Search

In salmon farming, the use of sterile triploids (3N) can mitigate the problem of escapees interbreeding with wild salmon. However, triploid salmon appear less tolerant to high water temperatures and low oxygen levels compared to diploids (2N). To investigate how the thermal performance and physiology of large (2.5 kg) triploid Atlantic salmon Salmo salar L. differs from those of diploids, both ploidies were subjected to water temperatures between 3 and 18∞C. The fish were exposed to reduced oxygen saturations (O2 sat, 70%), termed hypoxia, at 6 and 18∞C. Triploids fed more than diploids between 3 and 9∞C and at similar levels at 12∞C. At 15∞C, the feed intake significantly dropped in both ploidies, although more in triploids. During hypoxia, feed intake was higher in triploids at 6∞C and equal to diploids at 18∞C. The overall feed conversion ratio was similar between ploidies. Muscle energy phosphates were generally lower in triploids than diploids, while muscle glucose, blood haemoglobin and haematocrit were lower in triploids than diploids at ≥12∞C. Plasma lactate levels tended to be higher in triploids and increased with increasing temperature and at hypoxia in both ploidies. Plasma cortisol increased in both ploidies at high temperatures and was highest in triploids under hypoxic conditions at 18∞C. Triploids had a higher cataract score at the start of the experiment and developed more cataracts throughout the experiment. The present findings show that large triploid Atlantic salmon perform better at colder water temperatures compared to diploids and differ in parts of their physiological expression at increasing and high temperature.

Abstract: The rate of rerupture of repaired Achilles tendon in young and athletic populations remains high despite improvement in surgical techniques, suture design, and postsurgical management. Acellular biological matrices can be used to enhance the immediate strength of repaired tendons and to serve as scaffolds for cell in-growth and constructive tissue remodeling. A number of commercially available matrices have been used clinically, albeit with varying degrees of success and failure. The disparity is likely attributable to the different physical and biochemical properties of individual matrices. In this study, we investigated the biomechanical characteristics of 2 different acellular collagen matrices, namely TissueMend® and GraftJacket®, using a sheep Achilles tendon repair model. Static and cyclic creep, cyclic and linear construct stiffness, maximum load to failure, and displacement at maximum load were determined at time zero. We found that the maximum load to failure, displacement, and ultimate failure mode were similar between tendons augmented with either acellular collagen matrix; however, TissueMend augmentation yielded lower creep and smaller construct elongation than did GraftJacket. The results indicated that the strength of TissueMend-augmented tendons and GraftJacket-augmented tendons was not statistically significantly different, although tendons augmented with TissueMend displayed greater stiffness, which may be clinically advantageous in the restoration of ruptured tendons. [ABSTRACT FROM AUTHOR]

Astaxanthin (Ax) determines the flesh redness of a salmonid fish which is the most desirable quality indicator by consumers. Fish cannot synthesize Ax de novo, therefore, the only way to increase flesh redness is to increase dietary input or improve the absorption and retention rate of dietary Ax. As a hydrophobic carotenoid, the absorption of Ax can be modulated by other lipid molecules in the diet. The present study explored the effect of three lipids, cholesterol (CH), phytosterol (PS), and docosahexaenoic acid (DHA) on Ax absorption, transport, and retention in rainbow trout. Dietary CH significantly improved Ax absorption by elevating plasma Ax levels ( p < 0.05); however, it had no effect on the whole body Ax or flesh color. Dietary PS appears to inhibit Ax absorption since fish had significantly ( p < 0.05) reduced whole body Ax. Dietary DHA appeared to have no effect on Ax absorption or retention. By comparing intestinal transcriptomes, a low density lipoprotein receptor ( ldlr ) gene was significantly downregulated in fish fed the CH diet as compared to the control diet. Since LDLR protein plays a major role in plasma lipoprotein turnover, we hypothesized that the inhibition of ldlr gene by high dietary CH resulted in higher retention of plasma Ax. The elevation of plasma Ax was not reflected in higher flesh coloration, which suggested other limiting factors governing Ax retention in the muscle. On the other hand, the transcriptomic and proteomic analyses found no changes of genes or proteins involved in Ax absorption, transport, or excretion in fish fed PS or DHA diets as compared to the control diet. In conclusion, this study has suggested that CH promotes Ax absorption by regulating lipoprotein retention and provide evidence for improving Ax absorption via dietary modulation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Yang Jin et al.)

Proteins present in blood samples from Atlantic salmon ( Salmo salar ) infected with salmon lice ( Lepeophtheirus salmonis ) were analyzed using liquid chromatography-high-resolution mass spectrometry. Bioinformatic analyses revealed 1820 proteins, of which 58 were assigned to lice. Among these, peroxiredoxin-2, an antioxidant protein, was found relevant with respect to blood feeding of the parasite. The three-dimensional structure analysis of the protein revealed a surface amino acid sequence of interest. A 13-amino-acid peptide was selected as a potential antigen due to its predicted solubility, antigenicity, probable non-allergenic, and non-toxic nature. This peroxiredoxin-2-derived peptide was synthesized, combined with a commercially available adjuvant, and used for vaccination. The test vaccine demonstrated a 60-70% protection rate against early-stage Lepeophtheirus salmonis infection in a challenge trial in Norway. Additionally, the vaccine was tested against salmon lice ( Caligus rogercresseyi ) in Chile, where a remarkable 92% reduction in the number of adult lice was observed. Thus, in combination with the selected adjuvant, the peptide showed antigenic potential, making it a suitable candidate for future vaccine development. The approach described holds promise for the development of peptide vaccines against various ectoparasites feeding on blood or skin secretions of their hosts.

