A cell-type-specific error-correction signal in the posterior parietal cortex.

Neurons in the posterior parietal cortex contribute to the execution of goal-directed navigation1 and other decision-making tasks2-4. Although molecular studies have catalogued more than 50 cortical cell types5, it remains unclear what distinct functions they have in this area. Here we identified a molecularly defined subset of somatostatin (Sst) inhibitory neurons that, in the mouse posterior parietal cortex, carry a cell-type-specific error-correction signal for navigation. We obtained repeatable experimental access to these cells using an adeno-associated virus in which gene expression is driven by an enhancer that functions specifically in a subset of Sst cells6. We found that during goal-directed navigation in a virtual environment, this subset of Sst neurons activates in a synchronous pattern that is distinct from the activity of surrounding neurons, including other Sst neurons. Using in vivo two-photon photostimulation and ex vivo paired patch-clamp recordings, we show that nearby cells of this Sst subtype excite each other through gap junctions, revealing a self-excitation circuit motif that contributes to the synchronous activity of this cell type. These cells selectively activate as mice execute course corrections for deviations in their virtual heading during navigation towards a reward location, for both self-induced and experimentally induced deviations. We propose that this subtype of Sst neurons provides a self-reinforcing and cell-type-specific error-correction signal in the posterior parietal cortex that may help with the execution and learning of accurate goal-directed navigation trajectories.

High-resolution maps show that rubber causes substantial deforestation.

Understanding the effects of cash crop expansion on natural forest is of fundamental importance. However, for most crops there are no remotely sensed global maps1, and global deforestation impacts are estimated using models and extrapolations. Natural rubber is an example of a principal commodity for which deforestation impacts have been highly uncertain, with estimates differing more than fivefold1-4. Here we harnessed Earth observation satellite data and cloud computing5 to produce high-resolution maps of rubber (10 m pixel size) and associated deforestation (30 m pixel size) for Southeast Asia. Our maps indicate that rubber-related forest loss has been substantially underestimated in policy, by the public and in recent reports6-8. Our direct remotely sensed observations show that deforestation for rubber is at least twofold to threefold higher than suggested by figures now widely used for setting policy4. With more than 4 million hectares of forest loss for rubber since 1993 (at least 2 million hectares since 2000) and more than 1 million hectares of rubber plantations established in Key Biodiversity Areas, the effects of rubber on biodiversity and ecosystem services in Southeast Asia could be extensive. Thus, rubber deserves more attention in domestic policy, within trade agreements and in incoming due-diligence legislation.

Costimulation via the tumor-necrosis factor receptor superfamily couples TCR signal strength to the thymic differentiation of regulatory T cells.

Regulatory T cells (Treg cells) express members of the tumor-necrosis factor (TNF) receptor superfamily (TNFRSF), but the role of those receptors in the thymic development of Treg cells is undefined. We found here that Treg cell progenitors had high expression of the TNFRSF members GITR, OX40 and TNFR2. Expression of those receptors correlated directly with the signal strength of the T cell antigen receptor (TCR) and required the coreceptor CD28 and the kinase TAK1. The neutralization of ligands that are members of the TNF superfamily (TNFSF) diminished the development of Treg cells. Conversely, TNFRSF agonists enhanced the differentiation of Treg cell progenitors by augmenting responsiveness of the interleukin 2 receptor (IL-2R) and transcription factor STAT5. Costimulation with the ligand of GITR elicited dose-dependent enrichment for cells of lower TCR affinity in the Treg cell repertoire. In vivo, combined inhibition of GITR, OX40 and TNFR2 abrogated the development of Treg cells. Thus, expression of members of the TNFRSF on Treg cell progenitors translated strong TCR signals into molecular parameters that specifically promoted the development of Treg cells and shaped the Treg cell repertoire.

Amphiphilic shuttle peptide delivers base editor ribonucleoprotein to correct the CFTR R553X mutation in well-differentiated airway epithelial cells.

