| 1. |
- Slotte, Tanja, et al.
(författare)
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The Capsella rubella genome and the genomic consequences of rapid mating system evolution
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:7, s. 831-U165
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Tidskriftsartikel (refereegranskat)abstract
- The shift from outcrossing to selfing is common in flowering plants(1,2), but the genomic consequences and the speed at which they emerge remain poorly understood. An excellent model for understanding the evolution of self fertilization is provided by Capsella rubella, which became self compatible <200,000 years ago. We report a C. rubella reference genome sequence and compare RNA expression and polymorphism patterns between C. rubella and its outcrossing progenitor Capsella grandiflora. We found a clear shift in the expression of genes associated with flowering phenotypes, similar to that seen in Arabidopsis, in which self fertilization evolved about 1 million years ago. Comparisons of the two Capsella species showed evidence of rapid genome-wide relaxation of purifying selection in C. rubella without a concomitant change in transposable element abundance. Overall we document that the transition to selfing may be typified by parallel shifts in gene expression, along with a measurable reduction of purifying selection.
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| 2. |
- Agren, Magnus S., et al.
(författare)
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Action of matrix metalloproteinases at restricted sites in colon anastomosis repair: an immunohistochemical and biochemical study
- 2006
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Ingår i: Surgery. - : Elsevier BV. - 1532-7361 .- 0039-6060. ; 140:1, s. 72-82
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Tidskriftsartikel (refereegranskat)abstract
- Background. Dehiscence of colon anastomosis is a common, serious and potentially life-threatening complication after colorectal operation. In experimental models, impaired biomechanic strength of colon anastomoses is preventable by general inhibitors of matrix metalloproteinases (MMPs) and associated with collagen loss, which indicates a possible link between MMP-mediated collagen degradation and dehiscence. The precise localization of collagen degradation within the anastomotic area and the specific MMPs responsible are unknown. Methods. We have analyzed distinct zones within anastomoses using a novel microdissection technique for collagen levels, collagenolytic activity exerted directly by endogenous proteinases, and MMP-8 and MMP-9 immunoreactivity and their collagenolytic activity. Results. The most pronounced collagen loss was observed in the suture-holding zone, showing a 29% drop compared with adjacent micro-areas of 3-day-old anastomoses. Only this specific tissue compartment underwent a dramatic and significant increase in collagenolysis, amounting to a loss of 10% of existing collagen molecules in 24 hours, and was abolished by metalloproteinase inhibitors. The tissue surrounding suture channels was heavily infiltrated with CD68-positive histiocytes that expressed MMP-8 and to a lesser extent MMP-9. The collagenolytic effect of the interstitial collagenase MMP-8 was synergistically potentiated by the gelatinase MMP-9 when added to colon biopsies incubated in vitro. Conclusions. The unique finding of this study was that the specific tissue holding the sutures of a colon anastomosis lost the most collagen presumably through induction and activation of multiple MMPs that may explain the beneficial effects of treatment with non-selective MMP antagonists.
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| 3. |
- Krarup, Peter-Martin, et al.
(författare)
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Rapid morphological changes and loss of collagen following experimental acute colonic obstruction
- 2013
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Ingår i: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 1432-1262 .- 0179-1958. ; 28:3, s. 341-347
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Tidskriftsartikel (refereegranskat)abstract
- Anastomosis of an acutely obstructed colon is associated with an increased risk of dehiscence. In experimental models, acute obstruction decreases collagen in the colonic wall, but the time course and propagation along the colon of the biochemical changes are unknown. Furthermore, there is a paucity of information on the correlation between these biochemical changes and histological features. Forty male Sprague Dawley rats were subjected to partial obstruction by placing a silicone ring around the left colon 30 mm above the reflection. Obstruction was maintained for 0, 1, 2, 3 or 4 days. Samples from five different locations along the colon were analysed on circumference, tissue water content, collagen concentration and histomorphology. Neutrophil and macrophage infiltration was characterized immunohistochemically. The colonic circumference and water content increased (p < 0.001), while the collagen concentration decreased by 48 % (p < 0.01) proximal to the obstruction already after 1 day. The degree of dilation and collagen reduction did not change significantly over the subsequent 3 days of obstruction, whereas the water content normalized by day 3. Mucosal and submucosal oedema and the relative neutrophil infiltration were highest after 1 day in the colonic segment proximal to the stenosis while the macrophage population continued to increase to day 4. Muscular necrosis in addition to ganglionitis and neuritis in the nervous plexus increased with duration of obstruction. The pronounced and rapid changes of the composition of cells and the extracellular matrix of the colonic wall following acute obstruction may be of guidance for present surgical treatments and future pharmacological interventions.
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| 4. |
- Mirastschijski, Ursula, et al.
(författare)
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Ectopic localization of matrix metalloproteinase-9 in chronic cutaneous wounds.
- 2002
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Ingår i: Human Pathology. - : Elsevier BV. - 1532-8392 .- 0046-8177. ; 33:3, s. 355-364
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Tidskriftsartikel (refereegranskat)abstract
- It has been hypothesized that excessive activity of matrix metalloproteinases (MMPs), in particular the gelatinases MMP-9 and MMP-2, contributes to poor healing of chronic skin ulcers. We compared MMP-9 and MMP-2 in wound margin biopsies of standardized acute partial-thickness wounds in healthy volunteers (n = 6) and in venous leg ulcer patients (n = 12) with those of chronic wounds of different etiologies (n = 34) by a combination of specific analyses of activity and protein localization. We also studied MMP-14 by immunohistochemistry and in situ hybridization in parallel. Neither MMP-9 (P =.814) nor MMP-2 (P =.742) endogenous activities differed significantly between acute and chronic wound tissues. Acute wound healing was characterized by induction of MMP-9 in the advancing epithelium. In chronic wounds, prominent MMP-9 immunostaining was seen in neutrophils and macrophages in the ulcer bed, but virtually no MMP-9 was detected in wound edge keratinocytes. MMP-2 was increased and activated with acute wound age. MMP-2 was found abundantly in dermal fibroblasts and endothelial cells beneath, but not in new epithelium of acute and chronic wounds. MMP-14 mRNA or protein was detected solely in the stroma of both acute and chronic wounds. In conclusion, the overall activity of gelatinases MMP-9 and MMP-2 was not increased in chronic wounds compared to normally healing wound tissues. Chronic nonhealing wounds may not be caused by excessive gelatinase activity, but are distinguished from healing wounds by an unfavorable distribution and persistance of MMP-9.
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| 5. |
- Mirastschijski, Ursula, et al.
(författare)
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Matrix metalloproteinase inhibitor BB-3103 unlike the serine proteinase inhibitor aprotinin abrogates epidermal healing of human skin wounds ex vivo.
- 2002
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 118:1, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- Several matrix metalloproteinases and serine proteinases are upregulated in migrating keratinocytes during cutaneous wound repair. Single cell culture studies indicate the necessity for matrix metalloproteinases but not for serine proteinases in keratinocyte locomotion. To account for epithelial-mesenchymal interactions, an ex vivo human skin wound model was used to investigate the contribution of matrix metalloproteinases and serine proteinases to wound healing by treatment with broad-spectrum inhibitors of matrix metalloproteinases (BB-3103) or serine proteinases (aprotinin). Human skin explants with circular 3 mm superficial defects were incubated in culture medium without (controls) or with the proteinase inhibitors for 7 d. BB-3103 abrogated epithelialization (p < 0.001), whereas aprotinin-treated wounds and controls were covered with new epithelium. Lack of epithelialization was unlikely due to cytotoxicity because the matrix metalloproteinase inhibitor did neither influence viability of cultured epidermal keratinocytes nor apoptosis in wounds. Involvement of specific matrix metalloproteinases in epithelialization was analyzed by gelatin zymography, western blotting, immunohistochemistry, and in situ hybridization. Wound healing was accompanied by active matrix metalloproteinase-1 and increased active matrix metalloproteinase-2 but irrespectively of active matrix metalloproteinase-9. BB-3103 blocked activation of matrix metalloproteinase-2 and matrix metalloproteinase-9 but not of matrix metalloproteinase-1. Active matrix metalloproteinase-2 localized solely to the dermis, whereas matrix metalloproteinase-9 was consistently found in new epithelium. Membrane-type 1 matrix metalloproteinase was undetectable in wound keratinocytes. BB-3103 and aprotinin reduced tumor necrosis factor-alpha in media but did not appreciably alter amounts of other soluble regulators of matrix metalloproteinases and epithelialization. Our findings demonstrate that keratinocyte migration is associated with active matrix metalloproteinase-2 but occurs independently of serine proteinases and active matrix metalloproteinase-9 in fibrin-deficient skin wound healing.
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