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- 2019
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Dahlqvist, Johanna, 1979-, et al.
(författare)
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Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
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Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Tidskriftsartikel (refereegranskat)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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| 6. |
- Ekman, Diana, et al.
(författare)
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Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:9, s. 3213-3218
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. Methods: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. Results: rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. Conclusions: Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
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| 9. |
- Khatri, B., et al.
(författare)
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Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
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| 10. |
- Larsson, Anders, et al.
(författare)
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Reference values for clinical chemistry tests during normal pregnancy
- 2008
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Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 115:7, s. 874-881
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Reference values are usually defined based on blood samples from healthy men or nonpregnant women. This is not optimal as many biological markers changes during pregnancy and adequate reference values are of importance for correct clinical decisions. There are only few studies on the variations of laboratory tests during normal pregnancies, especially during the first two trimesters. It is thus a need to establish such reference values. DESIGN: Longitudinal study of laboratory markers in normal pregnancies. SETTING: Uppsala University Hospital, Sweden. POPULATION: Healthy pregnant females. METHODS: We have studied 25 frequently used laboratory tests during 52 normal pregnancies. Each woman was sampled up to nine times and the samples were divided according to collection time into the following groups: gestational week 7-17; week 17-24; week 24- 28; week 28-31; week 31-34; week 34-38; predelivery (0-2 weeks before delivery) and postpartum (> 6 weeks after delivery). The 2.5 and 97.5 percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values. RESULTS: Reference intervals are reported for plasma alanine aminotransferase, albumin, alkaline phosphatase, pancreas amylase, apolipoprotein A1, apolipoprotein B, aspartate aminotransferase, bilirubin, calcium, chloride, creatinine, cystatin C, ferritin, gamma-glutamyltransferase, iron, lactate dehydrogenase, magnesium, phosphate, potassium, sodium, transferrin, triglycerides, thyroid-stimulating hormone, urate and urea during these pregnancy periods. CONCLUSIONS: Most of the analytes change during normal pregnancy. It is thus of importance to use special reference values during pregnancy.
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| 11. |
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| 12. |
- Lundtoft, Christian, et al.
(författare)
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The HLA region in ANCA-associated vasculitis : characterisation of genetic associations in a Scandinavian patient population
- 2024
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Ingår i: RMD Open. - : BMJ PUBLISHING GROUP. - 2056-5933. ; 10:2, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are inflammatory disorders with ANCA autoantibodies recognising either proteinase 3 (PR3-AAV) or myeloperoxidase (MPO-AAV). PR3-AAV and MPO-AAV have been associated with distinct loci in the human leucocyte antigen (HLA) region. While the association between MPO-AAV and HLA has been well characterised in East Asian populations where MPO-AAV is more common, studies in populations of European descent are limited. The aim of this study was to thoroughly characterise associations to the HLA region in Scandinavian patients with PR3-AAV as well as MPO-AAV.METHODS: Genotypes of single-nucleotide polymorphisms (SNPs) located in the HLA region were extracted from a targeted exome-sequencing dataset comprising Scandinavian AAV cases and controls. Classical HLA alleles were called using xHLA. After quality control, association analyses were performed of a joint SNP/classical HLA allele dataset for cases with PR3-AAV (n=411) and MPO-AAV (n=162) versus controls (n=1595). Disease-associated genetic variants were analysed for association with organ involvement, age at diagnosis and relapse, respectively.RESULTS: PR3-AAV was significantly associated with both HLA-DPB1*04:01 and rs1042335 at the HLA-DPB1 locus, also after stepwise conditional analysis. MPO-AAV was significantly associated with HLA-DRB1*04:04. Neither carriage of HLA-DPB1*04:01 alleles in PR3-AAV nor of HLA-DRB1*04:04 alleles in MPO-AAV were associated with organ involvement, age at diagnosis or relapse. CONCLUSIONS: The association to the HLA region was distinct in Scandinavian cases with MPO-AAV compared with cases of East Asian descent. In PR3-AAV, the two separate signals of association to the HLD-DPB1 region mediate potentially different functional effects.