Traumatic heterotopic ossification (HO) is frequently observed in Service Members following combat-related trauma. Estimates suggest that ~65% of wounded warriors who suffer limb loss or major extremity trauma will experience some type of HO formation. The development of HO delays rehabilitation and can prevent the use of a prosthetic. To date there are limited data to suggest a standard mechanism for preventing HO. This may be due to inadequate animal models not producing a similar bone structure as human HO. We recently showed that traumatic HO growth is possible in an ovine model. Within that study, we demonstrated that 65% of sheep developed a human-relevant hybrid traumatic HO bone structure after being exposed to a combination of seven combat-relevant factors. Although HO formed, we did not determine which traumatic factor contributed most. Therefore, in this study, we performed individual and various combinations of surgical/traumatic factors to determine their individual contribution to HO growth. Outcomes showed that the presence of mature biofilm stimulated a large region of bone growth, while bone trauma resulted in a localized bone response as indicated by jagged bone at the linea aspera. However, it was not until the combinatory factors were included that an HO structure similar to that of humans formed more readily in 60% of the sheep. In conclusion, data suggested that traumatic HO growth can develop following various traumatic factors, but a combination of known instigators yields higher frequency size and consistency of ectopic bone.

Photoplethysmography is a recent addition to physio-logging in Atlantic salmon which can be used for pulse oximetry provided that the properties for light propagation in salmon tissues are known. In this work, optical properties of three constituents of Atlantic salmon blood have been characterized using a photo spectrometer in the VIS-NIR range (450-920 nm). Furthermore, Atlantic salmon blood cell size has been measured using a Coulter counter as part of light scattering property evaluations. Results indicate that plasma contributes little to scattering and absorption for wavelengths typically used in pulse oximetry as opposed to blood cells which are highly scattering. Extinction spectra for oxygenated and deoxygenated hemoglobin indicate that Atlantic salmon hemoglobin is similar to that in humans. Pulse oximetry sensors originally intended for human applications may thus be used to estimate blood oxygenation levels for this species., (© 2023 The Authors. Journal of Biophotonics published by Wiley-VCH GmbH.)

Nephrocalcinosis is a widespread challenge in intensive production of salmon smolt. There is however no consensus on its aetiology, which makes it problematic to implement proper measures to limit its development. We performed a survey of nephrocalcinosis prevalence and environmental factors in 11 different hatcheries in Mid-Norway as well as a 6-month monitoring in one of the hatcheries. A multivariate analysis indicated that the most influencing factor for the prevalence of nephrocalcinosis was the supplementation of sea water during smolt production. In the 6-month monitoring, the hatchery introduced salinity in the production water prior to the change in day length. Mismatch in those environmental signals may increase the risk for developing nephrocalcinosis. Salinity fluctuations prior to smoltification can cause osmotic stress and result in unbalanced levels of ions in fish blood. This was clearly illustrated in our study, as the fish experienced chronic hypercalcaemia and hypermagnesaemia. Both magnesium and calcium are excreted over the kidneys and it is possible that their prolonged, elevated levels in plasma resulted in an oversaturation of the urine when finally excreted. This again could have led to the aggregation of calcium deposits within the kidney. This study indicates a relationship between osmotic stress induced by salinity changes in juvenile Atlantic salmon and the development of nephrocalcinosis. Other factors that may affect the severity of nephrocalcinosis are currently subjects for discussion., (© 2023 The Authors. Journal of Fish Diseases published by John Wiley & Sons Ltd.)

Farmed Atlantic salmon reared under natural seasonal changes in sea-cages had an elevated consumption of antioxidants during spring. It is, however, unclear if this response was caused by the increase in day length, temperature, or both. The present study examined redox processes in Atlantic salmon that were reared in indoor tanks at constant temperature (9 °C) under a simulated natural photoperiod. The experiment lasted for 6 months, from vernal to autumnal equinoxes, with the associated increase and subsequent decrease in day length. We found that intracellular antioxidants were depleted, and there was an increase in malondialdehyde (MDA) levels in the liver and muscle of Atlantic salmon with increasing day length. Antioxidant enzyme activity in liver and muscle and their related gene profiles was also affected, with a distinct upregulation of genes involved in maintaining redox homeostasis, such as peroxiredoxins in the brain in April. This study also revealed a nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated oxidative stress response in muscle and liver, suggesting that fish integrate environmental signals through redox signaling pathways. Furthermore, growth and expression profiles implicated in growth hormone (GH) signaling and cell cycle regulation coincided with stress patterns. The results demonstrate that a change in photoperiod without the concomitant increase in temperature is sufficient to stimulate growth and change the tissue oxidative state in Atlantic salmon during spring and early summer. These findings provide new insights into redox regulation mechanisms underlying the response to the changing photoperiod, and highlight a link between oxidative status and physiological function.

This study aims to assess the effects of different dietary n-6/n-3 long-chain polyunsaturated fatty acid ratios and CHO content in the immune response of gilthead seabream. For that purpose, gilthead sea bream juveniles (initial body weight = 47.5 g) were fed for 84 days with four isoproteic (47% crude protein) and isolipidic (18% crude lipids) diets with high (20%) or low (5%) level of gelatinized starch (HS or LS diets, respectively) and included approximately 2.4% ARA or DHA. At the end of the trial, the DHA-enriched groups presented increased red blood cell (RBC) count, hemoglobin, plasmatic nitric oxide (NO) content, and antiprotease and alternative complement activities. The ARA groups had increased thrombocyte count, and plasmatic bactericidal activity against Vibrio anguillarum was lower in the fish fed the ARA/LS diet. After the feeding trial, the fish were challenged with an intraperitoneal injection (i.p.) of killed Photobacterium damselae subsp. piscicida ( Phdp ) and sampled at 4 and 24 h after the challenge. At 4 h after i.p., the ARA groups presented increased plasma total immunoglobulins (Ig) and bactericidal activity against V. anguillarum . In addition, the fish fed the ARA/LS diet presented lower white blood cell (WBC) and alternative complement activity. At 24 h after i.p., the ARA groups presented increased RBC, WBC, and thrombocyte numbers, total IG, plasma peroxidase activity, and casp3 expression in the distal intestine. The HS groups presented increased plasma NO content and bactericidal activity against Phdp and decreased protease, antiprotease activity, and bactericidal activity against V. anguillarum . In conclusion, high dietary DHA levels seemed to improve the immune status of unchallenged gilthead sea bream juveniles, while high dietary ARA levels improved the fish immune response to a bacterial challenge. The energy provided by dietary starch seems to be important to promote a fast response by the fish immune system after a challenge.

Farmed Atlantic salmon (Salmo salar) welfare and performance can be strongly influenced by stress episodes caused by handling during farming practices. To better understand the changes occurring after an acute stress response, we exposed a group of Atlantic salmon parr to an acute stressor, which involved netting and transferring fish to several new holding tanks. We describe a time-course response to stress by sampling parr in groups before (T0) and 10, 20, 30, 45, 60, 120, 240, 300, and 330 min post-stress. A subgroup of fish was also subjected to the same stressor for a second time to assess their capacity to respond to the same challenge again within a short timeframe (ReStressed). Fish plasma was assessed for adrenocorticotropic hormone (ACTH), cortisol, and ions levels. Mucus cortisol levels were analyzed and compared with the plasma cortisol levels. At 5 selected time points (T0, 60, 90, 120, 240, and ReStressed), we compared the head kidney transcriptome profile of 10 fish per time point. The considerably delayed increase of ACTH in the plasma (60 min post-stress), and the earlier rise of cortisol levels (10 min post-stress), suggests that cortisol release could be triggered by more rapidly responding factors, such as the sympathetic system. This hypothesis may be supported by a high upregulation of several genes involved in synaptic triggering, observed both during the first and the second stress episodes. Furthermore, while the transcriptome profile showed few changes at 60 min post-stress, expression of genes in several immune-related pathways increased markedly with each successive time point, demonstrating the role of the immune system in fish coping capacity. Although many of the genes discussed in this paper are still poorly characterized, this study provides new insights regarding the mechanisms occurring during the stress response of salmon parr and may form the basis for a useful guideline on timing of sampling protocols., (© 2022. The Author(s).)

Nephrocalcinosis is a common disorder in farmed Atlantic salmon, but the consequences for the fish physiology are not well understood. We performed a transcriptome study in kidneys of Atlantic salmon (Salmo salar) smolts without and with severe chronic nephrocalcinosis (NC). The study revealed that numerous genes are differentially expressed in fish with NC compared with healthy salmon. The most evident changes in gene expression patterns in the NC group were a massive downregulation of metabolism and energy production, upregulation of signalling pathways important for tissue repair and function maintenance and upregulation of inflammatory responses. Overall, the extensive tissue damage and the gene regulation responses that affect salmon with severe nephrocalcinosis are highly likely to have dramatic consequences on fish survival., (© 2022 The Authors. Journal of Fish Diseases published by John Wiley & Sons Ltd.)

Accumulating evidence indicates a close relationship between oxidative stress and growth rate in fish. However, the underlying mechanisms of this relationship remain unclear. This study evaluated the combined effect of dietary antioxidants and growth hormone (GH) on the liver and the muscle redox status of Atlantic salmon. There were two sequential experimental phases (EP) termed EP1 and EP2, each lasting for 6 weeks. In EP1, Atlantic salmon were fed either low-(L, 230 mg/kg ascorbic acid (Asc), 120 mg/kg α-tocopherol (α-TOH)), or high-(H, 380 mg/kg Asc, 210 mg/kg α-TOH)vitamin diets. The vitamins were supplemented as stable forms and the feeding was continued in EP2. In EP2, half of the fish were implanted with 3 μL per g body weight of recombinant bovine GH (Posilac ® , 1 mg rbGH g BW -1 ) suspended in sesame oil, while the other half were held in different tanks and sham-implanted with similar volumes of the sesame oil vehicle. Here, we show that increasing high levels of vitamin C and E (diet H) increased their content in muscle and liver during EP1. GH implantation decreased vitamin C and E levels in both liver and muscle but increased malondialdehyde (MDA) levels only in the liver. GH also affected many genes and pathways of antioxidant enzymes and the redox balance. Among the most consistent were the upregulation of genes coding for the NADPH oxidase family (NOXs) and downregulation of the oxidative stress response transcription factor, nuclear factor-erythroid 2-related factor 2 (nrf2), and its downstream target genes in the liver. We verified that GH increases the growth rate until the end of the trail and induces an oxidative effect in the liver and muscle of Atlantic salmon. Dietary antioxidants do lower oxidative stress but have no effect on the growth rate. The present study is intended as a starting point to understand the potential interactions between growth and redox signaling in fish.

Spring viremia of carp virus (SVCV) can cause high mortality of fish. The aim of this study was to investigate the effects of Lactobacillus rhamnosus GCC-3 exopolysaccharides (GCC-3 EPS) on zebrafish ( Danio rerio ) infected with SVCV and elucidate the underlying mechanisms. Zebrafish were fed with a control diet or diet supplemented with 0.5% and 1% of GCC-3 EPS for 2 weeks. The results showed that supplementation of GCC-3 EPS significantly improved the survival rate of zebrafish compared with the control group. In addition, dietary 0.5% and 1% GCC-3 EPS significantly up-regulated the expression of genes related to type I interferon (IFN) antiviral immunity. Consistent with in vivo results, GCC-3 EPS significantly inhibited SVCV replication in zebrafish embryonic fibroblast (ZF4) cells while significantly increased the expression of type I IFN signaling pathway related genes. Furthermore, knocking down TANK-binding kinase 1 significantly blocked the antiviral effect of GCC-3 EPS. Dietary GCC-3 EPS improved gut microbiota, and the culture supernatant of GCC-3 EPS-associated microbiota significantly inhibited SVCV replication in ZF4 cells compared with the control-microbiota counterpart. In conclusion, our results indicate that dietary GCC-3 EPS can improve the resistance of zebrafish against SVCV infection, and the mechanism may involve enhanced type I interferon signaling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Li, Olsen, Ringø, Yang, Zhang, Ran and Zhou.)

Salmon is a rich source of health-promoting omega-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA), such as eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). The LC-PUFA biosynthetic pathway in Atlantic salmon is one of the most studied compared to other teleosts. This has largely been due to the massive replacement of LC-PUFA-rich ingredients in aquafeeds with terrestrial plant oils devoid of these essential fatty acids (EFA) which ultimately pushed dietary content towards the minimal requirement of EFA. The practice would also reduce tissue content of n-3 LC-PUFA compromising the nutritional value of salmon to the human consumer. These necessitated detailed studies of endogenous biosynthetic capability as a contributor to these EFA. This review seeks to provide a comprehensive and concise overview of the current knowledge about the molecular genetics of PUFA biosynthesis in Atlantic salmon, highlighting the enzymology and nutritional regulation as well as transcriptional control networks. Furthermore, we discuss the impact of genome duplication on the complexity of salmon LC-PUFA pathway and highlight probable implications on endogenous biosynthetic capabilities. Finally, we have also compiled and made available a large RNAseq dataset from 316 salmon liver samples together with an R-script visualization resource to aid in explorative and hypothesis-driven research into salmon lipid metabolism., (© 2022. The Author(s).)

High-fat diets (HFD) are harmful to fish health. Probiotics are commonly utilized to improve fish nutrition metabolism, immune response, and health. Nucleic acids of the probiotic bacterium can be hydrolyzed by nuclease to generate nucleotides. The present study aimed to evaluate the effects of stabilized fermentation product of nuclease-treated Cetobacterium somerae XMX-1 [XMX-1 (N)] on growth, non-specific immunity, and liver health of zebrafish ( Danio rerio ). Compared to the HFD group, 100 g/kg XMX-1 (N) significantly increased weight gain and decreased feed conversion ratio (FCR). However, 5 or 10 g/kg XMX-1 (N) had no influence on zebrafish growth. In addition, supplementation of 100 g/kg XMX-1 (N) significantly increased lysozyme activity and total antioxidant capacity in skin mucus, and the expression of inflammation related genes interleukin 1 beta ( IL-1 β), interleukin 10 ( IL-10 ), and interleukin 6 ( IL-6 ) in the gut as well as fatty acid oxidation related genes uncoupling protein 2 ( UCP2 ) and proliferator-activated receptor γ coactivator 1α ( PGC1 α) in the liver, while decreased the content of hepatic triacylglycerol (TAG) in zebrafish. The gene sequencing, 16S r RNA, showed that 100 g/kg XMX-1 (N) enhanced the relative abundance of Firmicutes while lowered Proteobacteria and Actinobacteria. 10 g/kg XMX-1 (N) significantly increased lysozyme activity and complement component 4 (C4) in skin mucus, and intestinal expression of inflammation-related genes. In the 5 g/kg XMX-1 (N) group, however, only an increase in C4 level in skin mucus was observed. Together, these results reveal that dietary supplementation with nuclease-treated C. somerae XMX-1 (N) has a dose-dependent beneficial effect on fish health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Hao, Xia, Olsen, Ringø, Yang, Zhang, Ran and Zhou.)

Succinate is widely used in the food and feed industry as an acidulant, flavoring additive, and antimicrobial agent. This study investigated the effects of dietary succinate on growth, energy budget, nutritional metabolism, protein succinylation, and gut microbiota composition of zebrafish. Zebrafish were fed a control-check (0% succinate) or four succinate-supplemented diets (0.05, 0.10, 0.15, and 0.2%) for 4 weeks. The results showed that dietary succinate at the 0.15% additive amount (S0.15) can optimally promote weight gain and feed intake. Whole body protein, fat, and energy deposition increased in the S0.15 group. Fasting plasma glucose level decreased in fish fed the S0.15 diet, along with improved glucose tolerance. Lipid synthesis in the intestine, liver, and muscle increased with S0.15 feeding. Diet with 0.15% succinate inhibited intestinal gluconeogenesis but promoted hepatic gluconeogenesis. Glycogen synthesis increased in the liver and muscle of S0.15-fed fish. Glycolysis was increased in the muscle of S0.15-fed fish. In addition, 0.15% succinate-supplemented diet inhibited protein degradation in the intestine, liver, and muscle. Interestingly, different protein succinylation patterns in the intestine and liver were observed in fish fed the S0.15 diet. Intestinal proteins with increased succinylation levels were enriched in the tricarboxylic acid cycle while proteins with decreased succinylation levels were enriched in pathways related to fatty acid and amino acid degradation. Hepatic proteins with increased succinylation levels were enriched in oxidative phosphorylation while proteins with decreased succinylation levels were enriched in the processes of protein processing and transport in the endoplasmic reticulum. Finally, fish fed the S0.15 diet had a higher abundance of Proteobacteria but a lower abundance of Fusobacteria and Cetobacterium . In conclusion, dietary succinate could promote growth and feed intake, promote lipid anabolism, improve glucose homeostasis, and spare protein. The effects of succinate on nutritional metabolism are associated with alterations in the levels of metabolic intermediates, transcriptional regulation, and protein succinylation levels. However, hepatic fat accumulation and gut microbiota dysbiosis induced by dietary succinate suggest potential risks of succinate application as a feed additive for fish. This study would be beneficial in understanding the application of succinate as an aquatic feed additive., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ding, Lu, Hao, Zhang, Yang, Olsen, Ringo, Ran, Zhang and Zhou.)

Being highly unsaturated, n -3 long-chain polyunsaturated fatty acids (LC-PUFAs) are prone to lipid peroxidation. In this study, zebrafish were fed with low-fat diet (LFD), high-fat diet (HFD), or 2% DHA-supplemented HFD (HFDHA2.0). To study the possible negative effects of the high level of dietary DHA, growth rates, blood chemistry, liver histology, hepatic oxidative stress, apoptosis, and inflammatory processes were assessed. The cell studies were used to quantify the effects of DHA and antioxidant on cellular lipid peroxidation and viability. The possible interaction between gut microbiota and zebrafish host was evaluated in vitro . HFDHA2.0 had no effect on hepatic lipid level but induced liver injury, oxidative stress, and hepatocellular apoptosis, including intrinsic and death receptor-induced apoptosis. Besides, the inclusion of 2% DHA in HFD increased the abundance of Proteobacteria in gut microbiota and serum endotoxin level. In the zebrafish liver cell model, DHA activated intrinsic apoptosis while the antioxidant 4-hydroxy-Tempo (tempo) inhibited the pro-apoptotic negative effects of DHA. The apoptosis induced by lipopolysaccharide (LPS) was unaffected by the addition of tempo. In conclusion, the excess DHA supplementation generates hepatocellular apoptosis-related injury to the liver. The processes might propagate along at least two routes, involving lipid peroxidation and gut microbiota-generated LPS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ding, Hao, Zhang, Yang, Olsen, Ringø, Ran, Zhang and Zhou.)

With the widespread use of high-fat diets (HFDs) in aquaculture, fatty livers are frequently observed in many fish species. The aim of this study was to investigate if docosahexaenoic acid (DHA) could be used to reduce the fatty liver in zebrafish generated by a 16% soybean oil-HFD over 2 weeks of feeding. The DHA was added to iso-lipidic HFD at 0.5, 1.0, and 2.0% of diet. Supplementation of DHA reduced growth and feed efficiency in a dose dependent manner being lowest in the HFDHA2.0 group. Hepatic triglyceride (TG) in zebrafish fed 0.5% DHA-supplemented HFD (HFDHA0.5) was significantly lower than in the HFD control. Transcriptional analyses of hepatic genes showed that lipid synthesis was reduced, while fatty acid β-oxidation was increased in the HFDHA0.5 group. Furthermore, the expression of Cyclin D1 in liver of zebrafish fed HFDHA0.5 was significantly reduced compared to that in fish fed HFD. In zebrafish liver cells, Cyclin D1 knockdown and blocking of Cyclin D1-CDK4 signal led to inhibited lipid biosynthesis and elevated lipid β-oxidation. Besides, DHA-supplemented diet resulted in a rich of Proteobacteria and Actinobacteriota in gut microbiota, which promoted lipid β-oxidation but did not alter the expression of Cyclin D1 in germ-free zebrafish model. In conclusion, DHA not only inhibits hepatic lipid synthesis and promotes lipid β-oxidation via Cyclin D1 inhibition, but also facilitates lipid β-oxidation via gut microbiota. This study reveals the lipid-lowering effects of DHA and highlights the importance of fatty acid composition when formulating fish HFD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ding, Hao, Zhang, Yang, Olsen, Ringø, Ran, Zhang and Zhou.)

Probiotics are widely used in aquafeeds and exhibited beneficial effects on fish by improving host health and resisting pathogens. However, probiotics applied to aquaculture are mainly from terrestrial sources instead of the host animal. The purpose of the work was to evaluate the effects of stabilized fermentation product of commensal Cetobacterium somerae XMX-1 on gut, liver health and antiviral immunity of zebrafish. A total of 240 zebrafish were assigned to the control (fed a basal diet) and XMX-1 group (fed a basal diet with 10 g XMX-1/kg diet). After four weeks feeding, growth performance, feed utilization, hepatic steatosis score, TAG, lipid metabolism related genes and serum ALT were evaluated. Furthermore, serum LPS, the expression of Hif-1α, intestinal inflammation score, antioxidant capability and gut microbiota were tested. The survival rate and the expression of antiviral genes were analyzed after challenge by spring viremia of carp virus (SVCV). Results showed that dietary XMX-1 did not affect growth of zebrafish. However, dietary XMX-1 significantly decreased the level of serum LPS, intestinal inflammation score and intestinal MDA, as well as increased T-AOC and the expression of Hif-1α in zebrafish intestine (p < 0.05). Furthermore, XMX-1 supplementation decreased the relative abundance of Proteobacteria and increased Firmicutes and Actinobacteria. Additionally, XMX-1 supplementation significantly decreased hepatic steatosis score, hepatic TAG, serum ALT and increased the expression of lipolysis genes versus control (p < 0.05). Zebrafish fed XMX-1 diet exhibited higher survival rate after SVCV challenge. Consistently, dietary XMX-1 fermentation product increased the expression of IFNφ2 and IFNφ3 after 2 days of SVCV challenge and the expression of IFNφ1, IFNφ2 and MxC after 4 days of SVCV challenge in the spleen in zebrafish versus control (p < 0.05). In conclusion, our results indicate that dietary XMX-1 can improve liver and gut health, while enhancing antiviral immunity of zebrafish., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Plain language summaries of peer-reviewed medical journal publications are a means of sharing research with a broad range of audiences and may improve the transparency, accountability, accessibility, discoverability, and inclusivity of medical research. There is currently an ongoing, industry-wide effort to establish consensus on plain language summaries, and initiatives are already in place that provide detailed guidance on plain language best practice, co-creation methods, patient-focused content, graphic and digital considerations, and publisher-specific guidelines. However, there remains a need for a foundational set of recommendations that complement existing initiatives to outline the minimum steps needed to develop discoverable, plain language summaries that are trustworthy, credible, and of high quality. Here, we present the Open Pharma recommendations for plain language summaries of peer-reviewed medical journal publications. These recommendations were initially developed by the Open Pharma Accessibility workstream and were extensively reviewed and refined during an expert roundtable and a focused, public consultation. Open Pharma is a multi-sponsor collaboration of pharmaceutical companies, non-pharmaceutical funders, publishers, patients, academics, regulators, editors, and societies seeking to identify and drive positive changes in the publishing of pharmaceutical company-funded research. We recommend that plain language summaries should be in the style of an abstract, free of technical jargon, unbiased, non-promotional, peer reviewed, and easily accessed. Plain language summaries should also meet the technical requirements to be indexed in directories such as PubMed. Ultimately, these recommendations are intended to be a concise outline of a minimum standard that provides top-line guidance on plain language summaries for authors, medical writers, publishers, and research funders.

Background: Dietary nucleotides (NTs) have been reported to affect hepatic function and composition. However, the effects on hepatic lipid deposition are less studied., Objectives: We aimed to identify the regulatory role of dietary NTs in hepatic lipid deposition of zebrafish and elucidate the underlying mechanisms., Methods: Zebrafish (60 ± 1.69 mg; 1 mo old) were fed control diet (16.2% energy as fat) or diet supplemented with 0.1% NTs or 0.02% AMP in feeding experiments 1 and 2. Experiment 3 was conducted with zebrafish larvae. In experiment 4, 1-mo-old zebrafish were fed a high-fat diet (HFD, 38.2% energy as fat) or an HFD supplemented with 0.1% NTs or 0.02% AMP. Hepatic lipid deposition was evaluated by triglyceride (TG) content and staining. Phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) was assayed by immunoblotting. Zebrafish liver (ZFL) cells were treated with exogenous adenosine. Small interfering RNA was used to knock down AMPK or nucleoside transporter SLC28a1 in ZFL cells. Vivo-morpholino was used to knock down AMPK in zebrafish larvae., Results: Dietary 0.1% NTs or 0.02% AMP reduced hepatic TGs by 62% and 32%, respectively, compared with control (P < 0.05). Dietary AMP enhanced hepatic AMPK and ACC phosphorylation. Consistently, exogenous adenosine enhanced AMPK and ACC phosphorylation by 111% and 53%, respectively, in ZFL cells (P < 0.01) and reduced TG content by 56% (P < 0.05). Knockdown of AMPK and SLC28a1 abolished the effect of adenosine on lipid deposition in ZFL cells, and AMPK morpholino blocked the hepatic lipid-lowering effect of dietary AMP in vivo. Finally, dietary NTs and AMP activated AMPK and attenuated hepatic lipid deposition (28% and 30%, P < 0.05) in fish fed an HFD., Conclusions: Dietary NTs and AMP reduce hepatic lipid deposition in zebrafish, which involves exogenous AMP-mediated AMPK activation. Our results suggest that dietary NTs can contribute to alleviation of hepatic steatosis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Heterotopic ossification (HO) refers to ectopic bone formation, typically in residual limbs following trauma and injury. A review of injuries from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) indicated that approximately 70% of war wounds involved the musculoskeletal system, largely in part from the use of improvised explosive devices (IED) and rocket-propelled grenades (RPG). HO is reported to occur in approximately 63%-65% of wounded warriors from OIF and OEF. Symptomatic HO may delay rehabilitation regimens since it often requires modifications to prosthetic limb componentry and socket size. There is limited evidence indicating a mechanism for preventing HO. This may be due to inadequate models, which do not produce HO bone structure that is morphologically similar to HO samples obtained from wounded warfighters injured in theatre. We hypothesized that using a high-power blast of air (shockwave) and simulated battlefield trauma (i.e. bone damage, tourniquet, bacteria, negative pressure wound therapy) in a large animal model, HO would form and have similar morphology to ectopic bone observed in clinical samples. Initial radiographic and micro-computed tomography (CT) data demonstrated ectopic bone growth in sheep 24 weeks post-procedure. Advanced histological and backscatter electron (BSE) analyses showed that 5 out of 8 (63%) sheep produced HO with similar morphology to clinical samples. We conclude that not all ectopic bone observed by radiograph or micro-CT in animal models is HO. Advanced histological and BSE analyses may improve confirmation of HO presence and morphology, which we demonstrated can be produced in a large animal model., Competing Interests: No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this article. There is no COI to report., (© 2021 Published by Elsevier Inc.)

A better understanding of carotenoid dynamics (transport, absorption, metabolism, and deposition) is essential to develop a better strategy to improve astaxanthin (Ax) retention in muscle of Atlantic salmon. To achieve that, a comparison of post-smolt salmon with (+ Ax) or without (- Ax) dietary Ax supplementation was established based on a transcriptomic approach targeting pyloric, hepatic, and muscular tissues. Results in post-smolts showed that the pyloric caeca transcriptome is more sensitive to dietary Ax supplementation compared to the other tissues. Key genes sensitive to Ax supplementation could be identified, such as cd36 in pylorus, agr2 in liver, or fbp1 in muscle. The most modulated genes in pylorus were related to absorption but also metabolism of Ax. Additionally, genes linked to upstream regulation of the ferroptosis pathway were significantly modulated in liver, evoking the involvement of Ax as an antioxidant in this process. Finally, the muscle seemed to be less impacted by dietary Ax supplementation, except for genes related to actin remodelling and glucose homeostasis. In conclusion, the transcriptome data generated from this study showed that Ax dynamics in Atlantic salmon is characterized by a high metabolism during absorption at pyloric caeca level. In liver, a link with a potential of ferroptosis process appears likely via cellular lipid peroxidation. Our data provide insights into a better understanding of molecular mechanisms involved in dietary Ax supplementation, as well as its beneficial effects in preventing oxidative stress and related inflammation in muscle., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The increasing replacement of fish oil (FO) by vegetable oils (VO) in aquafeeds for marine carnivorous species may lead to modifications of the dietary arachidonic (ARA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) levels and ratios that may compromise the fish immune status. Therefore, this study aimed to assess how different dietary ratios of ARA, EPA, and DHA modulate the immune response of gilthead sea bream juveniles. For that purpose, four isoproteic and isolipidic plant-based diets were formulated to include different dietary Long-Chain-Polyunsaturated Fatty Acids (LC-PUFA) ratios (%DM): Diet A (2.0% ARA: 0.2% EPA: 0.1% DHA); Diet B (1.0% ARA: 0.4% EPA: 0.4% DHA); Diet C (0% ARA: 0.6% EPA: 0.6% DHA); Diet D (0% ARA: 0.3% EPA: 1.5% DHA). Fish were fed the experimental diets for 56 days and then the haematological profile, humoral innate immune parameters, and expression of immune-related genes in the gut were determined. Our results showed that fish fed diet B exhibited an increase in the monocyte numbers, alternative complement activity, and bactericidal activity against Photobacterium damselae compared to the values found in fish fed other diets. Contrarily, peroxidase, antiproteases, and proteases activity and nitric oxide levels were not affected by the dietary treatments. Immune-related gene expression in the distal intestine did not show differences between dietary treatments. Overall, a diet with a balanced n-6 (ARA) and n-3 (EPA+DHA) LC-PUFA ratio seemed to better modulate the fish innate immune response, thus better preparing the fish innate immune system against potential immunological insults ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Propionate and propionyl-CoA accumulation have been associated with the development of mitochondrial dysfunction. In this study, we show that propionate induces intestinal damage in zebrafish when fed a high-fat diet (HFD). The intestinal damage was associated with oxidative stress owing to compromised superoxide dismutase 2 (Sod2) activity. Global lysine propionylation analysis of the intestinal samples showed that Sod2 was propionylated at lysine 132 (K132), and further biochemical assays demonstrated that K132 propionylation suppressed Sod2 activity. In addition, sirtuin 3 (Sirt3) played an important role in regulating Sod2 activity via modulating de-propionylation. Finally, we revealed that intestinal oxidative stress resulting from Sod2 propionylation contributed to compositional change of gut microbiota. Collectively, our results in this study show that there is a link between Sod2 propionylation and oxidative stress in zebrafish intestines and highlight the potential mechanism of intestinal problems associated with high propionate levels., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Late developmental stages of the marine copepods in the genus Calanus can spend extended periods in a dormant stage (diapause) that is preceded by the accumulation of large lipid stores. We assessed how lipid metabolism during development from the C4 stage to adult is altered in response to predation risk and varying food availability, to ultimately understand more of the metabolic processes during development in Calanus copepods. We used RNA sequencing to assess if perceived predation risk in combination with varied food availability affects expression of genes associated with lipid metabolism and diapause preparation in C. finmarchicus. The lipid metabolism response to predation risk differed depending on food availability, time and life stage. Predation risk caused upregulation of lipid catabolism with high food, and downregulation with low food. Under low food conditions, predation risk disrupted lipid accumulation. The copepods showed no clear signs of diapause preparation, supporting earlier observations of the importance of multiple environmental cues in inducing diapause in C. finmarchicus. This study demonstrates that lipid metabolism is a sensitive endpoint for the interacting environmental effects of predation pressure and food availability. As diapause may be controlled by lipid accumulation, our findings may contribute towards understanding processes that can ultimately influence diapause timing.

