A geroscience approach for Parkinson's disease: Conceptual framework and design of PROPAG-AGEING project

Advanced age is the major risk factor for idiopathic Parkinson's disease (PD), but to date the biological relationship between PD and ageing remains elusive. Here we describe the rationale and the design of the H2020 funded project “PROPAG-AGEING”, whose aim is to characterize the contribution of the ageing process to PD development. We summarize current evidences that support the existence of a continuum between ageing and PD and justify the use of a Geroscience approach to study PD. We focus in particular on the role of inflammaging, the chronic, low-grade inflammation characteristic of elderly physiology, which can propagate and transmit both locally and systemically. We then describe PROPAG-AGEING design, which is based on the multi-omic characterization of peripheral samples from clinically characterized drug-naïve and advanced PD, PD discordant twins, healthy controls and "super-controls", i.e. centenarians, who never showed clinical signs of motor disability, and their offspring. Omic results are then validated in a large number of samples, including in vitro models of dopaminergic neurons and healthy siblings of PD patients, who are at higher risk of developing PD, with the final aim of identifying the molecular perturbations that can deviate the trajectories of healthy ageing towards PD development

Heterogeneity of prodromal Parkinson symptoms in siblings of Parkinson disease patients

A prodromal phase of Parkinson’s disease (PD) may precede motor manifestations by decades. PD patients’ siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. 340 PD siblings from three sites (Bologna, Seville, Kassel/Goettingen) underwent clinical and neurological evaluations of PD markers. The German part of the cohort was compared with German de novo PD patients (dnPDs) and healthy controls (CTRs) from DeNoPa. Fifteen (4.4%) siblings presented with subtle signs of motor impairment, with MDS-UPDRS-III scores not clinically different from CTRs. Symptoms of orthostatic hypotension were present in 47 siblings (13.8%), no different to CTRs (p = 0.072). No differences were found for olfaction and overall cognition; German-siblings performed worse than CTRs in visuospatial-executive and language tasks. 3/147 siblings had video-polysomnography-confirmed REM sleep behavior disorder (RBD), none was positive on the RBD Screening Questionnaire. 173/300 siblings had <1% probability of having prodromal PD; 100 between 1 and 10%, 26 siblings between 10 and 80%, one fulfilled the criteria for prodromal PD. According to the current analysis, we cannot confirm the increased risk of PD siblings for prodromal PD. Siblings showed a heterogeneous distribution of prodromal PD markers and probability. Additional parameters, including strong disease markers, should be investigated to verify if these results depend on validity and sensitivity of prodromal PD criteria, or if siblings’ risk is not elevated

Metabolite and lipoprotein profiles reveal sex-related oxidative stress imbalance in de novo drug-naive Parkinson's disease patients

Parkinson’s disease (PD) is the neurological disorder showing the greatest rise in prevalence from 1990 to 2016. Despite clinical definition criteria and a tremendous effort to develop objective biomarkers, precise diagnosis of PD is still unavailable at early stage. In recent years, an increasing number of studies have used omic methods to unveil the molecular basis of PD, providing a detailed characterization of potentially pathological alterations in various biological specimens. Metabolomics could provide useful insights to deepen our knowledge of PD aetiopathogenesis, to identify signatures that distinguish groups of patients and uncover responsive biomarkers of PD that may be significant in early detection and in tracking the disease progression and drug treatment efficacy. The present work is the first large metabolomic study based on nuclear magnetic resonance (NMR) with an independent validation cohort aiming at the serum characterization of de novo drug-naive PD patients. Here, NMR is applied to sera from large training and independent validation cohorts of German subjects. Multivariate and univariate approaches are used to infer metabolic differences that characterize the metabolite and the lipoprotein profiles of newly diagnosed de novo drug-naive PD patients also in relation to the biological sex of the subjects in the study, evidencing a more pronounced fingerprint of the pathology in male patients. The presence of a validation cohort allowed us to confirm altered levels of acetone and cholesterol in male PD patients. By comparing the metabolites and lipoproteins levels among de novo drug-naive PD patients, age- and sex-matched healthy controls, and a group of advanced PD patients, we detected several descriptors of stronger oxidative stress

Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson’s disease patients

open101siThis work was supported by the Horizon 2020 Framework Programme (Grant number 634821, PROPAG-AGING).Advanced age represents one of the major risk factors for Parkinson’s Disease. Recent biomedical studies posit a role for microRNAs, also known to be remodelled during ageing. However, the relationship between microRNA remodelling and ageing in Parkinson’s Disease, has not been fully elucidated. Therefore, the aim of the present study is to unravel the relevance of microRNAs as biomarkers of Parkinson’s Disease within the ageing framework. We employed Next Generation Sequencing to profile serum microRNAs from samples informative for Parkinson’s Disease (recently diagnosed, drug-naïve) and healthy ageing (centenarians) plus healthy controls, age-matched with Parkinson’s Disease patients. Potential microRNA candidates markers, emerging from the combination of differential expression and network analyses, were further validated in an independent cohort including both drug-naïve and advanced Parkinson’s Disease patients, and healthy siblings of Parkinson’s Disease patients at higher genetic risk for developing the disease. While we did not find evidences of microRNAs co-regulated in Parkinson’s Disease and ageing, we report that hsa-miR-144-3p is consistently down-regulated in early Parkinson’s Disease patients. Moreover, interestingly, functional analysis revealed that hsa-miR-144-3p is involved in the regulation of coagulation, a process known to be altered in Parkinson’s Disease. Our results consistently show the down-regulation of hsa-mir144-3p in early Parkinson’s Disease, robustly confirmed across a variety of analytical and experimental analyses. These promising results ask for further research to unveil the functional details of the involvement of hsa-mir144-3p in Parkinson’s Disease.openZago E.; Dal Molin A.; Dimitri G.M.; Xumerle L.; Pirazzini C.; Bacalini M.G.; Maturo M.G.; Azevedo T.; Spasov S.; Gomez-Garre P.; Perinan M.T.; Jesus S.; Baldelli L.; Sambati L.; Calandra Buonaura G.; Garagnani P.; Provini F.; Cortelli P.; Mir P.; Trenkwalder C.; Mollenhauer B.; Franceschi C.; Lio P.; Nardini C.; Adarmes-Gomez A.; Azevedo T.; Bacalini M.G.; Baldelli L.; Bartoletti-Stella A.; Bhatia K.P.; Marta B.-T.; Boninsegna C.; Broli M.; Dolores B.-R.; Calandra-Buonaura G.; Capellari S.; Carrion-Claro M.; Cilea R.; Clayton R.; Cortelli P.; Molin A.D.; De Luca S.; De Massis P.; Dimitri G.M.; Doykov I.; Escuela-Martin R.; Fabbri G.; Franceschi C.; Gabellini A.; Garagnani P.; Giuliani C.; Gomez-Garre P.; Guaraldi P.; Hagg S.; Hallqvist J.; Halsband C.; Heywood W.; Houlden H.; Huertas I.; Jesus S.; Jylhava J.; Labrador-Espinosa M.A.; Licari C.; Lio P.; Luchinat C.; Macias D.; Macri S.; Magrinelli F.; Rodriguez J.F.M.; Massimo D.; Maturo M.G.; Mengozzi G.; Meoni G.; Mignani F.; Milazzo M.; Mills K.; Mir P.; Mollenhauer B.; Nardini C.; Nassetti S.A.; Pedersen N.L.; Perinan-Tocino M.T.; Pirazzini C.; Provini F.; Ravaioli F.; Sala C.; Sambati L.; Scaglione C.L.M.; Schade S.; Schreglmann S.; Spasov S.; Strom S.; Tejera-Parrado C.; Tenori L.; Trenkwalder C.; Turano P.; Valzania F.; Ortega R.V.; Williams D.; Xumerle L.; Zago E.Zago E.; Dal Molin A.; Dimitri G.M.; Xumerle L.; Pirazzini C.; Bacalini M.G.; Maturo M.G.; Azevedo T.; Spasov S.; Gomez-Garre P.; Perinan M.T.; Jesus S.; Baldelli L.; Sambati L.; Calandra Buonaura G.; Garagnani P.; Provini F.; Cortelli P.; Mir P.; Trenkwalder C.; Mollenhauer B.; Franceschi C.; Lio P.; Nardini C.; Adarmes-Gomez A.; Azevedo T.; Bacalini M.G.; Baldelli L.; Bartoletti-Stella A.; Bhatia K.P.; Marta B.-T.; Boninsegna C.; Broli M.; Dolores B.-R.; Calandra-Buonaura G.; Capellari S.; Carrion-Claro M.; Cilea R.; Clayton R.; Cortelli P.; Molin A.D.; De Luca S.; De Massis P.; Dimitri G.M.; Doykov I.; Escuela-Martin R.; Fabbri G.; Franceschi C.; Gabellini A.; Garagnani P.; Giuliani C.; Gomez-Garre P.; Guaraldi P.; Hagg S.; Hallqvist J.; Halsband C.; Heywood W.; Houlden H.; Huertas I.; Jesus S.; Jylhava J.; Labrador-Espinosa M.A.; Licari C.; Lio P.; Luchinat C.; Macias D.; Macri S.; Magrinelli F.; Rodriguez J.F.M.; Massimo D.; Maturo M.G.; Mengozzi G.; Meoni G.; Mignani F.; Milazzo M.; Mills K.; Mir P.; Mollenhauer B.; Nardini C.; Nassetti S.A.; Pedersen N.L.; Perinan-Tocino M.T.; Pirazzini C.; Provini F.; Ravaioli F.; Sala C.; Sambati L.; Scaglione C.L.M.; Schade S.; Schreglmann S.; Spasov S.; Strom S.; Tejera-Parrado C.; Tenori L.; Trenkwalder C.; Turano P.; Valzania F.; Ortega R.V.; Williams D.; Xumerle L.; Zago E

Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson’s disease patients

Advanced age represents one of the major risk factors for Parkinson’s Disease. Recent biomedical studies posit a role for microRNAs, also known to be remodelled during ageing. However, the relationship between microRNA remodelling and ageing in Parkinson’s Disease, has not been fully elucidated. Therefore, the aim of the present study is to unravel the relevance of microRNAs as biomarkers of Parkinson’s Disease within the ageing framework. We employed Next Generation Sequencing to profile serum microRNAs from samples informative for Parkinson’s Disease (recently diagnosed, drug-naïve) and healthy ageing (centenarians) plus healthy controls, age-matched with Parkinson’s Disease patients. Potential microRNA candidates markers, emerging from the combination of differential expression and network analyses, were further validated in an independent cohort including both drug-naïve and advanced Parkinson’s Disease patients, and healthy siblings of Parkinson’s Disease patients at higher genetic risk for developing the disease. While we did not find evidences of microRNAs co-regulated in Parkinson’s Disease and ageing, we report that hsa-miR-144-3p is consistently down-regulated in early Parkinson’s Disease patients. Moreover, interestingly, functional analysis revealed that hsa-miR-144-3p is involved in the regulation of coagulation, a process known to be altered in Parkinson’s Disease. Our results consistently show the down-regulation of hsa-mir144-3p in early Parkinson’s Disease, robustly confirmed across a variety of analytical and experimental analyses. These promising results ask for further research to unveil the functional details of the involvement of hsa-mir144-3p in Parkinson’s Disease

TALAT Lecture 2201.01: State of the Art

This lecture gives an introduction into use of aluminium in stressed applications, with examples of the past experiences and likely future developments. A general engineering background is an advantage but the subject matter is suitable for most audiences concerned with transport and structural applications.

Diritti e rovesci: cittadini si diventa. Sviluppare competenze sociali e civiche nella scuola primaria

