158 research outputs found
Solidalitätszuschlag –bezieht auf Wiederaufbauseinkommensteuer und Wideraufbaukörpersteuer in Japan-
CNOT1 regulates circadian behaviour through Per2 mRNA decay in a deadenylation-dependent manner
Circadian clocks are an endogenous internal timekeeping mechanism that drives the rhythmic expression of genes, controlling the 24 h oscillatory pattern in behaviour and physiology. It has been recently shown that post-transcriptional mechanisms are essential for controlling rhythmic gene expression. Controlling the stability of mRNA through poly(A) tail length modulation is one such mechanism. In this study, we show that Cnot1, encoding the scaffold protein of the CCR4-NOT deadenylase complex, is highly expressed in the suprachiasmatic nucleus, the master timekeeper. CNOT1 deficiency in mice results in circadian period lengthening and alterations in the mRNA and protein expression patterns of various clock genes, mainly Per2. Per2 mRNA exhibited a longer poly(A) tail and increased mRNA stability in Cnot1+/− mice. CNOT1 is recruited to Per2 mRNA through BRF1 (ZFP36L1), which itself oscillates in antiphase with Per2 mRNA. Upon Brf1 knockdown, Per2 mRNA is stabilized leading to increased PER2 expression levels. This suggests that CNOT1 plays a role in tuning and regulating the mammalian circadian clock.journal articl
Improvement of Fractional Flow Reserve after Percutaneous Coronary Intervention Does Not Necessarily Indicate Increased Coronary Flow
Coronary flow is expected to increase by epicardial lesion modification after successful percutaneous coronary intervention (PCI) in stable angina. According to the concept of fractional flow reserve (FFR), the improvement in FFR after PCI reflects the extent of coronary flow increase. However, this theory assumes that hyperaemic microvascular resistance does not change after PCI, which is being refuted in recent studies. The authors quantitated regional absolute coronary blood flow (ABF) before and after PCI using a thermodilution method and compared it with FFR in 28 patients with stable coronary artery disease who had undergone successful PCI. Although FFR indicated changes in ABF, with a mean difference of −5.5 ml/min, there was no significant relationship between individual changes in FFR and in ABF (R=0.27, p=0.16). The discrepancy was partly explained by changes in microvascular resistance following PCI. These results suggest that changes in FFR do not necessarily indicate an increase in absolute coronary blood flow following PCI in individual patients, although they could be correlated in a cohort level
- …