TY - JOUR A1 - Hauptstein, Julia A1 - Forster, Leonard A1 - Nadernezhad, Ali A1 - Horder, Hannes A1 - Stahlhut, Philipp A1 - Groll, Jürgen A1 - Blunk, Torsten A1 - Teßmar, Jörg T1 - Bioink Platform Utilizing Dual-Stage Crosslinking of Hyaluronic Acid Tailored for Chondrogenic Differentiation of Mesenchymal Stromal Cells JF - Macromolecular Bioscience N2 - 3D bioprinting often involves application of highly concentrated polymeric bioinks to enable fabrication of stable cell-hydrogel constructs, although poor cell survival, compromised stem cell differentiation, and an inhomogeneous distribution of newly produced extracellular matrix (ECM) are frequently observed. Therefore, this study presents a bioink platform using a new versatile dual-stage crosslinking approach based on thiolated hyaluronic acid (HA-SH), which not only provides stand-alone 3D printability but also facilitates effective chondrogenic differentiation of mesenchymal stromal cells. A range of HA-SH with different molecular weights is synthesized and crosslinked with acrylated (PEG-diacryl) and allylated (PEG-diallyl) polyethylene glycol in a two-step reaction scheme. The initial Michael addition is used to achieve ink printability, followed by UV-mediated thiol–ene reaction to stabilize the printed bioink for long-term cell culture. Bioinks with high molecular weight HA-SH (>200 kDa) require comparably low polymer content to facilitate bioprinting. This leads to superior quality of cartilaginous constructs which possess a coherent ECM and a strongly increased stiffness of long-term cultured constructs. The dual-stage system may serve as an example to design platforms using two independent crosslinking reactions at one functional group, which allows adjusting printability as well as material and biological properties of bioinks. KW - hyaluronic acid KW - biofabrication KW - chondrogenic differentiation KW - dual-stage crosslinking KW - extracellular matrix Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257556 VL - 22 IS - 2 ER - TY - JOUR A1 - Hendricks, Anne A1 - Müller, Sophie A1 - Fassnacht, Martin A1 - Germer, Christoph-Thomas A1 - Wiegering, Verena A. A1 - Wiegering, Armin A1 - Reibetanz, Joachim T1 - Impact of lymphadenectomy on the oncologic outcome of patients with adrenocortical carcinoma — a systematic review and meta-analysis JF - Cancers N2 - (1) Background: Locoregional lymphadenectomy (LND) in adrenocortical carcinoma (ACC) may impact oncological outcome, but the findings from individual studies are conflicting. The aim of this systematic review and meta-analysis was to determine the oncological value of LND in ACC by summarizing the available literature. (2) Methods: A systematic search on studies published until December 2020 was performed according to the PRISMA statement. The primary outcome was the impact of lymphadenectomy on overall survival (OS). Two separate meta-analyses were performed for studies including patients with localized ACC (stage I–III) and those including all tumor stages (I–IV). Secondary endpoints included postoperative mortality and length of hospital stay (LOS). (3) Results: 11 publications were identified for inclusion. All studies were retrospective studies, published between 2001–2020, and 5 were included in the meta-analysis. Three studies (N = 807 patients) reported the impact of LND on disease-specific survival in patients with stage I–III ACC and revealed a survival benefit of LND (hazard ratio (HR) = 0.42, 95% confidence interval (95% CI): 0.26–0.68). Based on results of studies including patients with ACC stage I–IV (2 studies, N = 3934 patients), LND was not associated with a survival benefit (HR = 1.00, 95% CI: 0.70–1.42). None of the included studies showed an association between LND and postoperative mortality or LOS. (4) Conclusion: Locoregional lymphadenectomy seems to offer an oncologic benefit in patients undergoing curative-intended surgery for localized ACC (stage I–III). KW - adrenocortical carcinoma KW - adrenal cancer KW - lymphadenectomy KW - lymph node dissection KW - LND KW - LNE KW - review KW - meta-analysis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254798 SN - 2072-6694 VL - 14 IS - 2 ER - TY - JOUR A1 - Ademmer, Martin A1 - Horn, Wolfram A1 - Quast, Josefine T1 - Stock market dynamics and the relative importance of domestic, foreign, and common shocks JF - International Journal of Finance & Economics N2 - We quantify the contemporaneous relationships among stock markets in the euro area, the United States, and a group of emerging economies over the period from 2008 to 2017. Exploiting the heteroskedasticity in the stock market data, we identify shocks that originated in the respective domestic markets and shocks that are common to all markets. Our results underline the leading role of the United States in international equity markets, but also point to the importance of indirect spillovers for all economies. Variance decompositions show that while domestic shocks explain the bigger part of the variation in each stock market, a substantial part of the variation in the euro area and the emerging economies can be attributed to foreign shocks. A comparison with a sample covering the pre‐crisis period from 1999 to 2007 suggests a strengthening of the linkages among global stock markets in recent years. In particular, the spillovers from advanced to emerging economies have become more pronounced. KW - financial linkages KW - heteroskedasticity KW - identification KW - spillovers KW - stock markets Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225729 VL - 27 IS - 4 SP - 3911 EP - 3923 ER - TY - JOUR A1 - Guggenberger, Konstanze V. A1 - Bley, Thorsten A. A1 - Vogt, Marius L. A1 - Urbach, Horst A1 - Meckel, Stephan T1 - High-Resolution Black Blood Vessel Wall Imaging in COVID-19 Encephalopathy-Is it Really Endotheliitis? JF - Clinical Neuroradiology N2 - No abstract available. KW - Covid-19 KW - encephalopathy KW - endotheliitis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-264794 VL - 32 IS - 1 ER - TY - JOUR A1 - Vogt, Marius L. A1 - Kollikowski, Alexander M. A1 - Weidner, Franziska A1 - Strinitz, Marc A1 - Feick, Jörn A1 - Essig, Fabian A1 - Neugebauer, Herrmann A1 - Haeusler, Karl Georg A1 - Pham, Mirko A1 - Maerz, Alexander T1 - Safety and Effectiveness of the New Generation APERIO® Hybrid Stent-retriever Device in Large Vessel Occlusion Stroke JF - Clinical Neuroradiology N2 - Background It is unknown whether technological advancement of stent-retriever devices influences typical observational indicators of safety or effectiveness. Methods Observational retrospective study of APERIO® (AP) vs. new generation APERIO® Hybrid (APH) (Acandis®, Pforzheim, Germany) stent-retriever device (01/2019–09/2020) for mechanical thrombectomy (MT) in large vessel occlusion (LVO) stroke. Primary effectiveness endpoint was successful recanalization eTICI (expanded Thrombolysis In Cerebral Ischemia) ≥ 2b67, primary safety endpoint was occurrence of hemorrhagic complications after MT. Secondary outcome measures were time from groin puncture to first pass and successful reperfusion, and the total number of passes needed to achieve the final recanalization result. Results A total of 298 patients with LVO stroke who were treated by MT matched the inclusion criteria: 148 patients (49.7%) treated with AP vs. 150 patients (50.3%) treated with new generation APH. Successful recanalization was not statistically different between both groups: 75.7% for AP vs. 79.3% for APH; p = 0.450. Postinterventional hemorrhagic complications and particularly subarachnoid hemorrhage as the entity possibly associated with stent-retriever device type was significantly less frequent in the group treated with the APH: 29.7% for AP and 16.0% for APH; p = 0.005; however, rates of symptomatic hemorrhage with clinical deterioration and in domo mortality were not statistically different. Neither the median number of stent-retriever passages needed to achieve final recanalization, time from groin puncture to first pass, time from groin puncture to final recanalization nor the number of cases in which successful recanalization could only be achieved by using a different stent-retriever as bail-out device differed between both groups. Conclusion In the specific example of the APERIO® stent-retriever device, we observed that further technological developments of the new generation device were not associated with disadvantages with respect to typical observational indicators of safety or effectiveness. KW - APERIO Hybrid KW - mechanical thrombectomy KW - stent-retriever device KW - stroke KW - APERIO Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-264817 VL - 32 IS - 1 ER - TY - JOUR A1 - Klement, Rainer J. A1 - Popp, Ilinca A1 - Kaul, David A1 - Ehret, Felix A1 - Grosu, Anca L. A1 - Polat, Bülent A1 - Sweeney, Reinhart A. A1 - Lewitzki, Victor T1 - Accelerated hyper-versus normofractionated radiochemotherapy with temozolomide in patients with glioblastoma: a multicenter retrospective analysis JF - Journal of Neuro-Oncology N2 - Background and Purpose The standard treatment of glioblastoma patients consists of surgery followed by normofractionated radiotherapy (NFRT) with concomitant and adjuvant temozolomide chemotherapy. Whether accelerated hyperfractionated radiotherapy (HFRT) yields comparable results to NFRT in combination with temozolomide has only sparsely been investigated. The objective of this study was to compare NFRT with HFRT in a multicenter analysis. Materials and Methods A total of 484 glioblastoma patients from four centers were retrospectively pooled and analyzed. Three-hundred-ten and 174 patients had been treated with NFRT (30 × 1.8 Gy or 30 × 2 Gy) and HFRT (37 × 1.6 Gy or 30 × 1.8 Gy twice/day), respectively. The primary outcome of interest was overall survival (OS) which was correlated with patient-, tumor- and treatment-related variables via univariable and multivariable Cox frailty models. For multivariable modeling, missing covariates were imputed using multiple imputation by chained equations, and a sensitivity analysis was performed on the complete-cases-only dataset. Results After a median follow-up of 15.7 months (range 0.8-88.6 months), median OS was 16.9 months (15.0-18.7 months) in the NFRT group and 14.9 months (13.2-17.3 months) in the HFRT group (p = 0.26). In multivariable frailty regression, better performance status, gross-total versus not gross-total resection, MGMT hypermethylation, IDH mutation, smaller planning target volume and salvage therapy were significantly associated with longer OS (all p < 0.01). Treatment differences (HFRT versus NFRT) had no significant effect on OS in either univariable or multivariable analysis. Conclusions Since HFRT with temozolomide was not associated with worse OS, we assume HFRT to be a potential option for patients wishing to shorten their treatment time. KW - temozolomide KW - accelerated hyperfractionation KW - altered fractionation KW - glioblastoma KW - radiotherapy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-269806 SN - 1573-7373 VL - 156 IS - 2 ER - TY - JOUR A1 - Kittel-Schneider, Sarah A1 - Felice, Ethel A1 - Buhagiar, Rachel A1 - Lambregtse-van den Berg, Mijke A1 - Wilson, Claire A. A1 - Banjac Baljak, Visnja A1 - Vujovic, Katarina Savic A1 - Medic, Branislava A1 - Opankovic, Ana A1 - Fonseca, Ana A1 - Lupattelli, Angela T1 - Treatment of peripartum depression with antidepressants and other psychotropic medications: a synthesis of clinical practice guidelines in Europe JF - International Journal of Environmental Research and Public Health N2 - This study examined (1) the availability and content of national CPGs for treatment of peripartum depression, including comorbid anxiety, with antidepressants and other psychotropics across Europe and (2) antidepressant and other psychotropic utilization data as an indicator of prescribers' compliance to the guidelines. We conducted a search using Medline and the Guidelines International Network database, combined with direct e-mail contact with national Riseup-PPD COST ACTION members and researchers within psychiatry. Of the 48 European countries examined, we screened 41 records and included 14 of them for full-text evaluation. After exclusion of ineligible and duplicate records, we included 12 CPGs. Multiple CPGs recommend antidepressant initiation or continuation based on maternal disease severity, non-response to first-line non-pharmacological interventions, and after risk-benefit assessment. Advice on treatment of comorbid anxiety is largely missing or unspecific. Antidepressant dispensing data suggest general prescribers' compliance with the preferred substances of the CPG, although country-specific differences were noted. To conclude, there is an urgent need for harmonized, up-to-date CPGs for pharmacological management of peripartum depression and comorbid anxiety in Europe. The recommendations need to be informed by the latest available evidence so that healthcare providers and women can make informed, evidence-based decisions about treatment choices. KW - clinical practice guideline KW - depression KW - anxiety KW - antidepressant KW - psychotropic medications KW - peripartum Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262130 SN - 1660-4601 VL - 19 IS - 4 ER - TY - JOUR A1 - Rudert, Maximilian T1 - Taking the next step in personalised orthopaedic implantation JF - Journal of Personalized Medicine N2 - No abstract available KW - personalised orthopaedic implantation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262089 SN - 2075-4426 VL - 12 IS - 3 ER - TY - JOUR A1 - Prezza, Gianluca A1 - Ryan, Daniel A1 - Mädler, Gohar A1 - Reichardt, Sarah A1 - Barquist, Lars A1 - Westermann, Alexander J. T1 - Comparative genomics provides structural and functional insights into Bacteroides RNA biology JF - Molecular Microbiology N2 - Bacteria employ noncoding RNA molecules for a wide range of biological processes, including scaffolding large molecular complexes, catalyzing chemical reactions, defending against phages, and controlling gene expression. Secondary structures, binding partners, and molecular mechanisms have been determined for numerous small noncoding RNAs (sRNAs) in model aerobic bacteria. However, technical hurdles have largely prevented analogous analyses in the anaerobic gut microbiota. While experimental techniques are being developed to investigate the sRNAs of gut commensals, computational tools and comparative genomics can provide immediate functional insight. Here, using Bacteroides thetaiotaomicron as a representative microbiota member, we illustrate how comparative genomics improves our understanding of RNA biology in an understudied gut bacterium. We investigate putative RNA-binding proteins and predict a Bacteroides cold-shock protein homolog to have an RNA-related function. We apply an in silico protocol incorporating both sequence and structural analysis to determine the consensus structures and conservation of nine Bacteroides noncoding RNA families. Using structure probing, we validate and refine these predictions and deposit them in the Rfam database. Through synteny analyses, we illustrate how genomic coconservation can serve as a predictor of sRNA function. Altogether, this work showcases the power of RNA informatics for investigating the RNA biology of anaerobic microbiota members. KW - BT_1884 KW - cold-shock protein KW - GibS KW - RNA-binding proteins KW - secondary structure KW - 6S RNA Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259594 VL - 117 IS - 1 ER - TY - JOUR A1 - Bahena, Paulina A1 - Daftarian, Narsis A1 - Maroofian, Reza A1 - Linares, Paola A1 - Villalobos, Daniel A1 - Mirrahimi, Mehraban A1 - Rad, Aboulfazl A1 - Doll, Julia A1 - Hofrichter, Michaela A. H. A1 - Koparir, Asuman A1 - Röder, Tabea A1 - Han, Seungbin A1 - Sabbaghi, Hamideh A1 - Ahmadieh, Hamid A1 - Behboudi, Hassan A1 - Villanueva-Mendoza, Cristina A1 - Cortés-Gonzalez, Vianney A1 - Zamora-Ortiz, Rocio A1 - Kohl, Susanne A1 - Kuehlewein, Laura A1 - Darvish, Hossein A1 - Alehabib, Elham A1 - La Arenas-Sordo, Maria de Luz A1 - Suri, Fatemeh A1 - Vona, Barbara A1 - Haaf, Thomas T1 - Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment JF - Human Genetics N2 - Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically and genetically heterogeneous. Moreover, several conditions with phenotypes overlapping Usher syndrome have been described. This makes the molecular diagnosis of hereditary deaf-blindness challenging. Here, we performed exome sequencing and analysis on 7 Mexican and 52 Iranian probands with combined retinal degeneration and hearing impairment (without intellectual disability). Clinical assessment involved ophthalmological examination and hearing loss questionnaire. Usher syndrome, most frequently due to biallelic variants in MYO7A (USH1B in 16 probands), USH2A (17 probands), and ADGRV1 (USH2C in 7 probands), was diagnosed in 44 of 59 (75%) unrelated probands. Almost half of the identified variants were novel. Nine of 59 (15%) probands displayed other genetic entities with dual sensory impairment, including Alström syndrome (3 patients), cone-rod dystrophy and hearing loss 1 (2 probands), and Heimler syndrome (1 patient). Unexpected findings included one proband each with Scheie syndrome, coenzyme Q10 deficiency, and pseudoxanthoma elasticum. In four probands, including three Usher cases, dual sensory impairment was either modified/aggravated or caused by variants in distinct genes associated with retinal degeneration and/or hearing loss. The overall diagnostic yield of whole exome analysis in our deaf-blind cohort was 92%. Two (3%) probands were partially solved and only 3 (5%) remained without any molecular diagnosis. In many cases, the molecular diagnosis is important to guide genetic counseling, to support prognostic outcomes and decisions with currently available and evolving treatment modalities. KW - Usher syndrome KW - hearing impairment KW - combined retinal dystrophy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267750 SN - 1432-1203 VL - 141 IS - 3-4 ER - TY - JOUR A1 - Svirin, Evgeniy A1 - Veniaminova, Ekaterina A1 - Costa-Nunes, João Pedro A1 - Gorlova, Anna A1 - Umriukhin, Aleksei A1 - Kalueff, Allan V. A1 - Proshin, Andrey A1 - Anthony, Daniel C. A1 - Nedorubov, Andrey A1 - Tse, Anna Chung Kwan A1 - Walitza, Susanne A1 - Lim, Lee Wei A1 - Lesch, Klaus-Peter A1 - Strekalova, Tatyana T1 - Predation stress causes excessive aggression in female mice with partial genetic inactivation of tryptophan hydroxylase-2: evidence for altered myelination-related processes JF - Cells N2 - The interaction between brain serotonin (5-HT) deficiency and environmental adversity may predispose females to excessive aggression. Specifically, complete inactivation of the gene encoding tryptophan hydroxylase-2 (Tph2) results in the absence of neuronal 5-HT synthesis and excessive aggressiveness in both male and female null mutant (Tph2\(^{−/−}\)) mice. In heterozygous male mice (Tph2\(^{+/−}\)), there is a moderate reduction in brain 5-HT levels, and when they are exposed to stress, they exhibit increased aggression. Here, we exposed female Tph2\(^{+/−}\) mice to a five-day rat predation stress paradigm and assessed their emotionality and social interaction/aggression-like behaviors. Tph2\(^{+/−}\) females exhibited excessive aggression and increased dominant behavior. Stressed mutants displayed altered gene expression of the 5-HT receptors Htr1a and Htr2a, glycogen synthase kinase-3 β (GSK-3β), and c-fos as well as myelination-related transcripts in the prefrontal cortex: myelin basic protein (Mbp), proteolipid protein 1 (Plp1), myelin-associated glycoprotein (Mag), and myelin oligodendrocyte glycoprotein (Mog). The expression of the plasticity markers synaptophysin (Syp) and cAMP response element binding protein (Creb), but not AMPA receptor subunit A2 (GluA2), were affected by genotype. Moreover, in a separate experiment, naïve female Tph2\(^{+/−}\) mice showed signs of enhanced stress resilience in the modified swim test with repeated swimming sessions. Taken together, the combination of a moderate reduction in brain 5-HT with environmental challenges results in behavioral changes in female mice that resemble the aggression-related behavior and resilience seen in stressed male mutants; additionally, the combination is comparable to the phenotype of null mutants lacking neuronal 5-HT. Changes in myelination-associated processes are suspected to underpin the molecular mechanisms leading to aggressive behavior. KW - tryptophan hydroxylase-2 (Tph2) KW - female aggression KW - 5-HT receptors KW - glycogen synthase kinase-3 β (GSK-3β) KW - myelination KW - predation stress Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267250 SN - 2073-4409 VL - 11 IS - 6 ER - TY - JOUR A1 - Surat, Güzin A1 - Meyer-Sautter, Pascal A1 - Rüsch, Jan A1 - Braun-Feldweg, Johannes A1 - Markus, Christian Karl A1 - Germer, Christoph-Thomas A1 - Lock, Johan Friso T1 - Cefazolin might be adequate for perioperative antibiotic prophylaxis in intra-abdominal infections without sepsis: a quality improvement study JF - Antibiotics N2 - Background: The adequate choice of perioperative antibiotic prophylaxis (PAP) could influence the risk of surgical site infections (SSIs) in general surgery. A new local PAP guideline was implemented in May 2017 and set the first-generation cefazolin (CFZ) instead the second-generation cefuroxime (CXM) as the new standard prophylactic antibiotic. The aim of this study was to compare the risk of SSIs after this implementation in intra-abdominal infections (IAIs) without sepsis. Methods: We performed a single center-quality improvement study at a 1500 bed sized university hospital in Germany analyzing patients after emergency surgery during 2016 to 2019 (n = 985), of which patients receiving CXM or CFZ were selected (n = 587). Propensity score matching was performed to ensure a comparable risk of SSIs in both groups. None-inferiority margin for SSIs was defined as 8% vs. 4%. Results: Two matched cohorts with respectively 196 patients were compared. The rate of SSIs was higher in the CFZ group (7.1% vs. 3.6%, p = 0.117) below the non-inferiority margin. The rate of other postoperative infections was significantly higher in the CFZ group (2.0% vs. 8.7%, p = 0.004). No other differences including postoperative morbidity, mortality or length-of-stay were observed. Conclusion: Perioperative antibiotic prophylaxis might be safely maintained by CFZ even in the treatment of intra-abdominal infections. KW - antimicrobial stewardship KW - antibiotic prescribing quality KW - low-risk intra-abdominal infections KW - perioperative antibiotic prophylaxis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270816 SN - 2079-6382 VL - 11 IS - 4 ER - TY - JOUR A1 - Dufner, Vera A1 - Kessler, Almuth Friederike A1 - Just, Larissa A1 - Hau, Peter A1 - Bumes, Elisabeth A1 - Pels, Hendrik Johannes A1 - Grauer, Oliver Martin A1 - Wiese, Bettina A1 - Löhr, Mario A1 - Jordan, Karin A1 - Strik, Herwig T1 - The emesis trial: depressive glioma patients are more affected by chemotherapy-induced nausea and vomiting JF - Frontiers in Neurology N2 - Purpose Glioma patients face a limited life expectancy and at the same time, they suffer from afflicting symptoms and undesired effects of tumor treatment. Apart from bone marrow suppression, standard chemotherapy with temozolomide causes nausea, emesis and loss of appetite. In this pilot study, we investigated how chemotherapy-induced nausea and vomiting (CINV) affects the patients' levels of depression and their quality of life. Methods In this prospective observational multicentre study (n = 87), nausea, emesis and loss of appetite were evaluated with an expanded MASCC questionnaire, covering 10 days during the first and the second cycle of chemotherapy. Quality of life was assessed with the EORTC QLQ-C30 and BN 20 questionnaire and levels of depression with the PHQ-9 inventory before and after the first and second cycle of chemotherapy. Results CINV affected a minor part of patients. If present, it reached its maximum at day 3 and decreased to baseline level not before day 8. Levels of depression increased significantly after the first cycle of chemotherapy, but decreased during the further course of treatment. Patients with higher levels of depression were more severely affected by CINV and showed a lower quality of life through all time-points. Conclusion We conclude that symptoms of depression should be perceived in advance and treated in order to avoid more severe side effects of tumor treatment. Additionally, in affected patients, delayed nausea was most prominent, pointing toward an activation of the NK1 receptor. We conclude that long acting antiemetics are necessary totreat temozolomide-induced nausea. KW - glioblastoma KW - chemotherapy KW - depression KW - nausea and emesis KW - quality of life Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262859 SN - 1664-2295 VL - 13 ER - TY - JOUR A1 - Gerhard‐Hartmann, Elena A1 - Jöhrens, Korinna A1 - Schinagl, Lisa‐Marie A1 - Zamó, Alberto A1 - Rosenwald, Andreas A1 - Anagnostopoulos, Ioannis A1 - Rosenfeldt, Mathias T1 - Epstein–Barr virus infection patterns in nodular lymphocyte‐predominant Hodgkin lymphoma JF - Histopathology N2 - Aims To investigate Epstein‐Barr virus (EBV) latency types in 19 cases of EBV‐positive nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL), as such information is currently incomplete. Methods and results Immunohistochemistry (IHC) for CD20, CD79a, PAX5, OCT2, CD30, CD15, CD3 and programmed cell death protein 1 was performed. For EBV detection, in‐situ hybridisation (ISH) for EBV‐encoded RNA (EBER) was employed combined with IHC for EBV‐encoded latent membrane protein (LMP)‐1, EBV‐encoded nuclear antigen (EBNA)‐2, and EBV‐encoded BZLF1. In 95% of the cases, neoplastic cells with features of Hodgkin and Reed–Sternberg (HRS) cells were present, mostly showing expression of CD30. In all cases, the B‐cell phenotype was largely intact, and delineation from classic Hodgkin lymphoma (CHL) was further supported by myocyte enhancer factor 2B (MEF2B) detection. All tumour cells were EBER‐positive except in two cases. EBV latency type II was most frequent (89%) and type I was rare. Cases with latency type I were CD30‐negative. Five cases contained some BZLF1‐positive and/or EBNA‐2‐positive bystander lymphocytes. Conclusions As HRS morphology of neoplastic cells and CD30 expression are frequent features of EBV‐positive NLPHL, preservation of the B‐cell transcription programme, MEF2B expression combined with NLPHL‐typical architecture and background composition facilitate distinction from CHL. EBER ISH is the method of choice to identify these cases. The majority present with EBV latency type II, and only rare cases present with latency type I, which can be associated with missing CD30 expression. The presence of occasional bystander lymphocytes expressing BZLF1 and/or EBNA‐2 and the partial EBV infection of neoplastic cells in some cases could indicate that EBV is either not primarily involved or is only a transient driver in the pathogenesis of EBV‐positive NLPHL. KW - EBV KW - Hodgkin lymphoma KW - latency type KW - NLPHL Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-276327 VL - 80 IS - 7 SP - 1071 EP - 1080 ER - TY - JOUR A1 - Uereyen, Soner A1 - Bachofer, Felix A1 - Kuenzer, Claudia T1 - A framework for multivariate analysis of land surface dynamics and driving variables — a case study for Indo-Gangetic river basins JF - Remote Sensing N2 - The analysis of the Earth system and interactions among its spheres is increasingly important to improve the understanding of global environmental change. In this regard, Earth observation (EO) is a valuable tool for monitoring of long term changes over the land surface and its features. Although investigations commonly study environmental change by means of a single EO-based land surface variable, a joint exploitation of multivariate land surface variables covering several spheres is still rarely performed. In this regard, we present a novel methodological framework for both, the automated processing of multisource time series to generate a unified multivariate feature space, as well as the application of statistical time series analysis techniques to quantify land surface change and driving variables. In particular, we unify multivariate time series over the last two decades including vegetation greenness, surface water area, snow cover area, and climatic, as well as hydrological variables. Furthermore, the statistical time series analyses include quantification of trends, changes in seasonality, and evaluation of drivers using the recently proposed causal discovery algorithm Peter and Clark Momentary Conditional Independence (PCMCI). We demonstrate the functionality of our methodological framework using Indo-Gangetic river basins in South Asia as a case study. The time series analyses reveal increasing trends in vegetation greenness being largely dependent on water availability, decreasing trends in snow cover area being mostly negatively coupled to temperature, and trends of surface water area to be spatially heterogeneous and linked to various driving variables. Overall, the obtained results highlight the value and suitability of this methodological framework with respect to global climate change research, enabling multivariate time series preparation, derivation of detailed information on significant trends and seasonality, as well as detection of causal links with minimal user intervention. This study is the first to use multivariate time series including several EO-based variables to analyze land surface dynamics over the last two decades using the causal discovery algorithm PCMCI. KW - time series analysis KW - trends KW - seasonality KW - partial correlation KW - causal networks KW - NDVI KW - snow cover area KW - surface water area KW - Indus-Ganges-Brahmaputra-Meghna KW - Himalaya Karakoram Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-255295 SN - 2072-4292 VL - 14 IS - 1 ER - TY - JOUR A1 - Bieniek, Maciej A1 - Sadecka, Katarzyna A1 - Szulakowska, Ludmiła A1 - Hawrylak, Paweł T1 - Theory of excitons in atomically thin semiconductors: tight-binding approach JF - Nanomaterials N2 - Atomically thin semiconductors from the transition metal dichalcogenide family are materials in which the optical response is dominated by strongly bound excitonic complexes. Here, we present a theory of excitons in two-dimensional semiconductors using a tight-binding model of the electronic structure. In the first part, we review extensive literature on 2D van der Waals materials, with particular focus on their optical response from both experimental and theoretical points of view. In the second part, we discuss our ab initio calculations of the electronic structure of MoS\(_2\), representative of a wide class of materials, and review our minimal tight-binding model, which reproduces low-energy physics around the Fermi level and, at the same time, allows for the understanding of their electronic structure. Next, we describe how electron-hole pair excitations from the mean-field-level ground state are constructed. The electron–electron interactions mix the electron-hole pair excitations, resulting in excitonic wave functions and energies obtained by solving the Bethe–Salpeter equation. This is enabled by the efficient computation of the Coulomb matrix elements optimized for two-dimensional crystals. Next, we discuss non-local screening in various geometries usually used in experiments. We conclude with a discussion of the fine structure and excited excitonic spectra. In particular, we discuss the effect of band nesting on the exciton fine structure; Coulomb interactions; and the topology of the wave functions, screening and dielectric environment. Finally, we follow by adding another layer and discuss excitons in heterostructures built from two-dimensional semiconductors. KW - tight-binding KW - excitons KW - Bethe–Salpeter equation KW - transition metal dichalcogenides Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275243 SN - 2079-4991 VL - 12 IS - 9 ER - TY - JOUR A1 - Noll, Niklas A1 - Krause, Ana-Maria A1 - Beuerle, Florian A1 - Würthner, Frank T1 - Enzyme-like water preorganization in a synthetic molecular cleft for homogeneous water oxidation catalysis JF - Nature Catalysis N2 - Inspired by the proficiency of natural enzymes, mimicking of nanoenvironments for precise substrate preorganisation is a promising strategy in catalyst design. However, artificial examples of enzyme-like activation of H\(_2\)O molecules for the challenging oxidative water splitting reaction are hardly explored. Here, we introduce a mononuclear Ru(bda) complex (M1, bda: 2,2’-bipyridine-6,6’-dicarboxylate) equipped with a bipyridine-functionalized ligand to preorganize H\(_2\)O molecules in front of the metal center as in enzymatic clefts. The confined pocket of M1 accelerates chemically driven water oxidation at pH 1 by facilitating a water nucleophilic attack pathway with a remarkable turnover frequency of 140 s\(^{−1}\) that is comparable to the oxygen-evolving complex of photosystem II. Single crystal X-ray analysis of M1 under catalytic conditions allowed the observation of a 7th H\(_2\)O ligand directly coordinated to a RuIII center. Via a well-defined hydrogen-bonding network, another H\(_2\)O substrate is preorganized for the crucial O–O bond formation via nucleophilic attack. KW - water oxidation KW - enzyme KW - catalysis KW - molecular KW - catalyst synthesis KW - catalytic mechanisms KW - homogeneous catalysis KW - photocatalysis KW - supramolecular chemistry Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-302897 N1 - This version of the article has been accepted for publication, after peer review and is subject to Springer Nature’s AM terms of use (https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms), but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1038/s41929-022-00843-x ET - accepted version ER - TY - JOUR A1 - Scheiner, Christin A1 - Grashoff, Jan A1 - Kleindienst, Nikolaus A1 - Buerger, Arne T1 - Mental disorders at the beginning of adolescence: Prevalence estimates in a sample aged 11-14 years JF - Public Health in Practice N2 - Objectives This study aims to provide a deeper insight into mental disorders in early adolescence. We report prevalence rates (mental health problems, depressive symptoms, eating disorders, NSSI, STBs) to be used in future studies and clinical ventures. We also expected to find gender differences, with girls being be more affected than boys are. Study design 877 adolescents (M = 12.43, SD = 0.65) from seven German high schools completed a series of questionnaires assessing their mental health (SDQ, PHQ-9, SEED, DSHI-9, Paykel Suicide Scale, FAS III). Methods We calculated cut-off-based prevalence estimates for mental health issues for the whole sample and compared estimates between genders. Results 12.5% of the sample reported general mental health problems. The estimated prevalence of depressive symptoms lay at of 11.5%. Additionally, 12.1% and 1.3% of the participants displayed relevant symptoms of anorexia or bulimia nervosa, respectively. A total of 10.8% reported engaging in non-suicidal self-injury (NSSI) at least once in their lifetime, of whom 5.6% reported repetitive NSSI. 30.1% of the participants described suicidal thoughts, 9.9% suicide plans, and 3.5% at least one suicide attempt. Girls were generally more affected than boys, except for bulimia nervosa, suicidal behavior, and partly NSSI. Conclusion Our findings corroborate the established relevance of early adolescence for the development of mental health problems and suggest that a substantial proportion of young adolescents suffer from such problems early on. Considering the ongoing COVID-19 pandemic and reported negative mental health consequences, the current findings underline the importance of preventive interventions to avoid the manifestation of mental disorders during adolescence. KW - STBS KW - depression KW - eating disorders KW - mental health KW - adolescence KW - prevalence KW - NSSI Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300404 VL - 4 ER - TY - JOUR A1 - Bauer, Nikolai A1 - Sperlich, Billy A1 - Holmberg, Hans-Christer A1 - Engel, Florian A. T1 - Effects of High-Intensity Interval Training in School on the Physical Performance and Health of Children and Adolescents: A Systematic Review with Meta-Analysis JF - Sports Medicine - Open N2 - Objectives To assess the impact of HIIT performed at school, i.e. both in connection with physical education (intra-PE) and extracurricular sports activities (extra-PE), on the physical fitness and health of children and adolescents. Methods PubMed and SPORTDiscus were searched systematically utilizing the following criteria for inclusion: (1) healthy children and adolescents (5–18 years old) of normal weight; (2) HIIT performed intra- and/or extra-PE for at least 5 days at an intensity ≥ 80% of maximal heart rate (HR\(_{max}\)) or peak oxygen uptake (VO\(_{2peak}\)) or as Functional HIIT; (3) comparison with a control (HIIT versus alternative interventions); and (4) pre- and post-analysis of parameters related to physical fitness and health. The outcomes with HIIT and the control interventions were compared utilizing Hedges’ g effect size (ES) and associated 95% confidence intervals. Results Eleven studies involving 707 participants who performed intra-PE and 388 participants extra-PE HIIT were included. In comparison with the control interventions, intra-PE HIIT improved mean ES for neuromuscular and anaerobic performance (ES jump performance: 5.89 ± 5.67 (range 1.88–9.90); ES number of push-ups: 6.22 (range n.a.); ES number of sit-ups: 2.66 ± 2.02 (range 1.24–4.09)), as well as ES fasting glucose levels (− 2.68 (range n.a.)) more effectively, with large effect sizes. Extra-PE HIIT improved mean ES for neuromuscular and anaerobic performance (ES jump performance: 1.81 (range n.a.); ES number of sit-ups: 2.60 (range n.a.)) to an even greater extent, again with large effect sizes. Neither form of HIIT was more beneficial for parameters related to cardiorespiratory fitness than the control interventions. Conclusion Compared to other forms of exercise (e.g. low-to-moderate-intensity running or walking), both intra- and extra-PE HIIT result in greater improvements in neuromuscular and anaerobic performance, as well as in fasting levels of glucose in school children. KW - adolescents KW - health-related fitness KW - physical fitness KW - children KW - high-intensity interval training KW - physical education Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301205 SN - 2199-1170 VL - 8 IS - 1 ER - TY - JOUR A1 - Gram, Maximilian A1 - Albertova, P. A1 - Schirmer, V. A1 - Blaimer, M. A1 - Gamer, M. A1 - Herrmann, M. J. A1 - Nordbeck, P. A1 - Jakob, P. M. T1 - Towards robust in vivo quantification of oscillating biomagnetic fields using Rotary Excitation based MRI JF - Scientific Reports N2 - Spin-lock based functional magnetic resonance imaging (fMRI) has the potential for direct spatially-resolved detection of neuronal activity and thus may represent an important step for basic research in neuroscience. In this work, the corresponding fundamental effect of Rotary EXcitation (REX) is investigated both in simulations as well as in phantom and in vivo experiments. An empirical law for predicting optimal spin-lock pulse durations for maximum magnetic field sensitivity was found. Experimental conditions were established that allow robust detection of ultra-weak magnetic field oscillations with simultaneous compensation of static field inhomogeneities. Furthermore, this work presents a novel concept for the emulation of brain activity utilizing the built-in MRI gradient system, which allows REX sequences to be validated in vivo under controlled and reproducible conditions. Via transmission of Rotary EXcitation (tREX), we successfully detected magnetic field oscillations in the lower nano-Tesla range in brain tissue. Moreover, tREX paves the way for the quantification of biomagnetic fields. KW - functional magnetic resonance imaging KW - Rotary EXcitation (REX) KW - oscillating biomagnetic fields Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300862 VL - 12 IS - 1 ER - TY - JOUR A1 - Müller, S. A1 - Spriestersbach, F. A1 - Min, C.-H. A1 - Fornari, C. I. A1 - Reinert, F. T1 - Molecular beam epitaxy of TmTe thin films on SrF\(_{2}\) (111) JF - AIP Advances N2 - The odd parity nature of 4f states characterized by strong spin–orbit coupling and electronic correlations has led to a search for novel topological phases among rare earth compounds, such as Kondo systems, heavy Fermions, and homogeneous mixed-valent materials. Our target system is thulium telluride thin films whose bandgap is expected to be tuned as a function of lattice parameter. We systematically investigate the growth conditions of TmxTey thin films on SrF\(_{2}\) (111) substrates by molecular beam epitaxy. The ratio between Te and Tm supply was precisely tuned, resulting in two different crystalline phases, which were confirmed by x-ray diffraction and x-ray photoemission spectroscopy. By investigating the crystalline quality as a function of the substrate temperature, the optimal growth conditions were identified for the desired Tm1Te1 phase. Additional low energy electron diffraction and reflective high energy electron diffraction measurements confirm the epitaxial growth of TmTe layers. X-ray reflectivity measurements demonstrate that homogeneous samples with sharp interfaces can be obtained for varied thicknesses. Our results provide a reliable guidance to prepare homogeneous high-quality TmTe thin films and thus serve as a basis for further electronic investigations. KW - thulium telluride KW - molecular beam epitaxy KW - thin films Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300876 VL - 12 IS - 2 ER - TY - JOUR A1 - Lichter, Katharina A1 - Paul, Mila Marie A1 - Pauli, Martin A1 - Schoch, Susanne A1 - Kollmannsberger, Philip A1 - Stigloher, Christian A1 - Heckmann, Manfred A1 - Sirén, Anna-Leena T1 - Ultrastructural analysis of wild-type and RIM1α knockout active zones in a large cortical synapse JF - Cell Reports N2 - Rab3A-interacting molecule (RIM) is crucial for fast Ca\(^{2+}\)-triggered synaptic vesicle (SV) release in presynaptic active zones (AZs). We investigated hippocampal giant mossy fiber bouton (MFB) AZ architecture in 3D using electron tomography of rapid cryo-immobilized acute brain slices in RIM1α\(^{−/−}\) and wild-type mice. In RIM1α\(^{−/−}\), AZs are larger with increased synaptic cleft widths and a 3-fold reduced number of tightly docked SVs (0–2 nm). The distance of tightly docked SVs to the AZ center is increased from 110 to 195 nm, and the width of their electron-dense material between outer SV membrane and AZ membrane is reduced. Furthermore, the SV pool in RIM1α\(^{−/−}\) is more heterogeneous. Thus, RIM1α, besides its role in tight SV docking, is crucial for synaptic architecture and vesicle pool organization in MFBs. KW - active zone KW - acute brain slices KW - CA3 KW - electron tomography KW - high-pressure freezing KW - hippocampal mossy fiber bouton KW - RIM1α KW - SV pool KW - synaptic ultrastructure KW - presynaptic Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300913 VL - 40 IS - 12 ER - TY - JOUR A1 - Jeanclos, Elisabeth A1 - Schlötzer, Jan A1 - Hadamek, Kerstin A1 - Yuan-Chen, Natalia A1 - Alwahsh, Mohammad A1 - Hollmann, Robert A1 - Fratz, Stefanie A1 - Yesilyurt-Gerhards, Dilan A1 - Frankenbach, Tina A1 - Engelmann, Daria A1 - Keller, Angelika A1 - Kaestner, Alexandra A1 - Schmitz, Werner A1 - Neuenschwander, Martin A1 - Hergenröder, Roland A1 - Sotriffer, Christoph A1 - von Kries, Jens Peter A1 - Schindelin, Hermann A1 - Gohla, Antje T1 - Glycolytic flux control by drugging phosphoglycolate phosphatase JF - Nature Communications N2 - Targeting the intrinsic metabolism of immune or tumor cells is a therapeutic strategy in autoimmunity, chronic inflammation or cancer. Metabolite repair enzymes may represent an alternative target class for selective metabolic inhibition, but pharmacological tools to test this concept are needed. Here, we demonstrate that phosphoglycolate phosphatase (PGP), a prototypical metabolite repair enzyme in glycolysis, is a pharmacologically actionable target. Using a combination of small molecule screening, protein crystallography, molecular dynamics simulations and NMR metabolomics, we discover and analyze a compound (CP1) that inhibits PGP with high selectivity and submicromolar potency. CP1 locks the phosphatase in a catalytically inactive conformation, dampens glycolytic flux, and phenocopies effects of cellular PGP-deficiency. This study provides key insights into effective and precise PGP targeting, at the same time validating an allosteric approach to control glycolysis that could advance discoveries of innovative therapeutic candidates. KW - phosphoglycolate phosphatase KW - glycolytic flux control KW - intrinsic metabolism Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300928 VL - 13 IS - 1 ER - TY - JOUR A1 - Schneider, Sonja Jasmin Maria A1 - Höhne, Christian A1 - Schneider, Martin A1 - Schmitter, Marc T1 - Photoacoustic tomography versus cone-beam computed tomography versus micro-computed tomography: Accuracy of 3D reconstructions of human teeth JF - PloS One N2 - Objectives In this in-vitro study, teeth were imaged using photoacoustic tomography (PAT), cone-beam computed tomography (CBCT), and micro-computed tomography (μ-CT). The study had aim: to identify the best wavelength for PAT images to determine the accuracy of the three imaging methods, and to determine whether PAT images of teeth can achieve acceptable reconstruction quality. Methods Nineteen human mandibular single-rooted incisors were extracted from patients with trauma or periodontitis. To determine the best wavelength for acquiring photoacoustic images, all 19 teeth were scanned in vitro with PAT, using different laser wavelengths between 680 and 960 nm. The images were analyzed using image analysis software. To assess the accuracy of PAT and compare it with the accuracy of CBCT, each tooth was also scanned in vitro using CBCT and the reference standard technique of μ-CT. Subsequently, three different three-dimensional models, one for each imaging technique, were created for each tooth. Finally, the three different three-dimensional models acquired for the same tooth were matched and analyzed regarding volume and surface. Results The highest quality tooth images were achieved using the 680 nm wavelength, which showed the best contrast ratio. The full geometry of the dental root (μ-CT compared with PAT) could be visualized with relative standard deviations of 0.12 mm for the surface and −7.33 mm3 for the volume (n = 19). The full geometry of the dental root (μ-CT compared with CBCT) could be visualized with relative standard deviations of 0.06 mm for the surface and −14.56 mm3 for the volume (n = 19). The difference between the PAT–μ-CT group and CBCT–μ-CT group regarding the total average of the root surface area was not significant (p>0.06). Conclusion Images, which were acquired using PAT at 680nm showed the best contrast ration, enabling the identification of dentin, cementum and the dental pulp. No significant differences were found between the PAT–μ-CT group and CBCT–μ-CT group regarding the total average of the RSA and the total volume. Thus, three-dimensional reconstructions based on in-vitro PAT are already of acceptable reconstruction quality. KW - teeth KW - imaging techniques KW - computer software KW - incisors KW - in vivo imaging KW - caries KW - magnetic resonance imaging KW - tomography Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301437 VL - 17 IS - 12 ER - TY - JOUR A1 - Aster, H-C A1 - Evdokimov, D. A1 - Braun, A. A1 - Üçeyler, N. A1 - Sommer, C. T1 - Analgesic Medication in Fibromyalgia Patients: A Cross-Sectional Study JF - Pain Research and Management N2 - There is no approved drug for fibromyalgia syndrome (FMS) in Europe. In the German S3 guideline, amitriptyline, duloxetine, and pregabalin are recommended for temporary use. The aim of this study was to cross-sectionally investigate the current practice of medication in FMS patients in Germany. We systematically interviewed 156 patients with FMS, while they were participating in a larger study. The patients had been stratified into