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The DNA-binding factor Ctcf critically controls gene expression in macrophages

Cellular & Molecular Immunology 2014年第1期11卷 58-70页

作者： Tatjana Nikolic Dowty Movita Margaretha EH Lambers Claudia Ribeiro de Almeida] Paula Biesta Kim Kreefft Marjolein JW de Bruijn Ingrid Bergen Niels Galjart Andre Boonstra Rudi Hendriks Department of Pulmonary Medicine Erasmus MC Rotterdam The Netherlands Department of Gastroenterology and Hepatology Erasmus MCRotterdam The Netherlands Department of Cell Biology and Genetics Erasmus MC Rotterdam The Netherlands Current address: Dr T Nikolic Department of Immunohematology and Blood Transfusion Leiden University Medical Center Leiden The Netherlands DrCR de Almeida Sir William Dunn School of Pathology University of Oxford Oxford UK. Both authors contributed equally

Macrophages play an important role in immunity and homeostasis. Upon pathogen recognition via specific receptors, they rapidly induce inflammatory responses. This process is tightly controlled at the transcriptional level. The DNA binding zinc-finger protein CCCTC-binding factor （Ctcf） is a crucial regulator of long-range chromatin interactions and coordinates specific communication between transcription factors and gene expression processes. In this study, the Ctcf gene was specifically deleted in myeloid cells by making use of the transgenic Cre-LoxP system. Conditional deletion of the Ctcfgene in myeloid cells induced a mild phenotype in vivo. Ctcf-deficient mice exhibited significantly reduced expression of major histocompatibility complex （MHC） class II in the liver. Ctcf-deficient macrophages demonstrated a normal surface phenotype and phagocytosis capacity. Upon Toll-like receptor （TLR） stimulation, they produced normal levels of the pro-inflammatory cytokines IL-12 and IL-6, but manifested a strongly impaired capacity to produce tumor-necrosis factor （TNF） and IL-IO, as well as to express the IL-IO family members IL-19, IL-20 and IL-24. Taken together, our data demonstrate a role of Ctcf that involves fine-tuning of macrophage function.

关键词： Ctcf IL-IO locus macrophage myeloid TLR

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Emerging analytical methods to characterize zeolite-based materials

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National Science Review 2022年第9期9卷 47-66页

作者： Sophie H.van Vreeswijk Bert M.Weckhuysen Inorganic Chemistry and Catalysis Debye Institute for NanomaterialsUtrecht University

Zeolites and zeolitic materials are,through their use in numerous conventional and sustainable applications,very important to our daily lives,including to foster the necessary transition to a more circular *** characterization of zeolite-based materials has a tremendous history and a great number of applications and properties of these materials have been discovered in the past *** review focuses on recently developed novel as well as more conventional techniques applied with the aim of better understanding zeolite-based *** explored analytical methods,*** probe tomography,scanning transmission X-ray microscopy,confocal fluorescence microscopy and photo-induced force microscopy,are discussed on their important contributions to the better understanding of zeolites as they mainly focus on the micro-to nanoscale chemical imaging and the revelation of structure-composition-performance *** other techniques have a long and established history,*** magnetic resonance,infrared,neutron scattering,electron microscopy and X-ray diffraction techniques,and have gone through increasing developments allowing the techniques to discover new and important features in zeolite-based *** to the increasing application of these methods,multiple techniques are nowadays used to study zeolites under working conditions(*** in situ/operando mode of analysis) providing new insights in reaction and deactivation mechanisms.

关键词： catalysis zeolites spectroscopy microscopy structure–composition–performance relationships

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Frequency-dependent resemblance of male-colored females to males in a damselfly

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Insect Science 2019年第5期26卷 958-962页

作者： Wicher Vos Jan Komdeur Martijn Hammers Behavioural and Physiological Ecology Groningen Institute for Evolutionary Life SciencesUniversity of GroningenGroningenThe Netherlands

Dear editor, Mimetic protection is most effective when mimics are relatively rare (Pfennig et al.,2001). In polymorphic damselfly species, male-colored female morphs may avoid costly male mating attempts because they are not immediately recognized as a suitable mating partner (van Gossum et al.,2008). We investigated morphological resemblance of male-colored females to males across six populations of the polymorphic blue-tailed damselfly lschmira elegans (Vander Linden). We found that male-colored females resembled males more closely with an increasing ratio of male-colored females to other female morphs. Our results suggest that the degree of mimetic fidelity is frequencydependent.

