Refine
Year of publication
Document Type
- Journal article (8463) (remove)
Language
Keywords
- Organische Chemie (122)
- Anorganische Chemie (119)
- Toxikologie (112)
- Medizin (98)
- inflammation (86)
- Biochemie (81)
- Chemie (68)
- cancer (66)
- gene expression (62)
- Psychologie (61)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (1400)
- Institut für Psychologie (391)
- Institut für Anorganische Chemie (383)
- Physikalisches Institut (377)
- Medizinische Klinik und Poliklinik II (353)
- Neurologische Klinik und Poliklinik (351)
- Medizinische Klinik und Poliklinik I (333)
- Institut für Organische Chemie (316)
- Institut für Molekulare Infektionsbiologie (304)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (259)
Sonstige beteiligte Institutionen
- Johns Hopkins School of Medicine (11)
- IZKF Nachwuchsgruppe Geweberegeneration für muskuloskelettale Erkrankungen (7)
- Clinical Trial Center (CTC) / Zentrale für Klinische Studien Würzburg (ZKSW) (5)
- Wilhelm-Conrad-Röntgen-Forschungszentrum für komplexe Materialsysteme (5)
- Bernhard-Heine-Centrum für Bewegungsforschung (4)
- Johns Hopkins University School of Medicine (4)
- Zentraleinheit Klinische Massenspektrometrie (4)
- Center for Interdisciplinary Clinical Research, Würzburg University, Würzburg, Germany (2)
- Interdisciplinary Center for Clinical Research (2)
- Interdisziplinäres Zentrum für Klinische Forschung (IZKF) (2)
ResearcherID
- D-1221-2009 (1)
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.
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.
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.
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.
4-Bromoctavalen und zwei (Brommethylen)homobenzvalene anstelle eines erwarteten Bromoctabisvalens
(1988)
No abstract available.
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.
3D visualization of movements can amplify motor cortex activation during subsequent motor imagery
(2015)
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.
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.
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.
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.
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.
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.
Background
Endovascular revascularization has become the first-line treatment of chronic mesenteric ischemia (CMI). The qualitative visual analysis of digital subtraction angiography (DSA) is dependent on observer experience and prone to interpretation errors. We evaluate the feasibility of 2D-Perfusion Angiography (2D-PA) for objective, quantitative treatment response assessment in CMI.
Methods
49 revascularizations in 39 patients with imaging based evidence of mesenteric vascular occlusive disease and clinical signs of CMI were included in this retrospective study. To assess perfusion changes by 2D-PA, DSA-series were post-processed using a dedicated, commercially available software. Regions of interest (ROI) were placed in the pre- and post-stenotic artery segment. In aorto-ostial disease, the inflow ROI was positioned at the mesenteric artery orifice. The ratios outflow to inflow ROI for peak density (PD), time to peak and area-under-the-curve (AUC) were computed and compared pre- and post-interventionally. We graded motion artifacts by means of a four-point scale. Feasibility of 2D-PA and changes of flow parameters were evaluated.
Results
Motion artifacts due to a mobile vessel location beneath the diaphragm or within the mesenteric root, branch vessel superimposition and inadequate contrast enhancement at the inflow ROI during manually conducted DSA-series via selective catheters owing to steep vessel angulation, necessitated exclusion of 26 measurements from quantitative flow evaluation. The feasibility rate was 47%. In 23 technically feasible assessments, PD\(_{outflow}\)/PD\(_{inflow}\) increased by 65% (p < 0.001) and AUC\(_{outflow}\)/AUC\(_{inflow}\) increased by 85% (p < 0.001). The time to peak density values in the outflow ROI accelerated only minimally without reaching statistical significance. Age, BMI, target vessel (celiac trunk, SMA or IMA), stenosis location (ostial or truncal), calcification severity, plaque composition or the presence of a complex stenosis did not reach statistical significance in their distribution among the feasible and non-feasible group (p > 0.05).
