1,692 research outputs found

    The extent of counterion dissociation at the interface of cationic diblock copolymer nanoparticles in non-polar solvents

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    Hypothesis Diblock copolymer nanoparticles prepared in non-polar solvents that are sterically stabilized but possess ionic functionality from the inclusion of cationic comonomers in the stabilizer shell are known to exhibit complex electrokinetic behavior (Chem. Sci. 9 (2018) 922–934). For example, core-shell nanoparticles with cationic comonomers located solely within the shell layer have lower magnitude electrophoretic mobilities than nanoparticles containing the same cationic comonomers located within the core, and nanoparticles prepared using a minor fraction of steric stabilizer chains containing cationic comonomer repeat units have comparable electrophoretic mobilities to nanoparticles prepared with this cationic comonomer solely located within the core. We hypothesize that these observations can be explained in terms of the strength of the Coulombic interaction between counterions and the nanoparticle interface. Experiments The highly-fluorinated anionic counterion associated with these cationic nanoparticles is studied by 19F nuclear magnetic resonance (NMR) spectroscopy in n-dodecane. This revealed only one type of 19F environment for a soluble macromolecular cation (the oil-soluble steric stabilizer chains used to prepare the nanoparticles), whereas two distinct environments were observed for the sterically-stabilized cationic nanoparticles. Both 19F diffusion NMR and 19F–13C heteronuclear single quantum correlation (HSQC) measurements support the existence of two environments for this counterion. Findings The existence of two distinct 19F environments for the highly-fluorinated anion associated with the sterically-stabilized nanoparticles demonstrates the presence of spectroscopically distinguishable populations of ion pairs and of fully dissociated free anions. 19F NMR spectra recorded for sterically-stabilized nanoparticles with a fully ionic shell (all stabilizer chains containing the cationic comonomer) and those with a partly ionic shell (10% of stabilizer chains containing the cationic comonomer) reveal a higher proportion of dissociated anions in the partly ionic case. This suggests a stronger Coulombic interaction between counterions and the cationic interface when the shell is fully ionic, which accounts for the observed reduction in the magnitude of the electrophoretic mobility

    Mixed micelles and gels of a hydrophilic poloxamine (Tetronic 1307) and miltefosine: Structural characterization by small-angle neutron scattering and in vitro evaluation for the treatment of leishmaniasis

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    Hypothesis/background: Tetronic is a family of four-armed amphiphilic block copolymers of polyethylene oxide (PEO) and polypropylene oxide (PPO) that self-aggregate to form micelles and hydrogels. Due to their temperature and pH-responsiveness, they are emerging as smart nanomaterials in the area of drug delivery. Here we propose the use of Tetronic 1307 (T1307) as a nanocarrier of miltefosine (MF), a zwitterionic alkylphospholipid highly active against leishmaniasis, one of the most threating neglected tropical diseases. Given the amphiphilic nature of the drug, both surfactants can combine to form mixed micelles, reducing the cytotoxicity of MF by lowering its dose and improving its internalization, hence its antileishmanial effect. Experiments: The structure of the T1307 micelles, MF micelles, mixed micelles and hydrogels, formed in buffered solution (pH = 7.4) at different concentrations has been investigated in-depth by a combination of small-angle neutron scattering (SANS), dynamic light scattering (DLS), fluorescence spectroscopy and nuclear magnetic resonance methods (1D, 2D NOESY, and diffusion NMR). The cytotoxicity of the aggregates in macrophages has been assessed, as well as the antileishmanial activity in both Leishmania major promastigotes and amastigotes. Findings: T1307 and MF combine into mixed aggregates over a wide range of temperatures and compositions, forming ellipsoidal core–shell mixed micelles. The shell is highly hydrated and comprises most of the PEO blocks, while the hydrophobic core contains the PO blocks and the MF along with a fraction of EO and water molecules, depending on the molar ratio in the mixture. The combination with T1307 amplified the leishmanicidal activity of the drug against both forms of the parasite and dramatically reduced drug cytotoxicity. T1307 micelles also showed a considerable leishmanicidal activity without exhibiting macrophage toxicity. These results support the use of T1307 as a MF carrier for the treatment of human and animal leishmaniasis, in its different clinical forms

