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- Semb, G, et al.
(författare)
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Erratum
- 2017
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Ingår i: Journal of plastic surgery and hand surgery. - 2000-6764. ; 51:2, s. 158-158
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Tidskriftsartikel (refereegranskat)
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- Andrabi, Syed Bilal Ahmad, et al.
(författare)
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Long noncoding RNA LIRIL2R modulates FOXP3 levels and suppressive function of human CD4+ regulatory T cells by regulating IL2RA
- 2024
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 121:23
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory T cells (Tregs) are central in controlling immune responses, and dysregulation of their function can lead to autoimmune disorders or cancer. Despite extensive studies on Tregs, the basis of epigenetic regulation of human Treg development and function is incompletely understood. Long intergenic noncoding RNAs (lincRNA)s are important for shaping and maintaining the epigenetic landscape in different cell types. In this study, we identified a gene on the chromosome 6p25.3 locus, encoding a lincRNA, that was up-regulated during early differentiation of human Tregs. The lincRNA regulated the expression of interleukin-2 receptor alpha (IL2RA), and we named it the lincRNA regulator of IL2RA (LIRIL2R). Through transcriptomics, epigenomics, and proteomics analysis of LIRIL2R-deficient Tregs, coupled with global profiling of LIRIL2R binding sites using chromatin isolation by RNA purification, followed by sequencing, we identified IL2RA as a target of LIRIL2R. This nuclear lincRNA binds upstream of the IL2RA locus and regulates its epigenetic landscape and transcription. CRISPR-mediated deletion of the LIRIL2R-bound region at the IL2RA locus resulted in reduced IL2RA expression. Notably, LIRIL2R deficiency led to reduced expression of Treg-signature genes (e.g., FOXP3, CTLA4, and PDCD1), upregulation of genes associated with effector T cells (e.g., SATB1 and GATA3), and loss of Treg-mediated suppression.
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- Andréll, Paulin, 1978, et al.
(författare)
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Long-term effects of spinal cord stimulation on angina symptoms and quality of life in patients with refractory angina pectoris--results from the European Angina Registry Link Study (EARL)
- 2010
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Ingår i: Heart. - 1355-6037. ; 96:14, s. 1132-1136
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the long-term effect of spinal cord stimulation (SCS) on angina symptoms and quality of life in patients with refractory angina pectoris defined as severe angina due to coronary artery disease resistant to conventional pharmacological therapy and/or revascularisation. METHODS: During 2003-2005, all patients with refractory angina referred for SCS treatment at 10 European centres were consecutively included in the European registry for refractory angina (European Angina Registry Link, EARL), a prospective, 3-year follow-up study. In the present study, the SCS-treated patients were followed-up regarding angina symptoms and quality of life assessed was with a generic (Short Form 36, SF-36) and a disease-specific (Seattle Angina Questionnaire, SAQ) quality of life questionnaire. RESULTS: In total, 235 patients were included in the study. After screening, 121 patients were implanted and followed up 12.1 months after implantation. The implanted patients reported fewer angina attacks (p<0.0001), reduced short-acting nitrate consumption (p<0.0001) and improved Canadian Cardiovascular Society class (p<0.0001). Furthermore, quality of life was significantly improved in all dimensions of the SF-36 and the SAQ. Seven (5.8%) of the implanted patients died within 1 year of follow up. CONCLUSIONS: SCS treatment is associated with symptom relief and improved quality of life in patients with refractory angina pectoris suffering from severe coronary artery disease.
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- Carlsson, Lena, et al.
(författare)
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Differences in the distribution of synemin, paranemin, and plectin in skeletal muscles of wild-type and desmin knock-out mice
- 2000
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Ingår i: Histochemistry and Cell Biology. - : Springer. - 0948-6143 .- 1432-119X. ; 114:1, s. 39-47
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Tidskriftsartikel (refereegranskat)abstract
- Mice lacking the gene encoding for the intermediate filament protein desmin have a surprisingly normal myofibrillar organization in skeletal muscle fibers, although myopathy develops in highly used muscles. In the present study we examined how synemin, paranemin, and plectin, three key cytoskeletal proteins related to desmin, are organized in normal and desmin knock-out (K/O) mice. We show that in wild-type mice, synemin, paranemin, and plectin were colocalized with desmin in Z-disc-associated striations and at the sarcolemma. All three proteins were also present at the myotendinous junctions and in the postsynaptic area of motor endplates. In the desmin K/O mice the distribution of plectin was unaffected, whereas synemin and paranemin were partly affected. The Z-disc-associated striations were in general no longer present in between the myofibrils. In contrast, at the myotendinous and neuromuscular junctions synemin and paranemin were still present. Our study shows that plectin differs from synemin and paranemin in its binding properties to the myofibrillar Z-discs and that the cytoskeleton in junctional areas is particularly complex in its organization.
