From the Cover: Photic memory for executive brain responses

Light is a powerful stimulant for human alertness and cognition, presumably acting through a photoreception system that heavily relies on the photopigment melanopsin. In humans, evidence for melanopsin involvement in light-driven cognitive stimulation remains indirect, due to the difficulty to selectively isolate its contribution. Therefore, a role for melanopsin in human cognitive regulation remains to be established. Here, sixteen participants underwent consecutive and identical functional MRI recordings, during which they performed a simple auditory detection task and a more difficult auditory working memory task, while continuously exposed to the same test light (515 nm). We show that the impact of test light on executive brain responses depends on the wavelength of the light to which individuals were exposed prior to each recording. Test-light impact on executive responses in widespread prefrontal areas and in the pulvinar increased when the participants had been exposed to longer (589 nm), but not shorter (461 nm), wavelength light, more than 1 h before. This wavelength-dependent impact of prior light exposure is consistent with recent theories of the light-driven melanopsin dual states. Our results emphasize the critical role of light for cognitive brain responses and are, to date, the strongest evidence in favor of a cognitive role for melanopsin, which may confer a form of “photic memory” to human cognitive brain function.One of the major advances in neuroscience in the last decade was the discovery of a novel class of ocular photoreceptors: the intrinsically photosensitive retinal ganglion cells (ipRGCs) that express melanopsin (1), a photopigment maximally sensitive to blue light (2–4). The finding of a new inner retinal photopigment has led to a complete reexamination of the role of the eye, which is now viewed as the site of two distinct photoreceptive systems: one for vision, based mainly on rods and cones, and one for the non–image-forming functions of light, primarily dependent on melanopsin. Animal data have demonstrated that the melanopsin photoreception system directly mediates the impact of light on sleep/wake regulation (5). In humans, light also regulates sleep and wakefulness and constitutes a powerful stimulant for alertness and cognition (6, 7). However, evidence for the involvement of melanopsin in this human light-driven stimulating impact remains indirect (8, 9), due to the difficulty of selectively isolating contributions of ipRGCs, rods, and/or cones. Therefore, the contribution of melanopsin to the impact of light on human alertness and cognition remains to be established.Photon capture by rod and cone photopigments converts the chromophore from a photosensitive to a photoinsensitive state, triggering phototransduction (10). To regain light sensitivity, the enzymatic retinoid cycle within the retinal pigment epithelium is required for regeneration of the chromophore back to the light-sensitive state. In contrast, melanopsin is a dual-state photopigment, in which photons drive both processes of phototransduction and part of chromophore regeneration (10–12). Recent rodent and human data suggest that exposure to longer wavelength light (590–620 nm; orange–red) triggers melanopsin chromophore regeneration and increases overall subsequent intrinsic photosensitivity of ipRGCs (13, 14). Conversely, exposure to shorter wavelength light (∼480 nm; blue) favors phototransduction and decreases overall subsequent ipRGCs intrinsic photosensitivity (13, 14). At the physiological level (12), the existence of two stable photon absorption states allows photoconversion of melanopsin between the 11-cis and all-trans isoforms of the photopigment-bound chromophore to drive both photic responses and restoration of light responsiveness (12, 14), similar to processes of invertebrate rhabdomeric photopigments (15). Melanopsin would thus act as a light-sensitive switch, with the 11-cis isoform maximally sensitive to 480-nm photons, whereas the all-trans isoform is most efficiently transformed by longer wavelengths. Prior short-wavelength light would therefore decrease the overall proportion of “phototransduction units” of ipRGCs, whereas longer-wavelength photons (∼590–620 nm) would increase the overall proportion of phototransduction units. At intermediate wavelengths near 515 nm, the two processes are in equilibrium, with the two effects counterbalancing each other (“isosbestic value”) (15).The present study aimed at determining melanopsin influence on human cognitive brain function based on this photic history hypothesis of its dual states. Based on the spectral sensitivity of the two states of melanopsin, we hypothesized that the impact of a given test light on cognitive brain responses would be increased, decreased, or intermediate after prior exposure to longer, shorter, or intermediate wavelength light, respectively.     

From the Cover: Species fluctuations sustained by a cyclic succession at the edge of chaos

