Publications by authors named "Alfredo Caceres"

RhoA plays a crucial role in neuronal polarization, where its action restraining axon outgrowth has been thoroughly studied. We now report that RhoA has not only an inhibitory but also a stimulatory effect on axon development depending on when and where exerts its action and the downstream effectors involved. In cultured hippocampal neurons, FRET imaging revealed that RhoA activity selectively localized in growth cones of undifferentiated neurites, whereas in developing axons it displayed a biphasic pattern, being low in nascent axons and high in elongating ones.

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Background: Acute flaccid myelitis (AFM) presents with acute onset of flaccid paralysis with involvement of the gray matter on magnetic resonance imaging (MRI) of the spinal cord. Studies have reported brain MRI abnormalities, but the characteristics have not been fully defined. In this multicenter study, we assessed the acute features and evolution of brain MRI abnormalities in AFM.

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Axon-dendrite formation is a crucial milestone in the life history of neurons. During this process, historically referred as "the establishment of polarity," newborn neurons undergo biochemical, morphological and functional transformations to generate the axonal and dendritic domains, which are the basis of neuronal wiring and connectivity. Since the implementation of primary cultures of rat hippocampal neurons by Gary Banker and Max Cowan in 1977, the community of neurobiologists has made significant achievements in decoding signals that trigger axo-dendritic specification.

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Neurons are highly polarized cells requiring precise regulation of trafficking and targeting of membrane proteins to generate and maintain different and specialized compartments, such as axons and dendrites. Disruption of the Golgi apparatus (GA) secretory pathway in developing neurons alters axon/dendritic formation. Therefore, detailed knowledge of the mechanisms underlying vesicles exiting from the GA is crucial for understanding neuronal polarity.

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Introduction And Importance: Gallstone ileus is an uncommon complication of cholelithiasis. It is usually presented as a small bowel obstruction. Elderly patients are commonly affected.

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Förster resonance energy transfer (FRET) imaging methods provide unique insight into the spatial distribution of energy transfer and (bio)molecular interaction events, though they deliver average information for an ensemble of events included in a diffraction-limited volume. Coupling super-resolution fluorescence microscopy and FRET has been a challenging and elusive task. Here, we present STED-FRET, a method of general applicability to obtain super-resolved energy transfer images.

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Single-molecule localization microscopy enables far-field imaging with lateral resolution in the range of 10 to 20 nanometres, exploiting the fact that the centre position of a single-molecule's image can be determined with much higher accuracy than the size of that image itself. However, attaining the same level of resolution in the axial (third) dimension remains challenging. Here, we present Supercritical Illumination Microscopy Photometric z-Localization with Enhanced Resolution (SIMPLER), a photometric method to decode the axial position of single molecules in a total internal reflection fluorescence microscope.

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The establishment of polarity is crucial for the physiology and wiring of neurons. Therefore, monitoring the axo-dendritic specification allows the mechanisms and signals associated with development, growth, and disease to be explored. Here, we describe major and minor steps to study polarity acquisition, using primary cultures of hippocampal neurons isolated from embryonic rat hippocampi, for monitoring.

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Mechanisms supporting axon growth and the establishment of neuronal polarity have remained largely disconnected from their genetic and epigenetic fundamentals. Recently, post-transcriptional modifications of histones involved in chromatin folding and transcription, and microRNAs controlling translation have emerged as regulators of axonal specification, growth, and guidance. In this article, we review novel evidence supporting the concept that epigenetic mechanisms work at both transcriptional and post-transcriptional levels to shape axons.

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Background: The presence of co-existent neuronal antibodies (neuronal-IgG) in patients with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG1) is not yet well understood.

Objectives: The aim of this study was to investigate the co-existence of a broad range of neuronal-IgG in MOG-IgG1+ patients.

Methods: MOG-IgG1+ patients were tested for 17 neuronal-IgGs in cerebrospinal fluid (CSF) and serum including NMDA-R-IgG, AMPA-R-IgG, GABAB-R-IgG, LGI1-IgG, CASPR2-IgG, GABAA-R-IgG, GAD65-IgG, mGLUR1-IgG, DPPX-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1,2,Tr, and ANNA1,2,3.

