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LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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Genes & Diseases 2024年第3期11卷 417-426页

作者： Zijian Xu elizabeth R.Davies Liudi Yao Yilu Zhou Juanjuan Li Aiman Alzetani Ben G.Marshall David Hancock Tim Wallis Julian Downward Rob M.ewing Donna e.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely *** previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(eMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine ***,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces eMT as a *** IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast ***,these data suggest that reduced autophagy caused by LKB1 inhibition can induce eMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39L Crosstalk eMT LKB1 Pulmonary fibrosis

Ground-based and additional science support for SMILe

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earth and Planetary Physics 2024年第1期8卷 275-298页

作者： J.A.Carter M.Dunlop C.Forsyth K.Oksavik e.Donovon A.Kavanagh S.e.Milan T.Sergienko R.C.Fear D.G.Sibeck M.Connors T.Yeoman X.Tan M.G.G.T.Taylor K.McWilliams J.Gjerloev R.Barnes D.D.Billet G.Chisham A.Dimmock M.P.Freeman D.-S.Han M.D.Hartinger S.-Y.W.Hsieh Z.-J.Hu M.K.James L.Juusola K.Kauristie e.A.Kronberg M.Lester J.Manuel J.Matzka I.McCrea Y.Miyoshi J.Rae L.Ren F.Sigernes e.Spanswick K.Sterne A.Steuwer T.Sun M.-T.Walach B.Walsh C.Wang J.Weygand J.Wild J.Yan J.Zhang Q.-H.Zhang Planetary Sciences Group School of Physics and AstronomyUniversity of LeicesterUniversity RoadLeicesterLE17RHUK Rutherford Appleton Laboratory Space Science Technology Facilities CouncilOxfordshireUK School of Space and environment Beihang UniversityBeijing 100191China Key Laboratory of Space environment Monitoring and Information Processing Ministry of Industry and Information TechnologyBeijing 100017China Department of Space and Climate Physics UCLMullard Space Science LaboratoryHolmbury St.MaryDorkingSurreyRH56NTUK Birkeland Centre for Space Science Department of Physics and Technology.University of BergenBergenNorway Department of Physics and Astronomy University of Calgary2500 University DriveCalgaryAlbertaCanada T2N 1N4 British Antarctic Survey CambridgeUK Swedish Institute of Space Physics KirunaSweden West Highfield Campus University of SouthamptonUniversity RoadSO171BJUK Goddard Space Flight Center NASAGreenbeltMarylandUSA Athabasca University AthabascaCanada eSTeC European Space AgencyNetherlands University of Saskatchewan SaskatoonCanada The Johns Hopkins University Applied Physics Laboratory LaurelMarylandUSA Swedish Institude of Space Physics UppsalaSE 75121Sweden Tongji University Shanghai 200092China Center for Space Plasma Physics Space Science Institute4765 Walnut Street Suite BBoulderColorado80301USA Polar Research Institute of China Shanghai 200136China Finnish Meteorological Institute(FMI) Finland Department of earth and environmental Sciences(Geophysics) Ludwig Maximilian University of Munich(LMU)MunichTheresienstr.41MunichD-80333Germany Canadian Space Agency MontrealCanada GFZ German Research Centre for Geosciences PotsdamGermany Nagoya University Institute for Space Earth Environment ResearchCenter for Integrated Data ScienceNagoyaAichiJP 464-8601 Northumbria University Newcastle upon TyneTyne and WearUK NE18ST National Space Science Center Chinese Academy SciencesBeijing 100190China Arctic Geophysics University Centre in Svalbard

The joint european Space Agency and Chinese Academy of Sciences Solar wind Magnetosphere Ionosphere Link explorer(SMILe)mission will explore global dynamics of the magnetosphere under varying solar wind and interplanetary magnetic field conditions,and simultaneously monitor the auroral response of the Northern Hemisphere *** these large-scale responses with medium and fine-scale measurements at a variety of cadences by additional ground-based and space-based instruments will enable a much greater scientific impact beyond the original goals of the SMILe ***,we describe current community efforts to prepare for SMILe,and the benefits and context various experiments that have explicitly expressed support for SMILe can offer.A dedicated group of international scientists representing many different experiment types and geographical locations,the Ground-based and Additional Science Working Group,is facilitating these *** include constructing an online SMILe Data Fusion Facility,the discussion of particular or special modes for experiments such as coherent and incoherent scatter radar,and the consideration of particular observing strategies and spacecraft *** anticipate growing interest and community engagement with the SMILe mission,and we welcome novel ideas and insights from the solar-terrestrial community.

关键词： magnetosphere ionosphere magnetosphere-ionosphere coupling ground-based experimentation SMILe conjunctions missions

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Storylines of family medicine Ⅴ:ways of thinking—honing the therapeutic self

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Family Medicine and Community Health 2024年第S3期12卷 43-51页

作者： William B Ventres Leslie A Stone Johanna F Shapiro Cynthia Haq Jéssica R B Leao Donald e Nease Jr Liz Grant Stewart W Mercer John C M Gillies Pablo González Blasco Maria Auxiliadora C De Benedetto Graziela Moreto Marcelo R Levites Jennifer e DeVoe William R Phillips Jane M Uygur Thomas R egnew Colette S Stanley Family and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family Medicine University of California Irvine School of MedicineIrvineCaliforniaUSA Faculty of Medicine University of Sao PauloSao PauloBrazil Family Medicine University of Colorado Anschutz Medical Campus School of MedicineAuroraColoradoUSA Usher Institute Edinburgh Medical SchoolUniversity of EdinburghEdinburghUK SOBRAMFA-Medical education and Humanism Sao PauloBrazil Family Medicine Oregon Health&Science University School of MedicinePortlandOregonUSA Family Medicine University of Washington School of MedicineSeattleWashingtonUSA General Practice Royal College of Surgeons in IrelandDublinIreland General Internal Medicine Geriatrics&Palliative MedicineTulane University School of MedicineNew OrleansLouisianaUSA

Storylines of Family Medicine is a 12-part series of thematically linked essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅴ:ways of thinking—honing the therapeutic self’,authors present the following sections:‘Reflective practice in action’,‘The doctor as drug—Balint groups’,‘Cultivating compassion’,‘Towards a humanistic approach to doctoring’,‘Intimacy in family medicine’,‘The many faces of suffering’,‘Transcending suffering’and‘The power of listening to stories.’May readers feel a deeper sense of their own therapeutic agency by reflecting on these essays.

关键词： illustration dimensions suffering

An Automated,Highly Selective Reaction Monitoring Instrument Using Molecular Rotational Resonance Spectroscopy

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Precision Chemistry 2024年第2期2卷 57-62页

作者： Ann Adele Byars Khushi R.Kompally emily Mechnick Reilly e.Sonstrom Alexander Mikhonin Justin L.Neill Ruth Boetzel James MacGregor Courtney Talicska Jian Li Yizhou Liu BrightSpec Inc.CharlottesvilleVirginia 22903United States Pfizer R&D uk Limited Sandwich CT139NJUnited Kingdom Analytical Research and Development Pfizer Research and DevelopmentGrotonConnecticut 06340United States

Online monitoring of chemical reactions by using analytical chemistry tools is a powerful way to maximize control over these *** this paper,we demonstrate the use of molecular rotational resonance,an emerging and extraordinarily selective spectroscopic technique,to perform automated reaction monitoring *** interface using a six-port valve with a calibrated sample loop,coupled to a temperature controlled inlet for analyte volatilization,was developed and *** reactions were chosen for initial characterization:an amine-aldehyde condensation reaction to form an imine product and an isotopic exchange reaction of aβ-ketoester with keto-enol *** spectrometer was able to provide kinetic information about the reaction and determine reaction *** the future,this system can be extended to detect and quantify impurities and characterize reaction selectivity,in addition to the reaction progress.

关键词： molecular rotational resonance spectroscopy reaction monitoring reaction kinetics isotopes process analytical technology

Amphibian metamorphosis as a model for studying the developmental actions of thyroid hormone

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Cell Research 1998年第4期8卷 259-272页

作者： TATA JAMSHeD R (National Institute for Medical Research, The Ridgeway,Mill Hill, London NW7 1AA, uk.Tel: +44-181-959 3666 Fax: +JJ-181-913 8583e-mail: jtata@nimr. mrc. ac. uk) National Institute for Medical Research London U.K.

The thyroid hormones L-thyroxine and triiodo-L-thyronine have profound effects on postembryonic development of most vertebrates. Analysis of their action in mammals is vitiated by the exposure of the developing foetus to a number of maternal factors which do not allow one to specifically define the role of thyroid hormone (TH)or that of other hormones and factors that modulate its action. Amphibian metamorphosis is obligatorily dependent on TH which can initiate all the diverse physiological manifestations of this postembryonic developmental process(morphogenesis, cell death, re-structuring, etc.) in free-living embryos and larvae of most anurans. This article will first describe the salient features of metamorphosis and its control by TH and other hormones. emphasis will be laid on the key role played by TH receptor (TR), in particular the phenomenon of TR gene autoinduction, in initiating the developmental action of TH. Finally, it will be argued that the findings on the control of amphibian metamorphosis enhance our understanding of the regulation of postembryonic development by TH in other vertebrate species.

关键词： Thyroid hormone metamorphosis postembryonic development thyroid hormone receptor autoinduction

Dysregulated bidirectional epithelial-mesenchymal crosstalk:A core determinant of lung fibrosis progression

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 27-33页

作者： Liudi Yao Zijian Xu Donna e.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK Clinical and experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK

Progressive lung fibrosis is characterized by dysregulated extracellular matrix(eCM)***-ing of disease pathogenesis remains limited and has prevented the development of effective *** an abnormal wound-healing response is strongly implicated in lung fibrosis initiation,factors that determine why fi-brosis progresses rather than regular tissue repair occur are not fully *** human lung fibrosis,there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial-mesenchymal transition(eMT),a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell-cell adhesion to gain migratory *** review will focus on the role of eMT and dysregulated epithelial-mesenchymal crosstalk in progressive lung fibrosis.

