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- L'Episcopo, F, et al.
(author)
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GSK-3β-induced Tau pathology drives hippocampal neuronal cell death in Huntington's disease : involvement of astrocyte-neuron interactions
- 2016
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In: Cell Death and Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 7, s. 1-14
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Journal article (peer-reviewed)abstract
- Glycogen synthase kinase-3β (GSK-3β) has emerged as a critical factor in several pathways involved in hippocampal neuronal maintenance and function. In Huntington's disease (HD), there are early hippocampal deficits both in patients and transgenic mouse models, which prompted us to investigate whether disease-specific changes in GSK-3β expression may underlie these abnormalities. Thirty-three postmortem hippocampal samples from HD patients (neuropathological grades 2-4) and age- and sex-matched normal control cases were analyzed using real-time quantitative reverse transcription PCRs (qPCRs) and immunohistochemistry. In vitro and in vivo studies looking at hippocampal pathology and GSK-3β were also undertaken in transgenic R6/2 and wild-type mice. We identified a disease and stage-dependent upregulation of GSK-3β mRNA and protein levels in the HD hippocampus, with the active isoform pGSK-3β-Tyr(216) being strongly expressed in dentate gyrus (DG) neurons and astrocytes at a time when phosphorylation of Tau at the AT8 epitope was also present in these same neurons. This upregulation of pGSK-3β-Tyr(216) was also found in the R6/2 hippocampus in vivo and linked to the increased vulnerability of primary hippocampal neurons in vitro. In addition, the increased expression of GSK-3β in the astrocytes of R6/2 mice appeared to be the main driver of Tau phosphorylation and caspase3 activation-induced neuronal death, at least in part via an exacerbated production of major proinflammatory mediators. This stage-dependent overactivation of GSK-3β in HD-affected hippocampal neurons and astrocytes therefore points to GSK-3β as being a critical factor in the pathological development of this condition. As such, therapeutic targeting of this pathway may help ameliorate neuronal dysfunction in HD.
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- Nagaraja, Ch., et al.
(author)
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Opening remarks
- 2016
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Conference paper (peer-reviewed)
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- Bonetti, F., et al.
(author)
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Challenging Models : Formalizing Quests in Gamified Systems for Behavioral Change
- 2023
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In: Proceedings - 2023 ACM/IEEE International Conference on Model Driven Engineering Languages and Systems Companion, MODELS-C 2023. - : Institute of Electrical and Electronics Engineers Inc.. - 9798350324983 ; , s. 747-756
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Conference paper (peer-reviewed)abstract
- Tasks performed by users in exchange for some reward, also known as quests or challenges, are one of the essential elements found in gamified systems, including systems for behavioral change. These elements can be tailored to specific players, according to their profile features and past performance, in order to deliver a more personalized and motivating experience. However, in order to automatically generate challenges, a formal, generalizable model of the essential building blocks of such game elements and their internal relations is needed. Although some work has been carried out in the past to define quests and challenges, a widely agreed-upon definition is still missing. Such an abstract definition should be employable across different application domains and scenarios and be flexible with respect to implementation details and human factors. In this work, we employ a model-driven approach to (1) propose a formal definition of quests and challenges in gamified systems, focusing on systems for behavioral change in the mobility domain, (2) model quests by means of a Domain-Specific Language implementing the proposed definition, and (3) take the first steps towards automatic rule generation by demonstrating a mapping between our model and Drools syntax compatible with an existing gamification engine. In particular, we illustrate how to ease the implementation of quests and challenges by using an example from an existing gamified system in the sustainable mobility domain.
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- Bucchiarone, A., et al.
(author)
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Gamifying model-based engineering : the PapyGame experience
- 2023
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In: Software and Systems Modeling. - : Springer Science and Business Media Deutschland GmbH. - 1619-1366 .- 1619-1374.
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Journal article (peer-reviewed)abstract
- Modeling is an essential and challenging activity in any engineering environment. It implies some hard-to-train skills such as abstraction and communication. Teachers, project leaders, and tool vendors have a hard time teaching or training their students, co-workers, or users. Gamification refers to the exploitation of gaming mechanisms for serious purposes, like promoting behavioral changes, soliciting participation and engagement in activities, etc. We investigate the introduction of gaming mechanisms in modeling tasks with the primary goal of supporting learning/training. The result has been the realization of a gamified modeling environment named PapyGame. In this article, we present the approach adopted for PapyGame implementation, the details on the gamification elements involved, and the derived conceptual architecture required for applying gamification in any modeling environment. Moreover, to demonstrate the benefits of using PapyGame for learning/training modeling, a set of user experience evaluations have been conducted. Correspondingly, we report the obtained results together with a set of future challenges we consider as critical to make gamified modeling a more effective education/training approach.
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- Cisbani, G, et al.
(author)
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Cystamine/cysteamine rescues the dopaminergic system and shows neurorestorative properties in an animal model of Parkinson's disease.
- 2015
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In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 82, s. 430-444
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Journal article (peer-reviewed)abstract
- The neuroprotective properties of cystamine identified in pre-clinical studies have fast-tracked this compound to clinical trials in Huntington's disease, showing tolerability and benefits on motor symptoms. We tested whether cystamine could have such properties in a Parkinson's disease murine model and now provide evidence that it can not only prevent the neurodegenerative process but also can reverse motor impairments created by a 6-hydroxydopamine lesion 3weeks post-surgery. Importantly, we report that cystamine has neurorestorative properties 5weeks post-lesion as seen on the number of nigral dopaminergic neurons which is comparable with treatments of cysteamine, the reduced form of cystamine used in the clinic, as well as rasagiline, increasingly prescribed in early parkinsonism. All three compounds induced neurite arborization of the remaining dopaminergic cells which was further confirmed in ex vivo dopaminergic explants derived from Pitx3-GFP mice. The disease-modifying effects displayed by cystamine/cysteamine would encourage clinical testing.
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