Mitochondrial Bol1 and Bol3 function as assembly factors for specific iron-sulfur proteins

Assembly of mitochondrial iron-sulfur (Fe/S) proteins is a key process of cells, and defects cause many rare diseases. In the first phase of this pathway, ten Fe/S cluster (ISC) assembly components synthesize and insert [2Fe-2S] clusters. The second phase is dedicated to the assembly of [4Fe-4S] proteins, yet this part is poorly understood. Here, we characterize the BOLA family proteins Bol1 and Bol3 as specific mitochondrial ISC assembly factors that facilitate [4Fe-4S] cluster insertion into a subset of mitochondrial proteins such as lipoate synthase and succinate dehydrogenase. Bol1-Bol3 perform largely overlapping functions, yet cannot replace the ISC protein Nfu1 that also participates in this phase of Fe/S protein biogenesis. Bol1 and Bol3 form dimeric complexes with both monothiol glutaredoxin Grx5 and Nfu1. Complex formation differentially influences the stability of the Grx5-Bol-shared Fe/S clusters. Our findings provide the biochemical basis for explaining the pathological phenotypes of patients with mutations in BOLA3. DOI: http://dx.doi.org/10.7554/eLife.16673.00

Development of local strontium ranelate delivery systems and long term in vitro drug release studies in osteogenic medium

Funding Information: The authors acknowledge financial support from the Latvian Academy of Sciences though the ERANet under the frame of EuroNanoMed-II (Nanoforosteo, Project number: Z/14/1187) and the Riga Technical University and Riga Stardiņš University Cooperation Research Project No. RTU/RSU-18. Publisher Copyright: © 2018, The Author(s).It has been recognized that the operative stabilization of osteoporotic fractures should be followed up with an appropriate osteoporosis treatment in order to decrease the risk of repeated fractures. Despite the good clinical results of strontium ranelate (SrRan) towards the osteoporosis treatment, high drug doses and long treatment period cause an increased risk of serious side effects. Novel local SrRan/poly(lactic acid) (SrRan/PLA) delivery systems containing from 3.57 ± 0.28 wt% to 24.39 ± 0.91 wt% of active substance were developed. In order to resemble the naturally occurring processes, osteogenic media (OM) was used as a release medium for long term (121 days) in vitro drug release studies and UV/VIS method for the determination of SrRan content in OM was developed and validated. Biomimetic calcium phosphate precipitates were found on the surface and in the pores of prepared delivery system after microcapsule exposure to OM for 121 days as well as SrRan particles, indicating that the release of the drug have not been completed within 121 days. In vitro cell viability evaluation approved no cytotoxic effects of microcapsule suspensions and extracts.publishersversionPeer reviewe

Supreme activity of gramicidin S against resistant, persistent and biofilm cells of staphylococci and enterococci.

Three promising antibacterial peptides were studied with regard to their ability to inhibit the growth and kill the cells of clinical strains of Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium. The multifunctional gramicidin S (GS) was the most potent, compared to the membranotropic temporin L (TL), being more effective than the innate-defence regulator IDR-1018 (IDR). These activities, compared across 16 strains as minimal bactericidal and minimal inhibitory concentrations (MIC), are independent of bacterial resistance pattern, phenotype variations and/or biofilm-forming potency. For S. aureus strains, complete killing is accomplished by all peptides at 5 × MIC. For E. faecalis strains, only GS exhibits a rapid bactericidal effect at 5 × MIC, while TL and IDR require higher concentrations. The biofilm-preventing activities of all peptides against the six strains with the largest biofilm biomass were compared. GS demonstrates the lowest minimal biofilm inhibiting concentrations, whereas TL and IDR are consistently less effective. In mature biofilms, only GS completely kills the cells of all studied strains. We compare the physicochemical properties, membranolytic activities, model pharmacokinetics and eukaryotic toxicities of the peptides and explain the bactericidal, antipersister and antibiofilm activities of GS by its elevated stability, pronounced cell-penetration ability and effective utilization of multiple modes of antibacterial action

Copolymerization of Ethylene with 4-Methyl-1,3-pentadiene Promoted by Titanium Complexes Containing a Tetradentate [OSSO]-Type Bis(phenolato) Ligand

Copolymerization of ethylene with 4-methyl-1,3-pentadiene (4-MPD) catalyzed by 1,4- dithabutanediyl-linked bis(phenolato) titanium complexes 1 and 2 activated by methylaluminoxane (MAO) produced exclusively ethylene-4-MPD copolymers with high activity. The copolymer microstructure can be varied by changing the ratio between the monomers in the copolymerization feed, affording copolymers with 4-MPD content up to 83%. The resulting copolymer are crystalline as shown by thermal analysis and by the X-ray powder diffraction profiles. The microstructural features were fully elucidated by 13CNMRspectroscopy revealing that the copolymers with various 4-MPDcontent show a strong tendency to the alternating microstructure which was confirmed by the kinetic elaboration

Mechanistic Studies on Conjugated Diene Polymerizations Promoted by a Titanium Complex Containing a Tetradentate [OSSO]-Type Bis(phenolato) Ligand

A thorough experimental and theoretical mechanistic study on the conjugated dienes polymerization promoted by the postmetallocene complex dichloro{1,4-dithiabutanediy1-2,2'-bis(4,6-di-tert-butyl-phenoxytitanium, 1, activated by methylaluminoxane (MAO), is presented. Experimental polymerization studies, previously reported on butadiene, isoprene, and 4-methyl-1,3-pentadiene, have been extended to E- and Z-1,3-pentadiene polymerizations and to ethylene-1,3-pentadiene copolymerizations. Complex 1/MAO showed to be unactive in the Z-1,3-pentadiene polymerization, whereas it was quite performing toward E-1,3-pentadiene, leading to a polymer containing a mixture of 1,2- and 1,4-trans units, with a prevalence of 1,2 units at low temperatures. Also for ethylene-1,3-pentadiene copolymerizations, complex 1/MAO showed good activity. The copolymer microstructure can be varied by changing the ratio between the monomers in the copolymerization feed, affording copolymers with 1,3-pentadiene content up to 36%. Density functional theory (DFT) mechanistic studies on butadiene, E- and Z-1,3-pentadiene polymerizations indicate that monomer insertions proceed through an allylic mechanism involving a syn-eta(3) coordination of the growing chain and a s-trans-eta(2) monomer insertion

Digitalization and computational thinking in lower secondary science education using the example of paper chromatography

Paper chromatography is a simple and harmless experiment suitable for lower secondary education. Besides the training of subject-specific contents, paper chromatography allows the application of modelling and simulation since the submicroscopic processes can be simplified in a way that they become understandable in lower secondary education. Here, the application of digital tools in addition to the experimental performance of paper chromatography in a compulsory STEM course in grade 6 is reported. Following a series of experiments, chromatography is at first simulated by a board game and then by computer simulations. Such simulation program allows the variation of the parameters in order to explore the model and to introduce the particle concept of matter and molecular interactions. The implementation with a graphical programming environment such as Scratch also allows the programming by pupils in this age group. In this way, it is possible to introduce modelling and simulation in an early stage as important contributions to scientific work in natural sciences