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Pazienza V.,Gastroenterology Unit | Borghesan M.,Gastroenterology Unit | Mazza T.,Bioinformatics Unit | Sheedfar F.,University of Groningen | And 8 more authors.

Non-alcoholic-fatty-liver-disease (NAFLD) encompasses conditions associated to fat deposition in the liver, which are generally deteriorated during the aging process. MacroH2A1, a variant of histone H2A, is a key transcriptional regulator involved in tumorigenic processes and cell senescence, and featuring two alternatively splicing isoforms macroH2A1.1 and macroH2A1.2. MacroH2A1.1 binds with high affinity O-acetyl ADP ribose, a small metabolite produced by the reaction catalysed by NAD+-dependent deacetylase SIRT1, whereas macroH2A1.2 is unable to do so. The functional significance of this binding is unknown. We previously reported that the hepatic levels of macroH2A1.1 and macroH2A1.2 are differentially expressed in mice models of NAFLD. Here we show that over-expression of macroH2A1.1, but not of macroH2A1.2, is able to protect hepatocytes against lipid accumulation. MacroH2A1.1 over-expressing cells display ameliorated glucose metabolism, reduced expression of lipidogenic genes and fatty acids content. SIRT1/macroH2A1.1-dependent epigenetic regulation of lipid metabolism may be relevant to NAFLD development. © Pazienza et al. Source

Martinez C.,IRTA - Institute of Agricultural-Alimentary Research and Technology | Coll-Bonfill N.,Institute Dinvestigacions Biomediques Agusti Pi i Sunyer | Aramburu J.,IRTA - Institute of Agricultural-Alimentary Research and Technology | Pallas V.,Institute Biologia Molecular Y Celular Of Plantas Upv Csic | And 2 more authors.
Virus Research

The movement protein (MP) of parietaria mottle virus (PMoV) is required for virus cell-to-cell movement. Bioinformatics analysis identified two hydrophilic non-contiguous regions (R1 and R2) rich in the basic amino acids lysine and arginine and with the predicted secondary structure of an α-helix. Different approaches were used to determine the implication of the R1 and R2 regions in RNA binding, plasmodesmata (PD) targeting and cell-to-cell movement. EMSA (Electrophoretic Mobility Shift Assay) showed that both regions have RNA-binding activity whereas that mutational analysis reported that either deletion of any of these regions, or loss of the basic amino acids, interfered with the viral intercellular movement. Subcellular localization studies showed that PMoV MP locates at PD. Mutants designed to impeded cell-to-cell movement failed to accumulate at PD indicating that basic residues in both R1 and R2 are critical for binding the MP at PD. © 2014 Elsevier B.V. Source

Laukkanen M.O.,IRCCS SDN | Vinciguerra M.,Euro Mediterranean Institute of Science and Technology IEMEST | Vinciguerra M.,Nottingham Trent University | Vinciguerra M.,University College London | And 2 more authors.
Trends in Molecular Medicine

The Timeless (Tim) gene, originally identified in Drosophila melanogaster and subsequently in mammals, is involved in the molecular clockwork that drives 24. h periodicity in physiology and behavior. The Tim protein is involved not only in circadian rhythmicity but also in embryonic development, cell cycle progression, DNA replication, and the DNA damage response (DDR). It is thus a multifaceted factor implicated in the maintenance of many cellular processes, tissue functions, and ultimately homeostasis of various organisms, from insects to humans. This review highlights the current knowledge of Tim functions, especially the most recent achievements, and illustrates the possible roles that this factor plays in the physiological preservation of health, as well as in the pathogenic mechanisms of related diseases. The Timeless (Tim) gene is evolutionarily conserved from insects to mammals. The Drosophila melanogaster Tim gene is involved in circadian rhythmicity, but the role mammalian Tim plays in this process is still debated.Tim, however, has been implicated in additional and distinct cellular processes comprising DNA replication and the DDR, telomere length and integrity maintenance, as well as cell cycle progression.The precise mechanisms of action of Tim in these processes, or Tim interactions with various protein partners, however, have not been completely elucidated.Tim plays a role in embryonic development and developmental apoptosis, suggesting a potential involvement in mechanisms of tissue regeneration, which could be exploited in translational research and regenerative medicine.Owing to the wide range of functions, Tim has drawn attention for its possible involvement in the pathogenesis of diverse diseases ranging from tumors to psychiatric conditions hallmarked by genetic mutations, alterations of circadian rhythmicity, and other so far unidentified events. Thus, Tim may well represent a therapeutic target in such conditions. © 2015 Elsevier Ltd. Source

Giacomarra M.,University of Palermo | Giacomarra M.,Euro Mediterranean Institute of Science and Technology IEMEST | Galati A.,University of Palermo | Crescimanno M.,University of Palermo | Tinervia S.,University of Palermo
Journal of Cleaner Production

Over the past few years, public attention has focused on the quality and safety control, traceability, and environmental issues surrounding food products. Several mandatory public standards and private voluntary schemes worldwide have been developed to address these concerns. Using survey data, this paper analyses the key factors affecting the adoption of voluntary quality standards in the wine industry and the existence of a relationship between the adoption of voluntary quality standards and economic performance, measured in terms of labour productivity and marketing behaviour. The survey involved 89 cellars, of which 68 were non-certified and 21 had one or more food quality certifications. Using the data collected, an index based on Euclidean distances was constructed to compare economic performance between certified and non-certified firms. The findings provide evidence that internal motivations drive entrepreneurs to adopt voluntary standards and that wineries adopting voluntary standards exhibit better economic performance than non-certified wine firms. From a managerial viewpoint, these results suggest that although the adoption of voluntary quality certifications does not have a direct effect in terms of a labour productivity increase, it entails a business management improvement. For policymakers, the results suggest a need to develop policies and establish more stable financial assistance for the internationalisation of wine firms, thereby supporting them through this transition. © 2015 Elsevier Ltd. Source

De Divitiis C.,Italian National Cancer Institute | Nasti G.,Italian National Cancer Institute | Montano M..,Italian National Cancer Institute | Fisichella R.,University of Catania | And 3 more authors.
World Journal of Gastroenterology

Colorectal cancer (CRC) represents one of the most commonly diagnosed cancers worldwide. It is the second leading cause of cancer death in Western Countries. In the last decade the survival of patients with metastatic CRC has improved dramatically. Due to the advent of new drugs (irinotecan and oxaliplatin) and target therapies (i.e. , bevacizumab, cetuximab and panitumab), the median overall survival has risen from about 12 mo in the mid nineties to 30 mo recently. Many questions needing of right collocations and more clearness still exist regarding the prognostic factors and the predictive factors of response to therapy. Despite advances in dosing and scheduling of chemotherapy in both adjuvant and advanced settings, and a greater emphasis on early detection, the outlook still remains poor for most patients. Molecular analyses have shown that the natural history of all CRCs is not the same. Individual patients with same stage tumours may have different long term prognosis and response to therapy. In addition, some prognostic variables are likely to be more important than others. Here we review the role of prognostic factors and predictive factors according to the recently published English literature. © 2014 Baishideng Publishing Group Inc. All rights reserved. Source

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