@article{NotzSchmalzingWedekinketal.2020, author = {Notz, Quirin and Schmalzing, Marc and Wedekink, Florian and Schlesinger, Tobias and Gernert, Michael and Herrmann, Johannes and Sorger, Lena and Weismann, Dirk and Schmid, Benedikt and Sitter, Magdalena and Schlegel, Nicolas and Kranke, Peter and Wischhusen, J{\"o}rg and Meybohm, Patrick and Lotz, Christopher}, title = {Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study}, series = {Frontiers in Immunology}, volume = {11}, journal = {Frontiers in Immunology}, issn = {1664-3224}, doi = {10.3389/fimmu.2020.581338}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212815}, year = {2020}, abstract = {Objectives The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS). Methods This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14th and May 28th 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed. Results All patients suffered from severe ARDS, 30.8\% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and na{\"i}ve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment. Conclusions Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience.}, language = {en} } @article{HottenrottSchlesingerHelmeretal.2020, author = {Hottenrott, Sebastian and Schlesinger, Tobias and Helmer, Philipp and Meybohm, Patrick and Alkatout, Ibrahim and Kranke, Peter}, title = {Do small incisions need only minimal anesthesia? — anesthetic management in laparoscopic and robotic surgery}, series = {Journal of Clinical Medicine}, volume = {9}, journal = {Journal of Clinical Medicine}, number = {12}, issn = {2077-0383}, doi = {10.3390/jcm9124058}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220039}, year = {2020}, abstract = {Laparoscopic techniques have established themselves as a major part of modern surgery. Their implementation in every surgical discipline has played a vital part in the reduction of perioperative morbidity and mortality. Precise robotic surgery, as an evolution of this, is shaping the present and future operating theatre that an anesthetist is facing. While incisions get smaller and the impact on the organism seems to dwindle, challenges for anesthetists do not lessen and could even become more demanding than in open procedures. This review focuses on the pathophysiological effects of contemporary laparoscopic and robotic procedures and summarizes anesthetic challenges and strategies for perioperative management.}, language = {en} } @article{NeefMeisenzahlKessleretal.2020, author = {Neef, Vanessa and Meisenzahl, David and Kessler, Paul and Raimann, Florian J. and Piekarski, Florian and Choorapoikayil, Suma and Fleege, Christoph and Zacharowski, Kai D. and Meybohm, Patrick and Meurer, Andrea}, title = {Implementation of an anaemia walk-in clinic: Feasibility and preliminary data from the Orthopedic University Hospital}, series = {Transfusion Medicine}, volume = {30}, journal = {Transfusion Medicine}, number = {6}, doi = {10.1111/tme.12740}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224594}, pages = {467 -- 474}, year = {2020}, abstract = {Background Approximately one in three patients suffers from preoperative anaemia. Even though haemoglobin is measured before surgery, anaemia management is not implemented in every hospital. Objective Here, we demonstrate the implementation of an anaemia walk-in clinic at an Orthopedic University Hospital. To improve the diagnosis of iron deficiency (ID), we examined whether reticulocyte haemoglobin (Ret-He) could be a useful additional parameter. Material and Methods In August 2019, an anaemia walk-in clinic was established. Between September and December 2019, major orthopaedic surgical patients were screened for preoperative anaemia. The primary endpoint was the incidence of preoperative anaemia. Secondary endpoints included Ret-He level, red blood cell (RBC) transfusion rate, in-hospital length of stay and anaemia at hospital discharge. Results A total of 104 patients were screened for anaemia. Preoperative anaemia rate was 20.6\%. Intravenous iron was supplemented in 23 patients. Transfusion of RBC units per patient (1.7 ± 1.2 vs. 0.2 ± 0.9; p = 0.004) and hospital length of stay (13.1 ± 4.8 days vs. 10.6 ± 5.1 days; p = 0.068) was increased in anaemic patients compared to non-anaemic patients. Ret-He values were significantly lower in patients with ID anaemia (33.3 pg [28.6-40.2 pg]) compared to patients with ID (35.3 pg [28.9-38.6 pg]; p = 0.015) or patients without anaemia (35.4 pg [30.2-39.4 pg]; p = 0.001). Conclusion Preoperative anaemia is common in orthopaedic patients. Our results proved the feasibility of an anaemia walk-in clinic to manage preoperative anaemia. Furthermore, our analysis supports the use of Ret-He as an additional parameter for the diagnosis of ID in surgical patients.}, language = {en} } @article{PaulKollmannsberger2020, author = {Paul, Torsten Johann and Kollmannsberger, Philip}, title = {Biological network growth in complex environments: A computational framework}, series = {PLoS Computational Biology}, volume = {16}, journal = {PLoS Computational Biology}, number = {11}, doi = {10.1371/journal.pcbi.1008003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231373}, year = {2020}, abstract = {Spatial biological networks are abundant on all scales of life, from single cells to ecosystems, and perform various important functions including signal transmission and nutrient transport. These biological functions depend on the architecture of the network, which emerges as the result of a dynamic, feedback-driven developmental process. While cell behavior during growth can be genetically encoded, the resulting network structure depends on spatial constraints and tissue architecture. Since network growth is often difficult to observe experimentally, computer simulations can help to understand how local cell behavior determines the resulting network architecture. We present here a computational framework based on directional statistics to model network formation in space and time under arbitrary spatial constraints. Growth is described as a biased correlated random walk where direction and branching depend on the local environmental conditions and constraints, which are presented as 3D multilayer grid. To demonstrate the application of our tool, we perform growth simulations of a dense network between cells and compare the results to experimental data from osteocyte networks in bone. Our generic framework might help to better understand how network patterns depend on spatial constraints, or to identify the biological cause of deviations from healthy network function. Author summary We present a novel modeling approach and computational implementation to better understand the development of spatial biological networks under the influence of external signals. Our tool allows us to study the relationship between local biological growth parameters and the emerging macroscopic network function using simulations. This computational approach can generate plausible network graphs that take local feedback into account and provide a basis for comparative studies using graph-based methods.}, language = {en} } @article{RestPhilipsDuennebackeetal.2020, author = {Rest, Christina and Philips, Divya Susan and D{\"u}nnebacke, Torsten and Sutar, Papri and Sampedro, Angel and Droste, J{\"o}rn and Stepanenko, Vladimir and Hansen, Michael Ryan and Albuquerque, Rodrigo Q. and Fern{\´a}ndez, Gustavo}, title = {Tuning Aqueous Supramolecular Polymerization by an Acid-Responsive Conformational Switch}, series = {Chemistry - A European Journal}, volume = {26}, journal = {Chemistry - A European Journal}, number = {44}, doi = {10.1002/chem.202001566}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218118}, pages = {10005 -- 10013}, year = {2020}, abstract = {Besides their widespread use in coordination chemistry, 2,2'-bipyridines are known for their ability to undergo cis-trans conformational changes in response to metal ions and acids, which has been primarily investigated at the molecular level. However, the exploitation of such conformational switching in self-assembly has remained unexplored. In this work, the use of 2,2'-bipyridines as acid-responsive conformational switches to tune supramolecular polymerization processes has been demonstrated. To achieve this goal, we have designed a bipyridine-based linear bolaamphiphile, 1, that forms ordered supramolecular polymers in aqueous media through cooperative aromatic and hydrophobic interactions. Interestingly, addition of acid (TFA) induces the monoprotonation of the 2,2'-bipyridine moiety, leading to a switch in the molecular conformation from a linear (trans) to a V-shaped (cis) state. This increase in molecular distortion along with electrostatic repulsions of the positively charged bipyridine-H\(^{+}\) units attenuate the aggregation tendency and induce a transformation from long fibers to shorter thinner fibers. Our findings may contribute to opening up new directions in molecular switches and stimuli-responsive supramolecular materials.}, language = {en} } @article{EvdokimovDinkelFranketal.2020, author = {Evdokimov, Dimitar and Dinkel, Philine and Frank, Johanna and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan}, title = {Characterization of dermal skin innervation in fibromyalgia syndrome}, series = {PLoS One}, volume = {15}, journal = {PLoS One}, number = {1}, doi = {10.1371/journal.pone.0227674}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229299}, year = {2020}, abstract = {Introduction We characterized dermal innervation in patients with fibromyalgia syndrome (FMS) as potential contribution to small fiber pathology. Methods Skin biopsies of the calf were collected (86 FMS patients, 35 healthy controls). Skin was immunoreacted with antibodies against protein gene product 9.5, calcitonine gene-related peptide, substance P, CD31, and neurofilament 200 for small fiber subtypes. We assessed two skin sections per patient; on each skin section, two dermal areas (150 x 700 mu m each) were investigated for dermal nerve fiber length (DNFL). Results In FMS patients we found reduced DNFL of fibers with vessel contact compared to healthy controls (p<0.05). There were no differences for the other nerve fiber subtypes. Discussion We found less dermal nerve fibers in contact with blood vessels in FMS patients than in controls. The pathophysiological relevance of this finding is unclear, but we suggest the possibility of a relationship with impaired thermal tolerance commonly reported by FMS patients.}, language = {en} } @article{WeissSchlegelTerpitzetal.2020, author = {Weiss, Esther and Schlegel, Jan and Terpitz, Ulrich and Weber, Michael and Linde, J{\"o}rg and Schmitt, Anna-Lena and H{\"u}nniger, Kerstin and Marischen, Lothar and Gamon, Florian and Bauer, Joachim and L{\"o}ffler, Claudia and Kurzai, Oliver and Morton, Charles Oliver and Sauer, Markus and Einsele, Hermann and Loeffler, Juergen}, title = {Reconstituting NK Cells After Allogeneic Stem Cell Transplantation Show Impaired Response to the Fungal Pathogen Aspergillus fumigatus}, series = {Frontiers in Immunology}, volume = {11}, journal = {Frontiers in Immunology}, issn = {1664-3224}, doi = {10.3389/fimmu.2020.02117}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212581}, year = {2020}, abstract = {Delayed natural killer (NK) cell reconstitution after allogeneic stem cell transplantation (alloSCT) is associated with a higher risk of developing invasive aspergillosis. The interaction of NK cells with the human pathogen Aspergillus (A.) fumigatus is mediated by the fungal recognition receptor CD56, which is relocated to the fungal interface after contact. Blocking of CD56 signaling inhibits the fungal mediated chemokine secretion of MIP-1α, MIP-1β, and RANTES and reduces cell activation, indicating a functional role of CD56 in fungal recognition. We collected peripheral blood from recipients of an allograft at defined time points after alloSCT (day 60, 90, 120, 180). NK cells were isolated, directly challenged with live A. fumigatus germ tubes, and cell function was analyzed and compared to healthy age and gender-matched individuals. After alloSCT, NK cells displayed a higher percentage of CD56\(^{bright}\)CD16\(^{dim}\) cells throughout the time of blood collection. However, CD56 binding and relocalization to the fungal contact side were decreased. We were able to correlate this deficiency to the administration of corticosteroid therapy that further negatively influenced the secretion of MIP-1α, MIP-1β, and RANTES. As a consequence, the treatment of healthy NK cells ex vivo with corticosteroids abrogated chemokine secretion measured by multiplex immunoassay. Furthermore, we analyzed NK cells regarding their actin cytoskeleton by Structured Illumination Microscopy (SIM) and flow cytometry and demonstrate an actin dysfunction of NK cells shown by reduced F-actin content after fungal co-cultivation early after alloSCT. This dysfunction remains until 180 days post-alloSCT, concluding that further actin-dependent cellular processes may be negatively influenced after alloSCT. To investigate the molecular pathomechansism, we compared CD56 receptor mobility on the plasma membrane of healthy and alloSCT primary NK cells by single-molecule tracking. The results were very robust and reproducible between tested conditions which point to a different molecular mechanism and emphasize the importance of proper CD56 mobility.