| 1. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 3. |
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- 2017
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In: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Journal article (peer-reviewed)
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| 4. |
- Abdesselam, A., et al.
(author)
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Engineering for the ATLAS SemiConductor Tracker (SCT) end-cap
- 2008
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In: Journal of Instrumentation. - 1748-0221. ; 3
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Journal article (peer-reviewed)abstract
- The ATLAS SemiConductor Tracker (SCT) is a silicon-strip tracking detector which forms part of the ATLAS inner detector. The SCT is designed to track charged particles produced in proton-proton collisions at the Large Hadron Collider (LHC) at CERN at an energy of 14 TeV. The tracker is made up of a central barrel and two identical end-caps. The barrel contains 2112 silicon modules, while each end-cap contains 988 modules. The overall tracking performance depends not only on the intrinsic measurement precision of the modules but also on the characteristics of the whole assembly, in particular, the stability and the total material budget. This paper describes the engineering design and construction of the SCT end-caps, which are required to support mechanically the silicon modules, supply services to them and provide a suitable environment within the inner detector. Critical engineering choices are highlighted and innovative solutions are presented - these will be of interest to other builders of large-scale tracking detectors. The SCT end-caps will be fully connected at the start of 2008. Further commissioning will continue, to be ready for proton-proton collision data in 2008.
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| 5. |
- Olalde, I., et al.
(author)
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The Beaker phenomenon and the genomic transformation of northwest Europe
- 2018
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 555:7695, s. 190-196
-
Journal article (peer-reviewed)abstract
- From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.
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| 6. |
- Romagnoni, A, et al.
(author)
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Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
-
Journal article (peer-reviewed)abstract
- Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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| 7. |
- Momozawa, Y, et al.
(author)
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IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
- 2018
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
-
Journal article (peer-reviewed)abstract
- GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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| 8. |
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| 9. |
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| 10. |
- Hawthorn, F., et al.
(author)
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TOI-836: A super-Earth and mini-Neptune transiting a nearby K-dwarf
- 2023
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 520:3, s. 3649-3668
-
Journal article (peer-reviewed)abstract
- We present the discovery of two exoplanets transiting TOI-836 (TIC 440887364) using data from TESS Sector 11 and Sector 38. TOI-836 is a bright (T = 8.5 mag), high proper motion (∼200 mas yr−1), low metallicity ([Fe/H]≈−0.28) K-dwarf with a mass of 0.68 ± 0.05 M and a radius of 0.67 ± 0.01 R. We obtain photometric follow-up observations with a variety of facilities, and we use these data sets to determine that the inner planet, TOI-836 b, is a 1.70 ± 0.07 R super-Earth in a 3.82-d orbit, placing it directly within the so-called ‘radius valley’. The outer planet, TOI-836 c, is a 2.59 ± 0.09 R mini-Neptune in an 8.60-d orbit. Radial velocity measurements reveal that TOI-836 b has a mass of 4.5 ± 0.9 M, while TOI-836 c has a mass of 9.6 ± 2.6 M. Photometric observations show Transit Timing Variations (TTVs) on the order of 20 min for TOI-836 c, although there are no detectable TTVs for TOI-836 b. The TTVs of planet TOI-836 c may be caused by an undetected exterior planet.
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| 11. |
- Chaturvedi, P., et al.
(author)
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TOI-1468: A system of two transiting planets, a super-Earth and a mini-Neptune, on opposite sides of the radius valley
- 2022
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
-
Journal article (peer-reviewed)abstract
- We report the discovery and characterization of two small transiting planets orbiting the bright M3.0V star TOI-1468 (LSPM J0106+1913), whose transit signals were detected in the photometric time series in three sectors of the TESS mission. We confirm the planetary nature of both of them using precise radial velocity measurements from the CARMENES and MAROON-X spectrographs, and supplement them with ground-based transit photometry. A joint analysis of all these data reveals that the shorter-period planet, TOI-1468 b (P-b = 1.88 d), has a planetary mass of M-b = 3.21 +/- 0.24M(circle plus) and a radius of R-b = 1.280(-0.039)(+0.038) R-circle plus, resulting in a density of rho(b) = 8.39(-0.92)(+1.05) g cm(-3), which is consistent with a mostly rocky composition. For the outer planet, TOI-1468 c (P-c = 15.53 d), we derive a mass of M-c = 6.64(-0.68)(+0.67) M-circle plus,aradius of R-c = 2.06 +/- 0.04 R-circle plus, and a bulk density of rho(c) = 2.00(-0.19)(+0.21) g cm(-3), which corresponds to a rocky core composition with a H/He gas envelope. These planets are located on opposite sides of the radius valley, making our system an interesting discovery as there are only a handful of other systems with the same properties. This discovery can further help determine a more precise location of the radius valley for small planets around M dwarfs and, therefore, shed more light on planet formation and evolution scenarios.
