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370 result(s) for "Pohl, Peter"
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The Oxford illustrated history of the Third Reich
At age thirty in 1919, Adolf Hitler had no accomplishments. He was a rootless loner, a corporal in a shattered army, without money or prospects. A little more than twenty years later, in autumn 1941, he directed his dynamic forces against the Soviet Union, and in December, the Germans were at the gates of Moscow and Leningrad. At that moment, Hitler appeared - however briefly - to be the most powerful ruler on the planet. Given this dramatic turn of events, it is little wonder that since 1945 generations of historians keep trying to explain how it all happened. This richly illustrated history provides a readable and fresh approach to the complex history of the Third Reich, from the coming to power of the Nazis in 1933 to the final collapse in 1945. Using photographs, paintings, propaganda images, and a host of other such materials from a wide range of sources, including official documents, cinema, and the photography of contemporary amateurs, foreigners, and the Allied armies, it distills our ideas about the period and provides a balanced and accessible account of the whole era.
Label-free and charge-sensitive dynamic imaging of lipid membrane hydration on millisecond time scales
Biological membranes are highly dynamic and complex lipid bilayers, responsible for the fate of living cells. To achieve this function, the hydrating environment is crucial. However, membrane imaging typically neglects water, focusing on the insertion of probes, resonant responses of lipids, or the hydrophobic core. Owing to a recent improvement of second-harmonic (SH) imaging throughput by three orders of magnitude, we show here that we can use SH microscopy to follow membrane hydration of freestanding lipid bilayers on millisecond time scales. Instead of using the UV/VIS resonant response of specific membrane-inserted fluorophores to record static SH images over time scales of >1,000 s, we SH imaged symmetric and asymmetric lipid membranes, while varying the ionic strength and pH of the adjacent solutions. We show that the nonresonant SH response of water molecules aligned by charge–dipole interactions with charged lipids can be used as a label-free probe of membrane structure and dynamics. Lipid domain diffusion is imaged label-free by means of the hydration of charged domains. The orientational ordering of water is used to construct electrostatic membrane potential maps. The average membrane potential depends quadratically on an applied external bias, which is modeled by nonlinear optical theory. Spatiotemporal fluctuations on the order of 100-mV changes in the membrane potential are seen. These changes imply that membranes are very dynamic, not only in their structure but also in their membrane potential landscape. This may have important consequences for membrane function, mechanical stability, and protein/pore distributions.
Tutorial for Stopped-Flow Water Flux Measurements: Why a Report about “Ultrafast Water Permeation through Nanochannels with a Densely Fluorous Interior Surface” Is Flawed
Millions of years of evolution have produced proteinaceous water channels (aquaporins) that combine perfect selectivity with a transport rate at the edge of the diffusion limit. However, Itoh et al. recently claimed in Science that artificial channels are 100 times faster and almost as selective. The published deflation kinetics of vesicles containing channels or channel elements indicate otherwise, since they do not demonstrate the facilitation of water transport. In an illustrated tutorial on the experimental basis of stopped-flow measurements, we point out flaws in data processing. In contrast to the assumption voiced in Science, individual vesicles cannot simultaneously shrink with two different kinetics. Moreover, vesicle deflation within the dead time of the instrument cannot be detected. Since flawed reports of ultrafast water channels in Science are not a one-hit-wonder as evidenced by a 2018 commentary by Horner and Pohl in Science, we further discuss the achievable limits of single-channel water permeability. After analyzing (i) diffusion limits for permeation through narrow channels and (ii) hydrodynamics in the surrounding reservoirs, we conclude that it is unlikely to fundamentally exceed the evolutionarily optimized water-channeling performance of the fastest aquaporins while maintaining near-perfect selectivity.