}, language = {en} } @article{LambovHensiekPoeppleretal.2020, author = {Lambov, Martin and Hensiek, Nicola and P{\"o}ppler, Ann-Christin and Lehmann, Matthias}, title = {Columnar Liquid Crystals from Star-Shaped Conjugated Mesogens as Nano-Reservoirs for Small Acceptors}, series = {ChemPlusChem}, volume = {85}, journal = {ChemPlusChem}, number = {10}, doi = {10.1002/cplu.202000341}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218014}, pages = {2219 -- 2229}, year = {2020}, abstract = {Shape-persistent conjugated mesogens with oligothiophene arms of different lengths have been synthesized. Such mesogens possess free intrinsic space between their conjugated arms. They form columnar liquid-crystalline phases, in which the void is filled by dense helical packing in the neat phase similar to an oligo(phenylene vinylene) derivative of equal size. The void can also be compensated by the inclusion of the small acceptor molecule 2,4,7-trinitrofluorenone. In solution, the acceptor interacts with the core as the largest π-surface, while in the solid material, it is incorporated between the arms and sandwiched by the star-shaped neighbours along the columnar assemblies. The TNF acceptors are not nanosegregated from the star-shaped donors, thus the liquid crystal structure converts to a nano-reservoir for TNF (endo-receptor). These host-guest arrangements are confirmed by comprehensive X-ray scattering experiments and solid-state NMR spectroscopy. This results in ordered columnar hexagonal phases at high temperatures, which change to helical columnar mesophases or to columnar soft crystals at room temperature.}, language = {en} } @article{LehmannOehlerZuberetal.2020, author = {Lehmann, Martin and Oehler, Beatrice and Zuber, Jonas and Malzahn, Uwe and Walles, Thorsten and Muellenbach, Ralf M. and Roewer, Norbert and Kredel, Markus}, title = {Redistribution of pulmonary ventilation after lung surgery detected with electrical impedance tomography}, series = {Acta Anaesthesiologica Scandinavica}, volume = {64}, journal = {Acta Anaesthesiologica Scandinavica}, number = {4}, doi = {10.1111/aas.13525}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213575}, pages = {517-525}, year = {2020}, abstract = {Background: Regional ventilation of the lung can be visualized by pulmonary electrical impedance tomography (EIT). The aim of this study was to examine the post-operative redistribution of regional ventilation after lung surgery dependent on the side of surgery and its association with forced vital capacity. Methods: In this prospective, observational cohort study 13 patients undergoing right and 13 patients undergoing left-sided open or video-thoracoscopic procedures have been investigated. Pre-operative measurements with EIT and spirometry were compared with data obtained 3 days post-operation. The center of ventilation (COV) within a 32 × 32 pixel matrix was calculated from EIT data. The transverse axis coordinate of COV, COVx (left/right), was modified to COVx′ (ipsilateral/contralateral). Thus, COVx′ shows a negative change if ventilation shifts contralateral independent of the side of surgery. This enabled testing with two-way ANOVA for repeated measurements (side, time). Results: The perioperative shift of COVx′ was dependent on the side of surgery (P = .007). Ventilation shifted away from the side of surgery after the right-sided surgery (COVx′-1.97 pixel matrix points, P < .001), but not after the left-sided surgery (COVx′-0.61, P = .425). The forced vital capacity (\%predicted) decreased from 94 (83-109)\% (median [quartiles]; [left-sided]) and 89 (80-97)\% (right-sided surgery) to 61 (59-66)\% and 62 (40-72)\% (P < .05), respectively. The perioperative changes in forced vital capacity (\%predicted) were weakly associated with the shift of COVx′. Conclusion: Only after right-sided lung surgery, EIT showed reduced ventilation on the side of surgery while vital capacity was markedly reduced in both groups.}, language = {en} } @article{FuhrmannTeschRomanosetal.2020, author = {Fuhrmann, Saskia and Tesch, Falko and Romanos, Marcel and Abraham, Susanne and Schmitt, Jochen}, title = {ADHD in school-age children is related to infant exposure to systemic H1-antihistamines}, series = {Allergy}, volume = {75}, journal = {Allergy}, number = {11}, doi = {10.1111/all.14411}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215982}, pages = {2956 -- 2957}, year = {2020}, language = {en} } @article{MichauxHansenJennichesetal.2020, author = {Michaux, Charlotte and Hansen, Elisabeth E. and Jenniches, Laura and Gerovac, Milan and Barquist, Lars and Vogel, J{\"o}rg}, title = {Single-Nucleotide RNA Maps for the Two Major Nosocomial Pathogens Enterococcus faecalis and Enterococcus faecium}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {10}, journal = {Frontiers in Cellular and Infection Microbiology}, issn = {2235-2988}, doi = {10.3389/fcimb.2020.600325}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217947}, year = {2020}, abstract = {Enterococcus faecalis and faecium are two major representative clinical strains of the Enterococcus genus and are sadly notorious to be part of the top agents responsible for nosocomial infections. Despite their critical implication in worldwide public healthcare, essential and available resources such as deep transcriptome annotations remain poor, which also limits our understanding of post-transcriptional control small regulatory RNA (sRNA) functions in these bacteria. Here, using the dRNA-seq technique in combination with ANNOgesic analysis, we successfully mapped and annotated transcription start sites (TSS) of both E. faecalis V583 and E. faecium AUS0004 at single nucleotide resolution. Analyzing bacteria in late exponential phase, we capture ~40\% (E. faecalis) and 43\% (E. faecium) of the annotated protein-coding genes, determine 5′ and 3′ UTR (untranslated region) length, and detect instances of leaderless mRNAs. The transcriptome maps revealed sRNA candidates in both bacteria, some found in previous studies and new ones. Expression of candidate sRNAs is being confirmed under biologically relevant environmental conditions. This comprehensive global TSS mapping atlas provides a valuable resource for RNA biology and gene expression analysis in the Enterococci. It can be accessed online at www.helmholtz-hiri.de/en/datasets/enterococcus through an instance of the genomic viewer JBrowse.}, language = {en} } @article{SiegerHovestadt2020, author = {Sieger, Charlotte Sophie and Hovestadt, Thomas}, title = {The degree of spatial variation relative to temporal variation influences evolution of dispersal}, series = {Oikos}, volume = {129}, journal = {Oikos}, number = {11}, doi = {10.1111/oik.07567}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239049}, pages = {1611 -- 1622}, year = {2020}, abstract = {In the face of ongoing global climate and land use change, organisms have multiple possibilities to cope with the modification of their environment. The two main possibilities are to either adapt locally or disperse to a more suitable habitat. The evolution of both local adaptation and dispersal interacts and can be influenced by the spatial and temporal variation (of e.g. temperature or precipitation). In an individual based model (IBM), we explore evolution of phenotypes in landscapes with varying degree of spatial relative to global temporal variation in order to examine its influence on the evolution of dispersal, niche optimum and niche width. The relationship between temporal and spatial variation did neither influence the evolution of local adaptation in the niche optimum nor of niche widths. Dispersal probability is highly influenced by the spatio-temporal relationship: with increasing spatial variation, dispersal probability decreases. Additionally, the shape of the distribution of the trait values over patch attributes switches from hump- to U-shaped. At low spatial variance more individuals emigrate from average habitats, at high spatial variance more from extreme habitats. The comparatively high dispersal probability in extreme patches of landscapes with a high spatial variation can be explained by evolutionary succession of two kinds of adaptive response. Early in the simulations, extreme patches in landscapes with a high spatial variability act as sink habitats, where population persistence depends on highly dispersive individuals with a wide niche. With ongoing evolution, local adaptation of the remaining individuals takes over, but simultaneously a possible bet-hedging strategy promotes higher dispersal probabilities in those habitats. Here, in generations that experience extreme shifts from the temporal mean of the patch attribute, the expected fitness becomes higher for dispersing individuals than for philopatric individuals. This means that under certain circumstances, both local adaptation and high dispersal probability can be selected for for coping with the projected environmental changes in the future.}, language = {en} } @article{Kretzschmar2020, author = {Kretzschmar, Kai}, title = {Cancer research using organoid technology}, series = {Journal of Molecular Medicine}, volume = {99}, journal = {Journal of Molecular Medicine}, issn = {0946-2716}, doi = {10.1007/s00109-020-01990-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235377}, pages = {501-515}, year = {2020}, abstract = {Organoid technology has rapidly transformed basic biomedical research and contributed to significant discoveries in the last decade. With the application of protocols to generate organoids from cancer tissue, organoid technology has opened up new opportunities for cancer research and therapy. Using organoid cultures derived from healthy tissues, different aspects of tumour initiation and progression are widely studied including the role of pathogens or specific cancer genes. Cancer organoid cultures, on the other hand, are applied to generate biobanks, perform drug screens, and study mutational signatures. With the incorporation of cellular components of the tumour microenvironment such as immune cells into the organoid cultures, the technology is now also exploited in the rapidly advancing field of immuno-oncology. In this review, I discuss how organoid technology is currently being utilised in cancer research and what obstacles are still to be overcome for its broader use in anti-cancer therapy.}, language = {en} } @article{IUedaWoersdoerferetal.2020, author = {I, Takashi and Ueda, Yuichiro and W{\"o}rsd{\"o}rfer, Philipp and Sumita, Yoshinori and Asahina, Izumi and Erg{\"u}n, S{\"u}leyman}, title = {Resident CD34-positive cells contribute to peri-endothelial cells and vascular morphogenesis in salivary gland after irradiation}, series = {Journal of Neural Transmission}, volume = {127}, journal = {Journal of Neural Transmission}, issn = {0300-9564}, doi = {10.1007/s00702-020-02256-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235613}, pages = {1467-1479}, year = {2020}, abstract = {Salivary gland (SG) hypofunction is a common post-radiotherapy complication. Besides the parenchymal damage after irradiation (IR), there are also effects on mesenchymal stem cells (MSCs) which were shown to contribute to regeneration and repair of damaged tissues by differentiating into stromal cell types or releasing vesicles and soluble factors supporting the healing processes. However, there are no adequate reports about their roles during SG damage and regeneration so far. Using an irradiated SG mouse model, we performed certain immunostainings on tissue sections of submandibular glands at different time points after IR. Immunostaining for CD31 revealed that already one day after IR, vascular impairment was induced at the level of capillaries. In addition, the expression of CD44—a marker