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The generation of axonal and dendritic domains is critical for brain circuitry assembly and physiology. Negative players, such as the RhoA-Rho coiled-coil-associated protein kinase (ROCK) signaling pathway, restrain axon development and polarization. Surprisingly, the genetic control of neuronal polarity has remained largely unexplored.

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Estrogen receptor α (ERα) is expressed in tissues as diverse as brains and mammary glands. In breast cancer, ERα is a key regulator of tumor progression. Therefore, understanding what activates ERα is critical for cancer treatment in particular and cell biology in general.

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Rotenone, a broad-spectrum insecticide, piscicide and pesticide, produces a complete and selective suppression of axonogenesis in cultured hippocampal neurons. This effect is associated with an inhibition of actin dynamics through activation of Ras homology member A (RhoA) activity. However, the upstream signaling mechanisms involved in rotenone-induced RhoA activation were unknown.

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Neurons are the most asymmetric cell types, with their axons commonly extending over lengths that are thousand times longer than the diameter of the cell soma. Fluorescence nanoscopy has recently unveiled that actin, spectrin and accompanying proteins form a membrane-associated periodic skeleton (MPS) that is ubiquitously present in mature axons from all neuronal types evaluated so far. The MPS is a regular supramolecular protein structure consisting of actin "rings" separated by spectrin tetramer "spacers".

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Axonal degeneration occurs in the developing nervous system for the appropriate establishment of mature circuits, and is also a hallmark of diverse neurodegenerative diseases. Despite recent interest in the field, little is known about the changes (and possible role) of the cytoskeleton during axonal degeneration. We studied the actin cytoskeleton in an in vitro model of developmental pruning induced by trophic factor withdrawal (TFW).

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Fluorescence nanoscopy imaging permits the observation of periodic supramolecular protein structures in their natural environment, as well as the unveiling of previously unknown protein periodic structures. Deciphering the biological functions of such protein nanostructures requires systematic and quantitative analysis of large number of images under different experimental conditions and specific stimuli. Here we present a method and an open source software for the automated quantification of protein periodic structures in super-resolved images.

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Here, will review current evidence regarding the signaling pathways and mechanisms underlying membrane addition at sites of active growth during axon formation. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 170-180, 2018.

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The amyloid precursor protein (APP) is a type I transmembrane glycoprotein better known for its participation in the physiopathology of Alzheimer disease as the source of the beta amyloid fragment. However, the physiological functions of the full length protein and its proteolytic fragments have remained elusive. APP was first described as a cell-surface receptor; nevertheless, increasing evidence highlighted APP as a cell adhesion molecule.

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Here we describe the use of confocal microscopy in combination with antibodies specific to Golgi proteins to visualize dendritic Golgi outposts (GOPs) in cultured hippocampal pyramidal neurons. We also describe the use of spinning disk confocal microscopy, in combination with ectopically expressed glycosyltransferases fused to GFP variants, to visualize GOPs in living neurons.

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Several reports have linked the presence of high titers of anti-Gg Abs with delayed recovery/poor prognosis in GBS. In most cases, failure to recover is associated with halted/deficient axon regeneration. Previous work identified that monoclonal and patient-derived anti-Gg Abs can act as inhibitory factors in an animal model of axon regeneration.

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ApoER2 and its ligand Reelin participate in neuronal migration during development. Upon receptor binding, Reelin induces the proteolytic processing of ApoER2 as well as the activation of signaling pathway, including small Rho GTPases. Besides its presence in the central nervous system (CNS), Reelin is also secreted by Schwann cells (SCs), the glial cells of the peripheral nervous system (PNS).

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The neuronal Golgi apparatus (GA) localizes to the perinuclear region and dendrites as tubulo-vesicular structures designated Golgi outposts (GOPs). Current evidence suggests that GOPs shape dendrite morphology and serve as platforms for the local delivery of synaptic receptors. However, the mechanisms underlying GOP formation remain a mystery.

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