| 1. |
- Birney, Ewan, et al.
(författare)
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Prepublication data sharing
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7261, s. 168-170
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Tidskriftsartikel (refereegranskat)abstract
- Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.
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| 2. |
- El-Sayed, Najib M., et al.
(författare)
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The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease.
- 2005
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5733, s. 409-15
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Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.
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| 3. |
- Gateva, Vesela, et al.
(författare)
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A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:11, s. 1228-1233
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 x 10(-8)): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P< or = 1 x 10(-5). A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 x 10(-3)) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.
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| 4. |
- Kessler, Richard, et al.
(författare)
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First-Year Sloan Digital Sky Survey-II Supernova Results : Hubble Diagram and Cosmological Parameters
- 2009
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 185:1, s. 32-84
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of the Hubble diagram for 103 Type Ia supernovae (SNe) with redshifts 0.04 < z < 0.42, discovered during the first season (Fall 2005) of the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey. These data fill in the redshift "desert" between low- and high-redshift SN Ia surveys. Within the framework of the MLCS2K2 light-curve fitting method, we use the SDSS-II SN sample to infer the mean reddening parameter for host galaxies, RV = 2.18 ± 0.14stat ± 0.48syst, and find that the intrinsic distribution of host-galaxy extinction is well fitted by an exponential function, P(AV ) = exp(-AV /τV), with τV = 0.334 ± 0.088 mag. We combine the SDSS-II measurements with new distance estimates for published SN data from the ESSENCE survey, the Supernova Legacy Survey (SNLS), the Hubble Space Telescope (HST), and a compilation of Nearby SN Ia measurements. A new feature in our analysis is the use of detailed Monte Carlo simulations of all surveys to account for selection biases, including those from spectroscopic targeting. Combining the SN Hubble diagram with measurements of baryon acoustic oscillations from the SDSS Luminous Red Galaxy sample and with cosmic microwave background temperature anisotropy measurements from the Wilkinson Microwave Anisotropy Probe, we estimate the cosmological parameters w and ΩM, assuming a spatially flat cosmological model (FwCDM) with constant dark energy equation of state parameter, w. We also consider constraints upon ΩM and ΩΛ for a cosmological constant model (ΛCDM) with w = -1 and non-zero spatial curvature. For the FwCDM model and the combined sample of 288 SNe Ia, we find w = -0.76 ± 0.07(stat) ± 0.11(syst), ΩM = 0.307 ± 0.019(stat) ± 0.023(syst) using MLCS2K2 and w = -0.96 ± 0.06(stat) ± 0.12(syst), ΩM = 0.265 ± 0.016(stat) ± 0.025(syst) using the SALT-II fitter. We trace the discrepancy between these results to a difference in the rest-frame UV model combined with a different luminosity correction from color variations; these differences mostly affect the distance estimates for the SNLS and HST SNe. We present detailed discussions of systematic errors for both light-curve methods and find that they both show data-model discrepancies in rest-frame U band. For the SALT-II approach, we also see strong evidence for redshift-dependence of the color-luminosity parameter (β). Restricting the analysis to the 136 SNe Ia in the Nearby+SDSS-II samples, we find much better agreement between the two analysis methods but with larger uncertainties: w = -0.92 ± 0.13(stat)+0.10 -0.33(syst) for MLCS2K2 and w = -0.92 ± 0.11(stat)+0.07 -0.15 (syst) for SALT-II.
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| 5. |
- Ollero, Anibal, et al.
(författare)
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Multiple Eyes in the Skies
- 2005
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Ingår i: IEEE robotics & automation magazine. - 1070-9932 .- 1558-223X. ; 12:2, s. 46-57
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Tidskriftsartikel (refereegranskat)abstract
- The management of environmental and industrial disasters, search and rescue operations, surveillance of natural scenarios, environmental monitoring, and many other field robotics applications require high mobility and the need to reach locations that are difficult to access with ground vehicles. In many cases, the use of aerial vehicles is the best way to approach the objective to get information or to deploy instrumentation. Unmanned air vehicles (UAVs) have significantly increased their flight performance and autonomous onboard processing capabilities in the last ten years. But a single aerial vehicle equipped with a large array of different sensors of various modalities is limited at any time to a single viewpoint. A team of aerial vehicles, however, can simultaneously collect information from multiple locations and exploit the information derived from multiple disparate points. Furthermore, having a team with multiple heterogeneous aerial vehicles offers additional advantages due to the possibility of beneficial complementarities of the vehicles.
