TY  - JOUR
A1  - Lanzendörfer, Franz
A1  - Christl, Manfred
T1  - 3,4-Bismethylentricyclo[3.1.0.0<sup>2,6</sup>]hexan - Synthese und Diels-Alder-Addition an Tetracyanethylen
N2  - No abstract available
Y1  - 1983
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30263
ER  - 
TY  - JOUR
A1  - Christl, Manfred
A1  - Herzog, C.
T1  - 3-(Phenylsulfonyl)tricyclo[4.1.0.0\(^{2,7}\)]hept-4-en-3-yllithium
N2  - Phenyl(tricyclo[4.1.0.0\^(^{2,7}\)] hept-4-en-3-yl)sulfone 8 has been prepared in two steps from 4,S-dlbromohomobenzvalene (6) and deprotonated to give the title compound 9. The carbon-13 NMR spectrum of 9 reveals a considerable interaction between the allyl anion moiety and the bicyclobutane system.
KW  - Organische Chemie
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58340
ER  - 
TY  - JOUR
A1  - Grunz, Jan-Peter
A1  - Wenig, Andreas Max
A1  - Kunz, Andreas Steven
A1  - Veyhl-Wichmann, Maike
A1  - Schmitt, Rainer
A1  - Gietzen, Carsten Herbert
A1  - Pennig, Lenhard
A1  - Herz, Stefan
A1  - Ergün, Süleyman
A1  - Bley, Thorsten Alexander
A1  - Gassenmaier, Tobias
T1  - 3D cone-beam CT with a twin robotic x-ray system in elbow imaging: comparison of image quality to high-resolution multidetector CT
JF  - European Radiology Experimental
N2  - Background
Elbow imaging is challenging with conventional multidetector computed tomography (MDCT), while cone-beam CT (CBCT) provides superior options. We compared intra-individually CBCT versus MDCT image quality in cadaveric elbows.

Methods
A twin robotic x-ray system with new CBCT mode and a high-resolution clinical MDCT were compared in 16 cadaveric elbows. Both systems were operated with a dedicated low-dose (LD) protocol (equivalent volume CT dose index [CTDI\(_{vol(16 cm)}\)] = 3.3 mGy) and a regular clinical scan dose (RD) protocol (CTDI\(_{vol(16 cm)}\) = 13.8 mGy). Image quality was evaluated by two radiologists (R1 and R2) on a seven-point Likert scale, and estimation of signal intensity in cancellous bone was conducted. Wilcoxon signed-rank tests and intraclass correlation coefficient (ICC) statistics were used.

Results
The CBCT prototype provided superior subjective image quality compared to MDCT scans (for RD, p ≤ 0.004; for LD, p ≤ 0.001). Image quality was rated very good or excellent in 100% of the cases by both readers for RD CBCT, 100% (R1) and 93.8% (R2) for LD CBCT, 62.6% and 43.8% for RD MDCT, and 0.0% and 0.0% for LD MDCT. Single-measure ICC was 0.95 (95% confidence interval 0.91–0.97; p < 0.001). Software-based assessment supported subjective findings with less “undecided” pixels in CBCT than dose-equivalent MDCT (p < 0.001). No significant difference was found between LD CBCT and RD MDCT.
Conclusions

In cadaveric elbow studies, the tested cone-beam CT prototype delivered superior image quality compared to high-end multidetector CT and showed a potential for considerable dose reduction.
KW  - Cancellous bone
KW  - Cone-beam computed tomography
KW  - Elbow
KW  - Elbow joint
KW  - Multidetector computed tomography
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229877
VL  - 4
ER  - 
TY  - JOUR
A1  - Gensler, Marius
A1  - Leikeim, Anna
A1  - Möllmann, Marc
A1  - Komma, Miriam
A1  - Heid, Susanne
A1  - Müller, Claudia
A1  - Boccaccini, Aldo R.
A1  - Salehi, Sahar
A1  - Groeber-Becker, Florian
A1  - Hansmann, Jan
T1  - 3D printing of bioreactors in tissue engineering: A generalised approach
JF  - PLoS One
N2  - 3D printing is a rapidly evolving field for biological (bioprinting) and non-biological applications. Due to a high degree of freedom for geometrical parameters in 3D printing, prototype printing of bioreactors is a promising approach in the field of Tissue Engineering. The variety of printers, materials, printing parameters and device settings is difficult to overview both for beginners as well as for most professionals. In order to address this problem, we designed a guidance including test bodies to elucidate the real printing performance for a given printer system. Therefore, performance parameters such as accuracy or mechanical stability of the test bodies are systematically analysed. Moreover, post processing steps such as sterilisation or cleaning are considered in the test procedure. The guidance presented here is also applicable to optimise the printer settings for a given printer device. As proof of concept, we compared fused filament fabrication, stereolithography and selective laser sintering as the three most used printing methods. We determined fused filament fabrication printing as the most economical solution, while stereolithography is most accurate and features the highest surface quality. Finally, we tested the applicability of our guidance by identifying a printer solution to manufacture a complex bioreactor for a perfused tissue construct. Due to its design, the manufacture via subtractive mechanical methods would be 21-fold more expensive than additive manufacturing and therefore, would result in three times the number of parts to be assembled subsequently. Using this bioreactor we showed a successful 14-day-culture of a biofabricated collagen-based tissue construct containing human dermal fibroblasts as the stromal part and a perfusable central channel with human microvascular endothelial cells. Our study indicates how the full potential of biofabrication can be exploited, as most printed tissues exhibit individual shapes and require storage under physiological conditions, after the bioprinting process.
KW  - stem cells
KW  - technology
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231368
VL  - 15
IS  - 11
ER  - 
TY  - JOUR
A1  - Westermaier, Thomas
A1  - Linsenmann, Thomas
A1  - Homola, György A.
A1  - Loehr, Mario
A1  - Stetter, Christian
A1  - Willner, Nadine
A1  - Ernestus, Ralf-Ingo
A1  - Soymosi, Laszlo
A1  - Vince, Giles H.
T1  - 3D rotational fluoroscopy for intraoperative clip control in patients with intracranial aneurysms – assessment of feasibility and image quality
JF  - BMC Medical Imaging
N2  - Background
Mobile 3D fluoroscopes have become increasingly available in neurosurgical operating rooms. In this series, the image quality and value of intraoperative 3D fluoroscopy with intravenous contrast agent for the evaluation of aneurysm occlusion and vessel patency after clip placement was assessed in patients who underwent surgery for intracranial aneurysms.

Materials and methods
Twelve patients were included in this retrospective analysis. Prior to surgery, a 360° rotational fluoroscopy scan was performed without contrast agent followed by another scan with 50 ml of intravenous iodine contrast agent. The image files of both scans were transferred to an Apple PowerMac® workstation, subtracted and reconstructed using OsiriX® free software. The procedure was repeated after clip placement. Both image sets were compared for assessment of aneurysm occlusion and vessel patency.

Results
Image acquisition and contrast administration caused no adverse effects. Image quality was sufficient to follow the patency of the vessels distal to the clip. Metal artifacts reduce the assessability of the immediate vicinity of the clip. Precise image subtraction and post-processing can reduce metal artifacts and make the clip-site assessable and depict larger neck-remnants.

Conclusion
This technique quickly supplies images at adequate quality to evaluate distal vessel patency after aneurysm clipping. Significant aneurysm remnants may be depicted as well. As it does not require visual control of all vessels that are supposed to be evaluated intraoperatively, this technique may be complementary to other intraoperative tools like indocyanine green videoangiography and micro-Doppler, especially for the assessment of larger aneurysms. At the momentary state of this technology, it cannot replace postoperative conventional angiography. However, 3D fluoroscopy and image post-processing are young technologies. Further technical developments are likely to result in improved image quality.
KW  - aneurysm surgery
KW  - clip control
KW  - angiography
KW  - 3D fluoroscopy
KW  - image quality
KW  - intraoperative
KW  - vessel patency
KW  - contrast
KW  - post-processing
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146381
VL  - 16
IS  - 30
ER  - 
TY  - JOUR
A1  - Dietl, Alexander
A1  - Prieschenk, Christine
A1  - Eckert, Franziska
A1  - Birner, Christoph
A1  - Luchner, Andreas
A1  - Maier, Lars S.
A1  - Buchner, Stefan
T1  - 3D vena contracta area after MitraClip© procedure: precise quantification of residual mitral regurgitation and identification of prognostic information
JF  - Cardiovascular Ultrasound
N2  - Background
Percutaneous mitral valve repair (PMVR) is increasingly performed in patients with severe mitral regurgitation (MR). Post-procedural MR grading is challenging and an unsettled issue. We hypothesised that the direct planimetry of vena contracta area (VCA) by 3D–transoesophageal echocardiography allows quantifying post-procedural MR and implies further prognostic relevance missed by the usual ordinal scale (grade I-IV).

Methods
Based on a single-centre PMVR registry containing 102 patients, the association of VCA reduction and patients’ functional capacity measured as six-minute walk distance (6 MW) was evaluated. 3D–colour-Doppler datasets were available before, during and 4 weeks after PMVR.

Results
Twenty nine patients (age 77.0 ± 5.8 years) with advanced heart failure (75.9% NYHA III/IV) and severe degenerative (34%) or functional (66%) MR were eligible. VCA was reduced in all patients by PMVR (0.99 ± 0.46 cm\(^2\) vs. 0.22 ± 0.15 cm\(^2\), p < 0.0001). It remained stable after median time of 33 days (p = 0.999). 6 MW improved after the procedure (257.5 ± 82.5 m vs. 295.7 ± 96.3 m, p < 0.01). Patients with a decrease in VCA less than the median VCA reduction showed a more distinct improvement in 6 MW than patients with better technical result (p < 0.05). This paradoxical finding was driven by inferior results in very large functional MR.

Conclusions
VCA improves the evaluation of small residual MR. Its post-procedural values remain stable during a short-term follow-up and imply prognostic information for the patients’ physical improvement. VCA might contribute to a more substantiated estimation of treatment success in the heterogeneous functional MR group.
KW  - percutaneous mitral valve repair
KW  - MitraClip
KW  - 3D echocardiography
KW  - vena contracta area
KW  - six-minute walk test
KW  - NT-proBNP
KW  - prognosis
KW  - functional mitral regurgitation
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225318
VL  - 16
ER  - 
TY  - JOUR
A1  - Sollfrank, Teresa
A1  - Hart, Daniel
A1  - Goodsell, Rachel
A1  - Foster, Jonathan
A1  - Tan, Tele
T1  - 3D visualization of movements can amplify motor cortex activation during subsequent motor imagery
JF  - Frontiers in Human Neuroscience
N2  - A repetitive movement practice by motor imagery (MI) can influence motor cortical excitability in the electroencephalogram (EEG). This study investigated if a realistic visualization in 3D of upper and lower limb movements can amplify motor related potentials during subsequent MI. We hypothesized that a richer sensory visualization might be more effective during instrumental conditioning, resulting in a more pronounced event related desynchronization (ERD) of the upper alpha band (10–12 Hz) over the sensorimotor cortices thereby potentially improving MI based brain-computer interface (BCI) protocols for motor rehabilitation. The results show a strong increase of the characteristic patterns of ERD of the upper alpha band components for left and right limb MI present over the sensorimotor areas in both visualization conditions. Overall, significant differences were observed as a function of visualization modality (VM; 2D vs. 3D). The largest upper alpha band power decrease was obtained during MI after a 3-dimensional visualization. In total in 12 out of 20 tasks the end-user of the 3D visualization group showed an enhanced upper alpha ERD relative to 2D VM group, with statistical significance in nine tasks.With a realistic visualization of the limb movements, we tried to increase motor cortex activation during subsequent MI. The feedback and the feedback environment should be inherently motivating and relevant for the learner and should have an appeal of novelty, real-world relevance or aesthetic value (Ryan and Deci, 2000; Merrill, 2007). Realistic visual feedback, consistent with the participant’s MI, might be helpful for accomplishing successful MI and the use of such feedback may assist in making BCI a more natural interface for MI based BCI rehabilitation.
KW  - 3-dimensional visualization
KW  - motor cortex activation
KW  - EEG
KW  - brain-computer interfaces
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126058
VL  - 9
IS  - 463
ER  - 
TY  - JOUR
A1  - Houben, Roland
A1  - Alimova, Pamela
A1  - Sarma, Bhavishya
A1  - Hesbacher, Sonja
A1  - Schulte, Carolin
A1  - Sarosi, Eva-Maria
A1  - Adam, Christian
A1  - Kervarrec, Thibault
A1  - Schrama, David
T1  - 4-[(5-methyl-1H-pyrazol-3-yl)amino]-2H-phenyl-1-phthalazinone inhibits MCPyV T antigen expression in Merkel cell carcinoma independent of Aurora kinase A
JF  - Cancers
N2  - Merkel cell carcinoma (MCC) is frequently caused by the Merkel cell polyomavirus (MCPyV), and MCPyV-positive tumor cells depend on expression of the virus-encoded T antigens (TA). Here, we identify 4-[(5-methyl-1H-pyrazol-3-yl)amino]-2H-phenyl-1-phthalazinone (PHT) — a reported inhibitor of Aurora kinase A — as a compound inhibiting growth of MCC cells by repressing noncoding control region (NCCR)-controlled TA transcription. Surprisingly, we find that TA repression is not caused by inhibition of Aurora kinase A. However, we demonstrate that β-catenin — a transcription factor repressed by active glycogen synthase kinase 3 (GSK3) — is activated by PHT, suggesting that PHT bears a hitherto unreported inhibitory activity against GSK3, a kinase known to function in promoting TA transcription. Indeed, applying an in vitro kinase assay, we demonstrate that PHT directly targets GSK3. Finally, we demonstrate that PHT exhibits in vivo antitumor activity in an MCC xenograft mouse model, suggesting a potential use in future therapeutic settings for MCC.
KW  - Merkel cell carcinoma
KW  - polyomavirus
KW  - large T antigen
KW  - phthalazinone pyrazole
KW  - glycogen synthase kinase 3
KW  - GSK3
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313547
SN  - 2072-6694
VL  - 15
IS  - 9
ER  - 
TY  - JOUR
A1  - Christl, Manfred
A1  - Nusser, R.
A1  - Herzog, C.
T1  - 4-Bromoctavalen und zwei (Brommethylen)homobenzvalene anstelle eines erwarteten Bromoctabisvalens
N2  - No abstract available.
KW  - Organische Chemie
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58409
ER  - 
TY  - JOUR
A1  - Wiedenmann, J.
A1  - Bocquillon, E.
A1  - Deacon, R.S.
A1  - Hartinger, S.
A1  - Herrmann, O.
A1  - Klapwijk, T.M.
A1  - Maier, L.
A1  - Ames, C.
A1  - Brüne, C.
A1  - Gould, C.
A1  - Oiwa, A.
A1  - Ishibashi, K.
A1  - Tarucha, S.
A1  - Buhmann, H.
A1  - Molenkamp, L.W.
T1  - 4π-periodic Josephson supercurrent in HgTe-based topological Josephson junctions
JF  - Nature Communications
N2  - The Josephson effect describes the generic appearance of a supercurrent in a weak link between two superconductors. Its exact physical nature deeply influences the properties of the supercurrent. In recent years, considerable efforts have focused on the coupling of superconductors to the surface states of a three-dimensional topological insulator. In such a material, an unconventional induced p-wave superconductivity should occur, with a doublet of topologically protected gapless Andreev bound states, whose energies vary 4π-periodically with the superconducting phase difference across the junction. In this article, we report the observation of an anomalous response to rf irradiation in a Josephson junction made of a HgTe weak link. The response is understood as due to a 4π-periodic contribution to the supercurrent, and its amplitude is compatible with the expected contribution of a gapless Andreev doublet. Our work opens the way to more elaborate experiments to investigate the induced superconductivity in a three-dimensional insulator.
KW  - Josephson effect
KW  - supercurrent
KW  - superconductors
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175353
VL  - 7
ER  - 
TY  - JOUR
A1  - Stopper, Helga
A1  - Pechan, R.
A1  - Schiffmann, D.
T1  - 5-azacytidine induces micronuclei in and morphological transformation of Syrian hamster embryo fibroblasts in the absence of unscheduled DNA synthesis
N2  - lt is known that 5-azacytidine (5-AC) induces tumors in several organs of rats and mice. The mechanisms of these effects are still poorly understood although it is known that 5-AC can be incorporated into DNA. Furthermore, it can inhibit DNA methylation. The known data on its clastogenic andjor gene mutation-inducing potential are still controversial. Therefore, we have investigated the kinds of genotoxic effects caused by 5-AC in Syrian hamster embryo (SHE) fibroblasts. Three different endp6ints (micronucleus formation, unscheduled DNA synthesis (UDS) and cell transforrnation) were assayed under similar conditions of metabolism and dose at target in this cell system. 5-AC induces morphological transformation of SHE cells, but not UDS. Therefore, 5-AC does not seem to cause repairable DNA lesions. Furthermore, our studies revealed that 5-AC is a potent inducer of mkronuclei in the SHE system. Immunocytochemical analysis revealed that a certain percentage of these contain kinetochores indicating that 5-AC may induce both clastogenic events and numerical chromosome changes.
KW  - Toxikologie
KW  - 5-Azacytidine
KW  - Micronuclei
KW  - Kinetochores
KW  - Unscheduled DNA synthesis
KW  - Cell transformation
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63443
ER  - 
TY  - JOUR
A1  - Karabeg, Margherita M.
A1  - Grauthoff, Sandra
A1  - Kollert, Sina Y.
A1  - Weidner, Magdalena
A1  - Heiming, Rebecca S.
A1  - Jansen, Friederike
A1  - Popp, Sandy
A1  - Kaiser, Sylvia
A1  - Lesch, Klaus-Peter
A1  - Sachser, Norbert
A1  - Schmitt, Angelika G.
A1  - Lewejohann, Lars
T1  - 5-HTT Deficiency Affects Neuroplasticity and Increases Stress Sensitivity Resulting in Altered Spatial Learning Performance in the Morris Water Maze but Not in the Barnes Maze
JF  - PLoS ONE
N2  - The purpose of this study was to evaluate whether spatial hippocampus-dependent learning is affected by the serotonergic system and stress. Therefore, 5-HTT knockout (-/-), heterozygous (+/-) and wildtype (+/+) mice were subjected to the Barnes maze (BM) and the Morris water maze (WM), the latter being discussed as more aversive. Additionally, immediate early gene (IEG) expression, hippocampal adult neurogenesis (aN), and blood plasma corticosterone were analyzed.

While the performance of 5-HTT-/- mice in the BM was undistinguishable from both other genotypes, they performed worse in the WM. However, in the course of the repeated WM trials 5-HTT-/- mice advanced to wildtype level. The experience of a single trial of either the WM or the BM resulted in increased plasma corticosterone levels in all genotypes. After several trials 5-HTT-/- mice exhibited higher corticosterone concentrations compared with both other genotypes in both tests. Corticosterone levels were highest in 5-HTT-/- mice tested in the WM indicating greater aversiveness of the WM and a greater stress sensitivity of 5-HTT deficient mice.

Quantitative immunohistochemistry in the hippocampus revealed increased cell counts positive for the IEG products cFos and Arc as well as for proliferation marker Ki67 and immature neuron marker NeuroD in 5-HTT-/- mice compared to 5-HTT+/+ mice, irrespective of the test. Most differences were found in the suprapyramidal blade of the dentate gyrus of the septal hippocampus. Ki67-immunohistochemistry revealed a genotype x environment interaction with 5-HTT genotype differences in naïve controls and WM experience exclusively yielding more Ki67-positive cells in 5-HTT+/+ mice. Moreover, in 5-HTT-/- mice we demonstrate that learning performance correlates with the extent of aN.

Overall, higher baseline IEG expression and increased an in the hippocampus of 5-HTT-/- mice together with increased stress sensitivity may constitute the neurobiological correlate of raised alertness, possibly impeding optimal learning performance in the more stressful WM.
KW  - immediate early genes
KW  - learning curves
KW  - animal performance
KW  - animal behavior
KW  - serotonin
KW  - learning
KW  - mice
KW  - hippocampus
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129978
VL  - 8
IS  - 10
ER  - 
TY  - JOUR
A1  - Popp, Sandy
A1  - Schmitt-Böhrer, Angelika
A1  - Langer, Simon
A1  - Hofmann, Ulrich
A1  - Hommers, Leif
A1  - Schuh, Kai
A1  - Frantz, Stefan
A1  - Lesch, Klaus-Peter
A1  - Frey, Anna
T1  - 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction
JF  - Journal of Clinical Medicine
N2  - Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally naïve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (−/−) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT−/− mice with infarct sizes >30% experienced 100% mortality, while 50% of 5-HTT+/− and 37% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI < 30%) 5-HTT−/− mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either 5-Htt genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT−/− mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice.
KW  - chronic heart failure
KW  - myocardial infarction
KW  - serotonin transporter deficient mice
KW  - anxiety
KW  - depression
KW  - behavior
KW  - inflammation
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242739
SN  - 2077-0383
VL  - 10
IS  - 14
ER  - 
TY  - JOUR
A1  - Chen, Y.
A1  - Palm, F.
A1  - Lesch, K. P.
A1  - Gerlach, M.
A1  - Moessner, R.
A1  - Sommer, C.
T1  - 5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, is responsible for complete Freund's adjuvant-induced thermal hyperalgesia in mice
N2  - Background: The role of serotonin (5-hydroxytrptamine, 5-HT) in the modulation of pain has been widely studied. Previous work led to the hypothesis that 5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, might by itself influence pain thresholds. Results: In the present study, we investigated the role of 5-HIAA in inflammatory pain induced by intraplantar injection of complete Freund’s adjuvant (CFA) into the hind paw of mice. Wild-type mice were compared to mice deficient of the 5-HT transporter (5-HTT-/- mice) using behavioral tests for hyperalgesia and high-performance liquid chromatography (HPLC) to determine tissue levels of 5-HIAA. Wild-type mice reproducibly developed thermal hyperalgesia and paw edema for 5 days after CFA injection. 5-HTT-/- mice treated with CFA had reduced thermal hyperalgesia on day 1 after CFA injection and normal responses to heat hereafter. The 5-HIAA levels in spinal cord and sciatic nerve as measured with HPLC were lower in 5-HTT-/- mice than in wild-type mice after CFA injection. Pretreatment of wild-type mice with intraperitoneal injection of para-chlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, resulted in depletion of the 5-HIAA content in spinal cord and sciatic nerve and decrease in thermal hyperalgesia in CFA injected mice. The application of exogenous 5-HIAA resulted in potentiation of thermal hyperalgesia induced by CFA in 5-HTT-/- mice and in wild-type mice pretreated with p- CPA, but not in wild-type mice without p-CPA pretreatment. Further, methysergide, a broad-spectrum serotonin receptor antagonist, had no effect on 5-HIAA-induced potentiation of thermal hyperalgesia in CFA-treated wildtype mice. Conclusion: Taken together, the present results suggest that 5-HIAA plays an important role in modulating peripheral thermal hyperalgesia in CFA induced inflammation, probably via a non-serotonin receptor mechanism.
KW  - Medizin
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68858
ER  - 
TY  - JOUR
A1  - Blömer, Nadja
A1  - Pachel, Christina
A1  - Hofmann, Urlich
A1  - Nordbeck, Peter
A1  - Bauer, Wolfgang
A1  - Mathes, Denise
A1  - Frey, Anna
A1  - Bayer, Barbara
A1  - Vogel, Benjamin
A1  - Ertl, Georg
T1  - 5-Lipoxygenase facilitates healing after myocardial infarction
JF  - Basic Research in Cardiology
N2  - Early healing after myocardial infarction (MI) is characterized by a strong inflammatory reaction. Most leukotrienes are pro-inflammatory and are therefore potential mediators of healing and remodeling after myocardial ischemia. The enzyme 5-lipoxygenase (5-LOX) has a key role in the transformation of arachidonic acid in leukotrienes. Thus, we tested the effect of 5-LOX on healing after MI. After chronic coronary artery ligation, early mortality was significantly increased in 5-LOX\(^{−/−}\) when compared to matching wildtype (WT) mice due to left ventricular rupture. This effect could be reproduced in mice treated with the 5-LOX inhibitor Zileuton. A perfusion mismatch due to the vasoactive potential of leukotrienes is not responsible for left ventricular rupture since local blood flow assessed by magnetic resonance perfusion measurements was not different. However, after MI, there was an accentuation of the inflammatory reaction with an increase of pro-inflammatory macrophages. Yet, mortality was not changed in chimeric mice (WT vs. 5-LOX\(^{−/−}\) bone marrow in 5-LOX\(^{−/−}\) animals), indicating that an altered function of 5-LOX\(^{−/−}\) inflammatory cells is not responsible for the phenotype. Collagen production and accumulation of fibroblasts were significantly reduced in 5-LOX\(^{−/−}\) mice in vivo after MI. This might be due to an impaired migration of 5-LOX\(^{−/−}\) fibroblasts, as shown in vitro to serum. In conclusion, a lack or inhibition of 5-LOX increases mortality after MI because of healing defects. This is not mediated by a change in local blood flow, but through an altered inflammation and/or fibroblast function.
KW  - lipoxygenase
KW  - myocardial infarction
KW  - extracellular matrix remodeling
KW  - inflammation
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132602
VL  - 108
IS  - 4
ER  - 
TY  - JOUR
A1  - Schmid, Michael
A1  - Steinlein, Claus
A1  - Lomb, Christian
A1  - Sperling, Karl
A1  - Neitzel, Heidemarie
T1  - 5-Methylcytosine-Rich Heterochromatin in the Indian Muntjac
JF  - Cytogenetic and Genome Research
N2  - Two 5-methylcytosine (5-MeC)-rich heterochromatic regions were demonstrated in metaphase chromosomes of the Indian muntjac by indirect immunofluorescence using a monoclonal anti-5-MeC antibody. The metaphases were obtained from diploid and triploid cell lines. A major region is located in the ‘neck' of the 3;X fusion chromosome and can be detected after denaturation of the chromosomal DNA with UV-light irradiation for 1 h. It is located exactly at the border of the X chromosome and the translocated autosome 3. A minor region is found in the centromeric region of the free autosome 3 after denaturing the chromosomal DNA for 3 h or longer. The structure and possible function of the major hypermethylated region as barrier against spreading of the X-inactivation process into the autosome 3 is discussed.
KW  - heterochromatin
KW  - immunofluorescence
KW  - Indian muntjac
KW  - 5-Methylcytosine
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196701
SN  - 1424-8581
SN  - 1424-859X
N1  - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL  - 147
IS  - 4
ER  - 
TY  - JOUR
A1  - Christl, Manfred
A1  - Leß, Roland
A1  - Müller, Heinrich
T1  - 6,7-Dimethylene-2,4-diphenylbicyclo[3.2.l]oct-3-en-2-yl Anion : A Test for the Origin of the Unusual Properties of the Bicyclo[3.2.l]octa-3,6-dien-2-yl Anion
N2  - No abstract available
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31547
ER  - 
TY  - JOUR
A1  - Li, Xiang
A1  - Samnick, Samuel
A1  - Lapa, Constantin
A1  - Israel, Ina
A1  - Buck, Andreas K.
A1  - Kreissl, Michael C.
A1  - Bauer, Wolfgang
T1  - 68Ga-DOTATATE PET/CT for the detection of inflammation of large arteries: correlation with18F-FDG, calcium burden and risk factors
N2  - Background: Ga-[1,4,7,10-tetraazacyclododecane-N,N0,N00,N000-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) positron emission tomography (PET) is commonly used for the visualization of somatostatin receptor (SSTR)-positive neuroendocrine tumors. SSTR is also known to be expressed on macrophages, which play a major role in inflammatory processes in the walls of coronary arteries and large vessels. Therefore, imaging SSTR expression has the potential to visualize vulnerable plaques. We assessed 68Ga-DOTATATE accumulation in large vessels in comparison to 18F-2-fluorodeoxyglucose (FDG) uptake, calcified plaques (CPs), and cardiovascular risk factors. Methods: Sixteen consecutive patients with neuroendocrine tumors or thyroid cancer underwent both 68Ga-DOTATATE and 18F-FDG PET/CT for staging or restaging purposes. Detailed clinical data, including common cardiovascular risk factors, were recorded. For a separate assessment, they were divided into a high-risk and a low-risk group. In each patient, we calculated the maximum target-to-background ratio (TBR) of eight arterial segments. The correlation of the TBRmean of both tracers with risk factors including plaque burden was assessed. Results: The mean TBR of 68Ga-DOTATATE in all large arteries correlated significantly with the presence of CPs (r = 0.52; p < 0.05), hypertension (r = 0.60; p < 0.05), age (r = 0.56; p < 0.05), and uptake of 18F-FDG (r = 0.64; p < 0.01). There was one significant correlation between 18F-FDG uptake and hypertension (0.58; p < 0.05). Out of the 37 sites with the highest focal 68Ga-DOTATATE uptake, 16 (43.2%) also had focal 18F-FDG uptake. Of 39 sites with the highest 18F-FDG uptake, only 11 (28.2%) had a colocalized 68Ga-DOTATATE accumulation. Conclusions: In this series of cancer patients, we found a stronger association of increased 68Ga-DOTATATE uptake with known risk factors of cardiovascular disease as compared to 18F-FDG, suggesting a potential role for plaque imaging in large arteries. Strikingly, we found that focal uptake of 68Ga-DOTATATE and 18F-FDG does not colocalize in a significant number of lesions.
KW  - Medizin
KW  - Atherosclerotic plaque
KW  - 68Ga-DOTATATE
KW  - Somatostatin receptor
KW  - Cardiovascular risk factors
KW  - Macrophage
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76231
ER  - 
TY  - JOUR
A1  - Christl, Manfred
A1  - Schreck, M.
T1  - 7-Arylbicyclo[4.2.0]oct-1-ene - Synthese durch [2+2]-Cycloadditionen von 1,2-Cyclohexadien sowie 1-Methyl-1,2-cyclohexadien und thermische Äquilibrierung der exo/endo-Isomeren
T1  - 7-Arylbicyclo[4.2.0]oct-1-eaes - Synthesis by [2+2]Cycloadditions of 1,2-Cyclohexadiene and 1-Methyl-l,l-cyclohexadiene and Thermal Equilibration of the exo/endo Isomers
N2  - Das exo/endo--lsomerenverhältnis Ja: Jb bei der bekannten [2 + 2]-Cycloaddition von Styrol an 1,2-Cyclohexadien (2) wurde als tempcraturabhingiaaefunden. Der Einsatz von (Z)-Dcutcriostyrollicfene den Beweis der Zweistufiakeit dieser Reaktion, und das Diradikal 4 wird als wahrscheinlichste Zwischenstufe anaesehen. Erhitzen von Jb auf 140-170°C führte zur Binstellung des thermodynamischen Gleichgewichts mit Ja (Ja:3b = 93:7), wobei wieder das Diradikal4 als Zwischenstufe fungieren dürfte. Mit Hilfe kinetischer Messungen ermittelte man die Aktivierungsparameter für das System Ja~ 3b. - Aus 2 und den Abfangreagenzien p-Methoxystyrol, 1,1-Diphenylethylen sowie 1-Phenylpropen gingen mit bescheidenen Ausbeuten die Titelverbindungen 6a, b, 7 bzw. 8 hervor. Analoa zu 2 wurde sein l-Methylderivat 13 aus 6,6-Dibrom-1-methylbicyclo[3.1.0]hexan (9) durch Methyllithium freigesetzt. In Gegenwart von Styrol entstand neben den Abfanaprodukten 14a, b auch das Dimere 12 von lJ. - Die 1H-NMR-Spektren der Titelverbindungen belegen eine starre Halbsesselkonformation des Cyclohexentcils mit äquatorial anellienem Cyclobutanring.
N2  - The exofendo ratio of tbe isomers 3a, b formed in the kuown [2 + 2] cycloaddition of styrene to 1 ,2-cyclohexadiene (2) has been found to depend on the tempcrature. The utilization of (Z)deuteriostyrene provided the proof of the stepwise nature of this reaction with thc diradical 4 as the most probable intennediatc. Heating of 3b at l40-170°C established the thermodynamic equilibrium between Ja and Jb (3a:3b = 93:7) and again 4 is assumed to be the intermediatc. By means of kinetic measurements the activation parameten ofthe system 3a ~ Jb have been detcrmined. - From 2 and the trapping reagents p-metboxystyrene, 1,1-diphenylethylene, and 1-phenylpropene the title compounds 6a, b, 7, and 8, respectively, were formed in low yields. In analogy to 2 its 1-methyl derivative 13 has been generated from 6,6-dibromo-l-methylbicyclo[3.t.O]hexane (9) with methyUithium. From the reaction in the presence of styrcne the trappina products 14a, b were isolated in addition to the dimer ll of 13. - The 1H NMR spectra of the title compounds support a rigid halfchair conformation of the cyclohexene moiety with the cyclobutane ring ancllatcd equatorially.
KW  - Organische Chemie
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58352
ER  - 
TY  - JOUR
A1  - Christl, Manfred
A1  - Leininger, Hartmut
T1  - 7-Azatetracyclo[4.1.0.0<sup>2,4</sup>.0<sup>3,5</sup>]heptan - ein neues Valenzisomeres des Azepins
N2  - No abstract available
Y1  - 1979
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30034
ER  - 
TY  - JOUR
A1  - Christl, Manfred
A1  - Brunn, E.
A1  - Roth, W. R.
A1  - Lennartz, H.-W.
T1  - 7-Methyl- and 7-Phenylcyclohepta-1,3,5-trienes from Benzvalene Via 3,3a,4,5,6,6a-Hexahydro-4,5,6-methenocyclopentapyrazoles and Tetracyclo[4.1.0.0\(^{2,4}\).0\(^{3,5}\)]heptanes
N2  - No abstract available
KW  - Organische Chemie
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58471
ER  - 
TY  - JOUR
A1  - Gunesch, Sandra
A1  - Hoffmann, Matthias
A1  - Kiermeier, Carolina
A1  - Fischer, Wolfgang
A1  - Pinto, Antonio F. M.
A1  - Maurice, Tangui
A1  - Maher, Pamela
A1  - Decker, Michael
T1  - 7-O-Esters of taxifolin with pronounced and overadditive effects in neuroprotection, anti-neuroinflammation, and amelioration of short-term memory impairment in vivo
JF  - Redox Biology
N2  - Alzheimer's disease (AD) is a multifactorial disease and the most common form of dementia. There are no treatments to cure, prevent or slow down the progression of the disease. Natural products hold considerable interest for the development of preventive neuroprotectants to treat neurodegenerative disorders like AD, due to their low toxicity and general beneficial effects on human health with their anti-inflammatory and antioxidant features. In this work we describe regioselective synthesis of 7-O-ester hybrids of the flavonoid taxifolin with the phenolic acids cinnamic and ferulic acid, namely 7-O-cinnamoyltaxifolin and 7-O-feruloyltaxifolin. The compounds show pronounced overadditive neuroprotective effects against oxytosis, ferroptosis and ATP depletion in the murine hippocampal neuron HT22 cell model. Furthermore, 7-O-cinnamoyltaxifolin and 7-O-feruloyltaxifolin reduced LPS-induced neuroinflammation in BV-2 microglia cells as assessed by effects on the levels of NO, IL6 and TNFα. In all in vitro assays the 7-O-esters of taxifolin and ferulic or cinnamic acid showed strong overadditive activity, significantly exceeding the effects of the individual components and the equimolar mixtures thereof, which were almost inactive in all of the assays at the tested concentrations. In vivo studies confirmed this overadditive effect. Treatment of an AD mouse model based on the injection of oligomerized Aβ\(_{25-35}\) peptide into the brain to cause neurotoxicity and subsequently memory deficits with 7-O-cinnamoyltaxifolin or 7-O-feruloyltaxifolin resulted in improved performance in an assay for short-term memory as compared to vehicle and mice treated with the respective equimolar mixtures. These results highlight the benefits of natural product hybrids as a novel compound class with potential use for drug discovery in neurodegenerative diseases due to their pharmacological profile that is distinct from the individual natural components.
KW  - Alzheimer's disease
KW  - Natural product hybrids
KW  - Flavonoids
KW  - Phenolic acids
KW  - Microglia
KW  - In vivo studies
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202718
VL  - 29
ER  - 
TY  - JOUR
A1  - Leininger, H.
A1  - Kemmer, P.
A1  - Beck, K.
A1  - Christl, M.
T1  - 7-Thiatetracyclo[4.1.0.0\(^{2,4}\).0\(^{3,5}\)]heptan (Benzvalensulfid) - Synthese und Reaktionen
N2  - No abstract available
KW  - Organische Chemie
Y1  - 1982
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58113
ER  - 
TY  - JOUR
A1  - Grunicke, H.
A1  - Pyerin, W.
A1  - Eisenbrand, G.
A1  - Havemann, K.
A1  - Rabes, H. M.
A1  - Molling, K.
A1  - Schwab, M.
A1  - Lutz, Werner K.
A1  - Wahrendorf, J.
A1  - Schirrmacher, V.
T1  - 7th International Symposium of the Division of Experimental Cancer Research (AEK) of the German Cancer Society : [Meeting report]
N2  - No abstract available
KW  - Toxikologie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60651
ER  - 
TY  - JOUR
A1  - Lohse, M. J.
A1  - Klotz, Karl-Norbert
A1  - Lindenborn Fotinos, J.
A1  - Reddington, M.
A1  - Schwabe, U.
A1  - Olsson, R. A.
T1  - 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) - a selective high affinity antagonist radioligand for A\(_1\) adenosine receptors
N2  - The properties of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as an antagonist ligand for A\(_1\) adenosirre receptors were examined and conipared with other radioligands for this receptor. DPCPX competitively antagonized both the inhibition of adenylate cyclase activity via A\(_1\) adenosirre receptors and the stimulationvia A\(_2\) adenosirre receptors. The K\(_i\)-values of this antagonism were 0.45 nM at the A\(_1\) receptor of rat fat cells, and 330 nM at the A\(_2\) receptor of human platelets, giving a more than 700-fold A\(_1\)-selectivity. A similar A\(_1\)-selectivity was determined in radioligand binding studies. Even at high concentrations, DPCPX did not significantly inhibit the soluble cAMPphosphodiesterase activity of human platelets. [\(^3\)H]DPCPX (105 Ci/mmol) bound in a saturable manner with high affinity to A\(_1\) receptors in membranes of bovine brain and heart, and rat brain and fat cells (K\(_D\) -values 50-190 pM). Its nonspecific binding was about 1% of total at K\(_D\) , except in bovine myocardial membranes (about 10%). Binding studies with bovine myocardial membranes allowed the analysis of both the high and low agonist affinity states of this receptor in a tissue with low receptor density. The binding properties of [\(^3\)H]DPCPX appear superior to those of other agonist and antagonist radioligands for the A\(_1\) receptor.
KW  - Toxikologie
KW  - Adenosine receptors
KW  - Adenylate cyclase
KW  - Phosphodiesterase
KW  - Xanthines
KW  - Radioligands
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60246
ER  - 
TY  - JOUR
A1  - Wiese, D.
A1  - Tacke, Reinhold
A1  - Wannagat, U.
T1  - 9,9-Dimethyl-10-(3-dimethylaminopropyl)-9-silaacridan, ein Sila-Analogon des Dimetacrins, und strukturverwandte Verbindungen
T1  - 9,9-Dimethyl-10-(3-dimethylaminopropyl)-9-silaacridane,a Sila-Analogue of Dimetacrine, and Structurally Related Compounds
N2  - Das Sila-Dimetacrin (3a), ein Sila-Analogon des Psychopharmakons Dimetacrin (2), und sein N,N-Diethylderivat 3 b sowie sein 3-Chlorderivat 3 c wurden, von den o-Halogenanilinen 4 a- c ausgehend, über die teilweise unbekannten Stufen 5 a- c bis 10a- d synthetisiert, in ihren Eigenschaften beschrieben und in ihrer Struktur über Elementaranalysen, \(^1\)H-NMR- und Massenspektren sichergestellt. Die Synthese des Zwischenproduktes Bis(2-bromphenyl)amin (9a) konnte optimiert werden.
N2  - Sila-dimetacrine (Ja), a sila-analogue of the psychotropic drug dimetacrine (2), and its N,N-diethyl derivative 3 b as well as its 3-chloro derivative 3 c were synthesized from o-haloanilines 4 a- c via the - partially unknown - intermediates S a- c to 10 a- d. Their properties are described and their structure is confirmed by eiemental analysis, \(^1\)H-NMR, and mass spectroscopy. The preparation of the intermediate bis(2-bromophenyl)amine (9a) could be improved.
KW  - Anorganische Chemie
Y1  - 1981
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63691
ER  - 
TY  - JOUR
A1  - Gerhard-Hartmann, Elena
A1  - Goergen, Helen
A1  - Bröckelmann, Paul J.
A1  - Mottok, Anja
A1  - Steinmüller, Tabea
A1  - Grund, Johanna
A1  - Zamò, Alberto
A1  - Ben-Neriah, Susana
A1  - Sasse, Stephanie
A1  - Borchmann, Sven
A1  - Fuchs, Michael
A1  - Borchmann, Peter
A1  - Reinke, Sarah
A1  - Engert, Andreas
A1  - Veldman, Johanna
A1  - Diepstra, Arjan
A1  - Klapper, Wolfram
A1  - Rosenwald, Andreas
T1  - 9p24.1 alterations and programmed cell death 1 ligand 1 expression in early stage unfavourable classical Hodgkin lymphoma: an analysis from the German Hodgkin Study Group NIVAHL trial
JF  - British Journal of Haematology
N2  - High programmed cell death 1 ligand 1 (PD-L1) protein expression and copy number alterations (CNAs) of the corresponding genomic locus 9p24.1 in Hodgkin- and Reed–Sternberg cells (HRSC) have been shown to be associated with favourable response to anti-PD-1 checkpoint inhibition in relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In the present study, we investigated baseline 9p24.1 status as well as PD-L1 and major histocompatibility complex (MHC) class I and II protein expression in 82 biopsies from patients with early stage unfavourable cHL treated with anti-PD-1-based first-line treatment in the German Hodgkin Study Group (GHSG) NIVAHL trial (ClinicalTrials.gov Identifier: NCT03004833). All evaluated specimens showed 9p24.1 CNA in HRSC to some extent, but with high intratumoral heterogeneity and an overall smaller range of alterations than reported in advanced-stage or r/r cHL. All but two cases (97%) showed PD-L1 expression by the tumour cells in variable amounts. While MHC-I was rarely expressed in >50% of HRSC, MHC-II expression in >50% of HRSC was found more frequently. No obvious impact of 9p24.1 CNA or PD-L1 and MHC-I/II expression on early response to the highly effective anti-PD-1-based NIVAHL first-line treatment was observed. Further studies evaluating an expanded panel of potential biomarkers are needed to optimally stratify anti-PD-1 first-line cHL treatment.
KW  - fluorescence in situ hybridisation
KW  - major histocompatibility complex
KW  - immune checkpoint blockade
KW  - classical Hodgkin lymphoma
KW  - CD274
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258358
VL  - 196
IS  - 1
ER  - 
TY  - JOUR
A1  - Hesselbach, Robert
T1  - <<Nous sommes en guerre sanitaire contre le COVID-19>> – A Corpus-based Approach of Official French, Italian, and Spanish Social Media Discourse in the Light of the Coronavirus Crisis
JF  - promptus - Würzburger Beiträge zur Romanistik
N2  - France, Italy, and Spain are three Romance-speaking countries which – at least in Europe – have been affected to a very high degree by the consequences of the Corona pandemic. This paper examines discursive strategies on social media (Twitter and Facebook) by the three heads of government/state of the aforementioned countries – namely Emmanuel Macron (France), Giuseppe Conte (Italy), and Pedro Sánchez (Spain)- from a corpuslinguistic point of view. For this purpose, a corpus was created which contains all Twitter and Facebook messages posted by these heads of government/state from the beginning of February until the end of April 2020. By applying corpus-linguistic methods we find that all three politicians consciously use social media to sensitize, inform, and – in view of a dramatic pandemic situation – unite their respective populations behind them.
KW  - corpus linguistics
KW  - coronavirus
KW  - Covid-19
KW  - political discourse
KW  - social media
KW  - lexical  co-occurrences
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244251
VL  - 6
ER  - 
TY  - JOUR
A1  - Christl, Manfred
A1  - Buchner, Wolfgang
T1  - <sup>13</sup>C-NMR-Spektren von Tetracyclo[4.1.0.0<sup>2,4</sup>.0<sup>3,5</sup>]heptanen, Tetracyclo[5.1.0.0<sup>2,4</sup>.0<sup>3,5</sup>]octanen und Tricyclo[4.1.0.0<sup>2,7</sup>]hept-3-enen. Ungewöhnliche beta- und gamma-Substituenteneffekte
N2  - No abstract available
Y1  - 1978
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30087
ER  - 
TY  - JOUR
A1  - Nose, Naoko
A1  - Nogami, Suguru
A1  - Koshino, Kazuhiro
A1  - Chen, Xinyu
A1  - Werner, Rudolf A.
A1  - Kashima, Soki
A1  - Rowe, Steven P.
A1  - Lapa, Constantin
A1  - Fukuchi, Kazuki
A1  - Higuchi, Takahiro
T1  - [18F]FDG-labelled stem cell PET imaging in different route of administrations and multiple animal species
JF  - Scientific Reports
N2  - Stem cell therapy holds great promise for tissue regeneration and cancer treatment, although its efficacy is still inconclusive and requires further understanding and optimization of the procedures. Non-invasive cell tracking can provide an important opportunity to monitor in vivo cell distribution in living subjects. Here, using a combination of positron emission tomography (PET) and in vitro 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) direct cell labelling, the feasibility of engrafted stem cell monitoring was tested in multiple animal species. Human mesenchymal stem cells (MSCs) were incubated with phosphate-buffered saline containing [18F]FDG for in vitro cell radiolabelling. The pre-labelled MSCs were administrated via peripheral vein in a mouse (n=1), rats (n=4), rabbits (n=4) and non-human primates (n=3), via carotid artery in rats (n=4) and non-human primates (n=3), and via intra-myocardial injection in rats (n=5). PET imaging was started 10 min after cell administration using a dedicated small animal PET system for a mouse and rats. A clinical PET system was used for the imaging of rabbits and non-human primates. After MSC administration via peripheral vein, PET imaging revealed intense radiotracer signal from the lung in all tested animal species including mouse, rat, rabbit, and non-human primate, suggesting administrated MSCs were trapped in the lung tissue. Furthermore, the distribution of the PET signal significantly differed based on the route of cell administration. Administration via carotid artery showed the highest activity in the head, and intra-myocardial injection increased signal from the heart. In vitro [18F]FDG MSC pre-labelling for PET imaging is feasible and allows non-invasive visualization of initial cell distribution after different routes of cell administration in multiple animal models. Those results highlight the potential use of that imaging approach for the understanding and optimization of stem cell therapy in translational research.
KW  - biomarkers
KW  - molecular medicine
KW  - stem-cell research
KW  - stem cells
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260590
VL  - 11
IS  - 1
ER  - 
TY  - JOUR
A1  - Breun, Maria
A1  - Monoranu, Camelia M.
A1  - Kessler, Almuth F.
A1  - Matthies, Cordula
A1  - Löhr, Mario
A1  - Hagemann, Carsten
A1  - Schirbel, Andreas
A1  - Rowe, Steven P.
A1  - Pomper, Martin G.
A1  - Buck, Andreas K.
A1  - Wester, Hans-Jürgen
A1  - Ernestus, Ralf-Ingo
A1  - Lapa, Constantin
T1  - [\(^{68}\)Ga]-Pentixafor PET/CT for CXCR4-mediated imaging of vestibular schwannomas
JF  - Frontiers in Oncology
N2  - We have recently demonstrated CXCR4 overexpression in vestibular schwannomas (VS). This study investigated the feasibility of CXCR4-directed positron emission tomography/computed tomography (PET/CT) imaging of VS using the radiolabeled chemokine ligand [\(^{68}\)Ga]Pentixafor.

Methods: 4 patients with 6 primarily diagnosed or pre-treated/observed VS were enrolled. All subjects underwent [\(^{68}\)Ga]Pentixafor PET/CT prior to surgical resection. Images were analyzed visually and semi-quantitatively for CXCR4 expression including calculation of tumor-to-background ratios (TBR). Immunohistochemistry served as standard of reference in three patients.

Results: [\(^{68}\)Ga]Pentixafor PET/CT was visually positive in all cases. SUV\(_{mean}\) and SUV\(_{max}\) were 3.0 ± 0.3 and 3.8 ± 0.4 and TBR\(_{mean}\) and TBR\(_{max}\) were 4.0 ± 1.4 and 5.0 ± 1.7, respectively. Histological analysis confirmed CXCR4 expression in tumors.

Conclusion: Non-invasive imaging of CXCR4 expression using [\(^{68}\)Ga]Pentixafor PET/CT of VS is feasible and could prove useful for in vivo assessment of CXCR4 expression.
KW  - vestibular schwannoma
KW  - CXCR4
KW  - PET/CT
KW  - molecular imaging
KW  - Pentixafor
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201863
VL  - 9
IS  - 503
ER  - 
TY  - JOUR
A1  - Lapa, Constantin
A1  - Schreder, Martin
A1  - Schirbel, Andreas
A1  - Samnick, Samuel
A1  - Kortüm, Klaus Martin
A1  - Herrmann, Ken
A1  - Kropf, Saskia
A1  - Einsele, Herrmann
A1  - Buck, Andreas K.
A1  - Wester, Hans-Jürgen
A1  - Knop, Stefan
A1  - Lückerath, Katharina
T1  - [\(^{68}\)Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - comparison to [\(^{18}\)F]FDG and laboratory values
JF  - Theranostics
N2  - Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [\(^{68}\)Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies.

Thirty-five patients with MM underwent [\(^{68}\)Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [\(^{18}\)F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity.

[\(^{68}\)Ga]Pentixafor-PET detected CXCR4-positive disease in 23/35 subjects (66%). CXCR4-positivity at PET was independent from myeloma subtypes, cytogenetics or any serological parameters and turned out as a negative prognostic factor. In the 19 patients in whom a comparison to [\(^{18}\)F]FDG was available, [\(^{68}\)Ga]Pentixafor-PET detected more lesions in 4/19 (21%) subjects, [\(^{18}\)F]FDG proved superior in 7/19 (37%). In the remaining 8/19 (42%) patients, both tracers detected an equal number of lesions. [\(^{18}\)F]FDG-PET positivity correlated with [\(^{68}\)Ga]Pentixafor-PET positivity (p=0.018).

[\(^{68}\)Ga]Pentixafor-PET provides further evidence that CXCR4 expression frequently occurs in advanced multiple myeloma, representing a negative prognostic factor and a potential target for myeloma specific treatment. However, selecting patients for CXCR4 directed therapies and prognostic stratification seem to be more relevant clinical applications for this novel imaging modality, rather than diagnostic imaging of myeloma.
KW  - medicine
KW  - multiple myeloma
KW  - FDG
KW  - molecular imaging
KW  - CXCR4
KW  - PET
KW  - radionuclide therapy
KW  - theranostics
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172106
VL  - 7
IS  - 1
ER  - 
TY  - JOUR
A1  - Ewing, William C.
A1  - Dellermann, Theresa
A1  - Angel Wong, Y. T.
A1  - Mattock, James D.
A1  - Vargas, Alfredo
A1  - Bryce, David L.
A1  - Dewhurst, Rian D.
A1  - Braunschweig, Holger
T1  - \(\pi\)‐Complexes of Diborynes with Main Group Atoms
JF  - Chemistry – An Asian Journal
N2  - We present herein an in‐depth study of complexes in which a molecule containing a boron‐boron triple bond is bound to tellurate cations. The analysis allows the description of these salts as true π complexes between the B−B triple bond and the tellurium center. These complexes thus extend the well‐known Dewar‐Chatt‐Duncanson model of bonding to compounds made up solely of p block elements. Structural, spectroscopic and computational evidence is offered to argue that a set of recently reported heterocycles consisting of phenyltellurium cations complexed to diborynes bear all the hallmarks of \(\pi\)‐complexes in the \(\pi\)‐complex/metallacycle continuum envisioned by Joseph Chatt. Described as such, these compounds are unique in representing the extreme of a metal‐free continuum with conventional unsaturated three‐membered rings (cyclopropenes, azirenes, borirenes) occupying the opposite end.
KW  - boron
KW  - main group elements
KW  - solid-state NMR
KW  - \(\pi\) interactions
KW  - multiple bonds
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214677
VL  - 15
IS  - 10
SP  - 1553
EP  - 1557
ER  - 
TY  - JOUR
A1  - Lapa, Constantin
A1  - Garcia-Velloso, Maria J.
A1  - Lückerath, Katharina
A1  - Samnick, Samuel
A1  - Schreder, Martin
A1  - Otero, Paula Rodriguez
A1  - Schmid, Jan-Stefan
A1  - Herrmann, Ken
A1  - Knop, Stefan
A1  - Buck, Andreas K.
A1  - Einsele, Hermann
A1  - San-Miguel, Jesus
A1  - Kortüm, Klaus Martin
T1  - \(^{11}\)C-methionine-PET in multiple myeloma: a combined study from two different institutions
JF  - Theranostics
N2  - \(^{11}\)C-methionine (MET) has recently emerged as an accurate marker of tumor burden and disease activity in patients with multiple myeloma (MM). This dual-center study aimed at further corroboration of the superiority of MET as positron emission tomography (PET) tracer for staging and re-staging MM, as compared to \(^{18}\)F-2`-deoxy-2`-fluoro-D-glucose (FDG).
78 patients with a history of solitary plasmacytoma (n=4), smoldering MM (SMM, n=5), and symptomatic MM (n=69) underwent both MET- and FDG-PET/computed tomography (CT) at the University Centers of Würzburg, Germany and Navarra, Spain. Scans were compared on a patient and on a lesion basis. Inter-reader agreement was also evaluated. In 2 patients, tumor biopsies for verification of discordant imaging results were available.
MET-PET detected focal lesions (FL) in 59/78 subjects (75.6%), whereas FDG-PET/CT showed lesions in only 47 patients (60.3%; p<0.01), accordingly disease activity would have been missed in 12 patients. Directed biopsies of discordant results confirmed MET-PET/CT results in both cases.
MET depicted more FL in 44 patients (56.4%; p<0.01), whereas in two patients (2/78), FDG proved superior. In the remainder (41.0%, 32/78), both tracers yielded comparable results. Inter-reader agreement for MET was higher than for FDG (κ = 0.82 vs κ = 0.72).
This study demonstrates higher sensitivity of MET in comparison to standard FDG to detect intra- and extramedullary MM including histologic evidence of FDG-negative, viable disease exclusively detectable by MET-PET/CT. MET holds the potential to replace FDG as functional imaging standard for staging and re-staging of MM.
KW  - medicine
KW  - PET/CT
KW  - \(^{11}\)C-methionine
KW  - multiple myeloma
KW  - FDG
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172038
VL  - 7
IS  - 11
ER  - 
TY  - JOUR
A1  - Lückerath, Katharina
A1  - Lapa, Constantin
A1  - Albert, Christa
A1  - Herrmann, Ken
A1  - Jörg, Gerhard
A1  - Samnick, Samuel
A1  - Einsele, Herrmann
A1  - Knop, Stefan
A1  - Buck, Andreas K.
T1  - \(^{11}\)C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma
JF  - Oncotarget
N2  - Multiple myeloma (MM) remains an essentially incurable hematologic malignancy. However, new treatment modalities and novel drugs have been introduced and thus additional tools for therapy monitoring are increasingly needed. Therefore, we evaluated the radiotracers \(^{11}\)C-Methionine (paraprotein-biosynthesis) and \(^{18}\)F-FDG (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome prediction. Influence of proteasome-inhibition on radiotracer-uptake of different MM cell-lines and patient-derived CD138\(^{+}\) plasma cells was analyzed and related to tumor-biology. Mice xenotransplanted with MM. 1S tumors underwent MET- and FDG-\(\mu\)PET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment with bortezomib were correlated to survival. Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by 30-79% as early as 24 h after bortezomib injection. No significant differences were detected thus early with FDG. This finding was confirmed in patient-derived MM cells. Importantly, early reduction of MET-but not FDG-uptake correlated with improved survival and reduced tumor burden in mice. Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy. Early changes in MET-uptake have predictive potential regarding response and survival. MET-PET holds promise to individualize therapies in MM in future.
KW  - positron emission tomography
KW  - imaging techniques
KW  - experience
KW  - \(^{11}\)C-Methionine-PET
KW  - treatment response
KW  - molecular imaging
KW  - multiple myeloma
KW  - management
KW  - \(^{18}\)F-FDG PET/CT
KW  - bone disease
KW  - stem-cell transplantation
KW  - esophagogastric junction
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148688
VL  - 6
IS  - 10
ER  - 
TY  - JOUR
A1  - Christl, Manfred
T1  - \(^{13}\)-NMR-Spektren von Bicyclo[n.1.0]kohlenwasserstoffen
N2  - No abstract available
KW  - Organische Chemie
Y1  - 1975
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-57977
ER  - 
TY  - JOUR
A1  - Christl, Manfred
A1  - Warren, J. D.
A1  - Hawkins, B. L.
A1  - Roberts, J. D.
T1  - \(^{13}\)C and \(^{15}\)N Nuclear Magnetic Resonance Spectroscopy of Nitrile Oxides and Related Reaction Products : Unexpected \(^{13}\)C and \(^{15}\)N Nuclear Magnetic Resonance Parameters of 2,4,6-Trimethylbenzonitrile Oxide
N2  - No abstract available
KW  - Organische Chemie
Y1  - 1973
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-57894
ER  - 
TY  - JOUR
A1  - Christl, Manfred
A1  - Herzog, C.
T1  - \(^{13}\)C-NMR-Spektroskopie: Besondere Hochfeldeffekte in Bicyclo[4.1.1]- und Tricyclo[5.1.0.0\(^{2,8}\)]octan-Systemen (1,3-Cycloheptadien-Effekt) und besondere Tieffeldeffekte in Dihalogenbicyclo[2.1.1]hex-2-enen (Cyclopenten-Effekt)
N2  - No abstract available
KW  - Organische Chemie
Y1  - 1986
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58334
ER  - 
TY  - JOUR
A1  - Beykan, Seval
A1  - Dam, Jan S.
A1  - Eberlein, Uta
A1  - Kaufmann, Jens
A1  - Kjærgaard, Benedict
A1  - Jødal, Lars
A1  - Bouterfa, Hakim
A1  - Bejot, Romain
A1  - Lassmann, Michael
A1  - Jensen, Svend Borup
T1  - \(^{177}\)Lu-OPS201 targeting somatostatin receptors: in vivo biodistribution and dosimetry in a pig model
JF  - EJNMMI Research
N2  - Background

\(^{177}\)Lu is used in peptide receptor radionuclide therapies for the treatment of neuroendocrine tumors. Based on the recent literature, SST2 antagonists are superior to agonists in tumor uptake. The compound OPS201 is the novel somatostatin antagonist showing the highest SST2 affinity. The aim of this study was to measure the in vivo biodistribution and dosimetry of \(^{177}\)Lu-OPS201 in five anesthetized Danish Landrace pigs as an appropriate substitute for humans to quantitatively assess the absorbed doses for future clinical applications.

Results

\(^{177}\)Lu-OPS201 was obtained with a specific activity ranging from 10 to 17 MBq/μg. Prior to administration, the radiochemical purity was measured as s > 99.7 % in all cases. After injection, fast clearance of the compound from the blood stream was observed. Less than 5 % of the injected activity was presented in blood 10 min after injection. A series of SPECT/CT and whole-body scans conducted until 10 days after intravenous injection showed uptake mostly in the liver, spine, and kidneys. There was no visible uptake in the spleen. Blood samples were taken to determine the time-activity curve in the blood. Time-activity curves and time-integrated activity coefficients were calculated for the organs showing visible uptake. Based on these data, the absorbed organ dose coefficients for a 70-kg patient were calculated with OLINDA/EXM. For humans after an injection of 5 GBq \(^{177}\)Lu-OPS201, the highest predicted absorbed doses are obtained for the kidneys (13.7 Gy), the osteogenic cells (3.9 Gy), the urinary bladder wall (1.8 Gy), and the liver (1.0 Gy). No metabolites of 177Lu-OPS201 were found by radio HPLC analysis. None of the absorbed doses calculated will exceed organ toxicity levels.

Conclusions

The \(^{177}\)Lu-OPS201 was well tolerated and caused no abnormal physiological or behavioral signs. In vivo distributions and absorbed doses of pigs are comparable to those observed in other publications. According to the biodistribution data in pigs, presented in this work, the expected radiation exposure in humans will be within the acceptable range.
KW  - lutetium-177
KW  - JR11
KW  - antagonist
KW  - dosimetry
KW  - neuroendocrine tumor (NET)
KW  - OPS201
KW  - pig model
KW  - PRRT
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146888
VL  - 6
IS  - 50
ER  - 
TY  - JOUR
A1  - Morales-Lozano, Maria I.
A1  - Viering, Oliver
A1  - Samnick, Samuel
A1  - Rodriguez-Otero, Paula
A1  - Buck, Andreas K.
A1  - Marcos-Jubilar, Maria
A1  - Rasche, Leo
A1  - Prieto, Elena
A1  - Kortüm, K. Martin
A1  - San-Miguel, Jesus
A1  - Garcia-Velloso, Maria J.
A1  - Lapa, Constantin
T1  - \(^{18}\)F-FDG and \(^{11}\)C-methionine PET/CT in newly diagnosed multiple myeloma patients: comparison of volume-based PET biomarkers
JF  - Cancers
N2  - \(^{11}\)C-methionine (\(^{11}\)C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher sensitivity and specificity than \(^{18}\)F-fluorodeoxyglucose (\(^{18}\)F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of \(^{11}\)C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to \(^{18}\)F-FDG. Twenty-two patients with newly diagnosed, treatment-naïve symptomatic MM who had undergone \(^{11}\)C-MET and \(^{18}\)F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion \(^{11}\)C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), \(^{11}\)C-MET detected more focal lesions (FL) than FDG (p < 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in \(^{11}\)C-MET than in \(^{18}\)F-FDG (p < 0.05, respectively). \(^{11}\)C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component; p < 0.05 versus p = n.s. respectively). This pilot study suggests that \(^{11}\)C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than \(^{18}\)F-FDG. Its implications for prognosis evaluation need further investigation.
KW  - multiple myeloma
KW  - methionine
KW  - total lesion glycolysis (TLG)
KW  - metabolic tumor volume (MTV)
KW  - total lesion methionine uptake (TLMU)
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203686
SN  - 2072-6694
VL  - 12
IS  - 4
ER  - 
TY  - JOUR
A1  - Werner, Rudolf A.
A1  - Derlin, Thorsten
A1  - Lapa, Constantin
A1  - Sheikbahaei, Sara
A1  - Higuchi, Takahiro
A1  - Giesel, Frederik L.
A1  - Behr, Spencer
A1  - Drzezga, Alexander
A1  - Kimura, Hiroyuki
A1  - Buck, Andreas K.
A1  - Bengel, Frank M.
A1  - Pomper, Martin G.
A1  - Gorin, Michael A.
A1  - Rowe, Steven P.
T1  - \(^{18}\)F-labeled, PSMA-targeted radiotracers: leveraging the advantages of radiofluorination for prostate cancer molecular imaging
JF  - Theranostics
N2  - Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with \(^{68}\)Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from \(^{68}\)Ga- to \(^{18}\)F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite \(^{68}\)Ge/\(^{68}\)Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, \(^{18}\)F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, \(^{18}\)F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging \(^{18}\)F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available \(^{18}\)F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.
KW  - Radiofluorine
KW  - prostate-specific membrane antigen
KW  - prostate cancer
KW  - \(^{18}\)F
KW  - PSMA
KW  - \(^{68}\)Ga
KW  - theranostics
KW  - radioligand therapy
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202559
SN  - 1838-7640
VL  - 10
IS  - 1
ER  - 
TY  - JOUR
A1  - Hertlein, Tobias
A1  - Sturm, Volker
A1  - Jakob, Peter
A1  - Ohlsen, Knut
T1  - \(^{19}\)F Magnetic Resonance Imaging of Perfluorocarbons for the Evaluation of Response to Antibiotic Therapy in a Staphylococcus aureus Infection Model
JF  - PLoS ONE
N2  - Background
The emergence of antibiotic resistant bacteria in recent decades has highlighted the importance of developing new drugs to treat infections. However, in addition to the design of new drugs, the development of accurate preclinical testing methods is essential. In vivo imaging technologies such as bioluminescence imaging (BLI) or magnetic resonance imaging (MRI) are promising approaches. In a previous study, we showed the effectiveness of \(^{19}\)F MRI using perfluorocarbon (PFC) emulsions for detecting the site of Staphylococcus aureus infection. In the present follow-up study, we investigated the use of this method for in vivo visualization of the effects of antibiotic therapy.

Methods/Principal findings
Mice were infected with S. aureus Xen29 and treated with 0.9% NaCl solution, vancomycin or linezolid. Mock treatment led to the highest bioluminescence values during infection followed by vancomycin treatment. Counting the number of colony-forming units (cfu) at 7 days post-infection (p.i.) showed the highest bacterial burden for the mock group and the lowest for the linezolid group. Administration of PFCs at day 2 p.i. led to the accumulation of \(^{19}\)F at the rim of the abscess in all mice (in the shape of a hollow sphere), and antibiotic treatment decreased the \(^{19}\)F signal intensity and volume. Linezolid showed the strongest effect. The BLI, cfu, and MRI results were comparable.

Conclusions
\(^{19}\)F-MRI with PFCs is an effective non-invasive method for assessing the effects of antibiotic therapy in vivo. This method does not depend on pathogen specific markers and can therefore be used to estimate the efficacy of antibacterial therapy against a broad range of clinically relevant pathogens, and to localize sites of infection.
KW  - staphylococcus aureus
KW  - abscesses
KW  - vancomycin
KW  - antibiotics
KW  - magnetic resonance imaging
KW  - emulsions
KW  - bioluminescence imaging
KW  - in vivo imaging
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130113
VL  - 8
IS  - 5
ER  - 
TY  - JOUR
A1  - Lapa, Constantin
A1  - Lückerath, Katharina
A1  - Kleinlein, Irene
A1  - Monoranu, Camelia Maria
A1  - Linsenmann, Thomas
A1  - Kessler, Almuth F.
A1  - Rudelius, Martina
A1  - Kropf, Saskia
A1  - Buck, Andreas K.
A1  - Ernestus, Ralf-Ingo
A1  - Wester, Hans-Jürgen
A1  - Löhr, Mario
A1  - Herrmann, Ken
T1  - \(^{68}\)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma
JF  - Theranostics
N2  - Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand \(^{68}\)Ga-Pentixafor.
15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent \(^{68}\)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-\(^{18}\)F-fluoroethyl)-L-tyrosine (\(^{18}\)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUV\(_{max}\), SUV\(_{mean}\)). Tumor-to-background ratios (TBR) were calculated for both PET probes. \(^{68}\)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples.
\(^{68}\)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUV\(_{mean}\) and SUV\(_{max}\) of 3.0±1.5 and 3.9±2.0 respectively. Respective values for \(^{18}\)F-FET were 4.4±2.0 (SUV\(_{mean}\)) and 5.3±2.3 (SUV\(_{max}\)). TBR for SUV\(_{mean}\) and SUV\(_{max}\) were higher for \(^{68}\)Ga-Pentixafor than for \(^{18}\)F-FET (SUV\(_{mean}\) 154.0±90.7 vs. 4.1±1.3; SUV\(_{max}\) 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high \(^{68}\)Ga-Pentixafor uptake; regions of the same tumor without apparent \(^{68}\)Ga-Pentixafor uptake showed no or low receptor expression.
In this pilot study, \(^{68}\)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, \(^{68}\)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy.
KW  - imaging
KW  - chemokine receptor-4
KW  - glioblastoma
KW  - positron emission tomography/computed tomography
KW  - \(^{68}\)Ga-Pentixafor
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168174
VL  - 6
IS  - 3
ER  - 
TY  - JOUR
A1  - Goettel, James T.
A1  - Gao, Haopeng
A1  - Dotzauer, Simon
A1  - Braunschweig, Holger
T1  - \(^{Me}\)CAAC=N\(^{-}\): A Cyclic (Alkyl)(Amino)Carbene Imino Ligand
JF  - Chemistry – A European Journal
N2  - A cyclic (alkyl)(amino)carbene (CAAC) has been shown to react with a covalent azide similar to the Staudinger reaction. The reaction of \(^{Me}\)CAAC with trimethylsilyl azide afforded the N‐silylated 2‐iminopyrrolidine (\(^{Me}\)CAAC=NSiMe\(_{3}\)), which was fully characterized. This compound undergoes hydrolysis to afford the 2‐iminopyrrolidine and trimethylsiloxane which co‐crystallize as a hydrogen‐bonded adduct. The N‐silylated 2‐iminopyrrolidine was used to transfer the novel pyrrolidine‐2‐iminato ligand onto both main‐group and transition‐metal centers. The reaction of the tetrabromodiborane bis(dimethyl sulfide) adduct with two equivalents of \(^{Me}\)CAAC=NSiMe\(_{3}\) afforded the disubstituted diborane. The reaction of \(^{Me}\)CAAC=NSiMe\(_{3}\) with TiCl\(_{4}\) and CpTiCl\(_{3}\) afforded \(^{Me}\)CAAC=NTiCl\(_{3}\) and \(^{Me}\)CAAC=NTiCl\(_{2}\)Cp, respectively.
KW  - boron
KW  - carbenes
KW  - imide ligands
KW  - nitrogen ligands
KW  - titanium
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212662
VL  - 26
IS  - 5
ER  - 
TY  - JOUR
A1  - Zopf, Kathrin
A1  - Frey, Kathrin R.
A1  - Kienitz, Tina
A1  - Ventz, Manfred
A1  - Bauer, Britta
A1  - Quinkler, Marcus
T1  - \(Bcl\)I polymorphism of the glucocorticoid receptor and adrenal crisis in primary adrenal insufficiency
JF  - Endocrine Connections
N2  - Context: Patients with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) are at a high risk of adrenal crisis (AC). Glucocorticoid sensitivity is at least partially genetically determined by polymorphisms of the glucocorticoid receptor (GR).
Objectives: To determine if a number of intercurrent illnesses and AC are associated with the GR gene polymorphism \(Bcl\)I in patients with PAI and CAH.
Design and patients: This prospective, longitudinal study over 37.7 ± 10.1 months included 47 PAI and 25 CAH patients. During the study period, intercurrent illness episodes and AC were documented.
Results: The study period covered 223 patient years in which 21 AC occurred (9.4 AC/100 pat years). There were no significant differences between \(Bcl\)I polymorphisms (CC (n=29), CG (n=34) and GG (n=9)) regarding BMI, hydrocortisone equivalent daily dose and blood pressure. We did not find a difference in the number of intercurrent illnesses/patient year among \(Bcl\)I polymorphisms (CC (1.5±1.4/pat year), CG (1.2±1.2/pat year) and GG (1.6±2.2/pat year)). The occurrence of AC was not significantly different among the homozygous (GG) genotype (32.5 AC/100 pat years), the CC genotype (6.7 AC/100 pat years) and the CG genotype (4.9 AC/100 pat years). Concomitant hypothyroidism was the highest in the GG genotype group (5/9), compared to others (CC (11/29) and CG (11/34)).
Conclusions: Although sample sizes were relatively small and results should be interpreted with caution, this study suggests that the GR gene polymorphism \(Bcl\)I may not be associated with the frequencies of intercurrent illnesses and AC.
KW  - medicine
KW  - adrenal crisis
KW  - adrenal insufficiency
KW  - cortisol
KW  - hydrocortisone
KW  - polyglandular autoimmune syndrome
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173276
VL  - 6
IS  - 8
ER  - 
TY  - JOUR
A1  - Allert, Stefanie
A1  - Förster, Toni M.
A1  - Svensson, Carl-Magnus
A1  - Richardson, Jonathan P.
A1  - Pawlik, Tony
A1  - Hebecker, Betty
A1  - Rudolphi, Sven
A1  - Juraschitz, Marc
A1  - Schaller, Martin
A1  - Blagojevic, Mariana
A1  - Morschhäuser, Joachim
A1  - Figge, Marc Thilo
A1  - Jacobsen, Ilse D.
A1  - Naglik, Julian R.
A1  - Kasper, Lydia
A1  - Mogavero, Selene
A1  - Hube, Bernhard
T1  - \(Candida\) \(albicans\)-Induced Epithelial Damage Mediates Translocation through Intestinal Barriers
JF  - mBio
N2  - Life-threatening systemic infections often occur due to the translocation of pathogens across the gut barrier and into the bloodstream. While the microbial and host mechanisms permitting bacterial gut translocation are well characterized, these mechanisms are still unclear for fungal pathogens such as Candida albicans, a leading cause of nosocomial fungal bloodstream infections. In this study, we dissected the cellular mechanisms of translocation of C. albicans across intestinal epithelia in vitro and identified fungal genes associated with this process. We show that fungal translocation is a dynamic process initiated by invasion and followed by cellular damage and loss of epithelial integrity. A screen of >2,000 C. albicans deletion mutants identified genes required for cellular damage of and translocation across enterocytes. Correlation analysis suggests that hypha formation, barrier damage above a minimum threshold level, and a decreased epithelial integrity are required for efficient fungal translocation. Translocation occurs predominantly via a transcellular route, which is associated with fungus-induced necrotic epithelial damage, but not apoptotic cell death. The cytolytic peptide toxin of C. albicans, candidalysin, was found to be essential for damage of enterocytes and was a key factor in subsequent fungal translocation, suggesting that transcellular translocation of C. albicans through intestinal layers is mediated by candidalysin. However, fungal invasion and low-level translocation can also occur via non-transcellular routes in a candidalysin-independent manner. This is the first study showing translocation of a human-pathogenic fungus across the intestinal barrier being mediated by a peptide toxin. IMPORTANCE Candida albicans, usually a harmless fungus colonizing human mucosae, can cause lethal bloodstream infections when it manages to translocate across the intestinal epithelium. This can result from antibiotic treatment, immune dysfunction, or intestinal damage (e.g., during surgery). However, fungal processes may also contribute. In this study, we investigated the translocation process of C. albicans using in vitro cell culture models. Translocation occurs as a stepwise process starting with invasion, followed by epithelial damage and loss of epithelial integrity. The ability to secrete candidalysin, a peptide toxin deriving from the hyphal protein Ece1, is key: C. albicans hyphae, secreting candidalysin, take advantage of a necrotic weakened epithelium to translocate through the intestinal layer.
KW  - Candida albicans
KW  - candidalysin
KW  - host cell damage
KW  - host cell invasion
KW  - intestinal barrier
KW  - necrosis
KW  - translocation
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221084
VL  - 9
IS  - 3
ER  - 
TY  - JOUR
A1  - Kühlhorn, Franziska
A1  - Rath, Matthias
A1  - Schmoeckel, Katrin
A1  - Cziupka, Katharina
A1  - Nguyen, Huu Hung
A1  - Hildebrandt, Petra
A1  - Hünig, Thomas
A1  - Sparwasser, Tim
A1  - Huehn, Jochen
A1  - Pötschke, Christian
A1  - Bröker, Barbara M.
T1  - \(Foxp3^+\) Regulatory T Cells Are Required for Recovery from Severe Sepsis
JF  - PLoS ONE
N2  - The role of regulatory T cells (Tregs) in bacterial sepsis remains controversial because antibody-mediated depletion experiments gave conflicting results. We employed DEREG mice (DEpletion of REGulatory T cells) and a caecal ligation and puncture model to elucidate the role of \(CD4^+Foxp3^+\) Tregs in sepsis. In DEREG mice natural Tregs can be visualized easily and selectively depleted by diphtheria toxin because the animals express the diphtheria toxin receptor and enhanced green fluorescent protein as a fusion protein under the control of the foxp3 locus. We confirmed rapid Treg-activation and an increased ratio of Tregs to Teffs in sepsis. Nevertheless, 24 h after sepsis induction, Treg-depleted and control mice showed equally strong inflammation, immune cell immigration into the peritoneum and bacterial dissemination. During the first 36 h of disease survival was not influenced by Treg-depletion. Later, however, only Treg-competent animals recovered from the insult. We conclude that the suppressive capacity of Tregs is not sufficient to control overwhelming inflammation and early mortality, but is a prerequisite for the recovery from severe sepsis.
KW  - CD4(+)CD25(+)
KW  - toll-like receptors
KW  - TGF-BETA
KW  - mediated suppression
KW  - polymicrobial sepsis
KW  - improves survival
KW  - adoptive transfer
KW  - infected mice
KW  - in-vivo
KW  - CD4(+)
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130940
VL  - 8
IS  - 5
ER  - 
TY  - JOUR
A1  - Breyer, Maximilian
A1  - Grüner, Julia
A1  - Klein, Alexandra
A1  - Finke, Laura
A1  - Klug, Katharina
A1  - Sauer, Markus
A1  - Üçeyler, Nurcan
T1  - \(In\) \(vitro\) characterization of cells derived from a patient with the GLA variant c.376A>G (p.S126G) highlights a non-pathogenic role in Fabry disease
JF  - Molecular Genetics and Metabolism Reports
N2  - Highlights
• The GLA variant S126G is not associated with Fabry symptoms in the presented case
• S126G has no effect on α-GAL A activity or Gb3 levels in this patient
• S126G sensory neurons show no electrophysiological abnormalities

Abstract
Fabry disease (FD) is a life-limiting disorder characterized by intracellular globotriaosylceramide (Gb3) accumulations. The underlying α-galactosidase A (α-GAL A) deficiency is caused by variants in the gene GLA. Variants of unknown significance (VUS) are frequently found in GLA and challenge clinical management. Here, we investigated a 49-year old man with cryptogenic lacunar cerebral stroke and the chance finding of the VUS S126G, who was sent to our center for diagnosis and initiation of a costly and life-long FD-specific treatment. We combined clinical examination with in vitro investigations of dermal fibroblasts (HDF), induced pluripotent stem cells (iPSC), and iPSC-derived sensory neurons. We analyzed α-GAL A activity in iPSC, Gb3 accumulation in all three cell types, and action potential firing in sensory neurons. Neurological examination and small nerve fiber assessment was normal except for reduced distal skin innervation. S126G iPSC showed normal α-GAL A activity compared to controls and no Gb3 deposits were found in all three cell types. Baseline electrophysiological characteristics of S126G neurons showed no difference compared to healthy controls as investigated by patch-clamp recordings. We pioneer multi-level cellular characterization of the VUS S126G using three cell types derived from a patient and provide further evidence for the benign nature of S126G in GLA, which is of great importance in the management of such cases in clinical practice.
KW  - Fabry disease
KW  - variants of unknown significance
KW  - C.376A>G (p.S126G)
KW  - globotriaosylceramide
KW  - induced pluripotent stem cells
KW  - sensory neurons
KW  - disease model
KW  - α-Galactosidase A
Y1  - 2024
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350295
SN  - 22144269
VL  - 38
ER  - 
TY  - JOUR
A1  - Pötters, Wilhelm
ED  - Hornung, Christoph
ED  - Lambrecht, Gabriella-Maria
ED  - Sendner, Annika
T1  - \(Spagna\) in Dantes poetischer Kosmologie
JF  - Kommunikation und Repräsentation in den romanischen Kulturen. Festschrift für Gerhard Penzkofer
N2  - Verstreut über den ganzen Text der Göttlichen Komödie kommen verschiedene geographische Namen vor, die sich auf Spanien beziehen. In mehreren dieser Fälle hat Dante die im wörtlichen Schriftsinn verwendeten toponymischen Zeichen als Elemente hermetisch wirkender Aussagen und damit offenbar als Indizien einer verborgenen Botschaft konzipiert. Zum Nachweis dieser These soll in den folgenden Betrachtungen erkundet werden, welche Funktion den im wissenschaftlichen Weltbild des Dichters verankerten spanischen Land- und Städtenamen in der Komposition des Epos zukommt. Damit möchte ich meinem Kollegen und Freund Gerhard Penzkofer für die vielen anregenden Gespräche danken, die wir – in den Jahren der gemeinsamen Tätigkeit in der Würzburger Romanistik – vor allem über cosas de España führen konnten. Da der vorliegende Band unter den von seiner Lehre inspirierten Leitbegriffen Kommunikation und Repräsentation steht, bietet es sich am Schluss an, die beiden Konzepte mit den vom Dichter diskutierten Termini sensus litteralis und sensus allegoricus in Beziehung zu setzen.
KW  - Dante
KW  - Spanien
KW  - Dante, Alighieri
KW  - Dante, Alighieri : Divina commedia
KW  - Göttliche Komödie
KW  - Spanien
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-152077
UR  - https://www.avm-verlag.de/detailview?no=5477-055
SN  - 9783954770557
PB  - AVM.edition
CY  - München
ER  - 
TY  - JOUR
A1  - Jannasch, Maren
A1  - Weigel, Tobias
A1  - Engelhardt, Lisa
A1  - Wiezoreck, Judith
A1  - Gaetzner, Sabine
A1  - Walles, Heike
A1  - Schmitz, Tobias
A1  - Hansmann, Jan
T1  - \({In}\) \({vitro}\) chemotaxis and tissue remodeling assays quantitatively characterize foreign body reaction
JF  - ALTEX - Alternatives to Animal Experimentation
N2  - Surgical implantation of a biomaterial triggers foreign-body-induced fibrous encapsulation. Two major mechanisms of this complex physiological process are (I) chemotaxis of fibroblasts from surrounding tissue to the implant region, followed by (II) tissue remodeling. As an alternative to animal studies, we here propose a process-aligned \({in}\) \({vitro}\) test platform to investigate the material dependency of fibroblast chemotaxis and tissue remodeling mediated by material-resident macrophages.
Embedded in a biomimetic three-dimensional collagen hydrogel, chemotaxis of fibroblasts in the direction of macrophage-material-conditioned cell culture supernatant was analyzed by live cell imaging. A combination of statistical analysis with a complementary parameterized random walk model allowed quantitative and qualitative characterization of the cellular walk process. We thereby identified an increasing macrophage-mediated chemotactic potential ranking of biomaterials from glass over polytetrafluorethylene to titanium. To address long-term effects of biomaterial-resident macrophages on fibroblasts in a three-dimensional microenvironment, we further studied tissue remodeling by applying macrophage-material-conditioned medium on fibrous \({in}\) \({vitro}\) tissue models. A high correlation of the \({in}\) \({vitro}\) tissue model to state of the art \({in}\) \({vivo}\) study data was found. Titanium exhibited a significantly lower tissue remodeling capacity compared to polytetrafluorethylene. With this approach, we identified a material dependency of both chemotaxis and tissue remodeling processes, strengthening knowledge on their specific contribution to the foreign body reaction.
KW  - medicine
KW  - foreign body reaction
KW  - fibroblast chemotaxis
KW  - tissue remodeling
KW  - in vitro
KW  - quanititative characterization
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172080
VL  - 34
IS  - 2
ER  - 
TY  - JOUR
T1  - \({ZZ}\) -> l(+)l(-)l '(+)l '(-) cross-section measurements and search for anomalous triple gauge couplings in 13 TeV \({pp}\) collisions with the ATLAS detector
JF  - Physical Review D
N2  - Measurements of ZZ production in the l(+)l(-)l'(+)l'(-) channel in proton-proton collisions at 13 TeV center-of-mass energy at the Large Hadron Collider are presented. The data correspond to 36.1 fb(-1) of collisions collected by the ATLAS experiment in 2015 and 2016. Here l and l ' stand for electrons or muons. Integrated and differential ZZ -> l(+)l(-)l'(+)l'(-) cross sections with Z -> l(+)l(-) candidate masses in the range of 66 GeV to 116 GeV are measured in a fiducial phase space corresponding to the detector acceptance and corrected for detector effects. The differential cross sections are presented in bins of twenty observables, including several that describe the jet activity. The integrated cross section is also extrapolated to a total phase space and to all standard model decays of Z bosons with mass between 66 GeV and 116 GeV, resulting in a value of 17.3 +/- 0.9 [+/- 0.6(start) +/- 0.5 (syst) +/- 0.6 (lumi)] pb. The measurements are found to be in good agreement with the standard model. A search for neutral triple gauge couplings is performed using the transverse momentum distribution of the leading Z boson candidate. No evidence for such couplings is found and exclusion limits are set on their parameters.
KW  - Parton Distributions
KW  - Events
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225844
VL  - 97
IS  - 3
ER  - 
TY  - JOUR
A1  - Massih, Bita
A1  - Veh, Alexander
A1  - Schenke, Maren
A1  - Mungwa, Simon
A1  - Seeger, Bettina
A1  - Selvaraj, Bhuvaneish T.
A1  - Chandran, Siddharthan
A1  - Reinhardt, Peter
A1  - Sterneckert, Jared
A1  - Hermann, Andreas
A1  - Sendtner, Michael
A1  - Lüningschrör, Patrick
T1  - A 3D cell culture system for bioengineering human neuromuscular junctions to model ALS
JF  - Frontiers in Cell and Developmental Biology
N2  - The signals that coordinate and control movement in vertebrates are transmitted from motoneurons (MNs) to their target muscle cells at neuromuscular junctions (NMJs). Human NMJs display unique structural and physiological features, which make them vulnerable to pathological processes. NMJs are an early target in the pathology of motoneuron diseases (MND). Synaptic dysfunction and synapse elimination precede MN loss suggesting that the NMJ is the starting point of the pathophysiological cascade leading to MN death. Therefore, the study of human MNs in health and disease requires cell culture systems that enable the connection to their target muscle cells for NMJ formation. Here, we present a human neuromuscular co-culture system consisting of induced pluripotent stem cell (iPSC)-derived MNs and 3D skeletal muscle tissue derived from myoblasts. We used self-microfabricated silicone dishes combined with Velcro hooks to support the formation of 3D muscle tissue in a defined extracellular matrix, which enhances NMJ function and maturity. Using a combination of immunohistochemistry, calcium imaging, and pharmacological stimulations, we characterized and confirmed the function of the 3D muscle tissue and the 3D neuromuscular co-cultures. Finally, we applied this system as an in vitro model to study the pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and found a decrease in neuromuscular coupling and muscle contraction in co-cultures with MNs harboring ALS-linked SOD1 mutation. In summary, the human 3D neuromuscular cell culture system presented here recapitulates aspects of human physiology in a controlled in vitro setting and is suitable for modeling of MND.
KW  - NMJ–neuromuscular junction
KW  - motoneuron (MN)
KW  - skeletal muscle
KW  - iPSC (induced pluripotent stem cells)
KW  - 3D cell culture
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304161
SN  - 2296-634X
VL  - 11
ER  - 
TY  - JOUR
A1  - Schneider, Verena
A1  - Kruse, Daniel
A1  - Bernardelli de Mattos, Ives
A1  - Zöphel, Saskia
A1  - Tiltmann, Kendra-Kathrin
A1  - Reigl, Amelie
A1  - Khan, Sarah
A1  - Funk, Martin
A1  - Bodenschatz, Karl
A1  - Groeber-Becker, Florian
T1  - A 3D in vitro model for burn wounds: monitoring of regeneration on the epidermal level
JF  - Biomedicines
N2  - Burns affect millions every year and a model to mimic the pathophysiology of such injuries in detail is required to better understand regeneration. The current gold standard for studying burn wounds are animal models, which are under criticism due to ethical considerations and a limited predictiveness. Here, we present a three-dimensional burn model, based on an open-source model, to monitor wound healing on the epidermal level. Skin equivalents were burned, using a preheated metal cylinder. The healing process was monitored regarding histomorphology, metabolic changes, inflammatory response and reepithelialization for 14 days. During this time, the wound size decreased from 25% to 5% of the model area and the inflammatory response (IL-1β, IL-6 and IL-8) showed a comparable course to wounding and healing in vivo. Additionally, the topical application of 5% dexpanthenol enhanced tissue morphology and the number of proliferative keratinocytes in the newly formed epidermis, but did not influence the overall reepithelialization rate. In summary, the model showed a comparable healing process to in vivo, and thus, offers the opportunity to better understand the physiology of thermal burn wound healing on the keratinocyte level.
KW  - skin models
KW  - open-source epidermis
KW  - wound model
KW  - impedance spectroscopy
KW  - wound physiology
KW  - burn wound
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246068
SN  - 2227-9059
VL  - 9
IS  - 9
ER  - 
TY  - JOUR
A1  - Kiesel, Matthias
A1  - Beyers, Inga
A1  - Kalisz, Adam
A1  - Joukhadar, Ralf
A1  - Wöckel, Achim
A1  - Herbert, Saskia-Laureen
A1  - Curtaz, Carolin
A1  - Wulff, Christine
T1  - A 3D printed model of the female pelvis for practical education of gynecological pelvic examination
JF  - 3D Printing in Medicine
N2  - Background
Pelvic palpation is a core component of every Gynecologic examination. It requires vigorous training, which is difficult due to its intimate nature, leading to a need of simulation. Up until now, there are mainly models available for mere palpation which do not offer adequate visualization of the concerning anatomical structures. In this study we present a 3D printed model of the female pelvis. It can improve both the practical teaching of gynecological pelvic examination for health care professionals and the spatial understanding of the relevant anatomy.

Methods
We developed a virtual, simplified model showing selected parts of the female pelvis. 3D printing was used to create a physical model.

Results
The life-size 3D printed model has the ability of being physically assembled step by step by its users. Consequently, it improves teaching especially when combining it with commercial phantoms, which are built solely for palpation training. This is achieved by correlating haptic and visual sensations with the resulting feedback received.

