| 1. |
- Adolfsson, Karl, et al.
(författare)
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Fluorescent Nanowire Heterostructures as a Versatile Tool for Biology Applications
- 2013
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 13:10, s. 4728-4732
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Tidskriftsartikel (refereegranskat)abstract
- Nanowires are increasingly used in biology, as sensors, as injection devices, and us model systems for toxicity studies. Currently, in situ visualization of nanowires in biological media is done using organic dyes, which a;:e prone to photobleaching, or using microscopy methods which either yield poor resolution or require a sophisticated setup. Here we show that inherently fluorescent nanowire axial heterostructnies c:an be used to localize and identify nanowires in cells and tissue; By synthesizing GaP GaInP nanowire heterostructures, with nonfluorescent GaP segments and fluorescent GaInP segments, we created a barcode labeling system enabling the distinction of the nanowire morphological and chemical properties using fluorescence microscopy. The GaInP photoluminescence stability, combined with the fact that the nanowires can be coated with different materials while retaining their fluorescence, make these nanowires promising tools for biological and nanotoxicological studies.
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| 2. |
- Adolfsson, Karl, et al.
(författare)
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Ingestion of gallium phosphide nanowires has no adverse effect on Drosophila tissue function.
- 2013
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Ingår i: Nanotechnology. - : IOP Publishing. - 0957-4484 .- 1361-6528. ; 24:28
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Tidskriftsartikel (refereegranskat)abstract
- Engineered nanoparticles have been under increasing scrutiny in recent years. High aspect ratio nanoparticles such as carbon nanotubes and nanowires have raised safety concerns due to their geometrical similarity to asbestos fibers. III-V epitaxial semiconductor nanowires are expected to be utilized in devices such as LEDs and solar cells and will thus be available to the public. In addition, clean-room staff fabricating and characterizing the nanowires are at risk of exposure, emphasizing the importance of investigating their possible toxicity. Here we investigated the effects of gallium phosphide nanowires on the fruit fly Drosophila melanogaster. Drosophila larvae and/or adults were exposed to gallium phosphide nanowires by ingestion with food. The toxicity and tissue interaction of the nanowires was evaluated by investigating tissue distribution, activation of immune response, genome-wide gene expression, life span, fecundity and somatic mutation rates. Our results show that gallium phosphide nanowires applied through the diet are not taken up into Drosophila tissues, do not elicit a measurable immune response or changes in genome-wide gene expression and do not significantly affect life span or somatic mutation rate.
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| 3. |
- Beech, Jason P., et al.
(författare)
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Cell morphology and deformability in deterministic lateral displacement devices
- 2011
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Ingår i: 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2011, MicroTAS 2011. - 9781618395955 ; 2, s. 1355-1357
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Konferensbidrag (refereegranskat)abstract
- Deterministic Lateral Displacement (DLD) devices have been used to separate particles based on size [1] and shape [2]. Here we show how DLD devices can also be used to separate particles based on their ability to deform under shear forces. Varying experimental conditions allows us to vary the relative contributions of size, morphology and deformability. The ability to distinguish between cells based on deformability with high resolution and throughput, in cheap and simple devices, could find highly interesting and relevant applications, for example in the detection of circulating tumor cells or malaria-infected blood cells.
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| 4. |
- Beech, Jason P., et al.
(författare)
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Sample preparation for single-cell whole chromosome analysis
- 2012
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Ingår i: Proceedings of the 16th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2012. - 9780979806452 ; , s. 998-999
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Konferensbidrag (refereegranskat)abstract
- In this work we present an integrated system for whole chromosome analysis of single bacterium. Using whole genome barcoding techniques, which offer direct and rapid microscopic visualization of the entire genome in one field-of-view, we aim to rapidly identify individual bacterium. We are developing our device to achieve the crucial, and difficult process of isolating a bacterium, removing the DNA in one piece and transferring it to a nano-channel for visualisation. In order to achieve control over the bacteria we encapsulate them in agarose, using flow focusing. The encapsulated bacteria can then be transported in microchannels to proximity with the nanochannels and then chemically lysis can be performed. Following lysis the intact genome can be extracted and transferred to the meandering nanochannel for analysis. We believe this device holds the potential to significantly decrease analysis times for single cell, whole genome analysis with the potential of opening up for automated, high-throughput genome analysis in microfluidic systems.
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| 5. |
- Beech, Jason, et al.
(författare)
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Sorting cells by size, shape and deformability
- 2012
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Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 12, s. 1048-1051
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Tidskriftsartikel (refereegranskat)abstract
- While size has been widely used as a parameter in cellular separations, in this communication we show how shape and deformability, a mainly untapped source of specificity in preparative and analytical microfluidic devices can be measured and used to separate cells. © 2012 The Royal Society of Chemistry.
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| 6. |
- Ceulemans, Shana, et al.
