Search results for "Mphi"
showing 10 items of 626 documents
Fluorinated Chaperone−β-Cyclodextrin Formulations for β-Glucocerebrosidase Activity Enhancement in Neuronopathic Gaucher Disease
2017
Amphiphilic glycomimetics encompassing a rigid, undistortable nor-tropane skeleton based on 1,6-anhydro-L-idonojirimycin and a polyfluorinated antenna, when formulated as the corresponding inclusion complexes with β-cyclodextrin (βCD), have been shown to behave as pharmacological chaperones (PCs) that efficiently rescue lysosomal β- glucocerebrosidase mutants associated to the neuronopathic variants of Gaucher disease (GD), including the highly refractory L444P/L444P and L444P/P415R single nucleotide polymorphs, in patient fibroblasts. The body of work here presented includes the design criteria for the PC prototype, the synthesis of a series of candidates, the characterization of the PC:βC…
Chronic myelogenous leukaemia exosomes modulate bone marrow microenvironment through activation of epidermal growth factor receptor
2016
Abstract Chronic myelogenous leukaemia (CML) is a clonal myeloproliferative disorder. Recent evidence indicates that altered crosstalk between CML and mesenchymal stromal cells may affect leukaemia survival; moreover, vesicles released by both tumour and non‐tumour cells into the microenvironment provide a suitable niche for cancer cell growth and survival. We previously demonstrated that leukaemic and stromal cells establish an exosome‐mediated bidirectional crosstalk leading to the production of IL8 in stromal cells, thus sustaining the survival of CML cells. Human cell lines used are LAMA84 (CML cells), HS5 (stromal cells) and bone marrow primary stromal cells; gene expression and protei…
Structural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2
2016
We show that a peptide from Chikungunya virus nsP3 protein spanning residues 1728–1744 binds the amphiphysin-2 (BIN1) Src homology-3 (SH3) domain with an unusually high affinity (Kd 24 nM). Our NMR solution complex structure together with isothermal titration calorimetry data on several related viral and cellular peptide ligands reveal that this exceptional affinity originates from interactions between multiple basic residues in the target peptide and the extensive negatively charged binding surface of amphiphysin-2 SH3. Remarkably, these arginines show no fixed conformation in the complex structure, indicating that a transient or fluctuating polyelectrostatic interaction accounts for this …
PHEA-PLA biocompatible nanoparticles by technique of solvent evaporation from multiple emulsions
2015
Nanocarriers of amphiphilic polymeric materials represent versatile delivery systems for poorly water soluble drugs. In this work the technique of solvent evaporation from multiple emulsions was applied to produce nanovectors based on new amphiphilic copolymer, the α,β-poly(N-2-hydroxyethyl)-DL-aspartamide-polylactic acid (PHEA-PLA), purposely synthesized to be used in the controlled release of active molecules poorly soluble in water. To this aim an amphiphilic derivative of PHEA, a hydrophilic polymer, was synthesized by derivatization of the polymeric backbone with hydrophobic grafts of polylactic acid (PLA). The achieved copolymer was thus used to produce nanoparticles loaded with α toc…
Gold nanostar–polymer hybrids for siRNA delivery: Polymer design towards colloidal stability and in vitro studies on breast cancer cells
2017
To overcome the low bioavailability of siRNA (small interfering RNA) and to improve their transfection efficiency, the use of non-viral delivery carriers is today a feasible approach to transform the discovery of these incredibly potent and versatile drugs into clinical practice. Polymer-modified gold nanoconstructs (AuNCs) are currently viewed as efficient and safe intracellular delivery carriers for siRNA, as they have the possibility to conjugate the ability to stably entrap and deliver siRNAs inside cells with the advantages of gold nanoparticles, which can act as theranostic agents and radiotherapy enhancers through laser-induced hyperthermia. In this study, AuNCs were prepared by coat…
Amphibians and squamate reptiles from the stratigraphic unit Xb of El Salt (Middle Palaeolithic; Alcoy, Spain): palaeoenvironmental and palaeoclimati…
2020
The locality of El Salt (Middle Paleolithic, Alcoy, Spain) is mainly known by having one of the youngest Neanderthals records of the southeastern Iberian Peninsula. In this work, we have analysed the herpetofaunal fossils from the upper part of stratigraphic unit Xb, dated at 52.3 ± 4.6 ka (MIS 3). The faunal list is composed by three taxa of anurans (Alyte obstetricans, Bufo bufo s.l., and Epidalea calamita), one taxon of blanid (Blanus cinereus s.l.), two taxa of lizards (Chalcides bedriagai and cf. Acanthodactylus erythrurus), and one taxon of snakes (cf. Rhinechis scalaris). All of them have a broad distribution range in the Mediterranean, with wide ecological preferences range. This as…
Ferro-pedrizite, NaLi2(Fe2+ 2Al2Li)Si8O22(OH)2, a new amphibole-supergroup mineral from the Sutlug pegmatite, Tyva Republic, Russia
2015
Ferro-pedrizite, a new amphibole-supergroup mineral was discovered in the Sutlug pegmatite occurrence situated in the Targi River Basin, Tyva Republic, Eastern Sibera, Russia. The associated minerals are quartz, albite, microcline, spodumene, cassiterite, beryl, columbite-(Mn), fergusonite-β-(Y), fluorapatite, schorl, trilithionite and fluorite. Ferro-pedrizite forms dark grey-blue to violet-blue acicular and long prismatic crystals up to 2 × 5 × 50 mm and their aggregates. D meas = 3.16(1) g/cm3 (by hydrostatic weighing), 3.13(1) g/cm3 (by flotation in heavy liquids); D calc = 3.135 g/cm3. Ferro-pedrizite is optically biaxial (−), α = 1.614(3), β = 1.638(3), γ = 1.653(3), 2 V meas = 75(5)°…
Poly(ethylene oxide)-block-poly(n-butyl acrylate)-block-poly(acrylic acid) triblock terpolymers with highly asymmetric hydrophilic blocks: synthesis …
2013
The synthesis and aggregation behaviour in aqueous media of novel amphiphilic poly(ethylene oxide)-block-poly(n-butyl acrylate)-block-poly(acrylic acid) (PEO–PnBA–PAA) triblock terpolymers were studied. Terpolymers composed of two highly asymmetric hydrophilic PEO (113 monomer units) and PAA (10–17 units) blocks, and a longer soft hydrophobic PnBA block (163 or 223 units) were synthesized by atom transfer radical polymerisation (ATRP) of n-butyl acrylate and tert-butyl acrylate (tBA), followed by selective hydrolysis of the PtBA blocks. These terpolymers are not directly soluble in water but form defined spherical micelles by employing the dialysis method as confirmed by dynamic light scatt…
Design of nonionic surfactants for supercritical carbon dioxide
1996
Interfacially active block copolymer amphiphiles have been synthesized and their self-assembly into micelles in supercritical carbon dioxide (CO 2 ) has been demonstrated with small-angle neutron scattering (SANS). These materials establish the design criteria for molecularly engineered surfactants that can stabilize and disperse otherwise insoluble matter into a CO 2 continuous phase. Polystyrene- b -poly(1,1-dihydroperfluorooctyl acrylate) copolymers self-assembled into polydisperse core-shell-type micelles as a result of the disparate solubility characteristics of the different block segments in CO 2 . These nonionic surfactants for CO 2 were shown by SANS to be capable of emulsifying u…
Buildup of Ultrathin Multilayer Films by a Self-Assembly Process: II. Consecutive Adsorption of Anionic and Cationic Bipolar Amphiphiles and Polyelec…
1991
We have recently reported on the consecutive physisorption of anionic and cationic bipolar amphiphiles onto charged surfaces, adsorbed out of aqueous solutions [1]. Here, we extend our previous concept to multipolar compounds such as polyelectrolytes. In contrast to the bipolar amphiphile system, it is not necessary to separate single charges by a rigid unit, when the polyelectrolyte is adsorbed from sufficiently concentrated solutions. In this case the physisorbed layer does not bind with all ionic groups to the surface and exposes free ionic groups at the new film/solution interface. Therefore a polyelectrolyte layer can replace a layer of bipolar amphiphiles in the consecutive buildup of…