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The importance of DHA intake to support fetal development and maternal health is well established. In this pilot study we applied the natural abundance approach to determine the contribution of 200 mg/day of DHA supplement to the plasma DHA pool in 19 healthy pregnant women on a free diet.Women received DHA, from pregnancy week 20 until delivery, from an algal source (N=13, Algae group) or from fish oil (N=6, Fish group) with slightly different content of 13C.We measured plasma phospholipids DHA 13C:12C ratio (reported as δ13C) prior to supplementation (T0), after 10 (T1) and 90 days (T2) and prior to delivery (T3).The δ13C of DHA in algae and fish supplements were -15.8±0.2 mUr and -25.3±0.2 mUr (p0.001).DHA δ13C in the Algae group increased from -27.7±1.6 mUr (T0) to -21.9±2.2 mUr (T3) (p0.001), whereas there were not significant changes in the Fish group (-27.8±0.9 mUr at T0 and -27.3±1.1 mUr at T3, p=0.09).In the Algae group 200 mg/day of DHA contributed to the plasma phospholipid pool by a median value of 53% (31-75% minimum and maximum). This estimation was not possible in the fish group.Our results demonstrate the feasibility of assessing the contribution of DHA from an algal source to the plasma DHA pool in pregnant women by the natural abundance approach. Plasma δ13C DHA did not change when consuming DHA of fish origin, with almost the same δ13C value of that of the pre-supplementation plasma δ13C DHA.

The rapid growth of digital technologies and the extraordinary amount of data that devices and applications collect each day are increasingly driving companies to radically transform the business architecture through which they create and appropriate value. However, companies may fail to extract value from digital transformation due to the disconnection between strategy formulation and strategy implementation. Through the analysis of three case studies of firms that digitally transformed their business—namely ABB, CNH Industrial, and Vodafone—this article presents a framework than can help companies implement their digital transformation strategy and thereby renovate their business model.

Objectives To evaluate the association between low regional cerebral oxygen saturation (rScO2) and neurodevelopment in preterm infants classified as no brain injury (NBI). Methods We retrospectively reviewed data of rScO2 monitoring during the first 3 days of life of infants with a gestational age (GA)>10H) and the 24 months neurodevelopment. Results Of the 185 patients who met the inclusion criteria, 31% were classified as BI infants and 69% NBI. BI compared to NBI infants had a significantly lower GA and a higher incidence of complications of prematurity. Mean rScO2 in the first 72 h of life was significantly lower in BI than NBI. NIRS>10H in NBI patients was negatively associated with neurodevelopmental scores both at the univariate and multivariate analysis (p>10H were found to have lower systemic oxygenation than their counterparts with rScO2 Conclusions NIRS>10H in NBI small preterm infants was found to be an independent predictor of neurodevelopment at 24 months and it was associated with low systemic saturation values.

BACKGROUND Early continuous positive airway pressure (CPAP) and surfactant replacement are effective treatments for neonatal respiratory distress syndrome (RDS). CPAP is the first line in preterm infants needing respiratory support, with surfactant replacement in case of CPAP failure (CPAP-F). OBJECTIVES To analyze incidence and factors associated with CPAP-F in preterm infants with RDS. DESIGN, SETTING AND PATIENTS Single-center retrospective database analysis (2004-2017) of inborn infants, gestational age (GA) 24 + 0/7-31 + 6/7 weeks, not intubated on admission to the neonatal intensive care unit, managed with CPAP. CPAP-F was defined as intubation and surfactant administration in the first 72 h of life; CPAP success (CPAP-S) was CPAP alone without need for additional RDS treatments. Demographic, respiratory, and clinical data associated with CPAP-F were studied using logistic regression analysis. RESULTS A total of 562 infants met the inclusion criteria: 252 (44.8%) were CPAP-F and 310 (55.2%) were CPAP-S. The CPAP-F, compared to CPAP-S group, had lower GA and birth weight, and were less likely to receive antenatal steroids or to be vaginal births. Logistic regression showed that the fraction of inspired oxygen (FiO2 ) ≥ 0.23 between 180 and 240 min of life (FiO2 180-240 min) was the strongest factor associated with CPAP-F (odds ratio: 16.01 [95% confidence interval: 10.34-24.81]). CONCLUSION FiO2 180-240 min was highly predictive of CPAP-F in preterm infants. With this model for surfactant administration/CPAP-F, 11.2% of infants would have unnecessarily received treatment, but importantly, 27.7% would have been treated much earlier, with a potential reduction in air leaks and duration of mechanical ventilation.

