1,721,082 research outputs found
Dynamic Compartmentalisation of Intracellular Sodium in collecting duct cells
Movie S1.avi - shows localised release of sodium green from a vesicle; Movie S2.avi - shows decrease in fluorescence of vesicle over time; Movie S3.mp4 - shows increase in fluorescence of one vesicle with decrease in fluorescence of second vesicle over time.Mullins, John. (2022). Dynamic Compartmentalisation of Intracellular Sodium in collecting duct cells, [moving image]. University of Edinburgh. Queen's Medical Research Institute. Centre for Cardiovascular Science. Molecular Physiology Lab. https://doi.org/10.7488/ds/3268
scRNA transcription profile of adult zebrafish podocytes
Background/Aims: The role of podocytes is well conserved across species from drosophila to teleosts, and mammals. Identifying the molecular markers that actively maintain the integrity of the podocyte will enable a greater understanding of the changes that lead to damage. Methods: We generated transgenic zebrafish, expressing fluorescent reporters driven by the podocin promoter, for the visualization and isolation of podocytes. We have conducted single cell RNA sequencing (scRNA-seq) on isolated podocytes from a zebrafish reporter line. Results: We demonstrated that the LifeAct-TagRFP-T fluorescent reporter faithfully replicated podocin expression in vivo. We were also able to show spontaneous GCaMP6s fluorescence using light sheet (single plane illumination) microscopy. We identified many podocyte transcripts, encoding proteins related to calcium-binding and actin filament assembly, in common with those expressed in human and mouse mature podocytes. Conclusion: We describe the establishment of novel transgenic zebrafish and their use to identify and isolate podocyte cells for the preparation of a scRNA-seq library from normal podocytes. The scRNA-seq data identifies distinct populations of cells and potential gene switching between clusters. These data provide a foundation for future comparative studies and for exploiting the zebrafish as a model for kidney development, disease, injury and repair.Mullins, John; Brown, Cara; Mullins, Linda. (2021). scRNA transcription profile of adult zebrafish podocytes, [dataset]. University of Edinburgh; BHF Centre for Cardiovascular Science. https://doi.org/10.7488/ds/3021
Loss of Adam10 disrupts ion transport in immortalised kidney collecting duct cells
The kidney cortical collecting duct (CCD) comprises of principal cells (PC), intercalated cells (IC) and the recently discovered intermediate cell type. Kidney pathology in a mouse model of the syndrome of apparent aldosterone excess (SAME) revealed plasticity of the cortical collecting duct (CCD), with altered principal cell (PC): intermediate cell: intercalated cell (IC) ratio. The self-immortalized mouse CCD cell line, mCCDcl1, shows functional characteristics of PCs but displays a range of cell types, including intermediate cells, making it ideal to study plasticity. We knocked out Adam10, a key component of the Notch pathway, in mCCDcl1 cells, using CRISPR-Cas9 technology, and isolated independent clones, which exhibited severely affected sodium transport capacity and loss of aldosterone response. Single-cell RNA sequencing revealed significantly reduced expression of major PC-specific markers, such as Scnn1g (gamma-ENaC) and Hsd11b2 (11ßHSD2), but no significant changes in transcription of components of the Notch pathway were observed. Immunostaining in the knockout clone confirmed the decrease in expression of gamma-ENaC and importantly, showed an altered, diffuse distribution of PC and IC markers, suggesting altered trafficking in the Adam10 knockout clone as an explanation for the loss of polarisation.Mullins, John; Assmus, Adrienne; Mullins, Linda. (2021). Loss of Adam10 disrupts ion transport in immortalised kidney collecting duct cells, [dataset]. University of Edinburgh; BHF Centre for Cardiovascular Science. https://doi.org/10.7488/ds/3022
CT Image datasets for highdose 16A2XXX and 16A3XXX
High dose microCT does not contribute towards improved microPET/CT image quantitative accuracy and can limit longitudinal scanning of small animals ABSTRACT Obtaining accurate quantitative measurements in preclinical Positron Emission Tomography/Computed Tomography (PET/CT) imaging is of paramount importance in biomedical research and helps supporting efficient translation of preclinical results to the clinic. The purpose of this study was two-fold: (1) to investigate the effects of different CT acquisition protocols on PET/CT image quality and data quantification; and (2) to evaluate the absorbed dose associated with varying CT parameters. Methods: An air/water quality control CT phantom, tissue equivalent material phantom, an in-house 3D printed phantom and an image quality PET/CT phantom were imaged using a Mediso nanoPET/CT scanner. Collected data was analyzed using PMOD software, VivoQuant software and National Electric Manufactures Association (NEMA) software implemented by Mediso. Measured Hounsfield Unit (HU) in collected CT images were compared to the known HU values and image noise was quantified. PET recovery coefficients (RC), uniformity and quantitative bias were also measured. Results: Only less than 2% and 1% of CT acquisition protocols yielded water HU values of less than -80 and air HU values of less than -840, respectively. Four out of eleven CT protocols resulted in more than 100 mGy absorbed dose. Different CT protocols did not impact PET uniformity and RC, and resulted in less than 4% overall bias relative to expected radioactive concentration. Conclusion: Preclinical CT protocols with increased exposure times can result in high absorbed doses to the small animals. These should be avoided, as they do not contributed towards improved microPET/CT image quantitative accuracy and could limit longitudinal scanning of small animals.McDougald, Wendy. (2019). CT Image datasets for highdose 16A2XXX and 16A3XXX, [image]. University of Edinburgh. Medical School. Centre for Cardiovascular Science. https://doi.org/10.7488/ds/2727
