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Global climate‐driven ocean warming has decreased dissolved oxygen (DO) levels (ocean deoxygenation) leading to expansions of hypoxic zones, which will affect the movements, behaviour, physiology and distributions of marine animals. However, the precise responses of animals to low DO remains poorly understood because movements and activity levels are seldom recorded alongside instantaneous DO in situ.We describe a new animal‐attached (dissolved oxygen measuring, DOME) archival tag with an optical oxygen sensor for recording DO, in addition to sensors for temperature and depth, a triaxial accelerometer for fine‐scale movements and activity, and a GPS for tag recovery. All sensors were integrated on a single electronic board.Calibration tests demonstrated small mean difference between DOME tag and factory‐calibrated DO sensors (mean relative error of 5%). No temporal drift occurred over a test period three times longer than the maximum deployment time. Deployments on four blue sharks (Prionace glauca) in the central North Atlantic Ocean showed regular vertical oscillations from the surface to a maximum of 404 m. Profiles from diving sharks recorded DO concentrations ranging from 217 to 272 μmol L−1, temperatures between 13°C and 23°C, and identified an oxygen maximum at ~45 m depth, all of which were consistent with ship‐based measurements. Interestingly, the percentage of time sharks spent burst swimming was greater in the top 85 m compared to deeper depths, potentially because of higher prey availability in the surface layer.The DOME tag described blue shark fine‐scale movements and activity levels in relation to accurately measured in situ DO and temperature, with the potential to offer new insights of animal performance in low oxygen environments. Development of a tag with physico‐chemical and movement sensors on a single electronic board is a first step towards satellite relay of these data over broader spatiotemporal scales (months over thousands of kilometres) to determine direct and indirect responses of marine animals to heatwave and deoxygenation events. [ABSTRACT FROM AUTHOR]

Levels of dissolved oxygen in open ocean and coastal waters are decreasing (ocean deoxygenation), with poorly understood effects on marine megafauna. All of the more than 1000 species of elasmobranchs (sharks, skates, and rays) are obligate water breathers, with a variety of life‐history strategies and oxygen requirements. This review demonstrates that although many elasmobranchs typically avoid hypoxic water, they also appear capable of withstanding mild to moderate hypoxia with changes in activity, ventilatory responses, alterations to circulatory and hematological parameters, and morphological alterations to gill structures. However, such strategies may be insufficient to withstand severe, progressive, or prolonged hypoxia or anoxia where anaerobic metabolic pathways may be used for limited periods. As water temperatures increase with climate warming, ectothermic elasmobranchs will exhibit elevated metabolic rates and are likely to be less able to tolerate the effects of even mild hypoxia associated with deoxygenation. As a result, sustained hypoxic conditions in warmer coastal or surface‐pelagic waters are likely to lead to shifts in elasmobranch distributions. Mass mortalities of elasmobranchs linked directly to deoxygenation have only rarely been observed but are likely underreported. One key concern is how reductions in habitat volume as a result of expanding hypoxia resulting from deoxygenation will influence interactions between elasmobranchs and industrial fisheries. Catch per unit of effort of threatened pelagic sharks by longline fisheries, for instance, has been shown to be higher above oxygen minimum zones compared to adjacent, normoxic regions, and attributed to vertical habitat compression of sharks overlapping with increased fishing effort. How a compound stressor such as marine heatwaves alters vulnerability to deoxygenation remains an open question. With over a third of elasmobranch species listed as endangered, a priority for conservation and management now lies in understanding and mitigating ocean deoxygenation effects in addition to population declines already occurring from overfishing. [ABSTRACT FROM AUTHOR]

