The pro-apoptotic K-Ras 4A proto-oncoprotein does not affect tumorigenesis in the ApcMin/+ mouse small intestine.

BACKGROUND: Alterations in gene splicing occur in human sporadic colorectal cancer (CRC) and may contribute to tumour progression. The K-ras proto-oncogene encodes two splice variants, K-ras 4A and 4B, and K-ras activating mutations which jointly affect both isoforms are prevalent in CRC. Past studies have established that splicing of both the K-ras oncogene and proto-oncogene is altered in CRC in favour of K-ras 4B. The present study addressed whether the K-Ras 4A proto-oncoprotein can suppress tumour development in the absence of its oncogenic allele, utilising the ApcMin/+ (Min) mouse that spontaneously develops intestinal tumours that do not harbour K-ras activating mutations, and the K-rastmDelta4A/tmDelta4A mouse that can express the K-ras 4B splice variant only. By this means tumorigenesis in the small intestine was compared between ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmDelta4A/tmDelta4A mice that can, and cannot, express the K-ras 4A proto-oncoprotein respectively. METHODS: The relative levels of expression of the K-ras splice variants in normal small intestine and small intestinal tumours were quantified by real-time RT-qPCR analysis. Inbred (C57BL/6) ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmDelta4A/tmDelta4A mice were generated and the genotypes confirmed by PCR analysis. Survival of stocks was compared by the Mantel-Haenszel test, and tumour number and area compared by Student's t-test in outwardly healthy mice at approximately 106 and 152 days of age. DNA sequencing of codons 12, 13 and 61 was performed to confirm the intestinal tumours did not harbour a K-ras activating mutation. RESULTS: The K-ras 4A transcript accounted for about 50% of K-ras expressed in the small intestine of both wild-type and Min mice. Tumours in the small intestine of Min mice showed increased levels of K-ras 4B transcript expression, but no appreciable change in K-ras 4A transcript levels. No K-ras activating mutations were detected in 27 intestinal tumours derived from Min and compound mutant Min mice. K-Ras 4A deficiency did not affect mouse survival, or tumour number, size or histopathology. CONCLUSION: The K-Ras 4A proto-oncoprotein does not exhibit tumour suppressor activity in the small intestine, even though the K-ras 4A/4B ratio is reduced in adenomas lacking K-ras activating mutations.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Plasma Electronics

Contains research objectives and reports on six research objectives.National Science Foundation (Grant G-24073)Lincoln Laboratory, Purchase Order DDL BB-107U. S. Air Force under Contract AF 19(628)-50

Death and organization: Heidegger’s thought on death and life in organizations

Mortality has not been given the attention it deserves within organization studies. Even when it has been considered, it is not usually in terms of its implications for own lives and ethical choices. In particular, Heidegger’s writing on death has been almost entirely ignored both in writing on death and writing on organizational ethics, despite his insights into how our mortality and the ethics of existence are linked. In this paper, we seek to address this omission by arguing that a consideration of death may yield important insights about the ethics of organizational life. Most important of these is that a Heideggerian approach to death brings us up against fundamental ethical questions such as what our lives are for, how they should be lived and how we relate to others. Heideggerarian thought also reconnects ethics and politics, as it is closely concerned with how we can collectively make institutions that support our life projects rather than thwart or diminish them

