Sapienza University of Rome

About: Sapienza University of Rome is a education organization based out in Rome, Lazio, Italy. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 62002 authors who have published 155468 publications receiving 4397244 citations. The organization is also known as: La Sapienza & Università La Sapienza di Roma.

Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle: Implications for myocardium regeneration

Abstract: The concept of tissue-restricted differentiation of postnatal stem cells has been challenged by recent evidence showing pluripotency for hematopoietic, mesenchymal, and neural stem cells. Furthermore, rare but well documented examples exist of already differentiated cells in developing mammals that change fate and trans-differentiate into another cell type. Here, we report that endothelial cells, either freshly isolated from embryonic vessels or established as homogenous cells in culture, differentiate into beating cardiomyocytes and express cardiac markers when cocultured with neonatal rat cardiomyocytes or when injected into postischemic adult mouse heart. Human umbilical vein endothelial cells also differentiate into cardiomyocytes under similar experimental conditions and transiently coexpress von Willebrand factor and sarcomeric myosin. In contrast, neural stem cells, which efficiently differentiate into skeletal muscle, differentiate into cardiomyocytes at a low rate. Fibroblast growth factor 2 and bone morphogenetic protein 4, which activate cardiac differentiation in embryonic cells, do not activate cardiogenesis in endothelial cells or stimulate trans-differentiation in coculture, suggesting that different signaling molecules are responsible for cardiac induction during embryogenesis and in successive periods of development. The fact that endothelial cells can generate cardiomyocytes sheds additional light on the plasticity of endothelial cells during development and opens perspectives for cell autologous replacement therapies.

Planck intermediate results: XLVI. Reduction of large-scale systematic effects in HFI polarization maps and estimation of the reionization optical depth

Abstract: This paper describes the identification, modelling, and removal of previously unexplained systematic effects in the polarization data of the Planck High Frequency Instrument (HFI) on large angular scales, including new mapmaking and calibration procedures, new and more complete end-to-end simulations, and a set of robust internal consistency checks on the resulting maps These maps, at 100, 143, 217, and 353 GHz, are early versions of those that will be released in final form later in 2016 The improvements allow us to determine the cosmic reionization optical depth τ using, for the first time, the low-multipole EE data from HFI, reducing significantly the central value and uncertainty, and hence the upper limit Two different likelihood procedures are used to constrain τ from two estimators of the CMB E- and B-mode angular power spectra at 100 and 143 GHz, after debiasing the spectra from a small remaining systematic contamination These all give fully consistent results A further consistency test is performed using cross-correlations derived from the Low Frequency Instrument maps of the Planck 2015 data release and the new HFI data For this purpose, end-to-end analyses of systematic effects from the two instruments are used to demonstrate the near independence of their dominant systematic error residuals The tightest result comes from the HFI-based τ posterior distribution using the maximum likelihood power spectrum estimator from EE data only, giving a value 0055 ± 0009 In a companion paper these results are discussed in the context of the best-fit PlanckΛCDM cosmological model and recent models of reionization

Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function

Abstract: HBV cccDNA, the template for transcription of all viral mRNAs, accumulates in the nucleus of infected cells as a stable episome organized into minichromosomes by histones and non-histone viral and cellular proteins. Using a cccDNA-specific chromatin immunoprecipitation (ChIP)-based quantitative assay, we have previously shown that transcription of the HBV minichromosome is regulated by epigenetic changes of cccDNA-bound histones and that modulation of the acetylation status of cccDNA-bound H3/H4 histones impacts on HBV replication. We now show that the cellular histone acetyltransferases CBP, p300, and PCAF/GCN5, and the histone deacetylases HDAC1 and hSirt1 are all recruited in vivo onto the cccDNA. We also found that the HBx regulatory protein produced in HBV replicating cells is recruited onto the cccDNA minichromosome, and the kinetics of HBx recruitment on the cccDNA parallels the HBV replication. As expected, an HBV mutant that does not express HBx is impaired in its replication, and exogenously expressed HBx transcomplements the replication defects. p300 recruitment is severely impaired, and cccDNA-bound histones are rapidly hypoacetylated in cells replicating the HBx mutant, whereas the recruitment of the histone deacetylases hSirt1 and HDAC1 is increased and occurs at earlier times. Finally, HBx mutant cccDNA transcribes significantly less pgRNA. Altogether our results further support the existence of a complex network of epigenetic events that influence cccDNA function and HBV replication and identify an epigenetic mechanism (i.e., to prevent cccDNA deacetylation) by which HBx controls HBV replication.

Bortezomib Plus Melphalan and Prednisone Compared With Melphalan and Prednisone in Previously Untreated Multiple Myeloma: Updated Follow-Up and Impact of Subsequent Therapy in the Phase III VISTA Trial

Abstract: Purpose The purpose of this study was to confirm overall survival (OS) and other clinical benefits with bortezomib, melphalan, and prednisone (VMP) versus melphalan and prednisone (MP) in the phase III VISTA (Velcade as Initial Standard Therapy in Multiple Myeloma) trial after prolonged follow-up, and evaluate the impact of subsequent therapies. Patients and Methods Previously untreated symptomatic patients with myeloma ineligible for high-dose therapy received up to nine 6-week cycles of VMP (n 344) or MP (n 338). Results With a median follow-up of 36.7 months, there was a 35% reduced risk of death with VMP versus MP (hazard ratio, 0.653; P .001); median OS was not reached with VMP versus 43 months with MP; 3-year OS rates were 68.5% versus 54.0%. Response rates to subsequent thalidomide(41% v 53%) and lenalidomide-based therapies (59% v 52%) appeared similar after VMP or MP; response rates to subsequent bortezomib-based therapy were 47% versus 59%. Among patients treated with VMP (n 178) and MP (n 233), median survival from start of subsequent therapy was 30.2 and 21.9 months, respectively, and there was no difference in survival from salvage among patients who received subsequent bortezomib, thalidomide, or lenalidomide. Rates of adverse events were higher with VMP versus MP during cycles 1 to 4, but similar during cycles 5 to 9. With VMP, 79% of peripheral neuropathy events improved within a median of 1.9 months; 60% completely resolved within a median of 5.7 months. Conclusion VMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent antimyeloma therapy. First-line bortezomib use does not induce more resistant relapse. VMP used upfront appears more beneficial than first treating with conventional agents and saving bortezomib- and other novel agent– based treatment until relapse. J Clin Oncol 28:2259-2266. © 2010 by American Society of Clinical Oncology