Reconstitution of Nucleosome Demethylation and Catalytic Properties of a Jumonji Histone Demethylase

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Highlights? Catalytic domain of JMJD2A (cJMJD2A) removes methyl marks in a distributive manner ? Homogeneously methylated nucleosomes were used as substrates ? Quantitative assay for nucleosome demethylation has been developed     

Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells

The benzo-fused dioxabicyclo[3.3.1]nonane core is the central framework in several natural products. Using this core, we had developed a novel nitrated [6,6,6]tricycle-derived compound containing an n-butyloxy group, namely, SK2. The anticancer potential of SK2 was not assessed. This study aimed to determine the antiproliferative function and investigated possible mechanisms of SK2 acting on oral cancer cells. SK2 preferentially killed oral cancer cells but caused no harmful effect on non-malignant oral cells. After the SK2 exposure of oral cancer cells, cells in the sub-G1 phase accumulated. This apoptosis-like outcome of SK2 treatment was validated to be apoptosis via observing an increasing annexin V population. Mechanistically, apoptosis signalers such as pancaspase, caspases 8, caspase 9, and caspase 3 were activated by SK2 in oral cancer cells. SK2 induced oxidative-stress-associated changes. Furthermore, SK2 caused DNA damage (γH2AX and 8-hydroxy-2′-deoxyguanosine). In conclusion, a novel nitrated [6,6,6]tricycle-derived compound, SK2, exhibits a preferential antiproliferative effect on oral cancer cells, accompanied by apoptosis, oxidative stress, and DNA damage.     

Absolute potassium cation affinities (PCAs) in the gas phase

The potassium cation affinities (PCAs) of 136 ligands (20 classes) in the gas phase were established by hybrid density functional theory calculations (B3-LYP with the 6-311+G(3df,2p) basis set). For these 136 ligands, 70 experimental values are available for comparison. Except for five specific PCA values-those of phenylalanine, cytosine, guanine, adenine (kinetic-method measurement), and Me(2)SO (by high-pressure mass spectrometric equilibrium measurement)-our theoretical estimates and the experimental affinities are in excellent agreement (mean absolute deviation (MAD) of 4.5 kJ mol(-1)). Comparisons with previously reported theoretical PCAs are also made. The effect of substituents on the modes of binding and the PCAs of unsubstituted parent ligands are discussed. Linear relations between Li+/Na+ and K+ affinities suggest that for the wide range of ligands studied here, the nature of binding between the cations and a given ligand is similar, and this allows the estimation of PCAs from known Li+ and/or Na+ affinities. Furthermore, empirical equations relating the PCAs of ligands with their dipole moments, polarizabilities (or molecular weights), and the number of binding sites were established. Such equations offer a simple method for estimating the PCAs of ligands not included in the present study.     

Tracking X‐ray‐derived redox changes in crystals of a methylamine dehydrogenase/amicyanin complex using single‐crystal UV/Vis microspectrophotometry

X‐ray exposure during crystallographic data collection can result in unintended redox changes in proteins containing functionally important redox centers. In order to directly monitor X‐ray‐derived redox changes in trapped oxidative half‐reaction intermediates of Paracoccus denitrificans methylamine dehydrogenase, a commercially available single‐crystal UV/Vis microspectrophotometer was installed on‐line at the BioCARS beamline 14‐BM‐C at the Advanced Photon Source, Argonne, USA. Monitoring the redox state of the intermediates during X‐ray exposure permitted the creation of a general multi‐crystal data collection strategy to generate true structures of each redox intermediate.     

Dynamic stability of rotor-bearing systems subjected to random axial forces

This paper investigates the lateral vibration of a spinning disk-shaft system supported by a pair of ball bearings and subjected to a pair of random axial forces at both ends. The axial forces are assumed as the sum of a static force and a random process with a zero mean. Due to the random axial forces, the rotor-bearing system may experience parametric random instability under certain situations. In this work, the finite element method is applied to yield a set of discretized system equations first. The set of discretized system equations is partially uncoupled by the modal analysis procedure suitable for gyroscopic systems. The stochastic averaging method is then adopted to obtain Ito's equations for the response amplitudes of the system. Finally the first- and second-moment stability criteria are utilized to determine the stability boundaries of the system. Numerical results show that the rotor-bearing system is always stable in the sense of the first-moment stability, and the effects of the average axial compressive force and the disk mass, which will lower all frequencies of the system, tend to destabilize the second-moment stability of the system.     

Use of ion chromatography with post-column reaction for the measurement of tribromide to evaluate bromate levels in drinking water

A user-friendly ion chromatography method in conjunction with a post-column reaction (PCR) achieves practical quantitation limits for the oxyhalides bromate and chlorite of 0.05 μg/l and 0.10 μg/l, respectively. This level of measurement allows for the accurate assessment of bromate contributed to finished drinking waters that have been chlorinated using sodium hypochlorite. The target sensitivity of oxyhalides in the presence of other major ion species typically found in drinking water is achieved by PCR using excess bromide under acidic conditions to form a tribromide species that is detected by ultraviolet spectrometry. The method setup involves non-hazardous materials, as opposed to other recently developed methods that employ somewhat hazardous chemicals for generating the reaction necessary for the detection of bromate at sub-μg/l levels. No pretreatment of the samples is required, other than filtration and quenching of oxidant residual.     