    Gold in the Dalradian terrane : a review of previous work

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    The Dalradian Supergroup comprises a Late Precambrian sequence of marine clastic sedimentary rocks and minor basic volcanic rocks which was folded and metamorphosed during the early Palaeozoic Caledonian Orogeny. Intrusive igneous rocks are widespread throughout the Dalradian terrane. The most important in terms of gold metallogenesis are the post-tectonic granites which comprise a diverse suite of calc-alkaline intrusions emplaced between 420 and 395 Ma. Numerous occurrences of gold in bedrock and alluvium are documented in the Dalradian terrane of Scotland. Mesothermal vein occurrences are the most important and include the Cononish deposit, near Tyndrum in Perthshire, where planning permission for mining has been granted. Gold mineralisation of several other styles, including intrusion-related, epithermal, stratiform and occurrences associated with mafic-ultramafic intrusions, is also present. This report has been compiled for the BGS Core Programme project ‘Sedimentary Basin Resources: Gold in orogenic extensional basins – the Dalradian’. This project, carried out between 1997–2000, was designed to investigate the factors controlling the distribution of gold in the Dalradian and to develop a predictive metallogenic model for gold mineralisation in this terrane. This report provides a` review of known gold occurrences and the results of past mineral exploration activity in the Dalradian terrane. The latter has been compiled from records held in BGS archives and the available data are summarised in a series of appendices. Exploration for metalliferous mineralisation has been carried out widely in the Dalradian terrane by commercial mining companies and by BGS. In the 1970s most work focused on Cu, Pb, Zn, Ni and Mo, while more recently, from 1981 onwards, precious metals (Au and PGE) were the prime target. Between 1972 and 1984 the DTI sought to encourage private-sector mineral exploration by the provision of grants under the Mineral Exploration and Investment Grants Act (MEIGA). About 150 reports derived from these projects are available on open-file at BGS. Exploration by BGS was carried out mainly through the DTI-funded Mineral Reconnaissance Programme (MRP), which ran between 1972 and 1997. Nearly 150 reports and associated data releases were produced by the MRP. Together the MEIGA and MRP reports have been the major sources of information used in this report. The combination of improved genetic models for gold deposits, the increased availability of multidisciplinary digital geoscience data and the information on previous exploration summarised in this report provides a sound basis for research on gold mineralisation in the Dalradian terrane. Potential exists in a range of settings that may host economic gold deposits

    Status of Grey Leaf Spot Disease In Kenyan Maize Production Ecosystems

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    Grey leaf spot disease (GLS), Cercospora zeae-maydis, which has previously been attributed to diverse pathogen species in other countries, has become a serious biotic constraint to production of maize ( Zea mays L.) in Kenya. It is necessary to determine the distribution and aetiology of the disease across all the maize production agro-ecologies in order to inform the development of appropriate management strategies against the disease. Samples were collected from maize growing areas in Kenya with GLS symptoms on maize crops and other plants. On the basis of cultural and morphological examinations, and restricted fragment length polymorphism and taxon-specific PCR analyses, Cercospora zeae-maydis group II and C. sorghi var. maydis were identified from typical GLS lesions on maize, with the former being predominant (>96% of the cases) and distributed throughout the country. The latter exhibited minor incidence (<4%) in western Kenya. Nucleotide sequence analyses further provided evidence that C. zeae-maydis group II and C. sorghi var. maydis were distinct fungi.La maladie de t\ue2che grise de la feuille (GLS), Cercospora zeae-maydis, attribu\ue9e aux esp\ue8ces de pathogens diverses dans d'autres pays, est devenue une s\ue9rieuse contrainte biotique \ue0 la production de ma\uefs ( Zea mays L.) au Kenya. Il est n\ue9cessaire de d\ue9terminer la distribution et l'\ue9tiologie de la maladie \ue0 travers toutes les r\ue9gions agro-\ue9cologques productrices de ma\uefs pour mieux d\ue9velopper des strat\ue9gies appropri\ue9es de gestion contre la maladie. Des \ue9chantillons \ue9taient recueillis dans des r\ue9gions producteurs du ma\uefs au Kenya tenant compte de la pr\ue9sence des sympt\uf4mes GLS sur les ma\uefs et autres cultures. Sur base des examens culturales et morphologiques ainsi que du polymorphisme de la longueur du fragment isol\ue9 et les analyses PCR du taxon sp\ue9cifique, Cercospora zeae-maydis le groupe II de Cercospora zeae-maydis et C. sorghi var. maydis \ue9taient identifi\ue9s par des l\ue9sions typiques de GLS sur le ma\uefs, ce dernier \ue9tant le plus pr\ue9dominant (> 96 % de tous les cas) et distribu\ue9 \ue0 travers tout le pays avec une incidence mineur de 4 % dans l'ouest du Kenya. L'analyse de s\ue9quences de nucl\ue9otides avait par la suite montr\ue9 avec evidence que le C. zeae-maydis group II et C. sorghi var. maydis \ue9taient de champignons distincts

