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      Neuroendocrine Coupling of Interoceptive Bacteria-Derived Cues to Foraging Behavior in C. elegans

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      1 , 2 , 2 , 3 , 1 , *
      bioRxiv
      Cold Spring Harbor Laboratory

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          Summary

          Animal internal state is modulated by nutrient intake, resulting in behavioral responses to changing food conditions. DAF-7 is a neuroendocrine TGF-beta ligand that regulates diverse food-related behaviors of Caenorhabditis elegans, including foraging behavior. Here, we show that in C. elegans, interoceptive cues from the ingestion of bacterial food inhibit the expression of DAF-7, a neuroendocrine TGF-beta ligand, from the ASJ pair of sensory neurons, whereas food deprivation in the presence of external chemosensory cues from bacteria promotes the expression of DAF-7 from the ASJ neurons. We show that SCD-2, the C. elegans ortholog of mammalian Anaplastic Lymphoma Kinase (ALK), which has been implicated in the central control of metabolism of mammals, functions in the AIA interneurons to regulate foraging behavior and cell-non-autonomously control the expression of DAF-7 from the ASJ neurons. Our data establish an SCD-2-dependent neuroendocrine DAF-7 gene expression feedback loop that couples the ingestion of bacterial food to foraging behavior.

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          THE GENETICS OF CAENORHABDITIS ELEGANS

          Methods are described for the isolation, complementation and mapping of mutants of Caenorhabditis elegans, a small free-living nematode worm. About 300 EMS-induced mutants affecting behavior and morphology have been characterized and about one hundred genes have been defined. Mutations in 77 of these alter the movement of the animal. Estimates of the induced mutation frequency of both the visible mutants and X chromosome lethals suggests that, just as in Drosophila, the genetic units in C.elegans are large.
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            The Structure of the Nervous System of the Nematode Caenorhabditis elegans

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              Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.

              The 2;5 chromosomal translocation occurs in most anaplastic large-cell non-Hodgkin's lymphomas arising from activated T lymphocytes. This rearrangement was shown to fuse the NPM nucleolar phosphoprotein gene on chromosome 5q35 to a previously unidentified protein tyrosine kinase gene, ALK, on chromosome 2p23. In the predicted hybrid protein, the amino terminus of nucleophosmin (NPM) is linked to the catalytic domain of anaplastic lymphoma kinase (ALK). Expressed in the small intestine, testis, and brain but not in normal lymphoid cells, ALK shows greatest sequence similarity to the insulin receptor subfamily of kinases. Unscheduled expression of the truncated ALK may contribute to malignant transformation in these lymphomas.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: ValidationRole: InvestigationRole: VisualizationRole: MethodologyRole: Writing — original draftRole: Writing — review & editing
                Role: InvestigationRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: SupervisionRole: Funding acquisitionRole: VisualizationRole: MethodologyRole: Writing — original draftRole: Writing — review & editing
                Journal
                bioRxiv
                BIORXIV
                bioRxiv
                Cold Spring Harbor Laboratory
                15 July 2023
                : 2023.07.15.549072
                Affiliations
                [1. ]Division of Infectious Diseases, Department of Pediatrics, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115
                [2. ]Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139
                [3. ]Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114
                Author notes
                Article
                10.1101/2023.07.15.549072
                10369937
                37503081
                78339fa1-851b-4bf5-8dd1-16348086cff2

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.

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