Although mathematical models and laboratory experiments have shown that species interactions can generate chaos, field evidence of chaos in natural ecosystems is rare. We report on a pristine rocky intertidal community located in one of the world’s oldest marine reserves that has displayed a complex cyclic succession for more than 20 y. Bare rock was colonized by barnacles and crustose algae, they were overgrown by mussels, and the subsequent detachment of the mussels returned bare rock again. These processes generated irregular species fluctuations, such that the species coexisted over many generations without ever approaching a stable equilibrium state. Analysis of the species fluctuations revealed a dominant periodicity of about 2 y, a global Lyapunov exponent statistically indistinguishable from zero, and local Lyapunov exponents that alternated systematically between negative and positive values. This pattern indicates that the community moved back and forth between stabilizing and chaotic dynamics during the cyclic succession. The results are supported by a patch-occupancy model predicting similar patterns when the species interactions were exposed to seasonal variation. Our findings show that natural ecosystems can sustain continued changes in species abundances and that seasonal forcing may push these nonequilibrium dynamics to the edge of chaos.Since ancient times, it is often argued that undisturbed ecosystems will approach some form of stable equilibrium, at which the populations of the species are maintained at relatively constant numbers (1, 2). However, ecological studies have criticized this idea of “the balance of nature” by pointing out that species abundances in natural ecosystems may remain in a perpetual state of change (3–5). For instance, intransitive competition can lead to a cyclic succession, supporting continued changes in community composition as the dominance is passed on from one species to another in an eternal loop (6–10). Recent theory predicts that seasonal forcing of a cyclic succession can produce quasiperiodic and chaotic species fluctuations (11, 12). Chaos has attracted ecologists’ attention, because it limits the long-term predictability of species abundances (13) and because these nonequilibrium dynamics can potentially sustain a high biodiversity (9). Chaos is predicted by various mathematical models (9, 14–16) and has been found in laboratory experiments with insect populations (17), microbial food webs (18), and plankton communities (5). However, field evidence of chaos in natural ecosystems is rare (19–21) and has never been documented in relation to cyclic succession.Chaos is commonly described as bounded aperiodic dynamics of a deterministic system that exhibits sensitive dependence on initial conditions (22). Sensitivity to initial conditions implies that small initial differences will grow exponentially in time, such that long-term prediction becomes impossible. In practice, however, a clear distinction between deterministic and stochastic fluctuations is often impossible, because the intrinsic dynamics of natural systems are influenced by exogenous stochastic variation. For instance, species fluctuations are not only caused by competition and predation but also affected by “environmental noise” generated by stochastic variation in weather conditions. During recent decades, considerable advances have been made in the analysis of chaos in the presence of noise (23–25). In particular, sensitive dependence on initial conditions can be estimated for noisy systems using Lyapunov exponents that quantify the extent to which environmental perturbations are amplified (or damped) by the intrinsic dynamics of the system.Here, we investigate the species dynamics of a rocky intertidal community in the Cape Rodney-Okakari Point Marine Reserve on the North Island of New Zealand (Fig. 1A). This reserve was established in 1975 as the first marine reserve in New Zealand. It offers ideal conditions for long-term studies of species interactions, because anthropogenic impacts have been kept to a minimum for several decades (26, 27). The rocky intertidal community is dominated by three sessile species: the honeycomb barnacle Chamaesipho columna (Spengler, 1790), the crustose brown alga Ralfsia cf confusa (described as Pseudolithoderma sp. in ref. 28), and the little black mussel Xenostrobus pulex (Lamarck, 1819). Interactions between these species have been described in previous studies (28–30). Barnacles colonize bare rock by gregarious settlement, developing extensive sheets that cover the rocky surface (29). Crustose algae settle on top of the barnacles but do not harm them. Rather, the crustose algae leave space for the barnacles’ waving cirri and benefit from nutrients released by barnacles (28). Xenostrobus mussel larvae cannot settle on smooth bare rock, but they settle gregariously on top of barnacles and crustose algae (29, 30). Xenostrobus mussels subsequently develop a dense carpet, killing the barnacles underneath. After the dead barnacles detach from the underlying rock, the mussel carpet is no longer anchored to any solid surface, and it is washed away by the daily tides (29). Hence, bare rock becomes available again, and the species succession starts anew (Fig. 1B).Open in a separate windowFig. 1.The rocky intertidal community. (A) Aerial view of the study site at Goat Island Bay. (B) Cyclic succession at the rocky intertidal site. First, barnacles settle on bare rock, and second, crustose algae invade. Third, mussels settle on top of the barnacles and crustose algae, forming a dense carpet that smothers the barnacles and algae underneath. Fourth, the mussels detach, bare rock becomes available again, and the cycle restarts. Drawn by Jan van Arkel (University of Amsterdam, Amsterdam, The Netherlands). (C) Time series were obtained from a permanent grid consisting of 20 plots and five nodes (A–E). The percentages of cover of barnacles, crustose algae, and bare rock were monitored in the plots, whereas mussel cover was estimated from photographs of the nodes. Ten plots and five nodes within the red line were used for the time series analysis.This paper analyzes the species fluctuations resulting from this hypothesized cyclic succession. Species abundances (expressed as percentage of cover) were monitored on a monthly basis for more than 20 y using a permanent grid (Fig. 1C and SI Appendix, Figs. S1–S5). We use the time series to determine common periodicities in the species fluctuations indicative of a cyclic succession and estimate local and global Lyapunov exponents as indicators of the potential presence of chaos. Finally, we compare the obtained results against a simple patch-occupancy model to assess whether the species interactions described above can, indeed, produce a cyclic succession characterized by chaotic species fluctuations.     

From the Cover: PNAS Plus: Intrathecal gene therapy rescues a model of demyelinating peripheral neuropathy

Inherited demyelinating peripheral neuropathies are progressive incurable diseases without effective treatment. To develop a gene therapy approach targeting myelinating Schwann cells that can be translatable, we delivered a lentiviral vector using a single lumbar intrathecal injection and a myelin-specific promoter. The human gene of interest, GJB1, which is mutated in X-linked Charcot–Marie–Tooth Disease (CMT1X), was delivered intrathecally into adult Gjb1-null mice, a genetically authentic model of CMT1X that develops a demyelinating peripheral neuropathy. We obtained widespread, stable, and cell-specific expression of connexin32 in up to 50% of Schwann cells in multiple lumbar spinal roots and peripheral nerves. Behavioral and electrophysiological analysis revealed significantly improved motor performance, quadriceps muscle contractility, and sciatic nerve conduction velocities. Furthermore, treated mice exhibited reduced numbers of demyelinated and remyelinated fibers and fewer inflammatory cells in lumbar motor roots, as well as in the femoral motor and sciatic nerves. This study demonstrates that a single intrathecal lentiviral gene delivery can lead to Schwann cell-specific expression in spinal roots extending to multiple peripheral nerves. This clinically relevant approach improves the phenotype of an inherited neuropathy mouse model and provides proof of principle for treating inherited demyelinating neuropathies.Inherited demyelinating neuropathies result from genetic defects in a variety of genes that are expressed by myelinating Schwann cells (1). These mutations are thought to cause demyelination in a cell-autonomous manner. Recessively inherited disorders cause loss of function, and dominantly inherited disorders cause haplotype insufficiency or toxic gain of function (2, 3). Achieving a therapeutic correction of these genetic defects requires either gene replacement or gene silencing approaches, ideally confined to myelinating Schwann cells (4).Various techniques for gene delivery to peripheral nerves have been attempted, including adenoviral (AV) and adeno-associated viral (AAV) vectors and ubiquitous promoters (5). Intramuscular and direct intraneural injections help restrict expression to Schwann cells, but the duration of expression is typically limited. Lentiviral vectors produce sustained expression and have been injected intraneurally in crushed sciatic nerves to achieve retrograde transport and gene expression in motor neurons (6) and locally to transduce Schwann cells (7). None of the approaches published to date has provided a Schwann cell-specific gene delivery method to achieve widespread and stable expression.We recently reported Schwann cell-specific expression driven by the rat myelin protein zero (Mpz) promoter of a neuropathy gene following intraneural lentiviral vector delivery, alleviating pathological changes in a model of X-linked Charcot–Marie–Tooth disease (CMT1X) (8). Expression was restricted to the injected sciatic nerve, however, thus limiting its usefulness for clinical applications.Here we report a gene delivery approach via a single lumbar intrathecal injection leading to stable Schwann cell gene expression in an unexpectedly widespread distribution—the lumbar spinal roots and along the entire length of the femoral and sciatic nerves. Using this approach to treat a mouse model of CMT1X resulted in significant behavioral, functional, and morphological improvement, providing an important advance toward treating inherited neuropathies.     

From the Cover: The point of no return in vetoing self-initiated movements

In humans, spontaneous movements are often preceded by early brain signals. One such signal is the readiness potential (RP) that gradually arises within the last second preceding a movement. An important question is whether people are able to cancel movements after the elicitation of such RPs, and if so until which point in time. Here, subjects played a game where they tried to press a button to earn points in a challenge with a brain–computer interface (BCI) that had been trained to detect their RPs in real time and to emit stop signals. Our data suggest that subjects can still veto a movement even after the onset of the RP. Cancellation of movements was possible if stop signals occurred earlier than 200 ms before movement onset, thus constituting a point of no return.It has been repeatedly shown that spontaneous movements are preceded by early brain signals (1–8). As early as a second before a simple voluntary movement, a so-called readiness potential (RP) is observed over motor-related brain regions (1–3, 5). The RP was found to precede the self-reported time of the “‘decision’ to act” (ref. 3, p. 623). Similar preparatory signals have been observed using invasive electrophysiology (8, 9) and functional MRI (7, 10), and have been demonstrated also for choices between multiple-response options (6, 7, 10), for abstract decisions (10), for perceptual choices (11), and for value-based decisions (12). To date, the exact nature and causal role of such early signals in decision making is debated (12–20).One important question is whether a person can still exert a veto by inhibiting the movement after onset of the RP (13, 18, 21, 22). One possibility is that the onset of the RP triggers a causal chain of events that unfolds in time and cannot be cancelled. The onset of the RP in this case would be akin to tipping the first stone in a row of dominoes. If there is no chance of intervening, the dominoes will gradually fall one-by-one until the last one is reached. This has been coined a ballistic stage of processing (23, 24). A different possibility is that participants can still terminate the process, akin to taking out a domino at some later stage in the chain and thus preventing the process from completing. Here, we directly tested this in a real-time experiment that required subjects to terminate their decision to move once a RP had been detected by a brain–computer interface (BCI) (25–31).     

From the Cover: Aquatic biodiversity enhances multiple nutritional benefits to humans

Humanity depends on biodiversity for health, well-being, and a stable environment. As biodiversity change accelerates, we are still discovering the full range of consequences for human health and well-being. Here, we test the hypothesis—derived from biodiversity–ecosystem functioning theory—that species richness and ecological functional diversity allow seafood diets to fulfill multiple nutritional requirements, a condition necessary for human health. We analyzed a newly synthesized dataset of 7,245 observations of nutrient and contaminant concentrations in 801 aquatic animal taxa and found that species with different ecological traits have distinct and complementary micronutrient profiles but little difference in protein content. The same complementarity mechanisms that generate positive biodiversity effects on ecosystem functioning in terrestrial ecosystems also operate in seafood assemblages, allowing more diverse diets to yield increased nutritional benefits independent of total biomass consumed. Notably, nutritional metrics that capture multiple micronutrients and fatty acids essential for human well-being depend more strongly on biodiversity than common ecological measures of function such as productivity, typically reported for grasslands and forests. Furthermore, we found that increasing species richness did not increase the amount of protein in seafood diets and also increased concentrations of toxic metal contaminants in the diet. Seafood-derived micronutrients and fatty acids are important for human health and are a pillar of global food and nutrition security. By drawing upon biodiversity–ecosystem functioning theory, we demonstrate that ecological concepts of biodiversity can deepen our understanding of nature’s benefits to people and unite sustainability goals for biodiversity and human well-being.

