| 3181. |
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| 3182. |
- Strandberg, Kristin, et al.
(författare)
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Blood-derived biomarkers correlate with clinical progression in Duchenne muscular dystrophy
- 2020
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Ingår i: Journal of Neuromuscular Diseases. - : IOS Press. - 2214-3599 .- 2214-3602. ; 7:3, s. 231-246
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Tidskriftsartikel (refereegranskat)abstract
- Background: Duchenne Muscular Dystrophy is a severe, incurable disorder caused by mutations in the dystrophin gene. The disease is characterized by decreased muscle function, impaired muscle regeneration and increased inflammation. In a clinical context, muscle deterioration, is evaluated using physical tests and analysis of muscle biopsies, which fail to accurately monitor the disease progression. Objectives: This study aims to confirm and asses the value of blood protein biomarkers as disease progression markers using one of the largest longitudinal collection of samples. Methods: A total of 560 samples, both serum and plasma, collected at three clinical sites are analyzed using a suspension bead array platform to assess 118 proteins targeted by 250 antibodies in microliter amount of samples. Results: Nine proteins are confirmed as disease progression biomarkers in both plasma and serum. Abundance of these biomarkers decreases as the disease progresses but follows different trajectories. While carbonic anhydrase 3, microtubule associated protein 4 and collagen type I alpha 1 chain decline rather constantly over time, myosin light chain 3, electron transfer flavoprotein A, troponin T, malate dehydrogenase 2, lactate dehydrogenase B and nestin plateaus in early teens. Electron transfer flavoprotein A, correlates with the outcome of 6-minutes-walking-test whereas malate dehydrogenase 2 together with myosin light chain 3, carbonic anhydrase 3 and nestin correlate with respiratory capacity. Conclusions: Nine biomarkers have been identified that correlate with disease milestones, functional tests and respiratory capacity. Together these biomarkers recapitulate different stages of the disorder that, if validated can improve disease progression monitoring.
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| 3183. |
- Strazhesko, Irina, et al.
(författare)
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Association of Insulin Resistance, Arterial Stiffness and Telomere Length in Adults Free of Cardiovascular Diseases.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammation and oxidative stress might be considered the key mechanisms of aging. Insulin resistance (IR) is a phenomenon related to inflammatory and oxidative stress. We tested the hypothesis that IR may be associated with cellular senescence, as measured by leukocyte telomere length (LTL), and arterial stiffness (core feature of arterial aging), as measured by carotid-femoral pulse wave velocity (c-f PWV).
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| 3184. |
- Street, Nathaniel Robert, et al.
(författare)
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The genetics and genomics of the drought response in Populus
- 2006
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Ingår i: The Plant Journal. - 0960-7412 .- 1365-313X. ; 48:3, s. 321-341
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Tidskriftsartikel (refereegranskat)abstract
- The genetic nature of tree adaptation to drought stress was examined by utilizing variation in the drought response of a full-sib second generation (F-2) mapping population from a cross between Populus trichocarpa (93-968) and P. deltoides Bart (ILL-129) and known to be highly divergent for a vast range of phenotypic traits. We combined phenotyping, quantitative trait loci (QTL) analysis and microarray experiments to demonstrate that 'genetical genomics' can be used to provide information on adaptation at the species level. The grandparents and F-2 population were subjected to soil drying, and contrasting responses to drought across genotypes, including leaf coloration, expansion and abscission, were observed, and QTL for these traits mapped. A subset of extreme genotypes exhibiting extreme sensitivity and insensitivity to drought on the basis of leaf abscission were defined, and microarray experiments conducted on these genotypes and the grandparent species. The extreme genotype groups induced a different set of genes: 215 and 125 genes differed in their expression response between groups in control and drought, respectively, suggesting species adaptation at the gene expression level. Co-location of differentially expressed genes with drought-specific and drought-responsive QTLs was examined, and these may represent candidate genes contributing to the variation in drought response.
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| 3185. |
- Stromberg, Sara, et al.
(författare)
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Transcriptional profiling of melanocytes from patients with vitiligo vulgaris
- 2008
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Ingår i: Pigment Cell & Melanoma Research. - 1755-1471. ; 21:2, s. 162-171
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Tidskriftsartikel (refereegranskat)abstract
- Vitiligo is a complex, polygenic disorder characterized by patchy loss of skin pigmentation due to abnormal melanocyte function. Both genetic and environmental etiological factors have been proposed for vitiligo and lack of molecular markers renders difficulties to predict development and progression of the disease. Identification of dysregulated genes has the potential to unravel biological pathways involved in vitiligo pathogenesis, facilitating discovery of potential biomarkers and novel therapeutic approaches. In this study, we characterized the transcriptional profile of melanocytes from vitiligo patients. Oligonucleotide microarrays containing similar to 16 000 unique genes were used to analyse mRNA expression in melanocytes from vitiligo patients and age-matched healthy controls. In total, 859 genes were identified as differentially expressed. A substantial number of these genes were involved in (i) melanocyte development, (ii) intracellular processing and trafficking of tyrosinase gene family proteins, (iii) packing and transportation of melanosomes, (iv) cell adhesion and (v) antigen processing and presentation. In conclusion, our results show a significantly different transcription profile in melanocytes from vitiligo patients compared with controls. Several genes of potential importance for the pathogenesis and development of vitiligo were identified. Our data indicate that autoimmunity involving melanocytes may be a secondary event in vitiligo patients caused by abnormal melanocyte function.
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| 3186. |
- Strömberg, Mattias, et al.
(författare)
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A magnetic nanobead-based bioassay provides sensitive detection of single- and biplex bacterial DNA using a portable AC susceptometer
- 2014
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Ingår i: Biotechnology Journal. - : Wiley. - 1860-6768 .- 1860-7314. ; 9:1, s. 137-145
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Tidskriftsartikel (refereegranskat)abstract
- Bioassays relying on magnetic read-out using probe-tagged magnetic nanobeads are potential platforms for low-cost biodiagnostic devices for pathogen detection. For optimal assay performance it is crucial to apply an easy, efficient and robust bead-probe conjugation protocol. In this paper, sensitive (1.5 pM) singleplex detection of bacterial DNA sequences is demonstrated in a portable AC susceptometer by a magnetic nanobead-based bioassay principle; the volume-amplified magnetic nanobead detection assay (VAM-NDA). Two bead sizes, 100 and 250 nm, are investigated along with a highly efficient, rapid, robust, and stable conjugation chemistry relying on the avidin-biotin interaction for bead-probe attachment. Avidin-biotin conjugation gives easy control of the number of detection probes per bead; thus allowing for systematic investigation of the impact of varying the detection probe surface coverage upon bead immobilization in rolling circle amplified DNA-coils. The existence of an optimal surface coverage is discussed. Biplex VAM-NDA detection is for the first time demonstrated in the susceptometer: Semi-quantitative results are obtained and it is concluded that the concentration of DNA-coils in the incubation volume is of crucial importance for target quantification. The present findings bring the development of commercial biodiagnostic devices relying on the VAM-NDA further towards implementation in point-of-care and outpatient settings.
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| 3187. |
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| 3188. |
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| 3189. |
- Strömberg, Mattias, et al.
(författare)
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Immobilization of oligonucleotide-functionalized magnetic nanobeads in DNA-coils studied by electron microscopy and atomic force microscopy
- 2011
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Ingår i: MRS Online Proceedings Library. - : Springer Science and Business Media LLC.
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Konferensbidrag (refereegranskat)abstract
- Immobilization of oligonucleotide-functionalized magnetic nanobeads by hybridization in DNA-coils formed by rolling circle amplification has been investigated using transmission electron microscopy (TEM) and atomic force microscopy (AFM). The TEM results supported earlier made observations that small beads with low oligonucleotide surface coverage preferably immobilize in the interior of the DNA-coils and do not tend to link several DNA-coils together whereas large beads with high surface coverage to a larger extent connect several DNA-coils together to clusters of several DNA-coils with beads. AFM provided direct visualization of the DNA-coils as thread-like objects. DNA-coils with immobilized beads appeared as a collection of beads with thread-like features in their near vicinity.
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| 3190. |
- Strömberg, Mattias, et al.
(författare)
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Interbead interactions within oligonucleotide functionalized ferrofluids suitable for magnetic biosensor applications
- 2007
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Ingår i: Journal of Physics D. - : IOP Publishing. - 0022-3727 .- 1361-6463. ; 40:5, s. 1320-1330
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Tidskriftsartikel (refereegranskat)abstract
- Interactions in oligonucleotide functionalized ferrofluids were investigated by measurements of frequency dependent complex magnetization in a superconducting quantum interference device. The ferrofluids consisted of aqueous suspensions of single-stranded oligonucleotide functionalized 130 nm sized magnetic beads, suitable for further use in magnetic biosensor applications based on changes in the Brownian relaxation behaviour of oligonucleotide-coated beads. The interbead interactions were found to depend strongly on the surface coverage by oligonucleotide molecules. At low surface coverage, aggregates of beads within the ferrofluid were formed, most likely due to interbead SS-crosslinking reactions. When the surface coverage increased, the entropic interbead repulsion arising from the thermal motion of oligonucleotide molecules began to stabilize the ferrofluid by preventing aggregation, and the crosslinking probability decreased. At a surface coverage, of ~40 oligonucleotides per bead, determined by a radioactive labelling analysis, an optimal configuration was obtained for which the ferrofluid behaved as consisting of almost non-interacting beads. At higher oligonucleotide functionalization degrees, the high coverage induced less thermal motion flexibility of the oligonucleotide chains which decreased the entropic repulsion effect. This in turn led to a higher crosslinking probability, as well as an increase in the hydrodynamic size of the beads. Thus, the ferrofluid sample of nearly non-interacting nature, in which an optimal degree of stabilization and the highest Brownian relaxation frequency are achieved in the low surface coverage region, may be considered as the most appropriate one for further use in magnetic biosensor applications, from both a functional and an economic point of view.
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