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- Mesilov, V., et al.
(författare)
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Insights into sulfur poisoning and regeneration of Cu-SSZ-13 catalysts: : In situ Cu and S K-edge XAS studies
- 2021
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Ingår i: Catalysis Science & Technology. - : Royal Society of Chemistry (RSC). - 2044-4753 .- 2044-4761. ; 11:16, s. 5619-5632
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Tidskriftsartikel (refereegranskat)abstract
- In situ Cu and S K-edge X-ray absorption spectroscopy (XAS) was used for the investigation of sulfur-poisoned and regenerated Cu-SSZ-13 selective catalytic reduction (SCR) catalysts. Highly dispersed sulfur in the oxidation state +6 was found in the catalysts. Even though a similar amount of sulfur was deposited in the catalysts poisoned at both 200 and 500 °C, a higher fraction of sulfur-free Cu species was seen for the catalyst poisoned at the higher temperature. Regeneration at 550 °C resulted in more sulfur-free Cu species in the catalyst poisoned at 500 °C, even though a higher amount of sulfur was detected in this catalyst compared to the regenerated catalyst poisoned at 200 °C. Inconsistencies between the amount of sulfur and the fraction of sulfur-free Cu species were attributed to the additional sulfur storage at sites that do not involve Cu. It was suggested that increased temperature of poisoning may facilitate the formation of Al sulfates along with Cu sulfates. These results provide the next step in detailed understanding of sulfur poisoning and regeneration of Cu-SSZ-13 catalysts.
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- Chen, Y. H., et al.
(författare)
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Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases
- 2023
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 55, s. 44-53
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic processes can influence disease risk and provide therapeutic targets. By conducting genome-wide association studies of 1,091 blood metabolites and 309 metabolite ratios, we identified associations with 690 metabolites at 248 loci and associations with 143 metabolite ratios at 69 loci. Integrating metabolite-gene and gene expression information identified 94 effector genes for 109 metabolites and 48 metabolite ratios. Using Mendelian randomization (MR), we identified 22 metabolites and 20 metabolite ratios having estimated causal effect on 12 traits and diseases, including orotate for estimated bone mineral density, alpha-hydroxyisovalerate for body mass index and ergothioneine for inflammatory bowel disease and asthma. We further measured the orotate level in a separate cohort and demonstrated that, consistent with MR, orotate levels were positively associated with incident hip fractures. This study provides a valuable resource describing the genetic architecture of metabolites and delivers insights into their roles in common diseases, thereby offering opportunities for therapeutic targets.
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- Gomez, A, et al.
(författare)
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ASSOCIATION OF OVERWEIGHT/OBESITY WITH IMPAIRED HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 664-665
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Patients with systemic lupus erythematosus (SLE) experience a considerably impaired health-related quality of life (HRQoL) compared with the general population. Previous literature has implied an association between high body mass index (BMI) and HRQoL diminutions. However, data are scarce and further exploration in large study populations and, importantly, with regard to the clinical significance of this association is needed.Objectives:The aim of this study was to determine whether overweight and/or obesity were associated with impaired physical and/or mental HRQoL aspects in the SLE population of two large clinical trials.Methods:We utilised pooled baseline data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) clinical trials of belimumab (N=1684). Access to data was granted by GlaxoSmithKline. The patients were stratified into four groups based on their body mass index (BMI), according to WHO guidelines. We conducted comparisons between non-overweight versus overweight, and non-obese versus obese SLE patients. HRQoL was self-reported using the Medical Outcomes Study (MOS) short form 36 (SF-36) health survey, the functional assessment of chronic illness therapy (FACIT)-Fatigue scale and the three-level EuroQol- 5 Dimension (EQ-5D) questionnaire. We explored whether the differences in scores were clinically meaningful using previously determined thresholds for minimal clinically important differences (MCIDs). The non-parametric Mann-Whitney U test was used for comparisons between different BMI groups. Linear regression analysis was next applied to test independence in multivariable models, adjusting for age, sex, ethnicity, disease duration, disease activity, organ damage and standard of care treatment.Results:Forty-four per cent (44%) of the patients had a BMI score over the normal range, and 18% were obese. The overweight group performed worse than the non-overweight with regard to FACIT-Fatigue scores (mean ± standard deviation: 27.7 ± 12.1 vs 32.0 ± 11.3; P<0.001), EQ-5D score (0.70 ± 0.19 vs 0.76 ± 0.18; P<0.001) and all SF-36 subscales and component summaries. The differences were greater than the MCIDs for physical component summary (PCS) scores (36.9 ± 9.3 vs 40.8 ± 9.6; P<0.001), physical functioning (53.3 ± 25.1 vs 63.6 ± 25-1; P<0.001), role physical (48.0 ± 27.1 vs 55.6 ± 26.9; P<0.001), bodily pain (43.8 ± 22.4 vs 52.5 ± 25.1; P<0.001), vitality (39.6 ± 21.7 vs 46.6 ± 21.3; P<0.001), and social functioning scores (55.8 ± 25.2 vs 62.6 ± 25.2; P<0.001). Likewise, obese patients reported worse FACIT-Fatigue scores (25.7 ± 11.9 vs 31.1 ± 11.6; P<0.001), EQ-5D scores (0.68 ± 0.20 vs 0.75 ± 0.18; P<0.001) and clinically important diminutions of HRQoL in all SF-36 items, except for the mental component summary (MCS), role emotional and mental health.In multivariable linear regression analysis, the overweight and obese group showed worse PCS scores (standardised coefficient: β=-0.09; P<0.001 and β=-0.13; P<0.001, respectively) and FACIT-Fatigue scores (β=-0.11; P<0.001 and β=-0.10; P<0.001, respectively), and overweight patients had significantly impaired MCS scores (β=-0.05; P=0.039), irrespective of other factors. High disease activity and organ damage were associated with impaired HRQoL in all aspects, while Asian patients reported better PCS scores (and β=0.29; P=0.007) and FACIT-Fatigue scores (β=0.33; P=0.002).Conclusion:BMI above normal was highly associated with HRQoL impairment, especially in physical aspects. Further survey to examine causality is warranted to support structured weight control strategies as an intervention towards a more favourable HRQoL.Disclosure of Interests:None declared
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- Hammarsjö, A., et al.