subgroups with and without a decrease in intraepidermal nerve fiber density. The drugs most commonly used to treat FMS pain were nonsteroidal anti-inflammatory drugs (NSAIDs) (41.0% of all patients), metamizole (22.4%), and amitriptyline (12.8%). The most frequent analgesic treatment regimen was “on demand” (53.9%), during pain attacks, while 35.1% of the drugs were administered daily and the remaining in other regimens. Median pain relief as self-rated by the patients on a numerical rating scale (0–10) was 2 points for NSAIDS, 2 for metamizole, and 1 for amitriptyline. Drugs that were discontinued due to lack of efficacy rather than side effects were acetaminophen, flupirtine, and selective serotonin reuptake inhibitors. Reduction in pain severity was best achieved by NSAIDs and metamizole. Our hypothesis that a decrease in intraepidermal nerve fiber density might represent a neuropathic subtype of FMS, which would be associated with better effectiveness of drugs targeting neuropathic pain, could not be confirmed in this cohort. Many FMS patients take “on-demand” medication that is not in line with current guidelines. More randomized clinical trials are needed to assess drug effects in FMS subgroups. KW - Fibromyalgia KW - analgesic medication KW - study Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300578 VL - 2022 ER - TY - JOUR A1 - Fayez, Shaimaa A1 - Bruhn, Torsten A1 - Feineis, Doris A1 - Assi, Laurent Aké A1 - Kushwaha, Prem Prakash A1 - Kumar, Shashank A1 - Bringmann, Gerhard T1 - Naphthylisoindolinone alkaloids: the first ring-contracted naphthylisoquinolines, from the tropical liana Ancistrocladus abbreviatus, with cytotoxic activity JF - RSC Advances N2 - The West African liana Ancistrocladus abbreviatus is a rich source of structurally most diverse naphthylisoquinoline alkaloids. From its roots, a series of four novel representatives, named ancistrobrevolines A–D (14–17) have now been isolated, displaying an unprecedented heterocyclic ring system, where the usual isoquinoline entity is replaced by a ring-contracted isoindolinone part. Their constitutions were elucidated by 1D and 2D NMR and HR-ESI-MS. The absolute configurations at the chiral axis and at the stereogenic center were assigned by using experimental and computational electronic circular dichroism (ECD) investigations and a ruthenium-mediated oxidative degradation, respectively. For the biosynthetic origin of the isoindolinones from ‘normal’ naphthyltetrahydroisoquinolines, a hypothetic pathway is presented. It involves oxidative decarboxylation steps leading to a ring contraction by a benzilic acid rearrangement. Ancistrobrevolines A (14) and B (15) were found to display moderate cytotoxic effects (up to 72%) against MCF-7 breast and A549 lung cancer cells and to reduce the formation of spheroids (mammospheres) in the breast cancer cell line. KW - Naphthylisoindolinone alkaloids Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300766 VL - 12 IS - 45 ER - TY - JOUR A1 - Achenbach, Leonard A1 - Huppertz, Gunnar A1 - Zeman, Florian A1 - Weber, Johannes A1 - Luig, Patrick A1 - Rudert, Maximilian A1 - Krutsch, Werner T1 - Multicomponent stretching and rubber band strengthening exercises do not reduce overuse shoulder injuries: a cluster randomised controlled trial with 579 handball athletes JF - BMJ Open Sport & Exercise Medicine N2 - Objectives Handball is associated with a high risk of overuse shoulder injury. This study investigated if an injury prevention programme effectively reduces overuse injury to the throwing shoulder of handball athletes. Methods 61 men’s and women’s handball teams (u-19 and senior athletes) were cluster-randomised into an intervention and a control group in the 2019–2020 season. Players of the intervention group regularly carried out an injury prevention programme. Both groups documented overuse shoulder injuries via an online questionnaire every second week. The primary endpoint was the prevalence of overuse injury to the throwing shoulder. Secondary endpoints were the influence of compliance on the primary endpoint and intensity of overuse shoulder symptoms measured by a shortened, handball-specific Western Ontario Shoulder Index (WOSI). Results 31 teams (295 players) in the intervention group and 30 teams (284 players) in the control group were included for analyses. The overall questionnaire response rate was 61%. The average prevalence of overuse shoulder injury did not significantly differ between the intervention group (n=109, 38.4% (95% CI 32.9% to 44.2%)) and the control group (n=106, 35.9% (95% CI 30.7% to 41.6%), p=0.542). Compliance with the intervention programme did not significantly affect overuse shoulder injury (p=0.893). Using generalised estimating equations for WOSI, the estimated mean for the intervention group was 44.6 points (95% CI 42.0 to 47.1) and 47.6 points for the control group (95% CI 44.9 to 50.3, p=0.111). Conclusions A multicomponent exercise programme using rubber bands and stretching did not significantly reduce the prevalence or symptoms of overuse throwing shoulder injury in handball athletes of both sexes. Randomised controlled study; level of evidence I. KW - handball KW - multicomponent stretching KW - shoulder injuries Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300770 SN - 2055-7647 VL - 8 IS - 1 ER - TY - JOUR A1 - Hebestreit, Helge A1 - Zeidler, Cornelia A1 - Schippers, Christopher A1 - de Zwaan, Martina A1 - Deckert, Jürgen A1 - Heuschmann, Peter A1 - Krauth, Christian A1 - Bullinger, Monika A1 - Berger, Alexandra A1 - Berneburg, Mark A1 - Brandstetter, Lilly A1 - Deibele, Anna A1 - Dieris-Hirche, Jan A1 - Graessner, Holm A1 - Gündel, Harald A1 - Herpertz, Stephan A1 - Heuft, Gereon A1 - Lapstich, Anne-Marie A1 - Lücke, Thomas A1 - Maisch, Tim A1 - Mundlos, Christine A1 - Petermann-Meyer, Andrea A1 - Müller, Susanne A1 - Ott, Stephan A1 - Pfister, Lisa A1 - Quitmann, Julia A1 - Romanos, Marcel A1 - Rutsch, Frank A1 - Schaubert, Kristina A1 - Schubert, Katharina A1 - Schulz, Jörg B. A1 - Schweiger, Susann A1 - Tüscher, Oliver A1 - Ungethüm, Kathrin A1 - Wagner, Thomas O. F. A1 - Haas, Kirsten T1 - Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study JF - Orphanet Journal of Rare Diseases N2 - Background In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process. Study design This multi-center, prospective controlled study has a two-phase cohort design. Methods Two cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD’s outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2). Outcomes Primary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30% in standard care to 40% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients’ quality of life and evaluation of care; and f) physicians’ satisfaction with the innovative care approach. Conclusions This is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease. KW - rare diseases KW - multi‑center cohort study KW - dual guidance Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300440 VL - 17 IS - 1 ER - TY - JOUR A1 - Lorenz, Delia A1 - Musacchio, Thomas A1 - Kunstmann, Erdmute A1 - Grauer, Eva A1 - Pluta, Natalie A1 - Stock, Annika A1 - Speer, Christian P. A1 - Hebestreit, Helge T1 - A case report of Sanfilippo syndrome - the long way to diagnosis JF - BMC Neurology N2 - Background Mucopolysaccharidosis type III (Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in the heparan-N-sulfatase enzyme involved in the catabolism of the glycosaminoglycan heparan sulfate. It is characterized by early nonspecific neuropsychiatric symptoms, followed by progressive neurocognitive impairment in combination with only mild somatic features. In this patient group with a broad clinical spectrum a significant genotype-phenotype correlation with some mutations leading to a slower progressive, attenuated course has been demonstrated. Case presentation Our patient had complications in the neonatal period and was diagnosed with Mucopolysaccharidosis IIIa only at the age of 28 years. He was compound heterozygous for the variants p.R245H and p.S298P, the latter having been shown to lead to a significantly milder phenotype. Conclusions The diagnostic delay is even more prolonged in this patient population with comorbidities and a slowly progressive course of the disease. KW - Mucopolysaccharidosis IIIa KW - diagnostic delay KW - genotype-phenotype correlation KW - p.S298P KW - p.R245H Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300465 VL - 22 IS - 1 ER - TY - JOUR A1 - Frey, Anna A1 - Leutritz, Tobias A1 - Backhaus, Joy A1 - Hörnlein, Alexander A1 - König, Sarah T1 - Item format statistics and readability of extended matching questions as an effective tool to assess medical students JF - Scientific Reports N2 - Testing based on multiple choice questions (MCQ) is one of the most established forms of assessment, not only in the medical field. Extended matching questions (EMQ) represent a specific type of MCQ designed to require higher levels of cognition, such as problem-solving. The purpose of this evaluation was to assess the suitability and efficiency of EMQ as an assessment method. EMQ were incorporated into the end-of-semester examination in internal medicine, in which 154 students participated, and compared with three established MCQ types. Item and examination quality were investigated, as well as readability and processing time. EMQ were slightly more difficult to score; however, both item discrimination and discrimination index were higher when compared to other item types. EMQ were found to be significantly longer and required more processing time, but readability was improved. Students judged EMQ as clearly challenging, but attributed significantly higher clinical relevance when compared to established MCQ formats. Using the Spearman-Brown prediction, only ten EMQ items would be needed to reproduce the Cronbach’s alpha value of 0.75 attained for the overall examination. EMQ proved to be both efficient and suitable when assessing medical students, demonstrating powerful characteristics of reliability. Their expanded use in favor of common MCQ could save examination time without losing out on statistical quality. KW - multiple choice questions KW - extended matching questions KW - medical students Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300485 VL - 12 IS - 1 ER - TY - JOUR A1 - Gram, Maximilian A1 - Gensler, Daniel A1 - Albertova, Petra A1 - Gutjahr, Fabian Tobias A1 - Lau, Kolja A1 - Arias-Loza, Paula-Anahi A1 - Jakob, Peter Michael A1 - Nordbeck, Peter T1 - Quantification correction for free-breathing myocardial T1ρ mapping in mice using a recursively derived description of a T\(_{1p}\)\(^{*}\) relaxation pathway JF - Journal of Cardiovascular Magnetic Resonance N2 - Background Fast and accurate T1ρ mapping in myocardium is still a major challenge, particularly in small animal models. The complex sequence design owing to electrocardiogram and respiratory gating leads to quantification errors in in vivo experiments, due to variations of the T\(_{1p}\) relaxation pathway. In this study, we present an improved quantification method for T\(_{1p}\) using a newly derived formalism of a T\(_{1p}\)\(^{*}\) relaxation pathway. Methods The new signal equation was derived by solving a recursion problem for spin-lock prepared fast gradient echo readouts. Based on Bloch simulations, we compared quantification errors using the common monoexponential model and our corrected model. The method was validated in phantom experiments and tested in vivo for myocardial T\(_{1p}\) mapping in mice. Here, the impact of the breath dependent spin recovery time T\(_{rec}\) on the quantification results was examined in detail. Results Simulations indicate that a correction is necessary, since systematically underestimated values are measured under in vivo conditions. In the phantom study, the mean quantification error could be reduced from − 7.4% to − 0.97%. In vivo, a correlation of uncorrected T\(_{1p}\) with the respiratory cycle was observed. Using the newly derived correction method, this correlation was significantly reduced from r = 0.708 (p < 0.001) to r = 0.204 and the standard deviation of left ventricular T\(_{1p}\) values in different animals was reduced by at least 39%. Conclusion The suggested quantification formalism enables fast and precise myocardial T\(_{1p}\) quantification for small animals during free breathing and can improve the comparability of study results. Our new technique offers a reasonable tool for assessing myocardial diseases, since pathologies that cause a change in heart or breathing rates do not lead to systematic misinterpretations. Besides, the derived signal equation can be used for sequence optimization or for subsequent correction of prior study results. KW - T1rho KW - radial KW - cardiac KW - correction KW - quantitative MRI KW - mapping KW - spin-lock KW - T1ρ Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300491 VL - 24 IS - 1 ER - TY - JOUR A1 - Deng, Chunchu A1 - Reinhard, Sebastian A1 - Hennlein, Luisa A1 - Eilts, Janna A1 - Sachs, Stefan A1 - Doose, Sören A1 - Jablonka, Sibylle A1 - Sauer, Markus A1 - Moradi, Mehri A1 - Sendtner, Michael T1 - Impaired dynamic interaction of axonal endoplasmic reticulum and ribosomes contributes to defective stimulus-response in spinal muscular atrophy JF - Translational Neurodegeneration N2 - Background: Axonal degeneration and defects in neuromuscular neurotransmission represent a pathological hallmark in spinal muscular atrophy (SMA) and other forms of motoneuron disease. These 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 changes. The dynamic interplay between the axonal endoplasmic reticulum (ER) and ribosomes is essential for stimulus-induced local translation in motor axons and presynaptic terminals. However, 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 SMA. Methods: Using super-resolution microscopy, proximity ligation assay (PLA) and live imaging of cultured motoneurons from a mouse model of SMA, we investigated the dynamics of the axonal ER and ribosome distribution and activation. Results: We observed that the dynamic remodeling of ER was impaired in axon terminals of Smn-deficient motoneurons. In 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 stimuli. Conclusions: 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. KW - spinal muscular atrophy KW - BDNF stimulation KW - dynamics of ribosomal assembly KW - presynaptic ER dynamics Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300649 SN - 2047-9158 VL - 11 IS - 1 ER - TY - JOUR A1 - Matsusaka, Yohji A1 - Chen, Xinyu A1 - Arias-Loza, Paula A1 - Werner, Rudolf A. A1 - Nose, Naoko A1 - Sasaki, Takanori A1 - Rowe, Steven P. A1 - Pomper, Martin G. A1 - Lapa, Constantin A1 - Higuchi, Takahiro T1 - In Vivo Functional Assessment of Sodium-Glucose Cotransporters (SGLTs) Using [\(^{18}\)F]Me4FDG PET in Rats JF - Molecular Imaging N2 - Background. Mediating glucose absorption in the small intestine and renal clearance, sodium glucose cotransporters (SGLTs) have emerged as an attractive therapeutic target in diabetic patients. A substantial fraction of patients, however, only achieve inadequate glycemic control. Thus, we aimed to assess the potential of the SGLT-targeting PET radiotracer alpha-methyl-4-deoxy-4-[\(^{18}\)F]fluoro-D-glucopyranoside ([\(^{18}\)F]Me4FDG) as a noninvasive intestinal and renal biomarker of SGLT-mediated glucose transport. Methods. We investigated healthy rats using a dedicated small animal PET system. Dynamic imaging was conducted after administration of the reference radiotracer 2-deoxy-2-[\(^{18}\)F]fluoro-D-glucose ([\(^{18}\)F]FDG), or the SGLT-targeting agent, [\(^{18}\)F]Me4FDG either directly into the digestive tract (for assessing intestinal absorption) or via the tail vein (for evaluating kidney excretion). To confirm the specificity of [18F]Me4FDG and responsiveness to treatment, a subset of animals was also pretreated with the SGLT inhibitor phlorizin. In this regard, an intraintestinal route of administration was used to assess tracer absorption in the digestive tract, while for renal assessment, phlorizin was injected intravenously (IV). Results. Serving as reference, intestinal administration of [\(^{18}\)F]FDG led to slow absorption with retention of % of administered radioactivity at 15 min. [\(^{18}\)F]Me4FDG, however, was rapidly absorbed into the blood and cleared from the intestine within 15 min, leading to markedly lower tracer retention of % (). Intraintestinal phlorizin led to marked increase of [\(^{18}\)F]Me4FDG uptake (15 min, %; vs. untreated controls), supporting the notion that this PET agent can measure adequate SGLT inhibition in the digestive tract. In the kidneys, radiotracer was also sensitive to SGLT inhibition. After IV injection, [\(^{18}\)F]Me4FDG reabsorption in the renal cortex was significantly suppressed by phlorizin when compared to untreated animals (%ID/g at 60 min, vs. untreated controls, ; ). Conclusion. As a noninvasive read-out of the concurrent SGLT expression in both the digestive tract and the renal cortex, [\(^{18}\)F]Me4FDG PET may serve as a surrogate marker for treatment response to SGLT inhibition. As such, [\(^{18}\)F]Me4FDG may enable improvement in glycemic control in diabetes by PET-based monitoring strategies. KW - Sodium-Glucose Cotransporters (SGLTs) KW - diabetes KW - rats Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300708 VL - 2022 ER - TY - JOUR A1 - Svensson, Sarah L. A1 - Sharma, Cynthia M. T1 - Small RNAs that target G-rich sequences are generated by diverse biogenesis pathways in Epsilonproteobacteria JF - Molecular Microbiology N2 - Bacterial small RNAs (sRNAs) are widespread post-transcriptional regulators that control bacterial stress responses and virulence. Nevertheless, little is known about how they arise and evolve. Homologs can be difficult to identify beyond the strain level using sequence-based approaches, and similar functionalities can arise by convergent evolution. Here, we found that the virulence-associated CJnc190 sRNA of the foodborne pathogen Campylobacter jejuni resembles the RepG sRNA from the gastric pathogen Helicobacter pylori. However, while both sRNAs bind G-rich sites in their target mRNAs using a C/U-rich loop, they largely differ in their biogenesis. RepG is transcribed from a stand-alone gene and does not require processing, whereas CJnc190 is transcribed from two promoters as precursors that are processed by RNase III and also has a cis-encoded antagonist, CJnc180. By comparing CJnc190 homologs in diverse Campylobacter species, we show that RNase III-dependent processing of CJnc190 appears to be a conserved feature even outside of C. jejuni. We also demonstrate the CJnc180 antisense partner is expressed in C. coli, yet here might be derived from the 3’UTR (untranslated region) of an upstream flagella-related gene. Our analysis of G-tract targeting sRNAs in Epsilonproteobacteria demonstrates that similar sRNAs can have markedly different biogenesis pathways. KW - sRNA biogenesis KW - Campylobacter jejuni KW - Helicobacter pylori KW - pathogenesis KW - RNase III Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259602 VL - 117 ER - TY - JOUR A1 - Kosmala, Aleksander A1 - Serfling, Sebastian E. A1 - Dreher, Niklas A1 - Lindner, Thomas A1 - Schirbel, Andreas A1 - Lapa, Constantin A1 - Higuchi, Takahiro A1 - Buck, Andreas K. A1 - Weich, Alexander A1 - Werner, Rudolf A. T1 - Associations between normal organs and tumor burden in patients imaged with fibroblast activation protein inhibitor-directed positron emission tomography JF - Cancers N2 - (1) Background: We aimed to quantitatively investigate [\(^{68}\)Ga]Ga-FAPI-04 uptake in normal organs and to assess a relationship with the extent of FAPI-avid tumor burden. (2) Methods: In this single-center retrospective analysis, thirty-four patients with solid cancers underwent a total of 40 [\(^{68}\)Ga]Ga-FAPI-04 PET/CT scans. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were established by placing volumes of interest (VOIs) in the heart, liver, spleen, pancreas, kidneys, and bone marrow. Total tumor burden was determined by manual segmentation of tumor lesions with increased uptake. For tumor burden, quantitative assessment included maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA = TV × SUV\(_{mean}\)). Associations between uptake in normal organs and tumor burden were investigated by applying Spearman's rank correlation coefficient. (3) Results: Median SUV\(_{mean}\) values were 2.15 in the pancreas (range, 1.05–9.91), 1.42 in the right (range, 0.57–3.06) and 1.41 in the left kidney (range, 0.73–2.97), 1.2 in the heart (range, 0.46–2.59), 0.86 in the spleen (range, 0.55–1.58), 0.65 in the liver (range, 0.31–2.11), and 0.57 in the bone marrow (range, 0.26–0.94). We observed a trend towards significance for uptake in the myocardium and tumor-derived SUV\(_{max}\) (ρ = 0.29, p = 0.07) and TV (ρ = −0.30, p = 0.06). No significant correlation was achieved for any of the other organs: SUV\(_{max}\) (ρ ≤ 0.1, p ≥ 0.42), TV (ρ ≤ 0.11, p ≥ 0.43), and FTA (ρ ≤ 0.14, p ≥ 0.38). In a sub-analysis exclusively investigating patients with high tumor burden, significant correlations of myocardial uptake with tumor SUV\(_{max}\) (ρ = 0.44; p = 0.03) and tumor-derived FTA with liver uptake (ρ = 0.47; p = 0.02) were recorded. (4) Conclusions: In this proof-of-concept study, quantification of [\(^{68}\)Ga]Ga-FAPI-04 PET showed no significant correlation between normal organs and tumor burden, except for a trend in the myocardium. Those preliminary findings may trigger future studies to determine possible implications for treatment with radioactive FAP-targeted drugs, as higher tumor load or uptake may not lead to decreased doses in the majority of normal organs. KW - PET KW - [\(^{68}\)Ga]Ga-FAPI KW - theranostics KW - radioligand therapy KW - fibroblast activation protein Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275154 SN - 2072-6694 VL - 14 IS - 11 ER - TY - JOUR A1 - Stoevesandt, Johanna A1 - Trautmann, Axel T1 - Risk factors in bee and Vespula venom allergy: state of the art JF - Allergo Journal International N2 - Background Correct recognition of risk factors enables individualized management and treatment of venom allergic patients. Methods Systematic research and review of current literature regarding the risk of (1) severe sting-induced anaphylaxis, (2) anaphylactic adverse event during venom immunotherapy (VIT), and (3) treatment failure. Results and discussion (1) Mastocytosis is the most important risk factor for severe sting-induced anaphylaxis. Hereditary α‑tryptasemia was recently identified as a genetic predictor of severe reactions. Older age is clearly associated with an increased risk; the respective impact of defined cardiovascular comorbidities has yet to be determined. Recent data do not support an aggravation of venom-induced anaphylaxis by intake of β‑blockers or angiotensin-converting enzyme (ACE) inhibitors. A higher risk in men can be attributed to more intensive exposure to stinging insects. (2) Anaphylactic side effects of VIT are most common during the buildup phase, particularly in the course of (ultra-)rush protocols involving a high number of injections and high cumulative daily doses. They are significantly more frequent during honeybee compared to Vespula VIT. Data supporting a negative effect of mastocytosis on the tolerability of VIT are scarce. Older age and cardiovascular medication are not associated with a higher incidence of VIT-induced anaphylaxis. (3) Relapsing anaphylactic reactions to both field and challenge stings are significantly more common during and after honeybee compared to Vespula VIT. Reports of severe field-sting reactions in mastocytosis patients suggest an increased risk of treatment failure which may be overcome by higher maintenance doses and longer duration of VIT. KW - mastocytosis KW - ACE inhibitor KW - age KW - Beta-blocker KW - hereditary alpha-tryptasemia KW - immunotherapy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270498 SN - 2197-0378 VL - 31 IS - 1 ER - TY - JOUR A1 - Ramler, Jacqueline A1 - Schwarzmann, Johannes A1 - Stoy, Andreas A1 - Lichtenberg, Crispin T1 - Two Faces of the Bi−O Bond: Photochemically and Thermally Induced