Base editing could correct nonsense mutations that cause cystic fibrosis (CF), but clinical development is limited by the lack of delivery methods that efficiently breach the barriers presented by airway epithelia. Here, we present a novel amphiphilic shuttle peptide based on the previously reported S10 peptide that substantially improved base editor ribonucleoprotein (RNP) delivery. Studies of the S10 secondary structure revealed that the alpha-helix formed by the endosomal leakage domain (ELD), but not the cell penetrating peptide (CPP), was functionally important for delivery. By isolating and extending the ELD, we created a novel shuttle peptide, termed S237. While S237 achieved lower delivery of green fluorescent protein, it outperformed S10 at Cas9 RNP delivery to cultured human airway epithelial cells and to pig airway epithelia in vivo, possibly due to its lower net charge. In well-differentiated primary human airway epithelial cell cultures, S237 achieved a 4.6-fold increase in base editor RNP delivery, correcting up to 9.4% of the cystic fibrosis transmembrane conductance regulator (CFTR) R553X allele and restoring CFTR channel function close to non-CF levels. These findings deepen the understanding of peptide-mediated delivery and offer a translational approach for base editor RNP delivery for CF airway disease.

Global collision-risk hotspots of marine traffic and the world's largest fish, the whale shark.

Marine traffic is increasing globally yet collisions with endangered megafauna such as whales, sea turtles, and planktivorous sharks go largely undetected or unreported. Collisions leading to mortality can have population-level consequences for endangered species. Hence, identifying simultaneous space use of megafauna and shipping throughout ranges may reveal as-yet-unknown spatial targets requiring conservation. However, global studies tracking megafauna and shipping occurrences are lacking. Here we combine satellite-tracked movements of the whale shark, Rhincodon typus, and vessel activity to show that 92% of sharks' horizontal space use and nearly 50% of vertical space use overlap with persistent large vessel (>300 gross tons) traffic. Collision-risk estimates correlated with reported whale shark mortality from ship strikes, indicating higher mortality in areas with greatest overlap. Hotspots of potential collision risk were evident in all major oceans, predominantly from overlap with cargo and tanker vessels, and were concentrated in gulf regions, where dense traffic co-occurred with seasonal shark movements. Nearly a third of whale shark hotspots overlapped with the highest collision-risk areas, with the last known locations of tracked sharks coinciding with busier shipping routes more often than expected. Depth-recording tags provided evidence for sinking, likely dead, whale sharks, suggesting substantial "cryptic" lethal ship strikes are possible, which could explain why whale shark population declines continue despite international protection and low fishing-induced mortality. Mitigation measures to reduce ship-strike risk should be considered to conserve this species and other ocean giants that are likely experiencing similar impacts from growing global vessel traffic.

Dynamic soaring decouples dynamic body acceleration and energetics in albatrosses.

Estimates of movement costs are essential for understanding energetic and life-history trade-offs. Although overall dynamic body acceleration (ODBA) derived from accelerometer data is widely used as a proxy for energy expenditure (EE) in free-ranging animals, its utility has not been tested in species that predominately use body rotations or exploit environmental energy for movement. We tested a suite of sensor-derived movement metrics as proxies for EE in two species of albatrosses, which routinely use dynamic soaring to extract energy from the wind to reduce movement costs. Birds were fitted with a combined heart-rate, accelerometer, magnetometer and GPS logger, and relationships between movement metrics and heart rate-derived V̇O2, an indirect measure of EE, were analyzed during different flight and activity modes. When birds were exclusively soaring, a metric derived from angular velocity on the yaw axis provided a useful proxy of EE. Thus, body rotations involved in dynamic soaring have clear energetic costs, albeit considerably lower than those of the muscle contractions required for flapping flight. We found that ODBA was not a useful proxy for EE in albatrosses when birds were exclusively soaring. As albatrosses spend much of their foraging trips soaring, ODBA alone was a poor predictor of EE in albatrosses. Despite the lower percentage of time flapping, the number of flaps was a useful metric when comparing EE across foraging trips. Our findings highlight that alternative metrics, beyond ODBA, may be required to estimate energy expenditure from inertial sensors in animals whose movements involve extensive body rotations.

Mediation of 6-year mid-childhood follow-up outcomes after pre-school social communication (PACT) therapy for autistic children: randomised controlled trial.

BACKGROUND: There are very few mechanistic studies of the long-term impact of psychosocial interventions in childhood. The parent-mediated Paediatric Autism Communication Therapy (PACT) RCT showed sustained effects on autistic child outcomes from pre-school to mid-childhood. We investigated the mechanism by which the PACT intervention achieved these effects. METHODS: Of 152 children randomised to receive PACT or treatment as usual between 2 and 5 years of age, 121 (79.6%) were followed 5-6 years after the endpoint at a mean age of 10.5 years. Assessors, blind to the intervention group, measured Autism Diagnostic Observation Scale Calibrated Severity Score (ADOS CSS) for child autistic behaviours and Teacher Vineland (TVABS) for adaptive behaviour in school. Hypothesised mediators were child communication initiations with caregivers in a standard play observation (Dyadic Communication Measure for Autism, DCMA). Hypothesised moderators of mediation were baseline child non-verbal age equivalent scores (AE), communication and symbolic development (CSBS) and 'insistence on sameness' (IS). Structural equation modelling was used in a repeated measures mediation design. RESULTS: Good model fits were obtained. The treatment effect on child dyadic initiation with the caregiver was sustained through the follow-up period. Increased child initiation at treatment midpoint mediated the majority (73%) of the treatment effect on follow-up ADOS CSS. A combination of partial mediation from midpoint child initiations and the direct effect of treatment also contributed to a near-significant total effect on follow-up TVABS. No moderation of this mediation was found for AE, CSBS or IS. CONCLUSIONS: Early sustained increase in an autistic child's communication initiation with their caregiver is largely responsible for the long-term effects from PACT therapy on autistic and adaptive behaviour outcomes. This supports the theoretical logic model of PACT therapy but also illuminates fundamental causal processes of social and adaptive development in autism over time: early social engagement in autism can be improved and this can have long-term generalised outcome effects.

AgAnimalGenomes: browsers for viewing and manually annotating farm animal genomes.

Current genome sequencing technologies have made it possible to generate highly contiguous genome assemblies for non-model animal species. Despite advances in genome assembly methods, there is still room for improvement in the delineation of specific gene features in the genomes. Here we present genome visualization and annotation tools to support seven livestock species (bovine, chicken, goat, horse, pig, sheep, and water buffalo), available in a new resource called AgAnimalGenomes. In addition to supporting the manual refinement of gene models, these browsers provide visualization tracks for hundreds of RNAseq experiments, as well as data generated by the Functional Annotation of Animal Genomes (FAANG) Consortium. For species with predicted gene sets from both Ensembl and RefSeq, the browsers provide special tracks showing the thousands of protein-coding genes that disagree across the two gene sources, serving as a valuable resource to alert researchers to gene model issues that may affect data interpretation. We describe the data and search methods available in the new genome browsers and how to use the provided tools to edit and create new gene models.

A framework to unlock marine bird energetics.

Energetics can provide novel insights into the roles of animals, but employing an energetics approach has traditionally required extensive empirical physiological data on the focal species, something that can be challenging for those that inhabit marine environments. There is therefore a demand for a framework through which to estimate energy expenditure from readily available data. We present the energetic costs associated with important time- and energy-intensive behaviours across nine families of marine bird (including seabirds, ducks, divers and grebes) and nine ecological guilds. We demonstrate a worked example, calculating the year-round energetic expenditure of the great auk, Pinguinus impennis, under three migration scenarios, thereby illustrating the capacity of this approach to make predictions for data-deficient species. We provide a comprehensive framework through which to model marine bird energetics and demonstrate the power of this approach to provide novel, quantitative insights into the influence of marine birds within their ecosystems.

Suramin analogues protect cartilage against osteoarthritic breakdown by increasing levels of tissue inhibitor of metalloproteinases 3 (TIMP-3) in the tissue.

Osteoarthritis is a chronic degenerative joint disease affecting millions of people worldwide, with no disease-modifying drugs currently available to treat the disease. Tissue inhibitor of metalloproteinases 3 (TIMP-3) is a potential therapeutic target in osteoarthritis because of its ability to inhibit the catabolic metalloproteinases that drive joint damage by degrading the cartilage extracellular matrix. We previously found that suramin inhibits cartilage degradation through its ability to block endocytosis and intracellular degradation of TIMP-3 by low-density lipoprotein receptor-related protein 1 (LRP1), and analysis of commercially available suramin analogues indicated the importance of the 1,3,5-trisulfonic acid substitutions on the terminal naphthalene rings for this activity. Here we describe synthesis and structure-activity relationship analysis of additional suramin analogues using ex vivo models of TIMP-3 trafficking and cartilage degradation. This showed that 1,3,6-trisulfonic acid substitution of the terminal naphthalene rings was also effective, and that the protective activity of suramin analogues depended on the presence of a rigid phenyl-containing central region, with para/para substitution of these phenyl rings being most favourable. Truncated analogues lost protective activity. The physicochemical characteristics of suramin and its analogues indicate that approaches such as intra-articular injection would be required to develop them for therapeutic use.

A neural circuit architecture for angular integration in Drosophila.