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| 12. |
- Tanskanen, T., et al.
(author)
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Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci
- 2018
-
In: International Journal of Cancer. - Stockholm : Wiley. - 0020-7136 .- 1097-0215. ; 142:3, s. 540-546
-
Journal article (peer-reviewed)abstract
- Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p=2.08 x 10(-4); OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50 x 10(-9); OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate<0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations.
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| 13. |
- Patterson, Nick, et al.
(author)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
-
In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
-
Journal article (peer-reviewed)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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| 14. |
- Downey, Harriet, et al.
(author)
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Training future generations to deliver evidence-based conservation and ecosystem management
- 2021
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In: Ecological Solutions and Evidence. - : Wiley. - 2688-8319. ; 2:1
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Research review (peer-reviewed)abstract
- 1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis.2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice.3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses.4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.
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| 15. |
- Franke, Andre, et al.
(author)
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Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
- 2010
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1118-1125
-
Journal article (peer-reviewed)abstract
- We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
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| 16. |
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| 17. |
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| 18. |
- Subjak, Jan, et al.
(author)
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TOI-503: The First Known Brown-dwarf Am-star Binary from the TESS Mission
- 2020
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In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 159:4
-
Journal article (peer-reviewed)abstract
- We report the discovery of an intermediate-mass transiting brown dwarf (BD), TOI-503b, from the TESS mission. TOI-503b is the first BD discovered by TESS, and it has circular orbit around a metallic-line A-type star with a period of P.=.3.6772.+/-.0.0001 days. The light curve from TESS indicates that TOI-503b transits its host star in a grazing manner, which limits the precision with which we measure the BD's radius ( = R 1.34+ R b 0.150.26 J). We obtained highresolution spectroscopic observations with the FIES, Ondr.ejov, PARAS, Tautenburg, and TRES spectrographs, and measured the mass of TOI-503b to be Mb.=.53.7.+/-.1.2 MJ. The host star has a mass of Ma.=.1.80.+/-.0.06Me, a radius of Ra.=.1.70.+/-.0.05Re, an effective temperature of Teff.=.7650.+/-.160 K, and a relatively high metallicity of 0.61.+/-.0.07 dex. We used stellar isochrones to derive the age of the system to be 180 Myr, which places its age between that of RIK 72b (a 10 Myr old BD in the Upper Scorpius stellar association) and AD 3116b (a 600 Myr old BD in the Praesepe cluster). Given the difficulty in measuring the tidal interactions between BDs and their host stars, we cannot precisely say whether this BD formed in situ or has had its orbit circularized by its host star over the relatively short age of the system. Instead, we offer an examination of plausible values for the tidal quality factor for the star and BD. TOI-503b joins a growing number of known short-period, intermediate-mass BDs orbiting mainsequence stars, and is the second such BD known to transit an A star, after HATS-70b. With the growth in the population in this regime, the driest region in the BD desert (35-55MJ sin i) is reforesting.
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| 19. |
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| 20. |
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| 21. |
- Naidu, R., et al.
(author)
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Per- and poly-fluoroalkyl substances (PFAS) : Current status and research needs
- 2020
-
In: Environmental Technology & Innovation. - : Elsevier BV. - 2352-1864. ; 19
-
Journal article (peer-reviewed)abstract
- An expert workshop focusing on per- and poly-fluoroalkyl substances (PFAS) was held in Adelaide, South Australia, Australia in September 2019 following the 8th International Contaminated Site Remediation Conference — CleanUp 2019. The workshop was organised by the Cooperative Research Centre for Contamination and Remediation of the Environment (CRC CARE) and was chaired by Professor Ravi Naidu, CEO and Managing Director of CRC CARE and Director of the Global Centre for Environmental Remediation at the University of Newcastle, NSW. The purpose of the workshop, which was attended by more than 50 experts in the field of contaminated land assessment and management, was to discuss the current state of play and research needs relating to PFAS contaminated sites. This paper provides a summary of the discussions and conclusions and lists actions and needs that the expert group identified as critical for pursuing successful PFAS management and remedy approaches.This paper is intended to capture the shared information, comments, and current thinking related to PFAS challenges and research needs as identified by the group of expert participants; the write up is not intended to be a complete dissertation on the science and work that has been carried out. With a fast-evolving subject and increased government and public attention on PFAS presence in the environment, the group was convened with the objective of providing value in contributing to solutions to the PFAS challenges that are faced both in Australia and internationally. The text contained herein provides references to observations and methods that the experts drew on in their discussions and in support of their commentary; documentation of the original references was not provided, and the reader should consult the scientific literature if further information and confirmation of observations is required. Following a brief on the background to PFAS challenges, the paper focusses on research gaps identified by experts with focus on Australian soils and groundwater including climatic patterns, an overview of PFAS research in Australia with emphasis on:RegulatoryAnalytical considerationsEcological and Human Health RisksFate and TransportRemediation and Risk Management.
