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Mutualistic and commensal interactions can have significant positive impacts on animal fitness and survival. However, behavioural interactions between pelagic animals living in offshore oceanic environments are little studied. Parasites can negatively effect the fitness of their hosts by draining resources and diverting energy from growth, reproduction, and other bodily functions. Pelagic fishes are hosts to a diverse array of parasites, however their environment provides few options for removal. Here we provide records of scraping behaviour of several pelagic teleost species, a behaviour that is likely used for parasite removal. These records span three ocean basins and, to the best of our knowledge, include the first records of scraping interactions involving tunas, blue sharks, and mako sharks as well as the first records of intraspecific scraping. We found that scrapers preferred scraping their head, eyes, gill cover, and lateral surfaces, areas where parasites are commonly found and where damage would likely have a substantial impact on fitness. Scraper species varied in their scraping preferences with tunas scraping mostly on the posterior caudal margins of sharks and occasionally conspecifics, while rainbow runner scraped in more varied locations on both sharks and conspecifics. Lengths of scrapers and scrapees were positively correlated and fish scraping on sharks were larger than those scraping on conspecifics, suggesting that risk of predation may be a limiting factor. We show that pelagic teleosts prefer to scrape on sharks rather than conspecifics or other teleosts and suggest that this behaviour may have a positive impact on teleost fitness by reducing parasite loads. The decline of shark populations in the global ocean and the reduction in mean size of many species may limit these interactions, eroding possible fitness benefits associated with this behaviour, and consequently placing more pressure on already highly targeted and vulnerable species.

Seamounts have been likened to “oases” of life in the comparative deserts of the open ocean, often harbouring high densities of threatened and exploited pelagic top predators. However, few such aggregations have been studied in any detail and the mechanisms that sustain them are poorly understood. Here, we present the findings of an integrated study of 3 previously unexplored seamounts in the tropical Atlantic, which aimed to investigate their significance as predator “hotspots” and inform their inclusion in one of world’s largest marine reserves. Baited underwater video and visual census transects revealed enhanced diversity and biomass of pelagic top predators, including elevated abundances of 7 species of sharks, predatory fish, and seabirds, within 5 km of 2 shallow seamounts (<100 m), but not a third deeper seamount (260 m). Hydroacoustic biomass of low- and mid-trophic level “prey” was also significantly elevated within 2.5 km of shallow seamounts. However, we found no evidence of enhanced primary productivity over any feature, suggesting high faunal biomass is sustained by exogenous energy inputs. Relative biomass enrichment also increased with trophic level, ranging from a 2-fold increase for zooplankton to a 41-fold increase for sharks. Tracking of the dominant predator species revealed that individual sharks (Galapagos, silky) and tuna (yellowfin, bigeye) often resided around seamounts for months to years, with evidence of connectivity between features, and (in the case of sharks) were spatially aggregated in localised hotspots that coincided with areas of high mid-trophic biomass. However, tuna and silky sharks also appeared to use seamounts as “hubs” in more extensive pelagic foraging ranges, which may help explain disproportionately high predator density. Our results reinforce the conservation significance of shallow seamounts for many marine top predators and offer fundamental insights into their functional roles as both prey “oases” and activity hubs for these species.

Marine fjords along the northern Labrador coast of Arctic Canada are influenced by freshwater, nutrients, and sediment inputs from ice fields and rivers. These ecosystems, further shaped by both Atlantic and Arctic water masses, are important habitats for fishes, marine mammals, seabirds, and marine invertebrates and are vital to the Labrador Inuit who have long depended on these areas for sustenance. Despite their ecological and socio-cultural importance, these marine ecosystems remain largely understudied. Here we conducted the first quantitative underwater scuba surveys, down to 12 m, of the nearshore marine ecology of Nachvak Fjord, which is surrounded by Torngat Mountains National Park located in Nunatsiavut, the Indigenous lands claim region of northeastern Canada. Our goal was to provide the Nunatsiavut Government with a baseline of the composition and environmental influences on the subtidal community in this isolated region as they work towards the creation of an Indigenous-led National Marine Conservation Area that includes Nachvak Fjord. We identified four major benthic habitat types: (1) boulders (2) rocks with sediment, (3) sediment with rocks, and (4) unconsolidated sediments, including sand, gravel, and cobble. Biogenic cover (e.g., kelp, coralline algae, and sediment) explained much of the variability in megabenthic invertebrate community structure. The kelp species Alaria esculenta , Saccharina latissima , and Laminaria solidungula dominated the boulder habitat outside of the fjord covering 35%, 13%, and 11% of the sea floor, respectively. In contrast, the middle and inner portions of the fjord were devoid of kelp and dominated by encrusting coralline algae. More diverse megabenthic invertebrate assemblages were detected within the fjord compared to the periphery. Fish assemblages were depauperate overall with the shorthorn sculpin, Myoxocephalus scorpius , and the Greenland cod, Gadus ogac , dominating total fish biomass contributing 64% and 30%, respectively. Understanding the composition and environmental influences within this fjord ecosystem not only contributes towards the protection of this ecological and culturally important region but serves as a baseline in a rapidly changing climatic region.

