Advanced gas-cooled reactor SIMFuel fabricated by Hot Isostatic Pressing: a feasibility investigation

The manufacture of a simulant UK Advanced Gas Cooled Reactor (AGR) spent nuclear fuel (SIMFuel) was achieved by Hot Isostatic Pressing (HIP). Characterisation of HIP AGR SIMFuels, tailored to burn ups of 25 GWd/t U and 43 GWd/t U (after 100 years cooling) demonstrated fission product partitioning, phase assemblage, microstructure and porosity in good agreement with spent nuclear fuels and SIMFuels, and AGR fuels in particular. A pivotal advantage of the application of the HIP manufacturing method is the retention of volatile fission products within the resultant SIMFuel as the result of using a hermetically-sealed container. This new approach to SIMFuel manufacture should enable the production of more accurate spent nuclear fuel surrogates to support research on spent fuel management, recycle, and disposal, and the thermal treatment of fuel residues and debris

The cardiac-restricted protein ADP-ribosylhydrolase-like 1 is essential for heart chamber outgrowth and acts on muscle actin filament assembly

AbstractAdprhl1, a member of the ADP-ribosylhydrolase protein family, is expressed exclusively in the developing heart of all vertebrates. In the amphibian Xenopus laevis, distribution of its mRNA is biased towards actively growing chamber myocardium. Morpholino oligonucleotide-mediated knockdown of all Adprhl1 variants inhibits striated myofibril assembly and prevents outgrowth of the ventricle. The resulting ventricles retain normal electrical conduction and express markers of chamber muscle differentiation but are functionally inert. Using a cardiac-specific Gal4 binary expression system, we show that the abundance of Adprhl1 protein in tadpole hearts is tightly controlled through a negative regulatory mechanism targeting the 5′-coding sequence of Xenopus adprhl1. Over-expression of full length (40kDa) Adprhl1 variants modified to escape such repression, also disrupts cardiac myofibrillogenesis. Disarrayed myofibrils persist that show extensive branching, with sarcomere division occurring at the actin-Z-disc boundary. Ultimately, Adprhl1-positive cells contain thin actin threads, connected to numerous circular branch points. Recombinant Adprhl1 can localize to stripes adjacent to the Z-disc, suggesting a direct role for Adprhl1 in modifying Z-disc and actin dynamics as heart chambers grow. Modelling the structure of Adprhl1 suggests this cardiac-specific protein is a pseudoenzyme, lacking key residues necessary for ADP-ribosylhydrolase catalytic activity

Genome-wide analysis of gene expression during Xenopus tropicalis tadpole tail regeneration

BACKGROUND: The molecular mechanisms governing vertebrate appendage regeneration remain poorly understood. Uncovering these mechanisms may lead to novel therapies aimed at alleviating human disfigurement and visible loss of function following injury. Here, we explore tadpole tail regeneration in Xenopus tropicalis, a diploid frog with a sequenced genome. RESULTS: We found that, like the traditionally used Xenopus laevis, the Xenopus tropicalis tadpole has the capacity to regenerate its tail following amputation, including its spinal cord, muscle, and major blood vessels. We examined gene expression using the Xenopus tropicalis Affymetrix genome array during three phases of regeneration, uncovering more than 1,000 genes that are significantly modulated during tail regeneration. Target validation, using RT-qPCR followed by gene ontology (GO) analysis, revealed a dynamic regulation of genes involved in the inflammatory response, intracellular metabolism, and energy regulation. Meta-analyses of the array data and validation by RT-qPCR and in situ hybridization uncovered a subset of genes upregulated during the early and intermediate phases of regeneration that are involved in the generation of NADP/H, suggesting that these pathways may be important for proper tail regeneration. CONCLUSIONS: The Xenopus tropicalis tadpole is a powerful model to elucidate the genetic mechanisms of vertebrate appendage regeneration. We have produced a novel and substantial microarray data set examining gene expression during vertebrate appendage regeneration

Fabrication, defect chemistry and microstructure of Mn-doped UO2

Mn-doped UO2 is under consideration for use as an accident tolerant nuclear fuel. We detail the synthesis of Mn-doped UO2 prepared via a wet co-precipitation method, which was refined to improve the yield of incorporated Mn. To verify the Mn-doped UO2 defect chemistry, X-ray absorption spectroscopy at the Mn K-edge was performed, in addition to X-ray diffraction, Raman spectroscopy and high-energy resolved fluorescence detection X-ray absorption near edge spectroscopy at the U M4-edge. It was established that Mn2+ directly substitutes for U4+ in the UO2 lattice, accompanied by oxygen vacancy (Ov) charge compensation. In contrast to other divalent-element doped UO2 materials, compelling evidence for U5+ in a charge compensating role was not found. This work furthers understanding of the structure and crystal chemistry of Mn-doped UO2, which could show potential advantages as a novel efficient advanced nuclear fuel

FGF10 promotes regional foetal cardiomyocyte proliferation and adult cardiomyocyte cell-cycle re-entry

