A2B Adenosine Receptors: When Outsiders May Become an Attractive Target to Treat Brain Ischemia or Demyelination

Adenosine is a signaling molecule, which, by activating its receptors, acts as an important player after cerebral ischemia. Here, we review data in the literature describing A_2BR-mediated effects in models of cerebral ischemia obtained in vivo by the occlusion of the middle cerebral artery (MCAo) or in vitro by oxygen-glucose deprivation (OGD) in hippocampal slices. Adenosine plays an apparently contradictory role in this receptor subtype depending on whether it is activated on neuro-glial cells or peripheral blood vessels and/or inflammatory cells after ischemia. Indeed, A_2BRs participate in the early glutamate-mediated excitotoxicity responsible for neuronal and synaptic loss in the CA1 hippocampus. On the contrary, later after ischemia, the same receptors have a protective role in tissue damage and functional impairments, reducing inflammatory cell infiltration and neuroinflammation by central and/or peripheral mechanisms. Of note, demyelination following brain ischemia, or autoimmune neuroinflammatory reactions, are also profoundly affected by A_2BRs since they are expressed by oligodendroglia where their activation inhibits cell maturation and expression of myelin-related proteins. In conclusion, data in the literature indicate the A_2BRs as putative therapeutic targets for the still unmet treatment of stroke or demyelinating diseases.     

Enhancing cultural recommendations through social and linked open data

In this article, we describe a hybrid recommender system (RS) in the artistic and cultural heritage area, which takes into account the activities on social media performed by the target user and her friends, and takes advantage of linked open data (LOD) sources. Concretely, the proposed RS (1) extracts information from Facebook by analyzing content generated by users and their friends; (2) performs disambiguation tasks through LOD tools; (3) profiles the active user as a social graph; (4) provides her with personalized suggestions of artistic and cultural resources in the surroundings of the user’s current location. The last point is performed by integrating collaborative filtering algorithms with semantic technologies in order to leverage LOD sources such as DBpedia and Europeana. Based on the recommended points of cultural interest, the proposed system is also able to suggest to the active user itineraries among them, which meet her preferences and needs and are sensitive to her physical and social contexts as well. Experimental results on real users showed the effectiveness of the different modules of the proposed recommender.

     

Transition‐Metal Dichalcogenide NiTe2: An Ambient‐Stable Material for Catalysis and Nanoelectronics

By means of theory and experiments, the application capability of nickel ditelluride (NiTe₂) transition‐metal dichalcogenide in catalysis and nanoelectronics is assessed. The Te surface termination forms a TeO₂ skin in an oxygen environment. In ambient atmosphere, passivation is achieved in less than 30 min with the TeO₂ skin having a thickness of about 7 Å. NiTe₂ shows outstanding tolerance to CO exposure and stability in water environment, with subsequent good performance in both hydrogen and oxygen evolution reactions. NiTe₂‐based devices consistently demonstrate superb ambient stability over a timescale as long as one month. Specifically, NiTe₂ has been implemented in a device that exhibits both superior performance and environmental stability at frequencies above 40 GHz, with possible applications as a receiver beyond the cutoff frequency of a nanotransistor.     

A water-soluble,mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices.

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Designing Dual Transglutaminase 2/Histone Deacetylase Inhibitors Effective at Halting Neuronal Death

In recent years there has been a clear consensus that neurodegenerative conditions can be better treated through concurrent modulation of different targets. Herein we report that combined inhibition of transglutaminase 2 (TG2) and histone deacetylases (HDACs) synergistically protects against toxic stimuli mediated by glutamate. Based on these findings, we designed and synthesized a series of novel dual TG2–HDAC binding agents. Compound 3 [(E)‐N‐hydroxy‐5‐(3‐(4‐(3‐oxo‐3‐(pyridin‐3‐yl)prop‐1‐en‐1‐yl)phenyl)thioureido)pentanamide] emerged as the most interesting of the series, being able to inhibit TG2 and HDACs both in vitro (TG2 IC₅₀=13.3±1.5 μm , HDAC1 IC₅₀=3.38±0.14 μm , HDAC6 IC₅₀=4.10±0.13 μm ) and in cell‐based assays. Furthermore, compound 3 does not exert any toxic effects in cortical neurons up to 50 μm and protects neurons against toxic insults induced by glutamate (5 mm ) with an EC₅₀ value of 3.7±0.5 μm .     

