Sjannie Lefevre

• Lau, Gigi Yik Chee; Gerber, Lucie; Johansen, Anette; Dahl, Helge Andre; Torp, May-Kristin & Bates, Georgina [Vis alle 11 forfattere av denne artikkelen] (2026). Mitochondrial responses to anoxia-reoxygenation exposure in crucian carp (Carassius carassius). Journal of Experimental Biology. ISSN 0022-0949. 229(4). doi: 10.1242/jeb.251839. Fulltekst i vitenarkiv
• Winklhofer, Magdalena; Nilsson, Göran Erik & Lefevre, Sjannie (2026). Long non-coding RNA transcripts in crucian carp brain – annotation and expression patterns in anoxia and reoxygenation. RNA Biology. ISSN 1547-6286. 23(1), s. 1–21. doi: 10.1080/15476286.2026.2643366. Fulltekst i vitenarkiv Vis sammendrag

  Long non-coding RNA transcripts (lncRNAs) are important regulators of various cellular processes, including gene expression. However, whether they are involved in the regulation of anoxia-induced transcriptomic changes in crucian carp ( Carassius carassius ), a species that can survive without oxygen for months at low temperatures, has remained unexplored. The existing genome annotation includes mainly protein-coding genes, which are more straightforward to annotate than the lower-expressed lncRNAs. Therefore, this study aimed to annotate lncRNAs in the crucian carp genome, investigate their potential involvement in regulating mRNA abundance in response to anoxia and reoxygenation, and further characterize any differentially regulated lncRNAs and their potential interaction partners (nearby genes). Using next-generation RNA sequencing of brain samples from crucian carp across normoxia, anoxia, and reoxygenation conditions (n=10 per group), 145,264 transcripts were assembled with a reference-guided approach. Using the bioinformatic tools CPC2, CNCI, CPAT, and FEELnc, we identified 6,072 lncRNAs among the assembled transcripts. We observed a substantial transcriptomic response to anoxia, with a total of 56,440 differentially expressed (DE) transcripts (adjusted p-value < 0.05; | log2(fold change)| > 0.38), including 1,321 lncRNAs. The FEELnc classification module identified multiple proximal RNA transcripts that may help to predict lncRNA functions, and due to their proximity to potential interaction partners (IPs), were likely cis -acting. Most (60%) of the interaction sites between DElncRNAs and their targets were located between genes (intergenic), predominantly on the same strand in intergenic subtypes, and primarily nested in the genic context. The log2-fold changes in RNA abundance of DE predicted IPs exhibited a positive correlation with the log2-fold changes of their corresponding DElncRNAs. These findings indicate that lncRNAs are at least co-expressed with and may regulate transcription of specific genes in crucian carp during anoxia and reoxygenation.

• Winklhofer, Magdalena; Andersen, Øivind & Lefevre, Sjannie (2025). Changes in DNA Methylation During Anoxia and Reoxygenation in Crucian Carp Brain. BioRxiv. ISSN 0362-4331. doi: 10.1101/2025.07.30.667361. Fulltekst i vitenarkiv Vis sammendrag

  Oxygen is essential for cellular metabolism, and its absence poses a severe risk to vertebrates. However, the crucian carp ( Carassius carassius ) can survive without oxygen for months due to physiological adaptations. This study investigates the role of epigenomic regulation, specifically DNA methylation, in response to anoxia and subsequent reoxygenation. Brain samples from crucian carp subjected to normoxia, anoxia, and reoxygenation (n = 4 per condition) were analyzed through transcriptome (mRNA) and whole-genome bisulfite sequencing. Results revealed a notable transcriptional response to anoxia, with 1,265 differentially expressed genes (DEGs) identified compared to normoxia. Using the machine-learning-based MethylScore, we found 14 genes with differentially methylated regions (DMRs) during anoxia. These DMR-associated genes did not meet the strict DEGs criteria (adjusted p-value < 0.05; absolute log2fold-change > 0.38), but 17 genes exhibited differences in mRNA abundance when focusing solely on DMRs. DMRs were primarily located within transcriptional start sites, and analysis of protein products revealed that genes involved in transcription regulation, protein trafficking, and signal transduction were differentially methylated and expressed under varying conditions. This study advances our understanding of epigenomic regulation in oxygen deprivation and highlights the potential in exploring alternative epigenomic mechanisms.

• Pesqueira, Laura Marian Valencia; Hoff, Siv Nam Khang; Tørresen, Ole Kristian; Jentoft, Sissel & Nilsson, Sjannie Lefevre (2025). Chromosome-level de novo genome assembly of wild, anoxia-tolerant crucian carp, Carassius carassius. Scientific Data. 12. doi: 10.1038/s41597-025-04813-3. Fulltekst i vitenarkiv Vis sammendrag

  Crucian carp (Carassius carassius), a member of the carp family (Cyprinidae), is known for its remarkable anoxia tolerance. The physiological responses and adaptations to anoxia are well documented, but there is a need for better understanding of the molecular regulation and evolutionary mechanisms behind these adaptations. Here we present a high-quality, functionally annotated, chromosome-level genome assembly that can facilitate such further studies. Genomic DNA was obtained from a wild-caught crucian carp specimen and used for PacBio long-read, Illumina short-read and Hi-C sequencing. Short-read mRNA data were used for structural annotation using the BRAKER3 pipeline, while PacBio long-read RNA sequencing data were used for annotation of untranslated regions and refinement of gene-isoform relationships, using the PASA pipeline. The full assembly had a contig-level N50 of 15Mbp in 290 scaffolds and 98.6% of the total length (1.65Gbp) placed in 50 chromosomes. Structural annotation resulted in 82,557 protein-coding transcripts (in 45,667 genes), with a BUSCO completeness of 99.6% and of which 77,370 matched a protein in the UniProtKB/Swiss-Prot database.

• Gerber, Lucie; Torp, May-Kristin; Nilsson, Göran Erik; Lefevre, Sjannie & Stensløkken, Kåre-Olav (2024). Differential production of mitochondrial reactive oxygen species between mouse (Mus musculus) and crucian carp (Carassius carassius). Acta Physiologica. ISSN 1748-1708. 240(12). doi: 10.1111/apha.14244. Fulltekst i vitenarkiv Vis sammendrag

  Aim In most vertebrates, oxygen deprivation and subsequent re-oxygenation are associated with mitochondrial impairment and excess production of reactive oxygen species (ROS) like hydrogen peroxide (H2O2). This in turn triggers a cascade of cell-damaging events in a temperature-dependent manner. The crucian carp (Carassius carassius) is one of few vertebrates that survives months without oxygen at cold temperatures and overcomes oxidative damage during re-oxygenation periods. Mitochondria of this anoxia-tolerant species therefore serve as an excellent model in translational research to study adaptation and resilience to low oxygen conditions and thermal variability. Methods Here, we used high-resolution respirometry on isolated mitochondria from hearts of crucian carp and the anoxia-intolerant mouse (Mus musculus), at 37 and 8°C; two temperatures relevant for transplantation medicine (i.e., graft preservation and subsequent rewarming). Results We find: (1) a striking difference in H2O2 release between the two species at 37°C despite comparable mitochondrial efficiency and capacity, (2) a massive H2O2 release after inhibition of complex V in mouse at 37°C that is absent in crucian carp, and prevented in mouse by incubation at 8°C or uncoupling with a protonophore at 37°C, and (3) indications that differences in mitochondrial complex I and II capacity and thermal sensitivity influence the release of mitochondrial H2O2 relative to respiration. Conclusion Our findings provide comparative insights into a spectrum of mitochondrial adaptations in vertebrates and the importance of thermal variability. Furthermore, the species- and temperature-related changes associated with mitochondria highlighted in this study may help identify mitochondria-based targets for translational medicine.

• Gerber, Lucie Claire Lola; Resseguier, Julien Alain Andre; Helle-Valle, Tellef; Farhat, Elie; Nilsson, Göran Erik & Nilsson, Sjannie Lefevre (2023). Expression of prolyl hydroxylase domains, the upstream regulators of HIF, in the brain of the anoxia-tolerant crucian carp during anoxia-reoxygenation. American Journal of Physiology. Regulatory Integrative and Comparative Physiology. ISSN 0363-6119. 326(2), s. R184–R195. doi: 10.1152/ajpregu.00211.2023. Fulltekst i vitenarkiv Vis sammendrag

  We report a profound upregulation of most egln paralog mRNA levels in anoxia and upon reoxygenation, with egln3ii showing the largest, a 17-fold increase, and highest relative mRNA abundance. The relative abundance of prolyl hydroxylase domain (PHD) proteins was maintained during anoxia and increased at reoxygenation. PHD immunoreactivity was localized to axonal branches with region-specific changes during anoxia-reoxygenation. These dynamic and regional changes in crucian carp, champion of anoxia tolerance, are most likely adaptive and call for further mechanistic studies.

• Lefevre, Sjannie & Nilsson, Göran E. (2023). Two decades of research on anoxia tolerance – mitochondria, -omics and physiological diversity. Journal of Experimental Biology. ISSN 0022-0949. 226(7), s. 1–10. doi: 10.1242/jeb.245584. Fulltekst i vitenarkiv Vis sammendrag

  Just over two decades ago, Bob Boutilier published a much-cited Review in this journal on the mechanisms of cell survival in hypoxia and hypothermia. Here, we celebrate this important Review by describing how our knowledge of the mechanisms behind anoxia tolerance have progressed since 2001, including new key roles of mitochondria, something Boutilier had started exploring. Evidence now suggests that, in anoxia-tolerant brains, mitochondria initiate responses aimed at suppressing electrical activity and energy use. These responses are largely dependent on gamma-aminobutyric acid (GABA) release. Animals that survive anoxia must also tolerate reoxygenation – a major challenge that could cause a massive production of damaging reactive oxygen species (ROS). Here, the handling of succinate, which builds up during anoxia, is critical. Interestingly, there are clear species differences in succinate handling among anoxia-tolerant vertebrates (Trachemys and Chrysemys turtles and crucian carp, Carassius carassius). Trachemys turtles suppress succinate build-up during anoxia, presumably to limit ROS production during reoxygenation. By contrast, in crucian carp, reduction of fumarate to succinate during anoxia appears to be essential for keeping their mitochondria charged and viable. Consequently, during anoxia, crucian carp accumulate much more succinate than Trachemys turtles. Moreover, during anoxia, succinate is apparently transported from crucian carp brain and heart to the liver, which handles succinate upon reoxygenation. This is one example of the striking physiological diversity among vertebrates that survive long-term anoxia. More examples are given, and we argue that -omics approaches are, and will be, helpful in providing new insight and moving the field forward.

• Downie, Adam T.; Lefevre, Sjannie; Illing, Björn; Harris, Jessica; Jarrold, Michael D. & McMcormick, Mark I. [Vis alle 8 forfattere av denne artikkelen] (2023). Rapid physiological and transcriptomic changes associated with oxygen delivery in larval anemonefish suggest a role in adaptation to life on hypoxic coral reefs. PLoS Biology. ISSN 1544-9173. 21(5), s. 1–28. doi: 10.1371/journal.pbio.3002102. Fulltekst i vitenarkiv Vis sammendrag

  Connectivity of coral reef fish populations relies on successful dispersal of a pelagic larval phase. Pelagic larvae must exhibit high swimming abilities to overcome ocean and reef currents, but once settling onto the reef, larvae transition to endure habitats that become hypoxic at night. Therefore, coral reef fish larvae must rapidly and dramatically shift their physiology over a short period of time. Taking an integrative, physiological approach, using swimming respirometry, and examining hypoxia tolerance and transcriptomics, we show that larvae of cinnamon anemonefish ( Amphiprion melanopus ) rapidly transition between “physiological extremes” at the end of their larval phase. Daily measurements of swimming larval anemonefish over their entire early development show that they initially have very high mass-specific oxygen uptake rates. However, oxygen uptake rates decrease midway through the larval phase. This occurs in conjunction with a switch in haemoglobin gene expression and increased expression of myoglobin, cytoglobin, and neuroglobin, which may all contribute to the observed increase in hypoxia tolerance. Our findings indicate that critical ontogenetic changes in the gene expression of oxygen-binding proteins may underpin the physiological mechanisms needed for successful larval recruitment to reefs.