The paper investigates the incentives of Salop-type oligopolistic firms to cooperate and the architecture of the resulting collaboration networks. We find that when spillovers are exogenous, firm profits are not affected by the network structure. On the contrary, with endogenous spillovers (absorptive capacity) firms tend to form less dense networks. We also seek out the architecture of socially efficient networks, showing that social welfare is maximised in the complete network. Also, given the network structure we conclude that a Salop industry could be characterized by a general tendency to under-connection.

Summary Background & aims Preterm infants are at increased risk of long-term neurodevelopmental disabilities (NDD). Long chain n-3 fatty acids play a key role during the development of the central nervous system and some studies in preterm infants showed benefits of docosahexaenoic acid and arachidonic acid supplementation for visual and cognitive development. In recent years fish oil has been added to the fat blend of intravenous (IV) lipid emulsions (LE) but to date scanty data are available on neurodevelopmental outcome of preterm infants that received fish oil containing LE. We studied the effect of fish oil containing IV LE vs standard IV LE on neurodevelopment in a large cohort of preterm infants who received routine parenteral nutrition (PN) from birth. Methods We retrospectively reviewed the neurodevelopmental outcome of 477 preterm infants (birth weight (BW): 400–1249 g and gestational age (GA) at birth: 24+0 - 35+6 weeks (W)) admitted to our NICU between Oct-2008 and June-2017, who received routine PN with different LE, with and without fish oil (IV-FO vs CNTR). We compared neurodevelopment at 2 years corrected age by the Bayley III development scale and the incidence of NDD. Results Demographics, birth data and the incidence of the main clinical short-term outcomes of prematurity were similar in the two groups (IV-FO: n = 178, GA 197 ± 14 days, BW 931 ± 182 g; CNTR: n = 192, GA 198 ± 15 days, BW 944 ± 194 g). No differences were found in maternal demographics nor in parental education between the two groups. Cognitive score was not significantly different between IV-FO and CNTR (92 ± 15 vs 93 ± 13, p = 0.5). No differences were found in motor and language scores, and in the incidence of NDD in the two groups. Conclusions Contrary to our hypothesis, the use of fish oil containing LE in a large cohort of preterm infants on routine PN did not result in better neurodevelopment. Large randomized controlled trials powered for neurodevelopment are needed to clarify the impact of the widely used fish oil containing LE on neurodevelopment of preterm infants.

Summary Objectives To study the association of hypertriglyceridemia and of lipid tolerance with clinical and nutritional data in preterm infants receiving routine parenteral nutrition. Design We retrospectively studied 672 preterm infants (gestational age 250 mg⋅dL−1. Lipid tolerance was defined as the ratio of plasma triglycerides to the intravenous lipid intake at the time of sampling. Variables associated to hypertriglyceridemia and to lipid tolerance were identified by multiple logistic and linear regression analyses. Results Hypertriglyceridemia occurred in 200 preterm infants (30%), ranging from 67% at 23 weeks to 16% at 31 weeks' gestation. In 138 infants (69%) hypertriglyceridemia occurred at a lipid intake of 2.5 g⋅kg−1 or less. Lipid tolerance was reduced especially in infants of less than 28 weeks’ gestation (14.3 ± 9.3 vs 18.8 ± 10.2, respectively, p Conclusion Preterm infants on routine parenteral nutrition were able to tolerate markedly lower intravenous lipid intakes than the recommended target values of current guidelines. Lipid tolerance was associated with some of the major complication of prematurity, possibly at risk of developing hypertriglyceridemia.

High dietary intakes of phytosterols (Phyto), such as those consumed by vegans and vegetarians, are not recommended for cholesterol-lowering in pregnant women (PW) because the safety of their use during pregnancy has not been fully established [1]. Information on Phyto in pregnancy is very limited.To characterize the maternal-fetal gradient of free and esterified Phyto at the time of delivery in humans.PW who had a term delivery at the Obstetrics and Gynecology Unit of the University Hospital of Padua (Padua, Italy), between November 2016 and March 2017, participated in the study. Fatty acids (FA), cholesterol (Chol), Chol metabolites (7-dehydrocholesterol, 7-DHChol; lathosterol, Latho; 7α-hydroxycholesterol, 7α-OHChol), and Phyto (campesterol, Camp; stigmasterol, Stigma; sitosterol, Sito) were measured in both maternal (MB) and cord blood (CB) at the time of delivery. Non-pregnant adult volunteers (Ref-NA) served as a reference.Thirty-four term PW and 12 Ref-NA signed informed consent and were studied. Plasma total Phyto concentrations in CB were up to 20-fold lower than in MB (p 0.05). Positive and significant correlations were found between total Phyto of MB-CB pairs (p 0.01), and between total FA and Camp of MB (p 0.05). Interestingly, free Chol to Chol ester ratio of CB did not differ from that of MB, and free Phyto to Phyto ester ratios were higher in CB than in MB (p 0.001). No differences were found between Phyto concentrations of MB and Ref-NA. However, free Chol to Chol ester ratio, and free Phyto to Phyto ester ratios were higher in MB than in Ref-NA (p 0.05). Chol synthesis, as indicated by 7-DHChol to 7α-OHChol, Latho to 7α-OHChol, and Latho to Sito ratios, was greatest in CB and lowest in Ref-NA.Our data suggest that free Phyto cross the human placenta more easily than Phyto ester. An elevated Stigma to Chol ratio in CB than in MB was also described for the first time. The impact of these findings on the neonatal outcomes remains to be elucidated.

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 13 C/12 C ratio of disaturated-phosphatidylcholine palmitate (DSPC-PA) in 7 lots of poractant alfa, produced over a year, and among bronchoalveolar lavages of 20 rabbits fed with a standard chow. A pilot study was performed in a rabbit model of lavage-induced surfactant deficiency: 7 control rabbits and 4 treated with exogenous surfactant. The contribution of exogenous surfactant to the alveolar pool was assessed after intra-tracheal administration of 200 mg/kg of poractant alfa. The 13 C content of DSPC-PA was measured by isotope ratio mass spectrometry. The mean DSPC-PA 13 C/12 C ratio of the 7 lots of poractant alfa was -18.8‰ with a SD of 0.1‰ (range: -18.9‰; -18.6‰). The mean 13 C/12 C ratio of surfactant DSPC recovered from the lung lavage of 20 rabbits was -28.8 ± 1.2‰ (range: -31.7‰; -25.7‰). The contribution of exogenous surfactant to the total alveolar surfactant could be calculated in the treated rabbits, and it ranged from 83.9% to 89.6%. This pilot study describes a novel method to measure the contribution of the exogenous surfactant to the alveolar pool. This method is based on the natural variation of 13 C, and therefore it does not require the use of chemically synthetized tracers. This method could be useful in human research and especially in surfactant replacement studies in preterm infants.

The manufacturing processes of commercial probiotic strains may be affected in different ways in the attempt to optimize yield, costs, functionality, or stability, influencing gene expression, protein patterns, or metabolic output. Aim of this work is to compare different samples of a high concentration (450 billion bacteria) multispecies (8 strains) formulation produced at two different manufacturing sites, United States of America (US) and Italy (IT), by applying a combination of functional proteomics, metabolomics, and in vivo analyses. Several protein-profile differences were detected between IT- and US-made products, with Lactobacillus paracasei, Streptococcus thermophilus, and Bifidobacteria being the main affected probiotics/microorganisms. Performing proton nuclear magnetic spectroscopy (1H-NMR), some discrepancies in amino acid, lactate, betaine and sucrose concentrations were also reported between the two products. Finally, we investigated the health-promoting and antiaging effects of both products in the model organism Caenorhabditis elegans. The integration of omics platforms with in vivo analysis has emerged as a powerful tool to assess manufacturing procedures.

