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B cell development is critically dependent on NFATc1 activity

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Cellular & Molecular Immunology 2019年第5期16卷 508-520页

作者： Sabrina Giampaolo Gabriela Wojcik stefan klein-Hessling Edgar Serfling Amiya K.Patra Department of Molecular Pathology Institute of PathologyUniversity of WürzburgJosef Schneider-Str.297080 WürzburgGermany Institute of Translational and Stratified Medicine Faculty of Medicine and DentistryUniversity of PlymouthPlymouth PL68BUUK Comprehensive Cancer Center Mainfranken University of WürzburgJosef Schneider-Str.697080 WürzburgGermany

B cell development in bone marrow is a precisely regulated complex process.Through successive stages of differentiation,which are regulated by a multitude of signaling pathways and an array of lineage-specific transcription factors,the common lymphoid progenitors ultimately give rise to mature B cells.Similar to early thymocyte development in the thymus,early B cell development in bone marrow is critically dependent on IL-7 signaling.During this IL-7-dependent stage of differentiation,several transcription factors,such as E2A,EBF1,and Pax5,among others,play indispensable roles in B lineage specification and maintenance.Although recent studies have implicated several other transcription factors in B cell development,the role of NFATc1 in early B cell developmental stages is not known.Here,using multiple gene-manipulated mouse models and applying various experimental methods,we show that NFATc1 activity is vital for early B cell differentiation.Lack of NFATc1 activity in pro-B cells suppresses EBF1 expression,impairs immunoglobulin gene rearrangement,and thereby preBCR formation,resulting in defective B cell development.Overall,deficiency in NFATc1 activity arrested the pro-B cell transition to the pre-B cell stage,leading to severe B cell lymphopenia.Our findings suggest that,along with other transcription factors,NFATc1 is a critical component of the signaling mechanism that facilitates early B cell differentiation.

关键词： Differentiation EBF1 NFATc1 Pro-B Pre-B

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诗意的宇宙

Grb-2-associated binder 1(Gab1) regulates postnatal ischemic and VEGF-induced angiogenesis through the protein kinase A-endothelial NOS pathway

作者： (奥)斯特凡·克莱因(stefan klein)

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Grb-2-associated binder 1(Gab1) regulates postnatal ischemic...

Gabl regulates postnatal ischemic and VEGF-induced angiogenesis via activation of the PKA-eNOS pathway

“细胞活动生命活力”——中国细胞生物学学会全体会员代...

作者： stefan klein-Heβling Masabumi Shibuya Department of Molecular Pathology Institute of PathologyUniversity of WiirzburgD-97080 WiirzburgGermany Department of Molecular Oncology Tokyo Medical and Dental UniversityTokyo 113-8510Japan

The intracellular signaling mechanisms underlying postnatal angiogenesis are incompletely understood. Herein we show that Grb-2-associated binder 1(Gab1) plays a critical role in ischemic and VEGF-induced angiogenesis.Endothelium-specific Gab1 KO(EGKO) mice displayed impaired angiogenesis in the ischemic hindlimb despite normal induction of VEGF expression.Matrigel plugs with VEGF implanted in EGKO mice induced fewer capillaries than those in control mice.The vessels and endothelial cells(ECs) derived from EGKO mice were defective in vascular sprouting and tube formation induced by VEGF. Biochemical analyses revealed a substantial reduction of endothelial NOS(eNOS) activation in Gab1-deficient vessels and ECs following VEGF stimulation.Interestingly,the phosphorylation of Akt,an enzyme known to promote VEGF-induced eNOS activation,was increased in Gab1-deficient vessels and ECs whereas protein kinase A(PKA) activity was significantly decreased.Introduction of an active form of PKA rescued VEGF-induced eNOS activation and tube formation in EGKO ECs.Reexpression of WT or mutant Gab1 molecules in EGKO ECs revealed requirement of Gab1/Shp2 association for the activation of PKA and eNOS.Taken together,these results identify Gab1 as a critical upstream signaling component in VEGF-induced eNOS activation and tube formation,which is dependent on PKA.Of note,this pathway is conserved in primary human ECs for VEGFinduced eNOS activation and tube formation,suggesting considerable potential in treatment of human ischemic diseases.

