HIV-1 capsid is involved in post-nuclear entry steps

BACKGROUND: HIV-1 capsid influences viral uncoating and nuclear import. Some capsid is detected in the nucleus but it is unclear if it has any function. We reported that the antibiotic Coumermycin-A1 (C-A1) inhibits HIV-1 integration and that a capsid mutation confers resistance to C-A1, suggesting that capsid might affect post-nuclear entry steps. RESULTS: Here we report that C-A1 inhibits HIV-1 integration in a capsid-dependent way. Using molecular docking, we identify an extended binding pocket delimited by two adjacent capsid monomers where C-A1 is predicted to bind. Isothermal titration calorimetry confirmed that C-A1 binds to hexameric capsid. Cyclosporine washout assays in Jurkat CD4+ T cells expressing engineered human TRIMCyp showed that C-A1 causes faster and greater escape from TRIMCyp restriction. Sub-cellular fractionation showed that small amounts of capsid accumulated in the nuclei of infected cells and C-A1 reduced the nuclear capsid. A105S and N74D capsid mutant viruses did not accumulate capsid in the nucleus, irrespective of C-A1 treatment. Depletion of Nup153, a nucleoporin located at the nuclear side of the nuclear pore that binds to HIV-1 capsid, made the virus less susceptible to TRIMCyp restriction, suggesting that Nup153 may help maintain some integrity of the viral core in the nucleus. Furthermore C-A1 increased binding of CPSF6, a nuclear protein, to capsid. CONCLUSIONS: Our results indicate that capsid is involved in post-nuclear entry steps preceding integration

Effects of replacing meat with soyabean in the diet on sex hormone concentrations in healthy adult males

A randomised crossover dietary intervention study was performed to evaluate the effects of replacing meat protein in the diet with a soyabean product, tofu, on blood concentrations of testosterone, dihydrotestosterone, androstanediol glucuronide, oestradiol, sex hormone-binding globulin (SHBG), and the free androgen index (total testosterone concentration/SHBG concentration x 100; FAI). Forty-two healthy adult males aged 35-62 years were studied. Diets were isoenergetic, with either 150 g lean meat or 290 g tofu daily providing an equivalent amount of macronutrients, with only the source of protein differing between the two diets. Each diet lasted for 4 weeks, with a 2-week interval between interventions. Fasting blood samples were taken between 07.00 and 09.30 hours. Urinary excretion of genistein and daidzein was significantly higher after the tofu diet (

Study of user-experience of an objective test (QbTest) to aid ADHD assessment and medication management: a multi-methods approach

Background The diagnosis and monitoring of Attention deficit hyperactivity disorder (ADHD) typically relies on subjective reports and observations. Objective continuous performance tests (CPTs) have been incorporated into some services to support clinical decision making. However, the feasibility and acceptability of adding such a test into routine practice is unknown. The study aimed to investigate the feasibility and acceptability of adding an objective computerised test to the routine assessment and monitoring of attention deficit hyperactivity disorder (ADHD). Methods Semi-structured interviews were conducted with clinicians (n = 10) and families (parents/young people, n = 20) who participated in a randomised controlled trial. Additionally, the same clinicians (n = 10) and families (n = 76) completed a survey assessing their experience of the QbTest. The study took place in child and adolescent mental health and community paediatric clinics across the UK. Interview transcripts were thematically analysed. Results Interviewed clinicians and families valued the QbTest for providing an objective, valid assessment of symptoms. The QbTest was noted to facilitate communication between clinicians, families and schools. However, whereas clinicians were more unanimous on the usefulness of the QbTest, survey findings showed that, although the majority of families found the test useful, less than half felt the QbTest helped them understand the clinician’s decision making around diagnosis and medication. The QbTest was seen as a potentially valuable tool to use early in the assessment process to streamline the care pathway. Although clinicians were conscious of the additional costs, these could be offset by reductions in time to diagnosis and the delivery of the test by a Healthcare Assistant. Conclusions The findings indicate the QbTest is an acceptable and feasible tool to implement in routine clinical settings. Clinicians should be mindful to discuss the QbTest results with families to enable their understanding and engagement with the process. Further findings from definitive trials are required to understand the cost/benefit; however, the findings from this study support the feasibility and acceptability of integrating QbTest in the ADHD care pathway

The Lipid lowering and Onset of Renal Disease (LORD) Trial: A randomized double blind placebo controlled trial assessing the effect of atorvastatin on the progression of kidney disease