In this, the second iteration of our continuing 'Harbingers of Change' project, over 160 early career researchers (ECRs) from eight countries were questioned about their scholarly communications. Three repeat in‐depth interviews were conducted over 2 years of the pandemic to chart changes in attitude and behaviour. This paper provides interview findings (and an extensive literature review) regarding the role played by social media platforms. It was prompted by an initial review of the data that highlighted significant changes in the attitudes and behaviour of Malaysian ECRs, especially in respect to WhatsApp. Data were provided from several open‐ended interview questions about social media, a few interviewer prompts for individual platform names, and, indirectly, from 'mentions' of individual platforms in answers to a range of questions about scholarly communications. Findings were: (1) 15 platforms were mentioned in respect to a range of scholarly activities, most notably visibility and reach; (2) Twitter (now X) was the most mentioned, by half the ECRs; (3) 'churn' is a notable observation, with large gains and losses in mentions occurring between interviews; (4) large differences between countries, with Malaysian ECRs very much leading on the adoption of social media and largely responsible for the rise of WhatsApp, French ECRs showing little interest, and China a different space where WeChat reigns supreme and foreign platforms are blocked. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The ITPR1 gene encodes the inositol 1,4,5‐trisphosphate (IP3) receptor type 1 (IP3R1), 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. [ABSTRACT FROM AUTHOR]

Many predator species make regular excursions from near-surface waters to the twilight (200 to 1,000 m) and midnight (1,000 to 3,000m) 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 >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. [ABSTRACT FROM AUTHOR]

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. Mathematical tools can be used to help identify pathological features from images of diseased lungs. Here, the authors used mathematical tools combined with high resolution multiplex imaging mass cytometry to show an association between immature neutrophils, CD8 T cells and proliferating alveolar epithelial cells in areas of maximal alveolar damage in COVID-19 lungs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Investigates whether junior researchers believe that the scholarly communication system is changing in a significant way, whether they have contributed to the changes they envisaged, whether the pandemic has fast‐forwarded change and what they thought a transformed system might look like. The data are drawn from the Harbingers‐2 project, which investigated the impact of the pandemic on the scholarly communications attitudes and behaviours of early career researchers (ECRs), employing repeat interviewing with around 170 science and social science junior researchers from eight countries. The article focuses on the findings of the last of three rounds of interviews, with comparisons made with the first round, held 18 months earlier, when the pandemic was most active. A majority of ECRs thought that there had been significant changes in the scholarly system, and a large minority thought that the pandemic was responsible. Most of them wanted a system that was more open in terms of open access and open data, with a third taking personal action to bring about change. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Here the authors identify that C16orf72 regulates BRCA1/Senataxin to promote replication fork recovery. These proteins act together in a pathway parallel to PARP1 to suppress R-loop accumulation in response to replication stress and confer resistance to PARP inhibitors. [ABSTRACT FROM AUTHOR]

This study's research aim is to discover how the COVID-19 pandemic impacts early career researchers' work lives, prospects, and scholarly communication behavior. Early career researchers (ECRs), including doctoral students, post-docs, and pre-tenure faculty, are the next generation of scientists, researchers, scholars, teachers, and academic leaders, and are considered "vulnerable" when compared to their more senior colleagues. Part of an eight-country study, we present findings from long semi-structured interviews of 22 ECRs within the sciences and social sciences from a variety of regions in the United States. Transcripts were approved by the participants and responses were coded into a project-approved spreadsheet for analysis. The coding sheets were multi-faceted, containing both quantitative and qualitative data. Key findings include loss of research productivity due to lab closures and/or human subject research. The most recurring negative impact is the loss of formal and informal in-person meetings. For the majority, the pandemic has not deterred ECRs to deviate from their chosen academic career paths. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Explores science and social science early career researchers' (ECRs) perceptions and experiences of peer review, seeking also to identify their views of any pandemic-associated changes that have taken place. Data are drawn from the Harbingers-2 project, which investigated the impact of the pandemic on scholarly communications. Peer review, one of the activities covered, is singled out as it proved to be the activity of greatest concern to ECRs. Findings are obtained from interviews, which covered around 167 ECRs from China, France, Malaysia, Poland, Russia, Spain, UK and US, supplemented by an international survey that took the data out to a bigger and wider audience for confirmation and generalisation. Results obtained are enhanced by comparisons with pre-pandemic evidence yielded by Harbingers-1, the forerunner of the present study, and anchored in an extensive review of the literature. Main findings are: 1) most ECRs were experienced in peer review, both as reviewers and authors, but few had formal training; 2) half the ECRs had a lot or some reservations as to whether peer review vouches for the trustworthiness of research; 3) inadequate reviewers and slow processes were the main peer review associated problems; 4) there was a strong feeling that some kind of compensation, whether monetary or reputational, could help in dealing with these problems; 5) the pandemic impacted most on the speed of processing, with the majority of ECRs saying it had slowed the process; 6) nearly everyone thought that any pandemic-induced impacts would be temporary. [ABSTRACT FROM AUTHOR]

Presents findings from a study into the attitudes and practices of pandemic‐era early career researchers (ECRs) in regard to obtaining access to the formally published scholarly literature, which focused on alternative providers, notably ResearchGate and Sci‐Hub. The study is a part of the Harbingers project that has been exploring the work lives and scholarly communication practices of ECRs in pre‐pandemic times and during the pandemic, and utilizes data from two rounds of interviews with around 170 ECRs from the sciences and social sciences in eight countries. Findings show that alternative providers, as represented by ResearchGate and Sci‐Hub, have become established and appear to be gaining ground. However, there are considerable country‐ and discipline‐associated differences. ECRs' country‐specific level of usage of the alternative providers is partly traceable to the adequacy of library provisions, although there are other factors at play in shaping ECRs' attitudes and practices, most notably convenience and time saving, as well as the fact that these platforms have become embedded in the scholarly dashboard. There is a dearth of evidence of the impact of the pandemic on ECRs' ways of obtaining scholarly papers. [ABSTRACT FROM AUTHOR]

After two‐years of repeat interviewing early career sciences/social sciences researchers from around the world about their work life and scholarly communications in pandemic‐times, the Harbingers‐2 project is in a position to release quantitative data on the pandemic's overall impact. The data comes from around 50 questions asked in the third and final round of interviews with 147 early career researchers (ECRs), which had a codifiable element to them (such as yes, no, do not know). The 19 scholarly topics covered include: pandemic‐related research; research funding; changes to the workplace/working from home; pandemic‐incurred stress and anxiety; teaching; employment security; career progression; mentoring; assessment (including metrics); collaboration; searching/finding information; ethics; networking; informal communication; publishing; sharing; pre‐prints; outreach; and scholarly transformations. The main findings are that in six broad aspects of ECRs' work‐life and scholarly behaviour, more than 50% of ECRs were impacted by the pandemic, with remote teaching having the greatest impact. By way of comparison, in another six aspects there was little change, least of all when it came to sharing activities. Among the countries studied, Malaysia stood out as being the most impacted, and of the disciplines it was the medical sciences and the soft social sciences most impacted. [ABSTRACT FROM AUTHOR]

Key points: 170 early career researchers interviewed three times over 2 years, have uniquely contributed towards a stress test of scholarly communications and cracks have been identified.The perfect storm created by the convergence of millennial values and the pandemic appears to have fast‐forwarded the cracking process, perhaps, for the good.The cracks in question are: (1) peer review; (2) reputational assessment; (3) unethical/questionable practices; (4) collaboration; (5) networking. [ABSTRACT FROM AUTHOR]