关键词： Gabl protein complex collateralization Tie2-Cre PKA substrate

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Gabl regulates postnatal ischemic and VEGF-induced angiogene...

Heterosis in plants:Manifestation in early seed development and prediction approaches to assist hybrid breeding

“细胞活动生命活力”——中国细胞生物学学会全体会员代...

作者：路瑶熊彦霍迎庆韩晶岩杨晓张荣利朱德生 stefan klein-Heβling 李军张小玉韩晓帆李艳丽沈兵何玉龙 Masabumi Shibuya 冯更生罗金才北京大学分子医学研究所血管生物学研究室北京大学天士力微循环中心解放军军事医学科学院

The intracellular signaling mechanisms underlying postnatal angiogenesis are incompletely understood.Herein we show that Grb-2-associated binder 1(Gab1) plays a critical role in ischemic and VEGF-induced angiogenesis.Endothelium-specific Gab1 knockout(EGKO) mice displayed impaired angiogenesis in the ischemic hindlimb despite normal induction of VEGF expression.Matrigel plugs with VEGF implanted in EGKO mice induced fewer capillaries than those in control mice.The vessels and endothelial cells(ECs) derived from EGKO mice were defective in vascular sprouting and tube formation induced by VEGF.Biochemical analyses revealed a substantial reduction of eNOS activation in Gab1-deficient vessels and ECs following VEGF stimulation.Interestingly,the phosphorylation of Akt,an enzyme known to promote VEGF-induced eNOS activation,was increased in Gab1-deficient vessels and ECs whereas PKA activity was significantly decreased.Introduction of an active form of PKA rescued VEGF-induced eNOS activation and tube formation in EGKO ECs.Re-expression of wild type or mutant Gab1 molecules in EGKO ECs revealed requirement of Gab1/Shp2 association for the activation of PKA and eNOS.Taken together,these results identify Gab1 as a critical upstream signaling component in VEGF-induced eNOS activation and tube formation,which is dependent on PKA.Of note,this pathway is conserved in primary human ECs for VEGF-induced eNOS activation and tube formation,suggesting considerable potential in treatment of human ischemic diseases.

关键词： VEGF Gab1

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Chinese Science Bulletin 2009年第14期54卷 2363-2375页

作者： THIEMANN Alexander MEYER Stephanie SCHOLTEN stefan Developmental Biology and Biotechnology Biocenter Klein FlottbekUniversity HamburgOhnhorststraβe 1822609 HamburgGermany Developmental Biology and Biotechnology Biocenter Klein FlottbekUniversity HamburgOhnhorststraβe 18 22609 HamburgGermany

Heterosis, or hybrid vigour, describes the superior performance of heterozygous hybrid individuals compared with their homozygous parental inbred lines. Although heterosis has been intensively used in plant breeding, the molecular and genetic mechanism underlying the phenomenon remains largely unknown. During the last years numerous laboratories initiated genomic approaches with new, often genome wide tools toward the elucidation of the molecular basis of heterosis. Various studies described differences in genome organization and gene expression of hybrids and their parental inbred lines. In maize, a considerable loss of co-linearity at many loci between different inbred lines was observed. Expression profile comparisons between inbred lines and hybrids revealed complex transcriptional networks specific for different developmental stages and tissues mainly in maize (Zea mays), rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana). Allele-specific expression data resolved the relative parental contributions and allowed figuring out the regulatory basis for expression variation in hybrids. Integrating all these complex expression data might help to get an idea about the molecular basis of heterosis. Thereby molecular processes during early seed development shortly after fertilization might be of particular importance, because the allelic interplay has to be coordinated after the unification of two diverse genomes and these processes might contribute to establish the basis for future performance of the sporophyte. Besides these fundamental interests in the molecular basis and manifestation of hybrid vigour applied aspects of the phenomenon are of high importance to support plant breeding and agriculture. Prediction methods are of special interest to identify the most promising parental lines of hybrid varieties, greatly reducing the financial effort and increasing the efficiency to develop new hybrid cultivars. Until now, most prediction approaches were based on genomic markers. The available heterosis associat

关键词：植物育种方法水稻基因表达

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用于燃油位置传感器的厚膜浆料(英文)

电子工业专用设备 2007年第3期36卷 53-60页

作者： stefan Flick Roland Kersting 罗庆生 Randy klein 贺利氏上海工业技术材料有限公司

现今的燃油传感器要求在汽车汽油箱的苛刻的化学环境里有低的电子噪声,长的耐磨寿命和高的信号传递。虽然燃油传感器基板的设计师通过结构设计和选择触点、电刷的安装等能够较大的提高性能,但厚膜导体必须符合相关要求。导体浆料是贵重... 详细信息

现今的燃油传感器要求在汽车汽油箱的苛刻的化学环境里有低的电子噪声,长的耐磨寿命和高的信号传递。虽然燃油传感器基板的设计师通过结构设计和选择触点、电刷的安装等能够较大的提高性能,但厚膜导体必须符合相关要求。导体浆料是贵重金属粉末混合物(例如Ag,Pd,Au,Pt和它们的合金、以及玻璃或氧化物粉末)悬浮于有机载体中而形成的。这些燃油传感器基板必须在包含水、酒精、有机酸、硫化合物、氟素的燃油中工作,要满足抗银离子迁移、抗化学腐蚀和耐磨性这些重要的特性。论述了一种应用于燃油传感器厚膜电路需求的导体浆料,以及工艺、机械和化学上的要求。并给出了详细的耐磨性、耐硫化及抗化学腐蚀的讨论,讨论了金属合金在导体中的作用,并用微结构分析和化学分析来评估材料。

关键词：厚膜燃油传感器耐磨性抗化学腐蚀

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多巴酚丁胺磁共振负荷实验与多巴酚丁胺超声心动图负荷实验诊断心肌缺血的比较

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岭南心血管病杂志 2000年第4期6卷 277-278页

作者：黄虔 Hans B. Lehmkuhl Wolfgang Bocksch Christoph klein Eckart Franz Axel Ellmer stefan Dreysse Eike Nagel 暨南大学医学院第一附属医院心内科广州510632 Department of Internal Medicine/Cardiology German Heart Institute and Charite Campus Virchow Humboldt University Berlin Germany

目的用多巴酚丁胺超声心动图负荷实验(DSE)分析室壁运动异常已是临床广泛采用的诊断心肌缺血的手段.本研究将用在超声心动图的多巴酚丁胺负荷实验方法与超高速磁共振成像结合起来,比较它和DSE对心肌缺血的诊断价值,探索冠心病无创伤性... 详细信息

目的用多巴酚丁胺超声心动图负荷实验(DSE)分析室壁运动异常已是临床广泛采用的诊断心肌缺血的手段.本研究将用在超声心动图的多巴酚丁胺负荷实验方法与超高速磁共振成像结合起来,比较它和DSE对心肌缺血的诊断价值,探索冠心病无创伤性诊断的新方法.

关键词：丁胺 1—氨基丁烷伯胺实验诊断心肌缺血磁共振多巴苯丙氨酸超声心动图超声波诊断

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Assessment of regional ventilation distribution:Comparison of vibration response imaging with electrical impedance tomography

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Assessment of regional ventilation distribution:Comparison o...

