Polymerization-Induced Polymersome Fusion

The dynamic interactions of membranes, particularly their fusion and fission, are critical for the transmission of chemical information between cells. Fusion is primarily driven by membrane tension built up through membrane deformation. For artificial polymersomes, fusion is commonly induced via the external application of a force field. Herein, fusion-promoted development of anisotropic tubular polymersomes (tubesomes) was achieved in the absence of an external force by exploiting the unique features of aqueous ring-opening metathesis polymerization-induced self-assembly (ROMPISA). The out-of-equilibrium tubesome morphology was found to arise spontaneously during polymerization, and the composition of each tubesome sample (purity and length distribution) could be manipulated simply by targeting different core-block degrees of polymerization (DPs). The evolution of tubesomes was shown to occur via fusion of “monomeric” spherical polymersomes, evidenced most notably by a step-growth-like relationship between the fraction of tubular to spherical nano-objects and the average number of fused particles per tubesome (analogous to monomer conversion and DP, respectively). Fusion was also confirmed by Förster resonance energy transfer (FRET) studies to show membrane blending and confocal microscopy imaging to show mixing of the polymersome lumens. We term this unique phenomenon polymerization-induced polymersome fusion, which operates via the buildup of membrane tension exerted by the growing polymer chains. Given the growing body of evidence demonstrating the importance of nanoparticle shape on biological activity, our methodology provides a facile route to reproducibly obtain samples containing mixtures of spherical and tubular polymersomes, or pure samples of tubesomes, of programmed length. Moreover, the capability to mix the interior aqueous compartments of polymersomes during polymerization-induced fusion also presents opportunities for its application in catalysis, small molecule trafficking, and drug delivery

Pressure- and stress-induced fabric transition in olivine from peridotites in the Western Gneiss Region (Norway): implications for mantle seismic anisotropy (supporting files)

The effects of pressure, water and differential stress on the crystallographic preferred orientation (CPO) of olivine were investigated by an integrated study on 13 peridotite samples from four areas in the Western Gneiss Region (WGR) of the Norwegian Caledonides. The highly depleted dunites are mantle residues after Archean melt extraction, while the garnet peridotites were formed by refertilization of the dunites via melt percolation in the Proterozoic. These orogenic peridotites were tectonically emplaced into Proterozoic gneisses and metasedimentary rocks of the WGR and were recrystallized under high-pressure (HP) to ultrahigh-pressure (UHP) conditions when the Baltic Shield was subducted beneath Laurentia during the 420–400 Ma Scandian orogeny. The CPOs of olivine, enstatite and diopside were measured using the electron backscatter diffraction technique. The weakly deformed garnet wehrlites and dunites from the HP central WGR (the Gurskøy, Almklovdalen and Tafjord areas) show the A-type olivine fabric defined by the [100] axis subparallel to the stretching lineation and the (010) plane subparallel to the foliation, which may be a relict fabric formed at high temperature and low strain rate in the mantle wedge prior to subduction. The [001](010) fabric (B-type) is observed in strongly sheared HP garnet peridotites and dunites from the Almklovdalen and Tafjord areas, suggesting the dominant activation of [001](010) slip system at high stress and high strain rate. Recrystallized fine olivine grains may develop a fabric different from porphyroclasts and record a gradual fabric transition. The olivine CPO in garnet lherzolites from Otrøy in the northernmost WGR is characterized by the concentration of [001] axes parallel to the stretching lineation and [100] axes normal to the foliation, indicating a prevailing [001](100) slip (C-type fabric) at P–T conditions of <6 GPa and 850–950 °C. Despite very different deformation microstructures, Fourier transform infrared analysis reveals very low water contents (<13 ppm H2O by the Paterson calibration) in olivine for both coarse porphyroclasts and recrystallized small grains, which is consistent with the high-degree partial melting of the peridotites during the Archean. Therefore, a combination of UHP and low temperature plays a more important role than water in promoting the C-type olivine fabric in a dry, cold and deeply subducted continental slab. With increasing subduction depths, the C-type olivine fabric will predominate over the A-type fabric and make the maximum P-wave velocity and shear wave splitting of peridotites normal to the foliation. However, the stress-induced fabric transition in olivine from the A-type to the B-type may be localized in shear zones and not distinguishable in seismic anisotropy observations

Roles of the variable P450 substrate recognition sites SRS1 and SRS6 in esfenvalerate metabolism by CYP6AE subfamily enzymes in Helicoverpa armigera.

The cotton bollworm P450s of the clustered CYP6AE subfamily share high sequence identities but differ dramatically in their capacity to metabolize xenobiotics, especially esfenvalerate. Among them, CYP6AE17 has the highest sequence identity with CYP6AE18 but shows ~7-fold higher metabolic efficiency. CYP6AE11 is most active towards esfenvalerate but CYP6AE20 is inactive even though the enzymes share 54.8% sequence identity. Sequence analysis revealed the SRS1 (Substrate Recognition Site) and SRS6 between CYP6AE17 and CYP6AE18, and SRS1 between CYP6AE11 and CYP6AE20 are the most variable among all six SRSs. In order to identify the key factors that underlie the observed catalytic difference, we exchanged these SRS sequences between two pairs of P450s and studied the activity of the resulting hybrid mutants or chimeras. In vitro metabolism showed that the CYP6AE17/18 chimeras had 2- and 14-fold decreased activities and the CYP6AE18/17 chimeras had 6- and 10-fold increased activities to esfenvalerate. Meanwhile, after exchanging SRS1 with each other, the CYP6AE11/20 chimera folded incorrectly but the CYP6AE20/11 chimera gained moderate activity to esfenvalerate. Molecular modelling showed that amino acids variants within SRS1 or SRS6 change the shape and chemical environment of the active sites, which may affect the ligand-binding interactions. These results indicate that the protein structure variation resulting from the sequence diversity of SRSs promotes the evolution of insect chemical defense and contributes to the development of insect resistance to pesticides

Function and pharmacology of glutamate-gated chloride channel exon 9 splice variants from the diamondback moth Plutella xylostella

Glutamate-gated chloride channels (GluCls) are found only in invertebrates and mediate fast inhibitory neurotransmission. The structural and functional diversity of GluCls are produced through assembly of multiple subunits and via posttranscriptional alternations. Alternative splicing is the most common way to achieve this in insect GluCls and splicing occurs primarily at exons 3 and 9. As expression pattern and pharmacological properties of exon 9 alternative splices in invertebrate GluCls remain poorly understood, the cDNAs encoding three alternative splice variants (9a, 9b and 9c) of the PxGluCl gene from the diamondback moth Plutella xylostella were constructed and their pharmacological characterizations were examined using electrophysiological studies. Alternative splicing of exon 9 had little to no impact on PxGluCl sensitivity towards the agonist glutamate when subunits were singly or co-expressed in Xenopus oocytes. In contrast, the allosteric modulator abamectin and the chloride channel blocker fipronil had differing effects on PxGluCl splice variants. PxGluCl9c channels were more resistant to abamectin and PxGluCl9b channels were more sensitive to fipronil than other homomeric channels. In addition, heteromeric channels containing different splice variants showed similar sensitivity to abamectin (except for 9c) and reduced sensitivity to fipronil than homomeric channels. These findings suggest that functionally indistinguishable but pharmacologically distinct GluCls could be formed in P. xylostella and that the upregulated constitutive expression of the specific variants may contribute to the evolution of insecticide resistance in P. xylostella and other arthropods

Marketing technology for adoption by small business

The adoption of technology for marketing is essential for the survival of small businesses and yet little is understood about owner-manager practice in this area. This paper aims to address that gap through a qualitative study of 24 owner-managed small businesses operating in the visitor economy. It found that there was a strong appetite for the adoption of technology for marketing and a clear recognition of its opportunities particularly related to how it could create a stronger market orientation and more agile marketing, adhering to the principles of effectual reasoning. However, the ability to take advantage of these opportunities was constrained by a lack of knowledge and in particular an inability to measure the return on investment. While the wider implications of the study are limited by the niche sample, a planning model for the adoption of technology for marketing is presented which can be tested through future research

Combined application of Raman spectroscopy and focused ion beam scanning electron microscopy on silicate melt inclusions to track metasomatism in spinel peridotite xenoliths

Liptai N. et al. ECROFI2019 absztrakt kötetben megjelent absztraktja (angol nyelven

Prolonged magmatism and growth of the Iran-Anatolia Cadomian continental arc segment in Northern Gondwana

Much of the crust of Iran and Anatolia, including their oldest exposed rocks, formed during an episode of intense convergent margin (arc) magmatism as a result of subduction of oceanic lithosphere beneath northern Gondwana from ca 620 Ma to ca 500 Ma, the Cadomian crust-forming event. Most igneous rocks formed between ca 570 and 525 Ma. Cadomian crust is well-known from western and southern Europe and from eastern North America but is much less well-known from Iran and Anatolia. We use published age and compositional data and contribute new data in order to better understand this ancient magmatic system. Cadomian magmatism included calc-alkaline igneous rocks of arc affinity in the main arc and alkalic igneous rocks that formed in a back-arc setting; these igneous rocks are associated with sedimentary rocks. Geochemical and isotopic modelling reveals that basaltic magmas were the main input, that these formed by partial melting in the upper mantle, and that basaltic magmas evolved further in deep crustal hot zones to form granitic magmas through a combination of assimilating older continental crust and fractional crystalization of basaltic magmas.This study was funded by the “ National Key Research and Development Program of China ( 2016YFE0203000 )” and by “ Chinese Academy of Sciences , President's International Fellowship Initiative (PIFI, 2019VCB0013 ). Financial support was also received from the Alexander von Humboldt Foundation in the form of a senior research grant and GEOMAR Helmholtz Centre while preparing these results for publication. FL gratefully acknowledges the PRIN2017 Project 20177BX42Z_001 (Intraplate deformation, magmatism and topographic evolution of a diffuse collisional belt: Insights into the geodynamics of the Arabia-Eurasia collisional zones) and the grant to Department of Science, Roma Tre University (MIUR-Italy Dipartimenti di Eccellenza, ARTICOLO 1, COMMI 314 – 337 LEGGE 232/2016 ). We thank Semih Gürsu for providing us bulk rock data from Derik complex of Turkey. Zircon U–Pb geochronology and and Lu–Hf isotope data were obtained using instrumentation funded by DEST Systemic Infrastructure Grants, ARC LIEF, NCRIS/AuScope, industry partners, and Macquarie University. All logistical support for field studies came from Damghan University. This is contribution 1544 from the ARC Centre of Excellence for Core to Crust Fluid Systems ( http://www.ccfs.mq.edu.au ) and 1412 in the GEMOC Key Centre ( http://www.gemoc.mq.edu.au ), and 1380 from UTD Geosciences and is related to IGCP-662. from the ARC Centre of Excellence for Core to Crust Fluid Systems ( http://www.ccfs.mq.edu.au ), xxxx from the GEMOC Key Centre ( http://www.gemoc.mq.edu.au ), and xxxx from UTD Geosciences and is related to IGCP-662

The South Asian genome

Genetics of disease Microarrays Variant genotypes Population genetics Sequence alignment AllelesThe genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.Whole genome sequencing to discover genetic variants underlying type-2 diabetes, coronary heart disease and related phenotypes amongst Indian Asians. Imperial College Healthcare NHS Trust cBRC 2011-13 (JS Kooner [PI], JC Chambers)

Generation of angiostatin-like fragments from plasminogen by prostate-specific antigen

Angiostatin, a potent inhibitor of angiogenesis, tumour growth and metastasis, is a biologically active fragment of plasminogen, containing the kringle domains 1–4. It is generated from plasminogen by limited proteolysis. We show that prostate-specific antigen (PSA), a serine proteinase secreted by human prostate and human prostate cancer cells, is able to convert Lys-plasminogen to biologically active angiostatin-like fragments, containing kringles 1–4, by limited proteolysis of peptide bond Glu439–Ala440 in vitro. In an in vitro morphogenesis assay, the purified angiostatin-like fragments inhibited proliferation and tubular formation of human umbilical vein endothelial cells with the same efficacy as angiostatin. This finding might help to understand growth characteristics of prostate cancer, which usually has low microvessel density and slow proliferation. © 1999 Cancer Research Campaig