| 1. |
- Ferreira, Sofia, et al.
(författare)
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Metabolic engineering strategies for butanol production in Escherichia coli
- 2020
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Ingår i: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 117:8, s. 2571-2587
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Forskningsöversikt (refereegranskat)abstract
- The global market of butanol is increasing due to its growing applications as solvent, flavoring agent, and chemical precursor of several other compounds. Recently, the superior properties of n-butanol as a biofuel over ethanol have stimulated even more interest. (Bio)butanol is natively produced together with ethanol and acetone by Clostridium species through acetone-butanol-ethanol fermentation, at noncompetitive, low titers compared to petrochemical production. Different butanol production pathways have been expressed in Escherichia coli, a more accessible host compared to Clostridium species, to improve butanol titers and rates. The bioproduction of butanol is here reviewed from a historical and theoretical perspective. All tested rational metabolic engineering strategies in E. coli to increase butanol titers are reviewed: manipulation of central carbon metabolism, elimination of competing pathways, cofactor balancing, development of new pathways, expression of homologous enzymes, consumption of different substrates, and molecular biology strategies. The progress in the field of metabolic modeling and pathway generation algorithms and their potential application to butanol production are also summarized here. The main goals are to gather all the strategies, evaluate the respective progress obtained, identify, and exploit the outstanding challenges.
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| 2. |
- Björn, Niclas, et al.
(författare)
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Genes and variants in hematopoiesis-related pathways are associated with gemcitabine/carboplatin-induced thrombocytopenia
- 2020
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Ingår i: The Pharmacogenomics Journal. - : Nature Publishing Group. - 1470-269X .- 1473-1150. ; 20:2, s. 179-191
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy-induced myelosuppression, including thrombocytopenia, is a recurrent problem during cancer treatments that may require dose alterations or cessations that could affect the antitumor effect of the treatment. To identify genetic markers associated with treatment-induced thrombocytopenia, we whole-exome sequenced 215 non-small cell lung cancer patients homogeneously treated with gemcitabine/carboplatin. The decrease in platelets (defined as nadir/baseline) was used to assess treatment-induced thrombocytopenia. Association between germline genetic variants and thrombocytopenia was analyzed at single-nucleotide variant (SNV) (based on the optimal false discovery rate, the severity of predicted consequence, and effect), gene, and pathway levels. These analyses identified 130 SNVs/INDELs and 25 genes associated with thrombocytopenia (P-value < 0.002). Twenty-three SNVs were validated in an independent genome-wide association study (GWAS). The top associations include rs34491125 in JMJD1C (P-value = 9.07 × 10−5), the validated variants rs10491684 in DOCK8 (P-value = 1.95 × 10−4), rs6118 in SERPINA5 (P-value = 5.83 × 10−4), and rs5877 in SERPINC1 (P-value = 1.07 × 10−3), and the genes CAPZA2 (P-value = 4.03 × 10−4) and SERPINC1 (P-value = 1.55 × 10−3). The SNVs in the top-scoring pathway “Factors involved in megakaryocyte development and platelet production” (P-value = 3.34 × 10−4) were used to construct weighted genetic risk score (wGRS) and logistic regression models that predict thrombocytopenia. The wGRS predict which patients are at high or low toxicity risk levels, for CTCAE (odds ratio (OR) = 22.35, P-value = 1.55 × 10−8), and decrease (OR = 66.82, P-value = 5.92 × 10−9). The logistic regression models predict CTCAE grades 3–4 (receiver operator characteristics (ROC) area under the curve (AUC) = 0.79), and large decrease (ROC AUC = 0.86). We identified and validated genetic variations within hematopoiesis-related pathways that provide a solid foundation for future studies using genetic markers for predicting chemotherapy-induced thrombocytopenia and personalizing treatments.
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| 3. |
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| 4. |
- Spetea, Cornelia, 1968
(författare)
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Energy-efficient cultivation of marine microalgae for biomass production : Final rapport: Energimyndigheten P45907-1
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This project has demonstrated the principle of rotational cultivation of marine microalgae and that species adapted to cold climates can provide higher productivity during cold periods. By using marine species, and thus seawater instead of freshwater in cultivation, the environmental impact is reduced. Society faces major challenges to produce sufficient amounts of biomass for energy and material, and microalgae have a great potential to complement sources from forestry and agriculture. At Nordic latitudes year-round microalgae cultivation is debatable due to seasonal variations in productivity. Shall the same species be used throughout the year or shall seasonal-adapted species be used? The aims of the project were to identify suitable algal strains for a potential annual rotation model, where different strains are rotated during three cultivation seasons, and to further develop and optimize an energy-efficient cultivation process for the marine environment. To achieve these aims, a laboratory study was performed where two marine microalgal strains out of 167 were selected for intended cultivation at the west coast of Sweden. One strain belongs to the species Nannochloropsis granulata and the other to Skeletonema marinoi. The strains were cultivated in three simulated growth seasons: summer, winter and spring, and thereafter compared. We show that Nannochloropsis produced more biomass with more incorporated energy in lipids during summer and spring (25 MJ kg-1 compared to about 45 MJ kg-1 for diesel), whereas Skeletonema produced more biomass rich in carbohydrates and proteins during winter. Skeletonema was in general more efficient in taking up phosphate. Based on our results, biomass production as energy feedstock would be energy efficient only during the summer on the Swedish west coast. Nevertheless, species could be rotated for different purposes during the year. Biomass production could be combined with nutrient recycling of wastewater, for example, from fish industry. Our project faces a challenge in boosting the biomass produced in winter, but this could be solved, for example, by optimization of the cultivation medium and temperature increase with heat wastewater or other heat waste. The summer species Nannochloropsis proved to withstand winter by activating different lipid metabolic pathways than the cold-adapted species Skeletonema uses. Enhanced synthesis of proteins, such as enzymes, in Skeletonema during winter may compensate for their reduced activities, promoting growth and biomass production even at low temperatures. More species need to be studied to find those with higher productivity under winter conditions. In practice, the work-related consequences of a rotational cultivation should be weighed against its benefits, relative to a shorter cultivation season in each application. Potential applications mainly include cleaning of air and seawater, production of energy, biomass and biomaterials for the industry.
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| 5. |
- Bengtsson-Palme, Johan, 1985
(författare)
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Microbial model communities: To understand complexity, harness the power of simplicity
- 2020
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Ingår i: Computational and Structural Biotechnology Journal. - : Elsevier BV. - 2001-0370. ; 18, s. 3987-4001
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Forskningsöversikt (refereegranskat)abstract
- Natural microbial communities are complex ecosystems with myriads of interactions. To deal with this complexity, we can apply lessons learned from the study of model organisms and try to find simpler systems that can shed light on the same questions. Here, microbial model communities are essential, as they can allow us to learn about the metabolic interactions, genetic mechanisms and ecological principles governing and structuring communities. A variety of microbial model communities of varying complexity have already been developed, representing different purposes, environments and phenomena. However, choosing a suitable model community for one's research question is no easy task. This review aims to be a guide in the selection process, which can help the researcher to select a sufficiently well-studied model community that also fulfills other relevant criteria. For example, a good model community should consist of species that are easy to grow, have been evaluated for community behaviors, provide simple readouts and – in some cases – be of relevance for natural ecosystems. Finally, there is a need to standardize growth conditions for microbial model communities and agree on definitions of community-specific phenomena and frameworks for community interactions. Such developments would be the key to harnessing the power of simplicity to start disentangling complex community interactions.
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| 6. |
- Ortiz Catalan, Max Jair, 1982, et al.
(författare)
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Self-Contained Neuromusculoskeletal Arm Prostheses
- 2020
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:18, s. 1732-1738
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Tidskriftsartikel (refereegranskat)abstract
- After transhumeral amputation, four patients had implantation of a self-contained, osseointegrated prosthesis with a neuromusculoskeletal interface that allowed intuitive control of the prosthetic hand and arm over 3 to 7 years. A video shows use of the prostheses in daily life. We report the use of a bone-anchored, self-contained robotic arm with both sensory and motor components over 3 to 7 years in four patients after transhumeral amputation. The implant allowed for bidirectional communication between a prosthetic hand and electrodes implanted in the nerves and muscles of the upper arm and was anchored to the humerus through osseointegration, the process in which bone cells attach to an artificial surface without formation of fibrous tissue. Use of the device did not require formal training and depended on the intuitive intent of the user to activate movement and sensory feedback from the prosthesis. Daily use resulted in increasing sensory acuity and effectiveness in work and other activities of daily life. (Funded by the Promobilia Foundation and others.)
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| 7. |
- Zhao, Meng, et al.
(författare)
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Pathway engineering in yeast for synthesizing the complex polyketide bikaverin
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Fungal polyketides display remarkable structural diversity and bioactivity, and therefore the biosynthesis and engineering of this large class of molecules is therapeutically significant. Here, we successfully recode, construct and characterize the biosynthetic pathway of bikaverin, a tetracyclic polyketide with antibiotic, antifungal and anticancer properties, in S. cerevisiae. We use a green fluorescent protein (GFP) mapping strategy to identify the low expression of Bik1 (polyketide synthase) as a major bottleneck step in the pathway, and a promoter exchange strategy is used to increase expression of Bik1 and bikaverin titer. Then, we use an enzyme-fusion strategy to directly couple the monooxygenase (Bik2) and methyltransferase (Bik3) to efficiently channel intermediates between modifying enzymes, leading to an improved titer of bikaverin at 202.75 mg/L with flask fermentation (273-fold higher than the initial titer). This study demonstrates that the biosynthesis of complex fungal polyketides can be established and efficiently engineered in S. cerevisiae, highlighting the potential for natural product synthesis and large-scale fermentation in yeast.
