| 1. |
- Cui, Qiao-Yu, et al.
(författare)
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The role of tree composition in Holocene fire history of the hemiboreal and southern boreal zones of southern Sweden, as revealed by the application of the Landscape Reconstruction Algorithm : Implications for biodiversity and climate-change issues
- 2013
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Ingår i: The Holocene. - : SAGE Publications. - 0959-6836 .- 1477-0911. ; 23:12, s. 1747-1763
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Tidskriftsartikel (refereegranskat)abstract
- We present a quantitative reconstruction of local forest history at two sites, Stavsåkra (hemiboreal zone) and Storasjö (southern boreal zone), in southern Sweden (province of Småland) to evaluate possible causes of contrasting Holocene fire histories in mid- and late Holocene. The Landscape Reconstruction Algorithm (LRA) is applied to evaluate between-site differences in the relative abundance of deciduous trees and Pinus (pine) and landscape/woodland openness during the Holocene. The LRA estimates of local vegetation abundance are compared with other proxies of local vegetation, that is, plant and beetle remains. The LRA results suggest that Pinus was a major tree taxon in the woodlands of Storasjö during mid- and late Holocene, while Tilia(linden) and Betula (birch) were dominant at Stavsåkra. The contrasting fire histories are shown to be strongly related to between-site differences in tree composition during mid-Holocene, 4000–2000 BC in particular. The archaeological/historical and beetle data indicate contrasting land uses from c. 1000BC (late Bronze Age/early Iron Age), grazing in open Calluna heaths at Stavsåkra and woodland grazing at Storasjö. Between-site differences in fire historyduring late Holocene were likely due to different land-use practices. Between-site differences in tree composition in mid-Holocene are best explainedby local climatic and geological/geomorphological differences between the hemiboreal and southern boreal zones of Småland, which might also be the primary cause of between-site differences in land-use histories during late Holocene. Maintenance of biodiversity at the landscape scale in the studyarea requires that existing old pine woodlands and Calluna heath are managed with fire and cattle grazing. Further climate warming might lead to higherprobabilities of climate-induces fire, in particular in pine-dominated woodlands.
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| 2. |
- Cunningham, Janet L., et al.
(författare)
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Connective tissue growth factor expression in endocrine tumors is associated with high stromal expression of alpha-smooth muscle actin
- 2010
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 163:4, s. 691-697
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Complications due to fibrosis development are common in patients with well-differentiated endocrine carcinomas in the small intestine (ileal carcinoids). Connective tissue growth factor (CTGF) expression in ileal carcinoids may be related to this fibrosis development. This study aimed to examine CTGF expression in relation to local myofibroblast differentiation in a large series of ileal carcinoids and in different types of endocrine tumors. METHODS Immunoreactivity (IR) for CTGF and α-smooth muscle actin (α-SMA), a marker for myofibroblasts, was compared in serial tumor tissue sections from 42 patients with ileal carcinoids and from 80 patients with other endocrine tumors. Western blot was performed on an additional 21 patients with ileal carcinoids. RESULTS CTGF IR was present in >50% of tumor cells in all 42 ileal carcinoids and in 2 out of 14 endocrine pancreatic tumors, 4 out of 6 rectal carcinoids, and 1 out of 5 lung carcinoids. Tumors with abundant CTGF expression also displayed α-SMA IR in stromal fibroblast-like cells, whereas other endocrine tumors displayed less or no CTGF and α-SMA IR. Protein bands corresponding to full-length CTGF (36-42 kDa) were detected in protein lysates from ileal carcinoids. CONCLUSION CTGF is uniquely prevalent in ileal carcinoids when compared with most other endocrine tumor types. Immunoreactive cells are adjacent areas with increased fibrovascular stroma that express α-SMA. This supports a potential role for CTGF in myofibroblast-mediated fibrosis associated with ileal carcinoids, and indicates that CTGF should be investigated as a target for future therapy.
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| 3. |
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| 4. |
- Hu, Lijuan, et al.
(författare)
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Retinoic acid increases proliferation of human osteoclast progenitors and inhibits RANKL-stimulated osteoclast differentiation by suppressing RANK
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:10, s. e13305-
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Tidskriftsartikel (refereegranskat)abstract
- It has been shown that high vitamin A intake is associated with bone fragility and fractures in both animals and humans. However, the mechanism by which vitamin A affects bones is unclear. In the present study, the direct effects of retinoic acid (RA) on human and murine osteoclastogenesis were evaluated using cultured peripheral blood CD14(+) monocytes and RAW264.7 cells. Both the activity of the osteoclast marker tartrate resistant acid phosphatase (TRAP) in culture supernatant and the expression of the genes involved in osteoclast differentiation together with bone resorption were measured. To our knowledge, this is the first time that the effects of RA on human osteoclast progenitors and mature osteoclasts have been studied in vitro. RA stimulated proliferation of osteoclast progenitors both from humans and mice. In contrast, RA inhibited differentiation of the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis of human and murine osteoclast progenitors via retinoic acid receptors (RARs). We also show that the mRNA levels of receptor activator of nuclear factor κB (RANK), the key initiating factor and osteoclast associated receptor for RANKL, were potently suppressed by RA in osteoclast progenitors. More importantly, RA abolished the RANK protein in osteoclast progenitors. This inhibition could be partially reversed by a RAR pan-antagonist. Furthermore, RA treatment suppressed the expression of the transcription factor nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and increased the expression of interferon regulatory factor-8 (IRF-8) in osteoclast progenitors via RARs. Also, RA demonstrated differential effects depending on the material supporting the cell culture. RA did not affect TRAP activity in the culture supernatant in the bone slice culture system, but inhibited the release of TRAP activity if cells were cultured on plastic. In conclusion, our results suggest that retinoic acid increases proliferation of human osteoclast progenitors and that it inhibits RANK-stimulated osteoclast differentiation by suppressing RANK.
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| 5. |
- Jacobson, Annica, et al.
(författare)
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Connective tissue growth factor in tumor pathogenesis
- 2012
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Ingår i: Fibrogenesis & Tissue Repair. - 1755-1536. ; 5:Suppl.1, s. S8-S8
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Tidskriftsartikel (refereegranskat)abstract
- Key roles for connective tissue growth factor (CTGF/CCN2) are demonstrated in the wound repair process where it promotes myofibroblast differentiation and angiogenesis. Similar mechanisms are active in tumor-reactive stroma where CTGF is expressed. Other potential roles include prevention of hypoxia-induced apoptosis and promoting epithelial-mesenchymal transistion (EMT). CTGF expression in tumors has been associated to both tumor suppression and progression. For example, CTGF expression in acute lymphoblastic leukemia, breast, pancreas and gastric cancer correlates to worse prognosis whereas the opposite is true for colorectal, lung and ovarian cancer. This discrepancy is not yet understood.High expression of CTGF is a hallmark of ileal carcinoids, which are well-differentiated endocrine carcinomas with serotonin production originating from the small intestine and proximal colon. These tumors maintain a high grade of differentiation and low proliferation. Despite this, they are malignant and most patients have metastatic disease at diagnosis. These tumors demonstrate several phenotypes potentially related to CTGF function namely: cell migration, absent tumor cell apoptosis, as well as, reactive and well vascularised myofibroblast rich stroma and fibrosis development locally and in distal organs. The presence of CTGF in other endocrine tumors indicates a role in the progression of well-differentiated tumors.
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| 7. |
- Lind, Thomas, et al.
(författare)
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High dietary intake of retinol leads to bone marrow hypoxia and diaphyseal endosteal mineralization in rats
- 2011
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 48:3, s. 496-506
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin A (retinol) is the only molecule known to induce spontaneous fractures in laboratory animals and we have identified retinol as a risk factor for fracture in humans. Since subsequent observational studies in humans and old animal data both show that high retinol intake appears to only have small effects on bone mineral density (BMD) we undertook a mechanistic study of how excess retinol reduces bone diameter while leaving BMD essentially unaffected. We fed growing rats high doses of retinol for only 1week. Bone analysis involved antibody-based methods, histology, pQCT, biomechanics and bone compartment-specific PCR together with Fourier Transform Infrared Spectroscopy of bone mineral. Excess dietary retinol induced weakening of bones with little apparent effect on BMD. Periosteal osteoclasts increased but unexpectedly endosteal osteoclasts disappeared and there was a reduction of osteoclastic serum markers. There was also a lack of capillary erythrocytes, endothelial cells and serum retinol transport protein in the endosteal/marrow compartment. A further indication of reduced endosteal/marrow blood flow was the increased expression of hypoxia-associated genes. Also, in contrast to the inhibitory effects in vitro, the marrow of retinol-treated rats showed increased expression of osteogenic genes. Finally, we show that hypervitaminotic bones have a higher degree of mineralization, which is in line with biomechanical data of preserved stiffness in spite of thinner bones. Together these novel findings suggest that a rapid primary effect of excess retinol on bone tissue is the impairment of endosteal/marrow blood flow leading to hypoxia and pathological endosteal mineralization.
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| 8. |
- Lind, Thomas, et al.
(författare)
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Microarray Profiling of Diaphyseal Bone of Rats Suffering from Hypervitaminosis A
- 2012
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 90:3, s. 219-229
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin A is the only known compound that produces spontaneous fractures in rats. In an effort to resolve the molecular mechanism behind this effect, we fed young male rats high doses of vitamin A and performed microarray analysis of diaphyseal bone with and without marrow after 1 week, i.e., just before the first fractures appeared. Of the differentially expressed genes in cortical bone, including marrow, 98% were upregulated. In contrast, hypervitaminotic cortical bone without marrow showed reduced expression of 37% of differentially expressed genes. Gene ontology (GO) analysis revealed that only samples containing bone marrow were associated with a GO term, which principally represented extracellular matrix. This is consistent with the histological findings of increased endosteal/marrow osteoblast number. Fourteen genes, including Cyp26b1, which is known to be upregulated by vitamin A, were selected and verified by real-time PCR. In addition, immunohistochemical staining of bone sections confirmed that the bone-specific molecule osteoadherin was upregulated. Further analysis of the major gene-expression changes revealed apparent augmented Wnt signaling in the sample containing bone marrow but reduced Wnt signaling in cortical bone. Moreover, induced expression of hypoxia-associated genes was found only in samples containing bone marrow. Together, these results highlight the importance of compartment-specific analysis of bone and corroborate previous observations of compartment-specific effects of vitamin A, with reduced activity in cortical bone but increased activity in the endosteal/marrow compartment. We specifically identify potential key osteoblast-, Wnt signaling-, and hypoxia-associated genes in the processes leading to spontaneous fractures.
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