(författare)
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Evidence for the involvement of the glucocorticoid receptor gene in bipolar disorder in an isolated northern Swedish population
- 2011
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Ingår i: Bipolar Disorders. - Malden, USA : John Wiley & Sons. - 1398-5647 .- 1399-5618. ; 13:7-8, s. 614-623
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis is one of the most consistent findings in the pathophysiology of mood disorders. The potential role of genes related to HPA axis function has been investigated extensively in major depression. However, in bipolar disorder (BPD) such studies are scarce. We performed a systematic HapMap-based association study of six genes crucial for HPA axis function in relation to BPD. Methods: Haplotype tagging single nucleotide polymorphisms (htSNPs) were selected in order to identify all haplotypes with a frequency of more than 1% in the genes encoding the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), corticotrophin releasing hormone receptor 1 (CRH-R1) and 2 (CRH-R2), CRH binding protein (CRH-BP), and FK binding protein 5 (FKBP5). This resulted in a total selection of 225 SNPs that were genotyped and analyzed in 309 BPD patients and 364 matched control individuals all originating from an isolated northern Swedish population. Results: Consistent evidence for an association with BPD was found for NR3C1, the gene encoding GR. Almost all SNPs in two adjacent haplotype blocks contributed to the positive signal, comprised of significant single marker, sliding window, and haplotype-specific p-values. All these results point to a moderately frequent (10–15%) susceptibility haplotype covering the entire coding region and 3? untranslated region (UTR) of NR3C1. Conclusions: This study contributes to the growing evidence for a role of the glucocorticoid receptor gene (NR3C1) in vulnerability to mood disorders, and BPD in particular, and warrants further in vitro investigation of the at-risk haplotypes with respect to disease etiology. However, this association might be restricted to this specific population, as it is observed in a rather small sample from an isolated population without replication, and data from large meta-analyses for genome-wide association studies in BPD do not show the GR as a very strong candidate.
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| 7. |
- Karling, Pontus, et al.
(författare)
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The relationship between the val158met catechol-o-methyltransferase (COMT) polymorphism and irritable bowel syndrome.
- 2011
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Ingår i: PloS one. - : Public Library of Science. - 1932-6203. ; 6:3, s. e18035-
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Tidskriftsartikel (refereegranskat)abstract
- Background The catechol-O-methyltransferase (COMT) enzyme has a key function in the degradation of catecholamines and a functional polymorphism is val158met. The val/val genotype results in a three to fourfold higher enzymatic activity compared with the met/met genotype, with the val/met genotype exhibiting intermediate activity. Since pain syndromes as well as anxiety and depression are associated to low and high COMT activity respectively and these conditions are all associated with irritable bowel syndrome (IBS) we wanted for the first time to explore the relationship between the polymorphism and IBS. Methodology/Principal Findings 867 subjects (445 women) representative of the general population and 70 consecutively sampled patients with IBS (61 women) were genotyped for the val158met polymorphism and the IBS patients filled out the Hospital-Anxiety-and-Depression-Scale (HADS) questionnaire, and an IBS symptom diary. Results There was a significantly higher occurrence of the val/val genotype in patients compared with controls (30% vs 20%; Chi2 (1) 3.98; p = 0.046) and a trend toward a lower occurrence of the val/met genotype in IBS patients compared with controls (39% vs 49%; Chi2 (1) 2.89; p = 0.089). Within the IBS patients the val/val carriers exhibited significantly increased bowel frequency (2.6 vs 1.8 stools per day; Chi2 (1) 5.3; p = 0.03) and a smaller proportion of stools with incomplete defecation (41% vs 68%; Chi2 (1) 4.3; p = 0.04) compared with the rest (val/met+met/met carriers). The val/val carriers also showed a trend for a smaller proportion of hard stools (0% vs 15%; Chi2 (1) 3.2; p = 0.08) and a higher frequency of postprandial defecation (26% vs 21%; Chi2 (1) 3.0; p = 0.08). Conclusions/Significance In this study we found an association between the val/val genotype of the val158met COMT gene and IBS as well as to specific IBS related bowel pattern in IBS patients.
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| 8. |
- Khoschnau, Shwan
(författare)
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Soft Tissue Aspects of the Shoulder Joint
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to study different aspects of the soft tissues of the shoulder joint. The variation in the quality of the tendons and ligaments can be explained by genetic factors. To test the hypothesis that collagen 1 α1 Sp1 polymorphism is related to the occurrence of cruciate ligament ruptures and shoulder dislocations, a total of 358 patients (233 patients with cruciate ligament ruptures and 126 with shoulder dislocations) were included in the study. We found a decreased risk of these injuries associated with collagen type 1 α1 Sp1 polymorphism. To study the mechanical properties of a better type of fixation of soft tissue to bone, 10 skeletally mature New Zealand white rabbits were operated bilaterally on the knees. The medial collateral ligaments were fixed by two types of plates one with a flat undersurface and the other with a pegged undersurface. After 4 weeks the force at failure, stiffness and energy uptake was almost double in the knees operated with the pegged plates. The prevalence and dysfunction of rotator cuff tears was investigated in 106 subjects who had never sought for their shoulder complaints, using Constant score, ultrasound and plain x-ray. The prevalence of full-thickness cuff tears was 30% (21% of all shoulders). The Constant score was lower in subjects with full-thickness tears. Partial-thickness tears and acromioclavicular joint osteoarthritis had no impact on shoulder complaints or Constant score. The subacromial index was lower for shoulders with full-thickness tears. Forty-eight patients with median age 56 years underwent subacromial decompression with or without acromioclavicular joint resection, investigated with MRI pre- and 3 months postoperatively. The Constant score and subjective shoulder value were measured preoperatively and at 3 and 6 months after surgery and even 2 years for subjective shoulder value. Two raters investigated the MRI. The results showed poor inter-rater reliability for MRI. However, both Constant score and subjective shoulder value improved over time. MRI is not a reliable method to study the capsular reaction after subacromial decompression due to high subjectivity of the radiologists.
