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RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian szymczuk Brendan Boyce daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael T.Collins Alison M.Boyce skeletal Disorders and Mineral Homeostasis section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

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A new oxidative pathway of nitric oxide production from oximes in plants

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Molecular Plant 2024年第1期17卷 178-198页

作者： Pedro Lopez-Gomez Javier Buezo Marina Urra Alfonso Cornejo Raquel Esteban Jorge Fernandez de los Reyes Estibaliz Urarte Estefania Rodriguez-Dobreva Alejandro Chamizo-Ampudia Alejandro Eguaras sebastian Wolf daniel Marino Victor Martinez-Merino Jose F.Moran Institute for Multidisciplinary Research in Applied Biology(IMAB) Department of SciencesPublic University of Navarre(UPNA)Avda.de Pamplona 12331192 MutilvaSpain Institute for Advanced Materials and Mathematics(INAMAT2) Department of SciencesPublic University of Navarre(UPNA)Campus de Arosadia31006 PamplonaSpain Department of Plant Biology and Ecology University of the Basque Country(UPV/EHU)Sarriena s/nApdo.64448080 BilbaoSpain Center for Plant Molecular Biology(ZMBP) University of TubingenGeschwister-Scholl-Platz72074 TubingenGermany Institute of Natural Resources and Agrobiology of salamanca(IRNAsA) Department of Plant-Microorganism InteractionsSpanish National Research Council(CSIC)Cordel de Merinas40-5237008SalamancaSpain Department of Biochemistry Area of Molecular BiologyVeterinary FacultyUniversity of LeonCampus de Vegazanas/n.24071 LeonSpain

Nitric oxide(NO)is an essential reactive oxygen species and a signal molecule in *** several studies have proposed the occurrence of oxidative NO production,only reductive routes for NO production,such as the nitrate(NO_(3)^(-))-upper-reductase pathway,have been evidenced to date in land ***,plants grown axenically with ammonium as the sole source of nitrogen exhibit contents of nitrite and NO3−,evidencing the existence of a metabolic pathway for oxidative production of *** hypothesized that oximes,such as indole-3-acetaldoxime(IAOx),a precursor to indole-3-acetic acid,are intermediate oxidation products in NO *** detected the production of NO from IAOx and other oximes catalyzed by peroxidase(POD)enzyme using both 4-amino-5-methylamino-2′,7′-difluorescein fluorescence and *** stimulated the reaction,while superoxide dismutase inhibited ***,mouse NO synthase can also use IAOx to produce NO at a lower rate than *** provided a full mechanism for POD-dependent NO production from IAOx consistent with the experimental data and supported by density functional theory *** showed that the addition of IAOx to extracts from Medicago truncatula increased the in vitro production of NO,while in vivo supplementation of IAOx and other oximes increased the number of lateral roots,as shown for NO donors,and a more than 10-fold increase in IAOx dehydratase ***,we found that in vivo supplementation of IAOx increased NO production in Arabidopsis thaliana wild-type plants,while prx33-34 mutant plants,defective in POD33-34,had reduced *** data show that the release of NO by IAOx,as well as its auxinic effect,explain the superroot ***,our study reveals that plants produce NO utilizing diverse molecules such as oximes,POD,and flavins,which are widely distributed in the plant kingdom,thus introducing a long-awaited oxidative pathway to NO production in plants.T

关键词： ammonium oxidation auxin nitric oxide oxime peroxidase root phenotype

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Adiponectin as a protective factor in hepatic steatosis

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World Journal of Gastroenterology 2005年第12期11卷 1737-1741页

作者： Nahum Méndez-sánchez Norberto C.Chávez-Tapia Antonio R.Villa Karla sánchez-Lara daniel Zamora-Valdés Martha H.ramos Misael Uribe Liver Research Unit Clinical Epidemiology Unit

AIM: Obesity and insulin resistance (IR) are closely related to hepatic steatosis (Hs), and adiponectin is a hepatic insulin sensitizer that has important effects in liver function. This study aims at investigating the relationship between serum adiponectin concentration and the presence of Hs. METHODs: We carried out a cross-sectional study in a check-up unit of a University Hospital in Mexico City. We enrolled 196 subjects, comprising 98 subjects with Hs (27 women, 71 men) and 98 controls (37 women and 61 men). Anthropometric, metabolic and biochemical variables were measured in the two groups. serum adiponectin and leptin concentrations were determined, their association with grade of Hs tested, and concentrations, according to quartiles, compared between cases and controls. X2 analysis for linear trends was used to test for a dose-response relationship and logistic regression analysis was conducted to test for a protective effect of adiponectin. REsULTs: The Hs subjects were older and more obese than controls, with a central obesity pattern. In the fourth quartile of adiponectin concentrations, Hs was less common and severe. In a multivariate model of the fourth quartile of the adiponectin concentrations, we observed a protective effect (OR = 0.17, 95%CI: 0.04-0.67, P= 0.01). In subjects with more severe Hs, we observed higher leptin concentrations, and caloric intakes, total fat and iron consumption were higher than in controls. CONCLUsION: The results of the present study suggest that a high serum concentration of adiponectin is associated with a protective effect against Hs.

