| 1. |
- Ahmed, Nabeela, et al.
(författare)
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Redefining the role of urban studies Early Career Academics in the post-COVID-19 university
- 2022
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Ingår i: City. - : Informa UK Limited. - 1360-4813 .- 1470-3629. ; 26:4, s. 562-586
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Tidskriftsartikel (refereegranskat)abstract
- We are an international collective of Early Career Academics (ECAs) who met throughout 2020 to explore the implications of COVID-19 on precarious academics. With this intervention, our aims are to voice commonly shared experiences and concerns and to reflect on the extent to which the pandemic offers opportunities to redefine Higher Education and research institutions, in a context of ongoing precarity and funding cuts. Specifically, we explore avenues to build solidarity across institutions and geographies, to ensure that the conduct of urban research, and support offered to ECAs, allows for more inclusivity, diversity, security and equitability.
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| 2. |
- Arvidsson, Ida, et al.
(författare)
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Shiga toxin-induced complement-mediated hemolysis and release of complement-coated red blood cell-derived microvesicles in hemolytic uremic syndrome.
- 2015
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 194:5, s. 2309-2318
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Tidskriftsartikel (refereegranskat)abstract
- Shiga toxin (Stx)-producing Escherichia coli (STEC) cause hemolytic uremic syndrome (HUS). This study investigated whether Stx2 induces hemolysis and whether complement is involved in the hemolytic process. RBCs and/or RBC-derived microvesicles from patients with STEC-HUS (n = 25) were investigated for the presence of C3 and C9 by flow cytometry. Patients exhibited increased C3 deposition on RBCs compared with controls (p < 0.001), as well as high levels of C3- and C9-bearing RBC-derived microvesicles during the acute phase, which decreased after recovery. Stx2 bound to P1 (k) and P2 (k) phenotype RBCs, expressing high levels of the P(k) Ag (globotriaosylceramide), the known Stx receptor. Stx2 induced the release of hemoglobin and lactate dehydrogenase in whole blood, indicating hemolysis. Stx2-induced hemolysis was not demonstrated in the absence of plasma and was inhibited by heat inactivation, as well as by the terminal complement pathway Ab eculizumab, the purinergic P2 receptor antagonist suramin, and EDTA. In the presence of whole blood or plasma/serum, Stx2 induced the release of RBC-derived microvesicles coated with C5b-9, a process that was inhibited by EDTA, in the absence of factor B, and by purinergic P2 receptor antagonists. Thus, complement-coated RBC-derived microvesicles are elevated in HUS patients and induced in vitro by incubation of RBCs with Stx2, which also induced hemolysis. The role of complement in Stx2-mediated hemolysis was demonstrated by its occurrence only in the presence of plasma and its abrogation by heat inactivation, EDTA, and eculizumab. Complement activation on RBCs could play a role in the hemolytic process occurring during STEC-HUS.
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| 3. |
- Canales, Giancarlo De La Torre, et al.
(författare)
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The role of tryptophan and its derivatives in musculoskeletal pains : A systematic review and meta-analysis
- 2024
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842.
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Forskningsöversikt (refereegranskat)abstract
- Background: Studies present ambiguous findings regarding the role of tryptophan and its metabolites, kynurenine and serotonin in chronic musculoskeletal pain. This systematic review aimed to investigate the expression of tryptophan and its metabolites, serotonin and kynurenine in patients with local and generalized chronic musculoskeletal pain in comparison with pain-free controls.Methods: An electronic search was conducted in the databases MEDLINE, CINAHL, EMBASE, the Cochrane Central Registry of Controlled Trials (CENTRAL) and Web of Science for clinical and observational trials from the beginning of each database to 21 April 2023. Out of 6734 articles, a total of 17 studies were included; 12 studies were used in the meta-analysis of serotonin, 3 regarding tryptophan and 2 studies for a narrative synthesis regarding kynurenine. Risk of bias was assessed using the quality assessment tool for observational cohort and cross-sectional studies of the National Heart, Lung, and Blood Institute, while the certainty of evidence was by GRADE.Results: All included studies showed a low risk of bias. The meta-analysis showed lower blood levels of tryptophan (p < .001; very low quality of evidence) and higher blood levels of serotonin (p < .001; very low-quality evidence) in patients with generalized musculoskeletal pain, when compared to pain-free individuals. In local chronic musculoskeletal pain, there were higher blood levels of serotonin (p=.251; very low quality of evidence) compared to pain-free individuals. Regarding kynurenine, the studies reported both higher and lower blood levels in generalized chronic musculoskeletal pain compared to pain-free individuals.Conclusions: The blood levels of tryptophan and its metabolites serotonin and kynurenine seem to influence chronic musculoskeletal pain.
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| 4. |
- Hellberg, Åsa, et al.
