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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 12. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 13. |
- Arnau-Soler, A, et al.
(författare)
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Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 14-
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Tidskriftsartikel (refereegranskat)abstract
- Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 × 10−6). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 × 10−9; total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 × 10−8; dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 × 10−8; dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 × 10−6). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 × 10−3). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.
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| 16. |
- Bhowmick, Asmit, et al.
(författare)
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Structural evidence for intermediates during O2 formation in photosystem II
- 2023
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 617:7961, s. 629-636
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Tidskriftsartikel (refereegranskat)abstract
- In natural photosynthesis, the light-driven splitting of water into electrons, protons and molecular oxygen forms the first step of the solar-to-chemical energy conversion process. The reaction takes place in photosystem II, where the Mn4CaO5 cluster first stores four oxidizing equivalents, the S0 to S4 intermediate states in the Kok cycle, sequentially generated by photochemical charge separations in the reaction center and then catalyzes the O–O bond formation chemistry. Here, we report room temperature snapshots by serial femtosecond X-ray crystallography to provide structural insights into the final reaction step of Kok’s photosynthetic water oxidation cycle, the S3→[S4]→S0 transition where O2 is formed and Kok’s water oxidation clock is reset. Our data reveal a complex sequence of events, which occur over micro- to milliseconds, comprising changes at the Mn4CaO5 cluster, its ligands and water pathways as well as controlled proton release through the hydrogen-bonding network of the Cl1 channel. Importantly, the extra O atom Ox, which was introduced as a bridging ligand between Ca and Mn1 during the S2→S3 transition, disappears or relocates in parallel with Yz reduction starting at approximately 700 μs after the third flash. The onset of O2 evolution, as indicated by the shortening of the Mn1–Mn4 distance, occurs at around 1,200 μs, signifying the presence of a reduced intermediate, possibly a bound peroxide.
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| 17. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 20. |
- Czamara, D, et al.
(författare)
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Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2548-
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
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| 21. |
- de Jong, S, et al.
(författare)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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| 26. |
- Graham, Marnie, 1980-
(författare)
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Postcolonial Nature Conservation and Collaboration in Urban Protected Areas : Everyday relations at Macassar Dunes/Wolfgat reserves, Cape Town, South Africa
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Protected areas and nature conservation are profoundly shaped by Western ideas, and are embedded within powerful discourses and colonising practices. This thesis examines how colonialism and apartheid shape contemporary practices of nature conservation in Cape Town in South Africa - its institutions, geographies and peoples. Through three empirical studies of collaborative arrangements at the Macassar Dunes/Wolfgat nature reserves, the thesis develops a postcolonial nature conservation perspective to explore how colonial legacies live on, are contested and are re-shaped through everyday practices. Departing from Margaret Kovach’s Indigenous methodology, interviews and participatory observations are used to focus on collaborations as they occur in the everyday relations between people and nature, on-reserve and in the adjoining township areas. This shows how collaborative arrangements bring together participants across historical and social divides, including municipal nature conservators and residents from apartheid-era racially-segregated townships. Results illustrate how colonising legacies persist at wider and institutional levels through exclusionary conservation practices, a focus on biodiversity preservation, and through sustained racialised relations. Nonetheless, this thesis argues that some of the most transformative collaborative practices occur within ad hoc, informal, and unmanaged interactions, involving deeply interpersonal and ethically challenging situations. Through these interactions, conservators and community participants are re-defining what it means to be ‘postcolonial nature conservators’ in Cape Town. These everyday practices engage difficult and fraught steps that allow us to consider what it means to belong, to reconcile and to be responsible to nature and to each other in a postcolonial city. With its focus on collaboration as everyday relations, the thesis brings to the literature one of the first in-depth studies of urban nature conservation from the rapidly growing cities of the global South. It contributes critical analyses to emerging debates around nature conservation, urban nature, and colonial legacies and opens crucial questions around expertise, knowledge, informality and poverty.
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| 30. |
- Hedman, Christina, 1966-, et al.
(författare)
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Epistemic Reciprocity Through a Decolonial Crip Literacy in Accommodated Language Education for Adults
- 2024
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Ingår i: Applied Linguistics. - 0142-6001 .- 1477-450X.
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Tidskriftsartikel (refereegranskat)abstract
- This linguistic ethnography was conducted in accommodated language education in Sweden, aimed at adult learners with deafness, hearing impairment, post-traumatic stress disorder, migration stress, or intellectual disability, here, focusing on the latter group, who attended Swedish language learning courses. We empirically investigate a decolonial crip literacy, by connecting language education to epistemic reciprocity. The decolonial lens is understood with regard to the marginalized and dis-abled body, under-represented in Applied Linguistics. More specifically, we focus on teacher positionality and ethical stance-taking among three of the teachers, to contribute an in-depth and situated account of a decolonial crip literacy, as counteracts of ableism and linguicism, and an orientation toward epistemic justice. Based on our linguistic ethnographic data, we suggest that the decolonial crip literacy project engages with disability-as-difference, positioning the dis-abled body as knower, via epistemic reciprocity, which is communicated through a multiplicity of communicative resources, materialities, and creativity. The paper contributes both to the theorizing of injustice in language education and to alternatives in pedagogical practice.
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| 31. |
- Hedman, Christina, 1966-, et al.
(författare)
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Epistemic Reciprocity Through a Decolonial Crip Literacy in Accommodated Language Education for Adults
- 2024
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Ingår i: Applied Linguistics. - 0142-6001 .- 1477-450X. ; , s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- This linguistic ethnography was conducted in accommodated language education in Sweden, aimed at adult learners with deafness, hearing impairment, post-traumatic stress disorder, migration stress, or intellectual disability, here, focusing on the latter group, who attended Swedish language learning courses. We empirically investigate a decolonial crip literacy, by connecting language education to epistemic reciprocity. The decolonial lens is understood with regard to the marginalized and dis-abled body, under-represented in Applied Linguistics. More specifcally, we focus on teacher positionality and ethical stance-taking among three of the teachers, to contribute an in-depth and situated account of a decolonial crip literacy, as counteracts of ableism and linguicism, and an orientation toward epistemic justice. Based on our linguistic ethnographic data, we suggest that the decolonial crip literacy project engages with disability-as-difference, positioning the dis-abled body as knower, via epistemic reciprocity, which is communicated through a multiplicity of communicative resources, materialities, and creativity. The paper contributes both to the theorizing of injustice in language education and to alternatives in pedagogical practice.
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| 32. |
- Ibrahim, Mohamed, et al.
(författare)
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Untangling the sequence of events during the S-2 -> S-3 transition in photosystem II and implications for the water oxidation mechanism
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 117:23, s. 12624-12635
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Tidskriftsartikel (refereegranskat)abstract
- In oxygenic photosynthesis, light-driven oxidation of water to molecular oxygen is carried out by the oxygen-evolving complex (OEC) in photosystem II (PS II). Recently, we reported the room-temperature structures of PS II in the four (semi)stable S-states, S-1, S-2, S-3, and S-0, showing that a water molecule is inserted during the S-2 -> S-3 transition, as a new bridging O(H)-ligand between Mn1 and Ca. To understand the sequence of events leading to the formation of this last stable intermediate state before O-2 formation, we recorded diffraction and Mn X-ray emission spectroscopy (XES) data at several time points during the S-2 -> S-3 transition. At the electron acceptor site, changes due to the two-electron redox chemistry at the quinones, QA and QB, are observed. At the donor site, tyrosine YZ and His190 H-bonded to it move by 50 mu s after the second flash, and Glu189 moves away from Ca. This is followed by Mn1 and Mn4 moving apart, and the insertion of OX(H) at the open coordination site of Mn1. This water, possibly a ligand of Ca, could be supplied via a "water wheel"-like arrangement of five waters next to the OEC that is connected by a large channel to the bulk solvent. XES spectra show that Mn oxidation (t of similar to 350 mu s) during the S-2 -> S-3 transition mirrors the appearance of OX electron density. This indicates that the oxidation state change and the insertion of water as a bridging atom between Mn1 and Ca are highly correlated.
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| 33. |
- Jencson, J. E., et al.
(författare)
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SPIRITS 16tn in NGC 3556 : A Heavily Obscured and Low-luminosity Supernova at 8.8 Mpc
- 2018
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 863:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the discovery by the SPitzer InfraRed Intensive Transients Survey (SPIRITS) of a likely supernova (SN) in NGC 3556 (M108) at only 8.8 Mpc that was not detected by optical searches. A luminous infrared (IR) transient at M [4.5] = −16.7 mag (Vega), SPIRITS 16tn is coincident with a dust lane in the inclined, star-forming disk of the host. Using observations in the IR, optical, and radio, we attempt to determine the nature of this event. We estimate A V ≈ 8–9 mag of extinction, placing it among the three most highly obscured IR-discovered SNe. The [4.5] light curve declined at a rate of 0.013 mag day−1, and the [3.6]–[4.5] color increased from 0.7 to 1.0 mag by 184.7 days post discovery. Optical/IR spectroscopy shows a red continuum but no clearly discernible features, preventing a definitive spectroscopic classification. Radio observations constrain the radio luminosity of SPIRITS 16tn to L ν 1024 erg s−1 Hz−1 between 3 and 15 GHz, excluding many varieties of core-collapse SNe. An SN Ia is ruled out by the observed IR color and lack of spectroscopic features from Fe-peak elements. SPIRITS 16tn was fainter at [4.5] than typical stripped-envelope SNe by ≈1 mag. Comparison of the spectral energy distribution to SNe II suggests that SPIRITS 16tn was both highly obscured and intrinsically dim, possibly akin to the low-luminosity SN 2005cs. We infer the presence of an IR dust echo powered by an initial peak luminosity of the transient of 5 × 1040 erg s−1 L peak 4 × 1043 erg s−1, consistent with the observed range for SNe II. This discovery illustrates the power of IR surveys to overcome the compounding effects of visible extinction and optically subluminous events in completing the inventory of nearby SNe.