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| 6. |
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| 7. |
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| 8. |
- Borgonovo, Luis, et al.
(författare)
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On the temporal variability classes found in long gamma-ray bursts with known redshift
- 2007
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 465:3, s. 765-775
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Tidskriftsartikel (refereegranskat)abstract
- Context: Based on the analysis of a small sample of BATSE and Konus gamma-ray bursts (GRBs) with know redshift it has been reported that the width of the autocorrelation function (ACF) shows a remarkable bimodal distribution in the rest-frame of the source. However, the origin of these two well-separated ACF classes remains unexplained. Aims: We study the properties of the bursts belonging to each ACF class and look for significant differences between them.Methods: We complement previous ACF analysis studying the corresponding power density spectra (PDS). With the addition of Beppo-SAX data and taken advantage of its broad-band capability, we not only increase the burst sample but we extend the analysis to X-ray energies.Results: The rest-frame PDS analysis at γ-ray energies shows that the two ACF classes are not simply characterised by a different low frequency cut-off, but they have a distinct variability as a whole in the studied frequency range. Both classes exhibit average PDS with power-law behaviour at high frequencies (f' ≥ 0.1 Hz) but significantly different slopes, with index values close to those of Brownian (-2) and Kolmogorov (-5/3) spectra for the narrow and broad classes respectively. The latter spectrum presents an additional PDS component, a low-frequency noise excess with a sharp cut-off at a characteristic frequency f'c ≃ 0.025 Hz, in conjunction with the small relative dispersion (~6%) of the ACF width in this class. At X-ray energies we find the power-law index unchanged for the broad class, but a significantly steeper slope in the narrow case (~-3). We interpret this as an indication that the broad class bursts have weaker spectral evolution than the narrow ones, as suggested also by our analysis of the ACF energy dependence. The low and high frequency PDS components may then arise from two radiating regions involving different emission mechanisms. We compare our GRB sample conditioned by afterglow detections with a complete, flux limited BATSE sample, finding a significant bias against narrow ACF bursts.
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| 9. |
- Cabaleiro-Lago, Celia, et al.
(författare)
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Characterization of alkane diol-CD complexes. Acid denitrosation of N-methyl-N-nitroso-p-toluenesulphonamide as a chemical probe
- 2006
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Ingår i: JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY. - Univ Vigo, Dept Quim Fis, Vigo 36200, Spain. Univ Santiago de Compostela, Dept Quim Fis, Santiago De Compostela 15706, Spain. : SPRINGER. - 1388-3127. ; 54:3-4, s. 209-216
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Tidskriftsartikel (refereegranskat)abstract
- A study was carried out on the acid denitrosation of N-methyl-N-nitroso-p-toluenesulfonamide (MNTS) in mixed systems made up of linear (geminal and terminal) alkyl diols and beta-cyclodextrin (CD). The alkyl diols used allowed us to vary the length of the hydrocarbon chain from 2 to 6 carbon atoms. The observed rate constant, k(obs), decreases in the presence of CD. The inhibition profile decreases as the as the number of carbons in the chain is increased. This behaviour can be interpreted as a consequence of a balance between the complexation processes of MNTS and the alkyl diols by the CD. At a constant CD concentration and increase in the diols concentration decreases the concentration of free cyclodextrin available to complex with MNTS molecules and therefore produces an increases in the observed rate constant. The results were interpreted in terms of two different models; trough the presupposition and non-presupposition of a stoichiometry for the CD-diols complex. Both models agreed quite well and allow us to determine the uncomplexed cyclodextrin concentration in each case as well as the stoichiometry of the complexes. The binding constant for both types of alkane diols increase with increasing the number of carbon in the chain. Besides, the binding constant of the alpha,beta-alkane diols is higher than for the analog alpha,beta-alkane diols. One of the main consequences of this study is that the acid denitrosation of MNTS can be use to obtain the stochiometry of the CD-diol complexes and to monitor the free cyclodextrin concentration.
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| 10. |
- de la Serna, Jorge Bernardino, et al.
