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Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity

Bone Research 2024年第1期12卷 180-198页

作者： Morten S.Hansen Kaja madsen Maria Price Kent Søe Yasunori Omata Mario M.Zaiss Caroline M.Gorvin Morten Frost Alexander Rauch Molecular Endocrinology Laboratory(KMEB) Department of EndocrinologyOdense University HospitalDK-5000 Odense CDenmark Department of Clinical Research Faculty of Health SciencesUniversity of Southern DenmarkDK-5000 Odense CDenmark Clinical Cell Biology Pathology Research UnitDepartment of Clinical ResearchUniversity of Southern DenmarkDK-5000 Odense CDenmark Institute of Metabolism and Systems Research(IMSR)and Centre for Diabetes Endocrinology and Metabolism(CEDAM)University of BirminghamBirmingham B152TTUK Centre for Membrane Proteins and Receptors(COMPARE) Universities of Birmingham and NottinghamBirmingham B152TTUK Department of Molecular Medicine University of Southern DenmarkDK-5000 Odense CDenmark Department of Orthopedic Surgery Faculty of MedicineThe University of TokyoTokyo 113-8655Japan Department of Internal Medicine 3 Rheumatology and ImmunologyFriedrich-Alexander-University Erlangen-Nürnberg(FAU)and Universitätsklinikum ErlangenD-91054 ErlangenGermany Deutsches Zentrum Immuntherapie(DZI) Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum ErlangenD-91054 ErlangenGermany Steno Diabetes Center Odense Odense University HospitalDK-5000 Odense CDenmark

Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone *** novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment *** study aimed to provide an overview of transcriptional reprogramming during human osteoclast *** were differentiated from CD14+monocytes from eight female *** sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across *** patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density *** analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional *** donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature *** expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and *** regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature *** conclus

关键词： osteoclast programming identif

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Meldonium-induced steatosis is associated with increased delta 6 desaturation and reduced elongation of n-6 polyunsaturated fatty acids

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Liver Research 2024年第3期8卷 152-164页

作者： Bodil Bjørndal Siri Lunde Tungland Pavol Bohov Magne OSydnes Simon N.Dankel Lise madsen Rolf K Berge Department of Clinical Science University of BergenBergenNorway Department of Sports Physical Activity and FoodWestern Norway University of Applied SciencesBergenNorway Department of Chemistry Bioscience and Environmental EngineeringUniversity of StavangerStavangerNorway Department of Clinical Medicine University of BergenBergenNorway Department of Heart Disease Haukeland University HospitalBergenNorway

Background and objective Metabolic associated fatty liver disease(MAFLD)is associated with abnormal lipid *** dysfunction is considered an important factor in the onset of MAFLD,whereas altered fatty acid composition has been linked to the severity of the *** acid(TTA),shown to induce mitochondrial proliferation and alter the fatty acid composition,was used to delay the accumulation of hepatic *** study aimed to evaluate how impaired mitochondrial fatty acid beta-oxidation affects fatty acid composition by incorporating meldonium into a high-carbohydrate *** C57BL/6 mice(n=40)were fed high-carbohydrate diets supplemented with meldonium,TTA,or a combination of meldonium and TTA for 21 *** levels were determined in liver samples,and fatty acid composition was measured in both liver and plasma ***,desaturase and elongase activities were *** hepatic activities and gene expression levels of enzymes involved in fatty acid metabolism were measured in liver samples,whereas carnitines,their precursors,and acylcarnitines were measured in plasma *** The meldonium-induced depletion of L-carnitine and mitochondrial fatty acid oxidation was confirmed by reduced plasma levels of L-carnitine and *** component analyses of the hepatic fatty acid composition revealed clustering dependent on meldonium and *** meldonium-induced increase in hepatic triacylglycerol levels correlated negatively with estimated activities of elongases and was associated with higher estimated activities of delta-6 desaturase(D6D;C18:4n-3/C18:3n-3 and C18:3n-6/C18:2n-6),and increased circulating levels of C18:4n-3 and C18:3n-6(gamma-linolenic acid).TTA mitigated meldonium-induced triacylglycerol levels by 80%and attenuated the estimated D6D activities,and elongation of n-6 polyunsaturated fatty acids(PUFAs).TTA also attenuated the meldonium-mediated reduction of C24:1n-

关键词： Steatosis Fatty acid composition Fatty acid oxidation Meldonium Desaturase Elongasen-6 polyunsaturated fatty acid

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Individualized brain mapping for navigated neuromodulation

