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Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development

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Bone Research 2024年第1期12卷 199-214页

作者： Laura J.Brylka Assil-Ramin Alimy Miriam E.A.Tschaffon-Müller Shan Jiang Tobias Malte Ballhause Anke Baranowsky Simon von Kroge Julian Delsmann Eva Pawlus Kian Eghbalian Klaus Püschel Astrid Schoppa Melanie Haffner-Luntzer David J.Beech Frank Timo Beil Michael Amling johannes keller Anita Ignatius Timur A.Yorgan Tim Rolvien Thorsten Schinke Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf20246 HamburgGermany Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-Eppendorf20246 HamburgGermany Institute of Orthopedic Research and Biomechanics University Medical Center UlmBadenWürttemberg89081 UlmGermany Department Legal Medicine University Medical Center Hamburg-Eppendorf20246 HamburgGermany Leeds Institute of Cardiovascular and Metabolic Medicine School of MedicineUniversity of LeedsLS29JT LeedsUK

Piezo proteins are mechanically activated ion channels,which are required for mechanosensing functions in a variety of cell *** we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for boneanabolic processes,there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in *** we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis(OA)*** with chondrocyte-specific inactivation of Piezo1(Piezo1^(Col2a1Cre)),but not of Piezo2,developed a near absence of trabecular bone below the chondrogenic growth plate ***,all Piezo1^(Col2a1Cre) animals displayed multiple fractures of rib bones at 7 days of age,which were located close to the growth *** skeletal growth was only mildly affected in these mice,OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of ***,when OA was induced by anterior cruciate ligament transection,only the chondrocyte inactivation of Piezo1,not of Piezo2,resulted in attenuated articular cartilage ***,osteophyte formation and maturation were also reduced in Piezo1^(Col2a1Cre) *** further observed increased Piezo1 protein abundance in cartilaginous zones of human ***,we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in ***,our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes,but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

关键词： Piezo1 markedly ossification

The role of sphingosine-1-phosphate in bone remodeling and osteoporosis

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Bone Research 2022年第2期10卷 265-273页

作者： Justus M.Grewe Paul-Richard Knapstein Antonia Donat Shan Jiang Daniel JSmit Weixin Xie johannes keller Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-Eppendorf20246 HamburgGermany Clinic and Polyclinic for Vascular Medicine University Heart Center Hamburg-Eppendorf20246 HamburgGermany Institute of Biochemistry and Signal Transduction University Medical Center Hamburg-Eppendorf20246 HamburgGermany

Osteoporosis is a systemic bone disease that affects more than 200 million people worldwide and is caused by the disruption of the equilibrium between osteoclastic bone resorption and osteoblastic bone formation. Sphingosine-1-phosphate(S1 P) is a natural,bioactive sphingolipid that has been shown to play a major role in cardiovascular and immunological pathologies by regulating biological and cellular processes, including migration, differentiation, proliferation and survival. Recent studies also suggest a central role for S1 P in bone diseases, including osteoporosis;however, the effects of S1 P, particularly in bone metabolism, remain to be further elucidated. In this review, we summarize the available literature on the role of S1 P in bone metabolism with a focus on osteoporosis. On the cellular level, S1 P acts as an osteoclast-osteoblast coupling factor to promote osteoblast proliferation and bone formation. Moreover, the recruitment of osteoclast precursors to resorption sites is regulated by the interplay of S1 P gradients and S1 P receptor expression. From a clinical perspective, increasing evidence suggests that systemically elevated S1 P blood levels may serve as an independent risk factor for osteoporosis-related fractures. Taken together, S1 P signaling is a potential therapeutic target and may serve as a novel biomarker in patients with systemic bone disease.

关键词： osteoporosis metabolism expression.

Application of dynamic image analysis to the optical characterisation of fibrous bulk material

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Particuology 2024年第7期90卷 51-60页

作者： johannes Lunewski Eberhard Schmidt Institute of Particle Technology University of WuppertalGermany

Dynamic image analysis provides an automated evaluation method to determine the size and shape of multiple particles. This method represents a common application for ordinary bulk material. The latest draft of ISO 13322–2:2021 describes the state of the art, but lacks instructions for handling fibrous bulk material. Interlocking fibres complicate the measurement conditions and require a disentanglement of fibrous samples during a pre-dispersion step. A further error source includes the fibre orientation inside the measurement zone of the device. If the thresholding algorithm fails to differentiate between the fibre projection area and the background, a subsequent image optimisation solves the problem. This article addresses the mentioned problems by analysing cotton cellulose and polyacrylonitrile fibres. Besides the execution of a pre-dispersion step, the experiments compare the discrepancies between dry and wet dispersion. Here, the software packages PAQXOS and ImageJ perform the image evaluation. In this case, the wet dispersion setup with a subsequent image evaluation by ImageJ provides comprehensible results.

关键词： Bootstrap method Dynamic image analysis Fibre diameter Fibre length distribution Natural fibres Synthetic fibres

Procalcitonin is expressed in osteoblasts and limits bone resorption through inhibition of macrophage migration during intermittent PTH treatment

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Bone Research 2022年第1期10卷 107-121页

作者： Anke Baranowsky Denise Jahn Shan Jiang Timur Yorgan Peter Ludewig Jessika Appelt Kai K.Albrecht Ellen Otto Paul Knapstein Antonia Donat Jack Winneberger Lana Rosenthal Paul Köhli Cordula Erdmann Melanie Fuchs Karl-Heinz Frosch Serafeim Tsitsilonis Michael Amling Thorsten Schinke johannes keller Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-EppendorfHamburg 20246Germany Department of Osteology and Biomechanics University Medical Center Hamburg-EppendorfHamburg 20246Germany Center for Musculoskeletal Surgery Charité-Universitätsmedizin BerlinBerlin 13353Germany Julius Wolff Institute for Biomechanics and Musculoskeletal Regeneration Charité-Universitätsmedizin BerlinBerlin 13353Germany Department of Neurology University Medical Center Hamburg-EppendorfHamburg 20251Germany Berlin Institute of Health Berlin 10178Germany

Intermittent injections of parathyroid hormone(iPTH) are applied clinically to stimulate bone formation by osteoblasts, although continuous elevation of parathyroid hormone(PTH) primarily results in increased bone resorption. Here, we identified Calca,encoding the sepsis biomarker procalcitonin(ProCT), as a novel target gene of PTH in murine osteoblasts that inhibits osteoclast formation. During iPTH treatment, mice lacking ProCT develop increased bone resorption with excessive osteoclast formation in both the long bones and axial skeleton. Mechanistically, ProCT inhibits the expression of key mediators involved in the recruitment of macrophages, representing osteoclast precursors. Accordingly, ProCT arrests macrophage migration and causes inhibition of early but not late osteoclastogenesis. In conclusion, our results reveal a potential role of osteoblast-derived ProCT in the bone microenvironment that is required to limit bone resorption during iPTH.

关键词： treatment representing skeleton

Unveiling the culprit:the fusobacterium lineage that populates colorectal cancer

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2349-2350页

作者： johannes Betge Matthias P.Ebert Department of Medicine Ⅱ Medical Faculty MannheimHeidelberg UniversityMannheimGermany Junior Clinical Cooperation Unit Translational Gastrointestinal Oncology and Preclinical Models German Cancer Research Center(DKFZ)HeidelbergGermany DKFZ Hector Cancer Institute at University Medical Center MannheimGermany MMPU Microbiota Drug Metabolism and Cancer Therapy European Molecular Biology LaboratoryHeidelbergGermany

In a recent study published in Nature,Zepeda-Rivera et al.1 discovered that one distinct clade of Fusobacterium nucleatum animalis(Fna)dominates the colorectal cancer(CRC)tumor *** work unravels a more precise understanding of a major bacterial species associated with CRC progression,thereby establishing a new focus for future studies,which may aid to develop improved microbiome-based diagnostics and treatments(Fig.1).

关键词： colorectal al. cancer

Wear dependent virtual flow rate sensor for progressing cavity pumps with deformable stator

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Petroleum Science 2024年第2期21卷 1346-1353页

作者： Jens Müller Sebastian Leonow johannes Schulz Christian Hansen Martin Monnigmann Ruhr-Universitat Bochum Universit atsstraûe 150Bochum44801Germany SEEPEX GmbH Scharnh olzstraûe 344Bottrop46240Germany

This contribution presents a novel wear dependent virtual flow rate sensor for single stage single lobe progressing cavity pumps. We study the wear-induced material loss of the pump components and the impact of this material loss on the volumetric efficiency. The results are combined with an established backflow model to implement a backflow calculation procedure that is adaptive to wear. We use a laboratory test setup with a highly abrasive fluid and operate a pump from new to worn condition to validate our approach. The obtained measurement data show that the presented virtual sensor is capable of calculating the flow rate of a pump being subject to wear during its regular operation.

关键词： Backflow Progressing cavity pump Virtual sensor Wear

Immune consequences of exercise in hypoxia:A narrative review

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Journal of Sport and Health Science 2024年第3期13卷 297-310,I0002页

作者： johannes Burtscher Qadar Pasha Neha Chanana Gregoire P.Millet Martin Burtscher Barbara Strasser Institute of Sport Sciences University of LausanneLausanne 1015Switzerland Institute of Hypoxia Research New Delhi 110067India Department of Biochemistry Jamia HamdardNew Delhi 110062India Department of Sport Science University of InnsbruckInnsbruck 6020Austria Faculty of Medicine Sigmund Freud Private UniversityVienna 1020Austria Ludwig Boltzmann Institute for Rehabilitation Research Vienna 1100Austria

Immune outcomes are key mediators of many health benefits of exercise and are determined by exercise type,dose(frequency/duration,intensity),and individual ***,reduced availability of ambient oxygen(hypoxia)modulates immune functions depending on the hypoxic dose and the individual capacity to respond to *** combined exercise and hypoxia(e.g.,high-altitude training)sculpts immune responses is not well understood,although such combinations are becoming increasingly ***,in this paper,we summarize the impact on immune responses of exercise and of hypoxia,both independently and together,with a focus on specialized cells in the innate and adaptive immune *** review the regulation of the immune system by tissue oxygen levels and the overlapping and distinct immune responses related to exercise and hypoxia,then we discuss how they may be modulated by nutritional ***,antioxidant,and anti-inflammatory mechanisms underlie many of the adaptations that can lead to improved cellular metabolism,resilience,and overall immune functions by regulating the survival,differentiation,activation,and migration of immune *** review shows that exercise and hypoxia can impair or complement/synergize with each other while regulating immune system *** acclimatization,training,and nutritional strategies can be used to avoid risks and tap into the synergistic potentials of the poorly studied immune consequences of exercising in a hypoxic state.

关键词： Altitude Exercise Hypoxia Immune response Training

A New Kind of Atomic Force Microscopy Scan Control Enabled by Artificial Intelligence:Concept for Achieving Tip and Sample Safety Through Asymmetric Control

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Nanomanufacturing and Metrology 2024年第2期7卷 50-59页

作者： johannes Degenhardt Mohammed Wassim Bounaim Nan Deng Rainer Tutsch Gaoliang Dai Physikalisch-Technische Bundesanstalt Bundesallee 10038116 BrunswickGermany Institut Für Prozessmess-und Sensortechnik Technische Universität Ilmenau EhrenbergstraBe 2998693 IlmenauGermany Institute of Production Metrology TU Braunschweig SchleinitzstraBe 2038106 BrunswickGermany

This paper introduces a paradigm shift in atomic force microscope(AFM)scan control,leveraging an artificial intelligence(AI)-based *** contrast to conventional control methods,which either show a limited performance,such as proportional integral differential(PID)control,or which purely focus on mathematical optimality as classical optimal control approaches,our proposed AI approach redefines the objective of control for achieving practical *** presented AI controller minimizes the root-mean-square control deviations in routine scans by a factor of about 4 compared to PID control in the presented setup and also showcases a distinctive asymmetric response in complex situations,prioritizing the safety of the AFM tip and sample instead of the lowest possible control *** development and testing of the AI control concept are performed on simulated AFM scans,demonstrating its huge potential.

关键词： Atomic force microscopy Artificial intelligence Deep reinforcement learning Optimal control

Genomic Mosaicism of the Brain:Origin,Impact,and Utility

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Neuroscience Bulletin 2024年第6期40卷 759-776页

作者： Jared H.Graham johannes C.M.Schlachetzki Xiaoxu Yang Martin W.Breuss Department of Pediatrics Section of Clinical Genetics and MetabolismUniversity of Colorado School of MedicineAurora80045-2581COUSA Department of Cellular and Molecular Medicine University of California San DiegoLa Jolla92093-0021San DiegoCAUSA Department of Neurosciences University of California San DiegoLa Jolla92093-0021San DiegoCAUSA Rady Children’s Institute for Genomic Medicine San Diego92123CAUSA

Genomic mosaicism describes the phenomenon where some but not all cells within a tissue harbor unique genetic ***,research focused on the impact of genomic mosaicism on clinical phenotype—motivated by its involvement in cancers and overgrowth *** recently,we increasingly shifted towards the plethora of neutral mosaic variants that can act as recorders of cellular lineage and environmental ***,we summarize the current state of the field of genomic mosaicism research with a special emphasis on our current understanding of this phenomenon in brain development and *** the field of genomic mosaicism has a rich history,technological advances in the last decade have changed our approaches and greatly improved our *** will provide current definitions and an overview of contemporary detection approaches for genomic ***,we will discuss the impact and utility of genomic mosaicism.

关键词： Genomics Brain development Brain homeostasis Genomic mosaicism