News Article | March 1, 2017
The experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment. ARC-Net, University of Verona: approval number 1885 from the Integrated University Hospital Trust (AOUI) Ethics Committee (Comitato Etico Azienda Ospedaliera Universitaria Integrata) approved in their meeting of 17 November 2010, documented by the ethics committee 52070/CE on 22 November 2010 and formalized by the Health Director of the AOUI on the order of the General Manager with protocol 52438 on 23 November 2010. APGI: Sydney South West Area Health Service Human Research Ethics Committee, western zone (protocol number 2006/54); Sydney Local Health District Human Research Ethics Committee (X11-0220); Northern Sydney Central Coast Health Harbour Human Research Ethics Committee (0612-251M); Royal Adelaide Hospital Human Research Ethics Committee (091107a); Metro South Human Research Ethics Committee (09/QPAH/220); South Metropolitan Area Health Service Human Research Ethics Committee (09/324); Southern Adelaide Health Service/Flinders University Human Research Ethics Committee (167/10); Sydney West Area Health Service Human Research Ethics Committee (Westmead campus) (HREC2002/3/4.19); The University of Queensland Medical Research Ethics Committee (2009000745); Greenslopes Private Hospital Ethics Committee (09/34); North Shore Private Hospital Ethics Committee. Baylor College of Medicine: Institutional Review Board protocol numbers H-29198 (Baylor College of Medicine tissue resource), H-21332 (Genomes and Genetics at the BCM-HGSC), and H-32711(Cancer Specimen Biobanking and Genomics). Patients were recruited and consent obtained for genomic sequencing through the ARC-Net Research Centre at Verona University, Australian Pancreatic Cancer Genome Initiative (APGI), and Baylor College of Medicine as part of the ICGC (www.icgc.org). A patient criterion for admission to the study was that they were clinically sporadic. This information was acquired through direct interviews with participants and a questionnaire regarding their personal history and that of relatives with regard to pancreas cancers and any other cancers during anamnesis. Clinical records were also used to clarify familial history based on patient indications. Samples were prospectively and consecutively acquired through institutions affiliated with the Australian Pancreatic Cancer Genome Initiative. Samples from the ARC-Net biobank are the result of consecutive collections from a single centre. All tissue samples were processed as previously described5151. Representative sections were reviewed independently by at least one additional pathologist with specific expertise in pancreatic diseases. Samples either had full face frozen sectioning performed in optimal cutting temperature (OCT) medium, or the ends excised and processed in formalin to verify the presence of tumour in the sample to be sequenced and to estimate the percentage of neoplastic cells in the sample relative to stromal cells. Macrodissection was performed if required to excise areas that did not contain neoplastic epithelium. Tumour cellularity was determined using SNP arrays (Illumina) and the qpure tool9. PanNET is a rare tumour type and the samples were collected via an international network. We estimate that with 98 unique patients in the discovery cohort, we will achieve 90% power for 90% of genes to detect mutations that occur at a frequency of ~10% above the background rate for PanNET (assuming a somatic mutation frequency of more than 2 per Mb)52. Cancer and matched normal colonic mucosa were collected at the time of surgical resection from the Royal Brisbane and Women’s Hospital and snap frozen in liquid nitrogen. A biallelic germline mutation in the MUTYH gene was detected by restriction fragment length polymorphism analysis and confirmed by automated sequencing to be the G382D mutation (or ENST00000450313.5 G396D, ClinVar#5294) in both alleles53. The primary antibodies used for immunohistochemical staining were: cytokeratin 8/18 (5D3, Novocastra), chromogranin A (DAK-A3, Dako), and CD99 (O13, Biolegend). Antibodies and staining conditions have been described elsewhere39. Whole-genome sequencing with 100-bp paired reads was performed with a HiSEQ2000 (Illumina). Sequence data were mapped to a GRCh37 using BWA and BAM files are available in the EGA (accession number: EGAS00001001732). Somatic mutations and germline variants were detected