    Global priorities for reduction of cetacean bycatch

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    Progress at reducing the scale and conservation impact of cetacean bycatch has been slow, sporadic, and limited to a few specific fisheries or circumstances. As a result, bycatch remains perhaps the greatest immediate and well-documented threat to cetacean populations globally. Having recognized the critical importance of reducing bycatch levels to prevent the depletion, and in some cases extinction, of cetacean populations, World Wildlife Fund-US launched a global bycatch initiative early in 2002. Their strategy calls on governmental and non-governmental bodies to move quickly, cooperatively, and thoughtfully to achieve bycatch reduction. As a supportive step, a working group was established to identify priorities and provide guidance on how financial and other resources should be invested to address bycatch issues. The group conducted a global survey of cetacean bycatch problems and identified a series of specific problems that should be addressed as priorities, with emphasis on: (1) situations that are especially critical (e.g. a species’ or population’s survival is immediately at risk from bycatch) and are not being addressed adequately; (2) circumstances where rapid progress could be made with a modest investment of resources; (3) situations in which bycatch is believed to pose a threat to cetaceans but a quantitative assessment is needed to verify the risk; and (4) fisheries in which a currently available solution (technical, socio-economic, or a combination) appears feasible

    Selective vulnerability of tripartite synapses in Amyotrophic Lateral Sclerosis

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    Authors would like to acknowledge the following funders: Motor Neurone Disease (MND) Association UK (Miles/Apr18/863-791), the Euan MacDonald Centre and Chief Scientist Office, The European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (695568 SYNNOVATE), Simons Foundation Autism Research Initiative (529085), and the Wellcome Trust (Technology Development grant 202932).Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder. Separate lines of evidence suggest that synapses and astrocytes play a role in the pathological mechanisms underlying ALS. Given that astrocytes make specialised contacts with some synapses, called tripartite synapses, we hypothesise that tripartite synapses could act as the fulcrum of disease in ALS. To test this hypothesis, we have performed an extensive microscopy-based investigation of synapses and tripartite synapses in the spinal cord of ALS model mice and post-mortem human tissue from ALS cases. We reveal widescale synaptic changes at the early symptomatic stages of the SOD1G93a mouse model. Super-resolution microscopy reveals that large complex postsynaptic structures are lost in ALS mice. Most surprisingly, tripartite synapses are selectively lost, while non-tripartite synapses remain in equal number to healthy controls. Finally, we also observe a similar selective loss of tripartite synapses in human post-mortem ALS spinal cords. From these data we conclude that tripartite synaptopathy is a key hallmark of ALS.Publisher PDFPeer reviewe

    Global priorities for reduction of cetacean bycatch. Scientific Committee document SC/56/BC2, International Whaling Commission, July 2004, Sorrento, Italy

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    Progress at reducing the scale and conservation impact of cetacean bycatch has been slow, sporadic and limited to a few specific fisheries or circumstances. As a result bycatch remains perhaps the greatest immediate and well-documented threat to cetacean populations globally. Having recognized the critical importance of reducing bycatch levels to prevent the depletion, and in some cases extinction, of cetacean populations, World Wildlife Fund-US launched a global bycatch initiative early in 2002. Their strategy calls on governmental and non-governmental bodies to move quickly, cooperatively and thoughtfully to achieve bycatch reduction. As a supportive step a working group was established to identify priorities and provide guidance on how financial and other resources should be invested to address bycatch issues. The group will conduct a global survey of cetacean bycatch problems, classify and rank those problems according to an agreed set of criteria and provide a clear rationale for each problem assigned high priority for funding and intervention. The working group will emphasise: (1) situations that are especially critical (e.g. a species’ or population’s survival is immediately at risk from bycatch) and are not being addressed adequately; (2) circumstances where rapid progress could be made with a modest investment of resources; (3) situations in which bycatch is believed to pose a threat to cetaceans but a quantitative assessment is needed to verify the risk; and (4) fisheries in which a currently available solution (technical, socioeconomic or a combination) appears feasible. The report of the working group will be directed at governmental decision makers, aid agencies, nongovernmental organizations and related audiences
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