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Several studies reported the association between total plasma phytosterol concentrations and the parenteral nutrition-associated cholestasis (PNAC). To date, no data are available on phytosterol esterification in animals and in humans during parenteral nutrition (PN). We measured free and esterified sterols (cholesterol, campesterol, stigmasterol, and sitosterol) plasma concentrations during PN in 16 preterm infants (500–1249 g of birth weight; Preterm-PN), in 11 term infants (Term-PN) and in 12 adults (Adult-PN). Gas chromatography–mass spectrometry was used for measurements. Plasma concentrations of free cholesterol (Free-CHO), free phytosterols (Free-PHY) and esterified phytosterols (Ester-PHY) were not different among the three PN groups. Esterified cholesterol (Ester-CHO) was statistically lower in Preterm-PN than Adult-PN. Preterm-PN had significantly higher Free-CHO/Ester-CHO and Free-PHY/Ester-PHY ratios than Adult-PN (Free-CHO/Ester-CHO: 1.1 ± 0.7 vs. 0.6 ± 0.2; Free-PHY/Ester-PHY: 4.1 ± 2.6 vs. 1.3 ± 0.8; *P

Amyloid-beta peptide accumulation in the brain is one of the main hallmarks of Alzheimer's disease. The amyloid aggregation process is associated with the generation of free radical species responsible for mitochondrial impairment and DNA damage that in turn activates poly(ADP-ribose)polymerase 1 (PARP-1). PARP-1 catalyzes the poly(ADP-ribosylation), a post-translational modification of proteins, cleaving the substrate NAD+ and transferring the ADP-ribose moieties to the enzyme itself or to an acceptor protein to form branched polymers of ADP-ribose. In this paper, we demonstrate that a mitochondrial dysfunction occurs in Alzheimer's transgenic mice TgCRND8, in SH-SY5Y treated with amyloid-beta and in 7PA2 cells. Moreover, PARP-1 activation contributes to the functional energetic decline affecting cytochrome oxidase IV protein levels, oxygen consumption rates, and membrane potential, resulting in cellular bioenergetic deficit. We also observed, for the first time, an increase of pyruvate kinase 2 expression, suggesting a modulation of the glycolytic pathway by PARP-1. PARP-1 inhibitors are able to restore both mitochondrial impairment and pyruvate kinase 2 expression. The overall data here presented indicate a pivotal role for this enzyme in the bioenergetic network of neuronal cells and open new perspectives for investigating molecular mechanisms underlying energy charge decline in Alzheimer's disease. In this scenario, PARP-1 inhibitors might represent a novel therapeutic intervention to rescue cellular energetic metabolism.

OBJECTIVE To assess oxygen diffusion at 36 weeks' post-menstrual age in preterm infants by means of the non-invasive oxygen saturation/fraction of inspired oxygen ratio (36w-SFR) and to identify factors associated with 36w-SFR - ie, gestational age (GA) and early respiratory disease patterns (ERP). METHODS Retrospective analysis of prospectively collected data. SETTING Neonatal Intensive Care Unit. PATIENTS 1005 preterm infants born below 32 weeks' GA. INTERVENTIONS 36w-SFR was the mean of SFR values over 24 h on the day infants reached 36 weeks' PMA. MAIN OUTCOME MEASURES 36w-SFR. STATISTICS descriptive statistics, univariate, and multivariate analysis to study associations of 36w-SFR, including GA and ERP. RESULTS 36w-SFR was significantly different between infants with and without bronchopulmonary dysplasia (BPD) (371 vs 467, P