using a previously described consensus mutation calling strategy11. Mutations were annotated with gene consequence using SNPeff. The pathogenicity of germline variants was predicted using cancer-specific and locus-specific genetic databases, medical literature, computational predictions with ENSEMBL Variant Effect Predictor (VEP) annotation, and second hits identified in the tumour genome. Intogen27 was used to find somatic genes that were significantly mutated. Somatic structural variants were identified using the qSV tool as previously described10, 11, 17. Coding mutations are included in supplementary tables and all mutations have been uploaded to the International Cancer Genome Consortium Data Coordination Center. Mutational signatures were predicted using a published framework14. Essentially, the 96-substitution classification was determined for each sample. The signatures were compared to other validated signatures and the prevalence of each signature per megabase was determined. Somatic copy number was estimated using high density SNP arrays and the GAP tool12. Arm level copy number data were clustered using Ward’s method, Euclidian distance. GISTIC13 was used to identify recurrent regions of copy number change. The whole genome sequence data was used to determine the length of the telomeres in each sample using the qMotif tool. Essentially, qMotif determines telomeric DNA content by calculating the number of reads that harbour the telomere motif (TTAGG), and then estimates the relative length of telomeres in the tumour compared to the normal. qMotif is available online (http://sourceforge.net/projects/adamajava). Telomere length was validated by qPCR as previously described54. RNASeq library preparation and sequencing were performed as previously described55. Essentially, sequencing reads were mapped to transcripts corresponding to ensemble 70 annotations using RSEM. RSEM data were normalized using TMM (weighted trimmed mean of M-values) as implemented in the R package ‘edgeR’. For downstream analyses, normalized RSEM data were converted to counts per million (c.p.m.) and log transformed. Genes without at least 1 c.p.m. in 20% of the sample were excluded from further analysis55. Unsupervised class discovery was performed using consensus clustering as implemented in the ConsensusClusterPlus R package56. The top 2,000 most variable genes were used as input. Differential gene expression analysis between representative samples was performed using the R package ‘edgeR’57. Ontology and pathway enrichment analysis was performed using the R package ‘dnet’58. PanNET class enrichment using published gene signatures44 was performed using Gene Set Variation Analysis (GSVA) as described previously55. Two strategies were used to verify fusion transcripts. For verification of EWSR1–BEND2 fusions, cDNAs were synthesized using the SuperScript VILO cDNA synthesis kit (Thermofisher) with 1 μg purified total RNA. For each fusion sequence, three samples were used: the PanNET sample containing the fusion, the PanNET sample without that fusion, and a non-neoplastic pancreatic sample. The RT–PCR product were evaluated on the Agilent 2100 Bioanalyzer (Agilent Technologies) and verified by sequencing using the 3130XL Genetic Analyzer (Life Technologies). Primers specific for EWSR1–BEND2 fusion genes are available upon request. To identify the EWSR1 fusion partner in the case ITNET_2045, a real-time RT–PCR translocation panel for detecting specific Ewing sarcoma fusion transcripts was applied as described59. Following identification of the fusion partner, PCR amplicons were subjected to sequencing using the 3130XL Genetic Analyzer. EWSR1 rearrangements were assayed on paraffin-embedded tissue sections using a commercial split-signal probe (Vysis LSI EWSR1 (22q12) Dual Colour, Break Apart Rearrangement FISH Probe Kit) that consists of a mixture of two FISH DNA probes. One probe (~500 kb) is labelled in SpectrumOrange and flanks the 5′ side of the EWSR1 gene, extending through intron 4, and the second probe (~1,100 kb) is labelled in SpectrumGreen and flanks the 3′ side of the EWSR1 gene, with a 7-kb gap between the two probes. With this setting, the assay enables the detection of rearrangements with breakpoints spanning introns 7–10 of the EWSR1 gene. Hybridization was performed according to the manufacturer’s instructions and scoring of tissue sections was assessed as described