Anticyclonic eddies aggregate pelagic predators in a subtropical gyre.

Ocean eddies are coherent, rotating features that can modulate pelagic ecosystems across many trophic levels. These mesoscale features, which are ubiquitous at mid-latitudes1, may increase productivity of nutrient-poor regions2,3, accumulate prey4 and modulate habitat conditions in the water column5. However, in nutrient-poor subtropical gyres-the largest marine biome-the role of eddies in modulating behaviour throughout the pelagic predator community remains unknown despite predictions for these gyres to expand6 and pelagic predators to become increasingly important for food security7. Using a large-scale fishery dataset in the North Pacific Subtropical Gyre, we show a pervasive pattern of increased pelagic predator catch inside anticyclonic eddies relative to cyclones and non-eddy areas. Our results indicate that increased mesopelagic prey abundance in anticyclone cores4,8 may be attracting diverse predators, forming ecological hotspots where these predators aggregate and exhibit increased abundance. In this energetically quiescent gyre, we expect that isolated mesoscale features (and the habitat conditions in them) exhibit primacy over peripheral submesoscale dynamics in structuring the foraging opportunities of pelagic predators. Our finding that eddies influence coupling of epi- to mesopelagic communities corroborates the growing evidence that deep scattering layer organisms are vital prey for a suite of commercially important predator species9 and, thus, provide valuable ecosystem services.

Linking vertical movements of large pelagic predators with distribution patterns of biomass in the open ocean.

Many predator species make regular excursions from near-surface waters to the twilight (200 to 1,000 m) and midnight (1,000 to 3,000 m) zones of the deep pelagic ocean. While the occurrence of significant vertical movements into the deep ocean has evolved independently across taxonomic groups, the functional role(s) and ecological significance of these movements remain poorly understood. Here, we integrate results from satellite tagging efforts with model predictions of deep prey layers in the North Atlantic Ocean to determine whether prey distributions are correlated with vertical habitat use across 12 species of predators. Using 3D movement data for 344 individuals who traversed nearly 1.5 million km of pelagic ocean in [Formula: see text]42,000 d, we found that nearly every tagged predator frequented the twilight zone and many made regular trips to the midnight zone. Using a predictive model, we found clear alignment of predator depth use with the expected location of deep pelagic prey for at least half of the predator species. We compared high-resolution predator data with shipboard acoustics and selected representative matches that highlight the opportunities and challenges in the analysis and synthesis of these data. While not all observed behavior was consistent with estimated prey availability at depth, our results suggest that deep pelagic biomass likely has high ecological value for a suite of commercially important predators in the open ocean. Careful consideration of the disruption to ecosystem services provided by pelagic food webs is needed before the potential costs and benefits of proceeding with extractive activities in the deep ocean can be evaluated.

Distinct evolutionary lineages of Schistocephalus parasites infecting co-occurring sculpin and stickleback fishes in Alaska.

Sculpins (coastrange and slimy) and sticklebacks (ninespine and threespine) are widely distributed fishes cohabiting 2 south-central Alaskan lakes (Aleknagik and Iliamna), and all these species are parasitized by cryptic diphyllobothriidean cestodes in the genus Schistocephalus. The goal of this investigation was to test for host-specific parasitic relationships between sculpins and sticklebacks based upon morphological traits (segment counts) and sequence variation across the NADH1 gene. A total of 446 plerocercoids was examined. Large, significant differences in mean segment counts were found between cestodes in sculpin (mean = 112; standard deviation [s.d.] = 15) and stickleback (mean = 86; s.d. = 9) hosts within and between lakes. Nucleotide sequence divergence between parasites from sculpin and stickleback hosts was 20.5%, and Bayesian phylogenetic analysis recovered 2 well-supported clades of cestodes reflecting intermediate host family (i.e. sculpin, Cottidae vs stickleback, Gasterosteidae). Our findings point to the presence of a distinct lineage of cryptic Schistocephalus in sculpins from Aleknagik and Iliamna lakes that warrants further investigation to determine appropriate evolutionary and taxonomic recognition.