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Chinese Medical Journal 2024年第5期137卷 508-523页

作者： Chaohong Gao Xia Wu Xinle Cheng Kristoffer Hougaard madsen Congying Chu Zhengyi Yang Lingzhong Fan Sino–Danish College University of Chinese Academy of SciencesBeijing 100190China Brainnetome Center National Laboratory of Pattern RecognitionInstitute of AutomationChinese Academy of SciencesBeijing 100190China School of Artificial Intelligence University of Chinese Academy of SciencesBeijing 100190China Department of Applied Mathematics and Computer Science Technical University of DenmarkKongens Lyngby 2800Denmark Danish Research Centre for Magnetic Resonance Centre for Functional and Diagnostic Imaging and ResearchCopenhagen University Hospital Amager and HvidovreHvidovre 2650Denmark CAS Center for Excellence in Brain Science and Intelligence Technology Institute of AutomationChinese Academy of SciencesBeijing 100190China School of Health and Life Sciences University of Health and Rehabilitation SciencesQingdaoShandong 266000China

The brain is a complex organ that requires precise mapping to understand its structure and *** atlases provide a powerful tool for studying brain circuits,discovering biological markers for early diagnosis,and developing personalized treatments for neuropsychiatric *** techniques,such as transcranial magnetic stimulation and deep brain stimulation,have revolutionized clinical therapies for neuropsychiatric ***,the lack of fine-scale brain atlases limits the precision and effectiveness of these *** in neuroimaging and machine learning techniques have led to the emergence of stereotactic-assisted neurosurgery and navigation ***,the individual variability among patients and the diversity of brain diseases make it necessary to develop personalized *** article provides an overview of recent advances in individualized brain mapping and navigated neuromodulation and discusses the methodological profiles,advantages,disadvantages,and future trends of these *** article concludes by posing open questions about the future development of individualized brain mapping and navigated neuromodulation.

关键词： Brain atlas Individualization Navigated neuromodulation Multimodal magnetic resonance imaging Transcranial magnetic stimulation Deep brain stimulation

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变废为宝:“蓝色循环”海洋塑料废物管理新策略

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Science Bulletin 2024年第8期69卷 993-996页

作者：余灏轩 Izni Zahidi Chow Ming Fai 梁东方 DagØivind madsen Department of Civil Engineering School of EngineeringMonash University MalaysiaBandar Sunway 47500Malaysia Monash Climate-Resilient Infrastructure Research Hub(M-CRInfra) School of EngineeringMonash University MalaysiaBandar Sunway 47500Malaysia Department of Engineering University of CambridgeCambridge CB21PZUK Davis School of Business Colorado Mesa UniversityGrand Junction 81501-3122USA

The"Blue Circle"vision,initiated by Zhejiang Province in China,represents a groundbreaking advancement in addressing marine plastic *** more than just an innovative concept,it embodies a future-forward approach to managing marine plastic waste,revealing the untapped potential in what was previously considered mere *** initiative,marrying scientific innovation with advanced technology,has been rightfully acknowledged with the prestigious2023 United Nations"Champions of the Earth"award,recognizing its innovative strategy in environmental stewardship(https://***/a/202310/31/***).

关键词： breaking debris initiated

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Evolutionary computing and machine learning for discovering of low-energy defect configurations

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npj Computational Materials 2021年第1期7卷 628-640页

作者： Marco Arrigoni Georg K.H.madsen Institute of Materials Chemistry TU WienViennaAustria

Density functional theory(DFT)has become a standard tool for the study of point defects in ***,finding the most stable defective structures remains a very challenging task as it involves the solution of a multimodal optimization problem with a high-dimensional objective ***,the approaches most commonly used to tackle this problem have been mostly empirical,heuristic,and/or based on domain *** this contribution,we describe an approach for exploring the potential energy surface(PES)based on the covariance matrix adaptation evolution strategy(CMA-ES)and supervised and unsupervised machine learning *** resulting algorithm depends only on a limited set of physically interpretable hyperparameters and the approach offers a systematic way for finding low-energy configurations of isolated point defects in *** demonstrate its applicability on different systems and show its ability to find known low-energy structures and discover additional ones as well.

