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Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia

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Genes & Diseases 2024年第1期11卷 413-429页

作者： Dongsheng Zhang Wenjuan Tang haitao Niu William Tse hai-Bin Ruan helmut Dolznig Thomas Knosel friedrich Karl-heinz Madeleine Themanns Jiang Wang Mingquan Song Lee Denson Lukas Kenner Richard Moriggl Yi Zheng Xiaonan han Division of hematology and Oncology Division of Cancer BiologyDepartment of MedicineMetroHealth Medical Center(MHMC)Case Western Reserve University(CWRU)School of MedicineClevelandOH 44109USA Cancer Genomics and Epigenomics Program Case Comprehensive Cancer CenterCase Western Reserve University(CWRU)ClevelandOH 44106USA Division of Gastroenterology Hepatology and NutritionCincinnati Children’s Hospital Medical Center(CCHMC)CincinnatiOH 45229USA Children’s hospital of Fudan University Shanghai 201102China School of Medicine Jinan UniversityGuangzhouGuangdong 510632China Laboratory Animal Science(ILAS) Chinese Academy of Medical Science(CAMS)and Peking Union Medical College(PUMC)Beijing 100006China Department of Integrative Biology and Physiology University of Minnesota Medical SchoolMinneapolisMI 55455USA Institute of Medical Genetics Medical University of ViennaVienna 1040Austria Institute of Pathology Ludwig-Maximilians-University MunichMunich 80539Germany Institute of Biochemistry II University Hospital JenaJena 07743Germany Laboratory Animal Pathology University of Veterinary Medicine ViennaVienna 1210Austria Department of Pathology University of CincinnatiCincinnatiOH 45221USA Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266005China Department of Pathology Medical University of ViennaVienna 1040Austria Ludwig Boltzmann Institute for Cancer Research Vienna 1090Austria Medical University of Vienna Vienna 1040Austria Institute of Animal Breeding and Genetics University of Veterinary Medicine ViennaVienna 1210Austria Division of Experimental hematology CCHMCCincinnatiOH 45229USA

CDC42 controls intestinal epithelial(IEC)stem cell(IESC)*** aberrant CDC42 initiates intestinal inflammation or neoplasia is *** utilized models of inflam-matory bowel diseases(IBD),colorectal cancer,aging,and IESC injury to determine the loss of intestinal Cdc42 upon inflammation and *** specimens were collected to determine the levels of CDC42 in IBD or colorectal ***42 floxed mice were crossed with Villin-Cre,Villin-CreERT2 and/or Lgr5-eGFP-IRES-CreERT2,or Bmi1-CreERT2 mice to generate Cdc42 deficient ***,colitis,aging,and intestinal organoid were used to evaluate CDC42 upon mucosal inflammation,IESC/progenitor regenerative capacity,and IEC *** studies revealed that increased CDC42 in colorectal cancer correlated with lower survival;in contrast,lower levels of CDC42 were found in the inflamed IBD *** Cdc42 depletion significantly reduced Lgr5+IEsCs,increased progenitors'hyperplasia,and induced mucosal inflammation,which led to crypt *** Cdc42 depletion markedly enhanced irra-diation-or chemical-induced *** or inhibition of Cdc42 reduced colonic Lgr5+IESC *** conclusion,depletion of Cdc42 reduces the IESC regeneration and IEC repair,leading to prolonged mucosal *** monogenic loss of Cdc42 in-duces mucosal inflammation,which could result in intestinal neoplasia in the context of aging.

关键词： Cell divisioncycle 42(CDC42) Colitis Colorectal cancer(CRC) Inflammatory bowel diseases(IBD) Intestinal epithelial cell(IEC) Intestinal epithelial stem cell(IESC) Irradiation

B-cell and antibody responses to SARS-CoV-2:infection,vaccination,and hybrid immunity

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Cellular & Molecular Immunology 2024年第2期21卷 144-158页

作者： Dennis Lapuente Thomas h.Winkler Matthias Tenbusch Institut für klinische und molekulare Virologie Universitätsklinikum Erlangen und Friedrich-Alexander-Universität(FAU)Erlangen-NürnbergSchlossgarten 491054 ErlangenGermany Department of Biology Division of GeneticsNikolaus-Fiebiger-Center for Molecular MedicineFriedrich-Alexander-Universität Erlangen-Nürnberg(FAU)ErlangenGermany Medical Immunology Campus Erlangen Friedrich-Alexander-Universität(FAU)Erlangen-NürnbergSchlossplatz 191054 ErlangenGermany

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in 2019 prompted scientific,medical,and biotech communities to investigate infection-and vaccine-induced immune responses in the context of this pathogen.B-cell and antibody responses are at the center of these investigations,as neutralizing antibodies(nAbs)are an important correlate of protection(COP)from infection and the primary target of SARS-CoV-2 vaccine *** addition to absolute levels,nAb longevity,neutralization breadth,immunoglobulin isotype and subtype composition,and presence at mucosal sites have become important topics for scientists and health policy *** recent pandemic was and still is a unique setting in which to study de novo and memory B-cell(MBC)and antibody responses in the dynamic interplay of infection-and vaccine-induced *** also provided an opportunity to explore new vaccine platforms,such as mRNA or adenoviral vector vaccines,in unprecedented cohort *** with the technological advances of recent years,this situation has provided detailed mechanistic insights into the development of B-cell and antibody responses but also revealed some unexpected *** this review,we summarize the key findings of the last 2.5 years regarding infection-and vaccine-induced B-cell immunity,which we believe are of significant value not only in the context of SARS-CoV-2 but also for future vaccination approaches in endemic and pandemic settings.

关键词： SARS-CoV-2 neutralizing antibodies memory responses vaccines IgG4

Next generation multiple access for IMT towards 2030 and beyond

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Science China(Information Sciences) 2024年第6期67卷 448-450页

作者： Zhiguo DING Robert SChOBER Pingzhi FAN h.Vincent POOR Department of Computer and Information Engineering Khalifa University Department of Electrical and Electronic Engineering University of Manchester Institute for Digital Communications Friedrich Alexander-University Erlangen-Nurnberg (FAU) CSNMT International Cooperation Research Center (MoST) Southwest Jiaotong University Department of Electrical and Computer Engineering Princeton University

Multiple access techniques are fundamental to the design of wireless communication systems,since many crucial components of such systems depend on the choice of the multiple access technique[1].For example,the use of ...

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Primary carbohydrate metabolism genes participate in heat-stress memory at the shoot apical meristem of Arabidopsis thaliana

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Molecular Plant 2024年第4期17卷 676-676页

作者： Justyna Jadwiga Olas Federico Apelt Maria Grazia Annunziata Sheeba John Sarah Isabel Richard Saurabh Gupta friedrich Kragler Salma Balazadeh Bernd Mueller-Roeber 不详

(Molecular Plant 14,1508-1524,September 62021)After the original publication of the above article,attentive readers identified errors in Figure 4h that needed correction as *** 4h contained the erroneous labels“10 DAP(7 DAT),”which should have each read,“7 DAP(4 DAT).”To avoid any confusion and ensure consistency across our figures,we modified some of the Col-0 images in a corrected version of Figure 4h below to resemble the exact same Col-0 images as in Figure *** details of the changes are as follows:rotation(Col-0 Primed,all timepoints;Col-0 Triggered,3 DAP and 5 DAP;Col-0 Primed/triggered,3 DAP and 5 DAP),replacement(Col-0 Triggered,7 DAP),and different cropping(Col-0 Primed/triggered,7 DAP).

关键词： Figure metabolism Prime

Foam rolling and stretching do not provide superior acute flexibility and stiffness improvements compared to any other warm-up intervention: A systematic review with meta-analysis

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Journal of Sport and health Science 2024年第4期13卷 509-520页

作者： Konstantin Warneke Gerit Plöschberger Lars h.Lohmann Eric Lichtenstein Daniel Jochum Stanislav D.Siegel Astrid Zech David G.Behm Institute of Sport Science University of KlagenfurtKlagenfurt am Wörthersee 9020Austria Department of human Motion Science and Exercise Physiology Friedrich Schiller UniversityJena 07749Germany Department Sport Exercise and HealthUniversity of BaselBasel 4052Switzerland Department of health Sciences and Technology ETH ZurichZurich 8092Switzerland School of human Kinetics and Recreation Memorial University of NewfoundlandSt.JohnsNL A1C 5S7Canada

Background:Acute improvement in range of motion(ROM)is a widely reported effect of stretching and foam rolling,which is commonly explained by changes in pain threshold and/or musculotendinous ***,these effects were also reported in response to various other active and passive interventions that induce responses such as enhanced muscle ***,we hypothesized that acute ROM enhancements could be induced by a wide variety of interventions other than stretching or foam rolling that promote an increase in muscle ***:After a systematic search in PubMed,Web of Science,and SPORTDiscus databases,38 studies comparing the effects of stretching and foam rolling with several other interventions on ROM and passive properties were *** studies had 1134 participants in total,and the data analysis resulted in 140 effect sizes(ESs).ES calculations were performed using robust variance estimation model with ***:Study quality of the included studies was classified as fair(PEDro score=4.58)with low to moderate certainty of *** showed no significant differences in ROM(ES=0.01,p=0.88),stiffness(ES=0.09,p=0.67),or passive peak torque(ES=-0.30,p=0.14)between stretching or foam rolling and the other identified *** plots revealed no publication ***:Based on current literature,our results challenge the established view on stretching and foam rolling as a recommended component of warm-up *** lack of significant difference between interventions suggests there is no need to emphasize stretching or foam rolling to induce acute ROM,passive peak torque increases,or stiffness reductions.

关键词： Range of motion Passive properties Muscletendon unit Muscle tissue

Beyond cost reduction:improving the value of energy storage in electricity systems

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碳中和(英文) 2022年第1期1卷 257-277页

作者： Maximilian Parzen Fabian Neumann Adriaan h.Van Der Weijde Daniel friedrich Aristides Kiprakis University of Edinburgh Institute for Energy SystemsEH93DW EdinburghUK Technische Universität Berlin Department of Digital Transformation in Energy Systems10587 BerlinGermany The Netherlands Organization for Applied Scientific Research(TNO) 2595 DA The HagueThe Netherlands

From a macro-energy system perspective,an energy storage is valuable if it contributes to meeting system objectives,including increasing economic value,reliability and *** most energy systems models,reliability and sustainability are forced by constraints,and if energy demand is exogenous,this leaves cost as the main metric for economic *** ways to improve storage technologies are to reduce their costs;however,the cheapest energy storage is not always the most valuable in energy *** techno-economical evaluation methods try to address the cost and value situation but do not judge the competitiveness of multiple technologies *** paper introduces the‘market potential method’as a new complementary valuation method guiding innovation of multiple energy *** market potential method derives the value of technologies by examining common deployment signals from energy system model outputs in a structured *** apply and compare this method to cost evaluation approaches in a renewables-based European power system model,covering diverse energy storage *** find that characteristics of high-cost hydrogen storage can be more valuable than low-cost hydrogen ***,we show that modifying the freedom of storage sizing and component interactions can make the energy system 10% cheaper and impact the value of *** results suggest looking beyond the pure cost reduction paradigm and focus on developing technologies with suitable value approaches that can lead to cheaper electricity systems in future.

关键词： Battery hydrogen Energy storage Energy system modelling Techno-economic analysis Technology development

Use of ionic liquid in leaching process of brass wastes for copper and zinc recovery

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International Journal of Minerals,Metallurgy and Materials 2014年第2期21卷 138-143页

作者： Ayfer Kilicarslan Muhlis Nezihi Saridede Srecko Stopic Bernd friedrich Department of Metallurgical and Materials Engineering (Davutpasa Campus) Yildiz Technical University Department of Process Metallurgy and Metal Recycling (IME) RWTH Aachen University

Brass ash from the industrial brass manufacturer in Turkey was leached using the solutions of ionic liquid （IL） 1-butyl-3-methyl-imi-dazolium hydrogen sulfate （[bmim]hSO4） at ambient pressure in the presence of hydrogen peroxide （h2O2） and potassium peroxymonosulfate （oxone） as the oxidants. Parameters affecting leaching efficiency, such as dissolution time, IL concentration, and oxidizing agent addition, were investigated. The results show that [bmim]hSO4 is an efficient IL for the brass ash leaching, providing the dissolution efficiencies of 99%for Zn and 24.82%for Cu at a concentration of 50vol%[bmim]hSO4 in the aqueous solution without any oxidant. however, more than 99%of zinc and 82%of copper are leached by the addition of 50vol%h2O2 to the [bmim]hSO4 solution. Nevertheless, the oxone does not show the promising oxidant behavior in leaching using [bmim]hSO4.

关键词： leaching recovery copper zinc ionic liquids oxidants

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The book of palms

Establishment,functional and genetic characterization of a colon derived large cell neuroendocrine carcinoma cell line

作者： Carl friedrich Philipp von Martius text by h. Walter Lack.

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World Journal of Gastroenterology 2018年第33期24卷 3749-3759页

作者： Michael Gock Christina S Mullins Christine harnack friedrich Prall Robert Ramer Anja Goder Oliver h Kramer Ernst Klar Michael Linnebacher Department of General Surgery University of RostockRostock 18055Germany Department of General Surgery Section of Molecular Oncology and ImmunotherapyUniversity of RostockRostock 18055Germany Institute of Pathology University of RostockRostock 18055Germany Institute of Pharmacology University of RostockRostock 18055Germany Institute of Toxicology University Medical Center MainzMainz 55131Germany

AIM To establish cell line and patient-derived xenograft(PDX) models for neuroendocrine carcinomas(NEC) which is highly desirable for gaining insight into tumor development as well as preclinical research includingbiomarker testing and drug response *** Cell line establishment was conducted from direct in vitro culturing of colonic NEC tissue(hROC57). A PDX could also successfully be established from vitally frozen tumor samples. Morphological features, invasive and migratory behavior of the hROC57 cells as well as expression of neuroendocrine markers were vastly analyzed. Phenotypic analysis was done by microscopy and multicolor flow cytometry. The extensive molecular-pathological profiling included mutation analysis, assessment of chromosomal and microsatellite instability; and in addition, fingerprinting(i.e., STR analysis) was performed from the cell line in direct comparison to primary patient-derived tissues and the PDX model established. Drug responsiveness was examined for a panel of chemotherapeutics in clinical use for the treatment of solid *** The established cell line hROC57 showed distinct morphological and molecular features of a poorly differentiated large-cell NEC with KI-67 > 50%. Molecular-pathological analysis revealed a Cp G island promoter methylation positive cell line with microsatellite instability being absent. The following mutation profile was observed: KRAS(wt), BRAF(mut). A high sensitivity to etoposide, cisplatin and 5-FU could be demonstrated while it was more resistant towards rapamycin. CONCLUSION We successfully established and characterized a novel patient-derived NEC cell line in parallel to a PDX model as a useful tool for further analysis of the biological characteristics and for development of novel diagnostic and therapeutic options for NEC.

关键词： Patient-derived tumor model Large cell neuroendocrine carcinoma Individualized medicine