Kinetic study of dissociation of Eu(III) complex with H8dotp (H8dotp = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylphosphonic acid))

The dissociation kinetics of the europium(III) complex with H₈dotp ligand was studied by means of molecular absorption spectroscopy in UV region at ionic strength 3.0 mol dm⁻³ (Na,H)ClO₄ and in temperature region 25-60 °C. Time-resolved laser-induced fluorescence spectroscopy (TRLIFS) was employed in order to determine the number of water molecules in the first coordination sphere of the europium(III) reaction intermediates and the final products. This technique was also utilized to deduce the composition of reaction intermediates in course of dissociation reaction simultaneously with calculation of rate constants and it demonstrates the elucidation of intimate reaction mechanism. The thermodynamic parameters for the formation of kinetic intermediate (ΔH⁰ = 11 ± 3 kJ mol⁻¹, ΔS⁰ = 41 ± 11 J K⁻¹ mol⁻¹) and the activation parameters (E_a = 69 ± 8 kJ mol⁻¹, ΔH^≠ = 67 ± 8 kJ mol⁻¹, ΔS^≠ = −83 ± 24 J K⁻¹ mol⁻¹) for the rate-determining step describing the complex dissociation were determined. The mechanism of proton-assisted reaction was proposed on the basis of the experimental data.     

Tetranuclear manganese(III) clusters containing both carboxylate and phosphonate bridging ligands

This paper reports two tetranuclear manganese clusters, namely, [Mn₄O₂(O₂CCH₃)₄(O₃PC₆H₁₁)₂(phen)₂] (1) and [Mn₄O₂(O₂CPh)₄ (O₃PC₆H₁₁)₂(bpy)₂] (2). Both contain a butterfly-like [Mn₄(μ₃-O)₂]⁸⁺ core. The neighboring Mn atoms within the core are bridged by the carboxylate groups, forming approximately a plane. The phosphonate ligands locate above and below the plane, and cap on top of the Mn₃O triangles by using its three phosphonate oxygen atoms. The magnetic measurements of complexes 1 and 2 reveal that dominant antiferromagnetic interactions are propagated between the magnetic centers.     

New t‐butyl based aspartate protecting groups preventing aspartimide formation in Fmoc SPPS

Obtaining homogenous aspartyl‐containing peptides via Fmoc/tBu chemistry is often an insurmountable obstacle. A generic solution for this issue utilising an optimised side‐chain protection strategy that minimises aspartimide formation would therefore be most desirable. To this end, we developed the following new derivatives: Fmoc‐Asp(OEpe)‐OH (Epe = 3‐ethyl‐3‐pentyl), Fmoc‐Asp(OPhp)‐OH (Php = 4‐n‐propyl‐4‐heptyl) and Fmoc‐Asp(OBno)‐OH (Bno = 5‐n‐butyl‐5‐nonyl). We have compared their effectiveness against that of Fmoc‐Asp(OtBu)‐OH and Fmoc‐Asp(OMpe)‐OH in the well‐established scorpion toxin II model peptide variants H‐Val‐Lys‐Asp‐Asn/Arg‐Tyr‐Ile‐OH by treatments of the peptidyl resins with the Fmoc removal reagents containing piperidine and DBU at both room and elevated temperatures. The new derivatives proved to be extremely effective in minimising aspartimide by‐products in each application. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.     

Microbial signature lipid biomarker analysis – an approach that is still preferred,even amid various method modifications

The lipid composition of microbial communities can indicate their response to changes in the surrounding environment induced by anthropogenic practices, chemical contamination or climatic conditions. A considerable number of analytical techniques exist for the examination of microbial lipids. This article reviews a selection of methods available for environmental samples as applied for lipid extraction, fractionation, derivatization and quantification. The discussion focuses on the origin of the standard methods, the different modified versions developed for investigation of microbial lipids, as well as the advantages and limitations of each. Current modifications to standard methods show a number of improvements for each of the different steps associated with analysis. The advantages and disadvantages of lipid analysis compared to other popular techniques are clarified. Accordingly, the preferential utilization of signature lipid biomarker analysis in current research is considered. It is clear from recent literature that this technique stays relevant – mainly for the variety of microbial properties that can be determined in a single analysis.     

A comparison of the LDL-cholesterol lowering efficacy of plant stanols and plant sterols over a continuous dose range: results of a meta-analysis of randomized, placebo-controlled trials

Purpose

To determine if plant stanols and plant sterols differ with respect to their low-density lipoprotein cholesterol (LDL-CH) lowering efficacies across a continuous dose range.

Methods

Dose-response relationships were evaluated separately for plant stanols and plant sterols and reductions in LDL-CH, using a first-order elimination function.

Results

Altogether, 113 publications and 1 unpublished study report (representing 182 strata) complied with the pre-defined inclusion and exclusion criteria and were included in the assessment. The maximal LDL-CH reductions for plant stanols (16.4%) and plant stanol ester (17.1%) were significantly greater than the maximal LDL-CH reductions for plant sterols (8.3%) and plant sterol ester (8.4%). These findings persisted in several additional analyses.

Discussion and conclusions

Intakes of plant stanols in excess of the recommended 2 g/day dose are associated with additional and dose-dependent reductions in LDL-CH, possibly resulting in further reductions in the risk of coronary heart disease (CHD).     

Nox2-derived ROS in PPARγ signaling and cell-cycle progression of lung alveolar epithelial cells

Reactive oxygen species (ROS) play important roles in peroxisome proliferator-activated receptor γ (PPARγ) signaling and cell-cycle regulation. However, the PPARγ redox-signaling pathways in lung alveolar epithelial cells remain unclear. In this study, we investigated the in vivo and in vitro effects of PPARγ activation on the levels of lung ROS production and cell-cycle progression using C57BL/6J wild-type and Nox2 knockout mice (n = 10) after intraperitoneal injection of a selective PPARγ agonist (GW1929, 5 mg/kg body wt, daily) for 14 days. Compared to vehicle-treated mice, GW1929 increased significantly the levels of ROS production in wild-type lungs, and this was accompanied by significant up-regulation of PPARγ, Nox2, PCNA, and cyclin D1 and phosphorylation of ERK1/2 and p38MAPK. These effects were absent in Nox2 knockout mice. In cultured alveolar epithelial cells, GW1929 (5 μM for 24 h) increased ROS production and promoted cell-cycle progression from G0/G1 into S and G2/M phases, and these effects were abolished by (1) adding a PPARγ antagonist (BADGE, 1 μM), (2) knockdown of PPARγ using siRNA, or (3) knockout of Nox2. In conclusion, PPARγ activation through Nox2-derived ROS promotes cell-cycle progression in normal mouse lungs and in cultured normal alveolar epithelial cells.     

Mechanism-based therapeutic approaches to rhabdomyolysis-induced renal failure

Rhabdomyolysis-induced renal failure represents up to 15% of all cases of acute renal failure. Many studies over the past 4 decades have demonstrated that accumulation of myoglobin in the kidney is central in the mechanism leading to kidney injury. However, some discussion exists regarding the mechanism mediating this oxidant injury. Although the free-iron-catalyzed Fenton reaction has been proposed to explain the tissue injury, more recent evidence strongly suggests that the main cause of oxidant injury is myoglobin redox cycling and generation of oxidized lipids. These molecules can propagate tissue injury and cause renal vasoconstriction, two of the three main conditions associated with acute renal failure. This review presents the evidence supporting the two mechanisms of oxidative injury, describes the central role of myoglobin redox cycling in the pathology of renal failure associated with rhabdomyolysis, and discusses the value of therapeutic interventions aiming at inhibiting myoglobin redox cycling for the treatment of rhabdomyolysis-induced renal failure.     

Sustained CaMKII activity mediates transient oxidative stress-induced long-term facilitation of L-type Ca(2+) current in cardiomyocytes

Oxidative stress remodels Ca²⁺ signaling in cardiomyocytes, which promotes altered heart function in various heart diseases. Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) was shown to be activated by oxidation, but whether and how CaMKII links oxidative stress to pathophysiological long-term changes in Ca²⁺ signaling remain unknown. Here, we present evidence demonstrating the role of CaMKII in transient oxidative stress-induced long-term facilitation (LTF) of L-type Ca²⁺ current (I_Ca,L) in rat cardiomyocytes. A 5-min exposure of 1 mM H₂O₂ induced an increase in I_Ca,L, and this increase was sustained for ~ 1 h. The CaMKII inhibitor KN-93 fully reversed H₂O₂-induced LTF of I_Ca,L, indicating that sustained CaMKII activity underlies this oxidative stress-induced memory. Simultaneous inhibition of oxidation and autophosphorylation of CaMKII prevented the maintenance of LTF, suggesting that both mechanisms contribute to sustained CaMKII activity. We further found that sarcoplasmic reticulum Ca²⁺ release and mitochondrial ROS generation have critical roles in sustaining CaMKII activity via autophosphorylation- and oxidation-dependent mechanisms. Finally, we show that long-term remodeling of the cardiac action potential is induced by H₂O₂ via CaMKII. In conclusion, CaMKII and mitochondria confer oxidative stress-induced pathological cellular memory that leads to cardiac arrhythmia.