Investigation into the mechanism of action of the antimicrobial peptide epilancin 15X

Addressing the current antibiotic-resistance challenge would be aided by the identification of compounds with novel mechanisms of action. Epilancin 15X, a lantibiotic produced by Staphylococcus epidermidis 15 × 154, displays antimicrobial activity in the submicromolar range against a subset of pathogenic Gram-positive bacteria. S. epidermidis is a common member of the human skin or mucosal microbiota. We here investigated the mechanism of action of epilancin 15X. The compound is bactericidal against Staphylococcus carnosus as well as Bacillus subtilis and appears to kill these bacteria by membrane disruption. Structure–activity relationship studies using engineered analogs show that its conserved positively charged residues and dehydroamino acids are important for bioactivity, but the N-terminal lactyl group is tolerant of changes. Epilancin 15X treatment negatively affects fatty acid synthesis, RNA translation, and DNA replication and transcription without affecting cell wall biosynthesis. The compound appears localized to the surface of bacteria and is most potent in disrupting the membranes of liposomes composed of negatively charged membrane lipids in a lipid II independent manner. Epilancin 15X does not elicit a LiaRS response in B. subtilis but did upregulate VraRS in S. carnosus. Treatment of S. carnosus or B. subtilis with epilancin 15X resulted in an aggregation phenotype in microscopy experiments. Collectively these studies provide new information on epilancin 15X activity

Aspects Regarding the Dielectric Heating of Small Wood Boards in Radio Frequency

This paper presents a quality analysis of the electromagnetic and thermal field coupling in the RF (Radio frequency) dielectric heating process, based on experimental determinations and the results obtained after the numerical modeling of an oak wood board dielectric heating, which was placed into a Staggered-Through and, respectively, into a Strayfield field applicator. The software for modeling used was Flux2D-7.40 with the Dielectro-Thermal module. The results obtained, the geometry of the applicator and the voltage applied on the electrodes represent useful information for the users of electrothermal processing in RF

Modelling the Process of Induction Heating in Volume of a Bar Strip Using Flux 2D Software, coupled with Minitab Experimental Design Software

The purpose of this optimization is the identification of optimal parameters for processing the workpiece (the OLC45 steel bar), using inductive heating in volume. Flux 9.3.2 software, in 2D plan, has been employed in order to perform numerical simulations, while Minitab software has been used to determine optimal parameters

Numerical Analysis of the Induction Heating in Volume of a Half-Finished Product, Neglecting the End Effect

In this work, Flux 2D software has been used. It has been coupled with an experimental design method, in order to model the induction heating in volume of a half-finished product, neglecting end effects

A Mechanistic Explanation for the Regioselectivity of Nonenzymatic RNA Primer Extension

A working model of nonenzymatic RNA primer extension could illuminate how prebiotic chemistry transitioned to biology. All currently known experimental reconstructions of nonenzymatic RNA primer extension yield a mixture of 2′-5′ and 3′-5′ internucleotide linkages. Although long seen as a major problem, the causes of the poor regioselectivity of the reaction are unknown. We used a combination of different leaving groups, nucleobases, and templating sequences to uncover the factors that yield selective formation of 3′-5′ internucleotide linkages. We found that fast and high yielding reactions selectively form 3′-5′ linkages. Additionally, in all cases with high 3′-5′ regioselectivity, Watson–Crick base pairing between the RNA monomers and the template is observed at the extension site and at the adjacent downstream position. Mismatched base-pairs and other factors that would perturb the geometry of the imidazolium bridged intermediate lower both the rate and regioselectivity of the reaction

Common and Potentially Prebiotic Origin for Precursors of Nucleotide Synthesis and Activation

We have recently shown that 2-aminoimidazole is a superior nucleotide activating group for nonenzymatic RNA copying. Here we describe a prebiotic synthesis of 2-aminoimidazole that shares a common mechanistic pathway with that of 2-aminooxazole, a previously described key intermediate in prebiotic nucleotide synthesis. In the presence of glycolaldehyde, cyanamide, phosphate and ammonium ion, both 2-aminoimidazole and 2-aminooxazole are produced, with higher concentrations of ammonium ion and acidic pH favoring the former. Given a 1:1 mixture of 2-aminoimidazole and 2-aminooxazole, glyceraldehyde preferentially reacts and cyclizes with the latter, forming a mixture of pentose aminooxazolines, and leaving free 2-aminoimidazole available for nucleotide activation. The common synthetic origin of 2-aminoimidazole and 2-aminooxazole and their distinct reactivities are suggestive of a reaction network that could lead to both the synthesis of RNA monomers and to their subsequent chemical activation

Guano-Derived δ\u3csup\u3e13\u3c/sup\u3eC-Based Paleo-Hydroclimate Record from Gaura cu Musca Cave, SW Romania

The δ13C values of 23 unevenly spaced guano samples from a 17-cm long clay sediment profile in Gaura cu Muscă Cave (GM), in SW Romania, made it possible to preliminarily characterize the Medieval Warm Period summer hydroclimate regime. The beginning of the sequence (AD 990) was rather wet for more than a century, before becoming progressively drier. After a brief, yet distinct wet period around AD 1170, drier conditions, with a possible shift from C3 to a mixed C3-dominated/C4 type vegetation (2 ‰ lower δ13C values), prevailed for almost half a century before the climate became colder and wetter at the onset of the Little Ice Age, when bats left the cave. The guano-inferred wet and dry intervals from the GM Cave are mirrored by changes in the color and amount of clay accumulated in the cave. They also agree well with reconstructions based on pollen and charcoal from peat bogs and δ13C and δ18O on speleothems from other Romanian sites. Overall, these results indicate that the δ13C of bat guano can provide a sensitive record of the short-term coupling between local/regional climate and the plant–insect–bat–guano system