| 1. |
- Ahnesjö, Jonas, 1969-, et al.
(author)
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The effect of exercising in different environments on heart rate and power output among older adults–a randomized crossover study
- 2022
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 17:11
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Journal article (peer-reviewed)abstract
- BackgroundA growing body of evidence suggests that exposure to nature is beneficial for human health. However, the observed health effect of nature may be mediated by physical activity and that humans are physically active at a higher intensity outdoors compared to when they are physical active indoors.ObjectiveThis study examines the variation of heart rate and power output for a fixed rating of perceived exertion in a group of healthy older adults in three different environments representing three levels of exposure to nature.MethodsTo this randomized, 3-by-3 crossover design study, healthy older adults (≥65 years) were recruited from local gyms. All participants participated in three experimental conditions; indoors, simulated outdoors and outdoor environments, in a randomized order. The participants exercised for 20 minutes at an intensity equivalent to a rating of 11–13 on the Borg scale for perceived exertion (RPE). Measurements of heart rate, power output (Watt) and ratings of perceived exertion were taken at minutes 1 to 6 and at minute 20. To examine the effect of the environment on heart rate and power, linear mixed models were used.ResultsIn all, 48 participants (56% females) were included in the analysis. No significant main effects on the outcomes were observed for power output (p = 0.073, η2 = 0.04) or heart rate (p = 0.067, η2 = 0.04)ConclusionNo significant effect on the outcomes was observed. However, borderline significant outcomes for power output or heart rate outdoors in nature, along with previous studies in the field, indicates that such an effect cannot be completely ruled out, but any effect is likely to be small. Future research examining health benefits of the independent exposure to nature are encouraged to adjust for the dose of physical activity.
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| 2. |
- Ara, Kazi Zubaida Gulshan, et al.
(author)
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Engineering CGTase to improve synthesis of alkyl glycosides
- 2021
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In: Glycobiology. - : Oxford University Press (OUP). - 1460-2423. ; 31:5, s. 603-612
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Journal article (peer-reviewed)abstract
- Alkyl glycoside surfactants with elongated carbohydrate chains are useful in different applications due to their improved biocompatibility. Cyclodextrin glucanotransferases can catalyse the elongation process through the coupling reaction. However, due to the presence of a hydrophobic tail, the interaction between an alkyl glycoside acceptor and the active site residues is weaker than the interaction with maltooligosaccharides at the corresponding site. Here we report the mutations of F197, G263 and E266 near the acceptor subsites in the CGTase CspCGT13 from Carboxydocella sp. The results showed that substitutions of both F197 and G263 were important for the binding of acceptor substrate dodecyl maltoside during coupling reaction. The double mutant F197Y/G263A showed enhanced coupling activity and displayed a 2-fold increase of the primary coupling product using γ-cyclodextrin as donor when compared to wildtype CspCGT13. Disproportionation activity was also reduced, which was also the case for another double mutant (F197Y/E266A) that however not showed the corresponding increase in coupling. A triple mutant F197Y/G263A/E266A maintained the increase in primary coupling product (1.8-fold increase) using dodecyl maltoside as acceptor, but disproportionation was approximately at the same level as in the double mutants. In addition, hydrolysis of starch was slightly increased by the F197Y and G263A substitutions, indicating that interactions at both positions influenced the selectivity between glycosyl and alkyl moieties.
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| 3. |
- Baccarini, Andrea, et al.
(author)
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Frequent new particle formation over the high Arctic pack ice by enhanced iodine emissions
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- In the central Arctic Ocean the formation of clouds and their properties are sensitive to the availability of cloud condensation nuclei (CCN). The vapors responsible for new particle formation (NPF), potentially leading to CCN, have remained unidentified since the first aerosol measurements in 1991. Here, we report that all the observed NPF events from the Arctic Ocean 2018 expedition are driven by iodic acid with little contribution from sulfuric acid. Iodic acid largely explains the growth of ultrafine particles (UFP) in most events. The iodic acid concentration increases significantly from summer towards autumn, possibly linked to the ocean freeze-up and a seasonal rise in ozone. This leads to a one order of magnitude higher UFP concentration in autumn. Measurements of cloud residuals suggest that particles smaller than 30nm in diameter can activate as CCN. Therefore, iodine NPF has the potential to influence cloud properties over the Arctic Ocean. Which vapors are responsible for new particle formation in the Arctic is largely unknown. Here, the authors show that the formation of new particles at the central Arctic Ocean is mainly driven by iodic acid and that particles smaller than 30nm in diameter can activate as cloud condensation nuclei.
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| 4. |
- Becker, Joel, et al.
(author)
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Resource profile and user guide of the Polygenic Index Repository
- 2021
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In: Nature Human Behaviour. - : Nature Research (part of Springer Nature). - 2397-3374. ; 51:6, s. 694-695
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Journal article (peer-reviewed)abstract
- Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs’ prediction accuracies, we constructed them using genome-wide association studies—some not previously published—from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the ‘additive SNP factor’. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
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| 5. |
- Berger, Karin, et al.
(author)
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Xylooligosaccharides Increase Bifidobacteria and Lachnospiraceae in Mice on a High-Fat Diet, with a Concomitant Increase in Short-Chain Fatty Acids, Especially Butyric Acid
- 2021
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In: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 69:12, s. 3617-3625
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Journal article (peer-reviewed)abstract
- Effects of xylooligosaccharides (XOSs) as well as a mixture of XOS, inulin, oligofructose, and partially hydrolyzed guar gum (MIX) in mice fed a high-fat diet (HFD) were studied. Control groups were fed an HFD or a low-fat diet. Special attention was paid to the cecal composition of the gut microbiota and formation of short-chain fatty acids, but metabolic parameters were also documented. The XOS group had significantly higher cecum levels of acetic, propionic, and butyric acids than the HFD group, and the butyric acid content was higher in the XOS than in the MIX group. The cecum microbiota of the XOS group contained more Bifidobacteria, Lachnospiraceae, and S24-7 bacteria than the HFD group. A tendency of lower body weight gain was observed on comparing the XOS and HFD groups. In conclusion, the XOS was shown to be a promising prebiotic candidate. The fiber diversity in the MIX diet did not provide any advantages compared to the XOS diet.
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| 6. |
- Bhattacharya, Abhishek, et al.
(author)
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Enzyme synergy for the production of arabinoxylo-oligosaccharides from highly substituted arabinoxylan and evaluation of their prebiotic potential
- 2020
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In: Lebensmittel-Wissenschaft + Technologie. - : Elsevier BV. - 0023-6438 .- 1096-1127. ; 131
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Journal article (peer-reviewed)abstract
- Wheat bran arabinoxylan can be converted by enzymatic hydrolysis into short arabinoxylo-oligosaccharides (AXOS) with prebiotic potential. Alkali extraction of arabinoxylan from wheat-bran offers advantages in terms of yield and results in arabinoxylan with highly-substituted regions which has been a challenge to hydrolyse using endoxylanases. We show that this hurdle can be overcome by selecting an arabinoxylanase that attacks these regions. The yield of AXOS can be increased by enzyme synergy, involving the hydrolysis of some arabinoxylan side groups. Thus, arabinoxylanase (CtXyl5At) from Clostridium thermocellum, belonging to subfamily 34 of glycoside hydrolase (GH) family 5 was investigated pertaining to its specificity for highly-substituted regions in the arabinoxylan-backbone. CtXyl5At preferentially hydrolysed the water-soluble fraction of alkali-extracted arabinoxylan. AXOS with DP 2-4 were determined as major products from CtXyl5At catalyzed hydrolysis. Increase in AXOS yield was observed with enzyme synergy, involving an initial treatment of soluble arabinoxylan with a GH43 alpha-L-arabinofuranosidase from Bifidobacterium adolescentis termed BaAXHd3 (30 degrees C, 6h), followed by hydrolysis with CtXyl5At (50 degrees C, 24h). The prebiotic potential of AXOS was shown by growth analysis using the human gut bacteria Bifidobacterium adolescentis ATCC 15703 and Roseburia hominis DSM 6839. Importantly, AXOS were utilized by the bacteria and short-chain fatty acids were produced.