CT Image datasets for highdose 16A0XXX and 16A1XXX
High dose microCT does not contribute towards improved microPET/CT image quantitative accuracy and can limit longitudinal scanning of small animals ABSTRACT Obtaining accurate quantitative measurements in preclinical Positron Emission Tomography/Computed Tomography (PET/CT) imaging is of paramount importance in biomedical research and helps supporting efficient translation of preclinical results to the clinic. The purpose of this study was two-fold: (1) to investigate the effects of different CT acquisition protocols on PET/CT image quality and data quantification; and (2) to evaluate the absorbed dose associated with varying CT parameters. Methods: An air/water quality control CT phantom, tissue equivalent material phantom, an in-house 3D printed phantom and an image quality PET/CT phantom were imaged using a Mediso nanoPET/CT scanner. Collected data was analyzed using PMOD software, VivoQuant software and National Electric Manufactures Association (NEMA) software implemented by Mediso. Measured Hounsfield Unit (HU) in collected CT images were compared to the known HU values and image noise was quantified. PET recovery coefficients (RC), uniformity and quantitative bias were also measured. Results: Only less than 2% and 1% of CT acquisition protocols yielded water HU values of less than -80 and air HU values of less than -840, respectively. Four out of eleven CT protocols resulted in more than 100 mGy absorbed dose. Different CT protocols did not impact PET uniformity and RC, and resulted in less than 4% overall bias relative to expected radioactive concentration. Conclusion: Preclinical CT protocols with increased exposure times can result in high absorbed doses to the small animals. These should be avoided, as they do not contributed towards improved microPET/CT image quantitative accuracy and could limit longitudinal scanning of small animals.McDougald, Wendy. (2019). CT Image datasets for highdose 16A0XXX and 16A1XXX, [image]. University of Edinburgh. Medical School. Centre for Cardiovascular Science. https://doi.org/10.7488/ds/2726
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
Effects of administration route on uptake kinetics of 18F‑sodium fluoride positron emission tomography in mice
18F-sodium fluoride (18F-NaF) is a positron emission tomography (PET) radiotracer widely used in skeletal imaging and has also been proposed as a biomarker of active calcification in atherosclerosis. Like most PET radiotracers, 18F-NaF is typically administered intravenously. However in small animal research intravenous administrations can be challenging, because partial paravenous injection is common due to the small calibre of the superficial tail veins and repeat administrations via tail veins can lead to tissue injury therefore limiting the total number of longitudinal scanning points. In this paper, the feasibility of using intra-peritoneal route of injection of 8F-NaF to study calcification in mice was studied by looking at the kinetic and uptake profiles of normal soft tissues and bones versus intra-vascular injections. Dynamic PET was performed for 60 min on nineteen isoflurane-anesthetized male Swiss mice after femoral artery (n = 7), femoral vein (n = 6) or intraperitoneal (n = 6) injection of 8F-NaF. PET data were reconstructed and the standardised uptake value (SUV) and standardised uptake value ratio (SUVr) were estimated from the last three frames between 45- and 60-min and 8F-NaF uptake constant (Ki) was derived by Patlak graphical analysis. In soft tissue, the 18F-NaF perfusion phase changes depending on the type on injection route, whereas the uptake phase is similar regardless of the administration route. In bone tissue SUV, SUVr and Ki measures were not significantly different between the three administration routes. Comparison between PET and CT measures showed that bones that had the highest CT density displayed the lowest PET activity and conversely, bones where CT units were low had high 8F-NaF uptake. Intraperitoneal injection is a valid and practical alternative to the intra-vascular injections in small-animal 18F-NaF PET imaging providing equivalent pharmacokinetic data. CT outcome measures report on sites of stablished calcification whereas PET measures sites of higher complexity and active calcification.Galofre, Zaniah; Alcaide Corral, Carlos; Tavares, Adriana A.. (2022). Effects of administration route on uptake kinetics of 18F‑sodium fluoride positron emission tomography in mice, [dataset]. University of Edinburgh. Centre for Cardiovascular Science. https://doi.org/10.7488/ds/3413
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