412 research outputs found
Heparan sulfate proteoglycans: The sweet side of development turns sour in mucopolysaccharidoses
Abstract Heparan sulfate proteoglycans (HSPGs) are complex carbohydrate-modified proteins ubiquitously expressed on cell surfaces, extracellular matrix and basement membrane of mammalian tissues. Beside to serve as structural constituents, they regulate multiple cellular activities. A critical involvement of HSPGs in development has been established, and perturbations of HSPG-dependent pathways are associated with many human diseases. Recent evidence suggest a role of HSPGs in the pathogenesis of mucopolysaccharidoses (MPSs) where the accumulation of undigested HS results in the loss of cellular functions, tissue damage and organ dysfunctions accounting for clinical manifestations which include central nervous system (CNS) involvement, degenerative joint disease and reduced bone growth. Current therapies are not curative but only ameliorate the disease symptoms. Here, we highlight the link between HSPG functions in the development of CNS and musculoskeletal structures and the etiology of some MPS phenotypes, suggesting that HSPGs may represent potential targets for the therapy of such incurable diseases
Midfrontal theta transcranial alternating current stimulation modulates behavioural adjustment after error execution
Cognitive control during conflict monitoring, error processing, and post-error adjustment appear to be associated with the occurrence of midfrontal theta (MFÏŽ). While this association is supported by correlational EEG studies, much less is known about the possible causal link between MFÏŽ and error and conflict processing. In the present study, we aimed to explore the role of band-specific effects in modulating the error system during a conflict resolution. In turn, we delivered transcranial alternating current stimulation (tACS) at different frequency bands (delta ÎŽ, theta Ξ, alpha α, beta ÎČ, gamma Îł) and sham stimulation over the medial frontal cortex (MFC) in 36 healthy participants performing a modified version of the Flanker task. Task performance and reports about the sensations (e.g. visual flickering, cutaneous burning) induced by the different frequency bands, were also recorded. We found that online Ξ-tACS increased the response speed to congruent stimuli after error execution with respect to sham stimulation. Importantly, the accuracy following the errors did not decrease because of speed-accuracy trade off. Moreover, tACS evoked visual and somatosensory sensations were significantly stronger at α-tACS and ÎČ-tACS compared to other frequencies. Our findings suggest that theta activity plays a causative role in modulating behavioural adjustments during perceptual choices in a stimulus-response conflict task. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Lt
Competitive binding of extracellular accumulated heparan sulfate reduces lysosomal storage defects and triggers neuronal differentiation in a model of Mucopolysaccharidosis IIIB.
Mucopolysaccharidoses (MPSs) are a group of inherited lysosomal storage disorders associated with the deficiency of lysosomal enzymes involved in glycosaminoglycan (GAG) degradation. The resulting cellular accumulation of GAGs is responsible for widespread tissue and organ dysfunctions. The MPS III, caused by mutations in the genes responsible for the degradation of heparan sulfate (HS), includes four subtypes (A, B, C, and D) that present significant neurological manifestations such as progressive cognitive decline and behavioral disorders. The established treatments for the MPS III do not cure the disease but only ameliorate non-neurological clinical symptoms. We previously demonstrated that the natural variant of the hepatocyte growth factor NK1 reduces the lysosomal pathology and reactivates impaired growth factor signaling in fibroblasts from MPS IIIB patients. Here, we show that the recombinant NK1 is effective in rescuing the morphological and functional dysfunctions of lysosomes in a neuronal cellular model of the MPS IIIB. More importantly, NK1 treatment is able to stimulate neuronal differentiation of neuroblastoma SK-NBE cells stable silenced for the NAGLU gene causative of the MPS IIIB. These results provide the basis for the development of a novel approach to possibly correct the neurological phenotypes of the MPS IIIB as well as of other MPSs characterized by the accumulation of HS and progressive neurodegeneration
Serotonin transporter transgenic (SERTcre) mouse line reveals developmental targets of serotonin specific reuptake inhibitors (SSRIs)
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Unveiling Oxygen Redox Activity in P2-Type NaxNi0.25Mn0.68O2 High-Energy Cathode for Na-Ion Batteries
Na-ion batteries are emerging as convenient energy-storage devices for large-scale applications. Enhanced energy density and cycling stability are key in the optimization of functional cathode materials such as P2-type layered transition metal oxides. High operating voltage can be achieved by enabling anionic reactions, but irreversibility of O2â/O2nâ/O2 evolution still limits this chance, leading to extra capacity at first cycle that is not fully recovered. Here, we dissect this intriguing oxygen redox activity in Mn-deficient NaxNi0.25Mn0.68O2 from first-principles, by analyzing the formation of oxygen vacancies and dioxygen complexes at different stages of sodiation. We identify low-energy intermediates that release molecular O2 at high voltage, and we show how to improve the overall cathode stability by partial substitution of Ni with Fe. These new atomistic insights on O2 formation mechanism set solid scientific foundations for inhibition and control of this process toward the rational design of new anionic redox-active cathode materials
Breaking Symmetry Rules Enhance the Options for Stereoselective Propene Polymerization Catalysis
An example of breaking "Ewen's symmetry rule" for olefin catalysis polymerization is proposed by DFT calculations. Catalyst precursors with Cs symmetry are suggested to promote the isotactic propene polymerization by a modification of the active site geometry obtained via coordination with AlH-alkyl species in solution. The origin of stereocontrol in olefin polymerization is due to a dual mechanism dictated by the chiral catalyst. These findings may expand the toolbox for promoting stereoselective olefin polymerization by transition metal catalysts
Ru-Doping of P2-NaxMn0.75Ni0.25O2-Layered Oxides for High-Energy Na-Ion Battery Cathodes: First-Principles Insights on Activation and Control of Reversible Oxide Redox Chemistry
Expression of orexin B and its receptor 2 in rat testis
The peptides orexin A (OxA) and orexin B (OxB) deriving from a common precursor molecule, prepro-orexin, by proteolytic cleavage, bind the two G-coupled OX1 and OX2 receptors. While OX1 selectively binds OxA, OX2 shows similar affinity for both orexins. Firstly discovered in the hypothalamus, orexins and their receptors have been found in other brain regions as well as in peripheral tissues of mammals, thus resulting involved in the regulation of a broad variety of physiological functions. While the functional localization of OxA and OX1 in the mammalian genital tract has been already described, the expression of OxB and OX2 and their potential role in the reproductive functions remain to be explored. Here, we investigated the presence of OxB and OX2 in the rat testis by immunohistochemical and biochemical analyses. The results definitely demonstrated the localization of OxB and OX2 in pachytene and second spermatocytes as well as in spermatids at all stages of the cycle of the seminiferous epithelium. The expression of both OX2 mRNA and protein in the rat testis was also established by RT-PCR and Western blotting, respectively. The analysis of the molecular mechanism of action of OxB in the rat testis showed that OxB, in contrast with OxA, is unable to promote steroidogenesis. These results translate into the regulation of diverse biological actions by OxA and OxB in the male gonad
Combined Structural, Chemometric, and Electrochemical Investigation of Vertically Aligned TiO2 Nanotubes for Na-ion Batteries
In the challenging scenario of anode materials for sodium-ion batteries, TiO2 nanotubes could represent a winning choice in terms of cost, scalability of the preparation procedure, and long-term stability upon reversible operation in electrochemical cells. In this work, a detailed physicochemical, computational, and electrochemical characterization is carried out on TiO2 nanotubes synthesized by varying growth time and heat treatment, viz. the two most significant experimental parameters during preparation. A chemometric approach is proposed to obtain a concrete and solid multivariate analysis of sodium battery electrode materials. Such a statistical approach, combined with prolonged galvanostatic cycling and density functional theory analysis, allows identifying anatase at high growth time as the TiO2 polymorph of choice as an anode material, thus creating a benchmark for sodium-ion batteries, which currently took the center stage of the research in the field of energy storage systems from renewables
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Investigating light-induced processes in covalent dye-catalyst assemblies for hydrogen production
The light-induced processes occurring in two dye-catalyst assemblies for light-driven hydrogen production were investigated by ultrafast transient absorption spectroscopy. These dyads consist of a push-pull organic dye based on a cyclopenta[1,2-b:5,4-bâ]dithiophene (CPDT) bridge, covalently linked to two different H2-evolving cobalt catalysts. Whatever the nature of the latter, photoinduced intramolecular electron transfer from the excited state of the dye to the catalytic center was never observed. Instead, and in sharp contrast to the reference dye, a fast intersystem crossing (ISC) populates a long-lived triplet excited state, which in turn non-radiatively decays to the ground state. This study thus shows how the interplay of different structures in a dye-catalyst assembly can lead to unexpected excited state behavior and might open up new possibilities in the area of organic triplet sensitizers. More importantly, a reductive quenching mechanism with an external electron donor must be considered to drive hydrogen production with these dye-catalyst assemblies. © 2020 by the authors. Licensee MDPI, Basel, Switzerland
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