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Alcohol-induced alterations of the hepatocyte cytoskeleton

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World Journal of Gastroenterology 2010年第11期16卷 1358-1365页

作者： bl.the d shepard Pamela L Tuma department of Biology The Catholic University of America

The hepatocyte cytoskeleton consists of three fi lamentous networks: microtubules, actin microfi laments and keratin intermediate filaments. Because of the abundance of the proteins that comprise each system and the central role each network plays in a variety of cellular processes, the three fi lament systems have been the focus of a host of studies aimed at understanding the progression of alcohol-induced liver injury. In this review, we will briefly discuss the hepatic organization of each cytoskeletal network and highlight some components of each system. We will also describe what is known about ethanol-induced changes in the dynamics and distributions of each cytoskeletal system and discuss what is known about changes in protein expression levels and post-translational modifi cations. Finally, we will describe the possible consequences of these cytoskeletal alterations on hepatocyte function and how they might contribute to the progression of liver disease.

关键词： Ethanol Hepatotoxicity Tubulin Actin Keratin

THE GLOBAL dUFORT-FRANKEL dIFFERENCE APPROXIMATION FOR NONLINEAR REACTION-dIFFUSION EQUATIONS

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Journal of Computational Mathematics 1998年第3期16卷 275-288页

作者： Lu, BN Wan, GH Guo, bl Xiangtan Univ Inst Computat & Appl Math Xiangtan 411105 Peoples R China Inst Appl Phys & Computat Math Lab Computat Phys Beijing 100088 Peoples R China Shaanzi Normal Univ Dept Math Xian 710062 Peoples R China Inst Appl Phys & Computat Math Ctr Nonlinear Studies Beijing 100088 Peoples R China

In this paper, the initial value problem of nonlinear reaction-diffusion equation is considered. The dufort-Frankel finite difference approximation for the long time scheme is given for the d-dimensional reaction-diffusion equation with the two different cases. The global solution and global attractor are discussed for the dufort-Frankel scheme. Moreover properties of the solution are studied. The error estimate is presented in a finite time region and in the global time region for some special cases. Finally the numerical results for the equation are investigated for Allen-Cahn equation and some other equations and the homoclinic orbit is simulated numerically.

关键词： global dufort-Frankel method reaction-diffusion equation global attractor error estimate numerical experiments

Electron–plasmon and electron–magnon scattering in ferromagnets from first principles by combining GW and GT self-energies

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npj Computational Materials 2021年第1期7卷 1619-1632页

作者： dmitrii Nabok Stefan blügel Christoph Friedrich Peter Grünberg Institut and Institut for Advanced Simulation Forschungszentrum JülichJülich 52425Germany

This work combines two powerful self-energy techniques:the well-known GW method and a self-energy recently developed by us that describes renormalization effects caused by the scattering of electrons with magnons and Stoner *** GT selfenergy,which is fully k-dependent and contains infinitely many spin-flip ladder diagrams,was shown to have a profound impact on the electronic band structure of Fe,Co,and *** the present work,we refine the method by combining GT with the GW *** resulting GWT spectral functions exhibit strong lifetime effects and emergent dispersion *** are in an overall better agreement with experimental spectra than those obtained with GW or GT alone,even showing partial improvements over local-spin-density approximation dynamical mean-field *** performed analysis provides a basis for applying the GWT technique to a wider class of magnetic materials.

关键词： materials theory infinitely

The AiidA-KKR plugin and its application to highthroughput impurity embedding into a topological insulator

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npj Computational Materials 2021年第1期7卷 108-116页

作者： Philipp Rüßmann Fabian Bertoldoand Stefan blügel Peter Grünberg Institut and Institute for Advanced Simulation Forschungszentrum Jülich and JARAD-52425 JülichGermany

The ever increasing availability of supercomputing resources led computer-based materials science into a new era of highthroughput ***,Pizzi et *** the AiidA framework that provides a way to automate calculations while allowing to store the full provenance of complex workflows in a *** present the development of the AiidA-KKR plugin that allows to perform a large number of ab initio impurity embedding calculations based on the relativistic full-potential Korringa-Kohn-Rostoker Green function *** capabilities of the AiidA-KKR plugin are demonstrated with the calculation of several thousand impurities embedded into the prototypical topological insulator *** results are collected in the JudiT database which we use to investigate chemical trends as well as Fermi level and layer dependence of physical properties of *** includes the study of spin moments,the impurity’s tendency to form in-gap states or its effect on the charge doping of the *** properties depend on the detailed electronic structure of the impurity embedded into the host crystal which highlights the need for ab initio calculations in order to get accurate predictions.

