Use of supplementary phenotype to identify additional rheumatoid arthritis loci in a linkage analysis of 342 UK affected sibling pair families

<p>Abstract</p> <p>Background</p> <p>Although rheumatoid arthritis has been shown to have moderately strong genetic component, both linked loci identified in linkage analyses and susceptibility variants from association studies are short of adequately accounting for a comprehensive catalogue of the molecular factors underlying this complex disease. The objective of this study was to use supplementary phenotype based on cumulative hazard of rheumatoid arthritis to identify linkage evidence for new and additional rheumatoid arthritis loci in a genome-wide linkage analysis of 342 affected sibling pair families from the United Kingdom.</p> <p>Methods</p> <p>Using proportional hazards model, we estimated cumulative hazard of rheumatoid arthritis and then used it as a quantitative trait in a non-parametric multipoint variance component linkage analysis with 353 microsatellite markers distributed across the 22 autosomal chromosomes.</p> <p>Results</p> <p>We identified 3 new loci with genome-wide suggestive linkage evidence for rheumatoid arthritis on 9q21.13, 15p11.1 and 20q13.33. Our results also confirmed previously reported linkage evidence in the HLA-DRB1 region on chromosome 6 and on locus 1q32.1.</p> <p>Conclusion</p> <p>This study demonstrates the potential for information gain through the use of supplementary phenotypes in genetic study of complex diseases to identify new and additional potential linked loci that are not detected by linkage analysis of traditional phenotypes; and our results provide further evidence of the involvement of multiple loci in the genetic aetiology of rheumatoid arthritis.</p

Typing and distribution of Plum pox virus isolates in Romania

Plum pox or Sharka, caused by Plum pox virus (PPV) is considered the most destructive disease of plum. Although PPV is widespread in all plum growing areas of Romania and causes serious yield losses, little is known about the variability of its isolates at a country level. For this reason, a large-scale study was performed with the aim of obtaining a picture of the prevalence and distribution of PPV strains in plum. During a three year survey, 200 PPV isolates collected from 23 different plum orchards from Transylvania, Moldavia and Muntenia areas were investigated. DASELISA and IC-RT-PCR were used for PPV detection. PPV strains were serologically determined by TAS-ELISA using PPV-D and PPV-M specific monoclonal antibodies. Molecular strain typing was done by IC/RT-PCR targeting three genomic regions corresponding to (Cter)CP, (Cter)NIb/(Nter)CP and CI. RFLP analysis was used to distinguish D and M strains, based on the RsaI polymorphism located in (Cter)CP. To confirm the presence of PPV-Rec strain, 13 PCR products spanning the (Cter)NIb/(Nter)CP were sequenced. Overall results showed that in Romania the predominant strain is PPV-D (73%), followed, with a much lower frequency, by PPV-Rec (14%). Mixed infections (PPV-D+PPVRec), which might generate additional variation by recombination, are also frequent (13%).Keywords: Romania, PPV strains, DAS/TAS-ELISA, IC/RT-PCR, RFLP, sequencin

Sequestration of Martian CO2 by mineral carbonation

Carbonation is the water-mediated replacement of silicate minerals, such as olivine, by carbonate, and is commonplace in the Earth’s crust. This reaction can remove significant quantities of CO2 from the atmosphere and store it over geological timescales. Here we present the first direct evidence for CO2 sequestration and storage on Mars by mineral carbonation. Electron beam imaging and analysis show that olivine and a plagioclase feldspar-rich mesostasis in the Lafayette meteorite have been replaced by carbonate. The susceptibility of olivine to replacement was enhanced by the presence of smectite veins along which CO2-rich fluids gained access to grain interiors. Lafayette was partially carbonated during the Amazonian, when liquid water was available intermittently and atmospheric CO2 concentrations were close to their present-day values. Earlier in Mars’ history, when the planet had a much thicker atmosphere and an active hydrosphere, carbonation is likely to have been an effective mechanism for sequestration of CO2

Modelling of Multi-Agent Systems: Experiences with Membrane Computing and Future Challenges

Formal modelling of Multi-Agent Systems (MAS) is a challenging task due to high complexity, interaction, parallelism and continuous change of roles and organisation between agents. In this paper we record our research experience on formal modelling of MAS. We review our research throughout the last decade, by describing the problems we have encountered and the decisions we have made towards resolving them and providing solutions. Much of this work involved membrane computing and classes of P Systems, such as Tissue and Population P Systems, targeted to the modelling of MAS whose dynamic structure is a prominent characteristic. More particularly, social insects (such as colonies of ants, bees, etc.), biology inspired swarms and systems with emergent behaviour are indicative examples for which we developed formal MAS models. Here, we aim to review our work and disseminate our findings to fellow researchers who might face similar challenges and, furthermore, to discuss important issues for advancing research on the application of membrane computing in MAS modelling.Comment: In Proceedings AMCA-POP 2010, arXiv:1008.314

