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Climatic warming elevates mortality for many salmonid populations during their physically challenging up-river spawning migrations, yet, the mechanisms underlying the increased mortality remain elusive. One hypothesis posits that a cardiac oxygen insufficiency impairs the heart’s capacity to pump sufficient oxygen to body tissues to sustain up-river swimming, especially in warm water when oxygen availability declines and cardiac and whole-animal oxygen demand increases. We tested this hypothesis by measuring cardiac and metabolic (cardiorespiratory) performance, and assessing the upper thermal tolerance of coho salmon ( Oncorhynchus kisutch ) during sustained swimming and acute warming. By surgically ligating the coronary artery, which naturally accumulates arteriosclerotic lesions in migrating salmon, we partially impaired oxygen supply to the heart. Coronary ligation caused drastic cardiac impairment during swimming, even at benign temperatures, and substantially constrained cardiorespiratory performance during swimming and progressive warming compared to sham-operated control fish. Furthermore, upper thermal tolerance during swimming was markedly reduced (by 4.4 °C) following ligation. While the cardiorespiratory capacity of female salmon was generally lower at higher temperatures compared to males, upper thermal tolerance during swimming was similar between sexes within treatment groups. Cardiac oxygen supply is a crucial determinant for the migratory capacity of salmon facing climatic environmental warming.

Mutation of Glass bottom boat, the Drosophila homologue of the bone morphogenetic protein or growth/differentiation factor (BMP/GDF) family of genes in vertebrates, has been shown to disrupt development of neuromuscular junctions (NMJ). Here we tested whether this same conclusion can be broadened to vertebrate BMP/GDF genes. This analysis was also extended to consider whether such genes are required for NMJ maintenance in post-larval stages, as this would argue that BMP genes are viable candidates for analysis in progressive neuromuscular disease. Zebrafish mutants harboring homozygous null mutations in the BMP-family gene gdf6a were raised to adulthood and assessed for neuromuscular deficits. Fish lacking gdf6a exhibited decreased endurance (∼ 50%, p = 0.005) compared to wild type, and this deficit progressively worsened with age. These fish also presented with significantly disrupted NMJ morphology (p = 0.009), and a lower abundance of spinal motor neurons (∼ 50%, p<0.001) compared to wild type. Noting the similarity of these symptoms to those of Amyotrophic Lateral Sclerosis (ALS) model mice and fish, we asked if mutations in gdf6a would enhance the phenotypes observed in the latter, i.e. in zebrafish over-expressing mutant Superoxide Dismutase 1 (SOD1). Amongst younger adult fish only bigenic fish harboring both the SOD1 transgene and gdf6a mutations, but not siblings with other combinations of these gene modifications, displayed significantly reduced endurance (75%, p<0.05) and strength/power (75%, p<0.05), as well as disrupted NMJ morphology (p<0.001) compared to wild type siblings. Bigenic fish also had lower survival rates compared to other genotypes. Thus conclusions regarding a role for BMP ligands in effecting NMJ can be extended to vertebrates, supporting conservation of mechanisms relevant to neuromuscular degenerative diseases. These conclusions synergize with past findings to argue for further analysis of GDF6 and other BMP genes as modifier loci, potentially affecting susceptibility to ALS and perhaps a broader suite of neurodegenerative diseases.

The swimming performance of fishes has generally been assessed using a stepped velocity test where the speed at fatigue is considered the critical swimming performance ( U crit ). Although this test was designed for fishes that swim in the water column, it has been applied to fishes that adhere to the substrate. Here we examined the extent to which substrate holding, slipping and swimming contributed to reaching U crit in an example substrate holding fish, the invasive round goby. A linear model indicated that each behavior contributed significantly to U crit , but that substrate holding was by far the biggest contributor (65.8 ± 3.9 % vs. 5.8 ± 0.9 and 28.4 ± 3.4 % slipping and swimming). We also used our behavioural analysis to determine the critical substrate holding speed ( U hold: 28.6 ± 1.1 cm s −1 ). We conclude that the U crit test can be applied to substrate holding fish but that it is not just an indication of critical swimming speed as is often considered and must be interpreted with caution.

The Arctic is warming at twice the global average rate; how native and non‐native anadromous fishes will respond remains largely unknown. Some native Arctic salmonids are already experiencing warm (>21°C), physically challenging migratory river conditions and large diurnal temperature fluctuations (>10°C). We conducted field and laboratory experiments to determine how these extreme conditions may affect the capacity for migration in Arctic and temperate salmonids. In adult migratory Arctic char, reflex impairment following a handling challenge increased with temperature, indicating more extensive fatigue. In Arctic char smolts, temperature did not affect initial critical swimming performance (Umax1), however, there was a threshold for repeat swimming performance (Umax2) near 20°C, above which recovery was impaired. Following a simulated diurnal warming scenario (11–21°C), Umax1 increased in rainbow trout and remained constant in Arctic char as in the field while Umax2 remained constant in rainbow trout it was drastically reduced in Arctic char. Furthermore, at warm temperatures, Arctic char were unable to recover to routine levels of oxygen uptake after exercise, while rainbow trout were. Warming also had more pronounced effects on blood composition and plasma glucose and lactate concentration in Arctic char than in rainbow trout. In general, rainbow trout, a temperate salmonid, had superior swimming performance, aerobic capacity, and warm tolerance than Arctic char, an Arctic salmonid. The present flow and temperature regimes in some Arctic rivers may restrict migration of native salmonids by limiting their ability to recover from fatiguing exercise. Non‐native, temperate salmonids are likely better suited to overcome these particular physical and thermal challenges. A plain language summary is available for this article. Plain Language Summary

The Arctic climate is changing rapidly, yet predicting how aquatic species will respond to these changes remains challenging given the lack of empirical data for most high-latitude taxa. Acoustic telemetry has recently emerged as an important methodology for understanding horizontal and vertical space-use patterns in fishes. Here, we used acoustic telemetry to document marine habitat use and depth/temperature preference of 26 anadromous Arctic char Salvelinus alpinus within the Kitikmeot Sea region of the Canadian central Arctic over 4 yr (2013−2016). Most detections (~70%) were within the top 3 m of the water column, and most were in estuarine (72.6%) vs. marine (27.4%) habitats. Arctic char preferred deeper waters later in the summer, but the temperature they occupied remained relatively constant throughout the marine feeding season (~5−8°C). Most Arctic char exhibited some degree of repetitive diving behavior, with individuals diving to 35 m. Diving activity increased later in the summer marine feeding season and is likely a response to the seasonal transition of their preferred prey to deeper waters as the season progresses. Finally, Arctic char preferred deeper waters with less ice cover and during the day, the latter suggesting potential diel patterns to marine habitat use. Finally, year-to-year variation in Arctic char depth and temperature use was very modest despite differences in climatic and ice conditions. This result suggests that habitat use is relatively fixed and may reflect their thermal and osmoregulatory physiology, which has important implications for forecasting the impacts of a changing Arctic on this economically valuable species.

Despite immense concern over amplified warming in the Arctic, physiological research to address related conservation issues for valuable cold-adapted fish, such as the Arctic char (Salvelinus alpinus), is lacking. This crucial knowledge gap is largely attributable to the practical and logistical challenges of conducting sensitive physiological investigations in remote field settings. Here, we used an innovative, mobile aquatic-research laboratory to assess the effects of temperature on aerobic metabolism and maximum heart rate (fHmax) of upriver migrating Arctic char in the Kitikmeot region of Nunavut in the central Canadian Arctic. Absolute aerobic scope was unchanged at temperatures from 4 to 16°C, while fHmax increased with temperature (Q10 = 2.1), as expected. However, fHmax fell precipitously below 4°C and it began to plateau above ~ 16°C, reaching a maximum at ~ 19°C before declining and becoming arrhythmic at ~ 21°C. Furthermore, recovery from exhaustive exercise appeared to be critically impaired above 16°C. The broad thermal range (~4–16°C) for increasing fHmax and maintaining absolute aerobic scope matches river temperatures commonly encountered by migrating Arctic char in this region. Nevertheless, river temperatures can exceed 20°C during warm events and our results confirm that such temperatures would limit exercise performance and thus impair migration in this species. Thus, unless Arctic char can rapidly acclimatize or alter its migration timing or location, which are both open questions, these impairments would likely impact population persistence and reduce lifetime fitness. As such, future conservation efforts should work towards quantifying and accounting for the impacts of warming, variable river temperatures on migration and reproductive success.

