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Gehrke, Peter ; Burg, Simon ; Peters, Ulrike ; Beikler, Thomas ; Fischer, Carsten ; Rupp, Frank ; Schweizer, Ernst ; Weigl, Paul ; Sader, Robert Alexander ; Smeets, Ralf ; Schäfer, Sogand
Objectives: A conometric concept was recently introduced in which conical implant abutments hold the matching crown copings by friction alone, eliminating the need for cement or screws. The aim of this in vitro study was to assess the presence of microgap formation and bacterial leakage at the Acuris conometric restorative interface of three different implant abutment systems. Material and methods: A total of 75 Acuris samples of three implant-abutment systems (Ankylos, Astra Tech EV, Xive) were subjected to microbiological (n = 60) and scanning electron microscopic (SEM) investigation (n = 15). Bacterial migration into and out of the conical coupling system were analyzed in an anaerobic workstation for 48, 96, 144, and 192 h. Bacterial DNA quantification using qrt-PCR was performed at each time point. The precision of the conometric coupling and internal fit of cemented CAD/CAM crowns on corresponding Acuris TiN copings were determined by means of SEM. Results: qrt-PCR results failed to demonstrate microbial leakage from or into the Acuris system. SEM analysis revealed minute punctate microgaps at the apical aspect of the conometric junction (2.04 to 2.64 µm), while mean cement gaps of 12 to 145 µm were observed at the crown-coping interface. Conclusions: The prosthetic morse taper connection of all systems examined does not allow bacterial passage. Marginal integrity and internal luting gap between the ceramic crown and the coping remained within the clinically acceptable limits. Clinical relevance: Conometrically seated single crowns provide sufficient sealing efficiency, relocating potential misfits from the crown-abutment interface to the crown-coping interface.
Kaufmann, Manfred ; Blank, Jörg ; Guggenmoser, Tobias ; Ungermann, Jörn ; Engel, Andreas ; Ern, Manfred ; Friedl-Vallon, Felix ; Gerber, Daniel ; Grooß, Jens-Uwe ; Günther, Gebhard ; Höpfner, Michael ; Kleinert, Anne ; Kretschmer, Ernst ; Latzko, Thomas ; Maucher, Guido ; Neubert, Tom ; Nordmeyer, Hans ; Oelhaf, Hermann ; Olschewski, Friedhelm ; Orphal, Johannes ; Preusse, Peter ; Schlager, Hans ; Schneider, Herbert ; Schüttemeyer, Dirk ; Stroh, Fred ; Suminska-Ebersoldt, Olga ; Vogel, Bärbel ; Volk, C.-Michael ; Woiwode, Wolfgang ; Riese, Martin
The three-dimensional quantification of small-scale processes in the upper troposphere and lower stratosphere is one of the challenges of current atmospheric research and requires the development of new measurement strategies. This work presents the first results from the newly developed Gimballed Limb Observer for Radiance Imaging of the Atmosphere (GLORIA) obtained during the ESSenCe (ESa Sounder Campaign) and TACTS/ESMVal (TACTS: Transport and composition in the upper troposphere/lowermost stratosphere, ESMVal: Earth System Model Validation) aircraft campaigns. The focus of this work is on the so-called dynamics-mode data characterized by a medium-spectral and a very-high-spatial resolution. The retrieval strategy for the derivation of two- and three-dimensional constituent fields in the upper troposphere and lower stratosphere is presented. Uncertainties of the main retrieval targets (temperature, O3, HNO3, and CFC-12) and their spatial resolution are discussed. During ESSenCe, high-resolution two-dimensional cross-sections have been obtained. Comparisons to collocated remote-sensing and in situ data indicate a good agreement between the data sets. During TACTS/ESMVal, a tomographic flight pattern to sense an intrusion of stratospheric air deep into the troposphere was performed. It was possible to reconstruct this filament at an unprecedented spatial resolution of better than 500 m vertically and 20 × 20 km horizontally.