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| 13. |
- Thorlacius, Guðný Ella, et al.
(författare)
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Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome
- 2021
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 60:2, s. 837-848
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesClinical presentation of primary Sjögren’s syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints.MethodsWe performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls.ResultsWe found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10−62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS.ConclusionTwo subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.
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| 17. |
- Blumenstock, T., et al.
(författare)
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Characterization and potential for reducing optical resonances in Fourier transform infrared spectrometers of the Network for the Detection of Atmospheric Composition Change (NDACC)
- 2021
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 14:2, s. 1239-1252
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Tidskriftsartikel (refereegranskat)abstract
- Although optical components in Fourier transform infrared (FTIR) spectrometers are preferably wedged, in practice, infrared spectra typically suffer from the effects of optical resonances ("channeling") affecting the retrieval of weakly absorbing gases. This study investigates the level of channeling of each FTIR spectrometer within the Network for the Detection of Atmospheric Composition Change (NDACC). Dedicated spectra were recorded by more than 20 NDACC FTIR spectrometers using a laboratory mid-infrared source and two detectors. In the indium antimonide (InSb) detector domain (1900-5000 cm-1), we found that the amplitude of the most pronounced channeling frequency amounts to 0.1 ‰ to 2.0 ‰ of the spectral background level, with a mean of (0:68±0:48) ‰ and a median of 0.60 ‰. In the mercury cadmium telluride (HgCdTe) detector domain (700-1300 cm-1), we find even stronger effects, with the largest amplitude ranging from 0.3 ‰ to 21 ‰ with a mean of (2:45±4:50) ‰ and a median of 1.2 ‰. For both detectors, the leading channeling frequencies are 0.9 and 0.11 or 0.23 cm-1 in most spectrometers. The observed spectral frequencies of 0.11 and 0.23 cm-1 correspond to the optical thickness of the beam splitter substrate. The 0.9 cm-1 channeling is caused by the air gap in between the beam splitter and compensator plate. Since the air gap is a significant source of channeling and the corresponding amplitude differs strongly between spectrometers, we propose new beam splitters with the wedge of the air gap increased to at least 0.8. We tested the insertion of spacers in a beam splitter's air gap to demonstrate that increasing the wedge of the air gap decreases the 0.9 cm-1 channeling amplitude significantly. A wedge of the air gap of 0.8 reduces the channeling amplitude by about 50 %, while a wedge of about 2 removes the 0.9 cm-1 channeling completely. This study shows the potential for reducing channeling in the FTIR spectrometers operated by the NDACC, thereby increasing the quality of recorded spectra across the network.
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| 19. |
- Boswell, M. T., et al.
(författare)
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Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS
- 2022
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Ingår i: Virus Evolution. - : Oxford University Press (OUP). - 2057-1577. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors – synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.
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| 20. |
- Cenit, MC, et al.
(författare)
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Influence of the IL6 gene in susceptibility to systemic sclerosis
- 2012
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 39:12, s. 2294-2302
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Tidskriftsartikel (refereegranskat)abstract
- Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotype expression of SSc.Methods.We performed a large metaanalysis including a total of 2749 cases and 3189 controls from 6 white populations (Germany, The Netherlands, Norway, Spain, Sweden, and United Kingdom). Three IL6 single-nucleotide polymorphisms (SNP; rs2069827, rs1800795, and rs2069840) were selected by SNP tagging and genotyped using TaqMan® allele discrimination technology.Results.Individual SNP metaanalysis showed no evidence of association of the 3 IL6 genetic variants with the global disease. Phenotype analyses revealed a significant association between the minor allele of rs2069840 and the limited cutaneous SSc clinical form (Bonferroni p = 0.036, OR 1.14, 95% CI 1.04–1.25). A trend of association between the minor allele of the rs1800795 and the diffuse cutaneous SSc clinical form was also evident (Bonferroni p = 0.072, OR 0.86, 95% CI 0.77–0.96). In the IL6 allelic combination analyses, the GGC allelic combination rs2069827-rs1800795-rs2069840 showed an association with overall SSc (Bonferroni p = 0.016, OR 1.13, 95% CI 1.04–1.23).Conclusion.Our results suggest that the IL6 gene may influence the development of SSc and its progression.
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| 25. |
- Edlund, T, et al.
(författare)
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Isolation of cDNA sequences coding for a part of human tissue plasminogen activator.
- 1983
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 80:2, s. 349-52
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Tidskriftsartikel (refereegranskat)abstract
- We have isolated a cDNA sequence coding for a part of human tissue plasminogen activator. mRNA coding for tissue plasminogen activator was partially purified, copied into double-stranded cDNA, and cloned into Escherichia coli. Two sets of partially overlapping oligodeoxynucleotide mixtures corresponding to all possible coding sequences for a known portion of the tissue plasminogen activator gene were prepared. One set was used as a probe to screen cDNA containing bacterial clones and both were used as probes in hybridization against purified plasmid DNA. Of 4,200 bacterial clones examined, 1 carried a plasmid that hybridized to both sets of oligonucleotides. This plasmid contained a 370-base-pair cDNA insert, which was shown by nucleotide sequence analysis to code for the cleavage site region in the one-chain form of the human tissue plasminogen activator.
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| 30. |
- Foka, Anna, 1981-, et al.
(författare)
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A Digital Periegesis : Implementing Spatial Research Infrastructures for Classical History and Archaeology
- 2023
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Ingår i: Digital Spatial Infrastructures and Worldviews in Pre-Modern Societies. - Leeds : ARC Humanities Press. - 9781641894692 - 9781802700794 ; , s. 205-223
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Bokkapitel (refereegranskat)abstract
- The classics have in many ways pioneered the application of digital methods to narrative spatial analysis and developed strong collaborative engagement with infrastructure, producing Pelagios, an ever-growing platform for a plethora of spatial databases and gazetteers, as well as Recogito a digital annotation tool. These two successful examples show a pressing need for community building around SRIs for early modern and medieval Scandinavia to ensure sustainable design, long-term preservation, and further collaborative development. This article discusses this development in the context of the digital periegesis project and the resources used for Pausanias's description of Greece
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| 31. |
- Foka, Anna, 1981-, et al.
(författare)
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Heritage metadata : a digital periegesis
- 2022
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Ingår i: Information and knowledge organisation in digital humanities. - Abingdon : Routledge. - 9780367675516 - 9780367675684 - 9781003131816 ; , s. 227-242
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Bokkapitel (refereegranskat)abstract
- Over the past decades the extraordinary growth of new technologies has made it possible to extract data from literary texts and analyse them using digital tools. This chapter focuses on the process of creating an enriched digital edition of Pausanias's Periegesis Hellados or Description of Greece. The purpose of this research is twofold: to identify 'heritage data' in Pausanias and to describe the technical and epistemological parameters of their aggregation and organisation. In answering the essentially digital humanities research question "how Pausanias's literary heritage information can be best organised and connected to the archaeological record on the ground", the Digital Periegesis project is charting and analysing the relevant digital tools and methods by which extensive semantic annotation and Linked Open Data (LOD) can facilitate the organisation of heritage information in Pausanias's text and its connection to actual archaeological finds. This chapter discusses the potential application of Geographic Information Science (GISc) and Geographic Information System (GIS) for such complex pre-cartesian narrative analysis. Finally, it emphasises the importance of building geo-spatially enriched digital editions collaboratively, involving discipline specialist researchers and information organisation experts, with the aim of interpreting histories of "place".
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| 32. |
- Foka, Anna, 1981-, et al.
