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Mast cells as rapid innate sensors of cytomegalovirus by TLR3/TRIF signaling-dependent and -independent mechanisms

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Cellular & Molecular Immunology 2015年第2期12卷 192-201页

作者： Marc Becker Niels AW Lemmermann Stefan Ebert Pamela Baars Angelique Renzaho jurgen Podlech Michael Stassen matthias j reddehase Institute for Immunology Research Center for Immunotherapy (FZI) at the University Medical Center of the Johannes Gutenberg University Mainz Germany Institute for Virology Research Center for Immunotherapy (FZI) at the University Medical Center of the Johannes Gutenberg University Mainz Germany These authors contributed equally to this work Co-senior authors

The succinct metaphor,‘the immune system＇s loaded gun＇, has been used to describe the role of mast cells （MCs） due to their storage of a wide range of potent pro-inflammatory and antimicrobial mediators in secretory granules that can be released almost instantly on demand to fight invaders. Located at host-environment boundaries and equipped with an arsenal of pattern recognition receptors, MCs are destined to be rapid innate sensors of pathogens penetrating endothelial and epithelial surfaces. Although the importance of MCs in antimicrobial and antiparasitic defense has long been appreciated, their role in raising the alarm against viral infections has been noted only recently. Work on cytomegalovirus （CMV） infection in the murine model has revealed MCs as players in a novel cross-talk axis between innate and adaptive immune surveillance of CMV, in that infection of MCs, which is associated with MC degranulation and release of the chemokine CCL5, enhances the recruitment of protective CD8 T cells to extravascular sites of virus replication, specifically to lung interstitium and alveolar epithelium. Here, we have expanded on these studies by investigating the conditions for MC activation and the consequent degranulation in response to host infection. Surprisingly, the data revealed two temporally and mechanistically distinct waves of MC activation： an almost instant indirect activation that depended on TLR3/TRIF signaling and delayed activation by direct infection of MCs that did not involve TLR3/rRIF signaling. Cell type-specific Cre-recombination that yielded eGFP-expressing reporter virus selectively originating from MCs identified MC as a new in vivo, first-hit target cell of productive murine CMV infection.

关键词： cytomegalovirus innate immunity mast cells mast cell-specific Cre-recombination TLR3FrRIF-signaling

Small extrachromosomal circular DNA in amyotrophic lateral sclerosis matter

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Neural Regeneration Research 2025年第5期20卷 1411-1413页

作者： Marcos j.Arauzo-Bravo Daniela Gerovska matthias Schwab Alexandra Kretz Computational Biology and Systems Biomedicine Biodonostia Health Research InstituteSan SebastianSpain Basque Foundation for Science IKERBASQUEBilbaoSpainMax Planck Institute for Molecular BiomedicineComputational Biology and Bioinformatics GroupMünsterNorth Rhine-WestphaliaGermany Department of Cell Biology and Histology Faculty of Medicine and NursingUniversity of Basque Country(UPV/EHU)LeioaSpain Department of Neurology Jena University HospitalJenaThuringiaGermany

Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.

关键词： amyotrophic sclerosis

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Error field penetration in j-TEXT tokamak based on two-fluid drift-MHD model

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Chinese Physics B 2024年第4期33卷 545-551页

作者：王文徐涛张仪 the j-TEXT team State Key Laboratory of Advanced Electromagnetic Technology International Joint Research Laboratory of Magnetic Confinement Fusion and Plasma PhysicsSchool of Electrical and Electronic EngineeringHuazhong University of Science and TechnologyWuhan 430074China

An externally generated resonant magnetic perturbation can induce complex non-ideal MHD responses in their resonant *** have studied the plasma responses using Fitzpatrick's improved two-fluid model and program *** calculated the error field penetration threshold for *** addition,we find that the island width increases slightly as the error field amplitude increases when the error field amplitude is below the critical penetration ***,the island width suddenly jumps to a large value because the shielding effect of the plasma against the error field disappears after the *** scanning the natural mode frequency,we find that the shielding effect of the plasma decreases as the natural mode frequency ***,we obtain the m/n=2/1 penetration threshold scaling on density and temperature.