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| 7. |
- Blomberg, Sara, et al.
(author)
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Bridging the Pressure Gap in CO Oxidation
- 2021
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In: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 11:15, s. 9128-9135
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Journal article (peer-reviewed)abstract
- Performing fundamental operando catalysis studies under realistic conditions is a key to further develop and increase the efficiency of industrial catalysts. Operando X-ray photoelectron spectroscopy (XPS) experiments have been limited to pressures, and the relevance for industrial applications has been questioned. Herein, we report on the CO oxidation experiment on Pd(100) performed at a total pressure of 1 bar using XPS. We investigate the light-off regime and the surface chemical composition at the atomistic level in the highly active phase. Furthermore, the observed gas-phase photoemission peaks of CO2, CO, and O2 indicate that the kinetics of the reaction during the light-off regime can be followed operando, and by studying the reaction rate of the reaction, the activation energy is calculated. The reaction was preceded by an in situ oxidation study in 7% O2 in He and a total pressure of 70 mbar to confirm the surface sensitivity and assignment of the oxygen-induced photoemission peaks. However, oxygen-induced photoemission peaks were not observed during the reaction studies, but instead, a metallic Pd phase is present in the highly active regime under the conditions applied. The novel XPS setup utilizes hard X-rays to enable high-pressure studies, combined with a grazing incident angle to increase the surface sensitivity of the measurement. Our findings demonstrate the possibilities of achieving chemical information of the catalyst, operando, on an atomistic level, under industrially relevant conditions.
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| 8. |
- Christmas, Matthew, et al.
(author)
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Evolutionary constraint and innovation across hundreds of placental mammals
- 2023
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
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Journal article (peer-reviewed)abstract
- Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (similar to 10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.
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| 9. |
- Gauffin, Helena, et al.
(author)
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Similar Profile and Magnitude of Cognitive Impairments in Focal and Generalized Epilepsy : A Pilot Study
- 2022
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In: Frontiers in Neurology. - Lausanne, Switzerland : Frontiers Media S.A.. - 1664-2295. ; 12
-
Journal article (peer-reviewed)abstract
- Introduction: Cognitive impairments in epilepsy are not well-understood. In addition, long-term emotional, interpersonal, and social consequences of the underlying disturbances are important to evaluate.Purpose: To compare cognitive function including language in young adults with focal or generalized epilepsy. In addition, quality of life and self-esteem were investigated.Patients and Methods: Young adults with no primary intellectual disability, 17 with focal epilepsy and 11 with generalized epilepsy participated and were compared to 28 healthy controls. Groups were matched on age (mean = 26 years), sex, and education. Participants were administered a battery of neuropsychological tasks and carried out self-ratings of quality of life, self-esteem, and psychological problems.Results: Similar impairments regarding cognitive function were noted in focal and generalized epilepsy. The cognitive domains tested were episodic long-term memory, executive functions, attention, working memory, visuospatial functions, and language. Both epilepsy groups had lower results compared to controls (effect sizes 0.24-1.07). The total number of convulsive seizures was predictive of episodic long-term memory function. Participants with focal epilepsy reported lower quality of life than participants with generalized epilepsy. Lowered self-esteem values were seen in both epilepsy groups and particularly in those with focal epilepsy. Along with measures of cognitive speed and depression, the total number of seizures explained more than 50% of variation in quality of life.Conclusion: Interestingly, similarities rather than differences characterized the widespread cognitive deficits that were seen in focal and generalized epilepsy, ranging from mild to moderate. These similarities were modified by quality of life and self-esteem. This study confirms the notion that epilepsy is a network disorder.
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| 10. |
- Guerini-Rocco, Elena, et al.
(author)
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Genomic aberrations and late recurrence in postmenopausal women with hormone receptor-positive early breast cancer: Results from the SOLE Trial.
- 2021
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In: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 27:2, s. 504-512
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Journal article (peer-reviewed)abstract
- Women with hormone-receptor-positive early breast cancers have a persistent risk of relapse and biomarkers for late recurrence are needed. We sought to identify tumor genomic aberrations associated with increased late recurrence risk.In a secondary analysis of Study of Letrozole Extension (SOLE) trial, a case-cohort-like sampling selected 598 primary breast cancer for targeted next-generation sequencing (NGS) analysis of gene mutations and copy number gains (CNG). Correlations of genomic aberrations with clinicopathologic factors and breast and distant recurrence free-intervals (BCFI and DRFI) were analyzed using weighted Cox models.Analysis of mutations and CNG was successfully performed for 403 and 350 samples, including 148 and 134 patients with breast cancer recurrences (median follow-up time: 5.2 years), respectively. The most frequent alterations were PIK3CA mutations (42%) and CNGs of CCND1 (15%), ERBB2 (10%), FGFR1 (8%) and MYC (8%). PIK3CA mutations and MYC CNG were associated with lower (p=0.03) and higher (p=0.004) tumor grade respectively; a higher Ki67 was seen in tumor with CCND1, ERBB2 and MYC CNGs (p=0.01, <0.001 and 0.03 respectively). FGFR1 CNG was associated with an increased risk of late events in univariate analyses (17/29 patients; BCFI: HR=3.2, 95%CI: 1.48-6.92, p =0.003; DRFI: HR=3.5, 95%CI: 1.61-7.75, p=0.002) and in multivariable models adjusted for clinicopathologic factors.Postmenopausal women with hormone receptor-positive early breast cancer harboring FGFR1 CNG had an increased risk of late recurrence despite extended therapy. FGFR1 CNG may represent a useful prognostic biomarker for late recurrence and a therapeutic target.
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| 11. |
- Halvorsen, Matthew, et al.
(author)
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Increased burden of ultra-rare structural variants localizing to boundaries of topologically associated domains in schizophrenia
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1, s. 1842-
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Journal article (peer-reviewed)abstract
- Despite considerable progress in schizophrenia genetics, most findings have been for large rare structural variants and common variants in well-imputed regions with few genes implicated from exome sequencing. Whole genome sequencing (WGS) can potentially provide a more complete enumeration of etiological genetic variation apart from the exome and regions of high linkage disequilibrium. We analyze high-coverage WGS data from 1162 Swedish schizophrenia cases and 936 ancestry-matched population controls. Our main objective is to evaluate the contribution to schizophrenia etiology from a variety of genetic variants accessible to WGS but not by previous technologies. Our results suggest that ultra-rare structural variants that affect the boundaries of topologically associated domains (TADs) increase risk for schizophrenia. Alterations in TAD boundaries may lead to dysregulation of gene expression. Future mechanistic studies will be needed to determine the precise functional effects of these variants on biology.
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| 12. |
- Holtstam, Dan, 1963-, et al.
(author)
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Fluorbritholite-(Nd), Ca2Nd3(SiO4)3F, a new and key mineral for neodymium sequestration in REE skarns
- 2023
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In: Mineralogical magazine. - 0026-461X .- 1471-8022. ; 87:5, s. 731-737
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Journal article (peer-reviewed)abstract
- Fluorbritholite-(Nd), ideally Ca2Nd3(SiO4)3F, is an approved mineral (IMA 2023-001) and constitutes a new member of the britholite group of the apatite supergroup. It occurs in skarn from the Malmkärra iron mine, Norberg, Västmanland (one of the Bastnäs-type deposits in Sweden), associated with calcite, dolomite, magnetite, lizardite, talc, fluorite, baryte, scheelite, gadolinite-(Nd) and other REE minerals. Fluorbritholite-(Nd) forms anhedral and small grains, rarely up to 250 µm across. They are brownish pink, transparent with a vitreous to greasy luster. The mineral is brittle, with an uneven or subconchoidal fracture, and lacks a cleavage. In thin section, the mineral is nonpleochroic, uniaxial (-). Dcalc = 4.92(1) g·cm-3 and ncalc = 1.795. The empirical chemical formula from electron microprobe (WDS) point analyses is (Ca1.62Nd0.97Ce0.83Y0.52Sm0.30Gd0.23Pr0.17La0.16Dy0.11Er0.03Tb0.03Ho0.01Yb0.01)Σ4.99(Si2.92P0.08As0.01)Σ3.01O12.00[O0.48F0.26(OH)0.14Cl0.10Br0.02]Σ1.00. The crystal structure of fluorbritholite-(Nd) was refined from single-crystal X-ray diffraction data to R1= 0.043 for 704 unique reflections. It belongs to the hexagonal system, space group P63/m, with unit cell parameters a = 9.5994(3), c = 6.9892(4) Å, V = 557.76(5) Å3 for Z = 2. Fluorbritholite-(Nd) and other britholite-group minerals are a major sink for neodymium in REE-bearing skarns of Bastnäs type.
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| 13. |
- Jiao, Enmiao, et al.
(author)
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Further Insight into Extractable (Organo)fluorine Mass Balance Analysis of Tap Water from Shanghai, China
- 2023
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In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 57:38, s. 14330-14339
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Journal article (peer-reviewed)abstract
- The ubiquitous occurrence of per- and polyfluoroalkyl substances (PFAS) and the detection of unexplained extractable organofluorine (EOF) in drinking water have raised growing concerns. A recent study reported the detection of inorganic fluorinated anions in German river systems, and therefore, in some samples, EOF may include some inorganic fluorinated anions. Thus, it might be more appropriate to use the term "extractable fluorine (EF) analysis" instead of the term EOF analysis. In this study, tap water samples (n = 39) from Shanghai were collected to assess the levels of EF/EOF, 35 target PFAS, two inorganic fluorinated anions (tetrafluoroborate (BF4-) and hexafluorophosphate (PF6-)), and novel PFAS through suspect screening and potential oxidizable precursors through oxidative conversion. The results showed that ultra-short PFAS were the largest contributors to target PFAS, accounting for up to 97% of ΣPFAS. To the best of our knowledge, this was the first time that bis(trifluoromethanesulfonyl)imide (NTf2) was reported in drinking water from China, and p-perfluorous nonenoxybenzenesulfonate (OBS) was also identified through suspect screening. Small amounts of precursors that can be oxidatively converted to PFCAs were noted after oxidative conversion. EF mass balance analysis revealed that target PFAS could only explain less than 36% of EF. However, the amounts of unexplained extractable fluorine were greatly reduced when BF4- and PF6- were included. These compounds further explained more than 44% of the EF, indicating the role of inorganic fluorinated anions in the mass balance analysis.
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| 14. |
- Jonsson, Lina, 1982, et al.
(author)
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Association of Occupational Dysfunction and Hospital Admissions With Different Polygenic Profiles in Bipolar Disorder.
- 2024
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In: The American journal of psychiatry. - 1535-7228. ; 181:7, s. 620-629
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Journal article (peer-reviewed)abstract
- Many but not all persons with bipolar disorder require hospital care because of severe mood episodes. Likewise, some but not all patients experience long-term occupational dysfunction that extends beyond acute mood episodes. It is not known whether these dissimilar outcomes of bipolar disorder are driven by different polygenic profiles. Here, polygenic scores (PGSs) for major psychiatric disorders and educational attainment were assessed for associations with occupational functioning and psychiatric hospital admissions in bipolar disorder.A total of 4,782 patients with bipolar disorder and 2,963 control subjects were genotyped and linked to Swedish national registers. Longitudinal measures from at least 10 years of registry data were used to derive percentage of years without employment, percentage of years with long-term sick leave, and mean number of psychiatric hospital admissions per year. Ordinal regression was used to test associations between outcomes and PGSs for bipolar disorder, schizophrenia, major depressive disorder, attention deficit hyperactivity disorder (ADHD), and educational attainment. Replication analyses of hospital admissions were conducted with data from the Bipolar Disorder Research Network cohort (N=4,219).Long-term sick leave and unemployment in bipolar disorder were significantly associated with PGSs for schizophrenia, ADHD, major depressive disorder, and educational attainment, but not with the PGS for bipolar disorder. By contrast, the number of hospital admissions per year was associated with higher PGSs for bipolar disorder and schizophrenia, but not with the other PGSs.Bipolar disorder severity (indexed by hospital admissions) was associated with a different polygenic profile than long-term occupational dysfunction. These findings have clinical implications, suggesting that mitigating occupational dysfunction requires interventions other than those deployed to prevent mood episodes.
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| 15. |
- Karlsson, Linn, et al.
(author)
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Physical and Chemical Properties of Cloud Droplet Residuals and Aerosol Particles During the Arctic Ocean 2018 Expedition
- 2022
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In: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 127:11
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Journal article (peer-reviewed)abstract
- Detailed knowledge of the physical and chemical properties and sources of particles that form clouds is especially important in pristine areas like the Arctic, where particle concentrations are often low and observations are sparse. Here, we present in situ cloud and aerosol measurements from the central Arctic Ocean in August–September 2018 combined with air parcel source analysis. We provide direct experimental evidence that Aitken mode particles (particles with diameters ≲70 nm) significantly contribute to cloud condensation nuclei (CCN) or cloud droplet residuals, especially after the freeze-up of the sea ice in the transition toward fall. These Aitken mode particles were associated with air that spent more time over the pack ice, while size distributions dominated by accumulation mode particles (particles with diameters ≳70 nm) showed a stronger contribution of oceanic air and slightly different source regions. This was accompanied by changes in the average chemical composition of the accumulation mode aerosol with an increased relative contribution of organic material toward fall. Addition of aerosol mass due to aqueous-phase chemistry during in-cloud processing was probably small over the pack ice given the fact that we observed very similar particle size distributions in both the whole-air and cloud droplet residual data. These aerosol–cloud interaction observations provide valuable insight into the origin and physical and chemical properties of CCN over the pristine central Arctic Ocean.
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| 16. |
- La Fleur, Linnea, et al.
(author)
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Targeting MARCO and IL-37R on immunosuppressive macrophages in lung cancer blocks regulatory T cells and supports cytotoxic lymphocyte function
- 2021
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In: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 81:4, s. 956-967
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Journal article (peer-reviewed)abstract
- The progression and metastatic capacity of solid tumors are strongly influenced by immune cells in the tumor microenvironment. In non-small cell lung cancer (NSCLC), accumulation of anti-inflammatory tumor-associated macrophages (TAMs) is associated with worse clinical outcome and resistance to therapy. Here we investigated the immune landscape of NSCLC in the presence of pro-tumoral TAMs expressing the macrophage receptor with collagenous structure (MARCO). MARCO-expressing TAM numbers correlated with increased occurrence of regulatory T cells and effector T cells and decreased Natural Killer (NK) cells in these tumors. Furthermore, transcriptomic data from the tumors uncovered a correlation between MARCO expression and the anti-inflammatory cytokine IL-37. In vitro studies subsequently showed that lung cancer cells polarized macrophages to express MARCO and gain an immune-suppressive phenotype through the release of IL-37. MARCO-expressing TAMs blocked cytotoxic T cell and NK cell activation, inhibiting their proliferation, cytokine production, and tumor killing capacity. Mechanistically, MARCO+ macrophages enhanced regulatory T (Treg) cell proliferation and IL-10 production and diminished CD8 T cell activities. Targeting MARCO or IL-37 receptor (IL-37R) by antibody or CRISPR knockout of IL-37 in lung cancer cell lines repolarized TAMs, resulting in recovered cytolytic activity and anti-tumoral capacity of NK cells and T cells and down-modulated Treg cell activities. In summary, our data demonstrate a novel immune therapeutic approach targeting human TAMs immune suppression of NK and T cell anti-tumor activities.
