| 1. |
- Cockerill, Christopher Alan, 1994-, et al.
(författare)
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Genomic Consequences of Fragmentation in the Endangered Fennoscandian Arctic Fox (Vulpes lagopus)
- 2022
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Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Accelerating climate change is causing severe habitat fragmentation in the Arctic, threatening the persistence of many cold-adapted species. The Scandinavian arctic fox (Vulpes lagopus) is highly fragmented, with a once continuous, circumpolar distribution, it struggled to recover from a demographic bottleneck in the late 19th century. The future persistence of the entire Scandinavian population is highly dependent on the northernmost Fennoscandian subpopulations (Scandinavia and the Kola Peninsula), to provide a link to the viable Siberian population. By analyzing 43 arctic fox genomes, we quantified genomic variation and inbreeding in these populations. Signatures of genome erosion increased from Siberia to northern Sweden indicating a stepping-stone model of connectivity. In northern Fennoscandia, runs of homozygosity (ROH) were on average ~1.47-fold longer than ROH found in Siberia, stretching almost entire scaffolds. Moreover, consistent with recent inbreeding, northern Fennoscandia harbored more homozygous deleterious mutations, whereas Siberia had more in heterozygous state. This study underlines the value of documenting genome erosion following population fragmentation to identify areas requiring conservation priority. With the increasing fragmentation and isolation of Arctic habitats due to global warming, understanding the genomic and demographic consequences is vital for maintaining evolutionary potential and preventing local extinctions.
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| 2. |
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| 3. |
- Dalén, Johan, et al.
(författare)
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Health-Care and Societal Costs Associated with Non-Persistence with Subcutaneous TNF-α Inhibitors in the Treatment of Inflammatory Arthritis (IA) : A Retrospective Observational Study
- 2022
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Ingår i: Advances in Therapy. - : Springer Science and Business Media LLC. - 0741-238X .- 1865-8652. ; 39:6, s. 2468-2486
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Tidskriftsartikel (refereegranskat)abstract
- Objective: A few studies have suggested that patients with inflammatory arthritis (IA) who remain persistent with subcutaneous TNF-α inhibitors (SC-TNFi) incur lower health care costs than patients who discontinue treatment, whereas data on the impact of non-persistence on indirect costs are largely lacking. Furthermore, existing estimates are based on fixed follow-ups, in relation to treatment initiation, and therefore do not measure costs in direct relation to treatment discontinuation. Therefore, by capturing costs in direct relation to treatment discontinuation, this study aimed to estimate direct and indirect costs associated with non-persistence with SC-TNFis in IA. Methods: Adult Swedish biologic-naïve IA patients initiating biologic treatment with a SC-TNFi (adalimumab, etanercept, certolizumab or golimumab) between May 6, 2010, and December 31, 2017, were identified in population-based registers with almost complete coverage. IA was defined as a diagnosis of rheumatic arthritis, ankylosing spondylitis/unspecified spondyloarthritis or psoriatic arthritis. Non-persistent patients were matched on propensity score to patients persistent with treatment by at least an additional 12 months. This enabled comparisons of direct healthcare costs and indirect costs for sick leave and disability pension, respectively, 12 months before and 12 months after treatment discontinuation. Results: A balanced cohort of 486 matched pairs was generated. The total direct and indirect costs were significantly higher among non-persistent patients already during the 12 months before index ($20,802 [18,335–23,429] vs. $16,600 [14,331–18,696]). However, while non-persistent patients increased their total direct and indirect costs, persistent patients significantly decreased the same, further widening the difference in costs during the 12-month period after index date ($22,161 [19,754–24,556] vs. $13,465 [11,415–15,729]). Conclusions: Among biologic-naïve Swedish IA patients treated with SC-TNFis, persistent patients incurred about 40% lower aggregated direct and indirect costs compared to non-persistent patients the year following SC-TNFi discontinuation. This highlights the impact of treatment persistence from an economic viewpoint, adding further aspects to the clinical perspective.
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| 4. |
- Dalén, Johan, et al.
