Lysine Ethylation by Histone Lysine Methyltransferases

Biomedicinally important histone lysine methyltransferases (KMTs) catalyze the transfer of a methyl group from S-adenosylmethionine (AdoMet) cosubstrate to lysine residues in histones and other proteins. Herein, experimental and computational investigations on human KMT-catalyzed ethylation of histone peptides by using S-adenosylethionine (AdoEth) and Se-adenosylselenoethionine (AdoSeEth) cosubstrates are reported. MALDI-TOF MS experiments reveal that, unlike monomethyltransferases SETD7 and SETD8, methyltransferases G9a and G9a-like protein (GLP) do have the capacity to ethylate lysine residues in histone peptides, and that cosubstrates follow the efficiency trend AdoMet>AdoSeEth>AdoEth. G9a and GLP can also catalyze AdoSeEth-mediated ethylation of ornithine and produce histone peptides bearing lysine residues with different alkyl groups, such as H3K9meet and H3K9me2et. Molecular dynamics and free energy simulations based on quantum mechanics/molecular mechanics potential supported the experimental findings by providing an insight into the geometry and energetics of the enzymatic methyl/ethyl transfer process.     

Rottlerin: Structure Modifications and KCNQ1/KCNE1 Ion Channel Activity

The slow delayed rectifier potassium current (I_Ks) is formed by the KCNQ1 (K_v7.1) channel, an ion channel of four α-subunits that modulates KCNE1 β-subunits. I_Ks is central to the repolarization of the cardiac action potential. Loss of function mutation reducing ventricular cardiac I_Ks cause the long-QT syndrome (LQTS), a disorder that predisposes patients to arrhythmia and sudden death. Current therapy for LQTS is inadequate. Rottlerin, a natural product of the kamala tree, activates I_Ks and has the potential to provide a new strategy for rational drug therapy. In this study, we show that simple modifications such as penta-acetylation or penta-methylation of rottlerin blunts activation activity. Total synthesis was used to prepare side-chain-modified derivatives that slowed down KCNQ1/KCNE1 channel deactivation to different degrees. A binding hypothesis of rottlerin is provided that opens the way to improved I_Ks activators as novel therapeutics for the treatment of LQTS.     

Comparison of three air samplers for the collection of four nebulized respiratory viruses - Collection of respiratory viruses from air –

Viral respiratory tract infections are a leading cause of morbidity and mortality worldwide. Unfortunately, the transmission routes and shedding kinetics of respiratory viruses remain poorly understood. Air sampling techniques to quantify infectious viruses in the air are indispensable to improve intervention strategies to control and prevent spreading of respiratory viruses. Here, the collection of infectious virus with the six-stage Andersen cascade impactor was optimized with semi-solid gelatin as collection surface. Subsequently, the collection efficiency of the cascade impactor, the SKC BioSampler, and an in-house developed electrostatic precipitator was compared. In an in vitro set-up, influenza A virus, human metapneumovirus, parainfluenza virus type 3, and respiratory syncytial virus were nebulized and the amount of collected infectious virus and viral RNA was quantified with each air sampler. Whereas only low amounts of virus were collected using the electrostatic precipitator, high amounts were collected with the BioSampler and cascade impactor. The BioSampler allowed straight-forward sampling in liquid medium, whereas the more laborious cascade impactor allowed size fractionation of virus-containing particles. Depending on the research question, either the BioSampler or the cascade impactor can be applied in laboratory and field settings, such as hospitals to gain more insight into the transmission routes of respiratory viruses.     

Laser sealing of plasma-sprayed calcia-stabilized zirconia

On leave from Scientific Research Council, Baghdad, Iraq.     

Extractive spectrophotometric method for determination of metribuzin herbicide and application of factorial design in optimization of various factors

A simple extractive spectrophotometric method has been described for the determination of metribuzin herbicide. Metribuzin was reacted with copper and a stable complex in the presence of ammonia (0.2M) at pH 10.5 was formed. The resulting yellow coloured complex was extracted in chloroform and showed absorption maxima at 340 nm. Beer's law was obeyed in the range of 0.8-25 microg mL(-1) with molar absorptivity of 5.67 x 10(3)L mol(-1)cm(-1). The composition of the complex was studied by Job's method of continuous variation and the results indicated that the mole ratio of metribuzin:Cu(2+) is 2:1. The optimum reaction conditions for complexation and other analytical parameters were evaluated. A two-level factorial design was also used to determine the effect of different parameters and their interaction on metribuzin:Cu(2+) complex formed. The method was successfully applied for the determination of metribuzin in commercial formulations and real samples.     

Influence of Preheating Temperature on Microstructure Evolution and Hardness of High-Speed Steel AISI M50 Processed by Laser Powder Bed Fusion

The laser powder bed fusion (LPBF) technology has been involved in the tooling industry to produce tools with complex geometry and integrated functions. However, tool steels with high carbon content tend to crack due to the thermal stresses during the LPBF process. One solution is increasing the powder bed temperature to avoid large thermal gradients. In the present study, the influence of the preheating temperature on microstructure and corresponding hardness is systematically investigated. With the help of time–temperature–transformation diagram, the phase evolution during the LPBF process is systematically explained. AISI M50 samples are produced by LPBF from room temperature to a preheating temperature of 650 °C. Higher preheating temperatures shift the optimal laser parameter window to lower volume energy densities. A cellular/dendritic microstructure formed during the rapid solidification with retained austenite is located at the interdendritic regions. Moreover, a high preheating temperature reduces the retained austenite fraction, specifically from 39% without preheating to 7.6% at 650 °C preheating temperature.     

Perfluorinated compounds in the Asian atmosphere

There is interest in the production, use, and environmental occurrence of perfluorinated compounds (PFCs) across Asia and the Asian contributions to the burden of these compounds reaching the Arctic and other remote regions via long-range transport. A spatial survey of perfluorinated compounds was therefore undertaken across China, India, and Japan in 2009 using passive air samplers. Target analytes were fluorotelomer olefins (FTOs), acrylates (FTAs), alcohols (FTOHs), sulfonamides, and sulfonamidoethanols. Wide variations in concentrations and mixtures of compounds were apparent from the study. Generally the FTOHs were the most abundant, followed by 8:2 FTO in China and Japan and by the sulfonamides in India. There was a general decline in PFC concentration from urban, rural, to remote locations. Background stations reflected regional differences in air mass composition. A site in the west Pacific Ocean exhibited a Japanese profile in which 8:2 FTO and 8:2 FTOH were predominant. In contrast, a southern Indian profile with high 4:2 FTOH concentrations was observed at a background site in southern China.     

Metabolic activity and symbiotic interactions of lactic acid bacteria and yeasts isolated from water kefir

Water kefir is a mildly sour and alcoholic drink fermented by a stable microbial multispecies community. With its high sugar content and low amino acid concentration water kefir medium represents a demanding habitat. In this ecological niche only well adapted microorganisms which are fit to the consortium are able to grow and mutually provide essential nutrients. The synergism between main representatives of water kefir yeasts and lactobacilli was studied in a co-culture model system. Co-cultivation of yeasts and lactobacilli in water kefir medium significantly increased cell yield of all interaction partners, delineating the interaction of these water kefir isolates as mutualism. The support of Zygotorulaspora (Z.) florentina was due to the acidification of the medium by the lactobacilli, whereas lactobacilli are improved in growth by the disposal of essential nutrients produced by yeasts. The trophic interaction between Lactobacillus (Lb.) hordei and yeasts is constituted by the release of amino acids and Vitamin B₆ from yeasts, whereas Lb. nagelii is supported in growth by their production of amino acids. The interaction of Z. florentina and Lb. nagelii was further examined to reveal that co-cultivation induced the yeast to release arginine, which was essential for Lb. nagelii.     

Digital shinrin-yoku: do nature experiences in virtual reality reduce stress and increase well-being as strongly as similar experiences in a physical forest?

Virtual Reality - Shinrin-yoku or forest bathing refers to a therapeutic, immersive nature experience that aids to improve well-being. The goal of the current research was to compare the effects of...