543 research outputs found

    INVESTIGATING GLUTAMATE TOXICITY ASSOCIATED TO PARK2 MUTATIONS IN PRE-CLINICAL MODELS OF PARKINSON¿S DISEASE.

    No full text
    ABSTRACT Background: Park2 mutations cause Autosomal Recessive Juvenile Parkinsonism (ARJP), characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Park2 encodes for a ubiquitin-ligase protein whose mutation upregulates Gluk2, a subunit of the glutamate kainate receptor (KAR), expressed in SNpc neurons. Park2 is highly expressed also in astrocytes and KARs upregulation may induce excitotoxicity both in DA neurons and glia, leading to an early synaptopathy, neuroinflamation and neurodegeneration. Aims and Objectives: 1. To generate Park2 induced pluripotent stem cells (iPSCs)-derived in vitro cellular models; 2. To characterize Park2 iPSCs-derived in vitro cellular models; 3. to test glutamate toxicity due to KAR upregulation in Park2 cellular models. Materials and Methods: Fibroblasts and lymphocytes from Park2 patients and age-matched controls were reprogrammed into iPSCs. The iPSCs were further differentiated into dopaminergic neurons, astrocytes and mesencephalic organoids were generated and differentiated. Protein expression profile was analysed through western blot (WB), qPCR and immunofluorescence (IF). Electrophysiology assessment was performed on dopaminergic neurons and midbrain organoids in order to better functionally profile these models. Results: Gluk2 levels resulted significantly increased in PARK2 midbrain organoids compared to CTR both at WB (p< 0.001) and qPCR analyses (p< 0.001). Gluk2 levels resulted also significantly enhanced in PARK2 astrocytes both at WB (p< 0.05) and qPCR analyses (p< 0.05). TH mRNA and protein levels were significantly increased both in PARK2 dopaminergic neurons (WB p< 0.01; qPCR p< 0.0001; IF p< 0.0001) and midbrain organoids (WB p< 0.01; qPCR p< 0.0001; IF p< 0.0001) compared to CTR. Glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes, resulted enhanced in PARK2 astrocytes and especially in PARK2 midbrain organoids (WB p< 0.001; IF p< 0.01). EAAT2, the astrocytic glutamate transporter resulted reduced in mutated lines (WB p< 0.01). Calcium-imaging and HD-MEAs show an oscillatory augmented reactivity in PARK2 midbrain organoids. Conclusions and perspectives: Gluk2 expression was enhanced in PARK2 astrocytes and midbrain organoids, confirming the previous finding that Park2 mutations lead to KAR upregulation (Maraschi A, 2014). Neuronal reactivity was also found increased in PARK2 midbrain organoids at electrophysiology assessment, maybe linked to glutamate dysregulation. Two innovative findings emerged from this study. First of all, that TH expression resulted increased in PARK2, supporting previous finding that stated an augmented dopamine turnover and a reduced dopamine re-uptake (Jiang H., 2012). This is an impairment that happens early in the neurodegenerative process and that could consequently lead to an excessive oxidative stress and consequent neurodegeneration. The second original result is that PARK2 is associated to an increased astrocytic reactivity and a possible dysfunction of astrocytic glutamate transporter EAAT2. This finding means that astrocytes play a key role in neurodegeneration although it is not clear whether they contribute to the initiation or propagation of it. Their increased reactivity could be the consequence of a glutamate toxicity or glutamate toxicity could result from reactive astrocytes dysfunction, not able to process the excessive glutamate influx. Further studies are required in order to establish Park2 role in TH expression regulation, in astrocytic reactivity induction and in glutamate toxicity

    Data of cost-optimal solutions and retrofit design methods for school renovation in a warm climate

    No full text
    Abstract"Efficient Solutions and Cost-Optimal Analysis for Existing School Buildings" (Paolo Maria Congedo, Delia D’Agostino, Cristina Baglivo, Giuliano Tornese, Ilaria Zacà) [1] is the paper that refers to this article. It reports the data related to the establishment of several variants of energy efficient retrofit measures selected for two existing school buildings located in the Mediterranean area. In compliance with the cost-optimal analysis described in the Energy Performance of Buildings Directive and its guidelines (EU, Directive, EU 244,) [2,3], these data are useful for the integration of renewable energy sources and high performance technical systems for school renovation. The data of cost-efficient high performance solutions are provided in tables that are explained within the following sections.The data focus on the describe school refurbishment sector to which European policies and investments are directed. A methodological approach already used in previous studies about new buildings is followed (Baglivo Cristina, Congedo Paolo Maria, D׳Agostino Delia, Zacà Ilaria, 2015; IlariaZacà, Delia D’Agostino, Paolo Maria Congedo, Cristina Baglivo; Baglivo Cristina, Congedo Paolo Maria, D’Agostino Delia, Zacà Ilaria, 2015; Ilaria Zacà, Delia D’Agostino, Paolo Maria Congedo, Cristina Baglivo, 2015; Paolo Maria Congedo, Cristina Baglivo, IlariaZacà, Delia D’Agostino,2015) [4–8]. The files give the cost-optimal solutions for a kindergarten (REF1) and a nursery (REF2) school located in Sanarica and Squinzano (province of Lecce Southern Italy). The two reference buildings differ for construction period, materials and systems.The eleven tables provided contain data about the localization of the buildings, geometrical features and thermal properties of the envelope, as well as the energy efficiency measures related to walls, windows, heating, cooling, dhw and renewables. Output values of energy consumption, gas emission and costs are given for a financial and a macro-economic analysis.This data article provides 288 and 96 combinations for REF1 and REF2, respectively. The output values are obtained using the software ProCasaClima 2015v.2.0

    Author Correction: Gluten consumption and inflammation affect the development of celiac disease in at-risk children

    No full text
    The original version of this Article contained an error in the spelling of the authors Renata Auricchio, Ilaria Calabrese, Martina Galatola, Donatella Cielo, Fortunata Carbone, Marianna Mancuso, Giuseppe Matarese, Riccardo Troncone, Salvatore Auricchio & Luigi Greco which were incorrectly given as Auricchio Renata, Calabrese Ilaria, Galatola Martina, Cielo Donatella, Carbone Fortunata, Mancuso Marianna, Matarese Giuseppe, Troncone Riccardo, Auricchio Salvatore & Greco Luigi. The original article has been corrected

    Environmental policies and social impacts. Suggestions from Europeans cities

    No full text
    Are we really sure that green and sustainable are always good for everyone? Ilaria Beretta tries to go beyond the rhetoric of sustainability to understand more deeply the interconnection between economy, society and environment in urban contexts, in the belief that only empirical research and the analysis of data can lead to a correct reading, which is as objective as possible, of the complex reality in which we live. The author, through a comparison between European and U.S. American cities, focuses in particular on policies related to climate change and land use, showing how these, if not properly monitored in their social effects, risk contributing to the tightening of social inequalities, through processes such as ecological and green gentrification. The volume is structured in three parts. In the first section, she illustrates the main European Union’s sustainability and environmental urban policies, focusing on climate change and land use strategies. The second chapter provides a conceptual framework through the environmental justice paradigm, as it applies in Europe and in U.S. Finally, the third chapter offers an empirical analysis of ecological and green gentrification processes, comparing American and European realities, and highlighting how context-specific differences can have profound effects on the manifestation (or not) of these phenomena

    Rappresentanze e rappresentazioni del lavoro. La sequenza corporazioni, mutualismo e sindacato

    No full text
    La produzione storiografica di Luigi Trezzi consente una aggiornata riflessione sugli elementi di continuità tra le esperienze comunitarie e associative del periodo preindustriale e gli assetti socio-istituzionali conseguenti l'affermazione nel nostro Paese della società industriale tra Ottocento e Novecento. L'attitudine alla resilienza delle relazioni comunitarie, a fronte delle fratture indotte dalle relazioni di mercato, merita particolare attenzione oggi tanto alla luce delle criticità determinate dal tendenziale superamento della crisi di inizio millennio quanto delle potenzialità di nuovi paradigmi emergenti

    El Tlacuache Núm. 458 (2011). 458 Año 11 (2011) marzo. El Tlacuache

    No full text
    Reflexiones sobre la migración en la Costa Chica Oaxaqueña Cuando el teléfono suena...por Alejandra A. Ramírez López. -Fronteras Lugares irreales / lugares hiperreales por Ilaria Bologna

    Werner Sombart and the global society. Anticipations from a classic author of sociology

    No full text
    The article examines the most salient works in which the sociologist Werner Sombart saw the dimension of globality as a social element, constitutive of mo- dernity and its future. The aim is to understand the role of globality, as an idea and a phenomenon, in the constitution in all aspects of society (economic, political, cultural, anthropological). The Works to which the article refers show a global society, one that goes from the time of Sombart to the present day, as the author had already envisioned in all their potentialities and criticalities

    Self Portrait of an Italian Historian as a Woman on the Train

    No full text
    Thirty years on from publication of her first book, and amidst epoch-making changes to the university system, especially in Italy, the author reconstructs her own intellectual and professional story. In this ego histoire Ilaria Porciani goes over the milestones and encounters of her working life, as well as some material and institutional career aspects of an Italian woman historian across the turn of the millennium
    corecore