elsewhere60, counting at least 100 nuclei per slide. Recurrently mutated genes identified by whole-genome sequencing were independently evaluated in a series of 62 PaNETs from the ARC-Net Research Centre, University of Verona. Four Ion Ampliseq Custom panels (Thermofisher) were designed to target the entire coding regions and flanking intron–exon junctions of the following genes: MEN1, DAXX, ATRX, PTEN and TSC2 (panel 1); DEPDC5, TSC1 and SETD2 (panel 2); ARID1A and MTOR (panel 3); CHEK2 and MUTYH (panel 4). Twenty nanograms of DNA were used per multiplex PCR amplification. The quality of the obtained libraries was evaluated by the Agilent 2100 Bioanalyzer on chip electrophoresis. Emulsion PCR was performed with the OneTouch system (Thermofisher). Sequencing was run on the Ion Torrent Personal Genome Machine (PGM, Thermofisher) loaded with 316 or 318 chips. Data analysis, including alignment to the hg19 human reference genome and variant calling, was done using Torrent Suite Software v4.0 (Thermofisher). Filtered variants were annotated using a custom pipeline based on the Variant Effector Predictor (VEP) software. Alignments were visually verified with the Integrative Genomics Viewer: IGV v2.3 (Broad Institute). There is no contiguous structure available for CHEK2, so we produced a model of isoform C using PDBid 3i6w61 as a template for predicting the structure of sequence O96017. Modelling was carried out within the YASARA suite of programs62 and consisted of an initial BLAST search for suitable templates followed by alignment, building of loops not present in selected template structure and energy minimization in explicit solvent. Modelling was carried out in the absence of a phosphopeptide ligand, which was added on completion by aligning the model with structure 1GXC and merging the ligand contained therein with the model structure. Similarly, MUTYH is represented by discontinuous structures and so this too was modelled using PDBids 3N5N and 4YPR as templates together with sequence NP_036354.1. Having constructed both models, amino acid substitutions were carried out to make the wild-type sequences conform to the variants described above. Each substitution was carried out independently and the resulting variant structures were subject to simulated annealing energy minimization using the AMBER force field. The resulting energy-minimized structures formed the basis of the predictions. CHEK2 site mutants were generated by site-directed mutagenesis of wild-type pCMV–FLAG CHEK2 (primer sequences in Supplementary Table 16). Proteins were expressed in HEK293T, a highly transfectable derivative of HEK293 cells that were retrieved from the cell culture bank at the QIMR Berghofer medical research institute. Cells were authenticated by STR profiling and were negative for mycoplasma. Transfected cells were lysed in NP-40 modified RIPA with protease and phosphatase inhibitors. Protein expression levels were analysed by western blotting with anti-FLAG antibodies and imaging HRP luminescent signal on a CCD camera (Fuji) and quantifying in MultiGauge software (Fuji). Kinase assays were performed using recombinant GST–CDC25C (amino acids 200–256) as substrate, essentially as described63. Kinase assay quantification was performed by scintillation counting of excised gel bands in OptiPhase scintillant (Perkin Elmer) using a Tri-Carb 2100TR beta counter (Packard). Counts for each reaction set were expressed as a fraction of the wild type. All experiments were performed at least three times. The date of diagnosis and the date and cause of death for each patient were obtained from the Central Cancer Registry and treating clinicians. Median survival was estimated using the Kaplan–Meier method and the difference was tested using the log-rank test. P values of less than 0.05 were considered statistically significant. The hazard ratio and its 95% confidence interval were estimated using Cox proportional hazard regression modelling. The correlation between DAXX or ATRX mutational status and other clinico-pathological variables was calculated using the χ2 test. Statistical analysis was performed using StatView 5.0 Software (Abacus Systems). Disease-specific survival was used as the primary endpoint. Genome sequencing data presented in this study have been submitted to the European Genome-Phenome Archive under accession number EGAS00001001732 (https://www.ebi.ac.uk/ega/search/site/EGAS00001001732).
