A Deep Dive into VDAC1 Conformational Diversity Using All-Atom Simulations Provides New Insights into the Structural Origin of the Closed States

The voltage-dependent anion channel 1 (VDAC1) is a crucial mitochondrial transporter that controls the flow of ions and respiratory metabolites entering or exiting mitochondria. As a voltage-gated channel, VDAC1 can switch between a high-conducting “open” state and a low-conducting “closed” state emerging at high transmembrane (TM) potentials. Although cell homeostasis depends on channel gating to regulate the transport of ions and metabolites, structural hallmarks characterizing the closed states remain unknown. Here, we performed microsecond accelerated molecular dynamics to highlight a vast region of VDAC1 conformational landscape accessible at typical voltages known to promote closure. Conformers exhibiting durable subconducting properties inherent to closed states were identified. In all cases, the low conductance was due to the particular positioning of an unfolded part of the N-terminus, which obstructed the channel pore. While the N-terminal tail was found to be sensitive to voltage orientation, our models suggest that stable low-conducting states of VDAC1 predominantly take place from disordered events and do not result from the displacement of a voltage sensor or a significant change in the pore. In addition, our results were consistent with conductance jumps observed experimentally and corroborated a recent study describing entropy as a key factor for VDAC gating.     

Litter fall, litter stocks and decomposition rates in rainforest and agroforestry sites in central Amazonia

The sustainability of agroforestry systems in Amazonia was assessed from their litter dynamics and decomposition. Litter fall and litter stocks were determined from July 1997 to March 1999 in four sites in central Amazonia: a primary rainforest, a 13-year-old secondary forest, and two sites of a polyculture forestry system which consisted of four planted tree species of commercial use amidst upcoming secondary growth. The average annual litter fall in the undisturbed primary rainforest (FLO) was 8.4 t ha^–1 year^–1, which is within the range of litter fall in other rainforests in the region. It was similar in one of the two polyculture sites (8.3 t ha^–1 year^–1), but lower in the secondary forest and in the second polyculture site. In the litter fall in secondary forest and agroforestry sites, the leaf portion was higher (76–82% of total litter fall) than in FLO, due to reduced fine matter and wood fall. Leaf litter fall variability was much lower in the plantation sites than in the forests, which is explained by the much more homogeneous stand structure of the plantations. The quality of the produced litter, measured as C/N ratio, differed significantly between the primary forest site and one polyculture and the secondary forest site. The cumulative input of nitrogen through litter fall was 144 kg ha^–1 year^–1 in FLO, and 91–112 kg ha^–1 year^–1 in the polycultures and the secondary forest. Litter fall was not correlated with soil parameters, but had a significant linear regression with canopy closure. For the primary rainforest, litter fall was also (inversely) correlated with monthly rainfall. Litter fall was higher in the first year (1997–1998; an El Niño period) than in 1998–1999. Litter stocks on the forest floor were highest in the secondary forest (24.7 t ha^–1), and much lower in the polyculture sites (15.1–16.2 t ha^–1) and the primary forest (12.0 t ha^–1). There were no differences in the relative N content (C/N ratio) of the litter stocks between the sites, but the larger stocks led to higher absolute N contents in the litter layer in the secondary forest. From the monthly values of litter stocks (S) and litter fall (P), the decomposition coefficient k _e=P/S was calculated, which was, on average, highest for the primary forest (0.059), followed by the polyculture systems (0.040–0.042), and by the secondary forest (0.024). Thus, due to low decomposition rates, the secondary forest site showed large litter accumulations in spite of a relatively low litter fall. In contrast, the primary forest showed high litter fall but low stocks, due to high decomposition rates. The decomposition coefficients of the polyculture systems ranged between the primary and the secondary forest. The reduced decomposition rates in the man-managed agroecosystems indicate quantitative and/or qualitative changes in the decomposer communities of these systems that lead to a higher build-up of litter stocks on the forest floor. However, the decomposer systems in the polyculture sites still were more functional than in the site of non-managed secondary growth. Thus, from a soil biological viewpoint, ecologically sustainable low-input agroforestry in Amazonia will benefit from the application of these polyculture systems.     

Preparation of morphology controlled Th1 − xUxO2 sintered pellets from low-temperature precursors

Dense sintered samples of Th_1 − xU_xO₂ solid solutions were prepared from the initial precipitation of oxalate precursors through two different wet chemical routes, based either on the direct precipitation of the cations or on the use of hydrothermal method. For both low-temperature precursors, the specific surface area was followed versus the heating temperature and the influence of the conversion step on the oxide powder reactivity was evidenced since it allowed to obtain reactive surfaces in the range of 15-45 m² g⁻¹ without any additional grinding step. From dilatometric studies, the operating conditions required for the complete densification of the Th_1 − xU_xO₂ pellets were set to a heat treatment of 3 h at 1500 °C. In these conditions, the density of the samples lies between 94% and 99% of the calculated value whatever the preparation method chosen which appeared very promising compared to the results already reported under inert atmosphere. The initial precipitation of low-temperature precursors thus allowed to lower the sintering temperature by about 100 °C while the use of hydrothermal conditions significantly improved the cationic distribution in the sintered samples, as shown from EPMA statistical experiments.     

Dye–fiber interactions in PET fibers: Hydrogen bonding studied by IR‐spectroscopy

Dye–fiber interactions are studied in poly (ethylene terephthalate) fibers by FT‐IR spectroscopy. It is shown for the first time that DRIFTS (diffuse reflectance infrared Fourier transform spectroscopy) serves as an easy applicable and accurate technique for the study of fibrous structures. This article focuses on the possible hydrogen bond interactions in the dye–fiber system, where the PET fibers are dyed with anthraquinone‐based disperse dyes. The dyes and related anthraquinone structures are studied in both the dilute solution state, the solid state, and as present in the PET fibers. It is proven that 1‐amino anthraquinones show strong “chelate‐type” intramolecular hydrogen bonding in all three states. In the fibers an important supplementary intermolecular hydrogen bonding with the C?O groups in the PET fiber is observed. The extend of hydrogen bonding seems to be prone to dye concentration variations. Further analysis by modulated differential scanning calorimetry links the hydrogen bonding to an intrinsic plasticizing effect of the dyes affecting the dye diffusion process. This thus offers a tool for the fundamental understanding of the dyeing process and possible observed differences in dyeing behavior in dye–fiber systems. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Mechanistic study of drying of alkyd resins using (Z,Z)- and (E,E)-3,6-nonadiene as model substances

The cobalt-catalysed autoxidative drying of alkyd resins was studied using (Z,Z)-3,6-nonadiene and (E,E)-3,6-nonadiene as model compounds. A large number of reaction products were isolated from the autoxidation mixture using HPLC and preparative size exclusion chromatography and identified with ¹H- and ¹³C-NMR. The identified compounds comprised C₉ hydroperoxides, endoperoxides, epoxides, aldehydes and ketones and some other oxidation products. Their chemical structures pointed to three different types of oxidation processes taking place. Besides the main radical autoxidation reaction, evidence was found for photo-sensitized oxidation involving singlet oxygen. Thirdly, epoxidation occurs via peracids or hydroperoxides formed as intermediates. Because of the large number of possible isomers having very similar physical properties, isolation of dimers required considerable effort. Nevertheless, two dimers were isolated and characterized. Their structures indicate crosslinking to occur by recombination of radicals as termination reaction.     

The synthesis of tetrahedral bipyridyl metallo-octupoles with large second- and third-order nonlinear optical properties

Two new 4,4′-bis(donor)-6,6′-diphenyl- 2,2′-bipyridine ligands and their corresponding D_2d (Cu^I, Ag^I, Zn^II) octupolar metal complexes were synthesized, and their linear and nonlinear optical properties were investigated. A single crystal X-ray structure was also determined for the bis[4,4′-bis(diethylaminostyryl)-6,6′-diphenyl-bipyridine]copper(I) complex, which revealed a distorded pseudo-tetrahedral geometry. Molecular second-order nonlinear optical properties were determined for the complexes using the Harmonic Light Scatterring technique at 1.91 μm. These metallo-chromophores display large first hyperpolarizabilities β_1.91 in the range of 211-340 × 10⁻³⁰ esu, which increase with the Lewis acidity of the metal ion. The two-photon absorption properties of the bipyridyl ligands and related complexes were determined using either the two-photon emission method for fluorescent compounds or the open aperture Z-scan technique for non emissive ones. The complexes display red-shifted two-photon absorption bands compared to their metal-ion free chromophores, as well as a large increase of the maximum two-photon absorption cross-sections.     

Oxidative catabolism of α-tocopherol in rat liver microsomes

The goal of this study was to clarify the mechanism responsible for the catabolism of α-tocopherol. The vitamin, bound to albumin, was incubated with rat liver microsomes and appeared to be broken down. Optimal production of the metabolite was obtained when 1 mg of microsomal protein was incubated with 36 μM of α-tocopherol in the presence of 1.5 mM of NADPH. Chromatographic and mass spectrometric analyses of the metabolite led to the conclusion that it consists of an ω-acid with an opened chroman ring, although we could not perform nuclear magnetic resonance analysis to confirm this. Our data show that α-tocopherol is ω-oxidized to a carboxylic acid and that this process can occur in rat liver microsomes in the presence of NADPH and O₂. The oxidation to the quinone structure appears to be a subsequent event that may be artifactual and/or catalyzed by a microsomal enzyme(s).     

miR-16-5p Is a Stably-Expressed Housekeeping MicroRNA in Breast Cancer Tissues from Primary Tumors and from Metastatic Sites

For quantitative microRNA analyses in formalin-fixed paraffin-embedded (FFPE) tissue, expression levels have to be normalized to endogenous controls. To investigate the most stably-expressed microRNAs in breast cancer and its surrounding tissue, we used tumor samples from primary tumors and from metastatic sites. MiRNA profiling using TaqMan^® Array Human MicroRNA Cards, enabling quantification of 754 unique human miRNAs, was performed in FFPE specimens from 58 patients with metastatic breast cancer. Forty-two (72%) samples were collected from primary tumors and 16 (28%) from metastases. In a cross-platform analysis of a validation cohort of 32 FFPE samples from patients with early breast cancer genome-wide microRNA expression analysis using SurePrintG3 miRNA (8 × 60 K)^® microarrays from Agilent^® was performed. Eleven microRNAs could be detected in all samples analyzed. Based on NormFinder and geNorm stability values and the high correlation (rho ≥ 0.8) with the median of all measured microRNAs, miR-16-5p, miR-29a-3p, miR-126-3p, and miR-222-3p are suitable single gene housekeeper candidates. In the cross-platform validation, 29 human microRNAs were strongly expressed (mean log2-intensity > 10) and 21 of these microRNAs including miR-16-5p and miR-29a-3p were also stably expressed (CV < 5%). Thus, miR-16-5p and miR-29a-3p are both strong housekeeper candidates. Their Normfinder stability values calculated across the primary tumor and metastases subgroup indicate that miR-29a-3p can be considered as the strongest housekeeper in a cohort with mainly samples from primary tumors, whereas miR-16-5p might perform better in a metastatic sample enriched cohort.     

A systematic comparison of PCA‐based Statistical Process Monitoring methods for high‐dimensional,time‐dependent Processes

High‐dimensional and time‐dependent data pose significant challenges to Statistical Process Monitoring. Most of the high‐dimensional methodologies to cope with these challenges rely on some form of Principal Component Analysis (PCA) model, usually classified as nonadaptive and adaptive. Nonadaptive methods include the static PCA approach and Dynamic Principal Component Analysis (DPCA) for data with autocorrelation. Methods, such as DPCA with Decorrelated Residuals, extend DPCA to further reduce the effects of autocorrelation and cross‐correlation on the monitoring statistics. Recursive Principal Component Analysis and Moving Window Principal Component Analysis, developed for nonstationary data, are adaptive. These fundamental methods will be systematically compared on high‐dimensional, time‐dependent processes (including the Tennessee Eastman benchmark process) to provide practitioners with guidelines for appropriate monitoring strategies and a sense of how they can be expected to perform. The selection of parameter values for the different methods is also discussed. Finally, the relevant challenges of modeling time‐dependent data are discussed, and areas of possible further research are highlighted. © 2016 American Institute of Chemical Engineers AIChE J, 62: 1478–1493, 2016