Allosteric modulation of beta1 integrin function induces lung repair in animal model of emphysema.

Emphysema is a progressive lung disease characterised by loss of lung parenchyma with associated functional changes including decreased tissue elastance. Here we report beta1 integrin is a novel target for tissue repair and regeneration in emphysema. We show a single dose of a monoclonal antibody against beta1 integrin induced both functional and structural reversal of elastase-induced lung injury in vivo, and we found that similar matrix remodelling changes occurred in human lung tissue. We also identified a potential mechanism of action as this allosteric modulation of beta1 integrin inhibited elastase-induced caspase activation, F-actin aggregate formation and changes in cellular ATP levels. This was accompanied by maintenance of beta1?integrin levels and inhibition of caveolin-1 phosphorylation. We propose that allosteric modulation of beta1 integrin-mediated mechanosensing prevents cell death associated with lung injury and progressive emphysema, thus allowing cells to survive and for repair and regeneration to ensue

eMouseAtlas, EMAGE, and the spatial dimension of the transcriptome

Abstract eMouseAtlas (www.emouseatlas.org) is a com-prehensive online resource to visualise mouse development and investigate gene expression in the mouse embryo. We have recently deployed a completely redesigned Mouse Anatomy Atlas website (www.emouseatlas.org/emap/ema) that allows users to view 3D embryo reconstructions, delineated anatomy, and high-resolution histological sec-tions. A new feature of the website is the IIP3D web tool that allows a user to view arbitrary sections of 3D embryo reconstructions using a web browser. This feature provides interactive access to very high-volume 3D images via a tiled pan-and-zoom style interface and circumvents the need to download large image files for visualisation. eMouseAtla

Integrated analysis of Wnt signalling system component gene expression

Wnt signalling controls patterning and differentiation across many tissues and organs of the developing embryo through temporally and spatially restricted expression of multi-gene families encoding ligands, receptors, pathway modulators and intracellular components. Here, we report an integrated analysis of key genes in the 3D space of the mouse embryo across multiple stages of development. We applied a method for 3D/3D image transformation to map all gene expression patterns to a single reference embryo for each stage, providing both visual analysis and volumetric mapping allowing computational methods to interrogate the combined expression patterns. We identify territories where multiple Wnt and Fzd genes are co-expressed and cross-compare all patterns, including all seven Wnt paralogous gene pairs. The comprehensive analysis revealed regions in the embryo where no Wnt or Fzd gene expression is detected, and where single Wnt genes are uniquely expressed. This work provides insight into a previously unappreciated level of organisation of expression patterns, as well as presenting a resource that can be utilised further by the research community for whole-system analysis

The ‘straight mouse’: defining anatomical axes in 3D embryo models

A primary objective of the eMouseAtlas Project is to enable 3D spatial mapping of whole embryo gene expression data to capture complex 3D patterns for indexing, visualization, cross-comparison and analysis. For this we have developed a spatio-temporal framework based on 3D models of embryos at different stages of development coupled with an anatomical ontology. Here we introduce a method of defining coordinate axes that correspond to the anatomical or biologically relevant anterior–posterior (A–P), dorsal–ventral (D–V) and left–right (L–R) directions. These enable more sophisticated query and analysis of the data with biologically relevant associations, and provide novel data visualizations that can reveal patterns that are otherwise difficult to detect in the standard 3D coordinate space. These anatomical coordinates are defined using the concept of a ‘straight mouse-embryo’ within which the anatomical coordinates are Cartesian. The straight embryo model has been mapped via a complex non-linear transform onto the standard embryo model. We explore the utility of this anatomical coordinate system in elucidating the spatial relationship of spatially mapped embryonic ‘Fibroblast growth factor’ gene expression patterns, and we discuss the importance of this technology in summarizing complex multimodal mouse embryo image data from gene expression and anatomy studies

Developing the eHistology Atlas

The eMouseAtlas project has undertaken to generate a new resource providing access to high-resolution colour images of the slides used in the renowned textbook ‘The Atlas of Mouse Development’ by Matthew H. Kaufman. The original histology slides were digitized, and the associated anatomy annotations captured for display in the new resource. These annotations were assigned to objects in the standard reference anatomy ontology, allowing the eHistology resource to be linked to other data resources including the Edinburgh Mouse Atlas Gene-Expression database (EMAGE) an the Mouse Genome Informatics (MGI) gene-expression database (GXD). The provision of the eHistology Atlas resource was assisted greatly by the expertise of the eMouseAtlas project in delivering large image datasets within a web environment, using IIP3D technology. This technology also permits future extensions to the resource through the addition of further layers of data and annotations to the resource. Database URL: www.emouseatlas.org/emap/eHistology/index.ph

GUDMAP - An Online GenitoUrinary Resource

The GenitoUrinary Development Molecular Anatomy Project (GUDMAP) is a consortium of laboratories working to provide the scientific and medical community with gene expression data and tools to facilitate research (see "www.gudmap.org":http://www.gudmap.org). The data provided by GUDMAP includes large _in situ_ hybridization screens (wholemount and section) and expression microarray analysis of components of the developing mouse urogenital system (including laser-captured material and FACS-isolated cells from transgenic reporter mice). In addition, a high-resolution anatomy ontology has been developed by members of the GUDMAP consortium to describe the subcompartments of the developing murine genitourinary tract. 

The GUDMAP Database Development Team and Editorial Office - both based in Edinburgh - function to ensure submission, curation, storage and presentation of the data submitted by the GUDMAP consortium. Our collective aim is twofold: 1) to simplify the process of submission so that data is publically available as soon as it is produced; and 2) to organize this information in a database and ensure that the online interface is continuously available and easy to use. Thus far, we have developed a range of tools that help both the submitter and the end user. These include: an online annotation tool that simplifies _in situ_ data submission through an ontology-based graphical user interface; a database interface that allows users to browse and query expression data, and to filter data by organ system; a heat-map display of microarray data and analyses. Furthermore, the Edinburgh team has developed a GUDMAP Disease Database that queries associations between genes, genitourinary diseases, and renal/urinary and reproductive phenotypes. In collaboration with GUDMAP consortium members at the CCHMC (Cincinnati Children's Hospital Medical Center), the Disease Database is being extended to include mammalian phenotypes mapped to OMIM entries. 

By virtue of its impressive dataset and its ease of use we hope that the GUDMAP Website will continue to serve as a powerful resource for biologists, clinicians and bioinformaticians with an interest in the urogenital system

Geophysical investigation of the neolithic Calanais landscape

YesThe northern and western isles of Scotland have proved fertile ground for archaeological investigation over the last 100 years. However, the nature of the landscape with its rugged coastlines and irregular topography, together with rapid peat growth rates, make for challenging surveying. Commonly, an archaeological monument or series of monuments is identified but little is known about the surrounding areas and, in particular, the palaeo-landscapes within which the monuments are located. This situation is exemplified by the standing stones of Calanais in Lewis. Here, surrounding peat bogs have buried a significant portion of the landscape around which the stones were first erected. This project identifies remote sensing geophysical techniques that are effective in mapping the buried (lost) landscape and thus aid better contextualisation of the stone monuments within it. Further, the project demonstrates the most appropriate techniques for prospecting across these buried landscapes for as yet unidentified stone features associated with the lives of the people who constructed the monuments.Scottish EnterpriseResearch Development Fund Publication Prize Award winner, December 2019

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries