Shark conservation requires mortality-limiting regulations amid global change.

Despite anti-finning laws aimed at conserving sharks, Worm et al. have revealed that global shark mortality rates have surprisingly risen over the past decade, driven in large part by increased demand for meat. Here, we discuss the importance of this study, underscoring the need for broader regulations addressing overall shark mortality amid threats from global change.

Highly active fish in low oxygen environments: vertical movements and behavioural responses of bigeye and yellowfin tunas to oxygen minimum zones in the eastern Pacific Ocean.

Oxygen minimum zones in the open ocean are predicted to significantly increase in volume over the coming decades as a result of anthropogenic climatic warming. The resulting reduction in dissolved oxygen (DO) in the pelagic realm is likely to have detrimental impacts on water-breathing organisms, particularly those with higher metabolic rates, such as billfish, tunas, and sharks. However, little is known about how free-living fish respond to low DO environments, and therefore, the effect increasing OMZs will have cannot be predicted reliably. Here, we compare the responses of two active predators (bigeye tuna Thunnus obesus and yellowfin tuna Thunnus albacares) to DO at depth throughout the eastern Pacific Ocean. Using time-series data from 267 tagged tunas (59,910 days) and 3D maps of modelled DO, we find that yellowfin tuna respond to low DO at depth by spending more time in shallower, more oxygenated waters. By contrast, bigeye tuna, which forage at deeper depths well below the thermocline, show fewer changes in their use of the water column. However, we find that bigeye tuna increased the frequency of brief upward vertical excursions they performed by four times when DO at depth was lower, but with no concomitant significant difference in temperature, suggesting that this behaviour is driven in part by the need to re-oxygenate following time spent in hypoxic waters. These findings suggest that increasing OMZs will impact the behaviour of these commercially important species, and it is therefore likely that other water-breathing predators with higher metabolic rates will face similar pressures. A more comprehensive understanding of the effect of shoaling OMZs on pelagic fish vertical habitat use, which may increase their vulnerability to surface fisheries, will be important to obtain if these effects are to be mitigated by future management actions. Supplementary Information: The online version contains supplementary material available at 10.1007/s00227-023-04366-2.

Detailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design.

BACKGROUND: The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP3 ) receptor type 1 (IP3 R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood. OBJECTIVES: We aimed to identify novel SCA29 and GLSP cases to define core phenotypes, describe the spectrum of missense variation across ITPR1, standardize the ITPR1 variant nomenclature, and investigate disease progression in relation to cerebellar atrophy. METHODS: Cases were identified using next-generation sequencing through the Deciphering Developmental Disorders study, the 100,000 Genomes project, and clinical collaborations. ITPR1 alternative splicing in the human cerebellum was investigated by quantitative polymerase chain reaction. RESULTS: We report the largest, multinational case series of 46 patients with 28 unique ITPR1 missense variants. Variants clustered in functional domains of the protein, especially in the N-terminal IP3 -binding domain, the carbonic anhydrase 8 (CA8)-binding region, and the C-terminal transmembrane channel domain. Variants outside these domains were of questionable clinical significance. Standardized transcript annotation, based on our ITPR1 transcript expression data, greatly facilitated analysis. Genotype-phenotype associations were highly variable. Importantly, while cerebellar atrophy was common, cerebellar volume loss did not correlate with symptom progression. CONCLUSIONS: This dataset represents the largest cohort of patients with ITPR1 missense variants, expanding the clinical spectrum of SCA29 and GLSP. Standardized transcript annotation is essential for future reporting. Our findings will aid in diagnostic interpretation in the clinic and guide selection of variants for preclinical studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

Single cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs.

Single cell spatial interrogation of the immune-structural interactions in COVID -19 lungs is challenging, mainly because of the marked cellular infiltrate and architecturally distorted microstructure. To address this, we develop a suite of mathematical tools to search for statistically significant co-locations amongst immune and structural cells identified using 37-plex imaging mass cytometry. This unbiased method reveals a cellular map interleaved with an inflammatory network of immature neutrophils, cytotoxic CD8 T cells, megakaryocytes and monocytes co-located with regenerating alveolar progenitors and endothelium. Of note, a highly active cluster of immature neutrophils and CD8 T cells, is found spatially linked with alveolar progenitor cells, and temporally with the diffuse alveolar damage stage. These findings offer further insights into how immune cells interact in the lungs of severe COVID-19 disease. We provide our pipeline [Spatial Omics Oxford Pipeline (SpOOx)] and visual-analytical tool, Multi-Dimensional Viewer (MDV) software, as a resource for spatial analysis.

A vision for incorporating human mobility in the study of human-wildlife interactions.

As human activities increasingly shape land- and seascapes, understanding human-wildlife interactions is imperative for preserving biodiversity. Habitats are impacted not only by static modifications, such as roads, buildings and other infrastructure, but also by the dynamic movement of people and their vehicles occurring over shorter time scales. Although there is increasing realization that both components of human activity substantially affect wildlife, capturing more dynamic processes in ecological studies has proved challenging. Here we propose a conceptual framework for developing a 'dynamic human footprint' that explicitly incorporates human mobility, providing a key link between anthropogenic stressors and ecological impacts across spatiotemporal scales. Specifically, the dynamic human footprint integrates a range of metrics to fully acknowledge the time-varying nature of human activities and to enable scale-appropriate assessments of their impacts on wildlife behaviour, demography and distributions. We review existing terrestrial and marine human-mobility data products and provide a roadmap for how these could be integrated and extended to enable more comprehensive analyses of human impacts on biodiversity in the Anthropocene.

C16orf72/HAPSTR1/TAPR1 functions with BRCA1/Senataxin to modulate replication-associated R-loops and confer resistance to PARP disruption.

While the toxicity of PARP inhibitors to cells with defects in homologous recombination (HR) is well established, other synthetic lethal interactions with PARP1/PARP2 disruption are poorly defined. To inform on these mechanisms we conducted a genome-wide screen for genes that are synthetic lethal with PARP1/2 gene disruption and identified C16orf72/HAPSTR1/TAPR1 as a novel modulator of replication-associated R-loops. C16orf72 is critical to facilitate replication fork restart, suppress DNA damage and maintain genome stability in response to replication stress. Importantly, C16orf72 and PARP1/2 function in parallel pathways to suppress DNA:RNA hybrids that accumulate at stalled replication forks. Mechanistically, this is achieved through an interaction of C16orf72 with BRCA1 and the RNA/DNA helicase Senataxin to facilitate their recruitment to RNA:DNA hybrids and confer resistance to PARP inhibitors. Together, this identifies a C16orf72/Senataxin/BRCA1-dependent pathway to suppress replication-associated R-loop accumulation, maintain genome stability and confer resistance to PARP inhibitors.

Direct measurement of cruising and burst swimming speeds of the shortfin mako shark (Isurus oxyrinchus) with estimates of field metabolic rate.

The shortfin mako shark is a large-bodied pursuit predator thought to be capable of the highest swimming speeds of any elasmobranch and potentially one of the highest energetic demands of any marine fish. Nonetheless, few direct speed measurements have been reported for this species. Here, animal-borne bio-loggers attached to two mako sharks were used to provide direct measurements of swimming speeds, kinematics and thermal physiology. Mean sustained (cruising) speed was 0.90 m s-1 (±0.07 s.d.) with a mean tail-beat frequency (TBF) of 0.51 Hz (±0.16 s.d.). The maximum burst speed recorded was 5.02 m s-1 (TBFmax = 3.65 Hz) from a 2 m long female. Burst swimming was sustained for 14 s (mean speed = 2.38 m s-1 ), leading to a 0.24°C increase in white muscle temperature in the 12.5 min after the burst. Routine field metabolic rate was estimated at 185.2 mg O2 kg-1 h-1 (at 18°C ambient temperature). Gliding behaviour (zero TBF) was more frequently observed after periods of high activity, especially after capture when internal (white muscle) temperature approached 21°C (ambient temperature: 18.3°C), indicating gliding probably functions as an energy recovery mechanism and limits further metabolic heat production. The results show shortfin mako sharks generally cruise at speeds similar to other endothermic fish - but faster than ectothermic sharks - with the maximum recorded burst speed being among the highest so far directly measured among sharks, tunas and billfishes. This newly recorded high-oxygen-demand performance of mako sharks suggests it may be particularly vulnerable to habitat loss due to climate-driven ocean deoxygenation.

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.

The NCI-MATCH trial: lessons for precision oncology.

The NCI-MATCH (Molecular Analysis for Therapy Choice) trial ( NCT02465060 ) was launched in 2015 as a genomically driven, signal-seeking precision medicine platform trial-largely for patients with treatment-refractory, malignant solid tumors. Having completed in 2023, it remains one of the largest tumor-agnostic, precision oncology trials undertaken to date. Nearly 6,000 patients underwent screening and molecular testing, with a total of 1,593 patients (inclusive of continued accrual from standard next-generation sequencing) being assigned to one of 38 substudies. Each substudy was a phase 2 trial of a therapy matched to a genomic alteration, with a primary endpoint of objective tumor response by RECIST criteria. In this Perspective, we summarize the outcomes of the initial 27 substudies in NCI-MATCH, which met its signal-seeking objective with 7/27 positive substudies (25.9%). We discuss key aspects of the design and operational conduct of the trial, highlighting important lessons for future precision medicine studies.

Juvenile survival and movements of two threatened oceanic sharks in the North Atlantic Ocean inferred from tag-recovery data.

Understanding population dynamics, movements, and fishing mortality is critical to establish effective shark conservation measures across international boundaries in the ocean. There are few survival and dispersal estimates of juveniles of oceanic shark species in the North Atlantic despite it being one of the most fished regions in the world. Here we provide estimates of dispersal, survival, and proportion of fishing mortality in the North Atlantic for two threatened oceanic sharks: the blue shark (Prionace glauca) and the shortfin mako shark (Isurus oxyrinchus). Our results are based on multi-event models applied to tag-recovery data of 700 blue sharks and 132 shortfin makos tagged over a decade. A total of 60 blue sharks (8.57% of tagged) and 30 makos (22.73%) were recovered by the longline fishery between 2009 and 2017. Tag-reporting rate (percentage of returned information when a tagged shark was caught) was estimated to be high (0.794 ± 0.232 SE). Mean annual survival, as predicted from the models, was higher for blue shark (0.835 ± 0.040 SE) than for shortfin mako (0.618 ± 0.189 SE). Models predicted that fishing caused more than a half of total mortality in the study area for both species (0.576 ± 0.209), and more than a third of tagged individuals dispersed from the study area permanently (0.359 ± 0.073). Our findings, focused mainly on juveniles from oceanic areas, contribute to a better understanding of shark population dynamics in the North Atlantic and highlight the need for further conservation measures for both blue shark and shortfin mako, such as implementing efficient bycatch mitigation measures and static/dynamic time-area closures in the open ocean.

The pandemic and changes in early career researchers' career prospects, research and publishing practices.

