| 1. |
- Filipek-Gorniok, Beata, et al.
(författare)
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Expression of chondroitin/dermatan sulfate glycosyltransferases during early zebrafish development
- 2013
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Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 242:8, s. 964-975
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chondroitin/dermatan sulfate (CS/DS) proteoglycans present in the extracellular matrix have important structural and regulatory functions. Results: Six human genes have previously been shown to catalyze CS/DS polymerization. Here we show that one of these genes, chpf, is represented by two copies in the zebrafish genome, chpfa and chpfb, while the other five human CS/DS glycosyltransferases csgalnact1, csgalnact2, chpf2, chsy1, and chsy3 all have single zebrafish orthologues. The putative zebrafish CS/DS glycosyltransferases are spatially and temporally expressed. Interestingly, overlapping expression of multiple glycosyltransferases coincides with high CS/DS deposition. Finally, whereas the relative levels of the related polysaccharide HS reach steady-state at around 2 days post fertilization, there is a continued relative increase of the CS amounts per larvae during the first 6 days of development, matching the increased cartilage formation. Conclusions: There are 7 CS/DS glycosyltransferases in zebrafish, which, based on homology, can be divided into the CSGALNACT, CHSY, and CHPF families. The overlap between intense CS/DS production and the expression of multiple CS/DS glycosyltransferases suggests that efficient CS/DS biosynthesis requires a combination of several glycosyltransferases.
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| 2. |
- Holmborn, Katarina, et al.
(författare)
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On the Roles and Regulation of Chondroitin Sulfate and Heparan Sulfate in Zebrafish Pharyngeal Cartilage Morphogenesis
- 2012
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 287:40, s. 33905-33916
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Tidskriftsartikel (refereegranskat)abstract
- The present study addresses the roles of heparan sulfate (HS) proteoglycans and chondroitin sulfate (CS) proteoglycans in the development of zebrafish pharyngeal cartilage structures. uxs1 and b3gat3 mutants, predicted to have impaired biosynthesis of both HS and CS because of defective formation of the common proteoglycan linkage tetrasaccharide were analyzed along with ext2 and extl3 mutants, predicted to have defective HS polymerization. Notably, the effects on HS and CS biosynthesis in the respective mutant strains were shown to differ from what had been hypothesized. In uxs1 and b3gat3 mutant larvae, biosynthesis of CS was shown to be virtually abolished, whereas these mutants still were capable of synthesizing 50% of the HS produced in control larvae. extl3 and ext2 mutants on the other hand were shown to synthesize reduced amounts of hypersulfated HS. Further, extl3 mutants produced higher levels of CS than control larvae, whereas morpholino-mediated suppression of csgalnact1/csgalnact2 resulted in increased HS biosynthesis. Thus, the balance of the Extl3 and Csgalnact1/Csgalnact2 proteins influences the HS/CS ratio. A characterization of the pharyngeal cartilage element morphologies in the single mutant strains, as well as in ext2;uxs1 double mutants, was conducted. A correlation between HS and CS production and phenotypes was found, such that impaired HS biosynthesis was shown to affect chondrocyte intercalation, whereas impaired CS biosynthesis inhibited formation of the extracellular matrix surrounding chondrocytes.
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| 3. |
- Abramsson, Alexandra, 1973, et al.
(författare)
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Defective N-sulfation of heparan sulfate proteoglycans limits PDGF-BB binding and pericyte recruitment in vascular development
- 2007
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Ingår i: GENES & DEVELOPMENT. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 21:3, s. 316-331
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Tidskriftsartikel (refereegranskat)abstract
- During vascular development, endothelial platelet-derived growth factor B (PDGF-B) is critical for pericyte recruitment. Deletion of the conserved C-terminal heparin-binding motif impairs PDGF-BB retention and pericyte recruitment in vivo, suggesting a potential role for heparan sulfate (HS) in PDGF-BB function during vascular development. We studied the participation of HS chains in pericyte recruitment using two mouse models with altered HS biosynthesis. Reduction of N-sulfation due to deficiency in N-deacetylase/N-sulfotransferase-1 attenuated PDGF-BB binding in vitro, and led to pericyte detachment and delayed pericyte migration in vivo. Reduced N-sulfation also impaired PDGF-BB signaling and directed cell migration, but not proliferation. In contrast, HS from glucuronyl C5-epimerase mutants, which is extensively N- and 6-O-sulfated, but lacks 2-O-sulfated L-iduronic acid residues, retained PDGF-BB in vitro, and pericyte recruitment in vivo was only transiently delayed. These observations were supported by in vitro characterization of the structural features in HS important for PDGF-BB binding. We conclude that pericyte recruitment requires HS with sufficiently extended and appropriately spaced N-sulfated domains to retain PDGF-BB and activate PDGF receptor β (PDGFRβ) signaling, whereas the detailed sequence of monosaccharide and sulfate residues does not appear to be important for this interaction.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Bandaru, Manoj Kumar, et al.
(författare)
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Zebrafish larvae as a model system for systematic characterization of drugs and genes in dyslipidemia and atherosclerosis
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Hundreds of loci have been robustly associated with circulating lipids, atherosclerosis and coronary artery disease; but for most loci the causal genes and mechanisms remain uncharacterized.Methods: We developed a semi-automated experimental pipeline for systematic, quantitative, large-scale characterization of mechanisms, drugs and genes associated with dyslipidemia and atherosclerosis in a zebrafish model system. We validated our pipeline using a dietary (n>2000), drug treatment (n>1000), and genetic intervention (n=384).Results: Our results show that five days of overfeeding and cholesterol supplementation had independent pro-atherogenic effects, which could be diminished by concomitant treatment with atorvastatin and ezetimibe. CRISPR-Cas9-induced mutations in orthologues of proof-of-concept genes resulted in higher LDL cholesterol levels (apoea), and more early stage atherosclerosis (apobb.1).Conclusions: In summary, our pipeline facilitates systematic, in vivo characterization of drugs and candidate genes to increase our understanding of disease etiology, and can likely help identify novel targets for therapeutic intervention.
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| 8. |
- Banote, Rakesh Kumar, et al.
(författare)
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Amyloid precursor protein-b facilitates cell adhesion during early development in zebrafish
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the biological function of amyloid beta (A beta) precursor protein (APP) beyond its role in Alzheimer's disease is emerging. Yet, its function during embryonic development is poorly understood. The zebrafish APP orthologue, Appb, is strongly expressed during early development but thus far has only been studied via morpholino-mediated knockdown. Zebrafish enables analysis of cellular processes in an ontogenic context, which is limited in many other vertebrates. We characterized zebrafish carrying a homozygous mutation that introduces a premature stop in exon 2 of the appb gene. We report that appb mutants are significantly smaller until 2 dpf and display perturbed enveloping layer (EVL) integrity and cell protrusions at the blastula stage. Moreover, appb mutants surviving beyond 48 hpf exhibited no behavioral defects at 6 dpf and developed into healthy and fertile adults. The expression of the app family member, appa, was also found to be altered in appb mutants. Taken together, we show that appb is involved in the initial development of zebrafish by supporting the integrity of the EVL, likely by mediating cell adhesion properties. The loss of Appb might then be compensated for by other app family members to maintain normal development.
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| 9. |
- Boisvert, Catherine Anne, 1978-
(författare)
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The Origin of Tetrapod Limbs and Girdles: Fossil and Developmental Evidence
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Around 375 million years ago, the first tetrapods appeared, marking one of the most important events in vertebrate evolutionary history. The fin to limb transition saw the appearance of fingers and a weight bearing pelvic girdle. While very little research has been done on the evolution of the tetrapod pelvic girdle, a fair amount has been done on the origins of fingers but some aspects remained controversial. A combination of palaeontology, developmental biology and comparative morphology was therefore used in this thesis to better understand the fin to limb transition. The pectoral fin of Panderichthys, a sarcopterygian fish closely related to tetrapods was CT-scanned and modeled in three dimensions and its pelvic girdle and fin were examined with traditional techniques. This information from the fossil record was integrated with comparisons of the development of the Australian lungfish, Neoceratodus forsteri, our closest living fish relative and the axolotl (Ambystoma mexicanum), a salamander representing well the condition of early tetrapods. Development of bone and cartilage was studied through clearing and staining and development of skeletal muscles through immunostaining. In situ hybridizations were performed on the lungfish to study the expression of Hoxd13, associated with the formation of digits in tetrapods. This work shows that the late expression phase of Hoxd13 is present in Neoceratodus and is associated with the formation of radials. Redescription of the pectoral fin of Panderichthys reveals that distal radials are present, which, in addition to other information, lead us to conclude that digits are not novelties in tetrapods but rather have evolved from the distal radials present in the fins of all sarcopterygian fish. The earliest tetrapods lack a full set of wrist + carpals/ankle + tarsal bones. Here, we propose that this region of the limbs evolved after fingers and toes through an expansion of the region between the proximal limb bones and the digits. As for the pelvic girdle, it is very primitive in Panderichthys but comparison of its development in Neoceratodus and Ambystoma suggest that the ischium evolved through the posterior expansion of the pubis and the ilium, through an elongation of the iliac process already present in sarcopterygian fishes. The results of this thesis help to better understand the fin to limb transition and show that it is more gradual than previously believed.
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| 10. |
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| 11. |
- Dahlman, Joakim, 1974-, et al.
(författare)
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Performance and Autonomic Responses during Motion Sickness
- 2009
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Ingår i: Human Factors. - : SAGE Publications. - 0018-7208 .- 1547-8181. ; 51:1, s. 56-66
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the study was to investigate how motion sickness, triggered by an optokinetic drum, affects short term memory performance and to explore autonomic responses to perceived motion sickness. Background: Previous research has found motion sickness to decrease performance, but it is not known how short term memory in particular is affected. Method: Thirty-eight healthy participants performed a listening span test while seated in a rotating optokinetic drum. Measurements of motion sickness, performance, heart rate, skin conductance, blood volume pulse, and pupil size were performed simultaneously throughout the experiment. Results: A total of 16 participants terminated the trial due to severe nausea, while the other 22 endured the full 25 minutes. Perceived motion sickness increased over time in both groups, but less among those who endured the trial. Short term memory performance decreased towards the end for those who terminated, while it increased for the other group. Results from the measured autonomic responses were ambiguous. Conclusion: The present study concludes that performance, measured as short term memory, declines as perceived motion sickness progresses. Application: This research has potential implications for command and control personnel in risk of developing motion sickness.
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| 12. |
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| 13. |
- Filipek-Górniok, Beata, 1983-
(författare)
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Glycosaminoglycan Biosynthesis in Zebrafish
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Proteoglycans (PGs) are composed of highly sulfated glycosaminoglycans chains (GAGs) attached to specific core proteins. They are present in extracellular matrices, on the cell surface and in storage granules of hematopoietic cells. Heparan sulfate (HS) and chondroitin/dermatan sulfate (CS/DS) GAGs play indispensable roles in a wide range of biological processes, where they can serve as protein carriers, be involved in growth factor or morphogen gradient formation and act as co-receptors in signaling processes. Protein binding abilities of GAGs are believed to be predominantly dependent on the arrangement of the sugar modifications, sulfation and epimerization, into specific oligosaccharide sequences. Although the process of HS and CS/DS assembly and modification is not fully understood, a set of GAG biosynthetic enzymes have been fairly well studied and several mutations in genes encoding for this Golgi machinery have been linked to human genetic disorders.This thesis focuses on the zebrafish N-deacetylase/N-sulfotransferase gene family, encoding key enzymes in HS chain modification, as well as glycosyltransferases responsible for chondroitin/dermatan sulfate elongation present in zebrafish. Our data illustrates the strict spatio-temporal expression of both the NDST enzymes (Paper I) and CS/DS glycosyltransferases (Paper II) in the developing zebrafish embryo. In Paper III we took advantage of the four preexisting zebrafish mutants with defective GAG biosynthesis. We could demonstrate a relation between HS content and the severity of the pectoral fin defects, and additionally correlate impaired HS biosynthesis with altered chondrocyte intercalation. Interestingly, altered CS biosynthesis resulted in loss of the chondrocyte extracellular matrix. One of the main findings was the demonstration of the ratio between the HS biosynthesis enzyme Extl3 and the Csgalnact1/Csgalnact2 proteins, as a main factor influencing the HS/CS ratio. In Paper IV we used the newly developed CRISPR/Cas9 technique to create a collection of zebrafish mutants with defective GAG biosynthetic machineries. Lack of phenotypes linked to null-mutations of most of the investigated genes is striking in this study.
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| 14. |
- Filipek-Gorniok, Beata, et al.
(författare)
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The Ndst Gene Family in Zebrafish : Role of Ndst1b in Pharyngeal Arch Formation
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate (HS) proteoglycans are ubiquitous components of the extracellular matrix and plasma membrane of metazoans. The sulfation pattern of the HS glycosaminoglycan chain is characteristic for each tissue and changes during development. The glucosaminyl N-deacetylase/N-sulfotransferase (NDST) enzymes catalyze N-deacetylation and N-sulfation during HS biosynthesis and have a key role in designing the sulfation pattern. We here report on the presence of five NDST genes in zebrafish. Zebrafish ndst1a, ndst1b, ndst2a and ndst2b represent duplicated mammalian orthologues of NDST1 and NDST2 that arose through teleost specific genome duplication. Interestingly, the single zebrafish orthologue ndst3, is equally similar to tetrapod Ndst3 and Ndst4. It is likely that a local duplication in the common ancestor of lobe-finned fish and tetrapods gave rise to these two genes. All zebrafish Ndst genes showed distinct but partially overlapping expression patterns during embryonic development. Morpholino knockdown of ndst1b resulted in delayed development, craniofacial cartilage abnormalities, shortened body and pectoral fin length, resembling some of the features of the Ndst1 mouse knockout.
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| 15. |
- Fischer, Sabine, et al.
(författare)
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Zebrafish Ext2 is necessary for Fgf and Wnt signaling, but not for Hh signaling
- 2011
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Ingår i: BMC Developmental Biology. - 1471-213X. ; 11, s. 53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heparan sulfate (HS) biosynthesis is tightly regulated during vertebrate embryo development. However, potential roles for HS biosynthesis in regulating the function of paracrine signaling molecules that bind to HS are incompletely understood.Results: In this report we have studied Fgf, Wnt and Hedgehog (Hh) signaling in ext2 mutants, where heparan sulfate content is low. We found that Fgf targeted gene expression is reduced in ext2 mutants and that the remaining expression is readily inhibited by SU5402, an FGF receptor inhibitor. In the ext2 mutants, Fgf signaling is shown to be affected during nervous system development and reduction of Fgf ligands in the mutants affects tail development. Also, Wnt signaling is affected in the ext2 mutants, as shown by a stronger phenotype in ext2 mutants injected with morpholinos that partially block translation of Wnt11 or Wnt5b, compared to injected wild type embryos. In contrast, Hh dependent signaling is apparently unaffected in the ext2 mutants; Hh targeted gene expression is not reduced, the Hh inhibitor cyclopamine is not more affective in the mutants and Hh dependent cell differentiation in the retina and in the myotome are normal in ext2 mutants. In addition, no genetic interaction between ext2 and shha during development could be detected.Conclusion: We conclude that ext2 is involved in Fgf and Wnt signaling but not in Hh signaling, revealing an unexpected specificity for ext2 in signaling pathways during embryonic development. Thus, our results support the hypothesis that regulation of heparan sulfate biosynthesis has distinct instructive functions for different signaling factors.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Förstberg, Johan, 1949-, et al.
(författare)
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Influence of different conditions of tilt compensation on motion and motion-related discomfort in high speed trains
- 1998
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Ingår i: Vehicle System Dynamics. - : Swets & Zeitlinger. - 0042-3114 .- 1744-5159. ; 29, s. 729-734
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Tidskriftsartikel (refereegranskat)abstract
- Train speed may be increased by constructing new railways with improved curve geometry or by using tilting trains. The tilting system compensates the lateral acceleration felt by the passengers in curves by tilting the car body, thus allowing trains to run 25-30 % faster on existing curved tracks with maintained good ride comfort. Although motion sickness in tilting trains seems to be a small problem for most passengers it can be a problem to those prone to nausea. To investigate the incidence of motion related discomfort and how different tilt compensation strategies influence the occurrence of such discomfort, a full-scale test ride was conducted on a curved track with a tilting train. Seventy healthy volunteers were employed, selected for high subjective sensitivity to nausea. Three conditions were tested using three different cars under three days. The test ride lasted about 3 hours. Four times per test ride the subjects answered a questionnaire concerning vegetative symptoms, fatigue, sleepiness and nausea. The test persons' overall estimation of average ride comfort was good in all conditions, however, some persons reported motion related discomfort due to motion sickness. A 55% degree of tilt compensation of the lateral acceleration (in the track plane) instead of the normal 70%, reduced the number of test persons reporting dizziness and nausea by about 30 - 50%. Discomfort correlates very poorly with a motion dose (time integrated) of vertical acceleration but instead correlates better with a motion dose of roll angle acceleration.
