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Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity

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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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Deciphering the controlling factors for phase transitions in zeolitic imidazolate frameworks

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National Science Review 2024年第4期11卷 151-163页

作者： Tao Du Shanwu Li Sudheer Ganisetti Mathieu Bauchy Yuanzheng Yue morten M.Smedskjaer Department of Chemistry and Bioscience Aalborg University Department of Mechanical Engineering-Engineering Mechanics Michigan Technological University Physics of Amo Rphous and Inorganic Solids Laboratory(PARISlab) Department of Civil and Environmental EngineeringUniversity of CaliforniaLos Angeles

Zeolitic imidazolate frameworks（ZIFs） feature complex phase transitions, including polymorphism,melting, vitrification, and polyamorphism. Experimentally probing their structural evolution during transitions involving amorphous phases is a significant challenge, especially at the medium-range length scale. To overcome this challenge, here we first train a deep learning-based force field to identify the structural characteristics of both crystalline and non-crystalline ZIF phases. This allows us to reproduce the structural evolution trend during the melting of crystals and formation of ZIF glasses at various length scales with an accuracy comparable to that of ab initio molecular dynamics, yet at a much lower computational cost. Based on this approach, we propose a new structural descriptor, namely, the ring orientation index, to capture the propensity for crystallization of ZIF-4(Zn（Im）2, Im = C3H3N2-) glasses, as well as for the formation of ZIF-zni(Zn（Im）2) out of the high-density amorphous phase. This crystal formation process is a result of the reorientation of imidazole rings by sacrificing the order of the structure around the zinc-centered tetrahedra. The outcomes of this work are useful for studying phase transitions in other metal-organic frameworks（MOFs） and may thus guide the development of MOF glasses.

关键词： metal-organic frameworks phase transitions melting glass formation transferable deep learning force field ring orientation

The flattening of spacetime hierarchy of the N,N-dimethyltryptamine brain state is characterized by harmonic decomposition of spacetime(HADES) framework

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National Science Review 2024年第5期11卷 46-55页

作者： Jakub Vohryzek Joana Cabral Christopher Timmermann Selen Atasoy Leor Roseman David J.Nutt Robin L.Carhart-Harris Gustavo Deco morten L.Kringelbach Centre for Eudaimonia and Human Flourishing Linacre CollegeDepartment of Psychiatry University of Oxford Department of Psychiatry University of Oxford Center for Music in the Brain Aarhus University Center for Brain and Cognition Computational Neuroscience GroupDepartment of Information and Communication TechnologiesUniversitat Pompeu Fabra Life and Health Sciences Research Institute School of MedicineUniversity of Minho ICVS/3B's-PT Government Associate Laboratory Centre for Psychedelic Research Department of Brain Sciences Imperial College London Departments of Neurology and Psychiatry University of California San Francisco Institució Catalana de la Recerca i Estudis Avan?ats (ICREA) Department of Neuropsychology Max Planck Institute for Human Cognitive and Brain Sciences School of Psychological Sciences Monash University

The human brain is a complex system, whose activity exhibits flexible and continuous reorganization across space and time. The decomposition of whole-brain recordings into harmonic modes has revealed a repertoire of gradient-like activity patterns associated with distinct brain functions. However, the way these activity patterns are expressed over time with their changes in various brain states remains unclear. Here, we investigate healthy participants taking the serotonergic psychedelic N,N-dimethyltryptamine(DMT) with the Harmonic Decomposition of Spacetime(HADES) framework that can characterize how different harmonic modes defined in space are expressed over time. HADES demonstrates significant decreases in contributions across most low-frequency harmonic modes in the DMT-induced brain state. When normalizing the contributions by condition(DMT and non-DMT), we detect a decrease specifically in the second functional harmonic, which represents the uni-to transmodal functional hierarchy of the brain,supporting the leading hypothesis that functional hierarchy is changed in psychedelics. Moreover, HADES'dynamic spacetime measures of fractional occupancy, life time and latent space provide a precise description of the significant changes of the spacetime hierarchical organization of brain activity in the psychedelic state.

关键词： spatio-temporal brain dynamics DMT harmonic modes

FunHoP:Enhanced Visualization and Analysis of Functionally Homologous Proteins in Complex Metabolic Networks

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Genomics, Proteomics & Bioinformatics 2021年第5期19卷 848-859页

作者： Kjersti Rise May-Britt Tessem Finn Drablos morten B.rye Department of Clinical and Molecular Medicine NTNU-Norwegian University of Science and TechnologyTrondheim NO-7491Norway Department of Circulation and Medical Imaging NTNU-Norwegian University of Science and TechnologyTrondheim NO-7491Norway Clinic of Surgery St.Olavs HospitalTrondheim University HospitalTrondheim NO-7491Norway

Cytoscape is often used for visualization and analysis of metabolic *** example,based on KEGG data,a reader for KEGG Markup Language(KGML)is used to load files into ***,although multiple genes can be responsible for the same reaction,the KGMLreader KEGGScape only presents the first listed gene in a network node for a given *** can lead to incorrect interpretations of the *** new method,FunHoP,shows all possible genes in each node,making the pathways more *** collapses all genes in a node into one measurement using read counts from *** that activity for an enzymatic reaction mainly depends upon the gene with the highest number of reads,and weighting the reads on gene length and ratio,a new expression value is calculated for the node as a *** expression at node level is then applied to the *** prostate cancer as model,we integrate RNA-seq data from two patient cohorts with metabolism data from *** we show that FunHoP gives more consistent pathways that are easier to interpret *** and documentation for running FunHoP can be found at https://***/kjerstirise/FunHoP.

关键词： Homologous proteins Metabolic network Pathway visualization and analysis RNA-seq KEGG Cytoscape

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