| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
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| 4. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 5. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 6. |
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| 7. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 8. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 10. |
- Abele, H., et al.
(författare)
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Particle physics at the European Spallation Source
- 2023
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Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 1023, s. 1-84
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Forskningsöversikt (refereegranskat)abstract
- Presently under construction in Lund, Sweden, the European Spallation Source (ESS) will be the world’s brightest neutron source. As such, it has the potential for a particle physics program with a unique reach and which is complementary to that available at other facilities. This paper describes proposed particle physics activities for the ESS. These encompass the exploitation of both the neutrons and neutrinos produced at the ESS for high precision (sensitivity) measurements (searches).
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| 11. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 12. |
- Liu, Kui, et al.
(författare)
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Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans
- 2009
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 119:4, s. 911-923
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Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.
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| 13. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 14. |
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| 15. |
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| 16. |
- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 17. |
- Leebens-Mack, James H., et al.
(författare)
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One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
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Tidskriftsartikel (refereegranskat)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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| 18. |
- Addazi, A., et al.
(författare)
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New high-sensitivity searches for neutrons converting into antineutrons and/or sterile neutrons at the HIBEAM/NNBAR experiment at the European Spallation Source
- 2021
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Ingår i: Journal of Physics G. - : Institute of Physics Publishing (IOPP). - 0954-3899 .- 1361-6471. ; 48:7
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Tidskriftsartikel (refereegranskat)abstract
- The violation of baryon number, , is an essential ingredient for the preferential creation of matter over antimatter needed to account for the observed baryon asymmetry in the Universe. However, such a process has yet to be experimentally observed. The HIBEAM/NNBAR program is a proposed two-stage experiment at the European Spallation Source to search for baryon number violation. The program will include high-sensitivity searches for processes that violate baryon number by one or two units: free neutron–antineutron oscillation () via mixing, neutron–antineutron oscillation via regeneration from a sterile neutron state (), and neutron disappearance (n → n'); the effective process of neutron regeneration () is also possible. The program can be used to discover and characterize mixing in the neutron, antineutron and sterile neutron sectors. The experiment addresses topical open questions such as the origins of baryogenesis and the nature of dark matter, and is sensitive to scales of new physics substantially in excess of those available at colliders. A goal of the program is to open a discovery window to neutron conversion probabilities (sensitivities) by up to three orders of magnitude compared with previous searches. The opportunity to make such a leap in sensitivity tests should not be squandered. The experiment pulls together a diverse international team of physicists from the particle (collider and low energy) and nuclear physics communities, while also including specialists in neutronics and magnetics.
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| 19. |
- Arzoumanian, Doris, et al.
(författare)
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Dust polarized emission observations of NGC 6334: BISTRO reveals the details of the complex but organized magnetic field structure of the high-mass star-forming hub-filament network
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 647
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Tidskriftsartikel (refereegranskat)abstract
- Context. Molecular filaments and hubs have received special attention recently thanks to new studies showing their key role in star formation. While the (column) density and velocity structures of both filaments and hubs have been carefully studied, their magnetic field (B-field) properties have yet to be characterized. Consequently, the role of B-fields in the formation and evolution of hub-filament systems is not well constrained. Aims. We aim to understand the role of the B-field and its interplay with turbulence and gravity in the dynamical evolution of the NGC 6334 filament network that harbours cluster-forming hubs and high-mass star formation. Methods. We present new observations of the dust polarized emission at 850 μm toward the 2 pc × 10 pc map of NGC 6334 at a spatial resolution of 0.09 pc obtained with the James Clerk Maxwell Telescope (JCMT) as part of the B-field In STar-forming Region Observations (BISTRO) survey. We study the distribution and dispersion of the polarized intensity (PI), the polarization fraction (PF), and the plane-of-The-sky B-field angle (χB_POS) toward the whole region, along the 10 pc-long ridge and along the sub-filaments connected to the ridge and the hubs. We derived the power spectra of the intensity and χBPOS along the ridge crest and compared them with the results obtained from simulated filaments. Results. The observations span 3 orders of magnitude in Stokes I and PI and 2 orders of magnitude in PF (from 0.2 to 20%). A large scatter in PI and PF is observed for a given value of I. Our analyses show a complex B-field structure when observed over the whole region ( 10 pc); however, at smaller scales (1 pc), χBPOS varies coherently along the crests of the filament network. The observed power spectrum of χBPOS can be well represented with a power law function with a slope of-1.33 ± 0.23, which is 20% shallower than that of I. We find that this result is compatible with the properties of simulated filaments and may indicate the physical processes at play in the formation and evolution of star-forming filaments. Along the sub-filaments, χBPOS rotates frombeing mostly perpendicular or randomly oriented with respect to the crests to mostly parallel as the sub-filaments merge with the ridge and hubs. This variation of the B-field structure along the sub-filaments may be tracing local velocity flows of infalling matter in the ridge and hubs. Our analysis also suggests a variation in the energy balance along the crests of these sub-filaments, from magnetically critical or supercritical at their far ends to magnetically subcritical near the ridge and hubs. We also detect an increase in PF toward the high-column density (NH2 â 1023 cm-2) star cluster-forming hubs. These latter large PF values may be explained by the increase in grain alignment efficiency due to stellar radiation from the newborn stars, combined with an ordered B-field structure. Conclusions. These observational results reveal for the first time the characteristics of the small-scale (down to 0.1 pc) B-field structure of a 10 pc-long hub-filament system. Our analyses show variations in the polarization properties along the sub-filaments that may be tracing the evolution of their physical properties during their interaction with the ridge and hubs. We also detect an impact of feedback from young high-mass stars on the local B-field structure and the polarization properties, which could put constraints on possible models for dust grain alignment and provide important hints as to the interplay between the star formation activity and interstellar B-fields.
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| 20. |
- Christopoulos, Arthur, et al.
(författare)
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THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.
- 2021
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Ingår i: British journal of pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 178 Suppl 1
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Forskningsöversikt (refereegranskat)abstract
- The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 21. |
- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 22. |
- Wang, J., et al.
(författare)
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Final report of the CCQM-K145 : Toxic and essential elements in bovine liver
- 2020
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Ingår i: Metrologia. - : IOP Publishing Ltd. - 0026-1394 .- 1681-7575. ; 57:1 A
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Tidskriftsartikel (refereegranskat)abstract
- Liver plays a major role in metabolism and acts as a source of energy for the body by storing glycogen. With the growing interest and investigation in the biological effects in recent years, it is important and necessary to develop accurate and comparable analytical methods for elements in bio-samples. It has, however, been 10 years since the tissue sample (bovine liver) of CCQM-K49 key comparison. The purpose of CCQM-K145 is to ensure the comparable and traceable measurement results for essential and toxic elements such as P, S, Zn, Mn, Ni, Mo, Sr, Cr, Co, Pb, As and Hg in bovine liver among NMIs and other designated measurement bodies worldwide. The comparison was agreed by IAWG as 6th IAWG Benchmarking Exercise with Zn and Ni as exemplary elements at the meeting in Korea in the early October 2016. The results of CCQM-K145 are expected to cover the measurement capability and support CMCs claiming for inorganic elements in the similar biological tissue materials and food samples. 30 NMIs and DIs registered in CCQM-K145. With respect to the methodology, a variety of techniques such as IDMS, ICP-OES, ICP-MS(non-ID), AAS and NAA were adopted by the participants. For Zn, Ni, Sr, Pb and Hg measurements, most participants chose ID-ICP-MS method, which showed the better performance in terms of consistency and reliability of the measurement results. In aspect of the traceability for the measurement results in CCQM-K145, most participants used their own (in house) CRMs or other NMI's CRMs to guarantee trace to SI unit. Most participants used similar matrix CRMs for quality control or method validation. Base on different statistic way to calculate the reference mass fraction values and associated uncertainties for each measurand, removal of the suspected extreme values, and discussion at the IAWG meetings, the median values are proposed as the KCRV for Zn, Ni, Mn, Mo, Cr, Pb and Hg; the arithmetic mean values are proposed as the KCRV for P, S, Sr, Co and As. In general, the performances of the majority of CCQM-K145 participants are very good, illustrating their measurement capabilities for Zn, Ni, P, S, Mn, Mo, Sr, Cr, As, Co, Pb and Hg in a complex biological tissue matrix. Bovine liver contains many kinds of nutrients and microelements, it can be regarded as a typical representative material of biological tissue and food. In CCQM-K145, the analytes involved alkali metals and transition elements, metalloids/semi-metals and non metals with a range of mass fraction from mg/g to μg/kg. CCQM-K145 also tested the ability of NMIs/DIs to determine elements that were easy to be lost and polluted, and interfered significantly. The chemical pretreatment methods of samples used in the comparison is suitable for general food and biological matrix samples. A variety of measurement methods used in the comparison represent the main instrumental technology for elemental analysis. Therefore, for supporting CMC claim, CCQM-K145 is readily applicable to measurement of more elements in a wide range of biological materials (including liquids and solids) and meat products. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
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| 23. |
- Alexander, Stephen P. H., et al.
