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- 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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- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Yakneen, S, et al.
(författare)
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Butler enables rapid cloud-based analysis of thousands of human genomes
- 2020
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Ingår i: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 38:3, s. 288-
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Tidskriftsartikel (refereegranskat)abstract
- We present Butler, a computational tool that facilitates large-scale genomic analyses on public and academic clouds. Butler includes innovative anomaly detection and self-healing functions that improve the efficiency of data processing and analysis by 43% compared with current approaches. Butler enabled processing of a 725-terabyte cancer genome dataset from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project in a time-efficient and uniform manner.
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- Yarza, P., et al.
(författare)
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Sequencing orphan species initiative (SOS): Filling the gaps in the 16S rRNA gene sequence database for all species with validly published names
- 2013
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Ingår i: Systematic and Applied Microbiology. - : Elsevier BV. - 0723-2020. ; 36:1, s. 69-73
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Tidskriftsartikel (refereegranskat)abstract
- High quality 16S ribosomal RNA (rRNA) gene sequences from the type strains of all species with validly published names, as defined by the International Code of Nomenclature of Bacteria, are a prerequisite for their accurate affiliations within the global genealogical classification and for the recognition of potential new taxa. During the last few years, the Living Tree Project (LTP) has taken care to create a high quality, aligned 16S and 23S rRNA gene sequence database of all type strains. However, the manual curation of the sequence dataset and type strain information revealed that a total of 552 “orphan” species (about 5.7% of the currently classified species) had to be excluded from the reference trees. Among them, 322 type strains were not represented by an SSU entry in the public sequence repositories. The remaining 230 type strains had to be discarded due to bad sequence quality. Since 2010, the LTP team has coordinated a network of researchers and culture collections in order to improve the situation by (re)-sequencing the type strains of these “orphan” species. As a result, we can now report 351 16S rRNA gene sequences of type strains. Nevertheless, 201 species could not be sequenced because cultivable type strains were not available (121), the cultures had either been lost or were never deposited in the first place (66), or it was not possible due to other constraints (14). The International Code of Nomenclature of Bacteria provides a number of mechanisms to deal with the problem of missing type strains and we recommend that due consideration be given to the appropriate mechanisms in order to help solve some of these issues.
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- Andreoli, María F, et al.
(författare)
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Pre-prandial plasma liver-expressed antimicrobial peptide 2 (LEAP2) concentration in humans is inversely associated with hunger sensation in a ghrelin independent manner.
- 2023
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Ingår i: European Journal of Nutrition. - 1436-6207 .- 1436-6215.
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The liver-expressed antimicrobial peptide 2 (LEAP2) is a newly recognized peptide hormone that acts via the growth hormone secretagogue receptor (GHSR) blunting the effects of ghrelin and displaying ghrelin-independent actions. Since the implications of LEAP2 are beginning to be elucidated, we investigated if plasma LEAP2 concentration varies with feeding status or sex and whether it is associated with glucose metabolism and appetite sensations.METHODS: We performed a single test meal study, in which plasma concentrations of LEAP2, ghrelin, insulin and glucose as well as visual analogue scales for hunger, desire to eat, prospective food consumption, fullness were assessed before and 60 min after breakfast in 44 participants (n = 21 females) with normal weight (NW) or overweight/obesity (OW/OB).RESULTS: Pre-prandial plasma LEAP2 concentration was ~ 1.6-fold higher whereas ghrelin was ~ 2.0-fold lower in individuals with OW/OB (p < 0.001) independently of sex. After adjusting for body mass index (BMI) and sex, pre-prandial plasma LEAP2 concentration displayed a direct relationship with BMI (β: 0.09; 95%CI: 0.05, 0.13; p < 0.001), fat mass (β: 0.05; 95%CI: 0.01, 0.09; p = 0.010) and glycemia (β: 0.24; 95%CI: 0.05, 0.43; p = 0.021), whereas plasma ghrelin concentration displayed an inverse relationship with BMI and fat mass but not with glycemia. Postprandial plasma LEAP2 concentration increased ~ 58% in females with OW/OB (p = 0.045) but not in females with NW or in males. Pre-prandial plasma LEAP2 concentration displayed an inverse relationship with hunger score (β: - 11.16; 95% CI: - 18.52, - 3.79; p = 0.004), in a BMI-, sex- and ghrelin-independent manner.CONCLUSIONS: LEAP2 emerges as a key hormone implicated in the regulation of metabolism and appetite in humans.TRIAL REGISTRATION: The study was retrospectively registered in clinicaltrials.gov (April 2023).CLINICALTRIALS: gov Identifier: NCT05815641.
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- Spring, C. A., et al.
(författare)
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Capturing Waste or Capturing Innovation? Comparing Self-Organising Potentials of Surplus Food Redistribution Initiatives to Prevent Food Waste
- 2020
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Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- The context for this article is the rapid international growth of (surplus) food redistribution initiatives. These are frequently reliant on networks of volunteer labour, often coordinated by digital means. Movements with these characteristics are increasingly viewed by researchers, policymakers and practitioners as cases of self-organisation. The article explores the nature and extent of self-organisation in food redistribution initiatives. Two contrasting UK initiatives were studied using ethnographic methods during a period of rapid expansion. The concept of self-organisation was operationalised using three dimensions-autonomy, expansion and governance. One initiative established food banks in close cooperation with corporate food actors. Its franchise charity model involved standardised safety protocols and significant centralised control. The other initiative deliberately pursued autonomy, rapid recruitment and de-centralised governance; nevertheless, collaboration with industry actors and a degree of centralised control became a (contested) part of the approach. We highlight the interplay of organisational agency and institutional structures affecting the self-organisation of surplus food redistribution, including ways in which movement dynamism can involve capture by dominant interests but also the seeds of transformative practices that challenge root causes of food waste, particularly food's commodification. Our analysis provides a way to compare the potentials of food charity vs mutual aid in effecting systemic change.
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| 18. |
- Spring, Frances A., et al.
(författare)
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Intercellular adhesion molecule-4 binds alpha(4)beta(1) and alpha(V)-family integrins through novel integrin-binding mechanisms
- 2001
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Ingår i: Blood. - 1528-0020. ; 98:2, s. 458-466
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Tidskriftsartikel (refereegranskat)abstract
- The LW blood group glycoprotein, ICAM-4, is a member of the intercellular adhesion molecule (ICAM) family expressed in erythroid cells. To begin to address the function of this molecule, ligands for ICAM-4 on hemopoietic and nonhemopoietic cell lines were identified. Peptide inhibition studies suggest that adhesion of cell lines to an ICAM-4-Fc construct is mediated by an LDV-inhibitable integrin on hemopoietic cells and an RGD-inhibitable integrin on nonhemopoietic cells. Antibody inhibition studies identified the hemopoietic integrin as alpha(4)beta(1.) Antibody inhibition studies on alpha(4)beta(1)-negative, nonhemopoietic cell lines suggested that adhesion of these cells is mediated by alpha(V) integrins (notably alpha(V)beta(1) and alpha(V)beta(5)). The structure of ICAM-4 modeled on the crystal structure of ICAM-2 was used to identify surface-exposed amino acid residues for site-directed mutagenesis. Neither an unusual LETS nor an LDV motif in the first domain of ICAM-4 was critical for integrin binding. ICAM-4 is the first ICAM family member shown to be a ligand for integrins other than those of the beta(2) family, and the data suggest that ICAM-4 has a novel integrin-binding site(s). These findings suggest a role for ICAM-4 in normal erythropoiesis and may also be relevant to the adhesive interactions of sickle cells.
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| 19. |
- Thornton, Nicole, et al.
(författare)
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Disruption of the tumour-associated EMP3 enhances erythroid proliferation and causes the MAM-negative phenotype
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The clinically important MAM blood group antigen is present on haematopoietic cells of all humans except rare MAM-negative individuals. Its molecular basis is unknown. By whole-exome sequencing we identify EMP3, encoding epithelial membrane protein 3 (EMP3), as a candidate gene, then demonstrate inactivating mutations in ten known MAM-negative individuals. We show that EMP3, a purported tumour suppressor in various solid tumours, is expressed in erythroid cells. Disruption of EMP3 by CRISPR/Cas9 gene editing in an immortalised human erythroid cell line (BEL-A2) abolishes MAM expression. We find EMP3 to associate with, and stabilise, CD44 in the plasma membrane. Furthermore, cultured erythroid progenitor cells from MAM-negative individuals show markedly increased proliferation and higher reticulocyte yields, suggesting an important regulatory role for EMP3 in erythropoiesis and control of cell production. Our data establish MAM as a new blood group system and demonstrate an interaction of EMP3 with the cell surface signalling molecule CD44.
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