Fieldwork in Victoria

In January this year, Richard Wright and Robert Glenney conducted excavations at Lancefield to try and determine whether the extinct marsupial fauna found in the lake deposits were associated with man

Victorian Relics Office

Description of functions and role of the Victoria State Relics Office

Summer Field Programme of the Victoria Archaeological Survey

The Summer Field Programme was devised to service the needs of the annual Field School. This year the School was based at Yambuk, a hamlet located approximately 20 km west of Port Fairy in the Western Distric

Crop Updates - 2003 Oilseeds

This session covers fifteen papers from different authors ACKNOWLEDGMENTS VARIETIES Large scale canola varietal evaluation in WA, Peter Nelson, Oilseeds WA Performance of IT and TT canola varieties in the medium and high rainfall agzones of WA 2001-02, Graham Walton, Hasan Zaheer and Paul Carmody, Department of Agriculture QUALITY Reproductive biology, cotyledon development and oil accumulation in canola, J.A. Fortescue and D.W. Turner, School of Plant Biology, Faculty of Natural and Agricultural Sciences, The University of Western Australia Plant and environmental factors affecting oil concentration in canola – a mini-review, D.W. Turner, School of Plant Biology, Faculty of Natural and Agricultural Sciences, The University of Western Australia Potential benefits from interspecific crosses between canola and ‘near canola’ quality Indian mustard, Janet Wroth, School of Plant Biology, The University of Western Australia (UWA), Wallace Cowling, School of Plant Biology, UWA and CBWA Pty Ltd, Anh-Van Pham, School of Mathematics and Statistics, UWA NUTRITION, AGRONOMY AND MACHINERY Timing of nitrogen application for producing canola grain and oil, R. F. Brennan, Department of Agriculture Managing canola for soil type and moisture stress, Paul Carmody and Hasan Zaheer Department of Agriculture Machinery lessons from 2002 – canola establishment, Glen Riethmuller, Greg Hamilton and Jo Hawksley, Department of Agriculture Machinery lessons from 2002 – harvesting short crops, Glen Riethmuller, Department of Agriculture Does increasing canola seeding rate reduce the competitiveness of grass weeds? Zaicou-Kunesch, C.M., Zaheer, S.H. and Eksteen, D, Department of Agriculture PESTS AND DISEASES Aphid damage to canola – not all cultivars are equal, Françoise A. Berlandier and Christiaan Valentine, Department of Agriculture Should we be worried about developing insecticide resistance in aphids? Owain Edwards, CSIRO Entomology Benefits provided by treating canola seed with imidacloprid seed dressing, Roger Jones, Brenda Coutts, Lisa Smith and Jenny Hawkes, Department of Agriculture, and Centre for Legumes in Mediterranean Agriculture Blackleg levels in canola in 2002, Ravjit Khangura1, Moin Salam1, Art J Diggle1 and Martin J Barbetti1,2 1Department of Agriculture, 2University of Western Australia DBM in canola, Kevin Walden, Department of Agricultur

Discovery of biphenylacetamide-derived inhibitors of BACE1 using de novo structure-based molecular design

β-Secretase (BACE1), the enzyme responsible for the first and rate-limiting step in the production of amyloid-β peptides, is an attractive target for the treatment of Alzheimer’s disease. In this study, we report the application of the de novo fragment-based molecular design program SPROUT to the discovery of a series of nonpeptide BACE1 inhibitors based upon a biphenylacetamide scaffold. The binding affinity of molecules based upon this designed molecular scaffold was increased from an initial BACE1 IC50 of 323 μM to 27 μM following the synthesis of a library of optimized ligands whose structures were refined using the recently developed SPROUT-HitOpt software. Although a number of inhibitors were found to exhibit cellular toxicity, one compound in the series was found to have useful BACE1 inhibitory activity in a cellular assay with minimal cellular toxicity. This work demonstrates the power of an in silico fragment-based molecular design approach in the discovery of novel BACE1 inhibitors

Opposing effects of monomeric and pentameric C-reactive protein on endothelial progenitor cells

