| 1. |
- Fu, Yifeng, 1984, et al.
(författare)
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Templated Growth of Covalently Bonded Three-Dimensional Carbon Nanotube Networks Originated from Graphene
- 2012
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Ingår i: Advanced Materials. - : Wiley. - 0935-9648 .- 1521-4095. ; 24:12, s. 1576-1581
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Tidskriftsartikel (refereegranskat)abstract
- A template-assisted method that enables the growth of covalently bonded three-dimensional carbon nanotubes (CNTs) originating from graphene at a large scale is demonstrated. Atomic force microscopy-based mechanical tests show that the covalently bonded CNT structure can effectively distribute external loading throughout the network to improve the mechanical strength of the material.
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| 2. |
- Han, Shangfeng, et al.
(författare)
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China's Energy Transition in the Power and Transport Sectors from a Substitution Perspective
- 2017
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Ingår i: Energies. - : MDPI AG. - 1996-1073. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Facing heavy air pollution, China needs to transition to a clean and sustainable energy system, especially in the power and transport sectors, which contribute the highest greenhouse gas (GHG) emissions. The core of an energy transition is energy substitution and energy technology improvement. In this paper, we forecast the levelized cost of electricity (LCOE) for power generation in 2030 in China. Cost-emission effectiveness of the substitution between new energy vehicles and conventional vehicles is also calculated in this study. The results indicate that solar photovoltaic (PV) and wind power will be cost comparative in the future. New energy vehicles are more expensive than conventional vehicles due to their higher manufacturer suggested retail price (MSRP). The cost-emission effectiveness of the substitution between new energy vehicles and conventional vehicles would be $96.7/ton or $114.8/ton. Gasoline prices, taxes, and vehicle insurance will be good directions for policy implementation after the ending of subsidies.
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| 3. |
- Koskiniemi, Sanna, et al.
(författare)
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Selection-driven genome reduction in bacteria
- 2012
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Ingår i: PLOS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 8:6, s. e1002787-
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Tidskriftsartikel (refereegranskat)abstract
- Gene loss by deletion is a common evolutionary process in bacteria, as exemplified by bacteria with small genomes that have evolved from bacteria with larger genomes by reductive processes. The driving force(s) for genome reduction remains unclear, and here we examined the hypothesis that gene loss is selected because carriage of superfluous genes confers a fitness cost to the bacterium. In the bacterium Salmonella enterica, we measured deletion rates at 11 chromosomal positions and the fitness effects of several spontaneous deletions. Deletion rates varied over 200-fold between different regions with the replication terminus region showing the highest rates. Approximately 25% of the examined deletions caused an increase in fitness under one or several growth conditions, and after serial passage of wild-type bacteria in rich medium for 1,000 generations we observed fixation of deletions that substantially increased bacterial fitness when reconstructed in a non-evolved bacterium. These results suggest that selection could be a significant driver of gene loss and reductive genome evolution.
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| 4. |
- Sun, Song, 1982-, et al.
(författare)
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A proactive genotype-to-patient-phenotype map for cystathionine beta-synthase
- 2020
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Ingår i: Genome Medicine. - : BMC. - 1756-994X .- 1756-994X. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background For the majority of rare clinical missense variants, pathogenicity status cannot currently be classified. Classical homocystinuria, characterized by elevated homocysteine in plasma and urine, is caused by variants in the cystathionine beta-synthase (CBS) gene, most of which are rare. With early detection, existing therapies are highly effective. Methods Damaging CBS variants can be detected based on their failure to restore growth in yeast cells lacking the yeast ortholog CYS4. This assay has only been applied reactively, after first observing a variant in patients. Using saturation codon-mutagenesis, en masse growth selection, and sequencing, we generated a comprehensive, proactive map of CBS missense variant function. Results Our CBS variant effect map far exceeds the performance of computational predictors of disease variants. Map scores correlated strongly with both disease severity (Spearman's rho = 0.9) and human clinical response to vitamin B-6 (rho = 0.93). Conclusions We demonstrate that highly multiplexed cell-based assays can yield proactive maps of variant function and patient response to therapy, even for rare variants not previously seen in the clinic.