Membrane Permeabilities of Ascorbic Acid and Ascorbate
Vitamin C (VC)—a collective term for the different oxidation and protonation forms of ascorbic acid (AscH)—is an essential micronutrient that serves as (i) a potent antioxidant and (ii) a cofactor of a manifold of enzymatic processes. Its role in health is related to redox balance maintenance, which is altered in diseases such as obesity, cancer, neurodegenerative diseases, hypertension, and autoimmune diseases. Despite its importance, VC uptake has been poorly investigated. Available literature values for the passive membrane permeability P of lipid bilayers for AscH scatter by about 10 orders of magnitude. Here, we show by voltage clamp that P − of AscH’s anionic form (ascorbate Asc − ) is negligible. To cross the membrane, Asc − picks up a proton in the membrane vicinity and releases it on the other side of the membrane. This leads to a near-membrane pH drop that was visualized by scanning pH microelectrodes. The AscH concentration dependent pH profiles indicated P   =   1.1   ±   0.1   ×   10 − 8   cm / s . Thus, AscH’s P is comparable to that of sorbitol and much lower than that of other weak acids like acetic acid or salicylic acid. The observation suggests that the capacity of the passive transcellular transport pathway across the lipid matrix does not suffice to ensure the required VC intake from the gastrointestinal tract.
Water at hydrophobic interfaces delays proton surface-to-bulk transfer and provides a pathway for lateral proton diffusion
Fast lateral proton migration along membranes is of vital importance for cellular energy homeostasis and various proton-coupled transport processes. It can only occur if attractive forces keep the proton at the interface. How to reconcile this high affinity to the membrane surface with high proton mobility is unclear. Here, we tested whether a minimalistic model interface between an apolar hydrophobic phase (n -decane) and an aqueous phase mimics the biological pathway for lateral proton migration. The observed diffusion span, on the order of tens of micrometers, and the high proton mobility were both similar to the values previously reported for lipid bilayers. Extensive ab initio simulations on the same water/ n -decane interface reproduced the experimentally derived free energy barrier for the excess proton. The free energy profile G H₊ adopts the shape of a well at the interface, having a width of two water molecules and a depth of 6 ± 2 RT . The hydroniums in direct contact with n -decane have a reduced mobility. However, the hydroniums in the second layer of water molecules are mobile. Their in silico diffusion coefficient matches that derived from our in vitro experiments, (5.7 ± 0.7) 10 ⁻⁵ cm ² s ⁻¹. Conceivably, these are the protons that allow for fast diffusion along biological membranes.
Photolipid excitation triggers depolarizing optocapacitive currents and action potentials
Optically-induced changes in membrane capacitance may regulate neuronal activity without requiring genetic modifications. Previously, they mainly relied on sudden temperature jumps due to light absorption by membrane-associated nanomaterials or water. Yet, nanomaterial targeting or the required high infrared light intensities obstruct broad applicability. Now, we propose a very versatile approach: photolipids (azobenzene-containing diacylglycerols) mediate light-triggered cellular de- or hyperpolarization. As planar bilayer experiments show, the respective currents emerge from millisecond-timescale changes in bilayer capacitance. UV light changes photolipid conformation, which awards embedding plasma membranes with increased capacitance and evokes depolarizing currents. They open voltage-gated sodium channels in cells, generating action potentials. Blue light reduces the area per photolipid, decreasing membrane capacitance and eliciting hyperpolarization. If present, mechanosensitive channels respond to the increased mechanical membrane tension, generating large depolarizing currents that elicit action potentials. Membrane self-insertion of administered photolipids and focused illumination allows cell excitation with high spatiotemporal control. Inspired by thermal optocapacitive approaches at regulating neuronal activity, the authors explore a photolipid-based non-thermal optocapacitive method that allows for regulating voltage-gated and mechanosensitive ion channels using light.
Filter gate closure inhibits ion but not water transport through potassium channels
The selectivity filter of K ⁺ channels is conserved throughout all kingdoms of life. Carbonyl groups of highly conserved amino acids point toward the lumen to act as surrogates for the water molecules of K ⁺ hydration. Ion conductivity is abrogated if some of these carbonyl groups flip out of the lumen, which happens (i) in the process of C-type inactivation or (ii) during filter collapse in the absence of K ⁺. Here, we show that K ⁺ channels remain permeable to water, even after entering such an electrically silent conformation. We reconstituted fluorescently labeled and constitutively open mutants of the bacterial K ⁺ channel KcsA into lipid vesicles that were either C-type inactivating or noninactivating. Fluorescence correlation spectroscopy allowed us to count both the number of proteoliposomes and the number of protein-containing micelles after solubilization, providing the number of reconstituted channels per proteoliposome. Quantification of the per-channel increment in proteoliposome water permeability with the aid of stopped-flow experiments yielded a unitary water permeability p f of (6.9 ± 0.6) × 10 ⁻¹³ cm ³⋅s ⁻¹ for both mutants. “Collapse” of the selectivity filter upon K ⁺ removal did not alter p f and was fully reversible, as demonstrated by current measurements through planar bilayers in a K ⁺-containing medium to which K ⁺-free proteoliposomes were fused. Water flow through KcsA is halved by 200 mM K ⁺ in the aqueous solution, which indicates an effective K ⁺ dissociation constant in that range for a singly occupied channel. This questions the widely accepted hypothesis that multiple K ⁺ ions in the selectivity filter act to mutually destabilize binding.