Crop Updates 2001 - Weeds

This session covers forty six papers from different authors: 1. INTRODUCTION, Vanessa Stewart, Agriculture Western Australia PLENARY 2. Wild radish – the implications for our rotations, David Bowran, Centre for Cropping Systems INTEGRATED WEED MANAGEMENT IWM system studies/demonstration sites 3. Integrated weed management: Cadoux, Alexandra Wallace, Agriculture Western Australia 4. A system approach to managing resistant ryegrass, Bill Roy, Agricultural Consulting and Research Services Pty Ltd, York 5. Long term herbicide resistance demonstration, Peter Newman, Agriculture Western Australia, Cameron Weeks, Tony Blake and Dave Nicholson 6. Integrated weed management: Katanning, Alexandra Wallace, Agriculture Western Australia 7. Integrated weed management: Merredin, Vanessa Stewart, Agriculture Western Australia 8. Short term pasture phases for weed control, Clinton Revell and Candy Hudson, Agriculture Western Australia Weed biology – implications for IWM 9. Competitivness of wild radish in a wheat-lupin rotation , Abul Hashem, Nerys Wilkins, and Terry Piper, Agriculture Western Australia 10. Population explosion and persistence of wild radish in a wheat-lupin rotation, Abul Hashem, Nerys Wilkins, Aik Cheam and Terry Piper , Agriculture Western Australia 11. Variation is seed dormancy and management of annual ryegrass, Amanda Ellery and Ross Chapman, CSIRO 12. Can we eradicate barley grass, Sally Peltzer, Agriculture Western Australia Adoption and modelling 13. Where to with RIM? Vanessa Stewart1 and Robert Barrett-Lennard2, 1Agriculture Western Australia, 2Western Australian Herbicide Resistance Initiative (WAHRI) 14. Multi-species RIM model, Marta Monjardino1,2, David Pannell2 and Stephen Powles1 1Western Australian Herbicide Resistance Initiative (WAHRI), 2ARE, University of Western Australia 15. What causes WA grain growers to adopt IWM practices? Rick Llewellyn, WAHRI/ARE, Faculty of Agriculture, University of WA New options for IWM? 16. Fuzzy tramlines for more yield and less weeds, Paul Blackwell Agriculture Western Australia, and Maurice Black, Harbour Lights Estate, Geraldton 17. Inter-row knockdowns for profitable lupins, Paul Blackwell, Agriculture Western Australia and Miles Obst, Farmer Mingenew 18. Row cropping and weed control in lupins, Mike Collins and Julie Roche, Agriculture Western Australia 19. Cross seedimg suppresses annual ryegrass and increases wheat yield, Abul Hashem, Dave Nicholson and Nerys Wilkins Agriculture Western Australia 20. Weed control by chaff burial, Mike Collins, Agriculture Western Australia HERBICIDE RESISTANCE 21. Resistance in wild oats to Fop and Dim herbicides in Western Australia, Abul Hashem and Harmohinder Dhammu, Agriculture Western Australia 22. Triazine and diflufenican resistance in wild radish: what it means to the lupin industry, Aik Cheam, Siew Lee, David Nicholson and Peter Newman, Agriculture Western Australia 23. Comparison if in situ v seed testing for determining herbicide resistance, Bill Roy, Agricultural Consulting and Research Services Pty Ltd, York HERBICIDE TOLERANCE 24. Phenoxy herbicide tolerance of wheat, Peter Newman and Dave Nicholson, Agriculture Western Australia 25. Tolerance of wheat to phenoxy herbicides, Harmohinder S. Dhammu, Terry Piper and Mario F. D\u27Antuono, Agriculture Western Australia 26. Herbicide tolerance of new wheats, Harmohinder S. Dhammu, Terry Piper and David F. Nicholson, Agriculture Western Australia 27. Herbicide tolerance of durum wheats, Harmohinder S. Dhammu, Terry Piper and David F. Nicholson, Agriculture Western Australia 28. Herbicide tolerance of new field pea varieties, Harmohinder S. Dhammu, Terry Piper, David F. Nicholson, and Mario F. D\u27Antuono, Agriculture Western Australia 29. Herbicide tolerance of Cooke field peas on marginal soil, Harmohinder S. Dhammu, Terry Piper, David F. Nicholson, and Mario F. D\u27Antuono, Agriculture Western Australia 30. Herbicide tolerance of some annual pasture legumes adapted to coarse textured sandy soils, Clinton Revell and Ian Rose, Agriculture Western Australia 31 Herbicide tolerance of some annual pasture legumes adapted to fine textured clay soils, Clinton Revell and Ian Rose, Agriculture Western Australia WEED CONTROL IN LUCERNE 32. Management of weeds for Lucerne establishment, Diana Fedorenko, Clayton Butterly, Stuart McAlpine, Terry Piper and David Bowran, Centre for Cropping Systems, Agriculture Western Australia 33. Management of weeds in the second year of Lucerne, Diana Fedorenko, Clayton Butterly, Stuart McAlpine, Terry Piper and David Bowran, Centre for Cropping Systems, Agriculture Western Australia 34. Residual effects of weed management in the third year of Lucerne, Diana Fedorenko, Clayton Butterly, Stuart McAlpine, Terry Piper and David Bowran, Centre for Cropping Systems, Agriculture Western Australia 35. Herbicide tolerance and weed control in Lucerne, Peter Newman, Dave Nicholson and Keith Devenish Agriculture Western Australia HERBICIDES – NEW PRODUCTS/PRODUCE USES; USE New products or product use 36. New herbicide options for canola, John Moore and Paul Matson, Agriculture Western Australia 37. Chemical broadleaf weed management in Peaola, Shannon Barraclough and Lionel Martin, Muresk Institute of Agriculture, Curtin University of Technology 38. Balance® - a new broad leaf herbicide for the chickpea industry, Mike Clarke, Jonas Hodgson and Lawrence Price, Aventis CropScience 39. Marshmallow – robust herbicide strategies, Craig Brown, IAMA Agribusiness 40. Affinity DF – a prospective option for selective in-crop marshmallow control, Gordon Cumming, Technical Officer, Crop Care Australasia 41. A new formulation of Carfentrazone-ethyl for pre-seeding knockdown control of broadleaved weeds including Marshmallow, Gordon Cumming, Technical Officer, Crop Care Australasia Herbicide use 42. Autumn applied trifluralin can be effective! Bill Crabtree, Scientific Officer, Western Australian No-Tillage Farmers Association 43. Which knockdown herbicide for small ryegrass? Peter Newman and Dave Nicholson, Agriculture Western Australia 44. Poor radish control with Group D herbicides in lupins, Peter Newman and Dave Nicholson, Agriculture Western Australia WEED ISSUES 45. Distribution and incidence of aphids and barley yellow dwarf virus in over-summering grasses in the WA wheatbelt, Jenny Hawkes and Roger Jones, CLIMA and Agriculture Western Australia 46. e-weed, Vanessa Stewart, Agriculture Western Australia CONTRIBUTING AUTHOR CONTACT DETAIL

Plasma Dynamics

Contains research objectives and summary of research on eighteen research projects split into seven sections and reports on four research projects.U.S. Atomic Energy Commission (Contract AT(l1-1)-3070)National Science Foundation (Grant GK-37979X1

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment