| 1. |
- Barkefors, Irmeli, et al.
(author)
-
Exocyst Complex Component 3-like 2 (EXOC3L2) Associates with the Exocyst Complex and Mediates Directional Migration of Endothelial Cells
- 2011
-
In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 286:27, s. 24189-24199
-
Journal article (peer-reviewed)abstract
- The exocyst is a protein complex that ensures spatial targeting of exocytotic vesicles to the plasma membrane. We present microarray data obtained from differentiating mouse embryonic stem cell cultures that identify an up-regulation of exocyst complex component 3-like 2 (exoc3l2) mRNA in sprouting blood vessels. Vascular expression of exoc3l2 is confirmed by qPCR analysis of different mouse tissues and immunofluorescence analyses of mouse brain sections. We detect an up-regulation of exoc3l2 mRNA synthesis in primary human endothelial cells in response to VEGFA, and this response is enhanced when the cells are grown on a three-dimensional collagen I matrix. Myc-tagged EXOC3L2 co-precipitates with the exocyst protein EXOC4, and immunofluorescence detection of EXOC3L2 shows partial subcellular colocalization with EXOC4 and EXOC7. Finally, we show that exoc3l2 silencing inhibits VEGF receptor 2 phosphorylation and VEGFA-directed migration of cultured endothelial cells.
|
|
| 2. |
- Fredlund, Elisabeth, et al.
(author)
-
Physiological characteristics of the biocontrol yeast Pichia anomala J121
- 2002
-
In: FEMS yeast research (Print). - : Elsevier. - 1567-1356 .- 1567-1364. ; 2:3, s. 395-402
-
Journal article (peer-reviewed)abstract
- The yeast Pichia anomala J121 prevents mold spoilage and enhances preservation of moist grain in malfunctioning storage systems. Development of P. anomala J121 as a biocontrol agent requires in-depth knowledge about its physiology. P. anomala J121 grew under strictly anaerobic conditions, at temperatures between 3degreesC and 37degreesC, at pH values between 2.0 and 12.4, and at a water activity of 0.92 (NaCl) and 0.85 (glycerol). It could assimilate a wide range of C- and N-sources and produce killer toxin. A selective medium containing starch, nitrate, acetic acid, and chloramphenicol was developed for P. anomala. P. anomala was equally sensitive as Candida albicans to common antifungal compounds. Growth ability at a range of environmental conditions contributes to the competitive ability of the biocontrol yeast P. anomala J121.
|
|
| 3. |
|
|
| 4. |
- Heldin, Johan, et al.
(author)
-
FGD5 sustains vascular endothelial growth factor A (VEGFA) signaling through inhibition of proteasome-mediated VEGF receptor 2 degradation
- 2017
-
In: Cellular Signalling. - : Elsevier BV. - 0898-6568 .- 1873-3913. ; 40, s. 125-132
-
Journal article (peer-reviewed)abstract
- The complete repertoire of endothelial functions elicited by FGD5, a guanine nucleotide exchange factor activating the Rho GTPase Cdc42, has yet to be elucidated. Here we explore FGD5's importance during vascular endothelial growth factor A (VEGFA) signaling via VEGF receptor 2 (VEGFR2) in human endothelial cells. In microvascular endothelial cells, FGD5 is located at the inner surface of the cell membrane as well as at the outer surface of EEAl-positive endosomes carrying VEGFR2. The latter finding prompted us to explore if FGD5 regulates VEGFR2 dynamics. We found that depletion of FGD5 in microvascular cells inhibited their migration towards a stable VEGFA gradient. Furthermore, depletion of FGD5 resulted in accelerated VEGFR2 degradation, which was reverted by lactacystin-mediated proteasomal inhibition. Our results thus suggest a mechanism whereby FGD5 sustains VEGFA signaling and endothelial cell chemotaxis via inhibition of proteasome-dependent VEGFR2 degradation.
|
|
| 5. |
|
|
| 6. |
- Johnson, Tomas, 1979, et al.