Species losses and range shifts because of climate change, harvesting, and other human activities are altering aquatic biodiversity locally and globally (1–5). In aquatic ecosystems, not only are some species severely depleted because of overfishing or habitat loss (3, 6–8), the ecosystem-level dimensions of biodiversity such as the total number of species and their functional diversity have also changed (9). Beyond the loss of particular species, changes in ecosystem-level dimensions of biodiversity threaten numerous ecosystem services to humans, which include the cultural, economic, or health benefits people derive from nature (10–13). In many regions, such as tropical coastal systems, the cumulative impacts of human activities are severe and associated with strong declines in taxonomic and ecological functional diversity (6) and coincide with regions with a high dependence of people upon wild-caught seafood for food and nutrition (14). In temperate regions, where some coastal communities depend on local wild seafood harvests to meet their nutritional needs (15, 16), species richness may be increasing as species recover from exploitation and warmer oceans allow species to expand their ranges into new territory (1, 2, 17).There is growing concern that biodiversity change leads to changes in human health and well-being (10, 13, 18). Specific and quantitative links between aquatic biodiversity and human health that distinguish contributions of species diversity from those of biomass, as predicted by biodiversity–ecosystem functioning theory, have not been established. At a time of unprecedented global change and increasing reliance on seafood to meet nutritional demands (19), there is an urgent need to understand how changing aquatic ecosystem structure may alter the provisioning of seafood-derived human nutrition.Seafood, consisting of wild-caught marine and freshwater finfish and invertebrates, provides an important source of protein and calories to humans. Additionally, unlike staple foods such as rice or other grains, seafood can address multiple dimensions of food and nutritional security simultaneously by providing essential micronutrients, such as vitamins, minerals, and polyunsaturated essential fatty acids critical to human health (19–22). Given the multiple attributes of seafood that are valuable to human health, it is possible that the diversity of an aquatic assemblage, distinct from the inclusion of any particularly nutritious species, could support human well-being consistent with a large body of evidence for biodiversity’s major contributions to ecological functions (11, 23–26). Dietary diversity is a basic tenet of a nutritious diet (27) and it is widely appreciated that diets composed of more food groups and more species are more nutritious (28–31). Ecological measures of dietary diversity (diet diversity, species richness, functional diversity, and Simpson’s index of evenness) have been associated with the nutritional value of diets in a range of contexts (27, 29, 32–38). These studies rely on relationships between species included in the diet (or other food intake measures) and nutritional adequacy of reported diets. However, a simple correlation between dietary diversity and a measure of dietary benefits provides only partial support for a claim that biodiversity benefits human well-being, consistent with the same ecological processes by which biodiversity supports numerous ecosystem functions and services (23, 26). We build upon this foundation of empirical relationships between diet diversity and diet quality by placing this question in the quantitative ecological theoretical framework that relates biodiversity to function (24, 25), thereby laying the groundwork for additional development of links between biodiversity science and our understanding of human well-being.Ecological theory predicts that biodiversity can be ecologically and economically important, apart from the importance of total biomass or the presence of particular species (23, 39). According to theory and over 500 explicit experimental tests (23, 40, 41), diversity in ecological communities and agricultural systems enhances ecosystem functioning by two mechanisms: 1) more diverse assemblages may outperform less diverse assemblages of the same density or biomass of individuals because more diverse assemblages will include more of the possible species and are therefore more likely to include high-performing species, assuming random processes of including species from the species pool (a selection effect), or 2) more diverse assemblages of a given density (or biomass) contain species with complementary functional traits, allowing them to function more efficiently (a complementarity effect) (25, 39). For aquatic animals, increased diversity enhances productivity of fish biomass (42) and also enhances temporal stability of biomass production and total yields (43, 44), providing economic and nutritional benefits to humans related to increased stability of harvests and production of biomass for consumption (43). However, when considering aquatic species from the perspective of human nutrition, functions other than biomass production become relevant because total seafood biomass consumption is not predictive of micronutrient benefits from seafood (45, 46).Here, we test a hypothesis central to ecological theory in the 21st century: whether biodiversity per se (species richness and ecological functional diversity), distinct from the identities and abundance of species, enhances human well-being (Fig. 1). We chose a measure of human well-being distinct from provision of protein, calories, or total yields—the micronutrient and essential fatty acid benefits of seafood. For increasing biodiversity per se (as opposed to increasing total seafood consumption) to enhance nutritional benefits as predicted by biodiversity–ecosystem functioning theory (25, 47), the amounts of various nutrients within edible tissues must differ among species, and furthermore, nutrient concentrations must trade off among species, such that species that have relatively high concentrations of some nutrients also have relatively low concentrations of others (25). Specifically, a “biodiversity effect” (sensu ref. 25) on nutritional benefits requires that concentrations of multiple nutrients are negatively correlated with each other, or uncorrelated, when compared among species, creating a complementary distribution of nutrients across species. In contrast, if nutrient concentrations in edible tissue are positively correlated for multiple nutrients across species such that, for example, a species containing high amounts of iron also has a high essential fatty acid concentration, thereby containing multiple nutrients in high concentrations simultaneously, seafood species or ecological functional diversity in the diet would not be important. In the case of positive correlations among nutrient concentrations, the ecosystem service of nutritional benefits would be enhanced by consuming more fish biomass or by selecting a few highly nutritious species, without considering species richness or ecological functional diversity.Open in a separate windowFig. 1.Aquatic biodiversity increases human well-being because edible species have distinct and complementary multinutrient profiles (A) and differ in mean micro- and macronutrient content (shown here relative to 10 and 25% thresholds of recommended dietary allowance, RDA, guidelines) for representative finfish (Abramis brama, Mullus surmuletus), mollusc (Mytilus galloprovincialis), and crustacean species (Nephrops norvegicus). Biodiversity–ecosystem functioning theory predicts that nutritional benefits, including the number of nutrient RDA targets met per 100 g portion (NT; i, iii) and minimum portion size (P_min; ii, iv) (B and E), are enhanced with increasing seafood species richness. Orange dots in B and E correspond to potential diets of high and low biodiversity levels. Seafood consumers with limited access to seafood each day may not reach RDA targets if diets are low in diversity (D–F versus A–C; gray shading indicates proportion of population that meets nutrient requirements). DHA: docosahexaenoic acid, EPA: eicosapentaenoic acid.We aimed to bridge two distinct theoretical frameworks—the biodiversity–ecosystem functioning theory and human nutrition science—by quantitatively testing for effects of aquatic species richness and ecological functional diversity (48, 49) in seafood diets on nutritional benefits via complementarity or selection effects. We used the public health measure of recommended dietary allowance (RDA) index to quantify nutritional benefits. RDAs are nutrient-based reference values that indicate the average daily dietary intake level that is sufficient to meet the nutrient requirement of nearly all (97 to 98%) healthy individuals in a particular life stage and gender group (50). Here, we used the RDA for females aged 19 to 50 y (SI Appendix, Tables S1 and S2; see SI Appendix, Table S1 for definitions of key terms). We measured nutritional value in terms of concentrations relative to RDAs, and we refer to these recommended amounts (or portions thereof) as “RDA targets” (SI Appendix, Tables S1 and S2 and Metrics). We quantified nutritional value in two ways: 1) the minimum amount of seafood tissue (in grams) required to meet given RDA targets (either for a single nutrient or the five micronutrients and fatty acids simultaneously; referred to as “minimum portion size required,” P_min [SI Appendix, Table S1, Eq. A1, and Metrics]) and 2) the number of nutrients that meet an RDA target in a single 100 g seafood portion (NT, SI Appendix, Table S1, Eq. A2). By considering nutritional value per unit biomass in both metrics, we avoided confounding diversity of seafood consumed with the total amount consumed (Metrics). We first tested two hypotheses: 1) seafood species richness increases NT because of complementarity in nutrient concentrations among species, and 2) seafood species richness increases the nutritional value of a 100 g edible portion of seafood, thereby lowering the minimum portion size, P_min, and improving the efficiency with which seafood consumers reach nutritional targets (Fig. 1). Following biodiversity–ecosystem functioning theory, we predicted that increased species richness is correlated with ecological functional diversity (51) in potential seafood diets and that ecological functional diversity is related to diversity in the concentration of essential elements and fatty acids that have nutritional value to human consumers, such that species and ecological functional diversity yields increased nutritional benefits. We also tested the hypothesis that seafood diversity increases total intake of heavy metal contaminants because some aquatic animals are known to bioaccumulate toxic metals in their tissues. For this reason, variation in bioaccumulation among species could lead to a biodiversity effect on contaminant intake that is detrimental to human health.In a global analysis of over 5,040 observations of nutrient concentrations in 547 aquatic species (SI Appendix, Fig. S1), we considered the provision of nutritional benefits to human consumers. To assess whether the relationships between biodiversity and human nutrition benefits depend on the geographic extent (global or local) over which seafood are harvested or accessed (11), we tested whether seafood species richness is associated with higher nutritional value at local scales (versus global scale) in traditional Indigenous seafood diets in North America (SI Appendix, Methods 1.4). Seafood is critical for Indigenous groups, who on average consume seafood at a rate that is 15 times higher than the global average per capita consumption rate (16). To test our hypotheses at the geographic scale of local consumer communities, we complemented our global analysis with additional analyses of 25 to 57 species in 14 geographically constrained groups of species consumed together as part of traditional Indigenous diets (SI Appendix, Methods 1.4).     

From the Cover: Outsourcing CO2 within China

Recent studies have shown that the high standard of living enjoyed by people in the richest countries often comes at the expense of CO₂ emissions produced with technologies of low efficiency in less affluent, developing countries. Less apparent is that this relationship between developed and developing can exist within a single country’s borders, with rich regions consuming and exporting high-value goods and services that depend upon production of low-cost and emission-intensive goods and services from poorer regions in the same country. As the world’s largest emitter of CO₂, China is a prominent and important example, struggling to balance rapid economic growth and environmental sustainability across provinces that are in very different stages of development. In this study, we track CO₂ emissions embodied in products traded among Chinese provinces and internationally. We find that 57% of China’s emissions are related to goods that are consumed outside of the province where they are produced. For instance, up to 80% of the emissions related to goods consumed in the highly developed coastal provinces are imported from less developed provinces in central and western China where many low–value-added but high–carbon-intensive goods are produced. Without policy attention to this sort of interprovincial carbon leakage, the less developed provinces will struggle to meet their emissions intensity targets, whereas the more developed provinces might achieve their own targets by further outsourcing. Consumption-based accounting of emissions can thus inform effective and equitable climate policy within China.     

From the Cover: Spiral precipitation patterns in confined chemical gardens

Chemical gardens are mineral aggregates that grow in three dimensions with plant-like forms and share properties with self-assembled structures like nanoscale tubes, brinicles, or chimneys at hydrothermal vents. The analysis of their shapes remains a challenge, as their growth is influenced by osmosis, buoyancy, and reaction–diffusion processes. Here we show that chemical gardens grown by injection of one reactant into the other in confined conditions feature a wealth of new patterns including spirals, flowers, and filaments. The confinement decreases the influence of buoyancy, reduces the spatial degrees of freedom, and allows analysis of the patterns by tools classically used to analyze 2D patterns. Injection moreover allows the study in controlled conditions of the effects of variable concentrations on the selected morphology. We illustrate these innovative aspects by characterizing quantitatively, with a simple geometrical model, a new class of self-similar logarithmic spirals observed in a large zone of the parameter space.Chemical gardens, discovered more than three centuries ago (1), are attracting nowadays increasing interest in disciplines as varied as chemistry, physics, nonlinear dynamics, and materials science. Indeed, they exhibit rich chemical, magnetic, and electrical properties due to the steep pH and electrochemical gradients established across their walls during their growth process (2). Moreover, they share common properties with structures ranging from nanoscale tubes in cement (3), corrosion filaments (4) to larger-scale brinicles (5), or chimneys at hydrothermal vents (6). This explains their success as prototypes to grow complex compartmentalized or layered self-organized materials, as chemical motors, as fuel cells, in microfluidics, as catalysts, and to study the origin of life (7–18). However, despite numerous experimental studies, understanding the properties of the wide variety of possible spatial structures and developing theoretical models of their growth remains a challenge.In 3D systems, only a qualitative basic picture for the formation of these structures is known. Precipitates are typically produced when a solid metal salt seed dissolves in a solution containing anions such as silicate. Initially, a semipermeable membrane forms, across which water is pumped by osmosis from the outer solution into the metal salt solution, further dissolving the salt. Above some internal pressure, the membrane breaks, and a buoyant jet of the generally less dense inner solution then rises and further precipitates in the outer solution, producing a collection of mineral shapes that resembles a garden. The growth of chemical gardens is thus driven in 3D by a complex coupling between osmotic, buoyancy, and reaction–diffusion processes (19, 20).Studies have attempted to generate reproducible micro- and nanotubes by reducing the erratic nature of the 3D growth of chemical gardens (10, 11, 13, 15, 21). They have for instance been studied in microgravity to suppress buoyancy (22, 23), or by injecting aqueous solutions of metallic salts directly into silicate solutions in 3D to dominate osmotic processes by controlled flows (10, 11). Analysis of their microstructure has also been done for different metallic salts, showing a difference of chemical composition on the inner and the outer tube surfaces (24, 25). The experimental characterization and modeling of the dynamics remains however dauntingly complex in 3D, which explains why progress in quantitative analysis remains so scarce.We show here that growing chemical gardens in a confined quasi-2D geometry by injecting one reagent solution into the other provides an innovative path to discover numerous original patterns, characterize quantitatively their properties, and explain their growth mechanism. A large variety of structures including spirals, filaments, worms, and flowers is obtained in a horizontal confined geometry when varying the reagent concentrations at a fixed flow rate. The patterns differ from those in 3D as the growth methodology decouples the different effects involved in the formation of classical chemical gardens. The buoyancy force is reduced by the vertical confinement, whereas injection decreases the influence of osmotic effects.     

