The Expression of Active CD11b Monocytes in Blood and Disease Progression in Amyotrophic Lateral Sclerosis

Monocytes expressing the inflammation suppressing active CD11b, a beta2 integrin, may regulate neuroinflammation and modify clinical outcomes in amyotrophic lateral sclerosis (ALS). In this single site, retrospective study, peripheral blood mononuclear cells from 38 individuals living with ALS and 20 non-neurological controls (NNC) were investigated using flow cytometry to study active CD11b integrin classical (CM), intermediate (IM) and non-classical (NCM) monocytes during ALS progression. Seventeen ALS participants were sampled at the baseline (V1) and at two additional time points (V2 and V3) for longitudinal analysis. Active CD11b+ CM frequencies increased steeply between the baseline and V3 (ANOVA repeated measurement, p < 0.001), and the V2/V1 ratio negatively correlated with the disease progression rate, similar to higher frequencies of active CD11b+ NCM at the baseline (R = −0.6567; p = 0.0031 and R = 0.3862; p = 0.0168, respectively). CD11b NCM, clinical covariates and neurofilament light-chain plasma concentration at the baseline predicted shorter survival in a multivariable and univariate analysis (CD11b NCM—HR: 1.05, CI: 1.01–1.11, p = 0.013. Log rank: above median: 43 months and below median: 21.22 months; p = 0.0022). Blood samples with the highest frequencies of active CD11b+ IM and NCM contained the lowest concentrations of soluble CD11b. Our preliminary data suggest that the levels of active CD11b+ monocytes and NCM in the blood predict different clinical outcomes in ALS.     

Differential Metabotypes in Synovial Fibroblasts and Synovial Fluid in Hip Osteoarthritis Patients Support Inflammatory Responses

Changes in cellular metabolism have been implicated in mediating the activated fibroblast phenotype in a number of chronic inflammatory disorders, including pulmonary fibrosis, renal disease and rheumatoid arthritis. The aim of this study was therefore to characterise the metabolic profile of synovial joint fluid and synovial fibroblasts under both basal and inflammatory conditions in a cohort of obese and normal-weight hip OA patients. Furthermore, we sought to ascertain whether modulation of a metabolic pathway in OA synovial fibroblasts could alter their inflammatory activity. Synovium and synovial fluid was obtained from hip OA patients, who were either of normal-weight or obese and were undergoing elective joint replacement surgery. The synovial fluid metabolome was determined by 1H NMR spectroscopy. The metabolic profile of isolated synovial fibroblasts in vitro was characterised by lactate secretion, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using the Seahorse XF Analyser. The effects of a small molecule pharmacological inhibitor and siRNA targeted at glutaminase-1 (GLS1) were assessed to probe the role of glutamine metabolism in OA synovial fibroblast function. Obese OA patient synovial fluid (n = 5) exhibited a different metabotype, compared to normal-weight patient fluid (n = 6), with significantly increased levels of 1, 3-dimethylurate, N-Nitrosodimethylamine, succinate, tyrosine, pyruvate, glucose, glycine and lactate, and enrichment of the glutamine–glutamate metabolic pathway, which correlated with increasing adiposity. In vitro, isolated obese OA fibroblasts exhibited greater basal lactate secretion and aerobic glycolysis, and increased mitochondrial respiration when stimulated with pro-inflammatory cytokine TNFα, compared to fibroblasts from normal-weight patients. Inhibition of GLS1 attenuated the TNFα-induced expression and secretion of IL-6 in OA synovial fibroblasts. These findings suggest that altered cellular metabolism underpins the inflammatory phenotype of OA fibroblasts, and that targeted inhibition of glutamine–glutamate metabolism may provide a route to reducing the pathological effects of joint inflammation in OA patients who are obese.     

3D model of a sector of the South Scotia Ridge (Antarctica)

A three-dimensional geological model was built to show and analyse a northern sector of the Scotia–Antarctica transform plate boundary.The South Scotia Ridge is a 400 km long submerged continental structural high representing the eastern continuation of the Antarctic Peninsula. South Scotia Ridge runs approximately in the E–W direction, separating Scotia Sea Plate from Antarctica Plates. Structures, due to the transform plate margin, are considered to be concentrated inside this continental high. The three-dimensional model, built using seismic profiles and a digital elevation model, is a powerful tool to visualize and help to understand deep geological structures. Maps and profiles, on the contrary, only give a two-dimensional view, and do not show the structure of the continental–oceanic boundary at depth.The model shows that the deformation style of the continental–oceanic boundary, and of the oceanic crust nearby, is related to the left-lateral movement of the main transform fault system. Furthermore, it seems to be connected to the orientation and geometry of the South Scotia Ridge with respect to the homogeneous deformation regime, which affects the entire Scotia Plate. Moving from west to east, the NW-dipping main fault surface becomes almost vertical with a sinistral strike–slip movement in the central sector. To the east, a south-dipping plane decreases its inclination and changes orientation (from E–W to ESE–WNW): here shortening features are visible.The three-dimensional geological model presents a western and central province wherein the continental–oceanic boundary involves the fragmented continental blocks, the continental slope, the oceanic basement and sediments. The sedimentary cover and the oceanic basement are not deformed in the eastern province.     

Sol–Gel Processing and Characterization of Pure and Metal-Doped SnO2 Thin Films

A chloride-based inorganic sol–gel route was used for preparing pure and metal (osmium, nickel, palladium, platinum)-doped SnO₂ sol. SnCl₄ was first reacted with propanol, then the resulting compound was hydrolyzed and subsequently mixed with solutions of the metal dopants. The obtained sols were used for depositing thin films by spin coating or for preparing powders by solvent evaporation at 110°C. FTIR spectroscopy and thermal analysis of the powders revealed that chlorine still bound to tin stabilized the sol against gelation by hindering the condensation reactions. Film characterizations showed that platinum and palladium, unlike nickel and osmium, were likely to form nanoparticles in the SnO₂ lattice. This result was discussed with regard to the different ways that platinum and palladium, on one hand, and nickel and osmium, on the other, modified the growth of SnO₂ grains and the film roughness and morphology. Dopants that formed nanoparticles (platinum, palladium) resulted in the roughest film, while dopants that did not form particles (nickel, osmium) resulted in SnO₂ grain size very close to that of pure SnO₂.     

An infrastructure to support cooperation of knowledge-level agents on the semantic Grid

Can a Knowledge-Level layer be located in the Semantic Grid infrastructure? Is it possible to design an Agent Communication Language (ACL) which enables Knowledge-Level agents to cooperate in a geographically distributed Semantic Grid despite nodes’ failures or malfunctions? This paper tries to address the above Semantic Grid challenges presenting an agent-based Open Service Architecture which integrates geographically distributed agents in a Semantic Grid. The architecture is well integrated with standard Internet components and technologies and supports communication among Knowledge-Level agents. The role of agents is to retrieve, execute and compose available services providing more sophisticated instances of them. Inter-agent communication is realized by exploiting an advanced Agent Communication Language which supports a fault-tolerant anonymous interaction protocol and satisfies a set of well defined Knowledge-Level programming requirements. Here, we present the design of the architecture and of the Agent Communication Language as well as their implementation. The architecture is evaluated by means of several case studies which highlight the main feature of our proposal. The main advantage of our approach is to demonstrate that different issues, such as high level inter-agent communication and fault tolerance, can be successfully integrated in Grid infrastructures which provide Web Services maintaining a clean design of the architecture and a Knowledge-Level characterization.