Open and cut: allosteric motion and membrane fission by dynamin superfamily proteins.

Cells have evolved diverse protein-based machinery to reshape, cut, or fuse their membrane-delimited compartments. Dynamin superfamily proteins are principal components of this machinery and use their ability to hydrolyze GTP and to polymerize into helices and rings to achieve these goals. Nucleotide-binding, hydrolysis, and exchange reactions drive significant conformational changes across the dynamin family, and these changes alter the shape and stability of supramolecular dynamin oligomers, as well as the ability of dynamins to bind receptors and membranes. Mutations that interfere with the conformational repertoire of these enzymes, and hence with membrane fission, exist in several inherited human diseases. Here, we discuss insights from new x-ray crystal structures and cryo-EM reconstructions that have enabled us to infer some of the allosteric dynamics for these proteins. Together, these studies help us to understand how dynamins perform mechanical work, as well as how specific mutants of dynamin family proteins exhibit pathogenic properties

Structural basis of bilayer deformation by membrane-associated scaffolds

The assembly of amphipathic lipids into fluid bilayers that are impermeable to macromolecules is fundamental to the existence of viruses, organelles, and cells. Conversely, membrane compartmentalization poses problems, since essential processes like cell division, cell migration, endo-, exo-, and transcytosis all require cells to remodel and even break their membranes without opening lethal leaks. Evolutionary forces have consequently generated proteins that can reversibly mold membranes into planes, spheres, cylinders, and saddle-shaped surfaces. Principally, the BAR (Bin, Amphiphysin, RVS) domain superfamily of proteins are recruited from the cytoplasm to induce or stabilize states of high membrane curvature, while the Dynamin superfamily of \u27large GTPases\u27 facilitate the fission of various vesicles and organelles. Members of the BAR domain superfamily often work in concert with members of the Dynamin superfamily to form and then fission membrane tubules. Here, we describe the membrane deforming properties of select F-BAR modules and the GTPase dynamin-1 that were discovered though reconstitution and direct visualization of these proteins as they shape and break model membranes

Going green: prospects for SME's to attain ISO 14001 and the challenges they face in the process

This research aimed to identify any common factors that have enabled and/or motivated SMEs to successfully implement ISO 14001 whilst the majority have not. It also identified what challenges and barriers SMEs face in doing so and how some have overcome these. The existing literature suggests that the majority of SMEs perceive their environmental impacts to be proportional to their size; have a poor understanding of environmental issues; have a poor awareness of environmental regulations; do that have the necessary expertise or leadership to address environmental issues and that SMEs with an environmental management system such as ISO 14001 are very much the minority. The main factors that influenced whether an SME had implemented ISO 14001 were: competitive advantage, regulatory compliance, supply chain pressures, leadership, expertise, resources and external support. This research used qualitative analysis of interviews with managers and directors from 8 SMEs with ISO 14001 and 4 without. All of the SMEs were based in the West Midlands or Staffordshire. Interviews were also conducted with 3 organisations offering support to businesses on environmental issues and with 1 large business who was engaging their suppliers (which included SMEs within this sample) on environmental issues. The research found that there were four main factors that enabled or motivated the SMEs to implement ISO 14001, these were: leadership, supply chain pressures, external support and SMEs' history and experience of accredited management systems. The main challenges that these business had to overcome and that prevented the other SMEs from achieving ISO 14001 were: achieving regulatory compliance, perceived financial cost, lack of perceived competitive advantage, access to relevant and affordable support and for those SMEs without ISO 14001 there was very little perceived external pressure or need for them to do so

Feedback between psychological science and policy in the context of same-sex couples

Psychological science informed recent policy changes granting increased rights for same-sex couples. Understanding that the link between science and policy goes both ways, how should policy inform the next generation of research concerning same-sex couples and sexual minority individuals? This article presents ways that psychological research influenced marriage policy and then puts forth suggestions for future research for the attention of scholars, funders, and policymakers. These include examinations of minority stress in the age of marriage equality; new stressors for same-sex couples including legal divorce; relationship expectations and experiences for emerging adults; and the potential impact of marriage equality for mixed-sex couples including a further challenge to strict gender roles in marriage. The article ends by acknowledging the need for continued application of research to emerging policy questions affecting same-sex couples and sexual minority individuals

Assessment of the nucleotide modifications in the high-resolution cryo-electron microscopy structure of the Escherichia coli 50S subunit.

Post-transcriptional ribosomal RNA (rRNA) modifications are present in all organisms, but their exact functional roles and positions are yet to be fully characterized. Modified nucleotides have been implicated in the stabilization of RNA structure and regulation of ribosome biogenesis and protein synthesis. In some instances, rRNA modifications can confer antibiotic resistance. High-resolution ribosome structures are thus necessary for precise determination of modified nucleotides' positions, a task that has previously been accomplished by X-ray crystallography. Here, we present a cryo-electron microscopy (cryo-EM) structure of the Escherichia coli 50S subunit at an average resolution of 2.2 Å as an additional approach for mapping modification sites. Our structure confirms known modifications present in 23S rRNA and additionally allows for localization of Mg2+ ions and their coordinated water molecules. Using our cryo-EM structure as a testbed, we developed a program for assessment of cryo-EM map quality. This program can be easily used on any RNA-containing cryo-EM structure, and an associated Coot plugin allows for visualization of validated modifications, making it highly accessible

Going green: prospects for SME's to attain ISO 14001 and the challenges they face in the process

This research aimed to identify any common factors that have enabled and/or motivated SMEs to successfully implement ISO 14001 whilst the majority have not. It also identified what challenges and barriers SMEs face in doing so and how some have overcome these. The existing literature suggests that the majority of SMEs perceive their environmental impacts to be proportional to their size; have a poor understanding of environmental issues; have a poor awareness of environmental regulations; do that have the necessary expertise or leadership to address environmental issues and that SMEs with an environmental management system such as ISO 14001 are very much the minority. The main factors that influenced whether an SME had implemented ISO 14001 were: competitive advantage, regulatory compliance, supply chain pressures, leadership, expertise, resources and external support. This research used qualitative analysis of interviews with managers and directors from 8 SMEs with ISO 14001 and 4 without. All of the SMEs were based in the West Midlands or Staffordshire. Interviews were also conducted with 3 organisations offering support to businesses on environmental issues and with 1 large business who was engaging their suppliers (which included SMEs within this sample) on environmental issues. The research found that there were four main factors that enabled or motivated the SMEs to implement ISO 14001, these were: leadership, supply chain pressures, external support and SMEs' history and experience of accredited management systems. The main challenges that these business had to overcome and that prevented the other SMEs from achieving ISO 14001 were: achieving regulatory compliance, perceived financial cost, lack of perceived competitive advantage, access to relevant and affordable support and for those SMEs without ISO 14001 there was very little perceived external pressure or need for them to do so.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The BAR Domain Superfamily: Membrane-Molding Macromolecules

Membrane-shaping proteins of the BAR domain superfamily are determinants of organelle biogenesis, membrane trafficking, cell division, and cell migration. An upsurge of research now reveals new principles of BAR domain-mediated membrane remodeling, enhancing our understanding of membrane curvature-mediated information processing