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| 8. |
- Chen, Hui, et al.
(författare)
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Refractive index of delignified wood for transparent biocomposites
- 2020
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Ingår i: RSC Advances. - 2046-2069. ; 10, s. 40719-40724
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Tidskriftsartikel (refereegranskat)abstract
- Refractive index (RI) determination for delignified wood templates is vital for transparent wood composite fabrication. Reported RIs in the literature are based on either single plant fibers or wood powder, measured by the immersion liquid method (ILM) combined with mathematical fitting. However, wood structure complexity and the physical background of the fitting were not considered. In this work, RIs of delignified wood templates were measured by the ILM combined with a light transmission model developed from the Fresnel reflection/refraction theory for composite materials. The RIs of delignified balsa wood are 1.536 ± 0.006 and 1.525 ± 0.008 at the wavelength of 589 nm for light propagating perpendicular and parallel to the wood fiber direction, respectively. For delignified birch wood, corresponding values are 1.537 ± 0.005 and 1.529 ± 0.006, respectively. The RI data for delignified wood scaffolds are important for tailoring optical properties of transparent wood biocomposites, and also vital in optical properties investigations by theoretical modelling of complex light propagation in transparent wood and related composites. The developed light transmission model in combination with the immersion liquid method can be used to determine the RI of complex porous or layered solid materials and composites.
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| 9. |
- Amiandamhen, Stephen, 1983-, et al.
(författare)
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Bioenergy production and utilization in different sectors in Sweden: A state of the art review
- 2020
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Ingår i: BioResources. - : University of North Carolina Press. - 1930-2126. ; 15:4, s. 9834-9857
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Forskningsöversikt (refereegranskat)abstract
- In the continual desire to reduce the environmental footprints of human activities, research efforts to provide cleaner energy is increasingly becoming vital. The effect of climate change on present and future existence, sustainable processes, and utilizations of renewable resources have been active topics within international discourse. In order to reduce the greenhouse gases emissions from traditional materials and processes, there has been a shift to more environmental friendly alternatives. The conversion of biomass to bioenergy, including biofuels has been considered to contribute to the future of climate change mitigation, although there are concerns about carbon balance from forest utilization. Bioenergy accounts for more than one-third of all energy used in Sweden and biomass has provided about 60% of the fuel for district heating. Apart from heat and electricity supply, the transport sector, with about 30% of global energy use, has a significant role in a sustainable bioenergy system. This review presents the state of the art in the Swedish bioenergy sector based on literature and Swedish Energy Agency’s current statistics. The review also discusses the overall bioenergy production and utilization in different sectors in Sweden. The current potential, challenges, and environmental considerations of bioenergy production are also discussed.
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| 10. |
- Walladbegi, Java, et al.
(författare)
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Three-dimensional bioprinting using a coaxial needle with viscous inks in bone tissue engineering - An in vitro study
- 2020
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Ingår i: Annals of Maxillofacial Surgery. - : Medknow. - 2249-3816 .- 2231-0746. ; 10:2, s. 370-376
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Vascularized autologous tissue grafts are considered 'gold standard' for the management of larger bony defects in the craniomaxillofacial area. This modality does however carry limitations, such as the absolute requirement for healthy donor tissues and recipient vessels. In addition, the significant morbidity of large bone graft is deterrent to fibula bone flap use. Therefore, less morbid strategies would be beneficial. The purpose of this study was to develop a printing method to manufacture scaffold structure with viable stem cells. Materials and Methods: In total, three different combinations of ground beta tri-calcium phosphate and CELLINK (bioinks) were printed with a nozzle to identify a suitable bioink for three-dimensional printing. Subsequently, a coaxial needle, with three different nozzle gauge combinations, was evaluated for printing of the bioinks. Scaffold structures (grids) were then printed alone and with additional adipose stem cells before being transferred into an active medium and incubated overnight. Following incubation, grid stability was evaluated by assessing the degree of maintained grid outline, and cell viability was determined using the live/dead cell assay. Results: Among the three evaluated combinations of bioinks, two resulted in good printability for bioprinting. Adequate printing was obtained with two out of the three nozzle gauge combinations tested. However, due to the smaller total opening, one combination revealed a better stability. Intact grids with maintained stability were obtained using Ink B23 and Ink B42, and approximately 80% of the printed stem cells were viable following 24 hours. Discussion: Using a coaxial needle enables printing of a stable scaffold with viable stem cells. Furthermore, cell viability is maintained after the bioprinting process.
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