratos ocupariam nas relações entre o Brasil e a Europa.Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Beyond Genetics: Metastasis as an Adaptive Response in Breast Cancer

Metastatic disease represents the primary cause of breast cancer (BC) mortality, yet it is still one of the most enigmatic processes in the biology of this tumor. Metastatic progression includes distinct phases: invasion, intravasation, hematogenous dissemination, extravasation and seeding at distant sites, micro-metastasis formation and metastatic outgrowth. Whole-genome sequencing analyses of primary BC and metastases revealed that BC metastatization is a non-genetically selected trait, rather the result of transcriptional and metabolic adaptation to the unfavorable microenvironmental conditions which cancer cells are exposed to (e.g., hypoxia, low nutrients, endoplasmic reticulum stress and chemotherapy administration). In this regard, the latest multi-omics analyses unveiled intra-tumor phenotypic heterogeneity, which determines the polyclonal nature of breast tumors and constitutes a challenge for clinicians, correlating with patient poor prognosis. The present work reviews BC classification and epidemiology, focusing on the impact of metastatic disease on patient prognosis and survival, while describing general principles and current in vitro/in vivo models of the BC metastatic cascade. The authors address here both genetic and phenotypic intrinsic heterogeneity of breast tumors, reporting the latest studies that support the role of the latter in metastatic spreading. Finally, the review illustrates the mechanisms underlying adaptive stress responses during BC metastatic progression

Isolation and mapping of EVX1, a human homeobox gene homologous to even-skipped, localized at the 5¢ end of HOX1 locus on chromosome 7

ABSTRACT (7, 8) . It is now well established that genes containing homeobox sequences encode nuclear proteins with regulatory functions i