TY - JOUR A1 - Carradec, Quentin A1 - Pelletier, Eric A1 - Da Silva, Corinne A1 - Alberti, Adriana A1 - Seeleuthner, Yoann A1 - Blanc-Mathieu, Romain A1 - Lima-Mendez, Gipsi A1 - Rocha, Fabio A1 - Tirichine, Leila A1 - Labadie, Karine A1 - Kirilovsky, Amos A1 - Bertrand, Alexis A1 - Engelen, Stefan A1 - Madoui, Mohammed-Amin A1 - Méheust, Raphaël A1 - Poulain, Julie A1 - Romac, Sarah A1 - Richter, Daniel J. A1 - Yoshikawa, Genki A1 - Dimier, Céline A1 - Kandels-Lewis, Stefanie A1 - Picheral, Marc A1 - Searson, Sarah A1 - Jaillon, Olivier A1 - Aury, Jean-Marc A1 - Karsenti, Eric A1 - Sullivan, Matthew B. A1 - Sunagawa, Shinichi A1 - Bork, Peer A1 - Not, Fabrice A1 - Hingamp, Pascal A1 - Raes, Jeroen A1 - Guidi, Lionel A1 - Ogata, Hiroyuki A1 - de Vargas, Colomban A1 - Iudicone, Daniele A1 - Bowler, Chris A1 - Wincker, Patrick T1 - A global ocean atlas of eukaryotic gene JF - Nature Communications N2 - While our knowledge about the roles of microbes and viruses in the ocean has increased tremendously due to recent advances in genomics and metagenomics, research on marine microbial eukaryotes and zooplankton has benefited much less from these new technologies because of their larger genomes, their enormous diversity, and largely unexplored physiologies. Here, we use a metatranscriptomics approach to capture expressed genes in open ocean Tara Oceans stations across four organismal size fractions. The individual sequence reads cluster into 116 million unigenes representing the largest reference collection of eukaryotic transcripts from any single biome. The catalog is used to unveil functions expressed by eukaryotic marine plankton, and to assess their functional biogeography. Almost half of the sequences have no similarity with known proteins, and a great number belong to new gene families with a restricted distribution in the ocean. Overall, the resource provides the foundations for exploring the roles of marine eukaryotes in ocean ecology and biogeochemistry. KW - genomics KW - marine biology KW - microbial ecology KW - water microbiology Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222250 VL - 9 ER - TY - JOUR A1 - Semler, Elisa A1 - Anderl-Straub, Sarah A1 - Uttner, Ingo A1 - Diehl-Schmid, Janine A1 - Danek, Adrian A1 - Einsiedler, Beate A1 - Fassbender, Klaus A1 - Fliessbach, Klaus A1 - Huppertz, Hans-Jürgen A1 - Jahn, Holger A1 - Kornhuber, Johannes A1 - Landwehrmeyer, Bernhard A1 - Lauer, Martin A1 - Muche, Rainer A1 - Prudlo, Johannes A1 - Schneider, Anja A1 - Schroeter, Matthias L. A1 - Ludolph, Albert C. A1 - Otto, Markus T1 - A language-based sum score for the course and therapeutic intervention in primary progressive aphasia JF - Alzheimer's Research & Therapy N2 - Background With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions. Methods We assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials. Results Significant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures. Conclusion Our findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies. KW - frontotemporal dementia KW - cognitive neuropsychology in dementia KW - assessment of cognitive disorders/dementia KW - volumetric MRI KW - aphasia Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236277 VL - 10 ER - TY - JOUR A1 - Schroeter, Matthias L. A1 - Pawelke, Sarah A1 - Bisenius, Sandrine A1 - Kynast, Jana A1 - Schuemberg, Katharina A1 - Polyakova, Maryna A1 - Anderl-Straub, Sarah A1 - Danek, Adrian A1 - Fassbender, Klaus A1 - Jahn, Holger A1 - Jessen, Frank A1 - Kornhuber, Johannes A1 - Lauer, Martin A1 - Prudlo, Johannes A1 - Schneider, Anja A1 - Uttner, Ingo A1 - Thöne-Otto, Angelika A1 - Otto, Markus A1 - Diehl-Schmid, Janine T1 - A Modified Reading the Mind in the Eyes Test Predicts Behavioral Variant Frontotemporal Dementia Better Than Executive Function Tests JF - Frontiers in Aging Neuroscience N2 - Behavioral variant frontotemporal dementia (bvFTD) is characterized by deep alterations in behavior and personality. Although revised diagnostic criteria agree for executive dysfunction as most characteristic, impairments in social cognition are also suggested. The study aimed at identifying those neuropsychological and behavioral parameters best discriminating between bvFTD and healthy controls. Eighty six patients were diagnosed with possible or probable bvFTD according to Rascovsky et al. (2011) and compared with 43 healthy age-matched controls. Neuropsychological performance was assessed with a modified Reading the Mind in the Eyes Test (RMET), Stroop task, Trail Making Test (TMT), Hamasch-Five-Point Test (H5PT), and semantic and phonemic verbal fluency tasks. Behavior was assessed with the Apathy Evaluation Scale, Frontal Systems Behavioral Scale, and Bayer Activities of Daily Living Scale. Each test’s discriminatory power was investigated by Receiver Operating Characteristic curves calculating the area under the curve (AUC). bvFTD patients performed significantly worse than healthy controls in all neuropsychological tests. Discriminatory power (AUC) was highest in behavioral questionnaires, high in verbal fluency tasks and the RMET, and lower in executive function tests such as the Stroop task, TMT and H5PT. As fluency tasks depend on several cognitive functions, not only executive functions, results suggest that the RMET discriminated better between bvFTD and control subjects than other executive tests. Social cognition should be incorporated into diagnostic criteria for bvFTD in the future, such as in the International Classification of Diseases (ICD)-11, as already suggested in the Diagnostic and Statistical Manual for Mental Disorders (DSM)-5. KW - behavioral variant frontotemporal dementia KW - diagnostic criteria KW - executive function KW - social cognition KW - theory of mind Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234254 VL - 10 ER - TY - INPR A1 - Höbartner, Claudia A1 - Steinmetzger, Christian A1 - Palanisamy, Navaneethan A1 - Gore, Kiran R. T1 - A multicolor large Stokes shift fluorogen-activating RNA aptamer with cationic chromophores T2 - Chemistry - A European Journal N2 - Large Stokes shift (LSS) fluorescent proteins (FPs) exploit excited state proton transfer pathways to enable fluorescence emission from the phenolate intermediate of their internal 4 hydroxybenzylidene imidazolone (HBI) chromophore. An RNA aptamer named Chili mimics LSS FPs by inducing highly Stokes-shifted emission from several new green and red HBI analogs that are non-fluorescent when free in solution. The ligands are bound by the RNA in their protonated phenol form and feature a cationic aromatic side chain for increased RNA affinity and reduced magnesium dependence. In combination with oxidative functional-ization at the C2 position of the imidazolone, this strategy yielded DMHBO\(^+\), which binds to the Chili aptamer with a low-nanomolar K\(_D\). Because of its highly red-shifted fluorescence emission at 592 nm, the Chili–DMHBO\(^+\) complex is an ideal fluorescence donor for Förster resonance energy transfer (FRET) to the rhodamine dye Atto 590 and will therefore find applications in FRET-based analytical RNA systems. KW - RNA Aptamer KW - fluorescence KW - large Stokes shift KW - fluorescent protein KW - fluorescent resonance energy transfer Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-174197 N1 - This is the pre-peer reviewed version of the following article: Steinmetzger, C. , Palanisamy, N. , Gore, K. . and Höbartner, C. (2018), A multicolor large Stokes shift fluorogen‐activating RNA aptamer with cationic chromophores. Chem. Eur. J. doi:10.1002/chem.201805882, which has been published in final form at https://doi.org/10.1002/chem.201805882. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. ER - TY - JOUR A1 - Balasubramanian, Srikkanth A1 - Skaf, Joseph A1 - Holzgrabe, Ulrike A1 - Bharti, Richa A1 - Förstner, Konrad U. A1 - Ziebuhr, Wilma A1 - Humeida, Ute H. A1 - Abdelmohsen, Usama R. A1 - Oelschlaeger, Tobias A. T1 - A new bioactive compound from the marine sponge-derived Streptomyces sp. SBT348 inhibits staphylococcal growth and biofilm formation JF - Frontiers in Microbiology N2 - Staphylococcus epidermidis, the common inhabitant of human skin and mucosal surfaces has emerged as an important pathogen in patients carrying surgical implants and medical devices. Entering the body via surgical sites and colonizing the medical devices through formation of multi-layered biofilms leads to refractory and persistent device-related infections (DRIs). Staphylococci organized in biofilms are more tolerant to antibiotics and immune responses, and thus are difficult-to-treat. The consequent morbidity and mortality, and economic losses in health care systems has strongly necessitated the need for development of new anti-bacterial and anti-biofilm-based therapeutics. In this study, we describe the biological activity of a marine sponge-derived Streptomyces sp. SBT348 extract in restraining staphylococcal growth and biofilm formation on polystyrene, glass, medically relevant titan metal, and silicone surfaces. A bioassay-guided fractionation was performed to isolate the active compound (SKC3) from the crude SBT348 extract. Our results demonstrated that SKC3 effectively inhibits the growth (MIC: 31.25 \(\mu\)g/ml) and biofilm formation (sub-MIC range: 1.95-<31.25 \(\mu\)g/ml) of S. epidermidis RP62A in vitro. Chemical characterization of SKC3 by heat and enzyme treatments, and mass spectrometry (HRMS) revealed its heat-stable and non-proteinaceous nature, and high molecular weight (1258.3 Da). Cytotoxicity profiling of SKC3 in vitro on mouse fibroblast (NIH/3T3) and macrophage (J774.1) cell lines, and in vivo on the greater wax moth larvae Galleria mellonella revealed its non-toxic nature at the effective dose. Transcriptome analysis of SKC3 treated S. epidermidis RP62A has further unmasked its negative effect on central metabolism such as carbon flux as well as, amino acid, lipid, and energy metabolism. Taken together, these findings suggest a potential of SKC3 as a putative drug to prevent staphylococcal DRIs. KW - marine sponges KW - Streptomyces KW - Staphylococci KW - device-related infections KW - bioassay-guided fractionation KW - transcriptome Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221408 VL - 9 ER - TY - THES A1 - Godbole, Amod Anand T1 - A new paradigm in GPCR signaling at the trans-Golgi network of thyroid cells T1 - Ein neues Model der GPCR Signaltransduktion am trans-Golgi-Netzwerk von Schilddrüsenzellen N2 - Whereas G-protein coupled receptors (GPCRs) have been long believed to signal through cyclic AMP exclusively at cell surface, our group has previously shown that GPCRs not only signal at the cell surface but can also continue doing so once internalized together with their ligands, leading to persistent cAMP production. This phenomenon, which we originally described for the thyroid stimulating hormone receptor (TSHR) in thyroid cells, has been observed also for other GPCRs. However, the intracellular compartment(s) responsible for such persistent signaling and its consequences on downstream effectors were insufficiently characterized. The aim of this study was to follow by live-cell imaging the trafficking of internalized TSHRs and other involved signaling proteins as well as to understand the consequences of signaling by internalized TSHRs on the downstream activation of protein kinase A (PKA). cAMP and PKA activity was measured in real-time in living