You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: ["HealthCareActivity", "InjuryOrPoisoning", "BodySubstance", "IntellectualProduct", "AnatomicalStructure", "SpatialConcept", "Chemical", "Bacterium", "MedicalDevice", "Organization", "BiomedicalOccupationOrDiscipline", "Finding", "BiologicFunction", "Virus", "ResearchActivity", "ClinicalAttribute", "PopulationGroup", "Eukaryote", "BodySystem", "Food", "ProfessionalOrOccupationalGroup"].

Please return the output as a JSON object of the format: {"Virus": ["HIV", ...], "Bacterium": ["MRSA", ...], "AnatomicalStructure": ["Lung", ...], "BodySystem": ["CNS", ...], "BodySubstance": ["Serum", ...], "Finding": ["Headache", ...], "InjuryOrPoisoning": ["Fracture", ...], "BiologicFunction": ["Death", ...], "HealthCareActivity": ["Biopsy", ...], "ResearchActivity": ["Clinical trial", ...], "MedicalDevice": ["Lenses", ...], "SpatialConcept": ["Camps", ...], "BiomedicalOccupationOrDiscipline": ["Forensic medicine", ...], "Organization": ["WHO", ...], "ProfessionalOrOccupationalGroup": ["Provider", ...], "PopulationGroup": ["Swimmers", ...], "Chemical": ["Gold", ...], "Food": ["Rice", ...], "IntellectualProduct": ["RPAM", ...], "ClinicalAttribute": ["Biomarker", ...], "Eukaryote": ["Dogs", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].

Only output the JSON object and do not include any additional text.

Abstract:

Basal ryanodine receptor activity suppresses autophagic flux The inositol 1,4,5-trisphosphate receptors (IP3Rs) and intracellular Ca(2+) signaling are critically involved in regulating different steps of autophagy, a lysosomal degradation pathway. The ryanodine receptors (RyR), intracellular Ca(2+)-release channels mainly expressed in excitable cell types including muscle and neurons, have however not yet been extensively studied in relation to autophagy. Yet, aberrant expression and excessive activity of RyRs in these tissues has been implicated in the onset of several diseases including Alzheimer's disease, where impaired autophagy regulation contributes to the pathology. In this study, we determined whether pharmacological RyR inhibition could modulate autophagic flux in ectopic RyR - expressing models, like HEK293 cells and in cell types that endogenously express RyR s, like C2C12 myoblasts and primary hippocampal neurons. Importantly, RyR3 overexpression in HEK293 cells impaired the autophagic flux. Conversely, in all cell models tested, pharmacological inhibition of endogenous or ectopically expressed RyRs, using dantrolene or ryanodine, augmented autophagic flux by increasing lysosomal turn-over (number of autophagosomes and autolysosomes measured as mCherry - LC3 punctae / cell increased from 70.37±7.81 in control HEK RyR3 cells to 111.18±7.72 and 98.14±7.31 after dantrolene and ryanodine treatments, respectively). Moreover, in differentiated C2C12 cells, transmission electron microscopy demonstrated that dantrolene treatment decreased the number of early autophagic vacuoles from 5.9±2.97 to 1.8±1.03 per cellular cross section. The modulation of the autophagic flux could be linked to the functional inhibition of RyR channels as both RyR inhibitors efficiently diminished the number of cells showing spontaneous RyR3 activity in the HEK293 cell model (from 41.14%±2.12 in control cells to 18.70%±2.25 and 9.74%±2.67 after dantrolene and ryanodine treatments, respectively). In conclusion, basal RyR -mediated Ca(2+)-release events suppress autophagic flux at the level of the lysosomes.
{"AnatomicalStructure": ["HEK293 cells", "autophagosomes", "tissues", "C2C12 myoblasts", "cell", "HEK RyR3 cells", "C2C12 cells", "HEK293 cell", "cells", "lysosomal", "lysosomes", "hippocampal", "vacuoles", "autolysosomes", "cellular", "neurons", "autophagic", "muscle"], "Bacterium": [], "BiologicFunction": ["Alzheimer\u0027s disease", "expressed", "express", "autophagy", "turn-over", "Ca(2+)-release events", "expressing", "ryanodine receptor activity", "expression", "regulation", "intracellular Ca(2+) signaling", "overexpression", "differentiated", "diseases", "regulating", "pharmacological", "intracellular Ca(2+)-release channels"], "BiomedicalOccupationOrDiscipline": [], "BodySubstance": [], "BodySystem": [], "Chemical": ["IP3Rs", "inhibitors", "inositol 1,4,5-trisphosphate receptors", "mCherry", "dantrolene", "ryanodine", "LC3 punctae", "RyRs", "RyR channels", "ryanodine receptors", "RyR", "RyR3"], "ClinicalAttribute": [], "Eukaryote": [], "Finding": ["excitable"], "Food": [], "HealthCareActivity": ["determined", "transmission electron microscopy", "treatments", "treatment"], "InjuryOrPoisoning": [], "IntellectualProduct": ["models", "cell types", "model"], "MedicalDevice": [], "Organization": [], "PopulationGroup": [], "ProfessionalOrOccupationalGroup": [], "ResearchActivity": ["studied", "study"], "SpatialConcept": ["cross section", "ectopically", "basal", "Basal", "ectopic", "modulate"], "Virus": []}