Drosophila melanogaster as an Animal Model for the Study of Pseudomonas aeruginosa Biofilm Infections In Vivo

Pseudomonas aeruginosa is an opportunistic pathogen capable of causing both acute and chronic infections in susceptible hosts. Chronic P. aeruginosa infections are thought to be caused by bacterial biofilms. Biofilms are highly structured, multicellular, microbial communities encased in an extracellular matrix that enable long-term survival in the host. The aim of this research was to develop an animal model that would allow an in vivo study of P. aeruginosa biofilm infections in a Drosophila melanogaster host. At 24 h post oral infection of Drosophila, P. aeruginosa biofilms localized to and were visualized in dissected Drosophila crops. These biofilms had a characteristic aggregate structure and an extracellular matrix composed of DNA and exopolysaccharide. P. aeruginosa cells recovered from in vivo grown biofilms had increased antibiotic resistance relative to planktonically grown cells. In vivo, biofilm formation was dependent on expression of the pel exopolysaccharide genes, as a pelB::lux mutant failed to form biofilms. The pelB::lux mutant was significantly more virulent than PAO1, while a hyperbiofilm strain (PAZHI3) demonstrated significantly less virulence than PAO1, as indicated by survival of infected flies at day 14 postinfection. Biofilm formation, by strains PAO1 and PAZHI3, in the crop was associated with induction of diptericin, cecropin A1 and drosomycin antimicrobial peptide gene expression 24 h postinfection. In contrast, infection with the non-biofilm forming strain pelB::lux resulted in decreased AMP gene expression in the fly. In summary, these results provide novel insights into host-pathogen interactions during P. aeruginosa oral infection of Drosophila and highlight the use of Drosophila as an infection model that permits the study of P. aeruginosa biofilms in vivo

Crop Updates 2010 - Farming Systems

This session covers twenty papers from different authors: Pests and Disease 1. Preserving phosphine for use in Grain Storage Industry, Christopher R Newman, Department of Agriculture and Food Farming Systems Research 2. Demonstrating the benefits of grazing canola in Western Australia, Jonathan England, Stephen Gherardi and Mohammad Amjad, Department of Agriculture and Food 3. Buloke barley yield when pasture-cropped across subtropical perennial pastures, David Ferris, Department of Agriculture and Food, Phil Ward and Roger Lawes, CSIRO 4. Is pasture cropping viable in WA? Grower perceptions and EverCrop initiatives to evaluate, David Ferris, Tim Wiley, Perry Dolling, Department of Agriculture and Food, Philip Barrett-Lennard, Evergreen farming 5. Best-bet management for dual-purpose canola, John Kirkegaard, Susan Sprague, Hugh Dove and Walter Kelman, CSIRO, Canberra, Peter Hamblin, Agritech Research, Young, NSW 6. Pasture in cropping systems – with and without sheep, Brad Nutt and Angelo Loi, Department of Agriculture and Food 7. Can technology substitute for a lupin break? Wayne Parker, Department of Agriculture and Food 8. Canola row spacing with and without long term stubble retention on a sandy clay loam at Merredin, Glen Riethmuller, Department of Agriculture and Food 9. Impact of stubble retention on water balance and crop yield, Phil Ward1, Ken Flower2,3, Neil Cordingley2 and Shayne Micin1, 1CSIRO, Wembley, Western Australia, 2Western Australian No-Till Farmers Association, 3University of Western Australia Analysis and Modelling 10. Using POAMA rainfall forecasts for crop management in South-West WA, Senthold Asseng1, Peter McIntosh2,3, Mike Pook2,3, James Risbey2,3, Guomin Wang3, Oscar Alves3, Ian Foster4, Imma Farre4 and Nirav Khimashia1, 1CSIRO Plant Industry, Perth, 2CSIRO Marine and Atmospheric Research, Hobart, 3Centre for Australian Weather and Climate Research (CAWCR), A partnership between the Australian Bureau of Meteorology and CSIRO, Melbourne, 4Department of Agriculture and Food 11. Adaption to changing climates and variability – results of the Agribusiness Changing Climates regional workshop, Anderson W3, Beard D3, Blake J3, Grieve R1, Lang M3, Lemon J3, McTaggart R3, Gray D3, Price M2 and Stephens D3, 1Roderick Grieve Farm Management Consultants, 2Coffey International P/L, 3Department of Agriculture and Food 12. Farmers’ management of seasonal variability and climate change in WA, DA Beard, DM Gray, P Carmody, Department of Agriculture and Food 13. Is there a value in having a frost forecast for wheat in South-West WA? Imma Farre1, Senthold Asseng2, Ian Foster1 and Doug Abrecht3, 1Department of Agriculture and Food, CSIRO, Floreat, 2CSIRO Plant Industry, Perth 3Department of Agriculture and Food, Centre for Cropping Systems 14. Does buying rainfall pay? Greg Kirk, Planfarm Agricultural Consultants 15. Which region in the WA wheatbelt makes best use of rainfall? Peter Rowe, Bankwest Agribusiness 16. POAMA – the Predictive Ocean-Atmosphere Model for Australia, Guomin Wang and Oscar Alves, Centre for Australian Weather and Climate Research (CAWCR), A partnership between the Australian Bureau of Meteorology and CSIRO, Melbourne 17. Exploring the link between water use efficiency and farm profitability, Cameron Weeks, Planfarm and Peter Tozer, PRT Consulting Precision Agriculture 18. A plethora of paddock information is available – how does it stack up? Derk Bakker, Department of Agriculture and Food 18. Variable rate prescription mapping for lime inputs based on electromagnetic surveying and deep soil testing, Frank D’Emden, Quenten Knight and Luke Marquis, Precision Agronomics, Australia 19. Trial design and analysis using precision agriculture and farmer’s equipment, Roger Lawes, CSIRO Sustainable Ecosystems, Centre for Environment and Life Sciences, Floreat 20. Farmer perspectives of precision agriculture in Western Australia: Issues and the way forward, Dr Roger Mandel, Curtin Universit

Rare coding variants in ten genes confer substantial risk for schizophrenia

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, PPeer reviewe

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead