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Observation of a single protein by ultrafast X-ray diffraction

Light(Science & Applications) 2024年第1期13卷 80-90页

作者： Tomas Ekeberg Dameli Assalauova Johan Bielecki Rebecca Boll Benedikt J.Daurer lutz a.eichacker Linda E.Franken Davide E.Galli Luca Gelisio Lars Gumprecht Laura H.Gunn Janos Hajdu Robert Hartmann Dirk Hasse Alexandr Ignatenko Jayanath Koliyadu Olena Kulyk Ruslan Kurta Markus Kuster Wolfgang Lugmayr Jannik Lübke Adrian P.Mancuso Tommaso Mazza Carl Nettelblad Yevheniy Ovcharenko Daniel E.Rivas Max Rose Amit K.Samanta Philipp Schmidt Egor Sobolev Nicusor Timneanu Sergey Usenko Daniel Westphal Tamme Wollweber Lena Worbs Paul Lourdu Xavier Hazem Yousef Kartik Ayyer Henry N.Chapman Jonas A.Sellberg Carolin Seuring Ivan A.Vartanyants Jochen Küpper Michael Meyer Filipe R.N.C.Maia Laboratory of Molecular Biophysics Department of Cell and Molecular BiologyUppsala UniversityHusargatan 3(Box 596)SE-75124 UppsalaSweden Deutsches Electronen-Synchrotron DESY Notkestrasse 8522607 HamburgGermany European XFEL Holzkoppel 422869 SchenefeldGermany Diamond Light Source Harwell Science&Innovation CampusDidcot OX110DEUK University of Stavanger Centre Organelle ResearchRichard-Johnsensgate 44021 StavangerNorway Leibniz Institute for Experimental Virology(HPI) Centre for Structural Systems BiologyNotkestraße 8522607 HamburgGermany Dipartimento di Fisica“Aldo Pontremoli” Universitàdegli Studi di Milanovia Celoria 1620133 MilanoItaly Center for Free-Electron Laser Science DESY22607 HamburgGermany Plant Biology Section School of Integrative Plant ScienceCornell UniversityIthacaNY 14853USA PNSensor GmbH Otto-Hahn-Ring 6D-81739 MünchenGermany Biomedical and X-Ray Physics Department of Applied PhysicsAlbaNova University CenterKTH Royal Institute of TechnologySE-10691 StockholmSweden ELI Beamlines/IoP Institute of Physics AS CR v.v.i.Na Slovance 218221 Prague 8Czech Republic Multi-User CryoEM Facility Centre for Structural Systems BiologyNotkestr.8522607 HamburgGermany University Medical Center Hamburg-Eppendorf(UKE) Martinistrasse 5220246 HamburgGermany The Hamburg Center for Ultrafast Imaging Universität HamburgLuruper Chaussee 14922761 HamburgGermany Department of Physics Universität HamburgLuruper Chaussee 14922761 HamburgGermany Department of Chemistry and Physics La Trobe Institute for Molecular ScienceLa Trobe UniversityMelbourneVIC 3086Australia Division of Scientific Computing Science for Life LaboratoryDepartment of Information TechnologyUppsala UniversityBox 337SE-75105 UppsalaSweden European Molecular Biology Laboratory c/o DESYNotkestrasse 8522607 HamburgGermany Department of Physics and Astronomy Uppsala UniversityBox 516SE-75120 UppsalaSweden Max Planck Institute for the Structure and Dynamics of Matter Luruper Chaussee 14922761 HamburgGe

The idea of using ultrashort X-ray pulses to obtain images of single proteins frozen in time has fascinated and inspired *** was one of the arguments for building X-ray free-electron *** to theory,the extremely intense pulses provide sufficient signal to dispense with using crystals as an amplifier,and the ultrashort pulse duration permits capturing the diffraction data before the sample inevitably *** was first demonstrated on biological samples a decade ago on the giant *** then,a large collaboration has been pushing the limit of the smallest sample that can be *** ability to capture snapshots on the timescale of atomic vibrations,while keeping the sample at room temperature,may allow probing the entire conformational phase space of *** we show the first observation of an X-ray diffraction pattern from a single protein,that of Escherichia coli GroEL which at 14 nm in diameter is the smallest biological sample ever imaged by X-rays,and demonstrate that the concept of diffraction before destruction extends to single *** the pattern,it is possible to determine the approximate orientation of the *** experiment demonstrates the feasibility of ultrafast imaging of single proteins,opening the way to single-molecule time-resolved studies on the femtosecond timescale.

关键词： smallest intense ultrafast

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A Systematic Analysis of Care Bundles for Severe Sepsis

A Systematic Analysis of Care Bundles for Severe Sepsis

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中国病理生理学会危重病医学专业委员会第八届全国大会暨中...

作者： Robert L.Danner Peter Q eichacker Charles Natanson MD NIH Clinical Center Bethesda MD 20892

＜正＞Severe sepsis bundles were developed to promote rapid adoption of selected therapies, benchmark hospital performance and ultimately improve patient outcomes. Valid, high-quality bundles require that individual components have unequivocal, proven benefits and an additive impact on the targeted outcome when combined

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Once is not enough:clinical trials in sepsis

Once is not enough:clinical trials in sepsis

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中国病理生理学会危重病医学专业委员会第八届全国大会暨中...

作者： Daniel A.Sweeney Robert L.Danner Peter Q.eichacker Charles Natanson Critical Care Medicine Department Clinical CenterNational Institutes of HealthBuilding 10Room 2C145BethesdaMD 20892-1662USA

＜正＞Introduction In this issue of Intensive Care Medicine,the steering committee members of the PROWESS-Shock trial pres- ent a balanced discussion of the controversies surrounding recombinant human activated protein C（rhAPC）and the challenges intrinsic to designing an industry-sponsored *** investigators have taken important steps to be transparent about financial conflicts of interest,to

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临床绩效评估标准应免受企业影响的侵蚀

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英国医学杂志中文版 2018年第10期21卷 559-563页

作者： Dharmvir S Jaswal Charles Natanson Peter Q eichacker Critical Care 张楠(译) 梁立智(校) 不详 Medicine Department Clinical Center National Institutes of Health Bethesda MD 20892 USA 首都医科大学公共卫生学院

Peter eichacker及其同事认为，美国支持脓毒症治疗指南的决定损坏了临床绩效评估标准，该标准的建立应基于科学证据以及免受潜在商业影响侵蚀的基本程序。提倡以证据为基础的临床绩效评估标准，指导患者的治疗，以改善患者结局，降低... 详细信息

Peter eichacker及其同事认为，美国支持脓毒症治疗指南的决定损坏了临床绩效评估标准，该标准的建立应基于科学证据以及免受潜在商业影响侵蚀的基本程序。提倡以证据为基础的临床绩效评估标准，指导患者的治疗，以改善患者结局，降低医疗成本。英国国家健康体系（NHS）的《质量与结局框架》（QOF）为英国全科医生勾勒出绩效评估标准的轮廓。

关键词：防护威胁工业表演

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荟萃分析：皮质激素对脓毒症存活与休克的影响依赖其剂量

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世界急危重病医学杂志 2004年第6期1卷 466-469,480页

作者： PeterC．Minneci KatherineJ．Deans StevenM．Banks PeterQ．eichacker CharlesNatanson 冯丽洁王佩燕

Background Previous meta- analyses demonstrated that high-dose glucocorticoids were not beneficial in sepsis. Recently,lower- dose glucocorticoids have been studiedPurpose To compare recent trials of glucocorticoids for sepsis with previous glucocorticoid trials. Data Sources Systematic MEDLINE search for studies published between 1988 and 2003. Study Selection Randomized, controlled trials of sepsis that examined the effects of glucocorticoids on survival or vasopressor requirements. Data Extraction Two investigators independently collected data on patient and study characteristics, treatment interventions, and outcomes. Data Synthesis The 5 included trials revealed a consistent and beneficial effect of glucocorticoids on survival(I^2=0%; relative benefit, 1.23, [95% CI, 1.01 to 1.50] ;P=0.036) and shock reversal(I^2=0%; relative benefit, 1.71 [CI, 1.29 to 2.26] ; P<0.001). These effects were the same regardless of adrenal function. In contrast, 8 trials published before 1989 demonstrated a survival disadvantage with steroid treatment(I^2=14% ; relative benefit, 0.89 [ CI, 0.82 to 0.97] ; P=0.008). In comparison with the earlier trials, the more recent trials administered steroids later after patients met enrollment criteria( median, 23 hours vs.<2 hours ; P=0.02) , for longer courses(6 days vs. 1 day; P=0.01) , and in lower total dosages(hydrocortisone equivalents, 1209 mg vs. 23975 mg;P=0.01 )to patients with higher control group mortality rates( mean, 57% vs. 34%; P=0.06) who were more likely to be vasopressor-dependent( 100% vs. 65% ; P=0.03). The relationship between steroid dose and survival was linear, characterized by benefit at low doses and increasing harm at higher doses(P=0.02). Limitations We could not analyze time-related improvements in medical care and potential bias secondary to nonreporting of negative study results. Conclusions Although short courses of high - dose glucocorticoids decreased survival during sepsis, a 5-to 7-day course of physiolog

关键词：皮质激素脓毒症存活休克感染性休克

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