Many animals keep track of their angular heading over time while navigating through their environment. However, a neural-circuit architecture for computing heading has not been experimentally defined in any species. Here we describe a set of clockwise- and anticlockwise-shifting neurons in the Drosophila central complex whose wiring and physiology provide a means to rotate an angular heading estimate based on the fly's angular velocity. We show that each class of shifting neurons exists in two subtypes, with spatiotemporal activity profiles that suggest different roles for each subtype at the start and end of tethered-walking turns. Shifting neurons are required for the heading system to properly track the fly's heading in the dark, and stimulation of these neurons induces predictable shifts in the heading signal. The central features of this biological circuit are analogous to those of computational models proposed for head-direction cells in rodents and may shed light on how neural systems, in general, perform integration.

Cost, risk, and avoidance of inbreeding in a cooperatively breeding bird.

Inbreeding is often avoided in natural populations by passive processes such as sex-biased dispersal. But, in many social animals, opposite-sexed adult relatives are spatially clustered, generating a risk of incest and hence selection for active inbreeding avoidance. Here we show that, in long-tailed tits (Aegithalos caudatus), a cooperative breeder that risks inbreeding by living alongside opposite-sex relatives, inbreeding carries fitness costs and is avoided by active kin discrimination during mate choice. First, we identified a positive association between heterozygosity and fitness, indicating that inbreeding is costly. We then compared relatedness within breeding pairs to that expected under multiple mate-choice models, finding that pair relatedness is consistent with avoidance of first-order kin as partners. Finally, we show that the similarity of vocal cues offers a plausible mechanism for discrimination against first-order kin during mate choice. Long-tailed tits are known to discriminate between the calls of close kin and nonkin, and they favor first-order kin in cooperative contexts, so we conclude that long-tailed tits use the same kin discrimination rule to avoid inbreeding as they do to direct help toward kin.

The Human Spectrum: A Phenomenological Enquiry within Neurodiversity.

INTRODUCTION: Autism has typically been characterized by its external manifestations rather than experienced phenomenology, with consequent impacts on both research and practice. There have recently been increasing calls for more phenomenological enquiry in autism, but little actual work reported. METHOD: A shared participatory phenomenological self-investigation was conducted, by the four authors, of lived experience across the autistic/non-autistic divide. The sample size was chosen as necessary for the feasibility and acceptability to participants of such work in this context. Roles of "researcher" and "interviewee" were purposefully alternated between participants to establish trust and reciprocity. Initial phenomenological reduction or bracketing was applied to the description and recording of each participant's intimate lived experience in a number of key domains across social relationships, the physical environment, development, and in adult life. These experiences were shared within dialogue to open them to investigation and questioning from the others, with alternating interviewer and respondent roles. A third step synthesized these shared observations across individuals into themes of continuity and difference. RESULTS: A number of emergent themes, such as the need for trust and reliability, and the impact of context on regulation of emotion, sociability, and empathy, showed striking commonalities between all participants. Other themes, such as primary sensory experience and social joining, pointed up more clear differences between autism and non-autism in development and the adult world. Themes of interest-focus and attention were marked by both commonalities and difference. CONCLUSIONS: This shared phenomenological method was taken as a first step within a new area of active investigation in autistic phenomenology. It proved successful in eliciting detailed information on self-experience. The results suggested hypotheses for a new understanding of autism within the wider "human" spectrum of experience; for instance, the common basic need for trust and social connection but striking differences in sensory experience. It suggested that some characteristics long thought intrinsic to autism, such as social mis-perception and reduced empathy, may be alternatively understood as state-dependent outcomes contingent on specific contexts and interactions. Implications are suggested for testing in further research, developmental theory, and intervention practice.

Debate: Neurodiversity, autism and healthcare.

We are at a time of unparalleled flux in our understanding of what autism is and now to respond to it, including our understanding of the role of clinical services. For any clinician working in the context of child development and child mental health services, the majority experience is probably of overwhelming demand, and then perhaps confusion. Referrals for neurodevelopmental conditions, and particularly autism, have become an increasing proportion of UK CAMHS referrals in recent years-with the consequent lengthening of wait times extending to years, sometimes equivalent to the whole length of a child's life up until that point. Services are struggling to develop response strategies to meet user frustration, a task not helped by the fact that most interventions in current use have no good evidence of effectiveness. Consequently, a plethora of local approaches and initiatives have developed. In this article I address these clinical and related issues. I discuss current different uses of the term autism, the relation to intellectual disability, and introduce a conceptualisation of autism as emergent and transactional, which is consistent with current developmental and intervention science. This could bridge between neurodiversity and clinical perspectives and implies a framing of early intervention support that has strong clinical trials evidence and provides the basis for a rational and pre-emptive evidenced care pathway, which I describe.