Conclusions
Compared to other vascular territories and indications, the feasibility of 2D-PA in mesenteric revascularization for CMI was limited. Unfavorable anatomic conditions contributed to a high rate of inconclusive 2D-PA results.
Growth, ageing and atherosclerotic plaque development alter the biomechanical forces acting on the vessel wall. However, monitoring the detailed local changes in wall shear stress (WSS) at distinct sites of the murine aortic arch over time has been challenging. Here, we studied the temporal and spatial changes in flow, WSS, oscillatory shear index (OSI) and elastic properties of healthy wildtype (WT, n = 5) and atherosclerotic apolipoprotein E-deficient (Apoe\(^{−/−}\), n = 6) mice during ageing and atherosclerosis using high-resolution 4D flow magnetic resonance imaging (MRI). Spatially resolved 2D projection maps of WSS and OSI of the complete aortic arch were generated, allowing the pixel-wise statistical analysis of inter- and intragroup hemodynamic changes over time and local correlations between WSS, pulse wave velocity (PWV), plaque and vessel wall characteristics. The study revealed converse differences of local hemodynamic profiles in healthy WT and atherosclerotic Apoe\(^{−/−}\) mice, and we identified the circumferential WSS as potential marker of plaque size and composition in advanced atherosclerosis and the radial strain as a potential marker for vascular elasticity. Two-dimensional (2D) projection maps of WSS and OSI, including statistical analysis provide a powerful tool to monitor local aortic hemodynamics during ageing and atherosclerosis. The correlation of spatially resolved hemodynamics and plaque characteristics could significantly improve our understanding of the impact of hemodynamics on atherosclerosis, which may be key to understand plaque progression towards vulnerability.
Salivary gland tumors are a rare tumor entity within malignant tumors of all tissues. The most common are malignant mucoepidermoid carcinoma, adenoid cystic carcinoma, and acinic cell carcinoma. Pleomorphic adenoma is the most recurrent form of benign salivary gland tumor. Due to their low incidence rates and complex histological patterns, they are difficult to diagnose accurately. Malignant tumors of the salivary glands are challenging in terms of differentiation because of their variability in histochemistry and translocations. Therefore, the primary goal of the study was to review the current literature to identify the recent developments in histochemical diagnostics and translocations for differentiating salivary gland tumors.
The 2,2,5,5-tetraorganyl-1,4-dioxa-2,5-disilacyclohexanes 2a-2c were prepared by condensation of the corresponding (hydroxymethyl)diorganylsilanes 1 a-1 c. The constitution of the heterocycles was confirmed by elemental analyses, cryoscopic measurements, mass spectrometry, and NMR-spectroscopic \((^1H, ^{13}C)\) investigations. The molecular structure of 2 b was determined by X-ray diffraction analysis.
2-Chloro-N\(^6\)-cyclopentyladenosine: a highly selective agonist at A\(_1\) adenosine receptors
(1988)
2-Chloro-N\(^6\)-cyclopentyladenosine (CCPA) was synthesized as a potential high affinity ligand for At adenosine receptors. Binding of [\(^3\)H]PIA to A1 receptors of rat brain membranes was inhibited by CCP A with a Ki-value of 0.4 nM, compared to a Ki-value of 0.8 nM for the parent compound N\(^6\)-cyclopentyladenosine (CPA). Binding of [\(^3\)H]NECA to A\(_2\) receptors of rat striatal membranes was inhibited with a Ki-value of 3900 nM, demonstrating an almost 10,000-fold A\(_1\)-selectivity of CCPA. CCP A inhibited the activity of rat fat cell membrane adenylate cyclase, a model for the A\(_1\) receptor, with an IC\(_{50}\)-value of 33 nM, and it stimulated the adenylate cyclase activity of human platelet membranes with an EC\(_{50}\)-value of 3500 nM. The more than 100-fold A\(_1\)-selectivity compares favourably with a 38-fold selectivity of CPA. Thus, CCPA is an agonist at A\(_1\) adenosine receptors with a 4-fold higher selectivity and 2-fold higher affinity than CPA, and a considerably higher selectivity than the standard At receptor agonist R-N\(^6\) -phenylisopropyladenosine (R-PIA). CCP A represents the agonist with the highest selectivity for A\(_1\) receptors reported so far.
The tritiated analogue of 2-chloro-N6-cyclopentyladenosine (CCPA), an adenosine derivative with subnanomolar affinity and a 10000-fold selectivity for A1 adenosine receptors, has been examined as a new agonist radioligand. [3H]CCP A was prepared with a specifi.c radioactivity of 1.58 TBqjmmol ( 43 Ci/mmol) and bound in a reversible manner to A1 receptors from rat brain membranes with a high affinity K0 -value of 0.2 nmol/1. In the presence of GTP a K0 -value of 13 nmol/1 was determined for the low affinity state for agonist binding. Competition of several adenosine receptor agonists and antagonists for [3H]CCPA binding to rat brain membranes confrrmed binding to an A1 receptor. Solubilized A1 receptors bound [3H]CCPA with similar affinity for the high affinity state. At solubilized receptors a reduced association rate was observed in the presence of MgC12, as has been shown for the agonist [ 3H]N6-phenylisopropyladenosine ([3H]PIA). [3H]CCPA was also used for detection of A1 receptors in rat cardio myocyte membranes, a tissue with a very low receptor density. A K0 -value of 0.4 nmol/1 and a Bmax-value of 16 fmol/ mg protein was determined in these membranes. In human platelet membranes no specific binding of [3H]CCPA was measured at concentrations up to 400 nmoljl, indicating that A2 receptors did not bind [3H]CCPA. Based on the subnanomolar affinity and the high selectivity for A1 receptors [ 3H]CCPA proved to be a useful agonist radioligand for characterization of A 1 adenosine receptors also in tissues with very low receptor density.
In the search for more selective A2-receptor agonists and on the basis that appropriate substitution at C2 is known to impart selectivity for A\(_2\) receptors, 2-alkynyladenosines 2a-d were resynthesized and evaluated in radioligand binding, adenylate cycla.se, and platelet aggregation studies. Binding of [\(^3\)H]NECA to A\(_2\) receptors of rat striatal membranes was inhibited by compounds 2a-d with K\(_i\) values ranging from 2.8 to 16.4 nM. 2-Alkynyladenosines also exhibited high-affmity binding at solubilized A\(_2\) receptors from human platelet membranes. Competition of 2-alkynyladenosines 2a-d for the antagonist radioligand [\(^3\)H]DPCPX and for the agonist [\(^3\)H]CCPA gave K\(_i\) values in the nanomolar range, and the compounds showed moderate A\(_2\) selectivity. In order to improve this selectivity, the correaponding 2-alkynyl derivatives of adenosine-5'-N-ethyluronamide 8a-d were synthesized and tested. A\(_1\) expected, the 5'-N-ethyluronamide derivatives retained the A\(_2\) affinity whereas the A\(_1\) affinity was attenuated, resulting in an up to 10-fold increase in A\(_2\) selectivity. A similar patternwas observed in adenylate cyclase assays andin platelet aggregation studies. A 30- to 45-fold selectivity for platelet A\(_2\) receptors compared to A\(_1\) receptors was found for compounds 8a-c in adenylate cyclase studies.
Two N-methylpyridinium compounds and analogous N-protonated salts of 2- and 2,7-substituted 4-pyridyl-pyrene compounds were synthesised and their crystal structures, photophysical properties both in solution and in the solid state, electrochemical and spectroelectrochemical properties were studied. Upon methylation or protonation, the emission maxima are significantly bathochromically shifted compared to the neutral compounds, although the absorption maxima remain almost unchanged. As a result, the cationic compounds show very large apparent Stokes shifts of up to 7200 cm\(^{-1}\). The N-methylpyridinium compounds have a single reduction at ca. −1.5 V vs. Fc/Fc\(^+\) in MeCN. While the reduction process was reversible for the 2,7-disubstituted compound, it was irreversible for the mono-substituted one. Experimental findings are complemented by DFT and TD-DFT calculations. Furthermore, the N-methylpyridinium compounds show strong interactions with calf thymus (ct)-DNA, presumably by intercalation, which paves the way for further applications of these multi-functional compounds as potential DNA-bioactive agents.
The He (I) photoelectron spectra of 2-bicyclo[2.1.l]hexene (1), 2,3-bis(methylene)bicyclo[2.1.l]hexane (3), and 3,4-bis(methylene)tricyclo[3.l.O.0\(^{2.6}\)]hexane (4) have been investigated. The assignment given is based on a ZDO model and semiempirical calculations. Tagether with the PE data of benzvalene (2), the reported data allow a comparison between 1-2 and 3-4. This yields a measure of the interactions between 8 cyclobutane or 8 bicyclobutane moiety and a double bond system within a ZDO model. The resonance integral found in the case of 1 and 3 amounts to -1.9 eV, that for 2 and 4, to -2.3 eV. The investigations furthermore reveal that the electronic factors which contribute to the higher reactivity of the bicyclobutane compounds amount to 5 kcal/mol.
2,2′-Bipyridyl is shown to spontaneously abstract a borylene fragment (R–B:) from various hypovalent boron compounds. This process is a redox reaction in which the bipyridine is reduced and becomes a dianionic substituent bound to boron through its two nitrogen atoms. Various transition metal–borylene complexes and diboranes, as a well as a diborene, take part in this reaction. In the latter case, our results show an intriguing example of the homolytic cleavage of a B═B double bond.
Tbe 2',3'-dideoxy analogue of the potent A\(_1\) receptor agonist, N\(^6\)-cyclohexyladenosine (CHA), was synthesized as a potential antagonist for the A\(_1\) adenosine receptor. In sturlies on adenylate cyclase 2',3'-dideoxy-N\(^6\)-cyclohexyladenosine (ddCHA) did not show agonist properties at A\(_1\) or at A\(_2\) receptors. However, it antagonized the inhibition by R-PIA of adenylate cyclase activity of fat cell membranes via A\(_1\) receptors with a K\(_i\) value of 13 \(\mu\)M. ddCHA competed for the binding of the selective A1 receptor antagonist, [\(^3\) HJ8-cyclopentyl-1,3-dipropylxantbine ([\(^3\)H]DPCPX), to rat brain membranes with a K\(_i\) value of 4.8 \(\mu\)M; GTP did not affect the competition curve. In contrast to the marked stereoselectivity of the A\(_1\) receptor for the cx- and the natural ß-anomer of adenosine, the cx-anomer of ddCHA showed a comparable affinity for the A\(_1\) receptor (K\(_i\) value 13.9 \8\mu\)M). These data indicate that the 2'- and 3'-hydroxy groups of adenosine and its derivatives are required foragonist activity at and high affinity binding to A\(_1\) adenosine receptors and for the distinction between the cx- and ß-forms.
BACKGROUND:
We observed a disproportional 18 F-fluorothymidine (F-FLT) uptake in follicular lymphoma (FL) relative to its low cell proliferation. We tested the hypothesis that the 'excess' uptake of 18 F-FLT in FL is related to error-prone DNA repair and investigated whether this also contributes to 18 F-FLT uptake in diffuse large B cell lymphoma (DLBCL).
METHODS:
We performed immunohistochemical stainings to assess the pure DNA replication marker MIB-1 as well as markers of both DNA replication and repair like PCNA, TK-1 and RPA1 on lymph node biopsies of 27 FLs and 35 DLBCLs. In 7 FL and 15 DLBCL patients, 18 F-FLT-PET had been performed.
RESULTS:
18 F-FLT uptake was lower in FL than in DLBCL (median SUVmax 5.7 vs. 8.9, p = 0,004), but the ratio of 18 F-FLT-SUVmax to percentage of MIB-1 positive cells was significantly higher in FL compared with DLBCL (p = 0.001). The median percentage of MIB-1 positive cells was 10% (range, 10% to 20%) in FL and 70% (40% to 80%) in DLBCL. In contrast, the median percentages of PCNA, TK-1 and RPA1 positive cells were 90% (range, 80 to 100), 90% (80 to 100) and 100% (80 to 100) in FL versus 90% (60 to 100), 90% (60 to 100) and 100% (80 to 100) in DLBCL, respectively.
CONCLUSIONS:
This is the first demonstration of a striking discordance between 18 F-FLT uptake in FL and tumour cell proliferation. High expression of DNA replication and repair markers compared with the pure proliferation marker MIB-1 in FL suggests that this discordance might be due to error-prone DNA repair. While DNA repair-related 18 F-FLT uptake considerably contributes to 18 F-FLT uptake in FL, its contribution to 18 F-FLT uptake in highly proliferative DLBCL is small. This apparently high contribution of DNA repair to the 18 F-FLT signal in FL may hamper studies where 18 F-FLT is used to assess response to cytostatic therapy or to distinguish between FL and transformed lymphoma.
The phylogeny of Euglenophyceae (Euglenozoa, Euglenida) has been discussed for decades with new genera being described in the last few years. In this study, we reconstruct a phylogeny using 18S rDNA sequence and structural data simultaneously. Using homology modeling, individual secondary structures were predicted. Sequence–structure data are encoded and automatically aligned. Here, we present a sequence–structure neighbor‐joining tree of more than 300 taxa classified as Euglenophyceae. Profile neighbor‐joining was used to resolve the basal branching pattern. Neighbor‐joining, maximum parsimony, and maximum likelihood analyses were performed using sequence–structure information for manually chosen subsets. All analyses supported the monophyly of Eutreptiella, Discoplastis, Lepocinclis, Strombomonas, Cryptoglena, Monomorphina, Euglenaria, and Colacium. Well‐supported topologies were generally consistent with previous studies using a combined dataset of genetic markers. Our study supports the simultaneous use of sequence and structural data to reconstruct more accurate and robust trees. The average bootstrap value is significantly higher than the average bootstrap value obtained from sequence‐only analyses, which is promising for resolving relationships between more closely related taxa.
Protothecosis is an infectious disease caused by organisms currently classified within the green algal genus Prototheca. The disease can manifest as cutaneous lesions, olecranon bursitis or disseminated or systemic infections in both immunocompetent and immunosuppressed patients. Concerning diagnostics, taxonomic validity is important. Prototheca, closely related to the Chlorella species complex, is known to be polyphyletic, branching with Auxenochlorella and Helicosporidium. The phylogeny of Prototheca was discussed and revisited several times in the last decade; new species have been described. Phylogenetic analyses were performed using ribosomal DNA (rDNA) and partial mitochondrial cytochrome b (cytb) sequence data. In this work we use Internal Transcribed Spacer 2 (ITS2) as well as 18S rDNA data. However, for the first time, we reconstruct phylogenetic relationships of Prototheca using primary sequence and RNA secondary structure information simultaneously, a concept shown to increase robustness and accuracy of phylogenetic tree estimation. Using encoded sequence-structure data, Neighbor-Joining, Maximum-Parsimony and Maximum-Likelihood methods yielded well-supported trees in agreement with other trees calculated on rDNA; but differ in several aspects from trees using cytb as a phylogenetic marker. ITS2 secondary structures of Prototheca sequences are in agreement with the well-known common core structure of eukaryotes but show unusual differences in their helix lengths. An elongation of the fourth helix of some species seems to have occurred independently in the course of evolution.
The aim of this study was to investigate the prognostic value of 18F-fluoro-deoxyglucose positron emission tomography–computed tomography (18F-FDG-PET/CT) in 37 patients with a history of multiple myeloma (MM) and suspected or confirmed recurrence after stem cell transplantation (SCT). All patients had been heavily pre-treated. Time to progression (TTP) and overall survival (OS) were correlated to a number of different PET-derived as well as clinical parameters. Impact on patient management was assessed.