(författare)
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The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
- 2023
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Ingår i: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 24. |
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| 25. |
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| 26. |
- Bakken, TE, et al.
(författare)
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Comparative cellular analysis of motor cortex in human, marmoset and mouse
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 111-
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Tidskriftsartikel (refereegranskat)abstract
- The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.
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| 27. |
- Arheimer, Berit, et al.
(författare)
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The IAHS Science for Solutions decade, with Hydrology Engaging Local People IN a Global world (HELPING)
- 2024
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Ingår i: Hydrological Sciences Journal. - 0262-6667 .- 2150-3435.
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Tidskriftsartikel (refereegranskat)abstract
- The new scientific decade (2023-2032) of the International Association of Hydrological Sciences (IAHS) aims at searching for sustainable solutions to undesired water conditions - may it be too little, too much or too polluted. Many of the current issues originate from global change, while solutions to problems must embrace local understanding and context. The decade will explore the current water crises by searching for actionable knowledge within three themes: global and local interactions, sustainable solutions and innovative cross-cutting methods. We capitalise on previous IAHS Scientific Decades shaping a trilogy; from Hydrological Predictions (PUB) to Change and Interdisciplinarity (Panta Rhei) to Solutions (HELPING). The vision is to solve fundamental water-related environmental and societal problems by engaging with other disciplines and local stakeholders. The decade endorses mutual learning and co-creation to progress towards UN sustainable development goals. Hence, HELPING is a vehicle for putting science in action, driven by scientists working on local hydrology in coordination with local, regional, and global processes.
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| 28. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 29. |
- Johnston, Jennifer J., et al.
(författare)
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Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations
- 2010
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 31:10, s. 1142-1154
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Tidskriftsartikel (refereegranskat)abstract
- A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial- digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria. Hum Mutat 31:1142-1154, 2010. (C) 2010 Wiley-Liss, Inc.
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| 30. |
- McKay, James D., et al.
(författare)
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A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
- 2011
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
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| 31. |
- Osorio, Ana, et al.
(författare)
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DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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| 32. |
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| 33. |
- Richards, Stephen, et al.
(författare)
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Genome Sequence of the Pea Aphid Acyrthosiphon pisum
- 2010
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
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Tidskriftsartikel (refereegranskat)abstract
- Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
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| 34. |
- Aleksandrova, Krasimira, et al.
(författare)
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A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 107:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. Results: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P-difference = .87) and after excluding case patients diagnosed within the first four follow-up years. Conclusions: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.
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| 35. |
- Davies, Stuart J., et al.
(författare)
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ForestGEO: Understanding forest diversity and dynamics through a global observatory network
- 2021
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207. ; 253
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Tidskriftsartikel (refereegranskat)abstract
- ForestGEO is a network of scientists and long-term forest dynamics plots (FDPs) spanning the Earth's major forest types. ForestGEO's mission is to advance understanding of the diversity and dynamics of forests and to strengthen global capacity for forest science research. ForestGEO is unique among forest plot networks in its large-scale plot dimensions, censusing of all stems ≥1 cm in diameter, inclusion of tropical, temperate and boreal forests, and investigation of additional biotic (e.g., arthropods) and abiotic (e.g., soils) drivers, which together provide a holistic view of forest functioning. The 71 FDPs in 27 countries include approximately 7.33 million living trees and about 12,000 species, representing 20% of the world's known tree diversity. With >1300 published papers, ForestGEO researchers have made significant contributions in two fundamental areas: species coexistence and diversity, and ecosystem functioning. Specifically, defining the major biotic and abiotic controls on the distribution and coexistence of species and functional types and on variation in species' demography has led to improved understanding of how the multiple dimensions of forest diversity are structured across space and time and how this diversity relates to the processes controlling the role of forests in the Earth system. Nevertheless, knowledge gaps remain that impede our ability to predict how forest diversity and function will respond to climate change and other stressors. Meeting these global research challenges requires major advances in standardizing taxonomy of tropical species, resolving the main drivers of forest dynamics, and integrating plot-based ground and remote sensing observations to scale up estimates of forest diversity and function, coupled with improved predictive models. However, they cannot be met without greater financial commitment to sustain the long-term research of ForestGEO and other forest plot networks, greatly expanded scientific capacity across the world's forested nations, and increased collaboration and integration among research networks and disciplines addressing forest science.
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| 36. |
- Hamdi, Yosr, et al.
(författare)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 37. |
- Huang, Chelsea X., et al.
(författare)
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TESS Spots a Hot Jupiter with an Inner Transiting Neptune
- 2020
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 892:1
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Tidskriftsartikel (refereegranskat)abstract
- Hot Jupiters are rarely accompanied by other planets within a factor of a few in orbital distance. Previously, only two such systems have been found. Here, we report the discovery of a third system using data from the Transiting Exoplanet Survey Satellite (TESS). The host star, TOI-1130, is an eleventh magnitude K-dwarf in Gaia G-band. It has two transiting planets: a Neptune-sized planet (3.65 ± 0.10 R\oplus) with a 4.1 days period, and a hot Jupiter (1.50-0.22+0.27 RJ) with an 8.4 days period. Precise radial-velocity observations show that the mass of the hot Jupiter is 0.974-0.044+0.043 MJ. For the inner Neptune, the data provide only an upper limit on the mass of 0.17 MJ (3σ). Nevertheless, we are confident that the inner planet is real, based on follow-up ground-based photometry and adaptive-optics imaging that rule out other plausible sources of the TESS transit signal. The unusual planetary architecture of and the brightness of the host star make TOI-1130 a good test case for planet formation theories, and an attractive target for future spectroscopic observations.
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| 38. |
- Marcouille, O., et al.
(författare)
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Production of high energy photons with in vacuum wigglers : From SOLEIL wiggler to MAXIV wiggler
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
-
Konferensbidrag (refereegranskat)abstract
- Small gap wigglers become more and more attractive to produce high photon fluxes in the hard X-ray photon range. They use magnet blocks of high magnetization which resists much better to heating (baking, synchrotron radiation) than in the past, produce high magnetic field with numerous periods and are very compact. They also are a very good alternative to superconducting technology which requires special infrastructure, heavy maintenance and is not running cost free. SOLEIL, operating presently at 2.75 GeV has designed and built an in-vacuum wiggler of 38 periods of 50 mm producing 2.1 T at a minimum gap of 5.5 mm to delivered photon beam between 20 keV and 50 keV. Already in operation, further improvements are presently in progress to push photons towards higher energy, in particular thanks to the operation at lower gap (4.5 mm). MAX IV and SOLEIL, in the frame of collaboration, ave built an upgraded version of the existing SOLEIL wiggler with the target to extend the spectral range at high energy (above 50 keV) but also at low energy (4 keV) with the same insertion device. The design of the existing magnetic system has been modified to reach 2.4 T at a minimum gap of 4.2 mm and includes taper operation to avoid undulator structure in the radiated spectrum at low energy.
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| 39. |
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| 40. |
- Stajich, Jason E., et al.
(författare)
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Insights into evolution of multicellular fungi from the assembled chromosomes of the mushroom Coprinopsis cinerea (Coprinus cinereus)
- 2010
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 107:26, s. 11889-11894
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Tidskriftsartikel (refereegranskat)abstract
- The mushroom Coprinopsis cinerea is a classic experimental model for multicellular development in fungi because it grows on defined media, completes its life cycle in 2 weeks, produces some 10(8) synchronized meiocytes, and can be manipulated at all stages in development by mutation and transformation. The 37-megabase genome of C. cinerea was sequenced and assembled into 13 chromosomes. Meiotic recombination rates vary greatly along the chromosomes, and retrotransposons are absent in large regions of the genome with low levels of meiotic recombination. Single-copy genes with identifiable orthologs in other basidiomycetes are predominant in low-recombination regions of the chromosome. In contrast, paralogous multicopy genes are found in the highly recombining regions, including a large family of protein kinases (FunK1) unique to multicellular fungi. Analyses of P450 and hydrophobin gene families confirmed that local gene duplications drive the expansions of paralogous copies and the expansions occur in independent lineages of Agaricomycotina fungi. Gene-expression patterns from microarrays were used to dissect the transcriptional program of dikaryon formation (mating). Several members of the FunK1 kinase family are differentially regulated during sexual morphogenesis, and coordinate regulation of adjacent duplications is rare. The genomes of C. cinerea and Laccaria bicolor, a symbiotic basidiomycete, share extensive regions of synteny. The largest syntenic blocks occur in regions with low meiotic recombination rates, no transposable elements, and tight gene spacing, where orthologous single-copy genes are overrepresented. The chromosome assembly of C. cinerea is an essential resource in understanding the evolution of multicellularity in the fungi.
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| 41. |
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| 42. |
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| 43. |
- Antoniou, Antonis C., et al.
(författare)
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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
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Tidskriftsartikel (refereegranskat)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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| 44. |
- Backman, Filip, 1991-, et al.
(författare)
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The development of the NNBAR experiment
- 2022
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Ingår i: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- The NNBAR experiment for the European Spallation Source will search for free neutrons converting to antineutrons with a sensitivity improvement of three orders of magnitude compared to the last such search. This paper describes progress towards a conceptual design report for NNBAR. The design of a moderator, neutron reflector, beamline, shielding and annihilation detector is reported. The simulations used form part of a model which will be used for optimisation of the experiment design and quantification of its sensitivity.
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| 45. |
- Doi, Yasuo, et al.
(författare)
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The JCMT BISTRO Survey: Magnetic Fields Associated with a Network of Filaments in NGC 1333
- 2020
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 899:1
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Tidskriftsartikel (refereegranskat)abstract
- We present new observations of the active star formation region NGC 1333 in the Perseus molecular cloud complex from the James Clerk Maxwell Telescope B-Fields In Star-forming Region Observations (BISTRO) survey with the POL-2 instrument. The BISTRO data cover the entire NGC 1333 complex (∼1.5 pc ? 2 pc) at 0.02 pc resolution and spatially resolve the polarized emission from individual filamentary structures for the first time. The inferred magnetic field structure is complex as a whole, with each individual filament aligned at different position angles relative to the local field orientation. We combine the BISTRO data with low- and high- resolution data derived from Planck and interferometers to study the multiscale magnetic field structure in this region. The magnetic field morphology drastically changes below a scale of ∼1 pc and remains continuous from the scales of filaments (∼0.1 pc) to that of protostellar envelopes (∼0.005 pc or ∼1000 au). Finally, we construct simple models in which we assume that the magnetic field is always perpendicular to the long axis of the filaments. We demonstrate that the observed variation of the relative orientation between the filament axes and the magnetic field angles are well reproduced by this model, taking into account the projection effects of the magnetic field and filaments relative to the plane of the sky. These projection effects may explain the apparent complexity of the magnetic field structure observed at the resolution of BISTRO data toward the filament network.
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| 46. |
- Eswaraiah, Chakali, et al.
(författare)
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The JCMT BISTRO Survey: Revealing the Diverse Magnetic Field Morphologies in Taurus Dense Cores with Sensitive Submillimeter Polarimetry
- 2021
-
Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 912:2
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Tidskriftsartikel (refereegranskat)abstract
- We have obtained sensitive dust continuum polarization observations at 850 μm in the B213 region of Taurus using POL-2 on SCUBA-2 at the James Clerk Maxwell Telescope as part of the B-fields in STar-forming Region Observations (BISTRO) survey. These observations allow us to probe magnetic field (B-field) at high spatial resolution (∼2000 au or ∼0.01 pc at 140 pc) in two protostellar cores (K04166 and K04169) and one prestellar core (Miz-8b) that lie within the B213 filament. Using the Davis-Chandrasekhar-Fermi method, we estimate the B-field strengths in K04166, K04169, and Miz-8b to be 38 ± 14, 44 ± 16, and 12 ± 5 μG, respectively. These cores show distinct mean B-field orientations. The B-field in K04166 is well ordered and aligned parallel to the orientations of the core minor axis, outflows, core rotation axis, and large-scale uniform B-field, in accordance with magnetically regulated star formation via ambipolar diffusion taking place in K04166. The B-field in K04169 is found to be ordered but oriented nearly perpendicular to the core minor axis and large-scale B-field and not well correlated with other axes. In contrast, Miz-8b exhibits a disordered B-field that shows no preferred alignment with the core minor axis or large-scale field. We found that only one core, K04166, retains a memory of the large-scale uniform B-field. The other two cores, K04169 and Miz-8b, are decoupled from the large-scale field. Such a complex B-field configuration could be caused by gas inflow onto the filament, even in the presence of a substantial magnetic flux.
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| 47. |
- Fisher, Matthew C., et al.
