Mathematical modeling of the relation between myosin phosphorylation and stress development in smooth muscles

In this paper the 4-state latch bridge model proposed by Rembold and Murphy is expanded; first by incorporation of the analytical expression of Ca2+ dependent MLCK activation from the work of Kato et al. and second, by inclusion of the myosin dephosphorylation based on the Michaelis-Menten kinetics. The analysis of the proposed model and the comparison with the original model results as well as with the experimental data is presented. The model is able to predict the steady-state isometric stress and the myosin phosphorylation in dependence on steady cytosolic [Ca2+] as well as the temporal evolution of the system in dependence on the input Ca2+ signal in the form of biphasic transient, whereby our model results are in several aspects in better agreement with experimental observations.     

Synthesis of mesoporous bimetallic Pt-Sn catalytic coatings from polynuclear precursors for fine organic synthesis processes

A new method is developed to obtain nanosized catalytic Pt-Sn/TiO₂ coatings on the inner surface of a capillary microreactor during adsorption of polynuclear carbonyl Pt-Sn complexes on mesoporous TiO₂. Titanium oxide sol prepared in the presence of template (Pluronic F127 surfactant) is supported in dynamic mode. Pt-Sn bimetallic catalysts with an average particle size of 1.5–2 nm are synthesized by adsorption of the bimetallic [Pt₃(CO)₃(SnCl₃)₂(SnCl₂·H₂O)] _n ^2n? complex followed by thermal treatment. Physicochemical properties of samples (thickness, structure and morphology, chemical composition of the material, electronic state, specific surface area, pore volume and size distribution) are characterized by a set of methods (HR TEM, SEM, powder XRD, XRF, XPS, low-temperature nitrogen adsorption). Conditions to prepare the uniform non-peelable Pt-Sn/TiO₂ coating on the inner surface of a silica capillary with good adhesion are determined. To increase the TiO₂ thickness, multilayered TiO₂ films are synthesized by layerby layer deposition. The coating thickness is found to increase with an increase in the capillary diameter. The coating of a capillary with a diameter of 0.55 mm after 14-fold deposition is characterized by a thickness of 2 μm and an average pore size of 5.4 nm. The solvent effect on the adsorption of Pt-Sn carbonyl complexes into the TiO₂ support is studied. The amount of the adsorbed complex increases in the following order: ethanol < acetone ～ tetrahydrofuran. The physicochemical properties of the active component (surface concentration, dispersion, and composition) can be fine-tuned by varying the deposition method, precursor concentration in the initial solution, and temperature conditions of activation treatment. The catalyst activity in citral hydrogenation was 0.06–0.54 min^?1, with the selectivity with respect to unsaturated alcohols reaching 90% at citral conversion above 95%.     

Functional silver nanostructured surfaces applied in SERS and SIMS

Present article deals with functionality of silver nanostructured surfaces prepared by potentiostatic electrochemical deposition on the paraffin impregnated graphite electrode as template‐free substrates. The effect of the electrodeposition conditions on two silver surface functions: analytical signal enhancement in Surface‐enhanced Raman spectroscopy and pre‐ionization function, applied in secondary ion mass spectrometry (SIMS) is reported. Functional silver nanostructured substrate was prepared at a potential ?850 mV with a deposition duration of 20 min. Analytical signal enhancement factors of 3.2 ×10⁵ for Raman peak at 649 cm^?1, 3.0×10⁵ for peak at 810 cm^?1 and 2.7×10⁵ for peak at 1539 cm^?1 were determined for Rhodamine 6G at deposited surface. Slight pre‐ionization effect has been observed in SIMS, and 1.2×10⁵ fold signal enhancement was established for fragment of Rhodamine 6G with m/z 429 (M‐CH₃‐Cl). Electrochemical preparation of nanostructures represents a step towards surface integration directly into miniaturized systems and sensors. Copyright © 2013 John Wiley & Sons, Ltd.     

Glycation sites of human plasma proteins are affected to different extents by hyperglycemic conditions in type 2 diabetes mellitus

Glucose can modify proteins in human blood, forming early glycation products (e.g., Amadori compounds), which can slowly degrade to advanced glycation endproducts (AGEs). AGEs contribute significantly to complications of diabetes mellitus and, thus, represent markers of advanced disease stages. They are, however, currently unsuitable for early diagnosis and therapeutic monitoring. Here, we report sensitive strategies to identify and relatively quantify protein glycation sites in human plasma samples obtained from type 2 diabetes mellitus (T2DM) patients and age-matched nondiabetic individuals using a bottom-up approach. Specifically, Amadori peptides were enriched from tryptic digests by boronic acid affinity chromatography, separated by reversed-phase chromatography, and analyzed on-line by high-resolution mass spectrometry. Among the 52 Amadori peptides studied here were 20 peptides resembling 19 glycation sites in six human proteins detected at statistically significantly higher levels in T2DM than in the normoglycemic controls. Four positions appeared to be unique for T2DM within the detection limit. All 19 glycation sites represent promising new biomarker candidates for early diagnosis of T2DM and adequate therapeutic control, as they may indicate early metabolic changes preceding T2DM. Graphical Abstract

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Synthesis and Biochemical Evaluation of Warhead-Decorated Psoralens as (Immuno)Proteasome Inhibitors

The immunoproteasome is a multicatalytic protease that is predominantly expressed in cells of hematopoietic origin. Its elevated expression has been associated with autoimmune diseases, various types of cancer, and inflammatory diseases. Selective inhibition of its catalytic activities is therefore a viable approach for the treatment of these diseases. However, the development of immunoproteasome-selective inhibitors with non-peptidic scaffolds remains a challenging task. We previously reported 7H-furo[3,2-g]chromen-7-one (psoralen)-based compounds with an oxathiazolone warhead as selective inhibitors of the chymotrypsin-like (β5i) subunit of immunoproteasome. Here, we describe the influence of the electrophilic warhead variations at position 3 of the psoralen core on the inhibitory potencies. Despite mapping the chemical space with different warheads, all compounds showed decreased inhibition of the β5i subunit of immunoproteasome in comparison to the parent oxathiazolone-based compound. Although suboptimal, these results provide crucial information about structure–activity relationships that will serve as guidance for the further design of (immuno)proteasome inhibitors.