Coordinated recruitment of Spir actin nucleators and myosin V motors to Rab11 vesicle membranes

There is growing evidence for a coupling of actin assembly and myosin motor activity in cells. However, mechanisms for recruitment of actin nucleators and motors on specific membrane compartments remain unclear. Here we report how Spir actin nucleators and myosin V motors coordinate their specific membrane recruitment. The myosin V globular tail domain (MyoV-GTD) interacts directly with an evolutionarily conserved Spir sequence motif. We determined crystal structures of MyoVa-GTD bound either to the Spir-2 motif or to Rab11 and show that a Spir-2:MyoVa:Rab11 complex can form. The ternary complex architecture explains how Rab11 vesicles support coordinated F-actin nucleation and myosin force generation for vesicle transport and tethering. New insights are also provided into how myosin activation can be coupled with the generation of actin tracks. Since MyoV binds several Rab GTPases, synchronized nucleator and motor targeting could provide a common mechanism to control force generation and motility in different cellular processes

Environmental impacts of lighting technologies: Life cycle assessment and sensitivity analysis

With two regulations, 244/2009 and 245/2009, the European Commission recently put into practice the EuP Directive in the area of lighting devices, aiming to improve energy efficiency in the domestic lighting sector. This article presents a comprehensive life cycle assessment comparison of four different lighting technologies: the tungsten lamp, the halogen lamp, the conventional fluorescent lamp and the compact fluorescent lamp. Taking advantage of the most up-to-date life cycle inventory database available (ecoinvent data version 2.01), all life cycle phases were assessed and the sensitivity of the results for varying assumptions analysed: different qualities of compact fluorescent lamps (production phase), different electricity mixes (use phase), and endof- life scenarios for WEEE recycling versus municipal solid waste incineration (disposal phase). A functional unit of “one hour of lighting” was defined and the environmental burdens for the whole life cycle for all four lamp types were calculated, showing a clearly lower impact for the two gas-discharge lamps, i.e. the fluorescent and the compact fluorescent lamp. Differences in the product quality of the compact fluorescent lamps reveal to have only a very small effect on the overall environmental performance of this lamp type; a decline of the actual life time of this lamp type doesn't result in a change of the rank order of the results of the here examined four lamp types. It was also shown that the environmental break-even point of the gasdischarge lamps is reached long before the end of their expected life-span. All in all, it can be concluded that a change from today's tungsten lamp technology to a low-energy-consuming technology such as the compact fluorescent lamp results in a substantial environmental benefit

Novel Benchtop Magnetic Particle Spectrometer for Process Monitoring of Magnetic Nanoparticle Synthesis

Magnetic nanoparticles combine unique magnetic properties that can be used in a variety of biomedical applications for therapy and diagnostics. These applications place high demands on the magnetic properties of nanoparticles. Thus, research, development, and quality assurance of magnetic nanoparticles requires powerful analytical methods that are capable of detecting relevant structural and, above all, magnetic parameters. By directly coupling nanoparticle synthesis with magnetic detectors, relevant nanoparticle properties can be obtained and evaluated, and adjustments can be made to the manufacturing process in real time. This work presents a sensitive and fast magnetic detector for online characterization of magnetic nanoparticles during their continuous micromixer synthesis. The detector is based on the measurement of the nonlinear dynamic magnetic response of magnetic nanoparticles exposed to an oscillating excitation at a frequency of 25 kHz, a technique also known as magnetic particle spectroscopy. Our results underline the excellent suitability of the developed magnetic online detection for coupling with magnetic nanoparticle synthesis based on the micromixer approach. The proven practicability and reliability of the detector for process monitoring forms the basis for further application fields, e.g., as a monitoring tool for chromatographic separation processes

Isolation of diborenes and their 90°-twisted diradical congeners

Molecules containing multiple bonds between atoms—most often in the form of olefins—are ubiquitous in nature, commerce, and science, and as such have a huge impact on everyday life. Given their prominence, over the last few decades, frequent attempts have been made to perturb the structure and reactivity of multiply-bound species through bending and twisting. However, only modest success has been achieved in the quest to completely twist double bonds in order to homolytically cleave the associated π bond. Here, we present the isolation of double-bond-containing species based on boron, as well as their fully twisted diradical congeners, by the incorporation of attached groups with different electronic properties. The compounds comprise a structurally authenticated set of diamagnetic multiply-bound and diradical singly-bound congeners of the same class of compound

Quantitative size-resolved characterization of mRNA nanoparticles by in-line coupling of asymmetrical-flow field-flow fractionation with small angle X-ray scattering

Abstract We present a generically applicable approach to determine an extensive set of size-dependent critical quality attributes inside nanoparticulate pharmaceutical products. By coupling asymmetrical-flow field-flow fractionation (AF4) measurements directly in-line with solution small angle X-ray scattering (SAXS), vital information such as (i) quantitative, absolute size distribution profiles, (ii) drug loading, (iii) size-dependent internal structures, and (iv) quantitative information on free drug is obtained. Here the validity of the method was demonstrated by characterizing complex mRNA-based lipid nanoparticle products. The approach is particularly applicable to particles in the size range of 100 nm and below, which is highly relevant for pharmaceutical products—both biologics and nanoparticles. The method can be applied as well in other fields, including structural biology and environmental sciences

Inverse supercritical fluid extraction as a sample preparation method for the analysis of the nanoparticle content in sunscreen agents

We demonstrate the use of inverse supercritical carbon dioxide (scCO2) extraction as a novel methodof sample preparation for the analysis of complex nanoparticle-containing samples, in our case a modelsunscreen agent with titanium dioxide nanoparticles. The sample was prepared for analysis in a simplifiedprocess using a lab scale supercritical fluid extraction system. The residual material was easily dispersedin an aqueous solution and analyzed by Asymmetrical Flow Field-Flow Fractionation (AF4) hyphenatedwith UV- and Multi-Angle Light Scattering detection. The obtained results allowed an unambiguousdetermination of the presence of nanoparticles within the sample, with almost no background fromthe matrix itself, and showed that the size distribution of the nanoparticles is essentially maintained.These results are especially relevant in view of recently introduced regulatory requirements concerningthe labeling of nanoparticle-containing products. The novel sample preparation method is potentiallyapplicable to commercial sunscreens or other emulsion-based cosmetic products and has importantecological advantages over currently used sample preparation techniques involving organic solvents.JRC.I.4-Nanobioscience

Isolation of diradical products of twisted double bonds

Molecules containing multiple bonds between atoms—most often in the form of olefins—are ubiquitous in nature, commerce, and science, and as such have a huge impact on everyday life. Given their prominence, over the last few decades, frequent attempts have been made to perturb the structure and reactivity of multiply-bound species through bending and twisting. However, only modest success has been achieved in the quest to completely twist double bonds in order to homolytically cleave the associated π bond. Here, we present the isolation of double-bond-containing species based on boron, as well as their fully twisted diradical congeners, by the incorporation of attached groups with different electronic properties. The compounds comprise a structurally authenticated set of diamagnetic multiply-bound and diradical singly-bound congeners of the same class of compound