No facilitator required for membrane transport of hydrogen sulfide
Hydrogen sulfide (H₂S) has emerged as a new and important member in the group of gaseous signaling molecules. However, the molecular transport mechanism has not yet been identified. Because of structural similarities with H₂O, it was hypothesized that aquaporins may facilitate H₂S transport across cell membranes. We tested this hypothesis by reconstituting the archeal aquaporin AfAQP from sulfide reducing bacteria Archaeoglobus fulgidus into planar membranes and by monitoring the resulting facilitation of osmotic water flow and H₂S flux. To measure H₂O and H₂S fluxes, respectively, sodium ion dilution and buffer acidification by proton release (H₂S [left arrow over right arrow] H⁺ + HS⁻) were recorded in the immediate membrane vicinity. Both sodium ion concentration and pH were measured by scanning ion-selective microelectrodes. A lower limit of lipid bilayer permeability to H₂S, PM,H₂S greater-than-or-equal 0.5 ± 0.4 cm/s was calculated by numerically solving the complete system of differential reaction diffusion equations and fitting the theoretical pH distribution to experimental pH profiles. Even though reconstitution of AfAQP significantly increased water permeability through planar lipid bilayers, PM,H₂S remained unchanged. These results indicate that lipid membranes may well act as a barrier to water transport although they do not oppose a significant resistance to H₂S diffusion. The fact that cholesterol and sphingomyelin reconstitution did not turn these membranes into an H₂S barrier indicates that H₂S transport through epithelial barriers, endothelial barriers, and membrane rafts also occurs by simple diffusion and does not require facilitation by membrane channels.
Wie viel Gegenwart verträgt die aktuelle literaturwissenschaftliche Kontextdiskussion?
In recent issues of KulturPoetik Jan Borkowski, Manfred Engel and Martina King contributed to a fruitful debate about the implications of context-oriented literary criticism and presented methodological alternatives to the status quo. My essay will outline some of their propositions and review other concepts, namely Moritz Baßler’s and Lutz Danneberg’s. My goal is to point out two tendencies in current approaches to context. On the one hand, most of the researchers find extratextual contexts negligible and suggest to exclude e. g. social elements or media-technological surroundings. On the other hand, the present seems to play a strange role among the contributions. Whereas the interpretations focus on historical artefacts in order to execute a clean selection of contexts, contemporary ›Lebenswelt‹ serves implicitly as an ideal for context variety and context accessibility. The second part of the essay therefore sketches out a context-oriented analysis of contemporary literature, using the example of Gerhard Henschel’s autofictional novels. With their use of cut-up techniques the novels guide us directly to the historical contexts of the writer’s relatively recent past. But with its formal choices and aesthetic preferences the ›text‹ also provides us with a ›key‹ for its reception in the actual literary field of contemporary Germany.
Protons migrate along interfacial water without significant contributions from jumps between ionizable groups on the membrane surface
Proton diffusion along membrane surfaces is thought to be essential for many cellular processes such as energy transduction. Commonly, it is treated as a succession of jumps between membrane-anchored proton-binding sites. Our experiments provide evidence for an alternative model. We released membrane-bound caged protons by UV flashes and monitored their arrival at distant sites by fluorescence measurements. The kinetics of the arrival is probed as a function of distance for different membranes and for different water isotopes. We found that proton diffusion along the membrane is fast even in the absence of ionizable groups in the membrane, and it decreases strongly in D2O as compared to H2O. We conclude that the fast proton transport along the membrane is dominated by diffusion via interfacial water, and not via ionizable lipid moieties.