Corporate Governance, dimensioni ed efficienza del settore bancario italiano

The Corporate Governance is supposed to influence significantly the economic performances of the firms. This paper investigates on the effects that some variables - like characteristics of the board director, the potential conflict of interest, the stock option - have on the economic results of a sample of Italian banks. The results of the analysis suggest that this variables, with others related to the scale, do matter

Experimental evidence of delocalized states in random dimer superlattices

We study the electronic properties of GaAs-AlGaAs superlattices with intentional correlated disorder by means of photoluminescence and vertical dc resistance. The results are compared to those obtained in ordered and uncorrelated disordered superlattices. We report the first experimental evidence that spatial correlations inhibit localization of states in disordered low-dimensional systems, as our previous theoretical calculations suggested, in contrast to the earlier belief that all eigenstates are localized.Comment: 4 pages, 5 figures. Physical Review Letters (in press

The Dual Behaviour of a GPCR Involved in Brain Damage an Repair: Forced Unbinding of the Receptor GPR17 Ligands from Wild Type and R255I Mutant Models Through a Computational Approach

GPR17 is a hybrid G-protein-coupled receptor activated by two unrelated ligand families, extracellular nucleotides and cysteinyl-leukotrienes, and involved in brain damage and repair. Its exploitment as a target for novel neuroreparative strategies depends on the elucidation of the molecular determinants driving binding of its ligands. We applied docking and molecular dynamics simulations to analyse the binding and the forced unbinding of two GPR17 ligands (the purinergic agonist UDP and the leukotriene receptor antagonist pranlukast) from both the wild-type receptor and a mutant model, where a basic residue hypothesized to be crucial for nucleotide binding had been mutated (R255I). Molecular dynamics suggested that GPR17 nucleotide binding pocket is enclosed between the helical bundle and EL2. The driving interaction involves R255 and the UDP phosphate moiety. Steered molecular dynamics experiments showed that the energy required to unbind UDP is higher for the wild-type receptor than for R255I. Three potential binding sites for pranlukast were found. In one of its preferential docking conformations, pranlukast tetrazole group is close to R255 and phenyl rings are placed into a subpocket highly conserved among GPCRs. Pulling forces developed to break polar and aromatic interactions of pranlukast were comparable. No differences between the wild-type receptor and the R255I receptor were found for the unbinding of pranlukast. These data suggest a crucial role for R255 in binding of nucleotides to GPR17. Aromatic interactions are instead likely to play a predominant role in the recognition of pranlukast, suggesting that two different binding subsites are present on GPR17

Identification of serine/threonine kinase and nucleotide-binding site–leucine-rich repeat (NBS-LRR) genes in the fire blight resistance quantitative trait locus of apple cultivar ‘Evereste’

Fire blight is the most destructive bacterial disease affecting apple (Malus×domestica) worldwide. So far, no resistance gene against fire blight has been characterized in apple, despite several resistance regions having been identified. A highly efficacious resistance quantitative trait locus (QTL) was localized on linkage group 12 (LG12) of the ornamental cultivar ‘Evereste’. A marker previously reported to be closely linked to this resistance was used to perform a chromosome landing. A bacterial artificial chromosome (BAC) clone of 189 kb carrying the fire blight resistance QTL was isolated and sequenced. New microsatellite markers were developed, and the genomic region containing the resistance locus was limited to 78 kb. A cluster of eight genes with homologies to already known resistance gene structures to bacterial diseases was identified and the corresponding gene transcription was verified. From this cluster, two genes were recognized in silico as the two most probable fire blight resistance genes showing homology with the Pto/Prf complex in tomato

Dysregulation of the GPR17 receptor in neuroinflammatory diseases: implications for remyelination in multiple sclerosis

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, in which inflammation and myelin disruption contribute to impaired in electrical conduction. Oligodendrocyte precursor cells (OPCs) are massively recruited to the site of injury to myelinate damaged axons, but in MS patients remyelination is often ineffective. For this reason, therapeutic strategies aimed at fostering this process could block/delay the development of the disease and the consequent disability. We have previously shown that the membrane receptor GPR17 timely regulates the early stages of OPC differentiation, but, after reaching its highest levels in immature oligodendrocytes, it has to be down-regulated to allow terminal maturation. Any defect in its expression pattern leads to impairment in oligodendrocyte differentiation. Interestingly, overexpression of GPR17 was found in rodent models of cerebral trauma, ischemia and in lysolecithin induced focal demyelination. Instead, little is known about GPR17 in a primary demyelinating disease such as MS. On this basis, aim of this work has been to characterize GPR17 alterations in a murine model of MS and in human post-mortem MS lesions. In spinal cord of mice subjected to experimental autoimmune encephalomyelitis (EAE), we observed a marked and persistent upregulation of GPR17 in the OPCs accumulating at demyelinating lesions. Moreover, fate-mapping experiments with transgenic GPR17iCreERT2-GFP reporter mice showed that this increased pool of proliferating cells is blocked at an intermediate stage of differentiation, and cannot fully complete the myelination process, likely due to unfavourable inflammatory environment. In a similar way, in post-mortem tissues from SPMS patients, many GPR17-positive activated OPCs accumulated at the border of active lesions. In particular, GPR17 was found mainly expressed by hypertrophic cells HLA (human leukocyte antigen or major histocompatibility complex) -positive at within the lesions, suggesting that GPR17 is involved in the reaction to damage in both OPCs and immune cells directly responding to inflammation. We conclude that the coordinated presence of GPR17 at the membrane of these cells at the lesion sites could be exploited as potential new target to support endogenous remyelination through advanced pharmacological approaches

GPR17 molecular modelling: interactions with non-conventional pro-inflammatory ligands

