Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

INVESTIGATION OF THE MECHANICAL BEHAVIOUR OF METAL-DIAMOND COMPOSITES

Metal-Diamond Composites (Me-CD) are a novel class of materials which has typical applications in the field of thermal management. Usually, due to the high volume fraction of diamonds inside the matrix, the mechanical behavior of such materials is quite brittle with low level of fracture stress and strain. However, with advanced innovations in the sintering processes, it is possible to obtain composite materials with a good level of strength and toughness. The great advantage of these materials is the possibility to combine the high thermal and electrical conductivity of diamonds with the strength of metals. Aim of this work is the investigation of the mechanical behavior of Me-CD from quasi-static to high strain-rate loading conditions. The temperature influence on mechanical properties is also evaluated

From flint to silicon, modern technologies applied to the understanding of history. The Italian Archaeological Mission in Iraqi Kurdistan

Dal 2011 La MAIKI opera nei governatorati di Erbil e Sulaimaniya, e focalizza le sue attivita\u300 sulla Cittadella di Erbil e sul sito di Paikuli. Gli studi storico-archeologici sui siti sono stati affiancati da importanti attivita\u300 di documentazione e gestione dei dati caratterizzate dall\u92'utilizzo di alcune tra le piu\u300 moderne risorse a disposizione

miR-196a Is Able to Restore the Aggressive Phenotype of Annexin A1 Knock-Out in Pancreatic Cancer Cells by CRISPR/Cas9 Genome Editing

Annexin A1 (ANXA1) is a Ca2+-binding protein that is involved in pancreatic cancer (PC) progression. It is able to mediate cytoskeletal organization maintaining a malignant phenotype. Our previous studies showed that ANXA1 Knock-Out (KO) MIA PaCa-2 cells partially lost their migratory and invasive capabilities and also the metastatization process appeared affected in vivo. Here, we investigated the microRNA (miRNA) profile in ANXA1 KO cells finding that the modification in miRNA expression suggests the significant involvement of ANXA1 in PC development. In this study, we focused on miR-196a which appeared down modulated in absence of ANXA1. This miRNA is a well known oncogenic factor in several tumour models and it is able to trigger the agents of the epithelial to mesenchymal transition (EMT), like ANXA1. Our results show that the reintroduction in ANXA1 KO cells of miR-196a through the mimic sequence restored the early aggressive phenotype of MIA PaCa-2. Then, ANXA1 seems to support the expression of miR-196a and its role. On the other hand, this miRNA is able to mediate cytoskeletal dynamics and other protein functions promoting PC cell migration and invasion. This work describes the correlation between ANXA1 and specific miRNA sequences, particularly miR-196a. These results could lead to further information on ANXA1 intracellular role in PC, explaining other aspects that are apart from its tumorigenic behaviour

Analysis of allelic distribution of ApoE promoter polymorphism: relation to gender, age at onset, and var epsilon epsilon 4 in a sample of sporardic AD patients.

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Allelic distribution of apolipoprotein E (ApoE) and ApoE promoter polymorphisms in patients with frontotemporal dementia.

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