关键词： function configuration finding

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Deposition of Nutrients From Harmattan Dust in Ghana, West Africa

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Pedosphere 2015年第4期25卷 613-621页

作者： Henrik BREUNING-madsen Theodore Wola AWADZI Gry LYNGSIE Institute of Geosciences and Natural Resource Management University of Copenhagen Department of Geography and Resource Development University of Ghana

In order to measure dust's nutrient input on farmland in different agro-ecological zones, Harmattan dust was sampled by mats with plastic straw in Ghana between 2002–2006. The inputs of total nutrients by Harmattan dust in Ghana per Harmattan period were about 1–2 kg Ca ha-1, 0.5–2 kg K ha-1, 0.5–1.5 kg Mg ha-1and less than 0.5 kg P ha-1. Compared with the annual input of nutrients by precipitation, the dust accounted for 10% or less of Ca, Mg and K but approximately 20%–40% of P. The input of nutrients by dust was only valid for areas with vegetation, because in areas with none or sparse vegetation, loss of soil due to wind erosion and hereby loss of nutrients might be significant. In farmland areas with bare and vegetated fields there seemed to be an internal redistribution of the nutrients and not a net gain of nutrients from outside the area(long-range transported dust). The input of P by dust might be of some importance in the traditional shifting cultivation systems, while the inputs of other three nutrients of Ca, Mg and K were so low that they must be considered insignificant. In the intensive agriculture systems with huge inputs of manures and fertilizers the nutrient input by dust is insignificant and could be neglected.

关键词： deposition rate dust deposition input of nutrient long-range transported dust nutrient concentration traditionalagricultural system

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Antimicrobial silicone skin adhesives facilitated by controlled octenidine release from glycerol compartments

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International Journal of Smart and Nano Materials 2023年第3期14卷 369-389页

作者： V.Chiaula J.Jeppe madsen F.B.madsen P.Mazurek A.C.Nielsen A.L.Skov Danish Polymer Centre Department of Chemical and Biochemical EngineeringTechnical University of DenmarkLyngbyDenmark GRD Technology–Adhesives Coloplast A/SHumlebækDenmark

For improved wound healing,antimicrobial adhesives are one path ***,with the current challenge of bacterial resistance,it is essential to choose the included drug *** is an obvious choice due to its broad antimicrobial efficacy and no reported bacterial *** its pure form,octenidine complexes efficiently with the platinum catalyst in the silicone composition,inhibiting the targeted hydrosilyla-tion reaction and hindering *** obstacle is overcome by screening octenidine with cyclodextrins in homogeneously dispersed glycerol droplets,suppressing Pt inhibition in the silicone *** efficiency is demonstrated using rheol-ogy,which shows that it is possible to incorporate one wt%of octenidine into glycerol–silicone adhesives in the presence of(2-hydroxypropyl)-β-cyclodextrin without affecting the adhe-sives’mechanical *** interaction between octeni-dine and(2-hydroxypropyl)-β-cyclodextrin through an inclusion complex is confirmed by ROESY *** this screening,octenidine is still released efficiently from the glycerol–silicone adhesives upon contact with water,and the resulting antimicrobial action is subsequently *** new technology constitutes a simple and efficient method for preparing wound care adhesives that actively inhibit the growth of four bacteria strains and one fungus.

关键词： Silicone adhesive skin adhesive active adhesive antimicrobial

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Impact of dietary L-arginine supply during early gestation on myofiber development in newborn pigs exposed to intra-uterine crowding

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Journal of Animal Science and Biotechnology 2017年第4期8卷 945-956页

作者： Johannes Gulmann madsen Camilo Pardo Michael Kreuzer Giuseppe Bee Agroscope Posieux la tioleyre 4 1725 Posieux Switzerland ETH Zurich Institute of Agricultural Sciences Universitsstrasse 2 8092 ZurichSwitzerland

Background: Intra-uterine crowding(IUC) observed in hyperprolific sows impairs myofiber hyperplasia and overall fetal growth. Arginine supplementation(ARG) in gestation diets has been shown to positively affect litter and muscle development. The study objective was to assess whether the effect of ARG on offspring characteristics, with special emphasis on myofiber hyperplasia, differs under IUC conditions from these responses,because in that situation growth retardation is particularly prevalent due to reduced fetal nutrient *** oviduct ligation(OL) was used as a model for an uncrowded and hyperprolificacy(IN) as a model for a crowded intra-uterine ***: Five OL and five IN sows were fed a diet supplemented daily with either 43 g L-alanine(Ctrl) or 25 g L-arginine from d 14 to 28 of gestation in a cross-over design(two periods: 5^( th) and 6^( th) parity). At farrowing, two male and two female offspring, respectively, with a low and intermediate birth weight(BtW) were selected. After euthanization, the Semitendinosus muscle(STM) was removed and weighed, and the light and dark portions(STM_d and STM_l) were prepared for myofiber histochemistry using ATPase staining and the entire STM for gene expression analysis of myogenesis-related genes using RT-qPCR. In addition, various organs were removed and weighed. Data were analyzed using the MIXED model in ***: No effect of either IUC or dietary treatment was found in litter characteristics. Offspring of ARG sows displayed a greater muscle area in STM(P < 0.01) as a result of the greater myofiber hyperplasia(P < 0.01). The increase was more distinct in the STM_l(P < 0.05) than in the STM_d(P = 0.131). Offspring of OL sows were heavier at birth(P < 0.01), had a heavier STM(P < 0.05), liver(P < 0.01) and kidney(P < 0.05), but when expressed relative to birth weight, these differences were absent. In addition, IUC had an effect(P < 0.05) on the expression of one of the myogenesis-related