Pluska, Lukas ; Jarosch, Ernst ; Zauber, Henrik ; Kniß, Andreas ; Waltho, Anita ; Bagola, Katrin ; Delbrück, Maximilian von ; Löhr, Frank ; Schulman, Brenda A. ; Selbach, Matthias ; Dötsch, Volker ; Sommer, Thomas
The assembly of a specific polymeric ubiquitin chain on a target protein is a key event in the regulation of numerous cellular processes. Yet, the mechanisms that govern the selective synthesis of particular polyubiquitin signals remain enigmatic. The homologous ubiquitin-conjugating (E2) enzymes Ubc1 (budding yeast) and Ube2K (mammals) exclusively generate polyubiquitin linked through lysine 48 (K48). Uniquely among E2 enzymes, Ubc1 and Ube2K harbor a ubiquitin-binding UBA domain with unknown function. We found that this UBA domain preferentially interacts with ubiquitin chains linked through lysine 63 (K63). Based on structural modeling, in vitro ubiquitination experiments, and NMR studies, we propose that the UBA domain aligns Ubc1 with K63-linked polyubiquitin and facilitates the selective assembly of K48/K63-branched ubiquitin conjugates. Genetic and proteomics experiments link the activity of the UBA domain, and hence the formation of this unusual ubiquitin chain topology, to the maintenance of cellular proteostasis.
Weissbecker, Juliane ; Boumrifak, Chokri ; Breyer, Maximilian ; Wießalla, Tristan ; Shevchenko, Vitaly ; Mager, Thomas ; Slavov, Chavdar ; Alekseev, Alexey ; Kovalev, Kirill ; Gordeliy, Valentin ; Bamberg, Ernst ; Wachtveitl, Josef
The new class of microbial rhodopsins, called xenorhodopsins (XeRs),[1] extends the versatility of this family by inward H+ pumps.[2–4] These pumps are an alternative optogenetic tool to the light-gated ion channels (e.g. ChR1,2), because the activation of electrically excitable cells by XeRs is independent from the surrounding physiological conditions. In this work we functionally and spectroscopically characterized XeR from Nanosalina (NsXeR).[1] The photodynamic behavior of NsXeR was investigated on the ps to s time scale elucidating the formation of the J and K and a previously unknown long-lived intermediate. The pH dependent kinetics reveal that alkalization of the surrounding medium accelerates the photocycle and the pump turnover. In patch-clamp experiments the blue-light illumination of NsXeR in the M state shows a potential-dependent vectoriality of the photocurrent transients, suggesting a variable accessibility of reprotonation of the retinal Schiff base. Insights on the kinetically independent switching mechanism could furthermore be obtained by mutational studies on the putative intracellular H+ acceptor D220.
Grünewald, Leon David ; Koch, Vitali ; Martin, Simon ; Yel, Ibrahim ; Eichler, Katrin ; Gruber-Rouh, Tatjana ; Lenga, Lukas Fabian ; Wichmann, Julian ; Alizadeh, Leona Soraja ; Albrecht, Moritz Hans Ernst ; Mader, Christoph ; Huizinga, Nicole A. ; D’Angelo, Tommaso ; Mazziotti, Silvio ; Wesarg, Stefan ; Vogl, Thomas J. ; Booz, Christian
Objectives: To evaluate the predictive value of volumetric bone mineral density (BMD) assessment of the lumbar spine derived from phantomless dual-energy CT (DECT)-based volumetric material decomposition as an indicator for the 2-year occurrence risk of osteoporosis-associated fractures. Methods: L1 of 92 patients (46 men, 46 women; mean age, 64 years, range, 19–103 years) who had undergone third-generation dual-source DECT between 01/2016 and 12/2018 was retrospectively analyzed. For phantomless BMD assessment, dedicated DECT postprocessing software using material decomposition was applied. Digital files of all patients were sighted for 2 years following DECT to obtain the incidence of osteoporotic fractures. Receiver operating characteristic (ROC) analysis was used to calculate cut-off values and logistic regression models were used to determine associations of BMD, sex, and age with the occurrence of osteoporotic fractures. Results: A DECT-derived BMD cut-off of 93.70 mg/cm3 yielded 85.45% sensitivity and 89.19% specificity for the prediction to sustain one or more osteoporosis-associated fractures within 2 years after BMD measurement. DECT-derived BMD was significantly associated with the occurrence of new fractures (odds ratio of 0.8710, 95% CI, 0.091–0.9375, p < .001), indicating a protective effect of increased DECT-derived BMD values. Overall AUC was 0.9373 (CI, 0.867–0.977, p < .001) for the differentiation of patients who sustained osteoporosis-associated fractures within 2 years of BMD assessment. Conclusions: Retrospective DECT-based volumetric BMD assessment can accurately predict the 2-year risk to sustain an osteoporosis-associated fracture in at-risk patients without requiring a calibration phantom. Lower DECT-based BMD values are strongly associated with an increased risk to sustain fragility fractures.
Key Points: Dual-energy CT–derived assessment of bone mineral density can identify patients at risk to sustain osteoporosis-associated fractures with a sensitivity of 85.45% and a specificity of 89.19%. The DECT-derived BMD threshold for identification of at-risk patients lies above the American College of Radiology (ACR) QCT guidelines for the identification of osteoporosis (93.70 mg/cm 3 vs 80 mg/cm 3 ).
Rybczyński, Maciej ; Alt, Christopher ; Antičić, Tome ; Baatar, B. ; Barna, Daniel ; Bartke, Jerzy ; Betev, Latchezar ; Białkowska, Helena ; Billmeier, Anja ; Blume, Christoph ; Boimska, Bożena ; Botje, Michiel ; Bracinik, Juraj ; Bramm, Roland ; Brun, René ; Bunčić, Predrag ; Cerny, Vladimír ; Christakoglou, Panagiotis ; Chvala, Ondrej ; Cramer, John G. ; Csató, Péter ; Darmenov, Nikolay ; Dimitrov, Anton ; Dinkelaker, Peter ; Eckardt, Volker ; Farantatos, Gerassimos ; Flierl, Dominik Bernhard ; Fodor, Zoltán ; Foka, Panagiota ; Freund, Peter ; Friese, Volker ; Gál, József ; Gaździcki, Marek ; Georgopoulos, George ; Gładysz-Dziaduś, Ewa ; Grebieszkow, Katarzyna ; Hegyi, Sándor ; Höhne, Claudia ; Kadija, Krešo ; Karev, Alexandre ; Kliemant, Michael ; Kniege, Stefan ; Kolesnikov, Vadim I. ; Kollegger, Thorsten ; Kornas, Ewelina ; Korus, Robert ; Kowalski, Marek ; Kraus, Ingrid ; Kreps, Michal ; Leeuwen, Marco van ; Lévai, Péter ; Litov, Leandr ; Lungwitz, Benjamin ; Makariev, Martin ; Malakhov, Aleksandr I. ; Markert, Christina ; Mateev, Matej D. ; Mayes, Bill W. ; Melkumov, Georgy L. ; Meurer, Christine ; Mischke, André ; Mitrovski, Michael Kosta ; Molnár, József ; Mrówczyński, Stanislaw ; Pálla, Gabriella ; Panagiotou, Apostolos D. ; Panayotov, Dobromir ; Petridis, Athanasios ; Pikna, Miroslav ; Pinsky, Lawrence ; Pühlhofer, Falk ; Reid, Jeffrey G. ; Renfordt, Rainer Arno Ernst ; Richard, Agnes Carol Joanna ; Roland, Christof ; Roland, Gunther ; Rybicki, Andrzej ; Sandoval, Andres ; Sann, Hans ; Schmitz, Norbert ; Seyboth, Peter ; Siklér, Ferenc ; Sitar, Branislav ; Skrzypczak, Ewa ; Stefanek, Grzegorz ; Stock, Reinhard ; Ströbele, Herbert ; Susa, Tatjana ; Szentpétery, Imre ; Sziklai, János ; Trainor, Thomas A. ; Trubnikov, Victor ; Varga, Dezsö ; Vassiliou, Maria ; Veres, Gábor I. ; Vesztergombi, György ; Vranić, Danilo ; Wetzler, Alexander Albert ; Włodarczyk, Zbigniew ; Yoo, In-Kwon ; Zaranek, Jacek ; Zimányi, József
System size dependence of multiplicity fluctuations of charged particles produced in nuclear collisions at 158 A GeV was studied in the NA49 CERN experiment. Results indicate a non-monotonic dependence of the scaled variance of the multiplicity distribution with a maximum for semi-peripheral Pb+Pb interactions with number of projectile participants of about 35. This effect is not observed in a string-hadronic model of nuclear collision HIJING.
Dürr, Katharina L. ; Tavraz, Neslihan Neslihan ; Dempski, Robert E. ; Bamberg, Ernst ; Friedrich, Thomas
The β-subunits of Na,K-ATPase and H,K-ATPase have important functions in maturation and plasma membrane targeting of the catalytic α-subunit but also modulate the transport activity of the holoenzymes. In this study, we show that tryptophan replacement of two highly conserved tyrosines in the transmembrane domain of both Na,K- and gastric H,K-ATPase β-subunits resulted in considerable shifts of the voltage-dependent E1P/E2P distributions toward the E1P state as inferred from presteady-state current and voltage clamp fluorometric measurements of tetramethylrhodamine-6-maleimide-labeled ATPases. The shifts in conformational equilibria were accompanied by significant decreases in the apparent affinities for extracellular K+ that were moderate for the Na,K-ATPase β-(Y39W,Y43W) mutation but much more pronounced for the corresponding H,K-ATPase β-(Y44W,Y48W) variant. Moreover in the Na,K-ATPase β-(Y39W,Y43W) mutant, the apparent rate constant for reverse binding of extracellular Na+ and the subsequent E2P-E1P conversion, as determined from transient current kinetics, was significantly accelerated, resulting in enhanced Na+ competition for extracellular K+ binding especially at extremely negative potentials. Analogously the reverse binding of extracellular protons and subsequent E2P-E1P conversion was accelerated by the H,K-ATPase β-(Y44W,Y48W) mutation, and H+ secretion was strongly impaired. Remarkably tryptophan replacements of residues in the M7 segment of Na,K- and H,K-ATPase α-subunits, which are at interacting distance to the β-tyrosines, resulted in similar E1 shifts, indicating their participation in stabilization of E2. Thus, interactions between selected residues within the transmembrane regions of α- and β-subunits of P2C-type ATPases exert an E2-stabilizing effect, which is of particular importance for efficient H+ pumping by H,K-ATPase under in vivo conditions.
The Na+/K+-ATPase maintains the physiological Na+ and K+ gradients across the plasma membrane in most animal cells. The functional unit of the ion pump is comprised of two mandatory subunits including the α-subunit, which mediates ATP hydrolysis and ion translocation, as well as the β-subunit, which acts as a chaperone to promote proper membrane insertion and trafficking in the plasma membrane. To examine the conformational dynamics between the α- and β-subunits of the Na+/K+-ATPase during ion transport, we have used fluorescence resonance energy transfer, under voltage clamp conditions on Xenopus laevis oocytes, to differentiate between two models that have been proposed for the relative orientation of the α- and β-subunits. These experiments were performed by measuring the time constant of irreversible donor fluorophore destruction with fluorescein-5-maleimide as the donor fluorophore and in the presence or absence of tetramethylrhodamine-6-maleimide as the acceptor fluorophore following labeling on the M3-M4 or M5-M6 loop of the α-subunit and the β-subunit. We have also used fluorescence resonance energy transfer to investigate the relative movement between the two subunits as the ion pump shuttles between the two main conformational states (E1 and E2) as described by the Albers-Post scheme. The results from this study have identified a model for the orientation of the β-subunit in relation to the α-subunit and suggest that the α- and β-subunits move toward each other during the E2 to E1 conformational transition.
Koenderink, Jan Bernhard ; Geibel, Sven ; Grabsch, Eva ; Pont, Jan J. H. H. M. de ; Bamberg, Ernst ; Friedrich, Thomas
Na,K-ATPase mediates net electrogenic transport by extruding three Na+ ions and importing two K+ ions across the plasma membrane during each reaction cycle. We mutated putative cation coordinating amino acids in transmembrane hairpin M5-M6 of rat Na,K-ATPase: Asp776 (Gln, Asp, Ala), Glu779 (Asp, Gln, Ala), Asp804 (Glu, Asn, Ala), and Asp808 (Glu, Asn, Ala). Electrogenic cation transport properties of these 12 mutants were analyzed in two-electrode voltage-clamp experiments on Xenopus laevis oocytes by measuring the voltage dependence of K+-stimulated stationary currents and pre-steady-state currents under electrogenic Na+/Na+ exchange conditions. Whereas mutants D804N, D804A, and D808A hardly showed any Na+/K+ pump currents, the other constructs could be classified according to the [K+] and voltage dependence of their stationary currents; mutants N776A and E779Q behaved similarly to the wild-type enzyme. Mutants E779D, E779A, D808E, and D808N had in common a decreased apparent affinity for extracellular K+. Mutants N776Q, N776D, and D804E showed large deviations from the wild-type behavior; the currents generated by mutant N776D showed weaker voltage dependence, and the current-voltage curves of mutants N776Q and D804E exhibited a negative slope. The apparent rate constants determined from transient Na+/Na+ exchange currents are rather voltage-independent and at potentials above -60 mV faster than the wild type. Thus, the characteristic voltage-dependent increase of the rate constants at hyperpolarizing potentials is almost absent in these mutants. Accordingly, dislocating the carboxamide or carboxyl group of Asn776 and Asp804, respectively, decreases the extracellular Na+ affinity.
The light-driven proton pump bacteriorhodopsin (BR) from Halobacterium salinarum is tightly regulated by the [H+] gradient and transmembrane potential. BR exhibits optoelectric properties, since spectral changes during the photocycle are kinetically controlled by voltage, which predestines BR for optical storage or processing devices. BR mutants with prolonged lifetime of the blue-shifted M intermediate would be advantageous, but the optoelectric properties of such mutants are still elusive. Using expression in Xenopus oocytes and two-electrode voltage-clamping, we analyzed photocurrents of BR mutants with kinetically destabilized (F171C, F219L) or stabilized (D96N, D96G) M intermediate in response to green light (to probe H+ pumping) and blue laser flashes (to probe accumulation/decay of M). These mutants have divergent M lifetimes. As for BR-WT, this strictly correlates with the voltage dependence of H+ pumping. BR-F171C and BR-F219L showed photocurrents similar to BR-WT. Yet, BR-F171C showed a weaker voltage dependence of proton pumping. For both mutants, blue laser flashes applied during and after green-light illumination showed reduced M accumulation and shorter M lifetime. In contrast, BR-D96G and BR-D96N exhibited small photocurrents, with nonlinear current-voltage curves, which increased strongly in the presence of azide. Blue laser flashes showed heavy M accumulation and prolonged M lifetime, which accounts for the strongly reduced H+ pumping rate. Hyperpolarizing potentials augmented these effects. The combination of M-stabilizing and -destabilizing mutations in BR-D96G/F171C/F219L (BR-tri) shows that disruption of the primary proton donor Asp-96 is fatal for BR as a proton pump. Mechanistically, M destabilizing mutations cannot compensate for the disruption of Asp-96. Accordingly, BR-tri and BR-D96G photocurrents were similar. However, BR-tri showed negative blue laser flash-induced currents even without actinic green light, indicating that Schiff base deprotonation in BR-tri exists in the dark, in line with previous spectroscopic investigations. Thus, M-stabilizing mutations, including the triple mutation, drastically interfere with electrochemical H+ gradient generation.