C-reactive protein (CRP) has been linked to the pathogenesis of atherosclerosis. The dissociation of native, pentameric (p)CRP to monomeric (m)CRP on the cell membrane of activated platelets has recently been demonstrated. The dissociation of pCRP to mCRP may explain local pro-inflammatory reactions at the site of developing atherosclerotic plaques. As a biomarker, pCRP predicts cardiovascular adverse events and so do reduced levels and function of circulating endothelial progenitor cells (EPCs). We hypothesised that mCRP and pCRP exert a differential effect on EPC function and differentiation. EPCs were treated with mCRP or pCRP for 72 h, respectively. Phenotypical characterisation was done by flow cytometry and immunofluorescence microscopy, while the effect of mCRP and pCRP on gene expression was examined by whole-genome gene expression analysis. The functional capacity of EPCs was determined by colony forming unit (CFU) assay and endothelial tube formation assay. Double staining for acetylated LDL and ulex lectin significantly decreased in cells treated with pCRP. The length of tubuli in a matrigel assay with HUVECs decreased significantly in response to pCRP, but not to mCRP. The number of CFUs increased after pCRP treatment. RNA expression profiling demonstrated that mCRP and pCRP cause highly contradictory gene regulation. Interferon-responsive genes (IFI44L, IFI44, IFI27, IFI 6, MX1, OAS2) were among the highly up-regulated genes after mCRP, but not after pCRP treatment. In conclusion, EPC phenotype, genotype and function were differentially affected by mCRP and pCRP, strongly arguing for differential roles of these two CRP conformations. The up-regulation of interferon-inducible genes in response to mCRP may constitute a mechanism for the local regulation of EPC function

"Nested" cryptic diversity in a widespread marine ecosystem engineer: a challenge for detecting biological invasions

<p>Abstract</p> <p>Background</p> <p>Ecosystem engineers facilitate habitat formation and enhance biodiversity, but when they become invasive, they present a critical threat to native communities because they can drastically alter the receiving habitat. Management of such species thus needs to be a priority, but the poorly resolved taxonomy of many ecosystem engineers represents a major obstacle to correctly identifying them as being either native or introduced. We address this dilemma by studying the sea squirt <it>Pyura stolonifera</it>, an important ecosystem engineer that dominates coastal communities particularly in the southern hemisphere. Using DNA sequence data from four independently evolving loci, we aimed to determine levels of cryptic diversity, the invasive or native status of each regional population, and the most appropriate sampling design for identifying the geographic ranges of each evolutionary unit.</p> <p>Results</p> <p>Extensive sampling in Africa, Australasia and South America revealed the existence of "nested" levels of cryptic diversity, in which at least five distinct species can be further subdivided into smaller-scale genetic lineages. The ranges of several evolutionary units are limited by well-documented biogeographic disjunctions. Evidence for both cryptic native diversity and the existence of invasive populations allows us to considerably refine our view of the native versus introduced status of the evolutionary units within <it>Pyura stolonifera </it>in the different coastal communities they dominate.</p> <p>Conclusions</p> <p>This study illustrates the degree of taxonomic complexity that can exist within widespread species for which there is little taxonomic expertise, and it highlights the challenges involved in distinguishing between indigenous and introduced populations. The fact that multiple genetic lineages can be native to a single geographic region indicates that it is imperative to obtain samples from as many different habitat types and biotic zones as possible when attempting to identify the source region of a putative invader. "Nested" cryptic diversity, and the difficulties in correctly identifying invasive species that arise from it, represent a major challenge for managing biodiversity.</p

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Deception and Self-Deception

Why are people so often overconfident? We conduct an experiment to test the hypothesis that people become overconfident to more effectively persuade or deceive others. After performing a cognitively challenging task, half of our subjects are informed that they can earn money by convincing others of their superior performance. The privately elicited beliefs of informed subjects are significantly more confident than the beliefs of subjects in the control condition. By generating exogenous variation in confidence with a noisy performance signal, we are also able to show that higher confidence indeed makes subjects more persuasive in the subsequent face-to-face interactions