Prosaposin is a regulator of progranulin levels and oligomerization

Progranulin (GRN) loss-of-function mutations leading to progranulin protein (PGRN) haploinsufficiency are prevalent genetic causes of frontotemporal dementia. Reports also indicated PGRN-mediated neuroprotection in models of Alzheimer’s and Parkinson’s disease; thus, increasing PGRN levels is a promising therapeutic for multiple disorders. To uncover novel PGRN regulators, we linked whole-genome sequence data from 920 individuals with plasma PGRN levels and identified the prosaposin (PSAP) locus as a new locus significantly associated with plasma PGRN levels. Here we show that both PSAP reduction and overexpression lead to significantly elevated extracellular PGRN levels. Intriguingly, PSAP knockdown increases PGRN monomers, whereas PSAP overexpression increases PGRN oligomers, partly through a protein–protein interaction. PSAP-induced changes in PGRN levels and oligomerization replicate in human-derived fibroblasts obtained from a GRN mutation carrier, further supporting PSAP as a potential PGRN-related therapeutic target. Future studies should focus on addressing the relevance and cellular mechanism by which PGRN oligomeric species provide neuroprotection

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1

Abnormal Expression Of Homeobox Genes And Transthyretin In C9Orf72 Expansion Carriers

Objective: We performed a genome-wide brain expression study to reveal the underpinnings of diseases linked to a repeat expansion in chromosome 9 open reading frame 72 (C9ORF72). Methods: The genome-wide expression profile was investigated in brain tissue obtained from C9ORF72 expansion carriers (n = 32), patients without this expansion (n = 30), and controls (n = 20). Using quantitative real-time PCR, findings were confirmed in our entire pathologic cohort of expansion carriers (n = 56) as well as nonexpansion carriers (n = 31) and controls (n = 20). Results: Our findings were most profound in the cerebellum, where we identified 40 differentially expressed genes, when comparing expansion carriers to patients without this expansion, including 22 genes that have a homeobox (e.g., HOX genes) and/or are located within the HOX gene cluster (top hit: homeobox A5 [HOXA5]). In addition to the upregulation of multiple homeobox genes that play a vital role in neuronal development, we noticed an upregulation of transthyretin (TTR), an extracellular protein that is thought to be involved in neuroprotection. Pathway analysis aligned with these findings and revealed enrichment for gene ontology processes involved in (anatomic) development (e.g., organ morphogenesis). Additional analyses uncovered that HOXA5 and TTR levels are associated with C9ORF72 variant 2 levels as well as with intron-containing transcript levels, and thus, disease-related changes in those transcripts may have triggered the upregulation of HOXA5 and TTR. Conclusions: In conclusion, our identification of genes involved in developmental processes and neuroprotection sheds light on potential compensatory mechanisms influencing the occurrence, presentation, and/or progression of C9ORF72-related diseases

