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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

Leaching of lanthanide and yttrium from a Central Appalachian coal and the ashes obtained at 550-950℃

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journal of Rare Earths 2022年第5期40卷 807-814,I0005页

作者： Ronghong Lin Yee Soong Bret H.Howard Murphy j.keller Elliot A.Roth Ping Wang Evan j.Granite U.S.Department of Energy National Energy Technology Laboratory626 Cochrans Mill RoadP.O.Box 10940PittsburghPA15236United States Keylogic Systems.Pittsburgh PA15236United States

In this work,we investigated leaching of lanthanide and yttrium(REY) from a Central Appalachian coal and its ashes obtained at 550-950℃ with the main purpose of understanding the impact of ashing temperature on REY leachability in water,ammonium sulfate,and hydrochloric *** is found that the coal contains a negligible amount of water-soluble REY,less than 1% ion-exchangeable REY,and about 28% of HCl-soluble *** leads to dramatic changes in REY leachability in both ammonium sulfate and hydrochloric acid solutions,which is believed to be related to transformation and redistribution of organically-associated REY in coal during the ashing *** temperature significantly affects REY leaching from coal ashes;higher ashing temperature results in lower REY leachability in both *** minerals may play a significant role in changing the leachability of REY after *** addition,the results also suggest that the organic matter in the coal is relatively enriched in heavy REY.

关键词： Acid leaching Cation exchange Coal Coal ash Rare earth elements Yttrium

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.

Effects of Resistant Starch on Symptoms,Fecal Markers,and Gut Microbiota in Parkinson’s Disease—The RESISTA-PD Trial

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Genomics, Proteomics & Bioinformatics 2022年第2期20卷 274-287页

作者： Anouck Becker Georges Pierre Schmartz Laura Groger Nadja Grammes Valentina Galata Hannah Philippeit jacqueline Weiland Nicole Ludwig Eckart Meese Sascha Tierling jorn Walter Andreas Schwiertz jorg Spiegel Gudrun Wagenpfeil Klaus Faßbender Andreas keller Marcus M.Unger Department of Neurology Saarland UniversityD-66421 HomburgGermany Chair for Clinical Bioinformatics Saarland UniversityD-66123 SaarbruckenGermany Department of Human Genetics Saarland UniversityD-66421 HomburgGermany Department of Genetics/Epigenetics Saarland UniversityD-66123 SaarbruckenGermany Institute of Microecology D-35745 HerbornGermany Institute of Medical Biometry Epidemiology and Medical InformaticsSaarland UniversityD-66421 HomburgGermany Department of Neurology Stanford UniversityPalo AltoCA 94305USA

The composition of the gut microbiota is linked to multiple diseases,including Parkinson’s disease(PD).Abundance of bacteria producing short-chain fatty acids(SCFAs)and fecal SCFA concentrations are reduced in *** exert various beneficial functions in *** the interventional,monocentric,open-label clinical trial “Effects of Resistant Starch on Bowel Habits,Short Chain Fatty Acids and Gut Microbiota in Parkinson’s Disease”(RESISTA-PD;ID:NCT02784145),we aimed at altering fecal SCFAs by an 8-week prebiotic intervention with resistant starch(RS).We enrolled 87 subjects in three study-arms:32 PD patients received RS(PD+RS),30 control subjects received RS,and 25 PD patients received solely dietary *** performed paired-end 100 bp length metagenomic sequencing of fecal samples using the BGISEQ platform at an average of 9.9 *** was *** the PD+RS group,fecal butyrate concentrations increased significantly,and fecal calprotectin concentrations dropped significantly after 8 weeks of RS ***,we observed a reduction in non-motor symptom load in the PD+RS *** reference-based analysis of metagenomes highlighted stable alpha-diversity and beta-diversity across the three groups,including bacteria producing ***-free analysis suggested punctual,yet pronounced differences in the metagenomic signature in the PD+RS ***-PD highlights that a prebiotic treatment with RS is safe and well-tolerated in *** stable alpha-diversity and beta-diversity alongside altered fecal butyrate and calprotectin concentrations call for long-term studies,also investigating whether RS is able to modify the clinical course of PD.

关键词： Parkinson’s disease Short-chain fatty acid Microbiota Metagenomics Intestinal inflammation

Under the surface:Pressure-induced planetary-scale waves,volcanic lightning,and gaseous clouds caused by the submarine eruption of Hunga Tonga-Hunga Ha'apai volcano

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Earthquake Research Advances 2022年第3期2卷 1-13页