thyroid cells using FRET-based sensors Epac1-camp and AKAR2 respectively. The results suggest that TSH co-internalizes with its receptor and that the internalized TSH/TSHR complexes traffic retrogradely to the trans-Golgi network (TGN). This study also provides evidence that these internalized TSH/TSHR complexes meet an intracellular pool of Gs proteins in sorting endosomes and in TGN and activate it there, as visualized in real-time using a conformational biosensor nanobody, Nb37. Acute Brefeldin A-induced Golgi collapse hinders the retrograde trafficking of TSH/TSHR complexes, leading to reduced cAMP production and PKA signaling. BFA pretreatment was also able to attenuate CREB phosphorylation suggesting that an intact Golgi/TGN organisation is essential for an efficient cAMP/PKA signaling by internalized TSH/TSHR complexes. Taken together this data provides evidence that internalized TSH/TSHR complexes meet and activate Gs proteins in sorting endosomes and at the TGN, leading to a local activation of PKA and consequently increased CREB activation. These findings suggest unexpected functions for receptor internalization, with major pathophysiological and pharmacological implications. N2 - G-Protein-gekoppelte Rezeptoren sind nur in Eukaryonten vorhandeln und bilden die größte und diverseste Familie von Zellmembranrezeptoren. Sie reagieren auf eine vielfältige Gruppe von Stimuli die verschiedene Effektoren aktivieren und damit nachgelagerte Signalkaskaden auslösen, die letztlich entscheidend für die Zellphysiologie sind. Die Regelung der Ligand-vermittelten Signaltransduktion wird hauptsächlich durch die Desensibilisierung des GPCR mittels Dephosphorylierung (katalysiert durch GRK) und zusätzlich durch Internalisierung des GPCR gesteuert. Die Annahme, dass GPCRs für cAMP nur an der Zellmembran signalisieren und nicht mehr sobald sie in die Zelle internalisiert wurden, konnte durch wegweisende unabhängige Forschung an GPCRs im Besonderen an TSHR und PTHR geändert werden. So konnte gezeigt werden, dass sie für cAMP nicht nur an der Zellmembran signalisieren, sondern auch, wenn sie in intrazelluläre Zellkompartimente internalisiert wurde. Dieses Phänomen („sustained signaling“ hier „anhaltende Signalisierung“) wurde seitdem für andere GPCRs (z.B. 2-AR, V2R und LHR) beschrieben. Aber die Zellkompartimente wurden für nachhaltige intrazelluläre Signale nicht ausreichend charakterisiert. Das Ziel dieser Arbeit war es die Bewegung und die dynamische Natur der möglichen signalisierenden Kompartimente mittels „real-time TIRF“-Mikroskopie und die Signalisierung unter Verwendung von „real-time FRET“ in primären Maus Schilddrüsenzellen zu untersuchen. Die vorliegende Arbeit berichtet, dass TSH/TSHR Komplexe internalisieren und ein signifikanter Teil, welcher vom Retromer Komplex angeführt wird, gelangt über den retrograden (rückwärts gerichteten) Transport in das trans-Golgi-Netzwerk (TGN). Diese TSH/TSHR-Komplexe treffen nicht in den frühen Endosomen auf die Gs-Proteine, sondern in den „Sortierer Endosomen“ und in dem TGN. Ein direkter Beweis für Gs Protein Aktivierung und Signaltransduktion am TGN und in Sortierer Endosomen konnte mittels des nanobody Nb37, einem spezifischen Biosensor für das aktive Gs Protein, erbracht werden. Es konnte gezeigt werden, dass die Sequestrierung von Nb37 an diesen Kompartimenten ein szintillierendes Verhalten in Zeit und Raum zeigt. Die vorliegende Arbeit zeigt, dass die katalytische Untereinheit der PKA am Golgi/TGN angereichert ist. Die Behandlung mit Brefeldin A führt zum Verlust dieser PKA Lokalisation am Golgi. Die Beschädigung und Reorganisation des TGN durch Brefeldin A führt zu a) einer abgeschwächten cAMP Reaktion b) einer dreiphasigen PKA Reaktion charakterisiert durch eine schnelle erste Phase, eine langsame (deutlich abgeschwächte) zweite Phase und eine verzögerte dritte Phase und schließlich c) einer abgeschwächte CREB Phosphorylierung. Es gibt Anzeichen dafür, dass die Reorganisation des TGN Kompartimente betrifft, die verantwortlich für intrazelluläre cAMP- und PKA-Signalisierung sind. Zusammenfassend lässt sich sagen, dass das TGN eines der Kompartimente ist, das für die anhaltende TSHR-Signalisierung verantwortlich ist. KW - G-Protein gekoppelte Rezeptoren KW - GPCR KW - thyroid stimulating hormone receptor KW - trans-Golgi network KW - Signaltransduktion KW - Golgi-Apparat KW - Schilddrüse Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147159 ER - TY - JOUR A1 - Reichert, Johannes C. A1 - von Rottkay, Eberhard A1 - Roth, Franz A1 - Renz, Tim A1 - Hausmann, Johannes A1 - Kranz, Julius A1 - Rackwitz, Lars A1 - Nöth, Ulrich A1 - Rudert, Maximilian T1 - A prospective randomized comparison of the minimally invasive direct anterior and the transgluteal approach for primary total hip arthroplasty JF - BMC Musculoskeletal Disorders N2 - Background: The presented prospective randomized controlled single-centre study compares the clinical outcome up to 12 months after total hip arthroplasty using a minimally invasive single-incision direct anterior (DAA) and a direct transgluteal lateral approach. Methods: A total of 123 arthroplasties were evaluated utilizing the Harris Hip Score (HHS), the extra short musculoskeletal functional assessment questionnaire (XSFMA), the Short Form 36 (SF-36) health survey, a Stepwatch™ Activity Monitor (SAM), and a timed 25 m foot walk (T25-FW). Postoperative x-ray images after THA were reviewed to determine inclination and stem positioning. Results: At final follow-up, the XSFMA functional index scores were 10.3 (anterior) and 15.08 (lateral) while the bother index summed up to a score of 15.8 (anterior) and 21.66 (lateral) respectively, thus only differing significantly for the functional index (p = 0.040 and p = 0.056). The SF-36 physical component score (PCS) was 47.49 (anterior) and 42.91 (lateral) while the mental component score (MCS) summed up to 55.0 (anterior) and 56.23 (lateral) with a significant difference evident for the PCS (p = 0.017; p = 0.714). Patients undergoing THA through a DAA undertook a mean of 6402 cycles per day while those who had undergone THA through a transgluteal approach undertook a mean of 5340 cycles per day (p = 0.012). Furthermore, the obtained outcome for the T25-FW with 18.4 s (anterior) and 19.75 s (lateral) and the maximum walking distance (5932 m and 5125 m) differed significantly (p = 0.046 and p = 0.045). The average HHS showed no significant difference equaling 92.4 points in the anterior group and 91.43 in the lateral group (p = 0.477). The radiographic analysis revealed an average cup inclination of 38.6° (anterior) and 40.28° (lateral) without signs of migration. Conclusion: In summary, our outcomes show that after 1 year THA through the direct anterior approach results in a higher patient activity compared to THA utilizing a transgluteal lateral approach while no differences regarding hip function are evident. KW - total hip arthroplasty KW - direct anterior approach KW - minimally invasive KW - transgluteal approach KW - prospective study Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176072 VL - 19 IS - 241 ER - TY - JOUR T1 - A search for pair-produced resonances in four-jet final states at root s=13 TeV with the ATLAS detector JF - The European Physical Journal C N2 - A search for massive coloured resonances which are pair-produced and decay into two jets is presented. The analysis uses 36.7 fb(-1) of root s = 13 TeV pp collision data recorded by the ATLAS experiment at the LHC in 2015 and 2016. No significant deviation from the background prediction is observed. Results are interpreted in a SUSY simplified model where the lightest supersymmetric particle is the top squark, (t) over tilde, which decays promptly into two quarks through R-parity-violating couplings. Top squarks with masses in the range 100 GeV < m((T) over tilde) < 410 GeV are excluded at 95% confidence level. If the decay is into a b-quark and a light quark, a dedicated selection requiring two b-tags is used to exclude masses in the ranges 100 GeV < m((t) over tilde) < 470 GeV and 480 GeV < m(<(t)over tilde>) < 610 GeV. Additional limits are set on the pair-production of massive colour-octet resonances. KW - Patron Distributions KW - Collicions KW - Extension KW - Squark KW - Supersymmetry KW - Color KW - Decay Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225465 VL - 78 IS - 250 ER - TY - JOUR T1 - A search for resonances decaying into a Higgs boson and a new particle \(X\) in the \({XH}\) -> \({qqbb}\) final state with the ATLAS detector JF - Physics letters B N2 - A search for heavy resonances decaying into a Higgs boson (H) and a new particle (X) is reported, utilizing 36.1 fb(-1) of proton-proton collision data at root s = 13 TeV collected during 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. The particle Xis assumed to decay to a pair of light quarks, and the fully hadronic final state XH -> q (q) over bar 'b (b) over bar is analysed. The search considers the regime of high XH resonance masses, where the X and H bosons are both highly Lorentz-boosted and are each reconstructed using a single jet with large radius parameter. A two-dimensional phase space of XH mass versus X mass is scanned for evidence of a signal, over a range of XH resonance mass values between 1 TeV and 4 TeV, and for X particles with masses from 50 GeV to 1000 GeV. All search results are consistent with the expectations for the background due to Standard Model processes, and 95% CL upper limits are set, as a function of XH and X masses, on the production cross-section of the XH -> q (q) over bar 'b (b) over bar resonance. (c) 2018 The Author(s). Published by Elsevier B.V. KW - Proton-Proton Collisions KW - Root-S=13 TEV KW - MASS Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225435 VL - 779 ER - TY - JOUR A1 - Wen, Lai A1 - Feil, Susanne A1 - Wolters, Markus A1 - Thunemann, Martin A1 - Regler, Frank A1 - Schmidt, Kjestine A1 - Friebe, Andreas A1 - Olbrich, Marcus A1 - Langer, Harald A1 - Gawaz, Meinrad A1 - de Wit, Cor A1 - Feil, Robert T1 - A shear-dependent NO-cGMP-cGKI cascade in platelets acts as an auto-regulatory brake of thrombosis JF - Nature Communications N2 - Mechanisms that limit thrombosis are poorly defined. One of the few known endogenous platelet inhibitors is nitric oxide (NO). NO activates NO sensitive guanylyl cyclase (NO-GC) in platelets, resulting in an increase of cyclic guanosine monophosphate (cGMP). Here we show, using cGMP sensor mice to study spatiotemporal dynamics of platelet cGMP, that NO-induced cGMP production in pre-activated platelets is strongly shear-dependent. We delineate a new mode of platelet-inhibitory mechanotransduction via shear-activated NO-GC followed by cGMP synthesis, activation of cGMP-dependent protein kinase I (cGKI), and suppression of Ca2+ signaling. Correlative profiling of cGMP dynamics and thrombus formation in vivo indicates that high cGMP concentrations in shear-exposed platelets at the thrombus periphery limit thrombosis, primarily through facilitation of thrombus dissolution. We propose that an increase in shear stress during thrombus growth activates the NO-cGMP-cGKI pathway, which acts as an auto-regulatory brake to prevent vessel occlusion, while preserving wound closure under low shear. KW - calcium signalling KW - fluorescence imaging KW - platelets KW - thrombosis Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233616 VL - 9 ER -