Absence of FDG-avid MM foci was a positive prognostic factor for both TTP and OS (p<0.01). Presence of >10 focal lesions correlated with both TTP (p<0.01) and OS (p<0.05). Interestingly, presence of >10 lesions in the appendicular skeleton proved to have the strongest association with disease progression. Intensity of glucose uptake and presence of extramedullary disease were associated with shorter TTP (p=0.037 and p=0.049, respectively). Manifestations in soft tissue structures turned out to be a strong negative predictor for both, TTP and OS (p<0.01, respectively). PET resulted in a change of management in 30% of patients.
Our data underline the prognostic value of 18F-FDG-PET/CT in MM patients also in the setting of post-SCT relapse. PET/CT has a significant impact on patient management.
This study aimed to explore the correlation between imaging patterns and clinical features in patients with smoldering multiple myeloma (SMM) who simultaneously underwent 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT). We retrieved and analyzed clinical characteristics and PET imaging data of 10 patients with SMM. We found a significant correlation between bone marrow (BM) plasma cell (PC) infiltration and mean standardized uptake values (SUV\(_{mean}\)) of lumbar vertebrae L2-L4 on 11C-Methionine PET/CT scans (r = 0.676, p = 0.031) and 68Ga-Pentixafor PET/CT scans (r = 0.839, p = 0.002). However, there was no significant correlation between BM involvement and SUV\(_{mean}\) of lumbar vertebrae L2-L4 on 18F-FDG PET/CT scans (r = 0.558, p = 0.093). Similarly, mean target-to-background ratios (TBR\(_{mean}\)) of lumbar vertebrae L2-L4 also correlated with bone marrow plasma cell (BMPC) infiltration in 11C-Methionine PET/CT (r = 0.789, p = 0.007) and 68Ga-Pentixafor PET/CT (r = 0.724, p = 0.018) PET/CT. In contrast, we did not observe a significant correlation between BMPC infiltration rate and TBR\(_{mean}\) in 18F-FDG PET/CT (r = 0.355, p = 0.313). Additionally, on 11C-Methionine PET/CT scans, we found a significant correlation between BMPC infiltration and TBR\(_{max}\) of lumbar vertebrae L2-L4 (r = 0.642, p = 0.045). In conclusion, 11C-Methionine and 68Ga-Pentixafor PET/CT demonstrate higher sensitivity than 18F-FDG PET/CT in detecting BM involvement in SMM.
Herein we devise and execute a new synthesis of a pristine boron-doped nanographene. Our target boron-doped nanographene was designed based on DFT calculations to possess a low LUMO energy level and a narrow band gap derived from its precise geometry and B-doping arrangement. Our synthesis of this target, a doubly B-doped hexabenzopentacene (B\(_{2}\)-HBP), employs six net C−H borylations of an alkene, comprising consecutive hydroboration/electrophilic borylation/dehydrogenation and BBr\(_{3}\)/AlCl\(_{3}\)/2,6-dichloropyridine-mediated C−H borylation steps. As predicted by our calculations, B\(_{2}\)-HBP absorbs strongly in the visible region and emits in the NIR up to 1150 nm in o-dichlorobenzene solutions. Furthermore, B\(_{2}\)-HBP possesses a very low LUMO level, showing two reversible reductions at −1.00 V and −1.17 V vs. Fc\(^{+}\)/Fc. Our methodology is surprisingly selective despite its implementation of unfunctionalized precursors and offers a new approach to the synthesis of pristine B-doped polycyclic aromatic hydrocarbons.