Summary Background & aims Long chain n-3 fatty acids (n-3 LCPUFA) play a pivotal role during central nervous system development and the provision of docosahexaenoic acid (DHA) is recommended for the preterm infant. However, there are concerns that oral fish oil, which is a good source of DHA, may adversely affect growth of preterm infants, as it decreases arachidonic acid (ARA). It has been about ten years since fish oil was added to the fat blend of intravenous (IV) lipid emulsions (LE) but information on growth and other clinical outcomes of preterm infants is still scarce. We studied the effect of fish oil containing IV LE vs standard IV LE on growth in a large cohort of preterm infants who received routine parenteral nutrition (PN). Methods We retrospectively reviewed growth data of 546 preterm infants with a birth weight (BW) Results Demographics, birth data and the incidence of the main complications of prematurity were similar between the two groups (IV-FO: n = 240, Gestational age (GA) 197 ± 16 d, BW 942 ± 181 g; CNTR: n = 237, GA 199 ± 17 d, BW 960 ± 197 g). No difference was found in PN and EN energy and macronutrient intakes from birth to 36+0W PMA, as well as in the proportion of human milk to infant milk formula. Weight gain from the regained BW to 36+0W PMA was slightly but significantly higher in IV-FO group: 17.3 ± 2.8 and 16.8 ± 2.7 g∙kg−1∙d−1, IV-FO and CNTR respectively (p = 0.03). There was no difference in length gain and head growth nor in body size at 36+0W PMA between the two groups. Conclusions The use of IV fish oil did not negatively affect weight gain in a cohort of preterm infants. Large randomized controlled trials are needed to assess the effect of IV fish oil on the complication of prematurity and on selected domains of infant development.

In 93 preterm infants ≤32 weeks of gestational age and 12 control infants, epithelial lining fluid disaturated-phosphatidylcholine, surfactant protein A and B, albumin, and myeloperoxidase activity were assessed after intubation and before exogenous surfactant administration. We found that disaturated-phosphatidylcholine, surfactant protein B, and myeloperoxidase were significantly higher in preterms with chorioamnionitis.

Variation of the isotopic abundance of selected nutrients and molecules has been used for pharmacological and kinetics studies under the premise that the administered molecule has a different isotopic enrichment from the isotopic background of the recipient subject. The aim of this study is to test the feasibility of assessing the contribution of exogenous surfactant phospholipids to the endogenous alveolar pool in vivo after exogenous surfactant replacement therapy in rabbits. The study consisted in measuring the consistency of

Parenteral nutrition-associated cholestasis (PNAC) has been linked to plasma accumulation of phytosterols in infants receiving vegetable-oil-based lipid emulsions (LE). To date, information on the ability of infants with PNAC to metabolize intravenous (IV) phytosterols has been very limited. We characterized plasma phytosterol half-life in very low birth weight (VLBW) preterm infants with PNAC. As part of a prospective cohort study, VLBW infants with PNAC underwent serial blood sample measurements of sitosterol (Sito), campesterol (Camp), and stigmasterol (Stigma). Infants without PNAC served as controls (CTRL, control infants). Thirty-seven PNAC infants and 14 CTRL were studied. On PN day 7 and PN day 14, PNAC infants had higher plasma phytosterol concentrations compared to those of CTRL (p < 0.05). A significant and positive correlation was found between plasma Camp, Stigma, Sito concentrations, and IV phytosterol intake from birth to PN day 7 (p = 0.001, p = 0.001, and p = 0.005, respectively). Stigma concentration was positively correlated with conjugated bilirubin on PN day 7 (p = 0.012). After stopping IV LE, half-lives of Camp, Stigma, and Sito became significantly longer in PNAC infants than in CTRL (Camp: 18.8 ±6.2 vs 11.8 ±3.0 days, p = 0.001; Stigma: 13.8 ±5.8 vs 9.4 ±3.4 days, p = 0.023; Sito: 15.3 ±5.0 vs 9.8 ±3.0 days, p = 0.002). In conclusion, phytosterols increased earlier during PN and were eliminated slowly after stopping IV LE in PNAC infants than in CTRL. The Stigma concentration on PN day 7 could represent an early marker of cholestasis. Our results provide additional evidence on the relationship between IV phytosterols and PNAC.

This paper presents a simple dynamic general equilibrium model with supply-side strategic interactions to study the economic effects of mitigating greenhouse gas emissions in an economy with an emission cap and oligopolistic firms competing on prices. With such endogenous market structure a gradual decarbonization policy is likely to induce higher markups, while the number of active firms displays a U-shaped behavior, first decreasing and then increasing. In the long run more firms are active, but they transfer a part of the compliance cost to households by charging a higher markup. The negative effects on the level of economic activity of this anti-competitive outcome are strongly mitigated by recycling policies.