(författare)
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Heritage Metadata : A Digital Periegesis
- 2021
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Ingår i: Information and Knowledge Organisation in Digital Humanities. - London and New York : Routledge. - 9781003131816 ; , s. 227-242
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Bokkapitel (refereegranskat)abstract
- Over the past decades the extraordinary growth of new technologies has made it possible to extract data from literary texts and analyse them using digital tools. This chapter focuses on the process of creating an enriched digital edition of Pausanias's Periegesis Hellados or Description of Greece. The purpose of this research is twofold: to identify ‘heritage data’ in Pausanias and to describe the technical and epistemological parameters of their aggregation and organisation. In answering the essentially digital humanities research question “how Pausanias's literary heritage information can be best organised and connected to the archaeological record on the ground”, the Digital Periegesis project is charting and analysing the relevant digital tools and methods by which extensive semantic annotation and Linked Open Data (LOD) can facilitate the organisation of heritage information in Pausanias's text and its connection to actual archaeological finds. This chapter discusses the potential application of Geographic Information Science (GISc) and Geographic Information System (GIS) for such complex pre-cartesian narrative analysis. Finally, it emphasises the importance of building geo-spatially enriched digital editions collaboratively, involving discipline specialist researchers and information organisation experts, with the aim of interpreting histories of “place”.
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| 33. |
- Foka, Anna, 1981-, et al.
(författare)
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Visualizing Pausanias’s Description of Greece with contemporary GIS
- 2022
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Ingår i: Digital Scholarship in the Humanities. - : Oxford University Press. - 2055-7671 .- 2055-768X. ; 37:3, s. 716-724
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Tidskriftsartikel (refereegranskat)abstract
- This progress article focuses on an overview of the potential and challenges of using contemporary Geographic Information System (GIS) applications for the visual rendering and analysis of textual spatial data. The case study is an ancient traveling narrative, Pausanias’s Description of Greece (Periegesis Hellados) which was written in the second century CE. First, we describe the process of converting the volumes to spatial data using a customized version of the open-source digital semantic annotation platform Recogito. Then the focus shifts to the implementation of collected and organized spatial data to a number of GIS applications: namely Google Maps, DARIAH Geo-Browser, Gephi, Palladio and ArcGIS. Through empirical experimentation with spatial data and their implementation in different platforms, our paper charts the ways in which contemporary GIS applications may be implemented to cast new light on ancient understandings of identity, space, and place.
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| 34. |
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| 35. |
- Franzen, Oscar, et al.
(författare)
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Draft genome sequencing of Giardia intestinalis assemblage B isolate GS : is human giardiasis caused by two different species?
- 2009
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 5:8, s. e1000560-
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Tidskriftsartikel (refereegranskat)abstract
- Giardia intestinalis is a major cause of diarrheal disease worldwide and two major Giardia genotypes, assemblages A and B, infect humans. The genome of assemblage A parasite WB was recently sequenced, and the structurally compact 11.7 Mbp genome contains simplified basic cellular machineries and metabolism. We here performed 454 sequencing to 16 x coverage of the assemblage B isolate GS, the only Giardia isolate successfully used to experimentally infect animals and humans. The two genomes show 77% nucleotide and 78% amino-acid identity in protein coding regions. Comparative analysis identified 28 unique GS and 3 unique WB protein coding genes, and the variable surface protein (VSP) repertoires of the two isolates are completely different. The promoters of several enzymes involved in the synthesis of the cyst-wall lack binding sites for encystation-specific transcription factors in GS. Several synteny-breaks were detected and verified. The tetraploid GS genome shows higher levels of overall allelic sequence polymorphism (0.5 versus <0.01% in WB). The genomic differences between WB and GS may explain some of the observed biological and clinical differences between the two isolates, and it suggests that assemblage A and B Giardia can be two different species.
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| 36. |
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| 37. |
- Goroshchuk, O, et al.
(författare)
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Polo-like kinases and acute leukemia
- 2019
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 38:1, s. 1-16
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Tidskriftsartikel (refereegranskat)
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| 38. |
- Goroshchuk, O, et al.
(författare)
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Targeting Plk1 with siRNNs in primary cells from pediatric B-cell acute lymphoblastic leukemia patients
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 2688-
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Tidskriftsartikel (refereegranskat)abstract
- B-cell acute lymphoblastic leukemia (B-ALL) accounts for nearly one fifth of all childhood cancers and current challenges in B-ALL treatment include resistance, relapse and late-onset side effects due to the chemotherapy. To overcome these hurdles, novel therapies need to be investigated. One promising target is Polo-like kinase 1 (Plk1), a key regulator of the cell cycle. In this study, the Plk family expression is investigated in primary peripheral blood and bone marrow mononuclear cells from ten pediatric B-ALL patients. For the first time, short interfering RiboNucleic Neutrals (siRNNs) that enter cells without a transfection reagent are used to target Plk1 mRNA in primary cells from pediatric B-ALL patients. Our results show that the expression of Plk1 and Plk4 is significantly higher in pediatric B-ALL patients compared to healthy donors. Moreover, treatment of primary peripheral blood and bone marrow mononuclear cells from pediatric B-ALL patients, cultured ex vivo, with Plk1-targeting siRNNs results in cleavage of Plk1 mRNA. Importantly, the Plk1 knockdown is specific and does not affect other Plk members in contrast to many small molecule Plk1 inhibitors. Thus, Plk1 is a potential therapeutic target in pediatric B-ALL and selective targeting of Plk1 can be achieved by the use of siRNNs.
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| 39. |
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| 40. |
- Hellström, D, et al.
(författare)
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Comparison of resource efficiency of systems for management of toilet waste and organic household waste
- 2003
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Ingår i: ; , s. 759-766
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Konferensbidrag (refereegranskat)abstract
- Using a system analysis approach compares different systems for handling and treatment of toilet waste and organic household waste. Design issues considered are source separation of urine, use of vacuum toilets and advanced nutrient recovery processes such as Reverse Osmosis (RO). All of the studied systems have low emissions of eutrophy ing compounds. Other environmental effects are mainly related to the amount of exergy used at each system. Source separating of urine is favourable if only a moderate (50 - 70 %) recycling potential for nutrients such as N and K is required. However, if hi gher recycling potential is required systems using nutrient recovery processes such as RO/evaporator are probably to prefer. For vacuum sy stems, the maximum amounts of flush water must be below 10 lit/p,d to make them reasonable efficient in terms of exergy consumption. The low-flush systems are less sensitive to the use of flush water in terms of exergy consumption.
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| 44. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 45. |
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| 46. |
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| 47. |
- Khatri, B, et al.
(författare)
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GENOME-WIDE ASSOCIATION STUDY OF SJOGREN'S SYNDROME IDENTIFIES TEN NEW RISK LOCI
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 30-31
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Sjögren’s syndrome (SS) is a complex autoimmune disease with exocrine gland dysfunction leading to substantial morbidity. There are 10 published genetic susceptibility loci.Objectives:Our genome-wide association study (GWAS) aimed to identify additional risk loci of genome-wide significance (GWS; p<5E-08) in European-derived primary SS.Methods:A total of 3232 cases and 17481 controls genotyped on GWAS arrays and 619 cases and 6171 controls genotyped on ImmunoChip (IC) arrays were imputed after quality control. Logistic regression was calculated adjusting for ancestry using the first 4 principal components to identify SS-associated SNPs. GWAS and IC results were meta-analyzed using weighted Z-scores. Bayesian statistics were used to assign posterior probabilities and define credible SNP sets for each locus. Bioinformatic analyses were used to predict functionality.Results:Seven novel loci exceeded GWS in the GWAS analysis:NAB1,MIR146A-PTTG1,XKR6,MAPT-CRHR1,RPTOR-CHMP6-BAIAP2,TYK2andSYNGR1. Meta-analysis with IC data identified three more novel loci exceeding GWS:CD247,PRDM1-ATG5andTNFAIP3. Several additional loci with suggestive association (p<1E-05) were also identified:ADAMTSL2,CGNL1andPHRF1.Several identified loci have reported functional implications in immune regulation and autoimmune disease. In lupus, rs2431697 correlated with rs2431098, which was shown to alterMIR146Aexpression, resulting in type I interferon pathway imbalance. Similarly,TYK2risk association reportedly drives interferon, IL10 and RET signaling pathways.PRDM1encodes Blimp-1, a master regulator of immune cell differentiation.CD247encodes the zeta subunit of the T cell receptor complex.XKR6is implicated in apoptotic cell ingestion.ATG5is also involved in apoptosis, as well as autophagy and antigen presentation.Additional bioinformatics analyses (Haploreg, Regulome DB, ENCODE, etc.) revealed immune-relevant functional implications for each risk locus. The SS-associated credible set included variants downstream ofTNFAIP3in a region reported to abolish looping between an enhancer and theTNFAIP3promoter in lupus and a coding variant that has been shown to alter NF-kB activity and neutrophil extra-cellular traps. The rs2293765 in the 5’ UTR ofNAB1showed evidence of enhancer/promoter activities. The rs2069235 in theSYNGR1locus showed enhancer and transcription start site activities in B and T cells. The rs7210219 in theMAPT-CRHR1locus showed enhancer/promotor activities in various tissues.Conclusion:We have identified ten novel genetic susceptibility loci associated with SS pathology. Our finding increases the current number of GWS regions in SS patients of European origin, from 10 to 20. Future work is needed to identify and characterize the functional variants in each region.Disclosure of Interests:Bhuwan Khatri: None declared, Tove Ragna Reksten: None declared, Kandice L Tessneer: None declared, Astrid Rasmussen Speakers bureau: Novartis, ThermoFischer, R Hal Scofield Grant/research support from: Pfizer, Simon J. Bowman Consultant of: Astrazeneca, Biogen, BMS, Celgene, Medimmune, MTPharma, Novartis, Ono, UCB, xtlbio, Glapagos, Speakers bureau: Novartis, Joel Guthridge Grant/research support from: Xencor, Bristol Myers Squibb, DXterity, Judith A. James Grant/research support from: Progentec Diagnostics, Inc, Consultant of: Abbvie, Novartis, Jannsen, Lars Ronnblom Grant/research support from: AZ, Speakers bureau: AZ, Blake M Warner: None declared, Xavier Mariette: None declared, Roald Omdal: None declared, Javier Martin Ibanez: None declared, Maria Teruel: None declared, Janicke Liaaen Jensen: None declared, Lara A Aqrawi: None declared, Øyvind Palm: None declared, Marie Wahren-Herlenius: None declared, Torsten Witte: None declared, Roland Jonsson: None declared, Maureen Rischmueller: None declared, A Darise Farris Speakers bureau: Biogen, Marta Alarcon-Riquelme: None declared, Wan-fai Ng: None declared, Kathy L Sivils: None declared, Gunnel Nordmark: None declared, Christopher Lessard: None declared
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- Koppel, M., et al.
(författare)
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Pore wall corrugation effect on the dynamics of adsorbed H2 studied by in situ quasi-elastic neutron scattering : Observation of two timescaled diffusion
- 2022
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Ingår i: Carbon. - : Elsevier Ltd. - 0008-6223 .- 1873-3891. ; 197, s. 359-367
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Tidskriftsartikel (refereegranskat)abstract
- The self-diffusion mechanisms for adsorbed H2 in different porous structures are investigated with in situ quasi-elastic neutron scattering method at a temperature range from 50 K to 100 K and at various H2 loadings. The porous structures of the carbon materials have been characterized by sorption analysis with four different gases and the results are correlated with previous in-depth analysis with small-angle neutron scattering method. Thus, an investigation discussing the effect of pore shape and size on the nature of adsorbed H2 self-diffusion is performed. It is shown that H2 adsorbed in nanometer-scale pores is self-diffusing in two distinguishable timescales. The effect of the pore, pore wall shape and corrugation on the fraction of confined and more mobile H2 is determined and analyzed. The increased corrugation of the pore walls is shown to have a stronger confining effect on the H2 motions. The difference of self-diffusional properties of the two H2 components are shown to be smaller when adsorbed in smoother-walled pores. This is attributed to the pore wall corrugation effect on the homogeneity of formed adsorbed layers.
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