192 research outputs found
Natriuretic peptide receptors regulate cytoprotective effects in an ex vivo human 3D/bioreactor model
No full textIntroductionThe present study examined the effect of C-type natriuretic peptide (CNP) and biomechanical signals on anabolic and catabolic activities in chondrocyte/agarose constructs.MethodsNatriuretic peptide (Npr) 2 and 3 expression were compared in non-diseased (grade 0/1) and diseased (grade IV) human cartilage by immunofluoresence microscopy and western blotting. In separate experiments, constructs were cultured under free-swelling conditions or subjected to dynamic compression with CNP, interleukin-1β (IL-1β), the Npr2 antagonist P19 or the Npr3 agonist cANF4-23. Nitric oxide (NO) production, prostaglandin E2 (PGE2) release, glycosaminoglycan (GAG) synthesis and CNP concentration were quantified using biochemical assays. Gene expression of Npr2, Npr3, CNP, aggrecan and collagen type II were assessed by real-time qPCR. Two-way ANOVA and a post hoc Bonferroni-corrected t-test were used to analyse the data.ResultsThe present study demonstrates increased expression of natriuretic peptide receptors in diseased or older cartilage (age 70) when compared to non-diseased tissue (age 60) which showed minimal expression. There was strong parallelism in the actions of CNP on cGMP induction resulting in enhanced GAG synthesis and reduction of NO and PGE2 release induced by IL-1β. Inhibition of Npr2 with P19 maintained catabolic activities whilst specific agonism of Npr3 with cANF4-23 had the opposite effect and reduced NO and PGE2 release. Co-stimulation with CNP and dynamic compression enhanced anabolic activities and inhibited catabolic effects induced by IL-1β. The presence of CNP and the Npr2 antagonist abolished the anabolic response to mechanical loading and prevented loading-induced inhibition of NO and PGE2 release. In contrast, the presence of the Npr3 agonist had the opposite effect and increased GAG synthesis and cGMP levels in response to mechanical loading and reduced NO and PGE2 release comparable to control samples. In addition, CNP concentration and natriuretic peptide receptor expression were increased with dynamic compression.ConclusionsMechanical loading mediates endogenous CNP release leading to increased natriuretic peptide signalling. The loading-induced CNP/Npr2/cGMP signalling route mediates anabolic events and prevents catabolic activities induced by IL-1β. The CNP pathway therefore represents a potentially chondroprotective intervention for patients with OA, particularly when combined with physiotherapeutic approaches to stimulate biomechanical signals.<br/
The race that stops the nation also holds many weird and wonderful stories
No full textIt's that first Tuesday in November again, which means that famous Australian horse race - you know the one - will be run this afternoon. It has produced many wonderful stories in its long history and today, author Wayne Peake writes about some of the lesser known (and rather quirky) Cup tales
Peake Creek Seismic, Gravity (P197046), gravity point data
No full textMaintenance and Update Frequency: notPlannedStatement: This Peake Creek Seismic, Gravity (P197046), gravity point data contains ground gravity point data for the Peake Creek Seismic, Gravity (P197046) survey acquired for Pexa Oil NL. This dataset contains a total of 378 point data values. The data is located in SA and were acquired in 1970. The point located data were collected in grid layout at an average station spacing of 533 metres.
Terrain corrections were calculated using the INTREPID Geophysics software package. The processed data are checked by GA geophysicists using standard methods for assessing quality to ensure that the final data are fit-for-purpose.
All data are provided in EPSG:4283 coordinates, Australian Height Datum (AHD) and gravity datum of AAGD07. The units are degrees, meters, and micrometres per second squared, respectively.
Reference:
Intrepid Geophysics, http://www.intrepid-geophysics.com.Gravity data measures small changes in gravity due to changes in the density of rocks beneath the Earth's surface. The data collected are processed via standard methods to ensure the response recorded is that due only to the rocks in the ground. The results produce datasets that can be interpreted to reveal the geological structure of the sub-surface. The processed data is checked for quality by GA geophysicists to ensure that the final data released by GA are fit-for-purpose.<br/> This Peake Creek Seismic, Gravity (P197046) contains a total of 378 point data values acquired at a spacing of 533 metres. The data is located in SA and were acquired in 1970, under project No. 197046 for Pexa Oil NL
Mount Peake-Crawford - Th equivalent concentration grid (AWAGS)
No full textMaintenance and Update Frequency: notPlannedStatement: This Mount Peake-Crawford - Th equivalent concentration grid (AWAGS) is an airborne-derived radiometric thorium grid for the NTGS Mount Peake-Crawford Magnetic, Radiometric and Elevation Survey, NT 2019. The survey was acquired under the project No. 1319 for the geological survey of NT. The grid has a cell size of 0.00019 degrees (approximately 20m). A total of 136990 line-kilometres of data at a line spacing of 200m and 60m terrain clearance were acquired to produce this grid. This radiometric thorium grid shows thorium element concentration of the NTGS Mount Peake-Crawford Magnetic, Radiometric and Elevation Survey, NT 2019 in units of parts per million (or ppm). Noise-adjusted singular value decomposition (NASVD) has been applied to the data. NASVD is a spectral component analysis procedure for the removal of noise from gamma-ray spectra. To constrain long wavelengths in the grid, an independent data set, the Australia-wide Airborne Geophysical Survey (AWAGS) airborne magnetic data, was used to control the base levels of the survey grid (Milligan et al., 2009). This survey grid is essentially levelled to AWAGS. Details of the specifications of individual airborne surveys can be found in the Fourteenth Edition of the Index of Airborne Geophysical Surveys (Percival, 2014). This Index is also available online at http://pid.geoscience.gov.au/dataset/79134.
References:
Milligan, P.R., Minty, B.R.S., Richardson, M. & Franklin, R., 2009. The Australia-wide Airborne Geophysical Survey accurate continental magnetic coverage. Preview, No. 138, p. 1-128,
Percival, P.J., 2014. Index of airborne geophysical surveys (Fourteenth Edition).The radiometric, or gamma-ray spectrometric method, measures the natural variations in the gamma-rays detected near the Earth's surface as the result of the natural radioactive decay of potassium (K), uranium (U) and thorium (Th). The data collected are processed via standard methods to ensure the response recorded is that due only to the rocks in the ground. The results produce datasets that can be interpreted to reveal the geological structure of the sub-surface. The processed data is checked for quality by GA geophysicists to ensure that the final data released by GA are fit-for-purpose.<br/>This radiometric thorium grid has a cell size of 0.00019 degrees (approximately 20m) and shows thorium element concentration of the NTGS Mount Peake-Crawford Magnetic, Radiometric and Elevation Survey, NT 2019 in units of parts per million (or ppm). The data used to produce this grid was acquired in 2019 by the NT Government, and consisted of 136990 line-kilometres of data at 200m line spacing and 60m terrain clearance. To constrain long wavelengths in the grid, an independent data set, the Australia-wide Airborne Geophysical Survey (AWAGS) airborne magnetic data, was used to control the base levels of the survey grid
Arunta Complex(Mt Peake,Napperby,Hermannsburg,Al.Springs),NT, 1976 (P437), radiometric line data, AWAGS levelled
No full textMaintenance and Update Frequency: notPlannedStatement: This Arunta Complex(Mt Peake,Napperby,Hermannsburg,Al.Springs),NT, 1976 (P437), radiometric line data, AWAGS levelled is an airborne-derived radiometric data for the Arunta Complex(Mt Peake,Napperby,Hermannsburg,Al.Springs),NT, 1976. The data was acquired under the project No. 437 for the geological survey of NT. A total of 38658 line-kilometres of data at a line spacing of 1500m were acquired during this survey. To constrain long wavelengths in the data, an independent data set, the Australia-wide Airborne Geophysical Survey (AWAGS) airborne magnetic data, was used to control the base levels of the survey data (Milligan et al., 2009). This survey data is essentially levelled to AWAGS. Noise-adjusted singular value decomposition (NASVD) has been applied to the data. NASVD is a spectral component analysis procedure for the removal of noise from gamma-ray spectra. Details of the specifications of individual airborne surveys can be found in the Fourteenth Edition of the Index of Airborne Geophysical Surveys (Percival, 2014). This Index is also available online at http://pid.geoscience.gov.au/dataset/79134.
