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- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 3. |
- Hendrikse, Natalie, et al.
(författare)
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Ancestral lysosomal enzymes with increased activity harbor therapeutic potential for treatment of Hunter syndrome
- 2021
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Ingår i: ISCIENCE. - : Elsevier BV. - 2589-0042. ; 24:3
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Tidskriftsartikel (refereegranskat)abstract
- We show the successful application of ancestral sequence reconstruction to enhance the activity of iduronate-2-sulfatase (IDS), thereby increasing its therapeutic potential for the treatment of Hunter syndrome-a lysosomal storage disease caused by impaired function of IDS. Current treatment, enzyme replacement therapy with recombinant human IDS, does not alleviate all symptoms, and an unmet medical need remains. We reconstructed putative ancestral sequences of mammalian IDS and compared them with extant IDS. Some ancestral variants displayed up to 2-fold higher activity than human IDS in in vitro assays and cleared more substrate in ex vivo experiments in patient fibroblasts. This could potentially allow for lower dosage or enhanced therapeutic effect in enzyme replacement therapy, thereby improving treatment outcomes and cost efficiency, as well as reducing treatment burden. In summary, we showed that ancestral sequence reconstruction can be applied to lysosomal enzymes that function in concert with modern enzymes and receptors in cells.
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| 4. |
- Hendrikse, Natalie M., et al.
(författare)
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Exploring the therapeutic potential of modern and ancestral phenylalanine/tyrosine ammonia-lyases as supplementary treatment of hereditary tyrosinemia
- 2020
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Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Phenylalanine/tyrosine ammonia-lyases (PAL/TALs) have been approved by the FDA for treatment of phenylketonuria and may harbour potential for complementary treatment of hereditary tyrosinemia Type I. Herein, we explore ancestral sequence reconstruction as an enzyme engineering tool to enhance the therapeutic potential of PAL/TALs. We reconstructed putative ancestors from fungi and compared their catalytic activity and stability to two modern fungal PAL/TALs. Surprisingly, most putative ancestors could be expressed as functional tetramers in Escherichia coli and thus retained their ability to oligomerize. All ancestral enzymes displayed increased thermostability compared to both modern enzymes, however, the increase in thermostability was accompanied by a loss in catalytic turnover. One reconstructed ancestral enzyme in particular could be interesting for further drug development, as its ratio of specific activities is more favourable towards tyrosine and it is more thermostable than both modern enzymes. Moreover, long-term stability assessment showed that this variant retained substantially more activity after prolonged incubation at 25 °C and 37 °C, as well as an increased resistance to incubation at 60 °C. Both of these factors are indicative of an extended shelf-life of biopharmaceuticals. We believe that ancestral sequence reconstruction has potential for enhancing the properties of enzyme therapeutics, especially with respect to stability. This work further illustrates that resurrection of putative ancestral oligomeric proteins is feasible and provides insight into the extent of conservation of a functional oligomerization surface area from ancestor to modern enzyme.
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| 5. |
- Hentati-Sundberg, Jonas, et al.
(författare)
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Seabird surveillance: combining CCTV and artificial intelligence for monitoring and research
- 2023
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Ingår i: Remote Sensing in Ecology and Conservation. - : Wiley. - 2056-3485. ; 9:4, s. 568-581
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Tidskriftsartikel (refereegranskat)abstract
- Ecological research and monitoring need to be able to rapidly convey information that can form the basis of scientifically sound management. Automated sensor systems, especially if combined with artificial intelligence, can contribute to such rapid high-resolution data retrieval. Here, we explore the prospects of automated methods to generate insights for seabirds, which are often monitored for their high conservation value and for being sentinels for marine ecosystem changes. We have developed a system of video surveillance combined with automated image processing, which we apply to common murres Uria aalge. The system uses a deep learning algorithm for object detection (YOLOv5) that has been trained on annotated images of adult birds, chicks and eggs, and outputs time, location, size and confidence level of all detections, frame-by-frame, in the supplied video material. A total of 144 million bird detections were generated from a breeding cliff over three complete breeding seasons (2019–2021). We demonstrate how object detection can be used to accurately monitor breeding phenology and chick growth. Our automated monitoring approach can also identify and quantify rare events that are easily missed in traditional monitoring, such as disturbances from predators. Further, combining automated video analysis with continuous measurements from a temperature logger allows us to study impacts of heat waves on nest attendance in high detail. Our automated system thus produces comparable, and in several cases significantly more detailed, data than those generated from observational field studies. By running in real time on the camera streams, it has the potential to supply researchers and managers with high-resolution up-to-date information on seabird population status. We describe how the system can be modified to fit various types of ecological research and monitoring goals and thereby provide up-to-date support for conservation and ecosystem management.
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| 10. |
- Lai, Chung-Chuan, et al.
(författare)
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Effect of substrate roughness and material selection on the microstructure of sputtering deposited boron carbide thin films
- 2022
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Ingår i: Surface & Coatings Technology. - Lausanne, Switzerland : Elsevier. - 0257-8972 .- 1879-3347. ; 433
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Tidskriftsartikel (refereegranskat)abstract
- Amorphous boron carbide (B4C) thin films are by far the most popular form for the neutron converting layers in the 10B-based neutron detectors, which are a rising trend in detector technologies in response to the increasing scarcity and price of 3He, the standard material for neutron detection. The microstructure of the B4C films is closely related to the important properties, e.g. density and adhesion, for the converting layers, which eventually affect the detection efficiency and the long-term stability of the detectors. To study the influence from substrates of different roughness and materials, the B4C films were deposited on polished Si substrates with Al, Ti, and Cu buffer layers and unpolished Si, Al, Ti, and Cu substrates by direct current magnetron sputtering at a substrate temperature of 623 K. The tapered columnar grains and nodular defects, generally observed in SEM images, indicated a strong shadowing effect where voids were introduced around the grains. The change in the grain size did not show a direct dependence to the substrate roughness, acquired from the surface profile, nor to the mass density of the films, obtained from reflectivity patterns. However, films with non-uniform size of columnar grains were deposited on substrates with high skewness, leading to a drop of mass density from ∼95% down to ∼70% of tabulated bulk density. On the other hand, similar microstructures and mass density were obtained from the films deposited on Al, Ti, and Cu of different roughness and good adhesion were observed from cross-cut adhesion tests, showing the reliability of sputtering deposited B4C films on common structural materials in neutron detectors.
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