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Alterations of Lymphoid Enhancer Factor-1 Isoform Expression in Solid Tumors and Acute Leukemias

Acta Biochimica et Biophysica Sinica 2005年第3期37卷 173-180页

作者： Wenbing WANG Ping JI Bjrn STEFFEN Ralf METZGER Paul M.SCHNEIDER Hartmut HALFTER Mark SCHRADER Wolfgang E.BERDEL Hubert SERVE Carsten MLLER-TIDOW Institute of Life Sciences,Jiangsu University,Zhenjiang 212013.China Hematology and Oncology.and Neurology,Department of Medicine,University of Mnster,D-48129 Mnster,Germany Dematology of Visceral and Vascular Surgery,University of Cologne,D-50931 Cologne,Germany Department of Urolooy,Free University Berlin,D-12200 Berlin. InstituteofLifeSciences JiangsuUniversityZhenjiang212013China

Two major transcripts of lymphoid enhancer factor-1(LEF-1)have been *** longisoform with β-catenin binding domain functions as a transcriptional enhancer *** short isoformderives from an intronic promoter and exhibits dominant negative ***,alterations of LEF-1isoforms distribution have been described in colon *** the current study we employed a quantitativereal-time reverse transcription PCR method(TaqMan)to analyze expression of LEF-1 isoforms in a largecohort of human tumor(n=304)and tumor-free control samples(n=56).The highest expression level ofLEF-1 was found in carcinoma samples whereas brain cancer samples expressed *** of LEF-1 was different in distinct cancer *** example,the mRNA level of LEF-1 was lower in testiculartumor samples compared with tumor-free control *** epithelial cancers,significant LEF-1expression was also found in hematopoietic *** hematological malignancies,overall LEF-1 level washigher in lymphocytic leukemias compared with myeloid leukemias and normal ***,acute myeloid leukemia and acute lymphocytic leukemia showed a significantly increased fraction of theoncogenic LEF-1 compared with chronic lymphocytic leukemia and chromc myeloid *** together,these data suggest that LEF-1 is abundantly expressed in human tumors and the ratio of the oncogenic andthe dominant negative short isoform altered not only in carcinomas but also in leukemia.

关键词： AML β-catenin isoform lymphoid enhancer factor(LEF-1) solid tumor

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Validation of Pore-Scale Simulations of Hydrodynamic Dispersion in Random Sphere Packings

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Communications in Computational Physics 2013年第3期13卷 801-822页

作者： Siarhei Khirevich Alexandra Holtzel Ulrich Tallarek Department of Chemistry Philipps-Universitat MarburgHans-Meerwein-Strasse35032 MarburgGermany

We employ the lattice Boltzmann method and random walk particle tracking to simulate the time evolution of hydrodynamic dispersion in bulk,random,monodisperse,hard-sphere packings with bed porosities(interparticle void volume fractions)between the random-close and the random-loose packing *** JodreyTory and Monte Carlo-based algorithms and a systematic variation of the packing protocols we generate a portfolio of packings,whose microstructures differ in their degree of heterogeneity(DoH).Because the DoH quantifies the heterogeneity of the void space distribution in a packing,the asymptotic longitudinal dispersion coefficient calculated for the packings increases with the packings’*** investigate the influence of packing length(up to 150 d_(p),where d_(p) is the sphere diameter)and grid resolution(up to 90 nodes per d_(p))on the simulated hydrodynamic dispersion coefficient,and demonstrate that the chosen packing dimensions of 10 d_(p)×10 d_(p)×70 d_(p) and the employed grid resolution of 60 nodes per d_(p) are sufficient to observe asymptotic behavior of the dispersion coefficient and to minimize finite size *** values of the dispersion coefficients calculated for the generated packings are compared with simulated as well as experimental data from the literature and yield good to excellent agreement.