From the Cover: Defense mutualisms enhance plant diversification

The ability of plants to form mutualistic relationships with animal defenders has long been suspected to influence their evolutionary success, both by decreasing extinction risk and by increasing opportunity for speciation through an expanded realized niche. Nonetheless, the hypothesis that defense mutualisms consistently enhance plant diversification across lineages has not been well tested due to a lack of phenotypic and phylogenetic information. Using a global analysis, we show that the >100 vascular plant families in which species have evolved extrafloral nectaries (EFNs), sugar-secreting organs that recruit arthropod mutualists, have twofold higher diversification rates than families that lack species with EFNs. Zooming in on six distantly related plant clades, trait-dependent diversification models confirmed the tendency for lineages with EFNs to display increased rates of diversification. These results were consistent across methodological approaches. Inference using reversible-jump Markov chain Monte Carlo (MCMC) to model the placement and number of rate shifts revealed that high net diversification rates in EFN clades were driven by an increased number of positive rate shifts following EFN evolution compared with sister clades, suggesting that EFNs may be indirect facilitators of diversification. Our replicated analysis indicates that defense mutualisms put lineages on a path toward increased diversification rates within and between clades, and is concordant with the hypothesis that mutualistic interactions with animals can have an impact on deep macroevolutionary patterns and enhance plant diversity.Ever since the key innovation hypothesis was first proposed in the 1940s (1, 2), the origination of novel traits has been a popular yet controversial explanation for the exceptional disparity in species richness observed across clades in the tree of life. Despite decades of research linking traits to diversification, we have remarkably few examples of traits that have been convincingly demonstrated to spur diversification repeatedly across independent, distantly related groups. Notable exceptions include a number of ecologically important traits mediating interactions between plants and animals (3–6), suggesting that these interactions may be particularly important drivers of macroevolutionary patterns. Here, we test the hypothesis that plant defense mutualisms, a widespread and classically studied ecological interaction whereby plants provide food rewards to arthropod bodyguards in return for protection against natural enemies (7), increase the evolutionary diversification rate of the plant lineages that participate in them. The morphological traits that mediate defense mutualisms represent well-studied examples of characters hypothesized to expand a plant’s niche via interactions with mutualists and influence species success in various environmental contexts (8). Although the costs and benefits of participating in defense mutualisms are well studied (9), the hypothesis that the ecological impact of defense mutualisms leaves a predictable macroevolutionary signature, increasing lineage diversification within and among clades of plants, has only been examined in a single genus (10).Defense mutualisms may have an impact on plant speciation and extinction rates via several mechanisms. Unlike the evolution of traits related to reproduction, which, more intuitively, could have an impact on lineage diversification (e.g., refs. 5, 11), the direct mechanism by which defense mutualisms are hypothesized to influence diversification is less obvious. One direct mechanism is a decreased incidence of damage and disease due to an enhanced defensive repertoire, which may allow for increased population sizes and, in turn, lower extinction rates (6). Additionally, by expanding the realized niche of a plant (12), defense mutualisms may broaden the range of habitats a plant can occupy (10), thereby increasing instances of allopatric speciation.However, in addition to these direct mechanisms, the evolution of mutualistic traits may facilitate diversification indirectly. First, if niche expansion results in the successful occupation of more environments, mutualistic traits may increase the probability a lineage will encounter conditions ripe with ecological opportunity (e.g., new adaptive zones), which, in turn, will drive increases in diversification. In other words, the evolution of a trait may enable subsequent diversification via increasing exposure to new environments, some of which will harbor external drivers of radiation, such as the uplift of a mountain range or unoccupied niches. Second, the evolution of defense mutualisms may free up resources for the plant, and thereby facilitate the evolution of other innovative traits that subsequently enhance diversification. These indirect effects need not be contingent on the existence of the direct effects mentioned above, and represent a largely overlooked hypothesis concerning how traits can affect diversification (13–15).We suggest that indirect impacts of trait evolution on diversification should be reflected in a phylogenetic pattern in which the origination of a trait is followed by an increased probability of subsequent, downstream rate shifts relative to clades that lack the trait (Fig. 1). Because the indirect effect of the trait is contingent upon additional conditions (e.g., ecological opportunity, the evolution of another trait), there may be a substantial lag between the origin of the trait and rate shifts. Alternatively, a direct effect of the trait on the diversification rate is consistent with a pattern whereby a sustained rate shift occurs concomitantly with, or on the same branch as, the origin of the trait on the phylogeny (Fig. 1). Direct and indirect patterns are not mutually exclusive, and both patterns may be detectable on a single phylogeny (Fig. 1).Open in a separate windowFig. 1.A conceptualization of phylogenetic patterns consistent with direct or indirect effects of EFNs (or any trait) on lineage diversification. A net change in diversification may be due to direct or indirect mechanisms. In the Upper Right, a rate shift occurs concomitantly with the origin of EFNs, consistent with a direct effect. If one or more shifts occur with some delay (Lower), this is consistent with a hypothesis that a trait has an indirect or context-dependent effect on diversification rates.We focus on the macroevolutionary consequences of the repeated origination of extrafloral nectaries (EFNs), nectar-secreting glands found on nonfloral plant tissues that provide food for a wide array of beneficial arthropod bodyguards (16). EFNs are well studied ecologically, and their only known function is defense against herbivores and microbial pathogens by attracting natural enemies (17). Such features have evolved hundreds of times and occur in about a quarter of all vascular plant families (18). Here, we first ask whether, across all vascular plants, families containing species with EFNs are associated with higher diversification rates than families without EFNs. We then focus in on the phylogenetic history and evolution of EFNs in six distantly related plant clades to evaluate whether EFNs are linked, directly or indirectly, to increased lineage diversification rates. As such, this study represents a replicated, multiscale test of the macroevolutionary consequences of a convergently evolved and ecologically important mutualistic trait.     