Formalizing REST APIs for web-based communication and SIP interworking

This paper proposes an instantaneous recovery route design scheme using multiple coding-aware link protection scenarios to achieve higher link cost reduction in the network. In this scheme, two protection scenarios, namely, (i) traffic splitting (TS), and (ii) two sources and a common destination (2SD) are used to integrate multiple sources and a common destination. The proposed scheme consists of two phases. In the first phase, the proposed scheme determines routes for 2SD and TS scenarios of all possible source-destination pairs to minimize the total link cost. In this phase, the network coding is applied to the common path within each scenario, individually. In the second phase, network coding is applied to the common path between two scenarios (or a scenario pair) in order to enhance the resource saving. This phase develops conditions that select the most appropriate combination of scenario pairs, such as TS–TS, 2SD–2SD, and 2SD–TS for network coding, including their proofs. Using these conditions, a heuristic algorithm is introduced in order to select the most appropriate combination of scenario pairs for further enhancing of resource saving. Simulation results show that the proposed scheme outperforms the conventional 1 + 1 protection scheme, the TS scenario, and the 2SD scenario in terms of link cost reduction in the network.     

Serviceability assessment of footbridges in unrestricted pedestrian traffic conditions

A critical analysis of the procedures available in the literature for the serviceability assessment of footbridges in unrestricted pedestrian traffic conditions is presented. Based on a full probabilistic model of the loading, Monte Carlo simulations are carried out and a critical discussion concerning the role of the statistical distribution of the random walking parameters on the footbridge dynamic response is provided. Furthermore, numerical results are compared with the ones obtained by simplified procedures. Finally, a graphical procedure is proposed which permits a simple evaluation of footbridge maximum acceleration as a function of the modal mass, damping ratio and expected average pedestrian flow.     

Size-controlled synthesis and NMR characterization of mesitylene-vinylsiloxanes stabilized Pt nanoparticles in solution

Pt nanoclusters have been generated by reaction of Pt vapour and mesitylene vapour and the role of the mesitylene/platinum ratio and the Pt particle size has been evaluated, quenching the resulting mesitylene solvated Pt atoms with 1,3-divinyltetramethyldisiloxane (DVS) as additional ligand. The Pt particle sizes have been estimated on the basis of DOSY (Diffusion-Ordered SpectroscopY) analysis and information on their structure features have been obtained by combined use of 2D NMR techniques.     

Age-Related Changes in the Matrisome of the Mouse Skeletal Muscle

Aging is characterized by a progressive decline of skeletal muscle (SM) mass and strength which may lead to sarcopenia in older persons. To date, a limited number of studies have been performed in the old SM looking at the whole, complex network of the extracellular matrix (i.e., matrisome) and its aging-associated changes. In this study, skeletal muscle proteins were isolated from whole gastrocnemius muscles of adult (12 mo.) and old (24 mo.) mice using three sequential extractions, each one analyzed by liquid chromatography with tandem mass spectrometry. Muscle sections were investigated using fluorescence- and transmission electron microscopy. This study provided the first characterization of the matrisome in the old SM demonstrating several statistically significantly increased matrisome proteins in the old vs. adult SM. Several proteomic findings were confirmed and expanded by morphological data. The current findings shed new light on the mutually cooperative interplay between cells and the extracellular environment in the aging SM. These data open the door for a better understanding of the mechanisms modulating myocellular behavior in aging (e.g., by altering mechano-sensing stimuli as well as signaling pathways) and their contribution to age-dependent muscle dysfunction.