(författare)
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Segregated Phases in Pulmonary Surfactant Membranes Do Not Show Coexistence of Lipid Populations with Differentiated Dynamic Properties
- 2009
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Ingår i: Biophysical Journal. - : Elsevier Inc. - 0006-3495. ; 97:5, s. 1381-1389
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Tidskriftsartikel (refereegranskat)abstract
- The composition of pulmonary surfactant membranes and films has evolved to support a complex lateral structure, including segregation of ordered/disordered phases maintained up to physiological temperatures. In this study, we have analyzed the temperature-dependent dynamic properties of native surfactant membranes and membranes reconstituted from two surfactant hydrophobic fractions (i.e., all the lipids plus the hydrophobic proteins SP-B and SP-C, or only the total lipid fraction). These preparations show micrometer-sized fluid ordered/disordered phase coexistence, associated with a broad endothermic transition ending close to 37°C. However, both types of membrane exhibit uniform lipid mobility when analyzed by electron paramagnetic resonance with different spin-labeled phospholipids. A similar feature is observed with pulse-field gradient NMR experiments on oriented membranes reconstituted from the two types of surfactant hydrophobic extract. These latter results suggest that lipid dynamics are similar in the coexisting fluid phases observed by fluorescence microscopy. Additionally, it is found that surfactant proteins significantly reduce the average intramolecular lipid mobility and translational diffusion of phospholipids in the membranes, and that removal of cholesterol has a profound impact on both the lateral structure and dynamics of surfactant lipid membranes. We believe that the particular lipid composition of surfactant imposes a highly dynamic framework on the membrane structure, as well as maintains a lateral organization that is poised at the edge of critical transitions occurring under physiological conditions.
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| 11. |
- Dedinaite, Andra, et al.
(författare)
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Solution properties of bottle-brush polyelectrolytes
- 2007
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Ingår i: PROCEEDINGS OF BALTIC POLYMER SYMPOSIUM 2007. - 9789955331506 ; , s. 112-116
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Konferensbidrag (refereegranskat)abstract
- Aqueous solution properties of bottle brush polyelectrolytes, where side-chains are attached to a polymer backbone, have been studied. The side chains consist of 45 units long poly(ethylene oxide) groups and the backbone is of the methacrylate type. Small-angle X-ray scattering (SAXS) was used to elucidate the solution conformation of this class of polymer and how it is affected by the side chain density and charge density. The effect of temperature on the solution conformation, and in particular the side chain extension, has also been quantified. At higher concentrations the interactions between the polymer chains in solution affects the scattering, and it is shown that this interaction is well described by a model originally developed for wormlike micelles.
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| 12. |
- Goncalves, Isabel, et al.
(författare)
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Activation of calpain-1 in human carotid artery atherosclerotic lesions
- 2009
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 9:26
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Tidskriftsartikel (refereegranskat)abstract
- Background: In a previous study, we observed that oxidized low-density lipoprotein-induced death of endothelial cells was calpain-1-dependent. The purpose of the present paper was to study the possible activation of calpain in human carotid plaques, and to compare calpain activity in the plaques from symptomatic patients with those obtained from patients without symptoms. Methods: Human atherosclerotic carotid plaques (n = 29, 12 associated with symptoms) were removed by endarterectomy. Calpain activity and apoptosis were detected by performing immunohistochemical analysis and TUNEL assay on human carotid plaque sections. An antibody specific for calpain-proteolyzed alpha-fodrin was used on western blots. Results: We found that calpain was activated in all the plaques and calpain activity colocalized with apoptotic cell death. Our observation of autoproteolytic cleavage of the 80 kDa subunit of calpain-1 provided further evidence for enzyme activity in the plaque samples. When calpain activity was quantified, we found that plaques from symptomatic patients displayed significantly lower calpain activity compared with asymptomatic plaques. Conclusion: These novel results suggest that calpain-1 is commonly active in carotid artery atherosclerotic plaques, and that calpain activity is colocalized with cell death and inversely associated with symptoms.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Miller, Webb, et al.
(författare)
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The mitochondrial genome sequence of the Tasmanian tiger (Thylacinus cynocephalus).
