214 research outputs found
Immunity and Inflammation: from complement system activation in Rheumatoid Arthritis to dysregulated immunometabolism in Systemic Lupus Erythematosus
No full textAutoimmune diseases such as Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) are characterized by a dysregulation of the immune system, leading to a persistent inflammatory condition and the production of several autoreactive antibodies. The first project here described is focused on the complement system activation in RA patients before and after the administration of Abatacept, a biological drug functionally interfering with the second signal of activation of T cells, leading to a reduction the inflammatory status of patients. Particularly, to access the possible dysregulation of this mechanism linked to the inflammatory milieu, plasma and peripheral blood samples from 30 patients with active RA have been analysed by ELISA assay for SC5b-9, C5a and IL-6 and by FACS analysis for the expression of C5a receptor (C5aR or CD88) and CD86 on inflammatory cells (T lymphocytes and monocytes). Patients with active RA showed higher plasma levels of SC5b-9 and IL-6 and increased expression of C5aR and CD86 in circulating monocytes and T cells, compared to healthy controls. After Abatacept treatment all these parameters are decreased. No changing in C5a plasma concentrations have been observed. Data collected confirm the efficacy of Abatacept by interfering in T cells activation, with a consequent decrease of IL-6 plasma levels and CD86 expression on inflammatory cells. Moreover, a possible role of Abatacept in the down regulation of the terminal pathway of CS activation by inhibiting C5b-9 formation could be speculated. The second part of the thesis reports preliminary results about the dysregulated immunometabolism in CD8+ T cells in SLE patients. In order to better understand the possible implication of this subpopulation poorly investigated in the onset of SLE, a comparison between the mitochondrial phenotype CD4+ and CD8+ T cells has been conducted using FACS analysis. The same technique has been used to measure the mitochondrial mass and the transmembrane potential, as well as the ROS production of CD8+ T cells. Then, real-time qPCR allowed the measurement of expression levels of both mitochondrial and IFN-signature related genes. No significant differences have been found between healthy controls and SLE patients concerning the activation phenotype of both CD4+ and CD8+ T cells. Interestingly, effector memory CD8+ T cells show an increment of both mitochondria mass and transmembrane potential in IFNhi SLE patients compared to healthy donors. The 3 results collected need to be implemented and confirmed with other experiment and the cohort should be amplified. Indeed, the project is still on going
Protective role of the dynamin inhibitor Dynasore against the cholesterol-dependent cytolysin of Trueperella pyogenes
No full textThe virulence of many Gram-positive bacteria depends on cholesterol-dependent cytolysins (CDCs), which form pores in eukaryotic cell plasma membranes. Pyolysin (PLO) from Trueperella pyogenes provided a unique opportunity to explore cellular responses to CDCs because it does not require thiol activation. Sublytic concentrations of PLO stimulated phosphorylation of MAPK ERK and p38 in primary stromal cells, and induced autophagy as determined by protein light-chain 3B cleavage. Although, inhibitors of MAPK or autophagy did not affect PLO-induced cytolysis. However, 10 μM 3-hydroxynaphthalene-2-carboxylic acid-(3,4-dihydroxybenzylidene)-hydrazide (Dynasore), a dynamin guanosine 5′-triphosphatase inhibitor, protected stromal cells against PLO-induced cytolysis as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (85 ± 17% versus 50 ± 9% cell viability), measuring extracellular ATP, and kinetic assays. This was a generalized mechanism because Dynasore also protected HeLa cells against streptolysin O. Furthermore, the effect was reversible, with stromal cell sensitivity to PLO restored within 30 minutes of Dynasore removal. The protective effect of Dynasore was not conferred by dynamin inhibition, induction of ERK phosphorylation, or Dynasore binding to PLO. Rather, Dynasore reduced cellular cholesterol and disrupted plasma membrane lipid rafts, similar to positive control methyl-β-cyclodextrin. Dynasore is a tractable tool to explore the complexity of cholesterol homeostasis in eukaryotic cells and to develop strategies to counter CDCs.—Preta, G., Lotti, V., Cronin, J. G., and Sheldon, I. M. Protective role of the dynamin inhibitor Dynasore against the cholesterol-dependent cytolysin of Trueperella pyogenes
Crosslink between SARS-CoV-2 replication and cystic fibrosis hallmarks
No full textSARS-CoV-2, the etiological cause of the COVID-19 pandemic, can cause severe illness in certain at-risk populations, including people with cystic fibrosis (pwCF). Nevertheless, several studies indicated that pwCF do not have higher risks of SARS-CoV-2 infection nor do they demonstrate worse clinical outcomes than those of the general population. Recent in vitro studies indicate cellular and molecular processes to be significant drivers in pwCF lower infection rates and milder symptoms than expected in cases of SARS-CoV-2 infection. These range from cytokine releases to biochemical alterations leading to morphological rearrangements inside the cells associated with CFTR impairment. Based on available data, the reported low incidence of SARS-CoV-2 infection among pwCF is likely a result of several variables linked to CFTR dysfunction, such as thick mucus, IL-6 reduction, altered ACE2 and TMPRSS2 processing and/or functioning, defective anions exchange, and autophagosome formation. An extensive analysis of the relation between SARS-CoV-2 infection and pwCF is essential to elucidate the mechanisms involved in this lower-than-expected infection impact and to possibly suggest potential new antiviral strategies
L'apprendimento per problemi. Una metodologia con funzione orientativa.