(author)
-
A Multi-Scale Simulation Method for the Prediction of Edge Wicking in Multi-Ply Paperboard
- 2015
-
In: Nordic Pulp and Paper Research Journal. - 2000-0669 .- 0283-2631. ; 30:4, s. 640-650
-
Journal article (peer-reviewed)abstract
- When liquid packaging board is made aseptic in the filling machine the unsealed edges of the board are exposed to a mixture of water and hydrogen peroxide. A high level of liquid penetration may lead to aesthetic as well as functional defects. To be able to make a priori predictions of the edge wicking properties of a certain paperboard material is therefore of great interest to the paper industry as well as to packaging manufacturers. In this paper an extended multi-scale model of edge wicking in multi-ply paperboard is presented. The geometric and physical properties of the paperboard are modeled on the micro-scale, and include fillers and fines. The absolute air permeabilities and pore size distributions are validated with experimental and tomographic values. On the macro-scale random porosity and sizing distributions, time and sizing dependent contact angles, and inter-ply dependence are modeled. Arbitrary shapes of the paperboard are handled through an unstructured 3D surface mesh. Stationary and transient edge wicking simulations are validated against experiments with excellent agreement. The simulations show that the diffusive menisci between the liquid and air phases together with the two-ply model is necessary to achieve good agreement with the transient edge wicking experiments.
|
|
| 7. |
- Larsson, Erik, 1975, et al.
(author)
-
Discovery of microvascular miRNAs using public gene expression data : miR-145 is expressed in pericytes and is a regulator of Fli1
- 2009
-
In: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 1:11, s. 108-
-
Journal article (peer-reviewed)abstract
- BACKGROUNDA function for the microRNA (miRNA) pathway in vascular development and angiogenesis has been firmly established. miRNAs with selective expression in the vasculature are attractive as possible targets in miRNA-based therapies. However, little is known about the expression of miRNAs in microvessels in vivo. Here, we identified candidate microvascular-selective miRNAs by screening public miRNA expression datasets.METHODSBioinformatics predictions of microvascular-selective expression were validated with real-time quantitative reverse transcription PCR on purified microvascular fragments from mouse. Pericyte expression was shown with in situ hybridization on tissue sections. Target sites were identified with 3' UTR luciferase assays, and migration was tested in a microfluid chemotaxis chamber.RESULTSmiR-145, miR-126, miR-24, and miR-23a were selectively expressed in microvascular fragments isolated from a range of tissues. In situ hybridization and analysis of Pdgfb retention motif mutant mice demonstrated predominant expression of miR-145 in pericytes. We identified the Ets transcription factor Friend leukemia virus integration 1 (Fli1) as a miR-145 target, and showed that elevated levels of miR-145 reduced migration of microvascular cells in response to growth factor gradients in vitro.CONCLUSIONSmiR-126, miR-24 and miR-23a are selectively expressed in microvascular endothelial cells in vivo, whereas miR-145 is expressed in pericytes. miR-145 targets the hematopoietic transcription factor Fli1 and blocks migration in response to growth factor gradients. Our findings have implications for vascular disease and provide necessary information for future drug design against miRNAs with selective expression in the microvasculature.
|
|
| 8. |
- Berglund, Torsten, et al.
(author)
-
One year of Neisseria gonorrhoeae isolates in Sweden : the prevalence study of antibiotic susceptibility shows relation to the geographic area of exposure
- 2002
-
In: International Journal of STD and AIDS (London). - : SAGE Publications. - 0956-4624 .- 1758-1052. ; 13:2, s. 109-114
-
Journal article (peer-reviewed)abstract
- The aim of this study was to compare epidemiological data with antibiotic susceptibility patterns, so as to characterize the risk of infection with a highly resistant Neisseria gonorrhoeae strain. N. gonorrhoeae strains isolated in Sweden from February 1998 through January 1999 were tested for antibiotic susceptibility. Epidemiological data were received from each clinician reporting a case of gonorrhoea and these data were linked to the N. gonorrhoeae strains. A total of 348 N. gonorrhoeae isolates, representing 89% of all Swedish cases diagnosed during the 12-month period, were tested for antibiotic susceptibility. Of all isolates, 24% were β-lactamase-producing, and 18% had decreased susceptibility to ciprofloxacin (MIC>0.064 mg/l). All isolates were fully susceptible to ceftriaxone and spectinomycin. More than 99% of the isolates were fully susceptible to azithromycin. The antibiotic susceptibility varied with the places where patients were exposed to infection. When exposed in Asia, 63% of the isolates showed reduced susceptibility to ciprofloxacin, compared with 0-8.5% of the isolates from patients exposed in other places (RR=8.5, P<0.001). Ciprofloxacin cannot be recommended as the first choice of treatment if the place of exposure was in Asia.
|
|
| 9. |
- Cirenajwis, Helena, et al.
(author)
-
Molecular stratification of metastatic melanoma using gene expression profiling: prediction of survival outcome and benefit from molecular targeted therapy.
- 2015
-
In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:14, s. 12297-12309
-
Journal article (peer-reviewed)abstract
- Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melanoma cohort and external cohorts to determine the prognostic and predictive significance of the gene expression phenotypes. We performed expression profiling on 214 cutaneous melanoma tumors and found an increased risk of developing distant metastases in the pigmentation (HR, 1.9; 95% CI, 1.05-3.28; P=0.03) and proliferative (HR, 2.8; 95% CI, 1.43-5.57; P=0.003) groups as compared to the high-immune response group. Further genetic characterization of melanomas using targeted deep-sequencing revealed similar mutational patterns across these phenotypes. We also used publicly available expression profiling data from melanoma patients treated with targeted or vaccine therapy in order to determine if our signatures predicted therapeutic response. In patients receiving targeted therapy, melanomas resistant to targeted therapy were enriched in the MITF-low proliferative subtype as compared to pre-treatment biopsies (P=0.02). In summary, the melanoma gene expression phenotypes are highly predictive of survival outcome and can further help to discriminate patients responding to targeted therapy.
|
|
| 10. |
- Fredlund, Elisabeth, et al.
(author)
-
Exploring the mode of action of Pichia anomala - a postharvest biocontrol yeast
- 2001
-
In: Yeast. - : John Wiley & Sons. - 0749-503X .- 1097-0061. ; 18, s. S212-S212
-
Journal article (other academic/artistic)abstract
- The ascomycetous yeast Pichia anomala J121, inhibits mould growth in malfunctioning airtight storage systems for moist animal feed grain. Extensive studies of P. anomala J121 have given detailed knowledge of growth physiology and limiting environmental factors, which is necessary to understand the inhibitory activity. Our main objective is to identify the mechanisms behind the inhibitory activity. We have two non-exclusive working hypothesis: I)P. anomala produces antifungal substances and II)P. anomala out-competes the mould for space, nutrients, and oxygen. We have found that volatile metabolites restrict radial growth and sporulation of moulds in mouth-to-mouth assays where agar plates are placed facing each other with the yeast inoculated on the upper plate and the mould on the lower. Previous studies of P. anomala have shown that it produces high quantities of ethyl acetate - a mould-inhibitory substance. We are working to identify homologous genes in P. anomala J121 to the acetyltransferase encoding genes ATF1 and ATF2 in Saccharomyces cerevisiae. Another approach has been to identify intra- and extracellular metabolites during aerobic and oxygen limited growth. Intracellular metabolites were identified by Magic Angle Spinning-High Resolution-Nuclear Magnetic Resonance (MAS-HR- NMR) that allows analysis of living cells. Extracellular metabolites were analysed with HPLC. Glycerol, well known for its role during osmotic stress, is accumulated in response to oxygen stress.
|
|
