6 research outputs found

    Biophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus

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    The functions performed by the concentric shells of multilayered dsRNA viruses require specific protein interactions that can be directly explored through their mechanical properties. We studied the stiffness, breaking force, critical strain and mechanical fatigue of individual Triple, Double and Single layered rotavirus (RV) particles. Our results, in combination with Finite Element simulations, demonstrate that the mechanics of the external layer provides the resistance needed to counteract the stringent conditions of extracellular media. Our experiments, in combination with electrostatic analyses, reveal a strong interaction between the two outer layers and how it is suppressed by the removal of calcium ions, a key step for transcription initiation. The intermediate layer presents weak hydrophobic interactions with the inner layer that allow the assembly and favor the conformational dynamics needed for transcription. Our work shows how the biophysical properties of the three shells are finely tuned to produce an infective RV virio

    Biophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus

    No full text
    The functions performed by the concentric shells of multilayered dsRNA viruses require specific protein interactions that can be directly explored through their mechanical properties. We studied the stiffness, breaking force, critical strain and mechanical fatigue of individual Triple, Double and Single layered rotavirus (RV) particles. Our results, in combination with Finite Element simulations, demonstrate that the mechanics of the external layer provides the resistance needed to counteract the stringent conditions of extracellular media. Our experiments, in combination with electrostatic analyses, reveal a strong interaction between the two outer layers and how it is suppressed by the removal of calcium ions, a key step for transcription initiation. The intermediate layer presents weak hydrophobic interactions with the inner layer that allow the assembly and favor the conformational dynamics needed for transcription. Our work shows how the biophysical properties of the three shells are finely tuned to produce an infective RV virio

    First Examples of Metal–Organic Frameworks with the Novel 3,3′-(1,2,4,5-Tetrazine-3,6-diyl)dibenzoic Spacer. Luminescence and Adsorption Properties

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    We report the synthesis of a novel ligand, 3,3′-(1,2,4,5-tetrazine-3,6-diyl)­dibenzoic acid (<b>1</b>). In this fragment, we have introduced two carboxylate groups with the aim of using this ligand as a linker to construct three-dimensional metal–organic frameworks (MOFs). We have been successful in the formation of zinc (<b>2</b>) and lanthanum (<b>3</b>) MOFs. The zinc compound is a two-dimensional structure, while the lanthanum material is a three-dimensional MOF with interesting channels. We include the luminescence and adsorption studies of these materials. Moreover, we have evaluated the in vitro toxicity of this novel ligand, concluding that it can be considered negligible

    Door‐In–Door‐Out Time Effect on Clinical Outcome According to Reperfusion Time in Endovascular Treatment

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    Background Door‐in–door‐out time (DIDO) in nonthrombectomy stroke centers is a key performance indicator in acute stroke care. Nonetheless, the relative importance of DIDO on outcome in patients transferred for endovascular treatment (EVT) is not widely known. Therefore, we aim to explore the association between DIDO and clinical outcome according to onset to reperfusion time in patients undergoing EVT. Methods Observational multicenter study including patients transferred to a thrombectomy‐capable center from a local stroke center who underwent thrombectomy. The primary outcome was favorable clinical outcome, as evaluated by a modified Rankin Scale score of 0 to 2 at 3 months. We evaluated the association between DIDO and clinical outcome according to onset to reperfusion time and factors related to shorter DIDO time. Results Among 2710 patients transferred for thrombectomy evaluation, 970 (43.8%) patients received EVT. Median baseline National Institutes of Health Stroke Scale and DIDO time were 12 (interquartile range [IQR], 6–19) and 83 minutes (IQR, 66–108), respectively. Among patients undergoing EVT, no association was found between DIDO and clinical outcome. Considering only patients treated in the early time window (onset to reperfusion time ≤240 minutes), patients with favorable outcome had a shorter DIDO (60 [IQR, 52–68] versus 73 [IQR, 61–83] minutes; P=0.013). A receiver operating characteristic curve identified a cutoff of 67 minutes of DIDO time that better predicted favorable outcome (sensitivity, 70%; specificity, 73%; area under the curve, 0.741). A multivariate analysis showed that DIDO ≤67 minutes emerged as an independent factor associated with favorable outcome (odds ratio [OR], 5.29 [95% CI, 1.38–20.27]; P=0.015). Door to computed tomography time was the only factor associated with DIDO ≤67 minutes (OR, 1.113 [95% CI, 1.018–1.261]; P=0.022) in a multivariate analysis in this time frame. Conclusions In transferred patients undergoing EVT, DIDO has a significant impact on clinical outcome, mainly in the first hours from stroke onset. A benchmark of 67 minutes in DIDO time is proposed. Shorter door to computed tomography time appears to be an independent factor associated to achieve DIDO time ≤67 minutes. Measures to optimize workflow into referral centers are warranted

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

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    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field
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