135 research outputs found
sj-pdf-1-eso-10.1177_23969873231183206 – Supplemental material for Prediction of response to thrombolysis in acute stroke using neural network analysis of CT perfusion imaging
No full textSupplemental material, sj-pdf-1-eso-10.1177_23969873231183206 for Prediction of response to thrombolysis in acute stroke using neural network analysis of CT perfusion imaging by Yutong Chen, Daniel J Tozer, Weiran Liu, Edward J Peake and Hugh S Markus in European Stroke Journal</p
sj-docx-1-wso-10.1177_17474930231169132 – Supplemental material for How often does white matter hyperintensity volume regress in cerebral small vessel disease?
No full textSupplemental material, sj-docx-1-wso-10.1177_17474930231169132 for How often does white matter hyperintensity volume regress in cerebral small vessel disease? by Robin B Brown, Daniel J Tozer, Marco Egle, Anil M Tuladhar, Frank-Erik de Leeuw and Hugh S Markus in International Journal of Stroke</p
sj-docx-1-eso-10.1177_23969873221100338 – Supplemental material for MINocyclinE to Reduce inflammation and blood brain barrier leakage in small Vessel diseAse (MINERVA) trial study protocol
No full textSupplemental material, sj-docx-1-eso-10.1177_23969873221100338 for MINocyclinE to Reduce inflammation and blood brain barrier leakage in small Vessel diseAse (MINERVA) trial study protocol by Robin B Brown, Daniel J Tozer, Laurence Loubière, Young T Hong, Tim D Fryer, Guy B Williams, Martin J Graves, Franklin I Aigbirhio, John T O’Brien and Hugh S Markus in European Stroke Journal</p
sj-docx-1-wso-10.1177_17474930241245613 – Supplemental material for Are central and systemic inflammation associated with fatigue in cerebral small vessel disease?
No full textSupplemental material, sj-docx-1-wso-10.1177_17474930241245613 for Are central and systemic inflammation associated with fatigue in cerebral small vessel disease? by Amy A Jolly, Robin B Brown, Daniel J Tozer, Young T Hong, Tim D Fryer, Franklin I Aigbirhio, John T O’Brien and Hugh S Markus in International Journal of Stroke</p
White and gray matter damage in primary progressive MS: The chicken or the egg?
No full textOBJECTIVE: The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex ("primary WM damage model"); and (2) cortical abnormalities predict later changes in connected WM tracts ("primary GM damage model"). METHODS: Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. RESULTS: The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. CONCLUSION: These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions
A longitudinal study of cortical grey matter lesion subtypes in relapse-onset multiple sclerosis
No full textBackground: Cortical grey matter (GM) lesions are common in multiple sclerosis (MS), but little is known about their temporal evolution. We investigated this in people with relapsing-remitting (RR) and secondary progressive (SP) MS. Methods: 27 people with RRMS, and 22 with SPMS were included in this study. Phase sensitive inversion recovery (PSIR) scans were acquired on two occasions. Cortical GM lesions were classified as intracortical (IC, only involving GM) and leucocortical (LC, mixed GM-white matter [WM]); WM lesions touching the cortex as juxtacortical (JC). On follow up scans, new IC, LC and JC lesions were identified, and any change in classification of lesions previously observed was noted. WM lesion counts in the whole brain were assessed on PD/T2-weighted scans. Results: Over a mean (SD) of 21.0 (5.8) months, the number of new IC lesions per person per year was greater in SPMS (1.6 [1.9]) than RRMS (0.8 [1.9]) (Mann-Whitney p=0.039). All new LC lesions arose from previously seen IC lesions (SPMS 1.4 [1.8] per person per year, and RRMS 1.1 [1.0]), and none arose de novo or from previously seen JC lesions. Changes in cortical GM (either new IC or IC converting to LC) lesion counts did not correlate with the changes in WM lesion counts. Conclusions: New cortical GM lesions rarely arise from the WM and the rate of new IC lesion formation is not closely linked with WM lesion accrual. IC lesion formation appears to be more common in SPMS than RRMS
Tumour cells expressing single VEGF isoforms display distinct growth, survival and migration characteristics
No full textVascular endothelial growth factor-A (VEGF) is produced by most cancer cells as multiple isoforms, which display distinct biological activities. VEGF plays an undisputed role in tumour growth, vascularisation and metastasis; nevertheless the functions of individual isoforms in these processes remain poorly understood. We investigated the effects of three main murine isoforms (VEGF188, 164 and 120) on tumour cell behaviour, using a panel of fibrosarcoma cells we developed that express them individually under endogenous promoter control. Fibrosarcomas expressing only VEGF188 (fs188) or wild type controls (fswt) were typically mesenchymal, formed ruffles and displayed strong matrix-binding activity. VEGF164- and VEGF120-producing cells (fs164 and fs120 respectively) were less typically mesenchymal, lacked ruffles but formed abundant cell-cell contacts. On 3D collagen, fs188 cells remained mesenchymal while fs164 and fs120 cells adopted rounded/amoeboid and a mix of rounded and elongated morphologies respectively. Consistent with their mesenchymal characteristics, fs188 cells migrated significantly faster than fs164 or fs120 cells on 2D surfaces while contractility inhibitors accelerated fs164 and fs120 cell migration. VEGF164/VEGF120 expression correlated with faster proliferation rates and lower levels of spontaneous apoptosis than VEGF188 expression. Nevertheless, VEGF188 was associated with constitutively active/phosphorylated AKT, ERK1/2 and Stat3 proteins. Differences in proliferation rates and apoptosis could be explained by defective signalling downstream of pAKT to FOXO and GSK3 in fs188 and fswt cells, which also correlated with p27/p21 cyclin-dependent kinase inhibitor over-expression. All cells expressed tyrosine kinase VEGF receptors, but these were not active/activatable suggesting that inherent differences between the cell lines are governed by endogenous VEGF isoform expression through complex interactions that are independent of tyrosine kinase receptor activation. VEGF isoforms are emerging as potential biomarkers for anti-VEGF therapies. Our results reveal novel roles of individual isoforms associated with cancer growth and metastasis and highlight the importance of understanding their diverse actions
Summary statistics accompanying the article "Genome-wide association study of the human brain functional connectome reveals strong vascular component underlying global network efficiency" in Scientific Reports (2022)
No full textSummary statistics for genome-wide association studies reported in:
Bell, S., Tozer, D.J., & Markus H.S. (2022). Genome-wide association study of the human brain functional connectome reveals strong vascular component underlying global network efficiency. Scientific Reports, DOI: 10.1038/s41598-022-19106-7.
