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Gsα^(R201C)and estrogen reveal different subsets of bone marrow adiponectin expressing osteogenic cells

Bone Research 2022年第4期10卷 784-798页

作者： Biagio Palmisano Rossella Labella Samantha Donsante Cristina Remoli Emanuela Spica Ilenia Coletta Giorgia Farinacci michele dello spedale venti Isabella Saggio Marta Serafini Pamela Gehron Robey Alessandro Corsi Mara Riminucci Department of Molecular Medicine Sapienza University of RomeRome 00161Italy Tettamanti Research Center Department of PediatricsUniversity of Milano Bicocca/Fondazione MBBMMonza 20900Italy Department of Biology and Biotechnology Sapienza University of RomeRome 00185Italy Institute of Structural Biology and School of Biological Sciences Nanyang Technological University 639798 SingaporeSingapore CNR Institute of Molecular Biology and Pathology Piazzale Aldo Moro 5Rome 00185Italy Skeletal Biology Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthDepartment of Health and Human ServicesBethesdaMD 20892USA

The Gsα/cAMP signaling pathway mediates the effect of a variety of hormones and factors that regulate the homeostasis of the post-natal ***,the dysregulated activity of Gsαdue to gain-of-function mutations (R201C/R201H)results in severe architectural and functional derangements of the entire bone/bone marrow *** the consequences of gain-of-function mutations of Gsαhave been extensively investigated in osteoblasts and in bone marrow osteoprogenitor cells at various differentiation stages,their effect in adipogenically-committed bone marrow stromal cells has remained *** generated a mouse model with expression of Gsα^(R201C) driven by the Adiponectin(Adq)***-Gsα^(R201C) mice developed a complex combination of metaphyseal,diaphyseal and cortical bone *** the metaphysis,Gsα^(R201C) caused an early phase of bone resorption followed by bone *** bone formation was sustained by cells that were traced by Adq-Cre and eventually resulted in a high trabecular bone mass *** the diaphysis,Gsα^(R201C),in combination with estrogen,triggered the osteogenic activity of Adq-Cre-targeted perivascular bone marrow stromal cells leading to intramedullary bone ***,consistent with the previously unnoticed presence of Adq-Cre-marked pericytes in intraosseous blood vessels,Gsα^(R201C) caused the development of a lytic phenotype that affected both cortical(increased porosity)and trabecular(tunneling resorption)*** results provide the first evidence that the Adq-cell network in the skeleton not only regulates bone resorption but also contributes to bone formation,and that the Gsα/cAMP pathway is a major modulator of both functions.

关键词： estrogen sustained skeleton

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A blockchain architecture for industrial applications

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Blockchain(Research and Applications) 2022年第4期3卷 1-13页

作者： Lodovica Marchesi michele Marchesi Roberto Tonelli Maria Ilaria Lunesu Department of Mathematics and Computer Science University of CagliariCagliari09124Italy

Blockchain and the programs running on it,called smart contracts,are increasingly applied in all fields where trust and strong certifications are *** work focuses on industrial applications of blockchains and not on cryptocurrencies or *** use frameworks to compare public and permissioned blockchains specifically suited for industrial *** also propose a complete solution based on Ethereum to implement a decentralized application,putting together in an original way,components and patterns already used and *** solution is characterized by a set of validator nodes running the blockchain using Proof-of-Authority or similar efficient consensus algorithms,by the use of an explorer enabling users to check the blockchain state,and the source code of the smart contracts running on *** time to time,the hash digest of the last mined block is written into a public blockchain to guarantee *** right to send transactions is granted by validator nodes to users by endowing them with the Ethers mined ***,the proposed approach has the same transparency and immutability as a public blockchain,largely reducing its drawbacks.

关键词： Permissioned blockchain Industrial application Information system Software application Ethereum

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