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| 9. |
- Maripuu, Martin, et al.
(författare)
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Relative Hypo-and Hypercortisolism Are Both Associated with Depression and Lower Quality of Life in Bipolar Disorder : A Cross-Sectional Study
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Depression in unipolar and bipolar disorders is associated with hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity. Also, unipolar disorder has recently been shown to exhibit HPA-axis hypoactivity. We studied for the first time how HPA-axis hypo-and hyperactivity relate to depression and disease burden in bipolar disorder. We were interested in studying hypocortisolism; characterized by increased HPA-axis negative feedback sensitivity and lower basal cortisol levels together with the opposite HPA-axis regulatory pattern of hypercortisolism. Methods: This cross-sectional study includes 145 type 1 and 2 bipolar outpatients and 145 matched controls. A dexamethasone-suppression-test (DST) measures the negative feedback sensitivity and a weight-adjusted very-low-dose DST was employed, which is sensitive in identifying hypocortisolism and hypercortisolism. The 25th and 75th percentiles of control post-DST values were used as cut-offs identifying patients exhibiting relative hypo-, and hypercortisolism. Self-report questionnaires were employed: Beck-Depression-Inventory (BDI), Montgomery-Asberg-Depression-Rating-Scale (MADRS-S), World-Health-Organization-Quality-of-Life-Assessment-100 and Global-Assessment-of-Functioning. Results: Patients exhibiting relative hypocortisolism expectedly exhibited lowered basal cortisol levels (p = 0.046). Patients exhibiting relative hypercortisolism expectedly exhibited elevated basal levels (p<0.001). Patients exhibiting relative hypocortisolism showed 1.9-2.0 (BDI, p = 0.017, MADRS-S, p = 0.37) and 6.0 (p<0.001) times increased frequencies of depression and low overall life quality compared with patients exhibiting mid post-DST values (eucortisolism). Adjusted Odds Ratios (OR:s) for depression ranged from 3.8-4.1 (BDI, p = 0.006, MADRS-S, p = 0.011) and was 23.4 (p<0.001) for life quality. Patients exhibiting relative hypercortisolism showed 1.9-2.4 (BDI, p = 0.017, MADRS-S, p = 0.003) and 4.7 (p<0.001) times higher frequencies of depression and low overall life quality compared with patients exhibiting eucortisolism. Adjusted OR: s for depression ranged from 2.2-2.7 (BDI, p = 0.068, MADRS-S, p = 0.045) and was 6.3 (p = 0.008) for life quality. Limitations: The cross-sectional design and lack of pre-established reference values of the DST employed. Conclusions: Relative hypocortisolism and relative hypercortisolism were associated with depression and lower life quality, providing novel insights into the detrimental role of stress in bipolar disorder.
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| 10. |
- Moens, Lotte N, et al.
(författare)
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PCM1 and schizophrenia : a replication study in the Northern Swedish population
- 2010
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Ingår i: American Journal of Medical Genetics. - : Wiley. - 0148-7299 .- 1096-8628. ; 153B:6, s. 1240-1243
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies implicated centrosomal dysfunction as a source of various neuropsychiatric disorders, including schizophrenia (SZ). Two recent reports [Gurling et al., 2006; Datta et al., 2008. Mol Psychiatry] described an association between polymorphisms in the PCM1 gene and SZ in a UK/Scottish population. In this study, we aimed to replicate these findings in a Northern Swedish association sample of 486 research subjects with SZ and 512 unrelated control individuals. We genotyped 12 previously described SNP markers and carried out haplotype analyses using the same multi-marker haplotypes previously reported. Though we could not replicate the association with SNPs rs445422 and rs208747, we did observe a significant protective association with intronic SNP rs13276297. Furthermore, we performed a meta-analysis comprising 1,794 SZ patients and 1,553 controls, which confirmed the previously reported association with rs445422 and rs208747. These data provide further evidence that PCM1-though certainly not a major risk factor in the Northern Swedish population-cannot be ruled out as a contributor to SZ risk and/or protection, and deserves further replication in larger populations to elucidate its role in disease etiology.
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