1,720,958 research outputs found
Connecting the dots: exploring the relationship between the arrangement of cortical porosity and the development of sex-specific whole bone phenotypes in cystine string protein alpha deficient mice
No full textNeurodegenerative diseases are characterised by synaptic loss and cognitive decline but are also typified by debilitating systemic comorbidities such as high prevalence of bone fracture. However, causative studies linking neurodegenerative diseases to bone fragility frequently omit the influence of bone porosity - a key contributor to bone strength - due to the size of pores within bone (frequently < 5 µm diameter) and their inaccessibility (within mineralised matrix). Bone porosity is comprised of a network of intracortical canals which house the bone vasculature and the mechanosensitive lacuna-canalicular network (LCN). Herein, this thesis aims to assess the morphology and organisation of porosity in a murine model of early synaptic loss - the cystine string protein alpha null mouse (CSPα-/-) - to understand how synaptic loss may alter bone phenotype. This will permit the characterization of links between CSPα-/- bone phenotypes on the whole bone scale, to the underpinning changes to the morphology, spatial arrangements and uniquely, on the cellular scale by visualising osteocytes within the LCN and relating osteocytes to their local mineral environment.This thesis describes four primary objectives: (i) Firstly, to characterize the development of bone phenotypes in CSPα-/- mice at multiple skeletal sites using micro computed tomography. Minor alterations to the endocranial anatomy of CSPα-/- mice and no changes to tibial trabecular morphology were observed. However, both male and female mice possess tibial cortical thinning and exclusively female CSPα-/- mice possess a deficit in tissue mineral density, establishing the tibial cortical bone as a site of interest. Subsequently, immunohistochemical approaches determined that CSPα is expressed by the bone vasculature, suggesting that in CSPα-/- mice intracortical canal structure or function may be affected. (ii) Synchrotron radiation computed tomography (SR CT) was thereby harnessed to study and establish the morphological and spatial arrangements of tibial cortical porosity in skeletally mature 13-month-old male WT mice. The tibiofibular junction (TFJ) was selected as a landmark site as it contains solely cortical bone, with image analysis tools developed to assess the morphology and spatial organization of pores, in addition to an alignment technique to separate the TFJ into quadrants. Together, these tools identified the posterior TFJ as a region possessing a distinct microstructural profile, with abundant intracortical canals surrounded by large canal-associated osteocyte lacunae. Importantly, conditional removal of a key angiogenic mitogen involved in angiogenic-osteogenic coupling – vascular endothelial growth factor (VEGF) in osteocalcin expressing cells (OcnVEGFKO) in mice – removed this population of large, canal-associated osteocyte lacunae in a sex specific manner. Study of OcnVEGFKO microstructure provided evidence that this unique posterior microstructural arrangement was not an anomaly, but rather, a deliberate coupling of abundant intracortical canals to large osteocyte lacunae to fulfil a specific function. (iii) However, when applied to CSPα-/- mice these tools revealed no differences in the arrangement of cortical porosity between WT and CSPα-/- mice, while microstructural heterogeneity was again observed. (iv) Finally, utilization of propagation-based enhanced phase contrast SR CT permitted the visualization of the cellular components lying within cortical pores - vasculature within intracortical canals and osteocytes within lacunae - which was used to assess their cellular structure and function. A convoluted neural network was developed to segment soft tissues from within cortical pores, revealing that canal-associated osteocytes were smaller in both male and female CSPα-/- mice, specifically within the posterior TFJ. Further, assessment of the local mineral surrounding posterior canal-associated osteocytes found that WT osteocytes possessed a region of low mineral density surrounding each lacuna, which extended to ~ 1 µm. However, exclusively female CSPα-/- mice possessed an extension of this hypo-dense region, with the hypo-mineral region surrounding canal-associated osteocytes extending to ~ 2 µm from the lacunae. Collectively, this thesis describes a sex-specific mineral deficit in female CSPα-/- mice, exclusively at the tibia. SR CT established the existence of region-specific arrangements of posterior osteocyte lacunae surrounding intracortical canals in WT mice, which is sex-specific in its facilitation by VEGF. Lastly, the value in assessing osteocyte subsets is highlighted through the identification of posterior, canal-associated osteocyte populations at the TFJ that contribute to the sex-specific deficit to bone mineral observed in female CSPα-/- mice. This finding provides potential functionality to this unique microstructural arrangement in CSPα-/- bone through the description of a region-specific association of low-density bone mineral surrounding canal-associated posterior osteocytes in female CSPα-/- mice. Together, it is hoped that this thesis highlights the importance and complexity of regional microstructural heterogeneity, linking microscale changes to bone porosity to altered murine bone macrostructure. Looking forward, it is hoped the continued study and understanding of these large, vasculature-associated osteocyte subpopulations could further our understanding of how changes to bone porosity could underpin the increased susceptibility to bone fracture of individuals living with neurodegenerative diseases.<br/
Dataset supporting the University of Southampton Doctoral Thesis "Connecting the dots: Exploring the relationship between the arrangement of cortical porosity and the development of sex specific whole bone phenotypes in cystine string protein alpha deficient mice".