关键词： plasma responses drift-MHD model error field penetration

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Storing Freshwater Versus Storing Electricity in Power Systems with High Freshwater Electric Demand

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journal of Modern Power Systems and Clean Energy 2024年第2期12卷 323-333页

作者： Mubarak j.Al-Mubarak Antonio j.Conejo Department of Electrical and Computer Engineering The Ohio State UniversityColumbusOHUSA Department of Electrical Engineering Kuwait UniversityP.O.Box 5969Safat 13060Kuwait Department of Integrated Systems Engineering and the Department of Electrical and Computer Engineering The Ohio State UniversityColumbusOH 43210USA IEEE

We consider a power system whose electric demand pertaining to freshwater production is high(high freshwater electric demand),as in the Middle East,and investigate the tradeoff of storing freshwater in tanks versus storing electricity in batteries at the day-ahead operation *** storing freshwater and storing electricity increase the actual electric demand at valley hours and decrease it at peak hours,which is generally beneficial in term of cost and ***,to what extent?We analyze this question considering three power systems with different generation-mix configurations,i.e.,a thermal-dominated mix,a renewable-dominated one,and a fully renewable *** generation-mix configurations are inspired by how power systems may evolve in different countries in the Middle *** production uncertainty is compactly modeled using chance *** draw conclusions on how both storage facilities(freshwater and electricity)complement each other to render an optimal operation of the power system.

关键词： Power system operation freshwater production and transportation coordination day-ahead scheduling

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Enhanced diagnostic workup increases pathological findings in patients with acute ischaemic stroke:results of the prospective HEBRAS study

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Stroke & Vascular Neurology 2024年第2期9卷 145-152,I0414-I0425页

作者： Simon Hellwig Thomas Krause jan F Scheitz juliane Herm Ulrike Grittner Nadja jauert jochen B Fiebach Mario Kasner Wolfram Doehner matthias Endres Rolf Wachter Thomas Elgeti Christian H Nolte Karl Georg Haeusler Department of Neurology with Experimental Neurology Charité-Universitätsmedizin Berlincorporate member of Freie Universität Berlin and Humboldt-Universität zu BerlinBerlinGermany Center for Stroke Research Berlin BerlinGermany Berlin Institute of Health at Charité–Universitätsmedizin Berlin BIH Biomedical Innovation AcademyBerlinGermany Department of Neurology Jüdisches Krankenhaus BerlinBerlinGermany German Center for Cardiovascular Diseases(DZHK) Partner Site BerlinBerlinGermany Institute of Biometry and Clinical Epidemiology Charité-Universitätsmedizin BerlinBerlinGermany BIH Center for Regenerative Therapies(BCRT) Berlin Institute of Health at Charité–Universitätsmedizin BerlinBerlinGermany Department of Cardiology Charité-Universitätsmedizin BerlinBerlinGermany Department of Cardiology Campus Benjamin FranklinCharité-Universitätsmedizin BerlinBerlinGermany German Center for Neurodegenerative Diseases(DZNE) Partner Site BerlinBerlinGermany Department of Cardiology University Hospital LeipzigLeipzigGermany Department of Radiology Charité-Universitätsmedizin BerlinBerlinGermany Department of Neurology University Hospital WürzburgWürzburgGermany

Background Stroke aetiology remains cryptogenic in a relevant proportion of patients with acute ischaemic stroke(AIS).We assessed whether enhanced diagnostic workup after AIS yields a higher rate of prespecified pathological findings compared with routine diagnostic care *** Hospitalised patients with AIS were prospectively enrolled in the investigator-initiated observational HEart and BRain Interfaces in Acute Ischaemic Stroke(HEBRAS)study at the Charité,Berlin,*** with AIS without known atrial fibrillation(AF)underwent cardiovascular MR imaging(CMR),MR-angiography of the aortic arch and prolonged Holter-ECG monitoring on top of routine diagnostic *** Among 356 patients with AIS(mean age 66 years,37.6%female),enhanced workup yielded a higher rate of prespecified pathological findings compared with routine care(17.7%vs 5.3%;p<0.001).Consequently,fewer patients were classified as cryptogenic after enhanced diagnostic workup(38.5%vs 45.5%,p<0.001).Routine care included echocardiography in 228(64.0%)*** was successfully performed in 292(82.0%)patients and revealed more often a prespecified pathological finding compared with routine echocardiography(16.1%vs 5.3%).Furthermore,study-related ECG monitoring(median duration 162 hours(IQR 98–210))detected AF in 16(4.5%)patients,while routine monitoring(median duration 51 hours(IQR 34–74))detected AF in seven(2.0%)*** Enhanced diagnostic workup revealed a higher rate of prespecified pathological findings in patients with AIS compared with routine diagnostic care and significantly reduced the proportion of patients with cryptogenic *** registration number NCT02142413.

关键词： routine patients prospective

Analysis of ancient mass extinction recoveries in marine environments: generating strategies for managing outcomes of the current mass extinction

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National Science Review 2024年第1期11卷 8-10页

作者： David j.Bottjer Department of Earth Sciences University of Southern California

The defining feature of a mass extinction and its associated recovery is the global amount of extinction that occurred[1]. However, there is finer-scale detail to the story, as seen in the ongoing modern mass extinction(the sixth mass extinction), which exhibits variable effects among marine ecosystems and environments, and hence geographic areas [1].

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Global weirding at mass extinction horizons

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National Science Review 2024年第1期11卷 10-12页

作者： Gregory j.Retallack Department of Earth Sciences University of Oregon

A strong motivation for studying mass extinctions is understanding how current climatic and biodiversity crises will affect creatures living on land such as ourselves. Perhaps the question is: how bad can it get? In that case, terrestrial Permian-Triassic mass extinctions are an irresistible worst-case scenario [1].

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Decoding the genetic program of micronucleus formation: linking chromosomal instability to human disease

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2840-2842页

作者： jörg Fahrer Division of Food Chemistry and Toxicology Department of ChemistryRPTU Kaiserslautern-Landau67663 KaiserslauternGermany

A recent study by Adams and colleagues published in Nature unveiled more than one hundred genes that are involved in micronucleus formation,1 which is a biomarker for genomic instability and associated with aging,cancer,and other disorders.2 As an outstanding achievement,the authors identified DSCC1(DNA Replication And Sister Chromatid Cohesion 1)as a critical gene protecting against early developmental defects,genomic instability,reduced proliferative capacity,cohesinopathy-related phenotypes,and tumor development in vivo.

关键词： chromosomal linking Replication

Necrotic enteritis and antibiotic-free production of broiler chickens:Challenges in testing and using alternative products

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Animal Nutrition 2024年第1期16卷 288-298页

作者： Robert j.Moore School of Science RMIT University

The global trend towards raising broiler chickens without the use of in-feed antibiotics(IFAs) means that there is an ongoing need to develop alternative treatments capable of delivering the benefits that IFAs previously provided. IFAs supported the productivity performance of chickens and played a key role in maintaining their health. Necrotic enteritis(NE) is an important disease of broilers that affects health,productivity, and welfare, and was previously well controlled by IFAs. However, with the reduction in IFA use, NE is resurgent in some countries. Vaccines and various feed additives, including pre-, pro-, and postbiotics, phytobiotics, fatty acids, and phage therapies have been introduced as alternative methods of NE control. While some of these feed additives have specific activity against the NE pathogen, Clostridium perfringens, most have the more general goal of reinforcing gut health. Extensive reviews of the effects of many of these feed additives on gut health have been published recently. Hence, rather than cover previously well reviewed areas of research this review focuses on the challenges and pitfalls in undertaking experimental assessment of alternative NE treatments and translating laboratory research to real world commercial production settings. The review is based on the author's particular experience,reading, thoughts, and analysis of the available information and inevitably presents a particular understanding that is likely to be at odds with others thinking on these issues. It is put forward to stimulate thinking and discussion on the issues covered.

关键词： Necrotic enteritis Clostridium perfringens Vaccines Feed additive Farm management