Autoimmunity to HSP60 during diet induced obesity in mice

Adaptive immunity has been implicated in adipose tissue inflammation, obesity and its adverse metabolic consequences. No obesity-related autoantigen has yet been identified, although heat shock protein 60 (HSP60) has been implicated in other autoimmune diseases. We investigated whether feeding a high-fat diet to C57BL/6J mice would cause autoimmunity to HSP60 and whether immunomodulation with peptides from HSP60 would reverse the resulting obesity or metabolic dysfunction. Obese mice had higher circulating levels of HSP60 associated with increased T-lymphocyte proliferation responses and the emergence of circulating IgG1 and IgG2c antibody levels against HSP60. Treatment with escalating doses of a mixture of three proven immunomodulatory HSP60 peptides did not reduce weight but completely reversed the increase in VLDL/LDL levels and partially reversed the glucose intolerance in obese mice. Obese mice mount an autoimmune response to HSP60, which partly underlies the resulting metabolic disturbances

Shaping Skeletal Growth by Modular Regulatory Elements in the Bmp5 Gene

Cartilage and bone are formed into a remarkable range of shapes and sizes that underlie many anatomical adaptations to different lifestyles in vertebrates. Although the morphological blueprints for individual cartilage and bony structures must somehow be encoded in the genome, we currently know little about the detailed genomic mechanisms that direct precise growth patterns for particular bones. We have carried out large-scale enhancer surveys to identify the regulatory architecture controlling developmental expression of the mouse Bmp5 gene, which encodes a secreted signaling molecule required for normal morphology of specific skeletal features. Although Bmp5 is expressed in many skeletal precursors, different enhancers control expression in individual bones. Remarkably, we show here that different enhancers also exist for highly restricted spatial subdomains along the surface of individual skeletal structures, including ribs and nasal cartilages. Transgenic, null, and regulatory mutations confirm that these anatomy-specific sequences are sufficient to trigger local changes in skeletal morphology and are required for establishing normal growth rates on separate bone surfaces. Our findings suggest that individual bones are composite structures whose detailed growth patterns are built from many smaller lineage and gene expression domains. Individual enhancers in BMP genes provide a genomic mechanism for controlling precise growth domains in particular cartilages and bones, making it possible to separately regulate skeletal anatomy at highly specific locations in the body

The 2010 Hans Cloos lecture : the contribution of urban geology to the development, regeneration and conservation of cities

Urban geology began to develop in the 1950s, particularly in California in relation to land-use planning, and led to Robert Legget publishing his seminal book “Cities and geology” in 1973. Urban geology has now become an important part of engineering geology. Research and practice has seen the evolution from single theme spatial datasets to multi-theme and multi-dimensional outputs for a wide range of users. In parallel to the development of these new outputs to aid urban development, regeneration and conservation, has been the growing recognition that city authorities need access to extensive databases of geo-information that are maintained in the long-term and renewed regularly. A further key advance has been the recognition that, in the urban environment, knowledge and understanding of the geology need to be integrated with those of other environmental topics (for example, biodiversity) and, increasingly, with the research of social scientists, economists and others. Despite these advances, it is suggested that the value of urban geology is not fully recognised by those charged with the management and improvement of the world’s cities. This may be because engineering geologists have failed to adequately demonstrate the benefits of urban geological applications in terms of cost and environmental improvement, have not communicated these benefits well enough and have not clearly shown the long-term contribution of geo-information to urban sustainability. Within this context future actions to improve the situation are proposed

Sedimentary recycling in arc magmas: geochemical and U–Pb–Hf–O constraints on the Mesoproterozoic Suldal Arc, SW Norway

The Hardangervidda-Rogaland Block within southwest Norway is host to ~1.52 to 1.48 Ga continental building and variable reworking during the ~1.1 to 0.9 Ga Sveconorwegian orogeny. Due to the lack of geochronological and geochemical data, the timing and tectonic setting of early Mesoproterozoic magmatism has long been ambiguous. This paper presents zircon U–Pb–Hf–O isotope data combined with whole-rock geochemistry to address the age and petrogenesis of basement units within the Suldal region, located in the centre of the Hardangervidda-Rogaland Block. The basement comprises variably deformed grey gneisses and granitoids that petrologically and geochemically resemble mature volcanic arc lithologies. U–Pb ages confirm that magmatism occurred from ~1,521 to 1,485 Ma, and conspicuously lack any xenocrystic inheritance of distinctly older crust. Hafnium isotope data range from εHf(initial) +1 to +11, suggesting a rather juvenile magmatic source, but with possible involvement of late Palaeoproterozoic crust. Oxygen isotope data range from mantle-like (δ18O ~5 ‰) to elevated (~10 ‰) suggesting involvement of low-temperature altered material (e.g., supracrustal rocks) in the magma source. The Hf–O isotope array is compatible with mixing between mantle-derived material with young low-temperature altered material (oceanic crust/sediments) and older low-temperature altered material (continent-derived sediments). This, combined with a lack of xenoliths and xenocrysts, exposed older crust, AFC trends and S-type geochemistry, all point to mixing within a deep-crustal magma-generation zone. A proposed model comprises accretion of altered oceanic crust and the overlying sediments to a pre-existing continental margin, underthrusting to the magma-generation zone and remobilisation during arc magmatism. The geodynamic setting for this arc magmatism is comparable with that seen in the Phanerozoic (e.g., the Sierra Nevada and Coast Range batholiths), with compositions in the Suldal Sector reaching those of average upper continental crust. As within these younger examples, factors that drive magmatism towards the composition of the average continental crust include the addition of sedimentary material to magma source regions, and delamination of cumulate material. Underthrusting of sedimentary materials and their subsequent involvement in arc magmatism is perhaps a more widespread mechanism involved in continental growth than is currently recognised. Finally, the Suldal Arc magmatism represents a significant juvenile crustal addition to SW Fennoscandia