References:
Milligan, P.R., Minty, B.R.S., Richardson, M. & Franklin, R., 2009. The Australia-wide Airborne Geophysical Survey accurate continental magnetic coverage. Preview, No. 138, p. 1-128,
Percival, P.J., 2014. Index of airborne geophysical surveys (Fourteenth Edition).The radiometric, or gamma-ray spectrometric method, measures the natural variations in the gamma-rays detected near the Earth's surface as the result of the natural radioactive decay of potassium (K), uranium (U) and thorium (Th). The data collected are processed via standard methods to ensure the response recorded is that due only to the rocks in the ground. The results produce datasets that can be interpreted to reveal the geological structure of the sub-surface. The processed data is checked for quality by GA geophysicists to ensure that the final data released by GA are fit-for-purpose.<br/> This Arunta Complex(Mt Peake,Napperby,Hermannsburg,Al.Springs),NT, 1976 (P437), radiometric line data, AWAGS levelled were acquired in 1976 by the NT Government, and consisted of 38658 line-kilometres of data at 1500m line spacing and 100m terrain clearance. To constrain long wavelengths in the data, an independent data set, the Australia-wide Airborne Geophysical Survey (AWAGS) airborne magnetic data, was used to control the base levels of the survey data. This survey data is essentially levelled to AWAGS
Merged Magnetic, Radiometric and Elevation Grids for the NTGS Mount Peake-Crawford Survey, 2019
No full textMaintenance and Update Frequency: asNeededStatement: Various grids were produced from the Mount Peake-Crawford Airborne Magnetic and Radiometric Survey dataset and simultaneously merged into a single grid file. The final grids retains all of the information from the input data and are levelled to the national map compilations produced by Geoscience Australia, as well as to the Australia-Wide Airborne Geophysical Surveys (AWAGS, Milligan et al., 2009). The merged grids have a cell size of 0.000189 degrees or approximately 20m.
Original point-located data is available from: https://geoscience.nt.gov.au/gemis/ntgsjspui/handle/1/89885. The final grids were generated from the NTGS dataset using Intrepid v5.6.4 and merged using a process developed within Geoscience Australia referred to as Grid Merge (Minty et al., 2003). The Grid Merge process is implemented in Intrepid software's Grid Merge Tool.
References
Milligan, P.R., Minty, B.R.S., Richardson, M. and Franklin, R., 2009. The Australia-wide Airborne Geophysical Survey accurate continental magnetic coverage. ASEG Extended Abstracts, 2009 (1), 1-9.
Minty, B.R.S., Milligan, P.R., Luyendyk, A.P.J. and Mackey, T., 2003, Merging airborne magnetic surveys into continental-scale compilations. Geophysics, 68 (3), 988-995.<b>Purpose</b><br/>Analysis<p>The Northern Territory Geological Survey (NTGS) designed the Mount Peake-Crawford survey to provide high resolution magnetic, radiometric and elevation data in the area. It is anticipated that the data from the survey would help attract explorers into ‘greenfield’ terranes and contribute to the discovery of the next generation of major mineral and energy deposits in the Northern Territory. A total of 120,000 line km of regional data (200m line spacing) and additional infill data (100m line spacing), flown at 60m flight height were acquired during the survey between July and October 2019. The survey was managed by Geoscience Australia. <br/><br/><p>Various grids were produced from the Mount Peake-Crawford Airborne Magnetic and Radiometric Survey dataset and simultaneously merged into a single grid file. The final grid retains all of the information from the input data and is levelled to the national map compilations produced by Geoscience Australia. The merged grids have a cell size of 20m. <br/><p>The following merged grids are available in this download:<br/><p>• Laser-derived digital elevation model grids (m). Height relative to the Australian Height Datum.<br/><p>• Radar-derived digital elevation model grids (m). Height relative to the Australian Height Datum.<br/><p>• Total magnetic intensity grid (nT).<br/><p>• Total magnetic intensity grid with variable reduction to the pole applied (nT).<br/><p>• Total magnetic intensity grid with variable reduction to the pole and first vertical derivative applied (nT/m).<br/><p>• NASVD-filtered potassium concentration grid (%).<br/><p>• NASVD-filtered thorium concentration grid (ppm).<br/><p>• NASVD-filtered uranium concentration grid (ppm)
