Institution
University of Florence
Education•Florence, Toscana, Italy•
About: University of Florence is a education organization based out in Florence, Toscana, Italy. It is known for research contribution in the topics: Population & Carbonic anhydrase. The organization has 27292 authors who have published 79599 publications receiving 2341684 citations. The organization is also known as: Università degli studi di Firenze & Universita degli studi di Firenze.
Papers published on a yearly basis
Papers
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TL;DR: The importance and prevalence of DNA hypermethylation in cancer and the potential value of hypomethylating agents in the treatment of human neoplasms are discussed and reviewed.
Abstract: Methylation of DNA is a biochemical modification that can influence gene expression and is involved in inactivating one of the two X chromosomes in women. Evidence that has accumulated in the past 10 years suggests that cancer cells usurp this physiologic mechanism and use it to their benefit by inactivating tumor suppressor genes and related proteins. However, the primary structure of the affected proteins remains intact; reversal of abnormalities in DNA methylation may therefore restore the tumor-suppressive function of these genes and provide a novel approach to cancer therapy. Two demethylating drugs, 5-azacytidine and 5-aza-deoxycytidine, are currently being tested in clinical trials, and several others are in preclinical development. In this article, the biological rationale for targeting aberrant methylation in cancer therapy is reviewed and completed phase I and II trials of this approach, some of which show promise for treatment of hematologic malignancies, are summarized.
417 citations
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TL;DR: Evidence is provided that intracellular ROS are generated after integrin engagement and that these oxidant intermediates are necessary for integrin signaling during fibroblast adhesion and spreading and a synergistic action of integrins and RTKs for redox signaling is proposed.
Abstract: Signal transduction by reactive oxygen species (ROS; "redox signaling") has recently come into focus in cellular biology studies. The signaling properties of ROS are largely due to the reversible oxidation of redox-sensitive target proteins, and especially of protein tyrosine phosphatases, whose activity is dependent on the redox state of a low pKa active site cysteine. A variety of mitogenic signals, including those released by receptor tyrosine kinase (RTKs) ligands and oncogenic H-Ras, involve as a critical downstream event the intracellular generation of ROS. Signaling by integrins is also essential for the growth of most cell types and is constantly integrated with growth factor signaling. We provide here evidence that intracellular ROS are generated after integrin engagement and that these oxidant intermediates are necessary for integrin signaling during fibroblast adhesion and spreading. Moreover, we propose a synergistic action of integrins and RTKs for redox signaling. Integrin-induced ROS are required to oxidize/inhibit the low molecular weight phosphotyrosine phosphatase, thereby preventing the enzyme from dephosphorylating and inactivating FAK. Accordingly, FAK phosphorylation and other downstream events, including MAPK phosphorylation, Src phosphorylation, focal adhesion formation, and cell spreading, are all significantly attenuated by inhibition of redox signaling. Hence, we have outlined a redox circuitry whereby, upon cell adhesion, oxidative inhibition of a protein tyrosine phosphatase promotes the phosphorylation/activation and the downstream signaling of FAK and, as a final event, cell adhesion and spreading onto fibronectin.
415 citations
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415 citations
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Harvard University1, Boston University2, National Institutes of Health3, University of Antwerp4, Imperial College London5, University of Toronto6, University of Minnesota7, University of Florence8, University of Turin9, Pierre-and-Marie-Curie University10, University of Massachusetts Medical School11, Mexican Social Security Institute12, University of Brescia13, University of Pavia14, Russian Academy15, Columbia University16, Life Technologies17
TL;DR: The inheritance of five polymorphic DNA markers from the proximal long arm of chromosome 21 in a large unselected series of pedi-grees with familial Alzheimer's disease suggests that Alzheimer's Disease is not a single entity, but rather results from genetic defects on chromosome 21 and from other genetic or nongenetic factors.
Abstract: Alzheimer's disease, a fatal neurodegenerative disorder of unknown aetiology, is usually considered to be a single disorder because of the general uniformity of the disease phenotype. Two recent genetic linkage studies revealed co-segregation of familial Alzheimer disease with the D21S1/S11 and D21S16 loci on chromosome 21. But two other studies, one of predominantly multiplex kindreds with a late age-of-onset, the other of a cadre of kindreds with a unique Volga German ethnic origin, found absence of linkage at least to D21S1/S11. So far it has not been possible to discern whether these conflicting reports reflect aetiological heterogeneity, differences in methods of pedigree selection, effects of confounding variables in the analysis (for example, diagnostic errors, assortative matings), or true non-replication. To resolve this issue, we have now examined the inheritance of five polymorphic DNA markers from the proximal long arm of chromosome 21 in a large unselected series of pedigrees with familial Alzheimer's disease. Our data suggest that Alzheimer's disease is not a single entity, but rather results from genetic defects on chromosome 21 and from other genetic or nongenetic factors.
415 citations
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TL;DR: In this paper, it was shown that the large QCD corrections to heavy flavour production due to small χ logarithms can be evaluated and resummed in closed form, including the coefficient factor, based on a k ⊥ -dependent factorization of the Born and structure function terms.
415 citations
Authors
Showing all 27699 results
Name | H-index | Papers | Citations |
---|---|---|---|
Charles A. Dinarello | 190 | 1058 | 139668 |
D. M. Strom | 176 | 3167 | 194314 |
Gregory Y.H. Lip | 169 | 3159 | 171742 |
Christopher M. Dobson | 150 | 1008 | 105475 |
Dirk Inzé | 149 | 647 | 74468 |
Thomas Hebbeker | 148 | 1984 | 114004 |
Marco Zanetti | 145 | 1439 | 104610 |
Richard B. Devereux | 144 | 962 | 116403 |
Gunther Roland | 141 | 1471 | 100681 |
Markus Klute | 139 | 1447 | 104196 |
Tariq Aziz | 138 | 1646 | 96586 |
Guido Tonelli | 138 | 1458 | 97248 |
Giorgio Trinchieri | 138 | 433 | 78028 |
Christof Roland | 137 | 1308 | 96632 |
Christoph Paus | 137 | 1585 | 100801 |