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- Egund, L., et al.
(författare)
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Longitudinal Measurements of FGF23, Sarcopenia, Frailty and Fracture in Older Community Dwelling Women
- 2023
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Ingår i: Journal of Frailty and Aging. - : SERDI. - 2260-1341 .- 2273-4309. ; 12, s. 166-174
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Tidskriftsartikel (refereegranskat)abstract
- Background: FGF23 has been associated with frailty and functional performance in older individuals, but the association to sarcopenia is unknown. Objectives: To investigate the association between FGF23, frailty, sarcopenia and fractures in older community dwelling women. Design: Prospective longitudinal cohort study. Setting: Malmö, Sweden. Participants: 995 75-year-old women, followed prospectively for ten years, with re-investigations after five (n=667) and ten (n=324) years. Measurements: C-terminal levels of FGF23 were measured and a frailty index of ‘deficits in health’ created. Sarcopenia was defined by low muscle mass and strength and “probable sarcopenia” by low muscle mass only. Incident fractures were continuously registered for 10-years. Based on tertiles of FGF23, odds ratio for frailty, sarcopenia and probable sarcopenia was investigated using logistic regression models adjusted for: eGFR, PTH, calcium, vitamin D and phosphate. Fracture-free survival during 10-year follow-up was depicted using Kaplan Meier curves. Results: While fracture-free survival did not differ between tertiles, women in the highest tertile of FGF23 had lower muscle strength and gait speed, and higher proportion with impaired mobility at baseline. At age 75, these women had higher odds of also being frail (ORadj 1.6 (95% CI 1.1–2.4)) and suffering from probable sarcopenia (ORadj 1.8 (95% CI 1.1–3.1)), but not sarcopenia. At follow-up the association between FGF23 and probable sarcopenia was not evident. While the association with frailty was attenuated at age 80 after adjustment (ORadj 1.6 (95% CI 1.0–2.5)), women in the highest tertile had higher odds of being frail at age 85 (ORadj 3.4 (95% CI 1.7–6.6)). Conclusions: FGF23 may be a promising clinical marker for muscle strength, functional performance, and frailty in older women, but not for future fragility fractures. Whether FGF23 is also associated with sarcopenia requires further investigation.
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- Gu, Y, et al.
(författare)
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Quick Hot Shot & Young Surgeon Presentation
- 2015
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Ingår i: Hernia : the journal of hernias and abdominal wall surgery. - 1248-9204. ; 19 Suppl 1, s. S77-84
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Tidskriftsartikel (refereegranskat)
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- Nyholm, O., et al.
(författare)
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Comparative Genomics and Characterization of Hybrid Shigatoxigenic and Enterotoxigenic Escherichia coli (STEC/ETEC) Strains
- 2015
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Background Shigatoxigenic Escherichia coli (STEC) and enterotoxigenic E. coli (ETEC) cause serious foodborne infections in humans. These two pathogroups are defined based on the pathogroup-associated virulence genes: stx encoding Shiga toxin (Stx) for STEC and elt encoding heat-labile and/or est encoding heat-stable enterotoxin (ST) for ETEC. The study investigated the genomics of STEC/ETEC hybrid strains to determine their phylogenetic position among E. coli and to define the virulence genes they harbor. The whole genomes of three STEC/ETEC strains possessing both stx and est genes were sequenced using PacBio RS sequencer. Two of the strains were isolated from the patients, one with hemolytic uremic syndrome, and one with diarrhea. The third strain was of bovine origin. Core genome analysis of the shared chromosomal genes and comparison with E. coli and Shigella spp. reference genomes was performed to determine the phylogenetic position of the STEC/ETEC strains. In addition, a set of virulence genes and ETEC colonization factors were extracted from the genomes. The production of Stx and ST were studied. The human STEC/ETEC strains clustered with strains representing ETEC, STEC, entero-aggregative E. coli, and commensal and laboratory-adapted E. coli. However, the bovine STEC/ETEC strain formed a remote cluster with two STECs of bovine origin. All three STEC/ETEC strains harbored several other virulence genes, apart from stx and est, and lacked ETEC colonization factors. Two STEC/ETEC strains produced both toxins and one strain Stx only. Conclusions This study shows that pathogroup-associated virulence genes of different E. coli can coexist in strains originating from different phylogenetic lineages. The possibility of virulence genes to be associated with several E. coli pathogroups should be taken into account in strain typing and in epidemiological surveillance. Development of novel hybrid E. coli strains may cause a new public health risk, which challenges the traditional diagnostics of E. coli infections.