Dravet syndrome, an epileptic encephalopathy affecting children, largely results from heterozygous loss-of-function mutations in the brain voltage-gated sodium channel gene SCN1A . Heterozygous Scn1a knockout ( Scn1a +/− ) mice recapitulate the severe epilepsy phenotype of Dravet syndrome and are an accepted animal model. Because clinical observations suggest conventional sodium channel blocking antiepileptic drugs may worsen the disease, we predicted the phenotype of Scn1a +/− mice would be exacerbated by GS967, a potent, unconventional sodium channel blocker. Unexpectedly, GS967 significantly improved survival of Scn1a +/− mice and suppressed spontaneous seizures. By contrast, lamotrigine exacerbated the seizure phenotype. Electrophysiological recordings of acutely dissociated neurons revealed that chronic GS967-treatment had no impact on evoked action potential firing frequency of interneurons, but did suppress aberrant spontaneous firing of pyramidal neurons and was associated with significantly lower sodium current density. Lamotrigine had no effects on neuronal excitability of either neuron subtype. Additionally, chronically GS967-treated Scn1a +/− mice exhibited normalized pyramidal neuron sodium current density and reduced hippocampal Na V 1.6 protein levels, whereas lamotrigine treatment had no effect on either pyramidal neuron sodium current or hippocampal Na V 1.6 levels. Our findings demonstrate unexpected efficacy of a novel sodium channel blocker in Dravet syndrome and suggest a potential mechanism involving a secondary change in Na V 1.6.

Tristan da Cunha Islands, an archipelago of four rocky volcanic islands situated in the South Atlantic Ocean and part of the United Kingdom Overseas Territories (UKOTs), present a rare example of a relatively unimpacted temperate marine ecosystem. We conducted the first quantitative surveys of nearshore kelp forests, offshore pelagic waters and deep sea habitats. Kelp forests had very low biodiversity and species richness, but high biomass and abundance of those species present. Spatial variation in assemblage structure for both nearshore fish and invertebrates/algae was greatest between the three northern islands and the southern island of Gough, where sea temperatures were on average 3-4o colder. Despite a lobster fishery that provides the bulk of the income to the Tristan islands, lobster abundance and biomass are comparable to or greater than many Marine Protected Areas in other parts of the world. Pelagic camera surveys documented a rich biodiversity offshore, including large numbers of juvenile blue sharks, Prionace glauca. Species richness and abundance in the deep sea is positively related to hard rocky substrate and biogenic habitats such as sea pens, crinoids, whip corals, and gorgonians were present at 40% of the deep camera deployments. We observed distinct differences in the deep fish community above and below ~750 m depth. Concurrent oceanographic sampling showed a discontinuity in temperature and salinity at this depth. While currently healthy, Tristan's marine ecosystem is not without potential threats: shipping traffic leading to wrecks and species introductions, pressure to increase fishing effort beyond sustainable levels and the impacts of climate change all could potentially increase in the coming years. The United Kingdom has committed to protection of marine environments across the UKOTs, including Tristan da Cunha and these results can be used to inform future management decisions as well as provide a baseline against which future monitoring can be based.

Pathogenic variants in SCN8A, which encodes the voltage-gated sodium (NaV) channel NaV1.6, associate with neurodevelopmental disorders, including developmental and epileptic encephalopathy. Previous approaches to determine SCN8A variant function may be confounded by use of a neonatally expressed, alternatively spliced isoform of NaV1.6 (NaV1.6N) and engineered mutations rendering the channel tetrodotoxin (TTX) resistant. We investigated the impact of SCN8A alternative splicing on variant function by comparing the functional attributes of 15 variants expressed in 2 developmentally regulated splice isoforms (NaV1.6N, NaV1.6A). We employed automated patch clamp recording to enhance throughput, and developed a neuronal cell line (ND7/LoNav) with low levels of endogenous NaV current to obviate the need for TTX-resistance mutations. Expression of NaV1.6N or NaV1.6A in ND7/LoNav cells generated NaV currents with small, but significant, differences in voltage dependence of activation and inactivation. TTX-resistant versions of both isoforms exhibited significant functional differences compared with the corresponding WT channels. We demonstrated that many of the 15 disease-associated variants studied exhibited isoform-dependent functional effects, and that many of the studied SCN8A variants exhibited functional properties that were not easily classified as either gain- or loss-of-function. Our work illustrates the value of considering molecular and cellular context when investigating SCN8A variants.