关键词： Dietary supplement Early gestation Intra-uterine growth restriction Myofiber hyperplasia Neonate Sow prolificacy

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Removal of chromophoric dissolved organic matter under combined photochemical and microbial degradation as a response to different irradiation intensities

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Journal of Environmental Sciences 2022年第8期34卷 76-86页

作者： Theis Kragh Kaj Sand-Jensen Emil Kristensen Ole Pedersen Mikkel madsen-Фterbye Department of Biology University of Southern DenmarkSyddanmark 5230Denmark Freshwater Biological Laboratory Department of BiologyUniversity of CopenhagenCopenhagen 2100Denmark

Throughout the freshwater continuum, Dissolved Organic Carbon(DOC) and the colored fraction, Chromophoric Dissolved Organic Material(CDOM), are continuously being added,removed, and transformed, resulting in changes in the chromophoricity and lability of organic matter over time. We examined, experimentally, the effect of increasing irradiationintensities on the combined photochemical and microbial degradation of CDOM and *** was done by using a simulated mixed water column: aged water from a humic lake was exposed to four irradiation-intensities – representing winter, early and late spring, and summer conditions(0.10, 0.16, 0.36, and 0.58 W/m^(2)) – and compared with dark controls over 37days. We found a linear relationship between CDOM degradation and irradiation-intensities up to 0.36 W/m^(2);the degradation rate saturated at higher intensities, both at specific wavelengths and for broader intervals. After 37 days at high irradiation-intensity, CDOM absorption of irradiation at 340 nm had been reduced by 41%;48% of DOC had been removed and DOC degradation continued to increase. Aromaticity(SUVA254) declined significantly over 37 days at the two lowest but not at the two highest UV-intensities;levels in unexposed control water remained constant. Direct observations of the humic lake showed that CDOM absorption of irradiation(340 nm) declined by 27% from winter to summer. A model based on hydrological CDOM input and CDOM degradation calculated from field measurements of UV-radiation and experimental CDOM degradation with UV-exposure from sunlight accurately predicted the annual course as observed in the lake. With no external CDOM input,92% of the CDOM could be degraded in a year. The results support the notion that combined photochemical and microbial CDOM degradation can be remarkably higher in lakes than previously thought and that humic lakes retain their color due to light absorption by ongoing CDOM input.

关键词： Biodegradation Brownification Carbon cycling CDOM DOC Humic lake Photobleaching UV-bleaching

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Degradation patterns of silicone-based dielectric elastomers in electrical fields

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International Journal of Smart and Nano Materials 2018年第4期9卷 217-232,I0001页

作者： Liyun Yu Frederikke B.madsen Anne L.Skov Danish Polymer Centre Department of Chemical and Biochemical EngineeringTechnical University of DenmarkKgs.LyngbyDenmark

Silicone elastomers have been heavily investigated as candidates for the flexible insulator material in dielectric elastomer transducers and are as such almost ideal candidates because of their inherent softness and ***,silicone elastomers suffer from low dielectric *** shortcoming has been attempted optimized through different approaches during recent *** optimization with the sole purpose of increasing the dielectric permittivity may lead to the introduction of problematic phenomena such as premature electrical breakdown due to high leakage currents of the thin elastomer *** this work,electrical breakdown phenomena of various types of permittivity-enhanced silicone elastomers are *** showed that different types of polymer backbone chemistries lead to differences in electrical breakdown patterns,which were revealed through SEM *** may pave the way towards a better understanding of electrical breakdown mechanisms of dielectric elastomers and potentially lead to materials with increased electrical breakdown strengths.

关键词： Silicone elastomers dielectric electrical breakdown voltage stabilization characterization

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