作者： David A.Yuen Melissa A.Scruggs Frank j.Spera Yingcai Zheng Hao Hu Stephen R.McNutt Glenn Thompson Kyle Mandli Barry R.keller Songqiao Shawn Wei Zhigang Peng Zili Zhou Francesco Mulargia Yuichiro Tanioka Columbia University Dept.of Applied Physics and Applied MathematicsNew YorkNY10027USA Ocean University of China School of Computer Science and Marine GeosciencesQingdao266100China University of California Santa BarbaraDept.of Earth Science1006 Webb HallUniversity of CaliforniaSanta BarbaraCA93106USA University of Houston Dept.of Earth and Atmospheric SciencesScience&Research Bldg.13507 Cullen Boulevard#312HoustonTX77004USA University of South Florida School of GeosciencesTampaFLUSA Mission Beach CAUSA Michigan State University Dept.of Earth and Environmental Sciences288 Farm Ln BldgRoom 207East LansingMI48824USA Georgia Institute of Technology School of Atmospheric and Earth SciencesNorth AvenueAtlantaGA30332USA University of Southern California Sonny Astani Dept.of Civil&Environmental EngineeringKaprielian HallLos AngelesCA90089-2531USA University of Bologna Dept.of Geological SciencesVia Zamboni3340126BolognaItaly Hokkaido University Division of Earth System ScienceN10W5SapporoHokkaido060-0810Japan

We present a narrative of the eruptive events culminating in the cataclysmic january 15, 2022 eruption of Hunga Tonga-Hunga Ha’apai Volcano by synthesizing diverse preliminary seismic, volcanological, sound wave, and lightning data available within the first few weeks after the eruption occurred. The first hour of eruptive activity produced fast-propagating tsunami waves, long-period seismic waves, loud audible sound waves, infrasonic waves, exceptionally intense volcanic lightning and an unsteady volcanic plume that transiently reached-at 58km-the Earth’s mesosphere. Energetic seismic signals were recorded worldwide and the globally stacked seismogram showed episodic seismic events within the most intense periods of phreatoplinian activity, and they correlated well with the infrasound pressure waveform recorded in Fiji. Gravity wave signals were strong enough to be observed over the entire planet in just the first few hours, with some circling the Earth multiple times subsequently. These large-amplitude, long-wavelength atmospheric disturbances come from the Earth’s atmosphere being forced by the magmatic mixture of tephra, melt and gasses emitted by the unsteady but quasicontinuous eruption from 0402±1–1800 UTC on january 15, 2022. Atmospheric forcing lasted much longer than rupturing from large earthquakes recorded on modern instruments, producing a type of shock wave that originated from the interaction between compressed air and ambient(wavy) sea surface. This scenario differs from conventional ideas of earthquake slip, landslides, or caldera collapse-generated tsunami waves because of the enormous(~1000x) volumetric change due to the supercritical nature of volatiles associated with the hot,volatile-rich phreatoplinian plume. The time series of plume altitude can be translated to volumetric discharge and mass flow rate. For an eruption duration of ~12 h, the eruptive volume and mass are estimated at 1.9 km^(3) and~2 900 Tg, respectively, corresponding to a VEI

关键词： Hunga Tonga-Hunga Ha'apai Atmospheric pressure wave Tsunami wave Volcanic lightning Phreatoplinian eruption

Intravenous haloperidol for the treatment of intractable vomiting,cyclical vomiting,and gastroparesis

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World journal of Emergency Medicine 2021年第3期12卷 228-231页

作者： Brad E.Schwartz Karen keller Baker Andrew j.Bleinberger Amina Lleshi Raul Cruz-Cano Department of Emergency Medicine University of Maryland Capital Region HealthUM Prince George’s Hospital CenterCheverly 20785USA Ross University School of Medicine Bridgetown Bridgetown 11093Barbados Department of Epidemiology and Biostatistics School of Public Health of the University of MarylandBaltimore 21201USA

Dear editor,The incidence of emergency department(ED)visits from gastroparesis and cannabinoid hyperemesis syndrome has increased by two folds over the past decade.[1-3]Roldan et al[4]reported that patients with these conditions often have prolonged ED stays and are likely to be hospitalized because of the danger of dehydration and challenges inherent in relieving *** analgesia is a particularly troublesome treatment modality;these conditions are often chronic with frequent recurrences,and repeated opiate therapy can cause opioid dependency and narcotic bowel syndrome.[5]Haloperidol(HP)and droperidol,members of the butyrophenone class,have potent antidopaminergic activity in the chemoreceptor trigger zone.[6,7]Intramuscular administration of HP is being used increasingly in the ED to treat nausea,vomiting secondary to gastroparesis,[6]intractable vomiting,[8]and cyclical vomiting.