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| 5. |
- Sun, Song, 1982-
(författare)
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Dynamics and Mechanisms of Adaptive Evolution in Bacteria
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Determining the properties of mutations is fundamental to understanding the mechanisms of adaptive evolution. The major goal of this thesis is to investigate the mechanisms of bacterial adaptation to new environments using experimental evolution. Different types of mutations were under investigations with a particular focus on genome rearrangements. Adaptive evolution experiments were focused on the development of bacterial resistance to antibiotics.In paper I, we performed stochastic simulations to examine the role of gene amplification in promoting the establishment of new gene functions. The results show that gene amplification can contribute to creation of new gene functions in nature. In paper II, the evolution of β-lactam resistance was studied by evolving S. typhimurium carrying a β-lactamase gene towards increased resistance against cephalosporins. Our results suggest that gene amplification is likely to provide an immediate solution at the early stage of adaptive evolution and subsequently facilitate further stable adaptation. In paper III, we isolated spontaneous deletion mutants with increased competitive fitness, which indicated that genome reduction could be driven by selection. To test this hypothesis, independent lineages of wild type S. typhimurium were serially passaged for 1000 generations and we observed fixation of deletions that significantly increased bacterial fitness when reconstructed in wild type genetic background. In paper IV, we developed a new strategy combining 454 pyrosequencing technology and a ‘split mapping’ computational method to identify unique junction sequences formed by spontaneous genome rearrangements. A high steady-state frequency of rearrangements in unselected bacterial populations was suggested from our results. In paper V, the rates, mechanisms and fitness effects of colistin resistance in S. typhimurium were determined. The high mutation rate and low fitness costs suggest that colistin resistance could develop in clinical settings. In paper VI, a novel Metallo-β-lactamase (MBL) with low resistance against β-lactam antibiotics was employed as the ancestral protein in a directed evolution experiment to examine how an enzyme evolves towards increased resistance. For most isolated mutants, in spite of their significantly increased resistance, both mRNA and protein levels were decreased as compared with the parental protein, suggesting that the catalytic activity had increased.
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| 6. |
- Sun, Song, 1982-, et al.
(författare)
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Evolution of increased ß-lactam resistance in an engineered Metallo-ß-lactamase
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The extensive use and misuse of antibiotics during the last 60 years has led to the evolution and global spread of a variety of resistance mechanisms. Of high medical importance are ß-lactamases, a group of enzymes that can hydrolyze the ß-lactam ring present in all ß-lactam antibiotics. Metallo-ß-lactamases (MBLs) are particularly problematic due to their ability to hydrolyze virtually all classes of ß-lactam antibiotics. A novel MBL (evMBL9) with low-level resistance against ß-lactam antibiotics was designed and employed as the ancestral MBL during an experiment to examine how an enzyme evolved towards increased resistance. We designed and synthesized a mutant library in which the substrate binding profile was varied by randomizing six amino acid residues. Mutants with increased resistance against seven different ß-lactam antibiotics (penicillin G, ampicillin, cefalotin, cefaclor, cefuroxime, cefoperazone and cefotaxime) were isolated and characterized. For the majority of mutants, in spite of their significantly increased resistance, both mRNA and protein levels were reduced (up to >20 fold) relative to those of parental evMBL9, indicating that the catalytic activities of these mutant MBLs were highly increased. Multivariate analysis showed that the majority of mutant enzymes became generalists, conferring increased resistance against most of the examined ß-lactams. The increased resistance and decreased protein level suggest that the improved hydrolysis in these novel MBLs is associated with decreased protein stability.
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| 7. |
- Sun, Song, 1982-, et al.
(författare)
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High frequencies of genome rearrangements in bacterial chromosomes
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Genome rearrangements have important effects on bacterial phenotypes and influence the evolution of bacterial genomes. Conventional strategies for characterizing rearrangements in bacterial genomes rely on comparisons of sequenced genomes from related species. However, the spectra of spontaneous rearrangements in supposedly homogenous and clonal bacterial populations are still poorly characterized. Here we used 454 pyrosequencing technology and a ‘split mapping’ computational method to identify unique junction sequences caused by spontaneous genome rearrangements in chemostat cultures of Salmonella enterica Var. Typhimurium LT2. We were able to confirm 22 unique junction sequences with a junction homology more than 10bp and this led to an estimation of 51 true junction sequences, of which 28, 12 and 11 were likely to be formed by deletion, duplication and inversion events, respectively. All experimentally confirmed rearrangements had short inverted (inversions) or direct (deletions and duplications) homologous repeat sequences at the endpoints. This study demonstrates the feasibility of genome wide characterization of spontaneous genome rearrangements in bacteria and the high steady-state frequency of rearrangements in bacterial populations.
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| 8. |
- Yang, Fan, et al.
(författare)
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Identifying pathogenicity of human variants via paralog-based yeast complementation
- 2017
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Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- To better understand the health implications of personal genomes, we now face a largely unmet challenge to identify functional variants within disease-associated genes. Functional variants can be identified by trans-species complementation, e.g., by failure to rescue a yeast strain bearing a mutation in an orthologous human gene. Although orthologous complementation assays are powerful predictors of pathogenic variation, they are available for only a few percent of human disease genes. Here we systematically examine the question of whether complementation assays based on paralogy relationships can expand the number of human disease genes with functional variant detection assays. We tested over 1,000 paralogous human-yeast gene pairs for complementation, yielding 34 complementation relationships, of which 33 (97%) were novel. We found that paralog-based assays identified disease variants with success on par with that of orthology-based assays. Combining all homology-based assay results, we found that complementation can often identify pathogenic variants outside the homologous sequence region, presumably because of global effects on protein folding or stability. Within our search space, paralogy-based complementation more than doubled the number of human disease genes with a yeast-based complementation assay for disease variation.
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