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| 17. |
- Linares-Pastén, Javier A, et al.
(author)
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Novel xylan-degrading enzymes from polysaccharide utilizing loci of Prevotella copri DSM18205
- 2021
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In: Glycobiology. - : Oxford University Press (OUP). - 1460-2423. ; 31:10, s. 1330-1349
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Journal article (peer-reviewed)abstract
- Prevotella copri is a bacterium that can be found in the human gastrointestinal tract (GIT). The role of P. copri in the GIT is unclear, and elevated numbers of the microbe have been reported both in dietary fiber-induced improvement in glucose metabolism but also in conjunction with certain inflammatory conditions. These findings raised our interest in investigating the possibility of P. copri to grow on xylan, and identify the enzyme systems playing a role in digestion of xylan-based dietary fibers. Two xylan degrading polysaccharide utilizing loci (PUL10 and 15) were found in the genome, with three and eight glycoside hydrolase (GH) -encoding genes, respectively. Three of them were successfully produced in Escherichia coli: One extracellular enzyme from GH43 (subfamily 12, in PUL10, 60 kDa) and two enzymes from PUL15, one extracellular GH10 (41 kDa), and one intracellular GH43 (subfamily 137 kDa). Based on our results, we propose that in PUL15, GH10 (1) is an extracellular endo-1,4-β-xylanase, that hydrolazes mainly glucuronosylated xylan polymers to xylooligosaccharides (XOS); while, GH43-1 in the same PUL, is an intracellular β-xylosidase, catalyzing complete hydrolysis of the XOS to xylose. In PUL10, the characterized GH43-12 is an arabinofuranosidase, with a role in degradation of arabinoxylan, catalyzing removal of arabinose-residues on xylan.
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| 18. |
- Luis, Ana S., et al.
(author)
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Sulfated glycan recognition by carbohydrate sulfatases of the human gut microbiota.
- 2022
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In: Nature chemical biology. - : Springer Science and Business Media LLC. - 1552-4469 .- 1552-4450. ; 18:8, s. 841-849
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Journal article (peer-reviewed)abstract
- Sulfated glycans are ubiquitous nutrient sources for microbial communities that have coevolved with eukaryotic hosts. Bacteria metabolize sulfated glycans by deploying carbohydrate sulfatases that remove sulfate esters. Despite the biological importance of sulfatases, the mechanisms underlying their ability to recognize their glycan substrate remain poorly understood. Here, we use structural biology to determine how sulfatases from the human gut microbiota recognize sulfated glycans. We reveal seven new carbohydrate sulfatase structures spanning four S1 sulfatase subfamilies. Structures of S1_16 and S1_46 represent novel structures of these subfamilies. Structures of S1_11 and S1_15 demonstrate how non-conserved regions of the protein drive specificity toward related but distinct glycan targets. Collectively, these data reveal that carbohydrate sulfatases are highly selective for the glycan component of their substrate. These data provide new approaches for probing sulfated glycan metabolism while revealing the roles carbohydrate sulfatases play in host glycan catabolism.
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| 19. |
- Norlander, Siri, et al.
(author)
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Novel thermostable GH5_34 arabinoxylanase with an atypical CBM6, displays activity on oat fibre xylan for prebiotic production
- 2023
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In: Glycobiology. - : Oxford University Press (OUP). - 1460-2423. ; 33:6, s. 490-502
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Journal article (peer-reviewed)abstract
- Carbohydrate active enzymes are valuable tools in cereal processing to valorise underutilized side streams. By solubilizing hemicellulose and modifying the fibre structure, novel food products with increased nutritional value can be created. In this study, a novel GH5_34 subfamily arabinoxylanase from Herbinix hemicellulosilytica, HhXyn5A, was identified, produced and extensively characterized, for the intended exploitation in cereal processing to solubilize potential prebiotic fibres; arabinoxylo-oligosaccharides (AXOS). The purified two-domain HhXyn5A (catalytic domain and CBM6) demonstrated high storage stability, showed a melting temperature Tm of 61 °C and optimum reaction conditions were determined to 55 °C and pH 6.5 on wheat arabinoxylan (WAX). HhXyn5A demonstrated activity on various commercial cereal arabinoxylans and produced prebiotic AXOS, while the sole catalytic domain of HhXyn5A did not demonstrate detectable activity. HhXyn5A demonstrated no side activity on oat β-glucan. In contrast to the commercially available homologue CtXyn5A, HhXyn5A gave a more specific HPAEC–PAD oligosaccharide product profile when using WAX and alkali extracted oat bran fibres as substrate. Results from multiple sequence alignment of GH5_34 enzymes, homology modelling of HhXyn5A and docking simulations with ligands XXXA3, XXXA3XX, and X5, concluded that the active site of HhXyl5A catalytic domain is highly conserved and can accommodate both shorter and longer AXOS ligands. However, significant structural dissimilarities between HhXyn5A and CtXyn5A in the binding cleft of CBM6, due to lack of important ligand interacting residues, is suggested to cause the observed differences in substrate specificity and product formation.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Salas-Veizaga, Daniel Martin, et al.
(author)
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A novel glycoside hydrolase 43-like enzyme from Clostridium boliviensis is an endo-xylanase and a candidate for xylooligosaccharide production from different xylan substrates
- 2024
-
In: Applied and Environmental Microbiology. - 0099-2240. ; 90:4
-
Journal article (peer-reviewed)abstract
- An uncharacterized gene encoding a glycoside hydrolase family 43-like enzyme from Clostridium boliviensis strain E-1 was identified from genomic sequence data, and the encoded enzyme, CbE1Xyn43-l, was produced in Escherichia coli. CbE1Xyn43-l (52.9 kDa) is a two-domain endo-β-xylanase consisting of a C-terminal CBM6 and a GH43-like catalytic domain. The positions of the catalytic dyad conserved in GH43, the catalytic base (Asp74), and proton donor (Glu240) were identified in alignments including GH43-enzymes of known 3D-structure from different subfamilies. CbE1Xyn43-l is active at pH 7.0–9.0, with optimum temperature at 65°C, and a more than 7 days’ half-life in irreversible deactivation studies at this temperature. The enzyme hydrolyzed birchwood xylan, quinoa stalks glucuronoarabinoxylan, and wheat arabinoxylan with xylotriose and xylotetraose as major hydrolysis products. CbE1Xyn43-l also released xylobiose from pNPX2 with low turnover (kcat of 0.044 s−1) but was inactive on pNPX, showing that a degree of polymerization of three (DP3) was the smallest hydrolyzable substrate. Divalent ions affected the specific activity on xylan substrates, which dependent on the ion could be increased or decreased. In conclusion, CbE1Xyn43-l from C. boliviensis strain E-1 is the first characterized member of a large group of homologous hypothetical proteins annotated as GH43-like and is a thermostable endo-xylanase, producing xylooligosaccharides of high DP (xylotriose and xylotetraose) producer.
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| 24. |
- Salas-Veizaga, Daniel Martin, et al.
(author)
-
Glucuronosylated and linear xylooligosaccharides from Quinoa stalks xylan as potential prebiotic source for growth of Bifidobacterium adolescentis and Weissella cibaria
- 2021
-
In: LWT - Food Science and Technology. - : Elsevier BV. - 0023-6438. ; 152
-
Journal article (peer-reviewed)abstract
- Quinoa stalks glucuronoarabinoxylan (QSGAX) has been extracted by alkali and further utilized for production of two-types of xylooligosaccharides (XOs): i) enzymatically produced glucuronosylated-XOs (GXOs), and ii) a dilute acid produced mixture of non-substituted/substituted XOs of different degree of polymerization (DP). The respective mixtures were then separately evaluated as prebiotics by analysis of their consumption by two phylogenetically different potential probiotic bacterial strains (Bifidobacterium adolescentis ATCC15703 and Weissella cibaria strain 92), from which release of short chain fatty acids (SCFA) was also monitored. The GXOs mixture was produced using a glucuronosyl-requiring family 30 glycoside hydrolase (GH) Bacteroides ovatus (BoXyn30A), while the XOs mixture was produced by a 30 min acid treatment of QSGAX with H2SO4 [24.5 g/L] at 90 °C. B. adolescentis consumed both GXOs and XOs (DP 2–6), in both cases releasing acetate, lactate, propionate, formate and butyrate as metabolic products. W. cibaria only consumed XOs (DP 2–4), releasing acetate, lactate and minor amounts of butyrate. This is the first study reporting the ability of GXOs consumption by B. adolescentis and shows the potential of GXOs to selectively stimulate B. adolescentis, while XOs stimulated both types of potential probiotics (B. adolescentis ATCC15703 and W. cibaria strain 92).
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| 25. |
- Sardari, Roya R.R., et al.
(author)
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HPAEC-PAD analysis for determination of the amino acid profiles in protein fractions from oat flour combined with correction of amino acid loss during hydrolysis
- 2023
-
In: Journal of Cereal Science. - : Elsevier BV. - 0733-5210. ; 109
-
Journal article (peer-reviewed)abstract
- Current derivatization-dependent approaches for amino acid composition analysis of cereal proteins have significant variability due to lack of direct analysis opportunities and loss of amino acids during protein-hydrolysis. To tackle these drawbacks, a novel direct, derivatization-free approach was successfully introduced, using HPAEC-PAD, and applied for analysis of hydrolyzed defatted oat flour and extracted flour protein fractions. The approach ensured reliable detection of amino acids, including L-tryptophan, as well as oxidation products of L-cysteine and L-methionine. A time course study, analysed by nonlinear least-square regression to determine rates of hydrolysis and loss of each amino acid, allowed comparison of the original mass fraction (AA0) of the respective amino acid in the oat flour mixture with the mass fraction obtained after 24 h hydrolysis (AA24). The difference between (AA0) and (AA24) was less than 0.05%, except for L-arginine (0.61%), glycine (0.14%), L-isoleucine (0.27%), and L-tryptophan (0.17%). The (AA0)s obtained corresponded to literature-data, and fitted with the amino acid composition estimated from deduced proteins encoded in the oat genome, except for L-arginine (27%) and L-glutamic acid/L-glutamine (10%). The amino acid composition estimation from sequence data indirectly confirmed that the high presence of L-arginine observed was a result of co-elution with unknown flour components.
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| 26. |
- Schiza, Aglaia, et al.
(author)
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Tumour-infiltrating lymphocytes add prognostic information for patients with low-risk DCIS : findings from the SweDCIS randomised radiotherapy trial
- 2022
-
In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 168, s. 128-137
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The immune microenvironment is an important modulator of tumour progression and treatment response. In invasive breast cancer, assessment of tumour-infiltrating lymphocytes (TILs) provides prognostic and predictive information. However, the clinical impact of TILs for ductal carcinoma in situ (DCIS) has not yet been demonstrated.PATIENTS AND METHODS: Post hoc analysis of the SweDCIS randomised radiotherapy trial including primary DCIS cases following breast-conserving surgery. TILs were assessed on haematoxylin-eosin sections (n = 711) according to the International Immuno-Oncology Biomarker Working Group guidelines. TILs-scores were analysed as continuous and dichotomised (≤5% versus >5%) variable regarding ipsilateral breast events (IBEs) as the predefined primary endpoint.RESULTS: Most women (61.9%) showed a TILs prevalence of ≤5%. High TILs-scores were associated with larger lesion size, human epidermal growth factor receptor 2 (HER2)-positivity, higher nuclear grade, and KI67-score. DCIS cases with high TILs prevalence had a significant increased cumulative IBE incidence at five years post-surgery (TILslow-versus TILshigh 9% versus 18%; p < 0.001). Among patients with HER2-negative DCIS, high TILs remained an independent poor prognosis marker for IBE risk in multivariable analysis with an adjusted hazard ratio of 2.41 [95%CI 1.17-4.95, p = 0.017]. Including TILs-status provided a refined stratification of patients with general low-risk DCIS (grade <3, size <25 mm, free margin). No interaction between TILs and radiotherapy benefits was detected.CONCLUSION: High TILs are associated with higher IBE risk over 5-years post-surgery, particularly for HER2-negative DCIS. Our data indicate that TILs should be integrated into the clinical workup to define patients with low-risk DCIS who can omit adjuvant therapy or patients with potential benefits from immunotherapy.
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| 27. |
- Schmitz, Eva, et al.
(author)
-
Altering the water holding capacity of potato pulp via structural modifications of the pectic polysaccharides
- 2021
-
In: Carbohydrate Polymer Technologies and Applications. - : Elsevier BV. - 2666-8939. ; 2
-
Journal article (peer-reviewed)abstract
- Potato pulp is a low value agricultural side stream with great valorisation potential as prebiotic food ingredient. An interesting functionality different from other prebiotics is its high water holding capacity (WHC). This study aims at exploring the relationship between physical and enzymatic modifications in the potato pulp and its WHC. Different temperature treatments and storage conditions were found to have a great influence on the WHC, freezing decreasing the WHC the least (15%) compared to fresh pulp. Ultrasonication of frozen pulp increased its WHC by 32%, while it did not have an effect on fresh pulp. Of the various tested enzymes, only protease led to an increase in WHC of fresh pulp (by 48%). The WHC of frozen and dry pulp could not be positively influenced by enzymatic treatment. Structurally, the potato pulps with increased WHC exhibited a larger surface area and more flaky structure.
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| 28. |
- Schmitz, Eva, et al.
(author)
-
Chemical and biochemical bleaching of oat hulls : The effect of hydrogen peroxide, laccase, xylanase and sonication on optical properties and chemical composition
- 2021
-
In: Biotechnology Reports. - : Elsevier BV. - 2215-017X. ; 30
-
Journal article (peer-reviewed)abstract
- Oat hulls are an excellent dietary fibre source for food supplements due to their rich lignocellulose composition as well as their great abundance as low-value agricultural side stream. For the production of white fibre supplements, a mild, but effective bleaching of the hulls is required. Chemical bleaching with hydrogen peroxide and sodium hydroxide was here found to be a suitable method increasing the CIE L* value (corresponds to a lightness value) above 85. The developed method is mild, retaining the hull's chemical composition. Only a minor decrease in coniferaldehyde structures upon bleaching was detected. Colour and chemical variabilities of oat hulls from different growth seasons did not influence the required bleaching conditions to achieve the desired optical properties. The inclusion of biochemical bleaching steps utilizing the xylanase Pentopan Mono BG, the laccase NS51003 and sonication was industrially not feasible as they could not reduce the required amount of subsequently applied bleaching chemicals significantly.