INTRODUCTION: As part of the Harbnger-2 project, this study aimed to discover the impact of the COVID-19 pandemic on junior researchers' work-life, career prospects, research and publishing practices and networking. METHODS: An online international survey of 800 early career researchers (ECRs) was conducted in 2022. A questionnaire was developed based on three rounds of interviews and distributed using multiple channels including publishers, social media, and direct email to ECRs. RESULTS: The impact of the pandemic on career prospects, morale, job security, productivity, ability to network and collaborate, and quality and speed of peer review has on the whole been more negative than positive. A quarter of ECRs shifted their research focus to pandemic-related topics and half of those who did, benefited largely due to increased productivity and impact. The majority worked remotely/from home and more than two-thirds of those who did so benefitted from it. While virtual or hybrid conferences have been embraced by the majority of ECRs, around a third still preferred face-to-face only conferences. The use of library online platforms, Sci-Hub, ResearchGate, Google Scholar and smartphone to search and access full-text papers increased. ECRs prioritised journals with fast submission procedures for the publishing of their papers and spent more time on increasing the visibility of their research. Fees were a problem for publishing open access. CONCLUSION: Although, generally, the pandemic negatively impacted many aspects of ECRs' work-life, certain research areas and individuals benefited from being more appreciated and valued, and, in some cases, resulted in increased resources, better productivity and greater impact. Changes, such as the use of digital technologies and remote working created new opportunities for some ECRs. While continuing work flexibility and hybrid conferences might benefit some ECRs, institutions should also take measures to help those ECRs whose career and productivity have been adversely impacted.

Seasonal variations in vitamin D do not change the musculoskeletal health of physically active ambulatory men with cerebral palsy: a longitudinal cross-sectional comparison study.

Increased levels of vitamin D in the summer months from natural seasonal variations in sun exposure have been linked to improvements in musculoskeletal health and function in UK populations; however, studies have shown that differences in lifestyles because of disability can inhibit the natural vitamin D increase in these populations. We hypothesized that men with cerebral palsy (CP) will experience smaller increases in 25-hydroxyvitamin D (25(OH)D) from winter to summer and men with CP will not experience any improvements in musculoskeletal health and function during the summer. A longitudinal observational study in 16 ambulant men with CP aged 21.0 ± 1.3 years and 16 healthy, physical activity matched, typically developed controls aged 25.4 ± 2.6 years, completed assessments of serum 25(OH)D and parathyroid hormone during winter and summer. Neuromuscular outcomes included vastus lateralis size, knee extensor strength, 10-m sprint, vertical jumps, and grip strength. Bone ultrasounds were performed to obtain radius and tibia T and Z scores. Men with CP and typically developed controls showed a 70.5% and 85.7% increase in serum 25(OH)D from winter to summer months, respectively. Neither group showed seasonal effect on neuromuscular outcomes muscle strength, size, vertical jump, or tibia and radius T and Z scores. A seasonal interaction effect was seen in the tibia T and Z scores (P < .05). In conclusion, there were similar seasonal increases in 25(OH)D observed in men with CP and typically developed controls, but serum 25(OH)D levels were still considered insufficient to improve bone or neuromuscular outcomes.

Circles in the sea: annual courtship "torus" behaviour of basking sharks Cetorhinus maximus identified in the eastern North Atlantic Ocean.

Groups of basking sharks engaged in circling behaviour are rarely observed, and their function remains enigmatic in the absence of detailed observations. Here, underwater and aerial video recordings of multiple circling groups of basking sharks during late summer (August and September 2016-2021) in the eastern North Atlantic Ocean showed groups numbering between 6 and 23 non-feeding individuals of both sexes. Sharks swam slowly in a rotating "torus" (diameter range: 17-39 m), with individuals layered vertically from the surface to a maximum depth of 16 m. Within a torus, sharks engaged in close-following, echelon, close-flank approach or parallel-swimming behaviours. Measured shark total body lengths were 5.4-9.5 m (mean LT : 7.3 m ± 0.9 s.d.; median: 7.2 m, n = 27), overlapping known lengths of sexually mature males and females. Males possessed large claspers with abrasions that were also observed on female pectoral fins. Female body colouration was paler than that of males, similar to colour changes observed during courtship and mating in other shark species. Individuals associated with most other members rapidly (within minutes), indicating toroidal behaviours facilitate multiple interactions. Sharks interacted through fin-fin and fin-body contacts, rolling to expose the ventral surfaces to following sharks, and breaching behaviour. Toruses formed in late summer when feeding aggregations in zooplankton-rich thermal fronts switched to non-feeding following and circling behaviours. Collectively, the observations explain a courtship function for toruses. This study highlights northeast Atlantic coastal waters as a critical habitat supporting courtship reproductive behaviour of endangered basking sharks, the first such habitat identified for this species globally.

