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Scavenger receptor BI: A multi-purpose player in cholesterol and steroid metabolism

World Journal of Gastroenterology 2010年第47期16卷 591-5924页

作者： Menno Hoekstra Theo JC van Berkel miranda van eck Division of Biopharmaceutics Leiden/Amsterdam Center for Drug Research Gorlaeus Laboratories

Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of SR-BI in cholesterol and steroid metabolism. SR-BI in hepatocytes is the sole molecule involved in selective uptake of cholesteryl esters from high-density lipoprotein (HDL). SR-BI plays a physiological role in binding and uptake of native apolipoprotein B (apoB)-containing lipoproteins by hepatocytes, which identif ies SR-BI as a multipurpose player in lipid uptake from the blood circulation into hepatocytes in mice. In adrenocortical cells, SR-BI mediates the selective uptake of HDL-cholesteryl esters, which is eff iciently coupled to the synthesis of glucocorticoids (i.e. corticosterone). SR-BI knockout mice suffer from adrenal glucocorticoid insuff iciency, which suggests that functional SR-BI protein is necessary for optimal adrenal steroidogenesis in mice. SR-BI in macrophages plays a dual role in cholesterol metabolism as it is able to take up cholesterol associated with HDL and apoBcontaining lipoproteins and can possibly facilitate cholesterol efflux to HDL. Absence of SR-BI is associated with thrombocytopenia and altered thrombosis susceptibility, which suggests a novel role for SR-BI in regulating platelet number and function in mice. Transgenic expression of cholesteryl ester transfer protein in humanized SR-BI knockout mice normalizes hepatic delivery of HDL-cholesteryl esters. However, other pathologies associated with SR-BI def iciency, i.e. increased atherosclerosis susceptibility, adrenal glucocorticoid insuffi ciency, and impaired platelet function are not normalized, which suggests an important role for SR-BI in cholesterol and steroid metabolism in man. In conclusion, generation of SR-BI knockout mice has signif icantly contributed to our knowledge of the physiological role of SR-BI. Studies using these mice have identif ied SR-BI as a

关键词： Scavenger receptor class B type Ⅰ Highdensity lipoprotein Cholesterol Lipoprotein metabolism Liver Macrophages Adrenal gland Platelets Steroido- genesis

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CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University Medical Center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

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Leukocyte ABC-transporter A1 and LDL receptor play independent roles in atherosclerosis:the potential contribution of T cells

Leukocyte ABC-transporter A1 and LDL receptor play independe...

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第九届全国免疫学学术大会

作者： Ying Zhao Jun Wang Laura Calpe-Berdiel Amanda C.Foks Bart Lammers Johan Kuiper Theo J.C.van Berkel miranda van eck Department of Pathology and Pathophysiology Soochow University Division of Biopharmaceutics Leiden/Amsterdam Center for Drug ResearchLeiden University Institute of Biology and Medical Sciences Soochow University

Background:LDL receptor(LDLr)and ABC-transporter A1(ABCA1)are two distinct players in cellular cholesterol *** recognizes apoprotein B100 and apoE in lipoproteins to mediate the uptake of cholesterol,while ABCA1 promotes excess cholesterol efttux to apoprotein ***:The present study aims to investigate whether LDLr deficiency influences the atheroprotective effects of leukocyte ABCA1 in *** and Results:LDLr-/-mice were transplanted with bone marrow from LDLr/ABCA1mice,LDLr/ABCA1/-mice,and their respective *** leukocyte ABCA1 deficiency reduced plasma cholesterol levels,after 8weeks of Western-type diet feeding,animals transplanted with LDLr/ABCA1and LDLr/ABCA1bone marrow developed 1.6-fold(p<0.01)and 1.4-fold(p<0.05)larger lesions,compared to their respective *** clearly indicates that the atheroprotection of leukocyte ABCA1 is not affected by ***-way ANOVA analysis also demonstrated that deletion of the leukocyte LDLr reduced lesion development(p<0.001),especially in the absence of leukocyte ***,leukocyte LDLr deficiency did not affect monocytosis,recruitment of moncocytes and macrophage foam cell ***,the deletion of leukocyte ABCA1 did reduce lymphocytosis and recruitment of T cells into the adventitia of lesions,associated with smaller lesion size in LDLr/ABCA1transplanted mice,indicating the potential contribution of lymphocytosis and recruitment ofT cells to ***:Leukocyte LDLr deficiency does not affect the atheroprotective effects of leukocyte ***,suppression of lymphocytosis and recruitment of T cells in the adventitia could contribute to the atheroprotection of Leukocyte LDLr deficiency and ABCA1.

