Aroyl-pyrrolyl hydroxyamides: influence of pyrrole C4-phenylacetyl substitution on histone deacetylase inhibition

The novel aroyl-pyrrolyl hydroxyamides 4 a-a' are analogues of the lead compound 3-(1-methyl-4-phenylacetyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamide (2) and are active as HDAC inhibitors. The benzene ring of 2 was substituted with a wide range of electron-donating and electron-withdrawing groups, and the effect was evaluated on three HDACs from maize, namely HD2, HD1-B (a class I HDAC), and HD1-A (a class II HDAC). Inhibition studies show that the benzene 3' and, to a lesser extent, 4' positions of 2 were the most suitable for the introduction of substituents, with the 3'-chloro (in 4 b) and the 3'-methyl (in 4 k) derivatives being the most potent compounds, reaching the same activity as SAHA. Inhibition data for 4 b,k against mouse HDAC1 were consistent with those observed in the maize enzyme. The substituent insertion on the benzene ring of 2 (compounds 4 a-a') abated the slight (3-fold) selectivity for class II HDACs displayed by 2. Compound 4 b showed interesting, dose-dependent antiproliferative and cytodifferentiation properties against human acute promyelocytic leukemia HL-60 cells.     

Conical Boron Nitride Nanorods Synthesized Via the Ball-Milling and Annealing Method

A boron nitride (BN) nanostructure, conical BN nanorod, has been synthesized in a large quantity on Si substrates for the first time via the ball-milling and annealing method. Nitridation of milled boron carbide (B₄C) powders was performed in nitrogen gas at 1300°C on the surface of the substrates to form the BN nanorods. The highly crystallized nanorods consist of conical BN basal layers stacked along the nanorod axis. Ball milling of the B₄C powders can significantly enhance the nitridation of the powders and thus facilitate the formation of nanorods during the annealing process.     

Thermogenic Effect from Nutritionally Enriched Coffee Consumption

Background  

The purpose of this study was to examine the effect of nutritionally enriched JavaFit™ (JF) coffee (450 mg of caffeine, 1200 mg of garcinia cambogia, 360 mg of citrus aurantium extract, and 225 mcg of chromium polynicotinate) on resting oxygen uptake (VO₂), respiratory exchange ratio (RER), heart rate (HR), and blood pressure (BP) in healthy and physically active individuals.     

Fracture mechanical analysis of two commercial polyoxymethylene homopolymer resins

This research addresses the fracture mechanical analysis of two commercially available polyoxymethylene homopolymer resins. Two types of experiments are used: monotonic fracture toughness tests and cyclic fatigue crack growth tests. The resulting total lifetimes in the fatigue crack growth tests are split up into the appropriate parts of crack growth initiation and fatigue crack propagation. Fracture surfaces of monotonic and cyclic tests are analyzed using light microscopy and scanning electron microscopy. Besides the mechanical tests, the morphology within the used compact tension specimens is examined in detail by using differential scanning calorimetry, small‐ and wide‐angle X‐ray scattering, and polarized light microscopy. The results are analyzed and discussed, considering observations in the previous studies published in the literature. It is shown that both materials can be well analyzed using linear elastic fracture mechanics and their fracture mechanical properties are presented in conjunction with a detailed documentation of the microstructure. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40831.     

Hydrogenation of p‐Nitrophenol to p‐Aminophenol as a Test Reaction for the Catalytic Activity of Supported Pt Catalysts

Hydrogenation of p‐nitrophenol (PNP) to p‐aminophenol (PAP) using NaBH₄ as a reducing agent was studied as a test reaction for determining the catalytic activity of supported Pt catalysts. The initial reaction rate, which is accessible within less than 10 min via online UV‐vis spectroscopy at room temperature, ambient pressure, and in water as solvent, was applied as measure for catalytic activity. For three Pt catalysts supported on porous SiO₂, porous glass, and Al₂O₃, respectively, significant differences in the catalytic activity by almost one order of magnitude were observed. However, especially in the case of very active catalysts, limitations of the reaction by internal or external mass transfer have to be considered.     