This study's research aim is to discover how the COVID-19 pandemic impacts early career researchers' work lives, prospects, and scholarly communication behavior. Early career researchers (ECRs), including doctoral students, post-docs, and pre-tenure faculty, are the next generation of scientists, researchers, scholars, teachers, and academic leaders, and are considered ''vulnerable'' when compared to their more senior colleagues. Part of an eight-country study, we present findings from long semi-structured interviews of 22 ECRs within the sciences and social sciences from a variety of regions in the United States. Transcripts were approved by the participants and responses were coded into a project-approved spreadsheet for analysis. The coding sheets were multi-faceted, containing both quantitative and qualitative data. Key findings include loss of research productivity due to lab closures and/or human subject research. The most recurring negative impact is the loss of formal and informal in-person meetings. For the majority, the pandemic has not deterred ECRs to deviate from their chosen academic career paths. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Around 170 early career researchers (ECRs) from 8 countries were interviewed about the whole range of their scholarly communication attitudes/behaviours during pandemic times and this paper analyses what they said about predatory journals in a wide range of scholarly communication contexts. Because of the delicacy of the topic there was just one question exclusively directed at predatory journals, which asked about policies rather than actions, which yielded nevertheless wide-ranging comments on the topic. ECRs also volunteered information on predatory journals in another half dozen questions, most notably including one on questionable research practices. The source of data was mainly the final interview of three undertaken, with some comparisons made to rounds one and two. Findings disclose the existence of a whole raft of formal and informal assessment policies/codes that direct ECRs to legitimate journals and away from predatory ones. Despite being junior, ECRs are very accultured to the criteria of what is considered as prestige and quality and believe predatory publishing is not even conceivable. They are far more concerned about low-quality research, preprints and borderline 'grey' journals. The pandemic has increased the level of questionable practices and low-quality research, but predatory journals were only singled out by a relatively small number of ECRs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Presents early data from an investigation of the work lives and scholarly communication practices of 177 early career researchers (ECRs) from eight countries. Utilizing mainly coded and textual data from interviews, the paper reports on the findings that pertain to publishing papers in peer reviewed journals. We examine which factors are taken into account when choosing the journal to publish their research in, identifying similarities/differences by country, age, academic status and discipline. Also, explored is whether the pandemic has changed decision‐making. Main findings are that the aim for ECRs is to publish in the 'best' journals, variably measured by prestige, impact factor, standards of peer review and indexation. Appropriateness of audience is the only factor unrelated to the quality of the journal that figures highly among the factors that guide ECRs in the process of selecting a journal. The pandemic has made little difference to the majority of ECRs when they decide on a journal for publishing their research. However, there is a greater awareness of the need for a faster turnover rate, brought on by the importance accorded to speedy publication during the pandemic. [ABSTRACT FROM AUTHOR]

Many factors influence how environmental DNA (eDNA) abundance varies in natural environments. One of the least studied contributors to eDNA variation is that of reproduction. Marine organisms that broadcast spawn are expected to shed increased quantities of DNA in association with the release of gametes and the elevated levels of activity associated with reproduction. To test this hypothesis at the community level, we present a year‐long eDNA time‐series of a temperate sea‐shelf fish assemblage combined with adult fish and ichthyoplankton abundance data. Our results show that eDNA is associated with species abundance estimated by conventional fish surveys at all life stages (adult, larval, and egg), and was on average 2.3‐fold more abundant during predicted fish reproductive periods. [ABSTRACT FROM AUTHOR]

After two-years of talking to around 170 early career science/social science researchers from China, France, Malaysia, Poland, Russia, Spain, UK and US about their work life and scholarly communications during the pandemic, the Harbingers-2 project is in possession of a mountain of verbatim data. The purpose of this paper is to highlight the kinds of comments ECRs are raising, with a focus on those that provide a particular interesting and illuminating take on ECRs' experiences under difficult times. Comments, for instance, that might challenge the established order of things or that presage big changes down the line. The selection of comments presented here were made by the national interviewers shortly after the completion of the last of three rounds of interviews (two interviews in the case of Russia). The understandings, appreciations and suggestions thus raised by the ECRs are insightful and constructive, which is what we might have expected from this cohort who are very much at the forefront of the research enterprise and veritable research workhorses. Sixteen broad scholarly topics are represented by quotes/comments, with the main focus of the comments on a subset of these: research performance and assessment, scholarly communication transformations, networking and collaboration, social media and access to information/libraries, which suggests, perhaps, where the action, concerns and interest mainly lie. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Using county-level analysis, this study demonstrates that there exists at most a minor relationship between the large, contemporary geographical variation in U.S. intergenerational income mobility and state-level policies. In addition to investigating the effects of specific policies, we introduce an omnibus test for state policy differences in total, based on the principle of geographic discontinuities. We further explore the discrepancy between these findings and the expected efficacy of mobility-enhancing policies seen in common, applied economic models and successful program evaluations. We conclude that the gap between quasi-experimental evaluations and observed policy effects presents pressing questions for further study. [ABSTRACT FROM AUTHOR]

