Innovazione e rete come chiavi del rilancio dei distretti

Associazione per lo Sviluppo del Distretto della Sedia (ASDI Sedia

Erythropoietin (EPO) receptor activity: in vitro effects of EPO derivatives.

In endothelial cells, Erythropoietin receptors (EPO-R) mediate the protective, proliferative and angiogenic effects of EPO and its analogues, which act on EPO-R as receptor agonists. Since hormonal receptors are known to undergo functional changes upon chronic exposure to their agonists, and since erythropoiesis stimulating agents (ESAs) are used for the long-term treatment of anemic states, it is crucial to dissect how the responsiveness of these receptors is regulated at vascular level after prolonged exposure to ESAs. In the present research, we investigated EPO-R desensitization/resensitization in human umbilical vein endothelial cells (HUVEC) upon exposure to three ESAs with different pharmacokinetic profiles: epoetin alpha (EPOα), darbepoetin alpha (DarboEPO) and continuous EPO-R activator (CERA). All these agonists induced the activation of the transcription factor STAT5, the intracellular pathway associated with EPO-R, with monophasic or biphasic kinetics for EPOa/DarboEPO and CERA, respectively. All epoetins induced EPO-R desensitization with a kinetics faster for CERA, with respect to EPOa and DarboEPO. However, recovery of receptor responsiveness was strictly dependent on the type of epoetin, the agonist concentration and the time of exposure to agonist (desensitization time). EPO-R resensitization occurred with faster kinetics after exposure to low epoetins concentrations for a short desensitization time. When the highest concentration of agonists was tested, recovery of receptor responsiveness was faster with CERA with respect to EPOa, and was completely absent with DarboEPO. Our results demonstrate the three ESAs regulate EPO-R resensitization in a highly different way, demonstrating that the type of molecule and the length of EPO-R stimulation are crucial factors in the control of EPO-R function in endothelial cells

Progetto preliminare per una biblioteca alla Spezia

La tesi si sviluppa in tre sezioni principali, a loro volta suddivise in capitoli e/o paragrafi: “SEZIONE 1 – fase informativa”, “SEZIONE 2 – dpp”, “SEZIONE 3 – il progetto”. La prima sezione raccoglie la fase di ricerca della tesi in cui si approfondiscono fondamentalmente due temi: il tema della città della Spezia da un punto di vista storico ed urbanistico e il tema della biblioteca da un punto di vista generale e locale. La seconda sezione contiene il documento preliminare all’avvio alla progettazione, cioè il dpp; come sarà in essa meglio specificato, con questo documento si delineano le linee guida per la progettazione sia da un punto di vista normativo che prestazionale. La terza sezione, infine, illustra il progetto realizzato, in forma preliminare, concretizzando le indicazioni contenute all’interno del dpp e motivando le scelte progettuali

Residence Time (RT), a new parameter to predict neurosteroidogenic efficacy of Translocator Protein (TSPO) ligands: N,N-dialkyl-2-arylindol-3-ylglyoxylamides, a case study

Targeting neuroactive steroid biosynthetic pathway by specific 18 kDa Translocator Protein (TSPO) ligands may represent a therapeutic approach in a variety of neurodegenerative and neuropsychiatric diseases. However, the lack of correlation between the binding affinity and the in vitro steroidogenic efficacy has limited the identification of lead compounds by a traditional affinity-based drug discovery strategy. Our recent researches indicate that the key factor for robust steroidogenic TSPO ligand efficacy is not the binding affinity per se, but rather the time the compound spends into the target, namely its Residence Time (RT). The assessment of this kinetic parameter during the in vitro characterization of compounds appears mandatory in order to obtain structure-efficacy relationships suitable for the future development of novel molecules with promising pharmacological properties

Trazodone treatment protects neuronal-like cells from inflammatory insult by inhibiting NF-κB, p38 and JNK

Growing evidence suggests that alterations of the inflammatory/immune system contribute to the pathogenesis of major depression and that inflammatory processes may influence the antidepressant treatment response. Depressed patients exhibit increased levels of inflammatory markers in both the periphery and brain, and high co-morbidity exists between depression and diseases associated with inflammatory alterations. Trazodone (TDZ) is a triazolopyridine derivative that belongs to the class of serotonin receptor antagonists and reuptake inhibitors. Although the trophic and protective properties of classic antidepressants have extensively been exploited, the effects of TDZ remain to be fully elucidated. In this study, the pharmacological activities of TDZ on human neuronal-like cells were investigated under both physiological and inflammatory conditions. An in vitro inflammatory model was established using lipopolysaccharide (LPS) and tumour necrosis factor-α (TNF-α), which efficiently mimic the stress-related changes in neurotrophic and pro-inflammatory genes.Our results showed that TDZ significantly increased the mRNA expression of both brain-derived nerve factor (BDNF) and cAMP response element-binding protein (CREB) and decreased the cellular release of the pro-inflammatory cytokine interferon gamma (IFN-γ) in neuronal-like cells.In contrast, neuronal cell treatment with LPS and TNF-α decreased the expression of CREB and BDNF and increased the expression of nuclear factor kappa B (NF-κB), a primary transcription factor that functions in inflammatory response initiation. Moreover, the two agents induced the release of pro-inflammatory cytokines (. i.e., interleukin-6 and IFN-γ) and decreased the production of the anti-inflammatory cytokine interleukin-10. TDZ pre-treatment completely reversed the decrease in cell viability and counteracted the decrease in BDNF and CREB expression mediated by LPS-TNF-α. In addition, the production of inflammatory mediators was inhibited, and the release of interleukin-10 was restored to control levels.Furthermore, the intracellular signalling mechanism regulating TDZ-elicited effects was specifically investigated. TDZ induced extracellular signal-regulated kinase (ERK) phosphorylation and inhibited constitutive p38 activation. Moreover, TDZ counteracted the activation of p38 and c-Jun NH2-terminal kinase (JNK) elicited by LPS-TNF-α, suggesting that the neuro-protective role of TDZ could be mediated by p38 and JNK.Overall, our results demonstrated that the protective effects of TDZ under inflammation in neuronal-like cells function by decreasing pro-inflammatory signalling and by enhancing anti-inflammatory signalling

Cytokine secretion responsiveness of lymphomonocytes following cortisol cell exposure: Sex differences

The stress hormone cortisol has been recognized as a coordinator of immune response. However, its different ability to modulate the release of inflammatory mediators in males and females has not been clarified yet. Indeed, the dissection of cortisol specific actions may be difficult due to the complex hormonal and physio-pathological individual status. Herein, the release of inflammatory mediators following increasing cortisol concentrations was investigated in an in vitro model of primary human male and female lymphomonocytes. The use of a defined cellular model to assess sex differences in inflammatory cytokine secretion could be useful to exclude the effects of divergent and fluctuating sex hormone levels occurring in vivo. Herein, the cells were challenged with cortisol concentrations resembling the plasma levels achieving in physiological and stressful conditions. The production of cytokines and other molecules involved in inflammatory process was determined. In basal conditions, male cells presented higher levels of some pro-inflammatory molecules (NF-kB and IDO-1 mRNAs, IL-6 and kynurenine) than female cells. Following cortisol exposure, the levels of the pro-inflammatory cytokines, IL-6 and IL-8, were increased in male cells. Conversely, in female cells IL-6 release was unchanged and IL-8 levels were decreased. Anti-inflammatory cytokines, IL-4 and IL-10, did not change in male cells and increased in female cells. Interestingly, kynurenine levels were higher in female cells than in male cells following cortisol stimulus. These results highlighted that cortisol differently affects male and female lymphomonocytes, shifting the cytokine release in favour of a pro-inflammatory pattern in male cells and an anti-inflammatory secretion profile in female cells, opening the way to study the influences of other stressful factors involved in the neurohumoral changes occurring in the response to stress conditions

Investigation on the Adsorption and Photooxidation of Glycerol at TiO2 Nanotubular Arrays

A study is presented on the adsorption of glycerol at TiO2as well as on its oxidative process during the contemporary water Photoelectro-splitting for hydrogen production. A deepening in the understanding on the working mechanism of the TiO2nanotubular photoanodes and on the interactions between glycerol and these structures has been gained through photocurrent tests, voltammetric scans, and EIS analysis. A range of wavelength of the incident radiation is investigated from 340 to 400 nm at which the effect of glycerol on the photocurrent is measured. Quantitative analysis of the EIS results is performed by the equivalent circuit approach

Boas práticas no Núcleo técnico audiovisual da FAC : uma campanha audiovisual

Trabalho de Conclusão de Curso (graduação)—Universidade de Brasília, Faculdade de Comunicação, Departamento de Audiovisual e Publicidade, habilitação em Audiovisual, 2020.Esse Trabalho de Conclusão de Curso constitui a formulação de uma campanha de conscientização interna sobre o manuseio correto dos equipamentos disponibilizados no Núcleo Técnico de Audiovisual da FAC. Busca-se fomentar o cenário de produções científicas da Faculdade de Comunicação, compreendendo a universidade pública como um espaço de amplo apoio à formação de seus estudantes, equipada e preparada. Baseado nos conceitos de comunicação pública, nas ideias de Darcy Ribeiro sobre a Universidade Utópica, e no potencial informativo do vídeo, o projeto explora diferentes possibilidades de aplicação da produção audiovisual para divulgar conhecimento científico. Também abre caminho para uma maior participação coletiva da comunidade acadêmica na manutenção do espaço universitário.This Course Completion Work constitutes the formulation of an internal awareness campaign on the correct handling of the equipment made available at FAC’s Audiovisual Technical Center. The aim is to promote the scientific production scenario of the Faculty of Communication, understanding the public university as a space of broad support for the training of its students, equipped and prepared. Based on the concepts of public communication, on the ideas of Darcy Ribeiro about the Utopian University, and on the informative potential of video, the project explores different possibilities of applying audiovisual production to disseminate scientific knowledge. It also opens the way for greater collective participation by the academic community in maintaining the university space

TSPO ligand residence time: a new parameter to predict compound neurosteroidogenic efficacy

The pharmacological activation of the cholesterol-binding Translocator Protein (TSPO) leads to an increase of endogenous steroids and neurosteroids determining benefic pleiotropic effects in several pathological conditions, including anxiety disorders. The relatively poor relationship between TSPO ligand binding affinities and steroidogenic efficacies prompted us to investigate the time (Residence Time, RT) that a number of compounds with phenylindolylglyoxylamide structure (PIGAs) spends in contact with the target. Here, given the poor availability of TSPO ligand kinetic parameters, a kinetic radioligand binding assay was set up and validated for RT determination using a theoretical mathematical model successfully applied to other ligand-target systems. TSPO ligand RT was quantified and the obtained results showed a positive correlation between the period for which a drug interacts with TSPO and the compound ability to stimulate steroidogenesis. Specifically, the TSPO ligand RT significantly fitted both with steroidogenic efficacy (Emax) and with area under the dose-response curve, a parameter combining drug potency and efficacy. A positive relation between RT and anxiolytic activity of three compounds was evidenced. In conclusion, RT could be a relevant parameter to predict the steroidogenic efficacy and the in vivo anxiolytic action of new TSPO ligands