226 research outputs found
Alternative propulsor for mobile transportation and technological machines wood complex
Лесные машины, оборудованные альтернативным движителем, способны передвигаться по любым типам поверхностей (подготовленным дорогам, пахоте, болоту, песку, заснеженной местности и т.д.) с минимальным негативным воздействием.Forestry machines equipped alternative propulsors are capable to move on any types of land surfaces (the prepared roads, plowed land, bog, the sand, snow-covered land and etc.) with the minimal negative influence
Correction: LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/β-catenin signalling in neuroblastoma
A Correction on:
LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/β-catenin signalling in neuroblastoma
Gabriella Cunha Vieira, S. Chockalingam, Zsombor Melegh, Alexander Greenhough, Sally Malik, Marianna Szemes, Ji Hyun Park, Abderrahmane Kaidi, Li Zhou, Daniel Catchpoole, Rhys Morgan, David O. Bates, Peter J. Gabb and Karim Malik
Original article: Oncotarget. 2015; 6:40053-67. DOI: 10.18632/oncotarget.5548.
The originally Figure 5 contains duplicate total-ERK panels.
The proper Figure 5 is attached. The authors sincerely apologize for this error
Hypomethylation and aberrant expression of the glioma pathogenesis-related 1 gene in Wilms tumors
Wilms tumors (WTs) have a complex etiology, displaying genetic and epigenetic changes, including loss of imprinting (LOI) and tumor suppressor gene silencing. To identify new regions of epigenetic perturbation in WTs, we screened kidney and tumor DNA using CpG island (CGI) tags associated with cancer-specific DNA methylation changes. One such tag corresponded to a paralog of the glioma pathogenesis-related 1/related to testis-specific, vespid, and pathogenesis proteins 1 (GLIPR1/RTVP-1) gene, previously reported to be a tumor-suppressor gene silenced by hypermethylation in prostate cancer. Here we report methylation analysis of the GLIPR1/RTVP-1 gene in WTs and normal fetal and pediatric kidneys. Hypomethylation of the GLIPR1/RTVP-1 5′-region in WTs relative to normal tissue is observed in 21/24 (87.5%) of WTs analyzed. Quantitative analysis of GLIPR1/RTVP-1 expression in 24 WTs showed elevated transcript levels in 16/24 WTs (67%), with 12 WTs displaying in excess of 20-fold overexpression relative to fetal kidney (FK) control samples. Immunohistochemical analysis of FK and WT corroborates the RNA expression data and reveals high GLIPR1/RTVP-1 in WT blastemal cells together with variable levels in stromal and epithelial components. Hypomethylation is also evident in the WT precursor lesions and nephrogenic rests (NRs), supporting a role for GLIPR1/RTVP-1 deregulation early in Wilms tumorigenesis. Our data show that, in addition to gene dosage changes arising from LOI and hypermethylation-induced gene silencing, gene activation resulting from hypomethylation is also prevalent in WTs. Copyright © 2007 Neoplasia Press, Inc. All rights reserved
Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells
© 2014 The Authors. Approximately half of poor prognosis neuroblastomas (NBs) are characterized by pathognomonic MYCN gene amplification and MYCN over-expression. Here we present data showing that short-interfering RNA mediated depletion of the protein arginine methyltransferase 5 (PRMT5) in cell-lines representative of NBs with MYCN gene amplification leads to greatly impaired growth and apoptosis. Growth suppression is not apparent in the MYCN-negative SH-SY5Y NB cell-line, or in two immortalized human fibroblast cell-lines. Immunoblotting of NB cell-lines shows that high PRMT5 expression is strongly associated with MYCN-amplification (P < 0.004, Mann-Whitney U-test) and immunohistochemical analysis of primary NBs reveals that whilst PRMT5 protein is ubiquitously expressed in the cytoplasm of most cells, MYCN-amplified tumours exhibit pronounced nuclear PRMT5 staining. PRMT5 knockdown in MYCN-overexpressing cells, including the SHEP-21N cell-line with inducible MYCN expression leads to a dramatic decrease in MYCN protein and MYCN-associated cell-death in SHEP-21N cells. Quantitative gene expression analysis and cycloheximide chase experiments suggest that PRMT5 regulates MYCN at a post-transcriptional level. Reciprocal co-immunoprecipitation experiments demonstrated that endogenous PRMT5 and MYCN interact in both SK-N-BE(2)C and NGP cell lines. By using liquid chromatography - tandem mass spectrometry (LC-MS/MS) analysis of immunoprecipitated MYCN protein, we identified several potential sites of arginine dimethylation on the MYCN protein. Together our studies implicate PRMT5 in a novel mode of MYCN post-translational regulation and suggest PRMT5 plays a major role in NB tumorigenesis. Small-molecule inhibitors of PRMT5 may therefore represent a novel therapeutic strategy for neuroblastoma and other cancers driven by the MYCN oncogene
