| 1. |
- Hansson, Lars-Olof, et al.
(author)
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Comparison between Chicken and Rabbit Antibody Based Particle Enhanced Cystatin C Reagents for Immunoturbidimetry
- 2008
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In: Journal of immunoassay & immunochemistry. - : Informa UK Limited. - 1532-1819 .- 1532-4230. ; 29:1, s. 1-9
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Journal article (peer-reviewed)abstract
- We have compared three commercial particle enhanced cystatin C reagents. One of the reagents utilizes chicken antibodies and the other two reagents are rabbit antibody based. We show that the chicken antibody based reagent yields a higher delta absorbance when reacting with the antigen. IgY coupled to latex particles show a strong scatter response even at high antigen concentrations in contrast to the steep decline in scatter previously reported for IgY antibodies in solution. The reagent also showed a low CV for duplicate samples. Laying hens thus seems as an interesting source of antibodies for particle-enhanced immunoassays.
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| 2. |
- Johansson, Håkan, 1972-, et al.
(author)
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Characterization of Campylobacter spp. isolated from wild birds in the Antarctic and Sub-Antarctic
- 2018
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:11
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Journal article (peer-reviewed)abstract
- A lack of knowledge of naturally occurring pathogens is limiting our ability to use the Antarctic to study the impact human-mediated introduction of infectious microorganisms have on this relatively uncontaminated environment. As no large-scale coordinated effort to remedy this lack of knowledge has taken place, we rely on smaller targeted efforts to both study present microorganisms and monitor the environment for introductions. In one such effort, we isolated Campylobacter species from fecal samples collected from wild birds in the Antarctic Peninsula and the sub-Antarctic island of South Georgia. Indeed, in South Georgia, we found Campylobacter lari and the closely related Campylobacter peloridis, but also distantly related human-associated multilocus sequence types of Campylobacter jejuni. In contrast, in the Antarctic Peninsula, we found C. tart and two closely related species, Campylobacter subantarcticus and Campylobacter volucris, but no signs of human introduction. In fact, our finding of human-associated sequence types of C. jejuni in South Georgia, but not in the Antarctic Peninsula, suggests that efforts to limit the spread of infectious microorganisms to the Antarctic have so far been successful in preventing the introduction of C. jejuni. However, we do not know how it came to South Georgia and whether the same mode of introduction could spread it from there to the Antarctic Peninsula.
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| 3. |
- Prokopenko, Inga, et al.
(author)
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A Central Role for GRB10 in Regulation of Islet Function in Man.
- 2014
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In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 10:4
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Journal article (peer-reviewed)abstract
- Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reduced insulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction of glucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation and possibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data also emphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father.
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| 4. |
- Reed, Evan, et al.
(author)
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Presence of autoantibodies in "seronegative" rheumatoid arthritis associates with classical risk factors and high disease activity
- 2020
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In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362. ; 22:1
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Journal article (peer-reviewed)abstract
- BackgroundRheumatoid arthritis (RA) is classified as seropositive or seronegative, depending on the presence/absence of rheumatoid factor (RF), primarily IgM RF, and/or anti-citrullinated protein antibodies (ACPA), commonly detected using anti-cyclic citrullinated peptide (CCP) assays. Known risk factors associate with the more severe seropositive form of RA; less is known about seronegative RA. Here, we examine risk factors and clinical phenotypes in relation to presence of autoantibodies in the RA subset that is traditionally defined as seronegative.MethodsAnti-CCP2 IgG, 19 ACPA fine-specificities, IgM/IgG/IgA RF, anti-carbamylated-protein (CarP) antibodies, and 17 other autoantibodies, were analysed in 2755 RA patients and 370 controls. Antibody prevalence, levels, and co-occurrence were examined, and associations with risk factors and disease activity during 5 years were investigated for different antibody-defined RA subsets.ResultsAutoantibodies were detected in a substantial proportion of the traditionally defined seronegative RA subset, with ACPA fine-specificities found in 30%, IgA/IgG RF in 9.4%, and anti-CarP antibodies in 16%, with a 9.6% co-occurrence of at least two types of RA-associated autoantibodies. HLA-DRB1 shared epitope (SE) associated with the presence of ACPA in anti-CCP2-negative RA; in anti-CCP2-positive RA, the SE association was defined by six ACPA fine-specificities with high co-occurrence. Smoking associated with RF, but not with ACPA, in anti-CCP2-negative RA. Presence of ACPA and RF, but not anti-CarP antibodies, in conventionally defined “seronegative” RA, associated with worse clinical outcome.Conclusions“Seronegative” RA is not truly a seronegative disease subset. Additional screening for ACPA fine-specificities and IgA/IgG RF defines a group of patients that resembles seropositive patients with respect to risk factors and clinical picture and may contribute to earlier diagnosis for a subset of anti-CCP2−/IgM RF− patients with a high need for active treatment.
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| 5. |
- Sherwood, Victoria, et al.
(author)
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WNT5A-mediated β-catenin-independent signalling is a novel regulator of cancer cell metabolism.