• Dahl, Helge-Andre; Johansen, Anette; Nilsson, Göran Erik & Lefevre, Sjannie (2021). The Metabolomic Response of Crucian Carp (Carassius carassius) to Anoxia and Reoxygenation Differs between Tissues and Hints at Uncharacterized Survival Strategies. Metabolites. 11(7), s. 1–26. doi: 10.3390/metabo11070435. Fulltekst i vitenarkiv Vis sammendrag

  The anoxia-tolerant crucian carp (Carassius carassius) has been studied in detail for numerous years, with particular focus on unravelling the underlying physiological mechanisms of anoxia tolerance. However, relatively little work has been focused on what occurs beyond anoxia, and often the focus is a single organ or tissue type. In this study, we quantified more than 100 metabolites by capillary electrophoresis-mass spectrometry (CE-MS) in brain, heart, liver, and blood plasma from four experimental groups, being normoxic (control) fish, anoxia-exposed fish, and two groups that had been exposed to anoxia followed by reoxygenation for either 3 h or 24 h. The heart, which maintains cardiac output during anoxia, unexpectedly, was slower to recover compared to the brain and liver, mainly due to a slower return to control concentrations of the energy-carrying compounds ATP, GTP, and phosphocreatine. Crucian carp accumulated amino acids in most tissues, and also surprisingly high levels of succinate in all tissues investigated during anoxia. Purine catabolism was enhanced, leading to accumulation of uric acid during anoxia and increasing urea formation that continued into 24 h of reoxygenation. These tissue-specific differences in accumulation and distribution of the metabolites may indicate an intricate system of transport between tissues, opening for new avenues of investigation of possible mechanisms aimed at reducing the generation of reactive oxygen species (ROS) and resultant tissue damage during reoxygenation.

• Lefevre, Sjannie; Wang, Tobias & McKenzie, David J. (2021). The role of mechanistic physiology in investigating impacts of global warming on fishes. Journal of Experimental Biology. ISSN 0022-0949. 224, s. 1–13. doi: 10.1242/jeb.238840. Fulltekst i vitenarkiv Vis sammendrag

  ABSTRACT Warming of aquatic environments as a result of climate change is already having measurable impacts on fishes, manifested as changes in phenology, range shifts and reductions in body size. Understanding the physiological mechanisms underlying these seemingly universal patterns is crucial if we are to reliably predict the fate of fish populations with future warming. This includes an understanding of mechanisms for acute thermal tolerance, as extreme heatwaves may be a major driver of observed effects. The hypothesis of gill oxygen limitation (GOL) is claimed to explain asymptotic fish growth, and why some fish species are decreasing in size with warming; but its underlying assumptions conflict with established knowledge and direct mechanistic evidence is lacking. The hypothesis of oxygen- and capacity-limited thermal tolerance (OCLTT) has stimulated a wave of research into the role of oxygen supply capacity and thermal performance curves for aerobic scope, but results vary greatly between species, indicating that it is unlikely to be a universal mechanism. As thermal performance curves remain important for incorporating physiological tolerance into models, we discuss potentially fruitful alternatives to aerobic scope, notably specific dynamic action and growth rate. We consider the limitations of estimating acute thermal tolerance by a single rapid measure whose mechanism of action is not known. We emphasise the continued importance of experimental physiology, particularly in advancing our understanding of underlying mechanisms, but also the challenge of making this knowledge relevant to the more complex reality.

• Lefevre, Sjannie (2019). Effects of high CO2 on oxygen consumption rates, aerobic scope and swimming performance. I Grosell, Martin; Munday, Philip L.; Farrell, P. & Brauner, Colin J. (Red.), Carbon Dioxide. Elsevier. ISSN 9780128176092. s. 195–244. doi: 10.1016/bs.fp.2019.08.001. Fulltekst i vitenarkiv
• Thomsen, Mikkel T; Lefevre, Sjannie; Nilsson, Göran Erik; Wang, Tobias & Bayley, Mark (2019). Effects of lactate ions on the cardiorespiratory system in rainbow trout (Oncorhynchus mykiss). American Journal of Physiology. Regulatory Integrative and Comparative Physiology. ISSN 0363-6119. 316(5), s. R607–R620. doi: 10.1152/ajpregu.00395.2018. Fulltekst i vitenarkiv Vis sammendrag

  Lactate ions are involved in several physiological processes, including a direct stimulation of the carotid body, causing increased ventilation in mammals. A similar mechanism eliciting ventilatory stimulation in other vertebrate classes has been demonstrated, but it remains to be thoroughly investigated. Here, we investigated the effects of lactate ions on the cardiorespiratory system in swimming rainbow trout by manipulating the blood lactate concentration. Lactate elicited a vigorous, dose-dependent elevation of ventilation and bradycardia at physiologically relevant concentrations at constant pH. After this initial confirmation, we examined the chiral specificity of the response and found that only l-lactate induced these effects. By removal of the afferent inputs from the first gill arch, the response was greatly attenuated, and a comparison of the responses to injections up- and downstream of the gills collectively demonstrated that the lactate response was initiated by branchial cells. Injection of specific receptor antagonists revealed that a blockade of serotonergic receptors, which are involved in the hypoxic ventilatory response, significantly reduced the lactate response. Finally, we identified two putative lactate receptors based on sequence homology and found that both were expressed at substantially higher levels in the gills. We propose that lactate ions modulate ventilation by stimulating branchial oxygen-sensing cells, thus eliciting a cardiorespiratory response through receptors likely to have originated early in vertebrate evolution.

