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Circadian Rhythms

Akhtar et al 2002 Review: SCN exerts control through neural and endocrine mechanisms. Clock genes use autoregulatory feedback loops. Cell cycle genes and metabolic genes are commonly circadian.
Levi & Schibler 2007 Review: BMAL1, CLOCK and NPAS2 (positive limb) form heterodimers and activate genes of the -ve limb like Cryptochrome and Per. REV-ERBa also represses Bmal1 transcription, regulated by both +ve and -ve genes. Rhythm may be in phosphorylation not level.
Ramsey et al 2009 NAMPT generates NAD, with levels varying diurnally along with NAD+. Oscillations last 48hrs ex vivo. CLOCK and BMAL1 regulate NAMPT, NAD+ represses CLOCK and BMAL1 via SIRT1. CLOCK found bound to NAMPT promoters by chromatin immunoprecipitation (ChIP).
O'Neill & Reddy 2011 Peroxidoredoxins can be hyperoxidised by their substrate, levels of hyperoxidised peroxidoredoxins showed rhythmicity even after leaving the body. Levels were altered by temperature variations mimicking those in the body. Rhythmicity without a nucleus.
Reddy & O'Neill 2010 Review: Clocks control for temperature. Bmal1 is both a clock gene and a tumour suppressor owing to cell cycle control. Moore and Zucker discovered SCN rhythmicity separately in 1972. CV disease, stroke and cancers linked to shift work and dysregulation.
Balsalobre et al 1998 Used serum shock (feeding with a serum-rich medium) to synchronise and demonstrate the presence of clocks in cell culture lines (25yrs ex vivo). Serum shock is a mechanism by which SCN regulates.
Etchegaray et al 2003 Used chromatin immunoprecipitation. Pulled up acetylated histone H3 then used PCR to quantify the amount of circadian DNA bound. Circadian changes in histone acetylation observed. Southern blot shows acetylated histone interacts with clock gene DNA.
Hirayama et al 2007 Bmal1 acetylation by CLOCK facilitates Cry1 (cryptochrome) recruitment casing transcriptional repression. SDS PGAE used to measure Bmal1 acetylation. Mutatin Bmal1 acetylated residue preventd Cry regulation, mutating adjacent residue had no effect.
Filipski et al 2003 Tumour growth is accelerated by partial or complete SCN electrolytic destruction. Sham destruction had no effect, partial ablation far less effective due to compensation. Tumour weight was increased 2-3x
Matthews et al 1964 A given dose of halothane has a toxicity of 5% to 76% depending on when it is given, shows wide variability in survival rates.
Fischer-Perroudon & Jouvet 1974 Description of a man who went 4 months without sleep. Some hallucinations of family members and leg vasoconstriction, didnt report tiredness.
Cuesta et al 2012 Methamphetamine adds a 2nd component to circadian rhythm. In a mouse model of Huntingtons methamphetamine causes a total breakdown of routine (no 2nd component). Defect is present before other symptoms. Unable to show this component in humans, ethics.
Marcheva et al 2010 Luciferase tied to Per2 and pancreatic islets isolated, showed Beta cell rhythmicity in wt but not Clock mutants. Clock- (global) and Bmal1- (pancreas specific) mouse groups had reduced insulin and increased glucose (whole animal, not isolate)
Created by: Jonmassie



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