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Hepatocyte cytoskeleton during ischemia and reperfusion -influence of ANP-mediated p38 MAPK activation

World Journal of Gastroenterology 2005年第47期11卷 7418-7429页

作者： Melanie Keller Alexander L Gerbes Stefanie Kulhanek-Heinze Tobias Gerwig Uwe Grützner nico van rooijen Angelika M Vollmar Alexandra K Kiemer Department of Pharmacy Centre of Drug ResearchUniversity of MunichButenandtstr. 5-1381377 MunichGermany Department of Medicine Ⅱ Klinikum GroβhadernUniversity of MunichMarchionistr. 1781377 MunichGermany Angelika M Vollmar Alexandra K KiemerDepartment of PharmacyCentre of Drug ResearchUniversity of MunichButenandtstr. 5-1381377 MunichGermany Department of Pharmacy Centre of Drug ResearchUniversity of MunichButenandtstr. 5-1381377 MunichGermany Department of Medicine ⅡKlinikum GroβhadernUniversity of MunichMarchionistr. 1781377 MunichGermany Institute for Surgical Research Klinikum GroβhadernUniversity of MunichMarchionistr. 1781377 MunichGermany Vrije Universiteit VUMCDepartment of Molecular Cell BiologyFaculty of Medicine1081 BT AmsterdamThe Netherlands

AIM： To determine functional consequences of this activation, whereby we focused on a potential regulation of the hepatocyte cytoskeleton during ischernia and reperfusion. METHODS： For in vivo experiments, animals received ANP （5 μg/kg） intravenously. In a different experimental setting, isolated rat livers were perfused with KH-buffer ＋ANP （200 nmol/L）＋SB203580 （2 μmol/L）. Livers were then kept under ischernic conditions for 24 h, and either transplanted or reperfused. Actin, Hsp27, and phosphorylated Hsp27 were determined by Western blotting, p38 MAPK activity by in vitro phosphorylation assay. F-actin distribution was determined by confocal microscopy. RESULTS： We first confirmed that ANP preconditioning leads to an activation of p38 MAPK and observed alterations of the cytoskeleton in hepatocytes of ANP- preconditioned organs. ANP induced an increase of hepatic F-actin after ischemia, which could be prevented by the p38 MAPK inhibitor SB203580 but had no effect on bile flow. After ischemia untreated livers showed a translocation of Hsp27 towards the cytoskeleton and an increase in total Hsp27, whereas ANP preconditioning prohibited translocation but caused an augmentation of Hsp27 phosphorylation. This effect is also mediated via p38 MAPK, since it was abrogated by the p38 MAPK inhibitor SB203580. CONCLUSION： This study reveals that ANP-mediated p38 MAPK activation leads to changes in hepatocyte cytoskeleton involving an elevation of phosphorylated Hsp27 and thereby for the first time shows functional consequences of ANP-induced hepatic p38 MAPK activation.

关键词： Hormonal preconditioning Atrial natriuretic peptide Hsp 27 Actin Polymerization

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布鲁氏菌引起的巨噬细胞依赖性树突状细胞迁移与免疫应答

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细胞与分子免疫学杂志 2009年第6期25卷 495-497页

作者：韩丽滨董炳梅李妍何媛娜 nico van rooijen 王少华付景丽王家鑫河北农业大学动物科技学院免疫学实验室河北农业大学生命科学学院河北保定071000 阿姆斯特丹自由大学分子细胞生物学系

目的:研究阴道巨噬细胞清除后小鼠对布鲁氏菌疫苗的免疫应答机制。方法:BALB/c小鼠60只随机分为3组,每组20只,实验组小鼠阴道内滴注脂质体包裹的clodronate以清除阴道巨噬细胞,3d后阴道滴注10μL布鲁氏菌疫苗(含6×108个布鲁氏菌)。同... 详细信息

