Minimal size of a barchan dune

Barchans are dunes of high mobility which have a crescent shape and propagate under conditions of unidirectional wind. However, sand dunes only appear above a critical size, which scales with the saturation distance of the sand flux [P. Hersen, S. Douady, and B. Andreotti, Phys. Rev. Lett. {\bf{89,}} 264301 (2002); B. Andreotti, P. Claudin, and S. Douady, Eur. Phys. J. B {\bf{28,}} 321 (2002); G. Sauermann, K. Kroy, and H. J. Herrmann, Phys. Rev. E {\bf{64,}} 31305 (2001)]. It has been suggested by P. Hersen, S. Douady, and B. Andreotti, Phys. Rev. Lett. {\bf{89,}} 264301 (2002) that this flux fetch distance is itself constant. Indeed, this could not explain the proto size of barchan dunes, which often occur in coastal areas of high litoral drift, and the scale of dunes on Mars. In the present work, we show from three dimensional calculations of sand transport that the size and the shape of the minimal barchan dune depend on the wind friction speed and the sand flux on the area between dunes in a field. Our results explain the common appearance of barchans a few tens of centimeter high which are observed along coasts. Furthermore, we find that the rate at which grains enter saltation on Mars is one order of magnitude higher than on Earth, and is relevant to correctly obtain the minimal dune size on Mars.Comment: 11 pages, 10 figure

Cardiac magnetic resonance assessment of central and peripheral vascular function in patients undergoing renal sympathetic denervation as predictor for blood pressure response

Background: Most trials regarding catheter-based renal sympathetic denervation (RDN) describe a proportion of patients without blood pressure response. Recently, we were able to show arterial stiffness, measured by invasive pulse wave velocity (IPWV), seems to be an excellent predictor for blood pressure response. However, given the invasiveness, IPWV is less suitable as a selection criterion for patients undergoing RDN. Consequently, we aimed to investigate the value of cardiac magnetic resonance (CMR) based measures of arterial stiffness in predicting the outcome of RDN compared to IPWV as reference. Methods: Patients underwent CMR prior to RDN to assess ascending aortic distensibility (AAD), total arterial compliance (TAC), and systemic vascular resistance (SVR). In a second step, central aortic blood pressure was estimated from ascending aortic area change and flow sequences and used to re-calculate total arterial compliance (cTAC). Additionally, IPWV was acquired. Results: Thirty-two patients (24 responders and 8 non-responders) were available for analysis. AAD, TAC and cTAC were higher in responders, IPWV was higher in non-responders. SVR was not different between the groups. Patients with AAD, cTAC or TAC above median and IPWV below median had significantly better BP response. Receiver operating characteristic (ROC) curves predicting blood pressure response for IPWV, AAD, cTAC and TAC revealed areas under the curve of 0.849, 0.828, 0.776 and 0.753 (p = 0.004, 0.006, 0.021 and 0.035). Conclusions: Beyond IPWV, AAD, cTAC and TAC appear as useful outcome predictors for RDN in patients with hypertension. CMR-derived markers of arterial stiffness might serve as non-invasive selection criteria for RDN

From:E to Z and back again: Reversible photoisomerisation of an isolated charge-tagged azobenzene

Substituted azobenzenes serve as chromophores and actuators in a wide range of molecular photoswitches. Here, tandem ion mobility spectrometry coupled with laser excitation is used to investigate the photoisomerisation of selected E and Z isomers of the charge-tagged azobenzene, methyl orange. Both isomers display a weak S1(nπ∗) photoisomerisation response in the blue part of the spectrum peaking at 440 nm and a more intense S2(ππ∗) photoisomerisation response in the near-UV with maxima at 370 and 310 nm for the E and Z isomers, respectively. The 60 nm separation between the S2(ππ∗) photo-response maxima for the two isomers allows them to be separately addressed in the gas phase and to be reversibly photoisomerised using different colours of light. This is an essential characteristic of an ideal photoswitch. The study demonstrates that a sequence of light pulses at different stages in an ion mobility spectrometer can be deployed to generate and probe isomers that cannot be electrosprayed directly from solution or produced through collisions in the ion source

The Level of Isoprostanes as a Non-invasive Marker for in vivo Lipid Peroxidation in Secondary Progressive Multiple Sclerosis

Oxidative stress leads to lipid peroxidation and may contribute to the pathogenesis of lesions in multiple sclerosis (MS), an autoimmune disease characterized by inflammatory as well as degenerative phenomena. Isoprostanes are prostaglandin-like compounds which are formed by free radical catalysed peroxidation of arachidonic acid esterified in membrane phospholipids. They are a new class of sensitive specific markers for in vivo lipid peroxidation. In this study 26 patients (15 females and 11 males; mean age 48.2 ± 15.2 year; mean disease duration 10.0 ± 6.5 year) with secondary progressive MS (SPMS) and 12 healthy controls were enrolled. In patients with multiple sclerosis the lipid peroxidation as the level of urine isoprostanes and the level of thiobarbituric acid reactive species (TBARS) in plasma were estimated. Moreover, we estimated the total antioxidative status (TAS) in plasma. It was found that the urine isoprostanes level was over 6-fold elevated in patients with SPMS than in control (P < 0.001). In SPMS patients TBARS level was also statistically higher than in controls (P < 0.01). However, we did not observed any difference of TAS level in serum between SPMS patients and controls (P > 0.05). In patients with SPMS the lipid peroxidation and oxidative stress measured as the increased level of isoprostanes was observed. Thus, we suggest that the level of isoprostanes may be used as non-invasive marker for a determination of oxidative stress what in turn, together with clinical symptoms, may determine an specific antioxidative therapy in SPMS patients

Flexibility of a biotinylated ligand in artificial metalloenzymes based on streptavidin—an insight from molecular dynamics simulations with classical and ab initio force fields

In the field of enzymatic catalysis, creating activity from a non catalytic scaffold is a daunting task. Introduction of a catalytically active moiety within a protein scaffold offers an attractive means for the creation of artificial metalloenzymes. With this goal in mind, introduction of a biotinylated d6-piano-stool complex within streptavidin (SAV) affords enantioselective artificial transfer-hydrogenases for the reduction of prochiral ketones. Based on an X-ray crystal structure of a highly selective hybrid catalyst, displaying significant disorder around the biotinylated catalyst [η6-(p-cymene)Ru(Biot-p-L)Cl], we report on molecular dynamics simulations to shed light on the protein–cofactor interactions and contacts. The results of these simulations with classical force field indicate that the SAV-biotin and SAV-catalyst complexes are more stable than ligand-free SAV. The point mutations introduced did not affect significantly the overall behavior of SAV and, unexpectedly, the P64G substitution did not provide additional flexibility to the protein scaffold. The metal-cofactor proved to be conformationally flexible, and the S112K or P64G mutants proved to enhance this effect in the most pronounced way. The network of intermolecular hydrogen bonds is efficient at stabilizing the position of biotin, but much less at fixing the conformation of an extended biotinylated ligand. This leads to a relative conformational freedom of the metal-cofactor, and a poorly localized catalytic metal moiety. MD calculations with ab initio potential function suggest that the hydrogen bonds alone are not sufficient factors for full stabilization of the biotin. The hydrophobic biotin-binding pocket (and generally protein scaffold) maintains the hydrogen bonds between biotin and protein

Dynamic Allostery in the Methionine Repressor Revealed by Force Distribution Analysis

Many fundamental cellular processes such as gene expression are tightly regulated by protein allostery. Allosteric signal propagation from the regulatory to the active site requires long-range communication, the molecular mechanism of which remains a matter of debate. A classical example for long-range allostery is the activation of the methionine repressor MetJ, a transcription factor. Binding of its co-repressor SAM increases its affinity for DNA several-fold, but has no visible conformational effect on its DNA binding interface. Our molecular dynamics simulations indicate correlated domain motions within MetJ, and quenching of these dynamics upon SAM binding entropically favors DNA binding. From monitoring conformational fluctuations alone, it is not obvious how the presence of SAM is communicated through the largely rigid core of MetJ and how SAM thereby is able to regulate MetJ dynamics. We here directly monitored the propagation of internal forces through the MetJ structure, instead of relying on conformational changes as conventionally done. Our force distribution analysis successfully revealed the molecular network for strain propagation, which connects collective domain motions through the protein core. Parts of the network are directly affected by SAM binding, giving rise to the observed quenching of fluctuations. Our results are in good agreement with experimental data. The force distribution analysis suggests itself as a valuable tool to gain insight into the molecular function of a whole class of allosteric proteins

Catalytic Cycle of Multicopper Oxidases Studied by Combined Quantum- and Molecular-Mechanical Free-Energy Perturbation Methods

We have used combined quantum mechanical and molecular mechanical free-energy perturbation methods in combination with explicit solvent simulations to study the reaction mechanism of the multicopper oxidases, in particular the regeneration of the reduced state from the native intermediate. For 52 putative states of the trinuclear copper cluster, differing in the oxidation states of the copper ions and the protonation states of water- and O2-derived ligands, we have studied redox potentials, acidity constants, isomerisation reactions, as well as water- and O2 binding reactions. Thereby, we can propose a full reaction mechanism of the multicopper oxidases with atomic detail. We also show that the two copper sites in the protein communicate so that redox potentials and acidity constants of one site are affected by up to 0.2 V or 3 pKa units by a change in the oxidation state of the other site

Characterization of the thermal and photoinduced reactions of photochromic spiropyrans in aqueous solution

Six water-soluble spiropyran derivatives have been characterized with respect to the thermal and photoinduced reactions over a broad pH-interval. A comprehensive kinetic model was formulated including the spiro- and the merocyanine isomers, the respective protonated forms, and the hydrolysis products. The experimental studies on the hydrolysis reaction mechanism were supplemented by calculations using quantum mechanical (QM) models employing density functional theory. The results show that (1) the substitution pattern dramatically influences the pKa-values of the protonated forms as well as the rates of the thermal isomerization reactions, (2) water is the nucleophile in the hydrolysis reaction around neutral pH, (3) the phenolate oxygen of the merocyanine form plays a key role in the hydrolysis reaction. Hence, the nonprotonated merocyanine isomer is susceptible to hydrolysis, whereas the corresponding protonated form is stable toward hydrolytic degradation

An Abundant Dysfunctional Apolipoprotein A1 in Human Atheroma

Recent studies have indicated that high-density lipoproteins (HDLs) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma are dysfunctional and are extensively oxidized by myeloperoxidase (MPO). In vitro oxidation of either apoA1 or HDL particles by MPO impairs their cholesterol acceptor function. Here, using phage display affinity maturation, we developed a high-affinity monoclonal antibody that specifically recognizes both apoA1 and HDL that have been modified by the MPO-H2O2-Cl− system. An oxindolyl alanine (2-OH-Trp) moiety at Trp72 of apoA1 is the immunogenic epitope. Mutagenesis studies confirmed a critical role for apoA1 Trp72 in MPO-mediated inhibition of the ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol acceptor activity of apoA1 in vitro and in vivo. ApoA1 containing a 2-OH-Trp72 group (oxTrp72-apoA1) is in low abundance within the circulation but accounts for 20% of the apoA1 in atherosclerosis-laden arteries. OxTrp72-apoA1 recovered from human atheroma or plasma is lipid poor, virtually devoid of cholesterol acceptor activity and demonstrated both a potent proinflammatory activity on endothelial cells and an impaired HDL biogenesis activity in vivo. Elevated oxTrp72-apoA1 levels in subjects presenting to a cardiology clinic (n = 627) were associated with increased cardiovascular disease risk. Circulating oxTrp72-apoA1 levels may serve as a way to monitor a proatherogenic process in the artery wall