Background: There is evidence that dyslipidemia is associated with chronic kidney disease (CKD). Experimental studies have established that lipids are damaging to the kidney and animal intervention studies show statins attenuate this damage. Small clinical trials, meta-analyses, observational studies and post-hoc analyses of cardiovascular intervention studies all support the concept that statins can reduce kidney damage in humans. Based on this background, a double blind randomized placebo controlled trial was designed to assess the effectiveness of atorvastatin 10 mg on slowing the progression of kidney disease in a population of patients with CKD

Crop Updates - 2003 Lupins

This session covers twenty one papers from different authors LUPIN ISSUES AND R & D DIRECTIONS Mark Sweetingham, Department of Agriculture ACKNOWLEDGEMENTS VARIETIES AND BREEDING New lupin line for release – WALAN2141, Bevan J, Buirchell, Mark Sweetingham, Geoff Thomas, Amelia McLarty, Harmohinder Dhammu and CVT and Lupin Breeding teams, Department of Agriculture Lupin variety trial, Martin Harries and Wayne Parker, Department of Agriculture Herbicide tolerance of new lupins, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Department of Agriculture YELLOW AND ALBUS LUPINS Selection for high lupin yield under terminal drought, Jairo A. Palta1&2, Neil C. Turner1&2 Bob French2&3 and Bevan Buirchell2&3 , 1CSIRO Plant Industry, Floreat, WA, 2CLIMA, University of Western Australia, Crawley, WA, 3Department of Agriculture Outcrossing and isolation distance in yellow lupins, Kedar Adhikari, Bevan Buirchell and Katia Stefanova, Department of Agriculture Development of aphid tolerant yellow lupins in Western Australia, Kedar Adhikari, Bevan Buirchell, Mark Sweetingham and Françoise Berlandier, Department of Agriculture ESTABLISHMENT Development of anthracnose resistant albus lupins for Western Australia, Kedar Adhikari, Bevan Buirchell, Mark Sweetingham and Geoff Thomas, Department of Agriculture Lupin sowing methods for improved yields, Glen Riethmuller, Department of Agriculture Moisture delving = more reliable lupin establishment, Paul Blackwell and Wayne Parker, Department of Agriculture Effect of time of sewing, plant density and row orientation on lupins at various row spacings, Geoff Fosbery, Farm Focus Consultants, Bill Crabtree, Crabtree Consulting and Tracy Gilham, WANTFA Influence of row spacing on water stress and water use of lupins, Bob French and Laurie Wahlsten, Department of Agriculture AGRONOMY Effect on lupin protein and yield from variety, planting time and seed rate, Pierre Fievez, Pierre Fievez and Associates Lupin row cropping: herbicides to band, shield design and economics, Mike Collins, WANTFA and John Holmes, 4 Farmers Harvest options for narrow leaf lupins, Martin Harries and Dirranie Kirby, Department of Agriculture NUTRITION Additional nutrients on lupin yield and protein, Pierre Fievez, Pierre Fievez and Associates Demonstrating the effect of phosphorous placement on yields of narrow leaf lupin and yellow lupin on high phosphorus retention soils, Martin Harries and Wayne Parker, Department of Agriculture PESTS AND DISEASES How far are anthracnose spores spread by rain splash? Geoff Thomas, Mark Sweetingham and Ken Adcock, Department of Agriculture Height of cereal stubble affects spread of lupin anthracnose, Geoff Thomas, Bill MacLeod and Ken Adcock, Department of Agriculture Controlling non-necrotic strains of bean yellow mosaic virus in lupins by cultural methods, Roger Jones and Rohan Prince, Department of Agriculture, and Centre for Legumes in Mediterranean Agriculture MARKET DEVELOPMENT Australian sweet lupin – is it the next human health food? Stuart Johnson, Deakin University; Ramon Hall, ARC SPIRT PhD Scholar; Madeleine Ball, University of Tasmania; Sofia Sipsas and David Petterson; Department of Agriculture CONTACT DETAILS FOR PRINCIPAL AUTHOR

Accurate Whole-Genome Sequencing and Haplotyping from 10 to 20 Human Cells

Recent advances in whole genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, Long Fragment Read (LFR) technology, similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only ~100 pg of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants (SNVs) were assembled into long haplotype contigs. Removal of false positive SNVs not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10 Mb. Cost-effective and accurate genome sequencing and haplotyping from 10-20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications

Crop Updates 2001 - Lupins

This session covers twenty six papers from different authors: INTRODUCTION, 1. Introduction, Dr Mark Sweetingham LUPIN RESEARCH AND INDUSTRY DEVELOPMENT, Agriculture Western Australia VARIETIES 2. Lupin variety performance: Are you making the most of it? Bevan J. Buirchell, Agriculture Western Australia 3. Adaption of restricted-branching lupins in Western Australia, Bob French and Laurie Wahlsten, Agriculture Western Australia 4. Isolated microspore culture of lupin for production of doubled haploids, Dr Janet Wroth, Dr Kirsty Bayliss and A/Prof. Wallace Cowling, Plant Sciences, Faculty of Agriculture, The University of Western Australia NUTRITION 5. Banding manganese fertiliser below the seed increases seed yields of narrow-leafed lupins, R.F. Brennan, Agriculture Western Australia 6. Residual value of manganese fertiliser for lupin grain production, R.F. Brennan, Agriculture Western Australia AGRONOMY 7. Lupin seeding density, Miles Dracup, Agriculture Western Australia, Nick Galwey, University of Western Australia and Bob Thomson, University of Western AustraliaPESTS AND DISEASES 8. Anthracnose in lupins – understanding the risk, Moin Salam, Art Diggle, Geoff Thomas, Mark Sweetinghamand Bill O’Neill, Agriculture Western Australia 9. Implications of the ‘green bridge’ for viral and fungal disease carry-over between seasons, Debbie Thackray, Agriculture Western Australia and Centre for Legumes in Mediterranean Agriculture 10. Insect pest development in WA via the ‘green bridge’, Kevin Walden, Agriculture Western Australia 11. Lupin anthracnose – seed infection thresholds, Geoff Thomas, Agriculture Western Australia 12. Identification and characterisation of resistance genes to Phomopsis blight in narrow-leafed lupin, M. Shankar1, M.W. Sweetingham1&2 and W.A. Cowling1&3 , 1Co-operative Research Centre for Legumes in Mediterranean Agriculture, 2Agriculture Western Australia, 3Plant Sciences 13. Plant disease diagnostics, Dominie Wright and Nichole Burges, Agriculture Western Australia 14. Detection of strains of Phomopsis exhibiting species preference in lupins, M. Shankar, 1Co-operative Research Centre for Legumes in Mediterranean Agriculture and M.W. Sweetingham, Agriculture Western Australia 15. Potential alternate host for the lupin anthracnose pathogen, Geoff Thomasa, Hu’aan Yangb, Mark Sweetinghamab and Ming Pei Youa, aAgriculture Western Australia, bCooperative Research Centre for Legumes in Mediterranean Agriculture WEEDS 16. Wild radish – the implications for our rotations, Dr David Bowran, Centre for Cropping Systems 17. Competitiveness of wild radish in a wheat – lupin rotation, Abul Hashem, Nerys Wilkins, and Terry Piper, Agriculture Western Australia 18. Population explosion and persistence of wild radish in a wheat-lupin rotation, Abul Hashem, Nerys Wilkins, Aik Cheam and Terry Piper, Agriculture Western Australia 19. Inter-row knockdowns for profitable lupins, Paul Blackwell, Agriculture Western Australia, Miles Obst, Mingenew 20. Is it safe to use 2,4-D Ester 80% pre-sowing when furrow sowing lupins? Andrew Sandison, Elders Ltd QUALITY AND MARKET DEVELOPMENT 21. Lupin protein – what we know, Bill O’Neill, Agriculture Western Australia 22. Foliar N application increases grain protein in lupins, Bob French and Laurie Wahlsten, Agriculture Western Australia 23. Can lupin grain protein be increased with Flexi-N? Cameron Weeks, Erin Hasson, Mingenew-Irwin Group and Luigi Moreschi, CSBP futurefarm 24. Putting a value on lupin use in the aquaculture industry: a fishy business? Brett D. Glencross, Fisheries WA, Fremantle Maritime Centre, Fremantle 25. Selection for thinner seed coats and pod walls in lupins, Jon Clements, Centre for Legumes in Mediterranean Agriculture and Miles Dracup, Agriculture Western Australia 26. Assessing the nutritional benefit of Australian sweet lupin (Lupinus angustifolius) in human foods, Ramon Hall (SPIRT PhD scholar), Stuart Johnson, Madeleine Ball, Deakin University, Melbourne, Sofia Sipsas and David Petterson, Agriculture Western Australi