| 1. |
- Best, Mairi, et al.
(författare)
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EMSO: A distributed infrastructure for addressing geohazards and global ocean change
- 2014
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Ingår i: Oceanography. - : The Oceanography Society. - 1042-8275. ; 27:2, s. 167-169
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Tidskriftsartikel (refereegranskat)abstract
- The European Multidisciplinary Seafloor and water-column Observatory (EMSO; http://www.emso-eu.org) is addressing the next challenge in Earth-ocean science: how to coordinate data acquisition, analysis, archiving, access, and response to geohazards across provincial, national, regional, and international boundaries. Such coordination is needed to optimize the use of current and planned ocean observatory systems to (1) address national and regional public safety concerns about geohazards (e.g., earthquakes, submarine landslides, tsunamis) and (2) permit broadening of their scope toward monitoring environmental change on global ocean scales.
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| 2. |
- Best, Mairi M. R., et al.
(författare)
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The EMSO-ERIC Pan-European Consortium: Data Benefits and Lessons Learned as the Legal Entity Forms
- 2016
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Ingår i: Marine Technology Society journal. - 0025-3324. ; 50:3, s. 8-15
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Tidskriftsartikel (refereegranskat)abstract
- The European Multidisciplinary Seafloor and water-column Observatory (EMSO) European Research Infrastructure Consortium (ERIC) provides power, communications, sensors, and data infrastructure for continuous, high-resolution, (near-)real-time, interactive ocean observations across a multidisciplinary and interdisciplinary range of research areas including biology, geology, chemistry, physics, engineering, and computer science, from polar to subtropical environments, through the water column down to the abyss. Eleven deep-sea and four shallow nodes span from the Arctic through the Atlantic and Mediterranean, to the Black Sea. Coordination among the consortium nodes is being strengthened through the EMSOdev project (H2020), which will produce the EMSO Generic Instrument Module (EGIM). Early installations are now being upgraded, for example, at the Ligurian, Ionian, Azores, and Porcupine Abyssal Plain (PAP) nodes. Significant findings have been flowing in over the years; for example, high-frequency surface and subsurface water-column measurements of the PAP node show an increase in seawater pCO2 (from 339 μatm in 2003 to 353 μatm in 2011) with little variability in the mean air-sea CO2 flux. In the Central Eastern Atlantic, the Oceanic Platform of the Canary Islands open-ocean canary node (aka ESTOC station) has a long-standing time series on water column physical, biogeochemical, and acidification processes that have contributed to the assessment efforts of the Intergovernmental Panel on Climate Change (IPCC). EMSO not only brings together countries and disciplines but also allows the pooling of resources and coordination to assemble harmonized data into a comprehensive regional ocean picture, which will then be made available to researchers and stakeholders worldwide on an open and interoperable access basis.
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| 3. |
- Habicher, Judith, et al.
(författare)
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Chondroitin/dermatan sulfate glycosyltransferase genes are essential for craniofacial development
- 2022
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 18:2
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Tidskriftsartikel (refereegranskat)abstract
- Chondroitin/dermatan sulfate (CS/DS) proteoglycans are indispensable for animal development and homeostasis but the large number of enzymes involved in their biosynthesis have made CS/DS function a challenging problem to study genetically. In our study, we generated loss-of-function alleles in zebrafish genes encoding CS/DS biosynthetic enzymes and characterized the effect on development in single and double mutants. Homozygous mutants in chsy1, csgalnact1a, csgalnat2, chpfa, ust and chst7, respectively, develop to adults. However, csgalnact1a-/- fish develop distinct craniofacial defects while the chsy1-/- skeletal phenotype is milder and the remaining mutants display no gross morphological abnormalities. These results suggest a high redundancy for the CS/DS biosynthetic enzymes and to further reduce CS/DS biosynthesis we combined mutant alleles. The craniofacial phenotype is further enhanced in csgalnact1a-/-;chsy1-/- adults and csgalnact1a-/-;csgalnact2-/- larvae. While csgalnact1a-/-;csgalnact2-/- was the most affected allele combination in our study, CS/DS is still not completely abolished. Transcriptome analysis of chsy1-/-, csgalnact1a-/- and csgalnact1a-/-;csgalnact2-/- larvae revealed that the expression had changed in a similar way in the three mutant lines but no differential expression was found in any of fifty GAG biosynthesis enzymes identified. Thus, zebrafish larvae do not increase transcription of GAG biosynthesis genes as a consequence of decreased CS/DS biosynthesis. The new zebrafish lines develop phenotypes similar to clinical characteristics of several human congenital disorders making the mutants potentially useful to study disease mechanisms and treatment.
