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Variant signaling topology at the cancer cell–T-cell interface induced by a two-component T-cell engager

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Cellular & Molecular Immunology 2021年第6期18卷 1568-1570页

作者： Dina Kouhestani Maria Geis Saed Alsouri Thomas GPBumm Hermann Einsele markus sauer Gernot Stuhler Department of Internal Medicine II Hematology and OncologyUniversity Clinic WürzburgWürzburgGermany Department of Biotechnology and Biophysics University WürzburgWürzburgGermany

Bispecific T-cell-engaging antibodies(BiTEs)convey antigenic information from cancer to the T-lymphocyte-associated CD3 complex,thus redirecting immune effector cells to induce target cell *** antigenic information from transformed tissues is rarely unambiguous,we recently introduced novel T-cell-engaging antibody fragments called hemibodies for the combinatorial,ultraprecise targeting of cancer.1 Here,we report the unprecedented enhancement of the plasticity of immunological synapse(IS)formation and variant signaling topology at the cancer cell–T-cell interface induced by hemibodies compared to that induced by BiTEs.

关键词： cancer interface topology

Impaired dynamic interaction of axonal endoplasmic reticulum and ribosomes contributes to defective stimulus-response in spinal muscular atrophy

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Translational Neurodegeneration 2022年第1期11卷 474-495页

作者： Chunchu Deng Sebastian Reinhard Luisa Hennlein Janna Eilts Stefan Sachs Sören Doose Sibylle Jablonka markus sauer Mehri Moradi Michael Sendtner Institute of Clinical Neurobiology University Hospital Wuerzburg97078 Wür-zburgGermany Department of Biotechnology and Biophysics BiocenterJulius-Maximilians-University Wuerzburg97074 WürzburgGermany.

Background:Axonal degeneration and defects in neuromuscular neurotransmission represent a pathological hall-mark in spinal muscular atrophy(SMA)and other forms of motoneuron *** pathological changes do not only base on altered axonal and presynaptic architecture,but also on alterations in dynamic movements of organelles and subcellular structures that are not necessarily reflected by static histopathological *** dynamic inter-play between the axonal endoplasmic reticulum(ER)and ribosomes is essential for stimulus-induced local translation in motor axons and presynaptic ***,it remains enigmatic whether the ER and ribosome crosstalk is impaired in the presynaptic compartment of motoneurons with Smn(survival of motor neuron)deficiency that could contribute to axonopathy and presynaptic dysfunction in ***:Using super-resolution microscopy,proximity ligation assay(PLA)and live imaging of cultured motoneu-rons from a mouse model of SMA,we investigated the dynamics of the axonal ER and ribosome distribution and ***:We observed that the dynamic remodeling of ER was impaired in axon terminals of Smn-deficient *** addition,in axon terminals of Smn-deficient motoneurons,ribosomes failed to respond to the brain-derived neurotrophic factor stimulation,and did not undergo rapid association with the axonal ER in response to extracellular ***:These findings implicate impaired dynamic interplay between the ribosomes and ER in axon terminals of motoneurons as a contributor to the pathophysiology of SMA and possibly also other motoneuron diseases.

关键词： Spinal muscular atrophy Presynaptic ER dynamics Dynamics of ribosomal assembly BDNF stimulation

A New Set of Reversibly Photoswitchable Fluorescent Proteins for Use in Transgenic Plants

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Molecular Plant 2013年第5期6卷 1518-1530页

作者： Martina Lummer Fabian Humpert Matthias Wiedenubbert markus sauer Mark Schuttpelz Dorothee Staiger Molecular Cell Physiology Bielefeld University Universitatsstr. 25 33615 Bielefeld Germany Institute for Genome Research and Systems Biology CeBiTec 33615 Bielefeld Germany Biomolecular Photonics Bielefeld University Universitatsstr. 25 33615 Bielefeld Germany Biotechnology and Biophysics Julius-Maximilians-University Wurzburg Am Hubland 97074 Wurzburg Germany

Fluorescent reporter proteins that allow repeated switching between a fluorescent and a non-fluorescent state in response to specific wavelengths of light are novel tools for monitoring of protein trafficking and super-resolu- tion fluorescence microscopy in living organisms. Here, we describe variants of the reversibly photoswitchable fluores- cent proteins rsFastLime, bsDronpa, and Padron that have been codon-optimized for the use in transgenic Arabidopsis plants. The synthetic proteins, designated rsFastLIME-s, bsDRONPA-s, and PADRON C-s, showed photophysical properties and switching behavior comparable to those reported for the original proteins. By combining the ＇positively switchable＇ PADRON C-s with the ＇negatively switchable＇ rsFastLIME-s or bsDRONPA-s, two different fluorescent reporter proteins could be imaged at the same wavelength upon transient expression in Nicotiana benthamiana cells. Thus, co-localiza- tion analysis can be performed using only a single detection channel. Furthermore, the proteins were used to tag the RNA-binding protein AtGRP7 （Arabidopsis thaliana glycine-rich RNA-binding protein 7） in transgenic Arabidopsis plants. Because the new reversibly photoswitchable fluorescent proteins show an increase in signal strength during each pho- toactivation cycle, we were able to generate a large number of scans of the same region and reconstruct 3-D images of AtGRP7 expression in the root tip. Upon photoactivation of the AtGRP7：rsFastLIME-s fusion protein in a defined region of a transgenic Arabidopsis root, spreading of the fluorescence signal into adjacent regions was observed, indicating that movement from cell to cell can be monitored. Our results demonstrate that rsFastLIME-s, bsDRONPA-s, and PADRON C-s are versatile fluorescent markers in plants, Furthermore, the proteins also show strong fluorescence in mammalian cells including COS-7 and HeLa cells.

关键词： reversibly photoswitchable fluorescent protein codon usage Arabidopsis rsFastLIME-s bsDRONPA-s PADRON-s.

Sharpening emitter localization in front of a tuned mirror

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Light(Science & Applications) 2018年第1期7卷 71-78页

作者： Hannah S.Heil Benjamin Schreiber Ralph Götz Monika Emmerling Marie-Christine Dabauvalle Georg Krohne Sven Höfling Martin Kamp markus sauer Katrin G.Heinze Rudolf Virchow Center Research Center for Experimental BiomedicineUniversity of WürzburgJosef-Schneider-Str.297080 WürzburgGermany Department of Biotechnology and Biophysics BiozentrumUniversity of WürzburgAm Hubland97074 WürzburgGermany Technische Physik Physikalisches Institut and Wilhelm Conrad Röntgen-Center for Complex Material SystemsUniversity of WürzburgAm Hubland97074 WürzburgGermany Division of Electron Microscopy BiozentrumUniversity of WürzburgAm Hubland97074 WürzburgGermany SUPA School of Physics and AstronomyUniversity of St AndrewsSt Andrews KY169SSUK

Single-molecule localization microscopy(SMLM)aims for maximized precision and a high signal-to-noise *** features can be provided by placing the emitter in front of a metal-dielectric nanocoating that acts as a tuned mirror2–***,we demonstrate that a higher photon yield at a lower background on biocompatible metal-dielectric nanocoatings substantially improves SMLM performance and increases the localization precision by up to a factor of *** resolution improvement relies solely on easy-to-fabricate nanocoatings on standard glass coverslips and is spectrally and spatially tunable by the layer design and wavelength,as experimentally demonstrated for dual-color SMLM in cells.

关键词： emitter mirror tunable

Geoecological parameters indicate discrepancies between potential and actual forest area in the forest-steppe of Central Mongolia

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Forest Ecosystems 2021年第4期8卷 735-754页

作者： Michael Klinge Choimaa Dulamsuren Florian Schneider Stefan Erasmi Uudus Bayarsaikhan Daniela sauer markus Hauck Department of Physical Geography Institute of GeographyUniversity of GöttingenGoldschmidtstraBe 537077 GöttingenGermany Applied Vegetation Ecology Faculty of Environment and Natural ResourcesUniversity of FreiburgTennenbacher Str.479106 FreiburgGermany Institute of Farm Economics Thünen InstituteBundesallee 6338116 BraunschweigGermany Department of Biology School of Arts and SciencesNational University of MongoliaBaga toiruu 47Sukhbaatar duuregUlaanbaatarMongolia

Background:Forest distribution in the forest-steppe of Mongolia depends on relief,permafrost,and climate,and is highly sensitive to climate change and anthropogenic *** fires and logging decreased the forest area in the forest-steppe of *** intention of this study was to identify the geoecological parameters that control forest distribution and living-tree biomass in this semi-arid *** on these parameters,we aimed to delineate the area that forest might potentially occupy and to analyse the spatial patterns of actual and potential tree ***:We used a combination of various geographic methods in conjunction with statistical analyses to identify the key parameters controlling forest *** several field campaigns,we mapped tree biomass and ecological parameters in a study area within the Tarvagatai Nuruu National Park(central Mongolia).Forest areas,topographic parameters and vegetation indices were obtained from remote sensing *** correlations between forest distribution and living-tree biomass on one hand,and topographic parameters,climate data,and environmental conditions on the other hand,were used to delineate the area of potential forest distribution and to estimate total living-tree biomass for this ***:Presence of forest on slopes was controlled by the factors elevation,aspect,slope,mean annual precipitation,and mean growing-season *** these factors allowed for estimation of potential forest area but was less suitable for tree-biomass *** significant differences in mean living-tree biomass existed between sites exposed to different local conditions with respect to forest fire,exploitation,and soil *** biomass was reduced at forest edges(defined as 30m wide belt),in small fragmented and in large forest *** biomass in the study area was 20×10^(9) g(1,086 km^(2) forest area),whereas the potential tree biomass would reach up to 65×10^(9)

关键词： Biomass Fire Forest-steppe Geoecological factors Mongolia Permafrost

Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks

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Signal Transduction and Targeted Therapy 2022年第1期7卷 243-257页

作者： Louisa Ruhl Isabell Pink Jenny F.Kiihne Kerstin Beushausen Jana Keil Stella Christoph Andrea sauer Lennart Boblitz Julius Schmidt Sascha David Hans-Martin Jack Edith Roth markus Cornberg Thomas F.Schulz Tobias Welte Marius M.Hoper Christine S.Falk Institute of Transplant Immunology MHHDHanoverGermany Department of Pneumology MHHDHanoverGermany Department of Intensive Care Medicine University of ZurichCHZurichSwitzerland Division of Molecular Immunology Internal Medicine IIINikolaus-Fiebiger-Center of Molecular MedicineFriedrich-Alexander University Erlangen-NurnbergDErlangenGermany Department of Gastroenterology Hepatology and Endocrinology MHHDHanoverGermany Center for Individualized Infection Medicine CiiM HanoverGermany lnstitute of Virology MHHDHanoverGermany German Center for Infection Research DZIFTTU-IICHMarburgGermany Excellence Cluster 2155 RESIST MHHHanoverGermany German Center for Lung Diseases DZL/BREATH MarburgGermany

The systemic processes involved in the manifestation of life・threatening COVID-19 and in disease recovery are still incompletely understood,despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 *** define hallmarks of severe COVID-19 in acute disease(n=58)and in disease recovery in con valesce nt patie nts(n=28)from Han nover Medical School,we used flow cytometry and proteomics data with unsupervised clustering *** our observational study,we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and *** patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific *** core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe *** within this sign ature were associated with either disease progression or *** summary,our data suggest that besides a strong inflammatory response,severe COVID-19 is driven by endothelial activation and barrier disruption,whereby recovery depends on the regeneration of the endothelial integrity.

关键词： cytokine networks signature

Resonance-enhanced multi-octave supercontinuum generation in antiresonant hollow-core fibers

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Light(Science & Applications) 2017年第1期6卷 286-292页

作者： Rudrakant Sollapur Daniil Kartashov Michael Zürch Andreas Hoffmann Teodora Grigorova Gregor sauer Alexander Hartung Anka Schwuchow Joerg Bierlich Jens Kobelke Mario Chemnitz markus A Schmidt Christian Spielmann Institute of Optics and Quantum Electronics Abbe Center of PhotonicsFriedrich Schiller University07743 JenaThuringiaGermany Chemistry Department University of CaliforniaBerkeleyCA 94720USA Leibniz Institute of Photonic Technology e.V. 07745 JenaThuringiaGermany Otto Schott Institute of Material Research Abbe Center of PhotonicsFriedrich Schiller University07743 JenaThuringiaGermany Helmholtz Institute Jena 07743 JenaThuringiaGermany

Ultrafast supercontinuum generation in gas-filled waveguides is an enabling technology for many intriguing applications ranging from attosecond metrology towards biophotonics,with the amount of spectral broadening crucially depending on the pulse dispersion of the propagating *** this study,we show that structural resonances in a gas-filled antiresonant hollow core optical fiber provide an additional degree of freedom in dispersion engineering,which enables the generation of more than three octaves of broadband light that ranges from deep UV wavelengths to near *** observation relies on the introduction of a geometric-induced resonance in the spectral vicinity of the ultrafast pump laser,outperforming gas dispersion and yielding a unique dispersion profile independent of core size,which is highly relevant for scaling input *** a krypton-filled fiber,we observe spectral broadening from 200 nm to 1.7μm at an output energy of B 23μJ within a single optical mode across the entire spectral *** show that the frequency generation results from an accelerated fission process of solitonlike waveforms in a non-adiabatic dispersion regime associated with the emission of multiple phase-matched Cherenkov radiations on both sides of the *** effect,along with the dispersion tuning and scaling capabilities of the fiber geometry,enables coherent ultra-broadband and high-energy sources,which range from the UV to the mid‐infrared spectral range.

关键词： antiresonant hollow core fiber dispersion design nonlinear optics soliton dynamics supercontinuum generation