Extensive Spectroscopy and Photometry of the Type IIP Supernova 2013ej

We present extensive optical ($UBVRI$, $g'r'i'z'$, and open CCD) and near-infrared ($ZYJH$) photometry for the very nearby Type IIP SN ~2013ej extending from +1 to +461 days after shock breakout, estimated to be MJD $56496.9\pm0.3$. Substantial time series ultraviolet and optical spectroscopy obtained from +8 to +135 days are also presented. Considering well-observed SNe IIP from the literature, we derive $UBVRIJHK$ bolometric calibrations from $UBVRI$ and unfiltered measurements that potentially reach 2\% precision with a $B-V$ color-dependent correction. We observe moderately strong Si II $\lambda6355$ as early as +8 days. The photospheric velocity ($v_{\rm ph}$) is determined by modeling the spectra in the vicinity of Fe II $\lambda5169$ whenever observed, and interpolating at photometric epochs based on a semianalytic method. This gives $v_{\rm ph} = 4500\pm500$ km s$^{-1}$ at +50 days. We also observe spectral homogeneity of ultraviolet spectra at +10--12 days for SNe IIP, while variations are evident a week after explosion. Using the expanding photosphere method, from combined analysis of SN 2013ej and SN 2002ap, we estimate the distance to the host galaxy to be $9.0_{-0.6}^{+0.4}$ Mpc, consistent with distance estimates from other methods. Photometric and spectroscopic analysis during the plateau phase, which we estimated to be $94\pm7$ days long, yields an explosion energy of $0.9\pm0.3\times10^{51}$ ergs, a final pre-explosion progenitor mass of $15.2\pm4.2$~M$_\odot$ and a radius of $250\pm70$~R$_\odot$. We observe a broken exponential profile beyond +120 days, with a break point at +$183\pm16$ days. Measurements beyond this break time yield a $^{56}$Ni mass of $0.013\pm0.001$~M$_\odot$.Comment: 29 pages, 23 figures, 15 tables, Published in The Astrophisical Journa

The effects of stand characteristics on the understory vegetation in Quercus petraea and Q. cerris dominated forests

The shelterwood system used in Hungary has many effects on the composition and structure of the herb layer. The aim of our study was to identify the main variables that affect the occurence of herbs and seedlings in Turkey oak-sessile oak (Quercus cerris and Q. petraea) stands. The study was carried out in the Bükk mountains, Hungary. 122 sampling plots were established in 50-150 year old oak forests, where we studied the species composition and structure of the understorey and overstorey. The occurence of herbs was affected by canopy closure, the heterogenity and patchiness of the stand, the slope and the east-west component of the aspect. The composition of saplings was significantly explained by the ratio of the two major oak species in the stand and the proximity of the adult plants. An important result for forest management was that sessile oaks were able to regenerate almost only where they were dominant in the overstorey

Pervasive melt percolation reactions in ultra-depleted refractory harzburgites at the Mid-Atlantic Ridge, 15° 20′N : ODP Hole 1274A

Author Posting. © The Authors, 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Contributions to Mineralogy and Petrology 153 (2007): 303-319, doi:10.1007/s00410-006-0148-6.ODP Leg 209 Site 1274 mantle peridotites are highly refractory in terms of lack of residual clinopyroxene, olivine Mg# (up to 0.92) and spinel Cr# (~0.5), suggesting high degree of partial melting (>20%). Detailed studies of their microstructures show that they have extensively reacted with a pervading intergranular melt prior to cooling in the lithosphere, leading to crystallization of olivine, clinopyroxene and spinel at the expense of orthopyroxene. The least reacted harzburgites are too rich in orthopyroxene to be simple residues of low-pressure (spinel field) partial melting. Cu-rich sulfides that precipitated with the clinopyroxenes indicate that the intergranular melt was generated by no more than 12% melting of a MORB mantle or by more extensive melting of a clinopyroxene-rich lithology. Rare olivine-rich lherzolitic domains, characterized by relics of coarse clinopyroxenes intergrown with magmatic sulfides, support the second interpretation. Further, coarse and intergranular clinopyroxenes are highly depleted in REE, Zr and Ti. A two-stage partial melting/melt-rock reaction history is proposed, in which initial mantle underwent depletion and refertilization after an earlier high pressure (garnet field) melting event before upwelling and remelting beneath the present-day ridge. The ultra-depleted compositions were acquired through melt re-equilibration with residual harzburgites.Funding for this research was provided by Centre National de la Recherche Scientifique-Institut National des Sciences de l’Univers (Programme Dynamique et Evolution de la Terre Interne)

Limited Tumor Tissue Drug Penetration Contributes to Primary Resistance against Angiogenesis Inhibitors

Resistance mechanisms against antiangiogenic drugs are unclear. Here, we correlated the antitumor and antivascular properties of five different antiangiogenic receptor tyrosine kinase inhibitors (RTKIs) (motesanib, pazopanib, sorafenib, sunitinib, vatalanib) with their intratumoral distribution data obtained by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). In the first mouse model, only sunitinib exhibited broad-spectrum antivascular and antitumor activities by simultaneously suppressing vascular endothelial growth factor receptor-2 (VEGFR2) and desmin expression, and by increasing intratumoral hypoxia and inhibiting both tumor growth and vascularisation significantly. Importantly, the highest and most homogeneous intratumoral drug concentrations have been found in sunitinib-treated animals. In another animal model, where - in contrast to the first model - vatalanib was detectable at homogeneously high intratumoral concentrations, the drug significantly reduced tumor growth and angiogenesis. In conclusion, the tumor tissue penetration and thus the antiangiogenic and antitumor potential of antiangiogenic RTKIs vary among the tumor models and our study demonstrates the potential of MALDI-MSI to predict the efficacy of unlabelled small molecule antiangiogenic drugs in malignant tissue. Our approach is thus a major technical and preclinical advance demonstrating that primary resistance to angiogenesis inhibitors involves limited tumor tissue drug penetration. We also conclude that MALDI-MSI may significantly contribute to the improvement of antivascular cancer therapies