(författare)
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An update on the GLOB blood group system and collection.
- 2013
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Ingår i: Immunohematology. - 0894-203X. ; 29:1, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- The P blood group antigen of the GLOB system is a glycolipid structure, also known as globoside, on the red blood cells (RBCs) of almost all individuals worldwide. The P antigen is intimately related to the Pk and NOR antigens discussed in the review about the P1PK blood group system. Naturally occurring anti-P is present in the serum of individuals with the rare globoside-deficient phenotypes p, P1k, and P2k and has been implicated in hemolytic transfusion reactions as well as unfavorable outcomes of pregnancy. The molecular genetic basis of globoside deficiency is absence of functional P synthase as a result of mutations at the B3GALNT1 locus. Other related glycolipid structures, the LKE and PX2 antigens, remain in the GLOB blood group collection pending further evidence about the genes and gene products responsible for their synthesis.
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| 5. |
- Hellberg, Åsa, et al.
(författare)
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P1PK: the blood group system that changed its name and expanded.
- 2013
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Ingår i: Immunohematology. - 0894-203X. ; 29:1, s. 25-33
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Tidskriftsartikel (refereegranskat)abstract
- The antigens in the P1PK blood group system are carried on glycosphingolipids. The system currently includes three different antigens, P1, Pk, and NOR. The P1 antigen was disovered in 1927 by Landsteiner and Levine, and Pk and NOR were described in 1951 and 1982, respectively. As in the ABO system, naturally occurring antibodies of the immunoglobulin (Ig) M or IgG class, against the missing carbohydrate structures, can be present in the sera of people lacking the corresponding antigen. Anti-P1 is generally a weak and cold-reactive antibody not implicated in hemolytic transfusion reaction (HTR) or hemolytic disease of the fetus and newborn while Pk antibodies can cause HTR, and anti-NOR is regarded as a polyagglutinin. A higher frequency of miscarriage is seen in women with the rare phenotypes p, P1k, and P2k. Furthermore, the Pk and P1 antigens have wide tissue distributions and can act as host receptors for various pathogens and toxins. Why p individuals lack not only Pk and P expression but also P1 has been a longstanding enigma. Recently, it was shown that the same A4GALT-encoded galactosyltransferase synthesizes both the P1 and Pk antigens and that a polymorphism in a new exon in this gene predicts the P1 and P2 phenotypes.
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| 6. |
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| 7. |
- Ricci Hagman, Jennifer, et al.
(författare)
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An update on the GLOB blood group system (and former GLOB collection)
- 2018
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Ingår i: Immunohematology. - 0894-203X. ; 34:4, s. 161-163
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Tidskriftsartikel (refereegranskat)abstract
- CONCLUSIONS: The main change that has occurred in the GLOB blood group system since the GLOB review published in this journal in 2013 is the addition of an antigen. The high-prevalence PX2 antigen, originally recognized as the x2 glycosphingolipid, is expressed on red blood cells of most individuals and is elevated in the rare PP1Pk-negative p blood group phenotype. P synthase, encoded by B3GALNT1, was found to elongate paragloboside to PX2 by adding the terminal β3GalNAc moiety. Hence, PX2 was moved from the GLOB collection to the GLOB system. The presence of naturally-occurring anti-PX2 was noted in P1k and P2k individuals exhibiting nonfunctional P synthase. Although the clinical significance of this specificity remains unclear, a recommendation to avoid transfusing Pk patients with p phenotype blood has been made. Currently, 13 mutations at the highly conserved B3GALNT1 locus have been found to abolish P synthase function and are recognized as null alleles by the International Society of Blood Transfusion. A new allele with a missense mutation but resulting in normal expression of P has been assigned GLOB*02. Finally, the GLOB collection was made obsolete after the move of LKE antigen to the 901 series.
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| 8. |
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| 9. |
- Stenfelt, L., et al.
(författare)
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The P1 histo-blood group antigen is present on human red blood cell glycoproteins
- 2017
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Ingår i: Vox Sanguinis. - : Wiley. - 1423-0410 .- 0042-9007. ; 112:S1, s. 25-25
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Konferensbidrag (refereegranskat)abstract
- Background: The P1 antigen was first described in 1927 but not categorized with the Pk antigen in the P1PK histo-blood group system until 2010. Individuals of P1 phenotype have both the Pk and P1 antigens on their red blood cell (RBC) surface, while P2 individuals lack P1 and have lower amounts of Pk. Like in the ABO system, the antigens are carbohydrate epitopes built up stepwise by glycosyltransferases. The antigens of the P1PK system are synthesized by 4-a-galactosyltransferase (a1,4GalT) encoded by A4GALT. Gala4Gal-terminating antigens like Pk and P1 can function as receptors for P-fimbriated Escherichia coli (E. coli). Moreover, the terminal and internal Gala4Galb sequence is a known Shiga toxin receptor. Antibodies against the antigens of the P1PK system are naturally-occurring. Anti-P1 induced hemolytic transfusion reactions are rare but a few cases have been reported. The anti-P1PPk found in plasma from individuals of the p (P1PPk-) phenotype is also associated with recurrent miscarriages. In humans, a1,4GalT has been considered to extend glycans on glycosphingolipids exclusively. However, in certain other species, such as the pigeon, the P1 epitope resides on glycoproteins as well. Interestingly, the majority of the human A, B and H antigens are found on glycoproteins and they share the same precursor as P1, namely paragloboside. Aims: This work is based on a hypothesis stated years ago regarding the P1 glycoepitope. Haselberger et al. [FEBS Lett., 1982] published that P1 is carried on glycoproteins in humans. However, this was later contradicted firmly by Yang et al. [J Biol Chem., 1994]. The aim of this work was to find out if P1 is present on glycoproteins and if so, to characterize carrier candidates on human RBCs. Methods: RBCs from peripheral blood of apparently healthy volunteers were used for the study. P1 phenotyping and SNP genotyping was used to determine P1/P2 status. RBC glycans were digested with a-galactosidase from green coffee bean, a1,3- specific GH110 a-galactosidase of bacterial origin (B-zyme), papain, neuraminidase and/or peptide-N-glycosidase (PNGase) F. RBCs were lysed and the hemoglobin was washed away while the unsealed membranes were collected. Denatured membrane proteins were separated in SDS-PAGE and transferred to a low fluorescence PVDF membrane, immunoblotted with monoclonal anti-P1 and staining quantified in relation to total protein loaded. Results: We show clearly that P1 occurs on various glycoproteins, seen as a smearlike pattern in Western blots with cell membranes from P1 but not P2 or p RBCs. Furthermore, there was a significant difference between the staining of RBCs from P1-homozygous (stronger) and P1-heterozygous (weaker) individuals. The amount detected varied between samples of the same genotype, which is consistent with earlier studies of P1 expression on RBCs. A tendency toward a banding pattern suggested possible carriers at ∼50 and ∼100 kDa. P1 staining was lost after treatment of the RBCs with coffee bean a-galactosidase as the enzyme destroys the P1 epitope. PNGase F treatment reduced the P1 signal whilst B-zyme did not. Summary/Conclusions: This study provides data showing that P1 does indeed reside on human RBC glycoproteins and not only on glycosphingolipids. The epitope was detected in a gene-dose dependent manner on glycoproteins of P1-positive RBC membranes. The signal was reduced when using N-glycan-specific PNGase F, indicating that at least some of the epitopes are carried on N-glycans, which mimics the ABH antigens. Attempts to identify specific carrier proteins are in progress.
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| 10. |
- Stenfelt, Linn, et al.
(författare)
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The P1 histo-blood group antigen is present on human red blood cell glycoproteins
- 2019
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Ingår i: Transfusion. - : Wiley. - 0041-1132. ; 59:3, s. 1108-1117
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The P1 antigen was first described in 1927 and belongs to the P1PK histo-blood group system, together with Pk and NOR. The A4GALT-encoded 4-α-galactosyltransferase synthesizes these antigens and has been considered to extend glycolipids exclusively. However, contradicting studies have been published regarding the presence of P1 on human glycoproteins. In other species, P1 occurs on glycoproteins. Furthermore, human ABH antigens occur on both glycolipids and glycoproteins and are biochemically related to P1. Thus, we hypothesized that P1 is present on RBC glycoproteins in humans. STUDY DESIGN AND METHODS: RBCs of known P1/P2 status (phenotype and rs8138197 genotype) were used. The RBC surface glycans were modified with α-galactosidases, papain, and/or peptide-N-glycosidase F. RBC membrane proteins were analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis/immunoblot. A new P1/P2-allelic discrimination assay based on rs5751348 was validated. RESULTS: P1 occurs on various glycoproteins, seen as smearlike patterns in anti-P1-stained immunoblots with RBC membranes of P1 but not P2 or p phenotype. There was a significant difference between the staining of P1-homozygous and P1-heterozygous RBCs (P1P1 > P1P2), as well as intragenotypic variation. Immunoblotting banding patterns show major carriers at approximately 50 and 100 kDa. P1 staining was lost after treatment of RBCs with α-galactosidase of broad Galα-1,3/4/6-specificity. Peptide-N-glycosidase F treatment reduced the P1 signal, while papain or α-1,3-specific galactosidase did not. P1/P2 status was confirmed by a new rs5751348 assay. CONCLUSION: Our data indicate that the P1 antigen can reside on human RBC glycoproteins. Glycosidase studies suggest that at least part of the epitopes occur on N-glycans.
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