ORCID Profile
0000-0001-9066-6962
Current Organisation
University of South Australia
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Publisher: Springer Science and Business Media LLC
Date: 13-05-2019
DOI: 10.1038/S41598-019-43765-8
Abstract: The cellular origins of vasa vasorum are ill-defined and may involve circulating or local progenitor cells. We previously discovered that murine aortic adventitia contains Sca-1 + CD45 + progenitors that produce macrophages. Here we investigated whether they are also vasculogenic. In aortas of C57BL/6 mice, Sca-1 + CD45 + cells were localised to adventitia and lacked surface expression of endothelial markers ( % for CD31, CD144, TIE-2). In contrast, they did show expression of CD31, CD144, TIE-2 and VEGFR2 in atherosclerotic ApoE −/− aortas. Although Sca-1 + CD45 + cells from C57BL/6 aorta did not express CD31, they formed CD31 + colonies in endothelial differentiation media and produced interconnecting vascular-like cords in Matrigel that contained both endothelial cells and a small population of macrophages, which were located at branch points. Transfer of aortic Sca-1 + CD45 + cells generated endothelial cells and neovessels de novo in a hindlimb model of ischaemia and resulted in a 50% increase in perfusion compared to cell-free control. Similarly, their injection into the carotid adventitia of ApoE −/− mice produced donor-derived adventitial and peri-adventitial microvessels after atherogenic diet, suggestive of newly formed vasa vasorum. These findings show that beyond its content of macrophage progenitors, adventitial Sca-1 + CD45 + cells are also vasculogenic and may be a source of vasa vasorum during atherogenesis.
Publisher: Springer Science and Business Media LLC
Date: 09-01-2022
Publisher: Springer Science and Business Media LLC
Date: 22-06-2022
DOI: 10.1007/S11160-022-09716-9
Abstract: Coral reef fishes often exhibit specific or restricted depth distributions, but the factors (biotic or abiotic) that influence patterns of depth use are largely unknown. Given inherent biological gradients with depth (i.e. light, nutrients, habitat, temperature), it is expected that fishes may exploit certain depths within their environment to seek out more favourable conditions. This study used baited remote underwater video (BRUV) systems to document variation in the taxonomic and functional (trophic and size) structure of a fish assemblage along a shallow to upper-mesophotic depth gradient (13–71 m) at a submerged, offshore shoal in the northern Great Barrier Reef. BRUVs were deployed during two separate time periods (February and August 2017), to separately examine patterns of depth use. Both the relative abundance and ersity of reef fishes declined with depth, and there were pronounced differences in the taxonomic and functional structure of the fish assemblage across the depth gradient. In shallow habitats ( 30 m), the fish assemblage was dominated by herbivores, detritivores, planktivores and sessile invertivores, whereas the fish assemblage in deeper habitats ( 30 m) was dominated by piscivores and mobile invertivores. Depth and habitat type were also strong predictors for important fisheries species such as coral trout ( Plectropomus spp.), emperors ( Lethrinus spp.) and trevallies (Carangid spp.). We found limited evidence of temporal changes in depth and habitat use by fishes (including fisheries target species), although recorded temperatures were 4 °C higher in February 2017 compared to August 2017.
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.EXPHEM.2016.12.001
Abstract: The proliferation, differentiation, adhesion, and migration of hematopoietic stem and progenitor cells (HSPCs) are dependent upon bone marrow stromal cells (BMSCs). In this study, we found that human primitive HSPCs (CD34
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.MARENVRES.2022.105673
Abstract: Algal turfs are the most abundant benthic covering on reefs in many shallow-water marine ecosystems. The particulates and sediments bound within algal turfs can influence a multitude of functions within these ecosystems. Despite the global abundance and importance of algal turfs, comparison of algal turf-bound sediments is problematic due to a lack of standardisation across collection methods. Here we provide an overview of three methods (vacuum s ling, airlift s ling, and TurfPods), and the necessary equipment (including construction suggestions), commonly employed to quantify sediments from algal turfs. We review the purposes of these methods (e.g. quantification of standing stock versus net accumulation) and how methods can vary depending on the research question or monitoring protocol. By providing these details in a readily accessible format we hope to encourage a standardised set of approaches for marine benthic ecologists, geologists and managers, that facilitates further quantification and global comparisons of algal turf sediments.
