| 1. |
|
|
| 2. |
- Smith, Caroline M, et al.
(författare)
-
The response of the poplar transcriptome to wounding and subsequent infection by a viral pathogen
- 2004
-
Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 164, s. 123-136
-
Tidskriftsartikel (refereegranskat)abstract
- The Populus–Poplar Mosaic Virus (PopMV) pathosystem is the best characterized of all forest tree–virus interactions. The details of the host response to this virus are completely unknown.The transcript abundance for approximately 10 000 Populus genes was simultaneously interrogated using spotted cDNA microarrays. Relative transcript abundance was compared for RNA extracted from Populus leaves that were untreated, mock-inoculated leaves that were wounded by leaf abrasion and inoculated leaves that were abraded and then infected by virus.Statistical analysis of the microarray data identified suites of genes that exhibited increased or decreased transcript abundance in response to wounding, systemic PopMV infection or both together. Genes implicated in programmed cell death, and cell wall reinforcement were a major feature of the wound response, whereas genes encoding metallothionein-like proteins, and proteins implicated in cell wall remodelling were a major feature of the PopMV response.The identification of wound- and PopMV-regulated genes opens the door for future studies aimed at testing specific hypotheses related to the mechanisms used by forest trees to contend with stress.
|
|
| 3. |
|
|
| 4. |
- Buckley, Patrick G, et al.
(författare)
-
A full-coverage, high-resolution human chromosome 22 genomic microarrayfor clinical and research applications
- 2002
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 11:25, s. 3221-3229
-
Tidskriftsartikel (refereegranskat)abstract
- We have constructed the first comprehensive microarray representing a human chromosome for analysis of DNA copy number variation. This chromosome 22 array covers 34.7 Mb, representing 1.1% of the genome, with an average resolution of 75 kb. To demonstrate the utility of the array, we have applied it to profile acral melanoma, dermatofibrosarcoma, DiGeorge syndrome and neurofibromatosis 2. We accurately diagnosed homozygous/heterozygous deletions, amplifications/gains, IGLV/IGLC locus instability, and breakpoints of an imbalanced translocation. We further identified the 14-3-3 eta isoform as a candidate tumor suppressor in glioblastoma. Two significant methodological advances in array construction were also developed and validated. These include a strictly sequence defined, repeat-free, and non-redundant strategy for array preparation. This approach allows an increase in array resolution and analysis of any locus; disregarding common repeats, genomic clone availability and sequence redundancy. In addition, we report that the application of phi29 DNA polymerase is advantageous in microarray preparation. A broad spectrum of issues in medical research and diagnostics can be approached using the array. This well annotated and gene-rich autosome contains numerous uncharacterized disease genes. It is therefore crucial to associate these genes to specific 22q-related conditions and this array will be instrumental towards this goal. Furthermore, comprehensive epigenetic profiling of 22q-located genes and high-resolution analysis of replication timing across the entire chromosome can be studied using our array.
|
|
| 5. |
- Dollery, Clare M., et al.
(författare)
-
Neutrophil elastase in human atherosclerotic plaques : production by macrophages
- 2003
-
Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 107:22, s. 2829-2836
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Catabolism of the extracellular matrix (ECM) contributes to vascular remodeling in health and disease. Although metalloenzymes and cysteinyl proteinases have garnered much attention in this regard, the role of serine-dependent proteinases in vascular ECM degradation during atherogenesis remains unknown. We recently discovered the presence of the metalloproteinase MMP-8, traditionally associated only with neutrophils, in atheroma-related cells. Human neutrophil elastase (NE) plays a critical role in lung disease, but the paucity of neutrophils in the atheromatous plaque has led to neglect of its potential role in vascular biology. NE can digest elastin, fibrillar and nonfibrillar collagens, and other ECM components in addition to its ability to modify lipoproteins and modulate cytokine and MMP activity.METHODS AND RESULTS: Fibrous and atheromatous plaques but not normal arteries contained NE. In particular, NE abounded in the macrophage-rich shoulders of atheromatous plaques with histological features of vulnerability. Neutrophil elastase and macrophages colocalized in such vulnerable plaques (n=7). In situ hybridization revealed NE mRNA in macrophage-rich areas, indicating local production of this enzyme. Freshly isolated blood monocytes, monocyte-derived macrophages, and vascular endothelial cells in culture produced active NE and contained NE mRNA. Monocytes produced NE constitutively, with little regulation by cytokines IL-1beta, TNF-alpha, or IFN-gamma but released it when stimulated by CD40 ligand, a cytokine found in atheroma.CONCLUSIONS: These findings point to a novel role for the serine protease, neutrophil elastase, in matrix breakdown by macrophages, a critical process in adaptive remodeling of vessels and in the pathogenesis of arterial diseases.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Hedfalk, Kristina, 1969, et al.
(författare)
-
A Regulatory Domain in the C-terminal Extension of the Yeast Glycerol Channel Fps1p
- 2004
-
Ingår i: Journal of biological chemistry. ; 279:15, s. 14954-14960
-
Tidskriftsartikel (refereegranskat)abstract
- The Saccharomyces cerevisiae gene FPS1 encodes an aquaglyceroporin of the major intrinsic protein (MIP) family. The main function of Fps1p seems to be the efflux of glycerol in the adaptation of the yeast cell to lower external osmolarity. Fps1p is an atypical member of the family, because the protein is much larger (669 amino acids) than most MIPs due to long hydrophilic extensions in both termini. We have shown previously that a short domain in the N-terminal extension of the protein is required for restricting glycerol transport through the channel (Tamás, M. J., Karlgren, S., Bill, R. M., Hedfalk, K., Allegri, L., Ferreira, M., Thevelein, J. M., Rydström, J., Mullins, J. G. L., and Hohmann, S. (2003) J. Biol. Chem. 278, 63376345). Deletion of the N-terminal domain results in an unregulated channel, loss of glycerol, and osmosensitivity. In this work we have investigated the role of the Fps1p C terminus (139 amino acids). A set of eight truncations has been constructed and tested in vivo in a yeast fps1 strain. We have performed growth tests, membrane localization following cell fractionation, and glycerol accumulation measurements as well as an investigation of the osmotic stress response. Our results show that the C-terminal extension is also involved in restricting transport through Fps1p. We have identified a sequence of 12 amino acids, residues 535546, close to the sixth transmembrane domain. This element seems to be important for controlling Fps1p function. Similar to the N-terminal domain, the C-terminal domain is amphiphilic and has a potential to dip into the membrane
|
|
| 9. |
- Karlgren, Sara, 1975, et al.
(författare)
-
Identification of residues controlling transport through the yeast aquaglyceroporin Fps1 using a genetic screen
- 2004
-
Ingår i: European journal of biochemistry. - : Wiley. - 0014-2956. ; 271:4, s. 771-779
-
Tidskriftsartikel (refereegranskat)abstract
- Aquaporins and aquaglyceroporins mediate the transport of water and solutes across biological membranes. Saccharomyces cerevisiae Fps1 is an aquaglyceroporin that mediates controlled glycerol export during osmoregulation. The transport function of Fps1 is rapidly regulated by osmotic changes in an apparently unique way and distinct regions within the long N- and C-terminal extensions are needed for this regulation. In order to learn more about the mechanisms that control Fps1 we have set up a genetic screen for hyperactive Fps1 and isolated mutations in 14 distinct residues, all facing the inside of the cell. Five of the residues lie within the previously characterized N-terminal regulatory domain and two mutations are located within the approach to the first transmembrane domain. Three mutations cause truncation of the C-terminus, confirming previous studies on the importance of this region for channel control. Furthermore, the novel mutations identify two conserved residues in the channel-forming B-loop as critical for channel control. Structural modelling-based rationalization of the observed mutations supports the notion that the N-terminal regulatory domain and the B-loop could interact in channel control. Our findings provide a framework for further genetic and structural analysis to better understand the mechanism that controls Fps1 function by osmotic changes
|
|
| 10. |
- Karlsson, Caroline, et al.
(författare)
-
Pregnancy and lactation confer reversible bone loss in humans
- 2001
-
Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 12:10, s. 828-834
-
Tidskriftsartikel (refereegranskat)abstract
- The influence of pregnancy on bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry (DXA) in 73 women (mean age 29 years, range 20-44 years) postpartum. Fifty-five age-matched women served as controls. The influence of lactation was evaluated in 65 of the delivered women who were followed with repeated measurements, a mean of 4.5 +/- 0.1 and 11.5 +/- 0.1 months after the delivery. The influence of multiple pregnancies was evaluated in 39 premenopausal women (mean age 38 years, range 31-54 years) with a minimum of four pregnancies (range 4-7). Fifty-eight age-matched healthy premenopausal women with a maximum of two pregnancies (range 0-2) served as controls. Data are presented as mean +/- SEM. BMD data are adjusted for differences in total fat mass and total lean mass. Lumbar spine BMD was 7.6 +/- 0.1% and total body BMD 3.9 +/- 0.1% lower in women postpartum compared with controls (both p<0.001). BMD did not decrease significantly in non-breastfeeding mothers. Mothers breastfeeding for 1-6 months decreased femoral neck BMD by 2.0 +/- 1.0% during the first 5 months postpartum (p<0.001). No further BMD loss was seen between 5 and 12 months postpartum. Femoral neck BMD 12 months after delivery was 1.3 +/- 0.8% lower than after delivery in mothers breastfeeding for 1-6 months (p = 0.05). Mothers breastfeeding for more than 6 months decreased Ward's triangle BMD by 8.5 +/- 1.0% and lumbar spine BMD by 4.1 +/- 0.8% during the first 5 months postpartum (both p<0.05). No further BMD loss was seen between 5 and 12 months postpartum. Femoral neck BMD 12 months after delivery was 4.0 +/- 1.1% lower and Ward's triangle BMD 5.3 +/- 1.9% lower than after delivery in mothers breastfeeding for more than 6 months (both p<0.05). BMD loss was higher during the first 5 months following delivery in the lactating women compared with the non-lactating women (p<0.05 comparing lumbar spine BMD loss in lactating mothers versus non-lactating mothers). However, in women with a minimum of four pregnancies the BMD was no lower than in age-matched women with fewer pregnancies. Total duration of lactation was not correlated with the present BMD. In summary, pregnancy seem to confer a low BMD with additional BMD loss during 5 months of lactation. Even if complete restoration in BMD was not reached within 5 months of weaning, women with four pregnancies or more had a BMD no lower than women with two pregnancies or fewer. We conclude that neither an extended lactation period nor multiple pregnancies could be used as a risk factor when predicting women at risk for future osteoporosis.
|
|
