Identification of a Gene Regulatory Network Necessary for the Initiation of Oligodendrocyte Differentiation

Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes requires extensive changes in gene expression, which are partly mediated by post-translational modifications of nucleosomal histones. An essential modification for oligodendrocyte differentiation is the removal of acetyl groups from lysine residues which is catalyzed by histone deacetylases (HDACs). The transcriptional targets of HDAC activity within OPCs however, have remained elusive and have been identified in this study by interrogating the oligodendrocyte transcriptome. Using a novel algorithm that allows clustering of gene transcripts according to expression kinetics and expression levels, we defined major waves of co-regulated genes. The initial overall decrease in gene expression was followed by the up-regulation of genes involved in lipid metabolism and myelination. Functional annotation of the down-regulated gene clusters identified transcripts involved in cell cycle regulation, transcription, and RNA processing. To define whether these genes were the targets of HDAC activity, we cultured rat OPCs in the presence of trichostatin A (TSA), an HDAC inhibitor previously shown to inhibit oligodendrocyte differentiation. By overlaying the defined oligodendrocyte transcriptome with the list of ‘TSA sensitive’ genes, we determined that a high percentage of ‘TSA sensitive’ genes are part of a normal program of oligodendrocyte differentiation. TSA treatment increased the expression of genes whose down-regulation occurs very early after induction of OPC differentiation, but did not affect the expression of genes with a slower kinetic. Among the increased ‘TSA sensitive’ genes we detected several transcription factors including Id2, Egr1, and Sox11, whose down-regulation is critical for OPC differentiation. Thus, HDAC target genes include clusters of co-regulated genes involved in transcriptional repression. These results support a de-repression model of oligodendrocyte lineage progression that relies on the concurrent down-regulation of several inhibitors of differentiation

Somatic cell type specific gene transfer reveals a tumor-promoting function for p21Waf1/Cip1

How proteins participate in tumorigenesis can be obscured by their multifunctional nature. For example, depending on the cellular context, the cdk inhibitors can affect cell proliferation, cell motility, apoptosis, receptor tyrosine kinase signaling, and transcription. Thus, to determine how a protein contributes to tumorigenesis, we need to evaluate which functions are required in the developing tumor. Here we demonstrate that the RCAS/TvA system, originally developed to introduce oncogenes into somatic cells of mice, can be adapted to allow us to define the contribution that different functional domains make to tumor development. Studying the development of growth-factor-induced oligodendroglioma, we identified a critical role for the Cy elements in p21, and we showed that cyclin D1T286A, which accumulates in the nucleus of p21-deficient cells and binds to cdk4, could bypass the requirement for p21 during tumor development. These genetic results suggest that p21 acts through the cyclin D1–cdk4 complex to support tumor growth, and establish the utility of using a somatic cell modeling system for defining the contribution proteins make to tumor development

Immunotherapy in geriatric surgery [L'IMMUNOTERAPIA NEL PAZIENTE CHIRURGICO ANZIANO]

After some important comments regarding the physiopathology of the immune system in elderly patients, the Authors focus on the possibilities currently made available by the studies on therapeutic procedures (TPN) and substances which influence the defence mechanisms in high risk geriatric surgery. Owing to the preliminary nature of studies and the initial stage of research on immunotherapy, the subjects requires further clinical verification and more extensive research. It is certain, however, that the subject is of considerable interest due to its potential future clinical applications

Original method of the treatment of achalasic megaesophagus with EEA stapler [Originale metodica di trattamento del megaesofago acalasico con EEA stapler]

Esophageal sutures require the same general criteria applied for the realization of an intestinal suture. The lack of a serous membrane and the particular vascularization of the organ, though, make this portion of the gastroenteric tract very prone to serious complications. Undoubtedly, the introduction of new systems of suture renders easier, faster and more efficacious the work of the surgeon. In particular, the Authors stress the advantages that staplers can offer for the treatment of achalasic megaesophagus

Lymphatic laser-microsurgery: Experimental research and original clinical applications

The authors report their experimental studies and clinical observations regarding the use of CO2 laser in lymphatic microsurgery. The effects and advantages brought about by CO2 laser in their experimental studies on rats in performing lymphatic micro-anastomoses are particularly pointed out. g clinical observations of lympho-chyledema of lower limbs and genitalia, associated to chylous ascitis, are reported. Clinical outcome proved the remarkable advantages obtained by using laser ray welding power to cut and close insufficient and dilated lymphatic and chylous collectors. In over 3 year clinical follow-up no relapse of the pathology occurred in any patient