Publisher: Elsevier BV
Date: 08-2021
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.EXPHEM.2018.10.004
Abstract: The bone marrow stromal microenvironment contributes to the maintenance and function of hematopoietic stem rogenitor cells (HSPCs). The Eph receptor tyrosine kinase family members have been implicated in bone homeostasis and stromal support of HSPCs. The present study examined the influence of EfnB1-expressing osteogenic lineage on HSPC function. Mice with conditional deletion of EfnB1 in the osteogenic lineage (EfnB1
Publisher: Springer Science and Business Media LLC
Date: 16-10-2016
DOI: 10.1007/S12185-015-1886-X
Abstract: Bone marrow mesenchymal stromal/stem cells(BMSC) are fundamental regulatory elements of the hematopoietic stem cell niche however, the molecular signals that mediate BMSC support of hematopoiesis are poorly understood. Recent studies indicate that BMSC and hematopoietic stem rogenitors cells differentially express the Eph cell surface tyrosine kinase receptors, and their ephrinligands. Eph/ephrin interactions are thought to mediate cross-talk between BMSC and different hematopoietic cell populations to influence cell development, migration and function. This review summarizes Eph/ephrin interactions in the regulation of BMSC communication with hematopoietic stem rogenitor cells and discusses Eph/ephrintargeted therapeutic strategies that are currently being pursued or various hematotological malignancies.
Publisher: Oxford University Press (OUP)
Date: 23-06-2015
DOI: 10.1002/STEM.2069
Abstract: The tyrosine kinase receptor, EphB4, mediates cross-talk between stromal and hematopoietic populations during bone remodeling, fracture repair and arthritis, through its interactions with the ligand, ephrin-B2. This study demonstrated that transgenic EphB4 mice (EphB4 Tg), over-expressing EphB4 under the control of collagen type-1 promoter, exhibited higher frequencies of osteogenic cells and hematopoietic stem rogenitor cells (HSC), correlating with a higher frequency of long-term culture-initiating cells (LTC-IC), compared with wild type (WT) mice. EphB4 Tg stromal feeder layers displayed a greater capacity to support LTC-IC in vitro, where blocking EphB4/ephrin-B2 interactions decreased LTC-IC output. Similarly, short hairpin RNA-mediated EphB4 knockdown in human bone marrow stromal cells reduced their ability to support high ephrin-B2 expressing CD34+ HSC in LTC-IC cultures. Notably, irradiated EphB4 Tg mouse recipients displayed enhanced bone marrow reconstitution capacity and enhanced homing efficiency of transplanted donor hematopoietic stem rogenitor cells relative to WT controls. Studies examining the expression of hematopoietic supportive factors produced by stromal cells indicated that CXCL12, Angiopoietin-1, IL-6, FLT-3 ligand, and osteopontin expression were more highly expressed in EphB4 Tg stromal cells compared with WT controls. These findings indicate that EphB4 facilitates stromal-mediated support of hematopoiesis, and constitute a novel component of the HSC niche. Stem Cells 2015 :2838—2849
Publisher: Springer Science and Business Media LLC
Date: 14-01-2022
Publisher: Elsevier BV
Date: 07-2021
Publisher: CSIRO Publishing
Date: 2010
DOI: 10.1071/CP09140
Abstract: The identification of genetic variation using molecular markers is fundamental to modern plant breeding and research. The present study was undertaken to develop a resource of informative single nucleotide polymorphism (SNP) markers for molecular characterisation of Australian barley germplasm. In total, 190 SNP markers were developed and characterised using 88 elite barley lines and varieties, s ling genetic ersity relevant to Australian breeding programs, and a core set of 48 SNPs for distinguishing among the barley lines was identified. The utility of the core 48-SNP set for distinguishing barley lines and varieties using DNA extracted from grain s les was also assessed. Finally, the 48 SNPs in the core set were converted into simple PCR markers to enable co-dominant SNP genotyping on agarose gel. The SNP markers developed, and in particular the core 48-SNP set, provide a useful marker resource for assessing genetic relationships between in iduals and populations of current Australian barley germplasm. They are also useful for identity and purity testing of inbred lines in research, breeding, and commercial applications.
