Cryo-EM structure of the active, G-protein complexed, human CGRP receptor.

Calcitonin gene-related peptide (CGRP) is a widely expressed neuropeptide that has a major role in sensory neurotransmission. The CGRP receptor is a heterodimer of the calcitonin receptor-like receptor (CLR) class B G-protein-coupled receptor and a type 1 transmembrane domain protein, receptor activity-modifying protein 1 (RAMP1). Here we report the structure of the human CGRP receptor in complex with CGRP and the G-protein heterotrimer at 3.

The evaluation of anaemia in an older primary care population: retrospective population-based study.

Background: Anaemia is common in older people and the identification of potentially reversible haematinic deficiencies relies on appropriate investigation, often undertaken in primary care.

Aim: To determine the laboratory prevalence of anaemia, the types of anaemia observed, and the biochemical and haematological investigations undertaken to characterise any associated haematinic abnormality in older primary care patients.

Design & Setting: A retrospective primary care based study of patients aged >65 years undergoing a full blood count in Oxfordshire, UK between 1 January 2012 and 31 December 2013.

Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-thalassemia.

β-Thalassemia is one of the most common inherited anemias, with no effective cure for most patients. The pathophysiology reflects an imbalance between α- and β-globin chains with an excess of free α-globin chains causing ineffective erythropoiesis and hemolysis. When α-thalassemia is co-inherited with β-thalassemia, excess free α-globin chains are reduced significantly ameliorating the clinical severity.

The future of academic haematology.

Recent advances in the basic medical sciences, particularly cell biology and genomics, have great promise for the future development of all aspects of haematological practice. They will also impinge on the hitherto neglected fields of haematology, including haematology involving the care of the rapidly increasing number of elderly patients and the complex problems of haematological practice in the developing countries. To obtain the maximum benefit from these new developments it will be necessary to review the patterns of training of haematologists of the future at every level.

Glicentin-related pancreatic polypeptide inhibits glucose-stimulated insulin secretion from the isolated pancreas of adult male rats.

Peptides derived from the glucagon gene Gcg, for example, glucagon and glucagon-like peptide 1 (GLP-1), act as physiological regulators of fuel metabolism and are thus of major interest in the pathogenesis of diseases, such as type-2 diabetes and obesity, and their therapeutic management. Glicentin-related pancreatic polypeptide (GRPP) is a further, 30 amino acid Gcg-derived peptide identified in human, mouse, rat, and pig. However, the potential glucoregulatory function of this peptide is largely unknown.

Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment.

Gene expression during development and differentiation is regulated in a cell- and stage-specific manner by complex networks of intergenic and intragenic cis-regulatory elements whose numbers and representation in the genome far exceed those of structural genes. Using chromosome conformation capture, it is now possible to analyze in detail the interaction between enhancers, silencers, boundary elements and promoters at individual loci, but these techniques are not readily scalable. Here we present a high-throughput approach (Capture-C) to analyze cis interactions, interrogating hundreds of specific interactions at high resolution in a single experiment.

The worm has turned: unexpected similarities between the transcription of enhancers and promoters in the worm and mammalian genomes.

Our understanding of biological processes in humans is often based on examination of analogous processes in other organisms. The nematode worm Caenorhabditis elegans has been a particularly valuable model, leading to Nobel prize winning discoveries in development and genetics. Until recently, however, the worm has not been widely used as a model to study transcription due to the lack of a comprehensive catalogue of its RNA transcripts.

Identification of a pathway by which glucose regulates β-catenin signalling via the cAMP/protein kinase A pathway in β-cell models.

Pancreatic β-cells are highly responsive to changes in glucose, but the mechanisms involved are only partially understood. There is increasing evidence that the β-catenin signalling pathway plays an important role in regulating β-cell function, but the mechanisms regulating β-catenin signalling in these cells is not well understood. In the present study we show that β-catenin levels and downstream signalling are regulated by changes in glucose levels in INS-1E and β-TC6-F7 β-cell models.

MicroRNA expression in multiple myeloma is associated with genetic subtype, isotype and survival.

Background: MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including hematological malignancies. However, the role of microRNAs in the pathogenesis of multiple myeloma (MM) is only poorly understood. We therefore used microarray analysis to elucidate the complete miRNome (miRBase version 13.

Paediatric tuberculosis in a Pacific Islands community in New Zealand.

Objectives: To describe the demographic, clinical and management aspects of an outbreak of tuberculosis (TB) within a paediatric Pacific Island community in Auckland, New Zealand, in 2002-2003.

Methods: The index and source case are described along with details of the extensive contact tracing that was undertaken in this community.

Results: A total of 24 children were diagnosed with TB over an 11-month period.

Immunohistochemical detection of the calcitonin receptor-like receptor protein in the microvasculature of rat endothelium.

Calcitonin-gene-related peptide and adrenomedullin have similar and potent vascular effects, which appear to be mediated by the G protein-coupled calcitonin receptor-like (CRL) receptor. Using immunohistochemical and Western blot analyses, we have obtained novel evidence that CRL receptor is expressed in the rat vascular endothelium using an antibody to rat CRL receptor that we have raised and fully characterised. These results are an important basis for further studies aimed at determining the so far ill-defined functional significance of the extensive distribution of CRL receptor in the vascular endothelium.