GBA Mutations Influence the Release and Pathological Effects of Small Extracellular Vesicles from Fibroblasts of Patients with Parkinson’s Disease

Heterozygous mutations in the GBA gene, encoding the lysosomal enzyme glucocerebrosidase (GCase), are the strongest known genetic risk factor for Parkinson’s disease (PD). The molecular mechanisms underlying the increased PD risk and the variable phenotypes observed in carriers of different GBA mutations are not yet fully elucidated. Extracellular vesicles (EVs) have gained increasing importance in neurodegenerative diseases since they can vehiculate pathological molecules potentially promoting disease propagation. Accumulating evidence showed that perturbations of the endosomal–lysosomal pathway can affect EV release and composition. Here, we investigate the impact of GCase deficiency on EV release and their effect in recipient cells. EVs were purified by ultracentrifugation from the supernatant of fibroblast cell lines derived from PD patients with or without GBA mutations and quantified by nanoparticle tracking analysis. SH-SY5Y cells over-expressing alpha-synuclein (α-syn) were used to assess the ability of patient-derived small EVs to affect α-syn expression. We observed that defective GCase activity promotes the release of EVs, independently of mutation severity. Moreover, small EVs released from PD fibroblasts carrying severe mutations increased the intra-cellular levels of phosphorylated α-syn. In summary, our work shows that the dysregulation of small EV trafficking and alpha-synuclein mishandling may play a role in GBA-associated PD.     

Modelling the relationship between tensile strength and porosity in bioceramic scaffolds

A model describing the relationship between tensile strength and total porosity in brittle open-cell macroporous foams is developed and applied to silicate ceramic scaffolds produced by sponge replication and subsequent sinter-crystallization. The tensile strength of the scaffolds decreased from 7.4 to 2.3 MPa as the total porosity increased from 0.40 to 0.79. The results of the model, which is based on the concepts of fracture mechanics, were in good agreement with the experimental data (R² = 0.88), which supports the good predictive capability of the approach presented. In principle, this model could help biomaterials scientists not only to estimate the tensile strength of highly-porous bioactive glass and ceramic scaffolds, which is often difficult to determine experimentally, but also to improve the rational design of porous bioceramics with customized properties.     

The Ketogenic Diet Reduces the Harmful Effects of Stress on Gut Mitochondrial Biogenesis in a Rat Model of Irritable Bowel Syndrome

Functional alterations in irritable bowel syndrome have been associated with defects in bioenergetics and the mitochondrial network. Effects of high fat, adequate-protein, low carbohydrate ketogenic diet (KD) involve oxidative stress, inflammation, mitochondrial function, and biogenesis. The aim was to evaluate the KD efficacy in reducing the effects of stress on gut mitochondria. Newborn Wistar rats were exposed to maternal deprivation to induce IBS in adulthood. Intestinal inflammation (COX-2 and TRL-4); cellular redox status (SOD 1, SOD 2, PrxIII, mtDNA oxidatively modified purines); mitochondrial biogenesis (PPAR-γ, PGC-1α, COX-4, mtDNA content); and autophagy (Beclin-1, LC3 II) were evaluated in the colon of exposed rats fed with KD (IBD-KD) or standard diet (IBS-Std), and in unexposed controls (Ctrl). IBS-Std rats showed dysfunctional mitochondrial biogenesis (PPAR-γ, PGC-1α, COX-4, and mtDNA contents lower than in Ctrl) associated with inflammation and increased oxidative stress (higher levels of COX-2 and TLR-4, SOD 1, SOD 2, PrxIII, and oxidatively modified purines than in Ctrl). Loss of autophagy efficacy appeared from reduced levels of Beclin-1 and LC3 II. Feeding of animals with KD elicited compensatory mechanisms able to reduce inflammation, oxidative stress, restore mitochondrial function, and baseline autophagy, possibly via the upregulation of the PPAR-γ/PGC-1α axis.     

Determination of the Synthetic Cannabinoids JWH-122, JWH-210, UR-144 in Oral Fluid of Consumers by GC-MS and Quantification of Parent Compounds and Metabolites by UHPLC-MS/MS

The consumption of synthetic cannabinoids (SCs) has significantly increased in the last decade and the analysis of SCs and their metabolites in human specimens is gaining interest in clinical and forensic toxicology. A pilot study has been carried out using a combination of an initial last generation gas chromatography-mass spectrometry (GC-MS) screening method for the determination of JWH-122, JWH-210, UR-144) in oral fluid (OF) of consumers and an ultra-high performance liquid chromatography high resolution mass spectrometry (UHPLC-HRMS) confirmatory method for the quantification of the parent compounds and their metabolites in the same biological matrix. OF samples were simply liquid-liquid extracted before injecting in both chromatographic systems. The developed methods have been successfully validated and were linear from limit of quantification (LOQ) to 50 ng/mL OF. Recovery of analytes was always higher than 70% and matrix effect always lower than 15% whereas intra-assay and inter-assay precision and accuracy were always better than 16%. After smoking 1 mg JWH-122 or UR-144 and 3 mg JWH-210, maximum concentration of 4.00–3.14 ng/mL JWH-122, 8.10–7.30 ng/mL JWH-210 ng/mL and 7.40 and 6.81 ng/mL UR-144 were measured by GC-MS and UHPLC-HRMS respectively at 20 min after inhalation. Metabolites of JWH 122 and 210 were quantified in OF by UHPLC-HRMS, while that of UR144 was only detectable in traces. Our results provide for the first time information about disposition of these SCs and their metabolites in consumers OF. Last generation GC-MS has proven useful tool to identify and quantify parent SCs whereas UHPLC-HRMS also confirmed the presence of SCs metabolites in the OF of SCs consumers.     

Optimizing acido-basic profile of support in Ni supported La2O3+Al2O3 catalyst for dry reforming of methane

The increasing alarm of global warming always draws interest in reactions like dry reforming of methane (DRM) where both global warming gases (CO₂ and CH₄) are converted into value-added chemical building blocks, such as syngas. Nickel catalyst active sites along with support acid-base profiles play a key role in DRM. Herein, xLa₂O₃+(100-x) Al₂O₃ (x = 0, 10, 15, 20%) supports are prepared and followed by NiO dispersion over the produced support by impregnation method. It was tested for DRM reaction and characterized with TGA, XRD, TEM, IR, Surface area and porosity measurement, H₂-TPR, CO₂-TPD and NH₃-TPD techniques. Upon increasing the basic lanthana proportion in the acidic alumina support, the crystallinity of alumina and acidity of total support decline. Up to 15% Lanthana addition in support claims a low acid and rich basic surface including super basic sites (related to unidentate carbonates) which governed optimum catalytic performance 64% CH₄ conversion, 79% CO₂ conversion and H₂/CO ~ 1 up to 460-min in time on stream test. 20% lanthanum oxide loading led to inferior performance due to rapid loss of surface area, pore-volume, pore diameter, acidity and medium basic strength sites. Fine-tuning of acid-base lanthana-alumina support with dispersed Ni species are a means for understanding DRM.     

Multivariate Analysis of <Superscript>1</Superscript>H-NMR Spectra of Genetically Characterized Extra Virgin Olive Oils and Growth Soil Correlations

Mono-varietal extra virgin olive oils were micro-extracted from drupes that were selectively collected from 28 trees distributed in five different Southern Italian Apulian areas. Nuclear Magnetic Resonance (NMR) profiles of these oil samples were correlated to the genetic (young green material) and soil (samples collected within the foliage projection) data of the tree of origin. Genetic analysis, performed on the samples using SSRs (Simple Sequence Repeats) by 9 microsatellite loci, confirmed the specific cultivar assignment (among Cima di Mola, Coratina, Ogliarola, and Oliva Rossa cultivars). Chemometric methods applied to ¹H-NMR spectroscopic data were used for cultivar and geographical origin discrimination of the studied extra virgin olive oils. Linear Discriminant Analysis (LDA) afforded a high reliability degree for discriminating cultivars (almost 90% of prediction ability), and a good assigning ability for the geographical origin (Ogliarola and Coratina samples used as subsets). Soil analyses were performed for each tree. Regression analysis was applied to soil composition in order to correlate available nutrients and total metals with the content of fatty acids and minor components present in monovarietal extra virgin olive oils. In the case of oleic and linoleic fatty acids, and for some terpenes, B, Cr, Mn, Zn were found to give significant correlations. Zn and Mn were the most significant trace elements for all the correlations found (p < 0.01). The results obtained (genetic, spectroscopic and soil analyses) are discussed as a multidisciplinary approach for setting up a strategy for a cultivar and/or geographic origin certification committed database construction.     

Free vibrations of anisotropic doubly-curved shells and panels of revolution with a free-form meridian resting on Winkler–Pasternak elastic foundations

The Generalized Differential Quadrature (GDQ) method is applied to study the dynamic behavior of anisotropic doubly-curved shells and panels of revolution with a free-form meridian resting on Winkler–Pasternak elastic foundations. The First-order Shear Deformation Theory (FSDT) is used to analyze the above mentioned moderately thick structural elements. In order to include the effect of the initial curvature from the beginning of the theory formulation a generalization of the kinematical model is adopted for the Reissner–Mindlin and Toorani–Lakis theory. By so doing a generalization of the theory of anisotropic doubly-curved shells and panels of revolution is proposed. Simple Rational Bézier curves are used to define the meridian curve of the revolution structures. The Differential Quadrature (DQ) rule is introduced to determine the geometric parameters of the structures with a free-form meridian. Results are obtained taking the meridional and circumferential co-ordinates into account, without using the Fourier modal expansion methodology. Comparisons between the general formulation and the Classical Reissner–Mindlin and Classical Toorani–Lakis theory are presented. New results are presented in order to investigate the effects of the Winkler modulus, the Pasternak modulus and the inertia of the elastic foundation on the free vibrations of anisotropic shells of revolution with a free-form meridian.     

Earth-to-air heat exchangers for Italian climates

The European Energy Efficiency Building Directive 2002/91/CE, as well as other acts and funding programs, strongly promotes the adoption of passive strategies for buildings, in order to achieve indoor thermal comfort conditions above all in summer, so reducing or avoiding the use of air conditioning systems.In this paper, the energy performances achievable using an earth-to-air heat exchanger for an air-conditioned building have been evaluated for both winter and summer. By means of dynamic building energy performance simulation codes, the energy requirements of the systems have been analysed for different Italian climates, as a function of the main boundary conditions (such as the typology of soil, tube material, tube length and depth, velocity of the air crossing the tube, ventilation airflow rates, control modes). The earth-to-air heat exchanger has shown the highest efficiency for cold climates both in winter and summer.The possible coupling of this technology with other passive strategies has been also examined. Then, a technical-economic analysis has been carried out: this technology is economically acceptable (simple payback of 5–9 years) only in the cases of easy and cheap moving earth works; moreover, metallic tubes are not suitable.Finally, considering in summer a not fully air-conditioned building, only provided with diurnal ventilation coupled to an earth-to-air heat exchanger plus night-time ventilation, the possible indoor thermal comfort conditions have been evaluated.     

Neuroimaging computer-aided diagnosis systems for Alzheimer's disease

This paper has reviewed the state-of-the-art approaches for Computer Aided Diagnosis Systems (CADS) for Alzheimer's Disease (AD) using neuroimaging. Identification of the current approaches leads to improving the efficiency of these techniques. The analysis covered 110 articles published between 2009 and January 2018. Papers were chosen according to the Newcastle-Ottawa criteria. MeSH terms were “computer aided diagnosis systems for Alzheimer's disease” and “computer aided diagnosis systems methods for diagnosis of Alzheimer's disease”. CADS algorithms have been presented with specific methods. There is no standardized approach to determine the best one. This study has tables that aimed to conclude all methods in a precise way. Among them, Statistical Parametric Mapping (SPM), Principal Component Analysis (PCA), and Support Vector Machine (SVM) were the most common, respectively. CADS for AD could become important in clinical practice in the near future. The evaluation criteria approved their efficiency as a second opinion besides the neurologist.