| 11. |
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| 12. |
- Mikkelsen, Tarjei S, et al.
(författare)
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Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7141, s. 167-177
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Tidskriftsartikel (refereegranskat)abstract
- We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.
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| 13. |
- Rich, Rebecca L., et al.
(författare)
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A global benchmark study using affinity-based biosensors
- 2009
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216
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Tidskriftsartikel (refereegranskat)abstract
- To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
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| 14. |
- Thorfinn, Johan, et al.
(författare)
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Flexor Tendon Tissue Engineering: Temporal Distribution of Donor Tenocytes versus Recipient Cells
- 2009
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Ingår i: Plastic and reconstructive surgery (1963). - 0032-1052 .- 1529-4242. ; 124:6, s. 2019-2026
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tissue-engineered tendon material may address tendon shortages in mutilating hand injuries. Tenocytes from rabbit flexor tendon can be successfully seeded onto acellularized tendons that are used as tendon constructs. These constructs in vivo exhibit a population of tenocyte-like cells; however, it is not known to what extent these cells are of donor or recipient origin. Furthermore, the temporal distribution is also not known. Methods: Tenocytes from New Zealand male rabbits were cultured and seeded onto acellularized rabbit forepaw flexor tendons (n = 48). These tendon constructs were transplanted into female recipients. Tendons were examined after 3, 6, 12, and 30 weeks using fluorescent in situ hybridization to detect the Y chromosome in the male donor cells. One unseeded, acellularized allograft in each animal was used as a control. Results: The donor male tenocytes populate the epitenon and endotenon of the grafts at greater numbers than the recipient female tenocytes at 3 and 6 weeks. The donor and recipient tenocytes are present jointly in the grafts until 12 weeks. At 30 weeks, nearly all cells are recipient tenocyte-like cells. Conclusions: Donor male cells survive in decreasing numbers over time until 30 weeks. The presence of cells in tissue-engineered tendon grafts has been shown in prior studies to add to the strength of the constructs in vitro. This study shows that recipient cells can migrate into and repopulate the tendon construct. Cell seeding onto tendon material may create stronger constructs that will allow the initiation of motion earlier. (Plast. Reconstr. Surg. 124: 2019, 2009.)
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| 15. |
- Zhang, Fan, et al.
(författare)
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VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:15, s. 6152-6157
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Tidskriftsartikel (refereegranskat)abstract
- VEGF-B, a homolog of VEGF discovered a long time ago, has not been considered an important target in antiangiogenic therapy. Instead, it has received little attention from the field. In this study, using different animal models and multiple types of vascular cells, we revealed that although VEGF-B is dispensable for blood vessel growth, it is critical for their survival. Importantly, the survival effect of VEGF-B is not only on vascular endothelial cells, but also on pericytes, smooth muscle cells, and vascular stem/progenitor cells. In vivo, VEGF-B targeting inhibited both choroidal and retinal neovascularization. Mechanistically, we found that the vascular survival effect of VEGF-B is achieved by regulating the expression of many vascular prosurvival genes via both NP-1 and VEGFR-1. Our work thus indicates that the function of VEGF-B in the vascular system is to act as a "survival," rather than an "angiogenic" factor and that VEGF-B inhibition may offer new therapeutic opportunities to treat neovascular diseases.
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| 16. |
- Zody, Michael, 1968-, et al.
(författare)
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Analysis of the DNA sequence and duplication history of human chromosome 15
- 2006
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 440:7084, s. 671-675
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Tidskriftsartikel (refereegranskat)abstract
- Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplication in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome.
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