From the Cover: Climate shock effects and mediation in fisheries

Climate shocks can reorganize the social–ecological linkages in food-producing communities, leading to a sudden loss of key products in food systems. The extent and persistence of this reorganization are difficult to observe and summarize, but are critical aspects of predicting and rapidly assessing community vulnerability to extreme events. We apply network analysis to evaluate the impact of a climate shock—an unprecedented marine heatwave—on patterns of resource use in California fishing communities, which were severely affected through closures of the Dungeness crab fishery. The climate shock significantly modified flows of users between fishery resources during the closures. These modifications were predicted by pre-shock patterns of resource use and were associated with three strategies used by fishing community member vessels to respond to the closures: temporary exit from the food system, spillover of effort from the Dungeness crab fishery into other fisheries, and spatial shifts in where crab were landed. Regional differences in resource use patterns and vessel-level responses highlighted the Dungeness crab fishery as a seasonal “gilded trap” for northern California fishing communities. We also detected disparities in climate shock response based on vessel size, with larger vessels more likely to display spatial mobility. Our study demonstrates the importance of highly connected and decentralized networks of resource use in reducing the vulnerability of human communities to climate shocks.

Climate shocks threaten food systems around the world and are expected to increase in frequency and intensity under climate change (1–5). Distinct from climate change (e.g., long-term warming), climate shocks rapidly outstrip the capacity of a system to cope by inflicting unexpected and highly concentrated damage (6). Vulnerability of communities to climate shocks varies within and across food systems, depending on the severity of the shock and the sensitivity and adaptive capacity of community members (7). Communities that form the harvesting and processing base of food systems—especially agrarian and fishing communities—are often among the most vulnerable to climate shocks (8), as their resource-based economies operate at the interface of environment and society. Marine heatwaves represent one such climate shock of growing importance, as they impact fishing communities by compromising seafood safety, shifting species distributions, and lowering recruitment and survival of fished species (9–12).Diversifying harvest portfolios is one strategy used by fishers to manage risk (13–16). If marine heatwaves disproportionately affect a subset of species, fishers may respond by shifting participation into less affected fisheries. This response, referred to as “leakage” or “spillover” (17–21), restructures the networks that form as fishers participate in multiple fisheries (19–21). The topology of these fisheries participation networks can reveal the extent to which climate shocks lead to indirect or lasting changes in patterns of resource use within fishing communities and, by drawing on network theory, indicate the sensitivity of these communities to perturbations (18).The 2014–2016 North Pacific marine heatwave (12, 22) was a climate shock that led to a massive harmful algal bloom (HAB), contaminating Dungeness crab with biotoxins and compelling state managers to coordinate fishery closures along the entire US West Coast (23). In California, where the Dungeness crab fishery represents ∼26% of all annual fishery revenue (California Department of Fish and Wildlife; https://wildlife.ca.gov) and supports >25% of all commercial fishing vessels (Pacific Fisheries Information Network; http://pacfin.psmfc.org), the HAB significantly delayed the 2015–16 commercial Dungeness crab fishing season (24). California Dungeness crab landings for the 2015–16 season reached only 52% of the average catch from the previous 5 y, spurring Congress to appropriate >$25 million in federal disaster relief funding (25). Dungeness crab fishers reported shifting participation to alternative fisheries during the 2015–16 season to offset socioeconomic impacts (26, 27); however, to date there has been no quantitative demonstration of spillover from the Dungeness crab fishery, or analysis of how the resulting changes in fisheries participation networks may have varied geographically and persisted after the closures were lifted.Our study examined the impact of the 2015–16 Dungeness crab fishery closures (hereafter 2016 closures) on patterns of resource use in California fishing communities. We considered seven fishing communities representing a total of 2,516 individual fishing vessels (Table 1). We found significant changes in fisheries participation network topology during the 2016 closures, which corresponded with a severe reduction in fishing activity, spillover of fishing effort from the Dungeness crab fishery, and spatial variation in pre-shock network topology. Our analysis captured changing patterns of resource use during a severe climate shock, and demonstrated how this emergent social outcome in fishing communities can be predicted by pre-shock network metrics and related to the adaptive strategies of community member vessels. We discuss the implications of fishery management measures for adaptive decision making and network structure, and provide recommendations for sustainable fishery management during climate shocks.Table 1.Ports of landing and vessel counts for the seven California fishing communities included in this study

From the Cover: An estimate of the number of tropical tree species

The high species richness of tropical forests has long been recognized, yet there remains substantial uncertainty regarding the actual number of tropical tree species. Using a pantropical tree inventory database from closed canopy forests, consisting of 657,630 trees belonging to 11,371 species, we use a fitted value of Fisher’s alpha and an approximate pantropical stem total to estimate the minimum number of tropical forest tree species to fall between ∼40,000 and ∼53,000, i.e., at the high end of previous estimates. Contrary to common assumption, the Indo-Pacific region was found to be as species-rich as the Neotropics, with both regions having a minimum of ∼19,000–25,000 tree species. Continental Africa is relatively depauperate with a minimum of ