| 1. |
- 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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| 2. |
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| 3. |
- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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| 4. |
- Agudo, I., et al.
(författare)
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Panning for gold, but finding helium: Discovery of the ultra-stripped supernova SN 2019wxt from gravitational-wave follow-up observations
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 675
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Tidskriftsartikel (refereegranskat)abstract
- We present the results from multi-wavelength observations of a transient discovered during an intensive follow-up campaign of S191213g, a gravitational wave (GW) event reported by the LIGO-Virgo Collaboration as a possible binary neutron star merger in a low latency search. This search yielded SN 2019wxt, a young transient in a galaxy whose sky position (in the 80% GW contour) and distance (∼150 Mpc) were plausibly compatible with the localisation uncertainty of the GW event. Initially, the transienta's tightly constrained age, its relatively faint peak magnitude (Mi ∼ -16.7 mag), and the r-band decline rate of ∼1 mag per 5 days appeared suggestive of a compact binary merger. However, SN 2019wxt spectroscopically resembled a type Ib supernova, and analysis of the optical-near-infrared evolution rapidly led to the conclusion that while it could not be associated with S191213g, it nevertheless represented an extreme outcome of stellar evolution. By modelling the light curve, we estimated an ejecta mass of only ∼0.1 M·, with 56Ni comprising ∼20% of this. We were broadly able to reproduce its spectral evolution with a composition dominated by helium and oxygen, with trace amounts of calcium. We considered various progenitor channels that could give rise to the observed properties of SN 2019wxt and concluded that an ultra-stripped origin in a binary system is the most likely explanation. Disentangling genuine electromagnetic counterparts to GW events from transients such as SN 2019wxt soon after discovery is challenging: in a bid to characterise this level of contamination, we estimated the rate of events with a volumetric rate density comparable to that of SN 2019wxt and found that around one such event per week can occur within the typical GW localisation area of O4 alerts out to a luminosity distance of 500 Mpc, beyond which it would become fainter than the typical depth of current electromagnetic follow-up campaigns.
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| 5. |
- Fulton, Christopher J., et al.
(författare)
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Macroalgal meadow habitats support fish and fisheries in diverse tropical seascapes
- 2020
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Ingår i: Fish and Fisheries. - : Wiley. - 1467-2960 .- 1467-2979. ; 21:4, s. 700-717
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Tidskriftsartikel (refereegranskat)abstract
- Canopy-forming macroalgae can construct extensive meadow habitats in tropical seascapes occupied by fishes that span a diversity of taxa, life-history stages and ecological roles. Our synthesis assessed whether these tropical macroalgal habitats have unique fish assemblages, provide fish nurseries and support local fisheries. We also applied a meta-analysis of independent surveys across 23 tropical reef locations in 11 countries to examine how macroalgal canopy condition is related to the abundance of macroalgal-associated fishes. Over 627 fish species were documented in tropical macroalgal meadows, with 218 of these taxa exhibiting higher local abundance within this habitat (cf. nearby coral reef) during at least one life-history stage. Major overlap (40%-43%) in local fish species richness among macroalgal and seagrass or coral reef habitats suggest macroalgal meadows may provide an important habitat refuge. Moreover, the prominence of juvenile fishes suggests macroalgal meadows facilitate the triphasic life cycle of many fishes occupying diverse tropical seascapes. Correlations between macroalgal canopy structure and juvenile abundance suggests macroalgal habitat condition can influence levels of replenishment in tropical fish populations, including the majority of macroalgal-associated fishes that are targeted by commercial, subsistence or recreational fisheries. While many macroalgal-associated fishery species are of minor commercial value, their local importance for food and livelihood security can be substantial (e.g. up to 60% of landings in Kenyan reef fisheries). Given that macroalgal canopy condition can vary substantially with sea temperature, there is a high likelihood that climate change will impact macroalgal-associated fish and fisheries.
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| 6. |
- Wilson, Shaun K., et al.
