Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection.

Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV), and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses, including SUDV, and a cross-reactive mAb that completely protected guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections.

A synergistic mindsets intervention protects adolescents from stress.

Social-evaluative stressors-experiences in which people feel they could be judged negatively-pose a major threat to adolescent mental health1-3 and can cause young people to disengage from stressful pursuits, resulting in missed opportunities to acquire valuable skills. Here we show that replicable benefits for the stress responses of adolescents can be achieved with a short (around 30-min), scalable 'synergistic mindsets' intervention. This intervention, which is a self-administered online training module, synergistically targets both growth mindsets4 (the idea that intelligence can be developed) and stress-can-be-enhancing mindsets5 (the idea that one's physiological stress response can fuel optimal performance). In six double-blind, randomized, controlled experiments that were conducted with secondary and post-secondary students in the United States, the synergistic mindsets intervention improved stress-related cognitions (study 1, n = 2,717; study 2, n = 755), cardiovascular reactivity (study 3, n = 160; study 4, n = 200), daily cortisol levels (study 5, n = 118 students, n = 1,213 observations), psychological well-being (studies 4 and 5), academic success (study 5) and anxiety symptoms during the 2020 COVID-19 lockdowns (study 6, n = 341). Heterogeneity analyses (studies 3, 5 and 6) and a four-cell experiment (study 4) showed that the benefits of the intervention depended on addressing both mindsets-growth and stress-synergistically. Confidence in these conclusions comes from a conservative, Bayesian machine-learning statistical method for detecting heterogeneous effects6. Thus, our research has identified a treatment for adolescent stress that could, in principle, be scaled nationally at low cost.

A values-aligned intervention fosters growth mindset-supportive teaching and reduces inequality in educational outcomes.

Group-based educational disparities are smaller in classrooms where teachers express a belief that students can improve their abilities. However, a scalable method for motivating teachers to adopt such growth mindset-supportive teaching practices has remained elusive. In part, this is because teachers often already face overwhelming demands on their time and attention and have reason to be skeptical of the professional development advice they receive from researchers and other experts. We designed an intervention that overcame these obstacles and successfully motivated high-school teachers to adopt specific practices that support students' growth mindsets. The intervention used the values-alignment approach. This approach motivates behavioral change by framing a desired behavior as aligned with a core value-one that is an important criterion for status and admiration in the relevant social reference group. First, using qualitative interviews and a nationally representative survey of teachers, we identified a relevant core value: inspiring students' enthusiastic engagement with learning. Next, we designed a ~45-min, self-administered, online intervention that persuaded teachers to view growth mindset-supportive practices as a way to foster such student engagement and thus live up to that value. We randomly assigned 155 teachers (5,393 students) to receive the intervention and 164 teachers (6,167 students) to receive a control module. The growth mindset-supportive teaching intervention successfully promoted teachers' adoption of the suggested practices, overcoming major barriers to changing teachers' classroom practices that other scalable approaches have failed to surmount. The intervention also substantially improved student achievement in socioeconomically disadvantaged classes, reducing inequality in educational outcomes.

Academic publishing requires linguistically inclusive policies.

Scientific knowledge is produced in multiple languages but is predominantly published in English. This practice creates a language barrier to generate and transfer scientific knowledge between communities with diverse linguistic backgrounds, hindering the ability of scholars and communities to address global challenges and achieve diversity and equity in science, technology, engineering and mathematics (STEM). To overcome those barriers, publishers and journals should provide a fair system that supports non-native English speakers and disseminates knowledge across the globe. We surveyed policies of 736 journals in biological sciences to assess their linguistic inclusivity, identify predictors of inclusivity, and propose actions to overcome language barriers in academic publishing. Our assessment revealed a grim landscape where most journals were making minimal efforts to overcome language barriers. The impact factor of journals was negatively associated with adopting a number of inclusive policies whereas ownership by a scientific society tended to have a positive association. Contrary to our expectations, the proportion of both open access articles and editors based in non-English speaking countries did not have a major positive association with the adoption of linguistically inclusive policies. We proposed a set of actions to overcome language barriers in academic publishing, including the renegotiation of power dynamics between publishers and editorial boards.

Collagen Networks under Indentation and Compression Behave Like Cellular Solids.

Simple synthetic and natural hydrogels can be formulated to have elastic moduli that match biological tissues, leading to their widespread application as model systems for tissue engineering, medical device development, and drug delivery vehicles. However, two different hydrogels having the same elastic modulus but differing in microstructure or nanostructure can exhibit drastically different mechanical responses, including their poroelasticity, lubricity, and load bearing capabilities. Here, we investigate the mechanical response of collagen-1 networks to local and bulk compressive loads. We compare these results to the behavior of polyacrylamide, a fundamentally different class of hydrogel network consisting of flexible polymer chains. We find that the high bending rigidity of collagen fibers, which suppresses entropic bending fluctuations and osmotic pressure, facilitates the bulk compression of collagen networks under infinitesimal applied stress. These results are fundamentally different from the behavior of flexible polymer networks in which the entropic thermal fluctuations of the polymer chains result in an osmotic pressure that must first be overcome before bulk compression can occur. Furthermore, we observe minimal transverse strain during the axial loading of collagen networks, a behavior reminiscent of open-celled cellular solids. Inspired by these results, we applied mechanical models of cellular solids to predict the elastic moduli of the collagen networks and found agreement with the moduli values measured through contact indentation. Collectively, these results suggest that unlike flexible polymer networks that are often considered incompressible, collagen hydrogels behave like rigid porous solids that volumetrically compress and expel water rather than spreading laterally under applied normal loads.

Diversity in invasive species management networks.

Effective management of invasive species requires collaboration across a range of stakeholders. These stakeholders exhibit diverse attributes such as organisation types, operational scale, objectives, and roles within projects. Identifying the diverse attributes of stakeholders is beneficial for increasing collaboration success while minimising potential conflicts among multiple stakeholders when managing invasive species across landscapes. Despite the increasing number of studies on connections among stakeholders, there is little understanding of the diverse attributes of stakeholders involved in invasive species management. This is a notable gap because the diversity of stakeholders is one of the significant factors that can influence collaboration success. To bridge this knowledge gap, we used a social network approach to identify the attributes of stakeholders that influence their participation in collaborations using a case study of invasive wild pig (Sus scrofa) management in Queensland, Australia. Our findings suggest that even though the overall stakeholder network was diverse, the stakeholder network at the project level exhibited a lack of diversity on average, particularly regarding the scale of operation and type of organisation. In other words, stakeholders are highly likely to form ties in projects involving other stakeholders from similar types of organisations or operational scales. We suggest that targeting a greater diversity of stakeholders across types of organisations and scales of operations might enhance the success of collaborative invasive species management.

Investigating the Sequence Specific Adsorption Behavior of Polypeptides at the Solid/Liquid Interface.

Polymer adsorption at the solid/liquid interface depends not only on the chemical composition of the polymer but also on the specific placement of the monomers along the polymer sequence. However, challenges in designing polymers with well-controlled sequences have limited explorations into the role of polymer sequence on adsorption behavior to molecular simulations. Here, we demonstrate how the sequence control offered by polypeptide synthesis can be utilized to study the effects small changes in polymer sequence have on polymer adsorption behavior at the solid/liquid interface. Through a combination of quartz crystal microbalance with dissipation monitoring and total internal reflection ellipsometry, we study the adsorption behavior of three polypeptides, consisting of 90% lysine and 10% cysteine, onto a gold surface. We find different mechanisms are responsible for the adsorption of polypeptides and the resulting conformation on the surface. The initial adsorption of the polypeptides is driven by electrostatic interactions between the polylysine and the gold surface. Once adsorbed, the cysteine undergoes a thiol-Au reaction with the surface, altering the conformation of the polymer layer. Our findings suggest the conformation of the polypeptide layer is dependent on the placement of the cysteines within the sequence; polypeptide chains with evenly spaced cysteine groups adopt a more tightly bound "train" conformation as compared to polypeptides with closely grouped cysteine groups. We envision that the methodologies presented here to study sequence specific adsorption behaviors using polypeptides could be a valuable tool to complement molecular simulations studies.

Enhanced study of facial soft tissues using a novel large scale histology technique.

The safety and effectiveness of facial cosmetic surgery procedures are dependent on detailed 3D understanding of the complex surgical anatomy of the face. Traditional, small sample size anatomical dissection studies have limitations in providing definitive clarification of the fascial layers of the face, and especially in their relationship with the facial nerve, and their reaction to surgical manipulation. The objective study of large tissue areas is required to effectively demonstrate the broader architecture. Conventional histology techniques were modified to handle extraordinarily large tissue samples to fulfill this requirement. Full-thickness soft tissue samples (skin to bone) of maximum length 18 cm, width 4 cm, and tissue thickness 1 cm, were harvested from 20 hemifaces of 15 fresh human cadavers (mean age at death = 81 years). After fixation, the samples were processed with an automated processor using paraffin wax for 156 h, sectioned at 30 µm, collected on gelatin-chromium-coated glass slides, stained with a Masson's Trichrome technique and photographed. Using this technique, excellent visualization was obtained of the fascial connective tissue and its relationship with the facial mimetic muscles, muscles of mastication and salivary glands in 73 large histological slides. The resulting slides improved the study of the platysma and superficial musculo-aponeurotic system (SMAS), the spaces and ligaments, the malar fat pad, and the facial nerve in relations to the deep fascia. Additionally, surgically induced changes in the soft-tissue organization were successfully visualized. This technique enables improved insight into the broad structural architecture and histomorphology of large-scale facial tissues.

How success is evaluated in collaborative invasive species management: A systematic review.

Invasive species are one of the most pressing global challenges for biodiversity and agriculture. They can cause species extinctions, ecosystem alterations, crop damage, and spread harmful diseases across broad regions. Overcoming this challenge requires collaborative management efforts that span multiple land tenures and jurisdictions. Despite evidence on the importance and approaches to collaboration, there is little understanding of how success is evaluated in the invasive species management literature. This is a major gap, considering evaluating success is crucial for enhancing the efficacy of future management projects. To overcome this knowledge gap, we systematically reviewed the published literature to identify the stages at which success is evaluated - that is, the Process stage (collaborative management actions and Processes), Outputs stage (results of management actions to protect environmental, economic, and social values) and Outcomes stage (effects of Outputs on environmental, economic, and social values) of collaborative invasive species management projects. We also assessed what indicators were used to identify success and whether these evaluations vary across different characteristics of collaborative invasive species management. Our literature search detected 1406 papers, of which 58 met our selection criteria. Out of these, the majority of papers evaluated success across two stages (n = 25, 43.1%), whereas only ten (17.2%) papers evaluated success across all stages. Outputs were the most commonly evaluated stage (n = 40, 68.9%). The most widely used indicators of success for these stages included increased collaboration of stakeholders (Process stage), the number of captured/eradicated/controlled invasive species (Outputs stage) and change in biodiversity values, such as the number of threatened species (Outcomes stage). Most indicators of success were environmentally focused. We highlight the need to align the indicators of success and evaluation stages with the fundamental objectives of the projects to increase the effectiveness of evaluations and thereby maximise the benefits of collaborative invasive species management.

Invasive wild pigs (Sus scrofa) as a human-mediated source of soil carbon emissions: Uncertainties and future directions.

Invasive wild pigs (Sus scrofa) have been spread by humans outside of their native range and are now established on every continent except Antarctica. Through their uprooting of soil, they affect societal and environmental values. Our recent article explored another threat from their soil disturbance: greenhouse gas emissions (O'Bryan et al., Global Change Biology, 2021). In response to our paper, Don (Global Change Biology, 2021) claims there is no threat to global soil carbon stocks by wild pigs. While we did not investigate soil carbon stocks, we examine uncertainties regarding soil carbon emissions from wild pig uprooting and their implications for management and future research.

Unrecognized threat to global soil carbon by a widespread invasive species.

Most of Earth's terrestrial carbon is stored in the soil and can be released as carbon dioxide (CO2 ) when disturbed. Although humans are known to exacerbate soil CO2 emissions through land-use change, we know little about the global carbon footprint of invasive species. We predict the soil area disturbed and resulting CO2 emissions from wild pigs (Sus scrofa), a pervasive human-spread vertebrate that uproots soil. We do this using models of wild pig population density, soil damage, and their effect on soil carbon emissions. Our models suggest that wild pigs are uprooting a median area of 36,214 km2 (mean of 123,517 km2 ) in their non-native range, with a 95% prediction interval (PI) of 14,208 km2 -634,238 km2 . This soil disturbance results in median emissions of 4.9 million metric tonnes (MMT) CO2 per year (equivalent to 1.1 million passenger vehicles or 0.4% of annual emissions from land use, land-use change, and forestry; mean of 16.7 MMT) but that it is highly uncertain (95% PI, 0.3-94 MMT CO2 ) due to variability in wild pig density and soil dynamics. This uncertainty points to an urgent need for more research on the contribution of wild pigs to soil damage, not only for the reduction of anthropogenically related carbon emissions, but also for co-benefits to biodiversity and food security that are crucial for sustainable development.

Hotspots of human impact on threatened terrestrial vertebrates.

Conserving threatened species requires identifying where across their range they are being impacted by threats, yet this remains unresolved across most of Earth. Here, we present a global analysis of cumulative human impacts on threatened species by using a spatial framework that jointly considers the co-occurrence of eight threatening processes and the distribution of 5,457 terrestrial vertebrates. We show that impacts to species are widespread, occurring across 84% of Earth's surface, and identify hotspots of impacted species richness and coolspots of unimpacted species richness. Almost one-quarter of assessed species are impacted across >90% of their distribution, and approximately 7% are impacted across their entire range. These results foreshadow localised extirpations and potential extinctions without conservation action. The spatial framework developed here offers a tool for defining strategies to directly mitigate the threats driving species' declines, providing essential information for future national and global conservation agendas.

Correction: Hotspots of human impact on threatened terrestrial vertebrates.

[This corrects the article DOI: 10.1371/journal.pbio.3000158.].

Nanoparticle dynamics in hydrogel networks with controlled defects.

The effect of nanoscale defects on nanoparticle dynamics in defective tetra-poly(ethylene glycol) (tetra-PEG) hydrogels is investigated using single particle tracking. In a swollen nearly homogeneous hydrogel, PEG-functionalized quantum dot (QD) probes with a similar hydrodynamic diameter (dh = 15.1 nm) to the mesh size (〈ξs〉 = 16.3 nm), are primarily immobile. As defects are introduced to the network by reaction-tuning, both the percentage of mobile QDs and the size of displacements increase as the number and size of the defects increase with hydrolysis time, although a large portion of the QDs remain immobile. To probe the effect of nanoparticle size on dynamics in defective networks, the transport of dh = 47.1 nm fluorescent polystyrene (PS) and dh = 9.6 nm PEG-functionalized QDs is investigated. The PS nanoparticles are immobile in all hydrogels, even in highly defective networks with an open structure. Conversely, the smaller QDs are more sensitive to perturbations in the network structure with an increased percentage of mobile particles and larger diffusion coefficients compared to the larger QDs and PS nanoparticles. The differences in nanoparticle mobility as a function of size suggests that particles of different sizes probe different length scales of the defects, indicating that metrics such as the confinement ratio alone cannot predict bulk dynamics in these systems. This study provides insight into designing hydrogels with controlled transport properties, with particular importance for degradable hydrogels for drug delivery applications.

Replicator degrees of freedom allow publication of misleading failures to replicate.

In recent years, the field of psychology has begun to conduct replication tests on a large scale. Here, we show that "replicator degrees of freedom" make it far too easy to obtain and publish false-negative replication results, even while appearing to adhere to strict methodological standards. Specifically, using data from an ongoing debate, we show that commonly exercised flexibility at the experimental design and data analysis stages of replication testing can make it appear that a finding was not replicated when, in fact, it was. The debate that we focus on is representative, on key dimensions, of a large number of other replication tests in psychology that have been published in recent years, suggesting that the lessons of this analysis may be far reaching. The problems with current practice in replication science that we uncover here are particularly worrisome because they are not adequately addressed by the field's standard remedies, including preregistration. Implications for how the field could develop more effective methodological standards for replication are discussed.

Functional Interactions of Kluyveromyces lactis Telomerase Reverse Transcriptase with the Three-Way Junction and the Template Domains of Telomerase RNA.

The ribonucleoprotein telomerase contains two essential components: telomerase RNA (TER) and telomerase reverse transcriptase (TERT, Est2 in yeast). A small portion of TER, termed the template, is copied by TERT onto the chromosome ends, thus compensating for sequence loss due to incomplete DNA replication and nuclease action. Although telomerase RNA is highly divergent in sequence and length across fungi and mammals, structural motifs essential for telomerase function are conserved. Here, we show that Est2 from the budding yeast Kluyveromyces lactis (klEst2) binds specifically to an essential three-way junction (TWJ) structure in K. lactis TER, which shares a conserved structure and sequence features with the essential CR4-CR5 domain of vertebrate telomerase RNA. klEst2 also binds specifically to the template domain, independently and mutually exclusive of its interaction with TWJ. Furthermore, we present the high-resolution structure of the klEst2 telomerase RNA-binding domain (klTRBD). Mutations introduced in vivo in klTRBD based on the solved structure or in TWJ based on its predicted RNA structure caused severe telomere shortening. These results demonstrate the conservation and importance of these domains and the multiple protein-RNA interactions between Est2 and TER for telomerase function.

Capillary forces drive buckling, plastic deformation, and break-up of 3D printed beams.

Capillary forces acting at the interfaces of soft materials lead to deformations over the scale of the elastocapillary length. When surface stresses exceed a material's yield stress, a plastocapillary effect is expected to arise, resulting in yielding and plastic deformation. Here, we explore the interfacial instabilities of 3D-printed fluid and elastic beams embedded within viscoelastic fluids and elastic solid support materials. Interfacial instabilities are driven by the immiscibility between the paired phases or their solvents. We find that the stability of an embedded structure is predicted from the balance between the yield stress of the elastic solid, τy, the apparent interfacial tension between the materials, γ', and the radius of the beam, r, such that τy > γ'/r. When the capillary forces are sufficiently large, we observe yielding and failure of the 3D printed beams. Furthermore, we observe new coiling and buckling instabilities emerging when elastic beams are embedded within viscous fluid support materials. The coiling behavior appear analogous to elastic rope coiling whereas the buckling instability follows the scaling behavior predicted from Euler-Bernoulli beam theory.

