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P. Paggi - Neuronal response to experimental interruption of the neural circuit the plasminogen enzymatic cascade in the reaction to axotomy of rat sympathetic neurons. Mol Cell Neurosci. 2007, 36:174-84. 90 Lombardi L, De Stefano ME, Paggi P. Components of the NGF signaling complex are altered in mdx mouse superior cervical ganglion and its target organs. Neurobiol Dis. 2008, 32:402-11. Fig. 1 - Changes in plasmin(ogen) immunolabeling in control and injured (5 postoperative days) SCGs. (A-C and inset) Control SCG. (A) Plasmin(ogen) immunolabeling is scanty. At this magnification, blood vessels (arrows) are recognizable as the most immunopositive structures inside the ganglion. (B) At high magnification, immunopositive nerve fiber-like structures (arrowheads), bearing varicosities, are seen in between ganglionic neurons. (C and inset) Strongly immunopositive non-neuronal cells (double arrows) abut ganglionic neurons and emit long processes (arrowheads), which surround the neuronal perikaryon. (D) After post-ganglionic nerve crush, plasmin(ogen) immunolabeling increases notably, filling all the extracellular spaces. Scale bars: A, D: 50 µm; B, C and inset: 25 µm (De Stefano et al., 2007).
P a r t i c i p a n t s : Stefano Cacchione, researcher; Sabrina Pisano, post-doc fellow; Alessandra Galati, Emanuela Micheli, PhD students. C o l l a b o r a t i o n s : Dipartimento di Chimica, Sapienza-Università di Roma (Prof. Armandodoriano Bianco, Prof. Pasquale De Santis, Prof. Giancarlo Ortaggi, Dr. Marco Franceschin, Dr. Anita Scipioni); Dipartimento di Chimica delle Sostanze Naturali, Università di Napoli “Federico II” (Prof. Luciano Mayol, Dr. Michela Varra); Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK (Dr. Daniela Rhodes, Dr. Linda Chapman); Laboratory of Molecular and Cellular Biology, ENS, Lyon (Prof. Eric Gilson). Report of Activity Telomeres are the special nucleoprotein structures that protect chromosome ends from both recombination and degradation. In humans, telomeres consist of TTAGGG repeats about 10 kbp long, ending in a 3’ G-rich overhang. As a consequence of incomplete DNA replication at chromosome termini, telomeres progressively shorten in replicating cells, till they reach a critical length that leads to cellular senescence. In germ line cells, telomere loss is counteracted by the reverse transcriptase enzyme telomerase, which adds telomeric repeats to the 3’ ends of the chromosomes using as template its RNA moiety. Both telomere length regulation and the maintenance of a correct end-capping structure are essential for cell and organism survival. Most tumors show aberrant telomerase expression levels, that allow cells to divide indefinitely. The long human telomeres are organized in tightly packed nucleosomes separated by 10-20 bp of linker DNA. Two proteins, TRF1 and TRF2, bind to doublestranded TTAGGG repeats, whereas POT1 recognizes single-stranded G-rich overhangs. Telomere structure is still poorly defined. A sound model is the Principal investigator: Maria Savino Professor of Biophysical Chemistry Dipartimento di Genetica e Biologia Molecolare Tel: (+39) 06 49912238; Fax: (+39) 06 4440812 maria.savino@uniroma1.it 91 Molecular recognition in biomolecules - AREA 4 Structural and superstructural features of human telomeric chromatin t-loop, a closed protective structure in which the 3’ overhang circles back and insert into the upstream duplex telomeric DNA region. The G-rich singlestranded extension can also fold to form a structure named G-quadruplex, a four-stranded structure stabilized by cations at physiological concentrations. The emerging view is that telomeres are dynamic structures that interconvert among different structures along with the cell cycle and differentiation. Whereas the roles played by telomere-binding proteins in the regulation of telomere length and stability have been widely studied, little is known about the involvement of nucleosomes in telomere structure and functions, and about the interplay between nucleosomes and specific telomeric proteins. In the past years, we demonstrated that telomeric nucleosomes are the least stable nucleosomes so far studied and occupy multiple isoenergetic positions, as a consequence of the 6 bp telomeric DNA periodicity, which is out of phase with the DNA double helical repeat, Furthermore, AFM studies on nucleosomal arrays reconstituted in vitro showed that the very short spacing of human telomeric nucleosomes (157 bp) depends mainly on the intrinsic physical properties of telomeric DNA. Finally, we found that hTRF1 is able to specifically recognize telomeric binding sites located within nucleosomes, inducing alterations in nucleosome structure without dissociation of histone subunits. All these findings suggest that nucleosomes may play a relevant role in telomere function and dynamics. In the past two years we focused on two main issues: 1) The role of nucleosomes in telomere dynamics and their interplay with TRF proteins; 2) Human telomere G-quadruplex structures as targets for anticancer strategies. Intrinsic and induced mobility of telomeric nucleosomes Chromatin remodeling is a major player in the regulation of biological processes, through the action of ATP-dependent remodeling complexes. By means of
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Istituto Pasteur Fondazione Cenci B
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Contents Forward by Paolo Amati, P
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Research area 6: New antimicrobial
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REPORT OF ACTIVITY 2007-2008 Boards
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REPORT OF ACTIVITY 2007-2008 Dario
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REPORT OF ACTIVITY 2007-2008 Meetin
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AREA1 Molecular biology of microorg
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P. Amati - Role of the early phases
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A. Boffi - Escherichia coli strains
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D. De Biase - The glutamate-based a
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A. Faggioni - Control of latency an
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Paola Londei - Translational regula
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A structural biology study of schis
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P a r t i c i p a n t s : Luigi Lem
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P a r t i c i p a n t s : Gianni Pr
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P a r t i c i p a n t s : Lucia Nen
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P a r t i c i p a n t s : Alessandr
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P a r t i c i p a n t s : Maurizio
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AREA3 Molecular genetics of eukaryo
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F. Ascenzioni - Development and ana
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P. Ballario - Molecular machines an
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I. Bozzoni - RNA-RNA and RNA-protei
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P. Caiafa - Crosstalk between poly(
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G. Camilloni - DNA topoisomerases a
Page 52 and 53: P. Costantino - The role of the DAG
Page 54 and 55: M. d’Erme - Epigenetic modificati
Page 56 and 57: P. Dimitri - Drosophila melanogaste
Page 58 and 59: L. Fabiani - DNA replication mechan
Page 60 and 61: C. Falcone - New tools in decipheri
Page 62 and 63: L. Frontali - New complex mitochond
Page 64 and 65: M. Gatti - The role of membrane tra
Page 66 and 67: A. Giacomello - Biology and physiol
Page 68 and 69: A. Gulino - Regulation of the Hedge
Page 70 and 71: M. Levrero - Histone Acetyltransfer
Page 72 and 73: F. Mangia - Molecular regulation of
Page 74 and 75: A. Musarò - Study of the molecular
Page 76 and 77: R. Negri - Role of the presumptive
Page 78 and 79: S. Pimpinelli - Heterochromatin, ge
Page 80 and 81: M. Stefanini - Biological character
Page 82 and 83: M. Tripodi - Molecular mechanisms o
Page 84 and 85: C. Turano - Roles of ERp57 in DNA r
Page 86 and 87: G. Zardo - Identification of novel
Page 89 and 90: P a r t i c i p a n t s : Carlo Tra
Page 91 and 92: P a r t i c i p a n t s : Giulia De
Page 93 and 94: P a r t i c i p a n t s : Giovanna
Page 95 and 96: P a r t i c i p a n t s : Francesco
Page 97 and 98: P a r t i c i p a n t s : Bruno Bot
Page 99 and 100: P a r t i c i p a n t s : Sergio Fu
Page 101: P a r t i c i p a n t s : Maria Egl
Page 105: AREA5 Cellular and molecular immuno
Page 108 and 109: V. Barnaba - Innovative strategies
Page 110 and 111: R. Foà - Potential role of miRNAS
Page 112 and 113: E. Piccolella - Analysis of the mol
Page 114 and 115: A. Santoni - Molecular mechanism un
Page 116 and 117: I. Screpanti - Analysis of the role
Page 118 and 119: R. Sorrentino - The role of HLA-B27
Page 120 and 121: L. Tuosto - CD28 co-stimulatory mol
Page 122 and 123: E. Ziparo - The role of Toll Like R
Page 125 and 126: Peptide effectors of innate immunit
Page 127 and 128: P a r t i c i p a n t s : Gustavo P
Page 129 and 130: P a r t i c i p a n t s : Roberta C
Page 131 and 132: P a r t i c i p a n t s : Giovanna
Page 133 and 134: P a r t i c i p a n t s : Livia Di
Page 135 and 136: P a r t i c i p a n t s : Marino Ar
Page 137: AREA7 Biology of malaria and other
Page 140 and 141: Della Torre - Petrarca - Bionomical
Page 142 and 143: A. Tramontano - Computational Analy
Page 145 and 146: Year 2007 Barile L, Chimenti I, Gae
Page 147 and 148: Puglisi R, Bevilacqua A, Carlomagno
Page 149 and 150: BIBLIOGRAPHY Conigliaro A, Colletti
Page 151 and 152: BIBLIOGRAPHY Muscolini M, Cianfrocc
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