Histone modifications influence gene expression in complex ways. The RNA interference (RNAi) machinery can repress transcription by recruiting histone-modifying enzymes to chromatin, although it is not clear whether this is a general mechanism for gene silencing or whether it requires repeated sequences such as long terminal repeats (LTRs). We analyzed the global effects of the Clr3 and Clr6 hi...

The receptor for CGRP (calcitonin gene-related peptide) is a heterodimer between a GPCR (G-protein-coupled receptor), CLR (calcitonin receptor-like receptor) and an accessory protein, RAMP1 (receptor activity-modifying protein 1). Models have been produced of RAMP1 and CLR. It is likely that the C-terminus of CGRP interacts with the extracellular N-termini of CLR and RAMP1; the extreme N-termin...

Machine learning approaches offer the potential to systematically identify transcriptional regulatory interactions from a compendium of microarray expression profiles. However, experimental validation of the performance of these methods at the genome scale has remained elusive. Here we assess the global performance of four existing classes of inference algorithms using 445 Escherichia coli Affy...

Abstract Agonist bias occurs when different ligands produce distinct signalling outputs acting at the same receptor. However, its physiological relevance is not always clear. Using primary human cells and gene editing techniques, we demonstrate endogenous agonist with consequences for calcitonin receptor-like receptor, CLR. By switching receptor-activity modifying protein (RAMP) associated CLR ...

Background and Aims: Platelet-to-lymphocyte ratio (PLR) has been shown to predict prognosis of cancers. We aimed to evaluate the prognostic value of stratification of PLR in patients after curative liver resection (CLR) for hepatocellular carcinoma (HCC). Methods: A total of 1804 patients who underwent CLR for suspected HCC between January 2007 and January 2014 were screened for the study. All ...

Formation of centromeric heterochromatin in fission yeast requires the combined action of chromatin modifying enzymes and small RNAs derived from centromeric transcripts. Positive feedback mechanisms that link the RNAi pathway and the Clr4/Suv39h1 histone H3K9 methyltransferase complex (Clr-C) result in requirements for H3K9 methylation for full siRNA production and for siRNA production to achi...

Renal clearance (CLR), a major route of elimination for many drugs and drug metabolites, represents the net result of glomerular filtration, active secretion and reabsorption, and passive reabsorption. The aim of this study was to develop quantitative structurepharmacokinetic relationships (QSPKR) to predict CLR of drugs or drug-like compounds in humans. Human CLR data for 382 compounds were ob...

OBJECTIVE To test effectiveness of the Early Detection, Intervention, and Prevention of Psychosis Program in preventing the onset of severe psychosis and improving functioning in a national sample of at-risk youth. METHODS In a risk-based allocation study design, 337 youth (age 12-25) at risk of psychosis were assigned to treatment groups based on severity of positive symptoms. Those at clini...

Adrenomedullin (AM) and intermedin (IMD; adrenomedulln-2) are vasodilator peptides related to calcitonin gene-related peptide (CGRP). The actions of these peptides are mediated by the calcitonin receptor-like receptor (CLR) in association with one of three receptor activity-modifying proteins. CGRP is selective for CLR/receptor activity modifying protein (RAMP)1, AM for CLR/RAMP2 and -3, and IM...

Otitis media (OM) is a group of inflammatory diseases of the middle ear (ME), regardless of cause or pathological mechanism. Among the molecular biological studies assessing the pathology of OM are investigations into the expression of C-type lectin receptors (CLR) in the ME and Eustachian tube (ET). To date, nine studies have evaluated CLR expression in the ME and ET. The expression of individ...