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| 29. |
- Schmitz, Eva, et al.
(author)
-
Lignocellulose degradation for the bioeconomy: The potential of enzyme synergies between xylanases, ferulic acid esterase and laccase for the production of arabinoxylo-oligosaccharides
- 2022
-
In: Bioresource Technology. - : Elsevier BV. - 0960-8524. ; 343
-
Journal article (peer-reviewed)abstract
- The success of establishing bioeconomies replacing current economies based on fossil resources largely depends on our ability to degrade recalcitrant lignocellulosic biomass. This study explores the potential of employing various enzymes acting synergistically on previously pretreated agricultural side streams (corn bran, oat hull, soluble and insoluble oat bran). Degrees of synergy (oligosaccharide yield obtained with the enzyme combination divided by the sum of yields obtained with individual enzymes) of up to 88 were obtained. Combinations of a ferulic acid esterase and xylanases resulted in synergy on all substrates, while a laccase and xylanases only acted synergistically on the more recalcitrant substrates. Synergy between different xylanases (glycoside hydrolase (GH) families 5 and 11) was observed particularly on oat hulls, producing a yield of 57%. The synergistic ability of the enzymes was found to be partly due to the increased enzyme stability when in combination with the substrates.
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| 30. |
- Schmitz, Eva, et al.
(author)
-
Novel Function of CtXyn5A from Acetivibrio thermocellus : Dual Arabinoxylanase and Feruloyl Esterase Activity in the Same Active Site
- 2023
-
In: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 24:3
-
Journal article (peer-reviewed)abstract
- Uncharacterized side activities of enzymes can have significant effects on reaction products and yields. Hence, their identification and characterization are crucial for the development of successful reaction systems. Here, we report the presence of feruloyl esterase activity in CtXyn5A from Acetivibrio thermocellus, besides its well-known arabinoxylanase activity, for the first time. Activity analysis of enzyme variants mutated in the catalytic nucleophile, Glu279, confirmed removal of all activity for E279A and E279L, and increased esterase activity while removing xylanase activity for E279S, allowing the proposal that both reaction types are catalysed in the same active site in two subsequential steps. The ferulic acid substituent is cleaved off first, followed by hydrolysis of the xylan backbone. The esterase activity on complex carbohydrates was found to be higher than the one of a designated ferulic acid esterase (E-FAERU). Therefore, we conclude that the enzyme exhibits a dual function rather than an esterase side activity.
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| 31. |
- Schmitz, Eva, et al.
(author)
-
Novel Function of CtXyn5A from Acetivibrio thermocellus: Dual Arabinoxylanase and Feruloyl Esterase Activity Occur in the Same Active Site
- 2022
-
Other publication (other academic/artistic)abstract
- Uncharacterized side activities of enzymes can have significant negative effects on reaction products and yields. Hence, their identification and characterization is crucial for the development of successful reaction systems. Here, we report the presence of feruloyl esterase activity in CtXyn5A from Acetivibrio thermocellus besides its well-known arabinoxylanase activity for the first time. Both reaction types appear to be catalysed in the same active site in two subsequential steps. The ferulic acid substituent is cleaved off first, followed by the hydrolysis of the xylan backbone. The esterase activity on complex carbohydrates was found to be higher than the one of a designated ferulic acid esterase (E-FAERU). Therefore, we conclude that the enzyme exhibits a dual function rather than an esterase side activity.
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| 32. |
- Schmitz, Eva, et al.
(author)
-
Ultrasound Assisted Alkaline Pre‐treatment Efficiently Solubilises Hemicellulose from Oat Hulls
- 2021
-
In: Waste and Biomass Valorization. - : Springer Science and Business Media LLC. - 1877-2641 .- 1877-265X. ; 12:10, s. 5371-5381
-
Journal article (peer-reviewed)abstract
- The establishment of sustainable bioeconomies requires the utilization of new renewable biomaterials. One such material currently seen as a waste product is oat hulls. Oat hulls exhibit a great potential for the production of dietary fibres due to their exceptionally large hemicellulose content (35%). Their recalcitrant structure however requires a suitable pre-treatment method to access and process the hemicellulose. After a screening of various physical, chemical and physico-chemical pre-treatment methods, including autoclaving, ultrasonication, microwave-, deep eutectic solvents-, as well as alkaline treatments, a combined ultrasonication and alkali pre-treatment method was here found to be the most suitable. A factorial design resulted in optimized conditions of 10 min ultrasonication in water, followed by an incubation in 5 M NaOH at 80 ºC for 9 h yielding solubilisation of 72% of all hemicellulose in the hulls. The method was shown to efficiently break the ester bonds between ferulic acid and the hemicellulose main chain, contributing to its solubilisation. Graphic Abstract: [Figure not available: see fulltext.]
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| 33. |
- Schmitz, Eva, et al.
(author)
-
Warming weathers changes the chemical composition of oat hulls
- 2020
-
In: Plant Biology. - : Wiley. - 1438-8677 .- 1435-8603. ; 22:6, s. 1086-1091
-
Journal article (peer-reviewed)abstract
- The current threats of climate change are driving attention away from the petrochemical industry towards more sustainable and bio‐based production processes for fuels and speciality chemicals. These processes require suitable low‐cost starting material. One potential material assessed here is the oat hull. Its overall chemical composition has so far not been fully characterized. Furthermore, it is not known how it is affected by extreme weather events.Oat hulls (Kerstin and Galant varieties) grown during ‘normal’ weather years (2016 and 2017) are compared to the harvest of the warmer and drier year (2018). Standard methods for determination of plant chemical composition, with focus on carbohydrate composition, are utilized.Oat hulls grown in ‘normal’ weather conditions (2017) are rich in lignocellulose (84%), consisting of 35% hemicellulose, 25% lignin and 23% cellulose. Arabinoxylan was found to be the major biopolymer (32%). However, this composition is greatly influenced by weather variations during the oat growth phase. A lignocellulose reduction of 25% was recorded in the warmer and drier 2018 harvest. Additionally, a 6.6‐fold increase in starch content, a four‐fold increase in protein content and a 60% decrease in phenolic content was noted.Due to its high lignocellulose composition, with an exceptionally large hemicellulose fraction, the chemical composition of oat hulls is unique among agricultural by‐products. However, this characteristic is significantly reduced when grown in warmer and drier weather, which could compromise its suitability for use in a successful biorefinery.
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| 34. |
- Siegel, Karolina, 1990-, et al.
(author)
-
Using Novel Molecular-Level Chemical Composition Observations of High Arctic Organic Aerosol for Predictions of Cloud Condensation Nuclei
- 2022
-
In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:19, s. 13888-13899
-
Journal article (peer-reviewed)abstract
- Predictions of cloud droplet activation in the late summertime (September) central Arctic Ocean are made using κ-Kohler theory with novel observations of the aerosol chemical composition from a high-resolution time-of-flight chemical ionization mass spectrometer with a filter inlet for gases and aerosols (FIGAERO-CIMS) and an aerosol mass spectrometer (AMS), deployed during the Arctic Ocean 2018 expedition onboard the Swedish icebreaker Oden. We find that the hygroscopicity parameter κ of the total aerosol is 0.39 ± 0.19 (mean ± std). The predicted activation diameter of ∼25 to 130 nm particles is overestimated by 5%, leading to an underestimation of the cloud condensation nuclei (CCN) number concentration by 4-8%. From this, we conclude that the aerosol in the High Arctic late summer is acidic and therefore highly cloud active, with a substantial CCN contribution from Aitken mode particles. Variability in the predicted activation diameter is addressed mainly as a result of uncertainties in the aerosol size distribution measurements. The organic κ was on average 0.13, close to the commonly assumed κ of 0.1, and therefore did not significantly influence the predictions. These conclusions are supported by laboratory experiments of the activation potential of seven organic compounds selected as representative of the measured aerosol.
