| 1. |
|
|
| 2. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
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.
|
|
| 3. |
- De Leoz, M. L. A., et al.
(författare)
-
NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods
- 2020
-
Ingår i: Molecular & Cellular Proteomics. - 1535-9476. ; 19:1, s. 11-30
-
Tidskriftsartikel (refereegranskat)abstract
- A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories. Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
|
|
| 4. |
- Han, L., et al.
(författare)
-
Cell transcriptomic atlas of the non-human primate Macaca fascicularis
- 2022
-
Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 604:7907, s. 723-731
-
Tidskriftsartikel (refereegranskat)abstract
- Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell–cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.
|
|
| 5. |
- Wang, H. Y., et al.
(författare)
-
Cellular Analysis and Comparative Transcriptomics Reveal the Tolerance Mechanisms of Candida tropicalis Toward Phenol
- 2020
-
Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Phenol is a ubiquitous pollutant and can contaminate natural water resources. Hence, the removal of phenol from wastewater is of significant importance. A series of biological methods were used to remove phenol based on the natural ability of microorganisms to degrade phenol, but the tolerance mechanism of phenol-degraded strains to phenol are not very clear. Morphological observation on Candida tropicalis showed that phenol caused the reactive oxygen species (ROS) accumulation, damaging the mitochondrial and the endoplasmic reticulum. On the basis of transcriptome data and cell wall susceptibility analysis, it was found that C. tropicalis prevented phenol-caused cell damage through improvement of cell wall resistance, maintenance of high-fidelity DNA replication, intracellular protein homeostasis, organelle integrity, and kept the intracellular phenol concentration at a low level through cell-wall remodeling and removal of excess phenol via MDR/MXR transporters. The knowledge obtained will promote the genetic modification of yeast strains in general to tolerate the high concentrations of phenol and improve their efficiency of phenol degradation.
|
|
| 6. |
|
|
| 7. |
- Li, Q., et al.
(författare)
-
Discovery of new strains for furfural degradation using adaptive laboratory evolution in Saccharomyces cerevisiae
- 2023
-
Ingår i: Journal of Hazardous Materials. - 0304-3894. ; 459
-
Tidskriftsartikel (refereegranskat)abstract
- In industrial production, the excessive discharge of furfural can pose harm to soil microorganisms, aquatic an-imals and plants, as well as humans. Therefore, it is crucial to develop efficient and cost-effective methods for degrading furfural in the environment. Currently, the use of Saccharomyces cerevisiae for furfural degradation in water has shown effectiveness, but there is a need to explore improved efficiency and tolerance in S. cerevisiae for this purpose. In this study, we isolated and evolved highly efficient furfural degradation strains, namely YBA_08 and F60C. These strains exhibited remarkable capabilities, degrading 59% and 99% furfural in the YPD medium after 72 h of incubation, significantly higher than the 31% achieved by the model strain S288C. Through analysis of the efficient degradation mechanism in the evolutionary strain F60C, we discovered a 326% increase in the total amount of NADH and NADPH. This increase likely promotes faster furfural degradation through intracel-lular aldehyde reductases. Moreover, the decrease in NADPH content led to a 406% increase in glutathione content at the background level, which protects cells from damage caused by reactive oxygen species. Mutations and differential expression related to cell cycle and cell wall synthesis were observed, enabling cell survival in the presence of furfural and facilitating rapid furfural degradation and growth recovery. Based on these findings, it is speculated that strains YBA_08 and F60C have the potential to contribute to furfural degradation in water and the production of furfuryl alcohol, ethanol, and FDCA in biorefinery processes.
|
|
| 8. |
- Huang, C. Y., et al.
(författare)
-
The Cardamine enshiensis genome reveals whole genome duplication and insight into selenium hyperaccumulation and tolerance
- 2021
-
Ingår i: Cell Discovery. - : Springer Science and Business Media LLC. - 2056-5968. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- Cardamine enshiensis is a well-known selenium (Se)-hyperaccumulating plant. Se is an essential trace element associated with many health benefits. Despite its critical importance, genomic information of this species is limited. Here, we report a chromosome-level genome assembly of C. enshiensis, which consists of 443.4 Mb in 16 chromosomes with a scaffold N50 of 24 Mb. To elucidate the mechanism of Se tolerance and hyperaccumulation in C. enshiensis, we generated and analyzed a dataset encompassing genomes, transcriptomes, and metabolomes. The results reveal that flavonoid, glutathione, and lignin biosynthetic pathways may play important roles in protecting C. enshiensis from stress induced by Se. Hi-C analysis of chromatin interaction patterns showed that the chromatin of C. enshiensis is partitioned into A and B compartments, and strong interactions between the two telomeres of each chromosome were correlated with histone modifications, epigenetic markers, DNA methylation, and RNA abundance. Se supplementation could affect the 3D chromatin architecture of C. enshiensis at the compartment level. Genes with compartment changes after Se treatment were involved in selenocompound metabolism, and genes in regions with topologically associated domain insulation participated in cellular responses to Se, Se binding, and flavonoid biosynthesis. This multiomics research provides molecular insight into the mechanism underlying Se tolerance and hyperaccumulation in C. enshiensis.
|
|
| 9. |
|
|
| 10. |
- Wu, T. Q., et al.