of acinar cells—diminished gradually after IR and, by 20 weeks, almost disappeared. In contrast, the number of CD34-positive cells significantly increased 4 weeks after IR and some of the CD34-positive cells were found to reside within the adventitia of arteries and veins. Laser confocal microscopic analyses revealed an accumulation of CD34-positive cells within the area of damaged capillaries where they were in close contact to the CD31-positive endothelial cells. At 4 weeks after IR, a fraction of the CD34-positive cells underwent differentiation into α-SMA-positive cells, which suggests that they may contribute to regeneration of smooth muscle cells and/or pericytes covering the small vessels from the outside. In conclusion, SG-resident CD34-positive cells represent a population of progenitors that could contribute to new vessel formation and/or remodeling of the pre-existing vessels after IR and thus, might be an important player during SG tissue healing.}, language = {en} } @article{PempGeppertWigmannetal.2020, author = {Pemp, Daniela and Geppert, Leo N. and Wigmann, Claudia and Kleider, Carolin and Hauptstein, Ren{\´e} and Schmalbach, Katja and Ickstadt, Katja and Esch, Harald L. and Lehrmann, Leane}, title = {Influence of breast cancer risk factors and intramammary biotransformation on estrogen homeostasis in the human breast}, series = {Archives of Toxicology}, volume = {94}, journal = {Archives of Toxicology}, issn = {0340-5761}, doi = {10.1007/s00204-020-02807-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235335}, pages = {3013-3025}, year = {2020}, abstract = {Understanding intramammary estrogen homeostasis constitutes the basis of understanding the role of lifestyle factors in breast cancer etiology. Thus, the aim of the present study was to identify variables influencing levels of the estrogens present in normal breast glandular and adipose tissues (GLT and ADT, i.e., 17β-estradiol, estrone, estrone-3-sulfate, and 2-methoxy-estrone) by multiple linear regression models. Explanatory variables (exVARs) considered were (a) levels of metabolic precursors as well as levels of transcripts encoding proteins involved in estrogen (biotrans)formation, (b) data on breast cancer risk factors (i.e., body mass index, BMI, intake of estrogen-active drugs, and smoking) collected by questionnaire, and (c) tissue characteristics (i.e., mass percentage of oil, oil\%, and lobule type of the GLT). Levels of estrogens in GLT and ADT were influenced by both extramammary production (menopausal status, intake of estrogen-active drugs, and BMI) thus showing that variables known to affect levels of circulating estrogens influence estrogen levels in breast tissues as well for the first time. Moreover, intratissue (biotrans)formation (by aromatase, hydroxysteroid-17beta-dehydrogenase 2, and beta-glucuronidase) influenced intratissue estrogen levels, as well. Distinct differences were observed between the exVARs exhibiting significant influence on (a) levels of specific estrogens and (b) the same dependent variables in GLT and ADT. Since oil\% and lobule type of GLT influenced levels of some estrogens, these variables may be included in tissue characterization to prevent sample bias. In conclusion, evidence for the intracrine activity of the human breast supports biotransformation-based strategies for breast cancer prevention. The susceptibility of estrogen homeostasis to systemic and tissue-specific modulation renders both beneficial and adverse effects of further variables associated with lifestyle and the environment possible.}, language = {en} } @article{WoersdoerferIAsahinaetal.2020, author = {W{\"o}rsd{\"o}rfer, Philipp and I, Takashi and Asahina, Izumi and Sumita, Yoshinori and Erg{\"u}n, S{\"u}leyman}, title = {Do not keep it simple: recent advances in the generation of complex organoids}, series = {Journal of Neural Transmission}, volume = {127}, journal = {Journal of Neural Transmission}, issn = {0300-9564}, doi = {10.1007/s00702-020-02198-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235628}, pages = {1569-1577}, year = {2020}, abstract = {3D cell culture models which closely resemble real human tissues are of high interest for disease modelling, drug screening as well as a deeper understanding of human developmental biology. Such structures are termed organoids. Within the last years, several human organoid models were described. These are usually stem cell derived, arise by self-organization, mimic mechanisms of normal tissue development, show typical organ morphogenesis and recapitulate at least some organ specific functions. Many tissues have been reproduced in vitro such as gut, liver, lung, kidney and brain. The resulting entities can be either derived from an adult stem cell population, or generated from pluripotent stem cells using a specific differentiation protocol. However, many organoid models only recapitulate the organs parenchyma but are devoid of stromal components such as blood vessels, connective tissue and inflammatory cells. Recent studies show that the incorporation of endothelial and mesenchymal cells into organoids improved their maturation and might be required to create fully functional micro-tissues, which will allow deeper insights into human embryogenesis as well as disease development and progression. In this review article, we will summarize and discuss recent works trying to incorporate stromal components into organoids, with a special focus on neural organoid models.}, language = {en} } @article{BoffHenriqueFriedeletal.2020, author = {Boff, Samuel and Henrique, Jessica Amaral and Friedel, Anna and Raizer, Josu{\´e}}, title = {Disentangling the path of pollinator attraction in temporarily colored flowers}, series = {International Journal of Tropical Insect Science}, volume = {41}, journal = {International Journal of Tropical Insect Science}, doi = {10.1007/s42690-020-00323-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235402}, pages = {1305-1311}, year = {2020}, abstract = {Plants may use different strategies to attract pollinators in long distance (e.g. floral display) and in short distance (e.g. ratio between differentially colored flowers) scales. The Verbenaceae Lantana canescens Kunth is a wide spread species in open sites of the Brazilian Pantanal wetland. Individuals of this generalist species can produce a variable number of open inflorescences with yellow and white flowers that are organized in whorls. In this study we tested the hypothesis that increased floral display (long distance attraction) and the ratio between yellow and white flowers (short distance attraction) enhances the number of pollinator species and individuals. We observed flower visitors and calculated floral parameters in 38 plots of 1 m2 each, that contained a varying number of flowering L. canescens individuals. Non-metric multidimensional scaling and Bray-Curtis distances were used to account for flower visitor composition and the relative visitation rate, respectively. We used a structural equation model to test the power of each predictor variable on the visitation rate and a covariance analysis to disentangle the effect of each independent variable on the frequency of plant-pollinator interactions. We found that the number of flower visitors and the visitation rate increased with increasing number of inflorescences. Disentangling long and short distance attraction indicated that the number of inflorescences (per plot) and the number of yellow flowers (yellowing effect) contributed most to flower visitation at long and short distance, respectively.}, language = {en} } @article{DeckertOzawa2020, author = {Deckert, J{\"u}rgen and Ozawa, Hiroki}, title = {The joint Nagasaki-W{\"u}rzburg approach to challenges and perspectives in neuropsychiatric and regenerative research}, series = {Journal of Neural Transmission}, volume = {127}, journal = {Journal of Neural Transmission}, issn = {0300-9564}, doi = {10.1007/s00702-020-02263-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235359}, pages = {1447-1448}, year = {2020}, abstract = {No abstract available.}, language = {en} } @book{Reuter2020, author = {Reuter, Oliver M.}, title = {Erfahrungsverankerte Rezeption : Eine Methode zur Verzahnung von Produktion und Rezeption}, edition = {1. Auflage}, publisher = {kopaed}, isbn = {978-3-86736-580-2}, doi = {10.25972/OPUS-34528}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-346008}, publisher = {Universit{\"a}t W{\"u}rzburg}, pages = {210}, year = {2020}, abstract = {Eine Rezeption auf den von Kindern und Jugendlichen selbst gemachten Erfahrungen aufzubauen, ist das zentrale Anliegen der ausgef{\"u}hrten Methode zur Verschr{\"a}nkung von produktiven und rezeptiven Anteilen im Kunstunterricht. Indem vor der Rezeption eine bildnerische Praxis stattfindet, k{\"o}nnen Ideen und Vorstellungen selbst{\"a}ndig und individuell entwickelt und in Bilder {\"u}bersetzt werden. Bei der erfahrungsverankerten Vermittlung basiert die Rezeption auf einer Schnittmenge zwischen eigenen Handlungen im bildnerischen oder darstellenden Prozess und zentralen Aspekten des Werks. Solche Referenzpunkte zwischen der Produktion und der Rezeption k{\"o}nnen im Material, im Thema, in der Gattung, im bildnerischen Verfahren oder in einer k{\"u}nstlerischen Strategie ausfindig gemacht werden. Sie dienen dazu, Einsichten, Einstellungen, Kenntnisse und Wissen aus der Produktion in die Rezeption mitzunehmen. Somit ist die Methode der erfahrungsverankerten Rezeption gleichermaßen geeignet f{\"u}r die Vermittlung historischer wie f{\"u}r zeitgen{\"o}ssischer Kunst. Nach der Darlegung und Konturierung der Konzeption zeigt die Publikation Wege auf, die erfahrungsverankerte Rezeption in Unterricht zu {\"u}berf{\"u}hren. Exemplarische Unterrichtsskizzen illustrieren die Umsetzung im Kunstunterricht.}, subject = {Erfahrung}, language = {de} } @article{Geiger2020, author = {Geiger, Dietmar}, title = {Plant glucose transporter structure and function}, series = {Pfl{\"u}gers Archiv - European Journal of Physiology}, volume = {472}, journal = {Pfl{\"u}gers Archiv - European Journal of Physiology}, number = {9}, doi = {10.1007/s00424-020-02449-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280643}, pages = {1111-1128}, year = {2020}, abstract = {The carbohydrate D-glucose is the main source of energy in living organisms. In contrast to animals, as well as most fungi, bacteria, and archaea, plants are capable to synthesize a surplus of sugars characterizing them as autothrophic organisms. Thus, plants are de facto the source of all food on earth, either directly or indirectly via feed to livestock. Glucose is stored as polymeric glucan, in animals as glycogen and in plants as starch. Despite serving a general source for metabolic energy and energy storage, glucose is the main building block for cellulose synthesis and represents the metabolic starting point of carboxylate- and amino acid synthesis. Finally yet importantly, glucose functions as signalling molecule conveying the plant metabolic status for adjustment of growth, development, and survival. Therefore, cell-to-cell and long-distance transport of photoassimilates/sugars throughout the plant body require the fine-tuned activity of sugar transporters facilitating the transport across membranes. The functional plant counterparts of the animal sodium/glucose transporters (SGLTs) are represented by the proton-coupled sugar transport proteins (STPs) of the plant monosaccharide transporter(-like) family (MST). In the framework of this special issue on "Glucose Transporters in Health and Disease," this review gives an overview of the function and structure of plant STPs in comparison to the respective knowledge obtained with the animal Na+-coupled glucose transporters (SGLTs).}, language = {en} } @article{RiedererterMeulen2020, author = {Riederer, Peter and ter Meulen, Volker}, title = {Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses}, series = {Journal of Neural Transmission}, volume = {127}, journal = {Journal of Neural Transmission}, number = {9}, issn = {0300-9564}, doi = {10.1007/s00702-020-02230-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-314637}, pages = {1217-1228}, year = {2020}, abstract = {While there is abounding literature on virus-induced pathology in general and coronavirus in particular, recent evidence accumulates showing distinct and deleterious brain affection. As the respiratory tract connects to the brain without protection of the blood-brain barrier, SARS-CoV-2 might in the early invasive phase attack the cardiorespiratory centres located in the medulla/pons areas, giving rise to disturbances of respiration and cardiac problems. Furthermore, brainstem regions are at risk to lose their functional integrity. Therefore, long-term neurological as well as psychiatric symptomatology and eventual respective disorders cannot be excluded as evidenced from influenza-A triggered post-encephalitic Parkinsonism and HIV-1 triggered AIDS-dementia complex. From the available evidences for coronavirus-induced brain pathology, this review concludes a number of unmet needs for further research strategies like human postmortem brain analyses. SARS-CoV-2 mirroring experimental animal brain studies, characterization of time-dependent and region-dependent spreading behaviours of coronaviruses, enlightening of pathological mechanisms after coronavirus infection using long-term animal models and clinical observations of patients having had COVID-19 infection are calling to develop both protective strategies and drug discoveries to avoid early and late coronavirus-induced functional brain disturbances, symptoms and eventually disorders. To fight SARS-CoV-2, it is an urgent need to enforce clinical, molecular biological, neurochemical and genetic research including brain-related studies on a worldwide harmonized basis.}, language = {en} } @article{DashkovskiyKapustyanSchmid2020, author = {Dashkovskiy, Sergey and Kapustyan, Oleksiy and Schmid, Jochen}, title = {A local input-to-state stability result w.r.t. attractors of nonlinear reaction-diffusion equations}, series = {Mathematics of Control, Signals, and Systems}, volume = {32}, journal = {Mathematics of Control, Signals, and Systems}, number = {3}, doi = {10.1007/s00498-020-00256-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281099}, pages = {309-326}, year = {2020}, abstract = {We establish the local input-to-state stability of a large class of disturbed nonlinear reaction-diffusion equations w.r.t. the global attractor of the respective undisturbed system.}, language = {en} } @article{ElhfnawyElsalamawyAbdelraoufetal.2020, author = {Elhfnawy, Ahmed Mohamed and Elsalamawy, Doaa and Abdelraouf, Mervat and Schliesser, Mira and Volkmann, Jens and Fluri, Felix}, title = {Red flags for a concomitant giant cell arteritis in patients with vertebrobasilar stroke: a cross-sectional study and systematic review}, series = {Acta Neurologica Belgica}, volume = {120}, journal = {Acta Neurologica Belgica}, number = {6}, issn = {0300-9009}, doi = {10.1007/s13760-020-01344-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-315610}, pages = {1389-1398}, year = {2020}, abstract = {Giant cell arteritis (GCA) may affect the brain-supplying arteries, resulting in ischemic stroke, whereby the vertebrobasilar territory is most often involved. Since etiology is unknown in 25\% of stroke patients and GCA is hardly considered as a cause, we examined in a pilot study, whether screening for GCA after vertebrobasilar stroke might unmask an otherwise missed disease. Consecutive patients with vertebrobasilar stroke were prospectively screened for GCA using erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin, and halo sign of the temporal and vertebral artery on ultrasound. Furthermore, we conducted a systematic literature review for relevant studies. Sixty-five patients were included, and two patients (3.1\%) were diagnosed with GCA. Patients with GCA were older in age (median 85 versus 69 years, p = 0.02). ESR and CRP were significantly increased and hemoglobin was significantly lower in GCA patients compared to non-GCA patients (median, 75 versus 11 mm in 1 h, p = 0.001; 3.84 versus 0.25 mg/dl, p = 0.01, 10.4 versus 14.6 mg/dl, p = 0.003, respectively). Multiple stenoses/occlusions in the vertebrobasilar territory affected our two GCA patients (100\%), but only five (7.9\%) non-GCA patients (p = 0.01). Our literature review identified 13 articles with 136 stroke patients with concomitant GCA. Those were old in age. Headache, increased inflammatory markers, and anemia were frequently reported. Multiple stenoses/occlusions in the vertebrobasilar territory affected around 70\% of stroke patients with GCA. Increased inflammatory markers, older age, anemia, and multiple stenoses/occlusions in the vertebrobasilar territory may be regarded as red flags for GCA among patients with vertebrobasilar stroke.}, language = {en} } @article{HaufNiedingSeger2020, author = {Hauf, Juliane E. K. and Nieding, Gerhild and Seger, Benedikt T.}, title = {The development of dynamic perceptual simulations during sentence comprehension}, series = {Cognitive Processing}, volume = {21}, journal = {Cognitive Processing}, number = {2}, doi = {10.1007/s10339-020-00959-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283665}, pages = {197-208}, year = {2020}, abstract = {Based on an embodied account of language comprehension, this study investigated the dynamic characteristics of children and adults' perceptual simulations during sentence comprehension, using a novel paradigm to assess the perceptual simulation of objects moving up and down a vertical axis. The participants comprised adults (N = 40) and 6-, 8-, and 10-year-old children (N = 116). After listening in experimental trials to sentences implying that objects moved upward or downward, the participants were shown pictures and had to decide as quickly as possible whether the objects depicted had been mentioned in the sentences. The target pictures moved either up or down and then stopped in the middle of the screen. All age groups' reaction times were found to be shorter when the objects moved in the directions that the sentences implied. Age exerted no developmental effect on reaction times. The findings suggest that dynamic perceptual simulations are fundamental to language comprehension in text recipients aged 6 and older.