University of Coimbra

About: University of Coimbra is a education organization based out in Coimbra, Portugal. It is known for research contribution in the topics: Population & Context (language use). The organization has 14318 authors who have published 43067 publications receiving 994733 citations. The organization is also known as: UC & Universidade dos Estudos Gerais.

Chd1 regulates open chromatin and pluripotency of embryonic stem cells

Abstract: An open chromatin largely devoid of heterochromatin is a hallmark of stem cells. It remains unknown whether an open chromatin is necessary for the differentiation potential of stem cells, and which molecules are needed to maintain open chromatin. Here we show that the chromatin remodelling factor Chd1 is required to maintain the open chromatin of pluripotent mouse embryonic stem cells. Chd1 is a euchromatin protein that associates with the promoters of active genes, and downregulation of Chd1 leads to accumulation of heterochromatin. Chd1-deficient embryonic stem cells are no longer pluripotent, because they are incapable of giving rise to primitive endoderm and have a high propensity for neural differentiation. Furthermore, Chd1 is required for efficient reprogramming of fibroblasts to the pluripotent stem cell state. Our results indicate that Chd1 is essential for open chromatin and pluripotency of embryonic stem cells, and for somatic cell reprogramming to the pluripotent state.

Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways.

Abstract: Neurotrophins protect neurons against glutamate excitotoxicity, but the signaling mechanisms have not been fully elucidated. We studied the role of the phosphatidylinositol 3-kinase (PI3-K) and Ras/mitogen-activated protein kinase (MAPK) pathways in the protection of cultured hippocampal neurons from glutamate induced apoptotic cell death, characterized by nuclear condensation and activation of caspase-3-like enzymes. Pre-incubation with the neurotrophin brain-derived neurotrophic factor (BDNF), for 24 h, reduced glutamate-evoked apoptotic morphology and caspase-3-like activity, and transiently increased the activity of the PI3-K and of the Ras/MAPK pathways. Inhibition of the PI3-K and of the Ras/MAPK signaling pathways abrogated the protective effect of BDNF against glutamate-induced neuronal death and similar effects were observed upon inhibition of protein synthesis. Moreover, incubation of hippocampal neurons with BDNF, for 24 h, increased Bcl-2 protein levels. The results indicate that the protective effect of BDNF in hippocampal neurons against glutamate toxicity is mediated by the PI3-K and the Ras/MAPK signaling pathways, and involves a longterm change in protein synthesis.

Excited-state proton transfer reactions I. Fundamentals and intermolecular reactions

Abstract: Theoretical models that have been proposed and applied to proton transfer reactions are reviewed in this work. Simple models, like the Eigen model, Marcus theory and the intersecting state model, are applied to excited-state intermolecular proton transfers. The kinetics and thermodynamics of proton transfers occuring in the singlet states of aromatic molecules with OH, NH3+, NH2 and CO substituents are reviewed.

New insights on the anticancer properties of dietary polyphenols.

Abstract: Cancer, one of the major causes of death across the world, has shown to be a largely preventable disease, highly susceptible to modulation by dietary factors. Phenolic compounds, abundant in vegetables and fruits ubiquitous in diet, were described to play an important role as chemopreventive agents. Since conventional therapeutic and surgical approaches have not been able to control the incidence of most cancer types, the development of chemopreventive strategies is an urgent priority in public health. The current diet phenolic intake is often insufficient to protect from mutagens (either exogenous or endogenous), which leads to the need for dietary supplementation as an alternative approach. Research efforts are placing increasing emphasis on identifying the biological mechanisms and in particular the signal transduction pathways related to the chemopreventive activities of these compounds. These effects are believed to occur by the regulation of signaling pathways such as nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) or mitogen-activated protein kinases (MAPK). Dietary polyphenols can exert their effects on these pathways separately or sequentially and in addition the occurrence of crosstalk between these pathways cannot be overlooked. By modulating cell signaling pathways, polyphenols activate cell death signals and induce apoptosis in precancerous or malignant cells resulting in the inhibition of cancer development or progression. However, regulation of cell signaling pathways by dietary polyphenols can also lead to cell proliferation/survival or inflammatory responses due to increased expression of several genes. The present review summarizes the most recent advances providing new insights into the molecular mechanisms underlying the promising anticarcinogenic activity of dietary polyphenols.