关键词： LDL receptor ABCA1 lymphocytosis T lymphocytes atherosclerosis

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Leukocyte ABC-transporter A1 and LDL Receptor Play Independent Roles in Atherosclerosis： the Potential Contribution of T Cells

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中国动脉硬化杂志 2013年第9期21卷 I0075-I0075页

作者： Ying Zhao Jun Wang Laura Calpe-Berdiel Amanda C. Foks Bart Lammers Johan Kuiper Theo J.C. van Berkel miranda van eck Department of Pathology and Pathophysiology Soochow University Suzhou Jiangsu 215123 China Division of Biopharmaeeutics leiden~Amsterdam Center for Drug Research leiden University leiden 2333 CCThe Netherlands Institute of Biology and Medical Sciences Soochow University Suzhou Jiangsu 215123 China

Objective The present study aims to investigate whether LDL receptor (LDLR) deficiency influences the atheroprotective effects of leukocyte ABC-transporter A1 (ABCA1) in vivo. Methods and Results LDLR -/- mice were transplanted with bone marrow from LDLR -/-/ABCA1 -/- mice, LDLR + / +/ABCA1 -/- mice, and their respective controls. Although leukocyte ABCA1defi- ciency reduced plasma cholesterol levels, after 8 weeks of Western-type diet feeding, animals transplanted with LDLR / /ABCA1 /- and LDLR + / +/ABCA1 -/- bone marrow developed 1.6-fold ( P < 0. 01 ) and 1.4-fold ( P < 0. 05 ) larger lesions, compared to their respective controls. This clearly indicates that the atheroprotection of leukocyte ABCA1 is not affected by LDLR. Two-way ANOVA analysis also demonstrated that deletion of the leukocyte LDLR reduced lesion development ( P < 0. 001 ) , especially in the absence of leukocyte ABCA1. However, leukocyte LDLR deficiency does not affect monocytosis, recruitment of moncocytes and macrophage foam cell formation. Interestingly, the deletion of leukocyte ABCA1did reduce lymphocytosis and recruitment of T cells into the ad- ventitia of lesions. These effects are associated with smaller lesion size in LDLR -/-/ABCA1 -/- transplanted mice, indicating the potential contribution of lymphocytosis and recruitment of T cells to atherogenesis. Conclusions Leukocyte LDLR deficiency does not affect the atheroprotective effects of leukocyte ABCA1, and vice versa. Furthermore, suppression of lymphocytosis and T cell re- cruitment into the adventitia could contribute to the atheroprotection of leukocyte LDLR deficiency and ABCA1.

关键词：低密度脂蛋白受体动脉粥样硬化 ABCA1 白细胞减少 T细胞转运子单核细胞增多淋巴细胞

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Leukocyte ABCA1 is atheroprotective in absence of ApoAI

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中国病理生理杂志 2012年第11期 2009-2009页

作者： Laura CALPE-BERDIEL Josep JULVE Joan Carles ESCOL-GIL Amanda FOKS Ronald J.van DER SLUIS Johan KUIPER Francisco BLANCO-VACA Theo J.C.van BERKEL Jan-Albert KUIVENHOVEN miranda van eck Department of Pathophysiology School of Biology and Basic Medical SciencesSoochow UniversitySuzhou 215123China IIB Sant Pau and CIBER de Diabetes y Enfermedades Metabólicas Asociadas CIBERDEMBarcelonaSpain 3. Division of BiopharmaceuticsLeiden/Amsterdam Center for Drug ResearchGorlaeus LaboratoriesLeiden UniversityLeidenNetherlands Departament de Bioquímicali Biologia Molecular Universitat Autònoma de BarcelonaBarcelonaSpain Department of Vascular Medicine Academic Medical CenterUniversity of AmsterdamAmsterdamNetherlands

AIM:ABC-transporter A1(ABCA1)facilitates cellular cholesterol efflux to lipid-free/poor apolipoproteins,including apolipoprotein AI(ApoAI).The aim of the present study was to investigate the importance of ApoAI for AB... 详细信息

关键词： Leukocyte ABCA1 is atheroprotective in absence of ApoAI

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Analyzing the activities of visitors of the Leiden Ranking website

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Journal of Data and Information Science 2018年第3期3卷 81-98页

作者： Nees Jan van eck Ludo Waltman Centre for Science and Technology Studies Leiden University

Purpose： To get a better understanding of the way in which university rankings are ***/methodology/approach： Detailed analysis of the activities of visitors of the website of the CWTS Leiden ***： Visitors of the Leiden Ranking website originate disproportionally from specific countries. They are more interested in impact indicators than in collaboration indicators, while they are about equally interested in size-dependent indicators and size-independent indicators. Many visitors do not seem to realize that they should decide themselves which criterion they consider most appropriate for ranking *** limitations： The analysis is restricted to the website of a single university ranking. Moreover, the analysis does not provide any detailed insights into the motivations of visitors of university ranking *** implications： The Leiden Ranking website may need to be improved in order to make more clear to visitors that they should decide themselves which criterion they want to use for ranking ***/value： This is the first analysis of the activities of visitors of a university ranking website.

关键词： CWTS Leiden Rankin University rankingg University ranking website Weblog analysis

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Investigation of Li-ion transport in Li7P3S11 and solid-state lithium batteries

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Journal of Energy Chemistry 2019年第11期28卷 1-7页

作者： Chuang Yu Swapna Ganapathy Ernst R.H.van eck Lambert van Eijck Niek de Klerk Erik M.Kelder Marnix Wagemaker Department of Radiation Science and Technology Delft University of TechnologyMekelweg 152629JB Delftthe Netherlands Institute for Molecules and Materials Radboud University NijmegenHeyendaalseweg 1356525 AJ Nijmegenthe Netherlands

The high Li-ion conductivity of the Li7P3S11 sulfide-based solid electrolyte makes it a promising candidate for all-solid-state lithium batteries. The Li-ion transport over electrode-electrolyte and electrolyteelectrolyte interfaces, vital for the performance of solid-state batteries, is investigated by impedance spectroscopy and solid-state NMR experiments. An all-solid-state Li-ion battery is assembled with the Li7P3S11 electrolyte, nano-Li2S cathode and Li-In foil anode, showing a relatively large initial discharge capacity of 1139.5 m Ah/g at a current density of 0.064 m A/cm^ 2 retaining 850.0 m Ah/g after 30 cycles. Electrochemical impedance spectroscopy suggests that the decrease in capacity over cycling is due to the increased interfacial resistance between the electrode and the electrolyte. 1D exchange ^7Li NMR quantifies the interfacial Li-ion transport between the uncycled electrode and the electrolyte, resulting in a diffusion coefficient of 1.70(3) ×10^-14cm^2/s at 333 K and an energy barrier of 0.132 e V for the Li-ion transport between Li2S cathode and Li7P3S11 electrolyte. This indicates that the barrier for Li-ion transport over the electrode-electrolyte interface is small. However, the small diffusion coefficient for Li-ion diffusion between the Li2S and the Li7P3S11 suggests that these contact interfaces between electrode and electrolyte are relatively scarce, challenging the performance of these solid-state batteries.

关键词： U7P3S11 Li-ion transport Spin-lattice NMR Exchange NMR Solid-state battery

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Understanding Genetic Load in Potato for Hybrid Diploid Breeding

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Molecular Plant 2019年第7期12卷 896-898页

作者： Christian W.B.Bachem Herman J.van eck Michiel E.de Vries Plant Breeding Wageningen University and Research Wageningen the Netherlands Solynta Wageningen the Netherlands

Recently, Zhang et al.(2019) have managed to provide abundant evidence to support long-held theories regarding mechanisms of inbreeding depression and potential effects of heterosis that are likely to have a considerable impact on potato breeding in the future (Figure 1). Despite its large genetic variation regarding yield, harvest index, and water use efficiency, potato breeding has attained only negligible advances in the most important breeding goals such as yield, tuber quality, and abiotic stress tolerance, and only modest progress in pathogen resistance. This low level of improvement is clearly due to the complexity of breeding a heterozygous tetraploid outbreeder rather than to the lack of genetic potential available in wild and cultivated material. In contrast, breeding at the diploid level, in particular in combination with self-compatibility, will allow the fixation of beneficial alleles to homozygosity.

关键词： Genetic Load Potato Hybrid Diploid Breeding

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Tomato fruit as a model for tissue-specific gene silencing in crop plants

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Horticulture Research 2020年第1期7卷 839-845页

作者： Ari Feder Sarah Jensen Anquan Wang Lance Courtney Lesley Middleton Joyce van eck Yongsheng Liu James J.Giovannoni Boyce Thompson Institute for Plant Research Cornell UniversityIthacaNYUSA Section of Plant Breeding and Genetics Cornell UniversityIthacaNYUSA School of Biotechnology and Food Engineering Hefei University of Technology230009 HefeiChina Section of Plant Biology Cornell UniversityIthacaNYUSA US Department of Agriculture–Agricultural Research Service Robert W.Holley Center for Agriculture and HealthIthacaNYUSA

Use of CRISPR-Cas9(Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)-CRISPR-associated 9)-mediated genome editing has proliferated for use in numerous plant species to modify gene function and expression,usually in the context of either transient or stably inherited genetic *** extremely useful in many applications,modification of some loci yields outcomes detrimental to further experimental evaluation or viability of the target *** of Cas9 under a promoter conferring gene knockouts in a tissue-specific subset of genomes has been demonstrated in insect and animal models,and recently in *** developed an in planta GFP(green fluorescent protein)assay system to demonstrate fruit-specific gene editing in tomato using a phosphoenolpyruvate carboxylase 2 gene *** then targeted a SET-domain containing polycomb protein,SlEZ2,previously shown to yield pleiotropic phenotypes when targeted via ^(35)S-driven RNA interference and we were able to characterize fruit phenotypes absent additional developmental ***-specific gene editing will have applications in assessing function of essential genes otherwise difficult to study via germline modifications and will provide routes to edited genomes in tissues that could not otherwise be recovered when their germline modification perturbs their normal development.

关键词： otherwise specific editing

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Management of gastroesophageal reflux disease: Patient and physician communication challenges and shared decision making

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World Journal of Clinical Cases 2018年第15期6卷 892-900页

作者： Scott Klenzak Igor Danelisen Grace D Brannan Melissa A Holland miranda AL van Tilburg Department of Psychiatry Cape Fear Valley Health System School of Osteopathic Medicine Campbell University College of Pharmacy and Health Sciences Campbell University Division of Gastroenterology and Hepatology School of Medicine University of North Carolina University of Washington

Gastroesophageal reflux disease(GERD) is a common upper esophageal condition and typical symptoms can include heartburn and sensation of regurgitation while atypical symptoms include chronic cough, asthma, hoarseness, dyspepsia and nausea. Typically, diag-nosis is presumptive given the presence of typical and atypical symptoms and is an indication for empiric therapy. Treatment management can include lifestyle modifications and/or medication therapy with proton pump inhibitor(PPI) class being the preferred and most effective. Complete symptom resolution is not always achieved and long-term PPI therapy can put patients at risk for serious side effects and needless expense. The brain-gut connection and hypervigilance plays an important role in symptom resolution and treatment success, especially in the case of non-PPI responders. Hypervigilance is a combination of increased esophageal sensory sensitivity in combination with exaggerated threat perception surrounding esophageal symptoms. Hypervigilance requires a different approach to GERD managements, where continued PPI therapy and surgery are usually not recommended. Rather, helping physicians and patients understand the brain-gut connection can guide and improve *** and reassurance should be the main pillars or treatment. However, it is important not to suggest the symptoms are due to anxiety alone, this often leads to patient dissatisfaction. Patient dissatisfaction with treatment reveals the need for a more patient-centered approach to GERD management and better communication between patients and providers. Shared decision making(SDM) with the incorporation of patient-reported outcomes(PRO) promotes patient adherence and satisfaction. SDM is a joint discussion between clinician and patient in which a mutually shared solution is explored for GERD symptoms. For SDM to work the physician needs to capture patients' perceptions which may not be obtained in the standard interview. This can be done through the

关键词： Gastroesophageal reflux disease Psychosocial Patient-physician communication Shared decision making Patient-reported outcomes Patient satisfaction

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