Background: With declining wild fish populations, farmed salmon has gained popularity as a source for healthy long-chain highly unsaturated fatty acids (LC-HUFA). However, the introduction of plant oil in farmed salmon feeds has reduced the content of these beneficial LC-HUFA. The synthetic capability for LC-HUFAs depends upon the dietary precursor fatty acids and the genetic potential, thus there is a need for in-depth understanding of LC-HUFA synthetic genes and their interactions with other genes involved in lipid metabolism. Several key genes of LC-HUFA synthesis in salmon belong to the fatty acid desaturases 2 (fads2) family. The present study applied whole transcriptome analysis on two CRISPR-mutated salmon strains (crispants), 1) Δ6abc/5 Mt with mutations in Δ5fads2, Δ6fads2-a, Δ6fads2-b and Δ6fads2-c genes, and 2) Δ6bc Mt with mutations in Δ6fads2-b and Δ6fads2-c genes. Our purpose is to evaluate the genetic effect fads2 mutations have on other lipid metabolism pathways in fish, as well as to investigate mosaicism in a commercial species with a very long embryonal period., Results: Both Δ6abc/5 Mt and Δ6bc Mt crispants demonstrated high percentage of indels within all intended target genes, though different indel types and percentage were observed between individuals. The Δ6abc/5 Mt fish displayed several disruptive indels which resulted in over 100 differentially expressed genes (DEGs) enriched in lipid metabolism pathways in liver. This includes up-regulation of srebp1 genes which are known key transcription regulators of lipid metabolism as well as a number of down-stream genes involved in fatty acid de-novo synthesis, fatty acid β-oxidation and lipogenesis. Both elovl5 and elovl2 genes were not changed, suggesting that the genes were not targeted by Srebp1. The mutation of Δ6bc Mt surprisingly resulted in over 3000 DEGs which were enriched in factors encoding genes involved in mRNA regulation and stability., Conclusions: CRISPR-Cas9 can efficiently mutate multiple fads2 genes simultaneously in salmon. The results of the present study have provided new information on the transcriptional regulations of lipid metabolism genes after reduction of LC-HUFA synthesis pathways in salmon.

Penaeid prawns are considered as most demanding fishery resources. The current study aims to purify and characterize lectin from the haemolymph of Penaeus semisulcatus. The semisulcatus-lectin was purified by affinity chromatography using mannose coupled Sepharose CL-4B column and purified lectin exhibited a single band of 66 kDa in SDS-PAGE. The purity and crystalline structure of purified lectin was confirmed by HPLC and X-ray diffraction analysis. Semisulcatus-lectin exhibited yeast agglutination activity against Saccharomyces cerevisiae and agglutinated human erythrocytes. Semisulcatus-lectin was evaluated for phenol oxidase activation and phagocytic activities. It was observed that semisulcatus-lectin had antibacterial activity against Gram-negative Vibrio parahaemolyticus and Aeromonas hydrophila, suggesting a potential therapeutic strategy in aquaculture industry for disease management., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aquaculture, the farming of fish and seafood, is recognized as a highly efficient system for producing protein for human consumption. In contrast, many terrestrial animal protein production systems are inefficient, impacting land use and exacerbating climate change. Humankind needs to adopt a more plant-centric diet, the only exception being fish consumed as both a source of protein and essential dietary nutrients such as omega-3 fatty acids. Here we consider the implications of such a transition, and the challenges that aquaculture must overcome to increase productivity within planetary boundaries. We consider how agriculture, specifically crops, can provide solutions for aquaculture, especially the sectors that are dependent on marine ingredients. For example, agriculture can provide experience with managing monocultures and new technologies such as genetically modified crops tailored specifically for use in aquaculture. We propose that a closer connection between agriculture and aquaculture will create a resilient food system capable of meeting increasing dietary and nutritional demands without exhausting planetary resources., (© 2020. Springer Nature Limited.)

Lactobacilli comprise an important group of probiotics for both human and animals. The emerging concern regarding safety problems associated with live microbial cells is enhancing the interest in using cell components and metabolites derived from probiotic strains. Here, we define cell structural components and metabolites of probiotic bacteria as paraprobiotics and postbiotics, respectively. Paraprobiotics and postbiotics produced from Lactobacilli consist of a wide range of molecules including peptidoglycans, surface proteins, cell wall polysaccharides, secreted proteins, bacteriocins, and organic acids, which mediate positive effect on the host, such as immunomodulatory, anti-tumor, antimicrobial, and barrier-preservation effects. In this review, we systematically summarize the paraprobiotics and postbiotics derived from Lactobacilli and their beneficial functions. We also discuss the mechanisms underlying their beneficial effects on the host, and their interaction with the host cells. This review may boost our understanding on the benefits and molecular mechanisms associated with paraprobiotics and probiotics from Lactobacilli , which may promote their applications in humans and animals., (Copyright © 2020 Teame, Wang, Xie, Zhang, Yang, Ding, Gao, Olsen, Ran and Zhou.)

The present work assessed the effects of dietary ratios of essential fatty acids, arachidonic (ARA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), on liver and intestine oxidative status, intestinal histomorphology and gut microbiota of gilthead sea bream. Four isoproteic and isolipidic plant-based diets were formulated containing a vegetable oil blend as the main lipid source. Diets were supplemented with ARA/EPA/DHA levels (%DM) equivalent to: 2%:0.2%:0.1% (Diet A); 1.0%:0.4%:0.4% (Diet B); 0%:0.6%:0.6% (Diet C); 0%:0.3%:1.5% (Diet D) and tested in triplicate groups for 56 days. Lipid peroxidation was higher in fish fed diets C and D while no differences were reported between diets regarding total, oxidized, and reduced glutathione, and oxidative stress index. Glutathione reductase was higher in fish fed diet A than diets C and D. No histological alterations were observed in the distal intestine. Lower microbiota diversity was observed in intestinal mucosa of fish fed diet C than A, while diets C and D enabled the proliferation of health-promoting bacteria from Bacteroidetes phylum (Asinibacterium sp.) and the absence of pathogenic species like Edwardsiella tarda. Overall, results suggest that a balance between dietary ARA/EPA + DHA promotes gilthead sea bream juveniles' health however higher dietary content of n-3 LC-PUFA might limited the presence of microbial pathogens in intestinal mucosa.

Astaxanthin (Ax), the main carotenoid responsible for the distinct red flesh color in salmonids (Oncorhynchus, Salvelinus, Salmo, and Parahucho), is added to the diet of farmed fish at a substantial cost. Despite the great economical value for the salmon industry, the key molecular mechanisms involved in the regulation of muscle coloration are poorly understood. Chinook salmon (Oncorhynchus tshawytscha) represent an ideal model to study flesh coloration because they exhibit a distinct color polymorphism responsible for two color morphs, white and red flesh pigmented fish. This study was designed to identify the molecular basis for the development of red and white coloration of fish reared under the same experimental conditions and to better understand the absorption mechanism of Ax in salmonids. Pyloric caeca, liver, and muscle of both groups (n = 6 each) were selected as the most likely critical target organs to be involved respectively in the intestinal uptake, metabolism, and retention of Ax. Difference in the transcriptome profile of each tissue using next-generation sequencing technology was conducted. Ten KEGG pathways were significantly enriched for differentially expressed genes between red and white salmon pylorus tissue, while none for the transcriptome profile in the other two tissues. Differential expressed gene (DE) analyses showed that there were relatively few differences in muscle (31 DE genes, p < 0.05) and liver (43 DE genes, p < 0.05) of white and red Chinook salmon compared approximately 1125 DE genes characterized in the pylorus tissue, with several linked to Ax binding ability, absorption, and metabolism.

Domestication of animals imposes strong targeted selection for desired traits but can also result in unintended selection due to new domestic environments. Atlantic salmon (Salmo salmar) was domesticated in the 1970s and has subsequently been selected for faster growth in systematic breeding programmes. More recently, salmon aquaculture has replaced fish oils (FOs) with vegetable oils (VOs) in feed, radically changing the levels of essential long-chain polyunsaturated fatty acids (LC-PUFAs). Our aim here was to study the impact of domestication on metabolism and explore the hypothesis that the shift to VO diets has unintentionally selected for a domestication-specific lipid metabolism. We conducted a 96-day feeding trial of domesticated and wild salmon fed diets based on FOs, VOs or phospholipids, and compared transcriptomes and fatty acids in tissues involved in lipid absorption (pyloric caeca) and lipid turnover and synthesis (liver). Domesticated salmon had faster growth and higher gene expression in glucose and lipid metabolism compared to wild fish, possibly linked to differences in regulation of circadian rhythm pathways. Only the domesticated salmon increased expression of LC-PUFA synthesis genes when given VOs. This transcriptome response difference was mirrored at the physiological level, with domesticated salmon having higher LC-PUFA levels but lower 18:3n-3 and 18:2n-6 levels. In line with this, the VO diet decreased growth rate in wild but not domesticated salmon. Our study revealed a clear impact of domestication on transcriptomic regulation linked to metabolism and suggests that unintentional selection in the domestic environment has resulted in evolution of stronger compensatory mechanisms to a diet low in LC-PUFAs., (© 2020 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

The intestinal epithelium is a selectively permeable barrier for nutrients, electrolytes and water, while maintaining effective protection against pathogens. Combinations of stressors throughout an animal's life, especially in agriculture and aquaculture settings, may affect the regular operativity of this organ with negative consequences for animal welfare. In the current study, we report the effects of a three-week unpredictable chronic stress (UCS) period on the intestinal morphology and transcriptome response of Atlantic salmon ( Salmon salar ) parr midgut and hindgut. Midgut and hindgut from both control and UCS fish were collected for histology and RNA-sequencing analysis to identify respective changes in the membrane structures and putative genes and pathways responding to UCS. Histological analysis did not show any significant effect on morphometric parameters. In the midgut, 1030 genes were differentially expressed following UCS, resulting in 279 genes which were involved in 13 metabolic pathways, including tissue repair pathways. In the hindgut, following UCS, 591 differentially expressed genes were detected with 426 downregulated and 165 upregulated. A total of 53 genes were related to three pathways. Downregulated genes include cellular senescence pathways, p53 signalling and cytokine-cytokine receptor pathways. The overall results corroborate that salmon parr were at least partly habituating to the UCS treatment. In midgut, the main upregulation was related to cell growth and repair, while in the hindgut there were indications of the activated apoptotic pathway, reduced cell repair and inhibited immune/anti-inflammatory capacity. This may be the trade-off between habituating to UCS and health resilience. This study suggests possible integrated genetic regulatory mechanisms that are tuned when farmed Atlantic salmon parr attempt to cope with UCS., Competing Interests: We declare we have no competing interest., (© 2020 The Authors.)