- 2014
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In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 35:4, s. 784-794
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Journal article (peer-reviewed)abstract
- WNT5A has been identified as an important ligand in the malignant progression of a number of tumours. Although WNT5A signalling is often altered in cancer, the ligand's role as either a tumour suppressor or oncogene varies between tumour types and is a contemporary issue for investigators of β-catenin-independent WNT signalling in oncology. Here, we report that one of the initial effects of active WNT5A signalling in malignant melanoma cells is an alteration in cellular energy metabolism and specifically an increase in aerobic glycolysis. This was found to be at least in part due to an increase in active Akt signalling and lactate dehydrogenase (LDH) activity. The clinical relevance of these findings was strengthened by a strong correlation (P < 0.001) between the expression of WNT5A and LDH isoform V in a cohort of melanocytic neoplasms. We also found effects of WNT5A on energy metabolism in breast cancer cells, but rather than promoting aerobic glycolysis as it does in melanoma, WNT5A signalling increased oxidative phosphorylation rates in breast cancer cells. These findings support a new role for WNT5A in the metabolic reprogramming of cancer cells that is a context- dependent event.
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| 6. |
- Ablikim, M., et al.
(author)
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Probing CP symmetry and weak phases with entangled double-strange baryons
- 2022
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In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 606:7912, s. 64-69
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Journal article (peer-reviewed)abstract
- Though immensely successful, the standard model of particle physics does not offer any explanation as to why our Universe contains so much more matter than antimatter. A key to a dynamically generated matter-antimatter asymmetry is the existence of processes that violate the combined charge conjugation and parity (CP) symmetry(1). As such, precision tests of CP symmetry may be used to search for physics beyond the standard model. However, hadrons decay through an interplay of strong and weak processes, quantified in terms of relative phases between the amplitudes. Although previous experiments constructed CP observables that depend on both strong and weak phases, we present an approach where sequential two-body decays of entangled multi-strange baryon-antibaryon pairs provide a separation between these phases. Our method, exploiting spin entanglement between the double-strange baryon and its antiparticle(2) (+), has enabled a direct determination of the weak-phase difference, (xi(P) - xi(S)) = (1.2 +/- 3.4 +/- 0.8) x 10(-2) rad. Furthermore, three independent CP observables can be constructed from our measured parameters. The precision in the estimated parameters for a given data sample size is several orders of magnitude greater than achieved with previous methods(3). Finally, we provide an independent measurement of the recently debated Lambda decay parameter alpha(Lambda) (refs. (4,5)). The Lambda(Lambda) over bar asymmetry is in agreement with and compatible in precision to the most precise previous measurement(4).
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| 7. |
- Ahlén Bergman, Emma, et al.
(author)
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Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients
- 2018
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In: Clinical Epigenetics. - : BMC. - 1868-7083 .- 1868-7075. ; 10
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Journal article (peer-reviewed)abstract
- BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.
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| 8. |
- Andersson, Stefan S., et al.
(author)
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Mineral paragenesis and sulphide trace element distribution in the metamorphosed Lovisa Zn-Pb deposit, Bergslagen (Sweden), as revealed by 3D X-ray tomography, ore petrography and LA-ICP-MS analysis
- 2022
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In: Ore Geology Reviews. - : Elsevier BV. - 0169-1368 .- 1872-7360. ; 140
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Journal article (peer-reviewed)abstract
- This study encompasses the ore mineralogy, textures and sulphide trace element chemistry of the Palaeoproterozoic Lovisa stratiform Zn-Pb deposit and the stratigraphically underlying Lovisa Fe Formation in the Bergslagen ore province (Sweden). We investigate the relative timing of formation and subsequent modifications of its ores in relation to the c. 1.87-1.80 Ga Svecokarelian orogeny. The Lovisa Zn-Pb deposit consists of several different ore types. The massive sphalerite-galena ore is distinctly deformed, exhibiting a multiple-scale "ball ore" texture with rounded silicate clasts within a deformed, fine-grained sulphide matrix. Underlying the massive ore is a locally folded, sphalerite-rich laminated ore, interpreted to represent a metamorphosed relict primary lamination. Several generations of sphalerite-galena fracture fillings and veins occur adjacent to the main ore zones and they cross-cut early ductile structures and metamorphic features. The trace element signatures of the sphalerite-galena infillings generally mimic those of the two main ore zones, thus supporting an origin by localised remobilisation of the primary sulphide ore and demonstrating limited trace element redistribution during this process. In contrast, discrete sulphosalt-rich fracture fillings cross-cutting earlier galena-chalcopyriterich fracture fillings and veinlets in the Lovisa Fe Formation suggest a significant but still relatively localised redistribution of metals. Trace element mapping of sulphides from the Lovisa Zn-Pb deposit reveals that inclusion-free overgrowths on pyrite crystals are locally Co-enriched compared to the cores, which resulted from the redistribution of Co during late metamorphic processes. Combined textural and geochemical evidence suggest that the originally syngenetic exhalative sulphide ore at Lovisa was locally strongly affected by polyphase deformation and remobilisation. This was initiated during the first stage of amphibolite facies grade regional metamorphism and deformation (D1, c. 1.87-1.85 Ga) but is mostly evident from the later stages (D2) and the evolution to retrograde and brittle conditions (c. 1.83-1.80 Ga and later).
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| 10. |
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