关键词： editor female populations

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Irreducibility Properties of Keller Maps

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Algebra Colloquium 2016年第4期23卷 663-680页

作者： Michiel de Bondt Dan Yan Department of Mathematics Radboud University Nijmegen The Netherlands Department of Mathematics and Computer ScienceHunan Normal University Changsha 410006 China

Jedrzejewicz showed that a polynomial map over a field of characteristic zero is invertible, if and only if the corresponding endomorphism maps irreducible polynomials to irreducible polynomials. Furthermore, he showed that a polynomial map over a field of characteristic zero is a Keller map, if and only if the corresponding endomorphism maps irreducible polynomials to square-free polynomials. We show that the latter endomorphism maps other square-free polynomials to square-free polynomials as well. In connection with the above classification of invertible polynomial maps and the Jacobian Conjecture, we study irreducibility properties of several types of Keller maps, to each of which the Jacobian Conjecture can be reduced. Herewith, we generalize the result of Bakalarski that the components of cubic homogeneous Keller maps with a symmetric Jacobian matrix （over C and hence any field of characteristic zero） are irreducible. Furthermore, we show that the Jacobian Conjecture can even be reduced to any of these types with the extra condition that each affinely linear combination of the components of the polynomial map is irreducible. This is somewhat similar to reducing the planar Jacobian Conjecture to the so-called （planar） weak Jacobian Conjecture by Kaliman.

关键词： Jacobian Conjecture Keller map irreducible square-free weak JacobianConjecture

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Absence of complementary sex determination in two Leptopilina species(Figitidae,Hymenoptera)and a reconsideration of its incompatibility with endosymbiont-induced thelytoky

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Insect Science 2022年第3期29卷 900-914页

作者： Fangying Chen Martijn Schenkel Elzemiek Geuverink Louis van de Zande Leo W.Beukeboom Groningen Institute for Evolutionary Life Sciences University of GroningenP.O.Box 11103 Groningen9700 CCthe Netherlands

Complementary sex determination(CSD)is a widespread sex determination mechanism in haplodiploid *** CSD,sex is determined by the allelic state of one or multiple CSD *** at one or more loci leads to female development,whereas hemizygosity of haploid eggs and homozygosity of diploid eggs results in male ***(arrhenotokous)reproduction normally yields haploid male and diploid female *** asexual reproduction(thelytoky),diploidized unfertilized eggs develop into *** is often induced by bacterial endosymbionts that achieve egg diploidization by gamete *** gamete duplication leads to complete homozygosity,endosymbiont-induced thelytokous reproduction is presumed to be incompatible with CSD,which relies on heterozygosity for female ***,we excluded CSD in four Asobara(Braconidae)species and proposed a two-step mechanism for Wolbachia-induced thelytoky in Asobara ***,we conclusively reject CSD in two cynipid wasp species,Leptopilina heterotoma and Leptopilina *** further show that thelytoky in *** depends on Wolbachia titer but that diploidization and feminization steps cannot be separated,unlike in *** discuss what these results reveal about the sex determination mechanism of *** and the presumed incompatibility between CSD and endosymbiont-induced thelytoky in the Hymenoptera.

关键词： arrhenotoky haplodiploidy inbreeding sex determination thelytoky Wolbachia bacteria

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Telaprevir/boceprevir era: From bench to bed and back

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World Journal of Gastroenterology 2012年第43期18卷 6183-6188页

作者： Maikel P Peppelenbosch Harry LA Janssen Robert J de Knegt Department of Gastroenterology and Hepatology Erasmus MC-University Medical Center 3015 CE Rotterdam The Netherlands

Hepatitis C virus (HCV) infects approximately 200 million people worldwide. Interferon-based therapies have dominated over the past two decades. However, the overall response rates remain suboptimal. Thanks to the tremendous effort from both academia and industry, two serine protease inhibitors telaprevir and boceprevir for treating chronic hepatitis C have finally reached the clinic. Although these compounds are only approved for combination use with interferon and ribavirin in genotype 1 HCV infected chronic patients, the management of HCV patients however is now evolving incredibly. Here, we overviewed a series of landmark studies, regarding the clinical development of telaprevir and boceprevir. We discussed the mechanism-of-action of telaprevir/boceprevir and their potential application in HCV-positive liver transplantation patients. We further emphasized some emerging concerns with perspective of further development in this field.

关键词： Telaprevir Boceprevir Mechanism-of-action Clinical efficacy Liver transplantation patient Interferon Ribavirin

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An INDEHISCENT-Controlled Auxin Response Specifies the Separation Layer in Early Arabidopsis Fruit

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Molecular Plant 2016年第6期9卷 857-869页

作者： Kasper van Gelderen Martin van Rongen An'an Liu Anne Otten Remko Offringa Molecular and DeveLopmental Genetics Institute of Biology Leiden Leiden University Sylviusweg 72 2333 BE Leiden the Netherlands These authors contributed equally to this article. Present address: Plant EcophysJology Institute of Environmental Biology Utrecht University 3584 CH Utrecht the Netherlands Present address: Sainsbury Laboratory 47 Sateman Street Cambridge CB2 1LR UK

Seed dispersal is an important moment in the life cycle of a plant species. In Arabidopsis thaliana, it is dependent on transcription factor INDEHISCENT （IND）-mediated specification of a separation layer in the dehiscence zone found in the margin between the valves （carpel walls） and the central replum of the developing fruit. It was proposed that IND specifies the separation layer by inducing a local auxin minimum at late stages of fruit development. Here we show that morphological differences between the ind mutant and wild-type fruit already arise at early stages of fruit development, coinciding with strong IND expression in the valve margin. We show that IND-reduced PIN-FORMED3 （PIN3） auxin efflux carrier abundance leads to an increased auxin response in the valve margin during early fruit develop- ment, and that the concomitant cell divisions that form the dehiscence zone are lacking in ind mutant fruit. Moreover, IND promoter-driven ectopic expression of the AGC kinases PINOID （PID） and WAG2 induced indehiscence by expelling auxin from the valve margin at stages 14-16 of fruit development through increased PIN3 abundance. Our results show that IND, besides its role at late stages of Arabi- dopsis fruit development, functions at early stages to facilitate the auxin-triggered cell divisions that form the dehiscence zone.

关键词： seed dispersal polar auxin transport PINOID INDEHISCENT separation layer Arabidopsis

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Understanding and tuning blue-to-near-infrared photon cutting by the Tm^(3+)/Yb^(3+) couple

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Light(Science & Applications) 2020年第1期9卷 992-1000页

作者： Dechao Yu Ting Yu Arnoldus Jvan Bunningen Qinyuan Zhang Andries Meijerink Freddy T.Rabouw Debye Institute for Nanomaterials Science Utrecht UniversityPrincetonplein 13584 CC UtrechtThe Netherlands State Key Laboratory of Luminescence Materials and Devices Institute of Optical Communication MaterialsSouth China University of TechnologyGuangzhou 510641China

Lanthanide-based photon-cutting phosphors absorb high-energy photons and‘cut’them into multiple smaller excitation *** quanta are subsequently emitted,resulting in photon-conversion efficiencies exceeding *** photon-cutting process relies on energy transfer between optically active lanthanide ions doped in the ***,it is not always easy to determine,let alone predict,which energy-transfer mechanisms are operative in a particular *** makes the identification and design of new promising photon-cutting phosphors *** we unravel the possibility of using the Tm^(3+)/Yb^(3+) lanthanide couple for photon *** compare the performance of this couple in four different host *** energy transfer from Tm^(3+)to Yb^(3+) would enable blue-to-near-infrared conversion with 200% ***,we identify phonon-assisted cross-relaxation as the dominant Tm^(3+)-to-Yb^(3+) energy-transfer mechanism in YBO_(3),YAG,and Y_(2)O_(3).In NaYF_(4),in contrast,the low maximum phonon energy renders phonon-assisted cross-relaxation impossible,making the desired cooperative mechanism the dominant energy-transfer *** work demonstrates that previous claims of high photon-cutting efficiencies obtained with the Tm^(3+)/Yb^(3+) couple must be interpreted with ***,the Tm^(3+)/Yb^(3+) couple is potentially promising,but the host material-more specifically,its maximum phonon energy-has a critical effect on the energy-transfer mechanisms and thereby on the photon-cutting performance.

关键词： couple phonon lanthanide

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Sensitivity analysis and calibration of the Modified Universal Soil Loss Equation(MUSLE) for the upper Malewa Catchment,Kenya

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International Journal of Sediment research 2013年第3期28卷 368-383页

作者： V.O.ODONGO J.O.ONYANDO B.M.MUTUA P.R.van OEL R.BECHT University of Twente Faculty of Geoinformation Science&Earth Observation(ITC) Egerton University Department of Agricultural Engineering Wageningen University Water Resources Management Group

Simulation models are widely used for studying physical processes such as surface runoff,sediment transport and sediment yield in *** models need case-specific empirical data for parameterization before being applied especially in regions other than the ones they have been *** analysis is usually performed to determine the most influential factors of a model so that they can be prioritized for *** this way uncertainties in model outputs can be reduced *** study evaluates the commonly used modified universal soil loss equation(MUSLE) model used for sediment yield simulation for the case of the upper Malewa catchment in *** conceptual factors of the model are assessed relative to the hydrological factors in the ***,the sensitivity of the model to the choice of the objective function in calibration is *** Sobol’ sensitivity analysis method was used for evaluating the degree of sensitivity of the conceptual and hydrological factors for sediment yield simulations using the MUSLE ***-Sutcliffe Efficiency(NSE) and the modified Nash-Sutcliffe Efficiency(NSEm) are used to test the sensitivity of the model to the choice of the objective function and robustness of model performance with sediment data measured from upper Malewa catchment,*** results indicate that the conceptual factors are the most sensitive factors of the MUSLE model contributing about 66%of the variability in the output sediment *** variability of sediment yield output was also *** was attributed to interactions of input *** the upper Malewa catchment calibration of the MUSLE model indicates that the use of NSEm as an objective function provides stable results,which indicates that the model can satisfactorily be applied for sediment yield simulations.

关键词： MUSLE Sobol’sensitivity analysis Sediment yield Objective function Upper Malewa catchment

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Taking advantage of drug resistance, a new approach in the war on cancer

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Frontiers of Medicine 2018年第4期12卷 490-495页

作者： Liqin Wang Rene Bernards Division of Molecular Carcinogenesis Oncode Institute The Netherlands Cancer Institute Plesmanlaan 121 1066 CX Amsterdam The Netherlands

Identification of the driver mutations in cancer has resulted in the development of a new category of molecularly targeted anti-cancer drugs. However, as was the case with conventional chemotherapies, the effectiveness of these drugs is limited by the emergence of drug-resistant variants. While most cancer therapies are given in combinations that are designed to avoid drug resistance, we discuss here therapeutic approaches that take advantage of the changes in cancer cells that arise upon development of drug resistance. This approach is based on notion that drug resistance comes at a fitness cost to the cancer cell that can be exploited for therapeutic benefit. We discuss the development of sequential drug therapies in which the first therapy is not given with curative intent, but to induce a major new sensitivity that can be targeted with a second drug that selectively targets the acquired vulnerability. This concept of collateral sensitivity has hitherto not been used on a large scale in the clinic and holds great promise for future cancer therapy.

关键词： cancer drug resistance genetic screens senescence targeted therapy

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