We develop a model to examine the link formation and the stability of networks in a Hotelling-type oligopoly. We find that with two firms, the link formation depends on the degree of vertical differentiation regardless of the degree of horizontal differentiation, while, with a greater number of firms, link formation occurs when firms feature high horizontal differentiation but low vertical differentiation.

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.

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.

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.

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.

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.

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.

The intent of the present study was to investigate adenosine receptor sites in brain membranes of the saltwater teleost fish, Mullus surmuletus, using the A1 receptor selective agonist, [3H]CHA, and A2a receptor selective agonist [3H]CGS 21680. The A1 selective agonist, [3H]CHA, bound saturably, reversibly and with high affinity to a single-class of binding sites (Kd 1.47 nM; Bmax 100–190 fmol/mg protein, dependent on fish length). The A2a selective agonist, [3H]CGS 21680, also bound saturably, reversibly and with relative high affinity to a single-class of binding sites (Kd 44.2 nM; Bmax 150–300 fmol/mg protein dependent on fish length). In equilibrium competition experiments, adenosine analogous, NECA, CGS 21680, CHA, CPA, S-PIA, R-PIA, CPCA, DPMA, and xanthine antagonists, DPCPX, XAC, and THEO all displaced [3H]CHA and [3H]CGS 21680 specifically bound to brain membranes from Mullus surmuletus. Specific binding of both [3H]CHA and [3H]CGS 21680 was inhibited by GDPβS. For [3H]CHA the IC50 value was 2.5 ± 0.1 μM, while for [3H]CGS 21680 the IC50 value was 7.7 ± 0.3 μM. Our results indicate that the high affinity binding sites for [3H]CHA have some pharmacological characteristics of mammalian A1 adenosine receptors, while the binding sites for [3H]CGS 21680 appear to be virtually identical to the binding sites for [3H]CHA.

Microglia-mediated inflammation in the central nervous system is a hallmark of the pathogenesis of several neurodegenerative diseases including Alzheimer's disease. Microglial cells activation follows the deposition of amyloid β fibrils and it is generally considered a triggering factor in the early steps of the onset of Alzheimer's disease. Although the initial engagement of microglia seems to play a neuroprotective role, many lines of evidence indicate that a persistent activation with the production of proinflammatory molecules contributes to dismantle neuronal activity and to induce neuronal loss occurring in neurodegenerative diseases. To date, limited proteomic data are available on activated microglial cells in response to extracellular amyloidogenic peptides. In this study, murine microglial cells have been employed to investigate the effects of amyloid β peptides in triggering microglial activation. The response was monitored at the proteome level through a two-dimensional gel electrophoresis-based approach. Results show only a limited number of differentially expressed proteins, among these a more acidic species of the cytosolic actin, and the 14-3-3e protein, found significantly upregulated in Aβ-activated cells. 14-3-3e belongs to a regulatory protein family involved in important cellular processes, including those leading to neurodegenerative diseases, and thus its increased expression suggests a role of this protein in tuning microglia activation.

The paper presents an application of the chaos theory to tourism, a sector in which operators' choices are particularly elaborate and complex. The dynamics of the tourist industry are, in fact, the result of close interactions between units of production, tourist flows, local authorities and natural resources. These interactions do not necessarily lead to a regular trend in the development of the tourist industry as proposed by Butler; on the contrary, irregularities of various types are very possible. The model microfounds rigorously on both the demand and the supply side. Firms and tourists operate under the hypothesis of limited rationality, the former in an oligopolistic context, the latter on the basis of mechanisms of evolutionary selection. Although not exhaustive, the model forms a theoretical platform that can be easily adapted to hypotheses and situations that differ from those originally hypothesized. As a consequence, this paper presents a series of numerical simulations. The results show the chaotic nature of a tourist flow, which limits the practicability of measures introduced to stabilise the system. In their place, measures are needed that stimulate a continuous reshaping of the system in relation to the factors that tend to change it.

Light-emitting objects are perceived as qualitatively different from light-reflecting objects, and the two categories elicit different cortical activity. However, it is unclear whether object luminosity is treated as an independent visual feature, comparable to orientation, motion or colour. Visual search tasks revealed that light-emitting targets led to efficient search when presented with light-reflecting distractors of similar luminance, but this efficiency was induced by the presence of luminance gradients producing the percept of luminosity rather than by luminosity itself. This implies that luminance gradients (not object luminosity) are encoded as features, questioning the existence of specific sensory mechanisms to detect light-emitting objects.