After two-years of repeat interviewing around 170 early career science/social science researchers from China, France, Malaysia, Poland, Russia, Spain, UK and US about their work life and scholarly communications in pandemic-times, the Harbingers project is now in possession of a mountain of data on what constitutes a very important academic topic. The purpose of the paper is to share the early highlights of the data, with a focus on the main and lasting impacts of the pandemic. The data presented comes from the national interviewers, who had conducted 3 rounds of interviews with their 20 or so early career researchers (ECRs) over two years and, thus, knew them well. They were asked to provide an ‘aerial view’ by identifying the most important impacts they had detected while things were still fresh in their minds. The main findings are that: 1) ECRs, the research workhorses, have generally proved to be resilient and perseverant and some have prospered; 2) the pandemic has fast-tracked researchers to a virtual and remote scholarly world, with all the advantages and disadvantages that comes with it. The data, however, is nuanced, with significant differences occurring between countries, especially China and France. The paper also updates a literature review on the topic previously published in this journal. [ABSTRACT FROM AUTHOR]

The accuracy and reliability of DNA metabarcoding analyses depend on the breadth and quality of the reference libraries that underpin them. However, there are limited options available to obtain and curate the huge volumes of sequence data that are available on public repositories such as NCBI and BOLD. Here, we provide a pipeline to download, clean and annotate mitochondrial DNA sequence data for a given list of fish species. Features of this pipeline include (a) support for multiple metabarcode markers; (b) searches on species synonyms and taxonomic name validation; (c) phylogeny assisted quality control for identification and removal of misannotated sequences; (d) automatically generated coverage reports for each new GenBank release update; and (e) citable, versioned DOIs. As an example we provide a ready‐to‐use curated reference library for the marine and freshwater fishes of the U.K. To augment this reference library for environmental DNA metabarcoding specifically, we generated 241 new MiFish‐12S sequences for 88 U.K. marine species, and make available new primer sets useful for sequencing these. This brings the coverage of common U.K. species for the MiFish‐12S fragment to 93%, opening new avenues for scaling up fish metabarcoding across wide spatial gradients. The Meta‐Fish‐Lib reference library and pipeline is hosted at https://github.com/genner-lab/meta-fish-lib. [ABSTRACT FROM AUTHOR]

α-Synuclein is critical in the pathogenesis of Parkinson's disease and related disorders, yet it remains unclear how its aggregation causes degeneration of human dopaminergic neurons. In this study, we induced α-synuclein aggregation in human iPSC-derived dopaminergic neurons using fibrils generated de novo or amplified in the presence of brain homogenates from Parkinson's disease or multiple system atrophy. Increased α-synuclein monomer levels promote seeded aggregation in a dose and time-dependent manner, which is associated with a further increase in α-synuclein gene expression. Progressive neuronal death is observed with brain-amplified fibrils and reversed by reduction of intraneuronal α-synuclein abundance. We identified 56 proteins differentially interacting with aggregates triggered by brain-amplified fibrils, including evasion of Parkinson's disease-associated deglycase DJ-1. Knockout of DJ-1 in iPSC-derived dopaminergic neurons enhance fibril-induced aggregation and neuronal death. Taken together, our results show that the toxicity of α-synuclein strains depends on aggregate burden, which is determined by monomer levels and conformation which dictates differential interactomes. Our study demonstrates how Parkinson's disease-associated genes influence the phenotypic manifestation of strains in human neurons. α-Synuclein aggregation contributes to Parkinson's disease and related disorders. Here the authors investigate patterns of α-synuclein aggregation in human dopaminergic neurons in response to fibrils derived from individuals with Parkinson's disease or multiple system atrophy. [ABSTRACT FROM AUTHOR]