关键词： vomiting gastro treatment

Problem Solving Solutions in Thermal Spray:HSE and Overspray

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有色金属（冶炼部分） 2008年第S1期 139-145页

作者： Hans keller joachim Beczkowiak Stefan Zimmermann Benno Gries jürgen Fischer H.C.Starck GmbH LaufenburgDeutschland H.C.Starck GmbH GoslarDeutschland

目前金属基材料的原材料成本对热喷涂涂层的经济性造成压力。特别是材料挥发和近期铼、钨、钴和镍基材料的价格增长,对各应用领域的许多涂层的经济性造成严重威胁。由于沉积效率的限制,喷涂中未沉积物问题变得越来越重要,不仅只是减少浪... 详细信息

目前金属基材料的原材料成本对热喷涂涂层的经济性造成压力。特别是材料挥发和近期铼、钨、钴和镍基材料的价格增长,对各应用领域的许多涂层的经济性造成严重威胁。由于沉积效率的限制,喷涂中未沉积物问题变得越来越重要,不仅只是减少浪费,还可以从材料自身价值角度去看。回收是解决这个问题的一个措施,特别是当废料中含有高价值金属时。欧洲执行的REACH(化学制品的注册、评估、授权)将会逐步强制淘汰标有有毒的材料和物质的使用。在热喷涂中使用这些有毒物质或使用热喷涂产品可能暂时是安全的,然而,从法律限制和从其他工业领域得到的指示表明,像WC-Co粉末这样的化学制品对人体有害。要想在将来的涂层工厂中保持竞争性,必须符合不断提高的更严格的环保和安全规程。

关键词：热喷涂粉末 WC-Co 健康和环保毒物学回收喷涂中未沉积物

Whole miRNome-wide Differential Co-expression of MicroRNAs

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Genomics, Proteomics & Bioinformatics 2012年第5期10卷 285-294页

作者： Cord F.Stehler Andreas keller Petra Leidinger Christina Backes Anoop Chandran jerg Wischhusen Benjamin Meder Eckart Meese Siemens Healthcare Strategy Department of Human Genetics Saarland University Interdisciplinary Center for Clinical Research University of Wuerzburg Department of Internal Medicine III Heidelberg University

Co-regulation of genes has been extensively analyzed, however, rather limited knowledge is available on co-regulations within the miRNome. We investigated differential co-expression of microRNAs （miRNAs） based on miRNome profiles of whole blood from 540 individuals. These include patients suffering from different cancer and non-cancer diseases, and unaffected controls. Using hierarchi- cal clustering, we found 9 significant clusters of co-expressed miRNAs containing 2-36 individual miRNAs. Through analyzing multiple sequencing alignments in the clusters, we found that co-expression of miRNAs is associated with both sequence similarity and genomic co-localization. We calculated correlations for all 371,953 pairs of miRNAs for all 540 individuals and identified 184 pairs of miRNAs with high correlation values. Out of these 184 pairs of miRNAs, 16 pairs （8.7%） were differentially co-expressed in unaffected controls, cancer patients and patients with non-cancer diseases. By computing correlated and anti-correlated miRNA pairs, we constructed a net- work with 184 putative co-regulations as edges and 100 miRNAs as nodes. Thereby, we detected specific clusters of miRNAs with high and low correlation values. Our approach represents the most comprehensive co-regulation analysis based on whole miRNome-wide expression profiling. Our findings further decrypt the interactions of miRNAs in normal and human pathological processes.

关键词： Co-expression Microarray MicroRNA Network analysis

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journal of Science in Sport and Exercise 2020年第2期2卷 173-182页

作者： joshua L.keller Terry j.Housh Ethan C.Hill Cory M.Smith Richard j.Schmidt Glen O.johnson Human Performance Laboratory Department of Nutrition and Health SciencesCollege of Education and Human SciencesUniversity of Nebraska-LincolnLincolnNE 68508USA Division of Kinesiology School of Kinesiology and Physical TherapyUniversity of Central FloridaOrlandoFL 32816USA Department of Kinesiology College of Health SciencesUniversity of Texas at El PasoEl PasoTX 79968USA

The purpose of this investigation was to use the RPE clamp protocol to examine sex-related differences in performance fati-gability and neuromuscular responses as the result of a sustained isometric leg extension muscle action anchored to RPE=*** adults(10 men,10 women)performed sustained muscle actions at RPE=2 for *** voluntary isometric contractions(MVIC)were performed prior to and following the sustained muscle ***(electromyographic and mechanomyographic)parameters and force were recorded,and the values were normalized to respective MVICs and cal-culated every 5%across the 5-min work *** artery blood flow(FABF)was assessed at pretest,immediately posttest,and 5-min *** regression was used to define the individual and composite normalized neuromuscular and force versus time relationships during the sustained muscle *** factorial ANOVAs were used to examine differences in performance fatigability and blood *** performance fatigability,the men(62.4±14.4 kg-43.1±11.5 kg)exhibited a significantly(P<0.05)greater decrease pretest to posttest in MVIC than the women(44.1±4.8 kg vs.38.1±6.1 kg).There were different fatigue-induced neuromuscular patterns of responses between the men and women across *** blood flow responses,however,there was no sex-related difference,but pretest(283.3±70.8 mL/min)was significantly(P<0.05)less than immediately posttest(424.5±133.5 mL/min)and 5-min posttest(324.4±78.3 mL/min).Thus,men demonstrated a greater degree of performance fatigability than the women,which was independent of differences in *** such as the neuromuscular system and muscle morphology likely contributed to the difference in performance fatigability.

关键词： Perception Resistance training Electromyography Fatigue Mechanomyography RPE clamp