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| 34. |
- Jencson, Jacob E., et al.
(författare)
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The SPIRITS Sample of Luminous Infrared Transients : Uncovering Hidden Supernovae and Dusty Stellar Outbursts in Nearby Galaxies
- 2019
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Ingår i: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 886:1
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Tidskriftsartikel (refereegranskat)abstract
- We present a systematic study of the most luminous (M-IR [Vega magnitudes] brighter than ?14) infrared (IR) transients discovered by the SPitzer InfraRed Intensive Transients Survey (SPIRITS) between 2014 and 2018 in nearby galaxies (D < 35 Mpc). The sample consists of nine events that span peak IR luminosities of M-[4.5],M-peak between ?14 and ?18.2, show IR colors between 0.2;<;([3.6]?[4.5]);<;3.0, and fade on timescales between 55 days;t(fade);<;480 days. The two reddest events (A(V) > 12) show multiple, luminous IR outbursts over several years and have directly detected, massive progenitors in archival imaging. With analyses of extensive, multiwavelength follow-up, we suggest the following possible classifications: five obscured core-collapse supernovae (CCSNe), two erupting massive stars, one luminous red nova, and one intermediate-luminosity red transient. We define a control sample of all optically discovered transients recovered in SPIRITS galaxies and satisfying the same selection criteria. The control sample consists of eight CCSNe and one Type;Iax SN. We find that 7 of the 13 CCSNe in the SPIRITS sample have lower bounds on their extinction of 2;A(V);<;8. We estimate a nominal fraction of CCSNe in nearby galaxies that are missed by optical surveys as high as
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| 37. |
- Paul, Prasanta, et al.
(författare)
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Development and Validation of a CE Method for the Determination of Tetracyclines with Capacitively Coupled Contactless Conductivity Detection
- 2019
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Ingår i: Chromatographia. - : SPRINGER HEIDELBERG. - 0009-5893 .- 1612-1112. ; 82:9, s. 1395-1403
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Tidskriftsartikel (refereegranskat)abstract
- In this study, a simple and robust capillary electrophoresis method with capacitively coupled contactless conductivity detection ((CD)-D-4) is developed for the determination of the tetracycline antibiotics (1) tetracycline, (2) chlortetracycline and (3) oxytetracycline. An uncoated, fused silica capillary (60.2 cm long, 75 mu m i.d.) and a solution of 50 mM tris(hydroxymethyl) aminomethane, 50 mM l-histidine and 5 mM methyl-beta-cyclodextrin, without pH adjustment (pH 8.76), was used as background electrolyte. Electrophoresis at + 25 kV showed a rapid analysis with sufficient resolution among the three antibiotics in the order of tetracycline, chlortetracycline and oxytetracycline. Successive inter-injection rinsing (20 psi) of the capillary ensured intra- and inter-day repeatability (0.9-2.2% RSD and 2.0-4.5% RSD, respectively, for relative peak areas). The method showed satisfactory performance in terms of selectivity, accuracy (99.3-101.4%) and linearity (R-2 = 0.999). Finally, the method was applied to commercial samples of tetracycline, oxytetracycline and chlortetracycline. This method can be applied for rapid quality control in developing countries in particular, and across the globe in general.
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| 39. |
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Ruptured Times : Advances in Visual Environmental Humanities
- 2021
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- This first issue of Annals of Crosscuts includes eleven richly textured films that speak from the growing environmental humanities with strong intent and originality. The films speaks to the theme of "Ruptured Times" and forms a testimony to the integrative ambitions of the environmental humanities. The contributors come from a range of disciplines, schools and practices including artistic research, urban and architectural studies, social movements of the urban south, political ecologies of water, studies of mining legacies, decolonial performance aesthetics, science studies and ethnographies of conservation, toxicity and more-than-human relations. Made in ten countries, at four continents, the films are the final outcomes of a collaborative peer-review process that started in the first half of 2019, screened at the Crosscuts festival in late 2019 and published as a film-based special issue at Zenodo, CERN, in 2021 with a reflection from chief editor Jacob von Heland.
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