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Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

Cellular & Molecular Immunology 2024年第1期21卷 33-46页

作者： anja meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel Brian Zanotti Michael V.Volin M.Asif Amin Myles J.Lewis Costantino Pitzalis Shiva Arami Joseph A.Karam Nadera J.Sweiss Shiva Shahrara Jesse Brown VA Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Division of Rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA Centre for Experimental Medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom Centre for Experimental Medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

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Failure of a T cell regulator: CD6 contributes to the aggravation of autoimmune inflammation

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Cellular & Molecular Immunology 2019年第9期16卷 733-734页

作者： anja meyer David M.Kofler Division of Clinical Immunology and Rheumatology Department I of Internal MedicineUniversity of CologneCologne 50937Germany

The scavenger-like lymphocyte receptor CD6 is a regulator of T cell functions,and is associated with autoimmune ***,the specific contribution of CD6 to autoimmunity remains *** physiological conditions,CD6 associates with the T cell antigen receptor(TCR)/CD3 complex at the center of the immunological synapse and regulates T cell responses through activation-dependent recruitment of the positive regulator SLP-76 and other downstream signaling effectors.1,2 In recent years,immune-activating and immune-inhibiting functions of CD6 have been reported,indicating a dual role of CD6 in T cell activation.1 It has been postulated that the strength of TCR activation determines whether CD6 enhances or inhibits TCR signaling.1 This possible counter-regulatory role of CD6 may contribute to the control of T cell responses.

关键词： autoimmune inflammation CD6

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Dysregulation of IL-34 ligation to SDC-1 mitigates collagen-induced arthritis

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Cellular & Molecular Immunology 2022年第9期19卷 1070-1072页

作者： anja meyer Ryan Sienes Brian Zanotti Katrien van Raemdonck Karol Palasiewicz Daniel P.Mass Michael V.Volin Shiva Shahrara Jesse Brown VA Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Department of Orthopedic Surgery The University of Illinois at ChicagoChicagoILUSA

IL-34 is a novel biomarker for rheumatoid arthritis(RA),as its serum levels are linked to C-reactive protein,erythrocyte sedimentation rate,rheumatoid factor(RF),IL-6 and radiographic progression[1,2].IL-34 reprograms naïve circulating M0 cells into glycolytic(CD14^(+)CD86^(+)GLUT1^(high))M34 macrophages(MΦs)by binding to its pathogenic receptor,SDC-1,which controls the activation of its coreceptor/M-CSFR[3].Glycolytic M34 MΦs are primed to differentiate into osteoclasts through SDC-1 ligation[3].

关键词： CD86 GLUT1 sedimentation

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Cannabinoids drive Th17 cell differentiation in patients with rheumatic autoimmune diseases

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Cellular & Molecular Immunology 2021年第3期18卷 764-766页

作者： Konstantin Kotschenreuther Iris Waque Shuaifeng Yan anja meyer Thom Haak Julia von Tresckow Joanna Schiller Lydia Gloyer Mara Dittrich-Salamon David M.Kofler Laboratory of Molecular Immunology and Division of Clinical Immunology and Rheumatology University of CologneCologneGermany DepartmentⅠof Internal Medicine University of CologneCologneGermany

The legalization of cannabinoids for medical use has reinforced their emerging role as a treatment of chronic pain in patients with cancer or rheumatic diseases.1,2 In addition to their role as pain relievers,evidence obtained from animal models suggests that cannabinoids have immunosuppressive properties.3 However,a definite immunosuppressive function of cannabinoids has not yet been confirmed in clinical trials.

关键词： rheumatic Th17 patients

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Is the speed of adjusting to environmental change condition dependent?An experiment with house mice(Mus musculus)

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Current Zoology 2024年第3期70卷 350-360页

作者： Karem Lopez-Hervas Neelam Porwal Mathilde Delacoux Alexandros Vezyrakis anja Guenther RG Behavioural Ecology of Individual Differences Max Planck Institute for Evolutionary Biology24306 PlönGermany Department of Evolutionary Biology Faculty of BiologyAdam Mickiewicz UniversityWieniawskiego 161-712 PoznańPoland Department for Collective Behaviour Max Planck Institute of Animal Behaviour78464 ConstanceGermany Centre for the Advanced Study of Collective Behaviour University of Konstanz78464 ConstanceGermany Animal Ecology Institute for Biochemistry and BiologyUniversity of Potsdam14469 PotsdamGermany

Environmental conditions change constantly either by anthropogenic perturbation or naturally across space and ***,a change in behavior is the frst response to changing *** fexibility can potentially improve an organism’s chances to survive and ***,we lack an understanding on the time-scale such behavioral adjustments need,how they actually affect reproduction and survival and whether behavioral adjustments are suffcient in keeping up with changing *** used house mice(Mus musculus)to test whether personality and life-history traits can adjust to an experimentally induced food-switch fexibly in adulthood or by intergenerational plasticity,that is,adjustments only becoming visible in the offspring *** lived in 6 experimental populations of semi-natural environments either on high or standard quality food for 4 *** showed previously that high-quality food induced better conditions and a less risk-prone ***,we tested whether the speed and/or magnitude of adjustment shows condition-dependency and whether adjustments incur ftness ***-history but not personality traits reacted fexibly to a food-switch,primarily by a direct reduction of reproduction and sloweddown *** whose parents received a food-switch developed a more active stress-coping personality and gained weight at a slower rate compared with their respective ***,the modulation of most traits was condition-dependent,with animals previously fed with high-quality food showing stronger *** study highlights that life-history and personality traits adjust at different speed toward environmental change,thus,highlighting the importance of the environment and the mode of response for evolutionary models.

关键词： animal personality context dependence environmental change Match-mismatch non-genetic inheritance phenotypic flexibility phenotypic plasticity

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A review of federated learning in renewable energy applications:Potential,challenges,and future directions

Energy and AI

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Energy and AI 2024年第3期17卷 444-457页

作者： Albin Grataloup Stefan Jonas Angela meyer Bern University of Applied Sciences School of Engineering and Computer ScienceQuellgasse 21Biel2501Switzerland Universitàdella Svizzera italiana Faculty of InformaticsVia la Santa 1Lugano-Viganello6962Switzerland Delft University of Technology Department of Geoscience and Remote SensingStevinweg 1Delft2628The Netherlands

Federated learning has recently emerged as a privacy-preserving distributed machine learning *** learning enables collaborative training of multiple clients and entire fleets without sharing the involved training *** preserving data privacy,federated learning has the potential to overcome the lack of data sharing in the renewable energy sector which is inhibiting innovation,research and *** paper provides an overview of federated learning in renewable energy *** discuss federated learning algorithms and survey their applications and case studies in renewable energy generation and *** also evaluate the potential and the challenges associated with federated learning applied in power and energy ***,we outline promising future research directions in federated learning for applications in renewable energy.

关键词： Federated learning Renewable energy Dis tributed learning Data heterogeneity Privacy Data sharing Wind energy Solar energy Buildings Review

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Promoting the production of challenging proteins via induced expression in CHO cells and modified cell-free lysates harboring T7 RNA polymerase and mutant eIF2α

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Synthetic and Systems Biotechnology 2024年第3期9卷 416-424页

作者： Jeffrey L.Schloßhauer Lena Tholen Alexander Korner Stefan Kubick Sofia Chatzopoulou anja Honow Anne Zemella Fraunhofer Project Group PZ-Syn of the Fraunhofer Institute for Cell Therapy and Immunology-IZI Branch Bioanalytics and Bioprocesses-IZI-BBAm MühlenbergPotsdamGermany Fraunhofer Institute for Cell Therapy and Immunology-IZI Branch Bioanalytics and Bioprocesses-IZI-BBAm MühlenbergPotsdamGermany Faculty of Health Sciences Joint Faculty of the Brandenburg University of Technology Cottbus-SenftenbergThe Brandenburg Medical School Theodor FontaneUniversity of PotsdamPotsdamGermany Institute for Chemistry and Biochemistry Laboratory of Protein BiochemistryFreie Universitat BerlinThielallee 6314195BerlinGermany Institute of Biotechnology Technische Universit¨at BerlinStraße des 17.Juni 13510623BerlinGermany New/era/mabs GmbH August-Bebel-Str.8914482PotsdamGermany

Chinese hamster ovary(CHO)cells are crucial in biopharmaceutical production due to their scalability and capacity for human-like post-translational ***,toxic proteins and membrane proteins are often difficult-to-express in living ***,cell-free protein synthesis can be *** study explores innovative strategies for enhancing the production of challenging proteins through the modification of CHO cells by investigating both,cell-based and cell-free approaches.A major result in our study involves the integration of a mutant eIF2 translation initiation factor and T7 RNA polymerase into CHO cell lysates for cell-free protein *** resulted in elevated yields,while eliminating the necessity for exogenous additions during cell-free production,thereby substantially enhancing ***,we explore the potential of the Rosa26 genomic site for the integration of T7 RNA polymerase and cell-based tetracycline-controlled protein *** findings provide promising advancements in bioproduction technologies,offering flexibility to switch between cell-free and cell-based protein production as needed.

关键词： Inducible expression CHO cells Cell-free protein synthesis CRISPR T7 RNA polymerase eIF2 Rosa26

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The role of extracorporeal life support and timing of repair in infants with congenital diaphragmatic hernia

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World Journal of Pediatric Surgery 2024年第2期7卷 90-99页

作者： Daniel B Gehle Logan C meyer Tim Jancelewicz Le Bonheur Children's Hospital University of Tennessee Health Science CenterMemphisTennesseeUSA

Extracorporeal life support(ECLS)serves as a rescue therapy for patients with congenital diaphragmatic hernia(CDH)and severe cardiopulmonary failure,and only half of these patients survive to *** costly intervention has a significant complication risk and is reserved for patients with the most severe disease physiology refractory to maximal cardiopulmonary *** contraindications to ECLS do exist such as coagulopathy,lethal chromosomal or congenital anomaly,very preterm birth,or very low birth weight,but many of these limits are being evaluated through further *** guidelines from the past decade vary in recommendations for ECLS use in patients with CDH but this therapy appears to have a survival benefit in the most severe subset of *** outcomes have been observed for patients treated at high-volume *** review details the evolving literature surrounding management paradigms for timing of CDH repair for patients receiving preoperative *** recent data support early repair following cannulation to avoid non-repair which is uniformly fatal in this *** ECLS runs are associated with decreased survival,and patient physiology should guide ECLS weaning and eventual decannulation rather than limiting patients to arbitrary run *** of care across centers is a major focus to limit unnecessary costs and improve short-term and long-term outcomes for these complex patients.

关键词： congenital life repair

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Efficient scar-free knock-ins of several kilobases in plants by engineered CRISPR-Cas endonucleases

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Molecular Plant 2024年第5期17卷 824-837页

作者： Tom Schreiber anja Prange Petra Schafer Thomas Iwen Ramona Grutzner Sylvestre Marillonnet Aurelie Lepage Marie Javelle Wyatt Paul Alain Tissier Department of Cell and Metabolic Biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany Limagrain Centre de RechercheRoute d’EnnezatCS 9012663720 ChappesFrance

In plants and mammals,non-homologous end-joining is the dominant pathway to repair DNA doublestrand breaks,making it challenging to generate knock-in *** this study,we identified two groups of exonucleases from the herpes virus and the bacteriophage T7 families that conferred an up to 38-fold increase in homology-directed repair frequencies when fused to Cas9/Cas12a in a tobacco mosaic virus-based transient assay in Nicotiana *** achieved precise and scar-free insertion of several kilobases of DNA both in transient and stable transformation *** Arabidopsis thaliana,fusion of Cas9 to a herpes virus family exonuclease led to 10-fold higher frequencies of knock-ins in the first generation of *** addition,we demonstrated stable and heritable knock-ins in wheat in 1%of the primary *** together,our results open perspectives for the routine production of heritable knock-in and gene replacement events in plants.

关键词： homology-directed repair knockin gene replacement CRISPR-Cas 50 exonuclease plants

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Role of homologous recombination/recombineering on human adenovirus genome engineering:Not the only but the most competent solution

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Engineering Microbiology 2024年第1期4卷 90-107页

作者： Lisa-Marie Dawson Montaha Alshawabkeh Katrin Schröer Fatima Arakrak anja Ehrhardt Wenli Zhang Virology and Microbiology Center for Biomedical Education and Research(ZBAF)School of MedicineFaculty of HealthWitten/Herdecke UniversityStockumer Str.1058453 WittenGermany

Adenoviruses typically cause mild illnesses,but severe diseases may occur primarily in immunodeficient individuals,particularly ***,adenoviruses have garnered significant interest as a versatile tool in gene therapy,tumor treatment,and vaccine vector *** the past two decades,the advent of recombineering,a method based on homologous recombination,has notably enhanced the utility of adenoviral vectors in therapeutic *** review summarizes recent advancements in the use of human adenoviral vectors in medicine and discusses the pivotal role of recombineering in the development of these ***,it highlights the current achievements and potential future impact of therapeutic adenoviral vectors.

关键词： Adenoviral vector Gene therapy Homologous recombination Oncolytic virus Vaccine vector

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