Il sistema di istruzione e formazione svolge un ruolo fondamentale per consentire alle persone di adattarsi in modo flessibile alla realtà odierna caratterizzata da rapidi mutamenti e forte interconnessione. Per la realizzazione personale, la cittadinanza attiva, l’inclusione sociale è, infatti, importante sviluppare, nell’intero arco di vita e dunque sin dall’età precoce, una serie di competenze chiave delineate nel quadro di riferimento europeo e comprensive di competenze “sociali e civiche”. Queste ultime, definite come “personali, interpersonali e interculturali”, riguardano la partecipazione alla vita sociale e lavorativa in società sempre più diversificate. La competenza sociale è collegata al benessere personale e collettivo. Basata sull’attitudine alla collaborazione, all’assertività e l’integrità, essa comprende la capacità di comunicare in modo costruttivo in ambienti diversi, di mostrare tolleranza, di esprimere e comprendere diversi punti di vista. La competenza civica, invece, dota le persone degli strumenti per partecipare attivamente alla vita democratica grazie alla conoscenza dei concetti sociopolitici e alla propria capacità di impegnarsi efficacemente con gli altri nella sfera pubblica. Considerato il quadro normativo europeo ora descritto, ci si può interrogare sulla presenza, nella letteratura psicologica, di costrutti utili per approfondire il tema dello sviluppo delle competenze sociali. Esse sono state oggetto di recenti ricerche riferite all’età prescolare (Elia, Cassibba 2009), mentre cresce l’importanza attribuita dagli studiosi al ruolo delle emozioni nello sviluppo relazionale e in quello morale (Barone, Bacchini 2009). Un’abbondante letteratura si è sviluppata, oltre sugli aspetti cognitivi ed emotivi dello sviluppo morale dei bambini, anche sul ruolo della scuola nell’educazione ai valori nelle democrazie multiculturali. Al centro della discussione si colloca la tensione tra la moralità e le strutture normative dei sistemi sociali: l’educazione morale spetta innanzitutto alla famiglia, ma la scuola non può rinunciare al suo ruolo formativo volto a facilitare l’interiorizzazione dei valori (Nucci, 2001). Nell’enfatizzare l’importanza dell’educazione al senso delle regole è stato osservato che proprio l’interiorizzazione dei valori, oltre che delle norme, consente di acquisire una maggiore capacità di gestione del sé e delle relazioni (Diana, 2005). Strettamente connessi agli studi sullo sviluppo morale sono quelli rivolti a indagare le modalità di interazione sociale tra gli individui, al fine del perseguimento del benessere collettivo. Nell’ambito delle ricerche incentrate sul comportamento prosociale, alcune mettono in luce i fattori che lo promuovo, altre testimoniano l’importanza delle sue manifestazioni precoci ai fini dell’adattamento e della salute in tutte le fasi della vita (Cattelino e al., 2006) e altre ancora documentano le relazioni tra empatia, ragionamento morale e prosocialità (Pastorelli e al., 2006). Il ruolo della scuola nella promozione della responsabilità individuale e dell’autonomia nelle scelte risulta particolarmente rilevante per il pieno sviluppo della personalità. Il diffondersi di dinamiche prosociali a scuola può essere favorito mediante la riflessione su di sé e l’attenzione all’altro, importante è anche l’elaborazione di strategie per potenziare, da un lato, l’efficacia nell’offerta di aiuto e, dall’altro, l’autoefficacia nella richiesta di aiuto. L’esperienza scolastica può favorire comportamenti prosociali orientati a una convivenza sociale positiva attraverso due canali principali: da un lato le relazioni con gli insegnanti e con i pari e, dall’altro, i contenuti curriculari (Cattelino e al., 2006). Per quanto riguarda i rapporti interpersonali a scuola, la creazione di una rete relazionale di qualità, basata su risorse individuali e di gruppo, e incentrata sul raggiungimento di obiettivi comuni, favorisce un clima classe positivo. Tra i fattori decisivi per la promozione di un clima classe positivo, centrale è il ruolo dell’insegnante come facilitatore delle relazioni e promotore dei processi di cambiamento

Emotional Intelligence, Self-efficacy,Job Satisfaction and Burnout in a Sample of Italian High School TeachersFacing Educational Reform

The work in progress we present consists of a series of studies about some psychological aspects of the teaching profession in times of high school system reform. The main purpose of this research project is to expand the body of findings on teacher emotional intelligence, an emerging topic in educational psychology, as it is demonstrated by a flourishing literature. The relationships between emotional intelligence, self-efficacy beliefs, job satisfaction and burnout will also be explored. A sample of about 250 Italian high school teachers are being recruited and asked to complete anonymously a battery of self-report questionnaires. Our work intends to be a significant contribution to the debate about emotional intelligence as a plausible protective factor against teachers’ vulnerability in times of increased performativity demand