Gliotransmission of D-serine promotes thirst-directed behaviors in Drosophila.

Thirst emerges from a range of cellular changes that ultimately motivate an animal to consume water. Although thirst-responsive neuronal signals have been reported, the full complement of brain responses is unclear. Here, we identify molecular and cellular adaptations in the brain using single-cell sequencing of water-deprived Drosophila. Water deficiency primarily altered the glial transcriptome. Screening the regulated genes revealed astrocytic expression of the astray-encoded phosphoserine phosphatase to bi-directionally regulate water consumption. Astray synthesizes the gliotransmitter D-serine, and vesicular release from astrocytes is required for drinking. Moreover, dietary D-serine rescues aay-dependent drinking deficits while facilitating water consumption and expression of water-seeking memory. D-serine action requires binding to neuronal NMDA-type glutamate receptors. Fly astrocytes contribute processes to tripartite synapses, and the proportion of astrocytes that are themselves activated by glutamate increases with water deprivation. We propose that thirst elevates astrocytic D-serine release, which awakens quiescent glutamatergic circuits to enhance water procurement.

The athletic characteristics of Olympic sports to assist anti-doping strategies.

The determinants of success in Olympic Games competition are specific to the athletic demands of the sporting event. A global evaluation to quantify the athletic demands across the spectrum of the Olympic Games sport events has not previously been conducted. Thus far, the interpretation and the comparison of sport physiological characteristics within anti-doping organisations (ADOs) risk assessments remains subjective without a standardised framework. Despite its subjective assessment, this information is a key component of any anti-doping programme. Sport characteristics inevitably influence the type of substances and/or methods used for doping purposes and should be captured through a comprehensive analysis. Seven applied sport scientists independently conducted an assessment to quantify the athletic demands across six preselected athletic variables. A principal component analysis was performed on the results of the panel's quantitative assessment for 160 Olympic sport events. Sport events were clustered using the Hierarchical Density Based Spatial Clustering of Applications with Noise (HDBSCAN) algorithm. The HDBSCAN identified 19 independent cluster groups; 36 sport events remained statistically unassigned to a cluster group representing unique and event-specific athletic demands. This investigation provides guidance to the anti-doping community to assist in the development of the sport specific physiology component of the risk assessment for Olympic Games disciplines. The dominant athletic characteristics to excel in each of these individual events will highlight areas of how athletes may strive to gain a competitive advantage through doping strategies, and inform the development of an effective and proportionate allocation of testing resources.

Autosomal Recessive Cerebellar Atrophy and Spastic Ataxia in Patients With Pathogenic Biallelic Variants in GEMIN5.

The hereditary ataxias are a heterogenous group of disorders with an increasing number of causative genes being described. Due to the clinical and genetic heterogeneity seen in these conditions, the majority of such individuals endure a diagnostic odyssey or remain undiagnosed. Defining the molecular etiology can bring insights into the responsible molecular pathways and eventually the identification of therapeutic targets. Here, we describe the identification of biallelic variants in the GEMIN5 gene among seven unrelated families with nine affected individuals presenting with spastic ataxia and cerebellar atrophy. GEMIN5, an RNA-binding protein, has been shown to regulate transcription and translation machinery. GEMIN5 is a component of small nuclear ribonucleoprotein (snRNP) complexes and helps in the assembly of the spliceosome complexes. We found that biallelic GEMIN5 variants cause structural abnormalities in the encoded protein and reduce expression of snRNP complex proteins in patient cells compared with unaffected controls. Finally, knocking out endogenous Gemin5 in mice caused early embryonic lethality, suggesting that Gemin5 expression is crucial for normal development. Our work further expands on the phenotypic spectrum associated with GEMIN5-related disease and implicates the role of GEMIN5 among patients with spastic ataxia, cerebellar atrophy, and motor predominant developmental delay.