关键词： Packing microstructure degree of heterogeneity packing algorithm hydrodynamic dispersion random sphere packings

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OsHYPK-mediated protein N-terminal acetylation coordinates plant development and abiotic stress responses in rice

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Molecular Plant 2022年第4期15卷 740-754页

作者： Xiaodi Gong Yaqian Huang Yan Liang Yundong Yuan Yuhao Liu Tongwen Han Shujia Li Hengbin Gao Bo Lv Xiahe Huang Eric Linster Yingchun Wang Markus Wirtz Yonghong Wang Institute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Crop Biology College of Life SciencesShandong Agriculture UniversityTaianShandong 271018China State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Centre for Organismal Studies Heidelberg University69120 HeidelbergGermany

N-terminal acetylation is one of the most common protein modifications in eukaryotes,and approximately 40%of human and plant proteomes are acetylated by ribosome-associated N-terminal acetyltransferase A(NatA)in a co-translational ***,the in vivo regulatory mechanism of NatA and the global impact of NatA-mediated N-terminal acetylation on protein fate remain ***,we identify Huntingtin Yeast partner K(HYPK),an evolutionarily conserved chaperone-like protein,as a positive regulator of NatA activity in *** found that loss of OsHYPK function leads to developmental defects in rice plant architecture but increased resistance to abiotic stresses,attributable to perturbation of the N-terminal acetylome and accelerated global protein ***,we demonstrated that OsHYPK is also a substrate of NatA and that N-terminal acetylation of OsHYPK promotes its own degradation,probably through the Ac/N-degron pathway,which could be induced by abiotic *** together,our findings suggest that the OsHYPK-NatA complex plays a critical role in coordinating plant development and stress responses by dynamically regulating NatA-mediated N-terminal acetylation and global protein turnover,which are essential for maintaining adaptive phenotypic plasticity in rice.

关键词： rice OsHYPK N-terminal acetylation protein turnover plant architecture stress response

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Dysregulated immunity in PID patients with low GARP expression on Tregs due to mutations in LRRC32

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Cellular & Molecular Immunology 2021年第7期18卷 1677-1691页

作者： Peter Lehmkuhl Magdalena Gentz Andres Caballero Garcia de Otezya Bodo Grimbacher Hendrik Schulze-Koops Alla Skapenko Division of Rheumatology and Clinical Immunology Department of Internal Medicine IVLudwig-Maximilians-University of MunichMunichGermany Institute for Immunodeficiency Centre of Chronic ImmunodeficiencyMedical CentreFaculty of MedicineAlbert-Ludwigs-University of FreiburgFreiburgGermany

Immune dysregulation diseases are characterized by heterogeneous clinical manifestations and may have severe disease *** identification of the genetic causes of these diseases therefore has critical clinical *** performed whole-exome sequencing of patients with immune dysregulation disorders and identified two patients with previously undescribed mutations in LRRC32,which encodes glycoprotein A repetitions predominant(GARP).These patients were characterized by markedly reduced numbers and frequencies of regulatory T cells(Tregs).Tregs with mutated LRRC32 exhibited strongly diminished cell-surface GARP expression and reduced suppressor *** a model of conditional Garp deficiency in mice,we confirmed increased susceptibility to inflammatory diseases once GARP expression on Tregs was *** deficiency led to an unstable Treg phenotype due to diminished Foxp3 protein acetylation and *** study reinforces the understanding of the immunological mechanisms of immune dysregulation and expands the knowledge on the immunological function of GARP as an important regulator of Treg stability.

关键词： T cells immune dysregulation autoimmunity

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Contact tracing-Old models and new challenges

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Infectious Disease Modelling 2021年第1期6卷 222-231页

作者： Johannes Müller Mirjam Kretzschmar Mathematical Institute Technical University of MunichBoltzmannstr.385748GarchingGermany Institute for Computational Biology Helmholtz Center Munich85764NeuherbergGermany Julius Center for Health Sciences and Primary Care University Medical Center UtrechtUtrecht UniversityHeidelberglaan 1003584CXUtrechtthe Netherlands

Contact tracing is an effective method to control emerging infectious *** the 1980’s,modellers are developing a consistent theory for contact tracing,with the aim to find effective and efficient implementations,and to assess the effects of contact tracing on the spread of an infectious *** the progress made in the area,there remain important open *** addition,technological developments,especially in the field of molecular biology(genetic sequencing of pathogens)and modern communication(digital contact tracing),have posed new challenges for the modelling *** the present paper,we discuss modelling approaches for contact tracing and identify some of the current challenges for the field.

