New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Energy Upgrading of Residential Building Stock: Use of Life Cycle Cost Analysis to Assess Interventions on Social Housing in Italy

The debate on the relevance of the global sustainability (including energy, environmental, social, economic, and political aspects) of building stock is becoming increasingly important in Europe. In this context, special attention is placed on the refurbishment of existing buildings, in particular those characterized by significant volumes and poor energy performance. Directive 2012/27/EU introduced stringent constraints (often disregarded) for public administrations to ensure a minimum yearly renovation quota of its building stock. This study describes how Life Cycle Cost analysis (LCC) can be used as a tool to identify the “cost-optimal level” among different design solutions to improve the energy performance of existing buildings. With this aim, a social housing building located in the town of Pisa (Italy) was chosen as the case study, for which two alternative renovation designs were compared using the LCC methodology to identify the optimal solution. The two alternatives were characterized by the same energy performance—one was based on the demolition of the existing building and the construction of a new building (with a wooden frame structure, as proposed by the public company owner of the building), while the other was based on the renovation of the existing building. This study can provide useful information, especially for designers and public authorities, about the relevance of the economic issues related to the renovation of social housing in a Mediterranean climate

Do green roofs really provide significant energy saving in a Mediterranean climate? Critical evaluation based on different case studies

Green roofs represent a growing technology that is spreading increasingly and rapidly throughout the building sector. The latest national and international regulations are promoting their application for refurbishments and new buildings to increase the energy efficiency of the building stock. In recent years, vegetative coverings have been studied to demonstrate their multiple benefits, such as the reduction of the urban heat island phenomenon and the increase in the albedo of cities. On the contrary, this study aims to verify the actual benefit of applying a green roof on a sloped cover compared with installing a highly insulated tiled roof. The EnergyPlus tool has been used to perform dynamic analyses, which has allowed to understand the behavior of two different stratigraphies in accordance with weather conditions, rain, and irrigation profiles. Results have shown that the installation of a green roof cannot always be considered the best solution for reducing building energy consumption, especially if compared with a classic highly insulated clay tile roof. In terms of summer air conditioning, the maximum saving is 0.72 kWh/m2. The presence of water in the soil has also been proven a crucial factor

Gli scavi archeologici dell\u2019Universit\ue0 di Padova ad Aquileia

Dal 2007 l\u2019Universit\ue0 di Padova \ue8 impegnata nella conduzione di una serie di scavi archeologici ad Aquileia. Le ricerche riguardano innanzitutto due abitazioni romane: la Casa delle Bestie ferite e la Casa di Tito Macro (\u2019fondi Cossar\u2019). Le indagini hanno permesso di definire in termini diacronici la storia delle due case, dalla loro fase di impianto alle principali trasformazioni edilizie e planimetriche, sino al loro definitivo abbandono. Per quanto riguarda l\u2019architettura pubblica, nell\u2019area archeologica dei \u2019fondi Cossar\u2019 \ue8 stato indagato anche un tratto dell\u2019angolo sud-orientale delle mura difensive di et\ue0 repubblicana. Pi\uf9 recente \ue8 infine lo scavo del teatro romano, avviato con lo scopo di determinarne la collocazione urbana, di definirne l\u2019articolazione planimetrica e architettonica e di precisarne le fasi di costruzione, di vita, di riutilizzo, di abbandono e di spoliazione. Since 2007 the University of Padua is conducting several archaeological excavations in Aquileia. Firstly, the research concern two different Roman houses: \u2019Casa delle Bestie Ferite\u2019 and \u2019Casa di Tito Macro\u2019 (\u2019fondi Cossar\u2019). The investigations carried out in the last years have allowed to sketch the development of these houses diachronically, from their construction to the main architectural and planimetrical transformations, until their final abandonment. As far as public architecture is concerned, part of the southeastern corner of the republican defensive walls was excavated in the \u2019Cossar\u2019 area. Finally, the latest investigations concern the Roman theatre. Objective of this project is to determine the location of the building in the urban context, to define the planimetrical and architectural layout and to specify its construction, life, reuse, abandonment and spoliation phases

The Mycoarray as an aid for diagnosis of an imported case of Histoplasmosis in an Italian traveler returning from Brasil

We describe an imported case of Histoplasmosis, whose serological profile was established by means of a protein-based microarray platform, the recently described mycoarray. Because of its peculiarities, such a novel tool greatly facilitates the rapid and multiparametric assessment of patients' serological status and lends itself to be employed as an aid in the diagnosis of primary mycoses, especially in non endemic countries

DIAGNOSI SIEROLOGICA, MEDIANTE MYCOARRAY, DI UN CASO DI ISTOPLASMOSI DA IMPORTAZIONE IN UN TURISTA ITALIANO DI RITORNO DAL BRASILE

Introduzione L’istoplasmosi, infezione granulomatosa provocata dal fungo dimorfo Histoplasma capsulatum, viene contratta per inalazione dei conidi in aree dove tale fungo è endemico. Date le manifestazioni cliniche aspecifiche, la diagnosi di laboratorio è estremamente importante per confermare il sospetto di malattia, soprattutto in aree come la nostra, in cui i casi, sebbene rari, possono essere sia da importazione che autoctoni. Recentemente, è stato messo a punto il “mycoarray”, un saggio multiparametrico rapido, in grado di rilevare anticorpi specifici nei confronti di Histoplasma ed altri funghi dimorfi (1). Metodi Estratti antigenici da funghi dimorfi (H. capsulatum, C. immitis, B. dermatitidis, P. brasiliensis) sono stati deposti su vetrini microarray mediante un sistema robotizzato ad alta precisione. I vetrini sono stati cimentati con il siero del paziente e la formazione degli immunocomplessi è stata rivelata utilizzando anticorpi secondari marcati in fluorescenza. Dopo lettura, mediante un apposito scanner, il segnale è stato quantificato ed analizzato. Risultati Il paziente (maschio italiano di 30 anni, di ritorno da un viaggio “on-the-road” in Brasile), era stato ricoverato per una febbre persistente che non rispondeva a terapia antibiotica empirica. A seguito della presenza di infiltrati e di linfoadenopatia mediastinica, rivelati mediante TAC del torace, è stata condotta una biopsia linfonodale suggestiva di infezione fungina da dimorfi. L’analisi del siero mediante mycoarray ha mostrato una elevata sieroreattività, IgG e IgM, nei confronti degli antigeni di H. capsulatum. Nessuna reattività è invece stata evidenziata nei confronti degli antigeni da altri funghi dimorfi (2). Conclusioni Grazie alle sue peculiarità (miniaturizzazione, multiparametricità e rapidità di esecuzione) il mycoarray si rivela uno strumento prezioso per facilitare la diagnosi rapida di micosi primitive, specialmente in paesi non endemici. Ringraziamenti Lavoro in parte supportato da MIUR, PRIN-200985J87J Bibliografia (1) Ardizzoni et al., (2011) New Microbiol, 34:307-16. (2) Ardizzoni et al., (2013) JTM, 20:336-

«Il pendolo della corte». Le oscillazioni della corte costituzionale tra l’anima “politica” e quella “giurisdizionale”. Dossier sulla giurisprudenza costituzionale

Il dossier contiene il risultato di una ricerca sulla giurisprudenza costituzionale svolta dai dottorandi in Scienze giuridiche, curriculum in Giustizia costituzionale e Diritti fondamentali, del Dipartimento di Giurisprudenza dell'Università degli Studi di Pisa. Il gruppo è stato coordinato da Giuliano Serges e Caterina Tomba. La ricerca aveva ad oggetto il tema "Le oscillazioni della Corte costituzionale tra l'anima 'politica' e quella 'giurisdizionale'"