24 research outputs found
TARGETING TYR682 RESIDUE ON THE AMYLOID PRECURSOR PROTEIN FOR THE DEVELOPMENT OF DIAGNOSTIC AND THERAPEUTIC STRATEGIES IN ALZHEIMER'S DISEASE
No full textNumerical Simulation of Liquid-structure Interaction Problem in a Tank of a Space Re-entry Vehicle
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TNF-α Levels Are Increased in Patients with Subjective Cognitive Impairment and Are Negatively Correlated with β Amyloid-42
No full textThe role of tumor necrosis factor-α (TNF-α) in Alzheimer’s disease (AD) has recently become a topic of debate. TNF-α levels increase in the blood of patients with AD, and amyloid beta (Aβ) plaques contain TNF-α deposits. The therapeutic efficacy of blocking TNF-α in patients with AD remains controversial as it is mostly based on preclinical studies. Thus, whether and how TNF-α contributes to amyloidogenic processes in AD is still an open question to be addressed. We analyzed plasma TNF-α and Aβ42 levels in patients with subjective cognitive impairment (SCI), mild cognitive impairment (MCI), and AD, and in healthy volunteers (HLT). In addition, we performed correlation analysis to evaluate whether changes in plasma TNF-α levels correlate with cognitive decline, Aβ42 levels, age, and BMI, which are all factors considered to contribute to or predispose individuals to AD. We found that TNF-α and Aβ42 plasma levels were higher in patients with AD than in HLT individuals. High TNF-α levels were also observed in patients with SCI, in whom TNF-α and Aβ42 levels were negatively correlated. Notably, TNF-α did not affect the amyloidogenic pathway in human microglial cultures exposed to 48 h of incubation, although it did trigger neuroinflammatory processes. These results imply that high TNF-α levels are more likely to be a clinical condition linked to AD than are direct contributors. Nonetheless, elevated levels of TNF-α in early-stage patients, like those with SCI and MCI, may provide a distinguishing feature for identifying clinical profiles that are at risk of having a poorer outcome in AD and could benefit from tailored therapies
Advances in peripheral blood biomarkers of patients with Alzheimer’s disease: Moving closer to personalized therapies
No full textRecently, measurable peripheral biomarkers in the plasma of patients with Alzheimer's disease (AD) have gained considerable clinical interest. Several studies have identified one or more blood signatures that may facilitate the development of novel diagnostic and therapeutic strategies. For instance, changes in peripheral amyloid β42 (Aβ42) levels have been largely investigated in patients with AD and correlated with the progression of the pathology, although with controversial results. In addition, tumor necrosis factor α (TNFα) has been identified as an inflammatory biomarker strongly associated with AD, and several studies have consistently suggested the pharmacological targeting of TNFα to reduce systemic inflammation and prevent neurotoxicity in AD. Moreover, alterations in plasma metabolite levels appear to predict the progression of systemic processes relevant to brain functions. In this study, we analyzed the changes in the levels of Aβ42, TNFα, and plasma metabolites in subjects with AD and compared the results with those in healthy elderly (HE) subjects. Differences in plasma metabolites of patients with AD were analyzed with respect to Aβ42, TNFα, and the Mini-Mental State Examination (MMSE) score, searching for plasma signatures that changed simultaneously. In addition, the phosphorylation levels of the Tyr682 residue of the amyloid precursor protein (APP), which we previously proposed as a biomarker of AD, were measured in five HE and five AD patients, in whom the levels of Aβ42, TNFα, and two plasma lipid metabolites increased simultaneously. Overall, this study highlights the potential of combining different plasma signatures to define specific clinical phenotypes of patient subgroups, thus paving the way for the stratification of patients with AD and development of personalized approaches
A Targeted Mass Spectrometry Approach to Identify Peripheral Changes in Metabolic Pathways of Patients with Alzheimer’s Disease
No full text: Alzheimer's disease (AD), a neurodegenerative disorder, is the most common cause of dementia in the elderly population. Since its original description, there has been intense debate regarding the factors that trigger its pathology. It is becoming apparent that AD is more than a brain disease and harms the whole-body metabolism. We analyzed 630 polar and apolar metabolites in the blood of 20 patients with AD and 20 healthy individuals, to determine whether the composition of plasma metabolites could offer additional indicators to evaluate any alterations in the metabolic pathways related to the illness. Multivariate statistical analysis showed that there were at least 25 significantly dysregulated metabolites in patients with AD compared with the controls. Two membrane lipid components, glycerophospholipids and ceramide, were upregulated, whereas glutamic acid, other phospholipids, and sphingolipids were downregulated. The data were analyzed using metabolite set enrichment analysis and pathway analysis using the KEGG library. The results showed that at least five pathways involved in the metabolism of polar compounds were dysregulated in patients with AD. Conversely, the lipid pathways did not show significant alterations. These results support the possibility of using metabolome analysis to understand alterations in the metabolic pathways related to AD pathophysiology
High-level-of-detail semantic 3D GIS for risk and damage representation of architectural heritage
No full textThe need to share information about architectural heritage effectively after a disaster event, in order to foster its preservation, requires the use of a common language between the involved actors and stakeholders. A database able to connect the architectural heritage representation with the data useful for hazard and risk analysis can thus be a powerful instrument. This paper outlines a methodology to represent 3D models of the architectural heritage, according to some existing standards data models, and relate their geometric features to the damage mechanisms that could occur after an earthquake. Among all the existing standard to represent cartographic, cultural heritage and hazard/risk information, respectively INSPIRE, CityGML, UNESCO, CIDOC-CRM, its extension MONDIS and the Getty Institute vocabularies, compliant to the CIDOC-CRM, have been taken into account. An INSPIRE extension has been proposed for increasing the level of detail (LoD) of the representation and improving the description of heritage buildings, adding some macro-elements and elements “feature types” connected with the damage mechanisms, identified in structural studies. The suggested method allows to archive, in a multi-scale database, 3D information with a very high level of detail about architectural heritage and can help structural engineers and conservator-restorers in preventing further damages through individuating useful targeted actions.Urban Data Scienc
Fables de La Fontaine: Tome Quatrième. Avec les figures d'Oudry dans l'édition Desaint et Saillant de 1755
No full textSee my comments on the first volume. My favorites on this trip through are CXCIV, Le Loup et les Bergers; CCX, Le Loup et le Rénard: CCXIX, Le Cerf malade; and CCXLIII, La Matrone d'Ephese (both plates).This is a hardbound book (hard cover)Language note: FrenchLa Fontain
Armonizzazione di standard spaziali e normativa antisismica: Una proposta per la rappresentazione semantica 3D del complesso architettonico di Tolentino
No full textThe need of effectively sharing information about architectural heritage affectedby disaster event, in order to foster its preservation, requires the adoption of acommon language and standards among the involved actors and stakeholders.The application of spatial and geographical databases, enabling to connect architectural heritage representation with the data useful for hazard and risk analysis, could facilitate the pre and post event estimation of vulnerability.This paper outlines a methodology to represent 3D models of the architecturalheritage according to some existing standards data models and thesauri inventories (INSPIRE, CityGML, UNESCO, CIDOC-CRM, MONDIS, Getty). Inaddition, as a consequence of the collaboration between the Geomatics group and the Structural and Seismic Engineering group of the Polytechnic of Turin, an integration of the database for a correlation between the geometric entities of structural components and their related earthquake damage mechanisms was tested.Urban Data Scienc
Challenges in LC-MS-based metabolomics for Alzheimer's disease early detection: targeted approaches versus untargeted approaches
No full textParallel polynomial preconditioners for the analysis of chaotic flows in Rayleigh - Benard convection
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