Summary Background Phytosterols in vegetable oil (VO)-based lipid emulsions (LE) likely contribute to parenteral nutrition-associated cholestasis (PNAC) in preterm infants. No characterization of plasma phytosterol half-lives has been done in very low birth weight (VLBW) preterm infants receiving parenteral nutrition (PN) with LE. Methods In a prospective cohort study, 45 VLBW preterm infants who received PN underwent serial blood sample measurements of sitosterol (SITO), campesterol (CAMP), and stigmasterol (STIGM). Plasma phytosterol half-lives were calculated from the phytosterol concentrations–decay curves by using a single-compartment model. Results After the stop of the intravenous LE, study infants had significantly lower plasma total CAMP, STIGM and SITO concentrations. The decay of plasma phytosterol concentrations was monoexponential. Half-life of plasma total CAMP, STIGM and SITO was 13.5 ± 6.9, 10.3 ± 4.5 and 10.3 ± 4.0 days, respectively. Plasma phytosterol half-lives did not correlate with gestational age, birth weight, cumulative phytosterol intakes and plasma conjugated bilirubin. Conclusion VLBW preterm infants on PN with LE had rather long plasma phytosterol half-lives similar to hypercholesterolemic adults and phytosterolemic homozygotes patients. We speculate that the accumulation of phytosterols could contribute to their vulnerability to PNAC. Clinical trial registry The Ethics Committee of Marche-Italy (DG/469); www.clinicaltrials.gov (identification number NCT02758834 ).

Few evidences about methods to harvest educational needs by health care professionals in internal medicine have been published. In this project the following objectives have been pursued: to express preferences by each health care worker; to evaluate the efficacy of an intranet-based survey in order to structure continuing medical education (CME) planning.We created a form based on 7 questions, exploring the following areas: knowledge, know-how, communication, transversal competencies. This survey, implemented on a google drive platform, was accessible through the Azienda Sanitaria Unica Regione (ASUR) Marche intranet. Each questionnaire was analyzed with Google drive and the results were discussed within Medicine Department Committee.103/228 health care workers responded to the survey. On the basis of health care workers preferences, financial resources, relevance, untreated topics in the previous 5 years and congruence with ASUR targets, heart failure, malnutrition and non-invasive mechanical ventilation were chosen as main topics for the year 2017 and practical training, internal courses and focus groups were planned.A relevant percentage of health care workers (45%) responded to our online survey and the analysis of the results has been used for planning users-centered educational courses; this approach represents a sure novelty in failure of published experiences about the relationship between collection of needs and CME planning.

In the responsiveness of microglia to toxic stimuli, plasma membrane proteins play a key role. In this study we treated with a synthetic beta amyloid peptide murine microglial cells metabolically differently labelled with stable isotope amino acids (SILAC). The plasma membrane was selectively enriched by a multi-stage aqueous two-phase partition system. We were able to identify by 1D-LC-MS/MS analyses 1577 proteins, most of them are plasma membrane proteins according to the Gene Ontology annotation. An unchanged level of amyloid receptors in this data set suggests that microglia preserve their responsiveness capability to the environment even after 24-h challenge with amyloid peptides. On the other hand, 14 proteins were observed to change their plasma membrane abundance to a statistically significant extent. Among these, we proposed as reliable biomarkers of the inflammatory microglia phenotype in AD damaged tissues MAP/microtubule affinity-regulating kinase 3 (MARK3), Interferon-induced transmembrane protein 3 (IFITM3), Annexins A5 and A7 (ANXA5, ANXA7) and Neuropilin-1 (NRP1), all proteins known to be involved in the inflammation processes and in microtubule network assembly rate.