Crop Updates 2006 - Weeds

This session covers thirty seven papers from different authors: 1. ACKNOWLEDGEMENTS, Alexandra Douglas, CONVENOR – WEEDS DEPARTMENT OF AGRICULTURE SPRAY TECHNOLOGY 2. Meeting the variable application goals with new application technology, Thomas M. Wolf, Agriculture and Agri-Food Canada, Saskatoon Research Centre 3. Spray nozzles for grass weed control, Harm van Rees, BCG (Birchip Cropping Group) 4. Boom sprayer setups – achieving coarse droplets with different operating parameters, Bill Gordon, Bill Gordon Consulting 5. Complying with product label requirements, Bill Gordon, Bill Gordon Consulting 6. IWM a proven performer over 5 years in 33 focus paddocks, Peter Newman and Glenn Adam, Department of Agriculture 7. Crop topping of wild radish in lupins and barley, how long is a piece of string? Peter Newman and Glenn Adam, Department of Agriculture 8. Determining the right timing to maximise seed set control of wild radish, Aik Cheam and Siew Lee, Department of Agriculture 9. Why weed wiping varies in success rates in broadacre crops? Aik Cheam1, Katherine Hollaway2, Siew Lee1, Brad Rayner1 and John Peirce1,1Department of Agriculture, 2Department of Primary Industries, Victoria 10. Are WA growers successfully managing herbicide resistant annual ryegrass? Rick Llewellynabc, Frank D’Emdena, Mechelle Owenb and Stephen Powlesb aCRC Australian Weed Management, School of Agricultural and Resource Economics, University of Western Australia; bWA Herbicide Resistance Initiative, University of Western Australia. cCurrent address: CSIRO Sustainable Ecosystems 11. Do herbicide resistant wild radish populations look different? Michael Walsh, Western Australian Herbicide Resistance Initiative, University of Western Australia 12. Can glyphosate and paraquat annual ryegrass reduce crop topping efficacy? Emma Glasfurd, Michael Walsh and Kathryn Steadman, Western Australian Herbicide Resistance Initiative, University of Western Australia 13. Tetraploid ryegrass for WA. Productive pasture phase AND defeating herbicide resistant ryegrass, Stephen Powlesa, David Ferrisab and Bevan Addisonc, aWA Herbicide Resistance Initiative, University of Western Australia; bDepartment of Agriculture, and cElders Limited 14. Long-term management impact on seedbank of wild radish with multiple resistance to diflufenican and triazines, Aik Cheam, Siew Lee, Dave Nicholson and Ruben Vargas, Department of Agriculture 15. East-west crop row orientation improves wheat and barley yields, Dr Shahab Pathan, Dr Abul Hashem, Nerys Wilkins and Catherine Borger3, Department of Agriculture, 3WAHRI, The University ofWestern Australia 16. Competitiveness of different lupin cultivars with wild radish, Dr Shahab Pathan, Dr Bob French and Dr Abul Hashem, Department of Agriculture 17. Managing herbicide resistant weeds through farming systems, Kari-Lee Falconer, Martin Harries and Chris Matthews, Department of Agriculture 18. Lupins tolerate in-row herbicides well, Peter Newman and Martin Harries, Department of Agriculture 19. Summer weeds can reduce wheat grain yield and protein, Dr Abul Hashem1, Dr Shahab Pathan1 and Vikki Osten3, 1Department Agriculture, 3Senior Agronomist, CRC for Australian Weed Management, Queensland Department of Primary Industries and Fisheries 20. Diuron post-emergent in lupins, the full story, Peter Newman and Glenn Adam, Department of Agriculture 21. Double incorporation of trifluralin, Peter Newman and Glenn Adam, Department of Agriculture 22. Herbicide tolerance of narrow leafed and yellow lupins, Harmohinder Dhammu, David Nicholson, Department of Agriculture 23. MIG narrow leaf lupin herbicide tolerance trial, Richard Quinlan, Planfarm Pty Ltd, Trials Coordinator MIG; Debbie Allen, Research Agronomist – MIG 24. Herbicide tolerance of new albus lupins, Harmohinder Dhammu, David Nicholson, Department of Agriculture 25. Field pea x herbicide tolerance, Mark Seymour and Harmohinder Dhammu, Research Officers, and Pam Burgess, Department of Agriculture 26. Faba bean variety x herbicide tolerance, Mark Seymour and Harmohinder Dhammu, Research Officers, and Pam Burgess, Department of Agriculture 27. Herbicide tolerance of new Kabili chickpeas, Harmohinder Dhammu, Owen Coppen and Chris Roberts, Department of Agriculture 28. Timing of phenoxys application in EAG Eagle Rock, Harmohinder Dhammu, David Nicholson, Department of Agriculture 29. Herbicide tolerance of new wheat varieties, Harmohinder Dhammu, David Nicholson, Department of Agriculture 30. Lathyrus sativus x herbicide tolerance, Mark Seymour, Department of Agriculture 31. Tolerance of annual pasture species to herbicides and mixtures containing diuron, Christiaan Valentine and David Ferris, Department of Agriculture 32. The impact of herbicides on pasture legume species – a summary of scientific trial results across 8 years, Christiaan Valentine and David Ferris, Department of Agriculture 33. The impact of spraytopping on pasture legume seed set, Christiaan Valentine and David Ferris, Department of Agriculture 34. Ascochyta interaction with Broadstrike in chickpeas, H.S. Dhammu1, A.K. Basandrai2,3, W.J. MacLeod1, 3 and C. Roberts1, 1Department of Agriculture, 2CSKHPAU, Dhaulakuan, Sirmour (HP), India and 3CLIMA 35. Best management practices for atrazine in broadacre crops, John Moore, Department of Agriculture, Neil Rothnie, Chemistry Centre of WA, Russell Speed, Department of Agriculture, John Simons, Department of Agriculture, and Ted Spadek, Chemistry Centre of WA 36. Biology and management of red dodder (Cuscuta planiflolia) – a new threat to the grains industry, Abul Hashem, Daya Patabendige and Chris Roberts, Department Agriculture 37. Help the wizard stop the green invaders! Michael Renton, Sally Peltzer and Art Diggle, Department of Agricultur