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| 22. |
- Timofeeva, Maria N, et al.
(author)
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Recurrent Coding Sequence Variation Explains Only A Small Fraction of the Genetic Architecture of Colorectal Cancer.
- 2015
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
-
Journal article (peer-reviewed)abstract
- Whilst common genetic variation in many non-coding genomic regulatory regions are known to impart risk of colorectal cancer (CRC), much of the heritability of CRC remains unexplained. To examine the role of recurrent coding sequence variation in CRC aetiology, we genotyped 12,638 CRCs cases and 29,045 controls from six European populations. Single-variant analysis identified a coding variant (rs3184504) in SH2B3 (12q24) associated with CRC risk (OR = 1.08, P = 3.9 × 10(-7)), and novel damaging coding variants in 3 genes previously tagged by GWAS efforts; rs16888728 (8q24) in UTP23 (OR = 1.15, P = 1.4 × 10(-7)); rs6580742 and rs12303082 (12q13) in FAM186A (OR = 1.11, P = 1.2 × 10(-7) and OR = 1.09, P = 7.4 × 10(-8)); rs1129406 (12q13) in ATF1 (OR = 1.11, P = 8.3 × 10(-9)), all reaching exome-wide significance levels. Gene based tests identified associations between CRC and PCDHGA genes (P < 2.90 × 10(-6)). We found an excess of rare, damaging variants in base-excision (P = 2.4 × 10(-4)) and DNA mismatch repair genes (P = 6.1 × 10(-4)) consistent with a recessive mode of inheritance. This study comprehensively explores the contribution of coding sequence variation to CRC risk, identifying associations with coding variation in 4 genes and PCDHG gene cluster and several candidate recessive alleles. However, these findings suggest that recurrent, low-frequency coding variants account for a minority of the unexplained heritability of CRC.
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| 23. |
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| 24. |
- Augustin, Livia S. A., et al.
(author)
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Dietary Fibre Consensus from the International Carbohydrate Quality Consortium (ICQC)
- 2020
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In: Nutrients. - : MDPI. - 2072-6643. ; 12:9
-
Journal article (peer-reviewed)abstract
- Dietary fibre is a generic term describing non-absorbed plant carbohydrates and small amounts of associated non-carbohydrate components. The main contributors of fibre to the diet are the cell walls of plant tissues, which are supramolecular polymer networks containing variable proportions of cellulose, hemicelluloses, pectic substances, and non-carbohydrate components, such as lignin. Other contributors of fibre are the intracellular storage oligosaccharides, such as fructans. A distinction needs to be made between intrinsic sources of dietary fibre and purified forms of fibre, given that the three-dimensional matrix of the plant cell wall confers benefits beyond fibre isolates. Movement through the digestive tract modifies the cell wall structure and may affect the interactions with the colonic microbes (e.g., small intestinally non-absorbed carbohydrates are broken down by bacteria to short-chain fatty acids, absorbed by colonocytes). These aspects, combined with the fibre associated components (e.g., micronutrients, polyphenols, phytosterols, and phytoestrogens), may contribute to the health outcomes seen with the consumption of dietary fibre. Therefore, where possible, processing should minimise the degradation of the plant cell wall structures to preserve some of its benefits. Food labelling should include dietary fibre values and distinguish between intrinsic and added fibre. Labelling may also help achieve the recommended intake of 14 g/1000 kcal/day.
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| 25. |
- Augustin, L S A, et al.
(author)
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Glycemic index, glycemic load and glycemic response: An International Scientific Consensus Summit from the International Carbohydrate Quality Consortium (ICQC).
- 2015
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In: Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 1590-3729 .- 0939-4753. ; 25:9, s. 795-815
-
Journal article (peer-reviewed)abstract
- Background and aims: The positive and negative health effects of dietary carbohydrates are of interest to both researchers and consumers. Methods: International experts on carbohydrate research held a scientific summit in Stresa, Italy, in June 2013 to discuss controversies surrounding the utility of the glycemic index (GI), glycemic load (GL) and glycemic response (GR). Results: The outcome was a scientific consensus statement which recognized the importance of postprandial glycemia in overall health, and the GI as a valid and reproducible method of classifying carbohydrate foods for this purpose. There was consensus that diets low in GI and GL were relevant to the prevention and management of diabetes and coronary heart disease, and probably obesity. Moderate to weak associations were observed for selected cancers. The group affirmed that diets low in GI and GL should always be considered in the context of diets otherwise understood as healthy, complementing additional ways of characterizing carbohydrate foods, such as fiber and whole grain content. Diets of low GI and GL were considered particularly important in individuals with insulin resistance. Conclusions: Given the high prevalence of diabetes and pre-diabetes worldwide and the consistency of the scientific evidence reviewed, the expert panel confirmed an urgent need to communicate information on GI and GL to the general public and health professionals, through channels such as national dietary guidelines, food composition tables and food labels.