(författare)
-
Fc gamma R-dependent apoptosis regulates tissue persistence of mucosal and connective tissue mast cells
- 2023
-
Ingår i: European Journal of Immunology. - 0014-2980. ; 53:8
-
Tidskriftsartikel (refereegranskat)abstract
- Rodent mast cells can be divided into two major subtypes: the mucosal mast cell (MMC) and the connective tissue mast cell (CTMC). A decade-old observation revealed a longer lifespan for CTMC compared with MMC. The precise mechanisms underlying such differential tissue persistence of mast cell subsets have not been described. In this study, we have discovered that mast cells expressing only one receptor, either Fc?RIIB or Fc?RIIIA, underwent caspase-independent apoptosis in response to IgG immune complex treatment. Lower frequencies of CTMC in mice that lacked either Fc?RIIB or Fc?RIIIA compared with WT mice were recorded, especially in aged mice. We proposed that this paradigm of Fc?R-mediated mast cell apoptosis could account for the more robust persistence of CTMC, which express both Fc?RIIB and Fc?RIIIA, than MMC, which express only Fc?RIIB. Importantly, we reproduced these results using a mast cell engraftment model, which ruled out possible confounding effects of mast cell recruitment or Fc?R expression by other cells on mast cell number regulation. In conclusion, our work has uncovered an Fc?R-dependent mast cell number regulation paradigm that might provide a mechanistic explanation for the long-observed differential mast cell subset persistence in tissues.
|
|
| 11. |
- Zou, X., et al.
(författare)
-
Sustainable offshore oil and gas fields development : Techno-economic feasibility analysis of wind–hydrogen–natural gas nexus
- 2021
-
Ingår i: Energy Reports. - : Elsevier Ltd. - 2352-4847. ; 7, s. 4470-4482
-
Tidskriftsartikel (refereegranskat)abstract
- Offshore oil and gas field development consumes quantities of electricity, which is usually provided by gas turbines. In order to alleviate the emission reduction pressure and the increasing pressure of energy saving, governments of the world have been promoting the reform of oil and gas fields for years. Nowadays, environmentally friendly alternatives to provide electricity are hotspots, such as the integration of traditional energy and renewable energy. However, the determination of system with great environmental and economic benefits is still controversial. This paper proposed a wind–hydrogen–natural gas nexus (WHNGN) system for sustainable offshore oil and gas fields development. Combining the optimization model with the techno-economic evaluation model, a comprehensive evaluation framework is established for techno-economic feasibility analysis. In addition to WHNGN system, another two systems are designed for comparison, including the traditional energy supply (TES) system and wind–natural gas nexus (WNGN) system. An offshore production platforms in Bohai Bay in China is taken as a case, and the results indicate that: (i) WNGN and WHNGN systems have significant economic benefits, total investment is decreased by 5,190 and 5,020 million $ respectively, and the WHNGN system increases 4,174 million $ profit; (ii) WNGN and WHNGN systems have significant environmental benefits, annual carbon emission is decreased by 15 and 40.2 million kg respectively; (iii) the system can be ranked by economic benefits as follows: WHNGN>WNGN>TES; and (iV) the WHNGN system is more advantageous in areas with high hydrogen and natural gas sales prices, such as China, Kazakhstan, Turkey, India, Malaysia and Indonesia.
|
|
| 12. |
- Chen, X., et al.
(författare)
-
Engineering stable radicals using photochromic triggers
- 2020
-
Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Long-standing radical species have raised noteworthy concerns in organic functional chemistry and materials. However, there remains a substantial challenge to produce long-standing radicals by light, because of the structural dilemmas between photoproduction and stabilization. Herein, we present a pyrrole and chloride assisted photochromic structure to address this issue. In this well-selected system, production and stabilization of a radical species were simultaneously found accompanied by a photochemical process in chloroform. Theoretical study and mechanism construction indicate that the designed π-system provides a superior spin-delocalization effect and a large steric effect, mostly avoiding possible consumptions and making the radical stable for hours even under an oxygen-saturated condition. Moreover, this radical system can be applied for a visualized and quantitative detection towards peroxides, such as 2,2,6,6-tetramethylpiperidine-1-oxyl, hydrogen peroxide, and ozone. As the detection relies on a radical capturing mechanism, a higher sensing rate was achieved compared to traditional redox techniques for peroxide detection.
|
|
| 13. |
|
|
| 14. |
- Pagnamenta, A. T., et al.
(författare)
-
An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy
- 2021
-
Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 144, s. 584-600
-
Tidskriftsartikel (refereegranskat)abstract
- The extracellular matrix comprises a network of macromolecules such as collagens, proteoglycans and glycoproteins. VWA1 (von Willebrand factor A domain containing 1) encodes a component of the extracellular matrix that interacts with perlecan/collagen VI, appears to be involved in stabilizing extracellular matrix structures, and demonstrates high expression levels in tibial nerve. Vwa1-deficient mice manifest with abnormal peripheral nerve structure/function; however, VWA1 variants have not previously been associated with human disease. By interrogating the genome sequences of 74 180 individuals from the 100K Genomes Project in combination with international gene-matching efforts and targeted sequencing, we identified 17 individuals from 15 families with an autosomal-recessive, non-length dependent, hereditary motor neuropathy and rare biallelic variants in VWA1. A single disease-associated allele p.(G25Rfs*74), a 10-bp repeat expansion, was observed in 14/15 families and was homozygous in 10/15. Given an allele frequency in European populations approaching 1/1000, the seven unrelated homozygote individuals ascertained from the 100K Genomes Project represents a substantial enrichment above expected. Haplotype analysis identified a shared 220 kb region suggesting that this founder mutation arose 47000 years ago. A wide age-range of patients (6-83 years) helped delineate the clinical phenotype over time. The commonest disease presentation in the cohort was an early-onset (mean 2.0 +/- 1.4 years) non-length-dependent axonal hereditary motor neuropathy, confirmed on electrophysiology, which will have to be differentiated from other predominantly or pure motor neuropathies and neuronopathies. Because of slow disease progression, ambulation was largely preserved. Neurophysiology, muscle histopathology, and muscle MRI findings typically revealed clear neurogenic changes with single isolated cases displaying additional myopathic process. We speculate that a few findings of myopathic changes might be secondary to chronic denervation rather than indicating an additional myopathic disease process. Duplex reverse transcription polymerase chain reaction and immunoblotting using patient fibroblasts revealed that the founder allele results in partial nonsense mediated decay and an absence of detectable protein. CRISPR and morpholino vwa1 modelling in zebrafish demonstrated reductions in motor neuron axonal growth, synaptic formation in the skeletal muscles and locomotive behaviour. In summary, we estimate that biallelic variants in VWA1 may be responsible for up to 1% of unexplained hereditary motor neuropathy cases in Europeans. The detailed clinical characterization provided here will facilitate targeted testing on suitable patient cohorts. This novel disease gene may have previously evaded detection because of high GC content, consequential low coverage and computational difficulties associated with robustly detecting repeat-expansions. Reviewing previously unsolved exomes using lower QC filters may generate further diagnoses.
|
|
| 15. |
|
|
| 16. |
- Zou, X., et al.
(författare)
-
Roadmap to urban energy internet : Techno-enviro-economic analysis of renewable electricity and natural gas integrated energy system
- 2022
-
Ingår i: Journal of Cleaner Production. - : Elsevier Ltd. - 0959-6526 .- 1879-1786. ; 373
-
Tidskriftsartikel (refereegranskat)abstract
- The integrated energy system which coordinates natural gas, renewable energy, and other energy subsystems is an effective way to promote a low-carbon economy. An effective framework for system assessment and optimisation is a critical issue. This paper takes a natural gas-wind-photovoltaic integrated energy system as the research object and uses the simulation software to analyse its techno-enviro-economic feasibility. Firstly, a mathematical model is customised to optimise the system installation and operation plans. Renewable electricity replaces some natural gas, resulting in pipeline pressure fluctuation. Here, the Stoner Pipeline Simulator software is used to simulate pipeline network operation to quantify the aforementioned pressure fluctuations. The proportion of renewable energy is gradually reduced until the network pressure fluctuation is less than 20% to ensure the stability of pipeline operation. Then, the optimal operation scheme can be determined. Taking three cities in Shandong, China, as cases, the results show that the proposed system is beneficial for urban energy internet development: (i) the total net present cost is reduced by 19.7%, 19.8%, and 20.8%, (ii) annual CO2 emission is reduced by 23.7%, 18.4%, and 12.2%; (iii) the levelised cost of energy is 0.142 $/kWh, 0.143$/kWh, and 0.153$/kWh.
|
|