Recent changes in the initiation liturgies: a comparative study
No full textIn this thesis the author examines the recent rites of initiation within the Orthodox, Roman Catholic, Church of England, and Methodist Churches. The object is two-fold: (l) to see whether there has been convergence in the recent liturgical practice and theological understanding of initiation; and (2)' to see the extent to which the rites of the present-day mark a deliberate return to the pool of symbolic actions and words that were current in the post-apostolic period (and maybe even earlier).From the witness of Scripture it is felt that no established practice was being set before us at that time, particularly as the primary role of Scripture is as a witness to Christ rather than as a manual of devotion. The establishing of normative procedures for initiation would seem to be a post-apostolic development which took distinctive eastern and western lines of development. The Orthodox Church continues to employ the ancient rites which extend back for over twelve hundred years, and its insistence on the unity of baptism, chrismation and eucharist in theological thought and administration is characteristic. The other denominations express in their recent rites the desire to return to an archetypal service, but at the same time wishing to maintain the validity of a fragmented initiation practice. The Church of England, .and Methodism which grew from it, show increasing use of ceremonial. Most of this had been removed from the Church of England's liturgy at the Reformation. Taking note of recent work by the World Council of Churches the author concludes that convergence in liturgy and theology, though incomplete, has taken place; and further, that faithful witness is borne to the practice and understanding of the early Church of the post-apostolic period. Some aspects may date from the New Testament times
A multi-model study of extracellular vesicles in bowel cancer invasion and metastasis
No full textColorectal cancer (CRC) has one of the highest rates of cancer mortality worldwide. Despite progress in improving screening rates, approximately 35% of CRC patients are diagnosed with stage IV (metastatic) disease which has poor prognosis. In vitro 3D models have been developed which provide useful platforms to explore biomolecular processes in pre-clinical studies of cancer and metastasis, enabling the characterisation of mechanisms which can then be applied to the improvement of diagnosis, prognosis and disease treatment. Extracellular vesicles (EVs) are now known to play a critical role in cancer progression. Not only do they support cancer progression towards metastasis, but as carriers of bioactive cargo, they also show promise as potential cancer biomarkers. In this study, organotypic 3D models mimicking cancer invasion and pre-metastatic niche (PMN) in lung were developed to explore the role of EVs in advanced CRC stages and to evaluate their potential as prognostic markers.
After validating a transwell system as an effective 3D model, this work establishes that CRC EVs induce the invasion of cancer cells in a stage-dependent manner, with metastatic SW620 EVs driving a more aggressive phenotype than SW480 EVs. Proteomic profiling of the PMN showed differences in protein content upon treatment and a list of potential m/z signals able to distinguish between SW480 and SW620 EV treatment was obtained by multivariate analysis. CRC EVs also induced α-smooth muscle actin (α-SMA) expression in fibroblasts, demonstrating activation of fibroblasts in the 3D model. Expression and activity of TG2, a multifunctional enzyme involved in cancer progression, was increased after CRC EVs treatment in the 3D model of invasion. This led to the exploration of the cell-specific expression of TG2 in a cancer cells/fibroblasts co-culture, which showed an EV-mediated increase of TG2 on the surface of cancer cells and a non-EV mediated decrease of TG2 expression in the fibroblast surface. TG2 activity was further explored in hepatic stellate cells, crucial cellular components of liver metastasis. Finally, a pilot biomarker study on a small cohort of patients was performed, using multivariate analysis of cell responses to plasma-derived EVs and was able to separate patients according to disease stage.
The 3D models established and validated provided biomolecular information about the complex milieu of factors involved in CRC progression, including EVs, thus confirming the importance of 3D culture modelling in pre-clinical research. Moreover, this study was able to demonstrate key roles of cancer EVs on cellular activities which could then be translated for the development of alternative screening and prognostic approaches which may have application in improving the early diagnosis of patients with CRC
Interaction and Functional Impact of Colorectal Cancer Extracellular Vesicles on Escherichia coli
No full textThe human gut microbiota plays a vital role in regulating various physiological processes, and alterations in the composition and function of the microbial community (dysbiosis) are associated with the pathogenesis of colorectal cancer (CRC). Although the causative link between CRC and microbiota is widely investigated, the underlying microbiota-tumour interactions are not well understood, yet. It is evident that CRC-derived extracellular vesicles (EVs) have an impact on various oncogeneses processes, however, their impact on the surrounding microbiota is not clear. Therefore, this project hypothesises that EVs have an impact on the microbiota, supporting the disease-linked interactions between host and microbiota, and contributing to dysbiosis.
CRC cell lines (SW480, SW620) were cultured in CELLine AD 1000 bioreactor flasks, blood was collected from CRC patients and healthy individuals, and colon tissue was collected from CRC patients. EVs were isolated from CRC-cell line culture media, blood plasma, and digested tissues by size-exclusion chromatography (SEC) and characterised by nanoparticle flow cytometry (NanoFCM), western blotting, ELISA, and transmission electron microscopy (TEM). Confocal microscopy, TEM, Flow cytometry, and EVs-enzymatic treatments were performed to assess the interactions between EVs and E. coli strains (E. coli MG1655 (Laboratory strain) and E. coli 11G5 (CRC-associated strain)). Also, the impact of the EVs on E. coli phenotypic characteristics, growth and biofilm formation, and bacterial transcriptome were assessed by turbidimetric assay, microtiter plate assay, and transcriptomic analysis, respectively.
NanoFCM analysis showed a high yield of EVs with characteristic size profiles, EV markers detection confirmed the presence of EVs, and TEM revealed the double-membranous structure of EVs. TEM analysis indicated an interaction between the EVs and E. coli with clear surface binding. Flow cytometry analysis showed that E. coli-EVs interactions are disease-stage specific and bacterial-strain specific. EV treatment had an impact on bacterial phenotypic characteristics; an increase in E. coli growth and a decrease in the ability of the bacteria to form biofilm were observed. It also resulted in an upregulation of genes which are involved in bacterial motility, the flagella structure of E. coli such as fliA, and a downregulation of genes involved in the zinc-ion uptake system such as ZinT. Overall, EVs appeared to be capable of mediating CRC-microbiome interactions and altering bacterial phenotypes; bacterial growth and ability to form biofilm
Transglutaminase-2 mediates the biomechanical properties of the colorectal cancer tissue microenvironment that contribute to disease progression
No full textColorectal cancer is the third most common cancer worldwide, and the fourth leading cause of malignancy-related mortality. This highlights the need to understand the processes driving this disease in order to develop new treatments and improve patient outcomes. A potential therapeutic target is the increased stiffness of the tumour microenvironment, which is linked to aggressive cancer cell behaviour by enhancing biomechanical signalling. In this study, we used an siRNA-based approach to investigate the contribution of the protein cross-linking enzyme transglutaminase-2 (TG2) to matrix remodelling and biomechanical properties of the tumour microenvironment. TG2 inhibited cancer cell growth in organotypic 3D fibroblast/SW480 co-culture models, and biomechanical analysis demonstrated that colorectal cancer cells induced fibroblast-mediated stiffness which was inhibited by silencing TG2. These biomechanical changes were associated with observed alterations to collagen fibre structure, notably fibre thickness. Our in vitro findings of collagen composition changes were also seen with imaging biopsied tissues from patients with colorectal cancer, with TG2 correlating positively with thicker collagen fibres, and associating with poor outcome as determined by disease recurrence post-surgery and overall survival. In conclusion, this study demonstrates a role for TG2 in the stromal response to invading tumour, leading to tissue stiffening and poor outcome in patients.</jats:p
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