News Article | February 20, 2017
Researchers at The University of Queensland's Australian Institute for Bioengineering and Nanotechnology (AIBN) have designed a virus-like nanoparticle (VNP) that delivers drugs directly to the cells where they are needed. The lead author of a paper on the topic, Dr Frank Sainsbury, said the VNP was made from the structural proteins that formed the virus's protective shell. "Viruses have evolved to contain and protect bioactive molecules," Dr Sainsbury said. "They've also evolved smart ways to get into cells and deliver these bioactive molecules. "The VNP is an empty shell. It looks like a virus but it's not infectious. This makes it safe to use as a targeted drug delivery system." With infectious viral genes removed, empty shells can be loaded with small molecules or proteins resulting in a stable, well-protected therapeutic package. The outside of the shell then determines where the package will go. The ability to send drugs directly to their target is a critical goal in the development of safe, effective therapeutics. Currently many drugs, including anti-cancer chemotherapies, must be administered at high doses in order to have a therapeutic effect. This can lead to harsh side effects because drugs can damage healthy cells as well as intended targets. Dr Sainsbury and his colleagues developed a VNP using the Bluetongue virus, which normally infects cows, sheep and other ruminants. They picked the virus because of its stable shell, made of hundreds of proteins that are known to bind to a molecule found in high levels around many cancer cells. Dr Sainsbury teamed up with Dr Michael Landsberg at UQ's School of Chemistry and Molecular Biosciences and researchers at the Institute for Molecular Bioscience and the UK's John Innes Centre. They were able to demonstrate that the porous VNPs could be filled with small molecules for drug delivery and it also was possible to design VNPs to contain larger molecules, such as therapeutic proteins. Importantly, the researchers showed VNPs were able to bind to breast cancer cells, and then be absorbed. Dr Sainsbury said the next step was to load the VNPs with anti-cancer drugs and see if they could kill cancer cells without harming healthy cells. Although VNPs are highly complex and difficult to synthesise, Dr Sainsbury said they could be easily produced in the leaves of Nicotiana benthamiana, a wild relative of tobacco. By providing plant cells with genetic instructions for making VNPs, the plant was able to assemble virus protein shells without any permanent change to the plant's own genetic code. Dr Sainsbury said one day greenhouses may be able to produce large amounts of the nanoparticles within days. "This research unlocks a myriad of potential applications in therapeutic delivery," Dr Sainsbury said. Because the nanoparticles they have designed are highly stable, the AIBN research team is exploring other biotechnology applications. Explore further: Plant-made virus shells could deliver drugs directly to cancer cells
News Article | February 15, 2017
A remarkable 250 million-year-old "terrible-headed lizard" fossil found in China shows an embryo inside the mother -- clear evidence for live birth. Head of The University of Queensland's School of Earth and Environmental Sciences and co-author Professor Jonathan Aitchison said the fossil unexpectedly provided the first evidence for live birth in an animal group previously thought to exclusively lay eggs. "Live birth is well known in mammals, where the mother has a placenta to nourish the developing embryo," Professor Aitchison said. "Live birth is also very common among lizards and snakes, where the babies sometimes 'hatch' inside their mother and emerge without a shelled egg." Until recently it was thought the third major group of living land vertebrates, the crocodiles and birds (part of the wider group Archosauromorpha) only laid eggs. "Indeed, egg-laying is the primitive state, seen at the base of reptiles, and in their ancestors such as amphibians and fishes," Professor Aitchison said. He said the new fossil was an unusual, long-necked marine animal called an archosauromorph that flourished in shallow seas of South China in the Middle Triassic Period. The creature was a fish-eater, snaking its long neck from side to side to snatch its prey. Its fossil was one of many astonishingly well-preserved specimens from new "Luoping biota" locations in south-western China. There were no known fossils like this (marine vertebrates of this age) from Australia. Lead author Professor Jun Liu from Hefei University of Technology China, said the researchers were "excited" when they first saw this embryonic specimen. "We were not sure if the embryonic specimen was the mother's last lunch or its unborn baby," Professor Liu said. "Upon further preparation and closer inspection, we discovered something unusual." He said the embryo was inside the mother's rib cage, and it faced forward; swallowed animals generally face backward because the predator swallows its prey head-first to help it go down its throat. Furthermore, the small reptile inside the mother was an example of the same species. "Further evolutionary analysis revealed the first case of live birth in such a wide group containing birds, crocodilians, dinosaurs and pterosaurs among others, and pushes back evidence of reproductive biology in the group by 50 million years," Professor Liu said. "Information on reproductive biology of archosauromorphs before the Jurassic Period was not available until our discovery, despite a 260 million-year history of the group." Professor Chris Organ from Montana State University said evolutionary analysis showed that this instance of live birth was also associated with genetic sex determination. "Some reptiles today, such as crocodiles, determine the sex of their offspring by the temperature inside the nest," he said. "We identified that Dinocephalosaurus, a distant ancestor of crocodiles, determined the sex of its babies genetically, like mammals and birds. "This new specimen from China rewrites our understanding of the evolution of reproductive systems." Professor Mike Benton of the University of Bristol said analysis of the evolutionary position of the new specimens showed no fundamental reason why archosauromorphs could not have evolved live birth. "This combination of live birth and genotypic sex determination seems to have been necessary for animals such as Dinocephalosaurus to become aquatic," he said. "It's great to see such an important step forward in our understanding of the evolution of a major group coming from a chance fossil find in a Chinese field." The work is part of ongoing wider collaborations between palaeontologists in China, the United States, the UK and Australia. The paper is published in the journal, Nature Communications.
