| 1. |
- Borozan, Ivan, et al.
(författare)
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Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with Fusobacterium nucleatum and Its Subspecies animalis
- 2022
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 31:1, s. 210-220
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fusobacterium nucleatum (F. nucleatum) activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis.Methods: We characterized F. nucleatum and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer-specific survival. We conducted deep sequencing of nusA, nusG, and bacterial 16s rRNA genes in tumors from 1,994 patients with colorectal cancer and assessed associations between F. nucleatum presence and clinical characteristics, colorectal cancer-specific mortality, and somatic mutations.Results: F. nucleatum, which was present in 10.3% of tumors, was detected in a higher proportion of right-sided and advanced-stage tumors, particularly subspecies animalis. Presence of F. nucleatum was associated with higher colorectal cancer-specific mortality (HR, 1.97; P = 0.0004). This association was restricted to nonhypermutated, microsatellite-stable tumors (HR, 2.13; P = 0.0002) and those who received chemotherapy [HR, 1.92; confidence interval (CI), 1.07-3.45; P = 0.029). Only F. nucleatum subspecies animalis, the main subspecies detected (65.8%), was associated with colorectal cancer-specific mortality (HR, 2.16; P = 0.0016), subspecies vincentii and nucleatum were not (HR, 1.07; P = 0.86). Additional adjustment for tumor stage suggests that the effect of F. nucleatum on mortality is partly driven by a stage shift. Presence of F. nucleatum was associated with microsatellite instable tumors, tumors with POLE exonuclease domain mutations, and ERBB3 mutations, and suggestively associated with TP53 mutations.Conclusions: F. nucleatum, and particularly subspecies animalis, was associated with a higher colorectal cancer-specific mortality and specific somatic mutated genes.
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| 2. |
- Chen, Zhishan, et al.
(författare)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 3. |
- Cooke, Steven J., et al.
(författare)
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Stewardship and management of freshwater ecosystems : From Leopold's land ethic to a freshwater ethic
- 2021
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Ingår i: Aquatic conservation. - : John Wiley & Sons. - 1052-7613 .- 1099-0755. ; 31, s. 1499-1511
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Tidskriftsartikel (refereegranskat)abstract
- 1. In 1949, Aldo Leopold formalized the concept of the 'land ethic', in what emerged as a foundational and transformational way of thinking about natural resource management, biodiversity conservation, and stewardship in terrestrial systems. Yet, the land ethic has inherent linkages to aquatic ecosystems; Leopold himself conducted research on rivers and lakes, and freshwater ecosystems figured widely in his writing. 2. We reflect on the land ethic and other aspects of Leopold's scholarship to identify key messages that provide insight into the stewardship and management of freshwater ecosystems around the globe. We also frame what we call the 'freshwater ethic' around Leopold's legacy. Although Leopold could not have envisaged the stressors affecting modern aquatic ecosystems, his core principles remain salient. These apply not only to ecosystem protection, but also to the ethics of modern conservation economics, sustainability, and the protection of natural capital, in which lakes, rivers, and wetlands now figure prominently. 3. We identify key 'Aldo-inspired' recommendations for protecting and restoring freshwater ecosystems in the Anthropocene that emanate directly from his writings (e.g. adopt an ecosystem approach, identify win-win-win scenarios, recognize the irreplaceability of wild waters, and strive for freshwater optimism). 4. In an epoch where links between people and nature are becoming more explicit in environmental management, policy, and governance, we suggest that Aldo Leopold's work illustrates how inspirational, seminal thinkers have offered leadership in this domain. We contend that today there is still much that can be learned from Leopold, especially by the next generation of environmental practitioners, to ensure the effective stewardship of our aquatic ecosystems. 5. We submit that the adoption of a freshwater ethic in parallel with Leopold's land ethic will enhance the stewardship of the world's increasingly threatened fresh waters by raising the profile of the plight of fresh waters and identifying enduring actions that, if embraced, will help conserve and restore biodiversity.
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| 4. |
- Fernandez-Rozadilla, Ceres, et al.
(författare)
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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
- 2023
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 55, s. 89-99
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
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| 5. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 6. |
- Nwaila, Glen T., et al.
(författare)
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Constraints on the Geometry and Gold Distribution in the Black Reef Formation of South Africa Using 3D Reflection Seismic Data and Micro-X-ray Computed Tomography
- 2022
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Ingår i: Natural Resources Research. - : Springer. - 1520-7439 .- 1573-8981. ; 31:3, s. 1225-1244
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Tidskriftsartikel (refereegranskat)abstract
- Geological and geophysical models are essential for developing reliable mine designs and mineral processing flowsheets. For mineral resource assessment, mine planning, and mineral processing, a deeper understanding of the orebody's features, geology, mineralogy, and variability is required. We investigated the gold-bearing Black Reef Formation in the West Rand and Carletonville goldfields of South Africa using approaches that are components of a transitional framework toward fully digitized mining: (1) high-resolution 3D reflection seismic data to model the orebody; (2) petrography to characterize Au and associated ore constituents (e.g., pyrite); and (3) 3D micro-X-ray computed tomography (µCT) and machine learning to determine mineral association and composition. Reflection seismic reveals that the Black Reef Formation is a planar horizon that dips < 10° and has a well-preserved and uneven paleotopography. Several large-scale faults and dikes (most dipping between 65° and 90°) crosscut the Black Reef Formation. Petrography reveals that gold is commonly associated with pyrite, implying that µCT can be used to assess gold grades using pyrite as a proxy. Moreover, we demonstrate that machine learning can be used to discriminate between pyrite and gold based on physical characteristics. The approaches in this study are intended to supplement rather than replace traditional methodologies. In this study, we demonstrated that they permit novel integration of micro-scale observations into macro-scale modeling, thus permitting better orebody assessment for exploration, resource estimation, mining, and metallurgical purposes. We envision that such integrated approaches will become a key component of future geometallurgical frameworks.
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| 7. |
- Papadakos, Konstantinos S, et al.
(författare)
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Sushi domain-containing protein 4 binds to epithelial growth factor receptor and initiates autophagy in an EGFR phosphorylation independent manner
- 2022
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Ingår i: Journal of Experimental and Clinical Cancer Research. - : Springer Science and Business Media LLC. - 1756-9966. ; 41:1, s. 363-363
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sushi domain-containing protein 4 (SUSD4) is a recently discovered protein with unknown cellular functions. We previously revealed that SUSD4 can act as complement inhibitor and as a potential tumor suppressor.METHODS: In a syngeneic mouse model of breast cancer, tumors expressing SUSD4 had a smaller volume compared with the corresponding mock control tumors. Additionally, data from three different expression databases and online analysis tools confirm that for breast cancer patients, high mRNA expression of SUSD4 in the tumor tissue correlates with a better prognosis. In vitro experiments utilized triple-negative breast cancer cell lines (BT-20 and MDA-MB-468) stably expressing SUSD4. Moreover, we established a cell line based on BT-20 in which the gene for EGFR was knocked out with the CRISPR-Cas9 method.RESULTS: We discovered that the Epithelial Growth Factor Receptor (EGFR) interacts with SUSD4. Furthermore, triple-negative breast cancer cell lines stably expressing SUSD4 had higher autophagic flux. The initiation of autophagy required the expression of EGFR but not phosphorylation of the receptor. Expression of SUSD4 in the breast cancer cells led to activation of the tumor suppressor LKB1 and consequently to the activation of AMPKα1. Finally, autophagy was initiated after stimulation of the ULK1, Atg14 and Beclin-1 axis in SUSD4 expressing cells.CONCLUSIONS: In this study we provide novel insight into the molecular mechanism of action whereby SUSD4 acts as an EGFR inhibitor without affecting the phosphorylation of the receptor and may potentially influence the recycling of EGFR to the plasma membrane.
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| 8. |
- Parchenko, Sergii, et al.
(författare)
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Orbital dynamics during an ultrafast insulator to metal transition
- 2020
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Ingår i: Physical Review Research. - : AMER PHYSICAL SOC. - 2643-1564. ; 2:2
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Tidskriftsartikel (refereegranskat)abstract
- We present ultrafast resonant inelastic x-ray scattering (RIXS) experiments performed at the vanadium L edge to track changes in the electronic structure of V2O3, a classical Mott-Hubbard material. The probed orbital excitations within the d shell of the V ion show a sub-ps time response, which evolves at later times to a state that appears electronically indistinguishable from the high-temperature metallic state. For low excitation fluences, a transient recovery or delay is observed, which could be related to a transient dimerization of the V-V bonds. Our results demonstrate the great potential for RIXS spectroscopy to study the ultrafast orbital dynamics in strongly correlated materials.
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| 9. |
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| 10. |
- Reid, Cameron J, et al.
(författare)
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A role for ColV plasmids in the evolution of pathogenic Escherichia coli ST58
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Escherichia coli ST58 has recently emerged as a globally disseminated uropathogen that often progresses to sepsis. Unlike most pandemic extra-intestinal pathogenic E. coli (ExPEC), which belong to pathogenic phylogroup B2, ST58 belongs to the environmental/commensal phylogroup B1. Here, we present a pan-genomic analysis of a global collection of 752 ST58 isolates from diverse sources. We identify a large ST58 sub-lineage characterized by near ubiquitous carriage of ColV plasmids, which carry genes encoding virulence factors, and by a distinct accessory genome including genes typical of the Yersiniabactin High Pathogenicity Island. This sub-lineage includes three-quarters of all ExPEC sequences in our study and has a broad host range, although poultry and porcine sources predominate. By contrast, strains isolated from cattle often lack ColV plasmids. Our data indicate that ColV plasmid acquisition contributed to the divergence of the major ST58 sub-lineage, and different sub-lineages inhabit poultry, swine and cattle.
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