}, language = {en} } @article{KosmalaGruschwitzVeldhoenetal.2020, author = {Kosmala, Aleksander and Gruschwitz, Philipp and Veldhoen, Simon and Weng, Andreas Max and Krauss, Bernhard and Bley, Thorsten Alexander and Petritsch, Bernhard}, title = {Dual-energy CT angiography in suspected pulmonary embolism: influence of injection protocols on image quality and perfused blood volume}, series = {The International Journal of Cardiovascular Imaging}, volume = {36}, journal = {The International Journal of Cardiovascular Imaging}, number = {10}, issn = {1569-5794}, doi = {10.1007/s10554-020-01911-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-314739}, pages = {2051-2059}, year = {2020}, abstract = {Abstract To compare intravenous contrast material (CM) injection protocols for dual-energy CT pulmonary angiography (CTPA) in patients with suspected acute pulmonary embolism with regard to image quality and pulmonary perfused blood volume (PBV) values. A total of 198 studies performed with four CM injection protocols varying in CM volume and iodine delivery rates (IDR) were retrospectively included: (A) 60 ml at 5 ml/s (IDR = 1.75gI/s), (B) 50 ml at 5 ml/s (IDR = 1.75gI/s), (C) 50 ml at 4 ml/s (IDR = 1.40gI/s), (D) 40 ml at 3 ml/s (IDR = 1.05gI/s). Image quality and PBV values at different resolution settings were compared. Pulmonary arterial tract attenuation was highest for protocol A (397 ± 110 HU; p vs. B = 0.13; vs. C = 0.02; vs. D < 0.001). CTPA image quality of protocol A was rated superior compared to protocols B and D by reader 1 (p = 0.01; < 0.001), and superior to protocols B, C and D by reader 2 (p < 0.001; 0.02; < 0.001). Otherwise, there were no significant differences in CTPA quality ratings. Subjective iodine map ratings did not vary significantly between protocols A, B, and C. Both readers rated protocol D inferior to all other protocols (p < 0.05). PBV values did not vary significantly between protocols A and B at resolution settings of 1, 4 and 10 (p = 0.10; 0.10; 0.09), while otherwise PBV values displayed a decreasing trend from protocol A to D (p < 0.05). Higher CM volume and IDR are associated with superior CTPA and iodine map quality and higher absolute PBV values.}, language = {en} } @article{AdolfBraunFussetal.2020, author = {Adolf, Christian and Braun, Leah T. and Fuss, Carmina T. and Hahner, Stefanie and K{\"u}nzel, Heike and Handgriff, Laura and Sturm, Lisa and Heinrich, Daniel A. and Schneider, Holger and Bidlingmaier, Martin and Reincke, Martin}, title = {Spironolactone reduces biochemical markers of bone turnover in postmenopausal women with primary aldosteronism}, series = {Endocrine}, volume = {69}, journal = {Endocrine}, number = {3}, issn = {1355-008X}, doi = {10.1007/s12020-020-02348-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-315966}, pages = {625-633}, year = {2020}, abstract = {Context Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Besides its deleterious impact on cardiovascular target organ damage, PA is considered to cause osteoporosis. Patients and methods We assessed bone turnover in a subset of 36 postmenopausal women with PA. 18 patients had unilateral PA and were treated by adrenalectomy, whereas 18 patients had bilateral PA and received mineralocorticoid receptor antagonist (MRA) therapy respectively. 18 age- and BMI-matched females served as controls. To estimate bone remodeling, we measured the bone turnover markers intact procollagen 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin and tartrate resistant acid phosphatase 5b in plasma by chemiluminescent immunoassays at time of diagnosis and one year after initiation of treatment. Study design Observational longitudinal cohort study. Setting Tertiary care hospital. Results Compared with controls, patients with PA had mildly elevated osteocalcin at baseline (p = 0.013), while the other bone markers were comparable between both groups. There were no differences between the unilateral and the bilateral PA subgroup. One year after initiation of MRA treatment with spironolactone bone resorption and bone formation markers had significantly decreased in patients with bilateral PA. In contrast, patients adrenalectomized because of unilateral PA showed no significant change of bone turnover markers. Conclusion This study shows that aldosterone excess in postmenopausal women with PA is not associated with a relevant increase of bone turnover markers at baseline. However, we observed a significant decrease of bone markers in patients treated with spironolactone, but not in patients treated by adrenalectomy.}, language = {en} } @article{GerlichAndreicaKueffneretal.2020, author = {Gerlich, C. and Andreica, I. and K{\"u}ffner, R. and Krause, D. and Lakomek, H. J. and Reusch, A. and Braun, J.}, title = {Evaluation einer Basisschulung f{\"u}r Patienten mit rheumatoider Arthritis}, series = {Zeitschrift f{\"u}r Rheumatologie}, volume = {79}, journal = {Zeitschrift f{\"u}r Rheumatologie}, doi = {10.1007/s00393-020-00769-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280359}, pages = {737-748}, year = {2020}, abstract = {Hintergrund Ein neues Rahmenkonzept hat die flexible Ableitung und Nutzung von rheumatologischen Schulungsprogrammen f{\"u}r unterschiedliche Versorgungsbereiche erm{\"o}glicht. Auf dieser Grundlage wurde eine 5‑st{\"u}ndige Basisschulung f{\"u}r Patienten mit rheumatoider Arthritis (RA) entwickelt, es wurden rheumatologische Fach{\"a}rzte und Psychologen trainiert, und dann wurde die Wirksamkeit nach dem Wirkmodell der Patientenschulung evaluiert. Methoden Mit dem Studiendesign einer extern randomisierten Wartekontrollgruppenstudie mit 3 Messzeitpunkten wurde gepr{\"u}ft, wie sich die 5‑st{\"u}ndige Basisschulung auf das Erkrankungs- und Behandlungswissen sowie auf die Gesundheitskompetenz von RA-Patienten (n = 249) auswirkt. Weitere Fragen betrafen Einstellungsparameter, Kommunikationskompetenz, Erkrankungsauswirkungen und die Zufriedenheit mit der Schulung. Die Auswertungen erfolgten auf Intention-to-treat-Basis mit Kovarianzanalysen f{\"u}r die Hauptzielgr{\"o}ßen unter Ber{\"u}cksichtigung des Ausgangswertes. Ergebnisse Die Analysen zeigen, dass die Basisschulung RA wirksam ist. Noch 3 Monate nach der Schulung verf{\"u}gten die Schulungsteilnehmer {\"u}ber mehr Wissen und Gesundheitskompetenz als die Wartekontrollgruppe mit kleinem bis mittelgroßem Effekt (d = 0,37 bzw. 0,38). In den Nebenzielgr{\"o}ßen zeigten sich mit Ausnahme der Krankheitskommunikation keine weiteren Schulungseffekte. Diskussion Die Basisschulung bietet eine gute Grundlage, auf der weitere Interventionen zur Verbesserung von Einstellungs- und Erkrankungsparametern aufbauen k{\"o}nnen. Sie eignet sich damit als zentraler Baustein f{\"u}r die rheumatologische Versorgung auf verschiedenen Ebenen.}, language = {de} }