Abstract Phenotypic plasticity is thought to be critical in allowing organisms to cope with environmental change, but the factors that limit this plasticity are poorly understood, which hampers predictions of species resilience to anthropogenic climate change. Here, we ask if limited plasticity in key traits constrains performance at high temperatures, using two California hatchery strains of rainbow trout (Oncorhynchus mykiss). Aerobic and anaerobic metabolic performance declined at a high but ecologically relevant acclimation temperature (24°C), suggesting performance cannot be maintained at this temperature, despite acclimation. Similarly, while both whole-organism thermal tolerance and hypoxia tolerance improved with acclimation to moderately elevated temperatures, compensation was limited at the highest acclimation temperature. These limits at the whole-organism level were aligned with limits at lower levels of biological organization. At the organ level, absolute scope to increase heart rate with acute warming (ΔƒHmax) did not increase between the upper two acclimation temperatures, and the safety margin for cardiac performance decreased at the highest acclimation temperature. At the cellular level, at 24°C, there were transcriptomic changes in the heart consistent with a cellular stress response. These limits across multiple levels of biological organization were observed under conditions that are ecologically relevant at the southern end of the species range, which suggests that thermal plasticity is likely insufficient to buffer rainbow trout against even modest anthropogenic warming in these regions. Lay Summary Understanding the boundaries of acclimation capacity in response to increased temperature can provide valuable insights into conservation and management. In rainbow trout, we show that acclimation limits occur at ecologically relevant temperatures and are aligned with thermal limits across molecular, physiological and whole-animal phenotypes.

Mutation of Glass bottom boat, the Drosophila homologue of the bone morphogenetic protein or growth/differentiation factor (BMP/GDF) family of genes in vertebrates, has been shown to disrupt development of neuromuscular junctions (NMJ). Here we tested whether this same conclusion can be broadened to vertebrate BMP/GDF genes. This analysis was also extended to consider whether such genes are required for NMJ maintenance in post-larval stages, as this would argue that BMP genes are viable candidates for analysis in progressive neuromuscular disease. Zebrafish mutants harboring homozygous null mutations in the BMP-family gene gdf6a were raised to adulthood and assessed for neuromuscular deficits. Fish lacking gdf6a exhibited decreased endurance (50%, p = 0.005) compared to wild type, and this deficit progressively worsened with age. These fish also presented with significantly disrupted NMJ morphology (p = 0.009), and a lower abundance of spinal motor neurons (50%, p<0.001) compared to wild type. Noting the similarity of these symptoms to those of Amyotrophic Lateral Sclerosis (ALS) model mice and fish, we asked if mutations in gdf6a would enhance the phenotypes observed in the latter, i.e. in zebrafish over-expressing mutant Superoxide Dismutase 1 (SOD1). Amongst younger adult fish only bigenic fish harboring both the SOD1 transgene and gdf6a mutations, but not siblings with other combinations of these gene modifications, displayed significantly reduced endurance (75%, p<0.05) and strength/power (75%, p<0.05), as well as disrupted NMJ morphology (p<0.001) compared to wild type siblings. Bigenic fish also had lower survival rates compared to other genotypes. Thus conclusions regarding a role for BMP ligands in effecting NMJ can be extended to vertebrates, supporting conservation of mechanisms relevant to neuromuscular degenerative diseases. These conclusions synergize with past findings to argue for further analysis of GDF6 and other BMP genes as modifier loci, potentially affecting susceptibility to ALS and perhaps a broader suite of neurodegenerative diseases.

In a randomized trial, patients with tricuspid regurgitation who were treated with transcatheter edge-to-edge repair had more favorable clinical outcomes at 1 year than did patients who received medical therapy.

Efficacy trials of antibody-inducing protein-in-adjuvant vaccines targeting the blood-stage Plasmodium falciparum malaria parasite have so far shown disappointing results. The induction of cell-mediated responses in conjunction with antibody responses is thought to be one alternative strategy that could achieve protective efficacy in humans. Here, we prepared chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) replication-deficient vectors encoding the well-studied P. falciparum blood-stage malaria antigen merozoite surface protein 1 (MSP1). A phase Ia clinical trial was conducted in healthy adults of a ChAd63-MVA MSP1 heterologous prime-boost immunization regime. The vaccine was safe and generally well tolerated. Fewer systemic adverse events (AEs) were observed following ChAd63 MSP1 than MVA MSP1 administration. Exceptionally strong T-cell responses were induced, and these displayed a mixed of CD4+ and CD8+ phenotype. Substantial MSP1-specific serum immunoglobulin G (IgG) antibody responses were also induced, which were capable of recognizing native parasite antigen, but these did not reach titers sufficient to neutralize P. falciparum parasites in vitro. This viral vectored vaccine regime is thus a leading approach for the induction of strong cellular and humoral immunogenicity against difficult disease targets in humans. Further studies are required to assess whether this strategy can achieve protective efficacy against blood-stage malaria infection.