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| 26. |
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| 27. |
- Benedict, Christian, et al.
(author)
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Acute sleep deprivation delays the glucagon-like peptide 1 peak response to breakfast in healthy men
- 2013
-
In: Nutrition & Diabetes. - : Springer Science and Business Media LLC. - 2044-4052. ; 3, s. e78-
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Previous experiments have demonstrated that acute sleep loss impairs glucose homeostasis and increases food intake in humans. The incretin hormone glucagon-like peptide 1 (GLP-1) enhances postprandial insulin secretion and promotes satiety. Hypothesizing that the detrimental metabolic effects of sleep curtailment imply alterations in GLP-1 signaling, we investigated 24-h serum total GLP-1 concentrations during total sleep deprivation (TSD) and a normal sleep/wake cycle (comprising similar to 8h of sleep) in 12 healthy young men. METHODS: Sessions started at 1800 h, and subjects were provided with standardized meals. Assessments of serum GLP-1 took place in 1.5- to 3-h intervals, focusing on the response to breakfast intake (3.8 MJ). RESULTS: Across conditions, 24-h concentration profiles of GLP-1 were characterized by the expected postprandial increases (P<0.001). Although there were no differences in magnitude between conditions (P>0.11), the postprandial GLP-1 peak response to breakfast intake was delayed by similar to 90 min following sleep loss in comparison with regular sleep (P<0.02). CONCLUSIONS: Results indicate that acute TSD exerts a mild, but discernible effect on the postprandial dynamics of circulating GLP-1 concentrations in healthy men.
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| 28. |
- Büntgen, Ulf, et al.
(author)
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Global wood anatomical perspective on the onset of the Late Antique Little Ice Age (LALIA) in the mid-6th century CE
- 2022
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In: Science Bulletin. - : Elsevier BV. - 2095-9273. ; 67:22, s. 2336-2344
-
Journal article (peer-reviewed)abstract
- Linked to major volcanic eruptions around 536 and 540 CE, the onset of the Late Antique Little Ice Age has been described as the coldest period of the past two millennia. The exact timing and spatial extent of this exceptional cold phase are, however, still under debate because of the limited resolution and geographical distribution of the available proxy archives. Here, we use 106 wood anatomical thin sections from 23 forest sites and 20 tree species in both hemispheres to search for cell-level fingerprints of ephemeral summer cooling between 530 and 550 CE. After cross-dating and double-staining, we identified 89 Blue Rings (lack of cell wall lignification), nine Frost Rings (cell deformation and collapse), and 93 Light Rings (reduced cell wall thickening) in the Northern Hemisphere. Our network reveals evidence for the strongest temperature depression between mid-July and early-August 536 CE across North America and Eurasia, whereas more localised cold spells occurred in the summers of 532, 540–43, and 548 CE. The lack of anatomical signatures in the austral trees suggests limited incursion of stratospheric volcanic aerosol into the Southern Hemisphere extra-tropics, that any forcing was mitigated by atmosphere-ocean dynamical responses and/or concentrated outside the growing season, or a combination of factors. Our findings demonstrate the advantage of wood anatomical investigations over traditional dendrochronological measurements, provide a benchmark for Earth system models, support cross-disciplinary studies into the entanglements of climate and history, and question the relevance of global climate averages.
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| 29. |
- Curia, S., et al.
(author)
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Green process for green materials : viable low-temperature lipase-catalysed synthesis of renewable telechelics in supercritical CO2
- 2015
-
In: Philosophical Transactions. Series A. - : Royal Society of London. - 1364-503X .- 1471-2962. ; 373:2057
-
Journal article (peer-reviewed)abstract
- We present a novel near-ambient-temperature approach to telechelic renewable polyesters by exploiting the unique properties of supercritical CO2 (scCO(2)). Bio-based commercially available monomers have been polymerized and functional telechelic materials with targeted molecular weight prepared by end-capping the chains with molecules containing reactive moieties in a one-pot reaction. The use of scCO(2) as a reaction medium facilitates the effective use of Candida antarctica Lipase B (CaLB) as a catalyst at a temperature as low as 35 degrees C, hence avoiding side reactions, maintaining the end-capper functionality and preserving the enzyme activity. The functionalized polymer products have been characterized by H-1 nuclear magnetic resonance spectroscopy, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry, gel permeation chromatography and differential scanning calorimetry in order to carefully assess their structural and thermal properties. We demonstrate that telechelic materials can be produced enzymatically at mild temperatures, in a solvent-free system and using renewably sourced monomers without pre-modification, by exploiting the unique properties of scCO(2). The macromolecules we prepare are ideal green precursors that can be further reacted to prepare useful bio-derived films and coatings.
