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Waddell N.,Queensland Institute of Medical Research | Waddell N.,Institute for Molecular Bioscience | Cocciardi S.,Queensland Institute of Medical Research | Johnson J.,Queensland Institute of Medical Research | And 9 more authors.
Journal of Pathology | Year: 2010

Tissue sample acquisition is a limiting step in many studies. There are many thousands of formalin-fixed, paraffin-embedded archival blocks collected around the world, but in contrast relatively few fresh frozen samples in tumour banks. Once samples are fixed in formalin, the RNA is degraded and traditional methods for gene expression profiling are not suitable. In this study, we have evaluated the ability of the whole genome DASL (cDNA-mediated Annealing, Selection, extension, and Ligation) assay from Illumina to perform transcriptomic analysis of archived breast tumour tissue in formalin-fixed, paraffin-embedded (FFPE) blocks. We profiled 76 familial breast tumours from cases carrying a BRCA1, BRCA2 or ATM mutation, or from non- BRCA1/2 families. We found that replicate samples correlated well with each other (r2 = 0.9-0.98). In 12/15 cases, the matched formalin-fixed and frozen samples predicted the same tumour molecular subtypes with confidence. These results demonstrate that the whole genome DASL assay is a valuable tool to profile degraded RNA from archival FFPE material. This assay will enable transcriptomic analysis of a large number of archival samples that are stored in pathology archives around the globe and consequently will have the potential to improve our understanding and characterization of many diseases. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Source


Han S.P.,University of Queensland | Kassahn K.S.,University of Queensland | Kassahn K.S.,Institute for Molecular Bioscience | Skarshewski A.,University of Queensland | And 3 more authors.
RNA | Year: 2010

The heterogeneous nuclear ribonucleoproteins (hnRNPs) A/B are a family of RNA-binding proteins that participate in various aspects of nucleic acid metabolism, including mRNA trafficking, telomere maintenance, and splicing. They are both regulators and targets of alternative splicing, and the patterns of alternative splicing of their transcripts have diverged between paralogs and between orthologs in different species. Surprisingly, the extent of this splicing variation and its implications for post-transcriptional regulation have remained largely unexplored. Here, we conducted a detailed analysis of hnRNP A/B sequences and expression patterns across six vertebrates. Alternative exons emerged via the introduction of new splice sites, changes in the strengths of existing splice sites, and the accumulation of auxiliary splicing regulatory motifs. Observed isoform expression patterns could be attributed to the frequency and strength of cis-elements. We found a trend toward increased splicing variation in mammals and identified novel alternatively spliced isoforms in human and chicken. Pulldown and translational assays demonstrated that the inclusion of alternative exons altered the affinity of hnRNP A/B proteins for their cognate nucleic acids and modified protein expression levels. As the hnRNPs A/B regulate several key steps in mRNA processing, the involvement of diverse hnRNP isoforms in multiple cellular contexts and species implies concomitant differences in the transcriptional output of these systems. We conclude that the emergence of alternative splicing in the hnRNPs A/B has contributed to the diversification of their roles in the regulation of alternative splicing and has thus added an unexpected layer of regulatory complexity to transcription in vertebrates. Copyright © 2010 RNA Society. Source


News Article
Site: http://phys.org/chemistry-news/

School of Biomedical Sciences researcher Dr Richard Clark said marine snail venom was a well-known and promising source of new pain drugs, but substantial hurdles had restrained progress. "Translating the venom's toxins into a viable drug has proved difficult," Dr Clark said. "But now we've been able to identify a core component of one of these conotoxins (toxins from cone snail venom) during laboratory tests. "We think this will make it much easier to translate the active ingredient into a useful drug." Dr Clark said a sea snail used its venom to immobilise prey and protect itself. "The venom's analgesic properties have been well researched," he said. "In this study, we've been able to shrink a particular conotoxin to its minimum necessary components for the pain relief properties to continue to work. "Using a laboratory rat model, we used the modified conotoxin to successfully treat pain generated in the colon, similar to that experienced by humans with irritable bowel syndrome. "Although the conotoxin has been modified, its pain relief properties remained as effective as the full-size model. "Simplifying the conotoxin will make a drug much faster and cheaper to develop." Dr Clark said further research was under way to improve the modified conotoxin's stability and to test its ability to treat other types of pain. The research, published in Angewandte Chemie International Edition, was undertaken in collaboration with Professor David Craik at UQ's Institute for Molecular Bioscience, Professor David Adams at the Royal Melbourne Institute of Technology and Associate Professor Stuart Brierley at the University of Adelaide. Explore further: Cone snails and plants used to develop oral drug for pain More information: Bodil B. Carstens et al. Structure-Activity Studies of Cysteine-Rich α-Conotoxins that Inhibit High-Voltage-Activated Calcium Channels via GABA Receptor Activation Reveal a Minimal Functional Motif , Angewandte Chemie International Edition (2016). DOI: 10.1002/anie.201600297