PURPOSE: This trial assessed the utility of applying tumor DNA sequencing to treatment selection for patients with advanced, refractory cancer and somatic mutations in one of four signaling pathways by comparing the efficacy of four study regimens that were either matched to the patient's aberrant pathway (experimental arm) or not matched to that pathway (control arm). MATERIALS AND METHODS: Adult patients with an actionable mutation of interest were randomly assigned 2:1 to receive either (1) a study regimen identified to target the aberrant pathway found in their tumor (veliparib with temozolomide or adavosertib with carboplatin [DNA repair pathway], everolimus [PI3K pathway], or trametinib [RAS/RAF/MEK pathway]), or (2) one of the same four regimens, but chosen from among those not targeting that pathway. RESULTS: Among 49 patients treated in the experimental arm, the objective response rate was 2% (95% CI, 0% to 10.9%). One of 20 patients (5%) in the experimental trametinib cohort had a partial response. There were no responses in the other cohorts. Although patients and physicians were blinded to the sequencing and random assignment results, a higher pretreatment dropout rate was observed in the control arm (22%) compared with the experimental arm (6%; P =.038), suggesting that some patients may have had prior tumor mutation profiling performed that led to a lack of participation in the control arm. CONCLUSION: Further investigation, better annotation of predictive biomarkers, and the development of more effective agents are necessary to inform treatment decisions in an era of precision cancer medicine. Increasing prevalence of tumor mutation profiling and preference for targeted therapy make it difficult to use a randomized phase II design to evaluate targeted therapy efficacy in an advanced disease setting. [ABSTRACT FROM AUTHOR]

The menstrual cycle is an important biological process in women that is associated with a range of physical symptoms, which can shape how women think, feel, and participate in activities of daily life. This study employed a mixed-methods design to investigate adult women's physical activity throughout the menstrual cycle. One hundred and twenty-eight participants completed an online questionnaire that explored events of the menstrual cycle (e.g., bleeding, pain, fatigue) and physical activity. Semistructured interviews with 21 questionnaire respondents unpacked individual experiences of physical activity throughout the menstrual cycle. From the questionnaire data, 44 participants were categorized as avoiders and 84 as nonavoiders of physical activity due to menstrual events. Avoiders of physical activity reported longer periods, heavier menstrual flow, and higher levels of fatigue and pain compared with nonavoiders. Interviews revealed that avoidance of physical activity ranged from complete avoidance to adaptation (e.g., types of exercise). Reasons for avoidance and adaptation of physical activity included menstrual symptoms, personal thoughts, and concerns about other people's views of the period. The present study findings emphasize the importance of not only evaluating prevalent physical symptoms, but also unpacking women's individual perspectives and established societal norms to better understand and normalize physical activity throughout the menstrual cycle. [ABSTRACT FROM AUTHOR]

In order to take account of the impact of the pandemic on the already changing scholarly communications and work-life of early career researchers (ECRs), the 4-year long Harbingers study was extended for another two years. As a precursor to the study (featuring interviews and a questionnaire survey), currently underway, an analytic review of the pertinent literature was undertaken and its results are presented here. The review focuses on the challenges faced by ECRs and how these compare to the ones more senior researchers have to tackle. In the examination of the literature three general questions are posed: Q1) What are the identifiable and forthcoming impacts of the pandemic-induced financial pressures felt in the Higher Education sector on ECRs' employment and career development prospects? Q2) What are the identifiable and forthcoming pandemic-associated disruptions in the pace/focus/direction of the research undertaking? Have any disruptions been predicted to exert an impact on ECRs' research activities, and if so, with what scholarly consequences? Q3) How is the work-life of ECRs shaping up under the virus-dictated rules of the 'new normal' in the research undertaking? What challenges, if any, arise from the changes in practices identified, and what might their potential consequences be for ECRs? The broad conclusion of the study is that the literature leaves little room for doubt: junior researchers are already disproportionally affected by and bear the burden of the ongoing pandemic-incurred hardships and they are likely to remain similarly impacted when more trials, still unfolding, materialise. [ABSTRACT FROM AUTHOR]

PURPOSE: This trial assessed the utility of applying tumor DNA sequencing to treatment selection for patients with advanced, refractory cancer and somatic mutations in one of four signaling pathways by comparing the efficacy of four study regimens that were either matched to the patient's aberrant pathway (experimental arm) or not matched to that pathway (control arm). MATERIALS AND METHODS: Adult patients with an actionable mutation of interest were randomly assigned 2:1 to receive either (1) a study regimen identified to target the aberrant pathway found in their tumor (veliparib with temozolomide or adavosertib with carboplatin [DNA repair pathway], everolimus [PI3K pathway], or trametinib [RAS/RAF/MEK pathway]), or (2) one of the same four regimens, but chosen from among those not targeting that pathway. RESULTS: Among 49 patients treated in the experimental arm, the objective response rate was 2% (95% CI, 0% to 10.9%). One of 20 patients (5%) in the experimental trametinib cohort had a partial response. There were no responses in the other cohorts. Although patients and physicians were blinded to the sequencing and random assignment results, a higher pretreatment dropout rate was observed in the control arm (22%) compared with the experimental arm (6%; P =.038), suggesting that some patients may have had prior tumor mutation profiling performed that led to a lack of participation in the control arm. CONCLUSION: Further investigation, better annotation of predictive biomarkers, and the development of more effective agents are necessary to inform treatment decisions in an era of precision cancer medicine. Increasing prevalence of tumor mutation profiling and preference for targeted therapy make it difficult to use a randomized phase II design to evaluate targeted therapy efficacy in an advanced disease setting. [ABSTRACT FROM AUTHOR]

Telemetry datasets are becoming increasingly large and covering a wider range of species using different technologies (GPS, Argos, light‐based geolocation). Together, such datasets hold tremendous potential to understand species' space use at broad spatial scale, through the development of species distribution or habitat suitability models (SDMs) to predict environmental dependencies of species across space and time. However, tracking datasets can be heavily biased and an assessment of how such biases affect SDM predictions, and therefore, our interpretation of animal distributions is lacking.We generated simulated tracks based on predetermined environmental values for a random predator and a central place forager, and then sampled positions from those tracks based on a combination of five common biases in tracking datasets: (a) tagging location; (b) tracking device; (c) data gaps within tracks; (d) premature tag detachment (or failure) and (e) different processing methods. We then used 240 combinations of the resulting biased simulated datasets to develop binomial generalised linear (GLM) and additive (GAM) models to estimate habitat suitability in different environmental sets (cool deep, cool coastal, warm deep and warm coastal environments).Our results show that tagging location and length of tracks have the largest effects in decreasing model performance, but that these biases can be overcome by adding a small percentage of additional, relatively less biased tracks to the dataset. In comparison, the effects from all other biases were almost negligible, including for low resolution tracking datasets for which sufficient tracks are available. We also highlight the need for a cautionary approach when using processing methods that can introduce other biases (e.g. interpolated locations). Similar trends were obtained for the random predator and the central place forager, but with relatively lower model performance for the latter.We provide evidence that even non‐GPS tracking datasets can be readily used to improve the knowledge of large‐scale space use by species without the need for detailed processing and tracking reconstruction. This is especially relevant in the current context of rapid increase in data acquisition and the urgent need to address the large spatial scale ecological consequences of global change. [ABSTRACT FROM AUTHOR]

Background: The proportion of tumors of various histologies that may respond to drugs targeted to molecular alterations is unknown. NCI-MATCH, a collaboration between ECOG-ACRIN Cancer Research Group and the National Cancer Institute, was initiated to find efficacy signals by matching patients with refractory malignancies to treatment targeted to potential tumor molecular drivers regardless of cancer histology.Methods: Trial development required assumptions about molecular target prevalence, accrual rates, treatment eligibility, and enrollment rates as well as consideration of logistical requirements. Central tumor profiling was performed with an investigational next-generation DNA-targeted sequencing assay of alterations in 143 genes, and protein expression of protein expression of phosphatase and tensin homolog, mutL homolog 1, mutS homolog 2, and RB transcriptional corepressor 1. Treatments were allocated with a validated computational platform (MATCHBOX). A preplanned interim analysis evaluated assumptions and feasibility in this novel trial.Results: At interim analysis, accrual was robust, tumor biopsies were safe (<1% severe events), and profiling success was 87.3%. Actionable molecular alteration frequency met expectations, but assignment and enrollment lagged due to histology exclusions and mismatch of resources to demand. To address this lag, we revised estimates of mutation frequencies, increased screening sample size, added treatments, and improved assay throughput and efficiency (93.9% completion and 14-day turnaround).Conclusions: The experiences in the design and implementation of the NCI-MATCH trial suggest that profiling from fresh tumor biopsies and assigning treatment can be performed efficiently in a large national network trial. The success of such trials necessitates a broad screening approach and many treatment options easily accessible to patients. [ABSTRACT FROM AUTHOR]