News Article | February 22, 2017
IMB Centre for Superbug Solutions Deputy Director Associate Professor Lachlan Coin said arming clinicians with this information could help them prescribe the most effective antibiotic for their patient. "Antibiotic resistance is a global challenge that threatens our ability to treat common infections," he said. "Sequencing a bacterial genome using standard techniques resulted in a genome splitting into hundreds of fragments which was impossible to piece together. "In particular, pathogenicity islands—which are crucial to identifying antibiotic resistance—usually split across multiple pieces. "For the past two years, we have used cutting-edge Oxford Nanopore Technologies sequencing devices to sequence bacterial genomes and understand how antibiotic resistance develops. "Because this technology is so new, we needed to develop a powerful method that could help us make the most of its results and really understand the genetic drivers of antibiotic resistance," Associate Professor Coin said. IMB Postdoctoral Researcher Dr Minh Duc Cao said the team developed a new method for analysis of sequencing data on the fly, which allowed them to quickly and accurately piece together complete genomes. "With our method, we can reconstruct an entire bacterial genome shortly after you switch on the machine and put in the DNA sample. "The speed is key as we're interested in predicting antibiotic resistance in real time on clinical samples, because when it comes to diagnosing and treating infections, every minute counts," he said. Associate Professor Coin said the method could be applied to help unravel the genomic causes of other diseases. "We would like to work towards finding new ways to apply this approach to help unravel other diseases, particularly cancer. "Cancer genomes are about 1000 times larger than bacterial genomes, so the powerful combination of this leading technology and our improved method holds enormous potential for rapid assembly of personalised tumour genomes," Associate Professor Coin said. The research was published in Nature Communications and was funded by The University of Queensland, National Health and Medical Research Council and the Australian Research Council. The University of Queensland's Institute for Molecular Bioscience Centre for Superbug Solutions will host the Solutions for Drug-Resistant Infections conference in Brisbane from 3-5 April 2017. The conference will bring international experts and advocates in the field to network and discuss new ways to solve the global challenge of drug-resistant infections. More information: Minh Duc Cao et al. Scaffolding and completing genome assemblies in real-time with nanopore sequencing, Nature Communications (2017). DOI: 10.1038/ncomms14515
News Article | February 15, 2017
SAINT-PREX, Switzerland--(BUSINESS WIRE)--Ferring today announced the recipients of the 2016-2017 Ferring Innovation Grants program, an annual initiative of the Ferring Research Institute (FRI) which provides grants of up to $100,000 for early stage research. The program focuses on novel extracellular drug targets addressable with peptides or proteins within Ferring’s core therapeutic areas: reproductive health, gastroenterology, urology, and endocrinology. The 2016-2017 awardees and their research subjects are: Stuart Brierley - Flinders University, Australia Venom-derived NaV1.1 inhibitors as novel candidates for treating chronic visceral pain associated with IBS James Deane - Hudson Institute of Medical Research, Australia Investigating the requirement for Notch and Hedgehog signalling in the endometrial stem/progenitor populations that cause endometriosis Marie van Dijk - University of Amsterdam, Netherlands ELABELA as a potential biomarker and therapeutic for pre-eclampsia Florenta Kullmann - University of Pittsburgh, USA Artemin: a novel target for treatment of interstitial cystitis/bladder pain syndrome Mireille Lahoud - Monash University, Australia The development of Clec12A-ligands as a therapeutic approach to regulate gastrointestinal inflammation Padma Murthi - Monash University, Australia Investigating the role of novel peptide receptor as an effective target to improve placental function in preeclampsia Markus Muttenthaler - The University of Queensland, Australia Mapping the location and function of oxytocin and vasopressin receptors throughout the gut Rodrigo Pacheco – Fundación Ciencia & Vida and Universidad Andres Bello, Santiago, Chile Targeting heteromers formed by G-protein coupled receptors involved in the gut-homing of T-cells in inflammatory bowel diseases Aritro Sen – The University of Rochester, USA Regulation of AMH expression by GDF9+BMP15 and FSH during follicular development as a novel therapeutic option “We look forward to the outcomes of the research being carried out by our grant awardees,” said Keith James, President of FRI and Senior Vice President, Research and Development. “Ferring is committed to stimulating basic research, with the ultimate aim of developing innovative products that improve the lives of patients.” Applications for the 2017-2018 Ferring Innovation Grants programme will open in spring/summer 2017. For more information on this year’s program, visit www.ferring-research.com/ferring-grants. About Ferring Research Institute Inc Located in San Diego, California Ferring Research Institute Inc. (FRI) is the global peptide therapeutics research center for Ferring Pharmaceuticals. FRI is committed to building a portfolio of novel, innovative peptide-based drugs and biologicals to address the high unmet medical need for patients in our therapeutic areas of interest. For more detailed information please visit www.ferring-research.com. About Ferring Pharmaceuticals Headquartered in Switzerland, Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group active in global markets. The company identifies, develops and markets innovative products in the areas of reproductive health, urology, gastroenterology, endocrinology and orthopaedics. Ferring has its own operating subsidiaries in nearly 60 countries and markets its products in 110 countries. To learn more about Ferring or its products please visit www.ferring.com.
