Suchergebnisse

By Molecular Dynamics simulations, we investigated the dynamics of isotropic fluids of colloidal nanotrimers whose interactions are described by varying the strength of attractive and repulsive terms of the Mie potential. To provide a consistent comparison between the systems described by different force fields, we determined the phase diagram and critical points of each system, characterised the morphology of high-density liquid phases at the same reduced temperature and density, and finally investigated their long-time relaxation dynamics. In particular, we detected an especially complex dynamics that unveils the existence of slow and fast nanotrimers and the resulting occurrence of non-Gaussianity, which develops at intermediate time scales. Deviations from Gaussianity are temporary and vanish within the timescales of the system's density fluctuations decay, when a Fickian-like diffusion regime is eventually observed. ; UK Engineering and Physical Sciences Research Council (EPSRC) ; IBM ; Maria Zambrano Senior distinguished researcher fellowship, financed by the European Union (NextGenerationEU program)

Neuroinflammation is one of the main physiopathological mechanisms of amyotrophic lateral sclerosis (ALS), produced by the chronic activation of microglia in the CNS. This process is triggered by the persistent activation of the ATP-gated P2X7 receptor (P2RX7, hereafter referred to as P2X7R). The present study aimed to evaluate the effects of the chronic treatment with the P2X7R antagonist JNJ-47965567 in the development and progression of ALS in the SOD1 murine model. SOD1 mice were intraperitoneally (i.p.) injected with either 30 mg/kg of JNJ-47965567 or vehicle 4 times per week, from pre-onset age (here, postnatal day 60; P60) until study endpoint. Body weight, motor coordination, phenotypic score, disease onset and survival were measured throughout the study, and compared between vehicle- and drug-injected groups. Treatment with the P2X7R antagonist JNJ-47965567 delayed disease onset, reduced body weight loss and improved motor coordination and phenotypic score in female SOD1 mice, although it did not increase lifespan. Interestingly, neither beneficial nor detrimental effects were observed in males in any of the analyzed parameters. Treatment did not affect motor neuron survival or ChAT, Iba-1 and P2X7R protein expression in endpoint individuals of mixed sexes. Overall, chronic administration of JNJ-47965567 for 4 times per week to SOD1 mice from pre-onset stage altered disease progression in female individuals while it did not have any effect in males. Our results suggest a partial, yet important, effect of P2X7R in the development and progression of ALS. G93A G93A G93A G93A ; This project was supported by the European Union's Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant agreement no. 766124; the Spanish Ministry of Science, Technology and Innovation (SAF2016-78892R); and Fundación Teófilo Hernando.