In order to take account of the impact of the pandemic on the already changing scholarly communications and work-life of early career researchers (ECRs), the 4-year long Harbingers study was extended for another two years. As a precursor to the study (featuring interviews and a questionnaire survey), currently underway, an analytic review of the pertinent literature was undertaken and its results are presented here. The review focuses on the challenges faced by ECRs and how these compare to the ones more senior researchers have to tackle. In the examination of the literature three general questions are posed: Q1) What are the identifiable and forthcoming impacts of the pandemic-induced financial pressures felt in the Higher Education sector on ECRs’ employment and career development prospects? Q2) What are the identifiable and forthcoming pandemic-associated disruptions in the pace/focus/direction of the research undertaking? Have any disruptions been predicted to exert an impact on ECRs’ research activities, and if so, with what scholarly consequences? Q3) How is the work-life of ECRs shaping up under the virus-dictated rules of the ‘new normal’ in the research undertaking? What challenges, if any, arise from the changes in practices identified, and what might their potential consequences be for ECRs? The broad conclusion of the study is that the literature leaves little room for doubt: junior researchers are already disproportionally affected by and bear the burden of the ongoing pandemic-incurred hardships and they are likely to remain similarly impacted when more trials, still unfolding, materialise. [ABSTRACT FROM AUTHOR]

Developing B cells can be positively or negatively selected by self-antigens, but the mechanisms that determine these outcomes are incompletely understood. Here, we show that a B cell intrinsic switch between positive and negative selection during ontogeny is determined by a change from Lin28b to let-7 gene expression. Ectopic expression of a Lin28b transgene in murine B cells restored the positive selection of autoreactive B-1 B cells by self-antigen in adult bone marrow. Analysis of antigen-specific immature B cells in early and late ontogeny identified Lin28b-dependent genes associated with B-1 B cell development, including Arid3a and Bhleh41, and Lin28b-independent effects are associated with the presence or absence of self-antigen. These findings identify cell intrinsic and extrinsic determinants of B cell fate during ontogeny and reconcile lineage and selection theories of B cell development. They explain how changes in the balance of positive and negative selection may be able to adapt to meet the immunological needs of an individual during its lifetime. [ABSTRACT FROM AUTHOR]

Migratory movements in response to seasonal resources often influence population structure and dynamics. Yet in mobile marine predators, population genetic consequences of such repetitious behaviour remain inaccessible without comprehensive sampling strategies. Temporal genetic sampling of seasonally recurring aggregations of planktivorous basking sharks, Cetorhinus maximus, in the Northeast Atlantic (NEA) affords an opportunity to resolve individual re-encounters at key sites with population connectivity and patterns of relatedness. Genetic tagging (19 microsatellites) revealed 18% of re-sampled individuals in the NEA demonstrated inter/multi-annual site-specific re-encounters. High genetic connectivity and migration between aggregation sites indicate the Irish Sea as an important movement corridor, with a contemporary effective population estimate (Ne) of 382 (CI = 241–830). We contrast the prevailing view of high gene flow across oceanic regions with evidence of population structure within the NEA, with early-season sharks off southwest Ireland possibly representing genetically distinct migrants. Finally, we found basking sharks surfacing together in the NEA are on average more related than expected by chance, suggesting a genetic consequence of, or a potential mechanism maintaining, site-specific re-encounters. Long-term temporal genetic monitoring is paramount in determining future viability of cosmopolitan marine species, identifying genetic units for conservation management, and for understanding aggregation structure and dynamics. [ABSTRACT FROM AUTHOR]