关键词： Lung fibrosis epithelial-mesenchymal transition(eMT) Crosstalk

The common language of space:a way of looking at the social,economic and environmental functioning of cities on a common basis

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Journal of environmental Sciences 1999年第3期11卷 344-349页

作者： Bill Hillier Bartlett School of Graduate Studies, University College London, Gower Street, London WC1e 6BT, U.K. e\|mail:b.hillier@ucl.ac.uk University College London 英国

This paper proposes that in addition to urban research which seeks to provide answers to policy questions, there is also a need for research which directly addresses the physical and spatial complexity of the built environment itself, and explores any effects it may in itself have on the functioning of the urban system. This type of research reflects the questions architects and urban designers typically ask, rather than those that preoccupy planners. For such research to be effective, the physical complexity variable must be controlled at the level at which real design decisions are made. “Space syntax” research attempts to do this by treating built environments as systems of space, analysing them “configurationally”, and trying to bring to light their underlying patterns and structures. Results from space syntax research into many aspects of urban space and how it works show a consistency which suggests that analysing spacial structure can be a general means of investigating the structure and function of cities. It may, in effect, be the common language of the city.

关键词： space syntax urban system London.

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Complex ammonium oxidation demands visualized resolution

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Science Bulletin 2024年第16期69卷 2478-2482页

作者： Zhihao Chen Yonghong Wu Jan Dolfing Shunyao Zhuang Baozhan Wang Dan Li Shan Huang Bruce e.Rittmann State Key Laboratory of Soil and Sustainable Agriculture Institute of Soil ScienceChinese Academy of SciencesNanjing 210008China Zigui Three Gorges Reservoir ecosystem Observation and Research Station of Ministry of Water Resources of the People’s Republic of ChinaYichang 443605China University of Chinese Academy of Sciences Beijing 100049China d College of Nanjing University of Chinese Academy of SciencesNanjing 211135China Faculty of energy and environment Northumbria UniversityNewcastle-upon-Tyne NE18QHUK Department of Microbiology College of Life SciencesNanjing Agricultural UniversityKey Laboratory of Agricultural and Environmental MicrobiologyMinistry of Agriculture and Rural AffairsNanjing 210095China College of Urban Construction Nanjing Tech UniversityNanjing 211816China Department of Civil and environmental engineering Princeton UniversityPrinceton NJ 08540USA Biodesign Swette Center for environmental Biotechnology Arizona State UniversityTempe AZ 85287-5701USA

The nitrogen cycle plays a vital role in sustaining productive and healthy ecosystems,with the microbial nitrogen cycle being a focal point in agriculture and eco-environmental *** these microbially mediated processes is ammonium(NH_(4)^(+))oxidation,the gatekeeper of the nitrogen *** understanding of ammonium oxidation is continuously evolving,thanks to recent research breakthroughs like comammox,Feammox,and dirammox[1-6].The increasing complexity of ammonium oxidation necessitates more precise and well-focused research tools beyond those commonly used today.

关键词： ammonium breakthrough precise

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Storylines of family medicine Ⅷ:clinical approaches

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Family Medicine and Community Health 2024年第S3期12卷 70-78页

作者： William B Ventres Leslie A Stone Lauren e Gibson-Oliver elizabeth Kyle Meehan Mari A Ricker David Loxterkamp Stacy A Ogbeide Frank V deGruy Megan R Mahoney Steven Lin Clare MacRae Stewart W Mercer Family and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family and Community Medicine The University of Arizona College of Medicine-TucsonTucsonArizonaUSA Bucksport Regional Health Center BucksportMaineUSA Family and Community Medicine UT Health San Antonio Long School of MedicineSan AntonioTexasUSA eugene S.Farley Jr.Health Policy CenterUniversity of Colorado Anschutz Medical Campus School of MedicineAuroraColoradoUSA Family and Community Medicine University of California San Francisco School of MedicineSan FranciscoCaliforniaUSA Division of Primary Care and Population Health Stanford MedicinePalo AltoCaliforniaUSA Usher Institute Edinburgh Medical SchoolUniversity of EdinburghEdinburghUK

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅷ:clinical approaches’,authors address the following themes:‘evaluation,diagnosis and managementⅠ—toward a working diagnosis’,‘evaluation,diagnosis and managementⅡ—process steps’,‘Interweaving integrative medicine and family medicine’,‘Halfway—the art of clinical judgment’,‘Seamless integration in family medicine—team-based care’,‘Technology—uncovering stories from noise’and‘Caring for patients with multiple long-term conditions’.May readers recognise in these essays the uniqueness of a family medicine approach to care.

关键词： uniqueness dimensions illustration