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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

New Record Ocean Temperatures and Related Climate Indicators in 2023

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Advances in Atmospheric Sciences 2024年第6期41卷 1068-1082页

作者： Lijing CHENG John ABRAHAM Kevin E.TRENBERTH tim BOYER Michael EMANN Jiang ZHU Fan WANG Fujiang YU Ricardo LOCARNINI John FASULLO Fei ZHENG Yuanlong LI Bin ZHANG Liying WAN Xingrong CHEN Dakui WANG Licheng FENG Xiangzhou SONG Yulong LIU Franco RESEGHETTI Simona SIMONCELLI Viktor GOURETSKI Gengxin CHEN Alexey MISHONOV Jim REAGAN Karina von SCHUCKMANN Yuying PAN Zhetao TAN Yujing ZHU Wangxu WEI Guancheng LI Qiuping REN Lijuan CAO Yayang LU International Center for Climate and Environment Sciences Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China University of St.Thomas School of EngineeringMinnesota 55105USA NSF National Center for Atmospheric Research BoulderColorado 80307USA University of Auckland Auckland 1010New Zealand National Oceanic and Atmospheric Administration National Centers for Environmental InformationSilver SpringMaryland 20910USA Department of Earth and Environmental Science University of PennsylvaniaPhiladelphiaPennsylvania 19104USA Institute of Oceanology Chinese Academy of SciencesQingdao 266071China National Marine Environmental Forecasting Center Ministry of Natural Resources of ChinaBeijing 100081China Oceanographic Data Center Chinese Academy of SciencesQingdao 266071China College of Oceanography Hohai UniversityNanjing 210098China National Marine Data and Information Service Tianjin 300171China Italian National Agency for New Technologies Energy and Sustainable Economic DevelopmentS.Teresa Research CenterLerici 19032Italy Istituto Nazionale di Geofisica e Vulcanologia Sede di BolognaBologna 40128Italy South China Sea Institute of Oceanology Chinese Academy of SciencesGuangzhou 510301China ESSIC/CISESS-MD University of MarylandCollege ParkMD20740USA Mercator Ocean International Toulouse 31400France Eco-Environmental Monitoring and Research Center Pearl River Valley and South China Sea Ecology and Environment AdministrationMinistry of Ecology and EnvironmentPRCGuangzhou 510611China National Meteorological Information Center China Meteorological AdministrationBeijing 100081China International Research Center of Big Data for Sustainable Development Goals Beijing 100094China

The global physical and biogeochemical environment has been substantially altered in response to increased atmospheric greenhouse gases from human *** 2023,the sea surface temperature(SST)and upper 2000 m ocean heat content(OHC)reached record *** 0–2000 m OHC in 2023 exceeded that of 2022 by 15±10 ZJ(1 Zetta Joules=1021 Joules)(updated IAP/CAS data);9±5 ZJ(NCEI/NOAA data).The Tropical Atlantic Ocean,the Mediterranean Sea,and southern oceans recorded their highest OHC observed since the *** with the onset of a strong El Niño,the global SST reached its record high in 2023 with an annual mean of~0.23℃ higher than 2022 and an astounding>0.3℃ above 2022 values for the second half of *** density stratification and spatial temperature inhomogeneity indexes reached their highest values in 2023.

关键词： ocean heat content salinity stratification global warming climate

Biophotonic sensors with integrated Si_(3)N_(4)-organic hybrid (SiNOH) lasers for point-of-care diagnostics

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Light(Science & Applications) 2021年第4期10卷 648-659页

作者： Daria Kohler Gregor Schindler Lothar hahn Johannes Milvich Andreas Hofmann Kerstin Lange Wolfgang Freude Christian Koos Institute of Photonics and Quantum Elearo nics(IPQ) Karlsruhe Institute of Technology(KIT)Engesserstrasse 576131 KarlsruheGermany lnstitute of Microstructure Technology(IMT) Karlsruhe Institute of Technology(KIT)Hermann-von-Helmholtz-Platz 176344 Eggenstein-LeopoldshafenGermany Robert Bosch GmbH Robert-Bosch-Campus 171272 RenningenGermany lnstitute for Autom ation and Applied Informatics(IAI) Karlsruhe Institute of Technology(KIT)Hermann-von-Helmholtz-Platz 176344 Eggenstein-LeopoldshafenGermany