Exploring state-of-the-art advances in targeted nanomedicines for managing acute and chronic inflammatory lung diseases
Diagnosis and treatment of lung diseases pose serious challenges. Currently, diagnostic as well as therapeutic methods show poor efficacy toward drug-resistant bacterial infections, while chemotherapy causes toxicity and nonspecific delivery of drugs. Advanced treatment methods that cure lung-related diseases, by enabling drug bioavailability via nasal passages during mucosal formation, which interferes with drug penetration to targeted sites, are in demand. Nanotechnology confers several advantages. Currently, different nanoparticles, or their combinations, are being used to enhance targeted drug delivery. Nanomedicine, a combination of nanoparticles and therapeutic agents, that delivers drugs to targeted sites increases the bioavailability of drugs at these sites. Thus, nanotechnology is superior to conventional chemotherapeutic strategies. Here, the authors review the latest advancements in nanomedicine-based drug-delivery methods for managing acute and chronic inflammatory lung diseases
Riboflavin/UVA Collagen Cross-Linking-Induced Changes in Normal and Keratoconus Corneal Stroma
Purpose To determine the effect of Ultraviolet-A collagen cross-linking with hypo-osmolar and iso-osmolar riboflavin solutions on stromal collagen ultrastructure in normal and keratoconus ex vivo human corneas. Methods Using small-angle X-ray scattering, measurements of collagen D-periodicity, fibril diameter and interfibrillar spacing were made at 1 mm intervals across six normal post-mortem corneas (two above physiological hydration (swollen) and four below (unswollen)) and two post-transplant keratoconus corneal buttons (one swollen; one unswollen), before and after hypo-osmolar cross-linking. The same parameters were measured in three other unswollen normal corneas before and after iso-osmolar cross-linking and in three pairs of swollen normal corneas, in which only the left was cross-linked (with iso-osmolar riboflavin). Results Hypo-osmolar cross-linking resulted in an increase in corneal hydration in all corneas. In the keratoconus corneas and unswollen normal corneas, this was accompanied by an increase in collagen interfibrillar spacing (p<0.001); an increase in fibril diameter was also seen in two out of four unswollen normal corneas and one unswollen keratoconus cornea (p<0.001). Iso-osmolar cross-linking resulted in a decrease in tissue hydration in the swollen normal corneas only. Although there was no consistent treatment-induced change in hydration in the unswollen normal samples, iso-osmolar cross-linking of these corneas did result in a compaction of collagen fibrils and a reduced fibril diameter (p<0.001); these changes were not seen in the swollen normal corneas. Collagen D-periodicity was not affected by either treatment. Conclusion The observed structural changes following Ultraviolet-A cross-linking with hypo-osmolar or iso-osmolar riboflavin solutions are more likely a consequence of treatment-induced changes in tissue hydration rather than cross-linking
Spliceosomal vulnerability of MYCN-amplified neuroblastoma is contingent on PRMT5-mediated regulation of epitranscriptomic and metabolomic pathways
Approximately 50% of poor prognosis neuroblastomas arise due to MYCN over-expression. We previously demonstrated that MYCN and PRMT5 proteins interact and PRMT5 knockdown led to apoptosis of MYCN amplified (MNA) neuroblastoma. Here we evaluate the highly selective first-in-class PRMT5 inhibitor GSK3203591 and its in vivo analogue GSK3326593 as targeted therapeutics for MNA neuroblastoma. Cell-line analyses show MYCN-dependent growth inhibition and apoptosis, with approximately 200-fold greater sensitivity of MNA neuroblastoma lines. RNA sequencing of three MNA neuroblastoma lines treated with GSK3203591 reveal deregulated MYCN transcriptional programmes and altered mRNA splicing, converging on key regulatory pathways such as DNA damage response, epitranscriptomics and cellular metabolism. Stable isotope labelling experiments in the same cell lines demonstrate that glutamine metabolism is impeded following GSK3203591 treatment, linking with disruption of the MLX/Mondo nutrient sensors via intron retention of MLX mRNA. Interestingly, glutaminase (GLS) protein decreases after GSK3203591 treatment despite unchanged transcript levels. We demonstrate that the RNA methyltransferase METTL3 and cognate reader YTHDF3 proteins are lowered following their mRNAs undergoing GSK3203591-induced splicing alterations, indicating epitranscriptomic regulation of GLS; accordingly, we observe decreases of GLS mRNA m6A methylation following GSK3203591 treatment, and decreased GLS protein following YTHDF3 knockdown. In vivo efficacy of GSK3326593 is confirmed by increased survival of Th-MYCN mice, with drug treatment triggering splicing events and protein decreases consistent with in vitro data. Together our study demonstrates the PRMT5-dependent spliceosomal vulnerability of MNA neuroblastoma and identifies the epitranscriptome and glutamine metabolism as critical determinants of this sensitivity
Crop Updates - 2009 Katanning
This session covers seventeen papers from different authors
GM canola – How will it affect the way I farm? Murray Scholz, 2008 Nuffield scholar, Southern NSW
Eight years of IWM smashes tyegrass seed banks by 98% over 31 focus paddocks, Peter Newman, Glenn Adam & Trevor Bell, Department of Agriculture and Food
The global economic climate and impacts on agriculture, profile on Michael Whitehead Rabobank New York
Lessons from five years of cropping systems research, W.K. Anderson, Department of Agriculture and Food
Case study of a 17year old agricultural lime trial, C. Gazey, Department of Agriculture and Food, J. Andrew, Precision SoilTech and R. Pearce, ConsultAg
Fertilising in a changing price environment, Bill Bowden, Wayne Pluske and Jeremy Lemon, Department of Agriculture and Food
Fact or Fiction: Who is telling the truth and how to tell the difference? D.C. Edmeades, agKnowledge Ltd, Hamilton
Forecast disease resistance profile for the Western Australian barley crop over the next three years, JJ Russell, Department of Agriculture and Food
Malting barley varieties differ in their flowering date and their response to change in sowing date, BH Paynter and JJ Russell, Department of Agriculture and Food
Decimating weed seed banks within non-crop phases for the benefit of subsequent crops, Dr Davis Ferris, Department of Agriculture and Food
Autumn cleaning yellow serradella pastures with broad spectrum herbicides – a novel weed control strategy that exploits delayed germination, Dr Davis Ferris, Department of Agriculture and Food
Emerging weeds in changing farming systems, Dr Abul Hashen, Department of Agriculture and Food
More glyphosate-resistant annual ryegrass populations within Western Australia, Dr Abul Hashem and Dr Catherine Borger, Department of Agriculture and Food
Reasons to use only the full label herbicide rate, Stephen B. Powels, Qin Yu, Mechelle Owen, Roberto Busi, Sudheesh Manalil, University of Western Australia
Flaxleaf fleabane – coming to a property near you! Sally Peltzer, Department of Agriculture and Food
Glyphosate – the consequences of cutting rates! Sally Peltzer and David Minkey, Department of Agriculture and Food
Benefits of crop rotations/break crops in managing soil moisture, soil health, weeds and disease – an overview, Raj Malik, Department of Agriculture and Foo
Crop Updates 2008 - Cereals
This session covers twenty four papers from different authors:
WHEAT AGRONOMY
1. Wheat variety performance in the Northern Agricultural Region in 2007, Christine Zaicou, Department of Agriculture and Food
2. Wheat variety performance on the Central Agricultural Region in 2007, Shahajahan Miyan, Department of Agriculture and Food
3. Response of wheat varieties to sowing time in the Great Southern and Lakes Region in 2007, Brenda Shackley and Steve Penny, Department of Agriculture and Food
4. Wheat variety performance in the South Coastal Region in 2007, Sarah Ellis, Department of Agriculture and Food
5. Flowering dates of wheat varieties in Western Australia in 2007, Darshan Sharma, Brenda Shackley and Christine Zaicou, Department of Agriculture and Food
BARLEY AGRONOMY
6. Barley variety options for Western Australia, Blakely Paynter, Andrea Hills and Jeff Russell, Department of Agriculture and Food
7. Vlaming A – the newest malting barley variety, Blakely Paynter, Jeff Russell and Andrea Hills, Department of Agriculture and Food
8. Barley yields higher in wide rows with stubble retained in a very dry season at Merredin, Glen Riethmuller, Bill Bowden and Paul Blackwell, Department of Agriculture and Food
HERBICIDE TOLERANCE
9. Herbicide tolerance of current/new wheat varieties, Dr Harmohinder Dhammu, Department of Agriculture and Food
10. Herbicide tolerance of new oat varieties, Dr Harmohinder Dhammu, Vince Lambert, and Chris Roberts,Department of Agriculture and Food
NUTRITION
11. Managing nitrogen inputs in malting barley, Andrea Hills and Blakely Paynter, Department of Agriculture and Food
12. Decision tools for optimal N on cereal crops, David and Sally Cox, Jeremy Lemon* and Andrea Hills*, *Department of Agriculture and Food