关键词： method topological embedding

The Ornithodolite as a tool to quantify animal space use and habitat selection: a case study with birds diving in tidal waters

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Integrative Zoology 2019年第1期14卷 4-16页

作者： Emma-Louise COLE James J WAGGITT Anders HEdENSTROM Marco PIANO Mark d.HOLTON Luca BÖRGER Emily L.C.shepard department of Biosciences Swansea UniversitySwanseaUK School of Ocean Sciences Bangor UniversityMenai BridgeUK department of Biology Lund UniversityEcology BuildingSweden Centre for Applied Marine Sciences Bangor UniversityMenai BridgeUK

Animal-attached technologies can be powerful means to quantify space use and behavior;however,there are also ethical implications associated with capturing and instrumenting ***,tagging approaches are not necessarily well-suited for examining the movements of multiple individuals within specific,local areas of ***,we assess a method of quantifying animal space use based on a modified theodolite with an inbuilt laser *** a database of>4200 tracks of migrating birds,we show that detection distance in-creases with bird body mass(range 5 g to>10 kg).The maximum distance recorded to a bird was 5500 m and measurement error was≤5 m for targets within this distance range:a level comparable to methods such as GPS *** go on to present a case study where this method was used to assess habitat selection in seabirds operating in dynamic coastal waters close to a tidal *** positional data with outputs from a hydrographic model revealed that great cormorants(Phalacrocorax carbo)appeared to be highly selective of current characteristics in space and time,exploiting areas where mean current speeds wered diving at times when turbulent energy levels were *** birds also oriented into tidal currents during *** together,this suggests that collision risks are low for cormorants at this site,as the 2 conditions avoided by cormorants(high mean current speeds and turbulence levels)are associated with operational tidal ***-all,we suggest that this modified theodolite system is well-suited to the quantification of movement in small areas associated with particular development strategies,including sustainable energy devices.

关键词： GPS habitat use movement ecology seabird tidal turbine

Tyrosine kinase of insulin-like growth factor receptor as target for novel treatment and prevention strategies of colorectal cancer

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World Journal of Gastroenterology 2006年第35期12卷 5635-5643页

作者： Michael Hpfner Andreas P Sutter Alexander Huether Viola Baradari Hans Scherübl Charité-Universittsmedizin Berlin Campus Benjamin Franklin Medical Clinic I Gastroenterology/Infectious Diseases/ Rheumatology Berlin Germany Klinik für Gastroenterologie und Gastrointestinale Onkologie Vivantes-Klinikum Am Urban Dieffenbachstr. 1 Berlin 10967 Germany

AIM： To investigate the antineoplastic potency of the novel insulin-like growth factor 1 receptor （IGF-1R） tyrosine kinase inhibitor （TKI） NVP-AEW541 in cell lines and primary cell cultures of human colorectal cancer （CRC）. METHOdS： Cells of primary colorectal carcinomas were from 8 patients. Immunostaining and crystal violet staining were used for analysis of growth factor receptor protein expression and detection of cell number changes, respectively. Cytotoxicity was determined by measuring the release of the cytoplasmic enzyme lactate dehydrogenase （LdH）. The proportion of apoptotic cells was determined by quantifying the percentage of sub-G1 （hypodiploid） cells. Cell cycle status reflected by the dNA content of the nuclei was detected by flow cytometry. RESULTS： NVP-AEW541 dose-dependently inhibited the proliferation of colorectal carcinoma cell lines and primary cell cultures by inducing apoptosis and cell cycle arrest. Apoptosis was characterized by caspase-3 activation and nuclear degradation. Cell cycle was arrested at the G1/S checkpoint. The NVP-AEW541-mediated cell cycle-related signaling involved the inactivation of Akt and extracellular signal-regulated kinase （ERK） 1/2, the upregulation of the cyclin-dependent kinase inhibitors p21^waf1/CIP1 and p27^kjp1, and the downregulation of the cell cycle promoter cyclin d1. Moreover, BAX was upregulated during NVP-AEW541-induced apoptosis, whereas Bcl-2 was downregulated. Measurement of LdH release showed that the antineoplastic effect of NVP-AEW541 was not due to general cytotoxicity of the compound. However, augmented antineoplastic effects were observed in combination treatments of NVP-AEW541 with either 5-FU, or the EGFR-antibody cetuximab, or the HMG-CoA-reductase inhibitor fluvastatin. CONCLUSION： IGF-1R-TK inhibition is a promising novel approach for either monoor combination treatment strategies of colorectal carcinoma and even for CRC chemoprevention.