• Lefevre, Sjannie; McKenzie, David J. & Nilsson, Göran Erik (2018). In modelling effects of global warming, invalid assumptions lead to unrealistic projections. Global Change Biology. ISSN 1354-1013. 24(2), s. 553–556. doi: 10.1111/gcb.13978. Fulltekst i vitenarkiv Vis sammendrag

  2017) provide new projections of future maximum fish weight (W∞). Based on criticism by Lefevre et al. (2017) they changed the scaling exponent for anabolism, dG. Here we find that changing both dG and the scaling exponent for catabolism, b, leads to the projection that fish may even become 98% smaller with a 1°C increase in temperature. This unrealistic outcome indicates that the current W∞ is unlikely to be explained by the Gill‐Oxygen Limitation Theory (GOLT) and, therefore, GOLT cannot be used as a mechanistic basis for model projections about fish size in a warmer world.

• Riggs, Claire L.; Summers, Amanda; Warren, Daniel E.; Nilsson, Göran Erik; Lefevre, Sjannie & Dowd, Wesley W. [Vis alle 8 forfattere av denne artikkelen] (2018). Small non-coding RNA expression and vertebrate anoxia tolerance. Frontiers in Genetics. 9:230, s. 1–22. doi: 10.3389/fgene.2018.00230. Fulltekst i vitenarkiv Vis sammendrag

  Background: Extreme anoxia tolerance requires a metabolic depression whose modulation could involve small non-coding RNAs (small ncRNAs), which are specific, rapid, and reversible regulators of gene expression. A previous study of small ncRNA expression in embryos of the annual killifish Austrofundulus limnaeus, the most anoxia-tolerant vertebrate known, revealed a specific expression pattern of small ncRNAs that could play important roles in anoxia tolerance. Here, we conduct a comparative study on the presence and expression of small ncRNAs in the most anoxia-tolerant representatives of several major vertebrate lineages, to investigate the evolution of and mechanisms supporting extreme anoxia tolerance. The epaulette shark (Hemiscyllium ocellatum), crucian carp (Carassius carassius), western painted turtle (Chrysemys picta bellii), and leopard frog (Rana pipiens) were exposed to anoxia and recovery, and small ncRNAs were sequenced from the brain (one of the most anoxia-sensitive tissues) prior to, during, and following exposure to anoxia. Results: Small ncRNA profiles were broadly conserved among species under normoxic conditions, and these expression patterns were largely conserved during exposure to anoxia. In contrast, differentially expressed genes are mostly unique to each species, suggesting that each species may have evolved distinct small ncRNA expression patterns in response to anoxia. Mitochondria-derived small ncRNAs (mitosRNAs) which have a robust response to anoxia in A. limnaeus embryos, were identified in the other anoxia tolerant vertebrates here but did not display a similarly robust response to anoxia. Conclusion: These findings support an overall stabilization of the small ncRNA transcriptome during exposure to anoxic insults, but also suggest that multiple small ncRNA expression pathways may support anoxia tolerance, as no conserved small ncRNA response was identified among the anoxia-tolerant vertebrates studied. This may reflect divergent strategies to achieve the same endpoint: anoxia tolerance. However, it may also indicate that there are multiple cellular pathways that can trigger the same cellular and physiological survival processes, including hypometabolism.

• Lefevre, Sjannie; McKenzie, David J. & Nilsson, Göran E. (2017). Models projecting the fate of fish populations under climate change need to be based on valid physiological mechanisms. Global Change Biology. ISSN 1354-1013. 23(9), s. 3449–3459. doi: 10.1111/gcb.13652. Fulltekst i vitenarkiv Vis sammendrag

  Some recent modelling papers projecting smaller fish sizes and catches in a warmer future are based on erroneous assumptions regarding (i) the scaling of gills with body mass and (ii) the energetic cost of ‘maintenance’. Assumption (i) posits that insurmountable geometric constraints prevent respiratory surface areas from growing as fast as body volume. It is argued that these constraints explain allometric scaling of energy metabolism, whereby larger fishes have relatively lower mass-specific metabolic rates. Assumption (ii) concludes that when fishes reach a certain size, basal oxygen demands will not be met, because of assumption (i). We here demonstrate unequivocally, by applying accepted physiological principles with reference to the existing literature, that these assumptions are not valid. Gills are folded surfaces, where the scaling of surface area to volume is not constrained by spherical geometry. The gill surface area can, in fact, increase linearly in proportion to gill volume and body mass. We cite the large body of evidence demonstrating that respiratory surface areas in fishes reflect metabolic needs, not vice versa, which explains the large interspecific variation in scaling of gill surface areas. Finally, we point out that future studies basing their predictions on models should incorporate factors for scaling of metabolic rate and for temperature effects on metabolism, which agree with measured values, and should account for interspecific variation in scaling and temperature effects. It is possible that some fishes will become smaller in the future, but to make reliable predictions the underlying mechanisms need to be identified and sought elsewhere than in geometric constraints on gill surface area. Furthermore, to ensure that useful information is conveyed to the public and policymakers about the possible effects of climate change, it is necessary to improve communication and congruity between fish physiologists and fisheries scientists. The final version of this research has been published in Global Change Biology. © 2017 Blackwell Publishing

• Lefevre, Sjannie; Stecyk, Jonathan Anthony William; Torp, May-Kristin; Løvold, Lisa Yuen; Sørensen, Christina & Johansen, Ida Beitnes [Vis alle 10 forfattere av denne artikkelen] (2017). Re-oxygenation after anoxia induces brain cell death and memory loss in the anoxia-tolerant crucian carp. Journal of Experimental Biology. ISSN 0022-0949. 220(21), s. 3883–3895. doi: 10.1242/jeb.165118. Fulltekst i vitenarkiv Vis sammendrag

  Crucian carp (Carassius carassius) survive without oxygen for several months, but it is unknown whether they are able to protect themselves from cell death normally caused by the absence, and particularly return, of oxygen. Here, we quantified cell death in brain tissue from crucian carp exposed to anoxia and re-oxygenation using the terminal deoxy-nucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, and cell proliferation by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) as well as PCNA mRNA expression. We also measured mRNA and protein expression of the apoptosis executer protease caspase 3, in laboratory fish exposed to anoxia and re-oxygenation and fish exposed to seasonal anoxia and re-oxygenation in their natural habitat over the year. Finally, a behavioural experiment was used to assess the ability to learn and remember how to navigate in a maze to find food, before and after exposure to anoxia and re-oxygenation. The number of TUNEL-positive cells in the telencephalon increased after 1 day of re-oxygenation following 7 days of anoxia, indicating increased cell death. However, there were no consistent changes in whole-brain expression of caspase 3 in either laboratory-exposed or naturally exposed fish, indicating that cell death might occur via caspase-independent pathways or necrosis. Re-oxygenated crucian carp appeared to have lost the memory of how to navigate in a maze (learnt prior to anoxia exposure), while the ability to learn remained intact. PCNA mRNA was elevated after re-oxygenation, indicating increased neurogenesis. We conclude that anoxia tolerance involves not only protection from damage but also repair after re-oxygenation.

• Lefevre, Sjannie; Bayley, Mark & Mckenzie, David J. (2016). Measuring oxygen uptake in fishes with bimodal respiration. Journal of Fish Biology. ISSN 0022-1112. 88(1), s. 206–231. doi: 10.1111/jfb.12698. Fulltekst i vitenarkiv
• Nilsson, Göran Erik & Lefevre, Sjannie (2016). Physiological challenges to fishes in a warmer and acidified future. Physiology. ISSN 1548-9213. 31(6), s. 409–417. doi: 10.1152/physiol.00055.2015. Fulltekst i vitenarkiv
• Mckenzie, David J.; Axelsson, Michael; Chabot, Denis; Claireaux, Guy; Cooke, Steven J. & Corner, Richard A. [Vis alle 29 forfattere av denne artikkelen] (2016). Conservation physiology of marine fishes: state of the art and prospects for policy. Conservation Physiology. 4(1). doi: 10.1093/conphys/cow046. Fulltekst i vitenarkiv
• Lefevre, Sjannie (2016). Are global warming and ocean acidification conspiring against marine ectotherms? Are meta-analysis of the respiratory effects of elevated temperature, high CO2, and their interaction. Conservation Physiology. 4(1). doi: 10.1093/conphys/cow009. Fulltekst i vitenarkiv
• Regan, Matthew D.; Turko, Andy J.; Heras, Joseph; Andersen, Mads Kuhlmann; Lefevre, Sjannie & Wang, Tobias [Vis alle 11 forfattere av denne artikkelen] (2016). Ambient CO2, fish behaviour and altered GABAergic neurotransmission: Exploring the mechanism of CO2-altered behaviour by taking a hypercapnia dweller down to low CO2 levels. Journal of Experimental Biology. ISSN 0022-0949. 219(1), s. 109–118. doi: 10.1242/jeb.131375. Fulltekst i vitenarkiv
• Lefevre, Sjannie; Findorf, Inge; Bayley, Mark; Huong, Do Thi Thanh & Wang, Tobias (2015). Increased temperature tolerance of the air-breathing Asian swamp eel Monopterus albus after high-temperature acclimation is not explained by improved cardiorespiratory performance. Journal of Fish Biology. ISSN 0022-1112. doi: 10.1111/jfb.12696. Fulltekst i vitenarkiv
• Lefevre, Sjannie; Watson, Sue-Ann; Munday, Philip L. & Nilsson, Göran Erik (2015). Will jumping snails prevail? Influence of near-future CO2, temperature and hypoxia on respiratory performance in the tropical conch Gibberulus gibberulus gibbosus. Journal of Experimental Biology. ISSN 0022-0949. 218(19), s. 2991–3001. doi: 10.1242/jeb.120717. Fulltekst i vitenarkiv
• Wang, Tobias; Lefevre, Sjannie; Iversen, Nina K.; Findorf, Inge; Buchanan, Rasmus & Mckenzie, David J. (2014). Anaemia only causes a small reduction in the upper critical temperature of sea bass: Is oxygen delivery the limiting factor for tolerance of acute warming in fishes? Journal of Experimental Biology. ISSN 0022-0949. 217(24), s. 4275–4278. doi: 10.1242/jeb.104166. Fulltekst i vitenarkiv
• Lefevre, Sjannie; Damsgaard, Christian; Pascale, Desirae R.; Nilsson, Göran Erik & Stecyk, Jonathan Anthony William (2014). Air breathing in the Arctic: influence of temperature, hypoxia, activity and restricted air access on respiratory physiology of the Alaska blackfish Dallia pectoralis. Journal of Experimental Biology. ISSN 0022-0949. 217(24), s. 4387–4398. doi: 10.1242/jeb.105023. Fulltekst i vitenarkiv
• Cook, D.G.; Brown, Eric Joel; Lefevre, Sjannie; Domenici, Paolo & Steffensen, John Fleng (2014). The response of striped surfperch embiotoca lateralis to progressive hypoxia: Swimming activity, shoal structure, and estimated metabolic expenditure. Journal of Experimental Marine Biology and Ecology. ISSN 0022-0981. 460, s. 162–169. doi: 10.1016/j.jembe.2014.07.002. Fulltekst i vitenarkiv
• Lefevre, Sjannie; Domenici, Paolo & Mckenzie, David J. (2014). Swimming in air-breathing fishes. Journal of Fish Biology. ISSN 0022-1112. 84(3), s. 661–681. doi: 10.1111/jfb.12308. Fulltekst i vitenarkiv
• Lefevre, Sjannie; Wang, Tobias; Huong, Do Thi Thanh; Phuong, Nguyen Thanh & Bayley, Mark (2013). Partitioning of oxygen uptake and cost of surfacing during swimming in the air-breathing catfish Pangasianodon hypophthalmus. Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology. ISSN 0174-1578. 183, s. 215–221. doi: 10.1007/s00360-012-0701-8. Fulltekst i vitenarkiv
• Watson, Sue; Lefevre, Sjannie; McCormick, Mark I.; Domenici, Paolo; Nilsson, Göran Erik & Munday, Philip L. (2013). Marine mollusc predator-escape behaviour altered by near-future carbon dioxide levels. Proceedings of the Royal Society of London. Biological Sciences. ISSN 0962-8452. 281(1774). doi: 10.1098/rspb.2013.2377. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Lefevre, Sjannie (2025). Cardiorespiratory responses of jumping snails to high temperature, exercise and hypoxia. Fulltekst i vitenarkiv
• Lefevre, Sjannie; Farhat, Elie & Damsgaard, Christian (2025). Spatial transcriptomics reveals region-specific responses to anoxia in the crucian carp brain. Fulltekst i vitenarkiv Vis sammendrag

  Aim The crucian carp (Carassius carassius) is a fish with a remarkable anoxia tolerance, enabling it to survive the Norwegian winters in the wild, where seasonal anoxia is common in small lakes and ponds. While the physiological mechanisms are well documented, there is still a need for better understanding regulation at the molecular and genetic level. The crucian carp brain overall shows a large transcriptional response to anoxia and reoxygenation but given that the brain is a complex and heterogenous tissue, we wanted to explore these transcriptional responses from a spatial perspective. Methods & Results We prepared brain sections from crucian carp that had been exposed to 5 days normoxia and 5 days anoxia, aiming for a transverse plane that would capture the telencephalon, optic tectum (and thalamus). These areas were chosen because previous studies have indicated increased cell death in anoxia and effects on learning and memory, functions associated with the telencephalon, and since it is well known that retinal activity and vision is reduced in anoxia. We used the Visium Spatial Gene Expression system from 10x Genomics to prepare mRNA libraries from the brain sections (four biological samples in each treatment group). Conclusions Based on the mRNA abundance data, we successfully identified brain areas with distinct gene expression patterns: 6 in the telencephalon, 4 in optic tectum, and 2 in thalamus. The study thus confirms the complexity of the crucian carp brain transcriptional response anoxia.

• Lefevre, Sjannie; Pesqueira, Laura Marian Valencia & Jentoft, Sissel (2024). De novo assembly of the crucian carp genome for the study of anoxia tolerance. Fulltekst i vitenarkiv Vis sammendrag

  The crucian carp (Carassius carassius) is a fish with a remarkable anoxia tolerance, enabling it to survive the Norwegian winters in the wild, where seasonal anoxia is common in small lakes and ponds. While the physiological mechanisms are well documented, there is still a need for better understanding regulation at the molecular and genetic level, and a fully sequenced, assembled and annotated genome will facilitate such studies. To obtain a high-quality genome assembly, we sequenced crucian carp genomic DNA using chromosome conformation capture (HiC), PacBio long-read sequencing, and short-read sequencing for error correction. The structural and functional annotation were produced using RNA-seq data, teleost ortholog proteins, and UTRs were annotated with the PASA-pipeline and long-read RNA sequencing (Iso-seq data). Functional annotation of proteins predicted by the structural gene models were obtained by performing protein motif searches using Diamond blast, InterProScan and UniProt. With this new genome assembly with structural and functional annotation of a wild specimen of Norwegian crucian carp, we can begin to formulate more hypotheses about mechanisms that support the physiological adaptations that the crucian carp employs in order to tolerate survival in anoxic environments. Furthermore, the crucian carp has a recent whole-genome duplication (shared with some other cyprinids like common carp and goldfish), which provides the opportunity for diversified functions of the multiple gene paralogs; diversions that can be further studied with a high-quality reference genome.

• Lefevre, Sjannie & Nilsson, Göran Erik (2024). Case study: The anoxia-tolerant crucian carp, Encyclopedia of Fish Physiology (Second Edition). Elsevier. ISSN 9780323997614. s. 148–158. doi: 10.1016/B978-0-323-90801-6.00105-1. Fulltekst i vitenarkiv
• Lefevre, Sjannie; Dahl, Helge Andre; Williams, Darryl; Jentoft, Sissel & Cossins, Andrew R. (2024). Changes in transcription-translation dynamics in crucian carp brain revealed by Riboseq. Fulltekst i vitenarkiv Vis sammendrag

  The physiological adaptations allowing the crucian carp (Carassius carassius) to survive anoxia are well characterised. At the whole-animal level, these adaptations are well understood, but we know less about the cellular and molecular mechanisms involved in regulating the response to anoxia. Genes, through their transcription and translation to protein products, are (assumingly) central to molecular, cellular and ultimately tissue function. A timely and appropriate change in gene expression is expected to coordinate the more long-term physiological responses to anoxia, and next-generation sequencing techniques and bioinformatics can provide is a global view of these changes. While it is reasonable to assume that changes in gene expression for a majority of genes leads to matching changes in translation and synthesis of proteins, the picture and conclusions that can be drawn will be more complete by looking not only at gene expression but also translation. By sequencing and quantifying both mRNA and ribosome-protected mRNA fragments (RPFs) in brain tissue from crucian carp exposed to normoxia, anoxia and re-oxygenation, we can determine the genes that are differentially expressed, as well as the degree to which the changes in mRNA expression lead to a change in translation. We can also assess whether changes in expression of RPFs are the result of altered transcription or altered translation efficiency. The data so far reveal that translation efficiency for some genes changes more rapidly than transcription in response to anoxia and particularly re-oxygenation, giving the crucian carp finer temporal control of the protein pool and hence cellular activities.

• Gerber, Lucie Claire Lola; Lundeberg, Jenny; Farhat, Elie; Nilsson, Göran Erik & Lefevre, Sjannie (2024). The key to living without oxygen? Succinate transport in the anoxia tolerant crucian carp. Fulltekst i vitenarkiv
• Winklhofer, Magdalena & Lefevre, Sjannie (2024). DNA Methylation Alterations During Anoxia and Reoxygenation in Crucian Carp Brain. Fulltekst i vitenarkiv
• Winklhofer, Magdalena & Lefevre, Sjannie (2024). Crucian carp’s fin-tastic tactics for anoxia survival - DNA methylation as an epigenetic switch to protect crucian carp during anoxia and reoxygenation. Fulltekst i vitenarkiv
• Gerber, Lucie Claire Lola; Torp, May-Kristin; Nilsson, Göran Erik; Lefevre, Sjannie & Stensløkken, Kåre-Olav (2023). Comparison of Cardiac Mitochondrial Function of an Anoxia Tolerant and Intolerant Vertebrate. Fulltekst i vitenarkiv
• Lefevre, Sjannie; Downie, Adam; Rummer, Jodie L. & Nilsson, Göran Erik (2022). Changes in haemoglobin gene expression during development of a coral reef fish. Fulltekst i vitenarkiv Vis sammendrag