(författare)
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Identifying Predictors of First-Line Subcutaneous TNF-Inhibitor Persistence in Patients with Inflammatory Arthritis : A Decision Tree Analysis by Indication
- 2023
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Ingår i: Advances in Therapy. - 0741-238X .- 1865-8652. ; 40:10, s. 4657-4674
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Treatment persistence is a proxy for efficacy, safety and patient satisfaction, and a switch in treatment or treatment discontinuation has been associated with increased indirect and direct costs in inflammatory arthritis (IA). Hence, there are both clinical and economic incentives for the identification of factors associated with treatment persistence. Until now, studies have mainly leveraged traditional regression analysis, but it has been suggested that novel approaches, such as statistical learning techniques, may improve our understanding of factors related to treatment persistence. Therefore, we set up a study using nationwide Swedish high-coverage administrative register data with the objective to identify patient groups with distinct persistence of subcutaneous tumor necrosis factor inhibitor (SC-TNFi) treatment in IA, using recursive partitioning, a statistical learning algorithm. Methods: IA was defined as a diagnosis of rheumatic arthritis (RA), ankylosing spondylitis/unspecified spondyloarthritis (AS/uSpA) or psoriatic arthritis (PsA). Adult swedish biologic-naïve patients with IA initiating biologic treatment with a SC-TNFi (adalimumab, etanercept, certolizumab or golimumab) between May 6, 2010, and December 31, 2017. Treatment persistence of SC-TNFi was derived based on prescription data and a defined standard daily dose. Patient characteristics, including age, sex, number of health care contacts, comorbidities and treatment, were collected at treatment initiation and 12 months before treatment initiation. Based on these characteristics, we used recursive partitioning in a conditional inference framework to identify patient groups with distinct SC-TNFi treatment persistence by IA diagnosis. Results: A total of 13,913 patients were included. Approximately 50% had RA, while 27% and 23% had AS/uSpA and PsA, respectively. The recursive partitioning algorithm identified sex and treatment as factors associated with SC-TNFi treatment persistence in PsA and AS/uSpA. Time on treatment in the groups with the lowest treatment persistence was similar across all three indications (9.5–11.3 months), whereas there was more variation in time on treatment across the groups with the highest treatment persistence (18.4–48.9 months). Conclusions: Women have low SC-TNFi treatment persistence in PsA and AS/uSpA whereas male sex and golimumab are associated with high treatment persistence in these indications. The factors associated with treatment persistence in RA were less distinct but may comprise disease activity and concurrent conventional systemic disease-modifying anti-rheumatic drug (DMARD) treatment.
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| 5. |
- Dalen, Love, et al.
(författare)
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Identifying Bird Remains Using Ancient DNA Barcoding
- 2017
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Ingår i: Genes. - : MDPI AG. - 2073-4425 .- 2073-4425. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Bird remains that are difficult to identify taxonomically using morphological methods, are common in the palaeontological record. Other types of challenging avian material include artefacts and food items from endangered taxa, as well as remains from aircraft strikes. We here present a DNA-based method that enables taxonomic identification of bird remains, even from material where the DNA is heavily degraded. The method is based on the amplification and sequencing of two short variable parts of the 16S region in the mitochondrial genome. To demonstrate the applicability of this approach, we evaluated the method on a set of Holocene and Late Pleistocene postcranial bird bones from several palaeontological and archaeological sites in Europe with good success.
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| 6. |
- Djureinovic, Tatjana, et al.
(författare)
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The CHEK2 1100delC variant in Swedish colorectal cancer
- 2006
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:6C, s. 4885-4888
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cell cycle checkpoint kinase 2 (CHEK2) 1100delC variant has recently been identified at high frequency in families with both breast and colorectal cancer, suggesting the possible role of this variant in colorectal cancer predisposition. PATIENTS AND METHODS: To evaluate the role of CHEK2 ll00delC among Swedish colorectal cancer patients, the variant frequency was determined in 174 selected familial cases, 644 unselected cases and 760 controls, as well as in l8 families used in the genome-wide linkage analysis, where weak linkage was seen for the region harboring the CHEK2 gene. RESULTS: CHEK2 l100delC was found in 1.15% of familial and in 0.93% of unselected cases, compared to 0.66% of controls, showing no significant difference between groups. One out of 45 familial cases with a family history of breast cancer was shown to be a carrier. The variant was not identified in the 18 families included in the linkage analysis. CONCLUSION: The CHEK2 1100delC was not significantly increased in Swedish colorectal cancer patients, however, in order to determine the role of the variant in colorectal cancer families with the history of breast cancer a larger sample size is needed.
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| 7. |
- Doncheva, Atanaska, I, et al.
(författare)
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Serglycin Is Involved in Adipose Tissue Inflammation in Obesity
- 2022
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 208:1, s. 121-132
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Tidskriftsartikel (refereegranskat)abstract
- Chronic local inflammation of adipose tissue is an important feature of obesity. Serglycin is a proteoglycan highly expressed by various immune cell types known to infiltrate adipose tissue under obese conditions. To investigate if serglycin expression has an impact on diet-induced adipose tissue inflammation, we subjected Srgn(+/+) and Srgn(-/-) mice (C57BL/6J genetic background) to an 8-wk high-fat and high-sucrose diet. The total body weight was the same in Srgn(+/+) and Srgn(-/-) mice after diet treatment. Expression of white adipose tissue genes linked to inflammatory pathways were lower in Srgn(-/)- mice. We also noted reduced total macrophage abundance, a reduced proportion of proinflammatory M1 macrophages, and reduced formation of crown-like structures in adipose tissue of Srgn(-/-) compared with Srgn(+/+) mice. Further, Srgn(-/-) mice had more medium-sized adipocytes and fewer large adipocytes. Differentiation of preadipocytes into adipocytes (3T3-L1) was accompanied by reduced Srgn mRNA expression. In line with this, analysis of single-cell RNA sequencing data from mouse and human adipose tissue supports that Srgn mRNA is predominantly expressed by various immune cells, with low expression in adipocytes. Srgn mRNA expression was higher in obese compared with lean humans and mice, accompanied by an increased expression of immune cell gene markers. SRGN and inflammatory marker mRNA expression was reduced upon substantial weight loss in patients after bariatric surgery. Taken together, this study introduces a role for serglycin in the regulation of obesity-induced adipose inflammation.