中国毒理学会第六届全国毒理学大会

作者： SHI Chang stefan BOEHME Alexander H BENTLEY Erik K HARTMANN Klaus U klein Marc BODENSTEIN Roman ULLRICH Klaus MARKSTALLER Department of Anaesthesiology Medical Centre of the Johannes Gutenberg-University Mainz National Beijing Center for Drug Safety Evaluation and Research Beijing Institute of Pharmacology and Toxicology

＜正＞OBJECTIVE Vibration response imaging（VRI） is a new bedside technology to monitor ventilation by detecting lung sound vibrations.It is currently unknown whether VRI is able to accurately monitor the local distribution of ventilation within the lungs.We therefore compared VRI to electrical impedance tomography（EIT）,an established technique used for the assessment of regional ventilation. METHODS For peer review,simultaneous EIT and VRI measurements were performed in the healthy and injured lungs（ALI;induced by saline lavage） at different PEEP levels（0,5,10,15 mbar） in nine piglets.Vibration energy amplitude（VEA） by VRI,and amplitudes of relative impedance changes（rel. AZ） by EIT,were evaluated in seven regions of interest（ROIs）.To assess the distribution of VT by VRI and EIT,absolute values were normalized to the VT obtained by simultaneous spirometry measurements. RESULTS Redistribution of ventilation by ALI and PEEP was detected by VRI and EIT.The linear correlation between pooled VT by VEA and rel.AZ was R =0.96.Bland-Altman analysis showed a bias of -1.07±24.71 ml and limits of agreement of -49.05 to +47.36 ml.Within the different ROIs, correlations of VT - distribution by EIT and VRI ranged between R values ofO.29 and 0.96.ALI and PEEP did not alter the agreement of VT between VRI and EIT.CONCLUSION Measurements of regional ventilation distribution by VRI are similar to those obtained by EIT.

关键词： electrical impedance lung injury ventilation vibration imaging

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宝马世界

城市环境设计 2020年第4期126卷 134-149页

作者：沃尔夫·狄·普瑞克斯 Paul Kath Tom Wiscombe Waltraut Hoheneder Mona Marbach Hans Aescht Beatrix Basting Guy Bebiè Chris Beccone Johannes Behrens Marcelo Bernardi Pawel Bodzak Verena Boyer Antja Bulthaup Claudia Buhmann Timo Carl Jan Chaldil Ing Tse Chen Tadeusz Chimiak Andrea Christmann Patrick Erhardt Stephan Exsternbrink Wolfgang Fiel Benedikt Frass Helmut Fr?tscher Volker Gessendorfer Andrea Graser Lukas Haller Markus Henning Armin Hess Jens Hoff Tamas Horvath Robert Huebser Astrid Jagersberger Marin Jurycz Gregor Kassl Areta Keller Markus Klausecker Tobias klein Martin Konrad Quirin Krumbholz Caroline Kufferath Marion Lattenmayer stefan Laub Wolfgang Leitgeb Andreas Mieling Karin Miesenberger Dennis Milam Elke Müller Henrike Münker Claudia Nehammer Martin Oberascher Alexander Ott stefan Pfefferle Florian Pfeifer Markus Pillhofer Ekkehard Rehfeld Goswin Rothenthal Wolfgang Ruthensteiner Jasmin Sauerbier Florian Schafschetzy Kristina Schinegger Karolin Schmidbaur Patrick Schneider Katharina Schneider Hubert Schoba Angus Schoenberger Andrea Sch?ning Anja Sorger Gernot Stangl Mark Steinmetz Sigrid Steinwender Martina Tippelskirch Dionicio Valdez Pascal Vauclair Akvile Rimantaite Andreas Weissenbach Heribert Wolfmayer Irina Zahler 2007 Ari Marcopoulos Gerald Zugmann Hélène Binet Duccio Malagamba Marcus Buck Christian Richters Richard Walch

项目大事记/CHRONOLOGY竞赛（一等奖）/Competition（1st Prize）:2001规划设计起始时间/Start of Planning:11/2001施工起始时间/Start of Construction:08/2003投入使用/Opening:20/10/2007-21/10/2007项目参数/PROJECT DATA用地面积/Site Area:约25 000m2/Approx. 25 000m2建筑毛面积/Gross Floor Area:约73 000m2（除坡道）=100%/Approx.73 000m2（excluding ramps）=100%地上建筑毛面积/Gross Floor Area above ground:约28 500m2=40%/Approx.28 500m2=40%地下建筑毛面积/Gross Floor Area underground:约44 500m2=60%/Approx.44 500m2=60%

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