Age of donor alters the effect of cyclic hydrostatic pressure on production by human macrophages and osteoblasts of sRANKL, OPG and RANK

BACKGROUND: Cyclic hydrostatic pressure within bone has been proposed both as a stimulus of aseptic implant loosening and associated bone resorption and of bone formation. We showed previously that cyclical hydrostatic pressure influenced macrophage synthesis of several factors linked to osteoclastogenesis. The osteoprotegerin/soluble receptor activator of NF-kappa β ligand /receptor activator of NF-kappa β (OPG/ RANKL/ RANK) triumvirate has been implicated in control of bone resorption under various circumstances. We studied whether cyclical pressure might affect bone turnover via effects on OPG/ sRANKL/ RANK. METHODS: In this study, cultures of human osteoblasts or macrophages (supplemented with osteoclastogenic factors) or co-cultures of macrophages and osteoblasts (from the same donor), were subjected to cyclic hydrostatic pressure. Secretion of OPG and sRANKL was assayed in the culture media and the cells were stained for RANK and osteoclast markers. Data were analysed by nonparametric statistics. RESULTS: In co-cultures of macrophages and osteoblasts, pressure modulated secretion of sRANKL or OPG in a variable manner. Examination of the OPG:sRANKL ratio in co cultures without pressurisation showed that the ratio was greater in donors <70 years at the time of operation (p < 0.05 Mann Whitney U) than it was in patients >70 years. However, with pressure the difference in the OPG:sRANKL ratios between young and old donors was not significant. It was striking that in some patients the OPG:sRANKL ratio increased with pressure whereas in some it decreased. The tendency was for the ratio to decrease with pressure in patients younger than 70 years, and increase in patients ≥ 70 years (Fishers exact p < 0.01). Cultures of osteoblasts alone showed a significant increase in both sRANKL and OPG with pressure, and again there was a decrease in the ratio of OPG:RANKL. Secretion of sRANKL by cultures of macrophages alone was not modulated by pressure. Only sRANKL was assayed in this study, but transmembrane RANKL may also be important in this system. Macrophages subjected to pressure (both alone and in co-culture) stained more strongly for RANK on immunohistochemstry than non-pressurized controls and 1,25-dihydroxyvitamin D(3 )(1,25 D(3)) further increased this. Immunocytochemical staining also demonstrated that more cells in pressurized co-cultures exhibited osteoclast markers (tartrate-resistant acid phosphatase, vitronectin receptor and multinuclearity) than did unpressurized controls. CONCLUSION: These data show that in co-cultures of osteoblasts and macrophages the ratio of OPG : sRANKL was decreased by pressure in younger patients but increased in older patients. As falls in this ratio promote bone resorption, this finding may be important in explaining the relatively high incidence of osteolysis around orthopaedic implants in young patients. The finding that secretion of OPG and sRANKL by osteoblasts in monoculture was sensitive to hydrostatic pressure, and that hydrostatic pressure stimulated the differentiation of macrophages into cells exhibiting osteoclast markers indicates that both osteoblasts and preosteoclasts are sensitive to cyclic pressure. However, the effects of pressure on cocultures were not simply additive and coculture appears useful to examine the interaction of these cell types. These findings have implications for future therapies for aseptic loosening and for the development of tests to predict the development of this condition

X-ray diffraction from bone employing annular and semi-annular beams

This is the final version of the article. Available from the publisher via the DOI in this record.There is a compelling need for accurate, low cost diagnostics to identify osteo-tissues that are associated with a high risk of fracture within an individual. To satisfy this requirement the quantification of bone characteristics such as 'bone quality' need to exceed that provided currently by densitometry. Bone mineral chemistry and microstructure can be determined from coherent x-ray scatter signatures of bone specimens. Therefore, if these signatures can be measured, in vivo, to an appropriate accuracy it should be possible by extending terms within a fracture risk model to improve fracture risk prediction.In this preliminary study we present an examination of a new x-ray diffraction technique that employs hollow annular and semi-annular beams to measure aspects of 'bone quality'. We present diffractograms obtained with our approach from ex vivo bone specimens at Mo Kα and W Kα energies. Primary data is parameterized to provide estimates of bone characteristics and to indicate the precision with which these can be determined.We acknowledge gratefully the funding provided by the UK Engineering and Physical Sciences Research Council (EPSRC) grant number EP/K020196/

Assembly of splicing complexes on exon 11 of the human insulin receptor gene does not correlate with splicing efficiency in-vitro

BACKGROUND: Incorporation of exon 11 of the insulin receptor gene is both developmentally and hormonally-regulated. Previously, we have shown the presence of enhancer and silencer elements that modulate the incorporation of the small 36-nucleotide exon. In this study, we investigated the role of inherent splice site strength in the alternative splicing decision and whether recognition of the splice sites is the major determinant of exon incorporation. RESULTS: We found that mutation of the flanking sub-optimal splice sites to consensus sequences caused the exon to be constitutively spliced in-vivo. These findings are consistent with the exon-definition model for splicing. In-vitro splicing of RNA templates containing exon 11 and portions of the upstream intron recapitulated the regulation seen in-vivo. Unexpectedly, we found that the splice sites are occupied and spliceosomal complex A was assembled on all templates in-vitro irrespective of splicing efficiency. CONCLUSION: These findings demonstrate that the exon-definition model explains alternative splicing of exon 11 in the IR gene in-vivo but not in-vitro. The in-vitro results suggest that the regulation occurs at a later step in spliceosome assembly on this exon

Combined measurements of prey availability explain habitat selection in foraging seabirds

Understanding links between habitat characteristics and foraging efficiency helps predict how environmental changes influence populations of top predators. This study examines whether measurements of prey (clupeids) availability varied over stratification gradients, and determined if any of those measurements coincided with aggregations of foraging seabirds (common guillemot Uria aalge and Manx shearwater Puffinus puffinus) in the Celtic Sea, UK. The probability of encountering foraging seabirds was highest around fronts between mixed and stratified water. Prey were denser and shallower in mixed water, whilst encounters with prey were most frequent in stratified water. Therefore, no single measurement of increased prey availability coincided with the location of fronts. However, when considered in combination, overall prey availability was highest in these areas. These results show that top predators may select foraging habitats by trading-off several measurements of prey availability. By showing that top predators select areas where prey switch between behaviours, these results also identify a mechanism that could explain the wider importance of edge habitats for these taxa. As offshore developments (e.g. marine renewable energy installations) change patterns of stratification, their construction may have consequences on the foraging efficiency of seabirds

Holographic dual of the Eguchi-Kawai mechanism

archiveprefix: arXiv primaryclass: hep-th reportnumber: NORDITA-2014-40, UUITP-03-14, QMUL-PH-14-08 slaccitation: %%CITATION = ARXIV:1404.0225;%%archiveprefix: arXiv primaryclass: hep-th reportnumber: NORDITA-2014-40, UUITP-03-14, QMUL-PH-14-08 slaccitation: %%CITATION = ARXIV:1404.0225;%%archiveprefix: arXiv primaryclass: hep-th reportnumber: NORDITA-2014-40, UUITP-03-14, QMUL-PH-14-08 slaccitation: %%CITATION = ARXIV:1404.0225;%%The work of K.Z. was supported by the ERC advanced grant No 341222, by the Marie Curie network GATIS of the European Union’s FP7 Programme under REA Grant Agreement No 317089, and by the Swedish Research Council (VR) grant 2013-4329. DY acknowledges NORDITA where this work was begun, during his time as a NORDITA fellow

Scheduling science on television: A comparative analysis of the representations of science in 11 European countries

While science-in-the-media is a useful vehicle for understanding the media, few scholars have used it that way: instead, they look at science-in-the-media as a way of understanding science-in-the-media and often end up attributing characteristics to science-in-the-media that are simply characteristics of the media, rather than of the science they see there. This point of view was argued by Jane Gregory and Steve Miller in 1998 in Science in Public. Science, they concluded, is not a special case in the mass media, understanding science-in-the-media is mostly about understanding the media (Gregory and Miller, 1998: 105). More than a decade later, research that looks for patterns or even determinants of science-in-the-media, be it in press or electronic media, is still very rare. There is interest in explaining the media’s selection of science content from a media perspective. Instead, the search for, and analysis of, several kinds of distortions in media representations of science have been leading topics of science-in-the-media research since its beginning in the USA at the end of the 1960s and remain influential today (see Lewenstein, 1994; Weigold, 2001; Kohring, 2005 for summaries). Only a relatively small amount of research has been conducted seeking to identify factors relevant to understanding how science is treated by the mass media in general and by television in particular. The current study addresses the lack of research in this area. Our research seeks to explore which constraints national media systems place on the volume and structure of science programming in television. In simpler terms, the main question this study is trying to address is why science-in-TV in Europe appears as it does. We seek to link research focussing on the detailed analysis of science representations on television (Silverstone, 1984; Collins, 1987; Hornig, 1990; Leon, 2008), and media research focussing on the historical genesis and current political regulation of national media systems (see for instance Hallin and Mancini, 2004; Napoli, 2004; Open Society Institute, 2005, 2008). The former studies provide deeper insights into the selection and reconstruction of scientific subject matters, which reflect and – at the same time – reinforce popular images of science. But their studies do not give much attention to production constraints or other relevant factors which could provide an insight into why media treat science as they do. The latter scholars inter alia shed light on distinct media policies in Europe which significantly influence national channel patterns. However, they do not refer to clearly defined content categories but to fairly rough distinctions such as information versus entertainment or fictional versus factual. Accordingly, we know more about historical roots and current practices of media regulation across Europe than we do about the effects of these different regimes on the provision of specific content in European societies

Effect of Systemic Matrix Metalloproteinase Inhibition on Periodontal Wound Repair: A Proof of Concept Trial

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141196/1/jper0441.pd