  Tropical reef fishes, such as the orange clownfish and other anemonefishes share a particular life history: The larvae hatch at the reef, go through a pelagic stage, after which the larvae return to the reef for settlement and maturation into adults. The two environments – coral reef and open sea – are vastly different, and poses unique challenges to the physiology of the fish. It has been shown that several species start out by having high maximum oxygen consumptions rates as larvae, but low hypoxia tolerance, a pattern that then reverses before or during the time of settlement. It has been hypothesised that shifting from low-affinity to high-affinity haemoglobin could be responsible for this pattern, but due to the very small size of the larvae, it has been difficult to investigate. In this study we used RNA sequencing to look at transcriptomic changes during larval development of the cinnamon clownfish (Amphiprion melanopus), focusing on the haemoglobin genes, which have different paralogs of the alpha and beta subunits. Larvae were bred and hatched in the lab, and sampled at 4, 6 and 9 days post-hatch. We found a clear shift from 4 to 9 days in the paralogs dominating the expression of both alpha and beta subunits. While investigation of the functional properties are still necessary to confirm that they switch from low- to high-affinity isoforms, specifically, the data supports the hypothesis that haemoglobin isoform switching occurs just before the larvae settle on the reef.

• Pesqueira, Laura Maria Valencia; Jentoft, Sissel & Lefevre, Sjannie (2022). De novo assembly of the crucian carp genome. Fulltekst i vitenarkiv Vis sammendrag

  The crucian carp (Carassius carassius) is a champion of anoxia tolerance and the physiological mechanisms are well documented. Still, there is a need for better understanding at the molecular and genetic level, and a fully sequenced, assembled and annotated genome will facilitate such studies. To obtain a high-quality genome assembly, we sequenced the crucian carp genome using methods such as chromosome conformation capture (HiC) and PacBio long-read sequencing, in addition to short-read sequencing for error correction. For annotation we are using full-length transcripts (IsoSeq data) as well as regular RNAseq data from both normoxic, anoxic and re-oxygenated crucian carp. The genome of crucian carp and other cyprinids consists of 50 chromosomes that originated from several whole-genome duplication events, with the most recent occurring 14 Mya. The presence of duplicated genes offers the possibility for evolutionary changes through the mechanism of expression dominance: one paralog remains most expressed, while the other paralog is free to change without compromising the expression integrity of the biological systems required for normal function. This is hypothesized to be the genetic mechanism having allowed the crucian carp and goldfish (Carassius auratus) pyruvate dehydroxylases to obtain the decarboxylation function necessary for conversion of pyruvate to acetaldehyde; an important metabolic process in the crucian carp’s survival strategy in anoxia. We expect that paralogs of other important genes may have undergone similar changes, and aim to elucidate any differences that may have arisen between the crucian carp and the goldfish due to the long domestication history of the latter.

• Lefevre, Sjannie & Dahl, Helge Andre (2022). Insights from ‘omics’ about crucian carp anoxia tolerance. Fulltekst i vitenarkiv Vis sammendrag

  The crucian carp (Carassius carassius) is extremely tolerant to the absence of oxygen. Its metabolically most active organs, such as the brain, can maintain function over extended periods of anoxia. Our research seeks to understand the cellular and molecular mechanisms involved in regulating the response of the crucian carp to anoxia. We take a discovery-driven approach, using metabolomics, transcriptomics and translatomics, to identify key mechanisms and signalling pathways behind the extreme anoxia tolerance. In this talk, I will present results on sequencing and quantification of mRNA and ribosome-protected (i.e. translated) mRNA fragments in brain tissue from crucian carp exposed to normoxia, anoxia and re-oxygenation, as well as metabolites from multiple tissues.