Publisher: Oxford University Press (OUP)
Date: 31-12-2016
DOI: 10.1002/STEM.2265
Abstract: Twist-1 encodes a basic helix-loop-helix transcription factor, known to contribute to mesodermal and skeletal tissue development. We have reported previously that Twist-1 maintains multipotent human bone marrow-derived mesenchymal stem/stromal cells (BMSC) in an immature state, enhances their life-span, and influences cell fate determination. In this study, human BMSC engineered to express high levels of Twist-1 were found to express elevated levels of the chemokine, CXCL12. Analysis of the CXCL12 proximal promoter using chromatin immunoprecipitation analysis identified several E-box DNA sites bound by Twist-1. Functional studies using a luciferase reporter construct showed that Twist-1 increased CXCL12 promoter activity in a dose dependent manner. Notably, Twist-1 over-expressing BMSC exhibited an enhanced capacity to maintain human CD34 + hematopoietic stem cells (HSC) in long-term culture-initiating cell (LTC-IC) assays. Moreover, the observed increase in HSC maintenance by Twist-1 over-expressing BMSC was blocked in the presence of the CXCL12 inhibitor, AMD3100. Supportive studies, using Twist-1 deficient heterozygous mice demonstrated a significant decrease in the frequency of stromal progenitors and increased numbers of osteoblasts within the bone. These observations correlated to a decreased incidence in the number of clonogenic stromal progenitors (colony forming unit–fibroblasts) and lower levels of CXCL12 in Twist-1 mutant mice. Furthermore, Twist-1 deficient murine stromal feeder layers, exhibited a significant decrease in CXCL12 levels and lower numbers of hematopoietic colonies in LTC-IC assays, compared with wild type controls. These findings demonstrate that Twist-1, which maintains BMSC at an immature state, endows them with an increased capacity for supporting hematopoiesis via direct activation of CXCL12 gene expression.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.MARENVRES.2021.105537
Abstract: The world's coral reef ecosystems are steadily being reconfigured by climate change. Lizard Island, on Australia's Great Barrier Reef, offers an opportunity to examine coral reef reassembly following disturbance, as this location has been impacted by consecutive tropical cyclones and consecutive coral bleaching events. Based on repeatedly monitoring the same 349 photoquadrats around Lizard Island over a 5-year period (2016-2021) we revealed that bleaching in 2016 drove a ∼50% reduction in hard coral cover, and a concomitant increase in algal turf cover. From 2018 to 2021, significant increases (>600%) in coral cover were detected on two semi-exposed reefs and were associated with substantial Acropora recruitment. By contrast, fourteen lagoonal and back reefs exhibited virtually no recovery nor Acropora recruitment. Given that the timeframe between disturbances is set to decrease, our results suggest that some recovery is possible immediately after severe cumulative disturbances, although this recovery may be highly spatially heterogenous.
Publisher: Springer Science and Business Media LLC
Date: 2008
Publisher: Springer Science and Business Media LLC
Date: 24-08-2018
DOI: 10.1038/S41598-018-31190-2
Abstract: The present study investigated the effects of conditional deletion of ephrinB1 in osteoprogenitor cells driven by the Osterix ( Osx ) promoter, on skeletal integrity in a murine model of ovariectomy-induced (OVX) osteoporosis. Histomorphometric and μCT analyses revealed that loss of ephrinB1 in sham Osx:cre-ephrinB1 fl/fl mice caused a reduction in trabecular bone comparable to OVX Osx:Cre mice, which was associated with a significant reduction in bone formation rates and decrease in osteoblast numbers. Interestingly, these observations were not exacerbated in OVX Osx:cre-ephrinB1 fl/fl mice. Furthermore, sham Osx:cre-ephrinB1 fl/fl mice displayed significantly higher osteoclast numbers and circulating degraded collagen type 1 compared to OVX Osx:Cre mice. Confirmation studies found that cultured monocytes expressing EphB2 formed fewer TRAP + multinucleated osteoclasts and exhibited lower resorption activity in the presence of soluble ephrinB1-Fc compared to IgG control. This inhibition of osteoclast formation and function induced by ephrinB1-Fc was reversed in the presence of an EphB2 chemical inhibitor. Collectively, these observations suggest that ephrinB1, expressed by osteoprogenitors, influences bone loss during the development of osteoporosis, by regulating both osteoblast and osteoclast formation and function, leading to a loss of skeletal integrity.
Publisher: The Company of Biologists
Date: 15-09-2010
DOI: 10.1242/JCS.063834
Abstract: Ovarian folliculogenesis is driven by the combined action of endocrine cues and paracrine factors. The oocyte secretes powerful mitogens, such as growth differentiation factor 9 (GDF9), that regulate granulosa cell proliferation, metabolism, steroidogenesis and differentiation. This study investigated the role of the epidermal growth factor receptor (EGFR)–extracellular signal-regulated kinase 1 and 2 (ERK1/2 also known as MAPK3/1) signaling pathway on GDF9 action on granulosa cells. Results show that mitogenic action of the oocyte is prevented by pharmacological inhibition of the EGFR–ERK1/2 pathway. Importantly, EGFR–ERK1/2 activity as well as rous sarcoma oncogene family kinases (SFK) are required for signaling through SMADs, mediating GDF9, activin A and TGFβ1 mitogenic action in granulosa cells. GDF9 could not activate ERK1/2 or affect EGF-stimulated ERK1/2 in granulosa cells. However, induction of the SMAD3-specific CAGA reporter by GDF9 in granulosa cells required active EGFR, SFKs and ERK1/2 as did GDF9-responsive gene expression. Finally, the EGFR–SFKs–ERK1/2 pathway was shown to be required for the maintenance of phosphorylation of the SMAD3 linker region. Together our results suggest that receptivity of granulosa cells to oocyte-secreted factors, including GDF9, is regulated by the level of activation of the EGFR and resulting ERK1/2 activity, through the requisite permissive phosphorylation of SMAD3 in the linker region. Our results indicate that oocyte-secreted TGFβ-like ligands and EGFR–ERK1/2 signaling are cooperatively required for the unique granulosa cell response to the signal from oocytes mediating granulosa cell survival and proliferation and hence the promotion of follicle growth and ovulation.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.BONE.2016.09.009
Abstract: The EphB receptor tyrosine kinase family and their ephrinB ligands have been implicated as mediators of skeletal development and bone homeostasis in humans, where mutations in ephrinB1 contribute to frontonasal dysplasia and coronal craniosynostosis. In mouse models, ephrinB1 has been shown to be a critical factor mediating osteoblast function. The present study examined the functional importance of ephrinB1 during endochondral ossification using the Cre recombination system with targeted deletion of ephrinB1 (EfnB1
Publisher: Springer Science and Business Media LLC
Date: 09-08-2008
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.MARENVRES.2022.105763
Abstract: Sediments are ubiquitous on coral reefs. However, studies of reef sediments have largely focused on isolated reservoirs, or processes, and rarely consider hydrodynamic drivers. We therefore provide a quantitative snapshot of sediment dynamics on a coral reef. Across a depth profile, we simultaneously examined: suspended sediments, sediment deposition and accumulation, and hydrodynamic and biological movement processes. We reveal the marked potential for the water column to deliver sediments. Currents carried 12.6 t of sediment over the 2,314 m
Publisher: American Chemical Society (ACS)
Date: 18-07-2023
Publisher: OMICS Publishing Group
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 22-09-2021
DOI: 10.1038/S41598-021-98239-7
Abstract: Thermal-stress events have changed the structure, bio ersity, and functioning of coral reefs. But how these disturbances affect the dynamics of in idual coral colonies remains unclear. By tracking the fate of 1069 in idual Acropora and massive Porites coral colonies for up to 5 years, spanning three bleaching events, we reveal striking genus-level differences in their demographic response to bleaching (mortality, growth, and recruitment). Although Acropora colonies were locally extirpated, substantial local recruitment and fast growth revealed a marked capacity for apparent recovery. By contrast, almost all massive Porites colonies survived and the majority grew in area yet no new colonies were detected over the 5 years. Our results highlight contrasting dynamics of boom-and-bust vs. protracted declines in two major coral groups. These dangerous demographics emphasise the need for caution when documenting the susceptibility and perceived resistance or recovery of corals to disturbances.
Publisher: American Society of Hematology
Date: 30-06-2022
Abstract: Inducing cell death by the sphingolipid ceramide is a potential anticancer strategy, but the underlying mechanisms remain poorly defined. In this study, triggering an accumulation of ceramide in acute myeloid leukemia (AML) cells by inhibition of sphingosine kinase induced an apoptotic integrated stress response (ISR) through protein kinase R–mediated activation of the master transcription factor ATF4. This effect led to transcription of the BH3-only protein Noxa and degradation of the prosurvival Mcl-1 protein on which AML cells are highly dependent for survival. Targeting this novel ISR pathway, in combination with the Bcl-2 inhibitor venetoclax, synergistically killed primary AML blasts, including those with venetoclax-resistant mutations, as well as immunophenotypic leukemic stem cells, and reduced leukemic engraftment in patient-derived AML xenografts. Collectively, these findings provide mechanistic insight into the anticancer effects of ceramide and preclinical evidence for new approaches to augment Bcl-2 inhibition in the therapy of AML and other cancers with high Mcl-1 dependency.
Start Date: 2020
End Date: 2021
Funder: University of South Australia
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