| 1341. |
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| 1342. |
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| 1343. |
- James, A., et al.
(författare)
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Serum periostin relates to type-2 inflammation and lung function in asthma : Data from the large population-based cohort Swedish GA(2)LEN
- 2017
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 72:11, s. 1753-1760
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPeriostin has been suggested as a novel, phenotype-specific biomarker for asthma driven by type 2 inflammation. However, large studies examining relationships between circulating periostin and patient characteristics are lacking and the suitability of periostin as a biomarker in asthma remains unclear.AimTo examine circulating periostin in healthy controls and subjects with asthma from the general population with different severity and treatment profiles, both with and without chronic rhinosinusitis (CRS), in relation to other biomarkers and clinical characteristics.MethodsSerum periostin was examined by ELISA in 1100 subjects aged 17-76 from the Swedish Global Allergy and Asthma European Network (GA(2)LEN) study, which included 463 asthmatics with/without chronic rhinosinusitis (CRS), 98 individuals with CRS only, and 206 healthy controls. Clinical tests included measurement of lung function, Fraction of exhaled NO (FeNO), IgE, urinary eosinophil-derived neurotoxin (U-EDN), and serum eosinophil cationic protein (S-ECP), as well as completion of questionnaires regarding respiratory symptoms, medication, and quality of life.ResultsAlthough median periostin values showed no differences when comparing disease groups with healthy controls, multiple regression analyses revealed that periostin was positively associated with higher FeNO, U-EDN, and total IgE. In patients with asthma, an inverse relationship with lung function was also observed. Current smoking was associated with decreased periostin levels, whereas increased age and lower body mass index (BMI) related to higher periostin levels in subjects both with and without asthma.ConclusionWe confirm associations between periostin and markers of type 2 inflammation, as well as lung function, and identify novel constitutional factors of importance to the use of periostin as a phenotype-specific biomarker in asthma.
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| 1344. |
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| 1345. |
- James, Hayley R, et al.
(författare)
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IgE Antibodies to Mammalian Allergens Are a Major Risk Factor for Prevalence, Severity, and Persistence of Asthma in Northern Sweden
- 2015
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 135:2, s. AB22-AB22
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- IgE to mammalian allergens can contribute significantly to asthma risk. Studying the details of the relationship between animal sensitization and asthma is simpler in an environment where mite, fungal, and cockroach allergens make little or no contribution to asthma risk. Methods: Quantitative assays for IgE to eight allergens were carried out on 963 sera from 19-year-olds in a population-based cohort in northern Sweden, and associations with questionnaire data from ages 7, 12, and 19 on asthma symptoms, diagnosis, and treatment were tested. Results: Overall, 79 (53%) of the students with a physician diagnosis of asthma were positive to one or more of the mammalian allergens (cat, dog, or horse danders) tested. Of the allergens assessed, only mammalian allergens, birch, and timothy grass pollen showed a significant relationship with asthma diagnosis. Multivariate analysis showed that high titer (>17.5 IU/ml) IgE to any mammalian allergen had the strongest relationship with asthma at age 19 (odds ratio 5.1 [3.0-8.6]). Furthermore, IgE to mammalian allergens gave an odds ratio of 8.5 [4.9-15] for asthma that started before age 12 and was still present at age 19. Sensitization to Fel d 1 and Fel d 4 was strongly associated with asthma and significantly reduced in cat owners. Conclusions: Sensitization to cat and dog related allergens, and specifically to the components Fel d 1 and Fel d 4, is a major risk factor for the persistence and severity of asthma in an area where these are the only significant perennial allergens.
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| 1346. |
- James, Rory Hennell, et al.
(författare)
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Functional reconstruction of a eukaryotic-like E1/E2/(RING) E3 ubiquitylation cascade from an uncultured archaeon
- 2017
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The covalent modification of protein substrates by ubiquitin regulates a diverse range of critical biological functions. Although it has been established that ubiquitin-like modifiers evolved from prokaryotic sulphur transfer proteins it is less clear how complex eukaryotic ubiquitylation system arose and diversified from these prokaryotic antecedents. The discovery of ubiquitin, E1-like, E2-like and small-RING finger (srfp) protein components in the Aigarchaeota and the Asgard archaea superphyla has provided a substantive step toward addressing this evolutionary question. Encoded in operons, these components are likely representative of the progenitor apparatus that founded the modern eukaryotic ubiquitin modification systems. Here we report that these proteins from the archaeon Candidatus ` Caldiarchaeum subterraneum' operate together as a bona fide ubiquitin modification system, mediating a sequential ubiquitylation cascade reminiscent of the eukaryotic process. Our observations support the hypothesis that complex eukaryotic ubiquitylation signalling pathways have developed from compact systems originally inherited from an archaeal ancestor.
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| 1347. |
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| 1348. |
- Jandrić, Petar, et al.
(författare)
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Teaching in the Age of Covid-19—1 Year Later
- 2021
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Ingår i: Postdigital Science and Education. - : Springer. - 2524-485X .- 2524-4868. ; 3:3, s. 1073-1223
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Tidskriftsartikel (refereegranskat)
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| 1349. |
- Janelidze, Shorena, et al.
(författare)
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Plasma Phosphorylated Tau 217 and Aβ42/40 to Predict Early Brain Aβ Accumulation in People Without Cognitive Impairment
- 2024
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Ingår i: JAMA NEUROLOGY. - 2168-6149 .- 2168-6157.
