Dataset Information

Proteasome function is required for biological timing throughout the twenty-four hour cycle.

ABSTRACT: Circadian clocks were, until recently, seen as a consequence of rhythmic transcription of clock components, directed by transcriptional/translational feedback loops (TTFLs). Oscillations of protein modification were then discovered in cyanobacteria. Canonical posttranslational signaling processes have known importance for clocks across taxa. More recently, evidence from the unicellular eukaryote Ostreococcus tauri revealed a transcription-independent, rhythmic protein modification shared in anucleate human cells. In this study, the Ostreococcus system reveals a central role for targeted protein degradation in the mechanism of circadian timing. The Ostreococcus clockwork contains a TTFL involving the morning-expressed CCA1 and evening-expressed TOC1 proteins. Cellular CCA1 and TOC1 protein content and degradation rates are analyzed qualitatively and quantitatively using luciferase reporter fusion proteins. CCA1 protein degradation rates, measured in high time resolution, feature a sharp clock-regulated peak under constant conditions. TOC1 degradation peaks in response to darkness. Targeted protein degradation, unlike transcription and translation, is shown to be essential to sustain TTFL rhythmicity throughout the circadian cycle. Although proteasomal degradation is not necessary for sustained posttranslational oscillations in transcriptionally inactive cells, TTFL and posttranslational oscillators are normally coupled, and proteasome function is crucial to sustain both.

SUBMITTER: van Ooijen G

PROVIDER: S-EPMC3102177 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proteasome function is required for biological timing throughout the twenty-four hour cycle.

van Ooijen Gerben G Dixon Laura E LE Troein Carl C Millar Andrew J AJ

Current biology : CB 20110428 10

Circadian clocks were, until recently, seen as a consequence of rhythmic transcription of clock components, directed by transcriptional/translational feedback loops (TTFLs). Oscillations of protein modification were then discovered in cyanobacteria. Canonical posttranslational signaling processes have known importance for clocks across taxa. More recently, evidence from the unicellular eukaryote Ostreococcus tauri revealed a transcription-independent, rhythmic protein modification shared in anuc ...[more]

PMID: 21530263

Similar Datasets

Project description:BackgroundPatients with apical hypertrophic cardiomyopathy (ApHCM) have marked inverted T-waves that vary over several years. Inverted T-waves in ApHCM are unstable, but it is unclear whether this change is due to coronary artery disease (CAD) or if it is a characteristic of ApHCM itself. We aimed to study the characteristics of inverted T-waves in patients with ApHCM over the course of 24 h to improve the diagnostic indices of ApHCM.MethodsWe examined 83 patients with ApHCM and 89 patients with CAD (who served as the control group). All patients underwent a 24-h dynamic electrocardiogram (ECG). We analyzed the average depth of inverted T-waves per minute and sorted them from shallow to deep; the sorted ECG segments at the 10th, 50th, and 90th positions of the T-wave were subsequently analyzed.ResultsThe amplitudes of inverted T-waves in ApHCM corresponding to the 10th, 50th, and 90th percentiles were -5.13 ± 4.11, -8.10 ± 4.55, and -10.9 ± 5.04 mm, respectively. Changes in the degree of inverted T-waves were greater in ApHCM than in CAD. T-wave amplitudes in ApHCM were strongly associated with heart rate and circadian rhythm and only weakly associated with CAD and posture. Maximum T-wave amplitudes in the CAD group were <10 mm, while 68% of patients with ApHCM had maximum T-wave amplitudes >10 mm, and all patients with ApHCM aged <50 years had maximum T-wave amplitudes >10 mm.ConclusionNotable variations in the T-waves of patients with ApHCM were observed over 24 h. ECG examinations during states of inactivity (comparable to sleep) improved the sensitivity of the diagnosis of ApHCM. Inverted T-wave amplitudes correlated with heart rate and circadian rhythm, where T-wave changes in ApHCM may be due to the normalization of abnormal T-waves effect. Identifying T-wave amplitudes >10 mm can effectively improve the diagnostic rate of ApHCM, especially in patients aged <50 years. The short-term change in T-waves in patients with ApHCM could serve as a novel index that will help in the diagnosis of ApHCM.

Project description:Background and objectivesCurrent guidelines recommend 24-hour urine testing in the evaluation and treatment of persons with high-risk urinary stone disease. However, how much clinicians use information from 24-hour urine testing to guide secondary prevention strategies is unknown. We sought to determine the degree to which clinicians initiate or continue stone disease-related medications in response to 24-hour urine testing.Design, setting, participants, & measurementsWe examined a national cohort of 130,489 patients with incident urinary stone disease in the Veterans Health Administration between 2007 and 2013 to determine whether prescription patterns for thiazide diuretics, alkali therapy, and allopurinol changed in response to 24-hour urine testing.ResultsStone formers who completed 24-hour urine testing (n=17,303; 13%) were significantly more likely to be prescribed thiazide diuretics, alkali therapy, and allopurinol compared with those who did not complete a 24-hour urine test (n=113,186; 87%). Prescription of thiazide diuretics increased in patients with hypercalciuria (9% absolute increase if urine calcium 201-400 mg/d; 21% absolute increase if urine calcium >400 mg/d, P<0.001). Prescription of alkali therapy increased in patients with hypocitraturia (24% absolute increase if urine citrate 201-400 mg/d; 34% absolute increase if urine citrate ≤200 mg/d, P<0.001). Prescription of allopurinol increased in patients with hyperuricosuria (18% absolute increase if urine uric acid >800 mg/d, P<0.001). Patients who had visited both a urologist and a nephrologist within 6 months of 24-hour urine testing were more likely to have been prescribed stone-related medications than patients who visited one, the other, or neither.ConclusionsClinicians adjust their treatment regimens in response to 24-hour urine testing by increasing the prescription of medications thought to reduce risk for urinary stone disease. Most patients who might benefit from targeted medications remain untreated.

Dataset Information

Proteasome function is required for biological timing throughout the twenty-four hour cycle.

Publications

Proteasome function is required for biological timing throughout the twenty-four hour cycle.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets