1,720,968 research outputs found
Elucidating the role of osteoblastderived vascular endothelial growth factor in the regulation of bone development: Sexually dimorphic effects and cellular mechanisms
No full textBone is highly vascularised and bone forming osteoblast-derived vascular endothelial growth factor (VEGF) has been reported to be a key regulator of bone development and bone repair. Sex differences during skeletal growth are well reported and this early divergence is thought to influence the onset and prevalence of degenerative bone pathologies in men and women with age. Although VEGF is critical during early bone development, little remains understood about the role that the vasculature plays in driving the sexual dimorphism in bone. Therefore, the main objective of my PhD was to improve understanding of the function of osteoblast-derived VEGF signalling in male and female bone development and mineralisation. For VEGF deletion in mature osteoblast cells, male and female mice carrying floxed alleles of VEGF and expressing Cre recombinase under the control of the osteocalcin promotor were compared and termed herein as OcnVEGFKO. The following aims were the focus of this thesis i) Quantification and validation of vascular phenotype within the bone cortex in male versus female adult OcnVEGFKO mice ii) Investigation of whole bone traits following osteoblast-VEGF deletion including bone geometry in males versus females, iii) Elucidation of the role of osteoblast-VEGF in prepubertal development and its direct effects on male and female osteoblast function and iv) Investigation into indirect effects of VEGF deletion in male and female osteoblasts on vascular endothelial cell function. High-resolution synchrotron computed tomography, histology and backscattered scanning electron microscopy at the tibiofibular junction revealed increased intracortical porosity (+2.73 fold increase, p<0.0001), increased vasculature (% blood vessel area; WT 0.54, OcnVEGFKO 3.6, p=0.05) and signs of widespread deficiency in matrix mineralisation in 16 week old male OcnVEGFKOs versus WT. In contrast, in female OcnVEGFKOs there were no notable alterations in intracortical porosity, vasculature or mineralisation, but an increase in lacunar density, volume and diameter versus WT. Comparable to the changes observed in 16 week old mice, analysis of 4 week old male and female tibia using SR CT identified increased intracortical canal volume in male OcnVEGFKOs versus WT only. Medium-resolution micro-CT enabled the quantification of changes in bone geometry along the whole tibial length. In 4 week old mice, bone architecture was significantly altered in male OcnVEGFKO versus WT. In 16 week old mice however, differences in bone geometry were identified in female OcnVEGFKO versus WT, but not in males. Trabecular measures were largely unaltered in 4 and 16 week old male and female OcnVEGFKOs versus WT. To assess the ii directionality of VEGF signalling and its contribution to observed sexual dimorphisms, LOBs were isolated from male and female Vegffl/fl mice in vitro. VEGF was deleted using Adenovirus-Cre (OBVEGFKO) to assess direct effects of VEGF deletion on OB function in males and females. OBVEGFKO had no significant effect on viability or alkaline phosphatase (ALP) elution in males or females versus WT. mRNA was extracted from OBVEGFKO and WT OBs and qPCR was utilised to measure changes in relative expression of mRNA. Negligible levels of Vegfr2 expression was identified in male and female OBs, in comparison to the endothelial cell (EC) lysate positive control. Expression of Ar, Esr1, Esr2, Rankl, Opg and Sost was unchanged in male and female OBs as a result of VEGFKO. Indirect effects of OBVEGFKO on EC functions were investigated and WT and OBVEGFKO conditioned media was collected from OBs and used to treat mouse bone marrow endothelial cells (MBMECs). Additional sexual dimorphism was identified here, with differential expression of genes implicated in angiogenesis and osteogenesis in OBVEGFKO versus WT represented by fold changes, including Igf-1 (female; +3.07, male; -2.33), Hif1-α (female; +1.22, male; -1.32), Runx2 (female; +3.43, male; -1.55) and Sost (female;+6.58, male; +3.21). Correlating with in vitro mechanistic findings of sexual dimorphism in endothelial cells driven by osteoblastderived VEGF, immunohistochemistry of tibia sections revealed high levels of sclerostin, a potent inhibitor of bone mineralisation in male OcnVEGFKO and localised to CD31 positive cells at the tibiofibular junction. My results propose that osteoblast-derived VEGF regulates osteoblast matrix mineralisation directly and vascularisation indirectly, that this regulation is distinct to males and females and results in divergent physical bone traits between sexes. Importantly my cell culture studies have found that these dimorphic bone phenotypes are linked to alterations in endothelial cell gene expression which could be targeted clinically to improve bone mineralisation. Targeting vascular signals to modulate bone formation distinctly in males and females could therefore provide a more effective way to treat degenerative bone disease in our ageing population
Commentary: A cost-effective method to enhance adenoviral transduction of primary murine osteoblasts and bone marrow stromal cells
No full textA Commentary onA cost-effective method to enhance adenoviral transduction of primary murine osteoblasts and bone marrow stromal cellsby Buo, A. M., Williams, M. S., Kerr, J. P., and Stains, J. P. (2016). Bone Res. 4:16021. doi: 10.1038/boneres.2016.2
Simultaneous visualisation of calcified bone microstructure and intracortical vasculature using synchrotron X-ray phase contrast-enhanced tomography
No full text3D imaging of the bone vasculature is of key importance in the understanding of skeletal disease. As blood vessels in bone are deeply encased in the calcified matrix, imaging techniques that are applicable to soft tissues are generally difficult or impossible to apply to the skeleton. While canals in cortical bone can readily be identified and characterised in X-ray computed tomographic data in 3D, the soft tissue comprising blood vessels that are putatively contained within the canal structures does not provide sufficient image contrast necessary for image segmentation. Here, we report an approach that allows for rapid, simultaneous visualisation of calcified bone tissue and the vasculature within the calcified bone matrix. Using synchrotron X-ray phase contrast-enhanced tomography we show exemplar data with intracortical capillaries uncovered at sub-micrometre level without the need for any staining or contrast agent. Using the tibiofibular junction of 15 week-old C57BL/6 mice post mortem, we show the bone cortical porosity simultaneously along with the soft tissue comprising the vasculature. Validation with histology confirms that we can resolve individual capillaries. This imaging approach could be easily applied to other skeletal sites and transgenic models, and could improve our understanding of the role the vasculature plays in bone disease
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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