Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance

Modified-live herpesvirus vaccines are widely used in humans and animals, but field strains can emerge that have a higher virulence and break vaccinal protection. Since the introduction of the first vaccine in the 1970s, Marek's disease virus overcame the vaccine barrier by the acquisition of numerous genomic mutations. However, the evolutionary adaptations in the herpesvirus genome responsible for the vaccine breaks have remained elusive. Here, we demonstrate that point mutations in the multifunctional meq gene acquired during evolution can significantly alter virulence. Defined mutations found in highly virulent strains also allowed the virus to overcome innate cellular responses and vaccinal protection. Concomitantly, the adaptations in meq enhanced virus shedding into the environment, likely providing a selective advantage for the virus. Our study provides the first experimental evidence that few point mutations in a single herpesviral gene result in drastically increased virulence, enhanced shedding, and escape from vaccinal protection

Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation

none14sìThe insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). The impact of N-glycosylation defects on IGF-1/IGF-1R signaling components is largely unknown. In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. Furthermore, reduced IGF-1R expression level was observed in ALG3-CDG, ALG8-CDG and in some PMM2-CDG fibroblasts. IGF-1-induced IGF-1R activation was lower in most PMM2-CDG fibroblasts and was associated with decreased ERK1/2 phosphorylation as compared to CTR. In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. ER-stress-related gene expression negatively correlated with fibroblasts IGF-1 secretion. This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG.openDi Patria, Laura; Annibalini, Giosuè; Morrone, Amelia; Ferri, Lorenzo; Saltarelli, Roberta; Galluzzi, Luca; Diotallevi, Aurora; Bocconcelli, Matteo; Donati, Maria Alice; Barone, Rita; Guerrini, Renzo; Jaeken, Jaak; Stocchi, Vilberto; Barbieri, ElenaDi Patria, Laura; Annibalini, Giosuè; Morrone, Amelia; Ferri, Lorenzo; Saltarelli, Roberta; Galluzzi, Luca; Diotallevi, Aurora; Bocconcelli, Matteo; Donati, Maria Alice; Barone, Rita; Guerrini, Renzo; Jaeken, Jaak; Stocchi, Vilberto; Barbieri, Elen

Parametric instabilities study in a shock ignition relevant regime

Inertial Confinement Fusion with Shock Ignition relies on a very strong shock created by a laser pulse at an intensity of the order of 10(16)W/cm(2). In this context, an experimental campaign at the Prague Asterix Laser System (PALS) has been carried out within the frame of the HiPER project. Two beams have been used, the first to create an extended preformed plasma (scale length of the order of hundreds of micrometers) on a planar target, the second to generate a strong shock wave. Different diagnostics were used to study both the shock breakout at the rear surface of the target and the laser-plasma coupling and parametric instabilities. This paper is focused on back-scattering analysis to measure the back-reflected energy and to characterize parametric instabilities such as stimulated Brillouin and Raman scattering. Our experimental data show that parametric instabilities do not play a strong role in the laser plasma coupling. Moreover, preliminary analysis of the back reflected light from the interaction region shows that less than 5% of the total incident laser energy was back-reflected, with only a small fraction of that light was originating from parametric instabilities

Laser-plasma coupling in the shock-ignition intensity regime

A novel approach to ICF called shock ignition, that relies on delivery of a very strong shock created by a laser pulse at intensities around 10 16 W cm-2, is investigated. In this context, an experiment using two beams from the Prague Asterix Laser System with time duration of 300 ps was performed at the PALS laboratory. The first beam at low intensity was used to create extended preformed plasma, and the second one to create a strong shock. Several diagnostics were used to characterize the preformed plasma and the interaction of the main pulse with the target

Rassegna storica salernitana. N.s. A. 26, n.2 (2008)

La Società Salernitana di Storia Patria aderisce al progetto EleA e autorizza la pubblicazione del fascicoloN.s. A. 26, n.2 (2008): Volpe Cacciatore, P., Un maestro: Italo Gallo, P. 9 ; Savino, E., Odoacre ed il 476 in Marcellino Comes, Cassiodoro e Giordane, P. 15 ; Torraca, L., Atti del santo apostolo ed evangelista Matteo di Simeone Metafraste, P. 31; Picariello, S., , Riorganizzazione del territorio irpino e dinamiche dell’insediamento fra tarda antichità e alto medioevo (290-849), P. 47; Becchetti, L., Nota di sfragistica alto medievale salernitana. Il sigillo di Gisulfo II, P. 93 ; Dell’Acqua, F., «Il grande foglio del mare»: gli avori di Salerno e il Mediterraneo medievale, P. 103 ; Gaglione, M., Note su di un legame accertato: la dinastia angioina ed il convento di S. Lorenzo Maggiore in Napoli, P. 125 ; Vitolo, G., Monarchia, ufficiali regi, comunità cittadine nel Mezzogiorno aragonese. Spunti da alcune fonti "impertinenti", P. 169 ; D’Arienzo, V., Note sulla dogana di Salerno e sul commercio di ferro nel 1526 e 1527, P. 195 ; Volpe, F., Note sulla popolazione di Santa Lucia Cilento, P. 209 ; Franco, A., Il sedile nobiliare di Sarno, P. 223 ; Carlone, G. e G. Lauriello, L'inventario della "speziaria" della Certosa di Padula e le proprietà terapeutiche dei farmaci, P. 273 ; Mello, M. Postille sulla fortuna di Paestum, P. 285 ; Federico E., Da Copersito all'isola dei Sireni. Le Ricerche su Capri di Rosario Mangani, P. 295 ; Scirocco, A., Le spine dell'unificazione amministrativa dopo l'unità d'Italia: il ritiro della moneta borbonica di rame nelle province meridionali (1861-1865), P. 307 ; Villani, P., Un ufficiale italiano in Cina e in Siberia (1918-1919) ; Cacciatore, G., Giovanni Cuomo. Le istituzioni culturali e la nascita del magistero, P. 343.Sul recto del frontespizio : fasc. 50 della Nuova Serie (Annata LXIX dalla fondazione

An experimental study of laser-plasma coupling in a shock-ignition relevant regime

[No abstract available