Objective Interpretation of clinical genetic testing, which identifies a potential genetic etiology in 25% of children with epilepsy, is limited by variants of uncertain significance. Understanding functional consequences of variants can help distinguish pathogenic from benign alleles. We combined automated patch clamp recording with neurophysiological simulations to discern genotype‐function‐phenotype correlations in a real‐world cohort of children with SCN1A‐associated epilepsy. Methods Clinical data were extracted for children with SCN1A variants identified by clinical genetic testing. Functional properties of non‐truncating NaV1.1 variant channels were determined using automated patch clamp recording. Functional data were incorporated into a parvalbumin‐positive (PV+) interneuron computer model to predict variant effects on neuron firing and were compared with longitudinal clinical data describing epilepsy types, neurocognitive outcomes, and medication response. Results Twelve SCN1A variants were identified (nine non‐truncating). Six non‐truncating variants exhibited no measurable sodium current in heterologous cells consistent with complete loss of function (LoF). Two variants caused either partial LoF (L479P) or a mixture of gain and loss of function (I1356M). The remaining non‐truncating variant (T1250M) exhibited normal function. Functional data changed classification of pathogenicity for six variants. Complete LoF variants were universally associated with seizure onset before one year of age and febrile seizures, and were often associated with drug resistant epilepsy and below average cognitive outcomes. Simulations demonstrated abnormal firing in heterozygous model neurons containing dysfunctional variants. Interpretation In SCN1A‐associated epilepsy, functional analysis and neuron simulation studies resolved variants of uncertain significance and correlated with aspects of phenotype and medication response.

Declines in pelagic wildlife weaken ecosystem functioning, drive biodiversity loss, and undermine food security and economic stability for many of the world's people. Both physical and biological drivers make these features important locations for foraging, reproduction, navigation, and other essential functions of pelagic wildlife (Garrigue et al., 2015; Maguire et al., 2023; Rogers, 2018). There are an estimated 37,889 seamounts in the global ocean, yet less than 4% have been surveyed (Yesson et al., 2021; Figure 1). [...]less than 6% are located in fully and highly protected MPAs (mpatlas.org; Grorud-Colvert et al., 2021). The protection of subsurface features will benefit pelagic biodiversity, as well as providing significant benefits in the conservation of important demersal fish assemblages (Galbraith et al., 2021) and many vulnerable benthic marine ecosystems such as deep reef communities given their higher concentration at these features (Rogers, 2018). Many seamounts, including those proximate to human populations, have significant biodiversity conservation value (Morato et al., 2010).

Objective We identified a novel de novo KCNT1 variant in a patient with early‐infantile epileptic encephalopathy (EIEE) and status dystonicus, a life‐threatening movement disorder. We determined the functional consequences of this variant on the encoded KNa1.1 channel to investigate the molecular mechanisms responsible for this disorder. Methods A retrospective case review of the proband is presented. We performed manual and automated electrophysiologic analyses of the KCNT1‐L437F variant expressed heterologously in Chinese hamster ovary (CHO) cells in the presence of channel activators/blockers. Results The KCNT1‐L437F variant, identified in a patient with refractory EIEE and status dystonicus, confers a gain‐of‐function channel phenotype characterized by instantaneous, voltage‐dependent activation. Channel openers do not further increase L437F channel function, suggesting maximal activation, whereas channel blockers similarly block wild‐type and variant channels. We further demonstrated that KCNT1 current can be measured on a high‐throughput automated electrophysiology platform with potential value for future screening of novel and repurposed pharmacotherapies. Interpretation A novel pathogenic variant in KCNT1 associated with early‐onset, medication‐refractory epilepsy and dystonia causes gain‐of‐function with rapid activation kinetics. Our findings extend the genotype–phenotype relationships of KCNT1 variants to include severe dystonia.

Objective We identified a novel de novo SCN2A variant (M1879T) associated with infantile‐onset epilepsy that responded dramatically to sodium channel blocker antiepileptic drugs. We analyzed the functional and pharmacological consequences of this variant to establish pathogenicity, and to correlate genotype with phenotype and clinical drug response. Methods The clinical and genetic features of an infant boy with epilepsy are presented. We investigated the effect of the variant using heterologously expressed recombinant human NaV1.2 channels. We performed whole‐cell patch clamp recording to determine the functional consequences and response to carbamazepine. Results The M1879T variant caused disturbances in channel inactivation including substantially depolarized voltage dependence of inactivation, slower time course of inactivation, and enhanced resurgent current that collectively represent a gain‐of‐function. Carbamazepine partially normalized the voltage dependence of inactivation and produced use‐dependent block of the variant channel at high pulsing frequencies. Carbamazepine also suppresses resurgent current conducted by M1879T channels, but this effect was explained primarily by reducing the peak transient current. Molecular modeling suggests that the M1879T variant disrupts contacts with nearby residues in the C‐terminal domain of the channel. Interpretation Our study demonstrates the value of conducting functional analyses of SCN2A variants of unknown significance to establish pathogenicity and genotype–phenotype correlations. We also show concordance of in vitro pharmacology using heterologous cells with the drug response observed clinically in a case of SCN2A‐associated epilepsy.