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| 8. |
- Elmhagen, Bodil, et al.
(författare)
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Interacting effects of change in climate, human population, land use, and water use on biodiversity and ecosystem services
- 2015
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Ingår i: Ecology & Society. - 1708-3087. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Human population growth and resource use, mediated by changes in climate, land use, and water use, increasingly impact biodiversity and ecosystem services provision. However, impacts of these drivers on biodiversity and ecosystem services are rarely analyzed simultaneously and remain largely unknown. An emerging question is how science can improve the understanding of change in biodiversity and ecosystem service delivery and of potential feedback mechanisms of adaptive governance. We analyzed past and future change in drivers in south-central Sweden. We used the analysis to identify main research challenges and outline important research tasks. Since the 19th century, our study area has experienced substantial and interlinked changes; a 1.6 degrees C temperature increase, rapid population growth, urbanization, and massive changes in land use and water use. Considerable future changes are also projected until the mid-21st century. However, little is known about the impacts on biodiversity and ecosystem services so far, and this in turn hampers future projections of such effects. Therefore, we urge scientists to explore interdisciplinary approaches designed to investigate change in multiple drivers, underlying mechanisms, and interactions over time, including assessment and analysis of matching-scale data from several disciplines. Such a perspective is needed for science to contribute to adaptive governance by constantly improving the understanding of linked change complexities and their impacts.
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| 9. |
- Lopes, Fernando, et al.
(författare)
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ER-stress mobilization of death-associated protein kinase-1-dependent xenophagy counteracts mitochondria stress-induced epithelial barrier dysfunction
- 2018
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Ingår i: Journal of Biological Chemistry. - : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. - 0021-9258 .- 1083-351X. ; 293:9, s. 3073-3087
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiome contributes to inflammatory bowel disease (IBD), in which bacteria can be present within the epithelium. Epithelial barrier function is decreased in IBD, and dysfunctional epithelial mitochondria and endoplasmic reticulum (ER) stress have been individually associated with IBD. We therefore hypothesized that the combination of ER and mitochondrial stresses significantly disrupt epithelial barrier function. Here, we treated human colonic biopsies, epithelial colonoids, and epithelial cells with an uncoupler of oxidative phosphorylation, dinitrophenol (DNP), with or without the ER stressor tunicamycin and assessed epithelial barrier function by monitoring internalization and translocation of commensal bacteria. We also examined barrier function and colitis in mice exposed to dextran sodium sulfate (DSS) or DNP and co-treated with DAPK6, an inhibitor of death-associated protein kinase 1 (DAPK1). Contrary to our hypothesis, induction of ER stress (i.e. the unfolded protein response) protected against decreased barrier function caused by the disruption of mitochondrial function. ER stress did not prevent DNP-driven uptake of bacteria; rather, specific mobilization of the ATF6 arm of ER stress and recruitment of DAP K1 resulted in enhanced autophagic killing (xenophagy) of bacteria. Of note, epithelia with a Crohns disease susceptibility mutation in the autophagy gene ATG16L.1 exhibited less xenophagy. Systemic delivery of the DAPK1 inhibitor DAPK6 increased bacterial translocation in DSS- or DNP-treated mice. We conclude that promoting ER stress ATF6 DAPK1 signaling in transporting enterocytes counters the transcellular passage of bacteria evoked by dysfunctional mitochondria, thereby reducing the potential for metabolic stress to reactivate or perpetuate inflammation.
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| 10. |
- Meen, Astri J., et al.
(författare)
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Obesity Is Associated with Distorted Proteoglycan Expression in Adipose Tissue
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:8
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Tidskriftsartikel (refereegranskat)abstract
- Proteoglycans are central components of the extracellular matrix (ECM) and binding partners for inflammatory chemokines. Morphological differences in the ECM and increased inflammation are prominent features of the white adipose tissues in patients with obesity. The impact of obesity and weight loss on the expression of specific proteoglycans in adipose tissue is not well known. This study aimed to investigate the relationship between adiposity and proteoglycan expression. We analyzed transcriptomic data from two human bariatric surgery cohorts. In addition, RT-qPCR was performed on adipose tissues from female and male mice fed a high-fat diet. Both visceral and subcutaneous adipose tissue depots were analyzed. Adipose mRNA expression of specific proteoglycans, proteoglycan biosynthetic enzymes, proteoglycan partner molecules, and other ECM-related proteins were altered in both human cohorts. We consistently observed more profound alterations in gene expression of ECM targets in the visceral adipose tissues after surgery (among others VCAN (p = 0.000309), OGN (p = 0.000976), GPC4 (p = 0.00525), COL1A1 (p = 0.00221)). Further, gene analyses in mice revealed sex differences in these two tissue compartments in obese mice. We suggest that adipose tissue repair is still in progress long after surgery, which may reflect challenges in remodeling increased adipose tissues. This study can provide the basis for more mechanistic studies on the role of proteoglycans in adipose tissues in obesity.
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