(författare)
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The contribution of macroalgae-associated fishes to small-scale tropical reef fisheries
- 2022
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Ingår i: Fish and Fisheries. - : Wiley. - 1467-2960 .- 1467-2979. ; 23:4, s. 847-861
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Tidskriftsartikel (refereegranskat)abstract
- Macroalgae-dominated reefs are a prominent habitat in tropical seascapes that support a diversity of fishes, including fishery target species. To what extent, then, do macroalgal habitats contribute to small-scale tropical reef fisheries? To address this question we: (1) Quantified the macroalgae-associated fish component in catches from 133 small-scale fisheries, (2) Compared life-history traits relevant to fishing (e.g. growth, longevity) in macroalgal and coral-associated fishes, (3) Examined how macroalgae-associated species can influence catch diversity, trophic level and vulnerability and (4) Explored how tropical fisheries change with the expansion of macroalgal habitats using a case study of fishery-independent data for Seychelles. Fish that utilised macroalgal habitats comprise 24% of the catch, but very few fished species relied entirely on macroalgal or coral habitats post-settlement. Macroalgal and coral-associated fishes had similar life-history traits, although vulnerability to fishing declined with increasing contribution of macroalgae association to the catch, whilst mean trophic level and diversity peaked when macroalgal-associated fish accounted for 20%–30% of catches. The Seychelles case study revealed similar total fish biomass on macroalgal and coral reefs, although the biomass of primary target species increased as macroalgae cover expanded. Our findings reinforce that multiple habitat types are needed to support tropical fishery stability and sustainability. Whilst coral habitats have been the focus of tropical fisheries management, we show the potential for macroalgae-associated fish to support catch size and diversity in ways that reduce vulnerability to overfishing. This is pertinent to seascapes where repeated disturbances are facilitating the replacement of coral reef with macroalgal habitats.
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| 7. |
- Bammer, G., et al.
(författare)
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Expertise in research integration and implementation for tackling complex problems: when is it needed, where can it be found and how can it be strengthened?
- 2020
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Ingår i: Palgrave Communications. - : Springer Science and Business Media LLC. - 2055-1045. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Expertise in research integration and implementation is an essential but often overlooked component of tackling complex societal and environmental problems. We focus on expertise relevant to any complex problem, especially contributory expertise, divided into 'knowing-that' and 'knowing-how.' We also deal with interactional expertise and the fact that much expertise is tacit. We explore three questions. First, in examining 'when is expertise in research integration and implementation required?,' we review tasks essential (a) to developing more comprehensive understandings of complex problems, plus possible ways to address them, and (b) for supporting implementation of those understandings into government policy, community practice, business and social innovation, or other initiatives. Second, in considering 'where can expertise in research integration and implementation currently be found?,' we describe three realms: (a) specific approaches, including interdisciplinarity, transdisciplinarity, systems thinking and sustainability science; (b) case-based experience that is independent of these specific approaches; and (c) research examining elements of integration and implementation, specifically considering unknowns and fostering innovation. We highlight examples of expertise in each realm and demonstrate how fragmentation currently precludes clear identification of research integration and implementation expertise. Third, in exploring 'what is required to strengthen expertise in research integration and implementation?,' we propose building a knowledge bank. We delve into three key challenges: compiling existing expertise, indexing and organising the expertise to make it widely accessible, and understanding and overcoming the core reasons for the existing fragmentation. A growing knowledge bank of expertise in research integration and implementation on the one hand, and accumulating success in addressing complex societal and environmental problems on the other, will form a virtuous cycle so that each strengthens the other. Building a coalition of researchers and institutions will ensure this expertise and its application are valued and sustained.
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| 8. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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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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| 9. |
- Bergström, Anders, et al.
(författare)
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Origins and genetic legacy of prehistoric dogs
- 2020
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6516, s. 557-563
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Tidskriftsartikel (refereegranskat)abstract
- Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry.
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| 10. |
- Carleo, Ilaria, et al.
(författare)
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The Multiplanet System TOI-421*
- 2020
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 160:3
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations-comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echelle Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution echelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements-and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of P-b = 5.19672 +/- 0.00049 days, a mass of M-b = 7.17 +/- 0.66 M-circle plus, and a radius of R-b = R-circle plus, whereas the outer warm Neptune, TOI-421 c, has a period of P-c = 16.06819 +/- 0.00035 days, a mass of M-c = 16.42(-1.04)(+1.06)M(circle plus), a radius of R-c = 5.09(-0.15)(+0.16)R(circle plus), and a density of rho(c) = 0.685(-0.072)(+0.080) cm(-3). With its characteristics, the outer planet (rho(c) = 0.685(-0.0072)(+0.080) cm(-3)) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Ly alpha transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed.
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| 11. |
- Laubenstein, Taryn, et al.