Building use-inspired species distribution models: Using multiple data types to examine and improve model performance.

Species distribution models (SDMs) are becoming an important tool for marine conservation and management. Yet while there is an increasing diversity and volume of marine biodiversity data for training SDMs, little practical guidance is available on how to leverage distinct data types to build robust models. We explored the effect of different data types on the fit, performance and predictive ability of SDMs by comparing models trained with four data types for a heavily exploited pelagic fish, the blue shark (Prionace glauca), in the Northwest Atlantic: two fishery dependent (conventional mark-recapture tags, fisheries observer records) and two fishery independent (satellite-linked electronic tags, pop-up archival tags). We found that all four data types can result in robust models, but differences among spatial predictions highlighted the need to consider ecological realism in model selection and interpretation regardless of data type. Differences among models were primarily attributed to biases in how each data type, and the associated representation of absences, sampled the environment and summarized the resulting species distributions. Outputs from model ensembles and a model trained on all pooled data both proved effective for combining inferences across data types and provided more ecologically realistic predictions than individual models. Our results provide valuable guidance for practitioners developing SDMs. With increasing access to diverse data sources, future work should further develop truly integrative modeling approaches that can explicitly leverage the strengths of individual data types while statistically accounting for limitations, such as sampling biases.

An enigmatic pelagic fish with internalized red muscle: A future regional endotherm or forever an ectotherm?

Ectothermy and endothermy in extant fishes are defined by distinct integrated suites of characters. Although only ⁓0.1% of fishes are known to have endothermic capacity, recent discoveries suggest that there may still be uncommon pelagic fish species with yet to be discovered endothermic traits. Among the most rarely encountered marine fishes, the louvar Luvarus imperialis is a remarkable example of adaptive evolution as the only extant pelagic species in the order Acanthuriformes (including surgeonfishes, tangs, unicornfishes and Moorish idol). Magnetic resonance imaging and gross necropsy did not yield evidence of cranial or visceral endothermy but revealed a central-posterior distribution of myotomal red muscle that is a mixture of the character states typifying ectotherms (lateral-posterior) and red muscle endotherms (central-anterior). Dissection of a specimen confirmed, and an osteological proxy supported, that L. imperialis has not evolved the vascular rete that is vital to retaining heat in the red muscle. The combination of presumably relying on caudal propulsion while exhibiting internal red muscle without associated retia is unique to L. imperialis among all extant fishes, raising the macroevolutionary question of whether this species - in geologic timescales - will remain an ectotherm or evolve red muscle endothermy.

Retention of a chromosomal inversion from an anadromous ancestor provides the genetic basis for alternative freshwater ecotypes in rainbow trout.

Migratory behaviour patterns in animals are controlled by a complex genetic architecture. Rainbow trout (Oncorhynchus mykiss) is a salmonid fish that spawns in streams but exhibits three primary life history pathways: stream-resident (fluvial), lake-migrant (adfluvial) and ocean-migrant (anadromous). Previous studies examining fluvial and anadromous O. mykiss have identified several genes associated with life history divergence including the presence of an inversion complex within chromosome 5 (Omy05) that appears to maintain a suite of linked genes controlling migratory behaviour. However, adfluvial trout are migratory without being anadromous, and the genetic basis for this life history has not been investigated from evolutionary perspectives. We sampled wild, native nonanadromous rainbow trout occupying connected stream and lake habitats in a southwest Alaskan watershed to determine whether these fish exhibit genetic divergence between fluvial and adfluvial ecotypes, and whether that divergence parallels that documented in fluvial and anadromous O. mykiss. Data from restriction site-associated DNA (RAD) sequencing revealed an association between frequencies of both the Omy05 inversion complex and other single nucleotide polymorphisms (SNPs) with habitat type (stream or lake), supporting the genetic divergence of fluvial and adfluvial individuals in sympatry. The presence of a genetic basis for migration into lakes, analogous to that documented for anadromy, indicates that the adfluvial ecotype must be recognized separately from the fluvial form of O. mykiss even though neither is anadromous. These results highlight the genetic architecture underlying migration and the importance of chromosomal inversions in promoting and sustaining intraspecific diversity.

Does lipid-correction introduce biases into isotopic mixing models? Implications for diet reconstruction studies.

Carbon isotopes are commonly used in trophic ecology to estimate consumer diet composition. This estimation is complicated by the fact that lipids exhibit a more depleted carbon signature (δ13C) than other macromolecules, and are often found at different concentrations among individual organisms. Some researchers argue that lipids bias diet reconstructions using stable isotopes and should be accounted for prior to analysis in food web mixing models, whereas others contend that removing lipids may result in erroneous interpretations of the trophic interactions under study. To highlight this disagreement on best practices for applying δ13C in food web studies, we sampled the recent literature to determine the frequency and method of lipid-correction. We then quantified the potential magnitude and source of bias in mixing model results from a theoretical example and case study of diet reconstruction. The literature was split nearly evenly as to whether lipid-correction was applied to δ13C data in mixing model estimates of diet composition. Comparative mixing model scenarios demonstrated that lipid-correction can substantially alter the estimated diet composition and interpretation of consumer foraging habits. Given the lack of consensus on whether or not to lipid-correct prey and/or consumers, and the associated variation in mixing model results, we call for the establishment of a unified framework that will guide diet reconstruction in stable isotope ecology. Uncertainty in the prevalence of direct routing versus de novo synthesis of lipids across ecosystems, taxa, and trophic levels must be resolved to better guide treatment of lipids in isotope studies using carbon.

Single-cell analysis of mesenchymal cells in permeable neural vasculature reveals novel diverse subpopulations of fibroblasts.

BACKGROUND: In the choroid plexus and pituitary gland, vasculature is known to have a permeable, fenestrated phenotype which allows for the free passage of molecules in contrast to the blood brain barrier observed in the rest of the CNS. The endothelium of these compartments, along with secretory, neural-lineage cells (choroid epithelium and pituitary endocrine cells) have been studied in detail, but less attention has been given to the perivascular mesenchymal cells of these compartments. METHODS: The Hic1CreERT2 Rosa26LSL-TdTomato mouse model was used in conjunction with a PdgfraH2B-EGFP mouse model to examine mesenchymal cells, which can be subdivided into Pdgfra+ fibroblasts and Pdgfra- pericytes within the choroid plexus (CP) and pituitary gland (PG), by histological, immunofluorescence staining and single-cell RNA-sequencing analyses. RESULTS: We found that both CP and PG possess substantial populations of distinct Hic1+ mesenchymal cells, including an abundance of Pdgfra+ fibroblasts. Within the pituitary, we identified distinct subpopulations of Hic1+ fibroblasts in the glandular anterior pituitary and the neurosecretory posterior pituitary. We also identified multiple distinct markers of CP, PG, and the meningeal mesenchymal compartment, including alkaline phosphatase, indole-n-methyltransferase and CD34. CONCLUSIONS: Novel, distinct subpopulations of mesenchymal cells can be found in permeable vascular interfaces, including the CP, PG, and meninges, and make distinct contributions to both organs through the production of structural proteins, enzymes, transporters, and trophic molecules.

