Objective. Increased nucleoside triphosphate pyrophosphohydrolase (NTPPPH) activity in chondrocytes is associated with cartilage matrix inorganic pyrophosphate (PPi) supersaturation in chondrocalcinosis. This study compared the roles of the transforming growth factor ␤ (TGF␤)-inducible plasma cell membrane glycoprotein-1 (PC-1) and the closely related B10 NTPPPH activities in chondrocyte PPi metabolism.Methods. NTPPPH expression was studied using reverse transcriptase-polymerase chain reaction and Western blotting. Transmembrane PC-1 (tmPC-1), water-soluble secretory PC-1 (secPC-1), and transmembrane B10 were expressed by adenoviral gene transfer or plasmid transfection, and expression of PPi was assessed in cultured articular chondrocytes and immortalized NTPPPH-deficient costal chondrocytes (TC28 cells).Results. PC-1 and B10 messenger RNA were demonstrated in articular cartilages in situ, in untreated cultured normal articular chondrocytes, and in TC28 cells. Expression of tmPC-1 and secPC-1, but not B10, rendered the NTPPPH-deficient TC28 cells able to increase expression of extracellular PPi, with or without addition of TGF␤ (10 ng/ml) to the media. More plasma membrane NTPPPH activity was detected in cells transfected with tmPC-1 than in cells transfected with B10. Furthermore, confocal microscopy with immunofluorescent staining of articular chondrocytes confirmed preferential plasma membrane localization of PC-1, relative to B10. Finally, both PC-1 and B10 increased the levels of intracellular PPi, but PC-1 and B10 appeared to act principally in different intracellular compartments (Golgi and post-Golgi versus pre-Golgi, respectively).Conclusion. PC-1 and B10 NTPPPH activities were not redundant in chondrocytes. Although increased PC-1 and B10 expression caused elevations in intracellular PPi, the major effects of PC-1 and B10 were exerted in distinct subcellular compartments. Moreover, PC-1 (transmembrane and secreted), but not B10, increased the levels of extracellular PPi. Differential expression of PC-1 and B10 could modulate cartilage mineralization in degenerative joint diseases.Articular cartilage chondrocytes have the unique ability to constitutively elaborate relatively large amounts of extracellular inorganic pyrophosphate (PPi), and cartilage is the major source of free PPi in joints (1-3). Moreover, in aging and osteoarthritic (OA) articular cartilage, a dysregulated increase in PPi elaboration in chondrocytes and other changes in the chondrocyte differentiation and matrix composition promote calcium Ms Moffa

In this work, the effect of pH on a nitrogen-doped ordered mesoporous carbon catalyst for the oxygen reduction reaction (ORR) is extensively investigated. Electrochemical methods, including cyclic voltammetry (CV), rotating ring-disk electrode (RRDE), and cathodic stripping voltammetry, are applied to investigate the electrochemical behavior in electrolyte solutions of different pHs (0–2, 7, 12–14). The CV result reveals that nitrogen-doped carbon has a variety of enriched reversible redox couples on the surface, and the pH has a significant effect. Whether these redox couples are electrochemically active or inactive to the ORR depends on the electrolyte used. In acid media, an oxygen molecule directly interacts with the redox couple, and its reduction proceeds by the surface-confined redox-mediation mechanism, yielding water as the product. Similarly, the first electron transfer in alkaline media is achieved by the surface-confined redox-mediation mechanism at the higher potentials. With decreasing potential, another parallel charge transfer process by the outer-sphere electron transfer mechanism gets pronounced, followed by parallel 2-e and 4-e reduction of oxygen. The proposed mechanisms are well supported by the following electrochemical results. At high potentials, the Tafel slope remains unchanged (60–70 mV dec–1) at all investigated pHs, and the reaction order of proton and hydroxyl ions is found to be 1 and −0.5, respectively, in acid and alkaline media. The electron transfer number is ∼4 at high potentials in both acid and alkaline media; however, at higher pHs, it shows a considerable decrease as the potential decreases, indicating the change in the reaction pathway. Finally, the nitrogen-doped carbon catalyst shows performance in alkaline media superior to that in acid media. Such a gap in performance is rationalized by considering the chemical change in the surface at different pH values.

Autoimmune lymphoproliferative syndrome (ALPS) is classically defined as a disease with defective FAS-mediated apoptosis (type I-III). Germline NRAS mutation was recently identified in type IV ALPS. We report 2 cases with ALPS-like disease with somatic KRAS mutation. Both cases were characterized by prominent autoimmune cytopenia and lymphoadenopathy/splenomegaly. These patients did not satisfy the diagnostic criteria for ALPS or juvenile myelomonocytic leukemia and are probably defined as a new disease entity of RAS-associated ALPS-like disease (RALD).

Haploinsufficiency of TNFAIP3 (A20) by a germline heterozygous mutation leads to the ALPS phenotype.

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Electro‐oxidation of glycerol affords a totally green route to produce high value‐added chemicals. Herein, we report a study on glycerol electro‐oxidation over a series of graphene nanosheet supported Pt (Pt/GNS), PtNi (PtNi/GNS), PtRu (PtRu/GNS), PtRh (PtRh/GNS), PtRuNi (PtRuNi/GNS), and PtRhNi (PtRhNi/GNS) catalysts in alkaline solution. The activity of the catalysts was evaluated by cyclic voltammetry, linear sweep voltammetry, and chronoamperometric measurements. The PtRh/GNS and PtRhNi/GNS catalysts exhibited superior activity in terms of higher current densities and lower onset potentials. The products of glycerol oxidation formed at potentials of −0.4, −0.1, and 0.2 V, were systematically analyzed by high performance liquid chromatography (HPLC). Five compounds as products from glycerol electro‐oxidation catalyzed by the prepared materials were found, including glyceraldehyde, glycolic acid, tartronic acid, glyceric acid and oxalate acid. The product distribution at the different potentials was investigated for all catalysts. A maximum glycolic acid selectivity of 65.4 % was obtained for the Pt/GNS catalyst at 0.2 V while a maximum glyceric acid selectivity of 47.7 % was achieved using the PtNi/GNS catalyst at −0.1 V. It was found that the introduction of Ru facilitated the formation of C3 products while the addition of Rh was beneficial for the formation of C2 products. Based on HPLC results, the pathways of glycerol electro‐oxidation by the prepared catalysts were proposed.

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