Calcium signaling is one of the most important signaling-pathways in all eukaryotes. One important target activated by an increased intracellular calcium concentration via calmodulin is the protein phosphatase calcineurin, which is composed of a catalytic subunit (calcineurin A) and a regulatory subunit (calcineurin B). The importance of calcium and calcineurin for the differentiation and development of the social amoeba Dictyostelium discoideum has already been shown by pharmacological approaches. However, so far only a RNAi-silenced calcineurin B mutant has been investigated on a molecular level. Here, we describe the construction and phenotypic investigation of a RNAi-silenced calcineurin A mutant. Phenotypic aberrations during development resemble those produced by silencing of calcineurin B with ectopic tip formation of the fruiting bodies. Additionally, we tested the response of the mutants under various stress conditions in liquid culture as well as during development. Both, calcineurin A and B RNAi-mutants, are hypersensitive during development towards cation stress. Besides its role in development, calcineurin is thus also involved in the stress response in D. discoideum. Further, our data imply that many functions of calcineurin are conserved among the eukaryotes.
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http://dx.doi.org/10.1002/jobm.201200574 | DOI Listing |
PLoS One
January 2025
Helsinki University Hospital, Abdominal Centre, Transplantation and Liver Surgery, and University of Helsinki, Helsinki, Finland.
Background: Patients with end-stage kidney disease often prefer home-based dialysis due to higher self-efficacy, which relates to improved medical treatment adherence. Kidney transplantation (KT) success depends on adhering to immunosuppressive medication post-transplant.
Objectives: To investigate whether adherence post-kidney transplantation (KT) and patients' attitudes toward immunosuppression were influenced by their prior dialysis type modality.
Curr Issues Mol Biol
December 2024
Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USA.
Tacrolimus and mycophenolate are important immunosuppressive agents used to prevent organ rejection in post-transplant patients. While highly effective, their use is associated with significant toxicity, requiring careful management. Tacrolimus, a calcineurin inhibitor, is linked to nephrotoxicity, neurotoxicity, metabolic disturbances such as diabetes mellitus and dyslipidemia, and cardiovascular complications such as hypertension and arrhythmias.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, United States.
Introduction: TNFα inhibitor (TNFi) immunogenicity in rheumatoid arthritis (RA) is a major obstacle to its therapeutic effectiveness. Although methotrexate (MTX) can mitigate TNFi immunogenicity, its adverse effects necessitate alternative strategies. Targeting nuclear factor of activated T cells (NFAT) transcription factors may protect against biologic immunogenicity.
View Article and Find Full Text PDFKidney Int
February 2025
Transplantation & Clinical Virology, Department of Biomedicine, University of Basel, Basel Switzerland. Electronic address:
BK polyomavirus remains a vexing issue in kidney transplantation. There are no antiviral drugs, and solely reducing immunosuppression is recommended for management. However, evidence from randomized controlled studies lacks defining clearance of BK polyomavirus-DNAemia and/or nephropathy as a primary outcome.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
National Institute of Biological Sciences, Beijing 102206, China.
Sleep need accumulates during waking and dissipates during sleep to maintain sleep homeostasis (process S). Besides the regulation of daily (baseline) sleep amount, homeostatic sleep regulation commonly refers to the universal phenomenon that sleep deprivation (SD) causes an increase of sleep need, hence, the amount and intensity of subsequent recovery sleep. The central regulators and signaling pathways that govern the baseline and homeostatic sleep regulations in mammals remain unclear.
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