| 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. |
- Zhang, Juqing, et al.
(författare)
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Super-enhancers conserved within placental mammals maintain stem cell pluripotency
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:40
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Tidskriftsartikel (refereegranskat)abstract
- Despite pluripotent stem cells sharing key transcription factors, their maintenance involves distinct genetic inputs. Emerging evidence suggests that super-enhancers (SEs) can function as master regulatory hubs to control cell identity and pluripotency in humans and mice. However, whether pluripotency-associated SEs share an evolutionary origin in mammals remains elusive. Here, we performed comprehensive comparative epigenomic and transcription factor binding analyses among pigs, humans, and mice to identify pluripotency-associated SEs. Like typical enhancers, SEs displayed rapid evolu-tion in mammals. We showed that BRD4 is an essential and conserved activator for mammalian pluripotency-associated SEs. Comparative motif enrichment analysis revealed 30 shared transcription factor binding motifs among the three species. The majority of transcriptional factors that bind to identified motifs are known regulators associated with pluripotency. Further, we discovered three pluripotency-associated SEs (SE-SOX2, SE-PIM1, and SE-FGFR1) that displayed remarkable conservation in pla-cental mammals and were sufficient to drive reporter gene expression in a pluripotency-dependent manner. Disruption of these conserved SEs through the CRISPR-Cas9 approach severely impaired stem cell pluripotency. Our study provides insights into the understanding of conserved regulatory mechanisms underlying the maintenance of plu-ripotency as well as species-specific modulation of the pluripotency-associated regula-tory networks in mammals.
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| 4. |
- Li, Jingjing, et al.
(författare)
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Photothermal Aerogel Beads Based on Polysaccharides: Controlled Fabrication and Hybrid Applications in Solar-Powered Interfacial Evaporation, Water Remediation, and Soil Enrichment
- 2022
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Ingår i: ACS Applied Materials & Interfaces. - : American Chemical Society (ACS). - 1944-8252 .- 1944-8244. ; 14:44, s. 50266-50279
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Tidskriftsartikel (refereegranskat)abstract
- Solar-powered interfacial evaporation has emerged as an innovative and sustainable technology for clean water production. However, the rapid, mass and shape-controlled fabrication of three-dimensional (3D) steam generators (SGs) for versatile hybrid applications remains challenging. Herein, composite aerogel beads with self-contained properties (i.e., hydrophilic, porous, photothermal, and durable) are developed and demonstrated for threefold hybrid applications including efficient solar-powered interfacial evaporation, water remediation, and controlled soil enrichment. The rational incorporation of selected polysaccharides enables us to fabricate bead-like aerogels with rapid gelation, continuous processing, and enhanced ion adsorption. The composite beads can attain a high water evaporation rate of 1.62 kg m-2 h-1 under 1 sun. Meanwhile, high phosphate adsorption capacity of over 120 mg g-1 is achieved in broad pH (2.5-12.4) and concentration (200-1000 mg L-1) ranges of phosphate solutions. Gratifyingly, we demonstrate the first example of recycling biomaterials from interfacial SGs for controlled nutrient release, soil enrichment, and sustainable agriculture. The phosphate-saturated beads can be gradually broken down in the soil. Macronutrients (N, P, and K) can be slowly released in 50 days, sustaining the plant germination and growth in a whole growth stage. This work shines light on the mass and controlled fabrication of aerogel beads based on double-network biopolymers, not merely scaling up solar-powered interfacial evaporation but also considering water remediation, waste material disposal, and value-added conversion.
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| 5. |
- Li, Shuangjun, et al.
(författare)
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Cyclic performance evaluation of CO2 adsorption using polyethylene terephthalate plastic-waste-derived activated carbon
- 2023
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Ingår i: Fuel. - : ELSEVIER SCI LTD. - 0016-2361 .- 1873-7153. ; 331
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Tidskriftsartikel (refereegranskat)abstract
- Polyethylene terephthalate (PET) plastic-waste-derived activated carbons have recently been developed and exhibit excellent CO(2 )adsorption uptake. However, the CO2-adsorption performance of such recycled materials has only been considered on a basic characterization level and has not yet been evaluated in carbon capture cycles, thereby making biased analyses inevitable. Consequently, a whole chain including the material, process, and cycle is essential for comprehensively analyzing and evaluating novel CO2 adsorbents. Therefore, in this study, various CO2-capture cycles using PET plastic-waste-derived activated carbon adsorbents were numerically simulated, the cyclic CO2-adsorption performances were evaluated, and the application scenario was optimized. A methodology for evaluating the cyclic CO2-adsorption performance of PET plastic-waste-derived activated carbon was proposed for CO(2 )capture. The results suggested that the temperature/vacuum swing adsorption cycle was superior and that its maximum exergy efficiency reached 32.90%.
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| 6. |
- Li, Shuai, et al.
(författare)
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Response strategies and biological applications of organic fluorescent thermometry: cell- and mitochondrion-level detection
- 2024
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Ingår i: Analytical Methods. - : ROYAL SOC CHEMISTRY. - 1759-9660 .- 1759-9679.
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Forskningsöversikt (refereegranskat)abstract
- Temperature homeostasis is critical for cells to perform their physiological functions. Among the diverse methods for temperature detection, fluorescent temperature probes stand out as a proven and effective tool, especially for monitoring temperature in cells and suborganelles, with a specific emphasis on mitochondria. The utilization of these probes provides a new opportunity to enhance our understanding of the mechanisms and interconnections underlying various physiological activities related to temperature homeostasis. However, the complexity and variability of cells and suborganelles necessitate fluorescent temperature probes with high resolution and sensitivity. To meet the demanding requirements for intracellular/subcellular temperature detection, several strategies have been developed, offering a range of options to address this challenge. This review examines four fundamental temperature-response strategies employed by small molecule and polymer probes, including intramolecular rotation, polarity sensitivity, Forster resonance energy transfer, and structural changes. The primary emphasis was placed on elucidating molecular design and biological applications specific to each type of probe. Furthermore, this review provides an insightful discussion on factors that may affect fluorescent thermometry, providing valuable perspectives for future development in the field. Finally, the review concludes by presenting cutting-edge response strategies and research insights for mitigating biases in temperature sensing. In this review, we primarily summarized four temperature-response strategies. Then, we further analyzed the chemical modifications and biological applications of the probes. Finally, we have provided a prospective on the future development of probes.
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| 7. |
- Rheinbay, E, et al.
(författare)
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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 102-
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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| 8. |
- Yuan, Shuai, et al.
(författare)
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Health effects of milk consumption : phenome-wide Mendelian randomization study
- 2022
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Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We performed phenome-wide Mendelian randomization analysis (MR-PheWAS), two-sample MR analysis, and systemic review to comprehensively explore the health effects of milk consumption in the European population.METHODS: Rs4988235 located upstream of the LCT gene was used as the instrumental variable for milk consumption. MR-PheWAS analysis was conducted to map the association of genetically predicted milk consumption with 1081 phenotypes in the UK Biobank study (n=339,197). The associations identified in MR-PheWAS were examined by two-sample MR analysis using data from the FinnGen study (n=260,405) and international consortia. A systematic review of MR studies on milk consumption was further performed.RESULTS: PheWAS and two-sample MR analyses found robust evidence in support of inverse associations of genetically predicted milk consumption with risk of cataract (odds ratio (OR) per 50 g/day increase in milk consumption, 0.89, 95% confidence interval (CI), 0.84-0.94; p=3.81×10-5), hypercholesterolemia (OR, 0.91, 95% CI 0.86-0.96; p=2.97×10-4), and anal and rectal polyps (OR, 0.85, 95% CI, 0.77-0.94; p=0.001). An inverse association for type 2 diabetes risk (OR, 0.92, 95% CI, 0.86-0.97; p=0.003) was observed in MR analysis based on genetic data with body mass index adjustment but not in the corresponding data without body mass index adjustment. The systematic review additionally found evidence that genetically predicted milk consumption was inversely associated with asthma, hay fever, multiple sclerosis, colorectal cancer, and Alzheimer's disease, and positively associated with Parkinson's disease, renal cell carcinoma, metabolic syndrome, overweight, and obesity.CONCLUSIONS: This study suggests several health effects of milk consumption in the European population.
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| 9. |
- Zhang, Han, et al.
(författare)
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Atopic dermatitis and chronic kidney disease : a bidirectional Mendelian randomization study
- 2023
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: A bidirectional association between atopic dermatitis and chronic kidney disease (CKD) has been revealed in observational studies, whereas the causality of this association was unclear. We conducted a Mendelian randomization study to determine the bidirectional causal association between atopic dermatitis and CKD.Methods: Independent genetic instruments associated with atopic dermatitis and CKD at the genome-wide significance level were chosen from corresponding meta-analyses of genome-wide association studies. Summary-level data for atopic dermatitis were obtained from the EAGLE Eczema consortium (30,047 cases and 40,835 controls) and FinnGen consortium (7,024 cases and 198,740 controls). Summary-level data for CKD were derived from CKDGen consortium (64,164 cases and 625,219 controls) and FinnGen consortium (3,902 cases and 212,841 controls). The inverse-variance weighted method was used in the main analysis and supplemented with three sensitivity analyses.Results: Genetic predisposition to atopic dermatitis was associated with an increased risk of CKD. For a one-unit increase in the prevalence of atopic dermatitis, the odds ratio of CKD was 1.07 (95% confidence interval: 1.01-1.12). In the reverse Mendelian randomization analysis, the odds ratio of atopic dermatitis was 1.14 (95% confidence interval: 1.03-1.26) for a one-unit increase in the prevalence of CKD. The associations persisted in sensitivity analyses and no pleiotropy was detected.Conclusion: This Mendelian randomization study suggests a bidirectional positive association between atopic dermatitis and CKD.
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| 10. |
- Carlevaro-Fita, J, et al.
(författare)
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Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis
- 2020
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 56-
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Tidskriftsartikel (refereegranskat)abstract
- Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.
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