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

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

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CONTINUITY PROPERTIES FOR bORN-JORDAN OPERATORS WITH SYMbOLS IN HÖRMANDER CLASSES AND MODULATION SPACES

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Acta Mathematica Scientia 2020年第6期40卷 1603-1626页

作者： Maurice de GOSSON joachim TOFT Faculty of Mathematics NuHAGUniversity of ViennaViennaAustria Department of Mathematics Linnæus UniversityVäxjöSweden

We show that the Weyl symbol of a born-Jordan operator is in the same class as the born-Jordan symbol,when Hörmander symbols and certain types of modulation spaces are used as symbol *** use these properties to carry ... 详细信息

关键词： quantization Schatten-von Neumann Feffermann-Phong's inequality

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Glaucoma-like damage induced by S100b injection is accompanied by microglial response

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Neural Regeneration Research 2022年第3期17卷 572-574页

作者： Teresa Tsai Stephanie C.joachim Experimental Eye Research Institute University Eye HospitalRuhr-University BochumBochumGermany

Glaucoma is currently the second leading cause of blindness *** to aging societies the number of patients suffering from this disease will further increase in the next ***,glaucoma can remain asymptomatic until it is rather far progressed,hence about 10–50% of patients are unaware they suffer from this *** is a progressive optic neuropathy associated with changes at the optic nerve head.

关键词： S100b injection damage

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Latent HIV-1 TAR Regulates 7SK-responsive P-TEFb Target Genes and Targets Cellular Immune Responses in the Absence of Tat

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Genomics, Proteomics & bioinformatics 2017年第5期15卷 313-323页

作者： Sebastian Eilebrecht bernd-joachim benecke Arndt G. benecke CNRS UMR8246 Université Pierre et Marie Curie Paris 75005 France ACSIOMA GmbH Technologiezentrum Ruhr Bochum 44799 Germany Center for Innate Immunity and Immune Disease University of Washington School of Medicine Seattle WA 98195 USA

The transactivating response element （TAR） structure of the nascent HIV-1 transcript is critically involved in the recruitment of inactive positive transcription elongation factor b （P-TEFb） to the promoter proximal paused RNA polymerase II. The viral transactivator Tat is responsible for subsequent P-TEFb activation in order to start efficient viral transcription elongation. In the absence of the viral transactivator of transcription （Tat）, e.g., during latency or in early stages of HIV tran- scription, TAR mediates an interaction of P-TEFb with its inhibitor hexamethylene bis-aeetamide- inducible protein 1 （HEXIM1）, keeping P-TEFb in its inactive form. In this study, we address the function of HIV-1 TAR in the absence of Tat by analyzing consequences of HIV-1 TAR overexpres- sion on host cellular gene expression. An RNA chimera consisting of Epstein-barr virus-expressed RNA 2 （EbER2） and HIV-1 TAR was developed to assure robust overexpression of TAR in HEK293 cells. The overexpression results in differential expression of more than 800 human genes. A significant proportion of these genes is involved in the suppression of cellular immune responses, including a significant set of 7SK-responsive P-TEFb target genes. Our findings identify a novel role for HIV-1 TAR in the absence of Tat, involving the interference with host cellular immune responses by targeting 7SK RNA-mediated gene expression and P-TEFb inactivation.

关键词： HIV-1 Latency TAR 7SK RNA Cellular immunity

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Computer animations of color markings revealthe function of visual threat signals inNeolamprologus pulcher

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Current Zoology 2017年第1期63卷 45-54页

作者： Valentina bALZARINI Michael TAbORSKY Fabienne VILLA joachim G. FROMMEN Institute of Ecology and Evolution Behavioral Ecology Division University of Bern Wohlenstrasse 50a 3032Hinterkappelen Switzerland

Visual signals, including changes in coloration and color patterns, are frequently used by animalsto convey information. During contests, body coloration and its changes can be used to assess anopponent＇s state or motivation. Communication of aggressive propensity is particularly importantin group-living animals with a stable dominance hierarchy, as the outcome of aggressive inter-actions determines the social rank of group members. Neolamprologus pulcher is a cooperativelybreeding cichlid showing frequent within-group aggression. both sexes exhibit two vertical blackstripes on the operculum that vary naturally in shape and darkness. During frontal threat displaysthese patterns are actively exposed to the opponent, suggesting a signaling function. To investi-gate the role of operculum stripes during contests we manipulated their darkness in computeranimated pictures of the fish. We recorded the responses in behavior and stripe darkness of testsubjects to which these animated pictures were presented. Individuals with initially darker stripeswere more aggressive against the animations and showed more operculum threat *** stripes of test subjects became darker after exposure to an animation exhibiting a paleoperculum than after exposure to a dark operculum animation, highlighting the role of the dark-ness of this color pattern in opponent assessment. We conclude that （i） the black stripes on theoperculum of N. pulcherare a reliable signal of aggression and dominance, （ii） these markings playan important role in opponent assessment, and （iii） 2D computer animations are well suited to elicitbiologically meaningful short-term aggressive responses in this widely used model system ofsocial evolution.