(författare)
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Threats to Australia's oceans and coasts : A systematic review
- 2023
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Ingår i: Ocean and Coastal Management. - : Elsevier. - 0964-5691 .- 1873-524X. ; 231
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Forskningsöversikt (refereegranskat)abstract
- Oceans and coasts provide important ecosystem, livelihood, and cultural values to humans and the planet but face current and future compounding threats from anthropogenic activities associated with expanding pop-ulations and their use of and reliance on these environments. To respond to and mitigate these threats, there is a need to first systematically understand and categorise them. This paper reviewed 226 articles from the period 2010-2020 on threats to Australia's oceans and coasts, resulting in the identification of a total of 307 threats. Threats were grouped into three broad categories - threats from use and extraction; environmental and human -induced threats; and policy and socio-political threats -then ranked by frequency. The most common 'threats from use and extraction' were recreational activities, non-point source pollution, and urban development; the most common 'environmental and human-induced threat' was increased temperatures; and the most common 'policy and socio-political threat' was policy gaps and failures (e.g., a lack of coastal climate adaptation policies). The identification of threats across all three categories increased over time; however, the identification of 'threats from use and extraction' increased most rapidly over the last four years (2017-2020). Threats were most often described for their impacts on environmental values (68%), followed by economic (14%), socio-cultural (12%), and Indigenous (6%) values. Only 45 of the 226 papers (20%) discussed multiple threats. The threats facing Australia's oceans and coasts are rising, cumulative, and multi-faceted, and the inherent tensions between varied uses, along with intensification of uses that derive short-term anthropogenic benefit, will continue to degrade the ecological sustainability of ocean and coastal systems if actions are not taken.
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| 12. |
- Norström, Albert, et al.
(författare)
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Principles for knowledge co-production in sustainability research
- 2020
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Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 3:3, s. 182-190
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Tidskriftsartikel (refereegranskat)abstract
- Research practice, funding agencies and global science organizations suggest that research aimed at addressing sustainability challenges is most effective when 'co-produced' by academics and non-academics. Co-production promises to address the complex nature of contemporary sustainability challenges better than more traditional scientific approaches. But definitions of knowledge co-production are diverse and often contradictory. We propose a set of four general principles that underlie high-quality knowledge co-production for sustainability research. Using these principles, we offer practical guidance on how to engage in meaningful co-productive practices, and how to evaluate their quality and success. Research addressing sustainability issues is more effective if 'co-produced' by academics and non-academics, but definitions of co-production vary. This Perspective presents four knowledge co-production principles for sustainability research and guides on how to engage in co-productive practices.
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| 13. |
- Srivastav, Shubham, et al.
(författare)
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SN 2020kyg and the rates of faint Iax supernovae from ATLAS
- 2022
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 511:2, s. 2708-2731
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Tidskriftsartikel (refereegranskat)abstract
- We present multiwavelength follow-up observations of the ATLAS discovered faint Iax supernova SN 2020kyg that peaked at an absolute magnitude of Mg ≈ −14.9 ± 0.2, making it another member of the faint Iax supernova population. The bolometric light curve requires only ≈7 × 10−3 M⊙ of radioactive 56Ni, with an ejected mass of Mej ∼ 0.4 M⊙ and a low kinetic energy of E ≈ 0.05 ± 0.02 × 1051 erg. We construct a homogeneous volume-limited sample of 902 transients observed by ATLAS within 100 Mpc during a 3.5 yr span. Using this sample, we constrain the rates of faint Iax (Mr ≳ −16) events within 60 Mpc at 12+14−8 per cent12−8+14 per cent of the SN Ia rate. The overall Iax rate, at 15+17−9 per cent15−9+17 per cent of the Ia rate, is dominated by the low-luminosity events, with luminous SNe Iax (Mr ≲ −17.5) like 2002cx and 2005hk, accounting for only 0.9+1.1−0.5 per cent0.9−0.5+1.1 per cent of the Ia rate (a 2σ upper limit of approximately 3 per cent). We favour the hybrid CONe WD + He star progenitor channel involving a failed deflagration of a near Chandrasekhar mass white dwarf, expected to leave a bound remnant and a surviving secondary companion, as a candidate explanation for faint Iax explosions. This scenario requires short delay times, consistent with the observed environments of SNe Iax. Furthermore, binary population synthesis calculations have suggested rates of 1−18 per cent1−18 per cent of the SN Ia rate for this channel, consistent with our rate estimates.
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