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Phase 3 trials of successful antiamyloid therapies in Alzheimer disease (AD) have demonstrated improved clinical efficacy in people with less severe disease. Plasma biomarkers will be essential for efficient screening of participants in future primary prevention clinical trials testing antiamyloid therapies in cognitively unimpaired (CU) individuals with initially low brain beta-amyloid (A beta) levels who are at high risk of accumulating A beta. OBJECTIVE To investigate if combining plasma biomarkers could be useful in predicting subsequent development of A beta pathology in CU individuals with subthreshold brain A beta levels (defined as A beta levels <40 Centiloids) at baseline. DESIGN, SETTING, AND PARTICIPANTS This was a longitudinal study including Swedish BioFINDER-2 (enrollment 2017-2022) and replication in 2 independent cohorts, the Knight Alzheimer Disease Research Center (Knight ADRC; enrollment 1988 and 2019) and Swedish BioFINDER-1 (enrollment 2009-2015). Included for analysis was a convenience sample of CU individuals with baseline plasma phosphorylated tau 217 (p-tau217) and A beta 42/40 assessments and A beta assessments with positron emission tomography (A beta-PET) or cerebrospinal fluid (CSF) A beta 42/40. Data were analyzed between April 2023 and May 2024. EXPOSURES Baseline plasma levels of A beta 42/40, p-tau217, the ratio of p-tau217 to nonphosphorylated tau (%p-tau217), p-tau231, and glial fibrillary acidic protein (GFAP). MAIN OUTCOMES AND MEASURES Cross-sectional and longitudinal PET and CSF measures of brain A beta pathology. RESULTS This study included 495 (BioFINDER-2), 283 (Knight ADRC), and 205 (BioFINDER-1) CU participants. In BioFINDER-2, the mean (SD) age was 65.7 (14.4) with 261 females (52.7%). When detecting abnormal CSF A beta-status, a combination of plasma %p-tau217 and A beta 42/40 showed better performance (area under the curve = 0.949; 95% CI, 0.929-0.970; P <.02) than individual biomarkers. In CU participants with subthreshold baseline A beta-PET, baseline plasma %p-tau217 and A beta 42/40 levels were significantly associated with baseline A beta-PET (n = 384) and increases in A beta-PET over time (n = 224). Associations of plasma %p-tau217 and A beta 42/40 and their interaction with baseline A beta-PET (%p-tau217: beta = 2.77; 95% CI, 1.84-3.70; A beta 42/40: beta = -1.64; 95% CI, -2.53 to -0.75; %p-tau217 x A beta 42/40: beta = -2.14; 95% CI, -2.79 to -1.49; P < .001) and longitudinal A beta-PET (%p-tau217: beta = 0.67; 95% CI, 0.48-0.87; A beta 42/40: beta = -0.33; 95% CI, -0.51 to -0.15; %p-tau217 x A beta 42/40: beta = -0.31; 95% CI, -0.44 to -0.18; P < .001) were also significant in the models combining the 2 baseline biomarkers as predictors. Similarly, baseline plasma p-tau217 and A beta 42/40 were independently associated with longitudinal A beta-PET in Knight ADRC (%p-tau217: beta = 0.71; 95% CI, 0.26-1.16; P = .002; A beta 42/40: beta = -0.74; 95% CI, -1.26 to -0.22; P = .006) and longitudinal CSF A beta 42/40 in BioFINDER-1 (p-tau217: beta = -0.0003; 95% CI, -0.0004 to -0.0001; P = .01; A beta 42/40: beta = 0.0004; 95% CI, 0.0002-0.0006; P < .001) in CU participants with subthreshold A beta levels at baseline. Plasma p-tau231 and GFAP did not provide any clear independent value. CONCLUSIONS AND RELEVANCE Results of this cohort study suggest that combining plasma p-tau217and A beta 42/40 levels could be useful for predicting development of A beta pathology in people with early stages of subthreshold A beta accumulation. These biomarkers might thus facilitate screening of participants for future primary prevention trials.
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| 1350. |
- Jepson, Paul D., et al.
(författare)
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PCB pollution continues to impact populations of orcas and other dolphins in European waters
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Organochlorine (OC) pesticides and the more persistent polychlorinated biphenyls (PCBs) have well-established dose-dependent toxicities to birds, fish and mammals in experimental studies, but the actual impact of OC pollutants on European marine top predators remains unknown. Here we show that several cetacean species have very high mean blubber PCB concentrations likely to cause population declines and suppress population recovery. In a large pan-European meta-analysis of stranded (n = 929) or biopsied (n = 152) cetaceans, three out of four species:-striped dolphins (SDs), bottlenose dolphins (BNDs) and killer whales (KWs) had mean PCB levels that markedly exceeded all known marine mammal PCB toxicity thresholds. Some locations (e.g. western Mediterranean Sea, south-west Iberian Peninsula) are global PCB "hotspots" for marine mammals. Blubber PCB concentrations initially declined following a mid-1980s EU ban, but have since stabilised in UK harbour porpoises and SDs in the western Mediterranean Sea. Some small or declining populations of BNDs and KWs in the NE Atlantic were associated with low recruitment, consistent with PCB-induced reproductive toxicity. Despite regulations and mitigation measures to reduce PCB pollution, their biomagnification in marine food webs continues to cause severe impacts among cetacean top predators in European seas.
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