Alterations in Epithelial and Mesenchymal Intestinal Gene Expression During Doxorubicin-Induced Mucositis in Mice

In the current study we aimed to gain insight into epithelial-mesenchymal cross-talk and progenitor compartment modulation during doxorubicin (DOX)-induced mucositis in mice. Intestinal segments were collected on various days after DOX treatment. DOX-induced damage at day 1–2 was characterized by increased epithelial proliferation and apoptosis and a decrease in the expression of epithelial differentiation markers. Concurrently, T-cell factor-4 (TCF4) levels increased and the epithelial differentiation enhancing factor, bone morphogenic protein-4 (BMP4), decreased. During severe damage (day 3), BMP4 levels were significantly increased, which inversely correlated with epithelial proliferation. At the same time, the expression of the epithelial differentiation markers was increasing again. At day 7, BMP4 levels were down-regulated, while the levels of the epithelial differentiation markers and TCF4 were normalized again. These data suggest that in response to DOX-induced damage, BMP4 and TCF4 are modulated in such a way that homeostasis of the progenitor compartment is partly preserved

Crop Updates 2001 - Grower Booklet

1. Strategies for leaf disease management in wheat, Jatinderpal Bhathal1, Cameron Weeks2, Kith Jayasena1 and Robert Loughman1, 1Agriculture Western Australia. 2Mingenew-Irwin Group Inc. 2. Burn stubble windrows: to diagnose soil fertility problems, Bill Bowden, Chris Gazey and Ross Brennan, Agriculture Western Australia 3. Rainfall – what happened in 2000 and the prospects for 2001, Ian Foster, Agriculture Western Australia 4. Strategies for leaf disease management in malting barley, K. Jayasena1, Q. Knight2 and R. Loughman1, 1Agriculture Western Australia, 2IAMA Agribusiness 5. Planning your cropping program in season 2001, Dr Ross Kingwell, Agriculture Western Australia and University of Western Australia 6. Rotational crops and varieties for management of root lesion nematodes in Western Australia, S.B. Sharma, S. Kelly and R. Loughman, Crop Improvement Institute, Agriculture Western Australia 7. When and where to grow oats, Glenn McDonald, Agriculture Western Australia 8. Managing Gairdner barley for quality, Kevin Young and Blakely Paynter, Agriculture Western Australia FARMING SYSTEMS, PASTURES AND WEEDS 9.Evaluation of pasture species for phase pasture systems, Keith Devenish, Agriculture Western Australia 10. Competitiveness of wild radish in a wheat – lupin rotation, Abul Hashem, Nerys Wilkins, and Terry Piper, Agriculture Western Australia 11. Can we eradicate barley grass? Sally Peltzer, Agriculture Western Australia 12. Short term pasture phase for weed control, Clinton Revell and Candy Hudson, Agriculture Western Australia 13. Herbicide tolerance of some annual pasture legumes adapted to coarse textured sandy soils, Clinton Revell and Ian Rose, Agriculture Western Australia 14. Integrated weed management: Cadoux, Alexandra Wallace, Agriculture Western Australia LUPINS 15. Inter-row knockdowns for profitable lupins, Paul Blackwell, Agriculture Western Australia and Miles Obst, farmer, Mingenew 16.. Wild radish – the implications for our rotations, Dr David Bowran, Centre for Cropping Systems 17. Lupin variety performance: Are you making the most of it? Bevan J. Buirchell, Senior Plant Breeder, Agriculture Western Australia 18. Anthracnose in lupins – understanding the risk, Moin Salam, Art Diggle, Geoff Thomas, Mark Sweetingham and Bill O’Neill, Agriculture Western Australia OILSEEDS 19. Effect of stubble, seeding technique and seed size on crop establishment and yield of canola, Rafiul Alam, Glen Riethmuller and Greg Hamilton, Agriculture Western Australia 20. Canola – More responses to lime, Chris Gazey and Paul Carmody,Agriculture Western Australia 22. Performance of new canola varieties in AGWEST variety trials in 2000, G. Walton, Crop Improvement Institute, Agriculture Western Australia PULSES 23. The ascochyta management package for 2001, B. MacLeod, Agriculture Western Australia 24. Herbicide tolerance of new field pea varieties and lines, M. Seymour, H. Dhammu, T. Piper, D. Nicholson, M. D\u27Antuono, Agriculture Western Australi

