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Measuring trace element concentrations in tissue can be a valuable approach to monitor animal health status. Temporal variation in the absorption, transport, and storage of elements between different tissues can, however, complicate the assessment of element-health relationships. Here, we measured concentrations of selected essential (copper (Cu), zinc (Zn), selenium (Se)) and non-essential (arsenic (As), cadmium (Cd), lead (Pb)) trace elements within blood, liver, kidney, and hair of fallow deer (Dama dama; N=20) and red deer (Cervus elaphus; N=21). Using multivariate regression and structural equation models, we estimated direct and indirect linkages between tissue-specific trace element profiles and long- (body condition) and short-term (serum protein biomarkers for acute inflammation, infection, and malnutrition) health indicators. Trace element concentrations varied markedly and were weakly correlated among tissues, with the exception of Se. After accounting for sex- and site-differences in trace element concentrations, body condition of red deer was directly, and positively, associated to trace element status in liver and hair, but not in kidney. For both deer species, trace element status in blood was directly linked to serum protein status with an indirect positive association to deer body condition. For fallow deer, no direct association between trace element status and body condition was detected in any of the tissues, possibly because of elemental homeostasis, and because all individuals were in good clinical health. This study shows that hair can serve as an effective, non-invasive, biomarker in deer health assessments, yet, to fully uncover trace element-health relationships a variety of sample matrices is preferred., (© 2023. The Author(s).)

Fungi are among the most diverse and ecologically important kingdoms in life. However, the distributional ranges of fungi remain largely unknown as do the ecological mechanisms that shape their distributions 1,2 . To provide an integrated view of the spatial and seasonal dynamics of fungi, we implemented a globally distributed standardized aerial sampling of fungal spores 3 . The vast majority of operational taxonomic units were detected within only one climatic zone, and the spatiotemporal patterns of species richness and community composition were mostly explained by annual mean air temperature. Tropical regions hosted the highest fungal diversity except for lichenized, ericoid mycorrhizal and ectomycorrhizal fungi, which reached their peak diversity in temperate regions. The sensitivity in climatic responses was associated with phylogenetic relatedness, suggesting that large-scale distributions of some fungal groups are partially constrained by their ancestral niche. There was a strong phylogenetic signal in seasonal sensitivity, suggesting that some groups of fungi have retained their ancestral trait of sporulating for only a short period. Overall, our results show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude. Our study reports patterns resembling those described for other major groups of organisms, thus making a major contribution to the long-standing debate on whether organisms with a microbial lifestyle follow the global biodiversity paradigms known for macroorganisms 4,5 ., (© 2024. The Author(s).)

Seasonally abundant arthropods are a crucial food source for many migratory birds that breed in the Arctic. In cold environments, the growth and emergence of arthropods are particularly tied to temperature. Thus, the phenology of arthropods is anticipated to undergo a rapid change in response to a warming climate, potentially leading to a trophic mismatch between migratory insectivorous birds and their prey. Using data from 19 sites spanning a wide temperature gradient from the Subarctic to the High Arctic, we investigated the effects of temperature on the phenology and biomass of arthropods available to shorebirds during their short breeding season at high latitudes. We hypothesized that prolonged exposure to warmer summer temperatures would generate earlier peaks in arthropod biomass, as well as higher peak and seasonal biomass. Across the temperature gradient encompassed by our study sites (>10°C in average summer temperatures), we found a 3-day shift in average peak date for every increment of 80 cumulative thawing degree-days. Interestingly, we found a linear relationship between temperature and arthropod biomass only below temperature thresholds. Higher temperatures were associated with higher peak and seasonal biomass below 106 and 177 cumulative thawing degree-days, respectively, between June 5 and July 15. Beyond these thresholds, no relationship was observed between temperature and arthropod biomass. Our results suggest that prolonged exposure to elevated temperatures can positively influence prey availability for some arctic birds. This positive effect could, in part, stem from changes in arthropod assemblages and may reduce the risk of trophic mismatch., (© 2024 His Majesty the King in Right of Canada and The Authors. Global Change Biology published by John Wiley & Sons Ltd. Reproduced with the permission of the Minister of Environment and Climate Change Canada. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Novel methods for sampling and characterizing biodiversity hold great promise for re-evaluating patterns of life across the planet. The sampling of airborne spores with a cyclone sampler, and the sequencing of their DNA, have been suggested as an efficient and well-calibrated tool for surveying fungal diversity across various environments. Here we present data originating from the Global Spore Sampling Project, comprising 2,768 samples collected during two years at 47 outdoor locations across the world. Each sample represents fungal DNA extracted from 24 m 3 of air. We applied a conservative bioinformatics pipeline that filtered out sequences that did not show strong evidence of representing a fungal species. The pipeline yielded 27,954 species-level operational taxonomic units (OTUs). Each OTU is accompanied by a probabilistic taxonomic classification, validated through comparison with expert evaluations. To examine the potential of the data for ecological analyses, we partitioned the variation in species distributions into spatial and seasonal components, showing a strong effect of the annual mean temperature on community composition., (© 2024. The Author(s).)

Background: As outlined by the dual control model (DCM), individual differences in the regulation of sexual arousal following sexual stimulation depend on two distinct neurophysiological processes: sexual excitation (SE) and sexual inhibition (SI). Although associations with sexual function, behavior, and cue processing have been demonstrated in previous research, underlying neural correlates remain insufficiently explored. Moreover, interactive effects of SE/SI as proposed by the DCM, as well as factors impacting SE/SI properties, such as the use of oral contraceptives (OCs), have not received adequate attention in existing research., Methods: 90 healthy, sexually active women ( n = 51 using OCs, n = 39 naturally cycling) completed an Emotional-Picture-Stroop-Paradigm (EPSP) while a 64-channel EEG was recorded. LPP amplitudes toward erotic and neutral stimuli were consecutively computed as a marker of motivational salience and approach motivation. Additionally, women provided self-reports of SE/SI and sexual function. Moderation analyses were performed to assess interactive effects of SE/SI in predicting LPP amplitudes and sexual function., Results: Sexual function was negatively associated with SI levels but unrelated to SE. Higher SI was associated with reduced LPP amplitudes in response to erotic stimuli. This negative association was, however, attenuated for women high in SE, suggesting interactive effects of SE/SI. Furthermore, women using OCs reported lower SE compared to naturally cycling women., Conclusion: The observed findings provide additional psychophysiological evidence supporting the DCM and underscore the relevance of interactive SE/SI effects in stimulus processing and approach motivation. They also highlight the possible impact of OCs on psychosexual variables that warrants further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Schmidt, Hennig and Munk.)

Arctic and alpine tundra ecosystems are large reservoirs of organic carbon 1,2 . Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere 3,4 . The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain 5-7 . This hampers the accuracy of global land carbon-climate feedback projections 7,8 . Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9-2.0 °C] in air and 0.4 °C [CI 0.2-0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22-38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration., (© 2024. The Author(s).)

Global climate change has altered the timing of seasonal events (i.e., phenology) for a diverse range of biota. Within and among species, however, the degree to which alterations in phenology match climate variability differ substantially. To better understand factors driving these differences, we evaluated variation in timing of nesting of eight Arctic-breeding shorebird species at 18 sites over a 23-year period. We used the Normalized Difference Vegetation Index as a proxy to determine the start of spring (SOS) growing season and quantified relationships between SOS and nest initiation dates as a measure of phenological responsiveness. Among species, we tested four life history traits (migration distance, seasonal timing of breeding, female body mass, expected female reproductive effort) as species-level predictors of responsiveness. For one species (Semipalmated Sandpiper), we also evaluated whether responsiveness varied across sites. Although no species in our study completely tracked annual variation in SOS, phenological responses were strongest for Western Sandpipers, Pectoral Sandpipers, and Red Phalaropes. Migration distance was the strongest additional predictor of responsiveness, with longer-distance migrant species generally tracking variation in SOS more closely than species that migrate shorter distances. Semipalmated Sandpipers are a widely distributed species, but adjustments in timing of nesting relative to variability in SOS did not vary across sites, suggesting that different breeding populations of this species were equally responsive to climate cues despite differing migration strategies. Our results unexpectedly show that long-distance migrants are more sensitive to local environmental conditions, which may help them to adapt to ongoing changes in climate., (© 2024 His Majesty the King in Right of Canada. Global Change Biology published by John Wiley & Sons Ltd. Reproduced with the permission of the Minister of Environment and Climate Change Canada.This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Shifts in phenology are among the key responses of organisms to climate change. When rates of phenological change differ between interacting species they may result in phenological asynchrony. Studies have found conflicting patterns concerning the direction and magnitude of changes in synchrony, which have been attributed to biological factors. A hitherto overlooked additional explanation are differences in the currency used to quantify resource phenology, such as abundance and biomass. Studying an insectivorous bird (the sanderling) and its prey, we show that the median date of cumulative arthropod biomass occurred, on average, 6.9 days after the median date of cumulative arthropod abundance. In some years this difference could be as large as 21 days. For 23 years, hatch dates of sanderlings became less synchronized with the median date of arthropod abundance, but more synchronized with the median date of arthropod biomass. The currency-specific trends can be explained by our finding that mean biomass per arthropod specimen increased with date. Using a conceptual simulation, we show that estimated rates of phenological change for abundance and biomass can differ depending on temporal shifts in the size distribution of resources. We conclude that studies of trophic mismatch based on different currencies for resource phenology can be incompatible with each other.

Reports of fading vole and lemming population cycles and persisting low populations in some parts of the Arctic have raised concerns about the spread of these fundamental changes to tundra food web dynamics. By compiling 24 unique time series of lemming population fluctuations across the circumpolar region, we show that virtually all populations displayed alternating periods of cyclic/non-cyclic fluctuations over the past four decades. Cyclic patterns were detected 55% of the time ( n = 649 years pooled across sites) with a median periodicity of 3.7 years, and non-cyclic periods were not more frequent in recent years. Overall, there was an indication for a negative effect of warm spells occurring during the snow onset period of the preceding year on lemming abundance. However, winter duration or early winter climatic conditions did not differ on average between cyclic and non-cyclic periods. Analysis of the time series shows that there is presently no Arctic-wide collapse of lemming cycles, even though cycles have been sporadic at most sites during the last decades. Although non-stationary dynamics appears a common feature of lemming populations also in the past, continued warming in early winter may decrease the frequency of periodic irruptions with negative consequences for tundra ecosystems.

Housing mobility programs and housing choice vouchers provide low-income families with a potentially-transformative opportunity to move to low-poverty neighborhoods. However, families often face barriers to attaining upward residential mobility; poor health may be one important barrier, although few studies have examined this hypothesis. We used the experimental Moving to Opportunity (MTO) Study, constructed residential trajectories, and linked neighborhood opportunity measures to over 14,000 addresses of 3526 families across 7 years. We used latent growth curve longitudinal models to test how baseline health modified effects of MTO housing voucher treatment on neighborhood opportunity trajectories. Results show that poor baseline health adversely influenced how the voucher induced upward mobility. Voucher receipt strongly promoted residential mobility if families were healthy; moreover the low-poverty neighborhood voucher plus counseling treatment promoted higher opportunity neighborhood attainment compared to controls, regardless of the baseline health of the family. However families with health vulnerabilities did not retain the same initial neighborhood gains conferred by the housing choice voucher treatment, as families without health vulnerabilities. These results suggest that housing counseling may be one necessary element to expand neighborhood choice into higher opportunity neighborhoods for families with health challenges. Providing housing vouchers alone are insufficient to promote low-income family high opportunity moves, for families who have disabilities or special needs. The implications of these results point to scaling up housing mobility programs, to provide tailored support for low-income families to use housing choice vouchers to make high opportunity moves, which is particularly necessary for families with health challenges., Competing Interests: Declaration of Interest Statement No potential conflict of interest was reported by the authors.

Genomic studies of species threatened by extinction are providing crucial information about evolutionary mechanisms and genetic consequences of population declines and bottlenecks. However, to understand how species avoid the extinction vortex, insights can be drawn by studying species that thrive despite past declines. Here, we studied the population genomics of the muskox (Ovibos moschatus), an Ice Age relict that was at the brink of extinction for thousands of years at the end of the Pleistocene yet appears to be thriving today. We analysed 108 whole genomes, including present-day individuals representing the current native range of both muskox subspecies, the white-faced and the barren-ground muskox (O. moschatus wardi and O. moschatus moschatus) and a ~21,000-year-old ancient individual from Siberia. We found that the muskox' demographic history was profoundly shaped by past climate changes and post-glacial re-colonizations. In particular, the white-faced muskox has the lowest genome-wide heterozygosity recorded in an ungulate. Yet, there is no evidence of inbreeding depression in native muskox populations. We hypothesize that this can be explained by the effect of long-term gradual population declines that allowed for purging of strongly deleterious mutations. This study provides insights into how species with a history of population bottlenecks, small population sizes and low genetic diversity survive against all odds., (© 2023 John Wiley & Sons Ltd.)

The bioavailability of essential and non-essential elements in vegetation is expected to influence the performance of free-ranging terrestrial herbivores. However, attempts to relate the use of geochemical landscapes by animal populations directly to reproductive output are currently lacking. Here we measured concentrations of 14 essential and non-essential elements in soil and vegetation samples collected in the Zackenberg valley, northeast Greenland, and linked these to environmental conditions to spatially predict and map geochemical landscapes. We then used long-term (1996-2021) survey data of muskoxen (Ovibos moschatus) to quantify annual variation in the relative use of essential and non-essential elements in vegetated sites and their relationship to calf recruitment the following year. Results showed that the relative use of the geochemical landscape by muskoxen varied substantially between years and differed among elements. Selection for vegetated sites with higher levels of the essential elements N, Cu, Se, and Mo was positively linked to annual calf recruitment. In contrast, selection for vegetated sites with higher concentrations of the non-essential elements As and Pb was negatively correlated to annual calf recruitment. Based on the concentrations measured in our study, we found no apparent associations between annual calf recruitment and levels of C, Mn, Co, Zn, Cd, Ba, Hg, and C:N ratio in the vegetation. We conclude that the spatial distribution and access to essential and non-essential elements are important drivers of reproductive output in muskoxen, which may also apply to other wildlife populations. The value of geochemical landscapes to assess habitat-performance relationships is likely to increase under future environmental change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

IL-3 has been reported to be involved in various inflammatory disorders, but its role in inflammatory bowel disease (IBD) has not been addressed so far. Here, we determined IL-3 expression in samples from patients with IBD and studied the impact of Il3 or Il3r deficiency on T cell-dependent experimental colitis. We explored the mechanical, cytoskeletal and migratory properties of Il3r -/- and Il3r +/+ T cells using real-time deformability cytometry, atomic force microscopy, scanning electron microscopy, fluorescence recovery after photobleaching and in vitro and in vivo cell trafficking assays. We observed that, in patients with IBD, the levels of IL-3 in the inflamed mucosa were increased. In vivo , experimental chronic colitis on T cell transfer was exacerbated in the absence of Il-3 or Il-3r signalling. This was attributable to Il-3r signalling-induced changes in kinase phosphorylation and actin cytoskeleton structure, resulting in increased mechanical deformability and enhanced egress of Tregs from the inflamed colon mucosa. Similarly, IL-3 controlled mechanobiology in human Tregs and was associated with increased mucosal Treg abundance in patients with IBD. Collectively, our data reveal that IL-3 signaling exerts an important regulatory role at the interface of biophysical and migratory T cell features in intestinal inflammation and suggest that this might be an interesting target for future intervention., Competing Interests: Competing interests: MFN has served as an advisor for Pentax, Giuliani, MSD, AbbVie, Janssen, Takeda and Boehringer. SZ received honoraria from Takeda, Roche, Galapagos, Ferring, Falk, Lilly and Janssen. MFN and SZ received research support from Takeda, Shire (a part of Takeda) and Roche. JG and MK are co-founders of Rivercyte GmbH, a company that develops biomedical applications for real-time deformability cytometry. The other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Animal habitat selection-central in both theoretical and applied ecology-may depend on behavioural motivations such as foraging, predator avoidance, and thermoregulation. Step-selection functions (SSFs) enable assessment of fine-scale habitat selection as a function of an animal's movement capacities and spatiotemporal variation in extrinsic conditions. If animal location data can be associated with behaviour, SSFs are an intuitive approach to quantify behaviour-specific habitat selection. Fitting SSFs separately for distinct behavioural states helped to uncover state-specific selection patterns. However, while the definition of the availability domain has been highlighted as the most critical aspect of SSFs, the influence of accounting for behaviour in the use-availability design has not been quantified yet. Using a predator-free population of high-arctic muskoxen Ovibos moschatus as a case study, we aimed to evaluate how (1) defining behaviour-specific availability domains, and/or (2) fitting separate behaviour-specific models impacts (a) model structure, (b) estimated selection coefficients and (c) model predictive performance as opposed to behaviour-unspecific approaches. To do so, we first applied hidden Markov models to infer different behavioural modes (resting, foraging, relocating) from hourly GPS positions (19 individuals, 153-1062 observation days/animal). Using SSFs, we then compared behaviour-specific versus behaviour-unspecific habitat selection in relation to terrain features, vegetation and snow conditions. Our results show that incorporating behaviour into the definition of the availability domain primarily impacts model structure (i.e. variable selection), whereas fitting separate behaviour-specific models mainly influences selection strength. Behaviour-specific availability domains improved predictive performance for foraging and relocating models (i.e. behaviours with medium to large spatial displacement), but decreased performance for resting models. Thus, even for a predator-free population subject to only negligible interspecific competition and human disturbance we found that accounting for behaviour in SSFs impacted model structure, selection coefficients and predictive performance. Our results indicate that for robust inference, both a behaviour-specific availability domain and behaviour-specific model fitting should be explored, especially for populations where strong spatiotemporal selection trade-offs are expected. This is particularly critical if wildlife habitat preferences are estimated to inform management and conservation initiatives., (© 2023 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.)

With the global change in climate, the Arctic has been pinpointed as the region experiencing the fastest rates of change. As a result, Arctic biological responses-such as shifts in phenology-are expected to outpace those at lower latitudes. 15 years ago, a decade-long dataset from Zackenberg in High Arctic Greenland revealed rapid rates of phenological change. 1 To explore how the timing of spring phenology has developed since, we revisit the Zackenberg time series on flowering plants, arthropods, and birds. Drawing on the full 25-year period of 1996-2020, we find little directional change in the timing of events despite ongoing climatic change. We attribute this finding to a shift in the temporal patterns of climate conditions, from previous directional change to current high inter-annual variability. Additionally, some taxa appear to have reached the limits of their phenological responses, resulting in a leveling off in their phenological responses in warm years. Our findings demonstrate the importance of long-term monitoring of taxa from across trophic levels within the community, allowing for detecting shifts in sensitivities and responses and thus for updated inference in the light of added information., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Tracking biodiversity shifts is central to understanding past, present, and future global changes. Recent advances in bioacoustics and the low cost of high-quality automatic recorders are revolutionizing studies in biogeography and community and behavioral ecology with a robust assessment of phenology, species occurrence, and individual activity. This large volume of acoustic recordings has recently generated a plethora of datasets that can now be handled automatically, mostly via big data methods such as deep learning. These approaches need high-quality annotations to classify and detect recorded sounds efficiently. However, very few strongly annotated datasets-that is, with detailed information on start and end time of each vocalization-are openly accessible to the public. Moreover, these datasets mostly cover temperate species and are usually limited to a single year of recordings. Here, we present ArcticBirdSounds, the first open-access, multisite, and multiyear strongly annotated dataset of arctic bird vocalizations. ArcticBirdSounds offers 20 h of annotated recordings over 2 years (2018, 2019), taken from 15 distinct plots within six locations across the Arctic, from Alaska to Greenland. Recordings cover the arctic vertebrates' breeding period and are evenly spaced during the day; they capture most species breeding there with 12,933 temporal annotations in 49 classes of sounds. While these data can be used for many pressing ecological questions, it is also a unique resource for methodological development to help meet the challenges of fast ecosystem transformations such as those happening in the Arctic. All data, including audio files, annotation files, and companion spreadsheets, are available in an Open Science Framework repository published under a CC BY 4.0 License., (© 2023 The Authors. Ecology published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

Parasites can exert a substantial influence on the ecology of wildlife populations by altering host condition. Our objectives were to estimate single and multiparasite-condition relationships for fallow deer ( Dama dama ) and red deer ( Cervus elaphus ) in Denmark and to assess potential health effects along the parasite burden gradient. Fallow deer hosted on average two endoparasite taxa per individual (min = 0, max = 5) while red deer carried on average five parasite taxa per individual (min = 2, max = 9). Body condition of both deer species was negatively related to presence of Trichuris ssp. eggs while body condition of red deer was positively related to antibodies of the protozoan Toxoplasma gondii . For the remaining parasite taxa (n = 12), we either found weak or no apparent association between infection and deer body condition or low prevalence levels restricted formal testing. Importantly, we detected a strong negative relationship between body condition and the sum of endoparasite taxa carried by individual hosts, a pattern that was evident in both deer species. We did not detect systemic inflammatory reactions, yet serology revealed reduced total protein and iron concentrations with increased parasite load in both deer species, likely due to maldigestion of forage or malabsorption of nutrients. Despite moderate sample sizes, our study highlights the importance of considering multiparasitism when assessing body condition impacts in deer populations. Moreover, we show how serum chemistry assays are a valuable diagnostic tool to detect subtle and sub-clinical health impacts of parasitism, even at low-level infestation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The severity of disease following infection with SARS-CoV-2 is determined by viral replication kinetics and host immunity, with early T cell responses and/or suppression of viraemia driving a favourable outcome. Recent studies uncovered a role for cholesterol metabolism in the SARS-CoV-2 life cycle and in T cell function. Here we show that blockade of the enzyme Acyl-CoA:cholesterol acyltransferase (ACAT) with Avasimibe inhibits SARS-CoV-2 pseudoparticle infection and disrupts the association of ACE2 and GM1 lipid rafts on the cell membrane, perturbing viral attachment. Imaging SARS-CoV-2 RNAs at the single cell level using a viral replicon model identifies the capacity of Avasimibe to limit the establishment of replication complexes required for RNA replication. Genetic studies to transiently silence or overexpress ACAT isoforms confirmed a role for ACAT in SARS-CoV-2 infection. Furthermore, Avasimibe boosts the expansion of functional SARS-CoV-2-specific T cells from the blood of patients sampled during the acute phase of infection. Thus, re-purposing of ACAT inhibitors provides a compelling therapeutic strategy for the treatment of COVID-19 to achieve both antiviral and immunomodulatory effects. Trial registration: NCT04318314., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: NMS, PACW, JAM and MKM hold an international patent entitled No.1917498.6 entitled “Treatment of Hepatitis B Virus (HBV) Infection” filed by applicant UCL Business Ltd and have received unrestricted project funding from Gilead Sciences to investigate effects of ACAT inhibitors in HBV infection., (Copyright: © 2023 Wing et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rationale: Analysis of stable isotopes in tissue and excreta may provide information about animal diets and their nutritional state. As body condition may have a major influence on reproduction, linking stable isotope values to animal demographic rates may help unravel the drivers behind animal population dynamics., Methods: We performed sequential analysis of δ 15 N values in guard hair from 21 muskoxen (Ovibos moschatus) from Zackenberg in high arctic Greenland. We were able to reconstruct the dietary history for the population over a 5-year period with contrasting environmental conditions. We examined the linkage between guard hair δ 15 N values in 12 three-month periods and muskox calf recruitment to detect critical periods for muskox reproduction. Finally, we conducted similar analyses of the correlation between environmental conditions (snow depth and air temperature) and calf recruitment., Results: δ 15 N values exhibited a clear seasonal pattern with high levels in summer and low levels in winter. However, large inter-annual variation was found in winter values, suggesting varying levels of catabolism depending on snow conditions. In particular δ 15 N values during January-March were linked to muskox recruitment rates, with higher values coinciding with lower calf recruitment. δ 15 N values were a better predictor of muskox recruitment rates than environmental conditions., Conclusions: Although environmental conditions may ultimately determine the dietary δ 15 N signal in muskox guard hairs, muskox calf recruitment was more strongly correlated with δ 15 N values than ambient snow and temperature. The period January-March, corresponding to late gestation, appears particularly critical for muskox reproduction., (© 2023 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

Insects provide key pollination services in most terrestrial biomes, but this service depends on a multistep interaction between insect and plant. An insect needs to visit a flower, receive pollen from the anthers, move to another conspecific flower, and finally deposit the pollen on a receptive stigma. Each of these steps may be affected by climate change, and focusing on only one of them (e.g., flower visitation) may miss important signals of change in service provision. In this study, we combine data on visitation, pollen transport, and single-visit pollen deposition to estimate functional outcomes in the high Arctic plant-pollinator network of Zackenberg, Northeast Greenland, a model system for global warming-associated impacts in pollination services. Over two decades of rapid climate warming, we sampled the network repeatedly: in 1996, 1997, 2010, 2011, and 2016. Although the flowering plant and insect communities and their interactions varied substantially between years, as expected based on highly variable Arctic weather, there was no detectable directional change in either the structure of flower-visitor networks or estimated pollen deposition. For flower-visitor networks compiled over a single week, species phenologies caused major within-year variation in network structure despite consistency across years. Weekly networks for the middle of the flowering season emerged as especially important because most pollination service can be expected to be provided by these large, highly nested networks. Our findings suggest that pollination ecosystem service in the high Arctic is remarkably resilient. This resilience may reflect the plasticity of Arctic biota as an adaptation to extreme and unpredictable weather. However, most pollination service was contributed by relatively few fly taxa (Diptera: Spilogona sanctipauli and Drymeia segnis [Muscidae] and species of Rhamphomyia [Empididae]). If these key pollinators are negatively affected by climate change, network structure and the pollination service that depends on it would be seriously compromised., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Ecological Monographs published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

The liver is bathed in bacterial products, including lipopolysaccharide transported from the intestinal portal vasculature, but maintains a state of tolerance that is exploited by persistent pathogens and tumours 1-4 . The cellular basis mediating this tolerance, yet allowing a switch to immunity or immunopathology, needs to be better understood for successful immunotherapy of liver diseases. Here we show that a variable proportion of CD8 + T cells compartmentalized in the human liver co-stain for CD14 and other prototypic myeloid membrane proteins and are enriched in close proximity to CD14 high myeloid cells in hepatic zone 2. CD14 + CD8 + T cells preferentially accumulate within the donor pool in liver allografts, among hepatic virus-specific and tumour-infiltrating responses, and in cirrhotic ascites. CD14 + CD8 + T cells exhibit increased turnover, activation and constitutive immunomodulatory features with high homeostatic IL-10 and IL-2 production ex vivo, and enhanced antiviral/anti-tumour effector function after TCR engagement. This CD14 + CD8 + T cell profile can be recapitulated by the acquisition of membrane proteins-including the lipopolysaccharide receptor complex-from mononuclear phagocytes, resulting in augmented tumour killing by TCR-redirected T cells in vitro. CD14 + CD8 + T cells express integrins and chemokine receptors that favour interactions with the local stroma, which can promote their induction through CXCL12. Lipopolysaccharide can also increase the frequency of CD14 + CD8 + T cells in vitro and in vivo, and skew their function towards the production of chemotactic and regenerative cytokines. Thus, bacterial products in the gut-liver axis and tissue stromal factors can tune liver immunity by driving myeloid instruction of CD8 + T cells with immunomodulatory ability., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The Arctic is warming at an alarming rate. While changes in plant community composition and phenology have been extensively reported, the effects of climate change on reproduction remain poorly understood. We quantified multidecadal changes in flower density for nine tundra plant species at a low- and a high-Arctic site in Greenland. We found substantial changes in flower density over time, but the temporal trends and drivers of flower density differed both between species and sites. Total flower density increased over time at the low-Arctic site, whereas the high-Arctic site showed no directional change. Within and between sites, the direction and rate of change differed among species, with varying effects of summer temperature, the temperature of the previous autumn and the timing of snowmelt. Finally, all species showed a strong trade-off in flower densities between successive years, suggesting an effective cost of reproduction. Overall, our results reveal region- and taxon-specific variation in the sensitivity and responses of co-occurring species to shared climatic drivers, and a clear cost of reproductive investment among Arctic plants. The ultimate effects of further changes in climate may thus be decoupled between species and across space, with critical knock-on effects on plant species dynamics, food web structure and overall ecosystem functioning., Supplementary Information: The online version contains supplementary material available at 10.1007/s00300-023-03164-2., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Author(s) 2023.)

Tenant-based rental assistance has received much attention as a tool to ameliorate American poverty and income segregation. We examined whether a tenant-based voucher program improves long-term exposure to neighborhood opportunity overall and across multiple domains-social/economic, educational, and health/environmental-among low-income families with children. We used data from the Moving to Opportunity (MTO) experiment (1994-2010) with a 10- to 15-year follow-up period and used an innovative and multidimensional measure of neighborhood opportunities for children. Compared with controls in public housing, MTO voucher recipients experienced improvement in neighborhood opportunity overall and across domains during the entire study period, with a larger treatment effect for families in the MTO voucher group who received supplementary housing counseling, than the Section 8 voucher group. Our results also suggests that effects of housing vouchers on neighborhood opportunity may not be uniform across subgroups. Results from model-based recursive partitioning for neighborhood opportunity identified several potential effect modifiers for housing vouchers, including study sites, health and developmental problems of household members, and having vehicle access.

Intactness is a commonly used measure of ecological integrity, especially when evaluating conservation status at the landscape scale. We argue that in the large and relatively unfragmented landscapes of the Arctic and sub-Arctic, intactness provides only partial insight for managers charged with maintaining ecological integrity. A recent landscape assessment suggests that 95% of Alaska shows no measured direct or indirect impacts of human development on the landscape. However, the current exceptionally high levels of intactness in Alaska, and throughout the Arctic and sub-Arctic, do not adequately reflect impacts to the region's ecological integrity caused by indirect stressors, such as a rapidly changing climate and the subsequent loss of the cryosphere. Thus, it can be difficult to measure, and manage, some of the conservation challenges presented by the ecological context of these systems. The dominant drivers of change, and their associated ecological and socioeconomic impacts, vary as systems decline in ecological integrity from very high to high, and to intermediate levels, but this is not well understood in the literature. Arctic and sub-Arctic systems, as well as other large intact areas, provide unique opportunities for conservation planning, but require tools and approaches appropriate to unfragmented landscapes undergoing rapid climate-driven ecological transformation. We conclude with possible directions for developing more appropriate metrics for measuring ecological integrity in these systems., (© 2022. The Author(s) under exclusive licence to Royal Swedish Academy of Sciences.)

Processes leading to range contractions and population declines of Arctic megafauna during the late Pleistocene and early Holocene are uncertain, with intense debate on the roles of human hunting, climatic change, and their synergy. Obstacles to a resolution have included an overreliance on correlative rather than process-explicit approaches for inferring drivers of distributional and demographic change. Here, we disentangle the ecological mechanisms and threats that were integral in the decline and extinction of the muskox (Ovibos moschatus) in Eurasia and in its expansion in North America using process-explicit macroecological models. The approach integrates modern and fossil occurrence records, ancient DNA, spatiotemporal reconstructions of past climatic change, species-specific population ecology, and the growth and spread of anatomically modern humans. We show that accurately reconstructing inferences of past demographic changes for muskox over the last 21,000 years require high dispersal abilities, large maximum densities, and a small Allee effect. Analyses of validated process-explicit projections indicate that climatic change was the primary driver of muskox distribution shifts and demographic changes across its previously extensive (circumpolar) range, with populations responding negatively to rapid warming events. Regional analyses show that the range collapse and extinction of the muskox in Europe (~13,000 years ago) was likely caused by humans operating in synergy with climatic warming. In Canada and Greenland, climatic change and human activities probably combined to drive recent population sizes. The impact of past climatic change on the range and extinction dynamics of muskox during the Pleistocene-Holocene transition signals a vulnerability of this species to future increased warming. By better establishing the ecological processes that shaped the distribution of the muskox through space and time, we show that process-explicit macroecological models have important applications for the future conservation and management of this iconic species in a warming Arctic., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Purpose: Neighborhood context may influence alcohol use, but effects may be heterogeneous, and prior evidence is threatened by confounding. We leveraged a housing voucher experiment to test whether housing vouchers' effects on alcohol use differed for families of children with and without socioemotional health or socioeconomic vulnerabilities., Trial Design: In the Moving to Opportunity (MTO) study, low-income families in public housing in five US cities were randomized in 1994 to 1998 to receive one of three treatments: (1) a housing voucher redeemable in a low-poverty neighborhood plus housing counseling, (2) a housing voucher without locational restriction, or (3) no voucher (control). Alcohol use was assessed 10 to 15 years later (2008 to 2010) in youth ages 13 to 20, N = 4600, and their mothers, N = 3200., Methods: Using intention-to-treat covariate-adjusted regression models, we interacted MTO treatment with baseline socioemotional health vulnerabilities, testing modifiers of treatment on alcohol use., Results: We found treatment effect modification by socioemotional factors. For youth, MTO voucher treatment, compared with controls, reduced the odds of ever drinking alcohol if youth had behavior problems (OR = 0.26, 95% CI [0.09, 0.72]) or problems at school (OR = 0.46, [0.26, 0.82]). MTO low-poverty treatment (vs. controls) also reduced the number of drinks if their health required special medicine/equipment (OR = 0.50 [0.32, 0.80]). Yet treatment effects were nonsignificant among youth without socioemotional vulnerabilities. Among mothers of children with learning problems, MTO voucher treatment (vs. controls) reduced past-month drinking (OR = 0.69 [0.47, 0.99]), but was harmful otherwise (OR = 1.22 [0.99, 1.45])., Conclusions: For low-income adolescents with special needs/socioemotional problems, housing vouchers protect against alcohol use., (© 2022 The Authors. Alcoholism: Clinical & Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcoholism.)

Aim: Macroecological studies that require habitat suitability data for many species often derive this information from expert opinion. However, expert-based information is inherently subjective and thus prone to errors. The increasing availability of GPS tracking data offers opportunities to evaluate and supplement expert-based information with detailed empirical evidence. Here, we compared expert-based habitat suitability information from the International Union for Conservation of Nature (IUCN) with habitat suitability information derived from GPS-tracking data of 1,498 individuals from 49 mammal species., Location: Worldwide., Time Period: 1998-2021., Major Taxa Studied: Forty-nine terrestrial mammal species., Methods: Using GPS data, we estimated two measures of habitat suitability for each individual animal: proportional habitat use (proportion of GPS locations within a habitat type), and selection ratio (habitat use relative to its availability). For each individual we then evaluated whether the GPS-based habitat suitability measures were in agreement with the IUCN data. To that end, we calculated the probability that the ranking of empirical habitat suitability measures was in agreement with IUCN's classification into suitable, marginal and unsuitable habitat types., Results: IUCN habitat suitability data were in accordance with the GPS data (> 95% probability of agreement) for 33 out of 49 species based on proportional habitat use estimates and for 25 out of 49 species based on selection ratios. In addition, 37 and 34 species had a > 50% probability of agreement based on proportional habitat use and selection ratios, respectively., Main Conclusions: We show how GPS-tracking data can be used to evaluate IUCN habitat suitability data. Our findings indicate that for the majority of species included in this study, it is appropriate to use IUCN habitat suitability data in macroecological studies. Furthermore, we show that GPS-tracking data can be used to identify and prioritize species and habitat types for re-evaluation of IUCN habitat suitability data., Competing Interests: The authors have no conflict of interest to declare., (© 2022 The Authors. Global Ecology and Biogeography published by John Wiley & Sons Ltd.)

The Omicron, or Pango lineage B.1.1.529, variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection against severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple BioNTech BNT162b2 messenger RNA-vaccinated health care workers (HCWs) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple-vaccinated individuals, but the magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCWs who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.

Grazing herbivores may affect soil microbial communities indirectly by impacting soil structure and vegetation composition. In high arctic environments, this impact is poorly elucidated, while having potentially wide-reaching effects on the ecosystem. This study examines how a key arctic herbivore, the muskox Ovibos moschatus, affects the soil microbial community in a high arctic fen. Environmental DNA was extracted from soil samples taken from grazed control plots and from muskox exclosures established 5 years prior. We sequenced amplicons of the 16S rRNA gene to provide insight into the microbial communities. We found that in the grazed control plots, microbial communities exhibited high evenness and displayed highly similar overall diversity. In plots where muskoxen had been excluded, microbial diversity was significantly reduced, and had more uneven intra-sample populations and overall lower ecological richness and evenness. We observed that the composition of microbial communities in grazed soils were significantly affected by the presence of muskoxen, as seen by elevated relative abundances of Bacteroides and Firmicutes, two major phyla found in muskox faeces. Furthermore, an increase in relative abundance of bacteria involved in degradation of recalcitrant carbohydrates and cycling of nitrogen was observed in grazed soil. Ungrazed soils displayed increased abundances of bacteria potentially involved in anaerobic oxidation of methane, whereas some methanogens were more abundant in grazed soils. This corroborates a previous finding that methane emissions are higher in arctic fens under muskox grazing. Our results show that the presence of large herbivores stimulates soil microbial diversity and has a homogenizing influence on the inter-species dynamics in soil microbial communities. The findings of this study, thus, improve our understanding of the effect of herbivore grazing on arctic ecosystems and the derived methane cycling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

With the growing appreciation of tissue-resident immunity, studying tissue-specific immune cells contributing to both homeostasis and disease is imperative. Here, we provide a protocol for the isolation of human intrahepatic leukocytes (IHL) maximizing viability, purity, and yield. Our protocol is scalable by tissue weight, allowing for reproducible and efficient IHL liberation suitable for functional characterization, cell isolation, and profiling by flow (or mass) cytometry. Furthermore, we provide a "guide" to determine an expected IHL yield per gram of tissue processed. For complete details on the use and execution of this protocol, please refer to Stegmann et al. (2016), Pallett et al. (2017), Easom et al. (2018), Swadling et al. (2020), Pallett et al. (2020), and Zakeri et al. (2022)., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Immunotherapy is now the standard of care for advanced hepatocellular carcinoma (HCC), yet many patients fail to respond. A major unmet goal is the boosting of T-cells with both strong HCC reactivity and the protective advantages of tissue-resident memory T-cells (T RM ). Here, we show that higher intratumoural frequencies of γδ T-cells, which have potential for HLA-unrestricted tumour reactivity, associate with enhanced HCC patient survival. We demonstrate that γδ T-cells exhibit bona fide tissue-residency in human liver and HCC, with γδT RM showing no egress from hepatic vasculature, persistence for >10 years and superior anti-tumour cytokine production. The Vγ9Vδ2 T-cell subset is selectively depleted in HCC but can efficiently target HCC cell lines sensitised to accumulate isopentenyl-pyrophosphate by the aminobisphosphonate Zoledronic acid. Aminobisphosphonate-based expansion of peripheral Vγ9Vδ2 T-cells recapitulates a T RM  phenotype and boosts cytotoxic potential. Thus, our data suggest more universally effective HCC immunotherapy may be achieved by combining aminobisphosphonates to induce Vγ9Vδ2T RM capable of replenishing the depleted pool, with additional intratumoural delivery to sensitise HCC to Vγ9Vδ2T RM -based targeting., (© 2022. The Author(s).)

Background/Aims: Exposure toward positive emotional cues with - and without - reproductive significance plays a crucial role in daily life and regarding well-being as well as mental health. While possible adverse effects of oral contraceptive (OC) use on female mental and sexual health are widely discussed, neural processing of positive emotional stimuli has not been systematically investigated in association with OC use. Considering reported effects on mood, well-being and sexual function, and proposed associations with depression, it was hypothesized that OC users showed reduced neural reactivity toward positive and erotic emotional stimuli during early as well as later stages of emotional processing and also rated these stimuli as less pleasant and less arousing compared to naturally cycling (NC) women. Method: Sixty-two female subjects (29 NC and 33 OC) were assessed at three time points across the natural menstrual cycle and corresponding time points of the OC regimen. Early (early posterior negativity, EPN) and late (late positive potential, LPP) event-related potentials in reaction to positive, erotic and neutral stimuli were collected during an Emotional Picture Stroop Paradigm (EPSP). At each appointment, subjects provided saliva samples for analysis of gonadal steroid concentration. Valence and arousal ratings were collected at the last appointment. Results: Oral contraceptive users had significantly lower endogenous estradiol and progesterone concentrations compared to NC women. No significant group differences in either subjective stimulus evaluations or neural reactivity toward positive and erotic emotional stimuli were observed. For the OC group, LPP amplitudes in reaction to erotic vs. neutral pictures differed significantly between measurement times across the OC regimen. Discussion: In this study, no evidence regarding alterations of neural reactivity toward positive and erotic stimuli in OC users compared to NC was found. Possible confounding factors and lines for future research are elaborated and discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schmidt, Hennig and Munk.)

Individuals with potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not necessarily develop PCR or antibody positivity, suggesting that some individuals may clear subclinical infection before seroconversion. T cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections 1-3 . Here we hypothesize that pre-existing memory T cell responses, with cross-protective potential against SARS-CoV-2 (refs. 4-11 ), would expand in vivo to support rapid viral control, aborting infection. We measured SARS-CoV-2-reactive T cells, including those against the early transcribed replication-transcription complex (RTC) 12,13 , in intensively monitored healthcare workers (HCWs) who tested repeatedly negative according to PCR, antibody binding and neutralization assays (seronegative HCWs (SN-HCWs)). SN-HCWs had stronger, more multispecific memory T cells compared with a cohort of unexposed individuals from before the pandemic (prepandemic cohort), and these cells were more frequently directed against the RTC than the structural-protein-dominated responses observed after detectable infection (matched concurrent cohort). SN-HCWs with the strongest RTC-specific T cells had an increase in IFI27, a robust early innate signature of SARS-CoV-2 (ref. 14 ), suggesting abortive infection. RNA polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and SARS-CoV-2 clades. RNA polymerase was preferentially targeted (among the regions tested) by T cells from prepandemic cohorts and SN-HCWs. RTC-epitope-specific T cells that cross-recognized HCoV variants were identified in SN-HCWs. Enriched pre-existing RNA-polymerase-specific T cells expanded in vivo to preferentially accumulate in the memory response after putative abortive compared to overt SARS-CoV-2 infection. Our data highlight RTC-specific T cells as targets for vaccines against endemic and emerging Coronaviridae., (© 2021. The Author(s).)

Background: Housing mobility impacts adolescent alcohol use, and the neighborhood built environment may impact this relationship. Methods: Moving to Opportunity (MTO) was a multi-site, three-arm, household-level experiment. MTO randomly assigned one of three treatment arms (1994-1997) allowing families living in public housing to (1) receive a voucher to be redeemed any neighborhood (2) receive a voucher to be redeemed in a neighborhood with less than 10% poverty (3) remain in public housing (control). MTO decreased girls' alcohol use, but increased boys' alcohol use. Treatment groups were pooled because they are similar conceptually and statistically on our primary outcome. Among youth aged 12-19 in 2001-2002 (N = 2829), we estimated controlled direct effects mediation of MTO treatment effects on youth with housing vouchers (N = 1950) vs. controls (N = 879) on past 30-day number of drinks per day on days drank, using gender-stratified Poisson regression. Mediators were density of on- and off-premises alcohol outlets per square mile at the families' census tract of residence in 1997. Results: Treatment group youth were randomized to live in 1997 census tracts with lower off-premises, but higher on-premises, outlet density. MTO treatment (vs. controls) decreased drinking for girls via alcohol outlet density, but only at higher levels of outlet density. Treatment was 18% more beneficial when girls moved to high density neighborhoods, compared to controls who stayed living in public housing in high density neighborhoods. Conclusion: Additional social processes unmeasured in the current study may play an important role in the alcohol use and other health risks for girls.

Using data from the Moving to Opportunity (MTO) experiment (1994-2002), this study examined how a multidimensional measure of neighborhood quality over time influenced adolescent psychological distress, using instrumental variable (IV) analysis. Neighborhood quality was operationalized with the independently validated 19-indicator Child Opportunity Index (COI), linked to MTO family addresses over 4-7 years. We examined whether being randomized to receive a housing subsidy (versus remaining in public housing) predicted neighborhood quality across time. Using IV analysis, we tested whether experimentally induced differences in COI across time predicted psychological distress on the Kessler Screening Scale for Psychological Distress (n = 2,829; mean β = -0.04 points (standard deviation, 1.12)). The MTO voucher treatment improved neighborhood quality for children as compared with in-place controls. A 1-standard-deviation change in COI since baseline predicted a 0.32-point lower psychological distress score for girls (β = -0.32, 95% confidence interval: -0.61, -0.03). Results were comparable but less precisely estimated when neighborhood quality was operationalized as simply average post-random-assignment COI (β = -0.36, 95% confidence interval: -0.74, 0.02). Effect estimates based on a COI excluding poverty and on the most recent COI measure were slightly larger than other operationalizations of neighborhood quality. Improving a multidimensional measure of neighborhood quality led to reductions in low-income girls' psychological distress, and this was estimated with high internal validity using IV methods., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Determining divergent metabolic requirements of T cells, and the viruses and tumours they fail to combat, could provide new therapeutic checkpoints. Inhibition of acyl-CoA:cholesterol acyltransferase (ACAT) has direct anti-carcinogenic activity. Here, we show that ACAT inhibition has antiviral activity against hepatitis B (HBV), as well as boosting protective anti-HBV and anti-hepatocellular carcinoma (HCC) T cells. ACAT inhibition reduces CD8 +  T cell neutral lipid droplets and promotes lipid microdomains, enhancing TCR signalling and TCR-independent bioenergetics. Dysfunctional HBV- and HCC-specific T cells are rescued by ACAT inhibitors directly ex vivo from human liver and tumour tissue respectively, including tissue-resident responses. ACAT inhibition enhances in vitro responsiveness of HBV-specific CD8 + T cells to PD-1 blockade and increases the functional avidity of TCR-gene-modified T cells. Finally, ACAT regulates HBV particle genesis in vitro, with inhibitors reducing both virions and subviral particles. Thus, ACAT inhibition provides a paradigm of a metabolic checkpoint able to constrain tumours and viruses but rescue exhausted T cells, rendering it an attractive therapeutic target for the functional cure of HBV and HBV-related HCC.

Species conservation in a rapidly changing world requires an improved understanding of how individuals and populations respond to changes in their environment across temporal scales. Increased warming in the Arctic puts this region at particular risk for rapid environmental change, with potentially devastating impacts on resident populations. Here, we make use of a parameterized full life cycle, individual-based energy budget model for wild muskoxen, coupling year-round environmental data with detailed ontogenic metabolic physiology. We show how winter food accessibility, summer food availability, and density dependence drive seasonal dynamics of energy storage and thus life history and population dynamics. Winter forage accessibility defined by snow depth, more than summer forage availability, was the primary determinant of muskox population dynamics through impacts on calf recruitment and longer term carryover effects of maternal investment. Simulations of various seasonal snow depth and plant biomass and quality profiles revealed that timing of and improved/limited winter forage accessibility had marked influence on calf recruitment (±10-80%). Impacts on recruitment were the cumulative result of condition-driven reproductive performance at multiple time points across the reproductive period (ovulation to calf weaning) as a trade-off between survival and reproduction. Seasonal and generational condition effects of snow-rich winters interacted with age structure and density to cause pronounced long-term consequences on population growth and structure, with predicted population recovery times from even moderate disturbances of 10 years or more. Our results show how alteration in winter forage accessibility, mediated by snow depth, impacts the dynamics of northern herbivore populations. Further, we present here a mechanistic and state-based model framework to assess future scenarios of environmental change, such as increased or decreased snowfall or plant biomass and quality to impact winter and summer forage availability across the Arctic., (© 2020 John Wiley & Sons Ltd.)

Habitat selection is expected to balance benefits and costs that maximizes fitness. Using a rare data set on collared lemming (Dicrostonyx groenlandicus) winter nest location spanning more than two decades, we show that lemmings actively select for Salix snow beds, likely due to its favorable micro-climate, and that lemming habitat selection was density-dependent. Lemmings nevertheless exhibited some flexibility in their habitat selection, which appeared to be influenced by the year-to-year variation in snow conditions. The likelihood of both lemming breeding and nest predation by stoats (Mustela erminea) was not directly linked to habitat despite a delicate interplay between habitat, nest size, breeding, and predation. Hence, the larger lemming nests were found in Salix snow beds, and these were more often used for breeding, but both larger nests and nests used for breeding were also predated more often than other nests. Our study provides a clear example of how density-dependent habitat selection acts to balance fitness in the various habitats utilized by collared lemmings.

Most birds incubate their eggs, which requires time and energy at the expense of other activities. Birds generally have two incubation strategies: biparental where both mates cooperate in incubating eggs, and uniparental where a single parent incubates. In harsh and unpredictable environments, incubation is challenging due to high energetic demands and variable resource availability. We studied the relationships between the incubation behaviour of sandpipers (genus Calidris) and two environmental variables: temperature and a proxy of primary productivity (i.e. NDVI). We investigated how these relationships vary between incubation strategies and across species among strategies. We also studied how the relationship between current temperature and incubation behaviour varies with previous day's temperature. We monitored the incubation behaviour of nine sandpiper species using thermologgers at 15 arctic sites between 2016 and 2019. We also used thermologgers to record the ground surface temperature at conspecific nest sites and extracted NDVI values from a remote sensing product. We found no relationship between either environmental variables and biparental incubation behaviour. Conversely, as ground-surface temperature increased, uniparental species decreased total duration of recesses (TDR) and mean duration of recesses (MDR), but increased number of recesses (NR). Moreover, small species showed stronger relationships with ground-surface temperature than large species. When all uniparental species were combined, an increase in NDVI was correlated with higher mean duration, total duration and number of recesses, but relationships varied widely across species. Finally, some uniparental species showed a lag effect with a higher nest attentiveness after a warm day while more recesses occurred after a cold day than was predicted based on current temperatures. We demonstrate the complex interplay between shorebird incubation strategies, incubation behaviour, and environmental conditions. Understanding how species respond to changes in their environment during incubation helps predict their future reproductive success., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Time series data on arthropod populations are critical for understanding the magnitude, direction, and drivers of change. However, most arthropod monitoring programs are short-lived and restricted in taxonomic resolution. Monitoring data from the Arctic are especially underrepresented, yet critical to uncovering and understanding some of the earliest biological responses to rapid environmental change. Clear imprints of climate on the behavior and life history of some Arctic arthropods have been demonstrated, but a synthesis of population-level abundance changes across taxa is lacking. We utilized 24 y of abundance data from Zackenberg in High-Arctic Greenland to assess trends in abundance and diversity and identify potential climatic drivers of abundance changes. Unlike findings from temperate systems, we found a nonlinear pattern, with total arthropod abundance gradually declining during 1996 to 2014, followed by a sharp increase. Family-level diversity showed the opposite pattern, suggesting increasing dominance of a small number of taxa. Total abundance masked more complicated trajectories of family-level abundance, which also frequently varied among habitats. Contrary to expectation in this extreme polar environment, winter and fall conditions and positive density-dependent feedbacks were more common determinants of arthropod dynamics than summer temperature. Together, these data highlight the complexity of characterizing climate change responses even in relatively simple Arctic food webs. Our results underscore the need for data reporting beyond overall trends in biomass or abundance and for including basic research on life history and ecology to achieve a more nuanced understanding of the sensitivity of Arctic and other arthropods to global changes., Competing Interests: The authors declare no competing interest.

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection., (Copyright © 2020, American Association for the Advancement of Science.)

