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Antidiabetic profiling of veramycins,polyketides accessible by biosynthesis,chemical synthesis and precursor-directed modification

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Organic Chemistry Frontiers 2022年第6期9卷 1604-1615页

作者： Denis Dardić Nils böhringer Alberto Plaza Florian Zubeil Juliane Pohl Svenja Sommer Leo Padva Jonathan becker Maria A.Patras Mona-Katharina bill Michael Kurz Luigi Toti Sven W.Görgens Sören M.M.Schuler Andrébillion Oliver Schwengers Paulus Wohlfart Alexander Goesmann Norbert Tennagels Andreas Vilcinskas Peter E.Hammann Till F.Schäberle Armin bauer Fraunhofer Institute for Molecular biology and Applied Ecology(IME) Branch for Bioresources35392 GießenGermany Justus-Liebig-University Gießen 35392 GießenGermany Sanofi-Aventis Deutschland GmbH R&D Integrated Drug Discovery65926 Frankfurt am MainGermany Sanofi-Aventis Deutschland GmbH R&D German Hub65926 Frankfurt am MainGermany German Center of Infection Research(DZIF) Partner Site Gießen-Marburg-Langen35392 GießenGermany

Seven new polyketides,termed veramycins,were isolated from a Streptomyces *** the Sanofi microbial strain collection along with their known congeners NFAT-133 and *** A,anα-pyrone congener of TM-123 and NFAT-133 showed an increased baseline deoxy-glucose uptake in the absence of insulin in a modified L6 rat skeletal muscle cell line(L6 GLUT4 AS160-like cells).In addition,both compounds slightly increased the sensitivity to insulin in this cell *** syntheses of NFAT-133,TM-123 and veramycin A were accomplished starting from a central building block,which bears the three contiguous stereogenic centers of this polyketide *** approach enables an efficient,selective and flexible access to all possible isomers of the stereotriad for further exploration of this series as a potential anti-diabetic lead structure as exemplified by the synthesis of an NFAT-133 ***,the corresponding biosynthetic gene cluster(bGC)was identified by genome sequencing and gene *** on feeding experiments,a biosynthetic pathway was proposed,which enabled access to new veramycin A analogs by precursor-directed biosynthesis.

关键词： synthesis directed isomers

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应用交替球管方位的快速双源CT行动态心肌应力灌注成像的初期研究

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国际医学放射学杂志 2010年第4期 396-397页

作者： F.bamberg E.Klotz T.Flohr A.becker C.R.becker b.Schmidt 赵芳 Department of Clinical Radiology University of Munich Grosshadern CampusMarchioninistrasse 1581377 MunichGermany

目的详述CT定量模型基础上局部心肌血流量(MbF)的原理,并示范其在活体上的应用。方法双源CT扫描采用动态扫描方案,包括每30s于心电图触发收缩末期交替球管方位获

关键词：双源球管灌注成像心肌 CT

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腹腔镜下先天性胆总管囊肿切除、肝管-空肠吻合术以及腹腔外罗克逊-“Y”形吻合术

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世界核心医学期刊文摘（儿科学分册） 2006年第2期2卷 39-40页

作者： Ure b.M. Nustede R. becker H. 李丹 Department of Pediatric Surgery University Medical School 30625 Hannover Germany

The authors present a 3-month-old patient with a congenital choledochal cyst, which was asymptomatic until treatment. On laparoscopy, a type I choledochal cyst was confirmed and excised laparoscopically. A Roux-en-Y anastomosis was constructed after exteriorization of the small bowel via the infraumbilical trocar incision. A laparoscopic end-to-side hepaticojejunostomy was carried out. The operation lasted 41/2 hours, without intraoperative problems. Oral food intake was started on day 2 and well tolerated with bile stained stools. Symptoms of bowel obstruction occurred on day 8. On minilaparotomy, the Roux-en-Y anastomosis was found to be adherent to the mesenterium of the colon, leading to obstruction. After mobilizing the loop, the postoperative course was uneventful. We conclude that laparoscopic resection of congenital choledochal cyst and choledochojejunostomy was feasible in the youngest patient operated on so far. However, adhesive small bowel obstruction can also occur, as after conventional operation, when the bowel is exteriorized for Roux-en-Y hepaticojejunostomy.

关键词： Ⅰ型先天性胆总管囊肿胆总管空肠吻合术胆总管囊肿切除术腹腔镜下肝管粘连性小肠梗阻肠梗阻症状腹腔镜检查端侧吻合术经口进食

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极简

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2016年

作者： (美)乔舒亚·贝克尔(Joshua becker)

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The right inferior frontal gyrus as pivotal node and effective regulator of the basal ganglia-thalamocortical response inhibition circuit

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Psychoradiology 2023年第1期3卷 242-253页

作者： Qian Zhuang Lei Qiao Lei Xu Shuxia Yao Shuaiyu Chen Xiaoxiao Zheng Jialin Li Meina Fu Keshuang Li Deniz Vatansever Stefania Ferraro Keith M.Kendrick benjamin becker The Center of Psychosomatia Medicine Sichuan Provincial Center for Mental HealthSichuan Provincial People's HospitalThe University of Eectronic Science and Technology of ChinaChengduSichuan Province 611731China Center for Cognition and brain Disorders The Affliated Hospital of Hangzhou Normal UniversityHangzhouZhejiang Province 11121 China School of Psychology Shenzhen UniversityShenzhen 518060China Institute of brain and Psychological Sciences Sichuan Normal UniversityChengdu610068China brain Cognition and brain Disease Institute(bCbDI) Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China School of Psychology and Cognitive Science East China Normal UniversityShanghai 200062China Institute of Science and Technology for brain-Inspired Itelligence Fudan UniversityShanghai 200433China State Key Laboratory of brain and Cognitive Sciences The University of Hong KongHong Kong 99077 China Department of Psychology The University of Hong Kong Hong Kong 990777 China

background:The involvement of specific basal ganglia-thalamocortical circuits in response inhibition has been extensively mapped in animal ***,the pivotal nodes and directed causal regulation within this inhibitory circuit in humans remains ***:The main aim of the present study was to determine the causal information flow and critical nodes in the basal ganglia-thalamocortical inhibitory circuits and also to examine whether these are modulated by biological factors(***)and behavioral ***:Here,we capitalize on the recent progress in robust and biologically plausible directed causal modeling(DCM-PEb)and a large response inhibition dataset(n=250)acquired with concomitant functional magnetic resonance imaging to determine key nodes,their causal regulation and modulation via biological variables(sex)and inhibitory performance in the inhibitory circuit encompassing the right inferior frontal gyrus(rIFG),caudate nucleus(rCau),globus pallidum(rGP),and thalamus(rThal).Results:The entire neural circuit exhibited high intrinsic connectivity and response inhibition critically increased causal projections from the rIFG to both rCau and *** comparison further demonstrated that response inhibition induced an increasing rIFG inflow and increased the causal regulation of this region over the rCau and *** addition,sex and performance influenced the functional architecture of the regulatory circuits such that women displayed increased rThal self-inhibition and decreased rThal to GP modulation,while better inhibitory performance was associated with stronger rThal to rIFG ***,control analyses did not reveal a similar key communication in a left lateralized ***:Together,these findings indicate a pivotal role of the rIFG as input and causal regulator of subcortical response inhibition nodes.

关键词： response inhibition basal ganglia inferior frontal gyrus effective connectivity DCM

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A MoClo-Compatible Toolbox of ECF Sigma Factor-based Regulatory Switches for Proteobacterial Chassis

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bioDesign Research 2024年第1期6卷 1-19页

作者： Doreen Meier Christian Rauch Marcel Wagner Paul Klemm Patrick blumenkamp Raphael Müller Eric Ellenberger Kinnari M.Karia Stefano Vecchione Javier Serrania Marcus Lechner Georg Fritz Alexander Goesmann Anke becker Center for Synthetic Microbiology(SYNMIKRO)and Department of biology Philipps-Universität MarburgMarburgGermany bioinformatics and Systems biology Justus-Liebig-Universität GiessenGiessenGermany The University of Western Australia School of Molecular SciencesPerthAustralia

The construction of complex synthetic gene circuits with predetermined and reliable output depends on orthogonal regulatory parts that do not inadvertently interfere with the host machinery or with other circuit ***,extracytoplasmic function sigma factors(ECFs),a diverse group of alternative sigma factors with distinct promoter specificities,were shown to have great potential as context-independent regulators,but so far,they have only been used in a few model ***,we show that the alphaproteobacterium Sinorhizobium meliloti,which has been proposed as a plant-associated bacterial chassis for synthetic biology,has a similar phylogenetic ECF acceptance range as the gammaproteobacterium Escherichia coli.A common set of orthogonal ECF-based regulators that can be used in both bacterial hosts was identified and used to create 2-step delay *** genetic circuits were implemented in single copy in *** by chromosomal integration using an established method that utilizes bacteriophage *** ***,we demonstrated the usability of single-copy pAbC plasmids as equivalent carriers of the synthetic *** circuits were either implemented on a single pAbC or modularly distributed on 3 such *** addition,we provide a toolbox containing pAbC plasmids compatible with the Golden Gate(MoClo)cloning standard and a library of basic parts that enable the construction of ECF-based circuits in *** and in *** work contributes to building a context-independent and species-overarching ECF-based toolbox for synthetic biology applications.

关键词： toolbox sigma chassis compatible factor-based moclo proteobacterial regulatory switches

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Ephrin-b2 is differentially expressed in the intestinal epithelium in Crohn's disease and contributes to accelerated epithelial wound healing in vitro

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World Journal of Gastroenterology 2005年第26期11卷 4024-4031页

作者： Christian Hafner Stefanie Meyer Thomas Langmann Gerd Schmitz Frauke bataille Ilja Hagen bernd becker Alexander Roesch Gerhard Rogler Michael Landthaler Thomas Vogt Department of Dermatology University Hospital of Regensburg D-93042 Regensburg Germany Department of Clinical Chemistry University Hospital of Regensburg D-93042 Regensburg Germany Institute of Pathology University Hospital of Regensburg D-93042 Regensburg Germany Department of Internal Medicine University Hospital of Regensburg D-93042 Regensburg Germany

AIM:Eph receptor tyrosine kinases and their membrane bound receptor-like ligands, the ephrins, represent a bi-directional cell-cell contact signaling system that directs epithelial movements in development. The meaning of this system in the adult human gut is unknown. We investigated the Eph/ephrin mRNA expression in the intestinal epithelium of healthy controls and patients with inflammatory bowel disease (IbD). METHODS: mRNA expression profiles of all Eph/ephrin family members in normal small intestine and colon were established by real-time RT-PCR. In addition, differential expression in IbD was investigated by cDNA array technology, and validated by both real-time RT-PCR and immunohistochemistry. Potential effects of enhanced Ephb/ephrin-b signaling were analyzed in an in vitro IEC-6 cell scratch wound model. RESULTS: Human adult intestinal mucosa exhibits a complex pattern of Eph receptors and ephrins. beside the known prominent co-expression of EphA2 and ephrinAl, we found abundantly co-expressed Ephb2 and ephrin-b1/2. Interestingly, cDNA array data, validated by real-time PCR and immunohistochemistry, showed upregulation of ephrin-b2 in both perilesional and lesional intestinal epithelial cells of IbD patients, suggesting a role in epithelial homeostasis. Stimulation of ephrin-b signaling in ephrin- b1/2 expressing rat IEC-6-cells with recombinant Ephb1-Fc resulted in a significant dose-dependent acceleration of wound closure. Furthermore, fluorescence microscopy showed that Ephb1-Fc induced coordinated migration of wound edge cells is associated with enhanced formation of lamellipodial protrusions into the wound, increased actin stress fiber assembly and production of laminin at the wound edge. CONCLUSION: Ephb/ephrin-b signaling might represent a novel protective mechanism that promotes intestinal epithelial wound healing, with potential impact on epithelial restitution in IbD.

关键词： Ephrin-b2 Crohn's disease IbD IEC-6 Wound healing Epithelial restitution

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白蚁的室内饲养和室内试验方法

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白蚁科技 1992年第1期9卷 23-33页

作者： Günther becker 宋晓钢

Ⅰ.白蚁的饲养、繁殖和试验的一般先决条件 A.生物学和繁殖 b.食物 C.通风、湿度和温度 D.有毒因子、病毒、寄生菌和天敌 E.容器、防止逃跑和观察 F.采集和搬运Ⅱ.饲养和繁殖 A.成虫和早期群体的饲养 b.木白蚁科的白蚁群体(干木白蚁) C... 详细信息

Ⅰ.白蚁的饲养、繁殖和试验的一般先决条件 A.生物学和繁殖 b.食物 C.通风、湿度和温度 D.有毒因子、病毒、寄生菌和天敌 E.容器、防止逃跑和观察 F.采集和搬运Ⅱ.饲养和繁殖 A.成虫和早期群体的饲养 b.木白蚁科的白蚁群体(干木白蚁) C.原白蚁科的白蚁群体(湿木白蚁) D.鼻白蚁科的白蚁群体(土木两栖性白蚁) E.白蚁科的白蚁群体(营巢性白蚁) Ⅲ.

关键词：白蚁室内饲养室内试验生物学

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The world of the cell / 6th ed.

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2006年

作者： becker Wayne M.Kleinsmith Lewis J. Hardin Jeff.

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抗病毒药物作用方式和人类病毒感染的化学治疗

抗病毒药物作用方式和人类病毒感染的化学治疗

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1980年

作者：陈鸿珊等译

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