Detecting forest response to droughts with global observations of vegetation water content

Droughts in a warming climate have become more common and more extreme, making understanding forest responses to water stress increasingly pressing. Analysis of water stress in trees has long focused on water potential in xylem and leaves, which influences stomatal closure and water flow through the soil-plant-atmosphere continuum. At the same time, changes of vegetation water content (VWC) are linked to a range of tree responses, including fluxes of water and carbon, mortality, flammability, and more. Unlike water potential, which requires demanding in situ measurements, VWC can be retrieved from remote sensing measurements, particularly at microwave frequencies using radar and radiometry. Here, we highlight key frontiers through which VWC has the potential to significantly increase our understanding of forest responses to water stress. To validate remote sensing observations of VWC at landscape scale and to better relate them to data assimilation model parameters, we introduce an ecosystem-scale analog of the pressure-volume curve, the non-linear relationship between average leaf or branch water potential and water content commonly used in plant hydraulics. The sources of variability in these ecosystem-scale pressure-volume curves and their relationship to forest response to water stress are discussed. We further show to what extent diel, seasonal, and decadal dynamics of VWC reflect variations in different processes relating the tree response to water stress. VWC can also be used for inferring belowground conditions-which are difficult to impossible to observe directly. Lastly, we discuss how a dedicated geostationary spaceborne observational system for VWC, when combined with existing datasets, can capture diel and seasonal water dynamics to advance the science and applications of global forest vulnerability to future droughts

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Characterization of the role of ribonucleases in Salmonella small RNA decay

In pathogenic bacteria, a large number of sRNAs coordinate adaptation to stress and expression of virulence genes. To better understand the turnover of regulatory sRNAs in the model pathogen, Salmonella typhimurium, we have constructed mutants for several ribonucleases (RNase E, RNase G, RNase III, PNPase) and Poly(A) Polymerase I. The expression profiles of four sRNAs conserved among many enterobacteria, CsrB, CsrC, MicA and SraL, were analysed and the processing and stability of these sRNAs was studied in the constructed strains. The degradosome was a common feature involved in the turnover of these four sRNAs. PAPI-mediated polyadenylation was the major factor governing SraL degradation. RNase III was revealed to strongly affect MicA decay. PNPase was shown to be important in the decay of these four sRNAs. The stability of CsrB and CsrC seemed to be independent of the RNA chaperone, Hfq, whereas the decay of SraL and MicA was Hfq-dependent. Taken together, the results of this study provide initial insight into the mechanisms of sRNA decay in Salmonella, and indicate specific contributions of the RNA decay machinery components to the turnover of individual sRNAs