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| 21. |
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| 22. |
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| 23. |
- Gjessing, Kristian, 1967-
(författare)
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Impact of medical and non-medical Factors on Quality and Costs in Primary Care : A Conscious Look at Subconcious Processes
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background / IntroductionPhysicians and patients may be influenced by more than just the medical facts of the situation at hand. The physician is a part of the sociocultural environment and is under influence of this. The physician could be afraid of making mistakes and thus choose the safest option. In addition, economic considerations may apply. The perceived continuity or quality of the communication may also influence medical decision-making. Patients may not think about what allergens they are exposed to. Differences in socioeconomy or perceived morbidity may influence the patient's or their family’s desire to see the doctor or to use medications like antibiotics.Material and MethodsIn Paper 1, referrals from two Primary Healthcare centers in Norway were compared to each other and to the other referrals that were received by the local hospital. In Paper 2, Influenza-Like Illness (ILI) for children 2-12 years old was monitored for 7 years, and costs of treatment and parental absence due to ill children were calculated using real numbers. In Paper 3, the number of antibiotic prescriptions was compared to the patient’s socioeconomic background, to investigate possible inequalities. Paper 4 compares asthma and atopy incidence to the number of antibiotic prescriptions, to investigate if asthma patients are more often treated with antibiotics than nonasthma patients are. The analyses are based on regional healthcare data and the prospective ABIS study.ResultsPaper 1 showed that locum doctors and regular General Practitioners had the same referral rates, but the locum doctors had a distribution of diagnoses that differed significantly from the regular GPs and from the other referrals.Paper 2 showed that parental absence due to children with ILI follows the seasonal influenza pattern closely. The main burden of consultations and costs is carried by Primary Care.Paper 3 showed that parent-reported infectious morbidity at age 5, is associated with a higher number of antibiotic prescriptions in later childhood (5-14 years). Family income is a factor, where children from Q1 (wealthiest) receive significantly fewer antibiotics than children from Q3-Q5.Paper 4 found that asthma/ fur allergy at age 5 was associated with more antibiotic prescriptions in later childhood, but that wide-spectrum antibiotics are rarely used. Doctors seem to adhere to national and regional guidelines.ConclusionsPrimary care physicians seem to be affected by their grade of continuity and length of employment in their referral diagnosis distribution. Influenza-like illness in children carries a substantial cost in terms of loss of production, healthcare encounters, and personal suffering for vulnerable individuals. Parents’ perceptions of morbidity seem to influence antibiotic demand in children, along with socioeconomic factors. Children with asthma or airway allergies seem to receive more antibiotic prescriptions, possibly due to increased infectious vulnerability or to allergic exposure unknown to the doctor.
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| 24. |
- Gorniok, Beata Filipek, et al.
(författare)
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Heparan Sulfate Biosynthesis in Zebrafish
- 2021
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Ingår i: Journal of Histochemistry and Cytochemistry. - LONDON ENGLAND : SAGE Publications. - 0022-1554 .- 1551-5044. ; 69:1, s. 49-60
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Forskningsöversikt (refereegranskat)abstract
- The biosynthesis of heparan sulfate (HS) proteoglycans occurs in the Golgi compartment of cells and will determine the sulfation pattern of HS chains, which in turn will have a large impact on the biological activity of the proteoglycans. Earlier studies in mice have demonstrated the importance of HS for embryonic development. In this review, the enzymes participating in zebrafish HS biosynthesis, along with a description of enzyme mutants available for functional studies, are presented. The consequences of the zebrafish genome duplication and maternal transcript contribution are briefly discussed as are the possibilities of CRISPR/Cas9 methodologies to use the zebrafish model system for studies of biosynthesis as well as proteoglycan biology.
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| 25. |
- Gorniok, Beata Filipek, et al.
(författare)
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The Nordic Zebrafish and Husbandry Meeting 2018
- 2019
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Ingår i: Zebrafish. - : MARY ANN LIEBERT, INC. - 1545-8547 .- 1557-8542. ; 16:3, s. 329-330
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Nordic zebrafish and husbandry meeting took place at Karolinska Institutet in Stockholm, November 7-9, 2018. More than 120 scientists from Europe joined this meeting, which also attracted world-leading keynote speakers such as Zoltan Varga, Didier Stainier, and Hernan Lopez-Schier. The meeting comprised both scientific as well as zebrafish husbandry and animal welfare sessions. This combination led to fruitful discussions, new collaborations as well as in the formation of a working group that will review and compile evidence-based husbandry guidelines for the local authorities. The success of this meeting emphasizes in general that smaller local conferences provide an excellent platform to establish local networks, to build up and share local infrastructures as well as to provide knowledge and help to peer researchers.
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| 26. |
- Griffiths, Gareth Wyn, et al.
(författare)
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Fish from Head to Tail : The 9th European Zebrafish Meeting in Oslo
- 2016
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Ingår i: Zebrafish. - : Mary Ann Liebert Inc. - 1545-8547 .- 1557-8542. ; 13:2, s. 132-137
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Tidskriftsartikel (refereegranskat)abstract
- The 9th European Zebrafish Meeting took place recently in Oslo (June 28-July 2, 2015). A total of 650 participants came to hear the latest research news focused on the zebrafish, Danio rerio, and to its distant evolutionary relative medaka, Oryzias latipes. The packed program included keynote and plenary talks, short oral presentations and poster sessions, workshops, and strategic discussions. The meeting was a great success and revealed dramatically how important the zebrafish in particular has become as a model system for topics, such as developmental biology, functional genomics, biomedicine, toxicology, and drug development. A new emphasis was given to its potential as a model for aquaculture, a topic of great economic interest to the host country Norway and for the future global food supply in general. Zebrafish husbandry as well as its use in teaching were also covered in separate workshops. As has become a tradition in these meetings, there was a well-attended Wellcome Trust Sanger Institute and ZFIN workshop focused on Zebrafish Genome Resources on the first day. The full EZM 2015 program with abstracts can be read and downloaded from the EZM 2015 Web site zebrafish2015.org.
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| 27. |
- Grobe, K, et al.
(författare)
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Heparan sulfate and development : differential roles of the N-acetylglucosamine N-deacetylase/N-sulfotransferase isozymes.
- 2002
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Ingår i: Biochimica et Biophysica Acta - General Subjects. - 0304-4165 .- 1872-8006. ; 1573:3, s. 209-215
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfates (HSs) are N- and O-sulfated polysaccharide components of proteoglycans, which are important constituents of the cell surface as well as the extracellular matrix. Heparin, with extensive clinical application as an anticoagulant, is a highly sulfated form of HS present within the granules of connective tissue type mast cells. The diverse functions of HS, which include the modulation of growth factor/cytokine activity, interaction with matrix proteins and binding of enzymes to cell surfaces, depend greatly on the presence of specific, high affinity regions on the chains. N-acetylglucosamine N-deacetylase/N-sulfotransferases, NDSTs, are an important group of enzymes in HS biosynthesis, initiating the sulfation of the polysaccharide chains and thus determining the generation of the high affinity sites. Here, we review the role of the four vertebrate NDSTs in HS biosynthesis as well as their regulated expression. The main emphasis is the phenotypes of mice lacking one or more of the NDSTs.
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| 28. |
- Gudmundsson, Sanna, 1989-, et al.
(författare)
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TAF1, associated with intellectual disability in humans, is essential for embryogenesis and regulates neurodevelopmental processes in zebrafish
- 2019
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The TATA-box binding protein associated factor 1 (TAF1) protein is a key unit of the transcription factor II D complex that serves a vital function during transcription initiation. Variants of TAF1 have been associated with neurodevelopmental disorders, but TAF1's molecular functions remain elusive. In this study, we present a five-generation family affected with X-linked intellectual disability that co-segregated with a TAF1 c. 3568C>T, p.(Arg1190Cys) variant. All affected males presented with intellectual disability and dysmorphic features, while heterozygous females were asymptomatic and had completely skewed X-chromosome inactivation. We investigated the role of TAF1 and its association to neurodevelopment by creating the first complete knockout model of the TAF1 orthologue in zebrafish. A crucial function of human TAF1 during embryogenesis can be inferred from the model, demonstrating that intact taf1 is essential for embryonic development. Transcriptome analysis of taf1 zebrafish knockout revealed enrichment for genes associated with neurodevelopmental processes. In conclusion, we propose that functional TAF1 is essential for embryonic development and specifically neurodevelopmental processes.
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| 29. |
- Gunja, Sethu Madhava Rao, 1986-, et al.
(författare)
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PARN acts as a maternal factor required for normal embryogenesis and telomere length maintenance in zebrafish
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Poly(A)-specific ribonuclease (PARN) is a 3’-5’ exoribonuclease that removes poly(A) tails of mRNAs and ncRNAs in eukaryotes. Mutations in the human PARN gene are associated with developmental delay and/or telomere biology disorders (TBDs). Here we have established a parn loss-of-function zebrafish model that recapitulates TBD symptoms and phenotypes displayed in human patients. Homozygous parn deficient zebrafish exhibited aberrant snoRNA profile, telomerase RNA maturation and shortening of telomere length over generations. In addition, we found that zygotic parn mutant embryos (Zparn) generated by crossing homozygous male and heterozygous females developed a spectrum of growth/developmental defects from embryonic stage to adult stage. The mutant embryos showed developmental defects with lethality during blastula and gastrulation where the maternal mRNAs need to be destabilized with the activation of zygotic transcription; larvae that surpassed the embryonic stage developed severe developmental defects like bent tail and cardiac edema; the fish that survived to adulthood have severe growth defects. Overall, the array of disease phenotypes observed in PARN mutant fish explains the importance of PARN at different stages of life and could provide a link to the mechanism of TBD penetrance in humans.
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| 30. |
- Gustafsson, Örjan, et al.
(författare)
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Colloid dynamics and transport of major elements through a boreal river - brackish bay mixing zone
- 2000
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Ingår i: Marine Chemistry. - 0304-4203 .- 1872-7581. ; 71:1-2, s. 1-21
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Tidskriftsartikel (refereegranskat)abstract
- A range of biogeochemical methodologies were applied to investigate how aggregation processes affected the phase distribution and mixing of Fe, Si, and organic carbon between the Kalix River and the Bothnic Bay, northernmost Baltic Sea (salinity≤3; the low-salinity zone (LSZ) was stretching over 60 km in the spring). During the dynamic springflood conditions studied, small 238U-234Th disequilibria, low sediment trap fluxes, laboratory mixing experiments, as well as results from an independent two-box, two-dimensional mixing model combine to suggest that no significant removal of Fe, Si, or organic C was occurring in the highly-resolved LSZ. While no conclusions may be drawn based solely on property-salinity plots over narrow salinity ranges, apparently linear graphs for Fe and Si over 3 separate years also suggest minimal removal in this regime. At the same time, size distributions both of elements -from cross-flow ultrafiltration - and of bulk suspended solids - from light scattering (photon correlation spectroscopy [PCS]) - indicated that significant aggregation was taking place.The aggregation-without-significant-settling scenario in this low-salinity mixing regime, with a geochemistry similar to that of neighboring Russian Arctic rivers, is hypothesized to result from a comparatively high organic-to-detrital matter characteristic of the aggregates. While first principles would indeed suggest that decreasing electrostatic repulsion during mixing lead to aggregation, a low specific density of mineral-poor amorphous organic aggregates may lead to transport of these authigenic particles further away from the river mouth. The role of detrital "sinkers" on vertical removal of suspended organic matter is discussed in the wider context of scavenging mechanisms in the ocean.
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| 31. |
- 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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| 32. |
- Habicher, Judith, et al.
(författare)
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Chondroitin / Dermatan Sulfate Modification Enzymes in Zebrafish Development
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Chondroitin/dermatan sulfate (CS/DS) proteoglycans consist of unbranched sulfated polysaccharide chains of repeating GalNAc-GlcA/IdoA disaccharide units, attached to serine residues on specific proteins. The CS/DS proteoglycans are abundant in the extracellular matrix where they have essential functions in tissue development and homeostasis. In this report a phylogenetic analysis of vertebrate genes coding for the enzymes that modify CS/DS is presented. We identify single orthologous genes in the zebrafish genome for the sulfotransferases chst7, chst11, chst13, chst14, chst15 and ust and the epimerase dse. In contrast, two copies were found for mammalian sulfotransferases CHST3 and CHST12 and the epimerase DSEL, named chst3a and chst3b, chst12a and chst12b, dsela and dselb, respectively. Expression of CS/DS modification enzymes is spatially and temporally regulated with a large variation between different genes. We found that CS/DS 4-O-sulfotransferases and 6-O-sulfotransferases as well as CS/DS epimerases show a strong and partly overlapping expression, whereas the expression is restricted for enzymes with ability to synthesize di-sulfated disaccharides. A structural analysis further showed that CS/DS sulfation increases during embryonic development mainly due to synthesis of 4-O-sulfated GalNAc while the proportion of 6-O-sulfated GalNAc increases in later developmental stages. Di-sulfated GalNAc synthesized by Chst15 and 2-O-sulfated GlcA/IdoA synthesized by Ust are rare, in accordance with the restricted expression of these enzymes. We also compared CS/DS composition with that of heparan sulfate (HS). Notably, CS/DS biosynthesis in early zebrafish development is more dynamic than HS biosynthesis. Furthermore, HS contains disaccharides with more than one sulfate group, which are virtually absent in CS/DS.
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| 33. |
- Habicher, Judith
(författare)
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Glycosaminoglycan Biosynthesis and Function in Zebrafish Development : Sugars Shaping Skeletons
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Heparan sulfate (HS) and chondroitin/dermatan sulfate (CS/DS) proteoglycans are glycosylated proteins with important roles in animal development and homeostasis. HS and CS/DS are long, linear glycosaminoglycan (GAG) polysaccharides and attached to a core protein they form proteoglycans. GAGs on proteoglycans are often modified by sulfate groups and mainly found in the extracellular matrix or associated to the cell membrane. They interact with different proteins, for example signaling molecules, and influence developmental processes. Cells in cartilage produce a functionally specialized dense extracellular matrix, full of proteoglycans. Using the zebrafish as a model to study GAG biosynthesis we discovered that HS production is prioritized over CS/DS production, if the availability of link structures is restricted. We also found that the effects of removing HS and CS/DS biosynthetic enzymes in zebrafish larvae typically differ from what could be hypothesized solely from knowledge of the activity of each enzyme. These findings indicated a highly complex regulation of GAG biosynthesis and we thus proceeded to identify novel GAG biosynthetic enzymes in zebrafish and characterized their expression during early development. Notably, strong expression of CS/DS glycosyltransferases was found in cartilage structures, correlating with a drastic increase of CS/DS synthesis after two days of development, and high CS/DS deposition in cartilage. Finally, to understand how different GAG biosynthetic enzymes affect zebrafish development, we decided to use the CRISPR/Cas9 technology to generate new loss of function alleles for enzymes in HS and CS/DS biosynthesis. Some mutants show disturbed larval development or adult morphology, but we found many mutants to develop into adults without major morphological abnormalities, suggesting a high redundancy for GAG biosynthetic enzymes. Many GAG glycosyltransferases and modification enzymes have multiple isoforms, suggesting that a combination of mutations in one individual will become necessary to study the loss of specific modifications. To conclude, the zebrafish model gives new insights into the GAG machinery and the CRSIPR/Cas9 technology allows for swift production of new loss of function zebrafish lines with defective GAG biosynthesis.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Hayes, Anthony J., et al.
(författare)
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Spinal Deformity in Aged Zebrafish Is Accompanied by Degenerative Changes to Their Vertebrae that Resemble Osteoarthritis
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9, s. e75787-
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Tidskriftsartikel (refereegranskat)abstract
- Age-related degenerative changes within the vertebral column are a significant cause of morbidity with considerable socio-economic impact worldwide. An improved understanding of these changes through the development of experimental models may lead to improvements in existing clinical treatment options. The zebrafish is a well-established model for the study of skeletogenesis with significant potential in gerontological research. With advancing age, zebrafish frequently develop gross deformities of their vertebral column, previously ascribed to reduced trunk muscle tone. In this study, we assess degenerative changes specifically within the bone and cartilage of the vertebral column of zebrafish at 1, 2 and 3-years of age. We show increased frequency and severity of spinal deformities/curvatures with age. Underlying the most severe phenotypes are partial or complete vertebral dislocations and focal thickening of the vertebral bone at the joint margins. MicroCT examination demonstrates small defects, fractures and morphological evidence suggestive of bone erosion and remodeling (i.e. osteophytes) within the vertebrae during aging, but no significant change in bone density. Light and electron microscopic examination reveal striking agerelated changes in cell morphology, suggestive of chondroptosis, and tissue remodelling of the vertebral cartilage, particularly within the pericellular micro-environment. Glycosaminoglycan analysis of the vertebral column by HPLC demonstrates a consistent, age-related increase in the yield of total chondroitin sulfate disaccharide, but no change in sulfation pattern, supported by immunohistochemical analysis. Immunohistochemistry strongly identifies all three chondroitin/dermatan sulphate isoforms (C-0-S, C-4-S/DS and C-6-S) within the vertebral cartilage, particularly within the pericellular micro-environment. In contrast, keratan sulfate immunolocalises specifically with the notochordal tissue of the intervertebral disc, and its labelling diminishes with age. In summary, these observations raise the prospect that zebrafish, in addition to modelling skeletal development, may have utility in modelling age-related degenerative changes that affect the skeleton during senescence.
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| 38. |
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| 39. |
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| 40. |
- Hort, Sofia, 1984-
(författare)
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Skrivprocesser på högskolan : Text, plats och materialitet i uppsatsskrivandet
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this study is to explore how students in a higher education context handle the writing of their final essay. Applying a sociomaterial approach, the study offers comprehensive case studies of students’ writing processes. The thesis attempts to show how student writers handle writing challenges through different technologies and at different places. It does so by implementing the Mobile Technologies Process Logs (MTPL)-method, wherein participating students take an active role to create and gather data on their own writing processes.The results show that some students’ textual work could be described in terms of being comprehensive, and hence handled through varied writing technologies at various writing places. These students write a lot of texts to move the writing process forward. Other writers take a more product-oriented view in their writing, and hence write through fewer technologies, at a few places, and with a wish to finish their final text product directly. Many of the students make explicit how they process the literature through writing texts. The knowledge production, the analysis, which is central to academic writing, seems however more implicit and difficult for the students to handle, specifically if having a product oriented view on writing. The results also show how students mobilize different textual actions to meet challenges that writing an (digital) essay implies. This work is clearly emplaced ,at diverse or at more homogenous writing places.It is significant to make textual strategies as well as the functions of writing technologies and place visible to all students. It seems vital at times where higher education, as well as the students entering this institution, are put in front of a raft of (new) challenges. At the same time as the idea of the bad student writer is prevailing, higher education institutions seem not to teach how an academic writing process could be managed in successful ways. This thesis contributes to this field of inquiry with results on how students’ writing processes can be characterized.
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| 41. |
- Ledin, Johan, et al.