- 2009
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 19:2, s. 213-20
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Tidskriftsartikel (refereegranskat)abstract
- We report the first two complete mitochondrial genome sequences of the thylacine (Thylacinus cynocephalus), or so-called Tasmanian tiger, extinct since 1936. The thylacine's phylogenetic position within australidelphian marsupials has long been debated, and here we provide strong support for the thylacine's basal position in Dasyuromorphia, aided by mitochondrial genome sequence that we generated from the extant numbat (Myrmecobius fasciatus). Surprisingly, both of our thylacine sequences differ by 11%-15% from putative thylacine mitochondrial genes in GenBank, with one of our samples originating from a direct offspring of the previously sequenced individual. Our data sample each mitochondrial nucleotide an average of 50 times, thereby providing the first high-fidelity reference sequence for thylacine population genetics. Our two sequences differ in only five nucleotides out of 15,452, hinting at a very low genetic diversity shortly before extinction. Despite the samples' heavy contamination with bacterial and human DNA and their temperate storage history, we estimate that as much as one-third of the total DNA in each sample is from the thylacine. The microbial content of the two thylacine samples was subjected to metagenomic analysis, and showed striking differences between a wild-captured individual and a born-in-captivity one. This study therefore adds to the growing evidence that extensive sequencing of museum collections is both feasible and desirable, and can yield complete genomes.
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| 19. |
- Morrison, John C., et al.
(författare)
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Numerical methods for solving the Hartree-Fock equations of diatomic molecules I.
- 2009
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Ingår i: Communications in Computational Physics. - 1815-2406 .- 1991-7120. ; 5:5, s. 959-985
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Tidskriftsartikel (refereegranskat)abstract
- The theory of domain decomposition is described and used to divide the variable domain of a diatomic molecule into separate regions which are solved independently. This approach makes it possible to use fast Krylov methods in the broad interior of the region while using explicit methods such as Gaussian elimination on the boundaries. As is demonstrated by solving a number of model problems, these methods enable one to obtain solutions of the relevant partial differential equations and eigenvalue equations accurate to six significant figures with a small amount of computational time. Since the numerical approach described in this article decomposes the variable space into separate regions where the equations are solved independently, our approach is very well-suited to parallel computing and offers the long term possibility of studying complex molecules by dividing them into smaller fragments that are calculated separately.
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| 20. |
- Normand, Philippe, et al.
(författare)
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Genome characteristics of facultatively symbiotic Frankia sp. strains reflect host range and host plant biogeography.
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 17:1, s. 7-15
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Tidskriftsartikel (refereegranskat)abstract
- Soil bacteria that also form mutualistic symbioses in plants encounter two major levels of selection. One occurs during adaptation to and survival in soil, and the other occurs in concert with host plant speciation and adaptation. Actinobacteria from the genus Frankia are facultative symbionts that form N2-fixing root nodules on diverse and globally distributed angiosperms in the "actinorhizal" symbioses. Three closely related clades of Frankia sp. strains are recognized; members of each clade infect a subset of plants from among eight angiosperm families. We sequenced the genomes from three strains; their sizes varied from 5.43 Mbp for a narrow host range strain (Frankia sp. strain HFPCcI3) to 7.50 Mbp for a medium host range strain (Frankia alni strain ACN14a) to 9.04 Mbp for a broad host range strain (Frankia sp. strain EAN1pec.) This size divergence is the largest yet reported for such closely related soil bacteria (97.8%–98.9% identity of 16S rRNA genes). The extent of gene deletion, duplication, and acquisition is in concert with the biogeographic history of the symbioses and host plant speciation. Host plant isolation favored genome contraction, whereas host plant diversification favored genome expansion. The results support the idea that major genome expansions as well as reductions can occur in facultative symbiotic soil bacteria as they respond to new environments in the context of their symbioses.
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| 21. |
- Rocha, Luis E C, 1981-
(författare)
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Noticia ruim corre depressa! : Bad news travels fast!
- 2009
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Ingår i: Revista Brasileira de Ensino de Fisica. - : Sociedade Brasileira de Fisica. - 1806-9126. ; 31:3, s. 313303-
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Tidskriftsartikel (refereegranskat)abstract
- Muitas provérbios surgem através da propria experiência cotidiana. Embora muitas dessas expressões sejam de entendimento direto por parte da populacão em geral, um olhar mais cuidadoso gera muitas questões e dúvidas a respeito da sua validade. Motivados por uma dessas expressões, no presente artigo, analisamos a transmissão de uma notícia numa rede de contatos eletrônicos (e-mails). Para tanto, são propostos protocolos de transmissão de notícia que reproduzem propriedades de sistemas reais. Esses protocolos são simulados numa rede real de e-mails e na rede aleatória proposta por P. Erdös e A. Rényi. Os resultados sugerem que uma notícia se espalha mais rapidamente na rede aleatória. A presenca de vértices concentradores de conexões (hubs) na rede real tende a atrair a notícia, prejudicando os vértices menos conectados.
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| 22. |
- Rocha, Luis E C, 1981-
(författare)
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Structural evolution of the Brazilian airport network
- 2009
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Ingår i: Journal of Statistical Mechanics. - Bristol : Institute of Physics. - 1742-5468. ; , s. 04020-
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Tidskriftsartikel (refereegranskat)abstract
- The aviation sector is profitable, but sensitive to economic fluctuations, geopolitical constraints and governmental regulations. As for other means of transportation, the relation between origin and destination results in a complex map of routes, which can be complemented with information associated with the routes themselves, for instance, frequency, traffic load and distance. The theory of networks provides a natural framework for investigating the dynamics on the resulting structure. Here, we investigate the structure and evolution of the Brazilian airport network (BAN) as regards several quantities: routes, connections, passengers and cargo. Some structural features are in accordance with previous results for other airport networks. The analysis of the evolution of the BAN shows that its structure is dynamic, with changes in the relative relevance of some airports and routes. The results indicate that the connections converge to specific routes. The network shrinks at the route level but grows in number of passengers and amount of cargo, which more than doubled during the period studied.
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| 23. |
- Sallis, James F, et al.
(författare)
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Neighborhood environments are related to physical activity among adults in 11 countries
- 2009
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Ingår i: American Journal of Preventive Medicine. - 0749-3797 .- 1873-2607. ; 36:6, s. 484-490
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundUnderstanding environmental correlates of physical activity can inform policy changes. Surveys were conducted in 11 countries using the same self-report environmental variables and the International Physical Activity Questionnaire, allowing analyses with pooled data.MethodsThe participating countries were Belgium, Brazil, Canada, Colombia, China (Hong Kong), Japan, Lithuania, New Zealand, Norway, Sweden, and the U.S., with a combined sample of 11,541 adults living in cities. Samples were reasonably representative, and seasons of data collection were comparable. Participants indicated whether seven environmental attributes were present in their neighborhood. Outcomes were measures of whether health-related guidelines for physical activity were met. Data were collected in 2002–2003 and analyzed in 2007. Logistic regression analyses evaluated associations of physical activity with environmental attributes, adjusted for age, gender, and clustering within country.ResultsFive of seven environmental variables were significantly related to meeting physical activity guidelines, ranging from access to low-cost recreation facilities (OR=1.16) to sidewalks on most streets (OR=1.47). A graded association was observed, with the most activity–supportive neighborhoods having 100% higher rates of sufficient physical activity compared to those with no supportive attributes.ConclusionsResults suggest neighborhoods built to support physical activity have a strong potential to contribute to increased physical activity. Designing neighborhoods to support physical activity can now be defined as an international public health issue.
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| 24. |
- Sanchez-Soto, Luis L., et al.
(författare)
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Maximally polarized states for quantum light fields
- 2007
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Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 76:4
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Tidskriftsartikel (refereegranskat)abstract
- The degree of polarization of a quantum field can be defined as its distance to an appropriate set of states. When we take unpolarized states as this reference set, the states optimizing this degree for a fixed average number of photons (N) over bar present a fairly symmetric, parabolic photon statistic, with a variance scaling as (N) over bar (2). Although no standard optical process yields such a statistic, we show that, to an excellent approximation, a highly squeezed vacuum can be taken as maximally polarized. We also consider the distance of a field to the set of its SU(2) transformed, finding that certain linear superpositions of SU(2) coherent states make this degree to be unity.
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| 25. |
- Verissimo, Ana, et al.