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| 4. |
- Knyazeva, Anastasia, 1995-, et al.
(författare)
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A chemical inhibitor of IST1-CHMP1B interaction impairs endosomal recycling and induces noncanonical LC3 lipidation
- 2024
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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. - 0027-8424 .- 1091-6490. ; 121:17
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Tidskriftsartikel (refereegranskat)abstract
- The endosomal sorting complex required for transport (ESCRT) machinery constitutes multisubunit protein complexes that play an essential role in membrane remodeling and trafficking. ESCRTs regulate a wide array of cellular processes, including cytokinetic abscission, cargo sorting into multivesicular bodies (MVBs), membrane repair, and autophagy. Given the versatile functionality of ESCRTs, and the intricate organizational structure of the ESCRT machinery, the targeted modulation of distinct ESCRT complexes is considerably challenging. This study presents a pseudonatural product targeting IST1-CHMP1B within the ESCRT-III complexes. The compound specifically disrupts the interaction between IST1 and CHMP1B, thereby inhibiting the formation of IST1-CHMP1B copolymers essential for normal-topology membrane scission events. While the compound has no impact on cytokinesis, MVB sorting, or biogenesis of extracellular vesicles, it rapidly inhibits transferrin receptor recycling in cells, resulting in the accumulation of transferrin in stalled sorting endosomes. Stalled endosomes become decorated by lipidated LC3, suggesting a link between noncanonical LC3 lipidation and inhibition of the IST1-CHMP1B complex.
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| 5. |
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| 6. |
- Laraia, Luca, et al.
(författare)
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The cholesterol transfer protein GRAMD1A regulates autophagosome biogenesis
- 2019
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Ingår i: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 15:7, s. 710-720
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Tidskriftsartikel (refereegranskat)abstract
- Autophagy mediates the degradation of damaged proteins, organelles and pathogens, and plays a key role in health and disease. Thus, the identification of new mechanisms involved in the regulation of autophagy is of major interest. In particular, little is known about the role of lipids and lipid-binding proteins in the early steps of autophagosome biogenesis. Using target-agnostic, high-content, image-based identification of indicative phenotypic changes induced by small molecules, we have identified autogramins as a new class of autophagy inhibitor. Autogramins selectively target the recently discovered cholesterol transfer protein GRAM domain-containing protein 1A (GRAMD1A, which had not previously been implicated in autophagy), and directly compete with cholesterol binding to the GRAMD1A StART domain. GRAMD1A accumulates at sites of autophagosome initiation, affects cholesterol distribution in response to starvation and is required for autophagosome biogenesis. These findings identify a new biological function of GRAMD1A and a new role for cholesterol in autophagy.
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| 7. |
- Leyhr, Jake, et al.
(författare)
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A novel cis-regulatory element drives early expression of Nkx3.2 in the gnathostome primary jaw joint
- 2022
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The acquisition of movable jaws was a major event during vertebrate evolution. The role of NK3 homeobox 2 (Nkx3.2) transcription factor in patterning the primary jaw joint of gnathostomes (jawed vertebrates) is well known, however knowledge about its regulatory mechanism is lacking. In this study, we report a proximal enhancer element of Nkx3.2 that is deeply conserved in most gnathostomes but undetectable in the jawless hagfish and lamprey. This enhancer is active in the developing jaw joint region of the zebrafish Danio rerio, and was thus designated as jaw joint regulatory sequence 1 (JRS1). We further show that JRS1 enhancer sequences from a range of gnathostome species, including a chondrichthyan and mammals, have the same activity in the jaw joint as the native zebrafish enhancer, indicating a high degree of functional conservation despite the divergence of cartilaginous and bony fish lineages or the transition of the primary jaw joint into the middle ear of mammals. Finally, we show that deletion of JRS1 from the zebrafish genome using CRISPR/Cas9 results in a significant reduction of early gene expression of nkx3.2 and leads to a transient jaw joint deformation and partial fusion. Emergence of this Nkx3.2 enhancer in early gnathostomes may have contributed to the origin and shaping of the articulating surfaces of vertebrate jaws.
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| 8. |
- Ruhl, Henry A., et al.