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| 18. |
- Ovaskainen, O., et al.
(författare)
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Combining high-throughput sequencing with fruit body surveys reveals contrasting life-history strategies in fungi
- 2013
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Ingår i: Isme Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 7:9, s. 1696-1709
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Tidskriftsartikel (refereegranskat)abstract
- Before the recent revolution in molecular biology, field studies on fungal communities were mostly confined to fruit bodies, whereas mycelial interactions were studied in the laboratory. Here we combine high-throughput sequencing with a fruit body inventory to study simultaneously mycelial and fruit body occurrences in a community of fungi inhabiting dead wood of Norway spruce. We studied mycelial occurrence by extracting DNA from wood samples followed by 454-sequencing of the ITS1 and ITS2 regions and an automated procedure for species identification. In total, we detected 198 species as mycelia and 137 species as fruit bodies. The correlation between mycelial and fruit body occurrences was high for the majority of the species, suggesting that high-throughput sequencing can successfully characterize the dominating fungal communities, despite possible biases related to sampling, PCR, sequencing and molecular identification. We used the fruit body and molecular data to test hypothesized links between life history and population dynamic parameters. We show that the species that have on average a high mycelial abundance also have a high fruiting rate and produce large fruit bodies, leading to a positive feedback loop in their population dynamics. Earlier studies have shown that species with specialized resource requirements are rarely seen fruiting, for which reason they are often classified as red-listed. We show with the help of high-throughput sequencing that some of these species are more abundant as mycelium in wood than what could be expected from their occurrence as fruit bodies.
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| 19. |
- Tin, Amy L., et al.
(författare)
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Pain as bad as you can imagine or extremely severe pain? A randomized controlled trial comparing two pain scale anchors
- 2023
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Ingår i: Journal of Patient-Reported Outcomes. - 2509-8020. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: A common method of pain assessment is the numerical rating scale, where patients are asked to rate their pain on a scale from 0 to 10, where 0 is “no pain” and 10 is “pain as bad as you can imagine”. We hypothesize such language is suboptimal as it involves a test of a cognitive skill, imagination, in the assessment of symptom severity. Methods: We used a large-scale online research registry, ResearchMatch, to conduct a randomized controlled trial to compare the distributions of pain scores of two different pain scale anchors. We recruited adults located in the United States who reported a chronic pain problem (> 3 months) and were currently in pain. Participants were randomized in a 1:1 ratio to receive pain assessment based on a modified Brief Pain Inventory (BPI), where the anchor for a score of 10 was either “extremely severe pain”, or the original BPI, with the anchor “pain as bad as you can imagine”. Participants in both groups also answered additional questions about pain, other symptomatology and creativity. Results: Data were obtained from 405 participants for the modified and 424 for the original BPI. Distribution of responses to pain questions were similar between groups (all p-values ≥ 0.12). We did not see evidence that the relationship between pain score and the anchor text differed based on self-perceived creativity (all interaction p-values ≥ 0.2). However, in the key analysis, correlations between current pain assessments and known correlates (fatigue, anxiety, depression, current pain compared to a typical day, pain compared to other people) were stronger for “extreme” vs. “imaginable” anchor text (p = 0.005). Conclusion: Pain rating scales should utilize the modified anchor text “extremely severe pain” instead of “pain as bad as you can imagine”. Further research should explore the effects of anchors for other symptoms.
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