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| 30. |
- Dunlop, Malcolm G, et al.
(author)
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Cumulative impact of 10 common genetic variants on colorectal cancer risk in 42,333 individuals from eight populations
- 2012
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In: Gut. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1468-3288 .- 0017-5749.
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data. DESIGN: Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39 266) and in combination with gender, age and FH (n=11 324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. RESULTS: The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2×10(-16)), confirmed in external validation sets (Sweden p=1.2×10(-6), Finland p=2×10(-5)). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. CONCLUSION: Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance.
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| 31. |
- Galvagnion, Celine, et al.
(author)
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Structural characterisation of α-synuclein-membrane interactions and the resulting aggregation using small angle scattering
- 2024
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In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 26:14, s. 10998-11013
-
Journal article (peer-reviewed)abstract
- The presence of amyloid fibrils is a hallmark of several neurodegenerative diseases. Some amyloidogenic proteins, such as alpha-synuclein and amyloid beta, interact with lipids, and this interaction can strongly favour the formation of amyloid fibrils. In particular the primary nucleation step, i.e. the de novo formation of amyloid fibrils, has been shown to be accelerated by lipids. However, the exact mechanism of this acceleration is still mostly unclear. Here we use a range of scattering methods, such as dynamic light scattering (DLS) and small angle X-ray and neutron scattering (SAXS and SANS) to obtain structural information on the binding of alpha-synuclein to model membranes formed from negatively charged lipids and their co-assembly into amyloid fibrils. We find that the model membranes take an active role in the reaction. The binding of alpha synuclein to the model membranes immediately induces a major structural change in the lipid assembly, which leads to a break-up into small and mostly disc- or rod-like lipid-protein particles. This transition can be reversed by temperature changes or proteolytic protein removal. Incubation of the small lipid-alpha-synuclein particles for several hours, however, leads to amyloid fibril formation, whereby the lipids are incorporated into the amyloid fibrils. alpha S binding to DLPS and DMPS leads to a ms fast reversible deformation into disks and rods. Upon further incubation, lipid rods elongate within the same time scale as that of amyloid formation confirming lipids co-assembly with alpha S into fibrils.
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| 32. |
- Galvagnion, Céline, et al.
(author)
-
Structural characterisation of α-synuclein-membrane interactions and the resulting aggregation using small angle scattering
- 2024
-
In: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 26:14, s. 10998-11013
-
Journal article (peer-reviewed)abstract
- The presence of amyloid fibrils is a hallmark of several neurodegenerative diseases. Some amyloidogenic proteins, such as α-synuclein and amyloid β, interact with lipids, and this interaction can strongly favour the formation of amyloid fibrils. In particular the primary nucleation step, i.e. the de novo formation of amyloid fibrils, has been shown to be accelerated by lipids. However, the exact mechanism of this acceleration is still mostly unclear. Here we use a range of scattering methods, such as dynamic light scattering (DLS) and small angle X-ray and neutron scattering (SAXS and SANS) to obtain structural information on the binding of α-synuclein to model membranes formed from negatively charged lipids and their co-assembly into amyloid fibrils. We find that the model membranes take an active role in the reaction. The binding of α synuclein to the model membranes immediately induces a major structural change in the lipid assembly, which leads to a break-up into small and mostly disc- or rod-like lipid-protein particles. This transition can be reversed by temperature changes or proteolytic protein removal. Incubation of the small lipid-α-synuclein particles for several hours, however, leads to amyloid fibril formation, whereby the lipids are incorporated into the amyloid fibrils.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Korell, Julia, et al.
(author)
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A population pharmacokinetic model for low-dose methotrexate and its polyglutamated metabolites in red blood cells.
- 2013
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In: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 52:6, s. 475-85
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Measurement of intracellular concentrations of methotrexate (MTX) and its polyglutamated metabolites (MTXGlu(2-5)) in red blood cells (RBCs) has been suggested as a potential means of monitoring low-dose MTX treatment of rheumatoid arthritis (RA). However, a possible correlation between RBC MTX and MTXGlu2-5 concentrations and clinical outcomes of MTX treatment in RA is debated. A better understanding of the dose-concentration-time relationship of MTX and MTXGlu(2-5) in RBCs by population pharmacokinetic modelling is desirable and will facilitate assessing a potential RBC concentration-effect relationship in the future.AIM: The purpose of this analysis was to describe the pharmacokinetics of MTX and MTXGlu(2-5) in RBCs. Secondary objectives included investigation of deglutamation reactions and the loss of MTX and MTXGlu(2-5) from the RBC.METHODS: A model was developed using NONMEM(®) version 7.2 based on RBC data obtained from 48 patients with RA receiving once-weekly low-dose MTX treatment. This model was linked to a fixed two-compartment model that was used to describe the pharmacokinetics of MTX in the plasma. A series of five compartments were used to describe the intracellular pharmacokinetics of MTX and MTXGlu(2-5) in RBCs. Biologically plausible covariates were tested for a significant effect on MTX plasma clearance and the intracellular volume of distribution of all MTX species in RBCs ([Formula: see text]). The developed model was used to test hypotheses related to the enzymatic deglutamation of MTXGlu(2-5) and potential loss of MTXGlu(2-5) from RBCs.RESULTS: The final RBC pharmacokinetic model required the intracellular volumes of distribution for the parent and metabolites to be set to the value estimated for the parent drug MTX alone, and the rate constants describing the polyglutamation steps were fixed at literature values. Significant covariates included effect of body surface area-adjusted estimated glomerular filtration rate on renal plasma clearance and effect of allometrically scaled total body weight with a fixed exponent of 0.75 on non-renal plasma clearance of MTX. The only significant covariate with an effect on [Formula: see text] was mean corpuscular volume (MCV). The model supported single deglutamation steps and a single mechanism of MTX and MTXGlu(2-5) loss from RBCs.CONCLUSIONS: The developed model enabled acceptable description of the intracellular kinetics of MTX and MTXGlu(2-5) in RBCs. In the future it can form the basis of a full pharmacokinetic-pharmacodynamic model to assess the time-RBC concentration-effect relationship of low-dose MTX treatment in RA.
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| 40. |
- Korell, Julia, et al.
(author)
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Comparison of intracellular methotrexate kinetics in red blood cells with the kinetics in other cell types
- 2014
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In: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 77:3, s. 493-497
-
Journal article (peer-reviewed)abstract
- AimTo assess the similarities in intracellular pharmacokinetics (PK) of methotrexate (MTX) in red blood cells (RBCs) and other cell lines. MethodsThree previously published PK models for intracellular MTX and MTX polyglutamate (MTXGlu(2-5)) concentrations were used: (i) a model for the kinetics in RBCs, (ii) a model for the kinetics in human breast cancer cells (HBCCs) and (iii) a model for the kinetics in various white blood cell (WBC) lines. All three models were used to simulate the response in a typical individual receiving 10mg oral MTX once weekly and the predicted steady-state concentrations (C-ss) and time to C-ss (t(ss)) were compared. ResultsThe HBCC model showed a lower C-ss for MTXGlu(2 and 3) and higher C-ss for MTXGlu(4 and 5) compared with the RBC PK model, while t(ss) and overall intracellular MTX exposure appeared similar. The WBC PK model showed much lower C-ss for the parent MTXGlu(1) and of t(ss) for all MTXGlu(n), as well as a much lower cumulative C-ss for MTXGlu(2-7) for the majority of the WBC cell lines. ConclusionRBC kinetics of MTX differ from the kinetics in other cell types such as WBCs and HBCCs to a variable degree. It is possible that similarly diverse profiles may exist across other cell lines, including those on the causal path in rheumatoid arthritis. Hence, there may not necessarily be a clear link between RBC MTX concentrations and disease control in rheumatoid arthritis.
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| 41. |
- Kozlov, Mikhail, V, et al.
(author)
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Climate shapes the spatiotemporal variation in color morph diversity and composition across the distribution range of Chrysomela lapponica leaf beetle
- 2022
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In: Insect Science. - : John Wiley & Sons. - 1672-9609 .- 1744-7917. ; 29:3, s. 942-955
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Journal article (peer-reviewed)abstract
- Color polymorphism offers rich opportunities for studying the eco-evolutionary mechanisms that drive the adaptations of local populations to heterogeneous and changing environments. We explored the color morph diversity and composition in a Chrysomela lapponica leaf beetle across its entire distribution range to test the hypothesis that environmental and climatic variables shape spatiotemporal variation in the phenotypic structure of a polymorphic species. We obtained information on 13 617 specimens of this beetle from museums, private collections, and websites. These specimens (collected from 1830-2020) originated from 959 localities spanning 33 degrees latitude, 178 degrees longitude, and 4200 m altitude. We classified the beetles into five color morphs and searched for environmental factors that could explain the variation in the level of polymorphism (quantified by the Shannon diversity index) and in the relative frequencies of individual color morphs. The highest level of polymorphism was found at high latitudes and altitudes. The color morphs differed in their climatic requirements; composition of colour morphs was independent of the geographic distance that separated populations but changed with collection year, longitude, mean July temperature and between-year temperature fluctuations. The proportion of melanic beetles, in line with the thermal melanism hypothesis, increased with increasing latitude and altitude and decreased with increasing climate seasonality. Melanic morph frequencies also declined during the past century, but only at high latitudes and altitudes where recent climate warming was especially strong. The observed patterns suggest that color polymorphism is especially advantageous for populations inhabiting unpredictable environments, presumably due to the different climatic requirements of coexisting color morphs.
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| 42. |
- Livesey, Geoffrey, et al.
(author)
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Dietary Glycemic Index and Load and the Risk of Type 2 Diabetes : A Systematic Review and Updated Meta-Analyses of Prospective Cohort Studies
- 2019
-
In: Nutrients. - : MDPI AG. - 2072-6643. ; 11:6
-
Research review (peer-reviewed)abstract
- Published meta-analyses indicate significant but inconsistent incident type-2 diabetes(T2D)-dietary glycemic index (GI) and glycemic load (GL) risk ratios or risk relations (RR). It is nowover a decade ago that a published meta-analysis used a predefined standard to identify validstudies. Considering valid studies only, and using random effects dose-response meta-analysis(DRM) while withdrawing spurious results (p < 0.05), we ascertained whether these relationswould support nutrition guidance, specifically for an RR > 1.20 with a lower 95% confidence limit>1.10 across typical intakes (approximately 10th to 90th percentiles of population intakes). Thecombined T2D-GI RR was 1.27 (1.15-1.40) (p < 0.001, n = 10 studies) per 10 units GI, while that forthe T2D-GL RR was 1.26 (1.15-1.37) (p < 0.001, n = 15) per 80 g/d GL in a 2000 kcal (8400 kJ) diet.The corresponding global DRM using restricted cubic splines were 1.87 (1.56-2.25) (p < 0.001, n =10) and 1.89 (1.66-2.16) (p < 0.001, n = 15) from 47.6 to 76.1 units GI and 73 to 257 g/d GL in a 2000kcal diet, respectively. In conclusion, among adults initially in good health, diets higher in GI or GLwere robustly associated with incident T2D. Together with mechanistic and other data, thissupports that consideration should be given to these dietary risk factors in nutrition advice.Concerning the public health relevance at the global level, our evidence indicates that GI and GLare substantial food markers predicting the development of T2D worldwide, for persons ofEuropean ancestry and of East Asian ancestry.
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| 43. |
- Livesey, Geoffrey, et al.
(author)
-
Dietary Glycemic Index and Load and the Risk of Type 2 Diabetes : Assessment of Causal Relations
- 2019
-
In: Nutrients. - : MDPI AG. - 2072-6643. ; 11:6
-
Research review (peer-reviewed)abstract
- While dietary factors are important modifiable risk factors for type 2 diabetes (T2D), the causal role of carbohydrate quality in nutrition remains controversial. Dietary glycemic index (GI) and glycemic load (GL) have been examined in relation to the risk of T2D in multiple prospective cohort studies. Previous meta-analyses indicate significant relations but consideration of causality has been minimal. Here, the results of our recent meta-analyses of prospective cohort studies of 4 to 26-y follow-up are interpreted in the context of the nine Bradford-Hill criteria for causality, that is: (1) Strength of Association, (2) Consistency, (3) Specificity, (4) Temporality, (5) Biological Gradient, (6) Plausibility, (7) Experimental evidence, (8) Analogy, and (9) Coherence. These criteria necessitated referral to a body of literature wider than prospective cohort studies alone, especially in criteria 6 to 9. In this analysis, all nine of the Hill's criteria were met for GI and GL indicating that we can be confident of a role for GI and GL as causal factors contributing to incident T2D. In addition, neither dietary fiber nor cereal fiber nor wholegrain were found to be reliable or effective surrogate measures of GI or GL. Finally, our cost-benefit analysis suggests food and nutrition advice favors lower GI or GL and would produce significant potential cost savings in national healthcare budgets. The high confidence in causal associations for incident T2D is sufficient to consider inclusion of GI and GL in food and nutrient-based recommendations.
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| 44. |
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| 45. |
- Manrique, Hector M., et al.
(author)
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The psychological foundations of reputation-based cooperation
- 2021
-
In: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : ROYAL SOC. - 0962-8436 .- 1471-2970. ; 376:1838
-
Research review (peer-reviewed)abstract
- Humans care about having a positive reputation, which may prompt them to help in scenarios where the return benefits are not obvious. Various game-theoretical models support the hypothesis that concern for reputation may stabilize cooperation beyond kin, pairs or small groups. However, such models are not explicit about the underlying psychological mechanisms that support reputation-based cooperation. These models therefore cannot account for the apparent rarity of reputation-based cooperation in other species. Here, we identify the cognitive mechanisms that may support reputation-based cooperation in the absence of language. We argue that a large working memory enhances the ability to delay gratification, to understand others mental states (which allows for perspective-taking and attribution of intentions) and to create and follow norms, which are key building blocks for increasingly complex reputation-based cooperation. We review the existing evidence for the appearance of these processes during human ontogeny as well as their presence in non-human apes and other vertebrates. Based on this review, we predict that most non-human species are cognitively constrained to show only simple forms of reputation-based cooperation. This article is part of the theme issue The language of cooperation: reputation and honest signalling.