(författare)
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Enzymatically active N-deacetylase/N-sulfotransferase-2 is present in liver but does not contribute to heparan sulfate N-sulfation
- 2006
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 281:47, s. 35727-35734
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate (HS) proteoglycans influence embryonic development through interactions with growth factors and morphogens. The interactions depend on HS structure, which is largely determined during biosynthesis by Golgi enzymes. NDST ( glucosaminyl N-deacetylase/N-sulfotransferase), responsible for HSN-sulfation, is a key enzyme directing further modifications including O-sulfation. To elucidate the roles of the different NDST isoforms in HS biosynthesis, we took advantage of mice with targeted mutations in NDST1 and NDST2 and used liver as our model organ. Of the four NDST isoforms, only NDST1 and NDST2 transcripts were shown to be expressed in control liver. The absence of NDST1 or NDST2 in the knock-out mice did not affect transcript levels of other NDST isoforms or other HS modification enzymes. Although the sulfation level of HS synthesized in NDST1(-/-) mice was drastically lowered, liver HS from wild-type mice, from NDST1(-/-), NDST2(-/-), and NDST1(-/-), NDST2(-/-) mice all had the same structure despite greatly reduced NDST enzyme activity (30% of control levels in NDST1(-/-) NDST2(-/-) embryonic day 18.5 embryos). Enzymatically active NDST2 was shown to be present in similar amounts in wild-type, NDST1(-/-), and NDST1(-/-) embryonic day 18.5 liver. Despite the substantial contribution of NDST2 to total NDST enzyme activity in embryonic day 18.5 liver (approximate to 40%), its presence did not appear to affect HS structure as long as NDST1 was also present. In NDST1(-/-) embryonic day 18.5 liver, in contrast, NDST2 was responsible for N-sulfation of the low sulfated HS. A tentative model to explain these results is presented.
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| 42. |
- Ledin, Johan, 1972-
(författare)
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Heparan Sulfate Biosynthesis – Clues from Knockout Mice
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the extracellular space, many specialized proteins are located to support cells and to mediate cell-cell signalling. One class of such molecules is heparan sulfate (HS) proteoglycans, which are proteins with different properties and locations but all of them decorated with long unbranched HS polysaccharide chains. During biosynthesis the HS chains are modified by sulfation and a C5-epimerase converts some glucuronic acid residues to iduronic acid. The patterns of the modifications vary distinctly between tissues and developing stages and give HS chains different affinity for biologically important proteins. Thus, the regulation of HS biosynthesis is likely to influence a wide variety of biological events.This thesis focuses on the biosynthesis of HS in animals with targeted disruptions in genes important for HS production. The N-deacetylase N-sulfotransferase (NDST) is a key enzyme in HS biosynthesis, directing other modifications. We show that NDST isoforms have very different roles in HS biosynthesis. Inactivation of NDST1 affects HS biosynthesis in all tissues. In embryonic liver HS from NDST1-/- mice the N-sulfation was decresed with twothirds, while the absence of NDST2 did not affect HS structure. In the absence of NDST1 in the liver, however, NDST2 is active in HS N-sulfation. In a study of embryonic stem cells lacking both NDST1 and NDST2, no N-sulfate groups could be detected. 6-O-sulfate groups were, however, still present at half of its normal level. This was an unexpected finding since 6-O-sulfotransferases have been thought to be strictly dependent on N-sulfate groups for substrate recognition.By adapting an automated method for HS analysis to mammalian tissues, we could extend our analyses to more tissues and other transgene models. We also developed a protocol to create a sensitive “fingerprint” of HS structure. With these methods we could determine the individual HS structure of different mouse tissues.
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| 43. |
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| 44. |
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| 45. |
- Ledin, Per, 1962-, et al.
(författare)
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Den multimodala sakprosan
- 2019
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Ingår i: Sakprosa. - : Universitetet i Oslo. - 1502-6000 .- 1891-5108. ; 11:4, s. 1-50
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Tidskriftsartikel (refereegranskat)abstract
- Alla sakprosatexter är multimodala, och denna artikel diskuterar relationen mellan sakprosaforskning och multimodalitetsforskning. Artikeln adresserar två frågor: Hur kan forskning om multimodalitet och sakprosa stimulera varandra? och Hur förhåller sig nordisk sakprosaforskning till en vidare multimodal forskningstradition? För att besvara dessa frågor tecknar artikeln multimodalitetstraditionens utveckling samt härleder sakprosabegreppets ursprung. I ljuset av såväl äldre som nutida sakprosaforskning argumenterar artikeln för att sakprosabegreppets multimodala potential huvudsakligen ligger i förledet sak eftersom det riktar ljuset mot textens roll som ett yttrande om verkligheten inom en institution. Således argumenterar artikeln att samspelet mellan verbalspråket och andra semiotiska resurser bör stå i centrum vid studiet av sakprosa, oberoende av om det handlar om ett samspel mellan verbalspråk och t.ex. visuella, rumsliga eller auditiva resurser. Detta pekar slutligen på nödvändigheten i att uppmärksamma hur olika affordanser – dvs. möjligheter och begränsningar – i olika semiotiska material används i olika kontexter. Därmed blir också efterledet prosa relevant, eftersom de riktar uppmärksamheten mot kvaliteter i uttrycket.
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| 46. |
- Ledin, Per, et al.
(författare)
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Den multimodala sakprosan : The Multi-modal Non-fiction (’sakprosa’)
- 2019
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Ingår i: Sakprosa. - Oslo, Norway : Universitetet i Oslo. - 1502-6000 .- 1891-5108. ; 11:4, s. 1-50
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Tidskriftsartikel (refereegranskat)abstract
- Alla sakprosatexter är multimodala, och denna artikel diskuterar relationen mellan sakprosaforskning och multimodalitetsforskning. Artikeln adresserar två frågor: Hur kan forskning om multimodalitet och sakprosa stimulera varandra? och Hur förhåller sig nordisk sakprosaforskning till en vidare multimodal forsknings-tradition? För att besvara dessa frågor tecknar artikeln multimodalitetstraditionens utveckling samt härleder sakprosabegreppets ursprung. I ljuset av såväl äldre som nutida sakprosaforskning argumenterar artikeln för att sakprosabegreppets multimodala potential huvudsakligen ligger i förledet sak eftersom det riktar ljuset mot textens roll som ett yttrande om verkligheten inom en institution. Således argumenterar artikeln att samspelet mellan verbalspråket och andra semiotiska resurser bör stå i centrum vid studiet av sakprosa, oberoende av om det handlar om ett samspel mellan verbalspråk och t.ex. visuella, rumsliga eller auditiva resurser. Detta pekar slutligen på nödvändigheten i att uppmärksamma hur olika affordanser – dvs. möjligheter och begränsningar – i olika semiotiska material används i olika kontexter. Därmed blir också efterledet prosa relevant, eftersom de riktar uppmärksamheten mot kvaliteter i uttrycket.
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| 47. |
- Morikawa, Masato, et al.
(författare)
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The ALK-1/SMAD/ATOH8 axis attenuates hypoxic responses and protects against the development of pulmonary arterial hypertension
- 2019
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Ingår i: Science Signaling. - : American Association for the Advancement of Science. - 1945-0877 .- 1937-9145. ; 12:607
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Tidskriftsartikel (refereegranskat)abstract
- Dysregulated bone morphogenetic protein (BMP) signaling in endothelial cells (ECs) is implicated in vascular diseases such as pulmonary arterial hypertension (PAH). Here, we showed that the transcription factor ATOH8 was a direct target of SMAD1/5 and was induced in a manner dependent on BMP but independent of Notch, another critical signaling pathway in ECs. In zebrafish and mice, inactivation of Atoh8 did not cause an arteriovenous malformation-like phenotype, which may arise because of dysregulated Notch signaling. In contrast, Atoh8-deficient mice exhibited a phenotype mimicking PAH, which included increased pulmonary arterial pressure and right ventricular hypertrophy. Moreover, ATOH8 expression was decreased in PAH patient lungs. We showed that in cells, ATOH8 interacted with hypoxia-inducible factor 2 alpha (HIF-2 alpha) and decreased its abundance, leading to reduced induction of HIF-2 alpha target genes in response to hypoxia. Together, these findings suggest that the BMP receptor type II/ALK-1/SMAD/ATOH8 axis may attenuate hypoxic responses in ECs in the pulmonary circulation and may help prevent the development of PAH.
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| 48. |
- Ringvall, Maria, et al.
(författare)
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Defective heparan sulfate biosynthesis and neonatal lethality in mice lacking N-deacetylase/N-sulfotransferase-1
- 2000
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 275:34, s. 25926-25930
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate is a sulfated polysaccharide present on most cell surfaces and in the extracellular matrix. In vivo functions of heparan sulfate can be studied in mouse strains lacking enzymes involved in the biosynthesis of heparan sulfate. Glucosaminyl N-deacetylase/N-suLfotransferase (NDST) catalyzes the first modifying step in the biosynthesis of the polysaccharide. This bifunctional enzyme occurs in several isoforms. We here report that targeted gene disruption of NDST-1 in the mouse results in a structural alteration of heparan sulfate in most basement membranes as revealed by immunohistochemical staining of fetal tissue sections using antibodies raised against heparan sulfate. Biochemical analysis of heparan sulfate purified from fibroblast cultures, lung, and liver of NDST-1-deficient embryos demonstrated a dramatic reduction in N-sulfate content. Most NDST-1-deficient embryos survive until birth; however, they turn out to be cyanotic and die neonatally in a condition resembling respiratory distress syndrome. In addition, a minor proportion of NDST-1 deficient embryos die during the embryonic period. The cause of the embryonic lethality is still obscure, but incompletely penetrant defects of the skull and the eyes have been observed.
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| 49. |
- Rothenbucher, Theresa S. P., et al.
(författare)
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Zebrafish embryo as a replacement model for initial biocompatibility studies of biomaterials and drug delivery systems
- 2019
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Ingår i: Acta Biomaterialia. - : ELSEVIER SCI LTD. - 1742-7061 .- 1878-7568. ; 100, s. 235-243
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Tidskriftsartikel (refereegranskat)abstract
- The development of new biomaterials and drug delivery systems necessitates animal experimentation to demonstrate biocompatibility and therapeutic efficacy. Reduction and replacement of the requirement to conduct experiment using full-grown animals has been achieved through utilising zebrafish embryos, a promising bridge model between in vitro and in vivo research. In this review, we consider how zebrafish embryos have been utilised to test both the biocompatibility of materials developed to interact with the human body and drug release studies. Furthermore, we outline the advantages and limitations of this model and review legal and ethical issues. We anticipate increasing application of the zebrafish model for biomaterial evaluation in the near future. Statement of significance This review aims to evaluate the potential application and suitability of the zebrafish model in the development of biomaterials and drug delivery systems. It creates scientific impact and interest because replacement models are desirable to the society and the scientific community. The continuous development of biomaterials calls for the need to provide solutions for biological testing. This review covers the topic of how the FET model can be applied to evaluate biocompatibility. Further, it explores the zebrafish from the wild-type to the mutant form, followed by a discussion about the ethical considerations and concerns when using the FET model. (C) 2019 Published by Elsevier Ltd on behalf of Acta Materialia Inc.
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| 50. |
- Sharma, Sumit, et al.
(författare)
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Detection of rotavirus- and norovirus-specific IgG memory B cells in tonsils
- 2019
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Ingår i: Journal of Medical Virology. - : WILEY. - 0146-6615 .- 1096-9071. ; 91:2, s. 326-329
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Tidskriftsartikel (refereegranskat)abstract
- Because rotavirus (RV) and norovirus (NoV) are transmitted through the fecal-oral route, tonsils due to their location within the oropharynx may sample or become infected with these viruses. We investigated if RV and NoV RNA/antigen, or virus-specific memory/plasma B cells can be detected in the tonsils. While neither RV/NoV antigen, nor genomic RNA was detected, 90% (27/30) of tonsils tested had RV- and NoV-specific IgG memory B cells. However, the mechanism explaining how these cells get there (whether because of local induction or homing after induction at other sites) and the role these cells might play during active infection is not yet clear.
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