目的:研究阴道巨噬细胞清除后小鼠对布鲁氏菌疫苗的免疫应答机制。方法:BALB/c小鼠60只随机分为3组,每组20只,实验组小鼠阴道内滴注脂质体包裹的clodronate以清除阴道巨噬细胞,3d后阴道滴注10μL布鲁氏菌疫苗(含6×108个布鲁氏菌)。同时设空脂质体对照组(不含clo-dronate)和PBS对照组。依次在12、24、36、72h收集小鼠阴道、髂内淋巴结和血液。采用免疫组织化学染色法观察阴道巨噬细胞清除效果和树突状细胞(DC)的迁移,并用ELISA法检测血清中IFN-γ和IL-4的含量。收集小鼠腹腔液制备巨噬细胞进行细胞培养,1.2×106个巨噬细胞中加入布鲁氏菌疫苗10μL,于不同时间点对巨噬细胞进行姬姆萨染色,观察巨噬细胞的变化。结果:清除巨噬细胞组小鼠接种布鲁氏菌疫苗后,髂内淋巴结中S-100阳性DC数量没有明显的变化,IFN-γ和IL-4的含量也没有明显的升高。非清除组中,不同的时间点,髂内淋巴结中S-100阳性DC明显增多,与PBS对照组相比,IFN-γ含量显著增高,而IL-4则没有明显变化。体外巨噬细胞负载布鲁氏菌疫苗发现,随着时间的延长,巨噬细胞吞噬布鲁氏菌逐渐增多,在12h,巨噬细胞开始出现坏死性凋亡。结论:小鼠在对布鲁氏菌疫苗的免疫应答中,DC的迁移是巨噬细胞依赖性的,并且这种依赖性有可能是由布鲁氏菌抗原成分在细胞间间接传递引起的。

关键词：巨噬细胞树突状细胞布鲁氏菌免疫应答

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迁移性树突状细胞与淋巴结内树突状细胞在抗***免疫应答中的作用

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中国免疫学杂志 2010年第8期26卷 675-678页

作者：曹志然董炳梅程君生王蓓何媛娜付景丽 nico van rooijen 丁家波毛开荣王家鑫河北大学医学部免疫学教研室保定071000 河北农业大学动物科技学院免疫学系保定071001 中国兽医药品监察所北京100081 Department of Molecular Cell Biology Faculty of MedicineVrije Universiteit Medisch Centrum

目的:研究迁移性树突状细胞与淋巴结内树突状细胞在抗猪布鲁氏菌免疫应答中的作用。方法:48只BALB/c小鼠随机分为3组:Ⅰ组为正常对照组,阴道滴注PBS;Ⅱ组为巨噬细胞(Mφ)清除组,每只小鼠阴道滴入清除剂;Ⅲ组为未清除Mφ组,每只小鼠阴道... 详细信息

目的:研究迁移性树突状细胞与淋巴结内树突状细胞在抗猪布鲁氏菌免疫应答中的作用。方法:48只BALB/c小鼠随机分为3组:Ⅰ组为正常对照组,阴道滴注PBS;Ⅱ组为巨噬细胞(Mφ)清除组,每只小鼠阴道滴入清除剂;Ⅲ组为未清除Mφ组,每只小鼠阴道滴注同体积的liposome-PBS;48小时后Ⅱ组、Ⅲ组均阴道接种猪布鲁氏菌,对照组阴道滴注PBS。各组小鼠分别在接种12、24、48和72小时采集血液和髂内淋巴结,采用免疫组织化学染色法观察淋巴结内树突状细胞(DC)的分布,用ELISA法检测血清中IFN-γ和IL-4的含量。结果:未清除Mφ组小鼠接种布鲁氏菌后髂内淋巴结内有大量DC迁移,至12小时血清IFN-γ水平显著增高,与对照组相比差异显著(P0.05)。结论:迁移性DC和淋巴结内DC在启动抗布鲁氏菌细胞免疫应答中均发挥重要作用,并具有协同作用的特点。

关键词：猪布鲁氏菌巨噬细胞树突状细胞淋巴结免疫应答

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Multisensory mechanisms of gait and balance in Parkinson’s disease:an integrative review

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Neural Regeneration Research 2025年第1期20卷 82-92页

作者： Stiven Roytman Rebecca Paalanen Giulia Carli Uros Marusic Prabesh Kanel Teus van Laar nico I.Bohnen Department of Radiology University of MichiganAnn ArborMIUSA Department of Neurology University of MichiganAnn ArborMIUSA Morris K.Udall Center of Excellence for Parkinson’s Disease Research University of MichiganAnn ArborMIUSA Institute for Kinesiology Research Science and Research Centre KoperKoperSlovenia Department of Health Sciences Alma Mater Europaea–ECMMariborSlovenia Parkinson’s Foundation Research Center of Excellence University of MichiganAnn ArborMIUSA Department of Neurology University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands Neurology Service and GRECC VA Ann Arbor Healthcare SystemAnn ArborMIUSA

Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging *** and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous *** effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory *** mechanisms which underpin the integration of these multisensory signals are the principal topic of the present *** multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older *** emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and *** the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s *** also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older ***,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.

关键词： aging balance encephalography functional magnetic resonance imaging gait multisensory integration Parkinson’s disease positron emission tomography somatosensory vestibular visual

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迁移性树突状细胞与淋巴结内树突状细胞在抗***免疫应答中的作用

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中国畜牧兽医学会动物传染病学分会第四次猪病防控学术研讨会

作者：董炳梅何媛娜付景丽 nico van rooijen 王家鑫河北农业大学动物科技学院免疫学实验室

目的:研究迁移性树突状细胞与淋巴结内树突状细胞在抗猪布鲁氏菌免疫应答中的作用。方法:48只BALB/c小鼠随机分为3组:Ⅰ组为正常对照组,阴道滴注PBS。Ⅱ组为巨噬细胞(MΦ)清除组,每只小鼠阴道滴入清除剂,Ⅲ组为未清除MΦ组,每只小鼠阴... 详细信息

目的:研究迁移性树突状细胞与淋巴结内树突状细胞在抗猪布鲁氏菌免疫应答中的作用。方法:48只BALB/c小鼠随机分为3组:Ⅰ组为正常对照组,阴道滴注PBS。Ⅱ组为巨噬细胞(MΦ)清除组,每只小鼠阴道滴入清除剂,Ⅲ组为未清除MΦ组,每只小鼠阴道滴注同体积的liposome-PBS。48h后Ⅱ组、Ⅲ组均阴道接种猪布鲁氏菌,对照组阴道滴注PBS。各组小鼠分别在12h,24h,48h和72h采集血液和髂内淋巴结,采用免疫组织化学染色法观察淋巴结内树突状细胞(DC)的分布,用ELISA法检测血清中IFN-γ和IL-4的含量。结果:未清除MΦ组小鼠接种布鲁氏菌后髂内淋巴结内有大量DC迁移,至12h血清IFN-γ水平显著增高,与对照组相比差异显著(p0.05)。结论:迁移性DC和淋巴结内DC在启动抗布鲁氏菌细胞免疫应答中均发挥重要作用,并具有协同作用的特点。

关键词：猪布鲁氏菌巨噬细胞树突状细胞淋巴结免疫应答

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A novel forecasting approach to schedule aggregated electric vehicle charging

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Energy and AI 2023年第4期14卷 522-535页

作者： nico Brinkel Lennard Visser Wilfried van Sark Tarek AlSkaif Copernicus Institute of Sustainable Development Utrecht UniversityPrincetonlaan 8aUtrecht3584 CBThe Netherlands Information Technology Group(INF) Wageningen University and Research(WUR)Hollandseweg 1Wageningen6706 KNThe Netherlands

To be able to schedule the charging demand of an electric vehicle fleet using smart charging,insight is required into different charging session characteristics of the considered fleet,including the number of charging sessions,their charging demand and arrival and departure *** use of forecasting techniques can reduce the uncertainty about these charging session characteristics,but since these characteristics are interrelated,this is not ***,forecasting frameworks that cover all required characteristics to schedule the charging of an electric vehicle fleet are absent in scientific *** cover this gap,this study proposes a novel approach for forecasting the charging requirements of an electric vehicle fleet,which can be used as input to schedule their aggregated charging *** the first step of this approach,the charging session characteristics of an electric vehicle fleet are translated to three parameter values that describe a virtual ***,optimal predictor variable and hyperparameter sets are *** serve as input for the last step,in which the virtual battery parameter values are *** approach has been tested on a real-world case study of public charging stations,considering a high number of predictor variables and different forecasting models(Multivariate Linear Regression,Random Forest,Artificial Neural Network and k-Nearest Neighbors).The results show that the different virtual battery parameters can be forecasted with high accuracy,reaching R^(2) scores up to 0.98 when considering 400 charging *** addition,the results indicate that the forecasting performance of all considered models is somehow similar and that only a low number of predictor variables are required to adequately forecast aggregated electric vehicle charging characteristics.