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| 46. |
- Myrskylä, M., et al.
(author)
-
Advantages of later motherhood
- 2017
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In: Der Gynäkologe. - : Springer Science and Business Media LLC. - 0017-5994 .- 1433-0393. ; 50:10, s. 767-772
-
Journal article (peer-reviewed)abstract
- BackgroundIn high-income countries childbearing has been increasingly postponed since the 1970s and it is crucial to understand the consequences of this demographic shift. The literature has tended to characterize later motherhood as a significant health threat for children and parents.ObjectivesWe contribute to this debate by reviewing recent evidence suggesting that an older maternal age can also have positive effects.MaterialsLiterature linking the age at parenthood with the sociodemographic characteristics of the parents, with macrolevel interactions, and with subjective well-being.MethodsComprehensive review of the existing literature.ResultsRecent studies show that there can also be advantages associated with later motherhood. First, whilst in past older mothers had low levels of education and large families, currently older mothers tend to have higher education and smaller families than their younger peers. Consequently, children born to older mothers in the past tended to have worse outcomes than children born to younger mothers, whilst the opposite is true in recent cohorts. Second, postponement of childbearing means that the child is born at a later date and in a later birth cohort, and may benefit from secular changes in the macroenvironment. Evidence shows that when the positive trends in the macroenvironment are strong they overweigh the negative effects of reproductive ageing. Third, existing studies show that happiness increases around and after childbirth among older mothers, whereas for younger mothers the effect does not exist or is short-lived.ConclusionThere are important sociodemographic pathways associated with postponement of childbearing which might compensate or even more than compensate for the biological disadvantages associated with reproductive ageing.
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| 47. |
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| 48. |
- Pan, Shan, et al.
(author)
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Assessment of the Relationship Between Methotrexate Polyglutamates in Red Blood Cells and Clinical Response in Patients Commencing Methotrexate for Rheumatoid Arthritis
- 2014
-
In: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 53:12, s. 1161-1170
-
Journal article (peer-reviewed)abstract
- Therapeutic drug monitoring in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX, MTXGlu(1)) has not been established. In this study, we aim to explore the relationship between red blood cell (RBC) concentrations of MTX and its polyglutamate metabolites (MTXGlu (n) ; n = 2, 3, 4, 5) and clinical response in RA patients commencing MTX. The binding activity of MTXGlu (n) to three putative enzymes involved in the MTX mechanism of action-dihydrofolate reductase, thymidylate synthase, and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase-was simulated. RBC MTXGlu (n) concentrations that gave the highest inhibition activity across all three enzymes were linked with the disease activity score DAS28-3v (C-reactive protein [CRP]). A population pharmacokinetic-pharmacodynamic model was developed to describe the relationship between RBC MTX polyglutamate concentrations and clinical response in 12 RA patients commencing MTX. The highest inhibition activity was with RBC MTXGlu(3-5). These polyglutamates were further evaluated for their relationship with DAS28-3v (CRP). Three of the 12 patients had a high DAS28-3v (CRP) at baseline (mean = 6.1) and showed a delayed response to MTX treatment. The remaining nine patients with a lower DAS28-3v (CRP) baseline (mean = 3.6) showed an immediate response. The developed MTX pharmacokinetic-pharmacodynamic model provided an acceptable description of the observed DAS28-3v (CRP) across all patients. The developed model describes a longitudinal relationship between RBC MTXGlu(3-5) concentrations and DAS28-3v (CRP) in patients with RA commencing MTX. Further work is required to determine whether measurement of RBC MTX polyglutamates might be useful for dose individualisation in patients with RA.
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| 49. |
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| 50. |
- Roberts, Gilbert, et al.
(author)
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The benefits of being seen to help others: indirect reciprocity and reputation-based partner choice
- 2021
-
In: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : ROYAL SOC. - 0962-8436 .- 1471-2970. ; 376:1838
-
Research review (peer-reviewed)abstract
- When one individual helps another, it benefits the recipient and may also gain a reputation for being cooperative. This may induce others to favour the helper in subsequent interactions, so investing in being seen to help others may be adaptive. The best-known mechanism for this is indirect reciprocity (IR), in which the profit comes from an observer who pays a cost to benefit the original helper. IR has attracted considerable theoretical and empirical interest, but it is not the only way in which cooperative reputations can bring benefits. Signalling theory proposes that paying a cost to benefit others is a strategic investment which benefits the signaller through changing receiver behaviour, in particular by being more likely to choose the signaller as a partner. This reputation-based partner choice can result in competitive helping whereby those who help are favoured as partners. These theories have been confused in the literature. We therefore set out the assumptions, the mechanisms and the predictions of each theory for how developing a cooperative reputation can be adaptive. The benefits of being seen to be cooperative may have been a major driver of sociality, especially in humans. This article is part of the theme issue The language of cooperation: reputation and honest signalling.
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