GPR17 is a class A-GPCRs operated by di erent classes of ligands, such as uracil nucleotides, cysteinyl-leukotrienes and oxysterols. Similar to other receptors of the same class, GPR17 can associate into homo- and hetero-dimers. Recent ndings suggest its promiscuous behavior namely the possibility to be operated by ligands able to transversely interact with more than one GPCRs. In fact, both GPR17 and CXCR2 are operated by oxysterols, and both GPR17 and CXCRn ligands have demonstrated roles in orchestrating in ammatory responses and oligodendrocyte precursor cell (OPC) di erentiation to myelinating cells in acute and chronic diseases of the CNS. Here we demonstrate that GPR17 can be activated by the chemokine stromal-derived factor-1 (SDF-1), a ligand of CXCR4 and CXCR7, and investigate the underlying molecular recognition mechanism, by combining in silico modelling data with in vitro validation in (i) a classical reference pharmacological assay for GPCR activity and (ii) a model of maturation of primary OPCs. We also demonstrate that cangrelor, a GPR17 orthosteric antagonist, can block the SDF-1-mediated activation of GPR17 in a concentration-dependent manner. The ability of GPR17 to respond to di erent classes of GPCR ligands suggests that this receptor modi es its function depending on changes occurring in the extracellular mileu changes occurring under speci c pathophysiological conditions and advocates it as a strategic target for neurodegenerative diseases with an in ammatory/immune component

Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed as chemopreventive agents for many tumours; however, the mechanism responsible for their anti-neoplastic activity remains elusive and the side effects due to cyclooxygenase (COX) inhibition prevent this clinical application. Methods: Molecular biology, in silico, cellular and in vivo tools, including innovative in vivo imaging and classical biochemical assays, were applied to identify and characterise the COX-independent anti-cancer mechanism of NSAIDs. Results: Here, we show that tumour-protective functions of NSAIDs and exisulind (a sulindac metabolite lacking anti-inflammatory activity) occur through a COX-independent mechanism. We demonstrate these NSAIDs counteract carcinogen-induced proliferation by inhibiting the sirtuin 1 (SIRT1) deacetylase activity, augmenting acetylation and activity of the tumour suppressor p53 and increasing the expression of the antiproliferative gene p21. These properties are shared by all NSAIDs except for ketoprofen lacking anti-cancer properties. The clinical interest of the mechanism identified is underlined by our finding that p53 is activated in mastectomy patients undergoing intraoperative ketorolac, a treatment associated with decreased relapse risk and increased survival. Conclusion: Our study, for the first-time, links NSAID chemopreventive activity with direct SIRT1 inhibition and activation of the p53/p21 anti-oncogenic pathway, suggesting a novel strategy for the design of tumour-protective drugs

Continuos clinical remission with biologics in Ulcerative Colitis: the A.U.R.O.R.A. comparative study

Comparative trials among biological drugs for the treatment of ulcerative colitis (UC) provided conflicting results. After patent expire of infliximab originator, adalimumab, infliximab biosimilar, golimumab and vedolizumab have been approved in Italy.We compared the efficacy of these four biologics in UC according to the concept of continuous clinical remission (CCR)

Gentamicin sulphate permeation through porcine intestinal epithelial cell monolayer

Gentamicin is an aminoglycoside antibiotic widely used in combination with dimethyl sulphoxide (DMSO) in topical drug formulations. It is not known, however, whether DMSO can enhance the permeation of gentamicin through biological membranes, leading to oto- and nephrotoxic side effects. A simple and reliable high-performance liquid chromatographic (HPLC) method was applied for the quantitative determination of gentamicin collected from the apical and basolateral compartments of the porcine intestinal epithelial cell line IPEC-J2 cell monolayer using fluorometric derivatisation of the analyte with fluorenylmethyloxycarbonyl chloride (FMOC) prior to chromatographic run in the presence and absence of 1% DMSO. The lack of change in transepithelial electrical resistance (TER) demonstrated that gentamicin and 1% DMSO did not affect IPEC-J2 cell monolayer integrity via the disruption of cell membranes. Chromatographic data also ascertained that gentamicin penetration across the cell monolayer even in the presence of 1% DMSO was negligible at 6 h after the beginning of apical gentamicin administration. This study further indicates that the addition of this organic solvent does not increase the incidence of toxic effects related to gentamicin permeation

Phagocytic ability of neutrophils and monocytes in neonates

<p>Abstract</p> <p>Background</p> <p>Infections by a variety of pathogens are a significant cause of morbidity and mortality during perinatal period. The susceptibility of neonates to bacterial infections has been attributed to immaturity of innate immunity. It is considered that one of the impaired mechanisms is the phagocytic function of neutrophils and monocytes. The purpose of the present study was to investigate the phagocytic ability of neonates at birth.</p> <p>Methods</p> <p>The phagocytic ability of neutrophils and monocytes of 42 neonates was determined using the Phagotest flow cytometry method, that assesses the intake of <it>E. Coli </it>by phagocytes, in cord blood and in peripheral blood 3 days after birth. Fifteen healthy adults were included in the study as controls.</p> <p>Results</p> <p>The phagocytic ability of neutrophils in the cord blood of neonates was significantly reduced compared to adults. The 3^rdpostnatal day the reduction of phagocytic ability of neutrophils was no longer significant compared to adults. The phagocytic ability of monocytes did not show any difference from that of adults either at birth or the 3^rdpostnatal day.</p> <p>Conclusions</p> <p>Our findings indicate that the intake of <it>E. Coli </it>by phagocytes is impaired at birth in both preterm and full term neonates compared to adults. This defect is transient, with the phagocytic ability in neonates reaching that of the adults 3 days after birth.</p