100-kHz shot-to-shot broadband data acquisition for high-repetition-rate pump–probe spectroscopy
(2014)
Shot-to-shot broadband detection is common in ultrafast pump–probe spectroscopy. Taking advantage of the intensity correlation of subsequent laser pulses improves the signal-to-noise ratio. Finite data readout times of CCD chips in the employed spectrometer and the maximum available speed of mechanical pump-beam choppers typically limit this approach to lasers with repetition rates of a few kHz. For high-repetition (≥ 100 kHz) systems, one typically averages over a larger number of laser shots leading to inferior signal-to-noise ratios or longer measurement times. Here we demonstrate broadband shot-to-shot detection in transient absorption spectroscopy with a 100-kHz femtosecond laser system. This is made possible using a home-built high-speed chopper with external laser synchronization and a fast CCD line camera. Shot-to-shot detection can reduce the data acquisition time by two orders of magnitude compared to few-kHz lasers while keeping the same signal-to-noise ratio.
This paper deals with the origin of the hundred-year old theory of tierras bajas and tierras altas, focusing on the description of vowel weakening within that theory developed in 1921 by Henríquez Ureña. I argue that the early conception of vowel weakening and its dialectal distribution has strongly influenced the kind of research we have been conducting about this phonetic feature to this day. The aim of this study therefore, is to sharpen our understanding of the former zeitgeist of research and to stimulate further big data-based studies on vowel weakening overcoming the traditional dialectal division of tierras bajas and tierras altas.
No abstract available
No abstract available
The 1,3-bis(tricyanoborane)imidazolate anion 1 was obtained in high yield from lithium imidazolate and B(CN)\(_3\)−pyridine adduct. Anion 1 is chemically very robust and thus allowed the isolation of the corresponding H\(_5\)O\(_2\)\(^+\) salt. Furthermore, monoanion 1 served as starting species for the novel dianionic N-heterocyclic carbene (NHC), 1,3-bis(tricyanoborane)imidazoline-2-ylidenate anion 3 that acts as ditopic ligand via the carbene center and the cyano groups at boron. First reactions of this new NHC 3 with methyl iodide, elemental selenium, and [Ni(CO)\(_4\)] led to the methylated imidazolate ion 4, the dianionic selenium adduct 5, and the dianionic nickel tricarbonyl complex 6. These NHC derivatives provide a first insight into the electronic and steric properties of the dianionic NHC 3. Especially the combination of properties, such as double negative charge, different coordination sites, large buried volume and good σ-donor and π-acceptor ability, make NHC 3 a unique and promising ligand and building block.
1,25-dihydroxyvitamin D3 (1,25D3) was reported to induce premature organismal aging in fibroblast growth factor-23 (Fgf23) and klotho deficient mice, which is of main interest as 1,25D3 supplementation of its precursor cholecalciferol is used in basic osteoporosis treatment. We wanted to know if 1,25D3 is able to modulate aging processes on a cellular level in human mesenchymal stem cells (hMSC). Effects of 100 nM 1,25D3 on hMSC were analyzed by cell proliferation and apoptosis assay, beta-galactosidase staining, VDR and surface marker immunocytochemistry, RT-PCR of 1,25D3-responsive, quiescence-and replicative senescence-associated genes. 1,25D3 treatment significantly inhibited hMSC proliferation and apoptosis after 72 h and delayed the development of replicative senescence in long-term cultures according to beta-galactosidase staining and P16 expression. Cell morphology changed from a fibroblast like appearance to broad and rounded shapes. Long term treatment did not induce lineage commitment in terms of osteogenic pathways but maintained their clonogenic capacity, their surface marker characteristics (expression of CD73, CD90, CD105) and their multipotency to develop towards the chondrogenic, adipogenic and osteogenic pathways. In conclusion, 1,25D3 delays replicative senescence in primary hMSC while the pro-aging effects seen in mouse models might mainly be due to elevated systemic phosphate levels, which propagate organismal aging.
In the molecular structure of the title compound, C34H58B2N2, each B atom of the diborane(4) is connected to one dimethylamino group and one Tip ligand (Tip = 2,4,6-triisopropylphenyl). These findings indicate that the increased steric demand of the Tip groups exerts influence solely on the B—B separation but not on the overall geometry of the title compound.
No abstract available
Reaktionen von 1,3-Butadien und einigen seiner Methylderivate mit 1a und 1- Methyl-1,2-cyclohexadien 1b sowie den Übergang der [2 + 2]-Cycloaddukte 2 und 3 in das bisher unbekannte 1,2,3,5,8,8a-HexahydronaphthaJin 4a und einige seiner Methylderivate
No abstract available
The isolation and structure elucidation of rac-dioncophyllacine A from the leaves of Triphyophyllun peltatum, is described. Unlike all other naphthylisoquinoline alkaloids, this fully dehydrogenated representative has an additional methoxy group at C-4, the position of which is deduced from NOE results. Dioncophyllacine A has a 7,1' site of the biaryl axis, as in dioncophylline A. Its constitution is confirmed by an X-ray structure analysis, which shows that the crystalline form of this new alkaloid is racemic.
Die erstmalige Synthese der (Thioacetoxy-S-methyl)diorganylsilane (CH\(_3\))\(_2\)Si(H)CH\(_2\)SC(O)CH\(_3\) (9) und (C\(_6\)H\(_5\))\(_2\)Si(H)CH\(_2\)SC(O)CH\(_3\) (10) und der (Mercaptomethyl) diorganylsilane (CH\(_3\))\(_2\)Si(H)CH\(_2\)SH (11) und (C\(_6\)H\(_5\))\(_2\)Si(H)CH\(_2\)SH (12) wird beschrieben. Während sich die Silane 9 und 10 leicht handhaben lassen, neigen die strukturanalogen (Hydroxymethyl)diorganylsilane (CH\(_3\))\(_2\)Si(H)CH\(_2\)OH (1) und (C\(_6\)H\(_5\))\(_2\)Si(H)CH\(_2\)OH (2) zu einer basenkatalysierten Zersetzung (Bildung oligomerer (polymerer) Alkoxysilane und Wasserstoff). Im Gegensatz zu den thermisch labilen (Acetoxymethyl)diorganylsilanen (CH\(_3\))\(_2\)Si(H)CH\(_2\)OC(O)CH\(_3\) (3) und (C\(_6\)H\(_5\))\(_2\)Si(H)CH\(_2\)OC(O)CH\(_3\) (4) (--+ Umlagerung zu den entsprechenden Acetoxy(methyl) diorganylsilanen (CH\(_3\)) \(_3\)SiOC(O)CH\(_3\) (5) und CH\(_3\)(C\(_6\)H\(_5\))\(_2\)SiOC(O)CH\(_3\) {6)) sind die Thio-Analoga 9 und 10 thermisch stabil (I-molare Lösungen in C\(_6\)D\(_6\), 30 h bei 180 o C).
(I\(_2\)GaS-i-C\(_3\)H\(_7\))\(_2\), das erste butterfly-Molekül mit vierfach koordiniertem Gallium
(1985)
No abstract available
No abstract available.
(Acetoxymethyl)methylphenylgerman: Synthese, thermisches Verhalten und olfaktorische Eigenschaften
(1991)
No abstract available.
Die Synthese der (2-Aminoethyl)cycloalkylphenylsilanole Sb (Sila-Trihexyphenidyl), 6b (SilaCycrimin), 7 b (Sila-Procyclidin) und Sb wird beschrieben. Sb- Sb wurden - ausgehend von Cl\(_2\)(C\(_6\)H\(_5\))SiCH = CH\(_2\) (9) - durch eine fünfstufige Reaktionsfolge mit einer Gesamtausbeute von 32- 40% erhalten. Am isolierten Ileum des Meerschweinchens wurden die C/Si-Paare Sa, b- 8a, b vergleichend auf ihre antimuskarinische Aktivität geprüft. Die durch die Sila-Substilution von Sa-8a erreichte Zunahme der Affinität zum Muskarinrezeptor ist deutlich weniger ausgeprägt als bei den strukturverwandten C/Si-Paaren I a, b- 4a, b.