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The North Atlantic Climate System Integrated Study (ACSIS) was a large multidisciplinary research programme funded by the UK's Natural Environment Research Council (NERC). ACSIS ran from 2016 to 2022 and brought together around 80 scientists from seven leading UK-based environmental research institutes to deliver major advances in the understanding of North Atlantic climate variability and extremes. Here, we present an overview of the data generated by the ACSIS programme. The datasets described cover the North Atlantic Ocean, the atmosphere above it (including its composition), and Arctic sea ice. Atmospheric composition datasets include measurements from seven aircraft campaigns (45 flights in total, 0–10 km altitude range) in the northeastern Atlantic (∼ 15–55° N, ∼ 40° W–5° E) made at intervals of 6 months to 2 years between February 2017 and May 2022. The flights measured chemical species (including greenhouse gases; ozone precursors; and volatile organic compounds – VOCs) and aerosols (organic aerosol – OA; SO4; NH4; NO3; and non-sea salt chloride – nss-Cl) (https://doi.org/10.5285/6285564c34a246fc9ba5ce053d85e5e7, FAAM et al., 2024). Ground-based stations at the Cape Verde Atmospheric Observatory (CVAO), Penlee Point Atmospheric Observatory (PPAO), and Plymouth Marine Laboratory (PML) recorded ozone, ozone precursors, halocarbons, greenhouse gases (CO2 and methane), SO2, and photolysis rates (CVAO; http://catalogue.ceda.ac.uk/uuid/81693aad69409100b1b9a247b9ae75d5, National Centre for Atmospheric Science et al., 2010); O3 and CH4 (PPAO, https://catalogue.ceda.ac.uk/uuid/8f1ff8ea77534e08b03983685990a9b0 (Plymouth Marine Laboratory and Yang, 2017); and aerosols (PML, https://doi.org/10.5285/e74491c96ef24df29a9342a3d57b5939, Smyth, 2024), respectively. Complementary model simulations of atmospheric composition were performed with the UK Earth System Model (UKESM1) for the period from 1982 to 2020 using Coupled Model Intercomparison Project Phase 6 (CMIP6) historical forcing up to 2014 and Shared Socioeconomic Pathways (SSP) scenario SSP3-7.0 from 2015 to 2020. Model temperature and winds were relaxed towards ERA reanalysis. Monthly mean model data for ozone, NO, NO2, CO, methane, stratospheric ozone tracers, and 30 regionally emitted tracers are available for download (https://data.ceda.ac.uk/badc/acsis/UKESM1-hindcasts, Abraham, 2024). ACSIS also generated new ocean heat content diagnostics (https://doi.org/10/g6wm, https://doi.org/10/g8g2, Moat et al., 2021a–b) and gridded temperature and salinity based on objectively mapped Argo measurements (https://doi.org/10.5285/fe8e524d-7f04-41f3-e053-6c86abc04d51 King, 2023). An ensemble of atmosphere-forced global-ocean sea-ice simulations using the NEMO-CICE model was performed with horizontal resolutions of 1/4 and 1/12° covering the period from 1958 to 2020 using several different atmosphere-reanalysis-based surface forcing datasets, supplemented by additional global simulations and stand-alone sea-ice model simulations with advanced sea-ice physics using the CICE model (http://catalogue.ceda.ac.uk/uuid/770a885a8bc34d51ad71e87ef346d6a8, Megann et al., 2021e). Output is stored as monthly averages and includes 3D potential temperature, salinity, zonal velocity, meridional velocity, and vertical velocity; 2D sea-surface height, mixed-layer depth, surface heat, and freshwater fluxes; ice concentration and thickness; and a wide variety of other variables. In addition to the data presented here, we provide a very brief overview of several other datasets that were generated during ACSIS and have been described previously in the literature.

Two structurally unrelated small molecule chemotypes, represented by compounds PAV-617 and PAV-951, with antiviral activity in cell culture against Mpox virus (formerly known as monkeypox virus) and human immunodeficiency virus (HIV) respectively, were studied for anti-cancer efficacy. Each exhibited apparent pan-cancer cytotoxicity with reasonable pharmacokinetics. Non-toxicity is demonstrated in a non-cancer cell line and in mice at doses achieving drug exposure at active concentrations. Anti-tumour properties of both chemotypes were validated in mouse xenografts against A549 human lung cancer and, for one of the chemotypes, against HT-29 colorectal cancer. The targets of these compounds are unconventional: each binds to a different transient, energy-dependent multi-protein complex. Treatment with these compounds alters the target multi-protein complexes in a manner that appears to remove a block, crucial for cancer survival and progression, on a homeostatic linkage between uncontrolled proliferation and apoptosis. These compounds provide starting points for development of novel, next-generation, non-toxic, pan-cancer therapeutics.

ABSTRACT Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections and hospitalization in infants and the elderly. Newly approved vaccines and the prophylactic antibody nirsevimab have heightened interest in RSV immunologic surveillance, necessitating the development of high-throughput assays assessing anti-RSV neutralizing activity. Quantitative viral neutralization remains the best correlate of protection for RSV infection and the gold standard for RSV immunological testing. Here, we developed a high-throughput RSV strain A2 focus-reduction neutralization test validated to Clinical Laboratory Improvement Amendments (CLIA)/ Good Clinical Laboratory Practices (GCLP) standards using both clinical specimens and commercially available reference sera. The assay is highly accurate, generating reference serum neutralizing titers within twofold of established assays, with an analytical measurement range between 8 and 1,798 international units per mL (IU/mL). Neutralizing activity measured by the assay strongly correlated with antibody titer determined via indirect enzyme-linked immunosorbent assay (ELISA) (ρ = 1.0, P = 0.0014). Individuals recently having tested positive via quantitative reverse transcription polymerase chain reaction (RT-qPCR) for RSV had a 9.1-fold higher geometric mean neutralizing titer relative to RSV PCR negatives (P-value = 0.09). The validated assay was then used to investigate the immunity debt hypothesis for resurgent RSV outbreaks in the 2022–2023 season, using adult clinical remnant sera sent for herpes simplex virus (HSV)-1/2 antibody testing. There was no difference in geometric mean anti-RSV neutralizing titers between sera sampled before and after the 2022–2023 RSV outbreak (P = 0.68). These data are consistent with limited changes in RSV-neutralizing antibody levels in adults across the 2022–23 RSV outbreak.IMPORTANCEPopulation surveillance studies of serum-neutralizing activity against RSV are crucial for evaluating RSV vaccine efficacy and vulnerabilities to new strains. Here, we designed and validated a high-throughput assay for assessing anti-RSV neutralizing activity, standardized its measurements for comparison with other methodologies, and demonstrated its applicability to real-world samples. Our assay is precise, linear, and yields measurements consistent with other standardized assays, offering a methodology useful for large-scale studies of RSV immunity. We also find no significant difference in neutralizing titers among adults between those taken before and after large RSV outbreaks associated with the latter stages of the coronavirus disease of 2019 (COVID-19) public health emergency, underlining the need for a greater understanding of the dynamics of serological responses to RSV infection.

The orientation dependency of the fatigue behaviour of laser powder bed fusion Ti-6Al-4V has been analyzed and rationalized. Seven build orientations relative to the build plate have been studied. The 75° specimen demonstrates the highest fatigue life owing to the optimal surface quality and low proportions of grains near-parallel to the loading direction. When the build orientation is 30° or below, only defects on the downward-facing surface serve as the fatigue crack initiation sites as a result of the poor surface quality. Beyond 45°, cracks begin to initiate from the otherward-facing surface owing to the reduced variation in Ra across the sample surface. The large variation in the size and number of pore clusters near the initiation site governs the highest fatigue scatter of the 75° specimen whereas the difference in crack initiation sites of the 45° specimen results in the large difference in fatigue life. Our results demonstrate that the orientation effect is a critical factor to consider for the design of fatigue-tolerant intricate components.

Abstract Selective serotonin reuptake inhibitors (SSRIs) are widely used for depression based on the monoamine deficiency hypothesis. However, the clinical use of these agents is controversial, in part because of their variable clinical efficacy and in part because of their delayed onset of action. Because of the complexities involved in replicating human disease and clinical dosing in animal models, the scientific community has not reached a consensus on the reasons for these phenomena. In this work, we create a theoretical hippocampal model incorporating escitalopram’s pharmacokinetics, pharmacodynamics (competitive and non-competitive inhibition, and serotonin transporter (SERT) internalization), inflammation, and receptor dynamics. With this model, we simulate chronic oral escitalopram in mice showing that days to weeks are needed for serotonin levels to reach steady-state. We show escitalopram’s chemical efficacy is diminished under inflammation. Our model thus offers mechanisms for how chronic escitalopram affects brain serotonin, emphasizing the importance of optimized dose and time for future antidepressant discoveries.

Abstract Non‐native annual grasses can dramatically alter fire frequency and reduce forage quality and biodiversity in the ecosystems they invade. Effective management techniques are needed to reduce these undesirable invasive species and maintain ecosystem services. Well‐timed management strategies, such as grazing, that are applied when invasive grasses are active prior to native plants can control invasive species spread and reduce their impact; however, anticipating the timing of key phenological stages that are susceptible to management over vast landscapes is difficult, as the phenology of these species can vary greatly over time and space. To address this challenge, we created range‐wide phenology forecasts for two problematic invasive annual grasses: cheatgrass (Bromus tectorum), and red brome (Bromus rubens). We tested a suite of 18 mechanistic phenology models using observations from monitoring experiments, volunteer science, herbarium records, timelapse camera imagery, and downscaled gridded climate data to identify the models that best predicted the dates of flowering and senescence of the two invasive grass species. We found that the timing of flowering and senescence of cheatgrass and red brome were best predicted by photothermal time models that had been adjusted for topography using gridded continuous heat‐insolation load index values. Phenology forecasts based on these models can help managers make decisions about when to schedule management actions such as grazing to reduce undesirable invasive grasses and promote forage production, quality, and biodiversity in grasslands; to predict the timing of greatest fire risk after annual grasses dry out; and to select remote sensing imagery to accurately map invasive grasses across topographic and latitudinal gradients. These phenology models also have the potential to be operationalized for within‐season or within‐year decision support.

The two deformation modes of meta-biomaterials during cyclic loading have been revealed: stochastic and deterministic strut failure processes. Biomimetic Voronoi structures with a range of strut thicknesses and number of cells per unit volume are printed. We show that when the strut thickness is 200 μm or above, the fatigue fracture process of the lattice is deterministic and the fatigue scatters are below 15%. As the strut is thinned to 150 μm, the local failures occur randomly within the structure, which may lead to a high fatigue scatter (>30%). The two distinct behaviours result from the processing limit of the laser powder bed fusion technique. We demonstrate that the fatigue scatter and the location of the failure process within the lattice are related to the probability that a cluster of unconnected struts larger than a critical value can exist within the lattice. Unlike solid parts, porosity hardly triggers any damage in metallic lattices during cyclic deformation. The discovery of the Janus-like failure process opens up our understanding of meta-biomaterials and defines the pathway towards the design of mechanically durable intricate implants.

Abtract Clinical circulating cell-free DNA (cfDNA) testing is now routine, however test accuracy remains limited. By understanding the life-cycle of cfDNA, we might identify opportunities to increase test performance. Here, we profile cfDNA release across a 24-cell line panel and utilize a cell-free CRISPR screen (cfCRISPR) to identify mediators of cfDNA release. Our panel outlines two distinct groups of cell lines: one which releases cfDNA fragmented similarly to clinical samples and purported as characteristic of apoptosis, and another which releases larger fragments associated with vesicular or necrotic DNA. Our cfCRISPR screens reveal that genes mediating cfDNA release are primarily involved with apoptosis, but also identify other subsets of genes such as RNA binding proteins as potential regulators of cfDNA release. We observe that both groups of cells lines identified primarily produce cfDNA through apoptosis. These results establish the utility of cfCRISPR, genetically validate apoptosis as a major mediator of DNA release in vitro, and implicate ways to improve cfDNA assays.

Abstract Analysis of DNA methylation in cell-free DNA reveals clinically relevant biomarkers but requires specialized protocols such as whole-genome bisulfite sequencing. Meanwhile, millions of cell-free DNA samples are being profiled by whole-genome sequencing. Here, we develop FinaleMe, a non-homogeneous Hidden Markov Model, to predict DNA methylation of cell-free DNA and, therefore, tissues-of-origin, directly from plasma whole-genome sequencing. We validate the performance with 80 pairs of deep and shallow-coverage whole-genome sequencing and whole-genome bisulfite sequencing data.

We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious viruses in multiple cell culture models for all six families of viruses causing most respiratory diseases in humans. In animals, this chemotype has been demonstrated efficacious for porcine epidemic diarrhoea virus (a coronavirus) and respiratory syncytial virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral life cycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. An advanced analog, PAV-104, is shown to be selective for the virally modified target, thereby avoiding host toxicity. Our findings suggest a new paradigm for understanding, and drugging, the host–virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease.

The title compound, [Co(C3H4N2)(C30H30N10)](BF4)2, is a five-coordinate CoII complex based on the neutral ligands tris[(1-benzyltriazol-4-yl)methyl]amine (tbta) and imidazole. It exhibits a distorted trigonal bipyramidal geometry in which the equatorial positions are occupied by the three N-atom donors from the triazole rings of the tripodal tbta ligand. The apical amine N-atom donor of tbta and the N-atom donor of the imidazole ligand occupy the axial positions of the coordination sphere. Two tetrafluoroborate anions provide charge balance in the crystal.

Abstract Protection from direct human impacts can safeguard marine life, yet ocean warming crosses marine protected area boundaries. Here, we test whether protection offers resilience to marine heatwaves from local to network scales. We examine 71,269 timeseries of population abundances for 2269 reef fish species surveyed in 357 protected versus 747 open sites worldwide. We quantify the stability of reef fish abundance from populations to metacommunities, considering responses of species and functional diversity including thermal affinity of different trophic groups. Overall, protection mitigates adverse effects of marine heatwaves on fish abundance, community stability, asynchronous fluctuations and functional richness. We find that local stability is positively related to distance from centers of high human density only in protected areas. We provide evidence that networks of protected areas have persistent reef fish communities in warming oceans by maintaining large populations and promoting stability at different levels of biological organization.

Abstract A network of marine reserves can enhance yield in depleted fisheries by protecting populations, particularly large, old spawners that supply larvae for interspersed fishing grounds. The ability of marine reserves to enhance sustainable fisheries is much less evident. We report empirical evidence of a marine reserve network improving yield regionally for a sustainable spiny lobster fishery, apparently through the spillover of adult lobsters and behavioral adaptation by the fishing fleet. Results of a Before-After, Control-Impact analysis found catch, effort, and Catch-Per-Unit Effort increased after the establishment of marine reserves in the northern region of the fishery where fishers responded by fishing intensively at reserve borders, but declined in the southern region where they vacated once productive fishing grounds. The adaptation of the northern region of the fishery may have been aided by a history of collaboration between fishers, scientists, and managers, highlighting the value of collaborative research and education programs for preparing fisheries to operate productively within a seascape that includes a large marine reserve network.

Abstract Macrocystis pyrifera (giant kelp), is a brown macroalga of great ecological importance as a primary producer and structure-forming foundational species that provides habitat for hundreds of species. It has many commercial uses (e.g. source of alginate, fertilizer, cosmetics, feedstock). One of the limitations to exploiting giant kelp’s economic potential and assisting in giant kelp conservation efforts is a lack of genomic tools like a high quality, contiguous reference genome with accurate gene annotations. Reference genomes attempt to capture the complete genomic sequence of an individual or species, and importantly provide a universal structure for comparison across a multitude of genetic experiments, both within and between species. We assembled the giant kelp genome of a haploid female gametophyte de novo using PacBio reads, then ordered contigs into chromosome level scaffolds using Hi-C. We found the giant kelp genome to be 537 MB, with a total of 35 scaffolds and 188 contigs. The assembly N50 is 13,669,674 with GC content of 50.37%. We assessed the genome completeness using BUSCO, and found giant kelp contained 94% of the BUSCO genes from the stramenopile clade. Annotation of the giant kelp genome revealed 25,919 genes. Additionally, we present genetic variation data based on 48 diploid giant kelp sporophytes from three different Southern California populations that confirms the population structure found in other studies of these populations. This work resulted in a high-quality giant kelp genome that greatly increases the genetic knowledge of this ecologically and economically vital species.

The field of oceanography is transitioning from data-poor to data-rich, thanks in part to increased deployment of in-situ platforms and sensors, such as those that instrument the US-funded Ocean Observatories Initiative (OOI). However, generating science-ready data products from these sensors, particularly those making biogeochemical measurements, often requires extensive end-user calibration and validation procedures, which can present a significant barrier. Openly available community-developed and -vetted Best Practices contribute to overcoming such barriers, but collaboratively developing user-friendly Best Practices can be challenging. Here we describe the process undertaken by the NSF-funded OOI Biogeochemical Sensor Data Working Group to develop Best Practices for creating science-ready biogeochemical data products from OOI data, culminating in the publication of the GOOS-endorsed OOI Biogeochemical Sensor Data Best Practices and User Guide. For Best Practices related to ocean observatories, engaging observatory staff is crucial, but having a “user-defined” process ensures the final product addresses user needs. Our process prioritized bringing together a diverse team and creating an inclusive environment where all participants could effectively contribute. Incorporating the perspectives of a wide range of experts and prospective end users through an iterative review process that included “Beta Testers’’ enabled us to produce a final product that combines technical information with a user-friendly structure that illustrates data analysis pipelines via flowcharts and worked examples accompanied by pseudo-code. Our process and its impact on improving the accessibility and utility of the end product provides a roadmap for other groups undertaking similar community-driven activities to develop and disseminate new Ocean Best Practices.

Background Prior research suggests that trematode rediae, a developmental stage of trematode parasites that reproduce clonally within a snail host, show evidence of division of labor (DOL). Single-species infections often have two morphologically distinct groups: small rediae, the ‘soldiers’, are active, aggressive, and do not appear to reproduce; large rediae, the ‘reproductives’, are larger, sluggish, and full of offspring. Most data supporting DOL come from trematodes infecting marine snails, while data from freshwater trematodes are more limited and generally do not supported DOL. The shorter lifespan typical of freshwater snails may partially explain this difference: defending a short-lived host at the expense of reproduction likely provides few advantages. Here, we present data from sixty-one colonies spanning twenty species of freshwater trematode exploring morphological and behavioral patterns commonly reported from marine trematodes believed to have DOL. Methods Trematode rediae were obtained from sixty-one infected snails collected in central Vermont, USA. A portion of the COI gene was sequenced to make tentative species identifications (‘COI species’). Samples of rediae were photographed, observed, and measured to look for DOL-associated patterns including a bimodal size distribution, absence of embryos in small rediae, and pronounced appendages and enlarged pharynges (mouthparts) in small rediae. Additional rediae were used to compare activity levels and likelihood to attack heterospecific trematodes in large vs. small rediae. Results Many of the tests for DOL-associated patterns showed mixed results, even among colonies of the same COI species. However, we note a few consistent patterns. First, small rediae of most colonies appeared capable of reproduction, and we saw no indication (admittedly based on a small sample size and possibly insufficient attack trial methodology) that small rediae were more active or aggressive. This differs from patterns reported from most marine trematodes. Second, the small rediae of most colonies had larger pharynges relative to their body size than large rediae, consistent with marine trematodes. We also observed that colonies of three sampled COI species appear to produce a group of large rediae that have distinctly large pharynges. Conclusions We conclude that these freshwater species likely do not have a group of specialized non-reproductive soldiers because small rediae of at least some colonies in almost every species do appear to produce embryos. We cannot rule out the possibility that small rediae act as a temporary soldier caste. We are intrigued by the presence of rediae with enlarged pharynges in some species and propose that they may serve an adaptive role, possibly similar to the defensive role of small ‘soldier’ rediae of marine trematodes. Large-pharynx rediae have been documented in other species previously, and we encourage future efforts to study these large-pharynx rediae.

Abstract The paradigm of past climate-driven range shifts structuring the distribution of marine intraspecific biodiversity lacks replication in biological models exposed to comparable limiting conditions in independent regions. This may lead to confounding effects unlinked to climate drivers. We aim to fill in this gap by asking whether the global distribution of intraspecific biodiversity of giant kelp (Macrocystis pyrifera) is explained by past climate changes occurring across the two hemispheres. We compared the species’ population genetic diversity and structure inferred with microsatellite markers, with range shifts and long-term refugial regions predicted with species distribution modelling (SDM) from the last glacial maximum (LGM) to the present. The broad antitropical distribution of Macrocystis pyrifera is composed by six significantly differentiated genetic groups, for which current genetic diversity levels match the expectations of past climate changes. Range shifts from the LGM to the present structured low latitude refugial regions where genetic relics with higher and unique diversity were found (particularly in the Channel Islands of California and in Peru), while post-glacial expansions following ~ 40% range contraction explained extensive regions with homogenous reduced diversity. The estimated effect of past climate-driven range shifts was comparable between hemispheres, largely demonstrating that the distribution of intraspecific marine biodiversity can be structured by comparable evolutionary forces across the global ocean. Additionally, the differentiation and endemicity of regional genetic groups, confers high conservation value to these localized intraspecific biodiversity hotspots of giant kelp forests.

IntroductionAerobic exercise has been shown to improve cancer-associated cognitive decline (CACD) in breast cancer survivors (BCS), and recent findings suggest that one mechanism by which exercise may reduce cognitive decline is through alteration of the brain's functional organization. Many cognitive abilities and measures of functional brain organization change with age and disease, typically reflected in cognitive decline and reduced differentiation of brain networks, or “modularity.” Although previous research has identified associations between lifestyle interventions, such as exercise, and increased modularity, no studies have examined these relationships in cancer populations. The primary aim of this study was to investigate the preliminary effects of a 12-week aerobic exercise program on changes in brain network modularity in BCS. As a secondary aim, we explored correlations between changes in modularity with moderate-to-vigorous physical activity (MVPA) and cognitive function. Data were exploratory and used for hypothesis generation for a future, larger study.MethodsParticipants included a subsample of 10 BCS (M age = 65.9 ± 9.3 years) from a larger pilot study (N = 30 BCS) who were randomized to a 12-week aerobic exercise program (AE) or usual care (UC). The present study collected brain magnetic resonance imaging, Actigraph accelerometry, and cognitive task performance at baseline and 3-month follow-up (i.e., post-intervention; n = 4 AE, n = 6 UC). Intervention effects on modularity, MVPA, and cognition were quantified as magnitude of change between groups (Cohen's d). Changes in modularity were further explored via paired t-tests within groups. Associations between changes in modularity, MVPA, and cognitive performance were explored using Spearman's correlations.ResultsThe magnitude of changes in modularity between groups were small-to-moderate and favored the AE group (d = 0.23 to d = 0.67 across thresholds). Paired t-tests revealed a significant increase in modularity in the AE group from baseline to 3-month follow-up (t = 3.08, p = 0.03, d = 1.17), but not in the UC group. The correlation between changes in MVPA and changes in modularity were not statistically significant (r = 0.36, p = 0.39), and correlations between modularity and cognitive performance yielded mixed effects by cognitive domain.DiscussionFindings suggest that aerobic exercise may influence functional brain network organization and cognition in BCS. These data warrant further investigation in larger exercise trials.

Abstract Paciorek and Wehner raise important questions around our use of the Mann‐Kendall nonparametric trend test on smoothed data for analyzing long‐term hydrometeorological trends in Zhang et al. (2021, https://doi.org/10.1029/2020gl092293). We thank them for initiating this important conversation and their gracious cooperation in exploring the issues addressed in their comment. In this reply we confirm the inflation of significant p‐values by our choice to smooth, illustrate the relatively minor impacts on the main conclusions of our paper, and add our voices to those of Paciorek and Wehner in highlighting the lack of methodology for hypothesis testing across multiple stations that have spatial structure (i.e., testing for regionally consistent trends).

Psychosocial stress has been shown to prime peripheral innate immune cells, which take on hyper-inflammatory phenotypes and are implicated in depressive-like behavior in mouse models. However, the impact of stress on cellular metabolic states that are thought to fuel inflammatory phenotypes in immune cells are unknown. Using single cell RNA-sequencing, we investigated mRNA enrichment of immunometabolic pathways in innate immune cells of the spleen in mice subjected to repeated social defeat stress (RSDS) or no stress (NS). RSDS mice displayed a significant increase in the number of splenic macrophages and granulocytes (p

Bulk metallic glasses (BMGs) are non-crystalline class of advanced materials and have found potential applications in the biomedical field. Although there are numerous conventional manufacturing approaches for processing BMGs, the most commonly used like copper-mould casting have some limitations. It is not easy to manage and control the critical cooling rate, especially when the fabrication of complex BMG geometries is involved. Other limitations of these techniques include the size constraints, non-flexibility, and the tooling and accessories are costly. The emergence of additive manufacturing (AM) has opened another promising manufacturing route for processing BMGs. AM processes, particularly laser powder-bed fusion (PBF-LB/M) builds parts layer-by-layer and successively fused the powder-melted feedstocks using prescribed computer-controlled laser scanner system, thereby forming a BMGs part upon sufficiently rapid cooling to ensure the glass forming-ability. PBF-LB/M overcomes the limitations of the pre-existing BMGs processing techniques by not only improving the part size, but also produces exceptionally complex structures and patient-specific implants. This review article aims to summarise and discuss the mechanism of BMGs formation through PBF-LB/M for biomedical applications and to highlight the current scientific and technological challenges as well as the future research perspectives towards overcoming the pore-mediated microcracks, partial crystallisation, brittleness and BMG size constraint.

Sessile invertebrates in Californian kelp forests exhibit prolonged changes to community structure following a marine heatwave event.

Post-traumatic stress disorder (PTSD) is a mental health disorder that arises after experiencing or witnessing a traumatic event. Despite affecting around 7% of the population, there are currently no definitive biological signatures or biomarkers used in the diagnosis of PTSD. Thus, the search for clinically relevant and reproducible biomarkers has been a major focus of the field. With significant advances of large-scale multi-omic studies that include genomic, proteomic, and metabolomic data, promising findings have been made, but the field still has fallen short. Amongst the possible biomarkers examined, one area is often overlooked, understudied, or inappropriately investigated: the field of redox biology. Redox molecules are free radical and/or reactive species that are generated as a consequence of the necessity of electron movement for life. These reactive molecules, too, are essential for life, but in excess are denoted as “oxidative stress” and often associated with many diseases. The few studies that have examined redox biology parameters have often utilized outdated and nonspecific methods, as well as have reported confounding results, which has made it difficult to conclude the role for redox in PTSD. Herein, we provide a foundation of how redox biology may underlie diseases like PTSD, critically examine redox studies of PTSD, and provide future directions the field can implement to enhance standardization, reproducibility, and accuracy of redox assessments for the use of diagnosis, prognosis, and therapy of this debilitating mental health disorder.

Abstract It is well documented that the recovery of dryland plant communities following wildfire can be variable, and that legacies of fire can have long‐lasting effects on aboveground plant communities. However, our understanding of the degree to which dryland soil seed banks, or the viable seeds in situ, are impacted by fire and their subsequent postfire succession remains extremely poor. To address this important knowledge gap, we used a time‐since‐fire approach to investigate soil seed bank community changes approximately 15 and 30 years after wildfire and to determine the influence of microsites (e.g., shrub vs. interspace) on seed bank composition. We assessed soil seed bank metrics across four North American deserts, including two cold desert sites (Colorado Plateau and Great Basin) and two warm desert sites (Chihuahuan and Sonoran). In greenhouse emergence trials, we found that seed bank characteristics diverged between warm and cold desert sites, such that warm desert sites had seed banks dominated by annual plants while our cold desert sites had seed banks with greater proportions of perennial species, regardless of fire history. In cold desert sites, fire significantly altered seed bank species composition even 30 years after fire. Shrub versus interspace microsites had no observed influence on seed bank composition in any desert. However, seed bank species richness was greater under shrubs in both warm deserts. Non‐native species were present in the seed banks of all deserts and some were particularly abundant in the burned sites. Despite the presence of native species in both burned and unburned seed banks, the presence of non‐native species suggests some degree of vulnerability to future disturbances because fire can create amplifying feedback with many non‐native plants. Our results highlight strong differences in fires' relationship with seed banks for warm and cold desert sites and lend insight into how fire relates to the composition and diversity of the seeds that play a fundamental role in future plant communities.

Nitrous acid, HONO, is a key net photolytic precursor to OH radicals in the atmospheric boundary layer. As OH is the dominant atmospheric oxidant, driving the removal of many primary pollutants and the formation of secondary species, a quantitative understanding of HONO sources is important to predict atmospheric oxidising capacity. While a number of HONO formation mechanisms have been identified, recent work has ascribed significant importance to the dark, ocean-surface-mediated conversion of NO2 to HONO in the coastal marine boundary layer. In order to evaluate the role of this mechanism, here we analyse measurements of HONO and related species obtained at two contrasting coastal locations – Cabo Verde (Atlantic Ocean, denoted Cape Verde herein), representative of the clean remote tropical marine boundary layer, and Weybourne (United Kingdom), representative of semi-polluted northern European coastal waters. As expected, higher average concentrations of HONO (70 ppt) were observed in marine air for the more anthropogenically influenced Weybourne location compared to Cape Verde (HONO < 5 ppt). At both sites, the approximately constant HONO/NO2 ratio at night pointed to a low importance for the dark, ocean-surface-mediated conversion of NO2 into HONO, whereas the midday maximum in the HONO/NO2 ratios indicated significant contributions from photo-enhanced HONO formation mechanisms (or other sources). We obtained an upper limit to the rate coefficient of dark, ocean-surface HONO-to-NO2 conversion of CHONO = 0.0011 ppb h−1 from the Cape Verde observations; this is a factor of 5 lower than the slowest rate reported previously. These results point to significant geographical variation in the predominant HONO formation mechanisms in marine environments and indicate that caution is required when extrapolating the importance of such mechanisms from individual study locations to assess regional and/or global impacts on oxidising capacity. As a significant fraction of atmospheric processing occurs in the marine boundary layer, particularly in the tropics, better constraint of the possible ocean surface source of HONO is important for a quantitative understanding of chemical processing of primary trace gases in the global atmospheric boundary layer and associated impacts upon air pollution and climate.

Abstract Despite the demonstrated effectiveness of vaccines, varying levels of hesitancy were observed among healthcare and long‐term care workers, who were prioritized in the roll out of COVID‐19 vaccines due to their high risk of exposure to SARS‐CoV‐2 transmission. However, the evidence around the measurable impact of various educational interventions to improve vaccine confidence is limited. The proposed scoping review is intended to explore any emerging research and experiences of delivering educational interventions to improve COVID‐19 vaccine confidence among health and long‐term care workforces. We aim to identify characteristics of both informal and formal educational interventions delivered during the pandemic to support COVID‐19 vaccine hesitancy. Using the guidance outlined by the Joanna Briggs Institute, we intend to search five databases including, Ovid MEDLINE and Web of Science, as well as grey literature. We will consider all study designs and reports in an effort to include a breadth of sources to ensure our review will capture preliminary evidence, as well as more exploratory experiences of COVID‐19 vaccine education delivery. Articles will be screened by three reviewers independently and the data will be charted, and results described narratively.

Abstract White‐nose syndrome (WNS) has decimated hibernating bat populations across eastern and central North America for over a decade. Disease severity is driven by the interaction between bat characteristics, the cold‐loving fungal agent, and the hibernation environment. While we further improve hibernation energetics models, we have yet to examine how spatial heterogeneity in host traits is linked to survival in this disease system. Here, we develop predictive spatial models of body mass for the little brown myotis (Myotis lucifugus) and reassess previous definitions of the duration of hibernation of this species. Using data from published literature, public databases, local experts, and our own fieldwork, we fit a series of generalized linear models with hypothesized abiotic drivers to create distribution‐wide predictions of prehibernation body fat and hibernation duration. Our results provide improved estimations of hibernation duration and identify a scaling relationship between body mass and body fat; this relationship allows for the first continuous estimates of prehibernation body mass and fat across the species' distribution. We used these results to inform a hibernation energetic model to create spatially varying fat use estimates for M. lucifugus. These results predict WNS mortality of M. lucifugus populations in western North America may be comparable to the substantial die‐off observed in eastern and central populations.

During service of a gas turbine engine, components may suffer instant overheating which is a concern to safe operations. Effect of short overheating on the tensile properties of a Ni-based superalloy Waspaloy has been studied due to its significant importance for practical applications. The results have shown that a combination of near supersolvus overheating at 1000 °C with very rapid cooling at a rate of 50 K/s is most detrimental case to the tensile properties of the material. This is attributed to the absence of γ′ and carbide re-precipitation and growth during cooling period. Microstructure change during overheating and cooling has been deduced using in-situ resistivity measurements. This work provides evidence that multilateral measurements including resistivity can shed light on the failure controlling parameters.

Atmospheric nitrogen oxides (NO + NO2 = NOx) have been measured at the Cape Verde Atmospheric Observatory (CVAO) in the tropical Atlantic (16∘51′ N, 24∘52′ W) since October 2006. These measurements represent a unique time series of NOx in the background remote troposphere. Nitrogen dioxide (NO2) is measured via photolytic conversion to nitric oxide (NO) by ultraviolet light-emitting diode arrays followed by chemiluminescence detection. Since the measurements began, a blue light converter (BLC) has been used for NO2 photolysis, with a maximum spectral output of 395 nm from 2006 to 2015 and of 385 nm from 2015 onwards. The original BLC used was constructed with a Teflon-like material and appeared to cause an overestimation of NO2 when illuminated. To avoid such interferences, a new additional photolytic converter (PLC) with a quartz photolysis cell (maximum spectral output also 385 nm) was implemented in March 2017. Once corrections are made for the NO2 artefact from the original BLC, the two NO2 converters are shown to give comparable NO2 mixing ratios (BLC = 0.99 × PLC + 0.7 ppt, linear least-squares regression), giving confidence in the quantitative measurement of NOx at very low levels. Data analysis methods for the NOx measurements made at CVAO have been developed and applied to the entire time series to produce an internally consistent and high-quality long-term data set. NO has a clear diurnal pattern with a maximum mixing ratio of 2–10 ppt during the day depending on the season and ∼ 0 ppt during the night. NO2 shows a fairly flat diurnal signal, although a small increase in daytime NOx is evident in some months. Monthly average mixing ratios of NO2 vary between 5 and 30 ppt depending on the season. Clear seasonal trends in NO and NO2 levels can be observed with a maximum in autumn and winter and a minimum in spring and summer.

Service learning offers a pedagogy by which adult students are guided toward understanding their potential for leadership in civic life and community development, strengthening the impact that universities have in communities. In this study, qualitative data is analyzed to determine how adult students perceive their service-learning experiences and what the university could do to involve them more in the future. Respondents provide some evidence that they value opportunities to give back to communities where they have a connection; appreciate hands-on learning that is integrated with classroom learning; benefit from placement experiences that build upon prior knowledge and skills; and prefer greater choice in the selection of their service-learning placement. As the number of adult students entering higher education continues to rise and their retention remains a challenge, understanding how these students are engaged by service learning becomes an important area of exploration for post-secondary institutions.

Global climate change has led to rising temperatures and to more frequent and intense climatic events, such as storms and droughts. Changes in climate and disturbance regimes can have non-additive effects on plant communities and result in complicated legacies we have yet to understand. This is especially true for tropical forests, which play a significant role in regulating global climate. We used understory vegetation data from the Tropical Responses to Altered Climate Experiment (TRACE) in Puerto Rico to evaluate how plant communities responded to climate warming and disturbance. The TRACE understory vegetation was exposed to a severe drought (2015), 2 years of experimental warming (4°C above ambient in half of the plots, 2016–2017 and 2018–2019), and two major hurricanes (Irma and María, September 2017). Woody seedlings and saplings were censused yearly from 2015 to 2019, with an additional census in 2015 after the drought ended. We evaluated disturbance-driven changes in species richness, diversity, and composition across ontogeny. We then used Bayesian predictive trait modeling to assess how species responded to disturbance and how this might influence the functional structure of the plant community. Our results show decreased seedling richness after hurricane disturbance, as well as increased sapling richness and diversity after warming. We found a shift in species composition through time for both seedlings and saplings, yet the individual effects of each disturbance were not significant. At both ontogenetic stages, we observed about twice as many species responding to experimental warming as those responding to drought and hurricanes. Predicted changes in functional structure point to disturbance-driven functional shifts toward a mixture of fast-growing and drought-tolerant species. Our findings demonstrate that the tropical forest understory community is more resistant to climatic stressors than expected, especially at the sapling stage. However, early signs of changes in species composition suggest that, in a warming climate with frequent droughts and hurricanes, plant communities might shift over time toward fast-growing or drought-tolerant species.

Abstract The conservation benefits of marine reserves are well established but their contribution to adjacent fisheries via spillover is less certain and context‐dependent. Theoretical predictions do not always match empirical evidence from individual reserves, so carefully designed studies are essential for accurately assessing spillover and its contribution to fisheries. Biomass buildup within reserves, and spillover from reserve borders, also usually takes time to develop. In 2003, a network of no‐take marine reserves was established in the Northern Channel Islands (NCI) of southern California (CA) to conserve biodiversity and to eventually enhance local fisheries through spillover of larvae, juveniles, and adults. The reserve network impacted the local CA spiny lobster (Panulirus interruptus) fishery by removing about 20% of fishing grounds in the NCI. In 2008, a collaborative fisheries research effort detected substantial lobster population increases within reserves, and an indication of the possible spillover of adult lobsters across reserve borders. To estimate whether and how much populations within reserves, and spillover from reserves, have increased through time, we repeated the sampling program 10 years later in 2018 at two of the three original reserves. Scientific trapping was conducted prior to the fishing season along a spatial gradient beginning deep within the reserves to reference sites located outside (≥2 km) of reserve borders. Results showed that legal‐sized lobster abundance in traps (catch per unit effort) increased by 125%–465% deep inside reserves, and by 223%–331% at sites near to reserve borders, and by nearly 400% just outside of reserve borders over the 10‐year period, thus indicating a substantial increase in spillover across reserve borders. A similar pattern was observed in lobster biomass caught in traps at the two reserves. This study demonstrates how spillover scales with biomass buildup and that collaborative fisheries research can be used to assess the efficacy of marine reserves as fishery management tools worldwide.

Abstract Marine Protected Areas (MPAs) are designed to enhance biodiversity and ecosystem services. Some MPAs are also established to benefit fisheries through increased egg and larval production, or the spillover of mobile juveniles and adults. Whether spillover influences fishery landings depend on the population status and movement patterns of target species both inside and outside of MPAs, as well as the status of the fishery and behavior of the fleet. We tested whether an increase in the lobster population inside two newly established MPAs influenced local catch, fishing effort, and catch-per-unit-effort (CPUE) within the sustainable California spiny lobster fishery. We found greater build-up of lobsters within MPAs relative to unprotected areas, and greater increases in fishing effort and total lobster catch, but not CPUE, in fishing zones containing MPAs vs. those without MPAs. Our results show that a 35% reduction in fishing area resulting from MPA designation was compensated for by a 225% increase in total catch after 6-years, thus indicating at a local scale that the trade-off of fishing ground for no-fishing zones benefitted the fishery.

Abstract In multihost disease systems, differences in mortality between species may reflect variation in host physiology, morphology, and behavior. In systems where the pathogen can persist in the environment, microclimate conditions, and the adaptation of the host to these conditions, may also impact mortality. White‐nose syndrome (WNS) is an emerging disease of hibernating bats caused by an environmentally persistent fungus, Pseudogymnoascus destructans. We assessed the effects of body mass, torpid metabolic rate, evaporative water loss, and hibernaculum temperature and water vapor deficit on predicted overwinter survival of bats infected by P. destructans. We used a hibernation energetics model in an individual‐based model framework to predict the probability of survival of nine bat species at eight sampling sites across North America. The model predicts time until fat exhaustion as a function of species‐specific host characteristics, hibernaculum microclimate, and fungal growth. We fit a linear model to determine relationships with each variable and predicted survival and semipartial correlation coefficients to determine the major drivers in variation in bat survival. We found host body mass and hibernaculum water vapor deficit explained over half of the variation in survival with WNS across species. As previous work on the interplay between host and pathogen physiology and the environment has focused on species with narrow microclimate preferences, our view on this relationship is limited. Our results highlight some key predictors of interspecific survival among western bat species and provide a framework to assess impacts of WNS as the fungus continues to spread into western North America.

Soil age is thought to be an important driver of ecosystem development. Here, the authors perform a global survey of soil chronosequences and meta-analysis to show that, contrary to expectations, soil age is a relatively minor ecosystem driver at the biome scale once other drivers such as parent material, climate, and vegetation type are accounted for.

Abstract The effects of climate change on tropical forests may have global consequences due to the forests’ high biodiversity and major role in the global carbon cycle. In this study, we document the effects of experimental warming on the abundance and composition of a tropical forest floor herbaceous plant community in the Luquillo Experimental Forest, Puerto Rico. This study was conducted within Tropical Responses to Altered Climate Experiment (TRACE) plots, which use infrared heaters under free‐air, open‐field conditions, to warm understory vegetation and soils + 4°C above nearby control plots. Hurricanes Irma and María damaged the heating infrastructure in the second year of warming, therefore, the study included one pretreatment year, one year of warming, and one year of hurricane response with no warming. We measured percent leaf cover of individual herbaceous species, fern population dynamics, and species richness and diversity within three warmed and three control plots. Results showed that one year of experimental warming did not significantly affect the cover of individual herbaceous species, fern population dynamics, species richness, or species diversity. In contrast, herbaceous cover increased from 20% to 70%, bare ground decreased from 70% to 6%, and species composition shifted pre to posthurricane. The negligible effects of warming may have been due to the short duration of the warming treatment or an understory that is somewhat resistant to higher temperatures. Our results suggest that climate extremes that are predicted to increase with climate change, such as hurricanes and droughts, may cause more abrupt changes in tropical forest understories than longer‐term sustained warming.

3D printing can allow for the efficient manufacturing of elaborate structures difficult to realise conventionally without waste, such as the hollow geometries of nickel-based superalloy aeronautic components. To fully exploit this method, we must move towards new alloys and processes.

Multiple endocrine neoplasia type 1 (MEN1), an autosomal domina nt disorder caused by MEN1 germline mutations, is characterised by parathyroid, pancreati c and pituitary tumours. MEN1 mutations also cause familial isolated primary hyperparathyroi dism (FIHP), a milder condition causing hyperparathyroidism only. Identical mutations can cause either MEN1 or FIHP in different families, thereby implicating a role for genetic modifiers in altering phenotypic expression of tumours. We therefore inve stigated the effects of genetic background and potential for genetic modifiers on tumour development in adult Men1+/- mice, which develop tumours of the parathyroids, pancreatic is lets, anterior pituitary, adrenal cortex and gonads, that had been backcrossed to generate C57BL/6 and 129S6/SvEv congenic strains. A total of 275 Men1+/- mice, aged 5–26 months were macroscopically studied, and this revealed that genetic backgro und significantly influenced the development of pituitary, adrenal and ovarian tumours, whic h occurred in mice over 12 months of age and more frequently in C57BL/6 females, 129S6/ SvEv males and 129S6/SvEv females, respectively. Moreover, pituitary and adrenal tumours developed earlier, in C57BL/6 males and 129S6/SvEv females, respectively, and pancreatic and testicular tumours developed earlier in 129S6/SvEv males. Furth ermore, glucagon-positive staining pancreatic tumours occurred more frequently in 129S6/S vEv Men1+/- mice. Whole genome sequence analysis of 129S6/SvEv and C57BL/6 Men1+/- mice revealed >54,000 different variants in >300 genes. These included, Coq7, Dmpk, Ccne2, Kras, Wnt2b, Il3ra and Tnfrsf10a, and qRT-PCR analysis revealed that Kras was significantly higher in pituitaries of male 129S6/SvEv mice. Thus, our results demonstrate that Kras and other genes could represent possible genetic modifiers of Men1.

Significant concerns have arisen over the past 3 y from the increased global spread of the mosquito-borne flavivirus, Zika. Accompanying this spread has been an increase in cases of the devastating birth defect microcephaly as well as of Guillain–Barré syndrome in adults in many affected countries. Currently there is no vaccine or therapy for this infection; however, we sought to develop a combination approach that provides more rapid and durable protection than traditional vaccination alone. A novel immune-based prophylaxis/therapy strategy entailing the facilitated delivery of a synthetic DNA consensus prME vaccine along with DNA-encoded anti-ZIKV envelope monoclonal antibodies (dMAb) were developed and evaluated for antiviral efficacy. This immediate and persistent protection strategy confers the ability to overcome shortcomings inherent with conventional active vaccination or passive immunotherapy. A collection of novel dMAbs were developed which were potent against ZIKV and could be expressed in serum within 24–48 h of in vivo administration. The DNA vaccine, from a previous development, was potent after adaptive immunity was developed, protecting against infection, brain and testes pathology in relevant mouse challenge models and in an NHP challenge. Delivery of potent dMAbs protected mice from the same murine viral challenge within days of delivery. Combined injection of dMAb and the DNA vaccine afforded rapid and long-lived protection in this challenge model, providing an important demonstration of the advantage of this synergistic approach to pandemic outbreaks.

Objectives: Acute kidney injury is common among the critically ill. However, the incidence, medication use, and outcomes of acute kidney injury have been variably described. We conducted a single-center, retrospective cohort study to examine the risk factors and correlates associated with acute kidney injury in critically ill adults with a particular focus on medication class usage. Methods: We reviewed the electronic medical records of all adult patients admitted to an intensive care unit between 1 February and 30 August 2020. Acute kidney injury was defined by the 2012 Kidney Disease: Improving Global Outcomes guidelines. Data included were demographics, comorbidities, symptoms, laboratory parameters, interventions, and outcomes. The primary outcome was acute kidney injury incidence. A Least Absolute Shrinkage and Selection Operator regression model was used to determine risk factors associated with acute kidney injury. Secondary outcomes including acute kidney injury recovery and intensive care unit mortality were analyzed using a Cox regression model. Results: Among 226 admitted patients, 108 (47.8%) experienced acute kidney injury. 37 (34.3%), 39 (36.1%), and 32 patients (29.6%) were classified as acute kidney injury stages I–III, respectively. Among the recovery and mortality cohorts, analgesics/sedatives, anti-infectives, and intravenous fluids were significant ( p -value

Monitoring is a crucial tool for measuring the progress and success of environmental policies and management programs. While many studies have evaluated the effectiveness of biodiversity sampling methods, few have compared their efficiency, which is crucial given the funding constraints present in all conservation efforts. In this study we demonstrate how existing analytical tools can be applied to (i) assess the relationship between sampling effort and resulting confidence in biodiversity metrics, and (ii) compare the efficiency of different methods for monitoring biodiversity. We tested this methodology on data from marine fish surveys, including: roving surveys within permanent areas, randomly placed belt transects, and randomly placed transects conducted by citizen scientists using a reduced species list. We constructed efficiency curves describing how increasing effort spent on each method reduced uncertainty in biodiversity estimates and the associated ability to detect change in diversity. All programs produced comparable measurements of species diversity for all metrics despite substantial differences in the species being surveyed by each method. The uncertainty of diversity estimations fell faster and reached a lower level for the roving diver method. Strikingly, the transect method conducted by citizen scientists performed almost identically to the more taxonomically resolved transect method conducted by professional scientists, suggesting that sampling strategies that recorded only a subset of species could still be effective, as long as the excluded species were chosen strategically. The methodology described here can guide decisions about how to measure biodiversity and optimize the resources available for monitoring, ultimately improving management outcomes.

Many enzymes in one-carbon metabolism (OCM) are up- or down-regulated by the sex hormones which vary diurnally and throughout the menstrual cycle. During pregnancy, estradiol and progesterone levels increase tremendously to modulate physiological changes in the reproductive system. In this work, we extend and improve an existing mathematical model of hepatic OCM to understand the dynamic metabolic changes that happen during the menstrual cycle and pregnancy due to estradiol variation. In particular, we add the polyamine drain on S-adenosyl methionine and the direct effects of estradiol on the enzymes cystathionine β-synthase (CBS), thymidylate synthase (TS), and dihydrofolate reductase (DHFR). We show that the homocysteine concentration varies inversely with estradiol concentration, discuss the fluctuations in 14 other one-carbon metabolites and velocities throughout the menstrual cycle, and draw comparisons with the literature. We then use the model to study the effects of vitamin B12, vitamin B6, and folate deficiencies and explain why homocysteine is not a good biomarker for vitamin deficiencies. Additionally, we compute homocysteine throughout pregnancy, and compare the results with experimental data. Our mathematical model explains how numerous homeostatic mechanisms in OCM function and provides new insights into how homocysteine and its deleterious effects are influenced by estradiol. The mathematical model can be used by others for further in silico experiments on changes in one-carbon metabolism during the menstrual cycle and pregnancy.