Synergistic antitumor effect of curcumin and dinitrosyl iron complexes for against melanoma cells

The aim of this study was to examine whether combining curcumin, a chemoprevention agent, and dinitrosyl iron complexes (DNICs) would have a synergistic cytotoxic effect on mouse melanoma B16-F10 cells in vitro. Three synthesized DNICs-[PPN] [(NO)₂Fe(SCH₂CONHCH₃)₂] (NC01), [PPN] [(NO)₂Fe(SCH₂CON(CH₃)₂)₂] (NC02), and [Na][(NO)₂Fe(SCH₂CON(CH₃)₂)₂] (NC03) were tested in this study. In vitro DNA cleavage assay showed all three DNICs could cause plasmid DNA damage through releasing NO under UV irradiation. The cytotoxicity assay demonstrated these DNICs were toxic to B16-F10 cells in vitro, and the estimated values of LD₅₀ (24 h of incubation) of NC01 and NC02 were 1 μM, while the values of LD₅₀ of NC03 was 200 μM. No synergistic cytotoxicity effect was noted in the treatments of the combinations of curcumin and DNICs. On the contrary, in the presence of NC03, the toxicity of curcumin was reduced. Using UV-Visible spectroscopy and fluorescence microscopy, we found NC03 might interact with curcumin and reduce the accumulation of curcumin in cells. Further experiments using the pretreatment of curcumin for 4 h followed by the treatment of NC03 showed the synergistic cytotoxic effect, while, the pretreatment of NC03 followed by the treatment of curcumin did not have any effect. This study provides the basis for further investigation on the effects of combinations of curcumin and other NO donors.     

Stable Anticancer Gold(III)–Porphyrin Complexes: Effects of Porphyrin Structure

In the design of physiologically stable anticancer gold(III) complexes, we have employed strongly chelating porphyrinato ligands to stabilize a gold(III) ion [Chem. Commun. 2003 , 1718; Coord. Chem. Rev. 2009 , 253, 1682]. In this work, a family of gold(III) tetraarylporphyrins with porphyrinato ligands containing different peripheral substituents on the meso‐aryl rings were prepared, and these complexes were used to study the structure–bioactivity relationship. The cytotoxic IC₅₀ values of [Au(Por)]⁺ (Por=porphyrinato ligand), which range from 0.033 to >100 μM , correlate with their lipophilicity and cellular uptake. Some of them induce apoptosis and display preferential cytotoxicity toward cancer cells than to normal noncancerous cells. A new gold(III)–porphyrin with saccharide conjugation [Au(4‐glucosyl‐TPP)]Cl ( 2 a ; H₂(4‐glucosyl‐TPP)=meso‐tetrakis(4‐β‐D ‐glucosylphenyl)porphyrin) exhibits significant cytostatic activity to cancer cells (IC₅₀=1.2–9.0 μM ) without causing cell death and is much less toxic to lung fibroblast cells (IC₅₀>100 μM ). The gold(III)–porphyrin complexes induce S‐phase cell‐cycle arrest of cancer cells as indicated by flow cytometric analysis, suggesting that the anticancer activity may be, in part, due to termination of DNA replication. The gold(III)–porphyrin complexes can bind to DNA in vitro with binding constants in the range of 4.9×10⁵ to 4.1×10⁶ dm³ mol^?1 as determined by absorption titration. Complexes 2 a and [Au(TMPyP)]Cl₅ ( 4 a ; [H₂TMPyP]⁴⁺=meso‐tetrakis(N‐methylpyridinium‐4‐yl)porphyrin) interact with DNA in a manner similar to the DNA intercalator ethidium bromide as revealed by gel mobility shift assays and viscosity measurements. Both of them also inhibited the topoisomerase I induced relaxation of supercoiled DNA. Complex 4 a , a gold(III) derivative of the known G‐quadruplex‐interactive porphyrin [H₂TMPyP]⁴⁺, can similarly inhibit the amplification of a DNA substrate containing G‐quadruplex structures in a polymerase chain reaction stop assay. In contrast to these reported complexes, complex 2 a and the parental gold(III)–porphyrin 1 a do not display a significant inhibitory effect (<10 %) on telomerase. Based on the results of protein expression analysis and computational docking experiments, the anti‐apoptotic bcl‐2 protein is a potential target for those gold(III)–porphyrin complexes with apoptosis‐inducing properties. Complex 2 a also displays prominent anti‐angiogenic properties in vitro. Taken together, the enhanced stabilization of the gold(III) ion and the ease of structural modification render porphyrins an attractive ligand system in the development of physiologically stable gold(III) complexes with anticancer and anti‐angiogenic activities.     

Nonlinear electro-optic characteristic in a photoexcited semiconductor

We study the transport properties of a GaAs-based Gunn device under local optical excitation via direct numerical simulation. The simulation results show that the hysteretic transition in between quenched and transit modes. The key mechanism for this kind of transition is related to the formation of a stationary and nonuniform hole profile around the notch regime. Therefore, the development of optical control of the microwave output is reported. In addition, the influence of impact ionization on this nonlinear semiconductor is also discussed in the present study.