News Article | March 10, 2016
Site: http://cleantechnica.com

A new study based on new modeling has shown that the average global temperature could rise by 1.5 degrees as early as 2020. According to a new study published by researchers from the University of Queensland and Griffith University in Australia, global warming could occur much more quickly than previously thought. The study is based on a new first-of-its-kind model which includes “energy use per person” as a predictive factor, rather than solely on economics or populations. The model forecasts that population and economic growth, combined with rising energy use per person could dramatically impact global energy demand, and subsequently CO2 emissions, making for an increase in the global average temperature by 1.5 degrees as early as 2020. “Nations at the 2015 UN Conference on Climate Change agreed to keep the rise in global average temperature below 2 degrees Celsius, preferably limiting it to 1.5 degrees to protect island states,” said Professor Hankamer, who along with Dr Liam Wagner developed the model. “Our model shows we may have less time left than expected to prevent world temperature from rising above these thresholds.” “World population is forecast to increase to over 9 billion people by 2050, which, together with international ‘pro-growth’ strategies, will lead to continually increasing energy demand.” As a result, according to Professor Hankamer, the global energy sector must transition away from fossil fuel-based energy sources towards renewable energy sources in an attempt to control global temperature averages. “The sun is by far the largest renewable energy source,” said Hankamer, a professor from the University of Queensland’s Institute for Molecular Bioscience. “In just two hours it delivers enough solar energy to the Earth’s surface to power the entire global economy for a year –  and now is the time to make the switch.” Hankamer also believes there currently exists a quick first step to bolster such a transition. “A cost-neutral strategy that governments should consider to fast track this transition is diverting the $500 billion used to subsidise the fossil fuel industry internationally to assist the global renewable sector.” “We have a choice: leave people in poverty and speed towards dangerous global warming through the increased use of fossil fuels, or transition rapidly to renewables,” added Dr Liam Wagner, who partnered with Professor Hankamer in developing the model. “As 80 per cent of world energy is used as fuels and only 20 per cent as electricity, renewable fuels in particular will be critical.”    Get CleanTechnica’s 1st (completely free) electric car report → “Electric Cars: What Early Adopters & First Followers Want.”   Come attend CleanTechnica’s 1st “Cleantech Revolution Tour” event → in Berlin, Germany, April 9–10.   Keep up to date with all the hottest cleantech news by subscribing to our (free) cleantech newsletter, or keep an eye on sector-specific news by getting our (also free) solar energy newsletter, electric vehicle newsletter, or wind energy newsletter.  


Achard M.E.S.,University of Queensland | Chen K.W.,University of Queensland | Sweet M.J.,Institute for Molecular Bioscience | Watts R.E.,University of Queensland | And 3 more authors.
Biochemical Journal | Year: 2013

Iron acquisition is an important aspect of the host-pathogen interaction. In the case of Salmonella it is established that catecholate siderophores are important for full virulence. In view of their very high affinity for ferric iron, functional studies of siderophores have been almost exclusively focused on their role in acquisition of iron from the host. In the present study, we investigated whether the siderophores (enterobactin and salmochelin) produced by Salmonella enterica sv. Typhimurium could act as antioxidants and protect from the oxidative stress encountered after macrophage invasion. Our results show that the ability to produce siderophores enhanced the survival of Salmonella in the macrophage mainly at the early stages of infection, coincident with the oxidative burst. Using siderophore biosynthetic and siderophore receptor mutants we demonstrated that salmochelin and enterobactin protect S. Typhimurium against ROS (reactive oxygen species) in vitro and that siderophores must be intracellular to confer full protection. We also investigated whether other chemically distinct siderophores (yersiniabactin and aerobactin) or the monomeric catechol 2,3-dihydroxy-benzoate could provide protection against oxidative stress and found that only catecholate siderophores have this property. Collectively, the results of the present study identify additional functions for siderophores during host-pathogen interactions. © 2013 Biochemical Society. Source

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