13. Wheat varieties respond differently to potassium application on potassium responsive soils, Paul Damon and Zed Rengel, Faculty of Natural and Agricultural Sciences, University of Western Australia
DISEASES
14. Leaf disease management in continuous barley in the northern and central grainbelt of WA, Geoff Thomas, Ciara Beard, Anne Smith, Kith Jayasena and Sean Kelly, Department of Agriculture and Food
15. Temperature and moisture requirements of leaf, stem and stripe rusts of wheat, Geoff Thomas, Rob Loughman and Bill MacLeod, Department of Agriculture and Food
16. Fungicide options for controlling diseases in oats, Raj Malik and Blakely Paynter, Department of Agriculture and Food
17. Survey of wheat root diseases under intensive cereal production in Western Australia during 2005-2007, Ravjit Khangura, William MacLeod, Vivien Vanstone, Colin Hanbury, Mehreteab Aberra, Gordon MacNish and Robert Loughman, Department of Agriculture and Food
18. Epidemiology studies on Wheat Streak Mosaic Virus in 2007, Brenda Coutts, Geoff Strickland, Monica Kehoe, Dustin Severtson and Roger Jones, Department of Agriculture and Food
19. Bacterial diseases that affect WA export hay quality, Dominie Wright and Megan Jordan, Department of Agriculture and Food
SOIL
20. Hardpan penetration ability of drought-stressed wheat under pot and field conditions, Xinhua He1, Eli Manyol1, Song-Ai Nio1, Imran Malik1, Tina Botwright-Acuña1,2and Len Wade1,3,1School of Plant Biology, University of Western Australia, 2Tasmanian Institute of Agricultural Research, University of Tasmania, TAS, 3E.H. Graham Centre, Charles Sturt University, NSW
HARVEST MANAGEMENT
21. Calculating the risk – the SEPWA Harvest Calculator, Nigel Metz, South East Premium Wheat Growers Association
22. The relationship between grain moisture and atmospheric conditions in cereal crop harvesting on the South Coast of WA, Nigel Metz, South East Premium Wheat Growers Association (SEPWA)
MARKETS
23. Varietal accreditation for Australian Barley, Linda Price, Barley Australia
STATISTICAL METHODS
24. Applying data mining tools to improve grain quality for growers, Dean Diepeveen1, Leisa Armstrong2, Peter Clarke1, Doug Abrecht1, Rudi Appels2 and Matthew Bellgard3,1Department of Agriculture and Food, Western Australia 2Edith Cowan University, Western Australia, 3Centre of Comparative Genomics, Murdoch Universit
Frequent Long-Range Epigenetic Silencing of Protocadherin Gene Clusters on Chromosome 5q31 in Wilms' Tumor
Wilms' tumour (WT) is a pediatric tumor of the kidney that arises via failure of the fetal developmental program. The absence of identifiable mutations in the majority of WTs suggests the frequent involvement of epigenetic aberrations in WT. We therefore conducted a genome-wide analysis of promoter hypermethylation in WTs and identified hypermethylation at chromosome 5q31 spanning 800 kilobases (kb) and more than 50 genes. The methylated genes all belong to α-, β-, and γ-protocadherin (PCDH) gene clusters (Human Genome Organization nomenclature PCDHA@, PCDHB@, and PCDHG@, respectively). This demonstrates that long-range epigenetic silencing (LRES) occurs in developmental tumors as well as in adult tumors. Bisulfite polymerase chain reaction analysis showed that PCDH hypermethylation is a frequent event found in all Wilms' tumor subtypes. Hypermethylation is concordant with reduced PCDH expression in tumors. WT precursor lesions showed no PCDH hypermethylation, suggesting that de novo PCDH hypermethylation occurs during malignant progression. Discrete boundaries of the PCDH domain are delimited by abrupt changes in histone modifications; unmethylated genes flanking the LRES are associated with permissive marks which are absent from methylated genes within the domain. Silenced genes are marked with non-permissive histone 3 lysine 9 dimethylation. Expression analysis of embryonic murine kidney and differentiating rat metanephric mesenchymal cells demonstrates that Pcdh expression is developmentally regulated and that Pcdhg@ genes are expressed in blastemal cells. Importantly, we show that PCDHs negatively regulate canonical Wnt signalling, as short-interfering RNA–induced reduction of PCDHG@ encoded proteins leads to elevated β-catenin protein, increased β-catenin/T-cell factor (TCF) reporter activity, and induction of Wnt target genes. Conversely, over-expression of PCDHs suppresses β-catenin/TCF-reporter activity and also inhibits colony formation and growth of cancer cells in soft agar. Thus PCDHs are candidate tumor suppressors that modulate regulatory pathways critical in development and disease, such as canonical Wnt signaling
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