News Article | February 15, 2017
Australia could save AUD $3.4 billion (USD $2.3 billion) in healthcare costs over the remaining lifetimes of all Australians alive in 2010 by instituting a combination of taxes on unhealthy foods and subsidies on fruits and vegetables, according to a new study published in PLOS Medicine by Linda Cobiac, from the University of Melbourne, Australia and colleagues. An increasing number of Western countries have implemented or proposed taxes on unhealthy foods and drinks in an attempt to curb rates of dietary-related diseases, however the cost-effectiveness of combining various taxes and subsidies is not well-understood. In the new study, researchers modeled the effect of taxes on saturated fat, salt, sugar, and sugar-sweetened beverages and a subsidy on fruits and vegetables on the Australian population of 22 million alive in 2010. They simulated how different combinations of these taxes and subsidies--designed so there would be less than a one percent change in total food expenditure for the average household--impacted the death and morbidity rates of Australians as well as healthcare spending over the remainder of their lives. The greatest impact, the researchers concluded, came from a sugar tax, which could avert 270,000 disability-adjusted life years (DALYs, or years of healthy lifespan across the population lost due to disease). "That is a gain of 1.2 years of healthy life for every 100 Australians alive in 2010," the authors say. "Few other public health interventions could deliver such health gains on average across the whole population." A salt tax was estimated to save 130,000 DALYS over the remainder of the lives of Australians alive in 2010, a saturated fat tax 97,000 DALYs, and a sugar-sweetened beverage tax 12,000 DALYs. Combined with taxes, the fruit and vegetable subsidies made for additional averted DALYs and reduced health sector spending, but on their own were not estimated to lead to a clear health benefit. Overall, when combined to maximize benefits, the taxes and subsidies could save an estimated 470,000 DALYs and reduce spending by AUD $3.4 billion (USD $2.3 billion). "Simulation studies, such as ours, have uncertainty. For example, we are reliant on other research estimating the responsiveness of the public to changes in food prices. There are also implementation issues for the food industry." "Nevertheless, this study adds to the growing evidence of large health benefits and cost-effectiveness of using taxes and regulatory measures to influence the consumption of healthy foods," the authors say. "We believe that with such large potential health benefits for the Australian population and large benefits in reducing health sector spending...the formulation of a tax and subsidy package should be given more prominent and serious consideration in public health nutrition strategy." "Several countries have imposed taxes on sugary drinks, with the UK the latest to consider such a policy. Our research suggests that even bigger health gains and cost savings may be possible with food taxes and subsidies on a wider range of foods." Funding: LJC was supported by a National Health and Medical Research Council Fellowship (Grant number 1036771; http://www. ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: LJC is a member of the Editorial Board of PLOS Medicine. Citation: Cobiac LJ, Tam K, Veerman L, Blakely T (2017) Taxes and Subsidies for Improving Diet and Population Health in Australia: A Cost-Effectiveness Modelling Study. PLoS Med 14(2): e1002232. doi:10.1371/journal.pmed.1002232 Centre for Health Policy, School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia School of Public Health, The University of Queensland, Herston, Queensland, Australia, Burden of Disease Epidemiology, Equity and Cost-Effectiveness Programme, Department of Public Health, University of Otago, Wellington, Wellington, New Zealand IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER: http://journals.
News Article | February 8, 2017
Australian researchers are a step closer to understanding immune sensitivities to well-known, and commonly prescribed, medications. Many drugs are successfully used to treat diseases, but can also have harmful side effects. While it has been known that some drugs can unpredictably impact on the functioning of the immune system, our understanding of this process has been unclear. The team investigated what drugs might activate a specialised type of immune cell, the MAIT cell (Mucosal associated invariant T cell). They found that some drugs prevented the MAIT cells from detecting infections (their main role in our immune system), while other drugs activated the immune system, which may be undesirable. The results, published in Nature Immunology overnight, may lead to a much better understanding of, and an explanation for, immune reactions by some people to certain kinds of drugs. The findings may also offer a way to control the actions of MAIT cells in certain illnesses for more positive patient outcomes. The multidisciplinary team of researchers are part of the ARC Centre of Excellence in Advanced Molecular Imaging, and stem from Monash University, The University of Melbourne and The University of Queensland. Access to national research infrastructure, including the Australian synchrotron, was instrumental to the success of this Australian research team. Dr Andrew Keller from Monash University's Biomedicine Discovery Institute said that T cells are an integral part of the body's immune system. "They protect the body by 'checking' other cells for signs of infection and activating the immune system when they detect an invader," he said. "This arrangement is dependent on both the T cells knowing what they're looking for, and the other cells in the body giving them useful information." PhD student Weijun Xu from The University of Queensland's Institute for Molecular Bioscience used computer modelling to predict chemical structures, drugs and drug-like molecules that might impact on MAIT cell function. Such small compounds included salicylates, non-steroidal anti-inflammatory drugs like diclofenac, and drug metabolites. University of Melbourne Dr Sidonia Eckle from the Peter Doherty Institute for Infection and Immunity said the implications point to possible links between known drug hypersensitivities and MAIT cells. "A greater understanding of the interaction between MAIT cells and other host cells will hopefully allow us to better predict and avoid therapeutics that influence and cause harm," she said. "It also offers the tantalising prospect of future therapies that manipulate MAIT cell behaviour, for example, by enhancing or suppressing immune responses to achieve beneficial clinical outcome." Article: Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells, Andrew N Keller, Sidonia B G Eckle, Weijun Xu, Ligong Liu, Victoria A Hughes, Jeffrey Y W Mak, Bronwyn S Meehan, Troi Pediongco, Richard W Birkinshaw, Zhenjun Chen, Huimeng Wang, Criselle D'Souza, Lars Kjer-Nielsen, Nicholas A Gherardin, Dale I Godfrey, Lyudmila Kostenko, Alexandra J Corbett, Anthony W Purcell, David P Fairlie, James McCluskey & Jamie Rossjohn, Nature Immunology, doi:10.1038/ni.3679, published online 6 February 2017.
News Article | February 22, 2017
Researchers from The University of Queensland’s Institute for Molecular Bioscience (IMB) have developed a faster and more accurate method for assembling genomes which could help clinicians rapidly identify antibiotic-resistant infections. IMB Centre for Superbug Solutions Deputy Director Associate Professor Lachlan Coin says arming clinicians with this information could help them prescribe the most effective antibiotic for their patient. “Antibiotic resistance is a global challenge that threatens our ability to treat common infections,” he says. “Sequencing a bacterial genome using standard techniques resulted in a genome splitting into hundreds of fragments which was impossible to piece together. “In particular, pathogenicity islands — which are crucial to identifying antibiotic resistance — usually split across multiple pieces. “For the past two years, we have used cutting-edge Oxford Nanopore Technologies sequencing devices to sequence bacterial genomes and understand how antibiotic resistance develops. “Because this technology is so new, we needed to develop a powerful method that could help us make the most of its results and really understand the genetic drivers of antibiotic resistance,” Coin says. IMB Postdoctoral Researcher Dr. Minh Duc Cao says the team developed a new method for analysis of sequencing data on the fly, which allowed them to quickly and accurately piece together complete genomes. “With our method, we can reconstruct an entire bacterial genome shortly after you switch on the machine and put in the DNA sample. “The speed is key as we’re interested in predicting antibiotic resistance in real time on clinical samples, because when it comes to diagnosing and treating infections, every minute counts,” he says. Coin says the method could be applied to help unravel the genomic causes of other diseases. “We would like to work towards finding new ways to apply this approach to help unravel other diseases, particularly cancer. “Cancer genomes are about 1000 times larger than bacterial genomes, so the powerful combination of this leading technology and our improved method holds enormous potential for rapid assembly of personalized tumor genomes,” Coin says. The research was published in Nature Communications and was funded by The University of Queensland, National Health and Medical Research Council, and the Australian Research Council.
