University of Perugia

About: University of Perugia is a education organization based out in Perugia, Umbria, Italy. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 13365 authors who have published 39516 publications receiving 1265601 citations. The organization is also known as: Universitá degli Studi di Perugia & Universita degli Studi di Perugia.

BRAF mutations in hairy-cell leukemia

Abstract: Background Hairy-cell leukemia (HCL) is a well-defined clinicopathological entity whose underlying genetic lesion is still obscure. Methods We searched for HCL-associated mutations by performing massively parallel sequencing of the whole exome of leukemic and matched normal cells purified from the peripheral blood of an index patient with HCL. Findings were validated by Sanger sequencing in 47 additional patients with HCL. Results Whole-exome sequencing identified five missense somatic clonal mutations that were confirmed on Sanger sequencing, including a heterozygous mutation in BRAF that results in the BRAF V600E variant protein. Since BRAF V600E is oncogenic in other tumors, further analyses were focused on this genetic lesion. The same BRAF mutation was noted in all the other 47 patients with HCL who were evaluated by means of Sanger sequencing. None of the 195 patients with other peripheral B-cell lymphomas or leukemias who were evaluated carried the BRAF V600E variant, including 38 patients with spl...

The endocrine function of adipose tissue: an update.

Abstract: Summary Adipose tissue secretes bioactive peptides, termed ‘adipokines’, which act locally and distally through autocrine, paracrine and endocrine effects. In obesity, increased production of most adipokines impacts on multiple functions such as appetite and energy balance, immunity, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism and haemostasis, all of which are linked with cardiovascular disease. Enhanced activity of the tumour necrosis factor and interleukin 6 are involved in the development of obesity-related insulin resistance. Angiotensinogen has been implicated in hypertension and plasminogen activating inhibitor-1 (PAI-1) in impaired fibrinolysis. Other adipokines like adiponectin and leptin, at least in physiological concentrations, are insulin sparing as they stimulate beta oxidation of fatty acids in skeletal muscle. The role of resistin is less understood. It is implicated in insulin resistance in rats, but probably not in humans. Reducing adipose tissue mass, through weight loss in association with exercise, can lower TNF- α and IL-6 levels and increase adiponectin concentrations, whereas drugs such as thiazolinediones increase endogenous adiponectin production. In-depth understanding of the pathophysiology and molecular actions of adipokines may, in the coming years, lead to effective therapeutic strategies designed to protect against atherosclerosis in obese patients

Detection of the characteristic pion-decay signature in supernova remnants

Abstract: Cosmic rays are particles (mostly protons) accelerated to relativistic speeds. Despite wide agreement that supernova remnants (SNRs) are the sources of galactic cosmic rays, unequivocal evidence for the acceleration of protons in these objects is still lacking. When accelerated protons encounter interstellar material, they produce neutral pions, which in turn decay into gamma rays. This offers a compelling way to detect the acceleration sites of protons. The identification of pion-decay gamma rays has been difficult because high-energy electrons also produce gamma rays via bremsstrahlung and inverse Compton scattering. We detected the characteristic pion-decay feature in the gamma-ray spectra of two SNRs, IC 443 and W44, with the Fermi Large Area Telescope. This detection provides direct evidence that cosmic-ray protons are accelerated in SNRs.

PML regulates p53 acetylation and premature senescence induced by oncogenic Ras

Abstract: The tumour suppressor p53 induces cellular senescence in response to oncogenic signals p53 activity is modulated by protein stability and post-translational modification, including phosphorylation and acetylation The mechanism of p53 activation by oncogenes remains largely unknown Here we report that the tumour suppressor PML regulates the p53 response to oncogenic signals We found that oncogenic Ras upregulates PML expression, and overexpression of PML induces senescence in a p53-dependent manner p53 is acetylated at lysine 382 upon Ras expression, an event that is essential for its biological function Ras induces re-localization of p53 and the CBP acetyltransferase within the PML nuclear bodies and induces the formation of a trimeric p53-PML-CBP complex Lastly, Ras-induced p53 acetylation, p53-CBP complex stabilization and senescence are lost in PML-/- fibroblasts Our data establish a link between PML and p53 and indicate that integrity of the PML bodies is required for p53 acetylation and senescence upon oncogene expression