Abstract
Complex brain networks play a central role in integrating activity across the human brain, and such networks can be identified in the absence of any external stimulus. We performed 10 genome-wide association studies of resting state network measures of intrinsic brain activity in up to 36,150 participants of European ancestry in the UK Biobank. We found that the heritability of global network efficiency was largely explained by blood oxygen level-dependent (BOLD) resting state fluctuation amplitudes (RSFA), which are thought to reflect the vascular component of the BOLD signal. RSFA itself had a significant genetic component and we identified 24 genomic loci associated with RSFA, 157 genes whose predicted expression correlated with it, and 3 proteins in the dorsolateral prefrontal cortex and 4 in plasma. We observed correlations with cardiovascular traits, and single-cell RNA specificity analyses revealed enrichment of vascular related cells. Our analyses also revealed a potential role of lipid transport, store-operated calcium channel activity, and inositol 1,4,5-trisphosphate binding in resting-state BOLD fluctuations. We conclude that that the heritability of global network efficiency is largely explained by the vascular component of the BOLD response as ascertained by RSFA, which itself has a significant genetic component.
Further information on the files uploaded here can be found in the README. Users interested in bulk downloading these summary statistics may find zenodo_get helpful.This work was undertaken using UK Biobank application number 36509.
This work was supported by a British Heart Foundation Programme Grant (RG/16/4/32218). H.S.M. is supported by a National Institute for Health Research (NIHR) Senior Investigator award. D.J.T is funded by the Medical Research Council under grant MR/No26896/1 for work unconnected to this study. This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215–20014). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funding organisations had no role in any of the following: design and conduct of the study; collection, management, analysis, and interpretation of the data; review, or approval of the manuscript
Evaluation of metadata workflows for the Glasgow ePrints and DSpace services
No full textThe institutional repositories at the University of Glasgow which began as part of the DAEDALUS project have developed into an integral part of Glasgow University Library's services. Using both EPrints.org and DSpace, they provide access to, and permit management of, the University's academic digital assets. This evaluation analyses and comments on the metadata workflows of these services, their support for metadata quality, and how changes in purpose, which have accompanied their transition from project to service, have influenced the repositories. This evaluation will be of benefit not only to DAEDALUS but also to other institutional repositories facing the transition from project development to operational service. The metadata workflows supporting the management and retrieval of ePrints offer a number of paths for metadata creation - each of which has seen shifts in their relative importance as the purpose of the repository has evolved and become clear. The management and retrieval of other academic content in the DSpace service is entirely mediated by repository staff and follows a basic workflow. The quality of metadata in both services has been maintained through staff training and the ongoing involvement of professional cataloguers. The strengths of both repository services lie in their clarity of purpose, utilisation of appropriate software to support those purposes and their successful integration into Glasgow's institutional context. Although they also present a significant opportunity, the new challenges faced by the repository services arise from the emerging involvement of non-specialists in the creation of records and their potential involvement in the administration of sections of the DSpace repository. To address these challenges, the repository services will have to maintain their clarity of purpose, monitor metadata quality, capitalise on opportunities for efficiency, and continue to significantly engage in advocacy and user training
Economic analysis of site-specific wheat management with respect to grain quality and separation of the different quality fractions
No full textThe paper analyzes site-specific and uniform management options for wheat production with respect to grain quality. Besides site-specific fertilization the economic potential of segregation of different grain qualities is the subject of this paper. Yield and quality response to fertilizer were taken from field experiments in Germany to calculate site-specific response functions. The economic optima were calculated for uniform management (UM), complete separate management of the subfields (SM), site-specific fertilization (SSF) and grain segregation (GS) for different price structures according to different grain qualities. The results show that over all price structures, highest economic potential was found with SM or SSF compared to UM. However, these management practices require the possibility to separately manage subfields (SM) or specific fertilization equipment and fertilizer algorithms (SSM). GS did not have a higher economic potential than UM. However, if required grain qualities are not met for the whole field, GS can substantially reduce profit losses by separating part of the grains and selling them at higher prices. This may save the farmer more than 50 € ha–1. In situations where higher grain qualities could only be obtained at the expense of yield penalties, premiums for higher grain qualities can create incentives for fertilizer rates beyond the yield maximizing rate. GS technologies may even boost this effect.site-specific nitrogen management, wheat quality, grain segregation., Crop Production/Industries,
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