Small‐Molecule Inhibitors of AF6 PDZ‐Mediated Protein–Protein Interactions

PDZ (PSD‐95, Dlg, ZO‐1) domains are ubiquitous interaction modules that are involved in many cellular signal transduction pathways. Interference with PDZ‐mediated protein–protein interactions has important implications in disease‐related signaling processes. For this reason, PDZ domains have gained attention as potential targets for inhibitor design and, in the long run, drug development. Herein we report the development of small molecules to probe the function of the PDZ domain from human AF6 (ALL1‐fused gene from chromosome 6), which is an essential component of cell–cell junctions. These compounds bind to AF6 PDZ with substantially higher affinity than the peptide (Ile‐Gln‐Ser‐Val‐Glu‐Val) derived from its natural ligand, EphB2. In intact cells, the compounds inhibit the AF6–Bcr interaction and interfere with epidermal growth factor (EGF)‐dependent signaling.     

Second harmonic atomic force microscopy imaging of live and fixed mammalian cells

Higher harmonic contributions in the movement of an oscillating atomic force microscopy (AFM) cantilever are generated by nonlinear tip–sample interactions, yielding additional information on structure and physical properties such as sample stiffness. Higher harmonic amplitudes are strongly enhanced in liquid compared to the operation in air, and were previously reported to result in better structural resolution in highly organized lattices of proteins in bacterial S-layers and viral capsids [J. Preiner, J. Tang, V. Pastushenko, P. Hinterdorfer, Phys. Rev. Lett. 99 (2007) 046102]. We compared first and second harmonics AFM imaging of live and fixed human lung epithelial cells, and microvascular endothelial cells from mouse myocardium (MyEnd). Phase–distance cycles revealed that the second harmonic phase is 8 times more sensitive than the first harmonic phase with respect to variations in the distance between cantilever and sample surface. Frequency spectra were acquired at different positions on living and fixed cells with second harmonic amplitude values correlating with the sample stiffness. We conclude that variations in sample stiffness and corresponding changes in the cantilever–sample distance, latter effect caused by the finite feedback response, result in second harmonic images with improved contrast and information that is not attainable in the fundamental frequency of an oscillating cantilever.     

Commissioning of a new ice-free anemometer: 2011 Field tests at WEICan

The main objective of this article is to present the results gathered during the commissioning of a new ice-free cup anemometer developed at Université Laval. These tests took place at the Wind Energy Institute of Canada (WEICan) between January 2011 and April 2011, whereby icing events occurred and through the observations in this paper will show the need for ice-free anemometers in the wind industry in cold climates. Unbiased wind measurements cannot be obtained without ice-free anemometers. At such sites, the use of unheated wind speed sensors during the resource assessment phase leads to higher uncertainty of the wind speed. The use of properly heated anemometers can reduce wind speed measurement uncertainty, thus reducing financial uncertainty. A crude estimation of the financial losses based on the number of icing hours and the number of installed MW is also proposed. Caution should be exerted when choosing and installing ice-free instruments. Under specific conditions, improperly heated anemometers can lead to less accurate wind measurements than unheated anemometers. Wind turbines safe operation could be jeopardized with the use of improperly heated anemometers.     

SPHERES, Jülich's high-flux neutron backscattering spectrometer at FRM II

SPHERES is a third-generation neutron backscattering spectrometer, located at the 20 MW German neutron source FRM II and operated by the Ju?lich Centre for Neutron Science. It offers an energy resolution (fwhm) better than 0.65 μeV, a dynamic range of ±?31 μeV, and a signal-to-noise ratio of up to 1750:1.     

Dynamic force microscopy imaging of native membranes

We employed magnetic ACmode atomic force microscopy (MACmode AFM) as a novel dynamic force microscopy method to image surfaces of biological membranes in their native environments. The lateral resolution achieved under optimized imaging conditions was in the nanometer range, even when the sample was only weakly attached to the support. Purple membranes (PM) from Halobacterium salinarum were used as a test standard for topographical imaging. The hexagonal arrangement of the bacteriorhodopsin trimers on the cytoplasmic side of PM was resolved with 1.5nm lateral accuracy, a resolution similar to images obtained in contact and tapping-mode AFM. Human rhinovirus 2 (HRV2) particles were attached to mica surfaces via nonspecific interactions. The capsid structure and 2nm sized protein loops of HRV2 were routinely obtained without any displacement of the virus. Globular and filamentous structures on living and fixed endothelial cells were observed with a resolution of 5-20nm. These examples show that MACmode AFM is a favorable method in studying the topography of soft and weakly attached biological samples with high resolution under physiological conditions.