| 1. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 2. |
- Abelson, Anna-Karin, et al.
(författare)
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STAT4 Associates with SLE through two independent effects that correlate with gene expression and act additively with IRF5 to increase risk
- 2009
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 68:11, s. 1746-1753
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To confirm and define the genetic association of STAT4 and systemic lupus erythematosus, investigate the possibility of correlations with differential splicing and/or expression levels, and genetic interaction with IRF5. METHODS: 30 tag SNPs were genotyped in an independent set of Spanish cases and controls. SNPs surviving correction for multiple tests were genotyped in 5 new sets of cases and controls for replication. STAT4 cDNA was analyzed by 5'-RACE PCR and sequencing. Expression levels were measured by quantitative PCR. RESULTS: In the fine-mapping, four SNPs were significant after correction for multiple testing, with rs3821236 and rs3024866 as the strongest signals, followed by the previously associated rs7574865, and by rs1467199. Association was replicated in all cohorts. After conditional regression analyses, two major independent signals represented by SNPs rs3821236 and rs7574865, remained significant across the sets. These SNPs belong to separate haplotype blocks. High levels of STAT4 expression correlated with SNPs rs3821236, rs3024866 (both in the same haplotype block) and rs7574865 but not with other SNPs. We also detected transcription of alternative tissue-specific exons 1, indicating presence of tissue-specific promoters of potential importance in the expression of STAT4. No interaction with associated SNPs of IRF5 was observed using regression analysis. CONCLUSIONS: These data confirm STAT4 as a susceptibility gene for SLE and suggest the presence of at least two functional variants affecting levels of STAT4. Our results also indicate that both genes STAT4 and IRF5 act additively to increase risk for SLE.
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| 3. |
- Espert, Ana, 1977-
(författare)
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Strategies for improving mechanical properties of polypropylene/cellulose composites
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The interest for polypropylene/cellulose composites has experienced a great increase in different applications such as car interiors and construction materials. Cellulose fibres are inexpensive, renewable, biodegradable, they present lower density and their mechanical properties can be compared to those of inorganic fillers. However, several factors must be considered when designing polypropylene/cellulose composites: the poor compatibility between the hydrophilic fibres and the hydrophobic thermoplastic matrix leads to a weak interface, which has to be improved by coupling agents; the hydrophilic nature of the fibres makes them very sensitive towards water absorption, which also leads to a loss of properties and swelling with subsequent dimensional instability; the reduced thermal stability of cellulose fibres leads to degradation of the fibres at thermoplastic processing temperatures producing odours in the final material; and finally the properties of composites are greatly influenced by the structure, size and quality of the fibres. Pulp fibres modified by different methods in order to enhance the compatibility fibre-matrix, were tested. Modified fibres led to improved mechanical properties and thermal behaviour when used in composites with recycled polypropylene. Four different types of natural fibres were used as reinforcement in two different polypropylene types: virgin and recycled polypropylene. The mechanical properties of the composites were mostly dependent on the fibre loading and slightly dependent on the type of fibre. Moreover, water absorption kinetics was studied by the Fickian diffusion theory. After absorption, a remarkable loss of properties was observed. Hydrolysed cellulose fibres showed a greater enhancing effect on polypropylene than non-hydrolysed cellulose fibres. This is attributed to the greater mechanical properties of reduced cellulose structures. The effect of using cellulose fibres in PP/clay nanocomposites was also studied. The interaction between the clay particles and the cellulose fibres and the combined effect of both reinforcements were believed to be the main reasons for the enhancing properties.
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| 4. |
- Kozyrev, Sergey V, et al.
(författare)
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Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 211-216
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies and complex genetic inheritance(1-3). In a genome-wide scan using 85,042 SNPs, we identified an association between SLE and a nonsynonymous substitution (rs10516487, R61H) in the B-cell scaffold protein with ankyrin repeats gene, BANK1. We replicated the association in four independent case-control sets (combined P = 3.7 x 10(-10); OR = 1.38). We analyzed BANK1 cDNA and found two isoforms, one full-length and the other alternatively spliced and lacking exon 2 (Delta 2), encoding a protein without a putative IP3R-binding domain. The transcripts were differentially expressed depending on a branch point-site SNP, rs17266594, in strong linkage disequilibrium (LD) with rs10516487. A third associated variant was found in the ankyrin domain (rs3733197, A383T). Our findings implicate BANK1 as a susceptibility gene for SLE, with variants affecting regulatory sites and key functional domains. The disease-associated variants could contribute to sustained B cell-receptor signaling and B-cell hyperactivity characteristic of this disease.
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| 9. |
- Talamillo, Ana, et al.
(författare)
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Sm3 is required for Drosophila melanogaster metamorphosis.
- 2008
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Ingår i: Development. ; 135:9, s. 1659-1668
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Tidskriftsartikel (refereegranskat)abstract
- Sumoylation, the covalent attachment of the small ubiquitin-related modifier SUMO to target proteins, regulates different cellular processes, although its role in the control of development remains unclear. We studied the role of sumoylation during Drosophila development by using RNAi to reduce smt3 mRNA levels in specific tissues. smt3 knockdown in the prothoracic gland, which controls key developmental processes through the synthesis and release of ecdysteroids, caused a 4-fold prolongation of larval life and completely blocked the transition from larval to pupal stages. The reduced ecdysteroid titer of smt3 knockdown compared with wild-type larvae explains this phenotype. In fact, after dietary administration of exogenous 20-hydroxyecdysone, knockdown larvae formed pupal cases. The phenotype is not due to massive cell death or degeneration of the prothoracic glands at the time when puparium formation should occur. Knockdown cells show alterations in expression levels and/or the subcellular localisation of enzymes and transcription factors involved in the regulation of ecdysteroid synthesis. In addition, they present reduced intracellular channels and a reduced content of lipid droplets and cholesterol, which could explain the deficit in steroidogenesis. In summary, our study indicates that Smt3 is required for the ecdysteroid synthesis pathway at the time of puparium formation.
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| 10. |
- Talamillo, Ana, et al.
(författare)
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Sumoylation is necessary for the metamorphosis of Drosophila melanogaster
- 2007
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Ingår i: European Drosophila Research Conference.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- To study in vivo the role of the ubiquitin-like protein Smt3 (Sumo) during Drosophila development, we generated transgenic flies carrying the transgene UAS-smt3i to reduce smt3 mRNA levels in specific groups of cells. Low smt3 in the prothoracic gland, the tissue responsible for the synthesis of ecdysteroids, prevents metamorphosis. RNAi knockdown larvae stop their development in their last larval stage and remain alive for up to a month, during which they continue to eat and gain weight. Their prothoracic glands have fewer, but larger cells than normal, similar to larvae mutant in lesswright, the homologue of the Sumo conjugating enzyme gene Ubc9. They also have lower ecdysteroid titre than WT. After dietary administration of exogenous ecdysone some of these larvae form pupal cases, but do not proceed further in development and die. However, addition of cholesterol or 7-dehydrocholesterol does not rescue the larval phenotype, indicating that sumoylation must be necessary for later steps in the ecdysteroid synthesis pathway. Interestingly, we observed that, in larvae with lower levels of smt3, as well as in lesswright mutants, the subcellular localization and expression levels of factors involved in the regulation of ecdysteroids synthesis, are altered, including Molting defective, Without children, _-Ftz transcription factor 1 and Disembodied. We also investigate the sumoylation capacity of these and other factors involved in ecdysteroid synthesis.
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