News Article | May 10, 2017
Climate change around Antarctica can severely affect Australia's rainfall and even influence the distribution of wet and dry zones across southeast Asia, an international study has revealed. Chelsea Korpanty of The University of Queensland's School of Biological Sciences worked on the study, which was led by Dr Jeroen Groeneveld from the Center of Marine and Environment Sciences at the University of Bremen, Germany. Ms Korpanty said global climate underwent significant change about 14 million years ago when the Antarctic ice sheet expanded. "The new study presents shallow-marine sediment records from the Australian continental shelf, providing the first empirical evidence linking high-altitude cooling around Antarctica to climate change in the subtropics during the Miocene era," she said. "Our data is consistent with the inference that expansion of sea ice around Antarctica resulted in a northward movement of the westerly winds. "In turn, this may have pushed tropical atmospheric circulation, shifting the main rainfall belt over large parts of Southeast Asia." The study used sediment cores drilled along the west coast of Australia during International Ocean Discovery Program Expedition 356 with the research vessel JOIDES Resolution, providing a long-term history of how rainfall and aridity changed on Earth from 16 to six million years ago. Ms Korpanty worked aboard the JOIDES in 2015 as a sedimentologist alongside scientists from 29 different international institutes and with expertise across paleontology, sedimentology, and physical geological properties. The results of the expedition, and the data published in the paper, provided an unprecedented climate record for western Australia, capturing when and how Antarctic climate changes affected Australian climate conditions. Dr Groeneveld said the new study had the enormous advantage of using a complete and thus continuous sediment record which had not been influenced by potential drilling disturbances. "Today the climate in western Australia varies from north to south - in the north the seasonal monsoon brings pronounced dry and wet seasons, farther south the climate is dry throughout the year, and in the south the westerly winds bring rain during the Australian winter," he said. Expedition 356 aimed to determine how this climate gradient developed over longer time periods, especially in the Miocene and Pliocene (16-six million years ago). Dr Groeneveld said that over longer timescales, tectonic changes played an important role, such as in the closing of the Indonesian Gateway and the northward movement of Australia away from Antarctica. "Global climate during the Miocene era was much warmer than today, and at the end of the middle Miocene a large part of Antarctica became glaciated and continued to cool the Southern Ocean into the late Miocene." The researchers used the natural gamma-ray data acquired with downhole logging during the expedition to reconstruct variations in river runoff and dust and relate these to a history of precipitation and aridity for western Australia. The findings are published in Science Advances (doi: 10.1126/sciadv.1602567).
News Article | April 17, 2017
People mislead themselves all day long. We tell ourselves we’re smarter and better looking than our friends, that our political party can do no wrong, that we’re too busy to help a colleague. In 1976, in the foreword to Richard Dawkins’s The Selfish Gene, the biologist Robert Trivers floated a novel explanation for such self-serving biases: We dupe ourselves in order to deceive others, creating social advantage. Now after four decades Trivers and his colleagues have published the first research supporting his idea. Psychologists have identified several ways of fooling ourselves: biased information-gathering, biased reasoning and biased recollections. The new work, forthcoming in the Journal of Economic Psychology, focuses on the first—the way we seek information that supports what we want to believe and avoid that which does not. In one experiment Trivers and his team asked 306 online participants to write a persuasive speech about a fictional man named Mark. They were told they would receive a bonus depending on how effective it was. Some were told to present Mark as likable, others were instructed to depict him as unlikable, the remaining subjects were directed to convey whatever impression they formed. To gather information about Mark, the participants watched a series of short videos, which they could stop observing at any intermission. For some viewers, most of the early videos presented Mark in a good light (recycling, returning a wallet), and they grew gradually darker (catcalling, punching a friend). For others, the videos went from dark to light. When incentivized to present Mark as likable, people who watched the likable videos first stopped watching sooner than those who saw unlikable videos first. The former did not wait for a complete picture as long as they got the information they needed to convince themselves, and others, of Mark’s goodness. In turn, their own opinions about Mark were more positive, which led their essays about his good nature to be more convincing, as rated by other participants. (A complementary process occurred for those paid to present Mark as bad.) “What’s so interesting is that we seem to intuitively understand that if we can get ourselves to believe something first, we’ll be more effective at getting others to believe it,” says William von Hippel, a psychologist at The University of Queensland, who co-authored the study. “So we process information in a biased fashion, we convince ourselves, and we convince others. The beauty is, those are the steps Trivers outlined—and they all lined up in one study.” In real life you are not being paid to talk about Mark but you may be selling a used car or debating a tax policy or arguing for a promotion—cases in which you benefit not from gaining and presenting an accurate picture of reality but from convincing someone of a particular point of view. One of the most common types of self-deception is self-enhancement. Psychologists have traditionally argued we evolved to overestimate our good qualities because it makes us feel good. But feeling good on its own has no bearing on survival or reproduction. Another assertion is self-enhancement boosts motivation, leading to greater accomplishment. But if motivation were the goal, then we would have just evolved to be more motivated, without the costs of reality distortion. Trivers argues that a glowing self-view makes others see us in the same light, leading to mating and cooperative opportunities. Supporting this argument, Cameron Anderson, a psychologist at the University of California, Berkeley, showed in 2012 that overconfident people are seen as more competent and have higher social status. “I believe there is a good possibility that self-deception evolved for the purpose of other-deception,” Anderson says. In another study, forthcoming in Social Psychological and Personality Science, von Hippel and collaborators tested all three arguments together, in a longitudinal fashion. Does overconfidence in one’s self increase mental health? Motivation? Popularity? Tracking almost 1,000 Australian high school boys for two years, the researchers found that over time, overconfidence about one’s athleticism and intelligence predicted neither better mental health nor better athletic or academic performance. Yet athletic overconfidence did predict greater popularity over time, supporting the idea that self-deception begets social advantage. (Intellectual self-enhancement may not have boosted popularity, the authors suggest, because among the teenage boys, smarts may have mattered less than sports.) Why did it take so long for experimental evidence for Trivers’ idea to emerge? In part, he says, because he is a theorist and did not test it until he met von Hippel. Other experimental psychologists didn’t test it because the theory was not well known in psychology, von Hippel and Anderson say. Further, they suggest, most psychologists saw self-esteem or motivation as reason enough for self-enhancement to evolve. Hugo Mercier, a researcher at the Institute for Cognitive Sciences in France who was not involved in the new studies, is familiar with the theory but questions it. He believes that in the long run overconfidence may backfire. He and others also debate whether motivated biases can strictly be called self-deception. “The whole concept is misleading,” he says. It’s not as though there is one part of us deliberately fooling another part of us that is the “self.” Trivers, von Hippel and Anderson of course disagree with Mercier on self-deception’s functionality and terminology. Von Hippel offers two pieces of wisdom regarding self-deception: “My Machiavellian advice is this is a tool that works,” he says. “If you need to convince somebody of something, if your career or social success depends on persuasion, then the first person who needs to be [convinced] is yourself.” On the defensive side, he says, whenever anyone tries to convince you of something, think about what might be motivating that person. Even if he is not lying to you, he may be deceiving both you and himself.
News Article | April 27, 2017
One year after launching iOS version of PPD ACT in the U.S. and Australia, UNC School of Medicine launches Android version and Canada launches iOS app to increase participation. CHAPEL HILL, N.C. - The UNC School of Medicine today launched the Android version of PPD ACTTM, a mobile app-based study helping to further the understanding of why some women suffer from Postpartum Depression (PPD) and others do not - critical knowledge for researchers working to find more effective treatments. PPD ACTTM, previously available for iOS only, is now available in the U.S. and Australia for Android devices and the iOS version is now available in Canada. Additionally, all users in the U.S. may access a new module to help researchers understand the economic impact and burden that PPD has on society. The app surveys women to identify those who have had symptoms of PPD and invites certain women to provide DNA samples so that researchers can study the genes of those affected by PPD. During its first year, approximately 14,000 women enrolled in the study, far surpassing expectations. PPD ACT was initially launched as an iPhone-based ResearchKit app, an open-source framework developed by Apple that allows researchers to create app-based studies with global reach. However, since approximately half of the U.S. population uses Android phones, as do many women in Australia, this new version of the app will open the doors for many more women to participate. Additionally, a Canadian team led by Women's College Hospital in Ontario, Canada, has received funding to expand the iOS app into Canada, responding to the numerous requests from Canadian women wanting to participate in the study. "The participation from the first year of the study is astounding and, frankly, unprecedented in terms of using the social media platform of an app to recruit women for study participation involving the donation of genetic samples," said Samantha Meltzer-Brody, MD, MPH, director of the Perinatal Psychiatry Program at the UNC Center for Women's Mood Disorders and lead researcher for the study. "Launching the Android version in the U.S. and Australia and expanding into Canada allows for an even larger group of women the opportunity to share their experiences so that we can more effectively diagnose and treat PPD in the future." This study is the first of its kind and uniquely designed for rapid collection of a large number of DNA samples required for genetic analysis. The eventual goal is to gather 50,000 samples from around the globe through continued expansion to additional countries. PPD ACTTM has also had impact beyond research. Many women have sought care and treatment based on symptoms that became apparent after completing the screening module of the app. "As someone who experienced a variation of PPD symptoms after the births of both of my daughters, I would have welcomed an application, in the privacy of my home, at my fingertips, to potentially help target the 'what and why' of this temporary mental health challenge," said patient Jamie Belsito. "In addition to gathering valuable data, PPD ACT is also starting a much-needed dialogue to help eradicate the stigma often associated with PPD, and to encourage more providers to thoroughly screen for and treat PPD." The U.S. version of the app will also now feature a module which will help researchers better understand the burden that PPD has on patients' quality of life, maternal function, bonding and utilization of health care services. Currently, researchers have an inadequate understanding of the economic burden and the cost of PPD on society. This health outcomes research is being conducted in collaboration with Sage Therapeutics, Inc. "Until now, the impact of PPD on individuals, their families, and society has been poorly understood. This research, undertaken by UNC, Sage and our collaborators, helps to provide a new, real-world, data-driven understanding of the disease burden postpartum depression patients experience and of their healthcare utilization," said Steve Kanes, MD, PhD, Chief Medical Officer at Sage. "We are very excited to collaborate with UNC in helping to further study the functional and economic impact of this complication of pregnancy." Android users in the U.S. and Australia will be able to download PPD ACTTM from Google Play. The app continues to be available for iPhone users as a free download from the App Store in the U.S. and Australia, and it is now also available in Canada. International research partners include The University of Queensland in Australia and Women's College Hospital in Toronto, Canada. To help spread the message, UNC has partnered with Postpartum Support International, which is dedicated to increasing awareness among public and professional communities about the emotional changes that women experience during pregnancy and postpartum. "Postpartum Support International is thrilled to partner with UNC on this pioneering study, and to collaborate with researchers around the world," said Ann Smith, president of Postpartum Support International. "We will spread the message and opportunity to participate through our global network of volunteers and professional members. We are confident that findings from this study will prevent suffering and increase positive outcomes for future generations." The app is intended for women 18 years or older who have previously given birth and believe they may have experienced or are currently experiencing signs or symptoms of PPD such as anxiety, depression, guilt, irritability or extreme sadness. To download the app or learn more about the study or PPD, visit pactforthecure.com. Patrick Sullivan, MD, Yeargen Distinguished Professor of Psychiatry and Genetics at the UNC School of Medicine, is a co-investigator in this project. Development of the app and support for the study are provided by the Foundation of Hope for research and treatment of mental illness; Sage Therapeutics, a neuroscience-focused company discovering medicines to treat life-threatening, rare CNS disorders; the UNC Departments of Genetics and Psychiatry; and the UNC Center for Health Innovation. Little Green Software, a full-service app development firm, developed the app. The UNC Center for Women's Mood Disorders is internationally known in the evaluation and treatment of women with mood disorders that occur during periods of hormonal change. Reproductive mood disorders include depression and anxiety disorders associated with the reproductive life cycle. To learn more, click here. Established by the UNC Health Care System (UNC HCS) and the UNC School of Medicine (UNC SOM), the Center for Health Innovation initiates, evaluates and supports the adoption of disruptive, patient-centered innovations in the delivery and financing of health care. The Center strives to provide rapid assessment, coordinated facilitation, program management, partnership development and funding for innovation. To learn more, click here.
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 | 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 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 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 | 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 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.