Protease-activated receptor-1 (PAR1) is the prototypic member of a family of four G-protein-coupled receptors that signal in response to extracellular proteases. In the peripheral nervous system, the expression and/or the role of PARs are still poorly investigated. High PAR1 mRNA expression was found in the rat dorsal root ganglia and the signal intensity of PAR1 mRNA increased in response to sciatic nerve transection. In the sciatic nerve, functional PAR1 receptor was reported at the level of non-compacted Schwann cell myelin microvilli of the nodes of Ranvier. Schwann cells are the principal population of glial cells of the peripheral nervous system which myelinate axons playing an important role during axonal regeneration and remyelination. The present study was undertaken in order to determine if the activation of PAR1 affects the neurotrophic properties of Schwann cells. Our results suggest that the stimulation of PAR1 could potentiate the Schwann cell ability to favour nerve regeneration. In fact, the conditioned medium obtained from Schwann cell cultures challenged with a specific PAR1 activating peptide (PAR1 AP) displays increased neuroprotective and neurotrophic properties with respect to the culture medium from untreated Schwann cells. The proteomic analysis of secreted proteins in untreated and PAR1 AP-treated Schwann cells allowed the identification of factors differentially expressed in the two samples. Some of them (such as macrophage migration inhibitory factor, matrix metalloproteinase-2, decorin, syndecan 4, complement C1r subcomponent, angiogenic factor with G patch and FHA domains 1) appear to be transcriptionally regulated after PAR1 AP treatment as shown by RT-PCR.

Schwann cells (SCs) regulate a wide variety of axonal functions in the peripheral nervous system, providing a supportive growth environment following nerve injury (1). Here we show that rat SCs express the protease-activated receptor-1 (PAR1) both in vivo and in vitro. PAR1 is a G-protein coupled receptor eliciting cellular responses to thrombin and other proteases (2). To investigate if PAR1 activation affects the neurotrophic properties of SCs, this receptor was activated by a specific agonist peptide (TFLLR) and the conditioned medium was transferred to PC12 pheocromocytoma cells for assessing cell survival and neurite outgrowth. Culture medium from SCs treated with 10 µM TFLLR reduced significantly the release of LDH and increased the viability of PC12 cells with respect to the medium of the untreated SCs. Furthermore, conditioned medium from TFLLR-treated SCs increased neurite outgrowth on PC12 cells respect to control medium from untreated cells. To identify putative neurotrophic candidates we performed proteomic analysis on SC secretoma and real time PCR experiments after PAR1 activation. Stimulation of SCs with TFLLR increased specifically the release of a subset of five proteins: Macrophage migration inhibitory factor (Mif), Aldose reductase (Akr1b1), Matrix metalloproteinase-2 (Mmp2), Syndecan-4 (Sdc) and Decorin (Dcn). At the same time there was a significant decrease in the level of three proteins: Complement C1r subcomponent (C1r), Complement component 1 Q subcomponent-binding protein (C1qbp) and Angiogenic factor with G patch and FHA domains 1 (Aggf1). These data indicate that PAR1 stimulation does induce the release by SCs of factors promoting cell survival and neuritogenesis. Among these proteins, Mif, Sdc, Dcn and Mmp2 are of particular interest., Italian Journal of Anatomy and Embryology, Vol. 121, No. 1 (Supplement) 2016

This paper investigates the economic consequences of migration in the Ramsey-type dynamic optimizing context. In contrast to Hazari and Agro (J Econ Dyn Control 28:141–151, 2003) conclusions, we show that migration unambiguously reduces the per-capita domestic consumption growth, whereas necessarily raises the long-run per-capita consumption of domestic residents when production is “sufficiently” reactive to capital changes. Our findings are consistent with several empirical studies and simulation analyses, suggesting that changes in technological adjustment in response to migrants inflows may take some years to translate into productivity, generating some crowding out effects. The gains for natives are likely to materialize in the long run when the specialization of natives adjusts, firms invest in capital and adopt appropriate technologies.

In this paper we consider the social efficiency of the regular R&D network of oligopolistic firms, where every firm has the same nu mber o f partners engaged in research activ ities. In the studies conducted by Goyal-Moraga (2003) and Korkmaz (2012), the social welfare is maximised at some intermediate and undetermined level of connectivity (degree) if the rate of spillovers is higher than an undetermined threshold. In order to analyse the impact of spillovers' rate on the socially desirable level of collaborative research, we p rovide the analytical determination of both optimal degree of R&D collaboration and threshold level of spillovers. We find that an increasing nu mber o f firms reduces the threshold level, thus making a partial connection more desirab le fro m a social point of view. We also show that for a s mall rate of spillovers, private and social incentives coincide and the efficient network is comp lete, while for sufficiently high level of spillovers firms tend to form too many links.

We analyse the dynamics of the distribution of democratic values in a population whereagents have heterogeneous preferences about democracy, distinguishing betweenfundamentalist-antidemocratic agents and pro-democracy agents. Cultural traits and normsare acquired through a process of intergenerational cultural transmission and socialization.The driving force in the equilibrium selection process is the education effort exerted byparents; this depends on the distribution of democratic values in the population and onexpectations about future policies affecting formal and informal institutions.The main result is that when fundamentalism is sufficiently diffused in all institutionaldimensions of social life, the imposition of formal democratic rules do not significantly affectsocial preferences. On the other hand the model shows how a cruel fundamentalistdictatorship cannot wholly destroy democratic preferences in the population; the sole result isa fictitious homologation of manifested attitudes, with no preferences dynamics and theprevious real attitudes immediately emerging as soon as dictatorship falls.

Microglia are macrophages within the central nervous system playing a central role in neurodegenerative disorders. Although the initial engagement of microglia seems to be neuroprotective, many lines of ev- idence indicate that its persistent activation contributes to dismantle neuronal activity and to induce neuronal loss. The molecular pathways that lead from amyloid interaction with membrane receptors to the microglial activation have been extensively investigated, although a definitive picture is not yet at hand. In this work, primary and immortalized microglial cells were treated with a synthetic form of Aβ peptides, and relative abundance of acetylated and phosphorylated STAT3 were assayed. Results high- light, for the first time, three distinctive sequential events: i) an earlier event marked by the increase in the level of STAT3 acetylated species, followed by ii) a later increase in the level of STAT3 phosphory- lated form, and finally iii) an involvement of phosphorylated STAT3 in the increase in expression of the 14-3-3 epsilon, a protein frequently associated with neurodegenerative diseases and known to be a marker of Aβ-activated microglia. These data outline a complex, time-dependent modification of STAT3 signal- ling triggered by amyloid in the microglial compartments, that once confirmed by in vivo experiments will broaden the knowledge of the molecular basis of amyloid neurotoxicity.

The attentional blink, a measure of the temporal dynamics of visual processing, has been documented to be more pronounced following brain lesions that are associated with visual neglect. This suggests that, in addition to their spatial bias in attention, neglect patients may have a prolonged dwell time for attention. Here the attentional dwell time was examined in patients with damage focused on either posterior parietal or frontal cortices. In three experiments, we show that there is an abnormally pronounced attentional dwell time, which does not differ in patients with posterior parietal and with frontal lobe lesions, and this is associated with a measure of selective attention but not with measures of spatial bias in selection. These data occurred both when we attempted to match patients and controls for overall differences in performance and when a single set stimulus exposure was used across participants. In Experiments 1 and 2, requiring report of colour-form conjunctions, there was evidence that the patients were also impaired at temporal binding, showing errors in feature combination across stimuli and in reporting in the correct temporal order. In Experiment 3, requiring only the report of features but introducing task switching led to similar results. The data suggest that damage to a frontoparietal network can compromise temporal selection of visual stimuli; however, this is not necessarily related to a deficit in hemispatial visual attention but it is to impaired target selection. We discuss the implications for understanding visual selection.

Recent studies have revealed the presence of a mesenchymal stem cell (MSC) population in human and in gilt granulosa cells (GCs), thus increasing the interest in identifying the same population in the bovine species. We first isolated GCs by scraping from bovine preovulatory follicles and then tested several different media to define the ideal conditions to select granulosa-derived stem cells. Although expressing MSC-associated markers, none of the media tested proven to be efficient in selecting MSC-like cells that were able to differentiate into mesodermic or ectodermic lineages. We performed another experimental approach exposing cells to a chemical stress, such as lowering of pH, as a system to select a more plastic population. Following the treatment, granulosa-specific granulose markers [follicle-stimulating hormone receptor (FSHR), follistatin (FST), and leukemia inhibitory factor receptor (LIFR)] were lost in bovine GCs, whereas an increase in multi- (CD29, CD44, CD73) and pluripotent (Oct-4 and c-Myc) genes was noticed. The stress allowed up-regulation of tumor necrosis factor-α and interleukin-1β expression and the dedifferentiation of GCs, which was demonstrated by differentiation studies. Indeed, pH-treated cells were able to differentiate into the mesodermic and ectodermic lineages, thus suggesting that the chemical stress allows for the selection of cells that are more prone to adjust and respond to the environmental changes.

Infection, neurodegeneration, and other conditions associated with loss of brain homeostasis, induce changes in microglial morphology, gene expression and function, generally referred to as “activation”. Alzheimer’s disease (AD) is the most common dementia and is characterized by neuroinflammatory changes, including alterations in the morphology and distribution of microglia and astrocytes, and deposition of complement and other inflammatory mediators. Our previous observations show that microglial cells challenged in vitro with amyloid peptides clustered and rounded up, dramatically changing their morphology. Besides, in these cells we observed the early acetylation and then the phosphorylation of STAT3 which is required for the expression of the epsilon isoform of 14-3-3, a marker of Abeta-activated microglia (1, 2). We applied affinity partitioning approach combined with high throughput mass spectrometric analysis in order to identify variation of proteins on plasma membrane of BV2 immortalized microglia upon treatment with amyloid peptides. By this method several proteins up- or down-regulated by amyloid treatment were identified in microglial plasma membrane. Among them annexins (5 and 7), IFITM3 and MARK3. These data have been confirmed in primary microglial cultures., Italian Journal of Anatomy and Embryology, Vol. 121, No. 1 (Supplement) 2016

In this paper we develop two simple discrete-time Ramsey models augmented with migrant workers to assess the impact of migration on per-capita domestic consumption. In one model we assume perfect substitutability between migrants and natives while in a second model we explore the effect of migration in the case of imperfect substitutability. We find that migration unambiguously rises per-capita domestic consumption growth in the case of perfect substitutability in the short as well as in the long run, while in the case of imperfect substitutability migration increases the long-run per-capita domestic consumption only if production is 'sufficiently' reactive to capital changes. Our findings are partially in contrast to similar analyses developed in continuous time (in particular those of Hazari and Sgro (2003) and Moy and Yip (2006)).

In this paper, we analyze the role of cooperation between firms through a model of growth and social capital. In a growth model à la Solow we incorporate the set of resources that a relational network has at its disposals, as a distinct production factor, and thus examine its dissemination through evolutionary type processes in firm interactions. Dynamic analysis of the model demonstrates that cooperation is able to increase the productivity of factors, fostering a higher rate of growth in the long term. The most significant result is that scarcity of social capital can produce a general collapse of the economic system in areas in which long term growth is usually sustained by the learning by doing and spillover of knowledge phenomena. This conclusion leads to reconsider the role of local development economic policies that should concentrate on activities that promote repeated interaction between firms proven to be cooperative or that encourage the formation of technological consortia.

The allocation of overt visual attention while viewing photographs of natural scenes is commonly thought to involve both bottom-up feature cues, such as luminance contrast, and top-down factors such as behavioural relevance and scene understanding. Profiting from the fact that light sources are highly visible but uninformative in visual scenes, we develop a mixture model approach that estimates the relative contribution of various low and high-level factors to patterns of eye movements whilst viewing natural scenes containing light sources. Low-level salience accounts predicted fixations at luminance contrast and at lights, whereas these factors played only a minor role in the observed human fixations. Conversely, human data were mostly explicable in terms of a central bias and a foreground preference. Moreover, observers were more likely to look near lights rather than directly at them, an effect that cannot be explained by low-level stimulus factors such as luminance or contrast. These and other results...