关键词： Contact tracing Mathematical models

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Powering Axons: Novel Functions of Oligodendrocytes in Energy Metabolism

Powering Axons: Novel Functions of Oligodendrocytes in Energ...

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中国神经科学学会第十二届全国学术会议

作者： Klaus-Armin Nave Max Planck Institute of Experimental Medicine

Myelin is the multilayered membrane ensheathment of axons, made by oligodendrocytes and Schwann cells, which enables rapid saltatory impulse propagation. However, myelin also deprives the insulated axonal compartment from the outside milieu and thus from rapid access to essentual metabolites, such as glucose. Thus for fastspiking axons with elevated energy consumption the myelin architecture poses a potential metabolic problem. In different mouse mutants with oligodendrocyte defects, we found that oligodendrocytes are required for both myelination and the survival of axons. In fact, two cellular functions in myelination and in axon support can be genetically uncoupled in different mutant mice. Recently, we discovered an underlying mechanism, by which oligodendroytes provide lactate to the axonal compartment for the generation of ATP. Trying to understand how lactate supply is matched to the real axonal energy needs, which can differ widely, we noticed that activation of oligodendroglial NMDA receptors（as a proxy for axonal spiking activity） causes the rapid redistribution of the glucose transporter GLUT1 and enhanced glucose import. In mice lacking oligodendroglial NMDA receptors, functional GLUT1 expression in the myelin compartment is reduced, which perturbs axon conduction, most visibly under metabolic stress and at higher spiking frequency. Reduced axonal ATP levels can be measured real time when using transgenic mice with neuronally expressed metabolic sensors. Loss of metabolic support by oligodendrocytes is likely a contributing factor for a range of myelin diseases, and is also relevant for neurodegenerative diseases, since long axons are a bottle neck of neuronal integrity.

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Quantum expander for gravitational-wave observatories

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Light(Science & Applications) 2019年第1期8卷 62-69页

作者： Mikhail Korobko Yiqiu Ma Yanbei Chen Roman Schnabel Institut für Laserphysik und Zentrum fur Optische Quantentechnologien Universitat HamburgLuruper Chaussee 14922761 HamburgGermany Theoretical Astrophysics 350-17 California Institute of TechnologyPasadenaCA 91125USA

The quantum uncertainty of laser light limits the sensitivity of gravitational-wave *** the past 30 years,techniques for squeezing the quantum uncertainty,as well as for enhancing gravitational-wave signals with optical resonators have been ***,however,have finite linewidths,and the high signal frequencies that are produced during the highly scientifically interesting ring-down of astrophysical compact-binary mergers still cannot be ***,we propose a purely optical approach for expanding the detection *** uses quantum uncertainty squeezing inside one of the optical resonators,compensating for the finite resonators’linewidths while keeping the low-frequency sensitivity *** quantum expander is intended to enhance the sensitivity of future gravitational-wave detectors,and we suggest the use of this new tool in other cavity-enhanced metrological experiments.

关键词： wave quantum unchanged

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Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer

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Cellular & Molecular Immunology 2021年第2期18卷 427-439页

作者： Yan Xu Zheng Xiang Mohammed Alnaggar Léonce Kouakanou Jiawei Li Junyi He Jiashuang Yang Yi Hu Yan Chen Li Lin Jianlei Hao Jingxia Li Jibing Chen Man Li Qingling Wu Christian Peters Qinghua Zhou Jianshuang Li Yingqing Liang Xiaohua Wang Baohui Han Meili Ma Dieter Kabelitz Kecheng Xu Wenwei Tu Yangzhe Wu Zhinan Yin The First Affiliated Hospital Faculty of Medical ScienceJinan UniversityGuangzhou510632GuangdongPR China Zhuhai Precision Medical Center Zhuhai People’s Hospital(Zhuhai Hospital Affiliated with Jinan University)Jinan UniversityZhuhai519000GuangdongPR China The Biomedical Translational Research Institute Jinan UniversityGuangzhou510632GuangdongPR China Department of Paediatrics and Adolescent Medicine Li Ka Shing Faculty of MedicineUniversity of Hong KongHong KongPR China Institute of Immunology Christian-Albrechts-University KielKielGermany Fuda Cancer Hospital Faculty of Medical ScienceJinan UniversityGuangzhou510665GuangdongPR China Shanghai Chest Hospital Shanghai Jiao Tong UniversityShanghaiPR China Tongji Chibi Hospital Tongji Medical CollegeHuazhong University of Science and TechnologyChibiHubeiPR China

Vγ9Vδ2 T cells are promising candidates for cellular tumor *** to their HLA-independent mode of action,allogeneic Vγ9Vδ2 T cells can be considered for clinical *** apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy,the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized,and clinical safety and efficacy also need to be ***,we developed a novel formula to improve the expansion of peripheralγδT cells from healthy ***,we used a humanized mouse model to validate the therapeutic efficacy of expandedγδT cells in vivo;furthermore,the expandedγδT cells were adoptively transferred into late-stage liver and lung cancer *** found that the expanded cells possessed significantly improved immune effector functions,including proliferation,differentiation,and cancer cell killing,both in vitro and in the humanized mouse ***,a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic Vγ9Vδ2 T *** these 132 patients,8 liver cancer patients and 10 lung cancer patients who received≥5 cell infusions showed greatly prolonged survival,which preliminarily verified the efficacy of allogeneic Vγ9Vδ2 T-cell *** clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy,which will inspire further clinical investigations and eventually benefit cancer patients.

关键词： Cancer immunotherapy Immunotherapy Translational immunology

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TRIM22 Inhibits the TRAF6-stimulated NF-κB Pathway by Targeting TAB2 for Degradation

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Virologica Sinica 2013年第4期28卷 209-215页

作者： Hui Qiu Fang Huang Han Xiao Binlian Sun Rongge Yang Research Group of HIV Molecular Epidemiology and Virology Center for Emerging Infectious Diseases The State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences

Tripartite motif containing 22 （TRIM22）, a member of the TRIM/RBCC family, has been reported to activate the nuclear factor-kappa B （NF-kB） pathway in unstimulated macrophage cell lines, but the detailed mechanisms governing this activation remains unclear. We investigated this mechanism in HEK293T cells. We found that overexpression of TRIM22 could activate the NF-kB pathway and conversely, could inhibit the tumor necrosis factor receptor-associated factor 6 （TRAF6）-stimulated NF-kB pathway in HEK293T cells. Further experiments showed that TRIM22 could decrease the self-ubiquitination of TRAF6, and interact with and degrade transforming growth factor-13 activated kinase 1 binding protein 2 （TAB2）, and that these effects could be partially rescued by a TRIM22 RING domain deletion mutant. Collectively, our data indicate that overexpression of TRIM22 may negatively regulate the TRAF6-stimulated NF-rd3 pathway by interacting with and degrading TAB2.

关键词： TRIM22 NF-kB pathway TRAF6 TAB2

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MicroProteins:Expanding functions and novel modes of regulation

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Molecular Plant 2021年第5期14卷 705-707页

作者： Kaushal Kumar Bhati Ulla Dolde Stephan Wenkel Louvain Institute of Biomolecular Sciences Catholic University of LouvainLouvain la Neuve 1348Belgium Plant Science Research Laboratory(LRSV) UMR5546 CNRS/Universite Toulouse 331320 Castanet-TolosanFrance Copenhagen Plant Science Centre Department of Plant&Environmental SciencesUniversity of CopenhagenThorvaldsensvej 401871 Frederiksberg CDenmark

MicroProteins are small,5-15-kDa single-domain proteins that are evolutionarily related to multi-domain proteins with sequence homology(Eguen et al.,2015).The single domain of microProteins is often a protein-protein interaction(PPI)-domain,through which they can interact with their multi-domain protein targets(Figure 1).The first experimental insight that microProteins exist and how they act came from the identification of the regulatory feedback mechanism of class III homeodomain-leucine zipper(HD-ZIPIII)transcription factors by LITTLE ZIPPER(ZPR)microProteins(Wenkel et al.,2007;Kim et al.,2008).In Arabidopsis,the LITTLE ZIPPER microProtein family consists of four members(ZPR1-4)containing only a leucine zipper *** HD-ZIPIII transcription factor REVOLUTA directly transcriptionally upregu-lates multiple ZPR *** proteins physically interact with their HD-ZIPIII targets and suppress their DNA binding ability.

关键词： domain. Figure insight

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