© The Author 2014. Aims Cardiomyocyte proliferation gradually declines during embryogenesis resulting in severely limited regenerative capacities in the adult heart. Understanding the developmental processes controlling cardiomyocyte proliferation may thus identify new therapeutic targets to modulate the cell-cycle activity of cardiomyocytes in the adult heart. This study aims to determine the mechanism by which fibroblast growth factor 10 (FGF10) controls foetal cardiomyocyte proliferation and to test the hypothesis that FGF10 promotes the proliferative capacity of adult cardiomyocytes. Methods and results Analysis of Fgf10-/- hearts and primary cardiomyocyte cultures reveals that altered ventricular morphology is associated with impaired proliferation of right but not left-ventricular myocytes. Decreased FOXO3 phosphorylation associated with up-regulated p27kip1 levelswas observed specifically in the right ventricle of Fgf10-/- hearts. In addition, cell-type-specific expression analysis revealed that Fgf10 and its receptor, Fgfr2b, are expressed in cardiomyocytes and not cardiac fibroblasts, consistent with a cell-type autonomous role of FGF10 in regulating regional specific myocyte proliferation in the foetal heart. Furthermore, we demonstrate that in vivo overexpression of Fgf10 in adult mice promotes cardiomyocyte but not cardiac fibroblast cell-cycle re-entry. Conclusion FGF10 regulates regional cardiomyocyte proliferation in the foetal heart through a FOXO3/p27kip1 pathway. In addition, FGF10 triggers cell-cycle re-entry of adult cardiomyocytes and is thus a potential target for cardiac repair

Hot Isostatic Pressing (HIP): A novel method to prepare Cr-doped UO2 nuclear fuel

The addition of Cr2O3 to modern UO2 fuel modifies the microstructure so that, through the generation of larger grains during fission, a higher proportion of fission gases can be accommodated. This reduces the pellet-cladding mechanical interaction of the fuel rods, allowing the fuels to be “burned” for longer than traditional UO2 fuel, thus maximising the energy obtained. We here describe the preparation of UO2 and Cr-doped UO2 using Hot Isostatic Pressing (HIP), as a potential method for fuel fabrication, and for development of analogue materials for spent nuclear fuel research. Characterization of the synthesised materials confirmed that high density UO2 was successfully formed, and that Cr was present as particles at grain boundaries and also within the UO2 matrix, possibly in a reduced form due to the processing conditions. In contrast to studies of Cr-doped UO2 synthesised by other methods, no significant changes to the grain size were observed in the presence of Cr

Mundane objects in the city: Laundry practices and the making and remaking of public/private sociality and space in London and New York

The paper considers how shifting laundry practices and technologies associated with dirty washing have over time summoned different spaces, socialities and socio-spatial assemblages in the city, enrolling different actors and multiple publics and constituting different associations, networks and relations in its wake as it travels from the home and back again. It argues that rather than being an inert object of unpleasant matter, whose encounter with humans has been largely restricted to certain categories of person for its transformation to re-use, and thus passed unnoticed, the paper explores how laundry practices have figured in producing and reproducing gendered (and classed) relations of labour, and enacting multiple socio-spatial, and gendered, relations and assemblages in the city, which have largely gone unnoticed in accounts of everyday urban life

Loss of Extreme Long-Range Enhancers in Human Neural Crest Drives a Craniofacial Disorder

Non-coding mutations at the far end of a large gene desert surrounding the SOX9 gene result in a human craniofacial disorder called Pierre Robin sequence (PRS). Leveraging a human stem cell differentiation model, we identify two clusters of enhancers within the PRS-associated region that regulate SOX9 expression during a restricted window of facial progenitor development at distances up to 1.45 Mb. Enhancers within the 1.45 Mb cluster exhibit highly synergistic activity that is dependent on the Coordinator motif. Using mouse models, we demonstrate that PRS phenotypic specificity arises from the convergence of two mechanisms: confinement of Sox9 dosage perturbation to developing facial structures through context-specific enhancer activity and heightened sensitivity of the lower jaw to Sox9 expression reduction. Overall, we characterize the longest-range human enhancers involved in congenital malformations, directly demonstrate that PRS is an enhanceropathy, and illustrate how small changes in gene expression can lead to morphological variation

Maternal iron deficiency perturbs embryonic cardiovascular development in mice.

Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene-environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women

A Novel Mouse c-fos Intronic Promoter That Responds to CREB and AP-1 Is Developmentally Regulated In Vivo

BACKGROUND: The c-fos proto-oncogene is an archetype for rapid and integrative transcriptional activation. Innumerable studies have focused on the canonical promoter, located upstream from the transcriptional start site. However, several regulatory sequences have been found in the first intron. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe an extremely conserved region in c-fos first intron that contains a putative TATA box, and functional TRE and CRE sites. This fragment drives reporter gene activation in fibroblasts, which is enhanced by increasing intracellular calcium and cAMP and by cotransfection of CREB or c-Fos/c-Jun expression vectors. We produced transgenic mice expressing a lacZ reporter controlled by the intronic promoter. Lac Z expression of this promoter is restricted to the developing central nervous system (CNS) and the mesenchyme of developing mammary buds in embryos 12.5 days post-conception, and to brain tissue in adults. RT-QPCR analysis of tissue mRNA, including the anlage of the mammary gland and the CNS, confirms the existence of a novel, nested mRNA initiated in the first intron. CONCLUSIONS/SIGNIFICANCE: Our results provide evidence for a novel, developmentally regulated promoter in the first intron of the c-fos gene