No full textDataset supporting the University of Southampton Doctoral Thesis "Connecting the dots: Exploring the relationship between the arrangement of cortical porosity and the development of sex specific whole bone phenotypes in cystine string protein alpha deficient mice".
This dataset contains:
- Results 1 - Chapter 3.zip
- Results 2 - Chapter 4.zip
- Results 3 - Chapter 5.zip
- Results 4 - Chapter 6.zip
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Historic ocean acidification of Loch Sween revealed by correlative geochemical imaging and high-resolution boron isotope analysis of Boreolithothamniom cf. soriferum
No full textOcean Acidification (OA) arises from the increase in atmospheric carbon dioxide concentration following the industrial revolution. The ecological and socio-economic consequences of OA were first identified around 10–15 years ago but remain poorly understood. This is particularly true in coastal regions where local processes can have dramatic consequences on pH trends through time, obscuring and compounding the long-term effects from rising atmospheric CO2. Here we explore the possibility of generating long records of coastal ocean pH using the skeletons of widely distributed coralline algae (CA). The skeletons of these slow growing (<1 mm/year) taxa often contain micron-scale heterogeneities, making sampling for high-resolution climate reconstructions using bulk sampling techniques difficult. Here we use laser ablation coupled to inductively coupled plasma mass spectrometers to generate high-resolution 2D images of the element/calcium ratios and boron isotope composition (δ11B) of a sample of Boreolithothamniom cf. soriferum from Loch Sween in Scotland, UK where we have been monitoring temperature since 2004 and pH during 2014. By carefully correlating the geochemical images with a scanning electron microscopy image we can segment them to remove the marginal portions of the skeleton, isolating the central growth axis to generate an age model and growth rate. The δ11B-pH is significantly elevated above the seawater pH in Loch Sween (8.4 to 8.9 vs. 7.9 to 8.1) consistent with other CA that show internal pH elevation. On a seasonal scale, internal pH is negatively correlated with temperature and also exhibits a long-term decline. By removing this temperature effect, internal pH can be correlated to seawater pH during the 2014 monitoring period allowing us to reconstruct a seawater acidification trend from 2004 to 2018 of -0.018 pH units per year, 10x higher than open ocean trends but consistent with contemporaneous monitoring efforts of UK coastal waters. Reconstructed aqueous CO2 suggests that prior to ∼2008 Loch Sween was a sink of CO2 but after this date, particularly during the early summer, it was a substantial CO2 source. Comparison of reconstructed aqueous CO2 with a record of calcification rate of our sample of Boreolithothamniom cf. soriferum suggests this acidification and associated rise in local seawater pCO2 may have freed this sample from carbon limitation leading to a recent increase in calcification
Dataset for Doctoral Thesis, Investigating the role of MHC class I molecules in immune evasion by transmissible tumour cells
No full textDataset supporting the doctoral thesis, 'Investigating the role of MHC class I molecules in immune evasion by transmissible tumour cells' (2024)
This dataset contains:
IHC-Analysis_Macros.zip
IHC-Images.zip
NGS_Devil-Host-MHCI-Sequencing(1).zip
NGS_Devil-Host-MHCI-Sequencing(2).zip
NGS-Analysis_Scripts.zip
Tasmanian-Devil-Biopsies-Metadata.csv</span
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
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