Dual-output kilohertz pump laser for high-energy picosecond OPCPA.

A dual-output thin-disk picosecond laser operating at 100 W with 1 kHz repetition rate is reported in this Letter. By electronically adjusting the amplitude of the optical seed pulses that are injected into the laser cavity, the energy extracted from the gain medium can be shared between two pulses. Amplified double pulses are subsequently spatially separated into two independent beams by a fast Pockels cell, compressed in one common compressor, and frequency-doubled with ∼70% efficiency. This approach significantly decreases strain on the optics, as well as nonlinear effects, and is advantageous for power scaling.

Individual variation explains ageing patterns in a cooperatively breeding bird, the long-tailed tit Aegithalos caudatus.

Alloparental care in cooperatively breeding species may alter breeder age-specific survival and reproduction and subsequently senescence. The helping behaviour itself might also undergo age-related change, and decisions to help in facultative cooperative breeders are likely to be affected by individual condition. Helpers in long-tailed tits Aegithalos caudatus assist relatives after failing to raise their own brood, with offspring from helped nests being more likely to recruit into the breeding population. Using data collected over 25 years, we examined the age trajectories of survival and reproduction in adult long-tailed tits to determine how these were affected by the presence or absence of helpers and how helper behaviour changed with age. There was evidence for increased reproductive performance with breeder age, but no effect of age on the probability of survival. We found no evidence of significant senescent decline in survival or reproductive performance, although individuals accrued less inclusive fitness in their last year of life. Lifetime reproductive success was positively related to both reproductive life span and body mass. Within a season, breeders that were assisted by helpers enjoyed greater reproductive success through enhanced offspring recruitment in the following year. We found no evidence that age affected an individual's propensity to help, or the amount of indirect fitness accrued through helping. We found a positive correlation between life span and multiple components of reproductive success, suggesting that individual variation in quality underpins age-related variation in fitness in this species. Helping decisions are driven by condition, and lifetime inclusive fitness of immigrants was predicted by body mass. These findings further support individual heterogeneity in quality being a major driver for fitness gains across the life course of long-tailed tits.

Site-dependent regulation of breeding success: Evidence for the buffer effect in the common guillemot, a colonially breeding seabird.

Density-dependent regulation can offer resilience to wild populations experiencing fluctuations in environmental conditions because, at lower population sizes, the average quality of habitats or resources is predicted to increase. Site-dependent regulation is a mechanism whereby individuals breed at the highest quality, most successful, sites, leaving poorer quality, less successful sites vacant. As population size increases, higher quality sites become limiting but when populations decline, lower quality sites are vacated first, offering resilience. This process is known as the 'buffer effect'. However, few studies have tested whether such regulation operates in populations experiencing changes in size and trend. We used data from a population of common guillemots Uria aalge, a colonially breeding seabird, to investigate the relationship between site occupancy probability, site quality and population size and trend. These data were collected at five sub-colonies spanning a 38-year period (1981-2018) comprising phases of population increase, decrease and recovery. We first tested whether site quality and population size in sub-colonies explained which sites were occupied for breeding, and if this was robust to changes in sub-colony trend. We then investigated whether disproportionate use of higher quality sites drove average site quality and breeding success across sub-colony sizes and trends. Finally, we tested whether individuals consistently occupied higher quality sites during periods of decline and recovery. Higher quality sites were disproportionality used when sub-colony size was smaller, resulting in higher average site quality and breeding success at lower population sizes. This relationship was unaffected by changes in sub-colony trend. However, contrary to the predictions of the buffer effect, new sites were established at a similar rate to historically occupied sites during sub-colony decline and recovery despite being of lower quality. Our results provide support for the buffer effect conferring resilience to populations, such that average breeding success was consistently higher at lower population size during all phases of population change. However, this process was tempered by the continued establishment of new, lower quality, sites which could act to slow population recovery after periods when colony size was low.

Epithelial-mesenchymal transition and bi- and multi-nucleated trophoblast cell formation in ovine conceptuses during the peri-implantation period.

Epithelial-mesenchymal transition (EMT), which is common in cancer metastasis, is also observed during developmental processes such as embryo implantation into the maternal endometrium in humans and rodents. However, this process has not been well characterized in the non-invasive type of implantation that occurs in ruminants. To understand whether EMT occurs in ruminant ungulates, ovine conceptuses (embryo plus extraembryonic membranes) from days 15 (P15: pre-attachment), 17 (P17: during attachment), and 21 (P21: post-attachment, day 0 = day of estrus) were evaluated. RNA-seq analysis revealed that the expression of EMT-related transcripts increased on P21. Real-time PCR and western blotting analyses indicated that levels of transcripts and proteins indicative of mesenchyme-related molecules increased on P21, but a minor expression of epithelium-related molecules remained. Immunohistochemical analysis revealed that E-cadherin (CDH1) was localized in the elongated trophectoderm on P15 and P17. On P21, CDH1 was localized to the trophectoderm and on the conceptus cells undergoing differentiation. Vimentin (VIM) was localized in the uterine stroma on P15 and P17, and its expression was observed at the edge of elongating trophoblast on P21. Further, it was found that some bi-nucleated trophoblast cells were present on P17; however, numerous bi- and multi-nucleated trophoblast cells on the uterine epithelium or next to the uterine stroma were found on P21. A minor expression of pregnancy-associated glycoprotein (PAG) transcripts was found on P15 and P17, but a definitive expression of PAGs, transcripts, and proteins was found on P21. Although further investigation is required, these observations indicate that bi-nucleated trophoblast cell formation begins on the day conceptus implantation to the maternal endometrium is initiated, followed by EMT in trophoblast cells. These results suggest that these sequential events are required if pregnancy is to be established in ruminants.

Development of a cost of illness inventory questionnaire for children with autism spectrum disorder in South Asia.

BACKGROUND: The economic burden of autism is substantial and includes a range of costs, including healthcare, education, productivity losses, informal care and respite care, among others. In India, approximately, 2 million children aged 2-9 years have autism. Given the likely substantial burden of illness and the need to identify effective and cost-effective interventions, this research aimed to produce a comprehensive cost of illness inventory (COII) suitable for children with autism in South Asia (India) to support future research. METHODS: A structured and iterative design process was followed to create the COII, including literature reviews, interviews with caregivers, pilot testing and translation. Across the development of the COII, thirty-two families were involved in the design and piloting of the tool. The COII was forward translated (from English to Hindi) and back translated. Each stage of the process of development of the COII resulted in the further refinement of the tool. RESULTS: Domains covered in the final COII include education, childcare, relocation, healthcare contacts (outpatient, inpatient, medical emergencies, investigations and medication), religious retreats and rituals, specialist equipment, workshops and training, special diet, support and care, certification, occupational adjustments and government rebates/schemes. Administration and completion of the COII determined it to be feasible to complete in 35 minutes by qualified and trained researchers. The final COII is hosted by REDCap Cloud and is a bilingual instrument (Hindi and English). CONCLUSIONS: The COII was developed using experiences gathered from an iterative process in a metropolitan area within the context of one low- and middle-income country (LMIC) setting, India. Compared to COII tools used for children with autism in high-income country settings, additional domains were required, such as complimentary medication (e.g. religious retreats and homeopathy). The COII will allow future research to quantify the cost of illness of autism in India from a broad perspective and will support relevant economic evaluations. Understanding the process of developing the questionnaire will help researchers working in LMICs needing to adapt the current COII or developing similar questionnaires.

Linking global drivers of agricultural trade to on-the-ground impacts on biodiversity.

Consumption of globally traded agricultural commodities like soy and palm oil is one of the primary causes of deforestation and biodiversity loss in some of the world's most species-rich ecosystems. However, the complexity of global supply chains has confounded efforts to reduce impacts. Companies and governments with sustainability commitments struggle to understand their own sourcing patterns, while the activities of more unscrupulous actors are conveniently masked by the opacity of global trade. We combine state-of-the-art material flow, economic trade, and biodiversity impact models to produce an innovative approach for understanding the impacts of trade on biodiversity loss and the roles of remote markets and actors. We do this for the production of soy in the Brazilian Cerrado, home to more than 5% of the world´s species. Distinct sourcing patterns of consumer countries and trading companies result in substantially different impacts on endemic species. Connections between individual buyers and specific hot spots explain the disproportionate impacts of some actors on endemic species and individual threatened species, such as the particular impact of European Union consumers on the recent habitat losses for the iconic giant anteater (Myrmecophaga tridactyla). In making these linkages explicit, our approach enables commodity buyers and investors to target their efforts much more closely to improve the sustainability of their supply chains in their sourcing regions while also transforming our ability to monitor the impact of such commitments over time.