The paper suggests a formulation of innovations implementation and transfer processes in the sphere of evolutionary games theory. The original model, in which uncooperative behaviours on the part of firms tend to prevail, is representative of the mistrust in establishing partnership, that we note in a productive system, like the Italian one, formed by SMEs. In order to obtain cooperative solutions as game outcome, it is necessary the participation of metamanagement institutions as the consortia assisted by local institutions (universities included). In two variants of our model, we study how by "one-to-many" (not any more by "one-to-one") interactions, and by repeated interactions, in addition to local institutions governance, cooperation can emerge and spread.

Protease-activated receptor-1 (PAR-1) is the prototypic member of a family of four G-protein-coupled receptors that signal in response to extracellular proteases. In the peripheral nervous system, the expression and/or the role of PARs are still poorly investigated. High PAR-1 mRNA expression was found in the rat dorsal root ganglia and the signal intensity of PAR-1 mRNA increased in response to sciatic nerve transection, both in the proximal and in the distal part of the lesioned nerve (1). Other authors revealed that functional PAR-1 receptor exists specifically in the non-compacted Schwann cell myelin microvilli at the nodes of Ranvier in the sciatic nerve (2). Schwann cells are the principal population of glial cells of the peripheral nervous system which myelinate axons playing an important role during axonal regeneration and remyelination (3). The present study was aimed to determine if the activation of PAR-1 affects the neurotrophic properties of Schwann cells. We observed a specific staining for PAR-1 in Schwann cells of rat sciatic nerve and also in primary Schwann cell cultures. To study the role of PAR-1 in Schwann cell cultures, we activated this receptor with a specific activating peptide (PAR-1 AP). Conditioned medium from PAR-1 AP-treated Schwann cells reduced the LDH release of PC12 cells respect to the medium of the untreated cells, suggesting that the stimulation of PAR-1 induces the production of pro-survival molecules. Also an increased neurite outgrowth on PC12 cells was observed using the conditioned medium from Schwann cells treated with PAR-1 AP respect to the control obtained from untreated cells. The synthesis and secretion of several factors produced by Schwann cells treated with PAR-1 AP were investigated by proteomics, western blot and RT-PCR analyses. By these experiments we identified as putative neurotrophic candidates some molecules, such as Macrophage migration inhibitory factor, Syndecan 4 and Annexin A2., Italian Journal of Anatomy and Embryology, Vol. 120, No. 1 (Supplement) 2015

PAR-1 (Protease-activated receptor–1) is a G-protein-coupled receptor that elicits cellular responses to extracellular proteases such as thrombin. In the peripheral nervous system (PNS), the expression and/or the role of PAR-1 are still poorly investigated. Several authors speculated that many functions in PNS, such as motor, secretory, vascular, nociceptive, inflammatory or regenerative processes, may be regulated by PARs (Vergnolle et al. 2003; Shavit et al., 2008; Wang et al., 2013). The present study was aimed to determine if PAR-1 activation affects neurotrophic properties of Schwann cells. By double immunofluorescence experiments we observed a specific staining for PAR-1 in S100β-positive cells of rat sciatic nerve and sciatic teased fibres. Moreover, PAR-1 was highly expressed in Schwann cell cultures obtained from both neonatal and adult rat sciatic nerves. When PAR-1 specific agonists were added to these cultures a higher proliferation rate was observed. Moreover, conditioned medium from primary Schwann cells treated with PAR-1 agonists increased cell survival and neurite outgrowth of PC12 cells. Therefore synthesis and secretion of several factors by Schwann cells treated with PAR-1 agonist peptides were investigated by RT-PCR, western blot and proteomics analysis. By these experiments some molecules, including extracellular matrix components and adhesion molecules, were identified as putative neurotrophic candidates., Italian Journal of Anatomy and Embryology, Vol 119, No 1 (Supplement) 2014

Microglia are resident macrophages in the central nervous system, whose participation against exogenous injuries and infections is mainly marked by an immediate release of inflammatory cytokines along with a toxic efflux of superoxide radicals. Indeed, many lines of evidence indicate that persistent activation of these cells turns their neuroprotective phenotype into a neurotoxic one, which contributes to destroy neuronal activity and induces neuronal loss in several neurodegeneration processes, such as Alzheimer's disease. In this study we attempted to fill-in the gap in our knowledge about redox regulation of amyloid activated microglia. With this aim, we carried out a robust and comprehensive characterization of the reversibly redox modified proteome both at the level of resting and amyloid-activated BV2 cells, an immortalised cell line of murine microglia. The approach we used combined the selective enrichment of reversible redox modified proteins through a biotin bait with nanoscale liquid chromatography tandem mass spectrometry of their proteolytic peptides. By this reliable approach, we identified 60 proteins changing the redox status of their selective cysteine residues upon treatment with the amyloidogenic Aβ25–35 peptide. These results assessed that in microglia stimulated by amyloids, redox modifications of the proteome specifically target proteins involved in crucial cell processes, i.e. those involved in the protein synthesis. In particular, for peroxiredoxin-6 (Prdx6) and Ras-related C3 botulinum toxin substrate 1 (Rac1) we suggest mechanisms through which reversible redox modifications could affect the peculiar role of microglia in amyloidogenic injury, which at the same time reinforce the oxidative burst and resist toward it. Moreover, the redox modulation we observed on chloride intracellular channel protein 1 (CLIC1) strengthens the structural and functional relationship between the oxidative stress and the metamorphic transition of this protein from a soluble form to an integral membrane form. The redox signatures we determined might also provide neurologists with more specific and reliable biomarkers to distinguish the diverse microglia status in neurodegeneration and then to drive targeted drug design.

A perpetual scarcity of public goods/services produces distortions of an individual's attitudes towards the cost of bureaucratic procedures: even if bureaucracy is not cumbersome, poverty induces people to perceive honesty as too expensive and to prefer illegal payments because they cannot completely satisfy their needs by following the legal bureaucratic procedures. So traditional anticorruption measures such as the increase in corruption costs or the organization of public education campaigns would not permanently reduce corruption levels if poverty remains diffused. Using an overlapping generation model based on a mechanism of cultural transmission, we study the evolution both of social attidudes towards bureaucratic corruption and the institutional framework. Theoretical analysis displays how in poorer countries corruption appears to be a permanent state; institutional reforms are blocked and the only relevant anticorruption intervention consists in public education campaigns. However, also in this case, we simply obtain a temporary reduction of corruption. We call this situation "the corruption trap" because the preferences of population always converge to equilibria with a very high proportion of corrupt agents and honesty is only a temporary state due to anticorruption measures. Similar situations could be observed in developed countries with high levels of corruption owing to unexpected institutional shoks. Finally, we empirically corroborate the model's implications in a cross-country framework, using both corruption indices and a new data-set which measures the population's expectation of future corruption for each country.

In this paper we analyze how firms’ R&D investment decisions, firms’ profits and social welfare are affected by absorptive capacity; that is, the ability of a firm to learn from other collaborating firms. The model developed is a strategic regular network where firms have the opportunity to form pair-wise collaborative links with other firms and then compete à la Cournot. Different to the existing literature, we find that firms’ R&D efforts could increase or decrease with the degree of the network, depending on the level of absorptive capacity, the market size and the network dimension. In particular, in the case of small market size and low learning effect, the connection between firms drives up research investments. Moreover, if absorptive capacity is sufficiently low, the research collaboration between firms turns out not to be desirable from a private point of view while, in line with the existing literature, social efficiency requires a complete or intermediate level of collaborative activity. We also show that the complete network is pair-wise stable and socially optimal for an intermediate level of spillover intensity, while the empty network maximizes firms’ profits when absorptive capacity is small, yet it is not pair-wise stable.

This article derives optimal fiscal rules within a stochastic model of Keynesian type in the context of Poole (1970). By using optimal control theory and applying the Hamilton–Jacobi–Bellman equation, we extend the original Poole results concerning the output stabilization properties of monetary policy to the case of fiscal policy. In particular, we look for the optimal setting of government expenditure and lump-sum taxation in the case that the fiscal authority wishes to keep the product close to a reference value and that the economy is assumed to be affected by stochastic disturbances of real and/or monetary type. According to our findings an expenditure rule is preferable to a taxation rule when the two instruments are independent. The introduction of a fiscal budget rule can make taxation preferable under a certain model parametrization.