(författare)
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Societal need for improved understanding of climate change, anthropogenic impacts, and geo-hazard warning drive development of ocean observatories in European Seas
- 2011
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Ingår i: Progress In Oceanography. ; 91:1, s. 1-33
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Tidskriftsartikel (refereegranskat)abstract
- Society’s needs for a network of in situ ocean observing systems cross many areas of earth and marine science. Here we review the science themes that benefit from data supplied from ocean observatories. Understanding from existing studies is fragmented to the extent that it lacks the coherent long-term monitoring needed to address questions at the scales essential to understand climate change and improve geo-hazard early warning. Data sets from the deep sea are particularly rare with long-term data available from only a few locations worldwide. These science areas have impacts on societal health and well-being and our awareness of ocean function in a shifting climate. Substantial efforts are underway to realise a network of open-ocean observatories around European Seas that will operate over multiple decades. Some systems are already collecting high-resolution data from surface, water column, seafloor, and sub-seafloor sensors linked to shore by satellite or cable connection in real or near-real time, along with samples and other data collected in a delayed mode. We expect that such observatories will contribute to answering major ocean science questions including: How can monitoring of factors such as seismic activity, pore fluid chemistry and pressure, and gas hydrate stability improve seismic, slope failure, and tsunami warning? What aspects of physical oceanography, biogeochemical cycling, and ecosystems will be most sensitive to climatic and anthropogenic change? What are natural versus anthropogenic changes? Most fundamentally, how are marine processes that occur at differing scales related? The development of ocean observatories provides a substantial opportunity for ocean science to evolve in Europe. Here we also describe some basic attributes of network design. Observatory networks provide the means to coordinate and integrate the collection of standardised data capable of bridging measurement scales across a dispersed area in European Seas adding needed certainty to estimates of future oceanic conditions. Observatory data can be analysed along with other data such as those from satellites, drifting floats, autonomous underwater vehicles, model analysis, and the known distribution and abundances of marine fauna in order to address some of the questions posed above. Standardised methods for information management are also becoming established to ensure better accessibility and traceability of these data sets and ultimately to increase their use for societal benefit. The connection of ocean observatory effort into larger frameworks including the Global Earth Observation System of Systems (GEOSS) and the Global Monitoring of Environment and Security (GMES) is integral to its success. It is in a greater integrated framework that the full potential of the component systems will be realised.
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| 9. |
- Tinetti, G., et al.
(författare)
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A chemical survey of exoplanets with ARIEL
- 2018
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 46:1, s. 135-209
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Tidskriftsartikel (refereegranskat)abstract
- Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.
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| 10. |
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| 11. |
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| 12. |
- Waldmann, Laura, et al.
(författare)
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The Broad Role of Nkx3.2 in the Development of the Zebrafish Axial Skeleton
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The transcription factor Nkx3.2 (Bapx1) is an important chondrocyte maturation inhibitor. Previous Nkx3.2 knock-down and overexpression studies in non-mammalian gnathostomes have focused on its role in primary jaw joint development, while little is known about the function of this gene in broader skeletal development. We generated CRISPR/Cas9 knockout of nkx3.2 in zebrafish and applied a range of techniques to characterize skeletal phenotypes at developmental stages from larva to adult, revealing fusions in bones of the occiput, the loss or deformation of bony elements derived from basiventral cartilages of the vertebrae, and an increased length of the proximal radials of the dorsal and anal fins. These phenotypes are reminiscent of Nkx3.2 knockout phenotypes in mammals, suggesting that the function of this gene in axial skeletal development is ancestral to osteichthyans. Our results highlight the broad role of nkx3.2 in zebrafish skeletal development and its context-specific functions in different skeletal elements.
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| 13. |
- Waldmann, Laura, et al.
(författare)
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The broad role of Nkx3.2 in the development of the zebrafish axial skeleton
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:8
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor Nkx3.2 (Bapx1) is an important chondrocyte maturation inhibitor. Previous Nkx3.2 knockdown and overexpression studies in non-mammalian gnathostomes have focused on its role in primary jaw joint development, while the function of this gene in broader skeletal development is not fully described. We generated a mutant allele of nkx3.2 in zebrafish with CRISPR/Cas9 and applied a range of techniques to characterize skeletal phenotypes at developmental stages from larva to adult, revealing loss of the jaw joint, fusions in bones of the occiput, morphological changes in the Weberian apparatus, and the loss or deformation of bony elements derived from basiventral cartilages of the vertebrae. Axial phenotypes are reminiscent of Nkx3.2 knockout in mammals, suggesting that the function of this gene in axial skeletal development is ancestral to osteichthyans. Our results highlight the broad role of nkx3.2 in zebrafish skeletal development and its context-specific functions in different skeletal elements.
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| 14. |
- Waldmann, Laura, et al.
(författare)
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The Role of Gdf5 in the Development of the Zebrafish Fin Endoskeleton
- 2022
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Ingår i: Developmental Dynamics. - : John Wiley & Sons. - 1058-8388 .- 1097-0177. ; 251:9, s. 1535-1549
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Tidskriftsartikel (refereegranskat)abstract
- The development of the vertebrate skeleton requires a complex interaction of multiple factors to facilitate correct shaping and positioning of bones and joints. Growth and differentiation factor 5 (Gdf5), a member of the transforming growth factor-beta family (TGF-beta) is involved in patterning appendicular skeletal elements including joints. Expression of gdf5 in zebrafish has been detected within the first pharyngeal arch jaw joint, fin mesenchyme condensations and segmentation zones in median fins, however little is known about the functional role of Gdf5 outside of Amniota. We generated CRISPR/Cas9 knockout of gdf5 in zebrafish and analysed the resulting phenotype at different developmental stages. Homozygous gdf5 mutant zebrafish display truncated median fin endoskeletal elements and loss of posterior radials in the pectoral fins. These findings are consistent with phenotypes observed in human and mouse appendicular skeleton in response to Gdf5 knockout, suggesting a broadly conserved role for Gdf5 in Osteichthyes.
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| 15. |
- Waldmann, Laura, 1991-
(författare)
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The role of Nkx3.2 and Gdf5 during zebrafish skeletal development
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The vertebrate skeleton is composed of bony and cartilaginous structures that are developed under the control of numerous genetic networks. The transcription factor Nkx3.2 and the signaling molecule Gdf5 play a fundamental role during joint development and chondrogenesis, a process whereby mesenchyme cells form precartilaginous condensations followed by chondrocyte differentiation. Mutations in these genes can lead to some rare human skeletal diseases and are furthermore thought to play a role during osteoarthritis, whereby the articular cartilage in synovial joints degrades. Both genes are fairly well studied in amniotes, but their full function and regulation are not completely understood. This thesis focuses on further characterization of Nkx3.2 and Gdf5 function, by using the zebrafish Danio rerio, a small vertebrate, as a model organism.We generated a CRISPR/Cas9 nkx3.2 mutant zebrafish line and detected broad phenotypes in the axial skeleton. Nkx3.2 deficiency in knockout zebrafish confirms previously reported jaw joint loss, but also revealed new phenotypes in the occipital region, the Weberian apparatus, the vertebrae and some fins.By identifying a cis-regulatory element of nkx3.2 in zebrafish, we were able to generate a transgenic zebrafish line labelling the developing jaw joint and jaw joint progenitor cells. This line enables detailed documentation of jaw joint development and paves the way for a better understanding of joint development. Knockout of this nkx3.2 enhancer sequence in zebrafish did not result in any phenotypic differences, indicating a redundant function. Besides the identification of a nkx3.2 enhancer in the zebrafish genome, we identified homologous nkx3.2 enhancer sequences in the genomes of multiple gnathostome species and found that they display a high degree of functional conservation.To study the role of Gdf5, we generated a CRISPR/Cas9 gdf5 mutant line. gdf5 mutant zebrafish displayed abnormalities in endoskeletal elements of all median and the pectoral fins showing truncation of median fin endoskeletal elements and partial absence of pectoral fin radials.Finally, we developed an optical projection tomography (OPT) based automated workflow to generate 3D reconstructions of in situ and skeletal-stained zebrafish embryos and larvae. The acquired imaging data of skeletal-stained larval zebrafish was subsequently used to quantify phenotypic differences between mutant and wild-type zebrafish groups. This technique allows for the identification of even subtle phenotypic differences at early stages of development.To conclude, the work presented in this thesis provides further understanding of the role of Nkx3.2 and Gdf5 during skeletogenesis in zebrafish and contributes to the development of zebrafish imaging techniques.
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| 16. |
- Zhang, Hanqing, et al.
(författare)
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zOPT: an open source optical projection tomography system and methods for rapid 3D zebrafish imaging
- 2020
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Ingår i: Biomedical Optics Express. - : The Optical Society. - 2156-7085. ; 11:8, s. 4290-4305
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Tidskriftsartikel (refereegranskat)abstract
- Optical projection tomography (OPT) is a 3D imaging alternative to conventional microscopy which allows imaging of millimeter-sized object with isotropic micrometer resolution. The zebrafish is an established model organism and an important tool used in genetic and chemical screening. The size and optical transparency of the embryo and larva makes them well suited for imaging using OPT. Here, we present an open-source implementation of an OPT platform, built around a customized sample stage, 3D-printed parts and open source algorithms optimized for the system. We developed a versatile automated workflow including a two-step image processing approach for correcting the center of rotation and generating accurate 3D reconstructions. Our results demonstrate high-quality 3D reconstruction using synthetic data as well as real data of live and fixed zebrafish. The presented 3D-printable OPT platform represents a fully open design, low-cost and rapid loading and unloading of samples. Our system offers the opportunity for researchers with different backgrounds to setup and run OPT for large scale experiments, particularly in studies using zebrafish larvae as their key model organism.
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