Early and efficient disease diagnosis with low-cost point-of-care devices is gaining importance for personalized medicine and public health *** this context,waveguide-(WG)-based optical biosensors on the siliconnitride(Si_(3)N_(4))platform represent a particularly promising option,offering highly sensitive detection of indicative biomarkers in multiplexed sensor arrays operated by light in the visible-wavelength ***,while passive Si_(3)N_(4)-based photonic circuits lend themselves to highly scalable mass production,the integration of low-cost light sources remains a *** this paper,we demonstrate optical biosensors that combine Si_(3)N_(4)sensor circuits with hybrid on-chip organic *** Si_(3)N_(4)-organic hybrid(SiNOH)lasers rely on a dye-doped cladding material that are deposited on top of a passive WG and that are optically pumped by an external light *** of the devices is simple:The underlying Si_(3)N_(4)WGs are structured in a single lithography step,and the organic gain medium is subsequently applied by dispensing,spin-coating,or ink-jet printing processes.A highly parallel read-out of the optical sensor signals is accomplished with a simple *** our proof-of-concept experiment,we demonstrate the viability of the approach by detecting different concentrations of fibrinogen in phosphate-buffered saline solutions with a sensor-length(L-)-related sensitivity of S/L=0.16 rad nM^(-1)mm^(-1).To our knowledge,this is the first demonstration of an integrated optical circuit driven by a co-integrated low-cost organic light *** expect that the versatility of the device concept,the simple operation principle,and the compatibility with cost-efficient mass production will make the concept a highly attractive option for applications in biophotonics and point-of-care diagnostics.

关键词： passive waveguide pumped

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实用老年病学

实用老年病学

The WNT1^(G177C) mutation specifically affects skeletal integrity in a mouse model of osteogenesis imperfecta type XV

1977年

作者： H.P.von hahn（瑞士、巴赛尔）编王士雯刘志德等译

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Bone Research 2021年第4期9卷 593-605页

作者： Nele Vollersen Wenbo Zhao tim Rolvien Fabiola Lange Felix Nikolai Schmidt Stephan Sonntag Doron Shmerling Simon von Kroge Kilian Elia Stockhausen Ahmed Sharaf Michaela Schweizer Meliha Karsak Bjorn Busse Ernesto Bockamp Oliver Semler Michael Amling Ralf Oheim Thorsten Schinke timur Alexander Yorgan Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf20246 HamburgGermany PolyGene AG 8153 RumlangSwitzerland ETH Phenomics Center(EPIC) ETH Zurich8092 ZurichSwitzerland Neuronal and Cellular Signal Transduction Center for Molecular Neurobiology Hamburg(ZMNH)University Medical Center Hamburg-Eppendorf20246 HamburgGermany Center for Molecular Neurobiology Hamburg(ZMNH) University Medical CenterHamburg-Eppendorf20246 HamburgGermany Institute for Translational Immunology and Research Center for Immunotherapy University Medical CenterJohannes Gutenberg UniversityD 55131 MainzGermany Faculty of Medicine and University Hospital Cologne Department of PediatricsUniversity of Cologne50937 CologneGermany

The recent identification of homozygous WNT1 mutations in individuals with osteogenesis imperfecta type XV(OI-XV)has suggested that WNT1 is a key ligand promoting the differentiation and function of bone-forming *** such aninfluence was supported by subsequent studies,a mouse model of OI-XV remained to be ***,we introduced a previously identified disease-causing mutation(G177C)into the murine Wnt1 *** Wnt1^(G177C/G177C)mice were viable and did not display defects in brain development,but the majority of 24-week-old Wnt1^(G177C/G177C)mice had skeletal *** increased bone fragility was not fully explained by reduced bone mass but also by impaired bone matrix ***,the homozygous presence of the G177C mutation did not interfere with the osteoanabolic influence of either parathyroid hormone injection or activating mutation of LRP5,the latter mimicking the effect of sclerostin ***,transcriptomic analyses revealed that short-term administration of WNT1 to osteogenic cells induced not only the expression of canonical WNT signaling targets but also the expression of genes encoding extracellular matrix *** together,our data demonstrate that regulating bone matrix quality is a primary function of *** further suggest that individuals with WNT1 mutations should profit from existing osteoanabolic therapies.

关键词： WNT1 skeletal impaired

Investigation of the function of CKMAP44 in the lateral geniculate nucleus

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Investigation of the function of CKMAP44 in the lateral geni...

New insights into carbon-based and MXene anodes for Na and K-ion storage: A review

中国神经科学学会第十二届全国学术会议

作者： Xufeng Chen Muhammad Aslam tim Gollisch Kevin Allen Jakob von Engelhardt Institute of Pathophysiology University Medical Center of the Johannes Gutenberg University Mainz Department of Ophthalmology University Medical Center G?ttingen Department of Clinical Neurobiology Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ)

Relay neurons in the dorsal lateral geniculate nucleus（d LGN） receive excitatory inputs form retinal ganglion cells via retinogeniculate synapses, which display strong short-term depression of AMPA receptors（AMPARs） mediated current. However, the underlying mechanism is still not clear. Here we identified CKAMP44 as a crucial AMPARs auxiliary protein in the dorsal lateral geniculate synapse, in which they promote AMPARs surface expression. Moreover, CKAMP44 helps to maintain shortterm plasticity of retinogeniculate synapses by slowing AMPARs recovery from desensitization. In addition, deletion of CKAMP44 increases the firing probability of relay neurons under high frequency stimulation on optic tract. Finally, in vivo unit recording in the d LGN showed that ON and OFF response of d LGN neurons were stronger in CKAMP44 knockout mice, demonstrating the importance of CKAMP44 modulated synaptic short-term depression for visual input integration.

关键词： CKAMP44 AMPA receptors desensitization short-term plasticity visual input integration

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Journal of Energy Chemistry 2021年第11期30卷 660-691,I0016页

作者： Zhensheng Hong Hajar Maleki tim Ludwig Yichao Zhen Michael Wilhelm Damin Lee Kwang-Ho Kim Sanjay Mathur Fujian Provincial Key Laboratory of Quantum Manipulation and New Energy Materials College of Physics and EnergyFujian Normal UniversityFuzhou 350117FujianChina Institute of Inorganic Chemistry University of CologneGreinstr.650939 CologneGermany Fujian Provincial Collaborative Innovation Center for Advanced High-Field Superconducting Materials and Engineering Fuzhou 350117FujianChina Global Frontiers of Hybrid Interfacial Materials Pusan National UniversitySouth Korea

Na-ion batteries and K-ion batteries are promising alternatives to vastly used lithium-ion batteries mainly due to the larger natural abundance of sodium and potassium resources. Carbon-based and MXene materials have received increasing attention due to their unique layered structure to accommodate the larger sodium and potassium ions. It’s proposed that ionic size disparity (K^(+): 1.38 Å;Na^(+): 0.97 Å;Li^(+): 0.76 Å) leads to sluggish intercalation and extraction kinetics in larger alkali metal ions (AMIs). Nevertheless, the electrochemical inactivity of sodium intercalation in graphite suggests that different chemical properties of AMs and their interactions with carbon host and electrolytes is crucial for interfacial instability and irreversible capacity loss. Structural modifications by expanding interlayer spacing and defect engineering enable reduced diffusion barriers and enhanced insertion of sodium or potassium, but it blurs the electrochemical performance between battery and capacitor. This review provides insight into 2D carbon materials and their architectures for Na and K-ion batteries through an in-depth analysis of structure–property interdependence and different electrochemical mechanisms supported by both experimental and theoretical data to discuss the promises and challenges of post-lithium batteries. Finally, the perspectives and potential directions regarding material design concepts for 2D carbon-based nanomaterials and MXene phases for metal-ion storage are proposed.

关键词： Na-ion batteries K-ion batteries Anode Carbon materials Structure design

Chemically Induced and Light-Independent Cryptochrome Photoreceptor Activation

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Molecular Plant 2008年第1期1卷 4-14页

作者： Gesa Rosenfeldt Rafael Munoz Viana Henning D. Mootz Albrecht G. von Arnim Alfred Batschauera FB Biologie-pflanzenphysiologie Philipps-Universitat Karl-von-Frisch-Str. 8 35032 Marburg Germany Universitat Dortmund FB Chemie-Chemische Biologie Otto-Hahn-Str. 6 44227 Dortmund Germany University of Tennessee Department of Biochemistry Cellular and Molecular Biology Waiters Life Sciences M407 Knoxville TN 37996-0840 USA

The cryptochrome photoreceptors of higher plants are dimeric proteins. Their N-terminal photosensory domain mediates dimerization, and the unique C-terminal extension （CCT） mediates signaling. We made use of the human FK506binding protein （FKBP） that binds with high affinity to rapamycin or rapamycin analogs （rapalogs）. The FKBP-rapamycin complex is recognized by another protein, FRB, thus allowing rapamycin-induced dimerization of two target proteins. Here we demonstrate by bioluminescence resonance energy transfer （BRET） assays the applicability of this regulated dimer- ization system to plants. Furthermore, we show that fusion proteins consisting of the C-terminal domain of Arabidopsis cryptochrome 2 fused to FKBP and FRB and coexpressed in Arabidopsis cells specifically induce the expression of cryptochrome-controlled reporter and endogenous genes in darkness upon incubation with the rapalog. These results demonstrate that the activation of cryptochrome signal transduction can be chemically induced in a dose-dependent fashion and uncoupled from the light signal, and provide the groundwork for gain-of-function experiments to study specifically the role of photoreceptors in darkness or in signaling cross-talk even under light conditions that activate members of all photoreceptor families.

关键词： C-terminal extension (CCT) FK506-binding protein (FKBP) bioluminescence resonance energy transfer (BRET)

HP30-2, a mitochondrial PRAT protein for import of signal sequence-less precursor proteins in Arabidopsis thaliana

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Journal of Integrative Plant Biology 2017年第8期59卷 535-551页

作者： Claudia Rossig John Gray Oscar Valdes Sachin Rustgi Diter von Wettstein Christiane Reinbothe Steffen Reinbothe Laboratory of Plant Molecular Genetics and Laboratory of Environmental and Systems Biology Grenoble-Alpes-University Grenoble France Department of Biological Sciences University of Toledo 2801 West Bancroft Street Toledo OH 43606 USA Department of Plant and Environmental Sciences Pee Dee Research and Education Center Clemson University Florence SC 29506 USA Department of Crop and Soil Sciences Washington State University Pullman WA 99164-6420 USA

Chloroplasts and mitochondria contain a family of putative preprotein and amino acid transporters designated PRAT. Here, we analyzed the role of two previously characterized PRAT protein family members, encoded by At3g49560 （HP30） and At5g24650 （HP30-2）, in planta using a combination of genetic, cell biological and biochemical approaches. Expression studies and green fluorescent protein tagging identified HP30-2 both in chloroplasts and mitochondria, whereas HP30 was located exclusively in chloroplasts. Biochemical evidence was obtained for an association of mitochondrial HP30-2 with two distinct protein complexes, one containing the inner membrane translocase tim22 and the other containing an alternative NAD（P）H dehydrogenase subunit （NDCI） implicated in a respiratory complex 1-1ike electron trans- port chain. Through its association with tim22, HP30-2 is involved in the uptake of carrier proteins and other, hydrophobic membrane proteins lacking cleavable N H2-terminal presequences, whereas HP30-2＇s interaction with NDC1 may permit controlling mitochondrial biogenesis and activity.

关键词： of as et in HP30-2,a mitochondrial PRAT protein for import of signal sequence-less precursor proteins in Arabidopsis thaliana for Figure NDC were tim RNAi that