(författare)
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Nuclear microscopy: A tool for and percutaneous absorption imaging elemental distribution in vivo
- 2007
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Ingår i: Microscopy Research and Technique. - : Wiley. - 1059-910X .- 1097-0029. ; 70:4, s. 302-309
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Tidskriftsartikel (refereegranskat)abstract
- Nuclear microscopy is a technique based on a focused beam of accelerated particles that has the ability of imaging the morphology of the tissue in vivo and of producing the correspondent elemental maps, whether in major, minor, or trace concentrations. These characteristics constitute a strong advantage in studying the morphology of human skin, its elemental distributions and the permeation mechanisms of chemical compounds. In this study, nuclear microscopy techniques such as scanning transmission ion microscopy and particle induced X-ray emission were applied simultaneously, to cryopreserved human skin samples with the purpose of obtaining high-resolution images of cells and tissue morphology. In addition, quantitative elemental profiling and mapping of phosphorus, calcium, chlorine, and potassium in skin cross-sections were obtained. This procedure accurately distinguishes the epidermal strata and dermis by overlapping in real time the elemental information with density images obtained from the transmitted beam. A validation procedure for elemental distributions in human skin based on differential density of epidermal strata and dermis was established. As demonstrated, this procedure can be used in future studies as a tool for the in vivo examination of trans-epidermal and -dermal delivery of products. .
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| 26. |
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| 27. |
- Webb, Ryan, et al.
(författare)
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A polymorphism within IL21R confers risk for systemic lupus erythematosus
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:8, s. 2402-2407
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Interleukin-21 (IL-21) is a member of the type I cytokine superfamily that has a variety of effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. The expression of IL-21 receptor (IL-21R) is reduced in the B cells of patients with systemic lupus erythematosus (SLE), while serum IL-21 levels are increased both in lupus patients and in some murine lupus models. We recently reported that polymorphisms within the IL21 gene are associated with increased susceptibility to SLE. The aim of this study was to examine the genetic association between single-nucleotide polymorphisms (SNPs) within IL21R and SLE. METHODS: We genotyped 17 SNPs in the IL21R gene in 2 large cohorts of lupus patients (a European-derived cohort and a Hispanic cohort) and in ethnically matched healthy controls. RESULTS: We identified and confirmed the association between rs3093301 within the IL21R gene and SLE in the 2 cohorts (meta-analysis odds ratio 1.16 [95% confidence interval 1.08-1.25], P=1.0x10(-4)). CONCLUSION: Our findings indicate that IL21R is a novel susceptibility gene for SLE.
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| 28. |
- Webb, Ryan, et al.
(författare)
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Variants within MECP2, a key transcription regulator, are associated with increased susceptibility to lupus and differential gene expression in patients with systemic lupus erythematosus
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:4, s. 1076-1084
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Both genetic and epigenetic factors play an important role in the pathogenesis of lupus. The aim of this study was to examine methyl-CpG-binding protein 2 gene (MECP2) polymorphisms in a large cohort of patients with lupus and control subjects, and to determine the functional consequences of the lupus-associated MECP2 haplotype. METHODS: We genotyped 18 single-nucleotide polymorphisms within MECP2, located on chromosome Xq28, in a large cohort of patients with lupus and control subjects of European descent. We studied the functional effects of the lupus-associated MECP2 haplotype by determining gene expression profiles in B cell lines in female lupus patients with and those without the lupus-associated MECP2 risk haplotype. RESULTS: We confirmed, replicated, and extended the genetic association between lupus and genetic markers within MECP2 in a large independent cohort of lupus patients and control subjects of European descent (odds ratio 1.35, P = 6.65 x 10(-11)). MECP2 is a dichotomous transcription regulator that either activates or represses gene expression. We identified 128 genes that are differentially expressed in lupus patients with the disease-associated MECP2 haplotype; most ( approximately 81%) were up-regulated. Genes that were up-regulated had significantly more CpG islands in their promoter regions compared with genes that were down-regulated. Gene ontology analysis using the differentially expressed genes revealed significant association with epigenetic regulatory mechanisms, suggesting that these genes are targets for MECP2 regulation in B cells. Furthermore, at least 13 of the 104 up-regulated genes are regulated by interferon. The disease-risk MECP2 haplotype was associated with increased expression of the MECP2 transcription coactivator CREB1 and decreased expression of the corepressor histone deacetylase 1. CONCLUSION: Polymorphism in the MECP2 locus is associated with lupus and, at least in part, contributes to the interferon signature observed in lupus patients.
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