Dehydrocoupling for Si−O Bond Formation JF - European Journal of Inorganic Chemistry N2 - The diorgano(bismuth)alcoholate [Bi((C\(_{6}\)H\(_{4}\)CH\(_{2}\))\(_{2}\)S)OPh] (1-OPh) has been synthesized and fully characterized. Stoichiometric reactions, UV/Vis spectroscopy, and (TD-)DFT calculations suggest its susceptibility to homolytic and heterolytic Bi−O bond cleavage under given reaction conditions. Using the dehydrocoupling of silanes with either TEMPO or phenol as model reactions, the catalytic competency of 1-OPh has been investigated (TEMPO=(tetramethyl-piperidin-1-yl)-oxyl). Different reaction pathways can deliberately be addressed by applying photochemical or thermal reaction conditions and by choosing radical or closed-shell substrates (TEMPO vs. phenol). Applied analytical techniques include NMR, UV/Vis, and EPR spectroscopy, mass spectrometry, single-crystal X-ray diffraction analysis, and (TD)-DFT calculations. KW - Bismuth KW - dehydrocoupling KW - radical reactions KW - chalcogens KW - catalysis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257428 VL - 2022 IS - 7 ER - TY - JOUR A1 - Kaya-Zeeb, Sinan A1 - Engelmayer, Lorenz A1 - Straßburger, Mara A1 - Bayer, Jasmin A1 - Bähre, Heike A1 - Seifert, Roland A1 - Scherf-Clavel, Oliver A1 - Thamm, Markus T1 - Octopamine drives honeybee thermogenesis JF - eLife N2 - In times of environmental change species have two options to survive: they either relocate to a new habitat or they adapt to the altered environment. Adaptation requires physiological plasticity and provides a selection benefit. In this regard, the Western honeybee (Apis mellifera) protrudes with its thermoregulatory capabilities, which enables a nearly worldwide distribution. Especially in the cold, shivering thermogenesis enables foraging as well as proper brood development and thus survival. In this study, we present octopamine signaling as a neurochemical prerequisite for honeybee thermogenesis: we were able to induce hypothermia by depleting octopamine in the flight muscles. Additionally, we could restore the ability to increase body temperature by administering octopamine. Thus, we conclude that octopamine signaling in the flight muscles is necessary for thermogenesis. Moreover, we show that these effects are mediated by β octopamine receptors. The significance of our results is highlighted by the fact the respective receptor genes underlie enormous selective pressure due to adaptation to cold climates. Finally, octopamine signaling in the service of thermogenesis might be a key strategy to survive in a changing environment. KW - honeybee KW - octopamine KW - thermogenesis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301327 VL - 11 ER - TY - JOUR A1 - Klein, Dennis A1 - Groh, Janos A1 - Yuan, Xidi A1 - Berve, Kristina A1 - Stassart, Ruth A1 - Fledrich, Robert A1 - Martini, Rudolf T1 - Early targeting of endoneurial macrophages alleviates the neuropathy and affects abnormal Schwann cell differentiation in a mouse model of Charcot-Marie-Tooth 1A JF - Glia N2 - We have previously shown that targeting endoneurial macrophages with the orally applied CSF-1 receptor specific kinase (c-FMS) inhibitor PLX5622 from the age of 3 months onwards led to a substantial alleviation of the neuropathy in mouse models of Charcot-Marie-Tooth (CMT) 1X and 1B disease, which are genetically-mediated nerve disorders not treatable in humans. The same approach failed in a model of CMT1A (PMP22-overexpressing mice, line C61), representing the most frequent form of CMT. This was unexpected since previous studies identified macrophages contributing to disease severity in the same CMT1A model. Here we re-approached the possibility of alleviating the neuropathy in a model of CMT1A by targeting macrophages at earlier time points. As a proof-of-principle experiment, we genetically inactivated colony-stimulating factor-1 (CSF-1) in CMT1A mice, which resulted in lower endoneurial macrophage numbers and alleviated the neuropathy. Based on these observations, we pharmacologically ablated macrophages in newborn CMT1A mice by feeding their lactating mothers with chow containing PLX5622, followed by treatment of the respective progenies after weaning until the age of 6 months. We found that peripheral neuropathy was substantially alleviated after early postnatal treatment, leading to preserved motor function in CMT1A mice. Moreover, macrophage depletion affected the altered Schwann cell differentiation phenotype. These findings underscore the targetable role of macrophage-mediated inflammation in peripheral nerves of inherited neuropathies, but also emphasize the need for an early treatment start confined to a narrow therapeutic time window in CMT1A models and potentially in respective patients. KW - colony stimulating factor 1 KW - Schwann cell differentiation KW - neuroinflammation KW - macrophage KW - inherited peripheral neuropathy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318714 VL - 70 IS - 6 SP - 1100 EP - 1116 ER - TY - JOUR A1 - Özdağ Acarlı, Ayşe Nur A1 - Klein, Thomas A1 - Egenolf, Nadine A1 - Sommer, Claudia A1 - Üçeyler, Nurcan T1 - Subepidermal Schwann cell counts correlate with skin innervation - an exploratory study JF - Muscle & Nerve N2 - Introduction/Aims Schwann cell clusters have been described at the murine dermis-epidermis border. We quantified dermal Schwann cells in the skin of patients with small-fiber neuropathy (SFN) compared with healthy controls to correlate with the clinical phenotype. Methods Skin punch biopsies from the lower legs of 28 patients with SFN (11 men, 17 women; median age, 54 [range, 19-73] years) and 9 healthy controls (five men, four women, median age, 34 [range, 25-69] years) were immunoreacted for S100 calcium-binding protein B as a Schwann cell marker, protein-gene product 9.5 as a pan-neuronal marker, and CD207 as a Langerhans cell marker. Intraepidermal nerve fiber density (IENFD) and subepidermal Schwann cell counts were determined. Results Skin samples of patients with SFN showed lower IENFD (P < .05), fewer Schwann cells per millimeter (P < .01), and fewer Schwann cell clusters per millimeter (P < .05) than controls. When comparing SFN patients with reduced (n = 13; median age, 53 [range, 19-73] years) and normal distal (n = 15, median age, 54 [range, 43-68] years) IENFD, the number of solitary Schwann cells per millimeter (p < .01) and subepidermal nerve fibers associated with Schwann cell branches (P < .05) were lower in patients with reduced IENFD. All three parameters correlated positively with distal IENFD (P < .05 to P < .01), whereas no correlation was found between Schwann cell counts and clinical pain characteristics. Discussion Our data raise questions about the mechanisms underlying the interdependence of dermal Schwann cells and skin innervation in SFN. The temporal course and functional impact of Schwann cell presence and kinetics need further investigation. KW - intraepidermal nerve fiber density KW - small-fiber neuropathy KW - skin punch biopsy KW - Schwann cell KW - neuropathic pain KW - innervation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318726 VL - 65 IS - 4 SP - 471 EP - 479 ER - TY - JOUR A1 - Li, Chang-An T1 - Topological states in two-dimensional Su-Schrieffer-Heeger models JF - Frontiers in Physics N2 - We study the topological properties of the generalized two-dimensional (2D) Su-Schrieffer-Heeger (SSH) models. We show that a pair of Dirac points appear in the Brillouin zone (BZ), consisting a semimetallic phase. Interestingly, the locations of these Dirac points are not pinned to any high-symmetry points of the BZ but tunable by model parameters. Moreover, the merging of two Dirac points undergoes a novel topological phase transition, which leads to either a weak topological insulator or a nodal-line metallic phase. We demonstrate these properties by constructing two specific models, which we referred as type-I and type-II 2D SSH models. The feasible experimental platforms to realize our models are also discussed. KW - su-schrieffer-heeger (SSH) models KW - topological states KW - two-dimensions KW - Dirac points KW - topological phase transitions Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267328 SN - 2296-424X VL - 10 ER - TY - JOUR A1 - Hartrampf, Philipp E. A1 - Weinzierl, Franz-Xaver A1 - Seitz, Anna Katharina A1 - Kübler, Hubert A1 - Essler, Markus A1 - Buck, Andreas K. A1 - Werner, Rudolf A. A1 - Bundschuh, Ralph A. T1 - Any decline in prostate-specific antigen levels identifies survivors scheduled for prostate-specific membrane antigen-directed radioligand therapy JF - The Prostate N2 - Background Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is increasingly incorporated in the therapeutic algorithm of patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to elucidate the predictive performance of early biochemical response for overall survival (OS). Materials and Methods In this bicentric analysis, we included 184 mCRPC patients treated with \(^{177}\)Lu-PSMA RLT. Response to treatment was defined as decrease in prostate-specific antigen (PSA) levels 8 weeks after the first cycle of RLT (any decline or >50% according to Prostate Cancer Working Group 3). OS of responders and nonresponders was then compared using Kaplan–Meier curves and log-rank comparison. Results A total of 114/184 patients (62.0%) showed any PSA decline (PSA response >50%, 55/184 [29.9%]). For individuals exhibiting a PSA decline >50%, OS of 19 months was significantly longer relative to nonresponders (13 months; hazard ratio of death [HR] = 0.64, 95% confidence interval [95% CI] = 0.44–0.93; p = 0.02). However, the difference was even more pronounced for any PSA decline, with an OS of 19 months in responders, but only 8 months in nonresponders (HR = 0.39, 95% CI = 0.25–0.60; p < 0.001). Conclusions In mCRPC patients scheduled for RLT, early biochemical response was tightly linked to prolonged survival, irrespective of the magnitude of PSA decline. As such, even in patients with PSA decrease of less than 50%, RLT should be continued. KW - prostate cancer KW - theranostics KW - PSMA‐617 KW - PSA response KW - PSMA I&T Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318766 VL - 82 IS - 14 SP - 1406 EP - 1412 ER - TY - JOUR A1 - Schreglmann, Sebastian R. A1 - Burke, Derek A1 - Batla, Amit A1 - Kresojevic, Nikola A1 - Wood, Nicholas A1 - Heales, Simon A1 - Bhatia, Kailash P. T1 - Cerebellar and Midbrain Lysosomal Enzyme Deficiency in Isolated Dystonia JF - Movement Disorders KW - dystonia KW - lysosomal enzyme KW - diagnostics Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318743 VL - 37 IS - 4 SP - 875 EP - 877 ER - TY - JOUR A1 - Schreglmann, Sebastian R. A1 - Bhatia, Kailash P. T1 - HOPS-Associated Neurological Disorders: Lysosomal Dysfunction as an Emerging Concept Underlying Dystonia JF - Movement Disorders Clinical Practice KW - dystonia KW - homotypic fusion and protein sorting KW - lysosomal dysfunction Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318736 VL - 9 IS - 4 SP - 452 EP - 453 ER - TY - JOUR A1 - Reinhard, Nils A1 - Bertolini, Enrico A1 - Saito, Aika A1 - Sekiguchi, Manabu A1 - Yoshii, Taishi A1 - Rieger, Dirk A1 - Helfrich‐Förster, Charlotte T1 - The lateral posterior clock neurons of Drosophila melanogaster express three neuropeptides and have multiple connections within the circadian clock network and beyond JF - Journal of Comparative Neurology N2 - Drosophila’s lateral posterior neurons (LPNs) belong to a small group of circadian clock neurons that is so far not characterized in detail. Thanks to a new highly specific split‐Gal4 line, here we describe LPNs’ morphology in fine detail, their synaptic connections, daily bimodal expression of neuropeptides, and propose a putative role of this cluster in controlling daily activity and sleep patterns. We found that the three LPNs are heterogeneous. Two of the neurons with similar morphology arborize in the superior medial and lateral protocerebrum and most likely promote sleep. One unique, possibly wakefulness‐promoting, neuron with wider arborizations extends from the superior lateral protocerebrum toward the anterior optic tubercle. Both LPN types exhibit manifold connections with the other circadian clock neurons, especially with those that control the flies’ morning and evening activity (M‐ and E‐neurons, respectively). In addition, they form synaptic connections with neurons of the mushroom bodies, the fan‐shaped body, and with many additional still unidentified neurons. We found that both LPN types rhythmically express three neuropeptides, Allostatin A, Allostatin C, and Diuretic Hormone 31 with maxima in the morning and the evening. The three LPN neuropeptides may, furthermore, signal to the insect hormonal center in the pars intercerebralis and contribute to rhythmic modulation of metabolism, feeding, and reproduction. We discuss our findings in the light of anatomical details gained by the recently published hemibrain of a single female fly on the electron microscopic level and of previous functional studies concerning the LPN. KW - activity KW - circadian clock neurons KW - insect brain KW - neuropeptides KW - sleep KW - trans‐Tango Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-276456 VL - 530 IS - 9 SP - 1507 EP - 1529 ER - TY - JOUR A1 - Kleiber, Nicole A1 - Lemus-Diaz, Nicolas A1 - Stiller, Carina A1 - Heinrichs, Marleen A1 - Mong-Quyen Mai, Mandy A1 - Hackert, Philipp A1 - Richter-Dennerlein, Ricarda A1 - Höbartner, Claudia A1 - Bohnsack, Katherine E. A1 - Bohnsack, Markus T. T1 - The RNA methyltransferase METTL8 installs m\(^3\)C\(_{32}\) in mitochondrial tRNAs\(^{Thr/Ser(UCN)}\) to optimise tRNA structure and mitochondrial translation JF - Nature Communication N2 - Modified nucleotides in tRNAs are important determinants of folding, structure and function. Here we identify METTL8 as a mitochondrial matrix protein and active RNA methyltransferase responsible for installing m\(^3\)C\(_{32}\) in the human mitochondrial (mt-)tRNA\(^{Thr}\) and mt-tRNA\(^{Ser(UCN)}\). METTL8 crosslinks to the anticodon stem loop (ASL) of many mt-tRNAs in cells, raising the question of how methylation target specificity is achieved. Dissection of mttRNA recognition elements revealed U\(_{34}\)G\(_{35}\) and t\(^6\)A\(_{37}\)/(ms\(^2\))i\(^6\)A\(_{37}\), present concomitantly only in the ASLs of the two substrate mt-tRNAs, as key determinants for METTL8-mediated methylation of C\(_{32}\). Several lines of evidence demonstrate the influence of U\(_{34}\), G\(_{35}\), and the m\(^3\)C\(_{32}\) and t\(^6\)A\(_{37}\)/(ms\(^2\))i\(^6\)A\(_{37}\) modifications in mt-tRNA\(^{Thr/Ser(UCN)}\) on the structure of these mt-tRNAs. Although mt-tRNA\(^{Thr/Ser(UCN)}\) lacking METTL8-mediated m\(^3\)C\(_{32}\) are efficiently aminoacylated and associate with mitochondrial ribosomes, mitochondrial translation is mildly impaired by lack of METTL8. Together these results define the cellular targets of METTL8 and shed new light on the role of m\(^3\)C\(_{32}\) within mt-tRNAs. KW - Modified Nucleotides in tRNAs KW - METTL8 KW - Mitochondrial Matrix Protein KW - RNA Methyltransferase KW - RNA KW - Enzymes KW - Organelles Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254592 VL - 13 ER - TY - JOUR A1 - Lasway, Julius V. A1 - Peters, Marcell K. A1 - Njovu, Henry K. A1 - Eardley, Connal A1 - Pauly, Alain A1 - Steffan‐Dewenter, Ingolf T1 - Agricultural intensification with seasonal fallow land promotes high bee diversity in Afrotropical drylands JF - Journal of Applied Ecology N2 - The exponential increase in the human population in tandem with increased food demand has caused agriculture to be the global‐dominant form of land use. Afrotropical drylands are currently facing the loss of natural savannah habitats and agricultural intensification with largely unknown consequences for bees. Here we investigate the effects of agricultural intensification on bee assemblages in the Afrotropical drylands of northern Tanzania. We disentangled the direct effects of agricultural intensification and temperature on bee richness from indirect effects mediated by changes in floral resources. We collected data from 24 study sites representing three levels of management intensity (natural savannah, moderate intensive and highly intensive agriculture) spanning an extensive gradient of mean annual temperature (MAT) in northern Tanzania. We used ordinary linear models and path analysis to test the effects of agricultural intensity and MAT on bee species richness, bee species composition and body‐size variation of bee communities. We found that bee species richness increased with agricultural intensity and with increasing temperature. The effects of agricultural intensity and temperature on bee species richness were mediated by the positive effects of agriculture and temperature on the richness of floral resources used by bees. During the off‐growing season, agricultural land was characterized by an extensive period of fallow land holding a very high density of flowering plants with unique bee species composition. The increase in bee diversity in agricultural habitats paralleled an increasing variation of bee body sizes with agricultural intensification that, however, diminished in environments with higher temperatures. Synthesis and applications. Our study reveals that bee assemblages in Afrotropical drylands benefit from agricultural intensification in the way it is currently practiced. However, further land‐use intensification, including year‐round irrigated crop monocultures and excessive use of agrochemicals, is likely to exert a negative impact on bee diversity and pollination services, as reported in temperate regions. Moreover, several bee species were restricted to natural savannah habitats. To conserve bee communities and guarantee pollination services in the region, a mixture of savannah and agriculture, with long periods of fallow land should be maintained. KW - bee abundance KW - bee body size KW - bee species richness KW - forage resources KW - inter‐tegular distance KW - mean annual temperature KW - northern Tanzania KW - species community composition Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311877 VL - 59 IS - 12 SP - 3014 EP - 3026 ER - TY - JOUR A1 - Sponsler, Douglas B. A1 - Requier, Fabrice A1 - Kallnik, Katharina A1 - Classen, Alice A1 - Maihoff, Fabienne A1 - Sieger, Johanna A1 - Steffan‐Dewenter, Ingolf T1 - Contrasting patterns of richness, abundance, and turnover in mountain bumble bees and their floral hosts JF - Ecology N2 - Environmental gradients generate and maintain biodiversity on Earth. Mountain slopes are among the most pronounced terrestrial environmental gradients, and the elevational structure of species and their interactions can provide unique insight into the processes that govern community assembly and function in mountain ecosystems. We recorded bumble bee–flower interactions over 3 years along a 1400‐m elevational gradient in the German Alps. Using nonlinear modeling techniques, we analyzed elevational patterns at the levels of abundance, species richness, species β‐diversity, and interaction β‐diversity. Though floral richness exhibited a midelevation peak, bumble bee richness increased with elevation before leveling off at the highest sites, demonstrating the exceptional adaptation of these bees to cold temperatures and short growing seasons. In terms of abundance, though, bumble bees exhibited divergent species‐level responses to elevation, with a clear separation between species preferring low versus high elevations. Overall interaction β‐diversity was mainly caused by strong turnover in the floral community, which exhibited a well‐defined threshold of β‐diversity rate at the tree line ecotone. Interaction β‐diversity increased sharply at the upper extreme of the elevation gradient (1800–2000 m), an interval over which we also saw steep decline in floral richness and abundance. Turnover of bumble bees along the elevation gradient was modest, with the highest rate of β‐diversity occurring over the interval from low‐ to mid‐elevation sites. The contrast between the relative robustness bumble bee communities and sensitivity of plant communities to the elevational gradient in our study suggests that the strongest effects of climate change on mountain bumble bees may be indirect effects mediated by the responses of their floral hosts, though bumble bee species that specialize in high‐elevation habitats may also experience significant direct effects of warming. KW - alpine plants KW - climate KW - elevation gradient KW - mountain ecology KW - pollination network Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287199 VL - 103 IS - 7 ER - TY - JOUR A1 - Gebert, Friederike A1 - Steffan‐Dewenter, Ingolf A1 - Kronbach, Patrick A1 - Peters, Marcell K. T1 - The role of diversity, body size and climate in dung removal: A correlative and experimental approach JF - Journal of Animal Ecology N2 - The mechanisms by which climatic changes influence ecosystem functions, that is, by a direct climatic control of ecosystem processes or by modifying richness and trait compositions of species communities, remain unresolved. This study is a contribution to this discourse by elucidating the linkages between climate, land use, biodiversity, body size and ecosystem functions. We disentangled direct climatic from biodiversity‐mediated effects by using dung removal by dung beetles as a model system and by combining correlative field data and exclosure experiments along an extensive elevational gradient on Mt. Kilimanjaro, Tanzania. Dung removal declined with increasing elevation, being associated with a strong reduction in the richness and body size traits of dung beetle communities. Climate influenced dung removal rates by modifying biodiversity rather than by direct effects. The biodiversity–ecosystem effect was driven by a change in the mean body size of dung beetles. Dung removal rates were strongly reduced when large dung beetles were experimentally excluded. This study underscores that climate influences ecosystem functions mainly by modifying biodiversity and underpins the important role of body size for dung removal. KW - altitudinal gradients KW - biodiversity–ecosystem functioning relationship KW - body size KW - diversity gradients KW - ecosystem services KW - land use KW - Scarabaeidae KW - temperature Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-293907 VL - 91 IS - 11 SP - 2181 EP - 2191 ER - TY - JOUR A1 - Kortmann, Mareike A1 - Roth, Nicolas A1 - Buse, Jörn A1 - Hilszczański, Jacek A1 - Jaworski, Tomasz A1 - Morinière, Jérôme A1 - Seidl, Rupert A1 - Thorn, Simon A1 - Müller, Jörg C. T1 - Arthropod dark taxa provide new insights into diversity responses to bark beetle infestations JF - Ecological Applications N2 - Natural disturbances are increasing around the globe, also impacting protected areas. Although previous studies have indicated that natural disturbances result in mainly positive effects on biodiversity, these analyses mostly focused on a few well established taxonomic groups, and thus uncertainty remains regarding the comprehensive impact of natural disturbances on biodiversity. Using Malaise traps and meta‐barcoding, we studied a broad range of arthropod taxa, including dark and cryptic taxa, along a gradient of bark beetle disturbance severities in five European national parks. We identified order‐level community thresholds of disturbance severity and classified barcode index numbers (BINs; a cluster system for DNA sequences, where each cluster corresponds to a species) as negative or positive disturbance indicators. Negative indicator BINs decreased above thresholds of low to medium disturbance severity (20%–30% of trees killed), whereas positive indicator BINs benefited from high disturbance severity (76%–98%). BINs allocated to a species name contained nearly as many positive as negative disturbance indicators, but dark and cryptic taxa, particularly Diptera and Hymenoptera in our data, contained higher numbers of negative disturbance indicator BINs. Analyses of changes in the richness of BINs showed variable responses of arthropods to disturbance severity at lower taxonomic levels, whereas no significant signal was detected at the order level due to the compensatory responses of the underlying taxa. We conclude that the analyses of dark taxa can offer new insights into biodiversity responses to disturbances. Our results suggest considerable potential for forest management to foster arthropod diversity, for example by maintaining both closed‐canopy forests (>70% cover) and open forests (<30% cover) on the landscape. KW - arthropods KW - biodiversity KW - conservation KW - metabarcoding KW - national park KW - natural disturbance KW - threshold indicator taxa analysis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-276392 VL - 32 IS - 2 ER - TY - JOUR A1 - Uhler, Johannes A1 - Haase, Peter A1 - Hoffmann, Lara A1 - Hothorn, Torsten A1 - Schmidl, Jürgen A1 - Stoll, Stefan A1 - Welti, Ellen A. R. A1 - Buse, Jörn A1 - Müller, Jörg T1 - A comparison of different Malaise trap types JF - Insect Conservation and Diversity N2 - Recent reports on insect decline have highlighted the need for long‐term data on insect communities towards identifying their trends and drivers. With the launch of many new insect monitoring schemes to investigate insect communities over large spatial and temporal scales, Malaise traps have become one of the most important tools due to the broad spectrum of species collected and reduced capture bias through passive sampling of insects day and night. However, Malaise traps can vary in size, shape, and colour, and it is unknown how these differences affect biomass, species richness, and composition of trap catch, making it difficult to compare results between studies. We compared five Malaise trap types (three variations of the Townes and two variations of the Bartak Malaise trap) to determine their effects on biomass and species richness as identified by metabarcoding. Insect biomass varied by 20%–55%, not strictly following trap size but varying with trap type. Total species richness was 20%–38% higher in the three Townes trap models compared to the Bartak traps. Bartak traps captured lower richness of highly mobile taxa but increased richness of ground‐dwelling taxa. The white roofed Townes trap captured a higher richness of pollinators. We find that biomass, total richness, and taxa group specific richness are all sensitive to Malaise trap type. Trap type should be carefully considered and aligned to match monitoring and research questions. Additionally, our estimates of trap type effects can be used to adjust results to facilitate comparisons across studies. KW - Bartak KW - biodiversity KW - insect communities KW - insect monitoring KW - Malaise trap KW - Townes KW - trap selectivity Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-293694 VL - 15 IS - 6 SP - 666 EP - 672 ER - TY - JOUR A1 - Kohl, Patrick L. A1 - Steffan‐Dewenter, Ingolf T1 - Nectar robbing rather than pollinator availability constrains reproduction of a bee‐flowered plant at high elevations JF - Ecosphere N2 - Abiotic factors are generally assumed to determine whether species can exist at the extreme ends of environmental gradients, for example, at high elevations, whereas the role of biotic interactions is less clear. On temperate mountains, insect‐pollinated plant species with bilaterally symmetrical flowers exhibit a parallel elevational decline in species richness and abundance with bees. This suggests that the lack of mutualistic interaction partners sets the elevational range limits of plants via a reduction in reproductive success. We used the bee‐pollinated mountain plant Clinopodium alpinum (Lamiaceae), which blooms along a continuous 1000‐m elevational gradient and has bilaterally symmetrical flowers, as a model to test the predicted parallel elevational decline in flower visitation and seed production. Although the community of flower visitors changed with elevation, the flower visitation rate by the most frequent visitors, bumble bees (33.8% of legitimate visits), and the overall rate of flower visitation by potential pollinators did not vary significantly with elevation. However, we discovered that nectar robbing by bumble bees and nectar theft by ants, two interactions with potentially negative effects on flowers, sharply increased with elevation. Seed set depended on pollinators across elevations and followed a weak hump‐shaped pattern, peaking at mid‐elevations and decreasing by about 20% toward both elevational range edges. Considering the mid‐ and high elevations, elevational variation in seed production could not be explained by legitimate bee visitation rates but was inversely correlated with the frequency of nectar robbing. Our observations challenge the hypothesis that a decrease in the availability of pollinators limits seed production of bee‐flowered plants at high elevations but suggest that an increase in negative interactions (nectar robbing and larceny) constrains reproductive success. KW - altitudinal gradients KW - bee pollination KW - chalcidoid wasps KW - climatic gradients KW - elevational diversity patterns KW - floral larceny KW - fly pollination KW - mountain ecosystems KW - plant–pollinator interactions KW - range limits KW - zygomorphy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287141 VL - 13 IS - 6 ER - TY - JOUR A1 - Hutmacher, Fabian A1 - Morgenroth, Karolina T1 - The beginning of the life story: The meaning of the earliest autobiographical memory from an adult perspective JF - Applied Cognitive Psychology N2 - Earliest autobiographical memories mark a potential beginning of our life story. However, their meaning has hardly been investigated. Against this background, participants (N = 182) were asked to think about two kinds of meaning: the meaning that the remembered event might have had in the moment of experience and the meaning that the memory of the event has for their present life situation. With respect to the meaning in the moment of experience, participants most frequently referred to situational characteristics. The meaning for the present life situation was most frequently related to aspects of the memory that told something about the person beyond the immediate context of the remembered event. Moreover, these meanings were more frequently associated with continuity than with a contrast between then and now. Apart from these overarching commonalities, our data also show that the earliest autobiographical memories of different people can tell very different stories. KW - earliest autobiographical memories KW - meaning-making KW - early memory KW - autobiographical memory KW - life story Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318610 SN - 0888-4080 VL - 36 IS - 3 SP - 612 EP - 622 ER - TY - JOUR A1 - Aldejohann, Alexander Maximilian A1 - Wiese-Posselt, Miriam A1 - Gastmeier, Petra A1 - Kurzai, Oliver T1 - Expert recommendations for prevention and management of Candida auris transmission JF - Mycoses N2 - Candida auris was first described as a yeast pathogen in 2009. Since then, the species has emerged worldwide. In contrast to most other Candida spp., C. auris frequently exhibits multi-drug resistance and is readily transmitted in hospital settings. While most detections so far are from colonised patients, C. auris does cause superficial and life-threatening invasive infections. During management of the first documented C. auris transmission in a German hospital, experts from the National Reference Centers for Invasive Fungal Infections (NRZMyk) and the National Reference Center for Surveillance of Nosocomial Infections screened available literature and integrated available knowledge on infection prevention and C. auris epidemiology and biology to enable optimal containment. Relevant recommendations developed during this process are summarised in this guidance document, intended to assist in management of C. auris transmission and potential outbreak situations. Rapid and effective measures to contain C. auris spread require a multi-disciplinary approach that includes clinical specialists of the affected unit, nursing staff, hospital hygiene, diagnostic microbiology, cleaning staff, hospital management and experts in diagnostic mycology / fungal infections. Action should be initiated in a step-wise process and relevant interventions differ between management of singular C. auris colonised / infected patients and detection of potential C. auris transmission or nosocomial outbreaks. KW - Candida auris KW - nosocomial transmission KW - infection prevention KW - expert recommendation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318570 VL - 65 IS - 6 SP - 590 EP - 598 ER - TY - JOUR A1 - Kolling, Markus A1 - Backhaus, Joy A1 - Hofmann, Norbert A1 - Keß, Stefan A1 - Krastl, Gabriel A1 - Soliman, Sebastian A1 - König, Sarah T1 - Students’ perception of three-dimensionally printed teeth in endodontic training JF - European Journal of Dental Education N2 - Introduction In endodontic education, there is a need for thorough training prior to students embarking on clinical treatment. The aim of this study was to use three-dimensional printing technology to create a new model and to compare its suitability for training purposes with resin blocks and extracted teeth. Materials and Methods Multi-jet-modelling (MJM) produced the 3D model replicating a common difficulty in root-canal morphology. An evaluation study comprising 88 students was run in the sixth semester (summer 2018 and winter 2018/2019). A new questionnaire assessed students’ perception of training models and educational environment. Welch's t-test analysed significant differences. Results The most pronounced differences between models were noted when rating material hardness, radiopacity, root-canal configuration and suitability for practising. Students estimated their learning outcome as greater with 3D-printed teeth compared to resin blocks. Three-dimensionally printed teeth received significantly lower ratings with regard to enthusiasm, the learning of fine motor skills and spatial awareness, when compared to human teeth (p ≤ .001). However, 3D-printed teeth were appreciated for additional benefits, such as their cleanliness, availability and standardisation of training opportunities with complex root-canal configurations. Conclusion Students preferred extracted human teeth to 3D-printed teeth with respect to their physical characteristics and training experience. However, educational advantages may compensate for the shortcomings. The new questionnaire proved both adequate and accurate to assess the models and educational environment in endodontic training. The new 3D-printed teeth enhanced the learning opportunities. KW - 3D-printed tooth KW - three-dimensional printing KW - teaching materials KW - root-canal treatment KW - endodontics KW - dental education Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318676 VL - 26 IS - 4 SP - 653 EP - 661 ER - TY - JOUR A1 - Friedrich, Maximilian U. A1 - Eldebakey, Hazem A1 - Roothans, Jonas A1 - Capetian, Philipp A1 - Zwergal, Andreas A1 - Volkmann, Jens A1 - Reich, Martin T1 - Current-dependent ocular tilt reaction in deep brain stimulation of the subthalamic nucleus: Evidence for an incerto-interstitial pathway? JF - European Journal of Neurology N2 - Background and purpose The aim was to characterize a combined vestibular, ocular motor and postural syndrome induced by deep brain stimulation (DBS) of the subthalamic nucleus in a patient with Parkinson's disease. Methods In a systematic DBS programming session, eye, head and trunk position in roll and pitch plane were documented as a function of stimulation amplitude and field direction. Repeat ocular coherence tomography was used to estimate ocular torsion. The interstitial nucleus of Cajal (INC), zona incerta (ZI) and ascending vestibular fibre tracts were segmented on magnetic resonance imaging using both individual and normative structural connectomic data. Thresholded symptom-associated volumes of tissue activated (VTA) were calculated based on documented stimulation parameters. Results Ipsilateral ocular tilt reaction and body lateropulsion as well as contralateral torsional nystagmus were elicited by the right electrode in a current-dependent manner and subsided after DBS deactivation. With increasing currents, binocular tonic upgaze and body retropulsion were observed. Symptoms were consistent with an irritative effect on the INC. Symptom-associated VTA was found to overlap with the dorsal ZI and the ipsilateral vestibulothalamic tract, while lying rather distant to the INC proper. A ZI-to-INC ‘incerto-interstitial’ tract with contact to the medial-uppermost portion of the VTA could be traced. Conclusion Unilateral stimulation of INC-related circuitry induces an ipsilateral vestibular, ocular motor and postural roll-plane syndrome, which converts into a pitch-plane syndrome when functional activation expands bilaterally. In this case, tractography points to an incerto-interstitial pathway, a tract previously only characterized in non-human primates. Directional current steering proved useful in managing this rare side effect. KW - deep brain stimulation KW - vestibular KW - movement disorders Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318700 VL - 29 IS - 5 SP - 1545 EP - 1549 ER - TY - JOUR A1 - Sommer, Claudia T1 - Natural course of Guillain-Barré syndrome JF - European Journal of Neurology KW - Guillain-Barré syndrome KW - intravenous immunoglobulin KW - immunomodulation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318757 VL - 29 IS - 10 SP - 2881 EP - 2882 ER - TY - JOUR A1 - Badr, Mohammad A1 - McFleder, Rhonda L. A1 - Wu, Jingjing A1 - Knorr, Susanne A1 - Koprich, James B. A1 - Hünig, Thomas A1 - Brotchie, Jonathan M. A1 - Volkmann, Jens A1 - Lutz, Manfred B. A1 - Ip, Chi Wang T1 - Expansion of regulatory T cells by CD28 superagonistic antibodies attenuates neurodegeneration in A53T-α-synuclein Parkinson’s disease mice JF - Journal of Neuroinflammation N2 - Background Regulatory CD4\(^+\)CD25\(^+\)FoxP3\(^+\) T cells (Treg) are a subgroup of T lymphocytes involved in maintaining immune balance. Disturbance of Treg number and impaired suppressive function of Treg correlate with Parkinson’s disease severity. Superagonistic anti-CD28 monoclonal antibodies (CD28SA) activate Treg and cause their expansion to create an anti-inflammatory environment. Methods Using the AAV1/2-A53T-α-synuclein Parkinson’s disease mouse model that overexpresses the pathogenic human A53T-α-synuclein (hαSyn) variant in dopaminergic neurons of the substantia nigra, we assessed the neuroprotective and disease-modifying efficacy of a single intraperitoneal dose of CD28SA given at an early disease stage. Results CD28SA led to Treg expansion 3 days after delivery in hαSyn Parkinson’s disease mice. At this timepoint, an early pro-inflammation was observed in vehicle-treated hαSyn Parkinson’s disease mice with elevated percentages of CD8\(^+\)CD69\(^+\) T cells in brain and increased levels of interleukin-2 (IL-2) in the cervical lymph nodes and spleen. These immune responses were suppressed in CD28SA-treated hαSyn Parkinson’s disease mice. Early treatment with CD28SA attenuated dopaminergic neurodegeneration in the SN of hαSyn Parkinson’s disease mice accompanied with reduced brain numbers of activated CD4\(^+\), CD8\(^+\) T cells and CD11b\(^+\) microglia observed at the late disease-stage 10 weeks after AAV injection. In contrast, a later treatment 4 weeks after AAV delivery failed to reduce dopaminergic neurodegeneration. Conclusions Our data indicate that immune modulation by Treg expansion at a timepoint of overt inflammation is effective for treatment of hαSyn Parkinson’s disease mice and suggest that the concept of early immune therapy could pose a disease-modifying option for Parkinson’s disease patients. KW - Parkinson’s disease KW - neuroinflammation KW - T cells KW - regulatory T cells KW - neuroprotection Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300580 VL - 19 ER - TY - JOUR A1 - Ramírez-Zavala, Bernardo A1 - Krüger, Ines A1 - Dunker, Christine A1 - Jacobsen, Ilse D. A1 - Morschhäuser, Joachim T1 - The protein kinase Ire1 has a Hac1-independent essential role in iron uptake and virulence of Candida albicans JF - PLoS Pathogens N2 - Protein kinases play central roles in virtually all signaling pathways that enable organisms to adapt to their environment. Microbial pathogens must cope with severely restricted iron availability in mammalian hosts to invade and establish themselves within infected tissues. To uncover protein kinase signaling pathways that are involved in the adaptation of the pathogenic yeast Candida albicans to iron limitation, we generated a comprehensive protein kinase deletion mutant library of a wild-type strain. Screening of this library revealed that the protein kinase Ire1, which has a conserved role in the response of eukaryotic cells to endoplasmic reticulum stress, is essential for growth of C. albicans under iron-limiting conditions. Ire1 was not necessary for the activity of the transcription factor Sef1, which regulates the response of the fungus to iron limitation, and Sef1 target genes that are induced by iron depletion were normally upregulated in ire1Δ mutants. Instead, Ire1 was required for proper localization of the high-affinity iron permease Ftr1 to the cell membrane. Intriguingly, iron limitation did not cause increased endoplasmic reticulum stress, and the transcription factor Hac1, which is activated by Ire1-mediated removal of the non-canonical intron in the HAC1 mRNA, was dispensable for Ftr1 localization to the cell membrane and growth under iron-limiting conditions. Nevertheless, expression of a pre-spliced HAC1 copy in ire1Δ mutants restored Ftr1 localization and rescued the growth defects of the mutants. Both ire1Δ and hac1Δ mutants were avirulent in a mouse model of systemic candidiasis, indicating that an appropriate response to endoplasmic reticulum stress is important for the virulence of C. albicans. However, the specific requirement of Ire1 for the functionality of the high-affinity iron permease Ftr1, a well-established virulence factor, even in the absence of endoplasmic reticulum stress uncovers a novel Hac1-independent essential role of Ire1 in iron acquisition and virulence of C. albicans. KW - protein kinase KW - Ire1 KW - Candida albicans Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300225 VL - 18 IS - 2 ER - TY - JOUR A1 - Neagoe, Raluca A. I. A1 - Gardiner, Elizabeth E. A1 - Stegner, David A1 - Nieswandt, Bernhard A1 - Watson, Steve P. A1 - Poulter, Natalie S. T1 - Rac inhibition causes impaired GPVI signalling in human platelets through GPVI shedding and reduction in PLCγ2 phosphorylation JF - International Journal of Molecular Sciences N2 - Rac1 is a small Rho GTPase that is activated in platelets upon stimulation with various ligands, including collagen and thrombin, which are ligands for the glycoprotein VI (GPVI) receptor and the protease-activated receptors, respectively. Rac1-deficient murine platelets have impaired lamellipodia formation, aggregation, and reduced PLCγ2 activation, but not phosphorylation. The objective of our study is to investigate the role of Rac1 in GPVI-dependent human platelet activation and downstream signalling. Therefore, we used human platelets stimulated using GPVI agonists (collagen and collagen-related peptide) in the presence of the Rac1-specific inhibitor EHT1864 and analysed platelet activation, aggregation, spreading, protein phosphorylation, and GPVI clustering and shedding. We observed that in human platelets, the inhibition of Rac1 by EHT1864 had no significant effect on GPVI clustering on collagen fibres but decreased the ability of platelets to spread or aggregate in response to GPVI agonists. Additionally, in contrast to what was observed in murine Rac1-deficient platelets, EHT1864 enhanced GPVI shedding in platelets and reduced the phosphorylation levels of PLCγ2 following GPVI activation. In conclusion, Rac1 activity is required for both human and murine platelet activation in response to GPVI-ligands, but Rac1’s mode of action differs between the two species. KW - platelets KW - Rac1 KW - glycoprotein VI KW - EHT1864 KW - GPVI shedding KW - phospholipase C gamma 2 Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284350 SN - 1422-0067 VL - 23 IS - 7 ER - TY - JOUR A1 - Jones, Jeffrey J. A1 - Huang, Shouguang A1 - Hedrich, Rainer A1 - Geilfus, Christoph‐Martin A1 - Roelfsema, M. Rob G. T1 - The green light gap: a window of opportunity for optogenetic control of stomatal movement JF - New Phytologist N2 - Green plants are equipped with photoreceptors that are capable of sensing radiation in the ultraviolet‐to‐blue and the red‐to‐far‐red parts of the light spectrum. However, plant cells are not particularly sensitive to green light (GL), and light which lies within this part of the spectrum does not efficiently trigger the opening of stomatal pores. Here, we discuss the current knowledge of stomatal responses to light, which are either provoked via photosynthetically active radiation or by specific blue light (BL) signaling pathways. The limited impact of GL on stomatal movements provides a unique option to use this light quality to control optogenetic tools. Recently, several of these tools have been optimized for use in plant biological research, either to control gene expression, or to provoke ion fluxes. Initial studies with the BL‐activated potassium channel BLINK1 showed that this tool can speed up stomatal movements. Moreover, the GL‐sensitive anion channel GtACR1 can induce stomatal closure, even at conditions that provoke stomatal opening in wild‐type plants. Given that crop plants in controlled‐environment agriculture and horticulture are often cultivated with artificial light sources (i.e. a combination of blue and red light from light‐emitting diodes), GL signals can be used as a remote‐control signal that controls stomatal transpiration and water consumption. KW - anion channel KW - channelrhodopsin KW - Chl KW - guard cell KW - ion channel KW - light‐gated KW - membrane potential KW - phototropin Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-293724 VL - 236 IS - 4 SP - 1237 EP - 1244 ER - TY - JOUR A1 - Streng, Andrea A1 - Prifert, Christiane A1 - Weissbrich, Benedikt A1 - Sauerbrei, Andreas A1 - Krumbholz, Andi A1 - Schmid-Ott, Ruprecht A1 - Liese, Johannes G. T1 - Similar severity of influenza primary and re-infections in pre-school children requiring outpatient treatment due to febrile acute respiratory illness: prospective, multicentre surveillance study (2013-2015) JF - BMC Infectious Diseases N2 - Background Influenza virus infections in immunologically naïve children (primary infection) may be more severe than in children with re-infections who are already immunologically primed. We compared frequency and severity of influenza virus primary and re-infections in pre-school children requiring outpatient treatment. Methods Influenza-unvaccinated children 1–5 years of age presenting at pediatric practices with febrile acute respiratory infection < 48 h after symptom onset were enrolled in a prospective, cross-sectional, multicenter surveillance study (2013–2015). Influenza types/subtypes were PCR-confirmed from oropharyngeal swabs. Influenza type/subtype-specific IgG antibodies serving as surrogate markers for immunological priming were determined using ELISA/hemagglutination inhibition assays. The acute influenza disease was defined as primary infection/re-infection by the absence/presence of influenza type-specific immunoglobulin G (IgG) and, in a second approach, by the absence/presence of subtype-specific IgG. Socio-demographic and clinical data were also recorded. Results Of 217 influenza infections, 178 were due to influenza A (87 [49%] primary infections, 91 [51%] re-infections) and 39 were due to influenza B (38 [97%] primary infections, one [3%] re-infection). Children with “influenza A primary infections” showed fever with respiratory symptoms for a shorter period than children with “influenza A re-infections” (median 3 vs. 4 days; age-adjusted p = 0.03); other disease characteristics were similar. If primary infections and re-infections were defined based on influenza A subtypes, 122 (87%) primary infections (78 “A(H3N2) primary infections”, 44 “A(H1N1)pdm09 primary infections”) and 18 (13%) re-infections could be classified (14 “A(H3N2) re-infections” and 4 “A(H1N1)pdm09 re-infections”). Per subtype, primary infections and re-infections were of similar disease severity. Children with re-infections defined on the subtype level usually had non-protective IgG titers against the subtype of their acute infection (16 of 18; 89%). Some patients infected by one of the influenza A subtypes showed protective IgG titers (≥ 1:40) against the other influenza A subtype (32/140; 23%). Conclusions Pre-school children with acute influenza A primary infections and re-infections presented with similar frequency in pediatric practices. Contrary to expectation, severity of acute “influenza A primary infections” and “influenza A re-infections” were similar. Most “influenza A re-infections” defined on the type level turned out to be primary infections when defined based on the subtype. On the subtype level, re-infections were rare and of similar disease severity as primary infections of the same subtype. Subtype level re-infections were usually associated with low IgG levels for the specific subtype of the acute infection, suggesting only short-time humoral immunity induced by previous infection by this subtype. Overall, the results indicated recurring influenza virus infections in this age group and no or only limited heterosubtypic antibody-mediated cross-protection. KW - influenza KW - children KW - disease severity KW - IgG KW - immunology Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265841 VL - 22 ER - TY - JOUR A1 - Lesch, Veronika A1 - König, Maximilian A1 - Kounev, Samuel A1 - Stein, Anthony A1 - Krupitzer, Christian T1 - Tackling the rich vehicle routing problem with nature-inspired algorithms JF - Applied Intelligence N2 - In the last decades, the classical Vehicle Routing Problem (VRP), i.e., assigning a set of orders to vehicles and planning their routes has been intensively researched. As only the assignment of order to vehicles and their routes is already an NP-complete problem, the application of these algorithms in practice often fails to take into account the constraints and restrictions that apply in real-world applications, the so called rich VRP (rVRP) and are limited to single aspects. In this work, we incorporate the main relevant real-world constraints and requirements. We propose a two-stage strategy and a Timeline algorithm for time windows and pause times, and apply a Genetic Algorithm (GA) and Ant Colony Optimization (ACO) individually to the problem to find optimal solutions. Our evaluation of eight different problem instances against four state-of-the-art algorithms shows that our approach handles all given constraints in a reasonable time. KW - logistics KW - rich vehicle routing problem KW - ant-colony optimization KW - genetic algorithm KW - real-world application Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-268942 SN - 1573-7497 VL - 52 ER - TY - JOUR A1 - Guggenberger, Konstanze Viktoria A1 - Torre, Giulia Dalla A1 - Ludwig, Ute A1 - Vogel, Patrick A1 - Weng, Andreas Max A1 - Vogt, Marius Lothar A1 - Fröhlich, Matthias A1 - Schmalzing, Marc A1 - Raithel, Esther A1 - Forman, Christoph A1 - Urbach, Horst A1 - Meckel, Stephan A1 - Bley, Thorsten Alexander T1 - Vasa vasorum of proximal cerebral arteries after dural crossing - potential imaging confounder in diagnosing intracranial vasculitis in elderly subjects on black-blood MRI JF - European Radiology N2 - Objectives Vessel wall enhancement (VWE) may be commonly seen on MRI images of asymptomatic subjects. This study aimed to characterize the VWE of the proximal internal carotid (ICA) and vertebral arteries (VA) in a non-vasculitic elderly patient cohort. Methods Cranial MRI scans at 3 Tesla were performed in 43 patients (aged ≥ 50 years) with known malignancy for exclusion of cerebral metastases. For vessel wall imaging (VWI), a high-resolution compressed-sensing black-blood 3D T1-weighted fast (turbo) spin echo sequence (T1 CS-SPACE prototype) was applied post gadolinium with an isotropic resolution of 0.55 mm. Bilateral proximal intradural ICA and VA segments were evaluated for presence, morphology, and longitudinal extension of VWE. Results Concentric VWE of the proximal intradural ICA was found in 13 (30%) patients, and of the proximal intradural VA in 39 (91%) patients. Mean longitudinal extension of VWE after dural entry was 13 mm in the VA and 2 mm in the ICA. In 14 of 39 patients (36%) with proximal intradural VWE, morphology of VWE was suggestive of the mere presence of vasa vasorum. In 25 patients (64 %), morphology indicated atherosclerotic lesions in addition to vasa vasorum. Conclusions Vasa vasorum may account for concentric VWE within the proximal 2 mm of the ICA and 13 mm of the VA after dural entry in elderly subjects. Concentric VWE in these locations should not be confused with large artery vasculitis. Distal to these segments, VWE may be more likely related to pathologic conditions such as vasculitis. KW - vertebral artery KW - magnetic resonance imaging KW - vasa vasorum KW - large artery vasculitis KW - Atherosclerosis, intracranial arteries Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266524 SN - 1432-1084 VL - 32 IS - 2 ER - TY - JOUR A1 - Wech, Tobias A1 - Ankenbrand, Markus Johannes A1 - Bley, Thorsten Alexander A1 - Heidenreich, Julius Frederik T1 - A data-driven semantic segmentation model for direct cardiac functional analysis based on undersampled radial MR cine series JF - Magnetic Resonance in Medicine N2 - Purpose Image acquisition and subsequent manual analysis of cardiac cine MRI is time-consuming. The purpose of this study was to train and evaluate a 3D artificial neural network for semantic segmentation of radially undersampled cardiac MRI to accelerate both scan time and postprocessing. Methods A database of Cartesian short-axis MR images of the heart (148,500 images, 484 examinations) was assembled from an openly accessible database and radial undersampling was simulated. A 3D U-Net architecture was pretrained for segmentation of undersampled spatiotemporal cine MRI. Transfer learning was then performed using samples from a second database, comprising 108 non-Cartesian radial cine series of the midventricular myocardium to optimize the performance for authentic data. The performance was evaluated for different levels of undersampling by the Dice similarity coefficient (DSC) with respect to reference labels, as well as by deriving ventricular volumes and myocardial masses. Results Without transfer learning, the pretrained model performed moderately on true radial data [maximum number of projections tested, P = 196; DSC = 0.87 (left ventricle), DSC = 0.76 (myocardium), and DSC =0.64 (right ventricle)]. After transfer learning with authentic data, the predictions achieved human level even for high undersampling rates (P = 33, DSC = 0.95, 0.87, and 0.93) without significant difference compared with segmentations derived from fully sampled data. Conclusion A 3D U-Net architecture can be used for semantic segmentation of radially undersampled cine acquisitions, achieving a performance comparable with human experts in fully sampled data. This approach can jointly accelerate time-consuming cine image acquisition and cumbersome manual image analysis. KW - undersampling KW - cardiovascular magnetic resonance (CMR) KW - deep learning KW - radial KW - semantic segmentation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257616 VL - 87 IS - 2 ER - TY - JOUR A1 - Römeis, Fabio A1 - Herweg, Fabian A1 - Müller, Daniel T1 - Salience bias and overwork JF - Games N2 - In this study, we enrich a standard principal–agent model with hidden action by introducing salience-biased perception on the agent's side. The agent's misguided focus on salient payoffs, which leads the agent's and the principal's probability assessments to diverge, has two effects: First, the agent focuses too much on obtaining a bonus, which facilitates incentive provision. Second, the principal may exploit the diverging probability assessments to relax participation. We show that salience bias can reverse the nature of the inefficiency arising from moral hazard; i.e., the principal does not necessarily provide insufficient incentives that result in inefficiently low effort but instead may well provide excessive incentives that result in inefficiently high effort. KW - context-dependent preferences KW - hidden action KW - moral hazard KW - overwork KW - salience theory Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-255213 SN - 2073-4336 VL - 13 IS - 1 ER - TY - JOUR A1 - Fleischmann, Pauline N. A1 - Grob, Robin A1 - Rössler, Wolfgang T1 - Magnetosensation during re-learning walks in desert ants (Cataglyphis nodus) JF - Journal of Comparative Physiology A N2 - At the beginning of their foraging careers, Cataglyphis desert ants calibrate their compass systems and learn the visual panorama surrounding the nest entrance. For that, they perform well-structured initial learning walks. During rotational body movements (pirouettes), naïve ants (novices) gaze back to the nest entrance to memorize their way back to the nest. To align their gaze directions, they rely on the geomagnetic field as a compass cue. In contrast, experienced ants (foragers) use celestial compass cues for path integration during food search. If the panorama at the nest entrance is changed, foragers perform re-learning walks prior to heading out on new foraging excursions. Here, we show that initial learning walks and re-learning walks are structurally different. During re-learning walks, foragers circle around the nest entrance before leaving the nest area to search for food. During pirouettes, they do not gaze back to the nest entrance. In addition, foragers do not use the magnetic field as a compass cue to align their gaze directions during re-learning walk pirouettes. Nevertheless, magnetic alterations during re-learning walks under manipulated panoramic conditions induce changes in nest-directed views indicating that foragers are still magnetosensitive in a cue conflict situation. KW - path integration KW - landmark panorama KW - learning and memory KW - magnetic compass KW - navigation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266556 SN - 1432-1351 VL - 208 IS - 1 ER - TY - JOUR A1 - Eisenberg, Philip A1 - Albert, Leon A1 - Teuffel, Jonathan A1 - Zitzow, Eric A1 - Michaelis, Claudia A1 - Jarick, Jane A1 - Sehlke, Clemens A1 - Große, Lisa A1 - Bader, Nicole A1 - Nunes-Alves, Ariane A1 - Kreikemeyer, Bernd A1 - Schindelin, Hermann A1 - Wade, Rebecca C. A1 - Fiedler, Tomas T1 - The Non-phosphorylating Glyceraldehyde-3-Phosphate Dehydrogenase GapN Is a Potential New Drug Target in Streptococcus pyogenes JF - Frontiers in Microbiology N2 - The strict human pathogen Streptococcus pyogenes causes infections of varying severity, ranging from self-limiting suppurative infections to life-threatening diseases like necrotizing fasciitis or streptococcal toxic shock syndrome. Here, we show that the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase GapN is an essential enzyme for S. pyogenes. GapN converts glyceraldehyde 3-phosphate into 3-phosphoglycerate coupled to the reduction of NADP to NADPH. The knock-down of gapN by antisense peptide nucleic acids (asPNA) significantly reduces viable bacterial counts of S. pyogenes laboratory and macrolide-resistant clinical strains in vitro. As S. pyogenes lacks the oxidative part of the pentose phosphate pathway, GapN appears to be the major NADPH source for the bacterium. Accordingly, other streptococci that carry a complete pentose phosphate pathway are not prone to asPNA-based gapN knock-down. Determination of the crystal structure of the S. pyogenes GapN apo-enzyme revealed an unusual cis-peptide in proximity to the catalytic binding site. Furthermore, using a structural modeling approach, we correctly predicted competitive inhibition of S. pyogenes GapN by erythrose 4-phosphate, indicating that our structural model can be used for in silico screening of specific GapN inhibitors. In conclusion, the data provided here reveal that GapN is a potential target for antimicrobial substances that selectively kill S. pyogenes and other streptococci that lack the oxidative part of the pentose phosphate pathway. KW - X-ray crystallography KW - homology modeling KW - computational docking KW - PNA (peptide nucleic acid) KW - NADPH KW - drug target KW - GapN Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262869 SN - 1664-302X VL - 13 ER - TY - JOUR A1 - Kakaroumpas, Spyridon A1 - Soler i Gibert, Odí T1 - Dyadic product BMO in the Bloom setting JF - Journal of the London Mathematical Society N2 - Ó. Blasco and S. Pott showed that the supremum of operator norms over L\(^{2}\) of all bicommutators (with the same symbol) of one-parameter Haar multipliers dominates the biparameter dyadic product BMO norm of the symbol itself. In the present work we extend this result to the Bloom setting, and to any exponent 1 < p < ∞. The main tool is a new characterization in terms of paraproducts and two-weight John–Nirenberg inequalities for dyadic product BMO in the Bloom setting. We also extend our results to the whole scale of indexed spaces between little bmo and product BMO in the general multiparameter setting, with the appropriate iterated commutator in each case. KW - dyadic product BMO KW - bicommutators KW - Bloom setting Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318602 SN - 0024-6107 VL - 106 IS - 2 SP - 899 EP - 935 ER - TY - JOUR A1 - Lübbe, Torben A1 - Lamarque, Laurent J. A1 - Delzon, Sylvain A1 - Torres Ruiz, José M. A1 - Burlett, Régis A1 - Leuschner, Christoph A1 - Schuldt, Bernhard T1 - High variation in hydraulic efficiency but not xylem safety between roots and branches in four temperate broad–leaved tree species JF - Functional Ecology N2 - Xylem hydraulic safety and efficiency are key traits determining tree fitness in a warmer and drier world. While numerous plant hydraulic studies have focused on branches, our understanding of root hydraulic functioning remains limited, although roots control water uptake, influence stomatal regulation and have commonly been considered as the most vulnerable organ along the hydraulic pathway. We investigated 11 traits related to xylem safety and efficiency along the hydraulic pathway in four temperate broad-leaved tree species. Continuous vessel tapering from coarse roots to stems and branches caused considerable reduction in hydraulic efficiency. Wood density was always lowest in roots, but did not decline linearly along the flow path. In contrast, xylem embolism resistance (P50) did not differ significantly between roots and branches, except for one species. The limited variation in xylem safety between organs did not adequately reflect the corresponding reductions in vessel diameter (by ~70%) and hydraulic efficiency (by ~85%). Although we did not observe any trade-off between xylem safety and specific conductivity, vessel diameter, vessel lumen fraction and wood density were related to embolism resistance, both across and partly within organs. We conclude that coarse roots are not highly vulnerable to xylem embolism as commonly believed, indicating that hydraulic failure during soil drying might be restricted to fine roots. KW - embolism resistance KW - wood density KW - wood anatomy KW - vulnerability curve KW - vessel tapering KW - flow path KW - hydraulic architecture KW - hydraulic conductivity Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318587 SN - 0269-8463 VL - 36 IS - 3 SP - 699 EP - 712 ER - TY - JOUR A1 - Janzen, Dieter A1 - Bakirci, Ezgi A1 - Faber, Jessica A1 - Andrade Mier, Mateo A1 - Hauptstein, Julia A1 - Pal, Arindam A1 - Forster, Leonard A1 - Hazur, Jonas A1 - Boccaccini, Aldo R. A1 - Detsch, Rainer A1 - Teßmar, Jörg A1 - Budday, Silvia A1 - Blunk, Torsten A1 - Dalton, Paul D. A1 - Villmann, Carmen T1 - Reinforced Hyaluronic Acid-Based Matrices Promote 3D Neuronal Network Formation JF - Advanced Healthcare Materials N2 - 3D neuronal cultures attempt to better replicate the in vivo environment to study neurological/neurodegenerative diseases compared to 2D models. A challenge to establish 3D neuron culture models is the low elastic modulus (30–500 Pa) of the native brain. Here, an ultra-soft matrix based on thiolated hyaluronic acid (HA-SH) reinforced with a microfiber frame is formulated and used. Hyaluronic acid represents an essential component of the brain extracellular matrix (ECM). Box-shaped frames with a microfiber spacing of 200 µm composed of 10-layers of poly(ɛ-caprolactone) (PCL) microfibers (9.7 ± 0.2 µm) made via melt electrowriting (MEW) are used to reinforce the HA-SH matrix which has an elastic modulus of 95 Pa. The neuronal viability is low in pure HA-SH matrix, however, when astrocytes are pre-seeded below this reinforced construct, they significantly support neuronal survival, network formation quantified by neurite length, and neuronal firing shown by Ca\(^{2+}\) imaging. The astrocyte-seeded HA-SH matrix is able to match the neuronal viability to the level of Matrigel, a gold standard matrix for neuronal culture for over two decades. Thus, this 3D MEW frame reinforced HA-SH composite with neurons and astrocytes constitutes a reliable and reproducible system to further study brain diseases. KW - 3D model systems KW - melt electrowriting KW - cortical neurons KW - astrocytes KW - Ca\(^{2+}\)-Imaging KW - hyaluronic acid Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318682 VL - 11 IS - 21 ER - TY - JOUR A1 - Rauch, Sebastian T1 - Analysing Long Term Spatial Mobility Patterns of Individuals and Large Groups Using 3D–GIS: A Sport Geographic Approach JF - Tijdschrift voor Economische en Sociale Geografie N2 - Individual mobility and human patterns analyses is receiving increasing attention in numerous interdisciplinary studies and publications using the concept of time-geography but is largely unknown to the subdiscipline of sports geography. Meanwhile the visualization and evaluation of large data of individual patterns are still a major challenge. While a qualitative, microscale view on spatial-temporal topics is more common in today's pattern research using mostly 24h time intervals, this work examines a quantitative approach focusing on an extended period of life. This paper presents a combination of time-geographic approaches with 3D-geoinformation systems and demonstrates their value for analysing individual mobility by implementing a path-homogeneity factor (HPA). Using the example of professional athletes, it is shown which groups display greater similarities in their career paths. While a high homogeneity suggests that groups make similar decisions through socially influenced processes, low values allow the assumption that external processes provide stronger, independent individual structures. KW - 3D GIS analysis KW - path analysis KW - individual mobility KW - geovisualization KW - sport geography KW - time geography Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318551 SN - 0040-747X VL - 113 IS - 3 SP - 257 EP - 272 ER - TY - JOUR A1 - Schilcher, Felix A1 - Hilsmann, Lioba A1 - Ankenbrand, Markus J. A1 - Krischke, Markus A1 - Mueller, Martin J. A1 - Steffan-Dewenter, Ingolf A1 - Scheiner, Ricarda T1 - Honeybees are buffered against undernourishment during larval stages JF - Frontiers in Insect Science N2 - The negative impact of juvenile undernourishment on adult behavior has been well reported for vertebrates, but relatively little is known about invertebrates. In honeybees, nutrition has long been known to affect task performance and timing of behavioral transitions. Whether and how a dietary restriction during larval development affects the task performance of adult honeybees is largely unknown. We raised honeybees in-vitro, varying the amount of a standardized diet (150 µl, 160 µl, 180 µl in total). Emerging adults were marked and inserted into established colonies. Behavioral performance of nurse bees and foragers was investigated and physiological factors known to be involved in the regulation of social organization were quantified. Surprisingly, adult honeybees raised under different feeding regimes did not differ in any of the behaviors observed. No differences were observed in physiological parameters apart from weight. Honeybees were lighter when undernourished (150 µl), while they were heavier under the overfed treatment (180 µl) compared to the control group raised under a normal diet (160 µl). These data suggest that dietary restrictions during larval development do not affect task performance or physiology in this social insect despite producing clear effects on adult weight. We speculate that possible effects of larval undernourishment might be compensated during the early period of adult life. KW - nutrition KW - juvenile hormone KW - nurse bees KW - foragers KW - triglycerides KW - undernourishment KW - task allocation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304646 SN - 2673-8600 VL - 2 ER - TY - JOUR A1 - Pietro-Garcia, Christian A1 - Hartmann, Oliver A1 - Reissland, Michaela A1 - Fischer, Thomas A1 - Maier, Carina R. A1 - Rosenfeldt, Mathias A1 - Schülein-Völk, Christina A1 - Klann, Kevin A1 - Kalb, Reinhard A1 - Dikic, Ivan A1 - Münch, Christian A1 - Diefenbacher, Markus E. T1 - Inhibition of USP28 overcomes Cisplatin-resistance of squamous tumors by suppression of the Fanconi anemia pathway JF - Cell Death and Differentiation N2 - Squamous cell carcinomas (SCC) frequently have an exceptionally high mutational burden. As consequence, they rapidly develop resistance to platinum-based chemotherapy and overall survival is limited. Novel therapeutic strategies are therefore urgently required. SCC express ∆Np63, which regulates the Fanconi Anemia (FA) DNA-damage response in cancer cells, thereby contributing to chemotherapy-resistance. Here we report that the deubiquitylase USP28 is recruited to sites of DNA damage in cisplatin-treated cells. ATR phosphorylates USP28 and increases its enzymatic activity. This phosphorylation event is required to positively regulate the DNA damage repair in SCC by stabilizing ∆Np63. Knock-down or inhibition of USP28 by a specific inhibitor weakens the ability of SCC to cope with DNA damage during platin-based chemotherapy. Hence, our study presents a novel mechanism by which ∆Np63 expressing SCC can be targeted to overcome chemotherapy resistance. Limited treatment options and low response rates to chemotherapy are particularly common in patients with squamous cancer. The SCC specific transcription factor ∆Np63 enhances the expression of Fanconi Anemia genes, thereby contributing to recombinational DNA repair and Cisplatin resistance. Targeting the USP28-∆Np63 axis in SCC tones down this DNA damage response pathways, thereby sensitizing SCC cells to cisplatin treatment. KW - USP28 KW - Cisplatin KW - squamous tumors Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-273014 SN - 1476-5403 VL - 29 IS - 3 ER - TY - JOUR A1 - Dashkovskiy, Sergey A1 - Slynko, Vitalii T1 - Stability conditions for impulsive dynamical systems JF - Mathematics of Control, Signals, and Systems N2 - In this work, we consider impulsive dynamical systems evolving on an infinite-dimensional space and subjected to external perturbations. We look for stability conditions that guarantee the input-to-state stability for such systems. Our new dwell-time conditions allow the situation, where both continuous and discrete dynamics can be unstable simultaneously. Lyapunov like methods are developed for this purpose. Illustrative finite and infinite dimensional examples are provided to demonstrate the application of the main results. These examples cannot be treated by any other published approach and demonstrate the effectiveness of our results. KW - lyapunov methods KW - stability KW - robustness KW - impulsive systems KW - infinite-dimensional systems KW - nonlinear systems KW - input-to-state stability Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-268390 SN - 1435-568X VL - 34 IS - 1 ER - TY - JOUR A1 - Abendroth, Johanna A1 - Nauroth, Peter A1 - Richter, Tobias A1 - Gollwitzer, Mario T1 - Non-strategic detection of identity-threatening information: Epistemic validation and identity defense may share a common cognitive basis JF - PLoS ONE N2 - Readers use prior knowledge to evaluate the validity of statements and detect false information without effort and strategic control. The present study expands this research by exploring whether people also non-strategically detect information that threatens their social identity. Participants (N = 77) completed a task in which they had to respond to a “True” or “False” probe after reading true, false, identity-threatening, or non-threatening sentences. Replicating previous studies, participants reacted more slowly to a positive probe (“True”) after reading false (vs. true) sentences. Notably, participants also reacted more slowly to a positive probe after reading identity-threatening (vs. non-threatening) sentences. These results provide first evidence that identity-threatening information, just as false information, is detected at a very early stage of information processing and lends support to the notion of a routine, non-strategic identity-defense mechanism. KW - social identity KW - cognitive basis KW - identity defense Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301019 VL - 17 IS - 1 ER - TY - JOUR A1 - Rolfes, Muriel A1 - Borde, Julika A1 - Möllenhoff, Kathrin A1 - Kayali, Mohamad A1 - Ernst, Corinna A1 - Gehrig, Andrea A1 - Sutter, Christian A1 - Ramser, Juliane A1 - Niederacher, Dieter A1 - Horváth, Judit A1 - Arnold, Norbert A1 - Meindl, Alfons A1 - Auber, Bernd A1 - Rump, Andreas A1 - Wang-Gohrke, Shan A1 - Ritter, Julia A1 - Hentschel, Julia A1 - Thiele, Holger A1 - Altmüller, Janine A1 - Nürnberg, Peter A1 - Rhiem, Kerstin A1 - Engel, Christoph A1 - Wappenschmidt, Barbara A1 - Schmutzler, Rita K. A1 - Hahnen, Eric A1 - Hauke, Jan T1 - Prevalence of cancer predisposition germline variants in male breast cancer patients: results of the German Consortium for Hereditary Breast and Ovarian Cancer JF - Cancers N2 - Male breast cancer (mBC) is associated with a high prevalence of pathogenic variants (PVs) in the BRCA2 gene; however, data regarding other BC predisposition genes are limited. In this retrospective multicenter study, we investigated the prevalence of PVs in BRCA1/2 and 23 non-BRCA1/2 genes using a sample of 614 patients with mBC, recruited through the centers of the German Consortium for Hereditary Breast and Ovarian Cancer. A high proportion of patients with mBC carried PVs in BRCA2 (23.0%, 142/614) and BRCA1 (4.6%, 28/614). The prevalence of BRCA1/2 PVs was 11.0% in patients with mBC without a family history of breast and/or ovarian cancer. Patients with BRCA1/2 PVs did not show an earlier disease onset than those without. The predominant clinical presentation of tumor phenotypes was estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, and HER2-negative (77.7%); further, 10.2% of the tumors were triple-positive, and 1.2% were triple-negative. No association was found between ER/PR/HER2 status and BRCA1/2 PV occurrence. Comparing the prevalence of protein-truncating variants (PTVs) between patients with mBC and control data (ExAC, n = 27,173) revealed significant associations of PTVs in both BRCA1 and BRCA2 with mBC (BRCA1: OR = 17.04, 95% CI = 10.54–26.82, p < 10\(^{−5}\); BRCA2: OR = 77.71, 95% CI = 58.71–102.33, p < 10\(^{−5}\)). A case-control investigation of 23 non-BRCA1/2 genes in 340 BRCA1/2-negative patients and ExAC controls revealed significant associations of PTVs in CHEK2, PALB2, and ATM with mBC (CHEK2: OR = 3.78, 95% CI = 1.59–7.71, p = 0.002; PALB2: OR = 14.77, 95% CI = 5.02–36.02, p < 10\(^{−5}\); ATM: OR = 3.36, 95% CI = 0.89–8.96, p = 0.04). Overall, our findings support the benefit of multi-gene panel testing in patients with mBC irrespective of their family history, age at disease onset, and tumor phenotype. KW - breast neoplasms KW - male breast cancer KW - breast cancer predisposition genes KW - genetic testing KW - familial breast cancer Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281758 SN - 2072-6694 VL - 14 IS - 13 ER - TY - JOUR A1 - Traub, Jan A1 - Otto, Markus A1 - Sell, Roxane A1 - Göpfert, Dennis A1 - Homola, György A1 - Steinacker, Petra A1 - Oeckl, Patrick A1 - Morbach, Caroline A1 - Frantz, Stefan A1 - Pham, Mirko A1 - Störk, Stefan A1 - Stoll, Guido A1 - Frey, Anna T1 - Serum phosphorylated tau protein 181 and neurofilament light chain in cognitively impaired heart failure patients JF - Alzheimer's Research & Therapy N2 - Background Chronic heart failure (HF) is known to increase the risk of developing Alzheimer’s dementia significantly. Thus, detecting and preventing mild cognitive impairment, which is common in patients with HF, is of great importance. Serum biomarkers are increasingly used in neurological disorders for diagnostics, monitoring, and prognostication of disease course. It remains unclear if neuronal biomarkers may help detect cognitive impairment in this high-risk population. Also, the influence of chronic HF and concomitant renal dysfunction on these biomarkers is not well understood. Methods Within the monocentric Cognition.Matters-HF study, we quantified the serum levels of phosphorylated tau protein 181 (pTau) and neurofilament light chain (NfL) of 146 extensively phenotyped chronic heart failure patients (aged 32 to 85 years; 15.1% women) using ultrasensitive bead-based single-molecule immunoassays. The clinical work-up included advanced cognitive testing and cerebral magnetic resonance imaging (MRI). Results Serum concentrations of NfL ranged from 5.4 to 215.0 pg/ml (median 26.4 pg/ml) and of pTau from 0.51 to 9.22 pg/ml (median 1.57 pg/ml). We detected mild cognitive impairment (i.e., T-score < 40 in at least one cognitive domain) in 60% of heart failure patients. pTau (p = 0.014), but not NfL, was elevated in this group. Both NfL (ρ = − 0.21; p = 0.013) and pTau (ρ = − 0.25; p = 0.002) related to the cognitive domain visual/verbal memory, as well as white matter hyperintensity volume and cerebral and hippocampal atrophy. In multivariable analysis, both biomarkers were independently influenced by age (T = 4.6 for pTau; T = 5.9 for NfL) and glomerular filtration rate (T = − 2.4 for pTau; T = − 3.4 for NfL). Markers of chronic heart failure, left atrial volume index (T = 4.6) and NT-proBNP (T = 2.8), were further cardiological determinants of pTau and NfL, respectively. In addition, pTau was also strongly affected by serum creatine kinase levels (T = 6.5) and ferritin (T = − 3.1). Conclusions pTau and NfL serum levels are strongly influenced by age-dependent renal and cardiac dysfunction. These findings point towards the need for longitudinal examinations and consideration of frequent comorbidities when using neuronal serum biomarkers. KW - Alzheimer’s dementia KW - heart failure KW - cognitive impairment KW - neurofilament light chain KW - phosphorylated tau protein KW - renal function KW - age Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300515 VL - 14 ER - TY - JOUR A1 - Dickson, John A1 - Eberlein, Uta A1 - Lassmann, Michael T1 - The effect of modern PET technology and techniques on the EANM paediatric dosage card JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - Aim Recent advancements in PET technology have brought with it significant improvements in PET performance and image quality. In particular, the extension of the axial field of view of PET systems, and the introduction of semiconductor technology into the PET detector, initially for PET/MR, and more recently available long-field-of-view PET/CT systems (≥ 25 cm) have brought a step change improvement in the sensitivity of PET scanners. Given the requirement to limit paediatric doses, this increase in sensitivity is extremely welcome for the imaging of children and young people. This is even more relevant with PET/MR, where the lack of CT exposures brings further dose reduction benefits to this population. In this short article, we give some details around the benefits around new PET technology including PET/MR and its implications on the EANM paediatric dosage card. Material and methods Reflecting on EANM adult guidance on injected activities, and making reference to bed overlap and the concept of MBq.min bed\(^{-1}\) kg\(^{-1}\), we use published data on image quality from PET/MR systems to update the paediatric dosage card for PET/MR and extended axial field of view (≥ 25 cm) PET/CT systems. However, this communication does not cover the expansion of paediatric dosing for the half-body and total-body scanners that have recently come to market. Results In analogy to the existing EANM dosage card, new parameters for the EANM paediatric dosage card were developed (class B, baseline value: 10.7 MBq, minimum recommended activity 10 MBq). The recommended administered activities for the systems considered in this communication range from 11 MBq [\(^{18}\)F]FDG for a child with a weight of 3 kg to 149 MBq [\(^{18}\)F]FDG for a paediatric patient weight of 68 kg, assuming a scan of 3 min per bed position. The mean effective dose over all ages (1 year and older) is 2.85 mSv. Conclusion With this, recommendations for paediatric dosing are given for systems that have not been considered previously. KW - PET KW - PET/MR systems KW - EANM dosage card Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265624 SN - 1619-7089 VL - 49 IS - 6 ER - TY - JOUR A1 - Fadillioglu, Cagla A1 - Kanus, Lisa A1 - Möhler, Felix A1 - Ringhof, Steffen A1 - Schindler, Hans J. A1 - Stein, Thorsten A1 - Hellmann, Daniel T1 - Influence of controlled masticatory muscle activity on dynamic reactive balance JF - Journal of Oral Rehabilitation N2 - Background The influence of the stomatognatic system on human posture control has been investigated under static conditions, but the effects on dynamic balance have not yet been considered. Objective Investigating the influence of different functional stomatognatic activities (jaw clenching (JAW), tongue pressing (TON) and habitual jaw position (HAB)) on postural performance during a dynamic reactive balance task. Methods Forty‐eight physically active and healthy adults were assigned to three groups differing in oral‐motor tasks (JAW, TON or HAB). Dynamic reactive balance was assessed by an oscillating platform which was externally perturbed in four directions. Performance was quantified by means of Lehr's damping ratio. Mean speeds of the selected anatomical regions (head, trunk, pelvis, knee and foot) were analysed to determine significant performance differences. Results The groups differed significantly in balance performance in direction F (i.e., forwards acceleration of the platform). Post hoc tests revealed that the JAW group had significantly better performance compared with both the HAB and TON groups. Better performance was associated with a decreased mean speed of the analysed anatomical regions. Conclusion JAW can improve dynamic reactive balance but the occurrence of positive effects seems to be task‐specific and not general. TON seems not to have any observable effects on dynamic reactive balance performance, at least when evaluating it with an oscillating platform. JAW might be a valuable strategy which could possibly reduce the risk of falls in elderly people; however, further investigations are still needed. KW - jaw clenching KW - perturbation KW - postural control KW - posturomed KW - stomatognatic system KW - tongue pressing Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262436 VL - 49 IS - 3 SP - 327 EP - 336 ER - TY - JOUR A1 - Hong, Yongseok A1 - Kim, Woojae A1 - Kim, Taeyeon A1 - Kaufmann, Christina A1 - Kim, Hyungjun A1 - Würthner, Frank A1 - Kim, Dongho T1 - Real-time Observation of Structural Dynamics Triggering Excimer Formation in a Perylene Bisimide Folda-dimer by Ultrafast Time-Domain Raman Spectroscopy JF - Angewandte Chemie International Edition N2 - In π-conjugated organic photovoltaic materials, an excimer state has been generally regarded as a trap state which hinders efficient excitation energy transport. But despite wide investigations of the excimer for overcoming the undesirable energy loss, the understanding of the relationship between the structure of the excimer in stacked organic compounds and its properties remains elusive. Here, we present the landscape of structural dynamics from the excimer formation to its relaxation in a co-facially stacked archetypical perylene bisimide folda-dimer using ultrafast time-domain Raman spectroscopy. We directly captured vibrational snapshots illustrating the ultrafast structural evolution triggering the excimer formation along the interchromophore coordinate on the complex excited-state potential surfaces and following evolution into a relaxed excimer state. Not only does this work showcase the ultrafast structural dynamics necessary for the excimer formation and control of excimer characteristics but also provides important criteria for designing the π-conjugated organic molecules. KW - excimer KW - vibrational coherence KW - time-resolved impulsive stimulated raman spectroscopy KW - structural dynamics KW - perylene bisimide Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318788 VL - 61 IS - 13 ER - TY - JOUR A1 - Reusch, Julia A1 - Wagenhäuser, Isabell A1 - Gabel, Alexander A1 - Eggestein, Annika A1 - Höhn, Anna A1 - Lâm, Thiên-Trí A1 - Frey, Anna A1 - Schubert-Unkmeir, Alexandra A1 - Dölken, Lars A1 - Frantz, Stefan A1 - Kurzai, Oliver A1 - Vogel, Ulrich A1 - Krone, Manuel A1 - Petri, Nils T1 - Influencing factors of anti-SARS-CoV-2-spike-IgG antibody titers in healthcare workers: A cross-section study JF - Journal of Medical Virology N2 - Against the background of the current COVID-19 infection dynamics with its rapid spread of SARS-CoV-2 variants of concern (VOC), the immunity and the vaccine prevention of healthcare workers (HCWs) against SARS-CoV-2 continues to be of high importance. This observational cross-section study assesses factors influencing the level of anti-SARS-CoV-2-spike IgG after SARS-CoV-2 infection or vaccination. One thousand seven hundred and fifty HCWs were recruited meeting the following inclusion criteria: age ≥18 years, PCR-confirmed SARS-CoV-2 infection convalescence and/or at least one dose of COVID-19 vaccination. anti-SARS-CoV-2-spike IgG titers were determined by SERION ELISA agile SARS-CoV-2 IgG. Mean anti-SARS-CoV-2-spike IgG levels increased significantly by number of COVID-19 vaccinations (92.2 BAU/ml for single, 140.9 BAU/ml for twice and 1144.3 BAU/ml for threefold vaccination). Hybrid COVID-19 immunized respondents (after infection and vaccination) had significantly higher antibody titers compared with convalescent only HCWs. Anti-SARS-CoV-2-spike IgG titers declined significantly with time after the second vaccination. Smoking and high age were associated with lower titers. Both recovered and vaccinated HCWs presented a predominantly good humoral immune response. Smoking and higher age limited the humoral SARS-CoV-2 immunity, adding to the risk of severe infections within this already health impaired collective. KW - anti‐SARS‐CoV‐2‐spike IgG KW - seroprevalence KW - SARS‐CoV‐2 infection KW - healthcare workers KW - COVID‐19 vaccination Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318659 VL - 95 IS - 1 ER - TY - JOUR A1 - Linz, Christian A1 - Faber, Julian A1 - Schmid, Reiner A1 - Kunz, Felix A1 - Böhm, Hartmut A1 - Hartmann, Stefan A1 - Schweitzer, Tilmann T1 - Using a 3D asymmetry index as a novel form for capturing complex three-dimensionality in positional plagiocephaly JF - Scientific Reports N2 - Positional plagiocephaly (PP) is the most common skull deformity in infants. Different classification systems exist for graduating the degree of PP, but all of these systems are based on two-dimensional (2D) parameters. This limitation leads to several problems stemming from the fact that 2D parameters are used to classify the three-dimensional (3D) shape of the head. We therefore evaluate existing measurement parameters and validate a newly developed 3D parameter for quantifying PP. Additionally, we present a new classification of PP based on a 3D parameter. 210 patients with PP and 50 patients without PP were included in this study. Existing parameters (2D and 3D) and newly developed volume parameters based on a 3D stereophotogrammetry scan were validated using ROC curves. Additionally, thresholds for the new 3D parameter of a 3D asymmetry index were assessed. The volume parameter 3D asymmetry index quantifies PP equally as well as the gold standard of 30° diagonal difference. Moreover, a 3D asymmetry index allows for a 3D-based classification of PP. The 3D asymmetry index can be used to define the degree of PP. It is easily applicable in stereophotogrammetric datasets and allows for comparability both intra- and inter-individually as well as for scientific analysis. KW - craniofacial orthodontics KW - physical examination KW - three-dimensional imaging Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300427 VL - 12 ER - TY - JOUR A1 - Mützel, Carina A1 - Farrell, Jeffrey M. A1 - Shoyama, Kazutaka A1 - Würthner, Frank T1 - 12b,24b-Diborahexabenzo[a,c,fg,l,n,qr]pentacene: A Low-LUMO Boron-Doped Polycyclic Aromatic Hydrocarbon JF - Angewandte Chemie International Edition N2 - Herein we devise and execute a new synthesis of a pristine boron-doped nanographene. Our target boron-doped nanographene was designed based on DFT calculations to possess a low LUMO energy level and a narrow band gap derived from its precise geometry and B-doping arrangement. Our synthesis of this target, a doubly B-doped hexabenzopentacene (B\(_{2}\)-HBP), employs six net C−H borylations of an alkene, comprising consecutive hydroboration/electrophilic borylation/dehydrogenation and BBr\(_{3}\)/AlCl\(_{3}\)/2,6-dichloropyridine-mediated C−H borylation steps. As predicted by our calculations, B\(_{2}\)-HBP absorbs strongly in the visible region and emits in the NIR up to 1150 nm in o-dichlorobenzene solutions. Furthermore, B\(_{2}\)-HBP possesses a very low LUMO level, showing two reversible reductions at −1.00 V and −1.17 V vs. Fc\(^{+}\)/Fc. Our methodology is surprisingly selective despite its implementation of unfunctionalized precursors and offers a new approach to the synthesis of pristine B-doped polycyclic aromatic hydrocarbons. KW - aromaticity KW - polycycles KW - pentacene KW - near infrared emitter KW - boron Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318808 VL - 61 IS - 8 ER - TY - JOUR A1 - Liu, Bin A1 - Vonhausen, Yvonne A1 - Schulz, Alexander A1 - Höbartner, Claudia A1 - Würthner, Frank T1 - Peptide Backbone Directed Self-Assembly of Merocyanine Oligomers into Duplex Structures JF - Angewandte Chemie International Edition N2 - The pseudopeptide backbone provided by N-(2-aminoethyl)-glycine oligomers with attached nucleobases has been widely utilized in peptide nucleic acids (PNAs) as DNA mimics. Here we demonstrate the suitability of this backbone for the formation of structurally defined dye stacks. Toward this goal a series of peptide merocyanine (PMC) dye oligomers connected to a N-(2-aminoethyl)-glycine backbone were prepared through peptide synthesis. Our concentration-, temperature- and solvent-dependent UV/Vis absorption studies show that under the control of dipole–dipole interactions, smaller-sized oligomers consisting of one, two or three dyes self-assemble into defined duplex structures containing two up to six chromophores. In contrast, upon further extension of the oligomer, the chosen peptide backbone cannot direct the formation of a defined duplex architecture anymore due to intramolecular aggregation between the dyes. For all aggregate species a moderate aggregation-induced emission enhancement is observed. KW - dipole-dipole interaction KW - peptide backbone KW - merocyanine KW - dye assembly KW - duplex structure Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318797 VL - 61 IS - 21 ER - TY - JOUR A1 - Ouyang, Guanghui A1 - Rühe, Jessica A1 - Zhang, Yang A1 - Lin, Mei-Jin A1 - Liu, Minghua A1 - Würthner, Frank T1 - Intramolecular Energy and Solvent-Dependent Chirality Transfer within a BINOL-Perylene Hetero-Cyclophane JF - Angewandte Chemie International Edition N2 - Multichromophoric macrocycles and cyclophanes are important supramolecular architectures for the elucidation of interchromophoric interactions originating from precise spatial organization. Herein, by combining an axially chiral binaphthol bisimide (BBI) and a bay-substituted conformationally labile twisted perylene bisimide (PBI) within a cyclophane of well-defined geometry, we report a chiral PBI hetero-cyclophane (BBI-PBI) that shows intramolecular energy and solvent-regulated chirality transfer from the BBI to the PBI subunit. Excellent spectral overlap and spatial arrangement of BBI and PBI lead to efficient excitation energy transfer and subsequent PBI emission with high quantum yield (80–98 %) in various solvents. In contrast, chirality transfer is strongly dependent on the respective solvent as revealed by circular dichroism (CD) spectroscopy. The combination of energy and chirality transfer affords a bright red circularly polarized luminescence (CPL) from the PBI chromophore by excitation of BBI. KW - chirality transfer KW - solvent effects KW - perylene bisimide KW - energy transfer KW - cyclophanes Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318818 VL - 61 IS - 31 ER - TY - JOUR A1 - Hofmann, Julian A1 - Spatz, Philipp A1 - Walther, Rasmus A1 - Gutmann, Marcus A1 - Maurice, Tangui A1 - Decker, Michael T1 - Synthesis and Biological Evaluation of Flavonoid-Cinnamic Acid Amide Hybrids with Distinct Activity against Neurodegeneration in Vitro and in Vivo JF - Chemistry-A European Journal N2 - Flavonoids are polyphenolic natural products and have shown significant potential as disease-modifying agents against neurodegenerative disorders like Alzheimer's disease (AD), with activities even in vivo. Hybridization of the natural products taxifolin and silibinin with cinnamic acid led to an overadditive effect of these compounds in several phenotypic screening assays related to neurodegeneration and AD. Therefore, we have exchanged the flavonoid part of the hybrids with different flavonoids, which show higher efficacy than taxifolin or silibinin, to improve the activity of the respective hybrids. Chemical connection between the flavonoid and cinnamic acid was realized by an amide instead of a labile ester bond to improve stability towards hydrolysis. To investigate the influence of a double bond at the C-ring of the flavonoid, the dehydro analogues of the respective hybrids were also synthesized. All compounds obtained show neuroprotection against oxytosis, ferroptosis and ATP-depletion, respectively, in the murine hippocampal cell line HT22. Interestingly, the taxifolin and the quercetin derivatives are the most active compounds, whereby the quercetin derivate shows even more pronounced activity than the taxifolin one in all assays applied. As aimed for, no hydrolysis product was found in cellular uptake experiments after 4 h whereas different metabolites were detected. Furthermore, the quercetin-cinnamic acid amide showed pronounced activity in an in vivo AD mouse model at a remarkably low dose of 0.3 mg/kg. KW - AD mouse modele KW - oxytosis/ferroptosis KW - natural product hybrids KW - Alzheimer's diseas Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318878 VL - 28 IS - 39 ER - TY - JOUR A1 - Scheidel, Sebastian A1 - Östreicher, Laurina A1 - Mark, Isabelle A1 - Pöppler, Ann-Christin T1 - You cannot fight the pressure: Structural rearrangements of active pharmaceutical ingredients under magic angle spinning JF - Magnetic Resonance in Chemistry N2 - Although solid-state nuclear magnetic resonance (NMR) is a versatile analytical tool to study polymorphs and phase transitions of pharmaceutical molecules and products, this work summarizes examples of spontaneous and unexpected (and unwanted) structural rearrangements and phase transitions (amorphous-to-crystalline and crystalline-to-crystalline) under magic angle spinning (MAS) conditions, some of them clearly being due to the pressure experienced by the samples. It is widely known that such changes can often be detected by X-ray powder diffraction (XRPD); here, the capability of solid-state NMR experiments with a special focus on \(^{1}\)H-\(^{13}\)C frequency-switched Lee–Goldburg heteronuclear correlation (FSLG HETCOR)/MAS NMR experiments to detect even subtle changes on a molecular level not observable by conventional 1D NMR experiments or XRPD is presented. Furthermore, it is shown that a polymorphic impurity combined with MAS can induce a crystalline-to-crystalline phase transition. This showcases that solid-state NMR is not always noninvasive and such changes upon MAS should be considered in particular when compounds are studied over longer time spans. KW - \(^{1}\)H-\(^{13}\)C HETCOR KW - API KW - structural changes KW - XRPD KW - solid-state NMR KW - MAS Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318838 VL - 60 IS - 6 SP - 572 EP - 582 ER - TY - JOUR A1 - Rau, Monika A1 - Buggisch, Peter A1 - Mauss, Stefan A1 - Boeker, Klaus H. W. A1 - Klinker, Hartwig A1 - Müller, Tobias A1 - Stoehr, Albrecht A1 - Schattenberg, Jörn M. A1 - Geier, Andreas T1 - Prognostic impact of steatosis in the clinical course of chronic HCV infection-Results from the German Hepatitis C-Registry JF - PLoS ONE N2 - Background Liver steatosis is often observed in chronic HCV infection and associated to genotype or comorbidities. NAFLD is an important risk factor for end-stage liver disease. We aimed to analyse the course of NAFLD as a concomitant disease in a cohort of HCV patients. Methods The German Hepatitis C-Registry is a national multicenter real-world cohort. In the current analysis, 8789 HCV patients were included and separated based on the presence of steatosis on ultrasound and/or histology. Fibrosis progression was assessed by transient elastography (TE), ultrasound or non-invasive surrogate scores. Results At the time of study inclusion 12.3% (n = 962) of HCV patients presented with steatosis (+S) (higher rate in GT-3). Diabetes mellitus was more frequent in GT-1 patients. HCV patients without steatosis (-S) had a slightly higher rate of fibrosis progression (FP) over time (30.3%) in contrast to HCV patients +S (26%). This effect was mainly observed in GT-3 patients (34.4% vs. 20.6%). A larger decrease of ALT, AST and GGT from baseline to FU-1 (4–24 weeks after EOT) was found in HCV patients (without FP) +S compared to -S. HCV patients -S and with FP presented more often metabolic comorbidities with a significantly higher BMI (+0.58kg/m\(^{2}\)) compared to patients -S without FP. This was particularly pronounced in patients with abnormal ALT. Conclusion Clinically diagnosed steatosis in HCV patients does not seem to contribute to significant FP in this unique cohort. The low prevalence of steatosis could reflect a lower awareness of fatty liver in HCV patients, as patients -S and with FP presented more metabolic risk factors. KW - steatosis KW - HCV infection KW - liver Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300549 VL - 17 IS - 6 ER - TY - JOUR A1 - Maihoff, Fabienne A1 - Bohlke, Kyte A1 - Brockmann, Axel A1 - Schmitt, Thomas T1 - Increased complexity of worker CHC profiles in Apis dorsata correlates with nesting ecology JF - PLoS ONE N2 - Cuticular hydrocarbons (CHC) are known to serve as discrimination cues and will trigger defence behaviour in a plethora of eusocial insects. However, little is known how about nestmate recognition ability selects for CHC diversification. In this study we investigate differences in CHC composition of four major honey bee species with respect to the differences in their nesting behavior. In contrast to A. mellifera, A. cerana and A. florea, the giant honey bee A. dorsata prefers to build their nests in aggregations with very small spatial distances between nests, which increases the probability of intrusions. Thus, A. dorsata exhibits a particularly challenging nesting behavior which we hypothesize should be accompanied with an improved nestmate recognition system. Comparative analyses of the worker CHC profiles indicate that A. dorsata workers exhibit a unique and more complex CHC profile than the other three honey bee species. This increased complexity is likely based on a developmental process that retains the capability to synthesize methyl-branched hydrocarbons as adults. Furthermore, two sets of behavioral experiments provide evidence that A. dorsata shows an improved nestmate discrimination ability compared to the phylogenetically ancestral A. florea, which is also open-nesting but does not form nest aggregations. The results of our study suggest that ecological traits like nesting in aggregation might be able to drive CHC profile diversification even in closely related insect species. KW - Apis dorsata KW - cuticular hydrocarbons KW - nesting Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301353 VL - 17 IS - 7 ER - TY - JOUR A1 - Reinhard, Sebastian A1 - Helmerich, Dominic A. A1 - Boras, Dominik A1 - Sauer, Markus A1 - Kollmannsberger, Philip T1 - ReCSAI: recursive compressed sensing artificial intelligence for confocal lifetime localization microscopy JF - BMC Bioinformatics N2 - Background Localization-based super-resolution microscopy resolves macromolecular structures down to a few nanometers by computationally reconstructing fluorescent emitter coordinates from diffraction-limited spots. The most commonly used algorithms are based on fitting parametric models of the point spread function (PSF) to a measured photon distribution. These algorithms make assumptions about the symmetry of the PSF and thus, do not work well with irregular, non-linear PSFs that occur for example in confocal lifetime imaging, where a laser is scanned across the sample. An alternative method for reconstructing sparse emitter sets from noisy, diffraction-limited images is compressed sensing, but due to its high computational cost it has not yet been widely adopted. Deep neural network fitters have recently emerged as a new competitive method for localization microscopy. They can learn to fit arbitrary PSFs, but require extensive simulated training data and do not generalize well. A method to efficiently fit the irregular PSFs from confocal lifetime localization microscopy combining the advantages of deep learning and compressed sensing would greatly improve the acquisition speed and throughput of this method. Results Here we introduce ReCSAI, a compressed sensing neural network to reconstruct localizations for confocal dSTORM, together with a simulation tool to generate training data. We implemented and compared different artificial network architectures, aiming to combine the advantages of compressed sensing and deep learning. We found that a U-Net with a recursive structure inspired by iterative compressed sensing showed the best results on realistic simulated datasets with noise, as well as on real experimentally measured confocal lifetime scanning data. Adding a trainable wavelet denoising layer as prior step further improved the reconstruction quality. Conclusions Our deep learning approach can reach a similar reconstruction accuracy for confocal dSTORM as frame binning with traditional fitting without requiring the acquisition of multiple frames. In addition, our work offers generic insights on the reconstruction of sparse measurements from noisy experimental data by combining compressed sensing and deep learning. We provide the trained networks, the code for network training and inference as well as the simulation tool as python code and Jupyter notebooks for easy reproducibility. KW - compressed sensing KW - AI KW - SMLM KW - FLIMbee KW - dSTORM Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299768 VL - 23 IS - 1 ER - TY - JOUR A1 - Pfister, Roland A1 - Foerster, Anna T1 - How to measure post-error slowing: The case of pre-error speeding JF - Behavior Research Methods N2 - Post-error slowing is one of the most widely employed measures to study cognitive and behavioral consequences of error commission. Several methods have been proposed to quantify the post-error slowing effect, and we discuss two main methods: The traditional method of comparing response times in correct post-error trials to response times of correct trials that follow another correct trial, and a more recent proposal of comparing response times in correct post-error trials to the corresponding correct pre-error trials. Based on thorough re-analyses of two datasets, we argue that the latter method provides an inflated estimate by also capturing the (partially) independent effect of pre-error speeding. We propose two solutions for improving the assessment of human error processing, both of which highlight the importance of distinguishing between initial pre-error speeding and later post-error slowing. KW - response-time analysis KW - post-error slowing KW - pre-error speeding KW - performance monitoring Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-273244 SN - 1554-3528 VL - 54 IS - 1 ER - TY - JOUR A1 - Feldheim, Jonas A1 - Kessler, Almuth F. A1 - Feldheim, Julia J. A1 - Schulz, Ellina A1 - Wend, David A1 - Lazaridis, Lazaros A1 - Kleinschnitz, Christoph A1 - Glas, Martin A1 - Ernestus, Ralf-Ingo A1 - Brandner, Sebastian A1 - Monoranu, Camelia M. A1 - Löhr, Mario A1 - Hagemann, Carsten T1 - Effects of long-term temozolomide treatment on glioblastoma and astrocytoma WHO grade 4 stem-like cells JF - International Journal of Molecular Sciences N2 - Glioblastoma leads to a fatal course within two years in more than two thirds of patients. An essential cornerstone of therapy is chemotherapy with temozolomide (TMZ). The effect of TMZ is counteracted by the cellular repair enzyme O\(^6\)-methylguanine-DNA methyltransferase (MGMT). The MGMT promoter methylation, the main regulator of MGMT expression, can change from primary tumor to recurrence, and TMZ may play a significant role in this process. To identify the potential mechanisms involved, three primary stem-like cell lines (one astrocytoma with the mutation of the isocitrate dehydrogenase (IDH), CNS WHO grade 4 (HGA)), and two glioblastoma (IDH-wildtype, CNS WHO grade 4) were treated with TMZ. The MGMT promoter methylation, migration, proliferation, and TMZ-response of the tumor cells were examined at different time points. The strong effects of TMZ treatment on the MGMT methylated cells were observed. Furthermore, TMZ led to a loss of the MGMT promoter hypermethylation and induced migratory rather than proliferative behavior. Cells with the unmethylated MGMT promoter showed more aggressive behavior after treatment, while HGA cells reacted heterogenously. Our study provides further evidence to consider the potential adverse effects of TMZ chemotherapy and a rationale for investigating potential relationships between TMZ treatment and change in the MGMT promoter methylation during relapse. KW - glioblastoma KW - astrocytoma KW - IDH KW - MGMT KW - therapy KW - temozolomide KW - cancer stem cells Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284417 SN - 1422-0067 VL - 23 IS - 9 ER - TY - JOUR A1 - Kayvanpour, Elham A1 - Wisdom, Michael A1 - Lackner, Maximilian K. A1 - Sedaghat-Hamedani, Farbod A1 - Boeckel, Jes-Niels A1 - Müller, Marion A1 - Eghbalian, Rose A1 - Dudek, Jan A1 - Doroudgar, Shirin A1 - Maack, Christoph A1 - Frey, Norbert A1 - Meder, Benjamin T1 - VARS2 depletion leads to activation of the integrated stress response and disruptions in mitochondrial fatty acid oxidation JF - International Journal of Molecular Sciences N2 - Mutations in mitochondrial aminoacyl-tRNA synthetases (mtARSs) have been reported in patients with mitochondriopathies: most commonly encephalopathy, but also cardiomyopathy. Through a GWAS, we showed possible associations between mitochondrial valyl-tRNA synthetase (VARS2) dysregulations and non-ischemic cardiomyopathy. We aimed to investigate the possible consequences of VARS2 depletion in zebrafish and cultured HEK293A cells. Transient VARS2 loss-of-function was induced in zebrafish embryos using Morpholinos. The enzymatic activity of VARS2 was measured in VARS2-depleted cells via northern blot. Heterozygous VARS2 knockout was established in HEK293A cells using CRISPR/Cas9 technology. BN-PAGE and SDS-PAGE were used to investigate electron transport chain (ETC) complexes, and the oxygen consumption rate and extracellular acidification rate were measured using a Seahorse XFe96 Analyzer. The activation of the integrated stress response (ISR) and possible disruptions in mitochondrial fatty acid oxidation (FAO) were explored using RT-qPCR and western blot. Zebrafish embryos with transient VARS2 loss-of-function showed features of heart failure as well as indications of CNS and skeletal muscle involvements. The enzymatic activity of VARS2 was significantly reduced in VARS2-depleted cells. Heterozygous VARS2-knockout cells showed a rearrangement of ETC complexes in favor of complexes III\(_2\), III\(_2\) + IV, and supercomplexes without significant respiratory chain deficiencies. These cells also showed the enhanced activation of the ISR, as indicated by increased eIF-2α phosphorylation and a significant increase in the transcript levels of ATF4, ATF5, and DDIT3 (CHOP), as well as disruptions in FAO. The activation of the ISR and disruptions in mitochondrial FAO may underlie the adaptive changes in VARS2-depleted cells. KW - VARS2 KW - heart failure KW - integrated stress response KW - mitochondrial FAO Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284590 SN - 1422-0067 VL - 23 IS - 13 ER - TY - JOUR A1 - Ghafoor, Hina A1 - Nordbeck, Peter A1 - Ritter, Oliver A1 - Pauli, Paul A1 - Schulz, Stefan M. T1 - Can Religiosity and Social Support Explain Effects of Trait Emotional Intelligence on Health-Related Quality of Life: A Cross-Cultural Study JF - Journal of Religion and Health N2 - Religion and social support along with trait emotional intelligence (EI) help individuals to reduce stress caused by difficult situations. Their implications may vary across cultures in reference to predicting health-related quality of life (HRQoL). A convenience sample of N = 200 chronic heart failure (CHF) patients was recruited at cardiology centers in Germany (n = 100) and Pakistan (n = 100). Results indicated that trait-EI predicted better mental component of HRQoL in Pakistani and German CHF patients. Friends as social support appeared relevant for German patients only. Qualitative data indicate an internal locus of control in German as compared to Pakistani patients. Strengthening the beneficial role of social support in Pakistani patients is one example of how the current findings may inspire culture-specific treatment to empower patients dealing with the detrimental effects of CHF. KW - cross-cultural comparison KW - chronic heart failure KW - religion KW - social support KW - trait emotional intelligence KW - health-related quality of life Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232823 SN - 0022-4197 VL - 61 IS - 1 ER - TY - JOUR A1 - Magliocca, Giorgia A1 - Mone, Pasquale A1 - Di Iorio, Biagio Raffaele A1 - Heidland, August A1 - Marzocco, Stefania T1 - Short-chain fatty acids in Chronic Kidney Disease: focus on inflammation and oxidative stress regulation JF - International Journal of Molecular Sciences N2 - Chronic Kidney Disease (CKD) is a debilitating disease associated with several secondary complications that increase comorbidity and mortality. In patients with CKD, there is a significant qualitative and quantitative alteration in the gut microbiota, which, consequently, also leads to reduced production of beneficial bacterial metabolites, such as short-chain fatty acids. Evidence supports the beneficial effects of short-chain fatty acids in modulating inflammation and oxidative stress, which are implicated in CKD pathogenesis and progression. Therefore, this review will provide an overview of the current knowledge, based on pre-clinical and clinical evidence, on the effect of SCFAs on CKD-associated inflammation and oxidative stress. KW - chronic kidney disease KW - short-chain fatty acids KW - oxidative stress KW - inflammation KW - uremic toxins Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284587 SN - 1422-0067 VL - 23 IS - 10 ER - TY - JOUR A1 - Reis, Moritz A1 - Pfister, Roland T1 - Being Observed Does Not Boost Rule Retrieval JF - Advances in Cognitive Psychology N2 - Previous research, mainly focusing on the situational preconditions of rule violations, indicates that feelings of being watched by other agents promote rule compliance. However, the cognitive underpinnings of this effect and of rule violations in general have only attracted little scientific attention yet. In this study, we investigated whether cues of being observed not only reduce the likelihood of violating rules but also affect the underlying cognitive processes of such behavior when still putting a rule violation into action. Therefore, we applied a motion-tracking paradigm in which participants could violate a simple stimulus-response mapping rule while being faced with pictures of either open or closed eyes. In line with prior research, temporal and spatial measures of the participants' movements indicated that violating this rule induced substantial cognitive conflict. However, conflict during rulebreaking was not moderated by the eye stimuli. This outcome suggests that rule retrieval constitutes an automatic process which is not or is only barely influenced by situational parameters. Moreover, our results imply that the effect of perceived observation on rule conformity is driven by normative influences on decision-making instead of social facilitation of dominant action tendencies. KW - rule retrieval KW - motion tracking KW - cognitive conflict KW - observation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301089 VL - 18 IS - 3 SP - 173 EP - 178 ER - TY - JOUR A1 - Schulz, Alexander A1 - Würthner, Frank T1 - Folding-induced fluorescence enhancement in a series of merocyanine hetero-folda-trimers JF - Angewandte Chemie International Edition N2 - Many dyes suffer from fast non-radiative decay pathways, thereby showing only short-lived excited states and weak photoluminescence. Here we show a pronounced fluorescence enhancement for a weakly fluorescent merocyanine (MC) dye by being co-facially stacked to other dyes in hetero-folda-trimer architectures. By means of fluorescence spectroscopy (lifetime, quantum yield) the fluorescence enhancement was explained by the rigidification of the emitting chromophore in the defined foldamer architecture and the presence of a non-forbidden lowest exciton state in H-coupled hetero-aggregates. This folding-induced fluorescence enhancement (FIFE) for specific sequences of π-stacked dyes points at a viable strategy toward improved fluorophores that relates to the approach used by nature in the green fluorescent protein (GFP). KW - organic chemistry KW - merocyanines KW - aggregation KW - dyes/pigments KW - fluorescence KW - folding Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256582 VL - 61 IS - 2 ER - TY - JOUR A1 - Penov, Kiril A1 - Radakovic, Dejan A1 - Madrahimov, Nodir A1 - Aleksic, Ivan T1 - Subacute Aortic Rupture Due to Mechanical Chest Compression with Indwelling Impella JF - The Thoracic and Cardiovascular Surgeon Reports N2 - Mechanical cardiopulmonary resuscitation (CPR) devices like Lund University Cardiopulmonary Assist System (LUCAS) cause more skeletal and visceral injuries than standard CPR. A 62-year-old woman with ST-elevation myocardial infarction was resuscitated with LUCAS and Impella CP for refractory cardiogenic shock during percutaneous coronary intervention. She suffered delayed ascending aortic rupture necessitating supracommissural ascending aortic replacement plus triple bypass grafting. Prolonged mechanical CPR with concomitant Impella may lead to aortic rupture. The combined use of LUCAS and Impella may have disastrous consequences. KW - cardiac catheterization/ intervention KW - shock (systemic, cardiac or circulatory) KW - circulatory assist devices Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300174 SN - 2194-7635 VL - 11 IS - 1 SP - e64 EP - e66 ER - TY - JOUR A1 - Pollmann, Stephan A1 - Toussaint, André A1 - Flentje, Michael A1 - Wegener, Sonja A1 - Lewitzki, Victor T1 - Dosimetric evaluation of commercially available flat vs. self-produced 3D-conformal silicone boluses for the head and neck region JF - Frontiers in Oncology N2 - Background Boluses are routinely used in radiotherapy to modify surface doses. Nevertheless, considerable dose discrepancies may occur in some cases due to fit inaccuracy of commercially available standard flat boluses. Moreover, due to the simple geometric design of conventional boluses, also surrounding healthy skin areas may be unintentionally covered, resulting in the unwanted dose buildup. With the fused deposition modeling (FDM) technique, there is a simple and possibly cost-effective way to solve these problems in routine clinical practice. This paper presents a procedure of self-manufacturing bespoke patient-specific silicone boluses and the evaluation of buildup and fit accuracy in comparison to standard rectangular commercially available silicone boluses. Methods 3D-conformal silicone boluses were custom-built to cover the surgical scar region of 25 patients who received adjuvant radiotherapy of head and neck cancer at the University Hospital Würzburg. During a standard CT-based planning procedure, a 5-mm-thick 3D bolus contour was generated to cover the radiopaque marked surgical scar with an additional safety margin. From these digital contours, molds were 3D printed and poured with silicone. Dose measurements for both types of boluses were performed with radiochromic films (EBT3) at three points per patient—at least one aimed to be in the high-dose area (scar) and one in the lower-dose area (spared healthy skin). Surface–bolus distance, which ideally should not be present, was determined from cone-beam CT performed for positioning control. The dosimetric influence of surface–bolus distance was also determined on slab phantom for different field sizes. The trial was performed with hardware that may be routinely available in every radiotherapy department, with the exception of the 3D printer. The required number of patients was determined based on the results of preparatory measurements with the help of the statistical consultancy of the University of Würzburg. The number of measuring points represents the total number of patients. Results In the high-dose area of the scar, there was a significantly better intended dose buildup of 2.45% (95%CI 0.0014–0.0477, p = 0.038, N = 30) in favor of a 3D-conformal bolus. Median distances between the body surface and bolus differed significantly between 3D-conformal and commercially available boluses (3.5 vs. 7.9 mm, p = 0.001). The surface dose at the slab phantom did not differ between commercially available and 3D-conformal boluses. Increasing the surface–bolus distance from 5 to 10 mm decreased the surface dose by approximately 2% and 11% in the 6 × 6- and 3 × 3-cm2 fields, respectively. In comparison to the commercially available bolus, an unintended dose buildup in the healthy skin areas was reduced by 25.9% (95%CI 19.5–32.3, p < 0.01, N = 37) using the 3D-conformal bolus limited to the region surrounding the surgical scar. Conclusions Using 3D-conformal boluses allows a comparison to the commercially available boluses’ dose buildup in the covered areas. Smaller field size is prone to a larger surface–bolus distance effect. Higher conformity of 3D-conformal boluses reduces this effect. This may be especially relevant for volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) techniques with a huge number of smaller fields. High conformity of 3D-conformal boluses reduces an unintended dose buildup in healthy skin. The limiting factor in the conformity of 3D-conformal boluses in our setting was the immobilization mask, which was produced primarily for the 3D boluses. The mask itself limited tight contact of subsequently produced 3D-conformal boluses to the mask-covered body areas. In this respect, bolus adjustment before mask fabrication will be done in the future setting. KW - flat silicone bolus KW - individual silicone bolus KW - 3D conformal silicone bolus KW - 3D printer KW - head and neck cancer KW - fused deposition modeling (FDM) KW - surface dose measurement KW - volumetric modulated arc therapy (VMAT) Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-283156 SN - 2234-943X VL - 12 ER -