| 1. |
- Bayne, Elizabeth H., et al.
(författare)
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Splicing factors facilitate RNAi-directed silencing in fission yeast
- 2008
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 322:5901, s. 602-606
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Tidskriftsartikel (refereegranskat)abstract
- Heterochromatin formation at fission yeast centromeres is directed by RNA interference (RNAi). Noncoding transcripts derived from centromeric repeats are processed into small interfering RNAs (siRNAs) that direct the RNA-induced transcriptional silencing (RITS) effector complex to engage centromer transcripts, resulting in recruitment of the histone H3 lysine 9 methyltransferase Clr4, and hence silencing. We have found that defects in specific splicing factors, but not splicing itself, affect the generation of centromeric siRNAs and consequently centromeric heterochromatin integrity. Moreover, splicing factors physically associate with Cid12, a component of the RNAi machinery, and with centromeric chromatin, consistent with a direct role in RNAi. We propose that spliceosomal complexes provide a platform for siRNA generation and hence facilitate effective centromere repeat silencing.
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| 2. |
- 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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| 3. |
- Djupedal, Ingela, et al.
(författare)
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Analysis of small RNA in fission yeast; centromeric siRNAs are potentially generated through a structured RNA
- 2009
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Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 28:24, s. 3832-3844
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Tidskriftsartikel (refereegranskat)abstract
- The formation of heterochromatin at the centromeres in fission yeast depends on transcription of the outer repeats. These transcripts are processed into siRNAs that target homologous loci for heterochromatin formation. Here, high throughput sequencing of small RNA provides a comprehensive analysis of centromere-derived small RNAs. We found that the centromeric small RNAs are Dcr1 dependent, carry 50-monophosphates and are associated with Ago1. The majority of centromeric small RNAs originate from two remarkably well-conserved sequences that are present in all centromeres. The high degree of similarity suggests that this non-coding sequence in itself may be of importance. Consistent with this, secondary structure-probing experiments indicate that this centromeric RNA is partially double-stranded and is processed by Dicer in vitro. We further demonstrate the existence of small centromeric RNA in rdp1D cells. Our data suggest a pathway for siRNA generation that is distinct from the well-documented model involving RITS/RDRC. We propose that primary transcripts fold into hairpin-like structures that may be processed by Dcr1 into siRNAs, and that these siRNAs may initiate heterochromatin formation independent of RDRC activity. The EMBO Journal (2009) 28, 3832-3844. doi: 10.1038/emboj.2009.351; Published online 26 November 2009
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| 4. |
- Malmsjö, Malin, et al.
(författare)
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Negative-pressure wound therapy using gauze or open-cell polyurethane foam: similar early effects on pressure transduction and tissue contraction in an experimental porcine wound model.
- 2009
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Ingår i: Wound Repair and Regeneration. - 1524-475X. ; 17:2, s. 200-205
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Tidskriftsartikel (refereegranskat)abstract
- Negative-pressure wound therapy (NPWT), also known as topical negative-pressure therapy, is widely used to manage wounds and accelerate healing. NPWT has so far been delivered mainly via open-cell polyurethane foam, but increasing interest has been directed toward delivering NPWT via gauze. In the present study, the early effects of NPWT on pressure transduction and wound contraction were examined in wounds filled with either polyurethane foam or gauze. An experimental setup of a porcine wound model was used, in which the animals were anesthetized for 12-14 hours. Negative pressures between -50 and -175 mmHg were applied in -25 mmHg increments. Wound bed pressure was measured using a saline filled catheter sutured to the bottom of the wound. The contraction of the wound edges was also determined. The recordings were performed upon reaching steady state, which typically occurred within 1 minute. For both fillers, wound bed negative pressure increased linearly with delivered vacuum with little deviation from set pressure (correlation coefficient 0.99 in both cases). Similar tissue contraction was observed when using foam and gauze. The most prominent contraction was observed in the range of 0 to -50 mmHg with greater vacuum only producing minor further movement of the wound edge. In conclusion, the present experimental study shows that gauze and foam are equally effective at delivering negative pressure and creating mechanical deformation of the wound.
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| 5. |
- Malmsjö, Malin, et al.
(författare)
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Wound edge microvascular blood flow: effects of negative pressure wound therapy using gauze or polyurethane foam.
- 2009
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Ingår i: Annals of Plastic Surgery. - 1536-3708. ; 63:6, s. 676-681
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine the effects of negative pressure wound therapy (NPWT) on wound edge microvascular blood flow, comparing different wound fillers. Wounds were created on the backs of 7 pigs. NPWT was applied, using either foam or gauze, at -50,-75, -100, -125, -150, or -175 mm Hg. Microvascular blood flow was measured in muscle tissue, subcutaneous tissue, and in the wound bed, at 0.5, 1, and 2.5 cm from the wound edge, using laser Doppler velocimetry. Similar patterns of blood flow response were observed when using foam or gauze. At 2.5 cm from the wound edge there was an increase in microvascular blood flow, while blood flow was decreased closer (0.5 cm) to the wound edge. The blood flow effects were similar at the different levels of negative pressure in muscle tissue, subcutaneous tissue, and in the wound bed. Altered microvascular blood flow to the wound edge may be one of the mechanisms by which NPWT facilitates healing.
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