Non-Coding RNA and Tumor Development in Neurofibromatosis Type 1: ANRIL Rs2151280 Is Associated with Optic Glioma Development and a Mild Phenotype in Neurofibromatosis Type 1 Patients

Non-coding RNAs (ncRNAs) are known to regulate gene expression at the transcriptional and post-transcriptional levels, chromatin remodeling, and signal transduction. The identification of different species of ncRNAs, microRNAs (miRNAs), circular RNAs (circRNAs), and long ncRNAs (lncRNAs)-and in some cases, their combined regulatory function on specific target genes-may help to elucidate their role in biological processes. NcRNAs' deregulation has an impact on the impairment of physiological programs, driving cells in cancer development. We here carried out a review of literature concerning the implication of ncRNAs on tumor development in neurofibromatosis type 1 (NF1), an inherited tumor predisposition syndrome. A number of miRNAs and a lncRNA has been implicated in NF1-associated tumors, such as malignant peripheral nerve sheath tumors (MPNSTs) and astrocytoma, as well as in the pathognomonic neurofibromas. Some authors reported that the lncRNA ANRIL was deregulated in the blood of NF1 patients with plexiform neurofibromas (PNFs), even if its role should be further elucidated. We here provided original data concerning the association of a specific genotype about ANRIL rs2151280 with the presence of optic gliomas and a mild expression of the NF1 phenotype. We also detected the LOH of ANRIL in different tumors from NF1 patients, supporting the involvement of ANRIL in some NF1-associated tumors. Our results suggest that ANRIL rs2151280 may be a potential diagnostic and prognostic marker, addressing early diagnosis of optic glioma and predicting the phenotype severity in NF1 patients

Abnormal DNA Methylation Induced by Hyperglycemia Reduces CXCR 4 Gene Expression in CD 34+ Stem Cells

Background CD 34+ stem/progenitor cells are involved in vascular homeostasis and in neovascularization of ischemic tissues. The number of circulating CD 34+ stem cells is a predictive biomarker of adverse cardiovascular outcomes in diabetic patients. Here, we provide evidence that hyperglycemia can be "memorized" by the stem cells through epigenetic changes that contribute to onset and maintenance of their dysfunction in diabetes mellitus. Methods and Results Cord-blood-derived CD 34+ stem cells exposed to high glucose displayed increased reactive oxygen species production, overexpression of p66shc gene, and downregulation of antioxidant genes catalase and manganese superoxide dismutase when compared with normoglycemic cells. This altered oxidative state was associated with impaired migration ability toward stromal-cell-derived factor 1 alpha and reduced protein and mRNA expression of the C-X-C chemokine receptor type 4 ( CXCR 4) receptor. The methylation analysis by bisulfite Sanger sequencing of the CXCR 4 promoter revealed a significant increase in DNA methylation density in high-glucose CD 34+ stem cells that negatively correlated with mRNA expression (Pearson r=-0.76; P=0.004). Consistently, we found, by chromatin immunoprecipitation assay, a more transcriptionally inactive chromatin conformation and reduced RNA polymerase II engagement on the CXCR 4 promoter. Notably, alteration of CXCR 4 DNA methylation, as well as transcriptional and functional defects, persisted in high-glucose CD 34+ stem cells despite recovery in normoglycemic conditions. Importantly, such an epigenetic modification was thoroughly confirmed in bone marrow CD 34+ stem cells isolated from sternal biopsies of diabetic patients undergoing coronary bypass surgery. Conclusions CD 34+ stem cells "memorize" the hyperglycemic environment in the form of epigenetic modifications that collude to alter CXCR 4 receptor expression and migration

Território e territorialidade no contexto hospitalar: uma abordagem interdisciplinar

Este artigo trata o hospital como território de organização complexa, atravessado por múltiplos interesses, que ocupa lugar crítico na prestação de serviços de saúde, lugar de construção de identidades profissionais, com grande reconhecimento social. O objetivo diz respeito a compreender o hospital na perspectiva interdisciplinar. Para tanto, buscou-se o referencial teórico referente às concepções de território e territorialidade, oriundas da geografia e de outros campos do conhecimento, como a ciência da saúde e a filosofia. A partir da interação entre estas disciplinas aborda-se o hospital como território de produção de atos de saúde formado por segmentos e superfícies, agenciamentos entre profissionais e usuários que se entrecortam em um emaranhado de linhas de segmentaridade; nós, redes e malhas que revelam a produção territorial; poder e disciplinamento e o saber-poder que revelam as relações sociais, efetivadas entre os sujeitos e o objeto, ou seja, as relações que se concretizam no território e significam territorialidade. Concluiu-se, então, que o território hospitalar, como os demais territórios, é a expressão concreta e abstrata do espaço apropriado, produzido, formado em sua multidimensionalidade, pelos atores sociais que o (re)definem constantemente em suas cotidianidades, num campo de forças relacionalmente emaranhado por poderes nas mais variadas intensidades

An optimization approach to the planning of Earth observing satellites

We describe a complex optimization problem related to the observation of the Earth surface through a constellation of agile satellites of the most recent generation equipped with Synthetic Aperture Radar instruments. We consider a model more detailed than those presented so far in the literature and we present some algorithms we have tested

An optimization approach to the planning of earth observing satellites

We describe a complex optimization problem related to the observation of the Earth surface through a constellation of agile satellites of the most recent generation equipped with Synthetic Aperture Radar instruments. We consider a model more detailed than those presented so far in the literature and we present some algorithms we have tested

Heuristic solution of a large-scale planning and scheduling problem for a constellation of earth observing satellites

We describe a complex optimization problem related to the observation of the Earth surface through a constellation of agile satellites of the most recent generation equipped with Synthetic Aperture Radar instruments. We consider a model more detailed than those presented so far in the literature and we present some fast heuristic algorithms

Methylation profiling by bisulfite sequencing analysis of the mtDNA Non-Coding Region in replicative and senescent Endothelial Cells

The regulation and function of Mitochondrial DNA (mtDNA) cytosine methylation (5mC) are largely unexplored. Mitochondria, Endothelial Cell (EC) senescence, and cardiovascular dysfunction are closely related. We extensively investigated the mtDNA Non-Coding Region (NCR) methylation pattern and its variations in EC replicative senescence. We observed previously undescribed 5mC clusters and a biased distribution of 5mC among DNA sites and throughout the NCR. The methylation pattern in senescent EC showed non-random variations, including the hypo-methylation of mtDNA replication regulatory sites. Additional experiments opened to a possible role for 5mC in D-loop formation, rather than in mitochondrial gene expression