| 1. |
- Evengård, Birgitta, 1952-, et al.
(författare)
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Healthy ecosystems for human and animal health : Science diplomacy for responsible development in the Arctic
- 2021
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Ingår i: Polar Record. - : Cambridges Institutes Press. - 0032-2474 .- 1475-3057. ; 57
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Tidskriftsartikel (refereegranskat)abstract
- Climate warming is occurring most rapidly in the Arctic, which is both a sentinel and a driver of further global change. Ecosystems and human societies are already affected by warming. Permafrost thaws and species are on the move, bringing pathogens and vectors to virgin areas. During a five-year project, the CLINF - a Nordic Center of Excellence, funded by the Nordic Council of Ministers, has worked with the One Health concept, integrating environmental data with human and animal disease data in predictive models and creating maps of dynamic processes affecting the spread of infectious diseases. It is shown that tularemia outbreaks can be predicted even at a regional level with a manageable level of uncertainty. To decrease uncertainty, rapid development of new and harmonised technologies and databases is needed from currently highly heterogeneous data sources. A major source of uncertainty for the future of contaminants and infectious diseases in the Arctic, however, is associated with which paths the majority of the globe chooses to follow in the future. Diplomacy is one of the most powerful tools Arctic nations have to influence these choices of other nations, supported by Arctic science and One Health approaches that recognise the interconnection between people, animals, plants and their shared environment at the local, regional, national and global levels as essential for achieving a sustainable development for both the Arctic and the globe.
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| 2. |
- Jonsson, Frida, et al.
(författare)
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Mutations in Collagen, Type XVII, Alpha 1 (COL17A1) Cause Epithelial Recurrent Erosion Dystrophy (ERED)
- 2015
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 36:4, s. 463-473
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Tidskriftsartikel (refereegranskat)abstract
- Corneal dystrophies are a clinically and genetically heterogeneous group of inherited disorders that bilaterally affect corneal transparency. They are defined according to the corneal layer affected and by their genetic cause. In this study, we identified a dominantly inherited epithelial recurrent erosion dystrophy (ERED)-like disease that is common in northern Sweden. Whole-exome sequencing resulted in the identification of a novel mutation, c.2816C>T, p.T939I, in the COL17A1 gene, which encodes collagen type XVII alpha 1. The variant segregated with disease in a genealogically expanded pedigree dating back 200 years. We also investigated a unique COL17A1 synonymous variant, c.3156C>T, identified in a previously reported unrelated dominant ERED-like family linked to a locus on chromosome 10q23-q24 encompassing COL17A1. We show that this variant introduces a cryptic donor site resulting in aberrant pre-mRNA splicing and is highly likely to be pathogenic. Bi-allelic COL17A1 mutations have previously been associated with a recessive skin disorder, junctional epidermolysis bullosa, with recurrent corneal erosions being reported in some cases. Our findings implicate presumed gain-of-function COL17A1 mutations causing dominantly inherited ERED and improve understanding of the underlying pathology.
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| 3. |
- Simonyté Sjödin, Kotryna, et al.
(författare)
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Temporal and long-term gut microbiota variation in allergic disease : a prospective study from infancy to school age
- 2019
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 74:1, s. 176-185
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Tidskriftsartikel (refereegranskat)abstract
- Background: Compositional changes in the early‐life gut microbiota have been implicated in IgE‐associated allergic diseases, but there is lack of longitudinal studies. We examined gut microbiota development from infancy to school age in relation to onset of IgE‐associated allergic diseases. At 8 years of age, we also examined the relationship between gut microbiota and T‐cell regulation, estimated as responses to polyclonal T‐cell activation.Methods: Stool samples were collected from 93 children at 4, 6, 13 months, and 8 years of age. The gut microbiota was profiled using 16S rRNA gene sequencing. Peripheral blood was drawn from all children, and mononuclear cells were polyclonally activated. Levels of IL‐10 and FOXP3 mRNA copies were determined using real‐time quantitative reverse transcriptase‐PCR.Results: At 8 years of age, 21 children were diagnosed with IgE‐associated allergic disease and 90% displayed allergic comorbidity. Seventy‐two children were nonallergic and nonsensitized. Statistical tests with multiple testing corrections demonstrated temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus in allergic compared to nonallergic children from infancy to school age. The gut microbiota of the allergic 8‐year‐olds was enriched in Bifidobacteriumand depleted of Lactobacillus, Enterococcus, and Lachnospira. In allergic 8‐year-olds, Faecalibacterium correlated with IL‐10 mRNA levels (rs = 0.49, Padj = 0.02) with the same trend for FOXP3 (rs = 0.39, Padj = 0.08).Conclusions: We identified both temporal and long‐term variation in the differential abundance of specific bacterial genera in children developing IgE‐associated allergic disease. Improved dietary interventions aiming at expanding immune‐modulatory taxa could be studied for prevention of allergic disease.
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| 4. |
- Sjödin, Kotryna Simonyte, et al.
(författare)
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Emerging evidence of the role of gut microbiota in the development of allergic diseases
- 2016
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Ingår i: Current Opinion in Allergy and Clinical Immunology. - 1528-4050 .- 1473-6322. ; 16:4, s. 390-395
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Forskningsöversikt (refereegranskat)abstract
- Purpose of review The purpose is to review recent studies examining the role of gut microbiota in allergic diseases and asthma.Recent findings Work in experimental models gives further evidence that a disturbed gut microbiota influences the propensity to develop allergic manifestations, and that changing the gut microbiota by dietary means (high fiber/acetate or prebiotics) in pregnancy may reduce the risk of allergic airways disease and food allergy in the offspring, respectively. The gut microbiome in established allergic disease and prior to disease onset has also been assessed in clinical trials. One study demonstrated a strong association between high abundance of Faecalibacterium prausnitzii and decreased levels of butyrate and propionate, and established eczema. Lower relative abundance of Ruminococcaceae appears to be implicated in food sensitization and to precede the development of atopic eczema. Decreased relative abundance of Lachnospira, Veillonella, Faecalibacterium, and Rothia in early infancy was reported to be associated with increased asthma risk. Inoculation of germ-free mice with these genera decreased airway inflammation in their offspring thereby proposing a causal role of bacteria in preventing allergic airways disease.Summary Gut microbiome research is an actively developing field. Although candidate bacterial taxa have been reported it still remains unclear which bacteria (or other microbes), in which numbers and combinations, and when during the gut colonization process may prevent allergic diseases and asthma. There is still a call for standardized approaches that will enable direct comparison of different studies.
