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

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.sant.goet. 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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Investigation of Instability of Lattice of Bi_2Sr_2CaCu_2O_x

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journal of Materials Science & Technology 1996年第3期12卷 175-179页

作者： Han ZHANG and Qingrong FENG (Dept. of Physics, Peking University, Beijing 100871, China)Y.Zhao(School of Materials Science and Engineering, University of New South Wales, Sydney 2052, NSW, Australia)F.Ritter and W.Assmus (Physikalisches Institut, j.W.goet Dept. of Physics Peking University Beijing 100871 China School of Materials Science and Engineering University of New South Wales Sydney NSW 2052 Australia Physikalisches Institut J.W.Goethe Universität 60054 Frankfurt am Main Germany

Bi2Sr2CaCu2Ox superconductor was studied by differential scanning calorimetry (DSC) and thermogravimetry (TG) in different atmospheres. It is discovered that there is a thermal anomaly in the DSC curve, associated with a weight loss in the TG curve before the melting of the sample. Careful thermal analysis and high temperature X-ray diffraction reveal that the thermal anomaly and the weight loss show an instability of the crystalline Iattice. By annealing the sample in oxygen and argon, respectively and then by TC measurement and thermal analysis, the coincidence of transition temperature with the instability is found. The coincidence is further confirmed by Y-doped 2212 phase.

关键词： Sr Bi

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Depicting the battle between nectarine and Monilinia laxa:the fruit developmental stage dictates the effectiveness of the host defenses and the pathogen’s infection strategies

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Horticulture Research 2020年第1期7卷 619-633页

作者： Marta Balsells-Llauradó Christian j.Silva josep Usall Núria Vall-llaura Sandra Serrano-Prieto Neus Teixidó saskia D.Mesquida-Pesci Antonieta de Cal Barbara Blanco-Ulate Rosario Torres IRTA XaRTA-PostharvestEdifici FruitcentreParc Científic i Tecnològic Agroalimentari de Lleida25003 LleidaCataloniaSpain Department of Plant Sciences University of CaliforniaDavisDavisCA 95616USA Department of Plant Protection INIACtra.de La Coruña Km.728040 MadridCommunity of MadridSpain

Infections by the fungus Monilinia laxa,the main cause of brown rot in Europe,result in considerable losses of stone ***,we present a comprehensive transcriptomic approach to unravel strategies deployed by nectarine fruit and *** during their *** used ***-inoculated immature and mature fruit,which was resistant and susceptible to brown rot,respectively,to perform a dual RNA-Seq *** immature fruit,host responses,pathogen biomass,and pathogen transcriptional activity peaked at 14–24 h post inoculation(hpi),at which point *** appeared to switch its transcriptional response to either quiescence or *** fruit experienced an exponential increase in host and pathogen activity beginning at 6 *** analyses in both host and pathogen highlighted differences in stage-dependent *** example,in immature fruit,*** unsuccessfully employed carbohydrate-active enzymes(CAZymes)for penetration,which the fruit was able to combat with tightly regulated hormone responses and an oxidative burst that challenged the pathogen’s survival at later time *** contrast,in mature fruit,*** was more dependent on proteolytic effectors than CAZymes,and was able to invest in filamentous growth early during the *** analyses of mature fruit infected with *** indicated that,while jasmonic acid activity was likely useful for defense,high ethylene activity may have promoted susceptibility through the induction of ripening ***,we identified *** genes that were highly induced in both quiescent and active infections and may serve as targets for control of brown rot.

关键词： fruit pathogen strategies

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An optimized medial parapatellar approach to the goat medial femoral condyle

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Animal Models and Experimental Medicine 2021年第1期4卷 54-58页

作者： Pieter P.W.van Hugten Ralph M.jeuken Alex K.Roth saskia Seeldrayers Peter j.Emans Laboratory for Experimental Orthopedics Department of Orthopedic SurgeryMaastricht University Medical CenterMaastrichtThe Netherlands Laboratory Animal Facility Maastricht UniversityMaastrichtThe Netherlands

Goats or sheep are the preferred animal model for the preclinical evaluation of cartilage repair techniques due to the similarity of the goat stifle joint to the human *** medial femoral condyle of the stifle joint is the preferred site for the assessment of articular cartilage repair,as this is the primary location for this type of lesion in the human *** surgical exposure of the medial femoral condyle is paramount to obtain reproducible results without surgical *** applying the standard human medial arthrotomy technique on the goat stifle joint,there are some key aspects to consider in order to prevent destabilization of the extensor apparatus and subsequent postoperative patellar dislocations with associated animal *** paper describes a modified surgical technique to approach the medial femoral condyle of the caprine stifle *** modified technique led to satisfactory exposure without postoperative incidence of patellar luxations and no long-term adverse effects on the joint.

