29 research outputs found

    II Congrés Internacional sobre Traducció : abril 1994 : actes

    Get PDF
    Machine learning-based approach unravels distinct pathological signatures induced by patient-derived α-synuclein seeds in monkeys. Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)-rich protein aggregates [termed "Lewy bodies" (LBs)], is a well-established characteristic of Parkinson's disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning-based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneratio

    Hydrophobically Modified Sulfobetaine Copolymers with Tunable Aqueous UCST through Postpolymerization Modification of Poly(pentafluorophenyl acrylate)

    Get PDF
    Polysulfobetaines, polymers carrying highly polar zwitterionic side chains, present a promising research field by virtue of their antifouling properties, hemocompatibility, and stimulus-responsive behavior. However, limited synthetic approaches exist to produce sulfobetaine copolymers comprising hydrophobic components. Postpolymerization modification of an activated ester precursor, poly(pentafluorophenyl acrylate), employing a zwitterionic amine, 3-((3-aminopropyl)dimethylammonio)propane-1-sulfonate, ADPS, is presented as a novel, one-step synthetic concept toward sulfobetaine (co)polymers. Modifications were performed in homogeneous solution using propylene carbonate as solvent with mixtures of ADPS and pentylamine, benzylamine, and dodecylamine producing a series of well-defined statistical acrylamido sulfobetaine copolymers containing hydrophobic pentyl, benzyl, or dodecylacrylamide comonomers with well-controllable molar composition as evidenced by NMR and FT-IR spectroscopy and size exclusion chromatography.This synthetic strategy was exploited to investigate, for the first time, the influence of hydrophobic modification on the upper critical solution temperature (UCST) of sulfobetaine copolymers in aqueous solution. Surprisingly, incorporation of pentyl groups was found to increase solubility over a wide composition range, whereas benzyl groups decreased solubility—an effect attributed to different entropic and enthalpic contributions of both functional groups. While UCST transitions of polysulfobetaines are typically limited to higher molar mass samples, incorporation of 0–65 mol % of benzyl groups into copolymers with molar masses of 25.5–34.5 kg/mol enabled sharp, reversible transitions from 6 to 82 °C in solutions containing up to 76 mM NaCl, as observed by optical transmittance and dynamic light scattering. Both synthesis and systematic UCST increase of sulfobetaine copolymers presented here are expected to expand the scope and applicability of these smart materials

    RAFT synthesis and stimulus-induced self-assembly in water of copolymers based on the biocompatible monomer 2-(Methacryloyloxy)ethyl phosphorylcholine

    No full text
    absReversible addition-fragmentation chain transfer (RAFT) radical polymerization, mediated by 4-cyanopentanoic acid dithiobenzoate and 4,4'-azobis(4-cyanovaleric acid) (V-501) in water at 70°C, of biocompatible 2-(meth- acryloyloxy)ethyl phosphorylcholine (MPC) yields a macro-chain transfer agent (CTA) that was employed in the synthesis of a range of stimulus-responsive AB diblock copolymers in protic media. Well-defined block copolymers of varying molar composition, with narrow molecular weight distributions (M w/M n = 1.10-1.24) were prepared with N,.N-diethylacrylamide (DEAm), 4-vinylbenzoic acid (VBZ), N(3-sulfopropyl)-N- methacryloyloxyethyl- N,N-dimethylammonium betaine (DMAPS), and the newly synthesized N,N-di-n-propylbenzylvinylamine (Dn- PBVA) in either methanol, 2,2,2-trifluoroethanol, or aqueous media. When a combination of 1H NMR spectroscopy and dynamic light scattering is used, it is shown that all block copolymers are capable of existing as molecularly dissolved chains in aqueous media with average hydrodynamic diameters of ~6-7 nm provided the aqueous environment is appropriately tuned. Similarly, these unimers can be induced to undergo self-assembly in the same aqueous environment provided the correct external stimulus (change in temperature, pH, or electrolyte concentration) is applied. In such instances, aggregates with average sizes in the range of ~22-180 nm are formed and are most likely due to the formation of polymeric micelles and vesicles. Such self-assembly is also completely reversible. Removal, or reversal, of the applied stimulus results in the reorganization to the unimeric state. ©2009 American Chemical Society
    corecore