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:

Potassium depletion stimulates Na-Cl cotransporter via phosphorylation and inactivation of the ubiquitin ligase Kelch-like 3 Kelch-like 3 (KLHL3) is a component of an E3 ubiquitin ligase complex that regulates blood pressure by targeting With-No-Lysine (WNK) kinases for degradation. Mutations in KLHL3 cause constitutively increased renal salt reabsorption and impaired K(+) secretion, resulting in hypertension and hyperkalemia. Although clinical studies have shown that dietary K(+) intake affects blood pressure, the mechanisms have been obscure. In this study, we demonstrate that the KLHL3 ubiquitin ligase complex is involved in the low- K(+) -mediated activation of Na-Cl cotransporter (NCC) in the kidney. In the distal convoluted tubules of mice eating a low-K(+) diet, we found increased KLHL3 phosphorylation at S433 (KLHL3(S433-P)), a modification that impairs WNK binding, and also reduced total KLHL3 levels. These changes are accompanied by the accumulation of the target substrate WNK4, and activation of the downstream kinases SPAK (STE20 / SPS1 -related proline-alanine-rich protein kinase) and OSR1 (oxidative stress-responsive 1), resulting in NCC phosphorylation and its accumulation at the plasma membrane. Increased phosphorylation of S433 was explained by increased levels of active, phosphorylated protein kinase C (but not protein kinase A), which directly phosphorylates S433. Moreover, in HEK cells expressing KLHL3 and WNK4, we showed that the activation of protein kinase C by phorbol 12-myristate 13-acetate induces KLHL3(S433-P) and increases WNK4 levels by abrogating its ubiquitination. These data demonstrate the role of KLHL3 in low- K(+) -mediated induction of NCC; this physiologic adaptation reduces distal electrogenic Na(+) reabsorption, preventing further renal K(+) loss but promoting increased blood pressure.
{"AnatomicalStructure": ["distal convoluted tubules", "renal", "plasma membrane", "HEK cells", "kidney"], "Bacterium": [], "BiologicFunction": ["Na(+) reabsorption", "blood pressure", "phosphorylates", "physiologic adaptation", "eating", "ubiquitination", "regulates", "secretion", "expressing", "phosphorylation", "hypertension", "Potassium depletion", "Mutations", "electrogenic"], "BiomedicalOccupationOrDiscipline": [], "BodySubstance": [], "BodySystem": [], "Chemical": ["SPS1", "STE20", "WNK", "ubiquitin ligase", "Kelch-like 3", "K(+)", "phorbol 12-myristate 13-acetate", "protein kinase C", "(KLHL3(S433-P))", "complex", "protein kinase A", "KLHL3(S433-P)", "OSR1", "NCC", "E3 ubiquitin ligase complex", "With-No-Lysine (WNK) kinases", "component", "proline-alanine-rich protein kinase", "kinases SPAK", "Na-Cl cotransporter", "WNK4", "oxidative stress-responsive 1", "KLHL3"], "ClinicalAttribute": [], "Eukaryote": ["mice"], "Finding": ["accumulation", "increased renal salt reabsorption", "modification", "hyperkalemia"], "Food": ["dietary K(+)"], "HealthCareActivity": ["low-K(+) diet"], "InjuryOrPoisoning": [], "IntellectualProduct": [], "MedicalDevice": [], "Organization": [], "PopulationGroup": [], "ProfessionalOrOccupationalGroup": [], "ResearchActivity": ["clinical studies"], "SpatialConcept": ["distal", "downstream"], "Virus": []}