关键词： approach arthrotomy cartilage condyle goats

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Bacterial Vector-Borne Plant Diseases:Unanswered Questions and Future Directions

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Molecular Plant 2020年第10期13卷 1379-1393页

作者： Weijie Huang Paola Reyes-Caldas Marina Mann Shirin Seifbarghi Alexandra Kahn Rodrigo P.P.Almeida Laure Béven Michelle Heck saskia A.Hogenhout Gitta Coaker Department of Crop Genetics John Innes CentreNorwich Research ParkNorwich NR47UHUK Department of Plant Pathology University of CaliforniaDavisCA95616USA Department of Plant Pathology and Plant-Microbe Biology Cornell UniversityIthacaNY 14853USA Department of Environmental Science Policy and ManagementUniversity of CaliforniaBerkeleyCA 94720USA UMR 1332 Biologie du Fruit et Pathologie Univ.BordeauxINRAEVillenave d'Ornon 33882 France Boyce Thompson Institute IthacaNY 14853USA Emerging Pests and Pathogens Research Unit Robert W.Holley CenterUSDA ARSIthacaNY 14853USA School of Environmental Sciences University of East AngliaNorwich Research ParkNorwich NR47T JUK

Vector-borne plant diseases have significant ecological and economic impacts,affecting farm profitability and forest composition throughout the *** vector-borne pathogens have evolved sophisticated strategies to interact with their hemipteran insect vectors and plant *** pathogens reside in plant vascular tissue,and their study represents an excellent opportunity to uncover novel biological mechanisms regulating intracellular pathogenesis and to contribute to the control of some of the world's most invasive emerging *** this perspective,we highlight recent advances and major unanswered questions in the realm of bacterial vector-borne disease,focusing on liberibacters,phytoplasmas,spiroplasmas,and Xylella fastidiosa.

关键词： liberibacter phytoplasma spiroplasma Xylella fastidiosa vector-borne disease effector plant immunity

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Long-term live-cell microscopy with labeled nanobodies delivered by laser-induced photoporation

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Nano Research 2020年第2期13卷 485-495页

作者： jing Liu Tim Hebbrecht Toon Brans Eef Parthoens saskia Lippens Chengnan Li Herlinde De Keersmaecker Winnok H.De Vos Stefaan C.De Smedt Rabah Boukherroub jan Gettemans Ranhua Xiong Kevin Braeckmans Laboratory of General Biochemistry and Physical Pharmacy Faculty of PharmacyGhent UniversityGhent B-9000Belgium Department of Biomolecular medicine Faculty of Medicine and Health SciencesGhent UniversityGhent B-9000Belgium VIB-UGent Center for Inflammation Research VIBGhent B-9000Belgium VIB Bioimaging Core Ghent VIBGhent B-9000Belgium Department of Biomedical Molecular Biology Ghent UniversityGhent B-9000Belgium Univ.Lille CNRSCentrale LilleISENUniv.ValenciennesUMR 8520-IEMNLille F-59000Franc Laboratory of Cell Biology and Histology Department of Veterinary SciencesUniversity of Antwerp2020 AntwerpBelgium Centre for Advanced Light Microscopy Ghent UniversityGhent B-9000Belgium

Fluorescence microscopy is the method of choice for studying intracellular ***,its success depends on *** of specific and stable markers.A prominent example of markers that are rapidly gaining interest are nanobodies(Nbs.-15 kDa),which can be functionalized with bright and photostable organic *** to their relatively small size and high specificity,Nbs offer great potential for high-quality long-term subcellular imaging,but suffer from the fact that they cannot spontaneously cross the plasma membrane of live *** have recently discovered that laser-induced photoporation is well suited to deliver extrinsic labels to living cells without compromising their *** a laser-based technology,it is readily compatible with light microscopy and the typical cell recipients used for *** by these promising initial results,we demonstrate here for the first time successful long-term imaging of specific subcellular structures with labeled nanobodies in living *** illustrate this using Nbs that target GFP/YFP-protein constructs accessible in the cytoplasm,actin-bundling protein Fascin,and the histone H2A/H2B *** an efficiency of more than 80%labeled cells and minimal toxicity(-2%),photoporation proved to be an excellent intracellular delivery method for ***-lapse microscopy revealed that cell division rate and migration remained unaffected,confirming excellent cell viability and *** conclude that laser-induced photoporation labeled Nbs can be easily delivered into living cells,laying the foundation for further development of a broad range of Nbs with intracellular targets as a toolbox for long-term live-cell microscopy.

关键词： laser-induced photoporation vapor nanobubble long-term microscopy imaging nanobody intracellular delivery living cell labeling

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Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods

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Cellular & Molecular Immunology 2021年第4期18卷 936-944页

作者： Berislav Bosnjak saskia Catherina Stein Stefanie Willenzon Anne Katrin Cordes Wolfram Puppe Gunter Bernhardt Inga Ravens Christiane Ritter Christian R.Schultze-Florey Nina Godecke jorg Martens Hannah Kleine-Weber Markus Hoffmann Anne Cossmann Mustafa Yilmaz Isabelle Pink Marius M.Hoeper Georg M.N.Behrens Stefan Pohlm ann Rainer Blasczyk Thomas F.Schulz Reinhold Forster Institute of Immunology Hannover Medical SchoolHannoverGermany lnstitute of Virology Hannover Medical SchoolHannoverGermany Department of Hematology HemostasisOncology and Stem Cell TransplantationHannover Medical SchoolHannoverGermany Institute of Transfusion Medicine and Transplant Engineering Hannover Medical SchoolHannoverGermany German Primate Center-Leibniz Institute for Primate Research GottingenGermany Faculty of Biology and Psychology University GottingenGottingenGermany Department of Rheum atology and Immunology Hannover Medical SchoolHannoverGermany Public Health Department HannoverGermany Department of Pneumology and German Centre of Lung Research(DZL) Hannover Medical SchoolHannoverGermany German Center for Infection Research(DZIF) partner site Hannover-BraunschweigHannoverGermany Cluster of Excellence RESIST(EXC 2155) Hannover Medical SchoolHannoverGermany

Neutralizing antibodies targeting the receptor-binding domain(RBD)of the SARS-CoV-2 spike(S)block severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry into cells via surface-expressed angiotensin-converting enzyme 2(ACE2).We used a surrogate virus neutralization test(sVNT)and SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus(VSV)vector-based neutralization assay(pVNT)to assess the degree to which serum antibodies from coronavirus disease 2019(COVID-19)convalescent patients interfere with the binding of SARS-CoV-2 S to *** tests revealed neutralizing anti-SARS-CoV-2 S antibodies in the sera of ~90% of mildly and 100% of severely affected COVID-19 convalescent ***,sVNT and pVNT results correlated strongly with each other and to the levels of anti-SARS-CoV-2 S1 IgG and IgA ***,levels of neutralizing antibodies correlated with the duration and severity of clinical symptoms but not with patient *** to pVNT,sVNT is less sophisticated and does not require any biosafety *** this assay is also much faster and cheaper,sVNT will not only be important for evaluating the prevalence of neutralizing antibodies in a population but also for identifying promising plasma donors for successful passive antibody therapy.

关键词： COVID-19 SARS-CoV-2 Neutralizing antibody Serum ELISA

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干辣椒风味物质气相色谱及质谱方法的研究

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辣椒杂志 2007年第1期5卷 41-47页

作者： saskia van Ruth Elena Boscaini Dagmar Mayr jonathan Pugh Maarten Posthumus 刘蓉刘志敏食品学院食品科学与营养专业科克大学 Institut für Ionenphysik利奥波德-费的南大学因思布鲁克市奥地利256020 应用研究实验室 MicromassUK.Ltd. 有机化学实验室食品学院Wageningen大学研究中心不详

用嗅觉测量法-气相色谱联用(GC-O),火焰离子检测器-气相色谱联用(GC-FID),质谱-气相色谱联用(GC-MS)三种气相色谱检测方法和常压化学离子化飞行时间质谱(APCI-TOFMS),质子传递反应质谱(PTR-MS)两种直接质谱检测方法来比较测定干辣椒中... 详细信息

用嗅觉测量法-气相色谱联用(GC-O),火焰离子检测器-气相色谱联用(GC-FID),质谱-气相色谱联用(GC-MS)三种气相色谱检测方法和常压化学离子化飞行时间质谱(APCI-TOFMS),质子传递反应质谱(PTR-MS)两种直接质谱检测方法来比较测定干辣椒中的挥发性香味成分。干辣椒的挥发性香味成分的大体描述最后由感官评定来确定。三种较显著的风味分别是:辣椒味、煮熟蔬菜味和青草味。用气质联用顶空分析法共有63种挥发性香味成分被分离出来。而嗅觉测量法-气相色谱联用(GC-O)认为其中的11种成分决定了辣椒的香味活跃程度。在所有的方法中普遍认为:3-甲基正丁醛是最活跃的香味成份,其次是2-甲基正丁醛。确定挥发性香味成分的多少主要是受测定方法的影响。色谱方法之间有很强的相关性(ρ=0.946)。直接质谱法相关性不显著(ρ=0.613)。经过不同方法的分析,我们发现,用GC-MS,GC-FID和PTR-MS三种方法检测出的挥发性香味成分并没有显著的不同,显著性的差异主要存在于PCI-TOFMS法和其工艺的不同(Pj Mass Spectrom223-224(2003)55-65)

关键词： APCI-TOFMS GC-FID GC-MS GC-O PTR-MS

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新生儿期接受体外膜氧合治疗的患儿5岁时的健康状况研究

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中国小儿急救医学 2013年第2期 126-126页

作者： Marlous j saskia j Hugo D 杨明北京和睦家医院

目的新生儿期接受过体外膜氧合(ECMO)治疗,日后可能出现体格和精神发育方面的问题。我们采用标准化数据比较了此类患儿的健康相关生存质量(health-related qualityof life,HRQOL)。设计前瞻性纵向追踪随访研究。场所一所三级大学医院的... 详细信息

目的新生儿期接受过体外膜氧合(ECMO)治疗,日后可能出现体格和精神发育方面的问题。我们采用标准化数据比较了此类患儿的健康相关生存质量(health-related qualityof life,HRQOL)。设计前瞻性纵向追踪随访研究。场所一所三级大学医院的门诊。对象1999年1月至2005年12月间在新生儿期曾接受过ECMO治疗的95例5岁儿童。干预无。测量指标和主要结果患儿5岁时采用儿童生存质量调查表(pediatric quality of life inventory,PedsQL)进行评估。对自己孩子进行了评估的74例患儿母亲较健康对照儿童家长的PedsQL打分明显偏低,反映HRQOL较差(平均差8.1,P<0.001)。31例(42%)患儿母亲的评分提示患儿HRQOL受损(低于正常参考范围1个标准差)。78例患儿给自己的评分显著低于健康对照儿童(平均差11.0,P<0.001),其中32例评分提示他们自己的HRQOL受损。从患儿母亲的评分结果看,ECMO治疗时间(R~2=0.009,P=0.010),合并慢性肺疾病(R~2=0.133,P=0.002)与总评分呈负相关。患儿5岁时神经运动功能、最大运动能力、行为、认知受损者生存质量也较差,但对患儿的情绪状况没有影响。结论新生儿期曾接受过ECMO治疗的患儿在5岁时HRQOL总体较差。因为情绪状况与健康状况未呈相关性,PedsQL更适合作健康状况评价,而非HRQOL评价工具。与其他研究者的结论相反,我们认为5岁儿童可能年龄太小,不适于对健康相关生存质量作自我评价。

关键词：体外膜氧合随访研究新生儿发病率生存质量自我报告

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