Is democracy exportable? A present-day political doctrine seems to recommend exporting democracy to those countries where diffused religious and social values do not allow the spontaneous growth of democratic institutions. In this paper we present a model that allows us to study the dynamics induced by the exogenous imposition of democracy, when the society is dominated by antidemocratic preferences. We analyze the dynamics of the distribution of democratic values in a population where agents have heterogeneous preferences about democracy, distinguishing between fundamentalist-antidemocratic agents and democratic agents (implicit references to Moslem societies are pervasive in this paper). Cultural traits and norms are acquired through a process of intergenerational cultural transmission and socialization. The driving force in the equilibrium selection process is the education effort exerted by parents; this depends on the distribution of democratic values in the population and on expectations about future policies affecting formal and informal institutions. The main result is that when fundamentalism is sufficiently diffused in all institutional dimensions of social life, the imposition of formal democratic rules do not significantly affect social preferences. This occurs because the existing democratic types perceive their children’s “conversion” to fundamentalism as less costly than the utility cost perceived by fundamentalist types when their children adopt democratic preferences: so fundamentalists’ education effort dominates the dynamic of preferences. As soon as the exogenous imposition is removed the system will again converge to fundamentalist and antidemocratic institutions. We argue that shortsighted behaviour like this by democratic agents might be strongly correlated to the level of economic development. On the other hand the model shows how a cruel fundamentalist dictatorship can not wholly destroy democratic preferences in the population; the sole result is a fictitious homologation of manifested attitudes, with no preferences dynamics and the previous real attitudes immediately emerging as soon as dictatorship falls. JEL classification: E13; P16 Keywords: Democracy, Cultural change, Formation of Preferences

L’approccio tradizionale allo studio della corruzione considera questo fenomeno la diretta conseguenza degli incentivi forniti da norme e vincoli formali agli agenti economici. Il modello sviluppato in questo articolo cerca di evidenziare i limiti di questo approccio, ridimensionando l’importanza delle riforme istituzionali nella lotta alla corruzione ed enfatizzando invece la centralità del ruolo svolto dalla natura delle preferenze sociali nell’affermazione di equilibri senza corruzione. La struttura del modello è quella di un gioco ad informazione incompleta in cui burocrate e utente si trovano a decidere se agire onestamente o illegalmente. Le preferenze dei due agenti sono distinte in base al grado di avversione alla corruzione che li rende più o meno favorevoli alla realizzazione di transazioni illegali. Ogni equilibrio è associato ad una particolare struttura dei costi della corruzione indicativa dello stato d’efficienza delle istituzioni. Miglioramenti istituzionali quindi possono produrre mutamenti nella struttura dei costi e degli incentivi alla corruzione, facilitando il passaggio ad equilibri in cui la strategia dominante è l’onestà. La logica istituzionalista tuttavia incontra seri ostacoli di applicazione; la riforma delle norme, che consentirebbe la riduzione dei livelli di corruzione, comporta costi di natura economica e politica, che nella maggioranza dei casi impediscono o rallentano il necessario cambiamento. La simulazione del modello sembra rivelare come in questi casi l’alternativa più efficace sia quella di un miglioramento strutturale delle preferenze della popolazione, attraverso campagne di sensibilizzazione. A parità di assetto istituzionale, infatti, una maggiore avversione alla corruzione aumenta la consapevolezza del danno sociale da essa arrecato, facilitando il passaggio ad equilibri senza corruzione. Effetti diametralmente opposti si producono se l’intervento punta ad un esclusivo miglioramento delle preferenze a livello burocratico. In questi casi, l’aumento della proporzione di burocrati avversi alla corruzione non riduce il loro potere decisionale e facilita il passaggio ad equilibri di “high bribery” dove gli utenti offrono tangenti relativamente più alte, permettendo ai burocrati di coprire anche i costi morali. Quando la corruzione è “istituzionalizzata”, quindi, il miglioramento delle preferenze a livello burocratico non produce una significativa riduzione dei livelli di corruzione.