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Dysfunction of the adhesion G protein-coupled receptor latrophilin 1(ADGRL1/LPHN1)increases the risk of obesity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2298-2311页

作者： Heba ZabriTorsten Schöneberg AndréNguyen Dietzsch Hadi Al-Hasani Joachim Altschmied Katharina Bottermann Jana Brendler Judith Haendeler Susanne Horn isabell Kaczmarek Antje Körner Kerstin Krause Kathrin Landgraf Diana Le Duc Laura Lehmann Stefan Lehr Stephanie Pick Albert Ricken Rene Schnorr Angela schulz Martina Strnadová Akhil Velluva Heba Zabri Torsten Schöneberg Doreen Thor Simone Prömel Rudolf Schönheimer Institute of Biochemistry Medical FacultyLeipzig UniversityLeipzigGermany Institute for Clinical Biochemistry and Pathobiochemistry Medical FacultyGerman Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University DüsseldorfDüsseldorfGermany German Center for Diabetes Research(DZD e.V.) Munich-NeuherbergGermany Cardiovascular Degeneration Clinical Chemistry and Laboratory DiagnosticsMedical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Cardiovascular Research Institute(CARID) Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Pharmacology Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Anatomy Medical FacultyLeipzig UniversityLeipzigGermany Center for Pediatric Research Hospital for Children and AdolescentsMedical FacultyLeipzig UniversityLeipzigGermany Helmholtz Institute for Metabolic Obesity and Vascular Research(HI-MAG)of the Helmholtz Zentrum München at the University of Leipzig and University Hospital LeipzigLeipzigGermany Department of Endocrinology NephrologyRheumatologyLeipzig University Medical CenterLeipzigGermany Institute of Human Genetics Leipzig University Medical CenterLeipzigGermany Institute of Cell Biology Department of BiologyHeinrich Heine University DüsseldorfDüsseldorfGermany School of Medicine University of Global Health EquityKigaliRwanda

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide *** the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity.G protein-coupled receptors(GPCRs)are among the main modulators of metabolism and energy ***,for instance,regulate appetite and satiety in certain hypothalamic neurons,as well as glucose and lipid metabolism and hormone secretion from *** in some GPCRs,such as the melanocortin receptor type 4(MC4R),have been associated with early-onset ***,we identified the adhesion GPCR latrophilin 1(ADGRL1/LPHN1)as a member of the regulating network governing food intake and the maintenance of energy *** of the highly conserved receptor in mice results in increased food consumption and severe obesity,accompanied by dysregulation of glucose ***,we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from ***,we propose that LPHN1 dysfunction is a risk factor for obesity development.

关键词： obesity metabolism intake

Embolic stroke of undetermined source:identification of patient subgroups for oral anticoagulation treatment

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Neural Regeneration Research 2022年第5期17卷 1005-1006页

作者： isabell Greeve Wolf-Rüdiger Schäbitz Department of Neurology Evangelisches Klinikum BethelUniversity of BielefeldCampus BethelBielefeldGermany

Background:Embolic stroke of undetermined source(ESUS),a subtype of cryptogenic stroke,was defined as acute ischemic stroke displaying an embolic or non-lacunar brain infarct pattern on imaging without significant extra or intracranial ipsilateral vessel stenosis or without an identifiable cardioembolic source such as atrial fibrillation(AF)or left ventricular thrombi(Hart et al.,2014).

关键词： al. acute stenosis

Mixed reproduction strategy and polyploidy facilitate dominance of Kobresia pygmaea on the Tibetan Plateau

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Journal of Plant Ecology 2016年第1期9卷 87-99页

作者： Elke Seeber Georg Miehe isabell Hensen Yongping Yang Botany Department Senckenberg Museum of Natural History GörlitzPO Box 300154D-02806 GörlitzGermany Department of Geobotany and Botanical Garden University Halle-WittenbergAm Kirchtor 1D-06108 Halle(Saale)Germany Department of Geography University MarburgDeutschhausstraße 10D-35032 MarburgGermany German Centre for Integrative Biodiversity Research(iDiv)Halle-Jena-Leipzig Deutscher Platz 5eD-04103 LeipzigGermany Kunming Institute of Botany Chinese Academy of SciencesHeilongtan 650204KunmingChina Present address Department of GeographyUniversity MarburgDeutschhausstraße 10D-35032 MarburgGermany

Aims The sedge Kobresia pygmaea is the dominant species of high-altitude pastures in Tibet,and it is the most important source of forage in animal *** present the first comprehensive reproduction study for this perennial key species that adopts a molecular approach and tests how sexual and vegetative reproduction,as well as ploidy,relate to survival and dominance under harsh *** We assessed inflorescence numbers of *** across two Tibetan alpine pastures with differing grazing *** was tested in untreated diaspores and then following mechanical and chemical *** a 4-year experiment,we assessed diaspore viability and seed bank *** eight microsatellite markers,we recorded multilocus genotypes in hierarchical grids and measured their ploidy using flow *** analysis of variance models were used to analyse data on sexual reproduction,while the complement of the Simpson index and the Shannon diversity index were used to characterize the spatial distribution of multilocus genotypes and clonal *** Findings Inflorescence production was high and differed significantly between years(2010:617±460 SD;2012:2015±1213 SD)but not between grazing *** viability was high(94%)and gradually decreased after 3 and 4 years of storage in the *** not exposed to further scarification failed to germinate,while mechanical and chemical(H2SO4)scarification increased germination to 9 and 44%,*** diversity was high,although in situ germination was rarely *** genotypes intersected and covered a mean area of 0.74 *** individuals were found to be tetraploid,with only 0.8%of all ramets being *** conclude that *** survives on the Tibetan Plateau by employing a mixed reproduction strategy involving both sexual and clonal *** species’adaptability and dominance is further facilitated by its *** pasture restoration usi

关键词： alpine rangelands clonal diversity flow cytometry grazing microsatellite analyses

CFD–DEM simulation of fine particles in a spouted bed apparatus with a Wurster tube

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Particuology 2019年第1期17卷 114-125页

作者： Paul Breuninger Dominik Weis isabell Behrendt Philipp Grohn Fabian Krull Sergiy Antonyuk Institute of Particle Process Engineering University of KaiserslauternGottlieb Daimler Str.. KaiserslauternGermany

In this work, a coupled computational fluid dynamics–discrete element method (CFD–DEM) approach was employed to evaluate the spouting behavior of fine, cohesive powders in a cylindrical spouted bed with a conical base and equipped with a Wurster tube. The particle and gas dynamics inside the apparatus were simulated with 1.7 million spherical ZrO2 particles with a particle size of 100 μm. For an accurate prediction of the interactions of cohesive particles in the spouted bed, the adhesion forces according to JKR theory were included in the Hertz–Tsuji contact model. The surface energy of the particles was varied over a wide range to determine the effect of the adhesion on the spouting (the fountain shape and maximum height as well as the distribution of the concentrations and velocities of particles in different zones of the apparatus). A detailed analysis of the collision dynamics was conducted. The spouting behavior of a spouted bed with the same dimensions, particles, and processing parameters was recorded with a high-speed camera. The CFD–DEM simulations showed good agreement with the experimentally captured spouting behavior.

关键词： CFD–DEM Spouted bed Wurster tube Cohesive powder

Multiple common garden experiments suggest lack of local adaptation in an invasive ornamental plant

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Journal of Plant Ecology 2011年第4期4卷 209-220页

作者： Susan K.Ebeling Jürg Stöcklin isabell Hensen Harald Auge Department of Community Ecology UFZHelmholtz Centre for Environmental Research(UFZ)Theodor-Lieser-Strasse 406120 HalleGermany Institute of Geobotany and Botanical Garden Martin-Luther-University Halle-WittenbergAm Kirchtor 106108 HalleGermany Institute of Botany University of BaselScho¨nbeinstrasse 6CH-4056 BaselSwitzerland

Adaptive evolution along geographic gradients of climatic conditions is suggested to facilitate the spread of invasive plant species,leading to clinal variation among populations in the introduced *** investigated whether adaptation to climate is also involved in the invasive spread of an ornamental shrub,Buddleja davidii,across western and central *** We combined a common garden experiment,replicated in three climatically different central European regions,with reciprocal transplantation to quantify genetic differentiation in growth and reproductive traits of 20 invasive *** ***,we compared compensatory regrowth among populations after clipping of stems to simulate mechanical *** Findings Our results do not provide evidence for clinal variation among invasive *** populations:populations responded similarly to the different environments,and trait values were not correlated to climatic conditions or geographic coordinates of their home ***,we did not detect differences in the compensatory ability of *** suppose that the invasive spread of *** has been facilitated by phenotypic plasticity rather than by adaptation to climate and that continent-wide shuffling of cultivars due to horticultural trade may have limited local adaptation so far.

关键词： Buddleja davidii reciprocal transplantation biological invasion geographic clines climatic conditions

Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks

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Signal Transduction and Targeted Therapy 2022年第1期7卷 243-257页

作者： Louisa Ruhl isabell Pink Jenny F.Kiihne Kerstin Beushausen Jana Keil Stella Christoph Andrea Sauer Lennart Boblitz Julius Schmidt Sascha David Hans-Martin Jack Edith Roth Markus Cornberg Thomas F.schulz Tobias Welte Marius M.Hoper Christine S.Falk Institute of Transplant Immunology MHHDHanoverGermany Department of Pneumology MHHDHanoverGermany Department of Intensive Care Medicine University of ZurichCHZurichSwitzerland Division of Molecular Immunology Internal Medicine IIINikolaus-Fiebiger-Center of Molecular MedicineFriedrich-Alexander University Erlangen-NurnbergDErlangenGermany Department of Gastroenterology Hepatology and Endocrinology MHHDHanoverGermany Center for Individualized Infection Medicine CiiM HanoverGermany lnstitute of Virology MHHDHanoverGermany German Center for Infection Research DZIFTTU-IICHMarburgGermany Excellence Cluster 2155 RESIST MHHHanoverGermany German Center for Lung Diseases DZL/BREATH MarburgGermany

The systemic processes involved in the manifestation of life・threatening COVID-19 and in disease recovery are still incompletely understood,despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 *** define hallmarks of severe COVID-19 in acute disease(n=58)and in disease recovery in con valesce nt patie nts(n=28)from Han nover Medical School,we used flow cytometry and proteomics data with unsupervised clustering *** our observational study,we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and *** patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific *** core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe *** within this sign ature were associated with either disease progression or *** summary,our data suggest that besides a strong inflammatory response,severe COVID-19 is driven by endothelial activation and barrier disruption,whereby recovery depends on the regeneration of the endothelial integrity.