关键词： Insulin-like growth factor receptor Tyrosine kinase Colorectal cancer Apoptosis Cell cycle arrest

Expression of c-kit receptor in human cholangiocarcinoma and in vivo treatment with imatinib mesilate in chimeric mice

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World Journal of Gastroenterology 2006年第10期12卷 1583-1590页

作者： Thomas Kamenz Karel Caca Thilo blüthner Andrea Tannapfel Joachim Mssner Marcus Wiedmann department of Internal Medicine Ⅱ University of Leipzig Philipp-Rosenthal-Str.2704103 LeipzigGermany Institute of Pathology University of Leipzig Liebigstr.2604103 LeipzigGermany

AIM： To investigate the c-kit expression in biliary tract cancer cell lines and histological sections from patients with extrahepatic cholangiocarcinoma （CC） and to evaluate the efficacy of in vitro and in vitro treatment with imatinib mesilate. METHOdS： The protein expression of c-kit in the human biliary tract cancer cell lines Mz-ChA-2 and EGI-1 and histological sections from 19 patients with extrahepatic CC was assessed by immunoblotting, immunocytochemistry, and immunohistochemistry. The anti-proliferative effect of imatinib mesilate on biliary tract cancer cell lines Mz-ChA-2 and EGI-1 was studied in vitro by automated cell counting. In addition, immunodeficient NMRI mice （Taconic^TM） were subcutaneously injected with 5 × 10^6 cells of cell lines MzChA-2 and EGI-1. After having reached a tumour volume of 200 mm^3, daily treatment was started intraperitoneally with imatinib mesilate at a dose of 50 mgikg or normal saline （NS）. Tumor volume was calculated with a Vernier caliper. After 14 d, mice were sacrificed with tumors excised and tumor mass determined.RESULTS： Immunoblotting revealed presence of c-kit in Mz-ChA-2 and absence in EGI-1 cells. Immunocytochemistry with c-kit antibodies displayed a cytoplasmatic and membraneous localization of receptor protein in Mz-ChA-2 cells and absence of c-kit in EGI-1 cells, c-kit was expressed in 7 of 19 （37%） extrahepatic humanCC tissue samples, 2 showed a moderate and 5 a rather weak immunostaining. Imatinib mesilate at a low concentration of 5 μmoliL caused a significant growth inhibition in the c-kit positive cell line Mz-ChA-2 （31%）, but not in the c-kit negative cell line EGI-1 （0%）（P〈0.05）. Imatinib mesilate at an intermediate concentration of 10 μmoliL inhibited cellular growth of both cell lines （51% vs 57%）. Imatinib mesilate at a higher concentration of 20 μmoliL seemed to have a general toxic effect on both cell lines. The IC50 values were 9.7 μmoliL and 11 μmoliL, respectively. After 14 d of in vitro treat

关键词： Cholangiocarcinoma Imatinib Tyrosine kinase inhibitor c-kit Chimeric mice

Signaling pathways involved in the inhibition of epidermal growth factor receptor by erlotinib in hepatocellular cancer

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World Journal of Gastroenterology 2006年第32期12卷 5160-5167页

作者： Alexander Huether Michael Hpfner Andreas P Sutter Viola Baradari detlef Schuppan Hans Scherübl Charité-Universittsmedizin Berlin Campus Benjamin Franklin Medical Clinic ⅠGastroenterology/Infectious Diseases/RheumatologyBerlinGermany Harvard Medical School Beth Israel deaconess Medical Center Division of Gastroenterology and HepatologyBostonUnited States

AIM： To examine the underlying mechanisms of erlotinib-induced growth inhibition in hepatocellular carcinoma （HCC）. METHOdS： Erlotinib-induced alterations in gene expression were evaluated using cdNA array technology; changes in protein expression and/or protein activation due to erlotinib treatment as well as IGF-1-induced EGFR transactivation were investigated using Western blotting. RESULTS： Erlotinib treatment inhibited the mitogen activated protein （MAP）-kinase pathway and signal transducer of activation and transcription （STAT）- mediated signaling which led to an altered expression of apoptosis and cell cycle regulating genes as demonstrated by cdNA array technology. Overexpression of proapoptotic factors like caspases and gadds associated with a down-regulation of antiapoptotic factors like Bcl-2, Bcl-XL or jun d accounted for erlotinib＇s potency to induce apoptosis. downregulation of cell cycle regulators promoting the G1/S-transition and overexpression of cyclin-dependent kinase inhibitors and gadds contributed to the induction of a G1/G0-arrest in response to erlotinib. Furthermore, we displayed the transactivation of EGFR-mediated signaling by the IGF-1-receptor and showed erlotinib＇s inhibitory effects on the receptor-receptor cross talk. CONCLUSION： Our study sheds light on the understanding of the mechanisms of action of EGFR-TK- inhibition in HCC-cells and thus might facilitate the design of combination therapies that act additively or synergistically. Moreover, our data on the pathways responding to erlotinib treatment could be helpful in predicting the responsiveness of tumors to EGFR-TKIs in the future.

关键词： Epidermal growth factor receptor Insulinlike growth factor receptor Tarceva^TM Signal transducerof activation and transcription Extracellular regulatedkinase Gene expression

Preclinical and clinical evidence of the association of colibactinproducing Escherichia coli with anxiety and depression in colon cancer

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World Journal of Gastroenterology 2024年第21期30卷 2817-2826页

作者： Fabien Rondepierre Maëva Meynier Johan Gagniere Vincent deneuvy Anissa deneuvy Gwenaelle Roche Elodie Baudu Bruno Pereira Richard Bonnet Nicolas Barnich Frédéric Antonio Carvalho denis Pezet Mathilde Bonnet Isabelle Jalenques Service de Psychiatrie de l’Adulte A et Psychologie Médicale CHU Clermont-FerrandClermont-Ferrand 63000France M2iSH UMR 1071INSERMUniversity of Clermont AuvergneINRAE USC 1382Clermont-Ferrand 63001France Neurodol UMR 1107INSERMUniversity of Clermont AuvergneClermont-Ferrand 63001France department of digestive Surgery CHU de Clermont-FerrandClermont-Ferrand 63001France Biostatistics Unit Department of Clinical Research and InnovationCHU Clermont-FerrandClermont-Ferrand 63000France department of Bacteriology CHU de Clermont-FerrandClermont-Ferrand 63001France UniversitéClermont Auvergne INPCNRSClermont Auvergne Institut PascalClermont-Ferrand 63000France

BACKGROUNd The association between the intestinal microbiota and psychiatric disorders is becoming increasingly *** gut microbiota contributes to colorectal carcinogenesis(CRC),as demonstrated with colibactin-producing Escherichia coli(CoPEC).AIM To evaluate the association between CoPEC prevalence and anxiety-and depressive-like behaviors with both preclinical and clinical *** Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric *** were compared according to the CoPEC *** parallel C57bl6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC *** behavior was assessed using the Elevated Plus Maze test,the Forced Swimming Test and the Behavior recognition system PhenoTyper®.RESULTS In a limited cohort,all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis,whereas only one patient(17%)without CoPEC *** result was confirmed in C57bl6/J wildtype mice and in a CRC susceptibility mouse model(adenomatous polyposis colimultiple intestinal neoplasia/+).Mice exhibited a significant increase in anxiety-and depressive-like behaviors after chronic infection with a CoPEC *** This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties.

关键词： Colorectal cancer Colibactin Escherichia coli Colibactin-producing Escherichia coli Inflammation Anxiety depression Behavior