Conclusion
The presented 3D printed model of the female pelvis can be of aid for visualizing and teaching pelvic anatomy and examination to medical staff. 3D printing provides the possibility of creating, multiplying, adapting and sharing such data worldwide with little investment of resources. Thus, an important contribution to the international medical community can be made for training this challenging examination.
KW  - gynecology
KW  - pelvic examination
KW  - pelvic palpation
KW  - 3D printing
KW  - FDM
KW  - SLA
KW  - teaching
KW  - visualization
KW  - education
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313347
VL  - 8
ER  - 
TY  - JOUR
A1  - Schmitt, Joachim
A1  - Lindner, Nathalie
T1  - A 3‐week multimodal intervention involving high‐intensity interval training in female cancer survivors: a randomized controlled trial
JF  - Physiological Reports
N2  - To compare the effects of a 3‐week multimodal rehabilitation involving supervised high‐intensity interval training (HIIT) on female breast cancer survivors with respect to key variables of aerobic fitness, body composition, energy expenditure, cancer‐related fatigue, and quality of life to those of a standard multimodal rehabilitation program. A randomized controlled trial design was administered. Twenty‐eight women, who had been treated for cancer were randomly assigned to either a group performing exercise of low‐to‐moderate intensity (LMIE; n = 14) or a group performing high‐intensity interval training (HIIT; n = 14) as part of a 3‐week multimodal rehabilitation program. No adverse events related to the exercise were reported. Work economy improved following both HIIT and LMIE, with improved peak oxygen uptake following LMIE. HIIT reduced mean total body fat mass with no change in body mass, muscle or fat‐free mass (best P < 0.06). LMIE increased muscle and total fat‐free body mass. Total energy expenditure (P = 0.45) did not change between the groups, whereas both improved quality of life to a similar high extent and lessened cancer‐related fatigue. This randomized controlled study demonstrates that HIIT can be performed by female cancer survivors without adverse health effects. Here, HIIT and LMIE both improved work economy, quality of life and cancer‐related fatigue, body composition or energy expenditure. Since the outcomes were similar, but HIIT takes less time, this may be a time‐efficient strategy for improving certain aspects of the health of female cancer survivors.
KW  - high-intensity interval training
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146455
VL  - 4
IS  - 3
ER  - 
TY  - JOUR
A1  - Sperlich, Billy
A1  - Hahn, Lea-Sofie
A1  - Edel, Antonia
A1  - Behr, Tino
A1  - Helmprobst, Julian
A1  - Leppich, Robert
A1  - Wallmann-Sperlich, Birgit
A1  - Holmberg, Hans-Christer
T1  - A 4-week intervention involving mobile-based daily 6-minute micro-sessions of functional high-intensity circuit training improves strength and quality of life, but not cardio-respiratory fitness of young untrained adults
JF  - Frontiers in Physiology
N2  - The present study was designed to assess the psycho-physiological responses of physically untrained individuals to mobile-based multi-stimulating, circuit-like, multiple-joint conditioning (Circuit\(_{HIIT}\)) performed either once (1xCircuitHIIT) or twice (2xCircuit\(_{HIIT}\)) daily for 4 weeks. In this single-center, two-arm randomized, controlled study, 24 men and women (age: 25 ± 5 years) first received no training instructions for 4 weeks and then performed 4 weeks of either 1xCircuitHIIT or 2xCircuit\(_{HIIT}\) (5 men and 7 women in each group) daily. The 1xCircuitHIIT and 2xCircuit\(_{HIIT}\) participants carried out 90.7 and 85.7% of all planned training sessions, respectively, with average heart rates during the 6-min sessions of 74.3 and 70.8% of maximal heart rate. Body, fat and fat-free mass, and metabolic rate at rest did not differ between the groups or between time-points of measurement. Heart rate while running at 6 km⋅h\(^{-1}\) declined after the intervention in both groups. Submaximal and peak oxygen uptake, the respiratory exchange ratio and heart rate recovery were not altered by either intervention. The maximal numbers of push-ups, leg-levers, burpees, 45°-one-legged squats and 30-s skipping, as well as perception of general health improved in both groups. Our 1xCircuit\(_{HIIT}\) or 2xCircuit\(_{HIIT}\) interventions improved certain parameters of functional strength and certain dimensions of quality of life in young untrained individuals. However, they were not sufficient to enhance cardio-respiratory fitness, in particular peak oxygen uptake.
KW  - aerobic fitness
KW  - body composition
KW  - functional training
KW  - mHealth
KW  - power training
KW  - V800
KW  - wearable
KW  - web-based apps
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176565
VL  - 9
IS  - 423
ER  - 
TY  - JOUR
A1  - Gilmore, Michael S.
A1  - Cruz-Rodz, Armando L.
A1  - Leimeister-Wächter, Michaela
A1  - Kreft, Jürgen
A1  - Goebel, Werner
T1  - A Bacillus cereus cytolytic determinant, cereolysin AB, which comprises the phospholipase C and sphingomyelinase genes: nucleotide sequence and genetic linkage
N2  - A cloned cytolytic determinant from the genome of Bacillus cereus GP-4 has been characterized at the molecular Ievel. Nucleotide sequence determination revealed the presence of two open reading frames. 8oth open reading frames were found by deletion and complementation analysis to be necessary for expression of the hemolytic phenotype by Bacillus subtilis and Escherichia coli hosts. The 5' open reading frame was found to be nearly identical to a recently reported phospholipase C gene derived from a mutant B. cereus strain which overexpresses the respective protein, and it conferred a lecithinase-positive phenotype to the B. subtilis host. The 3' open reading frame encoded a sphingomyelinase. The two tandemly encoded activities, phospholipase C and sphingomyelinase, constitute a biologically functional cytolytic determinant of B. cereus termed cereolysin AB.
KW  - Biologie
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60588
ER  - 
TY  - JOUR
A1  - Vona, Barbara
A1  - Mazaheri, Neda
A1  - Lin, Sheng-Jia
A1  - Dunbar, Lucy A.
A1  - Maroofian, Reza
A1  - Azaiez, Hela
A1  - Booth, Kevin T.
A1  - Vitry, Sandrine
A1  - Rad, Aboulfazl
A1  - Rüschendorf, Franz
A1  - Varshney, Pratishtha
A1  - Fowler, Ben
A1  - Beetz, Christian
A1  - Alagramam, Kumar N.
A1  - Murphy, David
A1  - Shariati, Gholamreza
A1  - Sedaghat, Alireza
A1  - Houlden, Henry
A1  - Petree, Cassidy
A1  - VijayKumar, Shruthi
A1  - Smith, Richard J. H.
A1  - Haaf, Thomas
A1  - El-Amraoui, Aziz
A1  - Bowl, Michael R.
A1  - Varshney, Gaurav K.
A1  - Galehdari, Hamid
T1  - A biallelic variant in CLRN2 causes non-syndromic hearing loss in humans
JF  - Human Genetics
N2  - Deafness, the most frequent sensory deficit in humans, is extremely heterogeneous with hundreds of genes involved. Clinical and genetic analyses of an extended consanguineous family with pre-lingual, moderate-to-profound autosomal recessive sensorineural hearing loss, allowed us to identify CLRN2, encoding a tetraspan protein, as a new deafness gene. Homozygosity mapping followed by exome sequencing identified a 14.96 Mb locus on chromosome 4p15.32p15.1 containing a likely pathogenic missense variant in CLRN2 (c.494C > A, NM_001079827.2) segregating with the disease. Using in vitro RNA splicing analysis, we show that the CLRN2 c.494C > A variant leads to two events: (1) the substitution of a highly conserved threonine (uncharged amino acid) to lysine (charged amino acid) at position 165, p.(Thr165Lys), and (2) aberrant splicing, with the retention of intron 2 resulting in a stop codon after 26 additional amino acids, p.(Gly146Lysfs*26). Expression studies and phenotyping of newly produced zebrafish and mouse models deficient for clarin 2 further confirm that clarin 2, expressed in the inner ear hair cells, is essential for normal organization and maintenance of the auditory hair bundles, and for hearing function. Together, our findings identify CLRN2 as a new deafness gene, which will impact future diagnosis and treatment for deaf patients.
KW  - deafness
KW  - CLRN2
KW  - gene
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267740
SN  - 1432-1203
VL  - 140
IS  - 6
ER  - 
TY  - JOUR
A1  - Doryab, Ali
A1  - Taskin, Mehmet Berat
A1  - Stahlhut, Philipp
A1  - Schröppel, Andreas
A1  - Orak, Sezer
A1  - Voss, Carola
A1  - Ahluwalia, Arti
A1  - Rehberg, Markus
A1  - Hilgendorff, Anne
A1  - Stöger, Tobias
A1  - Groll, Jürgen
A1  - Schmid, Otmar
T1  - A Bioinspired in vitro Lung Model to Study Particokinetics of Nano-/Microparticles Under Cyclic Stretch and Air-Liquid Interface Conditions
JF  - Frontiers in Bioengineering and Biotechnology
N2  - Evolution has endowed the lung with exceptional design providing a large surface area for gas exchange area (ca. 100 m\(^{2}\)) in a relatively small tissue volume (ca. 6 L). This is possible due to a complex tissue architecture that has resulted in one of the most challenging organs to be recreated in the lab. The need for realistic and robust in vitro lung models becomes even more evident as causal therapies, especially for chronic respiratory diseases, are lacking. Here, we describe the Cyclic In VItro Cell-stretch (CIVIC) “breathing” lung bioreactor for pulmonary epithelial cells at the air-liquid interface (ALI) experiencing cyclic stretch while monitoring stretch-related parameters (amplitude, frequency, and membrane elastic modulus) under real-time conditions. The previously described biomimetic copolymeric BETA membrane (5 μm thick, bioactive, porous, and elastic) was attempted to be improved for even more biomimetic permeability, elasticity (elastic modulus and stretchability), and bioactivity by changing its chemical composition. This biphasic membrane supports both the initial formation of a tight monolayer of pulmonary epithelial cells (A549 and 16HBE14o\(^{-}\)) under submerged conditions and the subsequent cell-stretch experiments at the ALI without preconditioning of the membrane. The newly manufactured versions of the BETA membrane did not improve the characteristics of the previously determined optimum BETA membrane (9.35% PCL and 6.34% gelatin [w/v solvent]). Hence, the optimum BETA membrane was used to investigate quantitatively the role of physiologic cyclic mechanical stretch (10% linear stretch; 0.33 Hz: light exercise conditions) on size-dependent cellular uptake and transepithelial transport of nanoparticles (100 nm) and microparticles (1,000 nm) for alveolar epithelial cells (A549) under ALI conditions. Our results show that physiologic stretch enhances cellular uptake of 100 nm nanoparticles across the epithelial cell barrier, but the barrier becomes permeable for both nano- and micron-sized particles (100 and 1,000 nm). This suggests that currently used static in vitro assays may underestimate cellular uptake and transbarrier transport of nanoparticles in the lung.
KW  - lung cell model
KW  - cyclic stretch
KW  - ALI culture
KW  - bioinspired membrane
KW  - particle study
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223830
SN  - 2296-4185
VL  - 9
ER  - 
TY  - JOUR
A1  - Doryab, Ali
A1  - Taskin, Mehmet Berat
A1  - Stahlhut, Philipp
A1  - Schröppel, Andreas
A1  - Wagner, Darcy E.
A1  - Groll, Jürgen
A1  - Schmid, Otmar
T1  - A Biomimetic, Copolymeric Membrane for Cell‐Stretch Experiments with Pulmonary Epithelial Cells at the Air‐Liquid Interface
JF  - Advanced Functional Materials
N2  - Chronic respiratory diseases are among the leading causes of death worldwide, but only symptomatic therapies are available for terminal illness. This in part reflects a lack of biomimetic in vitro models that can imitate the complex environment and physiology of the lung. Here, a copolymeric membrane consisting of poly(ε‐)caprolactone and gelatin with tunable properties, resembling the main characteristics of the alveolar basement membrane is introduced. The thin bioinspired membrane (≤5 μm) is stretchable (up to 25% linear strain) with appropriate surface wettability and porosity for culturing lung epithelial cells under air–liquid interface conditions. The unique biphasic concept of this membrane provides optimum characteristics for initial cell growth (phase I) and then switch to biomimetic properties for cyclic cell‐stretch experiments (phase II). It is showed that physiologic cyclic mechanical stretch improves formation of F‐actin cytoskeleton filaments and tight junctions while non‐physiologic over‐stretch induces cell apoptosis, activates inflammatory response (IL‐8), and impairs epithelial barrier integrity. It is also demonstrated that cyclic physiologic stretch can enhance the cellular uptake of nanoparticles. Since this membrane offers considerable advantages over currently used membranes, it may lead the way to more biomimetic in vitro models of the lung for translation of in vitro response studies into clinical outcome.
KW  - alveolar‐capillary barrier
KW  - cyclic mechanical stretch
KW  - hybrid polymers
KW  - in vitro cell‐stretch model
KW  - tunable ultra‐thin biphasic membrane
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225645
VL  - 31
IS  - 10
ER  - 
TY  - JOUR
A1  - Schmidt, Sven
A1  - Alt, Yvonne
A1  - Deoghare, Nikita
A1  - Krüger, Sarah
A1  - Kern, Anna
A1  - Rockel, Anna Frederike
A1  - Wagner, Nicole
A1  - Ergün, Süleyman
A1  - Wörsdörfer, Philipp
T1  - A blood vessel organoid model recapitulating aspects of vasculogenesis, angiogenesis and vessel wall maturation
JF  - Organoids
N2  - Blood vessel organoids are an important in vitro model to understand the underlying mechanisms of human blood vessel development and for toxicity testing or high throughput drug screening. Here we present a novel, cost-effective, and easy to manufacture vascular organoid model. To engineer the organoids, a defined number of human induced pluripotent stem cells are seeded in non-adhesive agarose coated wells of a 96-well plate and directed towards a lateral plate mesoderm fate by activation of Wnt and BMP4 signaling. We observe the formation of a circular layer of angioblasts around days 5–6. Induced by VEGF application, CD31\(^+\) vascular endothelial cells appear within this vasculogenic zone at approximately day 7 of organoid culture. These cells arrange to form a primitive vascular plexus from which angiogenic sprouting is observed after 10 days of culture. The differentiation outcome is highly reproducible, and the size of organoids is scalable depending on the number of starting cells. We observe that the initial vascular ring forms at the interface between two cell populations. The inner cellular compartment can be distinguished from the outer by the expression of GATA6, a marker of lateral plate mesoderm. Finally, 14-days-old organoids were transplanted on the chorioallantois membrane of chicken embryos resulting in a functional connection of the human vascular network to the chicken circulation. Perfusion of the vessels leads to vessel wall maturation and remodeling as indicated by the formation of a continuous layer of smooth muscle actin expressing cells enwrapping the endothelium. In summary, our organoid model recapitulates human vasculogenesis, angiogenesis as well as vessel wall maturation and therefore represents an easy and cost-effective tool to study all steps of blood vessel development and maturation directly in the human setting without animal experimentation.
KW  - organoid
KW  - blood vessel
KW  - vasculogenesis
KW  - angiogenesis
KW  - induced pluripotent stem cells
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284043
SN  - 2674-1172
VL  - 1
IS  - 1
SP  - 41
EP  - 53
ER  - 
TY  - JOUR
A1  - Homola, György A.
A1  - Jbabdi, Saad
A1  - Beckmann, Christian F.
A1  - Bartsch, Andreas J.
T1  - A Brain Network Processing the Age of Faces
N2  - Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke’s understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships.
KW  - Medizin
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75513
ER  - 
TY  - JOUR
A1  - Würthner, Frank
A1  - Noll, Niklas
T1  - A Calix[4]arene‐Based Cyclic Dinuclear Ruthenium Complex for Light‐Driven Catalytic Water Oxidation
JF  - Chemistry - A European Journal
N2  - A cyclic dinuclear ruthenium(bda) (bda: 2,2’‐bipyridine‐6,6’‐dicarboxylate) complex equipped with oligo(ethylene glycol)‐functionalized axial calix[4]arene ligands has been synthesized for homogenous catalytic water oxidation. This novel Ru(bda) macrocycle showed significantly increased catalytic activity in chemical and photocatalytic water oxidation compared to the archetype mononuclear reference [Ru(bda)(pic)\(_2\)]. Kinetic investigations, including kinetic isotope effect studies, disclosed a unimolecular water nucleophilic attack mechanism of this novel dinuclear water oxidation catalyst (WOC) under the involvement of the second coordination sphere. Photocatalytic water oxidation with this cyclic dinuclear Ru complex using [Ru(bpy)\(_3\)]Cl\(_2\) as a standard photosensitizer revealed a turnover frequency of 15.5 s\(^{−1}\) and a turnover number of 460. This so far highest photocatalytic performance reported for a Ru(bda) complex underlines the potential of this water‐soluble WOC for artificial photosynthesis.
KW  - water
KW  - oxidation
KW  - ruthenium
KW  - dinuclear
KW  - catalytic
KW  - artificial photosynthesis
KW  - homogenous catalysis
KW  - photocatalysis
KW  - ruthenium complexes
KW  - water oxidation
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230030
UR  - https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202004486
VL  - 27
IS  - 1
ER  - 
TY  - JOUR
A1  - Eulalio, Ana
A1  - Fröhlich, Kathrin S.
A1  - Mano, Miguel
A1  - Giacca, Mauro
A1  - Vogel, Jörg
T1  - A Candidate Approach Implicates the Secreted Salmonella Effector Protein SpvB in P-Body Disassembly
N2  - P-bodies are dynamic aggregates of RNA and proteins involved in several post-transcriptional regulation processes. Pbodies have been shown to play important roles in regulating viral infection, whereas their interplay with bacterial pathogens, specifically intracellular bacteria that extensively manipulate host cell pathways, remains unknown. Here, we report that Salmonella infection induces P-body disassembly in a cell type-specific manner, and independently of previously characterized pathways such as inhibition of host cell RNA synthesis or microRNA-mediated gene silencing. We show that the Salmonella-induced P-body disassembly depends on the activation of the SPI-2 encoded type 3 secretion system, and that the secreted effector protein SpvB plays a major role in this process. P-body disruption is also induced by the related pathogen, Shigella flexneri, arguing that this might be a new mechanism by which intracellular bacterial pathogens subvert host cell function.
KW  - Salmonella
KW  - RNS
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68928
ER  - 
TY  - JOUR
A1  - Bischoff, Joakim M.
A1  - Ringsted, Thomas K.
A1  - Petersen, Marian
A1  - Sommer, Claudia
A1  - Üçeyler, Nurcan
A1  - Werner, Mads U.
T1  - A Capsaicin (8%) Patch in the Treatment of Severe Persistent Inguinal Postherniorrhaphy Pain: A Randomized, Double-Blind, Placebo-Controlled Trial
JF  - PLOS ONE
N2  - Background: Persistent pain after inguinal herniorrhaphy is a disabling condition with a lack of evidence-based pharmacological treatment options. This randomized placebo-controlled trial investigated the efficacy of a capsaicin 8% cutaneous patch in the treatment of severe persistent inguinal postherniorrhaphy pain. Methods: Forty-six patients with persistent inguinal postherniorrhaphy pain were randomized to receive either a capsaicin 8% patch or a placebo patch. Pain intensity (Numerical Rating Scale [NRS 0-10]) was evaluated under standardized conditions (at rest, during movement, and during pressure) at baseline and at 1, 2 and 3 months after patch application. Skin punch biopsies for intraepidermal nerve fiber density (IENFD) measurements were taken at baseline and 1 month after patch application. Quantitative sensory testing was performed at baseline and at 1, 2, and 3 months after patch application. The primary outcome was comparisons of summed pain intensity differences (SPIDs) between capsaicin and placebo treatments at 1, 2 and 3 months after patch application (significance level P<0.01). Results: The maximum difference in SPID, between capsaicin and placebo treatments, was observed at 1 month after patch application, but the pain reduction was not significant (NRS, mean difference [95% CI]: 5.0 [0.09 to 9.9]; P=0.046). No differences in SPID between treatments were observed at 2 and 3 months after patch application. Changes in IENFD on the pain side, from baseline to 1 month after patch application, did not differ between capsaicin and placebo treatment: 1.9 [-0.1 to 3.9] and 0.6 [-1.2 to 2.5] fibers/mm, respectively (P=0.32). No significant changes in sensory function, sleep quality or psychological factors were associated with capsaicin patch treatment. Conclusions: The study did not demonstrate significant differences in pain relief between capsaicin and placebo treatment, although a trend toward pain improvement in capsaicin treated patients was observed 1 month after patch application.
KW  - postherpetic neuralgia
KW  - long-term pain
KW  - crossover trial
KW  - neuropathic pain
KW  - risk factors
KW  - cutaneous patch
KW  - scale
KW  - hernia repair
KW  - interference
KW  - validation
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115198
SN  - 1932-6203
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Bommakanti, R. K.
A1  - Klotz, Karl-Norbert
A1  - Dratz, E. A.
A1  - Jesaitis, A. J.
T1  - A carboxyl-terminal tail peptide of neutrophil chemotactic receptor disrupts its physical complex with G protein
N2  - No abstract available
KW  - Toxikologie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60456
ER  - 
TY  - JOUR
A1  - Rosenfeldt, Mathias T.
A1  - Hartmann, Elena M.
A1  - Leng, Corinna
A1  - Rosenwald, Andreas
A1  - Anagnostopoulos, Ioannis
T1  - A case of nodular lymphocyte predominant Hodgkin lymphoma with unexpected EBV-latency type
JF  - Annals of Hematology
N2  - No abstract available.
KW  - nodular lymphcyte
KW  - Hodgkin lymphoma
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232571
SN  - 0939-5555
VL  - 100
ER  - 
TY  - JOUR
A1  - Baur, Johannes
A1  - Schedelbeck, Ulla
A1  - Pulzer, Alina
A1  - Bluemel, Christina
A1  - Wild, Vanessa
A1  - Fassnacht, Martin
A1  - Steger, U.
T1  - A case report of a solitary pancreatic metastasis of an adrenocortical carcinoma
JF  - BMC Surgery
N2  - Background
Solitary metastases to the pancreas are rare. Therefore the value of resection in curative intention remains unclear. In the literature there are several promising reports about resection of solitary metastasis to the pancreas mainly of renal origin.

Case presentation
Here we report for the first time on the surgical therapy of a 1.5 cm solitary pancreatic metastasis of an adrenocortical carcinoma. The metastasis occurred almost 6 years after resection of the primary tumor. A partial pancreatoduodenectomy was performed and postoperatively adjuvant mitotane treatment was initiated. During the follow-up of 3 years after surgery no evidence of tumor recurrence occurred.

Conclusion
Resection of pancreatic tumors should be considered, even if the mass is suspicious for metastatic disease including recurrence of adrenocortical cancer.
KW  - surgical treatment
KW  - adrenocortical
KW  - carcinoma metastases to pancreas
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126130
VL  - 15
IS  - 93
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  - May-Mederake, Birgit
A1  - Shehata-Dieler, Wafaa
T1  - A Case Study Assessing the Auditory and Speech Development of Four Children Implanted with Cochlear Implants by the Chronological Age of 12 Months
JF  - Case Reports in Otolaryngology
N2  - Children with severe hearing loss most likely receive the greatest benefit from a cochlear implant (CI) when implanted at less than 2 years of age. Children with a hearing loss may also benefit greater from binaural sensory stimulation. Four children who received their first CI under 12 months of age were included in this study. Effects on auditory development were determined using the German LittlEARS Auditory Questionnaire, closed- and open-set monosyllabic word tests, aided free-field, the Mainzer and Göttinger speech discrimination tests, Monosyllabic-Trochee-Polysyllabic (MTP), and Listening Progress Profile (LiP). Speech production and grammar development were evaluated using a German language speech development test (SETK), reception of grammar test (TROG-D) and active vocabulary test (AWST-R). The data showed that children implanted under 12 months of age reached open-set monosyllabic word discrimination at an age of 24 months. LiP results improved over time, and children recognized 100% of words in the MTP test after 12 months. All children performed as well as or better than their hearing peers in speech production and grammar development. SETK showed that the speech development of these children was in general age appropriate. The data suggests that early hearing loss intervention benefits speech and language development and supports the trend towards early cochlear implantation. Furthermore, the data emphasizes the potential benefits associated with bilateral implantation.
KW  - Otolaryngolgy
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128750
VL  - 2013
IS  - 359218
ER  - 
TY  - JOUR
A1  - Dütting, Sebastian
A1  - Gaits-Iacovoni, Frederique
A1  - Stegner, David
A1  - Popp, Michael
A1  - Antkowiak, Adrien
A1  - van Eeuwijk, Judith M.M.
A1  - Nurden, Paquita
A1  - Stritt, Simon
A1  - Heib, Tobias
A1  - Aurbach, Katja
A1  - Angay, Oguzhan
A1  - Cherpokova, Deya
A1  - Heinz, Niels
A1  - Baig, Ayesha A.
A1  - Gorelashvili, Maximilian G.
A1  - Gerner, Frank
A1  - Heinze, Katrin G.
A1  - Ware, Jerry
A1  - Krohne, Georg
A1  - Ruggeri, Zaverio M.
A1  - Nurden, Alan T.
A1  - Schulze, Harald
A1  - Modlich, Ute
A1  - Pleines, Irina
A1  - Brakebusch, Cord
A1  - Nieswandt, Bernhard
T1  - A Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis
JF  - Nature Communications
N2  - Blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids. The molecular cues that control MK polarization towards sinusoids and limit transendothelial crossing to proplatelets remain unknown. Here, we show that the small GTPases Cdc42 and RhoA act as a regulatory circuit downstream of the MK-specific mechanoreceptor GPIb to coordinate polarized transendothelial platelet biogenesis. Functional deficiency of either GPIb or Cdc42 impairs transendothelial proplatelet formation. In the absence of RhoA, increased Cdc42 activity and MK hyperpolarization triggers GPIb-dependent transmigration of entire MKs into BM sinusoids. These findings position Cdc42 (go-signal) and RhoA (stop-signal) at the centre of a molecular checkpoint downstream of GPIb that controls transendothelial platelet biogenesis. Our results may open new avenues for the treatment of platelet production disorders and help to explain the thrombocytopenia in patients with Bernard–Soulier syndrome, a bleeding disorder caused by defects in GPIb-IX-V.
KW  - megakaryocytes
KW  - blood platelets
KW  - regulatory circuit downstream
KW  - glycoprotein Ib
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170797
VL  - 8
IS  - 15838
ER  - 
TY  - JOUR
A1  - Philipp, Marius
A1  - Dietz, Andreas
A1  - Ullmann, Tobias
A1  - Kuenzer, Claudia
T1  - A circum-Arctic monitoring framework for quantifying annual erosion rates of permafrost coasts
JF  - Remote Sensing
N2  - This study demonstrates a circum-Arctic monitoring framework for quantifying annual change of permafrost-affected coasts at a spatial resolution of 10 m. Frequent cloud coverage and challenging lighting conditions, including polar night, limit the usability of optical data in Arctic regions. For this reason, Synthetic Aperture RADAR (SAR) data in the form of annual median and standard deviation (sd) Sentinel-1 (S1) backscatter images covering the months June–September for the years 2017–2021 were computed. Annual composites for the year 2020 were hereby utilized as input for the generation of a high-quality coastline product via a Deep Learning (DL) workflow, covering 161,600 km of the Arctic coastline. The previously computed annual S1 composites for the years 2017 and 2021 were employed as input data for the Change Vector Analysis (CVA)-based coastal change investigation. The generated DL coastline product served hereby as a reference. Maximum erosion rates of up to 67 m per year could be observed based on 400 m coastline segments. Overall highest average annual erosion can be reported for the United States (Alaska) with 0.75 m per year, followed by Russia with 0.62 m per year. Out of all seas covered in this study, the Beaufort Sea featured the overall strongest average annual coastal erosion of 1.12 m. Several quality layers are provided for both the DL coastline product and the CVA-based coastal change analysis to assess the applicability and accuracy of the output products. The predicted coastal change rates show good agreement with findings published in previous literature. The proposed methods and data may act as a valuable tool for future analysis of permafrost loss and carbon emissions in Arctic coastal environments.
KW  - permafrost
KW  - coastal erosion
KW  - circum-Arctic
KW  - deep learning
KW  - change vector analysis
KW  - Google Earth Engine
KW  - synthetic aperture RADAR
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304447
SN  - 2072-4292
VL  - 15
IS  - 3
ER  - 
TY  - JOUR
A1  - White, P. Lewis
A1  - Springer, Jan
A1  - Wise, Matt P.
A1  - Einsele, Hermann
A1  - Löffler, Claudia
A1  - Seif, Michelle
A1  - Prommersberger, Sabrina
A1  - Backx, Matthijs
A1  - Löffler, Jürgen
T1  - A clinical case of COVID-19-associated pulmonary aspergillosis (CAPA), illustrating the challenges in diagnosis (despite overwhelming mycological evidence)
JF  - Journal of Fungi
N2  - The COVID-19 pandemic has resulted in large numbers of patients requiring critical care management. With the established association between severe respiratory virus infection and invasive pulmonary aspergillosis (7.6% for COVID-19-associated pulmonary aspergillosis (CAPA)), the pandemic places a significant number of patients at potential risk from secondary invasive fungal disease. We described a case of CAPA with substantial supporting mycological evidence, highlighting the need to employ strategic diagnostic algorithms and weighted definitions to improve the accuracy in diagnosing CAPA.
KW  - COVID-19
KW  - CAPA
KW  - diagnostics
KW  - Aspergillus
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-302438
SN  - 2309-608X
VL  - 8
IS  - 1
ER  - 
TY  - JOUR
A1  - Lutz, Werner K.
A1  - Schlatter, C.
T1  - A closed inhalation system for pharmacokinetic and metabolism studies of volatile compounds with small laboratory animals
N2  - In the inhalation system described an animal can be kept in the same atmosphere of a 2-liter desiccator for up to 24 h. The expired carbon dioxide is adsorbed with soda lime and the resulting reduced pressure is balanced by a supply of oxygen also used for the inflow of the chemical to be investigated. Urine and faeces can be collected ~eparately and the system allows a periodical control of the concentration of the chemical by sampling the air with needle and syringe.
KW  - Toxikologie
Y1  - 1978
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-80145
ER  - 
TY  - JOUR
A1  - Drescher, Nora
A1  - Klein, Alexandra-Maria
A1  - Schmitt, Thomas
A1  - Leonhardt, Sara Diana
T1  - A clue on bee glue: New insight into the sources and factors driving resin intake in honeybees (Apis mellifera)
JF  - PLoS ONE
N2  - Honeybees (Apis mellifera) are threatened by numerous pathogens and parasites. To prevent infections they apply cooperative behavioral defenses, such as allo-grooming and hygiene, or they use antimicrobial plant resin. Resin is a chemically complex and highly variable mixture of many bioactive compounds. Bees collect the sticky material from different plant species and use it for nest construction and protection. Despite its importance for colony health, comparatively little is known about the precise origins and variability in resin spectra collected by honeybees. To identify the botanical resin sources of A. mellifera in Western Europe we chemically compared resin loads of individual foragers and tree resins. We further examined the resin intake of 25 colonies from five different apiaries to assess the effect of location on variation in the spectra of collected resin. Across all colonies and apiaries, seven distinct resin types were categorized according to their color and chemical composition. Matches between bee-collected resin and tree resin indicated that bees used poplar (Populus balsamifera, P. x canadensis), birch (Betula alba), horse chestnut (Aesculus hippocastanum) and coniferous trees (either Picea abies or Pinus sylvestris) as resin sources. Our data reveal that honeybees collect a comparatively broad and variable spectrum of resin sources, thus assuring protection against a variety of antagonists sensitive to different resins and/or compounds. We further unravel distinct preferences for specific resins and resin chemotypes, indicating that honeybees selectively search for bioactive resin compounds.
KW  - Honey bees
KW  - Poplars
KW  - Trees
KW  - Forests
KW  - Chemical composition
KW  - Bees
KW  - Conifers
KW  - Phenols
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200935
VL  - 14
IS  - 2
ER  - 
TY  - JOUR
A1  - Marcus, U.
A1  - Vogel, U.
A1  - Schubert, A.
A1  - Claus, H.
A1  - Baetzing-Feigenbaum, J.
A1  - Hellenbrand, W.
A1  - Wichmann, O.
T1  - A cluster of invasive meningococcal disease in young men who have sex with men in Berlin, October 2012 to May 2013
JF  - Eurosurveillance
N2  - No abstract available.
KW  - meningococcal disease
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131711
VL  - 18
IS  - 28
ER  - 
TY  - JOUR
A1  - Schuhmann, Antonia
A1  - Scheiner, Ricarda
T1  - A combination of the frequent fungicides boscalid and dimoxystrobin with the neonicotinoid acetamiprid in field-realistic concentrations does not affect sucrose responsiveness and learning behavior of honeybees
JF  - Ecotoxicology and Environmental Safety
N2  - The increasing loss of pollinators over the last decades has become more and more evident. Intensive use of plant protection products is one key factor contributing to this decline. Especially the mixture of different plant protection products can pose an increased risk for pollinators as synergistic effects may occur. In this study we investigated the effect of the fungicide Cantus® Gold (boscalid/dimoxystrobin), the neonicotinoid insecticide Mospilan® (acetamiprid) and their mixture on honeybees. Since both plant protection products are frequently applied sequentially to the same plants (e.g. oilseed rape), their combination is a realistic scenario for honeybees. We investigated the mortality, the sucrose responsiveness and the differential olfactory learning performance of honeybees under controlled conditions in the laboratory to reduce environmental noise. Intact sucrose responsiveness and learning performance are of pivotal importance for the survival of individual honeybees as well as for the functioning of the entire colony. Treatment with two sublethal and field relevant concentrations of each plant protection product did not lead to any significant effects on these behaviors but affected the mortality rate. However, our study cannot exclude possible negative sublethal effects of these substances in higher concentrations. In addition, the honeybee seems to be quite robust when it comes to effects of plant protection products, while wild bees might be more sensitive.