关键词： Forecasting Electric vehicle smart charging Electric vehicle aggregation Virtual battery method

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Molecular mechanisms of heavy metal tolerance and evolution in invertebrates

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Insect Science 2009年第1期16卷 3-18页

作者： Thierry K. S. Janssens Dick Roelofs nico M. van Straalen Department of Animal Ecology Institute of Ecological Science VU University Amsterdam The Netherlands

Following the genomics revolution, our knowledge of the molecular mechanisms underlying defenses against stress has been greatly expanded. Under strong selective pressure many animals may evolve an enhanced stress tolerance. This can be achieved by altering the structure of proteins （through mutations in the coding regions of genes） or by altering the amount of protein （through changes in transcriptional regulation）. The latter type of evolution can be achieved by substitutions in the promoter of the gene of interest （cisregulatory change） or by altering the structure or amount of transcriptional regulator proteins （trans-regulatory change）. The metallothionein system is one of the best studied stress response systems in the context of heavy metals. Metallothionein expression is assumed to be regulated by metal transcription factor 1 （MTF-1）; however, up to now the involvement of MTF- 1 has only been proven for some vertebrates and Drosophila. Data on invertebrates such as nematodes and earthworms suggest that other mechanisms of metallothionein induction may be present. A detailed study of Cd tolerance was done for a species of soilliving springtail, Orchesella cincta. The metallothionein gene of this species is overexpressed in metal-exposed field populations. Analysis of the metallothionein promoter has demon- strated extensive polymorphisms that have a fimctional significance, as shown in bioreporter assays. In a study comparing 20 different populations, the frequency of a high-expresser promoter allele was positively correlated with the concentration of metals in soil, especially Cd. The springtail study shows that cis-regulatory change of genes involved in the cellular stress response may contribute to evolution of metal tolerance.

关键词： Collembola evolution heavy metals metallothionein metal transcription factor 1 Orchesella cincta tolerance

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Application of the Point-Descriptor-Precedence representation for micro-scale traffic analysis at a non-signalized T-junction

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Geo-Spatial Information Science 2023年第3期26卷 406-430页

作者： Amna Qayyum Bernard De Baets Laure De Cock Frank Witlox Guy De Tré nico van de Weghe Department of Geography Ghent UniversityGhentBelgium Department of Data Analysis and Mathematical Modelling Ghent UniversityGhentBelgium Department of Telecommunications and Information Processing Ghent UniversityGhentBelgium

An intersection of two or more roads poses a risk for potential conflicts among *** the reasons triggering such conflicts are not clear,as they might be too subtle for the human *** environment also plays a part in understanding where,when,and why a particular vehicle interaction has occurred in a certain ***,it is of paramount importance to dive deeper into the vehicle interaction at a micro-scale within the embedded geographical environment,particularly at the *** would in turn assist in evaluating the association of vehicle interactions with conflict risks and near-miss ***,detection of such micro traffic interactions could also be used to improvise the complexity of the already established transport ***,traffic at intersections has been explored mainly for flow estimation,capacity and width measurements,and traffic congestion,etc.,whereas the detection of micro-scale traffic interactions at intersections remains relatively *** this paper,we present a novel approach to retrieve and represent micro-scale traffic movement interactions at a non-signalized T-junction by extending a recently introduced qualitative spatiotemporal Point-Descriptor-Precedence(PDP)*** study how the PDP representation offers a fine solution to study the interaction of traffic flows at *** permits tracking the micro-movement of vehicles in much finer detail,which is used later to retrieve movement patterns from a motion *** conventional approaches,we start our approach with the actual movements before modeling the static intersection ***,with the aid of illustrative examples,we discuss how the length,width,and speed of the vehicles can be exploited in our approach to detect specific patterns more ***,we address the potential benefits of our approach for traffic safety assessment and how it can be extended to a network of

关键词： Vehicle interaction traffic research pattern identification traffic safety spatiotemporal representation movement pattern

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Definition of colorectal anastomotic leakage: A consensus survey among Dutch and Chinese colorectal surgeons

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World Journal of Gastroenterology 2017年第33期23卷 6172-6180页

作者： Stefanus J van rooijen Audrey CHM Jongen Zhou-qiao Wu Jia-fu Ji Gerrit D Slooter Rudi MH Roumen nicole D Bouvy Department of Surgery Máxima Medical Center NUTRIM School of Nutrition and Translational Research in Metabolism Department of Surgery Maastricht University Medical Center Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Ward I of Gastrointestinal Cancer CenterPeking University Cancer Hospital and Institute

AIM To determine the level of consensus on the definition of colorectal anastomotic leakage(CAL) among Dutch and Chinese colorectal *** Dutch and Chinese colorectal surgeons were asked to partake in an online questionnaire. Consensus in the online questionnaire was defined as > 80% agreement between respondents on various statements regarding a general definition of CAL,and regarding clinical and radiological diagnosis of the *** Fifty-nine Dutch and 202 Chinese dedicated colorectal surgeons participated in the online survey. Consensus was found on only one of the proposed elements of a general definition of CAL in both countries: ‘extravasation of contrast medium after rectal enema on a CT scan'. Another two were found relevant according to Dutch surgeons: ‘necrosis of the anastomosis found during reoperation',and ‘a radiological collection treated with percutaneous drainage'. No consensus was found for all other proposed elements that may be included in a general *** There is no universally accepted definition of CAL in the Netherlands and China. Diagnosis of CAL based on clinical manifestations remains a point of discussion in both countries. Dutch surgeons are more likely to report ‘subclinical' leaks as CAL,which partly explains the higher reported Dutch CAL rates.

关键词： Colorectal anastomotic leakage Colorectal surgery Definition Complication

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Tumour suppressor microRNAs contribute to drug resistance in malignant pleural mesothelioma by targeting anti-apoptotic pathways

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Cancer Drug Resistance 2019年第4期2卷 1193-1206页

作者： Marissa Williams Yuen Yee Cheng Monica Phimmachanh Patrick Winata nico van Zandwijk Glen Reid Asbestos Diseases Research Institute Sydney NSW2139Australia Sydney Medical School The University of SydneySydney NSW2050Australia Current address:Sydney Local Health District ConcordSydney NSW2194Australia Current address:Department of Pathology University of OtagoDunedin 9016New Zealand Current address:Garvan Institute of Medical Research DarlinghurstSydney NSW2010Australia

Aim:Aberrant microRNA expression is a common event in cancer drug resistance,however its involvement in malignant pleural mesothelioma(MPM)drug resistance is largely *** aimed to investigate the contribution of microRNAs to the resistance to drugs commonly used in the treatment of ***:Drug resistant MPM cell lines were generated by treatment with cisplatin,gemcitabine or *** of microRNAs was quantified using *** and drug sensitivity assays were carried out following transfection with microRNA mimics or BCL2 siRNAs combined with ***:Expression of miR-15a,miR-16 and miR-34a was downregulated in MPM cells with acquired drug *** with miR-15a or miR-16 mimics reversed the resistance to cisplatin,gemcitabine or vinorelbine,whereas miR-34a reversed cisplatin and vinorelbine resistance ***,in parental cell lines,miR-15a or miR-16 mimics sensitised cells to all drugs,whereas miR-34a increased response to cisplatin and *** microRNA expression increased drug-induced apoptosis and caused BCL2 mRNA and protein ***-mediated knockdown of BCL2 partly recapitulated the increase in drug sensitivity in cisplatin and vinorelbine treated ***:Drug-resistant MPM cell lines exhibited reduced expression of tumour suppressor *** tumour suppressor of microRNA expression sensitised both drug resistant and parental cell lines to chemotherapeutic agents,in part through targeting of *** together,these data suggest that miR-15a,miR-16 and miR-34a are involved in the acquired and intrinsic drug resistance phenotype of MPM cells.

关键词： Malignant pleural mesothelioma miR-15a miR-16 miR-34a BCL2 apoptosis

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