Publications by authors named "D Timothy Bishop"

2,018 Publications

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Sports compression garments improve resting markers of venous return and muscle blood flow in male basketball players.

J Sport Health Sci 2021 Jul 24. Epub 2021 Jul 24.

Institute for Health and Sport (iHeS), Victoria University, Footscray, VIC 3011, Australia; Department of Physiology, Australian Institute of Sport, Bruce, ACT 2617, Australia.

Background: The benefits associated with sports compression garments are thought to be closely related to enhanced blood flow. However, findings are equivocal, possibly due to heterogeneity in techniques used for measuring blood flow, garment types used, and pressures applied. This study combined Doppler ultrasound and near-infrared spectroscopy technologies to provide the first comprehensive assessment of the effects of three sports compression garment types on markers of venous return and muscle blood flow at rest.

Methods: Resting lower-limb blood flow measures (markers of venous return, muscle blood flow, muscle oxygenation) of 22 elite, junior, male basketball players (age, 17.2 ± 0.9 years, mean ± SD) were assessed in 4 separate conditions: no compression (CON), compression tights (TIGHTS), compression shorts (SHORTS), and compression socks (SOCKS). Markers of venous return (cross-sectional area, time-averaged mean and peak blood flow velocity, and venous blood flow) were measured via Doppler ultrasound at the popliteal and common femoral veins. Muscle blood flow and muscle oxygenation were measured in the gastrocnemius medialis and vastus lateralis using near-infrared spectroscopy.

Results: Popliteal markers of venous return were higher in TIGHTS compared to CON (p < 0.01) and SHORTS (p < 0.01), with SOCKS values higher compared with CON (p < 0.05). Common femoral vein markers of venous return were higher for all conditions compared to CON (p < 0.05), with TIGHTS values also higher compared to SOCKS (p < 0.05). Gastrocnemius medialis blood flow was higher for TIGHTS compared to CON (p = 0.000), SOCKS (p = 0.012) and SHORTS (p = 0.000), with SOCKS higher compared to SHORTS (p = 0.046). Vastus lateralis blood flow was higher for TIGHTS compared to CON (p = 0.028) and SOCKS (p = 0.019), with SHORTS also higher compared to CON (p = 0.012) and SOCKS (p = 0.005). Gastrocnemius medialis oxygenation was higher for TIGHTS compared to CON (p = 0.003), SOCKS (p = 0.033) and SHORTS (p = 0.003), with SOCKS higher compared to CON (p = 0.044) and SHORTS (p = 0.032). Vastus lateralis oxygenation was higher for TIGHTS compared to CON (p = 0.02) and SOCKS (p = 0.006).

Conclusion: Markers of venous return, muscle blood flow, and muscle oxygenation are increased with sports compression garments. TIGHTS were most effective, potentially due to the larger body area compressed.
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http://dx.doi.org/10.1016/j.jshs.2021.07.010DOI Listing
July 2021

Assessing the reproducibility of labelled antibody binding in quantitative multiplexed immuno-mass spectrometry imaging.

Anal Bioanal Chem 2021 Jul 25. Epub 2021 Jul 25.

Atomic Medicine Initiative, Faculty of Science, University of Technology Sydney, P.O. Box 123, Broadway, Ultimo, NSW, 2007, Australia.

Immuno-mass spectrometry imaging (iMSI) uses laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to determine the spatial expression of biomolecules in tissue sections following immunolabelling with antibodies conjugated to a metal reporter. As with all immunolabelling techniques, the binding efficiency of multiplexed staining can be affected by a number of factors including epitope blocking and other forms of steric hindrance. To date, the effects on the binding of metal-conjugated antibodies to their epitopes in a multiplexed analysis have yet to be quantitatively explored by iMSI. Here we describe a protocol to investigate the effects of multiplexing on reproducible binding using the muscle proteins, dystrophin, sarcospan, and myosin as a model, with antibodies conjugated with Maxpar® reagents before histological application to murine quadriceps sections using standard immunolabelling protocols and imaging with LA-ICP-MS. The antibodies were each individually applied to eight sections, and multiplexed to another eight sections. The average concentrations of the lanthanide analytes were determined, before statistical analyses found there was no significant difference between the individual and multiplexed application of the antibodies. These analyses provide a framework for ensuring reproducibility of antibody binding during multiplexed iMSI, which will allow quantitative exploration of protein-protein interactions and provide a greater understanding of fundamental biological processes during healthy and diseased states.
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http://dx.doi.org/10.1007/s00216-021-03536-9DOI Listing
July 2021

Identification of 22 susceptibility loci associated with testicular germ cell tumors.

Nat Commun 2021 07 23;12(1):4487. Epub 2021 Jul 23.

Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95 percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation.
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http://dx.doi.org/10.1038/s41467-021-24334-yDOI Listing
July 2021

Cell-type-specific meQTLs extend melanoma GWAS annotation beyond eQTLs and inform melanocyte gene-regulatory mechanisms.

Am J Hum Genet 2021 Jul 15. Epub 2021 Jul 15.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address:

Although expression quantitative trait loci (eQTLs) have been powerful in identifying susceptibility genes from genome-wide association study (GWAS) findings, most trait-associated loci are not explained by eQTLs alone. Alternative QTLs, including DNA methylation QTLs (meQTLs), are emerging, but cell-type-specific meQTLs using cells of disease origin have been lacking. Here, we established an meQTL dataset by using primary melanocytes from 106 individuals and identified 1,497,502 significant cis-meQTLs. Multi-QTL colocalization with meQTLs, eQTLs, and mRNA splice-junction QTLs from the same individuals together with imputed methylome-wide and transcriptome-wide association studies identified candidate susceptibility genes at 63% of melanoma GWAS loci. Among the three molecular QTLs, meQTLs were the single largest contributor. To compare melanocyte meQTLs with those from malignant melanomas, we performed meQTL analysis on skin cutaneous melanomas from The Cancer Genome Atlas (n = 444). A substantial proportion of meQTL probes (45.9%) in primary melanocytes is preserved in melanomas, while a smaller fraction of eQTL genes is preserved (12.7%). Integration of melanocyte multi-QTLs and melanoma meQTLs identified candidate susceptibility genes at 72% of melanoma GWAS loci. Beyond GWAS annotation, meQTL-eQTL colocalization in melanocytes suggested that 841 unique genes potentially share a causal variant with a nearby methylation probe in melanocytes. Finally, melanocyte trans-meQTLs identified a hotspot for rs12203592, a cis-eQTL of a transcription factor, IRF4, with 131 candidate target CpGs. Motif enrichment and IRF4 ChIP-seq analysis demonstrated that these target CpGs are enriched in IRF4 binding sites, suggesting an IRF4-mediated regulatory network. Our study highlights the utility of cell-type-specific meQTLs.
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http://dx.doi.org/10.1016/j.ajhg.2021.06.018DOI Listing
July 2021

Meiosis in Quarantine discussions lead to an action plan to increase diversity and inclusion within the genetics community.

PLoS Genet 2021 Jul 15;17(7):e1009648. Epub 2021 Jul 15.

Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America.

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http://dx.doi.org/10.1371/journal.pgen.1009648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282017PMC
July 2021
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