Highlights
• Mix of SBI fungicides and neonicotinoids can lead to synergistic effects for bees.
• Combination of non-SBI fungicide and neonicotinoid in field-realistic doses tested.
• Synergistic effect on mortality of honeybees.
• No effects on sucrose responsiveness and learning performance of honeybees.
• Synergistic effects by other pesticide mixtures or on wild bees cannot be excluded.
KW  - Apis mellifera
KW  - non-SBI fungicide
KW  - insecticide
KW  - pesticide mixture
KW  - synergistic effect
KW  - sublethal effect
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350047
VL  - 256
ER  - 
TY  - JOUR
A1  - Richter, Gesa M.
A1  - Kruppa, Jochen
A1  - Munz, Matthias
A1  - Wiehe, Ricarda
A1  - Häsler, Robert
A1  - Franke, Andre
A1  - Martins, Orlando
A1  - Jockel-Schneider, Yvonne
A1  - Bruckmann, Corinna
A1  - Dommisch, Henrik
A1  - Schaefer, Arne S.
T1  - A combined epigenome- and transcriptome-wide association study of the oral masticatory mucosa assigns CYP1B1 a central role for epithelial health in smokers
JF  - Clinical Epigenetics
N2  - Background
The oral mucosa has an important role in maintaining barrier integrity at the gateway to the gastrointestinal and respiratory tracts. Smoking is a strong environmental risk factor for the common oral inflammatory disease periodontitis and oral cancer. Cigarette smoke affects gene methylation and expression in various tissues. This is the first epigenome-wide association study (EWAS) that aimed to identify biologically active methylation marks of the oral masticatory mucosa that are associated with smoking.

Results
Ex vivo biopsies of 18 current smokers and 21 never smokers were analysed with the Infinium Methylation EPICBeadChip and combined with whole transcriptome RNA sequencing (RNA-Seq; 16 mio reads per sample) of the same samples. We analysed the associations of CpG methylation values with cigarette smoking and smoke pack year (SPY) levels in an analysis of covariance (ANCOVA). Nine CpGs were significantly associated with smoking status, with three CpGs mapping to the genetic region of CYP1B1 (cytochrome P450 family 1 subfamily B member 1;best p=5.5x10(-8)) and two mapping to AHRR (aryl-hydrocarbon receptor repressor; best p=5.9x10(-9)). In the SPY analysis, 61 CpG sites at 52 loci showed significant associations of the quantity of smoking with changes in methylation values. Here, the most significant association located to the gene CYP1B1, with p=4.0x10(-10). RNA-Seq data showed significantly increased expression of CYP1B1 in smokers compared to non-smokers (p=2.2x10(-14)), together with 13 significantly upregulated transcripts. Six transcripts were significantly downregulated. No differential expression was observed for AHRR. In vitro studies with gingival fibroblasts showed that cigarette smoke extract directly upregulated the expression of CYP1B1.

Conclusion
This study validated the established role of CYP1B1 and AHRR in xenobiotic metabolism of tobacco smoke and highlights the importance of epigenetic regulation for these genes. For the first time, we give evidence of this role for the oral masticatory mucosa.
KW  - EWAS
KW  - Methylation
KW  - Expression
KW  - Masticatory mucosa
KW  - CYP1B1
KW  - AHRR
KW  - Cytochrome P 450 pathway
KW  - OSCC
KW  - Smoking
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226175
VL  - 11
ER  - 
TY  - JOUR
A1  - El-Kareh, Lydia
A1  - Bihlmayer, Gustav
A1  - Buchter, Arne
A1  - Bentmann, Hendrik
A1  - Blügel, Stefan
A1  - Reinert, Friedrich
A1  - Bode, Matthias
T1  - A combined experimental and theoretical study of Rashba-split surface states on the ( √3x√3) Pb/Ag (111)R30° surface
N2  - We report on a combined low-temperature scanning tunneling spectroscopy (STS), angle-resolved photoemission spectroscopy (ARPES), and density functional theory (DFT) investigation of the ( √3x√3) Pb/Ag (111)R30° surface alloy which provides a giant Rashba-type spin splitting. With STS we observed spectroscopic features that are assigned to two hole-like Rashba-split bands in the unoccupied energy range. By means of STS and quantum interference mapping we determine the band onsets, splitting strengths, and dispersions for both bands. The unambiguous assignment of scattering vectors is achieved by comparison to ARPES measurements. While intra-band scattering is found for both Rashba bands, inter-band scattering is only observed in the occupied energy range. Spin- and orbitally-resolved band structures were obtained by DFT calculations. Considering the scattering between states of different spin- and orbital character, the apparent deviation between experimentally observed scattering events and the theoretically predicted spin polarization could be resolved.
KW  - Rashba effect
KW  - spin–orbit coupling
KW  - scanning tunneling microscopy
KW  - angle resolved photo emission spectroscopy
KW  - density functional theory
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112786
ER  - 
TY  - JOUR
A1  - Niewalda, Thomas
A1  - Völler, Thomas
A1  - Eschbach, Claire
A1  - Ehmer, Julia
A1  - Wen-Chuang, Chou
A1  - Timme, Marc
A1  - Fiala, André
A1  - Gerber, Bertram
T1  - A Combined Perceptual, Physico-Chemical, and Imaging Approach to 'Odour-Distances' Suggests a Categorizing Function of the Drosophila Antennal Lobe
JF  - PLoS One
N2  - How do physico-chemical stimulus features, perception, and physiology relate? Given the multi-layered and parallel architecture of brains, the question specifically is where physiological activity patterns correspond to stimulus features and/or perception. Perceived distances between six odour pairs are defined behaviourally from four independent odour recognition tasks. We find that, in register with the physico-chemical distances of these odours, perceived distances for 3octanol and n-amylacetate are consistently smallest in all four tasks, while the other five odour pairs are about equally distinct. Optical imaging in the antennal lobe, using a calcium sensor transgenically expressed in only first-order sensory or only second-order olfactory projection neurons, reveals that 3-octanol and n-amylacetate are distinctly represented in sensory neurons, but appear merged in projection neurons. These results may suggest that within-antennal lobe processing funnels sensory signals into behaviourally meaningful categories, in register with the physico-chemical relatedness of the odours.
KW  - organization
KW  - cameleon
KW  - honeybee
KW  - map
KW  - neurons
KW  - reveals
KW  - melanogaster
KW  - mushroom body
KW  - spatial representation
KW  - olfactory information
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133510
VL  - 6
IS  - 9
ER  - 
TY  - JOUR
A1  - Niewalda, Thomas
A1  - Völler, Thomas
A1  - Eschbach, Claire
A1  - Ehmer, Julia
A1  - Chou, Wen-Chuang
A1  - Timme, Marc
A1  - Fiala, André
A1  - Gerber, Bertram
T1  - A Combined Perceptual, Physico-Chemical, and ImagingApproach to ‘Odour-Distances’ Suggests a CategorizingFunction of the Drosophila Antennal Lobe
N2  - How do physico-chemical stimulus features, perception, and physiology relate? Given the multi-layered and parallel architecture of brains, the question specifically is where physiological activity patterns correspond to stimulus features and/ or perception. Perceived distances between six odour pairs are defined behaviourally from four independent odour recognition tasks. We find that, in register with the physico-chemical distances of these odours, perceived distances for 3-octanol and n-amylacetate are consistently smallest in all four tasks, while the other five odour pairs are about equally distinct. Optical imaging in the antennal lobe, using a calcium sensor transgenically expressed in only first-order sensory or only second-order olfactory projection neurons, reveals that 3-octanol and n-amylacetate are distinctly represented in sensory neurons, but appear merged in projection neurons. These results may suggest that within-antennal lobe processing funnels sensory signals into behaviourally meaningful categories, in register with the physico-chemical relatedness of the odours.
KW  - Drosophila Antennal Lobe
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-74769
ER  - 
TY  - JOUR
A1  - Kleikers, Pamela W. M.
A1  - Hooijmans, Carlijn
A1  - Göb, Eva
A1  - Langhauser, Friederike
A1  - Rewell, Sarah S. J.
A1  - Radermacher, Kim
A1  - Ritskes-Hoitinga, Merel
A1  - Howells, David W.
A1  - Kleinschnitz, Christoph
A1  - Schmidt, Harald H. H. W.
T1  - A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation
JF  - Scientific Reports
N2  - Biomedical research suffers from a dramatically poor translational success. For example, in ischemic stroke, a condition with a high medical need, over a thousand experimental drug targets were unsuccessful. Here, we adopt methods from clinical research for a late-stage pre-clinical meta-analysis (MA) and randomized confirmatory trial (pRCT) approach. A profound body of literature suggests NOX\(_{2}\) to be a major therapeutic target in stroke. Systematic review and MA of all available NOX\(_{2}\)\(^{-/y}\) studies revealed a positive publication bias and lack of statistical power to detect a relevant reduction in infarct size. A fully powered multi-center pRCT rejects NOX\(_{2}\) as a target to improve neurofunctional outcomes or achieve a translationally relevant infarct size reduction. Thus stringent statistical thresholds, reporting negative data and a MA-pRCT approach can ensure biomedical data validity and overcome risks of bias.
KW  - focal cerebral ischemia
KW  - darbepoetin alpha
KW  - mice
KW  - translational stroke research
KW  - colony-stimulating factor
KW  - NADPH oxidase inhibitors
KW  - chronic kidney disease
KW  - diabetes mellitus
KW  - oxidative stress
KW  - search filter
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151401
VL  - 5
IS  - 13428
ER  - 
TY  - JOUR
A1  - Ziegler, Georg C.
A1  - Ehlis, Ann-Christine
A1  - Weber, Heike
A1  - Vitale, Maria Rosaria
A1  - Zöller, Johanna E. M.
A1  - Ku, Hsing-Ping
A1  - Schiele, Miriam A.
A1  - Kürbitz, Laura I.
A1  - Romanos, Marcel
A1  - Pauli, Paul
A1  - Kalisch, Raffael
A1  - Zwanzger, Peter
A1  - Domschke, Katharina
A1  - Fallgatter, Andreas J.
A1  - Reif, Andreas
A1  - Lesch, Klaus-Peter
T1  - A Common CDH13 Variant is Associated with Low Agreeableness and Neural Responses to Working Memory Tasks in ADHD
JF  - Genes
N2  - The cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.
KW  - ADHD
KW  - CDH13
KW  - neurodevelopment
KW  - executive functions
KW  - working memory
KW  - Big Five
KW  - agreeableness
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245220
SN  - 2073-4425
VL  - 12
IS  - 9
ER  - 
TY  - JOUR
A1  - Ludwig, K. U.
A1  - Sämann, P.
A1  - Alexander, M.
A1  - Becker, J.
A1  - Bruder, J.
A1  - Moll, K.
A1  - Spieler, D.
A1  - Czisch, M.
A1  - Warnke, A.
A1  - Docherty, S. J.
A1  - Davis, O. S. P.
A1  - Plomin, R.
A1  - Nöthen, M. M.
A1  - Landerl, K.
A1  - Müller-Myhsok, B.
A1  - Hoffmann, P.
A1  - Schumacher, J.
A1  - Schulte-Körne, G.
A1  - Czamara, D.
T1  - A common variant in Myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults
JF  - Translational Psychiatry
N2  - The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities\((P_{comb}=7.71 x 10^{-10}, n=699)\), with an effect size of 4.87%. This association was also found in a sample from the general population (P=0.048, n=1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype.
KW  - disability
KW  - sulcal morphology
KW  - prelevance
KW  - identification
KW  - brain
KW  - cancer
KW  - association
KW  - developmental dyscalculia
KW  - tumor-suppressor gene
KW  - correlate
KW  - disorders
KW  - dyscalculia
KW  - dyslexia
KW  - genomic imaging
KW  - mathematics
KW  - quantitative trait
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131513
N1  - Supplementary Information accompanies the paper on the Translational Psychiatry website (http://www.nature.com/tp).
VL  - 3
IS  - e229
ER  - 
TY  - JOUR
A1  - Froudakis, G.
A1  - Zdetsis, A.
A1  - Mühlhäuser, M.
A1  - Engels, Bernd
A1  - Peyerimhoff, S. D.
T1  - A comparative ab initio study of the Si\(_2\)C\(_4\), Si\(_3\)C\(_3\), Si\(_4\)C\(_2\) clusters
N2  - Various structural possibilities for the Si\(_2\)C\(_4\) and Si\(_4\)C\(_2\) clusters are investigated by employing a basis set of triple-zeta plus polarization quality; electron correlation is generally accounted for by second-order M0ller-Plesset and, in certain instances, by higher-order perturbation (CASPT2) approaches. The building-up principle recently suggested from an analysis of Si\(_3\)C\(_3\) clusters is found to be fully operative for Si\(_2\)C\(_4\) and Si\(_4\)C\(_2\) clusters. A comparison of the structure and stability of various geometrical arrangements in the series C\(_6\) , Si\(_2\)C\(_4\) , Si\(_3\)C\(_3\) , Si\(_4\)C\(_2\), and Si\(_6\) shows that linear and planar structures become rapidly less stable if carbons are replaced by silicons and that the three-dimensional bipyramidal forms become less favorable as soon as silicons are exchanged by carbons in the parent Si\(_6\) structure. The effects can be rationalized in qualitative terms based on differences in silicon and carbon bonding.
KW  - Organische Chemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59097
ER  - 
TY  - JOUR
A1  - Jannasch, Maren
A1  - Gaetzner, Sabine
A1  - Weigel, Tobias
A1  - Walles, Heike
A1  - Schmitz, Tobias
A1  - Hansmann, Jan
T1  - A comparative multi-parametric in vitro model identifies the power of test conditions to predict the fibrotic tendency of a biomaterial
JF  - Scientific Reports
N2  - Despite growing effort to advance materials towards a low fibrotic progression, all implants elicit adverse tissue responses. Pre-clinical biomaterial assessment relies on animals testing, which can be complemented by in vitro tests to address the Russell and Burch’s 3R aspect of reducing animal burden. However, a poor correlation between in vitro and in vivo biomaterial assessments confirms a need for suitable in vitro biomaterial tests. The aim of the study was to identify a test setting, which is predictive and might be time- and cost-efficient. We demonstrated how sensitive in vitro biomaterial assessment based on human primary macrophages depends on test conditions. Moreover, possible clinical scenarios such as lipopolysaccharide contamination, contact to autologous blood plasma, and presence of IL-4 in an immune niche influence the outcome of a biomaterial ranking. Nevertheless, by using glass, titanium, polytetrafluorethylene, silicone, and polyethylene representing a specific material-induced fibrotic response and by comparison to literature data, we were able to identify a test condition that provides a high correlation to state-of-the-art in vivo studies. Most important, biomaterial ranking obtained under native plasma test conditions showed a high predictive accuracy compared to in vivo assessments, strengthening a biomimetic three-dimensional in vitro test platform.
KW  - inflammation
KW  - experimental models of disease
KW  - biomaterial tests
KW  - in vitro
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170908
VL  - 7
IS  - 1689
ER  - 
TY  - JOUR
A1  - Knorr, Johannes
A1  - Rudolf, Philipp
A1  - Nuernberger, Patrick
T1  - A comparative study on chirped-pulse upconversion and direct multichannel MCT detection
N2  - A comparative study is carried out on two spectroscopic techniques employed to detect ultrafast absorption changes in the mid-infrared spectral range, namely direct multichannel detection via HgCdTe (MCT) photodiode arrays and the newly established technique of chirped-pulse upconversion (CPU). Whereas both methods are meanwhile individually used in a routine manner, we directly juxtapose their applicability in femtosecond pump-probe experiments based on 1 kHz shot-to-shot data acquisition. Additionally, we examine different phase-matching conditions in the CPU scheme for a given mid-infrared spectrum, thereby simultaneously detecting signals which are separated by more than 200 cm−1.
KW  - Ultrafast spectroscopy
KW  - Upconversion
KW  - infrared spectroscopy
KW  - Lithium niobate
KW  - CCD, charge-coupled device
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111334
ER  - 
TY  - JOUR
A1  - Biscotti, Maria Assunta
A1  - Adolfi, Mateus Contar
A1  - Barucca, Marco
A1  - Forconi, Mariko
A1  - Pallavicini, Alberto
A1  - Gerdol, Marco
A1  - Canapa, Adriana
A1  - Schartl, Manfred
T1  - A comparative view on sex differentiation and gametogenesis genes in lungfish and coelacanths
JF  - Genome Biology and Evolution
N2  - Gonadal sex differentiation and reproduction are the keys to the perpetuation of favorable gene combinations and positively selected traits. In vertebrates, several gonad development features that differentiate tetrapods and fishes are likely to be, at least in part, related to the water-to-land transition. The collection of information from basal sarcopterygians, coelacanths, and lungfishes, is crucial to improve our understanding of the molecular evolution of pathways involved in reproductive functions, since these organisms are generally regarded as “living fossils” and as the direct ancestors of tetrapods. Here, we report for the first time the characterization of >50 genes related to sex differentiation and gametogenesis in Latimeria menadoensis and Protopterus annectens. Although the expression profiles of most genes is consistent with the intermediate position of basal sarcopterygians between actinopterygian fish and tetrapods, their phylogenetic placement and presence/absence patterns often reveal a closer affinity to the tetrapod orthologs. On the other hand, particular genes, for example, the male gonad factor gsdf (Gonadal Soma-Derived Factor), provide examples of ancestral traits shared with actinopterygians, which disappeared in the tetrapod lineage.
KW  - sex differentiation
KW  - Latimeria menadoensis
KW  - Protopterus annectens
KW  - evolution
KW  - testis
KW  - gametogenesis
KW  - ovary
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176774
VL  - 10
IS  - 6
ER  - 
TY  - JOUR
A1  - Duschl, Albert
A1  - Jahn, Ute
A1  - Bertling, Claudia
A1  - Sebald, Walter
T1  - A comparison of assays for the response of primary human T-cells upon stimulation with interleukin-2, interleukin-4 and interleukin-7
N2  - The most commonly used assay to quantitate the response of peripheral T~cells upon stimulation with growth factors is determination of incorporated (JH]TdR. We compared thls test to three other methods: 1. direct countlog of cells with a Coulter type counter as reference assay, 2. a colorimetric assay using the tetrazolium dye 3-[ 4,S-dimethylthiazol-l-yl]-2,5diphenyl tetrazolium (MTT), which is a cheap and increasingly popular non-radioactive method and 3. incorporation of the thymidine analog 5-bromo-2'-deoxyuridine detection with a monoclonal antibody on cytospins. Primary human PHA-blasts from >30 healthy individuals were stimulated with IL-2, IL-4 aod IL-7 and assayed with up to four different methods. We discuss the advantages and disadvantages of the assays used and tbe effects of differences between cell preparations. We observed no significant variations between individuals for the dose dependence, but the relative emctency of IL4 compared to IL-2 and IL-7 was variable. This was probably due to the slower response observed upon stimulation with this factor.
KW  - T-Lymphozyt
KW  - Interleukin 2
KW  - Interleukin 4
KW  - Interleukin 7
KW  - T-cells
KW  - proliferation assays
KW  - IL-2
KW  - IL-4
KW  - IL-7
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86750
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  - Paelecke-Habermann, Yvonne
A1  - Paelecke, Marko
A1  - Mauth, Juliane
A1  - Tschisgale, Juliane
A1  - Lindenmeyer, Johannes
A1  - Kübler, Andrea
T1  - A comparison of implicit and explicit reward learning in low risk alcohol users versus people who binge drink and people with alcohol dependence
JF  - Addictive Behaviors Reports
N2  - Chronic alcohol use leads to specific neurobiological alterations in the dopaminergic brain reward system, which probably are leading to a reward deficiency syndrome in alcohol dependence. The purpose of our study was to examine the effects of such hypothesized neurobiological alterations on the behavioral level, and more precisely on the implicit and explicit reward learning. Alcohol users were classified as dependent drinkers (using the DSM-IV criteria), binge drinkers (using criteria of the USA National Institute on Alcohol Abuse and Alcoholism) or low-risk drinkers (following recommendations of the Scientific board of trustees of the German Health Ministry). The final sample (n = 94) consisted of 36 low-risk alcohol users, 37 binge drinkers and 21 abstinent alcohol dependent patients. Participants were administered a probabilistic implicit reward learning task and an explicit reward- and punishment-based trial-and-error-learning task. Alcohol dependent patients showed a lower performance in implicit and explicit reward learning than low risk drinkers. Binge drinkers learned less than low-risk drinkers in the implicit learning task. The results support the assumption that binge drinking and alcohol dependence are related to a chronic reward deficit. Binge drinking accompanied by implicit reward learning deficits could increase the risk for the development of an alcohol dependence.
KW  - Alcohol dependence
KW  - Binge drinking
KW  - Low risk alcohol use
KW  - Implicit and explicit reward learning
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201406
VL  - 9
ER  - 
TY  - JOUR
A1  - Jahed, Razieh Rafiei
A1  - Kavousi, Mohammad Reza
A1  - Farashiani, Mohammad Ebrahim
A1  - Sagheb-Talebi, Khosro
A1  - Babanezhad, Manoochehr
A1  - Courbaud, Benoit
A1  - Wirtz, Roland
A1  - Müller, Jörg
A1  - Larrieu, Laurent
T1  - A comparison of the formation rates and composition of tree-related microhabitats in beech-dominated primeval Carpathian and Hyrcanian forests
JF  - Forests
N2  - Primeval forests in the temperate zone exist only as a few remnants, but theses serve as important reference areas for conservation. As key habitats, tree-related microhabitats (TreMs) are of intense interest to forest ecologists, but little is known about their natural composition and dynamics in different tree species. Beech forms a major part of the temperate forests that extend from Europe, home to European beech Fagus sylvatica L. (Fs), eastward to Iran, where Oriental beech Fagus orientalis Lipsky (Fo) is the dominant species. In this study, we compared TreMs in primeval forests of both species, using data from Fo growing in 25 inventory plots throughout the Hyrcanian forest belt in Iran and from Fs growing in a 9 ha permanent plot in the Uholka Forest of Ukraine. TreMs based on 47 types and 11 subgroups were recorded. Beech trees in the Hyrcanian forest had a higher mean diameter at breast height (dbh) than beech trees in Uholka and contained twice as many TreMs per hectare. Although the mean richness of TreMs per TreM bearing tree was similar in the two species, on the basis of the comparison single trees in two groups (n = 405 vs. 2251), the composition of the TreMs clearly differed, as the proportions of rot holes, root-buttress concavities, and crown deadwood were higher in the Hyrcanian Forest, and those of bark losses, exposed heartwood, and burrs and cankers higher in Uholka Forest. Estimates of TreMs dynamics based on dbh and using Weibull models showed a significantly faster cumulative increase of TreMs in Fo, in which saturation occurred already in trees with a dbh of 70–80 cm. By contrast, the increase in TreMs in Fs was continuous. In both species, the probability density was highest at a dbh of about 30 cm, but was twice as high in Fo. Because of limitations of our study design, the reason behind observed differences of TreM formation and composition between regions remains unclear, as it could be either result of the tree species or the environment, or their interaction. However, the observed differences were more likely the result of differences in the environment than in the two tree species. Nevertheless, our findings demonstrate that the Hyrcanian Forest, recently designated as a natural heritage site in Iran, is unique, not only as a tertiary relict or due to its endemic trees, herbs and arthropods, but also because of its TreMs, which form a distinct and rich habitat for associated taxa, including endemic saproxylic species.
KW  - TreMs
KW  - Fagus orientalis
KW  - Fagus sylvatica
KW  - primeval forest
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200849
SN  - 1999-4907
VL  - 11
IS  - 2
ER  - 
TY  - JOUR
A1  - Hagemann, Carsten
A1  - Anacker, Jelena
A1  - Ernestus, Ralf-Ingo
A1  - Vince, Giles H.
T1  - A complete compilation of matrix metalloproteinase expression in human malignant gliomas
JF  - World Journal of Clinical Oncology
N2  - Glioblastomas are characterized by an aggressive local growth pattern, a marked degree of invasiveness and poor prognosis. Tumor invasiveness is facilitated by the increased activity of proteolytic enzymes which are involved in destruction of the extracellular matrix of the surrounding healthy brain tissue. Elevated levels of matrix metalloproteinases (MMPs) were found in glioblastoma (GBM) cell-lines, as well as in GBM biopsies as compared with low-grade astrocytoma (LGA) and normal brain samples, indicating a role in malignant progression. A careful review of the available literature revealed that both the expression and role of several of the 23 human MMP proteins is controversely discussed and for some there are no data available at all. We therefore screened a panel of 15 LGA and 15 GBM biopsy samples for those MMPs for which there is either no, very limited or even contradictory data available. Hence, this is the first complete compilation of the expression pattern of all 23 human MMPs in astrocytic tumors. This study will support a better understanding of the specific expression patterns and interaction of proteolytic enzymes in malignant human glioma and may provide additional starting points for targeted patient therapy.
KW  - glioblastoma cell-lines
KW  - matrix metalloproteinase
KW  - glioblastoma multiforme
KW  - astrocytic tumor
KW  - expression pattern
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123982
VL  - 3
IS  - 5
ER  - 
TY  - JOUR
A1  - Pauls, Dennis
A1  - Blechschmidt, Christine
A1  - Frantzmann, Felix
A1  - el Jundi, Basil
A1  - Selcho, Mareike
T1  - A comprehensive anatomical map of the peripheral octopaminergic/tyraminergic system of Drosophila melanogaster
JF  - Scientific Reports
N2  - The modulation of an animal’s behavior through external sensory stimuli, previous experience and its internal state is crucial to survive in a constantly changing environment. In most insects, octopamine (OA) and its precursor tyramine (TA) modulate a variety of physiological processes and behaviors by shifting the organism from a relaxed or dormant condition to a responsive, excited and alerted state. Even though OA/TA neurons of the central brain are described on single cell level in Drosophila melanogaster, the periphery was largely omitted from anatomical studies. Given that OA/TA is involved in behaviors like feeding, flying and locomotion, which highly depend on a variety of peripheral organs, it is necessary to study the peripheral connections of these neurons to get a complete picture of the OA/TA circuitry. We here describe the anatomy of this aminergic system in relation to peripheral tissues of the entire fly. OA/TA neurons arborize onto skeletal muscles all over the body and innervate reproductive organs, the heart, the corpora allata, and sensory organs in the antennae, legs, wings and halteres underlining their relevance in modulating complex behaviors.
KW  - neural circuits
KW  - peripheral nervous system
KW  - Drosophila melanogaster
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177412
VL  - 8
IS  - 15314
ER  - 
TY  - JOUR
A1  - Peters, Simon
A1  - Fohmann, Ingo
A1  - Rudel, Thomas
A1  - Schubert-Unkmeir, Alexandra
T1  - A Comprehensive Review on the Interplay between Neisseria spp. and Host Sphingolipid Metabolites
JF  - Cells
N2  - Sphingolipids represent a class of structural related lipids involved in membrane biology and various cellular processes including cell growth, apoptosis, inflammation and migration. Over the past decade, sphingolipids have become the focus of intensive studies regarding their involvement in infectious diseases. Pathogens can manipulate the sphingolipid metabolism resulting in cell membrane reorganization and receptor recruitment to facilitate their entry. They may recruit specific host sphingolipid metabolites to establish a favorable niche for intracellular survival and proliferation. In contrast, some sphingolipid metabolites can also act as a first line defense against bacteria based on their antimicrobial activity. In this review, we will focus on the strategies employed by pathogenic Neisseria spp. to modulate the sphingolipid metabolism and hijack the sphingolipid balance in the host to promote cellular colonization, invasion and intracellular survival. Novel techniques and innovative approaches will be highlighted that allow imaging of sphingolipid derivatives in the host cell as well as in the pathogen.
KW  - sphingolipids
KW  - host–pathogen interaction
KW  - Neisseria meningitidis
KW  - Neisseria gonorrhoeae
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250203
SN  - 2073-4409
VL  - 10
IS  - 11
ER  - 
TY  - JOUR
A1  - Sander, Bodo
A1  - Xu, Wenshan
A1  - Eilers, Martin
A1  - Popov, Nikita
A1  - Lorenz, Sonja
T1  - A conformational switch regulates the ubiquitin ligase HUWE1
JF  - eLife
N2  - The human ubiquitin ligase HUWE1 has key roles in tumorigenesis, yet it is unkown how its activity is regulated. We present the crystal structure of a C-terminal part of HUWE1, including the catalytic domain, and reveal an asymmetric auto-inhibited dimer. We show that HUWE1 dimerizes in solution and self-associates in cells, and that both occurs through the crystallographic dimer interface. We demonstrate that HUWE1 is inhibited in cells and that it can be activated by disruption of the dimer interface. We identify a conserved segment in HUWE1 that counteracts dimer formation by associating with the dimerization region intramolecularly. Our studies reveal, intriguingly, that the tumor suppressor p14ARF binds to this segment and may thus shift the conformational equilibrium of HUWE1 toward the inactive state. We propose a model, in which the activity of HUWE1 underlies conformational control in response to physiological cues—a mechanism that may be exploited for cancer therapy.
KW  - Medicine
KW  - Structural Biology
KW  - Molecular Biophysics
KW  - HUWE1
KW  - HECT Ligase
KW  - Ubiquitin
KW  - P14ARF
KW  - X-Ray Chrystallography
KW  - Enzyme Regulation
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171862
VL  - 6
ER  - 
TY  - JOUR
A1  - Fröhlich, Kathrin S.
A1  - Papenfort, Kai
A1  - Berger, Allison A.
A1  - Vogel, Jörg
T1  - A conserved RpoS-dependent small RNA controls the synthesis of major porin OmpD
JF  - Nucleic Acids Research
N2  - A remarkable feature of many small non-coding RNAs (sRNAs) of Escherichia coli and Salmonella is their accumulation in the stationary phase of bacterial growth. Several stress response regulators and sigma factors have been reported to direct the transcription of stationary phase-specific sRNAs, but a widely conserved sRNA gene that is controlled by the major stationary phase and stress sigma factor, Sigma(S) (RpoS), has remained elusive. We have studied in Salmonella the conserved SdsR sRNA, previously known as RyeB, one of the most abundant stationary phase-specific sRNAs in E. coli. Alignments of the sdsR promoter region and genetic analysis strongly suggest that this sRNA gene is selectively transcribed by Sigma(S). We show that SdsR down-regulates the synthesis of the major Salmonella porin OmpD by Hfq-dependent base pairing; SdsR thus represents the fourth sRNA to regulate this major outer membrane porin. Similar to the InvR, MicC and RybB sRNAs, SdsR recognizes the ompD mRNA in the coding sequence, suggesting that this mRNA may be primarily targeted downstream of the start codon. The SdsR-binding site in ompD was localized by 3'-RACE, an experimental approach that promises to be of use in predicting other sRNA-target interactions in bacteria.
KW  - shock sigma factor
KW  - general stress response
KW  - down regulation
KW  - stationary phase
KW  - salmonella enterica
KW  - messenger RNA
KW  - escherichia coli
KW  - enterica serovar typhimurium
KW  - outer-membrane proteins
KW  - small noncoding RNAs
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134230
VL  - 40
IS  - 8
ER  - 
TY  - JOUR
A1  - Libre, Camille
A1  - Seissler, Tanja
A1  - Guerrero, Santiago
A1  - Batisse, Julien
A1  - Verriez, Cédric
A1  - Stupfler, Benjamin
A1  - Gilmer, Orian
A1  - Cabrera-Rodriguez, Romina
A1  - Weber, Melanie M.
A1  - Valenzuela-Fernandez, Agustin
A1  - Cimarelli, Andrea
A1  - Etienne, Lucie
A1  - Marquet, Roland
A1  - Paillart, Jean-Christophe
T1  - A conserved uORF regulates APOBEC3G translation and is targeted by HIV-1 Vif protein to repress the antiviral factor
JF  - Biomedicines
N2  - The HIV-1 Vif protein is essential for viral fitness and pathogenicity. Vif decreases expression of cellular restriction factors APOBEC3G (A3G), A3F, A3D and A3H, which inhibit HIV-1 replication by inducing hypermutation during reverse transcription. Vif counteracts A3G at several levels (transcription, translation, and protein degradation) that altogether reduce the levels of A3G in cells and prevent its incorporation into viral particles. How Vif affects A3G translation remains unclear. Here, we uncovered the importance of a short conserved uORF (upstream ORF) located within two critical stem-loop structures of the 5′ untranslated region (5′-UTR) of A3G mRNA for this process. A3G translation occurs through a combination of leaky scanning and translation re-initiation and the presence of an intact uORF decreases the extent of global A3G translation under normal conditions. Interestingly, the uORF is also absolutely required for Vif-mediated translation inhibition and redirection of A3G mRNA into stress granules. Overall, we discovered that A3G translation is regulated by a small uORF conserved in the human population and that Vif uses this specific feature to repress its translation.
KW  - HIV-1
KW  - APOBEC3G
KW  - Vif
KW  - mRNA
KW  - translation
KW  - uORF
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252147
SN  - 2227-9059
VL  - 10
IS  - 1
ER  - 
TY  - JOUR
A1  - Haack, J.
A1  - Hauck, C.
A1  - Klingenberg, C.
A1  - Pirner, M.
A1  - Warnecke, S.
T1  - A Consistent BGK Model with Velocity-Dependent Collision Frequency for Gas Mixtures
JF  - Journal of Statistical Physics
N2  - We derive a multi-species BGK model with velocity-dependent collision frequency for a non-reactive, multi-component gas mixture. The model is derived by minimizing a weighted entropy under the constraint that the number of particles of each species, total momentum, and total energy are conserved. We prove that this minimization problem admits a unique solution for very general collision frequencies. Moreover, we prove that the model satisfies an H-Theorem and characterize the form of equilibrium.
KW  - plasma physics
KW  - multi-fluid mixture
KW  - kinetic model
KW  - BGK approximation
KW  - velocity-dependent collision frequency
KW  - entropy minimization
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-269146
SN  - 1572-9613
VL  - 184
IS  - 3
ER  - 
TY  - JOUR
A1  - Hirsch, Martin
A1  - Krauss, Manuel E.
A1  - Opferkuch, Toby
A1  - Porod, Werner
A1  - Staub, Florian
T1  - A constrained supersymmetric left-right model
JF  - JOURNAL OF HIGH ENERGY PHYSICS
N2  - We present a supersymmetric left-right model which predicts gauge coupling unification close to the string scale and extra vector bosons at the TeV scale. The subtleties in constructing a model which is in agreement with the measured quark masses and mixing for such a low left-right breaking scale are discussed. It is shown that in the constrained version of this model radiative breaking of the gauge symmetries is possible and a SM-like Higgs is obtained. Additional CP-even scalars of a similar mass or even much lighter are possible. The expected mass hierarchies for the supersymmetric states differ clearly from those of the constrained MSSM. In particular, the lightest down-type squark, which is a mixture of the sbottom and extra vector-like states, is always lighter than the stop. We also comment on the model’s capability to explain current anomalies observed at the LHC.
KW  - supersymmetry
KW  - phenomenology
KW  - LHC
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168016
VL  - 03
IS  - 009
ER  -