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| 5. |
- Stattin, Eva-Lena, et al.
(författare)
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SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Autosomal recessive osteopetrosis (ARO) is a heterogeneous disorder, characterized by defective osteoclastic resorption of bone that results in increased bone density. We have studied nine individuals with an intermediate form of ARO, from the county of Vasterbotten in Northern Sweden. All afflicted individuals had an onset in early infancy with optic atrophy, and in four patients anemia was present at diagnosis. Tonsillar herniation, foramen magnum stenosis, and severe osteomyelitis of the jaw were common clinical features. Whole exome sequencing, verified by Sanger sequencing, identified a splice site mutation c.212 + 1 G > T in the SNX10 gene encoding sorting nexin 10. Sequence analysis of the SNX10 transcript in patients revealed activation of a cryptic splice site in intron 4 resulting in a frame shift and a premature stop (p.S66Nfs * 15). Haplotype analysis showed that all cases originated from a single mutational event, and the age of the mutation was estimated to be approximately 950 years. Functional analysis of osteoclast progenitors isolated from peripheral blood of patients revealed that stimulation with receptor activator of nuclear factor kappa-B ligand (RANKL) resulted in a robust formation of large, multinucleated osteoclasts which generated sealing zones; however these osteoclasts exhibited defective ruffled borders and were unable to resorb bone in vitro.
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| 6. |
- Stenberg, Per, 1974-, et al.
(författare)
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Buffering of segmental and chromosomal aneuploidies in Drosophila melanogaster
- 2009
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 5:5
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Tidskriftsartikel (refereegranskat)abstract
- Chromosomal instability, which involves the deletion and duplication of chromosomes or chromosome parts, is a common feature of cancers, and deficiency screens are commonly used to detect genes involved in various biological pathways. However, despite their importance, the effects of deficiencies, duplications, and chromosome losses on the regulation of whole chromosomes and large chromosome domains are largely unknown. Therefore, to explore these effects, we examined expression patterns of genes in several Drosophila deficiency hemizygotes and a duplication hemizygote using microarrays. The results indicate that genes expressed in deficiency hemizygotes are significantly buffered, and that the buffering effect is general rather than being mainly mediated by feedback regulation of individual genes. In addition, differentially expressed genes in haploid condition appear to be generally more strongly buffered than ubiquitously expressed genes in haploid condition, but, among genes present in triploid condition, ubiquitously expressed genes are generally more strongly buffered than differentially expressed genes. Furthermore, we show that the 4th chromosome is compensated in response to dose differences. Our results suggest general mechanisms have evolved that stimulate or repress gene expression of aneuploid regions as appropriate, and on the 4th chromosome of Drosophila this compensation is mediated by Painting of Fourth (POF).
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| 7. |
- West, Christina E., et al.
(författare)
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Gut microbiome and innate immune response patterns in IgE-associated eczema
- 2015
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 45:9, s. 1419-1429
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Tidskriftsartikel (refereegranskat)abstract
- Background Gut microbiome patterns have been associated with predisposition to eczema potentially through modulation of innate immune signaling. Objective We examined gut microbiome development in the first year of life in relation to innate immune responses and onset of IgE-associated eczema over the first 2.5 years in predisposed children due to maternal atopy [www.anzctr.org.au, trial ID ACTRN12606000280505]. Methods Microbial composition and diversity were analyzed with barcoded 16S rRNA 454 pyrosequencing in stool samples in pregnancy and at ages 1 week, 1 month and 12 months in infants (n=10) who developed IgE-associated eczema and infants who remained free of any allergic symptoms at 2.5 years of age (n=10). Microbiome data at 1 week and 1 month were analyzed in relation to previously assessed immune responses to TLR 2 and 4 ligands at 6 months of age. Results The relative abundance of Gram-positive Ruminococcaceae was lower at 1 week of age in infants developing IgE-associated eczema, compared with controls (p=0.0047). At that age, the relative abundance of Ruminococcus was inversely associated with TLR2 induced IL-6 (-0.567, p=0.042) and TNF-α (-0.597, p=0.032); there was also an inverse association between the abundance of Proteobacteria (comprising Gram-negative taxa) and TLR4 induced TNF-α (rs= -0.629, p=0.024). This relationship persisted at 1 month, with inverse associations between the relative abundance of Enterobacteriaceae (within the Protebacteria phylum) and TLR4 induced TNF-α (rs=-0.697, p=0.038) and Enterobacteriaceae and IL-6 (rs=-0.709, p=0.035). Mothers whose infants developed IgE-associated eczema had lower α-diversity of Bacteroidetes (p=0.04) although this was not seen later in their infants. At 1 year, α-diversity of Actinobacteria was lower in infants with IgE-associated eczema compared with controls (p=0.002). Conclusion and clinical relevance Our findings suggest that reduced relative abundance of potentially immunomodulatory gut bacteria is associated with exaggerated inflammatory cytokine responses to TLR ligands and subsequent development of IgE-associated eczema. This article is protected by copyright. All rights reserved.
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