关键词： cytokine networks signature

One-year outcome of percutaneous mitral valve repair in patients with severe symptomatic mitral valve regurgitation

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World Journal of Cardiology 2017年第1期9卷 39-46页

作者： Michael Gotzmann isabell Sprenger Aydan Ewers Andreas Mügge Leif Bosche Department of Cardiology Marien-Hospital WittenRuhr-University Cardiology and Angiology University-Hospital Bergmannsheil

AIM To investigate one-year outcomes after percutaneous mitral valve repair with Mitra Clip~? in patients with severe mitral regurgitation(MR). METHODS Our study investigated consecutive patients with symptomatic severe MR who underwent Mitra Clip~?implantation at the University Hospital Bergmannsheil from 2012 to 2014. The primary study end-point was all-cause mortality. Secondary end-points were degree of MR and functional status after percutaneous mitral valve *** The study population consisted of 46 consecutive patients(mean logistic Euro SCORE 32% ± 21%). The degree of MR decreased significantly(severe MR before Mitra Clip~? 100% vs after Mitra Clip~? 13%; P 817 pg/m L was associated with all-cause mortality(hazard ratio,6.074; 95%CI: 1.257-29.239; P = 0.012).CONCLUSION Percutaneous mitral valve repair with Mitra Clip~? has positive effects on hemodynamics and symptoms. Despite the study patients' multiple comorbidities and extremely high operative risk,one-year outcomes after Mitra Clip~? are favorable. Elevated B-type natriuretic peptide levels indicate poorer mid-term survival.

关键词： Severe mitral regurgitation Percutaneous mitral valve repair MitraClip^® One-year outcome

Frequent Expression Alterations of ETS Related Gene-1(ERG1)in Prostate Cancer Transcriptome Reveal Diagnostic and Prognostic Biomarker Potential

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Frequent Expression Alterations of ETS Related Gene-1(ERG1)i...

对于有症状女性高质量的双阅片及审核阅片在乳腺癌早期诊断中的优势

中华医学会病理学分会2005年学术年会

作者：刘爱军 Gyorgy Petrovics Syed Shaheduzzaman Bungo Furasato Martin Nau Lakshmi Ravindranath Albert Dobi Vasantha Srikantan isabell A Sesterhenn David G McLeod Maryanne Vahey Judd W Moul Shiv Srivastava Centerfor Prostate Disease Research US Military Cancer InstituteUniformed Services University Center for Prostate Disease Research US Military Cancer InstituteUniformed Services University Department of Genitourinary Pathology Armed Forces Institute of Pathology Laboratory of Functional Genomics Walter Reed Army Institute of Research Urology Service Walter Reed Army Medical Center

Transcription factors encoded by the ETS family of genes are central in integrating signals that regulate cell growth and differentiation, stress responses and tumorigenesis. This study, using laser microdissected paired benign and malignant prostate epithelial cells from prostate cancer (CaP) patients (n=114), identifies ERG, a member of the ETS transcription factor family, as the most frequently overexpressed poto-oncogene in the transcriptome of malignant prostate epithelial cells. Combined quantitative expression analysis of ERG with two other genes commonly overexpressed in CaP, AMACR and DD3, revealed overexpression of at least one of these three genes in virtually all cancer specimen (54 of 55). Therefore,

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国际医学放射学杂志 2012年第4期 394-394页

作者： W. Annika K. Smaragda K. Alexander G.N. isabell M.S. Beate F. Dorothea 秦乃珊 Institute of Clinical Epidemiology University Hospital Schleswig-Holstein Campus LuebeckRatzeburger Allee 160 (Haus 50) 23538 Luebeck Germany

摘要目的根据肿瘤检出率,原位癌发现比例以及为探查额外肿瘤需要提交专家阅片的病例数(需要进一步处理的病例数,NNT)证实双阅片及审核阅片的价值。方法QuaMaDi是一项质量认证的乳腺癌诊断计划,采用双体位(CC和MLO)乳腺X线摄影,如果病人... 详细信息

摘要目的根据肿瘤检出率,原位癌发现比例以及为探查额外肿瘤需要提交专家阅片的病例数(需要进一步处理的病例数,NNT)证实双阅片及审核阅片的价值。方法QuaMaDi是一项质量认证的乳腺癌诊断计划,采用双体位(CC和MLO)乳腺X线摄影,如果病人乳腺密度为美国放射学会(ACR)的3或4类时,辅以

关键词：乳腺肿瘤癌灶早期诊断乳腺X线摄影谈判诊断技术和流程