关键词： Adiponectin Hepatic steatosis Leptin Diet

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Application of near-infrared spectroscopy for fast germplasm analysis and classification in multi-environment using intact-seed peanut(Arachis hypogaea L.)

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Oil Crop science 2024年第2期9卷 132-141页

作者： Fentanesh Chekole Kassie Gilles Chaix Hermine Bille Ngalle Maguette seye Coura Fall Hodo-Abalo Tossim Aissatou sambou Olivier Gibert Fabrice Davrieux Joseph Martin Bell Jean-Francois Rami daniel Fonceka Joel Romaric Nguepjop Department of Plant Biology and Physiology Faculty of SciencesUniversity of Yaounde IYaoundeP.O.Box 337Cameroon Department of Plant science College of AgricultureWolaita Sodo UniversitySodoP.O.Box 138Ethiopia CIRAD UMR AGAP InstitutMontpellierFrance AGAP Institut Univ MontpellierCIRADINRAEInstitut AgroMontpellierFrance ChemHouse Research Group MontpellierFrance Centre D’Etudes Regional Pour L’Amelioration de L’Adaptation a La secheresse(CERAAs/IsRA) Route de KhomboleThiesBP 3320Senegal Dispositif de Recherche et de Formation en Partenariat Innovation et Amelioration Varietale en Afrique de L’Ouest(IAVAO)CERAASRoute de KhomboleThiesBP 3320Senegal CIRAD UMR QUALISUDSaint PierreFrance

Peanut is a worldwide oilseed crop and the need to assess germplasm in a non-destructive manner is important for seed nutritional *** this study,Near Infrared spectroscopy(NIRs)was applied to rapidly assess germplasm variability from whole seed of 699 samples,field-collected and assembled in four genetic and environmentbased sets:one set of 300 varieties of a core-collection and three sets of 133 genotypes of an interspecific population,evaluated in three environments in a large spatial scale of two countries,Mbalmayo and Bafia in Cameroon and Nioro in senegal,under rainfed *** elemental spectra were gathered on six subsets of seeds of each sample,after three rotation scans,with a spectral resolution of 16 cm-1over the spectral range of867 nm to 2530 *** were then processed by principal component analysis(PCA)coupled with Partial least squares-discriminant analysis(PLs-DA).As results,a huge variability was found between varieties and genotypes for all NIR wavelength within and between *** magnitude of genetic variation was particularly observed at 11 relevant wavelengths such as 1723 nm,usually related to oil content and fatty acid *** yielded the most chemical attributes in three significant PCs(i.e.,eigenvalues>10),which together captured 93%of the total variation,revealing genetic and environment structure of varieties and genotypes into four clusters,corresponding to the four samples *** pattern of genetic variability of the interspecific population covers,remarkably half of spectrum of the core-collection,turning out to be the ***,a PLs-DA model was developed and a strong accuracy of 99.6%was achieved for the four sets,aiming to classify each seed sample according to environment *** confusion matrix achieved for the two sets of Bafia and Nioro showed 100%of instances classified correctly with 100%at both sensitivity and specificity,confirming that their seed quality was different f

关键词： Groundnut Oilseed Near infrared spectroscopy Germplasm analysis Environment Nutritional Breeding

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再论贤能政治——“贤能”叙事的回归及重构

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探索与争鸣 2024年第3期 60-73,178页

作者：李东阳贝淡宁香港大学法学院中国香港999077

当代贤能政治论争由于采用不同的“贤能”叙事,一定程度上造成了语境错位与概念含混。为此需要在厘清“贤能”多重含义及历史叙事基础上,重新辨识传统贤能政治中合现代性的话语,建构贤能政治的现代叙事方式。基于“尚力”“尚财”“尚... 详细信息

当代贤能政治论争由于采用不同的“贤能”叙事,一定程度上造成了语境错位与概念含混。为此需要在厘清“贤能”多重含义及历史叙事基础上,重新辨识传统贤能政治中合现代性的话语,建构贤能政治的现代叙事方式。基于“尚力”“尚财”“尚德”三种元话语,传统贤能政治衍生出斗争与刑罚、祭祀与经纪、教化与吸纳六种主要叙事原理,并按照一定的发生逻辑与主从关系组合形塑了不同特征的贤能政治形态。现代贤能政治的话语场域应当由权力关系话语回归伦理关系话语,由纵向的传统伦理关系叙事重构横向的合现代性的伦理关系叙事。源于对家庭、家国、国际、自然、人机等差序关系的审慎思考,贤能政治能够为中国的国际形象提供积极正面的话语支持,也将为人类文明形态发展提供更多可能性。

关键词：贤能政治贤能 “贤能”叙事尚贤

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