News Article | January 26, 2017
Early puberty and childlessness are associated with an increased risk of early menopause. New research found that women who had their first periods before the age of 11 were 80 percent more prone to experiencing premature or early menopause. Approximately one in every 10 women experiences premature menopause, according to the international study. Information on this matter is important, as women with this condition are subjected to a higher risk of developing chronic conditions, such as cardiovascular disease, osteoporosis, or type 2 diabetes. The research, conducted at the University of Queensland, underlined that the risks of early or premature menopause are doubled when it comes to women who did not have children, compared to the ones who have two or more kids. "Women with either premature or early menopause face an increased risk of chronic conditions in later life and of early death. Findings from some studies suggest that early menarche and nulliparity are associated with early menopause, however overall the evidence is mixed," noted the research. As the research points out, getting the period early is associated with a five-fold increase in the risk of premature menopause, as well as a two-fold increase for early menopause. The results were obtained by comparison with women who started their periods at the age of 12, and who have at least two kids. In the context of the research, not having a child was considered to be an indicator of underlying fertility issues. The women who took part in the study came from a time period when fertility was not an issue, and very few women had access to fertility treatments. "We have to be cautious of generational differences but the results are relevant to younger generations of women where we are seeing increasingly early onset of puberty," noted Professor Gita Mishra from The University of Queensland. The research gathered data from 51,450 postmenopausal women, who had been part of nine observational studies carried out in the UK, Australia, Scandinavia, and Japan. At the same time, for researchers to extract more significant data about women's menopause timing, a series of factors should be made public at the doctor's. Among these, the age of the woman's mother when she reached menopause, the number of kids, the lifestyle choices (such as smoking) are very relevant in establishing a series of potential causal reactions. The normal age at which women should typically enter menopause is around 51-52, due to the fact that the ovaries run out of eggs. Approximately 20 percent of the women will have no symptom of menopause, except for not getting their period for twelve months. At the same time, menopause happening before the age of 50 is called premature or early menopause. "This may be due to primary ovarian insufficiency where the periods spontaneously stop, as a result of chemotherapy treatment for cancer or surgically induced menopause when the ovaries are removed," the organization Jean Hailes wrote on its website. Emotional, psychological, and physcal effects can be significant but treatment options are available to alleviate them. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.
News Article | February 24, 2017
The coral reefs all around the world are facing a crisis. About 90 percent of them are expected to die due to pollution and destructive fishing practices. To save the reefs from extinction, various philanthropists and conservationists have come up with a plan to save the remaining 10 percent of the reefs. The 50 Reefs Project plan touted to be the first global plan focusing on conservation of coral reefs was launched earlier this week at the Economist World Ocean Summit in Bali. This initiative has brought together various marine scientists and conservation practitioners with an aim of identifying 50 most-endangered coral reefs around the globe that stand a chance of suffering due to climate change. The initial list of the coral reefs is likely to be announced in the later part of 2017. Currently, it has been estimated that 90 percent of the coral reefs are likely to disappear by 2050. The 50 Reefs Project came into being after the Australian government stated that the Great Barrier Reef has been experiencing extensive bleaching since past four years. The initial budget of the project has been kept at $2 million. The project will be funded by Tiffany & Co. Foundation, Paul G. Allen Family Foundation and Bloomberg Philanthropies. The 50 Reefs Project plans to utilize three strategies to conserve the coral reefs. Firstly, the project aims at collaborating with scientists from all over the world to help decide the criteria on which the coral reefs will be chosen for conservation. The second strategy is to identify the critical needs and relevant solutions provided by scientists and conservation experts. Lastly, the project will house start a campaign to make people aware of the need to conserve coral reefs worldwide. The initial listing of the coral reefs will be prepared by using an algorithm, named "decision algorithm". The algorithm has been developed by the Centre for Excellence in Environmental Decisions at The University of Queensland. Reports suggest that independent panels of scientists will be examining the datasets associated to the project. The datasets would include current reef connectivity, reef biodiversity climate vulnerability and many more factors. The scientists will be focusing on critical efforts of conservation to ensure that the coral reef domain survives for longer period of time. "What we already know about the future of our coral reefs is alarming: Without immediate action, we could lose this crucial ecosystem entirely within a few short decades," said Paul G. Allen, co philanthropist of the 50 Reefs Project. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.