Publications by authors named "Agustin Corbat"

Notch signaling patterns the cochlear organ of Corti, and individuals with the JAG1/NOTCH2-related genetic disorder Alagille syndrome can thus experience hearing loss. We investigated the function of Jag1 in cochlear patterning and signaling using Jag1Ndr/Ndr mice, which are a model of Alagille syndrome. Jag1Ndr/Ndr mice exhibited expected vestibular and auditory deficits, a dose-dependent increase in ectopic inner hair cells, and a reduction in outer hair cells.

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Background & Aims: Alagille syndrome (ALGS) manifests with peripheral intrahepatic bile duct (IHBD) paucity, which can spontaneously resolve. In a model for ALGS, Jag1 mice, this occurs with distinct architectural mechanisms in hilar and peripheral IHBDs. Here, we investigated region-specific IHBD characteristics and addressed whether IGF1, a cholangiocyte mitogen that is downregulated in ALGS and in Jag1 mice, can improve biliary outcomes.

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Article Synopsis
  • Viral factories, which have a liquid-like nature, are essential for the transcription and replication processes in most viruses, including the respiratory syncytial virus (RSV).
  • The interaction between the phosphoprotein (P) and nucleoprotein (N) is crucial, as it regulates the formation and dissolution of these viral factories through a phase separation process.
  • This phase separation of P is typically kept in check by its structure but is activated when partnered with N or when certain sequences are removed, highlighting P's role as a "solvent-protein" in the organization of viral components.
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Smaug is a conserved translational regulator that binds numerous mRNAs, including nuclear transcripts that encode mitochondrial enzymes. Smaug orthologs form cytosolic membrane-less organelles (MLOs) in several organisms and cell types. We have performed single-molecule fluorescence in situ hybridization (FISH) assays that revealed that SDHB and UQCRC1 mRNAs associate with Smaug1 bodies in U2OS cells.

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Understanding signal propagation across biological networks requires to simultaneously monitor the dynamics of several nodes to uncover correlations masked by inherent intercellular variability. To monitor the enzymatic activity of more than two components over short time scales has proven challenging. Exploiting the narrow spectral width of homo-FRET-based biosensors, up to three activities can be imaged through fluorescence polarization anisotropy microscopy.

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Article Synopsis
  • In order to effectively study biological networks, it's crucial to measure multiple biological signals in single living cells due to variations between cells.
  • Researchers developed three unique FRET biosensors that can separately track different protein interactions to overcome the challenges of measuring more than two signals simultaneously.
  • By applying these biosensors to monitor caspase activity during apoptosis, the study demonstrates how their signals can be used to refine models of biological signaling networks and improve our understanding of how signals propagate within cells.
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