INTERNATIONALIZATION AND INNOVATION: THE CHALLENGES FOR EUROPE IN A CHANGING WORLD

A large part of the economic literature is unanimous in believing technological progress and openness to foreign trade are key variables to trigger the processes of stable and persistent economic growth. An in-depth analysis of these factors, thus, becomes necessary both to meet the challenges of the international market, and to strengthen the European integration process. This paper aims to provide an empirical analysis of the interaction between foreign trade and technological progress by performing a multidimensional scaling. This technique is used to produce a graphical representation of the 27 EU member states, in accordance to the degree of similarity or dissimilarity between them. The indicators used, and the indexes calculated, reflect the different degree of internationalization of each country's economy, the regulation of trade flows, investment in specific R&D and technological progress.International trade, integration, technological progress

Qualitative Attributes of Commercial Pig Meat from an Italian Native Breed: The Nero d'Abruzzo

The main objective of this study was to characterize the main qualitative properties of commercial meat obtained from the Nero d'Abruzzo pig, a native breed of Central Italy. In order to valorize this animal production, a direct comparison was made with commercial meat products obtained from hybrid pigs. Over a period of 30 days, 76 steaks for each breed were purchased from the market, and samples were analyzed for total lipid content, fatty acids profile, Coenzyme Q10 content, resistance of meat to oxidative processes, volatile profile of cooked meat and electrophoretic profile of myofibrillar and sarcoplasmic proteins. Results showed the Nero d'Abruzzo to be richer in fat, which, however, is characterized by a higher concentration of alpha-linolenic acid, to which are attributed important health benefits. The native breed was also richer in Coenzyme Q10, a compound credited with antioxidant potential, whose presence could explain the better oxidative stability of meat samples that were cooked and stored for up to 7 days at +4 degrees C. In support of this last data, our finding of the characterization of the volatile profile of cooked meat, at the end of the storage period, showed in Nero d'Abruzzo a reduction in the accumulation of hexanal, notoriously associated with oxidative events and the development of unpleasant aromatic notes. In conclusion, aspects that can justify the nutritional superiority of this niche production compared to meat coming from cosmopolitan breeds have been identified

Live imaging of effector cell trafficking and autoantigen recognition within the unfolding autoimmune encephalomyelitis lesion

We tracked pathogenic myelin basic protein-specific CD4+ effector T cells in early central nervous system (CNS) lesions of experimental autoimmune encephalomyelitis (EAE) by combining two-photon imaging and fluorescence video microscopy. We made two key observations: (a) the majority of the cells (65%) moved fast (maximal speed 25 μm/min) and apparently nondirected through the compact tissue; and (b) a second group of effector T cells (35%) appeared tethered to a fixed point. Polarization of T cell receptor and adhesion molecules (lymphocyte function-associated antigen 1) towards this fixed point suggests the formation of immune synapses. Nonpathogenic, ovalbumin-specific T cells were not tethered in the CNS and did not form synapse-like contacts, but moved through the tissue. After intrathecal injection of antigen, 40% of ovalbumin-specific T cells became tethered. Conversely, injection of anti–major histocompatibility complex class II antibodies profoundly reduced the number of stationary pathogenic T cells within the CNS (to 15%). We propose that rapid penetration of the CNS parenchyma by numerous autoimmune effector T cells along with multiple autoantigen-presentation events are responsible for the fulminate development of clinical EAE

Nicotinic acid adenine dinucleotide phosphate-mediated calcium signalling in effector T cells regulates autoimmunity of the central nervous system

Nicotinic acid adenine dinucleotide phosphate represents a newly identified second messenger in T cells involved in antigen receptor-mediated calcium signalling. Its function in vivo is, however, unknown due to the lack of biocompatible inhibitors. Using a recently developed inhibitor, we explored the role of nicotinic acid adenine dinucleotide phosphate in autoreactive effector T cells during experimental autoimmune encephalomyelitis, the animal model for multiple sclerosis. We provide in vitro and in vivo evidence that calcium signalling controlled by nicotinic acid adenine dinucleotide phosphate is relevant for the pathogenic potential of autoimmune effector T cells. Live two photon imaging and molecular analyses revealed that nicotinic acid adenine dinucleotide phosphate signalling regulates T cell motility and re-activation upon arrival in the nervous tissues. Treatment with the nicotinic acid adenine dinucleotide phosphate inhibitor significantly reduced both the number of stable arrests of effector T cells and their invasive capacity. The levels of pro-inflammatory cytokines interferon-gamma and interleukin-17 were strongly diminished. Consecutively, the clinical symptoms of experimental autoimmune encephalomyelitis were ameliorated. In vitro, antigen-triggered T cell proliferation and cytokine production were evenly suppressed. These inhibitory effects were reversible: after wash-out of the nicotinic acid adenine dinucleotide phosphate antagonist, the effector T cells fully regained their functions. The nicotinic acid derivative BZ194 induced this transient state of non-responsiveness specifically in post-activated effector T cells. Naïve and long-lived memory T cells, which express lower levels of the putative nicotinic acid adenine dinucleotide phosphate receptor, type 1 ryanodine receptor, were not targeted. T cell priming and recall responses in vivo were not reduced. These data indicate that the nicotinic acid adenine dinucleotide phosphate/calcium signalling pathway is essential for the recruitment and the activation of autoaggressive effector T cells within their target organ. Interference with this signalling pathway suppresses the formation of autoimmune inflammatory lesions and thus might qualify as a novel strategy for the treatment of T cell mediated autoimmune diseases