How Activin A Became a Therapeutic Target in Fibrodysplasia Ossificans Progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by episodic yet cumulative heterotopic ossification (HO) of skeletal muscles, tendons, ligaments, and fascia. FOP arises from missense mutations in Activin Receptor type I (ACVR1), a type I bone morphogenetic protein (BMP) receptor. Although initial findings implicated constitutive activity of FOP-variant ACVR1 (ACVR1FOP) and/or hyperactivation by BMPs, it was later shown that HO in FOP requires activation of ACVR1FOP by Activin A. Inhibition of Activin A completely prevents HO in FOP mice, indicating that Activin A is an obligate driver of HO in FOP, and excluding a key role for BMPs in this process. This discovery led to the clinical development of garetosmab, an investigational antibody that blocks Activin A. In a phase 2 trial, garetosmab inhibited new heterotopic bone lesion formation in FOP patients. In contrast, antibodies to ACVR1 activate ACVR1FOP and promote HO in FOP mice. Beyond their potential clinical relevance, these findings have enhanced our understanding of FOP's pathophysiology, leading to the identification of fibroadipogenic progenitors as the cells that form HO, and the discovery of non-signaling complexes between Activin A and wild type ACVR1 and their role in tempering HO, and are also starting to inform biological processes beyond FOP.

Hic1 identifies a specialized mesenchymal progenitor population in the embryonic limb responsible for bone superstructure formation.

The musculoskeletal system relies on the integration of multiple components with diverse physical properties, such as striated muscle, tendon, and bone, that enable locomotion and structural stability. This relies on the emergence of specialized, but poorly characterized, interfaces between these various elements during embryonic development. Within the appendicular skeleton, we show that a subset of mesenchymal progenitors (MPs), identified by Hic1, do not contribute to the primary cartilaginous anlagen but represent the MP population, whose progeny directly contribute to the interfaces that connect bone to tendon (entheses), tendon to muscle (myotendinous junctions), and the associated superstructures. Furthermore, deletion of Hic1 leads to skeletal defects reflective of deficient muscle-bone coupling and, consequently, perturbation of ambulation. Collectively, these findings show that Hic1 identifies a unique MP population that contributes to a secondary wave of bone sculpting critical to skeletal morphogenesis.

A shallow scattering layer structures the energy seascape of an open ocean predator.

Large predators frequent the open ocean where subsurface light drives visually based trophic interactions. However, we lack knowledge on how predators achieve energy balance in the unproductive open ocean where prey biomass is minimal in well-lit surface waters but high in dim midwaters in the form of scattering layers. We use an interdisciplinary approach to assess how the bioenergetics of scattering layer forays by a model predator vary across biomes. We show that the mean metabolic cost rate of daytime deep foraging dives to scattering layers decreases as much as 26% from coastal to pelagic biomes. The more favorable energetics offshore are enabled by the addition of a shallow scattering layer that, if not present, would otherwise necessitate costlier dives to deeper layers. The unprecedented importance of this shallow scattering layer challenges assumptions that the globally ubiquitous primary deep scattering layer constitutes the only mesopelagic resource regularly targeted by apex predators.

Cell diversity and plasticity during atrioventricular heart valve EMTs.

Epithelial-to-mesenchymal transitions (EMTs) of both endocardium and epicardium guide atrioventricular heart valve formation, but the cellular complexity and small scale of this tissue have restricted analyses. To circumvent these issues, we analyzed over 50,000 murine single-cell transcriptomes from embryonic day (E)7.75 hearts to E12.5 atrioventricular canals. We delineate mesenchymal and endocardial bifurcation during endocardial EMT, identify a distinct, transdifferentiating epicardial population during epicardial EMT, and reveal the activation of epithelial-mesenchymal plasticity during both processes. In Sox9-deficient valves, we observe increased epithelial-mesenchymal plasticity, indicating a role for SOX9 in promoting endothelial and mesenchymal cell fate decisions. Lastly, we deconvolve cell interactions guiding the initiation and progression of cardiac valve EMTs. Overall, these data reveal mechanisms of emergence of mesenchyme from endocardium or epicardium at single-cell resolution and will serve as an atlas of EMT initiation and progression with broad implications in regenerative medicine and cancer biology.

Widespread habitat loss and redistribution of marine top predators in a changing ocean.

The Northwest Atlantic Ocean and Gulf of Mexico are among the fastest warming ocean regions, a trend that is expected to continue through this century with far-reaching implications for marine ecosystems. We examine the distribution of 12 highly migratory top predator species using predictive models and project expected habitat changes using downscaled climate models. Our models predict widespread losses of suitable habitat for most species, concurrent with substantial northward displacement of core habitats >500 km. These changes include up to >70% loss of suitable habitat area for some commercially and ecologically important species. We also identify predicted hot spots of multi-species habitat loss focused offshore of the U.S. Southeast and Mid-Atlantic coasts. For several species, the predicted changes are already underway, which are likely to have substantial impacts on the efficacy of static regulatory frameworks used to manage highly migratory species. The ongoing and projected effects of climate change highlight the urgent need to adaptively and proactively manage dynamic marine ecosystems.

Cellular taxonomy of Hic1+ mesenchymal progenitor derivatives in the limb: from embryo to adult.

Tissue development and regeneration rely on the cooperation of multiple mesenchymal progenitor (MP) subpopulations. We recently identified Hic1 as a marker of quiescent MPs in multiple adult tissues. Here, we describe the embryonic origin of appendicular Hic1+ MPs and demonstrate that they arise in the hypaxial somite, and migrate into the developing limb at embryonic day 11.5, well after limb bud initiation. Time-resolved single-cell-omics analyses coupled with lineage tracing reveal that Hic1+ cells generate a unique MP hierarchy, that includes both recently identified adult universal fibroblast populations (Dpt+, Pi16+ and Dpt+ Col15a1+) and more specialised mesenchymal derivatives such as, peri and endoneurial cells, pericytes, bone marrow stromal cells, myotenocytes, tenocytes, fascia-resident fibroblasts, with limited contributions to chondrocytes and osteocytes within the skeletal elements. MPs endure within these compartments, continue to express Hic1 and represent a critical reservoir to support post-natal growth and regeneration.

The Functional and Ecological Significance of Deep Diving by Large Marine Predators.

Many large marine predators make excursions from surface waters to the deep ocean below 200 m. Moreover, the ability to access meso- and bathypelagic habitats has evolved independently across marine mammals, reptiles, birds, teleost fishes, and elasmobranchs. Theoretical and empirical evidence suggests a number of plausible functional hypotheses for deep-diving behavior. Developing ways to test among these hypotheses will, however, require new ways to quantify animal behavior and biophysical oceanographic processes at coherent spatiotemporal scales. Current knowledge gaps include quantifying ecological links between surface waters and mesopelagic habitats and the value of ecosystem services provided by biomass in the ocean twilight zone. Growing pressure for ocean twilight zone fisheries creates an urgent need to understand the importance of the deep pelagic ocean to large marine predators.

Murine Limb Bud Organ Cultures for Studying Musculoskeletal Development.

The biological signals that coordinate the three-dimensional outgrowth and patterning of the vertebrate limb bud have been well delineated. These include a number of vital embryonic signaling pathways, including the fibroblast growth factor, WNT, transforming growth factor, and hedgehog. Collectively these signals converge on multiple progenitor populations to drive the formation of a variety of tissues that make up the limb musculoskeletal system, such as muscle, tendon, cartilage, stroma, and bone. The basic mechanisms regulating the commitment and differentiation of diverse limb progenitor populations has been successfully modeled in vitro using high density primary limb mesenchymal or micromass cultures. However, this approach is limited in its ability to more faithfully recapitulate the assembly of progenitors into organized tissues that span the entire musculoskeletal system. Other biological systems have benefitted from the development and availability of three-dimensional organoid cultures which have transformed our understanding of tissue development, homeostasis and regeneration. Such a system does not exist that effectively models the complexity of limb development. However, limb bud organ cultures while still necessitating the use of collected embryonic tissue have proved to be a powerful model system to elucidate the molecular underpinning of musculoskeletal development. In this methods article, the derivation and use of limb bud organ cultures from murine limb buds will be described, along with strategies to manipulate signaling pathways, examine gene expression and for longitudinal lineage tracking.

Pathogenic Potential of Hic1-Expressing Cardiac Stromal Progenitors.

The cardiac stroma contains multipotent mesenchymal progenitors. However, lineage relationships within cardiac stromal cells are poorly defined. Here, we identified heart-resident PDGFRa+ SCA-1+ cells as cardiac fibro/adipogenic progenitors (cFAPs) and show that they respond to ischemic damage by generating fibrogenic cells. Pharmacological blockade of this differentiation step with an anti-fibrotic tyrosine kinase inhibitor decreases post-myocardial infarction (post-MI) remodeling and leads to improvement in cardiac function. In the undamaged heart, activation of cFAPs through lineage-specific deletion of the gene encoding the quiescence-associated factor HIC1 reveals additional pathogenic potential, causing fibrofatty infiltration within the myocardium and driving major pathological features pathognomonic in arrhythmogenic cardiomyopathy (AC). In this regard, cFAPs contribute to multiple pathogenic cell types within cardiac tissue and therapeutic strategies aimed at modifying their activity are expected to have tremendous benefit for the treatment of diverse cardiac diseases.

Hic1 Defines Quiescent Mesenchymal Progenitor Subpopulations with Distinct Functions and Fates in Skeletal Muscle Regeneration.

Many adult tissues contain resident stem cells, such as the Pax7+ satellite cells within skeletal muscle, that regenerate parenchymal elements following damage. Tissue-resident mesenchymal progenitors (MPs) also participate in regeneration, although their function and fate in this process are unclear. Here, we identify Hypermethylated in cancer 1 (Hic1) as a marker of MPs in skeletal muscle and further show that Hic1 deletion leads to MP hyperplasia. Single-cell RNA-seq and ATAC-seq analysis of Hic1+ MPs in skeletal muscle shows multiple subpopulations, which we further show have distinct functions and lineage potential. Hic1+ MPs orchestrate multiple aspects of skeletal muscle regeneration by providing stage-specific immunomodulation and trophic and mechanical support. During muscle regeneration, Hic1+ derivatives directly contribute to several mesenchymal compartments including Col22a1-expressing cells within the myotendinous junction. Collectively, these findings demonstrate that HIC1 regulates MP quiescence and identifies MP subpopulations with transient and enduring roles in muscle regeneration.

Potential Biological Control of Schistosomiasis by Fishes in the Lower Senegal River Basin.

More than 200 million people in sub-Saharan Africa are infected with schistosome parasites. Transmission of schistosomiasis occurs when people come into contact with larval schistosomes emitted from freshwater snails in the aquatic environment. Thus, controlling snails through augmenting or restoring their natural enemies, such as native predators and competitors, could offer sustainable control for this human disease. Fishes may reduce schistosomiasis transmission directly, by preying on snails or parasites, or indirectly, by competing with snails for food or by reducing availability of macrophyte habitat (i.e., aquatic plants) where snails feed and reproduce. To identify fishes that might serve as native biological control agents for schistosomiasis in the lower Senegal River basin-one of the highest transmission areas for human schistosomiasis globally-we surveyed the freshwater fish that inhabit shallow, nearshore habitats and conducted multivariate analyses with quantitative diet data for each of the fish species encountered. Ten of the 16 fish species we encountered exhibited diets that may result in direct (predation) and/or indirect (food competition and habitat removal) control of snails. Fish abundance was low, suggesting limited effects on schistosomiasis transmission by the contemporary fish community in the lower Senegal River basin in the wild. Here, we highlight some native species-such as tilapia, West African lungfish, and freshwater prawns-that could be aquacultured for local-scale biological control of schistosomiasis transmission.