1,238 research outputs found

    Viaggio nell'economia

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    Il viaggio nell'economia che ci propone il libro si svolge per tappe significative: il reddito, lo sviluppo, la moneta, le crisi finanziarie, gli squilibri internazionali. Nella convinzione che il ruolo dell'economista, al di là del lavoro teorico, sia anche quello di offrire strumenti utili a trasformare la realtà, migliorando il benessere della gente, gli autori con il loro contributo qualificato ma accessibile promuovono una comprensione più matura e consapevole in una materia che appassiona, perchè coinvolge tutti, ma respinge perchè ai più appare misteriosa

    Effect of neurosteroids on a model lipid bilayer including cholesterol: An Atomic Force Microscopy study

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    Amphiphilic molecules which have a biological effect on specific membrane proteins, could also affect lipid bilayer properties possibly resulting in a modulation of the overall membrane behavior. In light of this consideration, it is important to study the possible effects of amphiphilic molecule of pharmacological interest on model systems which recapitulate some of the main properties of the biological plasma membranes. In this work we studied the effect of a neurosteroid, Allopregnanolone (3α,5α-tetrahydroprogesterone or Allo), on a model bilayer composed by the ternary lipid mixture DOPC/bSM/chol. We chose ternary mixtures which present, at room temperature, a phase coexistence of liquid ordered (Lo) and liquid disordered (Ld) domains and which reside near to a critical point. We found that Allo, which is able to strongly partition in the lipid bilayer, induces a marked increase in the bilayer area and modifies the relative proportion of the two phases favoring the Ld phase. We also found that the neurosteroid shifts the miscibility temperature to higher values in a way similarly to what happenswhen the cholesterol concentration is decreased. Interestingly, an isoform of Allo, Isoallopregnanolone (3β,5α -tetrahydroprogesterone or isoAllo), known to inhibit the effects of Allo on GABAA receptors, has an opposite effect on the bilayer properties

    Effects of neurosteroids on a model membrane including cholesterol: A micropipette aspiration study

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    Amphiphilic molecules supposed to affect membrane protein activity could strongly interact also with the lipid component of the membrane itself. Neurosteroids are amphiphilic molecules that bind to plasma membrane receptors of cells in the central nervous system but their effect on membrane is still under debate. For this reason it is interesting to investigate their effects on pure lipid bilayers as model systems. Using the micropipette aspiration technique (MAT), here we studied the effects of a neurosteroid, allopregnanolone (3α,5α-tetrahydroprogesterone or Allo) and of one of its isoforms, isoallopregnanolone (3β,5α-tetrahydroprogesterone or isoAllo), on the physical properties of pure lipid bilayers composed by DOPC/bSM/chol. Allo is a well-known positive allosteric modulator of GABAA receptor activity while isoAllo acts as a non-competitive functional antagonist of Allo modulation. We found that Allo, when applied at nanomolar concentrations (50-200 nM) to a lipid bilayer model system including cholesterol, induces an increase of the lipid bilayer area and a decrease of the mechanical parameters. Conversely, isoAllo, decreases the lipid bilayer area and, when applied, at the same nanomolar concentrations, it does not affect significantly its mechanical parameters. We characterized the kinetics of Allo uptake by the lipid bilayer and we also discussed its aspects in relation to the slow kinetics of Allo gating effects on GABAA receptors. The overall results presented here show that a correlation exists between the modulation of Allo and isoAllo of GABAA receptor activity and their effects on a lipid bilayer model system containing cholesterol

    Giulia Veronica Varisco

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    The headword explains the biography and the contribution of the author Giulia Varisco to the children's literatur

    IS PREGNENOLONE SULFATE AN ENDOGENOUS MODULATOR OF NICOTINIC ACH RECEPTOR?

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    Pregnenolone sulfate (PregS) is an important endogenous modulator of brain activity. PregS reduces the inhibitory activity of GABAA receptors, increases excitatory neurotransmission potentiating NMDA receptors function, trafficking and glutamate release. These latter actions are mediated by PregS at the level of sigma I receptor, calcium and TRP channels [1]. The peleiotropic mechanism of action of PregS could explain some of the pharmacological effects of the steroid: in preclinical studies PregS is neuroprotective, it potentiates synaptic LTP and improve spatial cognitive performance in rats eventhough the pro-mnestic effect of PregS likely depends on the mode of administration and behavioral model being tested [2]. Because cholinergic transmission is fundamental for cognitive functions such as learning and memory we studied the effect of PregS on the activity of nicotinic Ach receptors (nAchR). Using the patch-clamp technique in the whole-cell configuration we tested PregS on the currents mediated by nAChRs expressed in SH-SY5Y cells and in neurons grown in primary cultures. In SH-SY5Y application of PregS reduced NIC (10 μM) - evoked currents with an IC50 in the low micromolar range (14+9 μM) and a maximal effect of 58+10 %. To investigate the mechanism of PregS antagonism we applied the same concentration (10 μM) of the neurosteroid together with different concentrations of NIC (from 5 to 100 μM). PregS effect was not dependent on agonist concentration suggesting a non competitive mechanism of action. The analysis of the dose-response curves of PregS effect at 10 and 100 μM NIC evidentiates that potency and efficacy of the steroid is unchanged. PregS reduces nAchR-mediated currents by increasing receptor desensitization and this effect is more pronounced at high agonist concentrations. Experiments in primary cultures of cortical and cerebellar neurons have confirmed the antagonistic effect of PregS on NIC-evoked current. The inhibitory effect of PregS of nAchR- mediated current cannot support its activity as cognitivie enhancer. To find a rationale it has to be taken into account an additional complexity resulting from the activity of PregS on a neuronal network: it is possible that the reduction of cholinergic activity be limited to specific inhibitory circuits and that the overall effect will be an improved excitatory neurotransmission. It is also conceivable that PregS effect could be served as a compensatory mechanis

    CAUSAL INFERENCE METHODS IN ENVIRONMENTAL EPIDEMIOLOGY: DIFFERENT APPROACHES TO EVALUATE THE HEALTH EFFECTS OF INDUSTRIAL AIR POLLUTION

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    This thesis represents not only the final milestone of my PhD program, but also the perfect conclusion to 7 years of research in the environmental epidemiology. I was lucky during all these years to be supported and helped by several people, that I would like finally to thank. First and foremost I wish to thank my advisors, Professor Rossella Miglio and MD Francesco Forastiere. I have been Rossella’s student since the age of nineteen, when I first started studying at the University of Bologna. She taught me everything I know regarding biostatistics and epidemiology, and guided me in my personal career, always leaving an open door for me to come back. And this is what happened. I couldn’t chose anyone else but her to be my PhD advisor. Rossella, I really want to thank you for always being there when I need, competent, kind and supportive. I also really want to thank Francesco, director of the Unit of Occupational Epidemiology at the Department of Epidemiology and my advisor for this thesis. He has been my mentor, inspiratory, my example of excellence as a researcher. During the time spent working together in Rome he has always been personally touched and involved in all the studies conducted, showing a passion that I have never seen anywhere else. Francesco, I want to thank you for infusing me, I hope, with at least a part of this passion. I can consider myself an epidemiologist thanks to you and your training. I would like to thank all the colleagues at the Department of Epidemiology in Rome, where I used to work until last year, especially Massimo, Daniela, Carla, Giulia, Chiara, Silvia, Francesca, Lisa, Martina, and many others, for their assistance, help, courage, strong emotions and support for staying sane during this doctoral adventure, and the years working together. I love you and I miss you a lot. The PhD can be very stressing and push you beyond your limits, especially when you have decided to leave your country and start a new life and a new job. I am lucky to have found amazing people who understood that and did everything to make this challenge easier. These people are my new colleagues in Paris, who, I think, where bored to be listening to me complaining every day because I could never rest after work to finish my thesis, that I had spent another weekend depressed studying...nevertheless, they were so understanding and always cheered me up. Among them I would like to thank in particular my new managers Perrine and Patricia, who gave me their unconditioned support and who believed in me. I would have never survived the first year of the PhD without my great colleagues of the 30° cycle in Bologna. They are all full of enthusiasm and optimism and remind me of how I used to be when I was their age. I haven’t gotten a chance to get to really know them since we’ve been all far the ones from the others in these past two years, but they’ve all been so friendly and I wish these younger students the best of luck

    The Economic Case for Electric Vehicles in Public Sector Fleets: An Italian Case Study

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    The paper investigates whether it makes economic sense to use electric vehicles (EVs) in the public sector fleet. Thanks to the data collected in 2018 in 77 public sector entities in an Italian region, Friuli Venezia Giulia, we compare the total cost of ownership of a battery electric vehicle with that of a similar internal combustion engine one. We provide estimates for four scenarios (status quo, social cost internalization, price discounts and a combination of the last two) for three groups of public entities (local health authorities, municipalities and special purpose authorities) regarding passenger cars and mixed-use small light commercial vehicles. We find that, with the current price and cost structure, it makes economic sense to adopt EVs for a positive although relatively small percentage of the public sector fleet

    Recognized Occupational Diseases in Italy's Friuli-Venezia Giulia and Liguria Regions (2010-2021)

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    Background: The study of recognized occupational diseases trend is important to understand the preventive approach needed in the future, however, while numbers of occupational diseases are available on web, data on incidence are missing. The aim of our study was to analyze the trend and the incidence rate ratio (IRR) of recognized occupational diseases in Italy, in Friuli-Venezia Giulia region (FVG) and Liguria region from 2010 to 2021. Methods: Numbers of recognized occupational diseases by the Italian National Insurance for Occupational Diseases (INAIL) were analyzed and incidence were calculated considered the total number of workforces in the area. A Poisson regression model was used to estimate incidence trends. Results: FVG region presented a higher incidence of all occupational diseases compared to Italy and to Liguria in the period considered. The overall incidence in 2019 was 175, 91.8 and 108 cases for 100,000 workers, for FVG, Liguria and Italy respectively. Musculoskeletal disorders (MSDs) were the majority of occupational diseases with 100, 51 and 82.8 cases per 100,000 workers, in FVG, Liguria and Italy, respectively. Incidence of occupational cancers was 16, 10 and 4.9 cases per 100,000 workers, in FVG, Liguria and Italy, respectively. The annual change of incidence from 2010 to 2019 was positive for MSDs (IRR 1.06; 95%CI 1.06 to 1.07) and decreasing for the other causes in Italy. In FVG region the trend was positive for MSDs (IRR 1.05;95%CI 1.04 to 1.06), for respiratory diseases (IRR 1.03; 95%CI 1.00 to 1.05) and pleural plaques (IRR 1.03; 95%CI 1.00 to 1.06). In Liguria the trend was positive for MSDs (IRR 1.17; 95% CI 1.15-1.19) and for pleural plaques (IRR 1.07; 95%CI 1.03-1.12). Stable trends were found for cancers. Declining trend was shown for noise induced hearing loss and skin diseases. Conclusions: FVG region presented a higher incidence of recognized occupational diseases compared to Liguria region and Italian data. Results that can be explained by a higher propensity of claiming for occupational diseases in workers, mainly for MSDs disorders. For cancers and asbestos-related diseases the higher incidence can be attributable to high exposure to asbestos in FVG and Liguria workers mainly in shipyard and dock activities
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