The Activation Status of Neuroantigen-specific T Cells in the Target Organ Determines the Clinical Outcome of Autoimmune Encephalomyelitis

The clinical picture of experimental autoimmune encephalomyelitis (EAE) is critically dependent on the nature of the target autoantigen and the genetic background of the experimental animals. Potentially lethal EAE is mediated by myelin basic protein (MBP)–specific T cells in Lewis rats, whereas transfer of S100β- or myelin oligodendrocyte glycoprotein (MOG)–specific T cells causes intense inflammatory response in the central nervous system (CNS) with minimal disease. However, in Dark Agouti rats, the pathogenicity of MOG-specific T cells resembles the one of MBP-specific T cells in the Lewis rat. Using retrovirally transduced green fluorescent T cells, we now report that differential disease activity reflects different levels of autoreactive effector T cell activation in their target tissue. Irrespective of their pathogenicity, the migratory activity, gene expression patterns, and immigration of green fluorescent protein+ T cells into the CNS were similar. However, exclusively highly pathogenic T cells were significantly reactivated within the CNS. Without local effector T cell activation, production of monocyte chemoattractants was insufficient to initiate and propagate a full inflammatory response. Low-level reactivation of weakly pathogenic T cells was not due to anergy because these cells could be activated by specific antigen in situ as well as after isolation ex vivo

INTERNATIONALIZATION AND INNOVATION: THE CHALLENGES FOR EUROPE IN A CHANGING WORLD

A large part of the economic literature is unanimous in believing technological progress and openness to foreign trade are key variables to trigger the processes of stable and persistent economic growth. An in-depth analysis of these factors, thus, becomes necessary both to meet the challenges of the international market, and to strengthen the European integration process. This paper aims to provide an empirical analysis of the interaction between foreign trade and technological progress by performing a multidimensional scaling. This technique is used to produce a graphical representation of the 27 EU member states, in accordance to the degree of similarity or dissimilarity between them. The indicators used, and the indexes calculated, reflect the different degree of internationalization of each countrys economy, the regulation of trade flows, investment in specific RD and technological progress

Trapped in the epineurium: early entry into the endoneurium is restricted to neuritogenic T cells in experimental autoimmune neuritis

Abstract Background Autoimmune polyneuropathies are acquired inflammatory disorders of the peripheral nervous system (PNS) characterized by inflammation, demyelination, and axonal degeneration. Although the pathogenesis has not been fully elucidated, T cells recognizing self-antigens are believed to initiate inflammation in a subgroup of patients. However, the route and time of T cell entry into the PNS have not yet been described in detail. In this study, we analyzed both kinetics as well as localization of retrovirally transfected green fluorescent protein (GFP)-expressing neuritogenic T lymphocytes in experimental autoimmune neuritis (EAN). Methods T lymphocytes obtained from rats following EAN induction by immunization with peripheral nerve protein peptide P255–78 were retrovirally engineered to express GFP. Non-specific T cells were negatively selected by in vitro restimulation, whereas GFP-expressing neuritogenic T cells (reactive to P255–78) were adoptively transferred into healthy rats (AT-EAN). Antigen-specific T cell tracking and localization was performed by flow cytometry and immunohistochemistry during the course of disease. Results After induction of autoimmune neuritis, P2-reactive T cells were detectable in the liver, spleen, lymph nodes, lung, peripheral blood, and the sciatic nerves with distinct kinetics. A significant number of GFP+ T cells appeared early in the lung with a peak at day four. In the peripheral nerves within the first days, GFP-negative T cells rapidly accumulated and exceeded the number of GFP-expressing cells, but did not enter the endoneurium. Very early after adoptive transfer, T cells are found in proximity to peripheral nerves and in the epineurium. However, only GFP-expressing neuritogenic T cells are able to enter the endoneurium from day five after transfer. Conclusions Our findings suggest that neuritogenic T cells invade the PNS early in the course of disease. However, neuritogenic T cells cross the blood-nerve barrier with a certain delay without preference to dorsal roots. Further understanding of the pathophysiological role of autoagressive T cells may help to improve therapeutic strategies in immune-mediated neuropathies