(författare)
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Development and worldwide use of non-lethal, and minimal population-level impact, protocols for the isolation of amphibian chytrid fungi
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Parasitic chytrid fungi have emerged as a significant threat to amphibian species worldwide, necessitating the development of techniques to isolate these pathogens into culture for research purposes. However, early methods of isolating chytrids from their hosts relied on killing amphibians. We modified a pre-existing protocol for isolating chytrids from infected animals to use toe clips and biopsies from toe webbing rather than euthanizing hosts, and distributed the protocol to researchers as part of the BiodivERsA project RACE; here called the RML protocol. In tandem, we developed a lethal procedure for isolating chytrids from tadpole mouthparts. Reviewing a database of use a decade after their inception, we find that these methods have been applied across 5 continents, 23 countries and in 62 amphibian species. Isolation of chytrids by the non-lethal RML protocol occured in 18% of attempts with 207 fungal isolates and three species of chytrid being recovered. Isolation of chytrids from tadpoles occured in 43% of attempts with 334 fungal isolates of one species (Batrachochytrium dendrobatidis) being recovered. Together, these methods have resulted in a significant reduction and refinement of our use of threatened amphibian species and have improved our ability to work with this group of emerging pathogens.
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| 48. |
- Hart, Lucy J. F., et al.
(författare)
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Understanding the Role of Triplet-Triplet Annihilation in Non-Fullerene Acceptor Organic Solar Cells
- 2023
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Ingår i: Advanced Energy Materials. - : WILEY-V C H VERLAG GMBH. - 1614-6832 .- 1614-6840. ; 13:36
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Tidskriftsartikel (refereegranskat)abstract
- Non-fullerene acceptors (NFAs) have enabled power conversion efficiencies exceeding 19% in organic solar cells (OSCs). However, the open-circuit voltage of OSCs remains low relative to their optical gap due to excessive non-radiative recombination, and this now limits performance. Here, an important aspect of OSC design is considered, namely management of the triplet exciton population formed after non-geminate charge recombination. By comparing the blends PM6:Y11 and PM6:Y6, it is shown that the greater crystallinity of the NFA domains in PM6:Y11 leads to a higher rate of triplet-triplet annihilation (TTA). This is attributed to the four times larger ground state dipole moment of Y11 versus Y6, which improves the long range NFA out-of-plane ordering. Since TTA converts a fraction of the non-emissive triplet states into bright singlet states, it has the potential to reduce non-radiative voltage losses. Through a kinetic analysis of the recombination processes under 1-Sun illumination, a framework is provided for determining the conditions under which TTA may improve OSC performance. If these could be satisfied, TTA has the potential to reduce non-radiative voltage losses by up to several tens of millivolts.
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| 49. |
- Kirby, Andrew, et al.
(författare)
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Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:3, s. 299-303
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Tidskriftsartikel (refereegranskat)abstract
- Although genetic lesions responsible for some mendelian disorders can be rapidly discovered through massively parallel sequencing of whole genomes or exomes, not all diseases readily yield to such efforts. We describe the illustrative case of the simple mendelian disorder medullary cystic kidney disease type 1 (MCKD1), mapped more than a decade ago to a 2-Mb region on chromosome 1. Ultimately, only by cloning, capillary sequencing and de novo assembly did we find that each of six families with MCKD1 harbors an equivalent but apparently independently arising mutation in sequence markedly under-represented in massively parallel sequencing data: the insertion of a single cytosine in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (similar to 1.5-5 kb), GC-rich (>80%) coding variable-number tandem repeat (VNTR) sequence in the MUC1 gene encoding mucin 1. These results provide a cautionary tale about the challenges in identifying the genes responsible for mendelian, let alone more complex, disorders through massively parallel sequencing.
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| 50. |
- O'Hanlon, Simon J., et al.
(författare)
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Recent Asian origin of chytrid fungi causing global amphibian declines
- 2018
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 360:6389, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Globalized infectious diseases are causing species declines worldwide, but their source often remains elusive. We used whole-genome sequencing to solve the spatiotemporal origins of themost devastating panzootic to date, caused by the fungus Batrachochytrium dendrobatidis, a proximate driver of global amphibian declines. We traced the source of B. dendrobatidis to the Korean peninsula, where one lineage, BdASIA-1, exhibits the genetic hallmarks of an ancestral population that seeded the panzootic. We date the emergence of this pathogen to the early 20th century, coinciding with the global expansion of commercial trade in amphibians, and we show that intercontinental transmission is ongoing. Our findings point to East Asia as a geographic hotspot for B. dendrobatidis biodiversity and the original source of these lineages that now parasitize amphibians worldwide.
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