TY - JOUR A1 - Roelofs, Freek A1 - Blackburn, Lindy A1 - Lindahl, Greg A1 - Doeleman, Sheperd S. A1 - Johnson, Michael D. A1 - Arras, Philipp A1 - Chatterjee, Koushik A1 - Emami, Razieh A1 - Fromm, Christian A1 - Fuentes, Antonio A1 - Knollmüller, Jakob A1 - Kosogorov, Nikita A1 - Müller, Hendrik A1 - Patel, Nimesh A1 - Raymond, Alexander A1 - Tiede, Paul A1 - Traianou, Efthalia A1 - Vega, Justin T1 - The ngEHT analysis challenges JF - Galaxies N2 - The next-generation Event Horizon Telescope (ngEHT) will be a significant enhancement of the Event Horizon Telescope (EHT) array, with ∼10 new antennas and instrumental upgrades of existing antennas. The increased uv-coverage, sensitivity, and frequency coverage allow a wide range of new science opportunities to be explored. The ngEHT Analysis Challenges have been launched to inform the development of the ngEHT array design, science objectives, and analysis pathways. For each challenge, synthetic EHT and ngEHT datasets are generated from theoretical source models and released to the challenge participants, who analyze the datasets using image reconstruction and other methods. The submitted analysis results are evaluated with quantitative metrics. In this work, we report on the first two ngEHT Analysis Challenges. These have focused on static and dynamical models of M87* and Sgr A* and shown that high-quality movies of the extended jet structure of M87* and near-horizon hourly timescale variability of Sgr A* can be reconstructed by the reference ngEHT array in realistic observing conditions using current analysis algorithms. We identify areas where there is still room for improvement of these algorithms and analysis strategies. Other science cases and arrays will be explored in future challenges. KW - very long baseline interferometry KW - black holes KW - active galactic nuclei KW - radio astronomy KW - imaging KW - instrument design KW - telescopes KW - algorithms KW - data analysis Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304976 SN - 2075-4434 VL - 11 IS - 1 ER - TY - JOUR A1 - Krstic, Jelena A1 - Herrmann, Marietta A1 - Gadjanski, Ivana A1 - Mojsilovic, Slavko T1 - Editorial: Microenvironment-derived stem cell plasticity JF - Frontiers in Cell and Developmental Biology N2 - No abstract available. KW - plasticity KW - stem cells KW - microenvironment KW - imaging KW - extracellular vesicles (EVs) KW - oxygen tension KW - tissue regeneration KW - immunomodulation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197424 SN - 2296-634X VL - 5 ER - TY - JOUR A1 - Porubsky, Stefan A1 - Popovic, Zoran V. A1 - Badve, Sunil A1 - Banz, Yara A1 - Berezowska, Sabina A1 - Borchert, Dietmar A1 - Brüggemann, Monika A1 - Gaiser, Timo A1 - Graeter, Thomas A1 - Hollaus, Peter A1 - Huettl, Katrin S. A1 - Kotrova, Michaela A1 - Kreft, Andreas A1 - Kugler, Christian A1 - Lötscher, Fabian A1 - Möller, Burkhard A1 - Ott, German A1 - Preissler, Gerhard A1 - Roessner, Eric A1 - Rosenwald, Andreas A1 - Ströbel, Philipp A1 - Marx, Alexander T1 - Thymic hyperplasia with lymphoepithelial sialadenitis (LESA)-like features: strong association with lymphomas and non-myasthenic autoimmune diseases JF - Cancers N2 - Thymic hyperplasia (TH) with lymphoepithelial sialadenitis (LESA)-like features (LESA-like TH) has been described as a tumor-like, benign proliferation of thymic epithelial cells and lymphoid follicles. We aimed to determine the frequency of lymphoma and autoimmunity in LESA-like TH and performed retrospective analysis of cases with LESA-like TH and/or thymic MALT-lymphoma. Among 36 patients (21 males) with LESA-like TH (age 52 years, 32–80; lesion diameter 7.0 cm, 1–14.5; median, range), five (14%) showed associated lymphomas, including four (11%) thymic MALT lymphomas and one (3%) diffuse large B-cell lymphoma. One additional case showed a clonal B-cell-receptor rearrangement without evidence of lymphoma. Twelve (33%) patients (7 women) suffered from partially overlapping autoimmune diseases: systemic lupus erythematosus (n = 4, 11%), rheumatoid arthritis (n = 3, 8%), myasthenia gravis (n = 2, 6%), asthma (n = 2, 6%), scleroderma, Sjögren syndrome, pure red cell aplasia, Grave’s disease and anti-IgLON5 syndrome (each n = 1, 3%). Among 11 primary thymic MALT lymphomas, remnants of LESA-like TH were found in two cases (18%). In summary, LESA-like TH shows a striking association with autoimmunity and predisposes to lymphomas. Thus, a hematologic and rheumatologic workup should become standard in patients diagnosed with LESA-like TH. Radiologists and clinicians should be aware of LESA-like TH as a differential diagnosis for mediastinal mass lesions in patients with autoimmune diseases. KW - autoimmune disease KW - imaging KW - LESA KW - lymphoma KW - myasthenia KW - pathology KW - surgery KW - thymus KW - thymic epithelial tumor KW - thymitis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223049 SN - 2072-6694 VL - 13 IS - 2 ER - TY - JOUR A1 - Hendricks, Anne A1 - Lenschow, Christina A1 - Kroiss, Matthias A1 - Buck, Andreas A1 - Kickuth, Ralph A1 - Germer, Christoph-Thomas A1 - Schlegel, Nicolas T1 - Evaluation of diagnostic efficacy for localization of parathyroid adenoma in patients with primary hyperparathyroidism undergoing repeat surgery JF - Langenbeck's Archives of Surgery N2 - Purpose Repeat surgery in patients with primary hyperparathyroidism (pHPT) is associated with an increased risk of complications and failure. This stresses the need for optimized strategies to accurately localize a parathyroid adenoma before repeat surgery is performed. However, evidence on the extent of required diagnostics for a structured approach is sparse. Methods A retrospective single-center evaluation of 28 patients with an indication for surgery due to pHPT and previous thyroid or parathyroid surgery was performed. Diagnostic workup, surgical approach, and outcome in terms of complications and successful removement of parathyroid adenoma with biochemical cure were evaluated. Results Neck ultrasound, sestamibi scintigraphy, C11-methionine PET-CT, and selective parathyroid hormone venous sampling, but not MRI imaging, effectively detected the presence of a parathyroid adenoma with high positive predictive values. Biochemical cure was revealed by normalization of calcium and parathormone levels 24-48h after surgery and was achieved in 26/28 patients (92.9%) with an overall low rate of complications. Concordant localization by at least two diagnostic modalities enabled focused surgery with success rates of 100%, whereas inconclusive localization significantly increased the rate of bilateral explorations and significantly reduced the rate of biochemical cure to 80%. Conclusion These findings suggest that two concordant diagnostic modalities are sufficient to accurately localize parathyroid adenoma before repeat surgery for pHPT. In cases of poor localization, extended diagnostic procedures are warranted to enhance surgical success rates. We suggest an algorithm for better orientation when repeat surgery is intended in patients with pHPT. KW - Primary hyperparathyroidism (pHPT) KW - preoperative localization KW - repeat surgery KW - diagnostics KW - imaging Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267520 SN - 1435-2451 VL - 406 IS - 5 ER - TY - JOUR A1 - Peters, Simon A1 - Kaiser, Lena A1 - Fink, Julian A1 - Schumacher, Fabian A1 - Perschin, Veronika A1 - Schlegel, Jan A1 - Sauer, Markus A1 - Stigloher, Christian A1 - Kleuser, Burkhard A1 - Seibel, Juergen A1 - Schubert-Unkmeir, Alexandra T1 - Click-correlative light and electron microscopy (click-AT-CLEM) for imaging and tracking azido-functionalized sphingolipids in bacteria JF - Scientific Reports N2 - Sphingolipids, including ceramides, are a diverse group of structurally related lipids composed of a sphingoid base backbone coupled to a fatty acid side chain and modified terminal hydroxyl group. Recently, it has been shown that sphingolipids show antimicrobial activity against a broad range of pathogenic microorganisms. The antimicrobial mechanism, however, remains so far elusive. Here, we introduce 'click-AT-CLEM', a labeling technique for correlated light and electron microscopy (CLEM) based on the super-resolution array tomography (srAT) approach and bio-orthogonal click chemistry for imaging of azido-tagged sphingolipids to directly visualize their interaction with the model Gram-negative bacterium Neisseria meningitidis at subcellular level. We observed ultrastructural damage of bacteria and disruption of the bacterial outer membrane induced by two azido-modified sphingolipids by scanning electron microscopy and transmission electron microscopy. Click-AT-CLEM imaging and mass spectrometry clearly revealed efficient incorporation of azido-tagged sphingolipids into the outer membrane of Gram-negative bacteria as underlying cause of their antimicrobial activity. KW - antimicrobials KW - biological techniques KW - imaging KW - microbiology KW - microbiology techniques KW - microscopy Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259147 VL - 11 IS - 1 ER - TY - JOUR A1 - Voigt, Gesche M. A1 - Thiele, Dominik A1 - Wetzke, Martin A1 - Weidemann, Jürgen A1 - Parpatt, Patricia‐Maria A1 - Welte, Tobias A1 - Seidenberg, Jürgen A1 - Vogelberg, Christian A1 - Koster, Holger A1 - Rohde, Gernot G. U. A1 - Härtel, Christoph A1 - Hansen, Gesine A1 - Kopp, Matthias V. T1 - Interobserver agreement in interpretation of chest radiographs for pediatric community acquired pneumonia: Findings of the pedCAPNETZ‐cohort JF - Pediatric Pulmonology N2 - Although chest radiograph (CXR) is commonly used in diagnosing pediatric community acquired pneumonia (pCAP), limited data on interobserver agreement among radiologists exist. PedCAPNETZ is a prospective, observational, and multicenter study on pCAP. N = 233 CXR from patients with clinical diagnosis of pCAP were retrieved and n = 12 CXR without pathological findings were added. All CXR were interpreted by a radiologist at the site of recruitment and by two external, blinded pediatric radiologists. To evaluate interobserver agreement, the reporting of presence or absence of pCAP in CXR was analyzed, and prevalence and bias‐adjusted kappa (PABAK) statistical testing was applied. Overall, n = 190 (82%) of CXR were confirmed as pCAP by two external pediatric radiologists. Compared with patients with pCAP negative CXR, patients with CXR‐confirmed pCAP displayed higher C‐reactive protein levels and a longer duration of symptoms before enrollment (p < .007). Further parameters, that is, age, respiratory rate, and oxygen saturation showed no significant difference. The interobserver agreement between the onsite radiologists and each of the two independent pediatric radiologists for the presence of pCAP was poor to fair (69%; PABAK = 0.39% and 76%; PABAK = 0.53, respectively). The concordance between the external radiologists was fair (81%; PABAK = 0.62). With regard to typical CXR findings for pCAP, chance corrected interrater agreement was highest for pleural effusions, infiltrates, and consolidations and lowest for interstitial patterns and peribronchial thickening. Our data show a poor interobserver agreement in the CXR‐based diagnosis of pCAP and emphasized the need for harmonized interpretation standards. KW - antibiotic therapy KW - imaging KW - infections: pneumonia KW - TB KW - viral Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244705 VL - 56 IS - 8 SP - 2676 EP - 2685 ER - TY - JOUR A1 - Li, Kunkun A1 - Prada, Juan A1 - Damineli, Daniel S. C. A1 - Liese, Anja A1 - Romeis, Tina A1 - Dandekar, Thomas A1 - Feijó, José A. A1 - Hedrich, Rainer A1 - Konrad, Kai Robert T1 - An optimized genetically encoded dual reporter for simultaneous ratio imaging of Ca\(^{2+}\) and H\(^{+}\) reveals new insights into ion signaling in plants JF - New Phytologist N2 - Whereas the role of calcium ions (Ca\(^{2+}\)) in plant signaling is well studied, the physiological significance of pH‐changes remains largely undefined. Here we developed CapHensor, an optimized dual‐reporter for simultaneous Ca\(^{2+}\) and pH ratio‐imaging and studied signaling events in pollen tubes (PTs), guard cells (GCs), and mesophyll cells (MCs). Monitoring spatio‐temporal relationships between membrane voltage, Ca\(^{2+}\)‐ and pH‐dynamics revealed interconnections previously not described. In tobacco PTs, we demonstrated Ca\(^{2+}\)‐dynamics lag behind pH‐dynamics during oscillatory growth, and pH correlates more with growth than Ca\(^{2+}\). In GCs, we demonstrated abscisic acid (ABA) to initiate stomatal closure via rapid cytosolic alkalization followed by Ca2+ elevation. Preventing the alkalization blocked GC ABA‐responses and even opened stomata in the presence of ABA, disclosing an important pH‐dependent GC signaling node. In MCs, a flg22‐induced membrane depolarization preceded Ca2+‐increases and cytosolic acidification by c. 2 min, suggesting a Ca\(^{2+}\)/pH‐independent early pathogen signaling step. Imaging Ca2+ and pH resolved similar cytosol and nuclear signals and demonstrated flg22, but not ABA and hydrogen peroxide to initiate rapid membrane voltage‐, Ca\(^{2+}\)‐ and pH‐responses. We propose close interrelation in Ca\(^{2+}\)‐ and pH‐signaling that is cell type‐ and stimulus‐specific and the pH having crucial roles in regulating PT growth and stomata movement. KW - abscisic acid (ABA) KW - calcium KW - flg22 KW - guard cells KW - imaging KW - ion signaling KW - pH KW - pollen tube Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239847 VL - 230 IS - 6 SP - 2292 EP - 2310 ER - TY - JOUR A1 - Rogowski-Lehmann, Natalie A1 - Geroula, Aikaterini A1 - Prejbisz, Aleksander A1 - Timmers, Henri J. L. M. A1 - Megerle, Felix A1 - Robledo, Mercedes A1 - Fassnacht, Martin A1 - Fliedner, Stephanie M. J. A1 - Reincke, Martin A1 - Stell, Anthony A1 - Januszewicz, Andrzej A1 - Lenders, Jacques W. M. A1 - Eisenhofer, Graeme A1 - Beuschlein, Felix T1 - Missed clinical clues in patients with pheochromocytoma/paraganglioma discovered by imaging JF - Endocrine Connections N2 - Background: Pheochromocytomas and paragangliomas (PPGLs) are rare but potentially harmful tumors that can vary in their clinical presentation. Tumors may be found due to signs and symptoms, as part of a hereditary syndrome or following an imaging procedure. Objective: To investigate potential differences in clinical presentation between PPGLs discovered by imaging (iPPGLs), symptomatic cases (sPPGLs) and those diagnosed during follow-up because of earlier disease/known hereditary mutations (fPPGL). Design: Prospective study protocol, which has enrolled patients from six European centers with confirmed PPGLs. Data were analyzed from 235 patients (37 iPPGLs, 36 sPPGLs, 27% fPPGLs) and compared for tumor volume, biochemical profile, mutation status, presence of metastases and self-reported symptoms. iPPGL patients were diagnosed at a significantly higher age than fPPGLs (P<0.001), found to have larger tumors (P=0.003) and higher metanephrine and normetanephrine levels at diagnosis (P=0.021). Significantly lower than in sPPGL, there was a relevant number of self-reported symptoms in iPPGL (2.9 vs 4.3 symptoms, P< 0.001). In 16.2% of iPPGL, mutations in susceptibility genes were detected, although this proportion was lower than that in fPPGL (60.9%) and sPPGL (21.5%). Patients with PPGLs detected by imaging were older, have higher tumor volume and more excessive hormonal secretion in comparison to those found as part of a surveillance program. Presence of typical symptoms indicates that in a relevant proportion of those patients, the PPGL diagnosis had been delayed. Precis: Pheochromocytoma/paraganglioma discovered by imaging are often symptomatic and carry a significant proportion of germline mutations in susceptibility genes. KW - pheochromocytoma KW - paraganglioma KW - imaging KW - signs and symptoms KW - prospective KW - Biochemical-Diagnosis KW - Plasma KW - MASS KW - Normetanephrine KW - Metanephrine KW - Paraganglioma KW - Society KW - Utility Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226481 VL - 7 IS - 11 ER - TY - JOUR A1 - Drakopoulos, Antonios A1 - Decker, Michael T1 - Development and Biological Applications of Fluorescent Opioid Ligands JF - ChemPlusChem N2 - Opioid receptors (ORs) are classified among the oldest and best investigated drug targets due to their fundamental role in the treatment of pain and related disorders. ORs are divided in three conventional subtypes (μ, κ, δ) and the non‐classical nocicepetin receptor. All ORs are family A G protein‐coupled receptors (GPCRs), and are located on the cell surface. Modern biophysical methods use light to investigate physiological processes at organismal, cellular and subcellular level. Many of these methods rely on fluorescent ligands, thus highlighting their importance. This review addresses the advancements in the development of opioid fluorescent ligands and their use in biological, pharmacological and imaging applications. KW - biophysics KW - fluorescent ligands KW - imaging KW - microscopy KW - opioid receptors Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216068 VL - 85 IS - 6 SP - 1354 EP - 1364 ER - TY - THES A1 - Griesbeck, Stefanie Ingrid T1 - A Very Positive Image of Boron: Triarylborane Chromophores for Live Cell Imaging T1 - Ein sehr positives Bild von Bor: Triarylboran Farbstoffe für Lebendzellenmikroskopie N2 - Efficient quadrupolar chromophores (A–pi–A) with triarylborane moieties as acceptors have been studied by the Marder group regarding their non‐linear optical properties and two‐photon absorption ability for many years. Within the present work, this class of dyes found applications in live‐cell imaging. Therefore, the dyes need to be water‐soluble and water‐stable in diluted aqueous solutions, which was examined in Chapter 2. Furthermore, the influence of the pi‐bridge on absorption and emission maxima, fluorescence quantum yields and especially the two-photon absorption properties of the chromophores was investigated in Chapter 3. In Chapter 4, a different strategy for the design of efficient two‐photon excited fluorescence imaging dyes was explored using dipoles (D–A) and octupoles (DA3). Finding the optimum balance between water‐stability and pi‐conjugation and, therefore, red‐shifted absorption and emission and high fluorescence quantum yields, was investigated in Chapter 5 N2 - Effiziente quadrupole Farbstoffe (A–pi–A) mit Triarylboraneinheiten als Akzeptoren wurden innerhalb der letzten Jahre von der Arbeitsgruppe Marder bezüglich ihrer nicht‐linearen optischen Eigenschaften und Zweiphotonenabsorptionsfähigkeiten untersucht. In der vorliegenden Arbeit wurde diese Farbstoffklasse zur Untersuchung lebender Zellen mittels Fluoreszenzmikroskopie angewendet. Hierzu müssen die Farbstoffe wasserlöslich und in verdünnten wässrigen Lösungen stabil sein. Dies wurde in Kapitel 2 untersucht. Außerdem wurde der Einfluss der pi‐Brücke auf das Absorptions‐ und Emissionsmaximum, die Fluoreszenzquantenausbeute und vor allem die Zweiphotonenabsorptionsfähigkeit untersucht (Kapitel 3). In Kapitel 4 wurden andere molekulare Designstrategien verfolgt um effiziente Zweiphotonenangeregtenfluoreszenzfarbstoffe zu erhalten. Dazu zählen die Strukturmotive des Dipols (D–A) und des Oktupols (DA3). Bestandteil des Kapitels 5 war die Optimierung zwischen Wasserstabilität und pi‐Konjugation und eine damit verbundene rotverschobene Absorption und Emission, sowie eine hohe Fluoreszenzquantenausbeute KW - Borane KW - Bor KW - Lumineszenz KW - Fluoreszenz KW - Zweiphotonenabsorption KW - imaging KW - luminescence KW - fluorescence KW - two-photon absorption KW - borane Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-179921 ER -