Biochemistry and Pharmacology - Research Publications

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Author: McConville, Malcolm × Author: Tull, Dedreia × Author: de Souza, David × End date: 2023 × Start date: 2020 × Type: Journal Article ×

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    Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying Mohr-Tranebjaerg syndrome (vol 8, e48828, 2020)
    Kang, Y ; Anderson, AJ ; Jackson, TD ; Palmer, CS ; De Souza, DP ; Fujihara, KM ; Stait, T ; Frazier, AE ; Clemons, NJ ; Tull, D ; Thorburn, DR ; McConville, MJ ; Ryan, MT ; Stroud, DA ; Stojanovski, D (ELIFE SCIENCES PUBLICATIONS LTD, 2020-03-18)
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    Metabolomics Provide Sensitive Insights into the Impacts of Low Level Environmental Contamination on Fish Health-A Pilot Study
    Long, SM ; Tull, DL ; De Souza, DP ; Kouremenos, KA ; Dayalan, S ; McConville, MJ ; Hassell, KL ; Pettigrove, VJ ; Gagnon, MM (MDPI, 2020-01)
    This exploratory study aims to investigate the health of sand flathead (Platycephalus bassensis) sampled from five sites in Port Phillip Bay, Australia using gas chromatography-mass spectrometry (GC-MS) metabolomics approaches. Three of the sites were the recipients of industrial, agricultural, and urban run-off and were considered urban sites, while the remaining two sites were remote from contaminant inputs, and hence classed as rural sites. Morphological parameters as well as polar and free fatty acid metabolites were used to investigate inter-site differences in fish health. Significant differences in liver somatic index (LSI) and metabolite abundance were observed between the urban and rural sites. Differences included higher LSI, an increased abundance of amino acids and energy metabolites, and reduced abundance of free fatty acids at the urban sites compared to the rural sites. These differences might be related to the additional energy requirements needed to cope with low-level contaminant exposure through energy demanding processes such as detoxification and antioxidant responses as well as differences in diet between the sites. In this study, we demonstrate that metabolomics approaches can offer a greater level of sensitivity compared to traditional parameters such as physiological parameters or biochemical markers of fish health, most of which showed no or little inter-site differences in the present study. Moreover, the metabolite responses are more informative than traditional biomarkers in terms of biological significance as disturbances in specific metabolic pathways can be identified.
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    Unique properties of a subset of human pluripotent stem cells with high capacity for self-renewal
    Lau, KX ; Mason, EA ; Kie, J ; De Souza, DP ; Kloehn, J ; Tull, D ; McConville, MJ ; Keniry, A ; Beck, T ; Blewitt, ME ; Ritchie, ME ; Naik, SH ; Zalcenstein, D ; Korn, O ; Su, S ; Romero, IG ; Spruce, C ; Baker, CL ; McGarr, TC ; Wells, CA ; Pera, MF (Nature Research, 2020-05-15)
    Archetypal human pluripotent stem cells (hPSC) are widely considered to be equivalent in developmental status to mouse epiblast stem cells, which correspond to pluripotent cells at a late post-implantation stage of embryogenesis. Heterogeneity within hPSC cultures complicates this interspecies comparison. Here we show that a subpopulation of archetypal hPSC enriched for high self-renewal capacity (ESR) has distinct properties relative to the bulk of the population, including a cell cycle with a very low G1 fraction and a metabolomic profile that reflects a combination of oxidative phosphorylation and glycolysis. ESR cells are pluripotent and capable of differentiation into primordial germ cell-like cells. Global DNA methylation levels in the ESR subpopulation are lower than those in mouse epiblast stem cells. Chromatin accessibility analysis revealed a unique set of open chromatin sites in ESR cells. RNA-seq at the subpopulation and single cell levels shows that, unlike mouse epiblast stem cells, the ESR subset of hPSC displays no lineage priming, and that it can be clearly distinguished from gastrulating and extraembryonic cell populations in the primate embryo. ESR hPSC correspond to an earlier stage of post-implantation development than mouse epiblast stem cells.