The identification and characterization of a novel protein, c19orf10, in the synovium

Joint inflammation and destruction have been linked to the deregulation of the highly synthetic fibroblast-like synoviocytes (FLSs), and much of our current understanding of the mechanisms that underlie synovitis has been collected from studies of FLSs. During a proteomic analysis of FLS cells, we identified a novel protein, c19orf10 (chromosome 19 open reading frame 10), that was produced in significant amounts by these cells. The present study provides a partial characterization of c19orf10 in FLSs, synovial fluid, and the synovium. Murine monoclonal and chicken polyclonal antibodies were produced against recombinant human c19orf10 protein and used to examine the distribution of c19orf10 in cultured FLSs and in synovial tissue sections from patients with rheumatoid arthritis or osteoarthritis. The intracellular staining pattern of c19orf10 is consistent with localization in the endoplasmic reticulum/Golgi distribution. Sections of rheumatoid arthritis and osteoarthritis synovia expressed similar patterns of c19orf10 distribution with perivascular and synovial lining staining. Double-staining in situ analysis suggests that fibroblast-like synovial cells produced c19orf10, whereas macrophages, B cells, or T cells produced little or none of this protein. There is evidence of secretion into the vascular space and the extracellular matrix surrounding the synovial lining. A competitive enzyme-linked immunosorbent assay confirmed the presence of microgram levels of c19orf10 in the synovial fluids of patients with one of various arthropathies. Collectively, these results suggest that c19orf10 is an FLS-derived protein that is secreted into the synovial fluid. However, the significance of this protein in synovial biology remains to be determined. The absence of known structural motifs or domains and its relatively late evolutionary appearance raise interesting questions about its function

The synovial proteome: analysis of fibroblast-like synoviocytes

The present studies were initiated to determine the protein expression patterns of fibroblast-like synovial (FLS) cells derived from the synovia of rheumatoid arthritis patients. The cellular proteins were separated by two-dimensional polyacrylamide gel electrophoresis and the in-gel digested proteins were analyzed by matrix-assisted laser desorption ionization mass spectrometry. A total of 368 spots were examined and 254 identifications were made. The studies identified a number of proteins that have been implicated in the normal or pathological FLS function (e.g. uridine diphosphoglucose dehydrogenase, galectin 1 and galectin 3) or that have been characterized as potential autoantigens in rheumatoid arthritis (e.g. BiP, colligin, HC gp-39). A novel uncharacterized protein product of chromosome 19 open reading frame 10 was also detected as an apparently major component of FLS cells. These results demonstrate the utility of high-content proteomic approaches in the analysis of FLS composition

Crop Updates 2002 - Lupins

This session covers twenty four papers from different authors: LUPIN INDUSTRY ISSUES AND RESEARCH DIRECTIONS ACKNOWLEDGMENTS Amelia McLarty LUPIN CONVENOR DEPARTMENT OF AGRICULTURE VARIETIES 1. Evaluation of lupinus mutabilis in Western Australia, Bob French, Laurie Wahlsten and Martin Harries, Department of Agriculture 2. Adaption of restricted-branching lupins in short-growing season environments, Bob French, Laurie Wahlsten, Department of Agriculture ESTABLISHMENT 3. Moisture delving for better lupin establishment, Dr Paul Blackwell, Department of Agriculture 4. Lupins, tramlines, 600mm rows, rolling and shield spraying … a good result in a dry season! Paul Blackwell and Mike Collins, Department of Agriculture 5. Lupin wider row spacing data and observations, Bill CrabtreeA, Geoff FosberyB, Angie RoeB, Mike CollinsCand Matt BeckettA,AWANTFA, BFarm Focus Consultants and CDepartment of Agriculture NUTRITION 6. Lupin genotypes respond differently to potash, Bob French and Laurie Wahlsten, Department of Agriculture 7. Consequence of radish competition on lupin nutrients in a wheat-lupin rotation, Abul Hashem and Nerys Wilkins, Department of Agriculture 8. Consequence of ryegrass competition on lupin nutrients in a wheat-lupin rotation, Abul Hashem and Nerys Wilkins, Department of Agriculture PESTS AND DISEASES 9. Fungicide sprays for control of lupin anthracnose, Geoff Thomas and Ken Adcock, Department of Agriculture 10. Estimated yield losses in lupin varieties from sowing anthracnose infected seed, Geoff Thomas, Department of Agriculture 11. Effect of variety and environment (northern and southern wheatbelt) on yield losses in lupins due to anthracnose, Geoff Thomas and Ken Adcock, Department of Agriculture, 12. A decision support system for the control of aphids and CMV in lupin crops, Debbie Thackray, Jenny Hawkes and Roger Jones, Centre for Legumes in Mediterranean Agriculture and Department of Agriculture 13. Integrated management strategies for virus diseases of lupin, Roger Jones, Crop Improvement Institute, Department of Agriculture, and Centre for Legumes in Mediterranean Agriculture, University of WA 14. Quantifying yield losses caused by the non-necrotic strain of BYMV in lupin, Roger Jones and Brenda Coutts, Department of Agriculture, and Centre for Legumes in Mediterranean Agriculture 15. Screening for pod resistance to phomopsis in various lupin species, Manisha Shankar1, Mark Sweetingham1&2and Bevan Buirchell2 1Co-operative Research Centre for Legumes in Mediterranean Agriculture, The University of Western Australia, 2 Department of Agriculture 16. Lupin disease diagnostics, Nichole Burges and Dominie Wright, Department of Agriculture QUALITY AND MARKET DEVELOPMENT 17. To GM or not to GM pulses – that is the question, Dr Susan J. Barker, The University of Western Australia 18. Towards a management package for grain protein in lupins, Bob French, Senior Research Officer, Department of Agriculture 19. Yield and seed protein response to foliar application of N among lupin genotypes, Jairo A Palta1&2, Bob French2&3and Neil C Turner1&2 , 1 CSIRO Plant Industry, Floreat Park, 2 CLIMA, University of Western Australia,3Department of Agriculture 20. Foliar nitrogen application to improve protein content in narrow-leafed lupin, Martin Harries, Bob French, Laurie Wahlsten, Department of Agriculture, Matt Evans, CSBP 21. Effect of time of swathing of lupins on grain protein content, Martin Harries, Department of Agriculture 22. Putting a value on protein premiums for the animal feed industries: Aquaculture, Brett Glencross and John Curnow, Department of Fisheries, Wayne Hawkins, Department of Agriculture 23. Progress in selecting for reduced seed hull and pod wall in lupin, Jon C. Clements, CLIMA, University of Western Australia 24. Contact details for principal author