• Lefevre, Sjannie (2022). Partitioning of oxygen uptake in air-breathing fishes. Fulltekst i vitenarkiv
• Lefevre, Sjannie; Downie, Adam; Rummer, Jodie L. & Nilsson, Göran Erik (2022). Changes in haemoglobin gene expression during development of a coral reef fish. Fulltekst i vitenarkiv
• Gerber, Lucie; Torp, May-Kristin; Nilsson, Göran Erik; Lefevre, Sjannie & Stensløkken, Kåre-Olav (2022). Improving organ preservation: Another lesson from the champion of anoxia tolerance, the crucian carp (C. carassius). Fulltekst i vitenarkiv
• Gerber, Lucie; Torp, May-Kristin; Nilsson, Göran Erik; Stensløkken, Kåre-Olav & Lefevre, Sjannie (2022). Mitochondrial Functions in the Anoxia Tolerant Crucian Carp. Fulltekst i vitenarkiv
• Gerber, Lucie; Torp, May-Kristin; Nilsson, Göran Erik; Lefevre, Sjannie & Stensløkken, Kåre-Olav (2022). Improving organ preservation: Another lesson from the champion of anoxia tolerance, the crucian carp (C. carassius). Fulltekst i vitenarkiv
• Gerber, Lucie; Helle-Valle, Tellef; Resseguier, Julien Alain Andre; Torp, May-Kristin; Dahl, Helge Andre & Nilsson, Göran Erik [Vis alle 8 forfattere av denne artikkelen] (2022). Prolyl Hydroxylase Domains in the Anoxia Tolerant Crucian Carp (c. carassius): Insights into the Regulation of the HIF Response to Anoxia-Reoxygenation. Fulltekst i vitenarkiv
• Gerber, Lucie; Helle-Valle, Tellef; Resseguier, Julien Alain Andre; Torp, May-Kristin; Dahl, Helge Andre & Nilsson, Göran Erik [Vis alle 8 forfattere av denne artikkelen] (2022). Prolyl Hydroxylase Domains in the Anoxia Tolerant Crucian Carp (c. carassius): Insights into the Regulation of the HIF Response to Anoxia-Reoxygenation. Fulltekst i vitenarkiv
• Lefevre, Sjannie (2021). Strategies that allow the crucian carp to survive periods of anoxia that would kill a mammal. Fulltekst i vitenarkiv
• Lefevre, Sjannie (2021). The role of transcription and translation dynamics in the response to anoxia and re-oxygenation in the crucian carp. Fulltekst i vitenarkiv
• Gerber, Lucie; Nilsson, Göran Erik & Lefevre, Sjannie (2021). Kan en fisk fra Nordmarka hjelpe oss? Fulltekst i vitenarkiv
• Lefevre, Sjannie; Lau, Gigi Yik Chee; Dahl, Helge-Andre & Nilsson, Göran Erik (2019). Crucian carp: mitochondria, anoxia and reoxygenation. Fulltekst i vitenarkiv
• Lefevre, Sjannie; Lau, Gigi Yik Chee; Dahl, Helge-Andre & Nilsson, Göran Erik (2019). Re-oxygenation resilience - the other aspect of the crucian carp’s anoxia tolerance. Fulltekst i vitenarkiv
• Lefevre, Sjannie; McKenzie, David J. & Nilsson, Göran Erik (2019). Global warming and future fish size: thoughts on the gill-oxygen limitation hypothesis. Fulltekst i vitenarkiv
• Lefevre, Sjannie (2019). Global warming and future fish size:What can we learn from the gill-oxygen limitation hypothesis (GOLT)? Fulltekst i vitenarkiv
• Lefevre, Sjannie (2019). SENSING AND ADAPTING TO OXYGEN AVAILABILITY: Fuelling the fire of life and the 2019 Nobel Prize. NBS-nytt. ISSN 0801-3535. 4. Fulltekst i vitenarkiv
• Lefevre, Sjannie (2018). Re-oxygenation resilience - the other element of the crucian carp's anoxia tolerance. Fulltekst i vitenarkiv
• Haugnes, Gunhild M.; Tallaksen, Lena M.; Vogt, Rolf David; Storelvmo, Trude; Hessen, Dag Olav & Stordal, Frode [Vis alle 9 forfattere av denne artikkelen] (2018). Klimaforskerne tar temperaturen på tropesommeren. [Journal]. Titan.uio.no. Fulltekst i vitenarkiv
• Jutfelt, Fredrik; Norin, Tommy; Ern, Rasmus; Overgaard, Johannes; Wang, Tobias & McKenzie, David J. [Vis alle 28 forfattere av denne artikkelen] (2018). Oxygen- and capacity-limited thermal tolerance: blurring ecology and physiology. Journal of Experimental Biology. ISSN 0022-0949. 221(1). doi: 10.1242/jeb.169615. Fulltekst i vitenarkiv
• Lefevre, Sjannie (2018). Long-term hypoxia acclimation has minor effects on respiratory physiology of Alaska blackfish. Fulltekst i vitenarkiv
• Lefevre, Sjannie (2018). Global warming and future fish size (or how not to interpret aerobic scope). Fulltekst i vitenarkiv
• Lefevre, Sjannie (2018). Global warming and future fish size: Unfounded assumptions lead to absurd predictions. Fulltekst i vitenarkiv
• Lefevre, Sjannie (2018). Are there CO2 effects on oxygen uptake as predicted by the OCLTT hypothesis? Fulltekst i vitenarkiv
• Dahl, Helge-Andre & Lefevre, Sjannie (2018). Protection against reperfusion injury: can insight be gained from crucian carp? Fulltekst i vitenarkiv
• Lefevre, Sjannie (2016). Are respiratory effects of global warming and ocean acidification explained by a unifying OCLTT concept? Fulltekst i vitenarkiv
• Lefevre, Sjannie (2016). The transcriptomic response of crucian carp to anoxia and re-oxygenation. Fulltekst i vitenarkiv
• Lefevre, Sjannie & Nilsson, Göran E. (2015). Temperature acclimation in jumping snails (Gibberulus gibberulus) reduces heart rate, but not oxygen uptake, and only marginally improves heat tolerance. Fulltekst i vitenarkiv
• Lefevre, Sjannie (2015). Snails in the fast-lane: Physiology and Climate Change perspectives. NBS-nytt. ISSN 0801-3535. 39(4), s. 20–21. Fulltekst i vitenarkiv
• Lefevre, Sjannie; Stecyk, Jonathan A. W.; Torp, May-Kristin & Nilsson, Göran Erik (2014). HOW TOLERANT IS AN ANOXIA-TOLERANT VERTEBRATE? Fulltekst i vitenarkiv Vis sammendrag

  The crucian carp Carassius carassius is capable of surviving without oxygen for several months, by carefully matching ATP supply and demand. It does so by exploiting its unique ability to produce ethanol as an anaerobic end-product and undergo partial metabolic rate suppression, shutting down non-vital functions such as vision. Even so, it is unknown if crucian carp are fully able to protect themselves from the damage (i.e. cell death), normally caused by absence and particularly re-entrance of oxygen. Here, we investigated the occurrence of apoptosis in brain of crucian carp exposed to normoxia, anoxia and re-oxygenation in the laboratory, using Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). We also measured mRNA and protein levels of the apoptosis executer protein Caspase 3 using quantitative real-time PCR and Western blotting. Additionally, Caspase 3 expression levels were measured in brains from crucian carp captured in their natural habitat at different months of the year. Overall, crucian carp appear to maintain apoptotic activity in anoxia, but there is a transient increase in the early re-oxygenation phase. In its natural habitat transcription of Caspase 3 is generally much down-regulated during the winter, but protein levels are maintained, with only a slight increase in the spring.

• Lefevre, Sjannie; Watson, Sue-Ann; Munday, Philip L. & Nilsson, Göran Erik (2014). Golbal warming: Will jumping snails prevail? Fulltekst i vitenarkiv
• Lefevre, Sjannie; Bayley, Mark; Mckenzie, David J. & Craig, John F. (2014). Air-breathing fishes. Journal of Fish Biology. ISSN 0022-1112. 84(3), s. 547–553. doi: 10.1111/jfb.12349. Fulltekst i vitenarkiv

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