关键词： aggression, agonistic behavior, animated pictures, cichlid fish, communication, cooperation, social, threat display.

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Identification and characterization of a novel bipartite nuclear localization signal in the hepatitis b virus polymerase

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World Journal of Gastroenterology 2013年第44期19卷 8000-8010页

作者： joachim Lupberger Stephanie Schaedler Alexander Peiran Eberhard Hildt Department of Medicine Ⅱ University of Freiburg D-79106 Freiburg Germany Inserm U748 Strasbourg France Division of Virology University Goettingen37073 Goettingen Germany Division of Virology Paul-Ehrlich-InstituteD-63325 Langen Germany

AIM: To characterize the nuclear import of hepatitis b virus (HbV) polymerase (P) and its relevance for the viral life cycle.METHODS: Sequence analysis was performed to predict functional motives within P. Phosphorylation of P was analyzed by in vitro phosphorylation. Phosphorylation site and nuclear localization signal (NLS) were destroyed by site directed mutagenesis. Functionality of the identified NLS was analyzed by confocal fluorescence microscopy and characterizing the karyopherin binding. Relevance of the structural motives for viral life cycle was studied by infection of primary Tupaia hepatocytes with HbV.RESULTS: We identified by sequence alignment and functional experiments a conserved bipartite NLS containing a casein kinase II (CKII) phosphorylation site located within the terminal protein domain (TP) of the HbV polymerase. Inhibition of CKII impairs the functionality of this NLS and thereby prevents the nuclear import of the polymerase. binding of the import factor karyopherin-α2 to the polymerase depends on its CKII-mediated phosphorylation of the bipartite NLS. In HbV-infected primary Tupaia hepatocytes CKII inhibition in the early phase (post entry phase) of the infection process prevents the establishment of the infection.CONCLUSION: based on these data it is suggested that during HbV infection the final import of the genome complex into the nucleus is mediated by a novel bipartite NLS localized in the TP domain of HbV polymerase.

关键词： Hepatitis b virus Nuclear localization signal Casein kinase II Trafficking Replication

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Initial nucleation of amorphous Si–b–C–N ceramics derived from polymer-precursors

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Journal of Materials Science & Technology 2019年第12期35卷 2851-2858页

作者： Ling-yan Li Hui Gu Vesna Srot Peter van Aken joachim bill Materials Genome Institute School of Materials Science and EngineeringShanghai University99 Shangda RoadShanghai200444China Stuttgart Center for Electron Microscopy Max-Planck-lnstitute for Solid-State ResearchHeisen bergs trasse 370569StuttgartGermany Institute of Materials Science University of StuttgartHeisenbergstrasse 570569StuttgartGermany

Nucleation behavior of amorphous Si–b–C–N ceramics derived from boron-modified polyvinylsilazane procusors was systematically investigated by transmission electron microscopy(TEM) combined with spatially-resolved electron energy-loss spectroscopy(EELS) analysis. The ceramics were pyrolyzed at1000℃ followed by further annealing in N2, and SiC nano-crystallites start to emerge at 1200℃ and dominate at 1500℃. Observed by high-angle annular dark-field imaging, bright and dark clusters were revealed as universal nano-structured features in ceramic matrices before and after nucleation, and the growth of cluster size saturated before reaching 5 nm at 1400℃. EELS analysis demonstrated the gradual development of bonding structures successively into SiC, graphetic bNCxand Si3N4 phases, as well as a constant presence of unexpected oxygen in the matrices. Furthermore, EELS profiling revealed the bright SiC clusters and less bright Si3N4-like clusters at 1200–1400℃. Since the amorphous matrix has already phase separated into SiCN and carbon clusters, another phase separation of SiCN into SiC and Si3N4-like clusters might occur by annealing to accompany their nucleation and growth, albeit one crystallized and another remained in amorphous structure. Hinderance of the cluster growth and further crystallization was owing to the formation of bNCxlayers that developed between SiC and Si3N4-like clusters as well as from the excessive oxygen to form the stable SiO2.

关键词： Precursor derived ceramics Si–b–C–N Nucleation High-angle annular dark-field imaging Electron energy-loss spectroscopy

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克立格估计的分析解释与协方差函数的代数确定

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地球科学（中国地质大学学报） 2000年第2期25卷 195-200页

作者：边少锋 joachim Menz 中国科学院测量与地球物理研究所武汉430077 TU bergakade mie Freiberg

首先引入利用旋转面作为基函数的函数逼近概念 ,在此基础上经过复杂的矩阵推导证明泛克立格法可表示为传统的带权最小二乘多项式拟合与以旋转面作为基函数的函数逼近 ,并在一定条件下 (随机场高度连续无块金效应 )论证了协方差 (即旋转... 详细信息

首先引入利用旋转面作为基函数的函数逼近概念 ,在此基础上经过复杂的矩阵推导证明泛克立格法可表示为传统的带权最小二乘多项式拟合与以旋转面作为基函数的函数逼近 ,并在一定条件下 (随机场高度连续无块金效应 )论证了协方差 (即旋转面 )的参数可通过数学分析的方法确定 ,给出了以高斯函数为例确定协方差函数的两个准则 .

关键词：克立格估计协方差函数地质统计学代数确定

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Diverged Copies of the Seed Regulatory Opaque-2 Gene by a Segmental Duplication in the Progenitor Genome of Rice, Sorghum, and Maize

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Molecular Plant 2008年第5期1卷 760-769页

作者： Jian-Hong Xu joachim Messing Waksman Institute of Microbiology Rutgers University 190 Frelinghuysen Road Piscataway NJ 08854 USA

Comparative analyses of the sequence of entire genomes have shown that gene duplications, chromosomal segmental duplications, or even whole genome duplications （WGD） have played prominent roles in the evolution of many eukaryotic species. Here, we used the ancient duplication of a well known transcription factor in maize, encoded by the Opaque-2 （O2） locus, to examine the general features of divergences of chromosomal segmental duplications in a lineagespecific manner. We took advantage of contiguous chromosomal sequence information in rice （Oryza sativa, Nipponbare）, sorghum （Sorghum bicolor, btx623）, and maize （Zea rnays, b73） that were aligned by conserved gene order （synteny）. This analysis showed that the maize 02 locus is contained within a 1.25 million base-pair （Mb） segment on chromosome 7, which was duplicated ≈56 million years ago （mya） before the split of rice and maize 50 mya. The duplicated region on chromosome I is only half the size and contains the maize OHP gene, which does not restore the O2 mutation although it encodes a protein with the same DNA and protein binding properties in endosperm. The segmental duplication is not only found in rice, but also in sorghum, which split from maize 11.9 mya. A detailed analysis of the duplicated regions provided examples for complex rearrangements including deletions, duplications, conversions, inversions, and translocations. Furthermore, the rice and sorghum genomes appeared to be more stable than the maize genome, probably because maize underwent allotetraploidization and then diploidization.

关键词：蛋白质结合高梁属基因基因组稻属氧胰岛素玉米

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Copper toxicosis gene MURRl is not changed in Wilson disease patients with normal blood ceruloplasmin levels

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World Journal of Gastroenterology 2006年第14期12卷 2239-2242页

作者： Karl Heinz Weiss Uta Merle Mark Schaefer Peter Ferenci joachim Fullekrug Wolfgang Stremmel Department of Gastroenterology University of Heidelberg Germany Department of Gastroenterology and Hepatology Medical University of Vienna Austria

AIM： To analyze our Wilson disease patient cohort （n = 106） for alterations in the gene coding for MURR1. METHODS： Patients with an established diagnosis of Wilson disease but normal ceruloplasmin blood levels were chosen for our study （n = 14）. Patients with two known disease-causing mutations in the ATPTb gene were not included. The three exons of the human MURR1 gene were sequenced after amplification of the genomic DNA by polymerase chain reaction. RESULTS： Our study did not reveal any mutations leading to an amino acid change in the MURR1 sequence of Wilson disease patients. A polymorphism at 472 bp of the coding sequence could be confirmed. CONCLUSION： The MURRI gene plays no role in the pathogenesis of Wilson disease patients with normal serum ceruloplasmin levels.

关键词： Wilson Disease ATPTb MURR1 COMMD1

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