The importance of Indigenous Peoples' lands for the conservation of terrestrial mammals.

Indigenous Peoples' lands cover over one-quarter of Earth's surface, a significant proportion of which is still free from industrial-level human impacts. As a result, Indigenous Peoples and their lands are crucial for the long-term persistence of Earth's biodiversity and ecosystem services. Yet, information on species composition on these lands globally remains largely unknown. We conducted the first comprehensive analysis of terrestrial mammal composition across mapped Indigenous lands based on data on area of habitat (AOH) for 4460 mammal species assessed by the International Union for Conservation of Nature. We overlaid each species' AOH on a current map of Indigenous lands and found that 2695 species (60% of assessed mammals) had ≥10% of their ranges on Indigenous Peoples' lands and 1009 species (23%) had >50% of their ranges on these lands. For threatened species, 473 (47%) occurred on Indigenous lands with 26% having >50% of their habitat on these lands. We also found that 935 mammal species (131 categorized as threatened) had ≥ 10% of their range on Indigenous Peoples' lands that had low human pressure. Our results show how important Indigenous Peoples' lands are to the successful implementation of conservation and sustainable development agendas worldwide.

La Importancia de las Tierras de los Pueblos Indígenas para la Conservación de los Mamíferos Terrestres Resumen Las tierras pertenecientes a pueblos indígenas cubren más de un cuarto de la superficie del planeta, una proporción importante que se encuentra aún libre de impactos humanos a nivel industrial. Como resultado, los pueblos indígenas y sus tierras son cruciales para la persistencia a largo plazo de la biodiversidad en la Tierra y de los servicios ecosistemicos. Sin embargo, la información sobre la composición de especies en estas tierras a nivel mundial todavía permanece desconocida en su mayoría. Realizamos el primer análisis integral de la composición de mamíferos terrestres a lo largo de las tierras indígenas mapeadas con base en los datos sobre el área del hábitat (ADH) de 4,460 especies de mamíferos valorados por la Unión Internacional para la Conservación de la Naturaleza. Sobrepusimos el ADH de cada especie en un mapa actual de tierras indígenas y encontramos que 2,695 especies (60% de los mamíferos valorados) tienen ≥10% de su distribución dentro de tierras de pueblos indígenas y que 1,009 especies (23%) tienen >50% de su distribución dentro de estas tierras. De las especies amenazadas, 473 (47%) ocurrieron en tierras indígenas.También descubrimos que 935 especies de mamíferos (131 categorizadas como amenazadas) tienen ≥ 10% de su distribución dentro de tierras de pueblos indígenas con baja presión humana. Nuestros resultados muestran cuán importantes son las tierras de los pueblos indígenas para la implementación exitosa de la conservación y las agendas globales de desarrollo sustentable.

3D aggregation of cells in packed microgel media.

In both natural and applied contexts, investigating cell self-assembly and aggregation within controlled 3D environments leads to improved understanding of how structured cell assemblies emerge, what determines their shapes and sizes, and whether their structural features are stable. However, the inherent limits of using solid scaffolding or liquid spheroid culture for this purpose restrict experimental freedom in studies of cell self-assembly. Here we investigate multi-cellular self-assembly using a 3D culture medium made from packed microgels as a bridge between the extremes of solid scaffolds and liquid culture. We find that cells dispersed at different volume fractions in this microgel-based 3D culture media aggregate into clusters of different sizes and shapes, forming large system-spanning networks at the highest cell densities. We find that the transitions between different states of assembly can be controlled by the level of cell-cell cohesion and by the yield stress of the packed microgel environment. Measurements of aggregate fractal dimension show that those with increased cell-cell cohesion are less sphere-like and more irregularly shaped, indicating that cell stickiness inhibits rearrangements in aggregates, in analogy to the assembly of colloids with strong cohesive bonds. Thus, the effective surface tension often expected to emerge from increased cell cohesion is suppressed in this type of cell self-assembly.

Correction: 3D aggregation of cells in packed microgel media.

Correction for '3D aggregation of cells in packed microgel media' by Cameron D. Morley et al., Soft Matter, 2020, DOI: 10.1039/d0sm00517g.