The Quiescent Intracluster Medium in the Core of the Perseus Cluster

Clusters of galaxies are the most massive gravitationally-bound objects in the Universe and are still forming. They are thus important probes of cosmological parameters and a host of astrophysical processes. Knowledge of the dynamics of the pervasive hot gas, which dominates in mass over stars in a cluster, is a crucial missing ingredient. It can enable new insights into mechanical energy injection by the central supermassive black hole and the use of hydrostatic equilibrium for the determination of cluster masses. X-rays from the core of the Perseus cluster are emitted by the 50 million K diffuse hot plasma filling its gravitational potential well. The Active Galactic Nucleus of the central galaxy NGC1275 is pumping jetted energy into the surrounding intracluster medium, creating buoyant bubbles filled with relativistic plasma. These likely induce motions in the intracluster medium and heat the inner gas preventing runaway radiative cooling; a process known as Active Galactic Nucleus Feedback. Here we report on Hitomi X-ray observations of the Perseus cluster core, which reveal a remarkably quiescent atmosphere where the gas has a line-of-sight velocity dispersion of 164+/-10 km/s in a region 30-60 kpc from the central nucleus. A gradient in the line-of-sight velocity of 150+/-70 km/s is found across the 60 kpc image of the cluster core. Turbulent pressure support in the gas is 4% or less of the thermodynamic pressure, with large scale shear at most doubling that estimate. We infer that total cluster masses determined from hydrostatic equilibrium in the central regions need little correction for turbulent pressure.Comment: 31 pages, 11 Figs, published in Nature July

Identifying and analysing protostellar disc fragments in smoothed particle hydrodynamics simulations

We present a new method of identifying protostellar disc fragments in a simulation based on density derivatives, and analyse our data using this and the existing CLUMPFIND method, which is based on an ordered search over all particles in gravitational potential energy. Using smoothed particle hydrodynamics, we carry out 9 simulations of a $0.25$ M$_{\odot}$ disc around a 1 M$_{\odot}$ star, all of which fragment to form at least 2 bound objects. We find that when using all particles ordered in gravitational potential space, only fragments that survive the duration of the simulation are detected. When we use the density derivative method, all fragments are detected, so the two methods are complementary, as using the two methods together allows us to identify all fragments, and to then determine those that are likely to be destroyed. We find a tentative empirical relationship between the dominant azimuthal wavenumber in the disc $m$ and the maximum semi-major axis a fragment may achieve in a simulation, such that $a_{\mathrm{max}}\propto\frac{1}{m}$. We find the fragment destruction rate to be around half that predicted from population synthesis models. This is due to fragment-fragment interactions in the early gas phase of the disc, which can cause scattering and eccentricity pumping on short timescales, and affects the fragment's internal structure. We therefore caution that measurements of eccentricity as a function of semi-major axis may not necessarily constrain the formation mechanism of giant planets and brown dwarfs.Comment: 22 pages, 22 figure

2016 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1003/thumbnail.jp

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio