758 research outputs found

    Multifractality of quantum wave packets

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    We study a version of the mathematical Ruijsenaars-Schneider model, and reinterpret it physically in order to describe the spreading with time of quantum wave packets in a system where multifractality can be tuned by varying a parameter. We compare different methods to measure the multifractality of wave packets, and identify the best one. We find the multifractality to decrease with time until it reaches an asymptotic limit, different from the mulifractality of eigenvectors, but related to it, as is the rate of the decrease. Our results could guide the study of experimental situations where multifractality is present in quantum systems.Comment: 6 pages, 4 figures, final version including a new figure (figure 1

    Lyapunov decay in quantum irreversibility

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    The Loschmidt echo -- also known as fidelity -- is a very useful tool to study irreversibility in quantum mechanics due to perturbations or imperfections. Many different regimes, as a function of time and strength of the perturbation, have been identified. For chaotic systems, there is a range of perturbation strengths where the decay of the Loschmidt echo is perturbation independent, and given by the classical Lyapunov exponent. But observation of the Lyapunov decay depends strongly on the type of initial state upon which an average is done. This dependence can be removed by averaging the fidelity over the Haar measure, and the Lyapunov regime is recovered, as it was shown for quantum maps. In this work we introduce an analogous quantity for systems with infinite dimensional Hilbert space, in particular the quantum stadium billiard, and we show clearly the universality of the Lyapunov regime.Comment: 8 pages, 6 figures. Accepted in Phil. Trans. R. Soc.

    Golgi Membrane Dynamics Viewed Through a Lens of Lipids

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    The striking morphology of the Golgi complex has fascinated cell biologists since its discovery over 100 years ago. Yet, despite intense efforts to understand how membrane flow relates to Golgi form and function, this organelle continues to baffle cell biologists and biochemists alike. Fundamental questions regarding Golgi function, while hotly debated, remain unresolved. While Golgi function is historically described from a protein-centric point of view, we now appreciate that conceptual frameworks for how lipid metabolism is integrated with Golgi biogenesis and function are essential for a mechanistic understanding of this fascinating organelle. It is from a lipid-centric perspective that we discuss the larger question of Golgi dynamics and membrane trafficking. We review the growing body of evidence for how lipid metabolism is integrally written into the engineering of the Golgi system, and highlight questions for future study

    Influenza virus differentially activates mTORC1 and mTORC2 signaling to maximize late stage replication

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    <div><p>Influenza A virus usurps host signaling factors to regulate its replication. One example is mTOR, a cellular regulator of protein synthesis, growth and motility. While the role of mTORC1 in viral infection has been studied, the mechanisms that induce mTORC1 activation and the substrates regulated by mTORC1 during influenza virus infection have not been established. In addition, the role of mTORC2 during influenza virus infection remains unknown. Here we show that mTORC2 and PDPK1 differentially phosphorylate AKT upon influenza virus infection. PDPK1-mediated phoshorylation of AKT at a distinct site is required for mTORC1 activation by influenza virus. On the other hand, the viral NS1 protein promotes phosphorylation of AKT at a different site via mTORC2, which is an activity dispensable for mTORC1 stimulation but known to regulate apoptosis. Influenza virus HA protein and down-regulation of the mTORC1 inhibitor REDD1 by the virus M2 protein promote mTORC1 activity. Systematic phosphoproteomics analysis performed in cells lacking the mTORC2 component Rictor in the absence or presence of Torin, an inhibitor of both mTORC1 and mTORC2, revealed mTORC1-dependent substrates regulated during infection. Members of pathways that regulate mTORC1 or are regulated by mTORC1 were identified, including constituents of the translation machinery that once activated can promote translation. mTORC1 activation supports viral protein expression and replication. As mTORC1 activation is optimal midway through the virus life cycle, the observed effects on viral protein expression likely support the late stages of influenza virus replication when infected cells undergo significant stress.</p></div

    NeuroTessMesh: A Tool for the Generation and Visualization of Neuron Meshes and Adaptive On-the-Fly Refinement

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    Gaining a better understanding of the human brain continues to be one of the greatest challenges for science, largely because of the overwhelming complexity of the brain and the difficulty of analyzing the features and behavior of dense neural networks. Regarding analysis, 3D visualization has proven to be a useful tool for the evaluation of complex systems. However, the large number of neurons in non-trivial circuits, together with their intricate geometry, makes the visualization of a neuronal scenario an extremely challenging computational problem. Previous work in this area dealt with the generation of 3D polygonal meshes that approximated the cells’ overall anatomy but did not attempt to deal with the extremely high storage and computational cost required to manage a complex scene. This paper presents NeuroTessMesh, a tool specifically designed to cope with many of the problems associated with the visualization of neural circuits that are comprised of large numbers of cells. In addition, this method facilitates the recovery and visualization of the 3D geometry of cells included in databases, such as NeuroMorpho, and provides the tools needed to approximate missing information such as the soma’s morphology. This method takes as its only input the available compact, yet incomplete, morphological tracings of the cells as acquired by neuroscientists. It uses a multiresolution approach that combines an initial, coarse mesh generation with subsequent on-the-fly adaptive mesh refinement stages using tessellation shaders. For the coarse mesh generation, a novel approach, based on the Finite Element Method, allows approximation of the 3D shape of the soma from its incomplete description. Subsequently, the adaptive refinement process performed in the graphic card generates meshes that provide good visual quality geometries at a reasonable computational cost, both in terms of memory and rendering time. All the described techniques have been integrated into NeuroTessMesh, available to the scientific community, to generate, visualize, and save the adaptive resolution meshes

    Hydrogen sulfide increases production of NADPH oxidase-dependent hydrogen peroxide and phospholipase D-derived phosphatidic acid in guard cell signaling

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    Hydrogen sulfide (H2S) is an important gaseous signaling molecule in plants that participates in stress responses and development. L-Cys desulfhydrase 1, one of the enzymatic sources of H2S in plants, participates in abscisic acid-induced stomatal closure. We combined pharmacological and genetic approaches to elucidate the involvement of H2S in stomatal closure and the interplay between H2S and other second messengers of the guard cell signaling network, such as hydrogen peroxide (H2O2) and phospholipase D (PLD)-derived phosphatidic acid in Arabidopsis (Arabidopsis thaliana). Both NADPH oxidase isoforms, respiratory burst oxidase homolog (RBOH)D and RBOHF, were required for H2S-induced stomatal closure. In vivo imaging using the cytosolic ratiometric fluorescent biosensor roGFP2-Orp1 revealed that H2S stimulates H2O2 production in Arabidopsis guard cells. Additionally, we observed an interplay between H2S and PLD activity in the regulation of reactive oxygen species production and stomatal movement. The PLDα1 and PLDδ isoforms were required for H2S-induced stomatal closure, and most of the H2S-dependent H2O2 production required the activity of PLDα1. Finally, we showed that H2S induced increases in the PLDδ-derived phosphatidic acid levels in guard cells. Our results revealed the involvement of H2S in the signaling network that controls stomatal closure, and suggest that H2S regulates NADPH oxidase and PLD activity in guard cells.Fil: Scuffi, Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina. Universidad Nacional de Mar del Plata; ArgentinaFil: Nietzel, Thomas. Westfalische Wilhelms Universitat; Alemania. Universitat Bonn; AlemaniaFil: Di Fino, Luciano Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina. Universidad Nacional de Mar del Plata; ArgentinaFil: Meyer, Andreas J.. Universitat Bonn; AlemaniaFil: Lamattina, Lorenzo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina. Universidad Nacional de Mar del Plata; ArgentinaFil: Schwarzlände, Markus. Westfalische Wilhelms Universitat; Alemania. Universitat Bonn; AlemaniaFil: Laxalt, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina. Universidad Nacional de Mar del Plata; ArgentinaFil: Garcia-Mata, Carlos. Universidad Nacional de Mar del Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentin

    NeuroEditor: a tool to edit and visualize neuronal morphologies

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    The digital extraction of detailed neuronal morphologies from microscopy data is an essential step in the study of neurons. Ever since Cajal’s work, the acquisition and analysis of neuron anatomy has yielded invaluable insight into the nervous system, which has led to our present understanding of many structural and functional aspects of the brain and the nervous system, well beyond the anatomical perspective. Obtaining detailed anatomical data, though, is not a simple task. Despite recent progress, acquiring neuron details still involves using labor-intensive, error prone methods that facilitate the introduction of inaccuracies and mistakes. In consequence, getting reliable morphological tracings usually needs the completion of post-processing steps that require user intervention to ensure the extracted data accuracy. Within this framework, this paper presents NeuroEditor, a new software tool for visualization, editing and correction of previously reconstructed neuronal tracings. This tool has been developed specifically for alleviating the burden associated with the acquisition of detailed morphologies. NeuroEditor offers a set of algorithms that can automatically detect the presence of potential errors in tracings. The tool facilitates users to explore an error with a simple mouse click so that it can be corrected manually or, where applicable, automatically. In some cases, this tool can also propose a set of actions to automatically correct a particular type of error. Additionally, this tool allows users to visualize and compare the original and modified tracings, also providing a 3D mesh that approximates the neuronal membrane. The approximation of this mesh is computed and recomputed on-the-fly, reflecting any instantaneous changes during the tracing process. Moreover, NeuroEditor can be easily extended by users, who can program their own algorithms in Python and run them within the tool. Last, this paper includes an example showing how users can easily define a customized workflow by applying a sequence of editing operations. The edited morphology can then be stored, together with the corresponding 3D mesh that approximates the neuronal membrane

    P-REX1-Independent, Calcium-Dependent RAC1 Hyperactivation in Prostate Cancer

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    The GTPase Rac1 is a well-established master regulator of cell motility and invasiveness contributing to cancer metastasis. Dysregulation of the Rac1 signaling pathway, resulting in elevated motile and invasive potential, has been reported in multiple cancers. However, there are limited studies on the regulation of Rac1 in prostate cancer. Here, we demonstrate that aggressive androgen-independent prostate cancer cells display marked hyperactivation of Rac1. This hyperactivation is independent of P-Rex1 activity or its direct activators, the PI3K product PIP3 and Gβγ subunits. Furthermore, we demonstrate that the motility and invasiveness of PC3 prostate cancer cells is independent of P-Rex1, supporting the analysis of publicly available datasets indicating no correlation between high P-Rex1 expression and cancer progression in patients. Rac1 hyperactivation was not related to the presence of activating Rac1 mutations and was insensitive to overexpression of a Rac-GAP or the silencing of specific Rac-GEFs expressed in prostate cancer cells. Interestingly, active Rac1 levels in these cells were markedly reduced by elevations in intracellular calcium or by serum stimulation, suggesting the presence of an alternative means of Rac1 regulation in prostate cancer that does not involve previously established paradigms.Centro de Investigaciones Inmunológicas Básicas y Aplicada

    Primary malignant melanoma of the biliary tract: A case report and literature review

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    BACKGROUND: Primary malignant melanoma of the biliary tract (MBT) is a rare condition whose diagnosis requires excluding a primary origin in another location. This paper reviews the most important characteristics of MBT cases published in the literature and reports a new case. The patient reported here is the first case of primary malignant melanoma of the biliary tract with pulmonary metastasis treated with immunotherapy. This patient remains disease-free 36 mo after the treatment of metastatic lung lesions. CASE SUMMARY: A 51-year-old man was admitted to the gastrointestinal department to study obstructive jaundice of a 1 wk clinical course. Magnetic resonance cholangiopancreatography revealed dilatation of the intrahepatic biliary tract and stenosis of the common hepatic duct. Given the suspicion of biliary tract neoplasia, cholecystectomy and resection of the common hepatic duct were performed with hepatic jejunostomy free of complications. Anatomo-pathological diagnosis was melanoma. After intervention, the patient was referred to the Department of Medical Oncology, where a primary origin was excluded in the skin, mucosa, and eyes. This confirmed diagnosis of primary biliary tract melanoma. Computed tomography was performed 12 mo after the procedure revealed several subcentimetric lung nodules. Wedge resection was performed. After confirming the diagnosis of pulmonary metastasis of primary melanoma of the biliary tract, the patient was started on immunotherapy with nivolumab. Tolerance to treatment was excellent. The patient remains disease-free 36 mo after the treatment of metastatic lung lesions. CONCLUSION: The patient reported here is the first case of primary malignant melanoma of the biliary tract with lung metastases successfully treated with immunotherapy
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