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| 35. |
- Sigström, Robert, 1982, et al.
(author)
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Association Between Polygenic Risk Scores and Outcome of ECT
- 2022
-
In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 179:11, s. 844-852
-
Journal article (peer-reviewed)abstract
- Identifying biomarkers associated with response to electroconvulsive therapy (ECT) may aid clinical decisions. The authors examined whether greater polygenic liabilities for major depressive disorder, bipolar disorder, and schizophrenia are associated with improvement following ECT for a major depressive episode.Between 2013 and 2017, patients who had at least one treatment series recorded in the Swedish National Quality Register for ECT were invited to provide a blood sample for genotyping. The present study included 2,320 participants (median age, 51 years; 62.8% women) who had received an ECT series for a major depressive episode (77.1% unipolar depression), who had a registered treatment outcome, and whose polygenic risk scores (PRSs) could be calculated. Ordinal logistic regression was used to estimate the effect of PRS on Clinical Global Impressions improvement scale (CGI-I) score after each ECT series.Greater PRS for major depressive disorder was significantly associated with less improvement on the CGI-I (odds ratio per standard deviation, 0.89, 95% CI=0.82, 0.96; R2=0.004), and greater PRS for bipolar disorder was associated with greater improvement on the CGI-I (odds ratio per standard deviation, 1.14, 95% CI=1.05, 1.23; R2=0.005) after ECT. PRS for schizophrenia was not associated with improvement. In an overlapping sample (N=1,207) with data on response and remission derived from the self-rated version of the Montgomery-Åsberg Depression Rating Scale, results were similar except that schizophrenia PRS was also associated with remission.Improvement after ECT is associated with polygenic liability for major depressive disorder and bipolar disorder, providing evidence of a genetic component for ECT clinical response. These liabilities may be considered along with clinical predictors in future prediction models of ECT outcomes.
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| 36. |
- Song, Jie, et al.
(author)
-
Key subphenotypes of bipolar disorder are differentially associated with polygenic liabilities for bipolar disorder, schizophrenia, and major depressive disorder
- 2024
-
In: MOLECULAR PSYCHIATRY. - 1359-4184 .- 1476-5578.
-
Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) features heterogenous clinical presentation and course of illness. It remains unclear how subphenotypes associate with genetic loadings of BD and related psychiatric disorders. We investigated associations between the subphenotypes and polygenic risk scores (PRS) for BD, schizophrenia, and major depressive disorder (MDD) in two BD cohorts from Sweden (N = 5180) and the UK (N = 2577). Participants were assessed through interviews and medical records for inter-episode remission, psychotic features during mood episodes, global assessment of functioning (GAF, function and symptom burden dimensions), and comorbid anxiety disorders. Meta-analyses based on both cohorts showed that inter-episode remission and GAF-function were positively correlated with BD-PRS but negatively correlated with schizophrenia-PRS (SCZ-PRS) and MDD-PRS. Moreover, BD-PRS was negatively, and MDD-PRS positively, associated with the risk of comorbid anxiety disorders. Finally, SCZ-PRS was positively associated with psychotic symptoms during mood episodes. Assuming a higher PRS of certain psychiatric disorders in cases with a positive family history, we further tested the associations between subphenotypes in index BD people and occurrence of BD, schizophrenia, or MDD in their relatives using Swedish national registries. BD patients with a relative diagnosed with BD had: (1) higher GAF and lower risk of comorbid anxiety than those with a relative diagnosed with schizophrenia or MDD, (2) lower risk of psychotic symptoms than those with a relative diagnosed with schizophrenia. Our findings shed light on the genetic underpinnings of the heterogeneity in clinical manifestations and course of illness in BD, which ultimately provide insights for developing personalized approaches to the diagnosis and treatment.
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| 37. |
- Sullivan, Patrick F., et al.
(author)
-
Leveraging base-pair mammalian constraint to understand genetic variation and human disease
- 2023
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643, s. 367-
-
Journal article (peer-reviewed)abstract
- Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function, agnostic to cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% of the human genome as significantly constrained and likely functional. We compared phyloP scores to genome annotation, association studies, copy-number variation, clinical genetics findings, and cancer data. Constrained positions are enriched for variants that explain common disease heritability more than other functional annotations. Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.
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| 38. |
- Svantesson, Eleonor, et al.
(author)
-
Clinical Outcomes After Anterior Cruciate Ligament Injury: Panther Symposium ACL Injury Clinical Outcomes Consensus Group.
- 2020
-
In: Orthopaedic journal of sports medicine. - 2325-9671. ; 8:7
-
Journal article (peer-reviewed)abstract
- A stringent outcome assessment is a key aspect of establishing evidence-based clinical guidelines for anterior cruciate ligament (ACL) injury treatment. To establish a standardized assessment of clinical outcome after ACL treatment, a consensus meeting including a multidisciplinary group of ACL experts was held at the ACL Consensus Meeting Panther Symposium, Pittsburgh, Pennsylvania, USA, in June 2019. The aim was to establish a consensus on what data should be reported when conducting an ACL outcome study, what specific outcome measurements should be used, and at what follow-up time those outcomes should be assessed. The group reached consensus on 9 statements by using a modified Delphi method. In general, outcomes after ACL treatment can be divided into 4 robust categories: early adverse events, patient-reported outcomes (PROs), ACL graft failure/recurrent ligament disruption, and clinical measures of knee function and structure. A comprehensive assessment after ACL treatment should aim to provide a complete overview of the treatment result, optimally including the various aspects of outcome categories. For most research questions, a minimum follow-up of 2 years with an optimal follow-up rate of 80% is necessary to achieve a comprehensive assessment. This should include clinical examination, any sustained reinjuries, validated knee-specific PROs, and health-related quality of life questionnaires. In the midterm to long-term follow-up, the presence of osteoarthritis should be evaluated. This consensus paper provides practical guidelines for how the aforementioned entities of outcomes should be reported and suggests the preferred tools for a reliable and valid assessment of outcome after ACL treatment.
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| 39. |
- Uwayezu, Jean Noel, et al.
(author)
-
Combination of separation and degradation methods after PFAS soil washing
- 2023
-
In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 907
-
Journal article (peer-reviewed)abstract
- The current study evaluated a three-stage treatment to remediate PFAS-contaminated soil. The treatment consisted of soil washing, foam fractionation (FF), and electrochemical oxidation (EO). The possibility of replacing the third stage, i.e., EO, with an adsorption process was also assessed. The contamination in the studied soils was dominated by perfluorooctane sulfonate (PFOS), with a concentration of 760 and 19 μg kg−1 in soil I and in soil II, accounting for 97 % and 70 % of all detected per-and polyfluoroalkyl substances (PFAS). Before applying a pilot treatment of soil, soil washing was performed on a laboratory scale, to evaluate the effect of soil particle size, initial pH and a liquid-to-soil ratio (L/S) on the leachability of PFAS. A pilot washing system generated soil leachate that was subsequently treated using FF and EO (or adsorption) and then reused for soil washing. The results indicated that the leaching of PFAS occurred easier in 0.063–1 mm particles than in the soil particles having a size below 0.063 mm. Both alkaline conditions and a continual replacement of the leaching solution increased the leachability of PFAS. The analysis using one-way ANOVA showed no statistical difference in means of PFOS washed out in laboratory and pilot scales. This allowed estimating twenty washing cycles using 120 L water to reach 95 % PFOS removal in 60 kg soil. The aeration process removed 95–99 % PFOS in every washing cycle. The EO and adsorption processes achieved similar results removing up to 97 % PFOS in concentrated soil leachate. The current study demonstrated a multi-stage treatment as an effective and cost-efficient method to permanently clean up PFAS-contaminated soil.
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| 40. |
- Uwayezu, Jean Noel, et al.
(author)
-
Combining electrochemistry and ultraviolet radiation for the degradation of per- and poly-fluoroalkyl substances in contaminated groundwater and wastewater
- 2023
-
In: Journal of Water Process Engineering. - : Elsevier. - 2214-7144. ; 54
-
Journal article (peer-reviewed)abstract
- Electrochemical and ultraviolet-based methods are advanced oxidation processes emerging as viable water and wastewater treatment options. In this study, a combination of these two methods (EO-UV) using boron-doped diamond (BDD) electrodes and ultraviolet radiation at both 185 and 254 nm was assessed for the degradation of poly-fluoroalkyl substances (PFAS). Sodium persulfate (Na2S2O8) and sodium sulfate (Na2SO4) were used as electrolytes. The method was investigated on model solutions containing perfluorooctanoic acid (PFOA) and perfluorosulfonic acid (PFOS). The method's effectiveness was assessed by comparing PFAS removal efficiencies and energy demands associated with the use of separate and combined treatments. The results showed that the highest removal of PFOA and PFOS was 96 % and 85 % respectively, which was achieved using EO-UV and persulfate electrolytes. Average removal efficiencies were 1.5–2 times higher in EO-UV than in EO and 4–6 times higher than in UV treatment. The degradation of PFAS under EO-UV and persulfate applied to PFAS-contaminated groundwater and wastewater reached 94 % PFOA and 88 % PFOS in groundwater and 51 % and 63 % in wastewater. The removal of the sum of eleven PFAS was 86 % and 66 % in groundwater and wastewater, respectively. The combination of EO, UV and persulfate was the most effective option for PFAS treatment at lower energy consumption.
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| 41. |
- Uwayezu, Jean Noel, et al.
(author)
-
Electrochemical degradation of per- and poly-fluoroalkyl substances using boron-doped diamond electrodes
- 2021
-
In: Journal of Environmental Management. - : Elsevier. - 0301-4797 .- 1095-8630. ; 290
-
Journal article (peer-reviewed)abstract
- Electrochemical degradation using boron-doped diamond (BDD) electrodes has been proven to be a promising technique for the treatment of water contaminated with per- and poly-fluoroalkyl substances (PFAS). Various studies have demonstrated that the extent of PFAS degradation is influenced by the composition of samples and electrochemical conditions. This study evaluated the significance of several factors, such as the current density, initial concentration of PFAS, concentration of electrolyte, treatment time, and their interactions on the degradation of PFAS. A 24 factorial design was applied to determine the effects of the investigated factors on the degradation of perfluorooctanoic acid (PFOA) and generation of fluoride in spiked water. The best-performing conditions were then applied to the degradation of PFAS in wastewater samples. The results revealed that current density and time were the most important factors for PFOA degradation. In contrast, a high initial concentration of electrolyte had no significant impact on the degradation of PFOA, whereas it decreased the generation of F−. The experimental design model indicated that the treatment of spiked water under a current density higher than 14 mA cm−2 for 3–4 h could degrade PFOA with an efficiency of up to 100% and generate an F− fraction of approximately 40–50%. The observed high PFOA degradation and a low concentration of PFAS degradation products indicated that the mineralization of PFOA was effective. Under the obtained best conditions, the degradation of PFOA in wastewater samples was 44–70%. The degradation efficiency for other PFAS in these samples was 65–80% for perfluorooctane sulfonic acid (PFOS) and 42–52% for 6–2 fluorotelomer sulfonate (6-2 FTSA). The presence of high total organic carbon (TOC) and chloride contents was found to be an important factor affecting the efficiency of PFAS electrochemical degradation in wastewater samples. The current study indicates that the tested method can effectively degrade PFAS in both water and wastewater and suggests that increasing the treatment time is needed to account for the presence of other oxidizable matrices.
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| 42. |
- Uwayezu, Jean Noel, et al.
(author)
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Validation of UV/persulfate as a PFAS treatment of industrial wastewater and environmental samples
- 2023
-
In: Journal of Water Process Engineering. - : Elsevier. - 2214-7144. ; 53
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Journal article (peer-reviewed)abstract
- The contamination of natural water and industrial wastewater with per- and polyfluoroalkyl substances (PFAS) occurs globally. Thus, proper technologies are required to reduce PFAS in the environment and mitigate the adverse effects of these pollutants on human health and the environment. This study used a 23 full factorial design to evaluate the importance of operating factors including the level of persulfate (PS), the initial concentration of PFAS, and the time to the photochemical degradation of PFAS via ultraviolet irradiation at 185/254 nm assisted with persulfate (PS/UV method) in spiked solution. The method was then applied to break down PFAS in industrial wastewater, landfill leachate and groundwater samples using the highest factor levels applied in the 23 full factorial design. The results showed that the three investigated factors played an important role in the degradation of PFAS. The highest PFAS degradation was 57 % perfluorobutanoic acid (PFBA), 80 % perfluorooctanoic acid (PFOA) and 60 % perfluorooctane sulfonate (PFOS) using 10 mg L−1 PFAS, 5 g L−1 PS for 4 h. The defluorination also increased in the presence of PS but decreased in the presence of potassium hydrogen phthalate, nitrates, and chlorides. The PS/UV method decreased the concentration of PFAS in wastewater samples by 20–25 % PFOS and 13–15 % perfluorohexane sulfonate (PFHxS). PFAS degradation in wastewater improved with increasing treatment time. Under the PS/UV treatment, the degradation of major PFAS in groundwater was 94 % 6–2 FTS, 75 % PFOA, 62 % PFOS and 61 % PFHxS. The removal of major compounds in landfill leachate reached up to 12 % PFHxA, 32 % PFPeA, 56 % PFOA and 43 % PFOS. Our study indicated matrix effects leading to decreased PFAS degradation in different contaminated waters. The level of PS should also be controlled to an optimal value because higher levels led to a decrease in treatment efficiency.
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| 43. |
- Vigren, Patrick, et al.
(author)
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Experiences of awake surgery in non-tumoural epilepsy in eloquent localizations
- 2020
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In: Clinical neurology and neurosurgery. - : ELSEVIER. - 0303-8467 .- 1872-6968. ; 199
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Journal article (peer-reviewed)abstract
- Background: Whilst modern awake intraoperative mapping has been widely accepted and implemented in the last decades in neuro-oncology, sparse reports have been published on the safety and efficiency of this approach in epilepsy surgery. Method: This article reports four cases with different locations of epileptogenic zones as examples of possible safe and efficient resections. Result: The results of the resections on seizure control were Engel 1 (no disabling seizures) in all cases and no patient experienced significant neurological deficits. Discussion: The discussion focuses on aspects of the future of epilepsy surgery in a hodotopical paradigm.
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| 44. |
- Watts, Nick, et al.
(author)
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The 2020 report of The Lancet Countdown on health and climate change : responding to converging crises
- 2021
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 397:10269, s. 129-170
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Research review (peer-reviewed)abstract
- The Lancet Countdown is an international collaboration established to provide an independent, global monitoring system dedicated to tracking the emerging health profile of the changing climate.The 2020 report presents 43 indicators across five sections: climate change impacts, exposures, and vulnerabilities; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. This report represents the findings and consensus of the 35 leading academic institutions and UN agencies that make up The Lancet Countdown, and draws on the expertise of climate scientists, geographers, engineers, experts in energy, food, and transport, economists, social, and political scientists, data scientists, public health professionals, and doctors.
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