Animals have adapted behavioral and physiological strategies to conserve energy during periods of adverse conditions. Heterothermy is one such adaptation used by endotherms. While heterothermy-fluctuations in body temperature and metabolic rate-has been shown in large vertebrates, little is known of the costs and benefits of this strategy, both in terms of energy and in terms of fitness. Hence, our objective was to model the energetics of seasonal heterothermy in the largest Arctic ungulate, the muskox ( Ovibos moschatus ), using an individual-based energy budget model of metabolic physiology. We found that the empirically based drop in body temperature (winter max ~-0.8°C) overwinter in adult females resulted in substantial fitness benefits in terms of reduced daily energy expenditure and body mass loss. Body mass and energy reserves were 8.98% and 14.46% greater in modeled heterotherms compared to normotherms by end of winter. Based on environmental simulations, we show that seasonal heterothermy can, to some extent, buffer the negative consequences of poor prewinter body condition or reduced winter food accessibility, leading to greater winter survival (+20%-30%) and spring energy reserves (+10%-30%), and thus increased probability of future reproductive success. These results indicate substantial adaptive short-term benefits of seasonal heterothermy at the individual level, with potential implications for long-term population dynamics in highly seasonal environments., Competing Interests: We declare no competing interests., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Climatic impacts are especially pronounced in the Arctic, which as a region is warming twice as fast as the rest of the globe. Here, we investigate how mean climatic conditions and rates of climatic change impact parasitoid insect communities in 16 localities across the Arctic. We focus on parasitoids in a widespread habitat, Dryas heathlands, and describe parasitoid community composition in terms of larval host use (i.e., parasitoid use of herbivorous Lepidoptera vs. pollinating Diptera) and functional groups differing in their closeness of host associations (koinobionts vs. idiobionts). Of the latter, we expect idiobionts-as being less fine-tuned to host development-to be generally less tolerant to cold temperatures, since they are confined to attacking hosts pupating and overwintering in relatively exposed locations. To further test our findings, we assess whether similar climatic variables are associated with host abundances in a 22 year time series from Northeast Greenland. We find sites which have experienced a temperature rise in summer while retaining cold winters to be dominated by parasitoids of Lepidoptera, with the reverse being true for the parasitoids of Diptera. The rate of summer temperature rise is further associated with higher levels of herbivory, suggesting higher availability of lepidopteran hosts and changes in ecosystem functioning. We also detect a matching signal over time, as higher summer temperatures, coupled with cold early winter soils, are related to high herbivory by lepidopteran larvae, and to declines in the abundance of dipteran pollinators. Collectively, our results suggest that in parts of the warming Arctic, Dryas is being simultaneously exposed to increased herbivory and reduced pollination. Our findings point to potential drastic and rapid consequences of climate change on multitrophic-level community structure and on ecosystem functioning and highlight the value of collaborative, systematic sampling effort., (© 2020 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

When plant species compete for pollinators, climate warming may cause directional change in flowering overlap, thereby shifting the strength of pollinator-mediated plant-plant interactions. Such shifts are likely accentuated in the rapidly warming Arctic. Targeting a plant community in Northeast Greenland, we asked (a) whether the relative phenology of plants is shifting with spatial variation in temperature, (b) whether local plants compete for pollination, and (c) whether shifts in climatic conditions are likely to affect this competition. We first searched for climatic imprints on relative species phenology along an elevational gradient. We then tested for signs of competition with increasing flower densities: reduced pollinator visits, reduced representation of plant species in pollen loads, and reduced seed production. Finally, we evaluated how climate change may affect this competition. Compared to a dominant species, Dryas integrifolia × octopetala, the relative timing of other species shifted along the environmental gradient, with Silene acaulis and Papaver radicatum flowering earlier toward higher elevation. This shift resulted in larger niche overlap, allowing for an increased potential for competition for pollination. Meanwhile, Dryas emerged as a superior competitor by attracting 97.2% of flower visits. Higher Dryas density resulted in reduced insect visits and less pollen of S. acaulis being carried by pollinators, causing reduced seed set by S. acaulis. Our results show that current variation in climate shifts the timing and flowering overlap between dominant and less-competitive plant species. With climate warming, such shifts in phenology within trophic levels may ultimately affect interactions between them, changing the strength of competition among plants., (© 2020 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

The existence and persistence of rhythmicity in animal activity during phases of environmental change is of interest in ecology, evolution and chronobiology. A wide diversity of biological rhythms in response to exogenous conditions and internal stimuli have been uncovered, especially for polar vertebrates. However, empirical data supporting circadian organization in behaviour of large ruminating herbivores remains inconclusive. Using year-round tracking data of the largest Arctic ruminant, the muskox ( Ovibos moschatus ), we modelled rhythmicity as a function of behaviour and environmental conditions. Behavioural states were classified based on patterns in hourly movements, and incorporated within a periodicity analyses framework. Although circadian rhythmicity in muskox behaviour was detected throughout the year, ultradian rhythmicity was most prevalent, especially when muskoxen were foraging and resting in mid-winter (continuous darkness). However, when combining circadian and ultradian rhythmicity together, the probability of behavioural rhythmicity declined with increasing photoperiod until largely disrupted in mid-summer (continuous light). Individuals that remained behaviourally rhythmic during mid-summer foraged in areas with lower plant productivity (NDVI) than individuals with arrhythmic behaviour. Based on our study, we conclude that muskoxen may use an interval timer to schedule their behavioural cycles when forage resources are low, but that the importance and duration of this timer are reduced once environmental conditions allow energetic reserves to be replenished ad libitum. We argue that alimentary function and metabolic requirements are critical determinants of biological rhythmicity in muskoxen, which probably applies to ruminating herbivores in general., Competing Interests: The authors declare no competing interests., (© 2020 The Authors.)

The human liver contains specialized subsets of mononuclear phagocytes (MNPs) and T cells, but whether these have definitive features of tissue residence (long-term retention, lack of egress) and/or can be replenished from the circulation remains unclear. Here we addressed these questions using HLA-mismatched liver allografts to discriminate the liver-resident (donor) from the infiltrating (recipient) immune composition. Allografts were rapidly infiltrated by recipient leukocytes, which recapitulated the liver myeloid and lymphoid composition, and underwent partial reprogramming with acquisition of CD68/CD206 on MNPs and CD69/CD103 on T cells. The small residual pool of donor cells persisting in allografts for over a decade contained CX3CR1hi/CD163hi/CD206hi Kupffer cells (KCs) and CXCR3hi tissue-resident memory T cells (TRM). CD8+ TRM were found in the local lymph nodes but were not detected egressing into the hepatic vein. Our findings inform organ transplantation and hepatic immunotherapy, revealing remarkably long-lived populations of KCs and TRM in human liver, which can be additionally supplemented by their circulating counterparts., Competing Interests: Disclosures: L.J. Pallett reported personal fees from Gilead Sciences outside the submitted work. O.E. Amin reported grants from Gilead Sciences outside the submitted work. X. Forns reported personal fees from Abbvie and personal fees from Gilead outside the submitted work. M.K. Maini reported grants from Gilead, grants from Hoffmann La Roche, grants from Immunocore, institutional fees from Gilead, institutional fees from Hoffmann La Roche, institutional fees from Immunocore, institutional fees from Abbvie, institutional fees from GSK, institutional fees from VIR, institutional fees from Galapagos NV, and institutional fees from Freeline outside the submitted work. No other disclosures were reported., (© 2020 Pallett et al.)

Background: The current study aimed to assess prevalence of mental disorders during Covid-19 pandemic- and respective lockdown in Germany, and potential behaviors/states that can have protective functions on preventing severe mental problems. Assessing prevalence of mental disorders, as well as to find potential protective variables is very important in order to determine people's psychological suffering. It provides the basis for teaching possible coping styles in order to prevent a major breakdown on mental health. Prevalence on mental disorders was expected to increase during the pandemic, especially depression, (general-/and health-) anxiety, panic attacks- and disorder, as well as obsessive-compulsive disorder. Additionally, potentially protective variables, such as resilience and coping, were included., Methods: N = 949 subjects completed an online-survey that asked for symptoms regarding depression, (health) anxiety, panic disorder, obsessive-compulsive disorder, and lock-down related behavior-starting 14 days after lockdown in Germany., Results: Prevalence of mental disorders in the current sample was much higher than usual prevalence of mental disorders, with 50.6% expressing at least one mental disorder. Resilience was associated with lower risks for any mental disorder (OR = 4.23, p < .0001, 95%CI = 3.21-5.57), as well as with any other measured mental illness (all ORs between = 2.82 for obsessive-compulsive disorder and OR = 41.44 for panic disorder, all p < .001). Similar results were obtained regarding coping (focus on positive)., Conclusion: Results are highly relevant in order to provide a glance on what substantial influence the current pandemic- and lockdown situation has on mental health across the country, and possibly across the world. Possible ways in order to prevent deterioration and help coping with the current situation are being elaborated and discussed., Competing Interests: The authors have declared that no competing interests exist.