No full textProblem based learning . A methodology for vocational training.
The author describes an educational project about vocational training which lasted 7 years.
The project had two main objectives:
1.to identify the students who didn’t want to go to high school and to help them to choose the best alternative for them (apprenticeship or professional training)
2. to plan and implement and evaluate a parallel program for those students. The Parallel Track was an innovative program which was student-centred and used interactive methods like : problem based learning (PBL), role playing sessions, site visits and short work experiences.
The Project followed several steps: teacher training activities, creation of a planning group, creation of educational materials, creation of students working groups, implementation of the educational activities. The Parallel track program lasted 4 months (20 sessions with students) and it was repeated for 7 years.
After 7 years it was held the evaluation of the impact of this Project. 140 students were invited to evaluate this project, 75 went for a semi-structured interviews. They said the Parallel Track program helped them to choose their career, 45% said that they well understood what was necessary to enter in the market labour, 25% understood what to do to look for a job
L’ambivalenza di Malebranche [Malebranche’s Ambivalence]
No full textMalebranche by Mariangela Priarolo is the only general introduction to Malebranche available in the Italian secondary literature. The main contents of this recent monograph are here examined in terms of the intertwining between religion and philosophy that is characteristic of Malebranche’s thought. The overlapping of and oscillation between faith and reason, between revealed religion and intellectual metaphysics are discussed. Finally, the reasons for the ‘disappearance’ of Malebranche as a prominent, classical author of reference in the 19th and 20th century philosophy are considered
L'ambivalenza di Malebranche
No full textMalebranche by Mariangela Priarolo is the only general introduction to Malebranche available in the Italian secondary literature. The main contents of this recent monograph are here examined in terms of the intertwining between religion and philosophy that is characteristic of Malebranche’s thought. The overlapping of and oscillation between faith and reason, between revealed religion and intellectual metaphysics are discussed. Finally, the reasons for the ‘disappearance’ of Malebranche as a prominent, classical author of reference in the 19th and 20th century philosophy are considered
Leibniz: The Philosopher-Scientist
No full textIn the context of an interdisciplinary approach aimed at pointing out the interconnections between science and philosophy in the early modern centuries, no author is probably more interesting than Leibniz
CBE: un modello per la formazione pertinente degli educatori
No full textCommunity based education (CBE) : an educational approach for a relevant training of social educator
The author describes the concept of Community based education and how it could be applied for the training of social educators.
Community based education is a means of implementing a community-oriented educational program. It consists of learning activities that “take place within the community where not only students but also teachers, members of the community and representatives of other sectors are actively engaged throughout the educational experience.”. CBE proposes a new Gestalt : the relationship among university, social services and the community.
In CBE students are sent in the community to identify and solve social and educational problems. Community is a group of individuals and families living together in a defined geographical area. Usually comprising a village, town or city.
The authors describes two educational methods which are used to prepare students before their visit and experience in the community: the learning contract and the Problem based learning sessions led by a tutor.
At the end there is the description of the UNI Program, funded by Kellogg Foundation which involved 15 Universities in Latin America
CFTR Inhibitors Display In Vitro Antiviral Activity against SARS-CoV-2
No full textSeveral reports have indicated that SARS-CoV-2 infection displays unexpected mild clinical manifestations in people with cystic fibrosis (pwCF), suggesting that CFTR expression and function may be involved in the SARS-CoV-2 life cycle. To evaluate the possible association of CFTR activity with SARS-CoV-2 replication, we tested the antiviral activity of two well-known CFTR inhibitors (IOWH-032 and PPQ-102) in wild type (WT)-CFTR bronchial cells. SARS-CoV-2 replication was inhibited by IOWH-032 treatment, with an IC50 of 4.52 μM, and by PPQ-102, with an IC50 of 15.92 μM. We confirmed this antiviral effect on primary cells (MucilAirTM wt-CFTR) using 10 μM IOWH-032. According to our results, CFTR inhibition can effectively tackle SARS-CoV-2 infection, suggesting that CFTR expression and function might play an important role in SARS-CoV-2 replication, revealing new perspectives on the mechanisms governing SARS-CoV-2 infection in both normal and CF individuals, as well as leading to potential novel treatments
L'apprendimento per problemi. Una metodologia con funzione orientativa.
No full textProblem based learning . A methodology for vocational training.
The author describes an educational project about vocational training which lasted 7 years.
The project had two main objectives:
1.to identify the students who didn’t want to go to high school and to help them to choose the best alternative for them (apprenticeship or professional training)
2. to plan and implement and evaluate a parallel program for those students. The Parallel Track was an innovative program which was student-centred and used interactive methods like : problem based learning (PBL), role playing sessions, site visits and short work experiences.
The Project followed several steps: teacher training activities, creation of a planning group, creation of educational materials, creation of students working groups, implementation of the educational activities. The Parallel track program lasted 4 months (20 sessions with students) and it was repeated for 7 years.
After 7 years it was held the evaluation of the impact of this Project. 140 students were invited to evaluate this project, 75 went for a semi-structured interviews. They said the Parallel Track program helped them to choose their career, 45% said that they well understood what was necessary to enter in the market labour, 25% understood what to do to look for a job
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