(författare)
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High diagnostic yield in skeletal ciliopathies using massively parallel genome sequencing, structural variant screening and RNA analyses
- 2021
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Ingår i: Journal of Human Genetics. - : Springer Nature. - 1434-5161 .- 1435-232X. ; 66:10, s. 995-1008
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Tidskriftsartikel (refereegranskat)abstract
- Skeletal ciliopathies are a heterogenous group of disorders with overlapping clinical and radiographic features including bone dysplasia and internal abnormalities. To date, pathogenic variants in at least 30 genes, coding for different structural cilia proteins, are reported to cause skeletal ciliopathies. Here, we summarize genetic and phenotypic features of 34 affected individuals from 29 families with skeletal ciliopathies. Molecular diagnostic testing was performed using massively parallel sequencing (MPS) in combination with copy number variant (CNV) analyses and in silico filtering for variants in known skeletal ciliopathy genes. We identified biallelic disease-causing variants in seven genes: DYNC2H1, KIAA0753, WDR19, C2CD3, TTC21B, EVC, and EVC2. Four variants located in non-canonical splice sites of DYNC2H1, EVC, and KIAA0753 led to aberrant splicing that was shown by sequencing of cDNA. Furthermore, CNV analyses showed an intragenic deletion of DYNC2H1 in one individual and a 6.7 Mb de novo deletion on chromosome 1q24q25 in another. In five unsolved cases, MPS was performed in family setting. In one proband we identified a de novo variant in PRKACA and in another we found a homozygous intragenic deletion of IFT74, removing the first coding exon and leading to expression of a shorter message predicted to result in loss of 40 amino acids at the N-terminus. These findings establish IFT74 as a new skeletal ciliopathy gene. In conclusion, combined single nucleotide variant, CNV and cDNA analyses lead to a high yield of genetic diagnoses (90%) in a cohort of patients with skeletal ciliopathies.
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| 7. |
- Hertzman, S., et al.
(författare)
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Nitrogen Solubility in Alloy Systems Relevant to Stainless Steels
- 2021
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Ingår i: Metallurgical and Materials Transactions. A. - : Springer Nature. - 1073-5623 .- 1543-1940. ; 52:9, s. 3811-3820
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Tidskriftsartikel (refereegranskat)abstract
- High-performance stainless steels are alloyed with nitrogen for several different reasons. For the austenitic grades, the kinetics of deleterious phase transformations are delayed, the strength is increased, and the corrosion resistance is improved. For duplex steels, the weldability and corrosion resistance depend directly on their nitrogen contents. Reliable databases are crucial for the development of new stainless steels and their processing. In order to calibrate the existing thermodynamic data, a series of experiments was undertaken. Several laboratory alloys in Fe–Cr–X systems, where X = Ni, Mn, Cu, were reacted with nitrogen gas at nitrogen activities 0.5 and 1 in the temperature range from 1050 °C to 1350 °C and subsequently analyzed for nitrogen solubility and phase constitution. A novel, simplified experimental technique was used, providing a dew point that is low enough to allow for fast nitrogen transport through the specimen surface, ensuring equilibrium conditions. The results are compared to thermodynamic equilibrium calculations.
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| 10. |
- Low, DY, et al.
(författare)
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Regional Diets Targeting Gut Microbial Dynamics to Support Prolonged Healthspan
- 2021
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Ingår i: Frontiers in microbiology. - : Frontiers Media SA. - 1664-302X. ; 12, s. 659465-
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Tidskriftsartikel (refereegranskat)abstract
- In the last 150 years, we have seen a significant increase in average life expectancy, associated with a shift from infectious to non-communicable diseases. The rising incidence of these diseases, for which age is often the largest risk factor, highlights the need for contemporary societies to improve healthy ageing for their growing silver generations. As ageing is an inevitable, non-reversing and highly individualised process, we need to better understand how non-genetic factors like diet choices and commensal gut microbes can modulate the biology of ageing. In this review, we discuss how geographical and ethnic variations influence habitual dietary patterns, nutrient structure, and gut microbial profiles with potential impact on the human healthspan. Several gut microbial genera have been associated with healthy elderly populations but are highly variable across populations. It seems unlikely that a universal pro-longevity gut microbiome exists. Rather, the optimal microbiome appears to be conditional on the microbial functionality acting on regional- and ethnicity-specific trends driven by cultural food context. We also highlight dietary and microbial factors that have been observed to elicit individual and clustered biological responses. Finally, we identify next generation avenues to modify otherwise fixed host functions and the individual ageing trajectory by manipulating the malleable gut microbiome with regionally adapted, personalised food intervention regimens targeted at prolonging human healthspan.
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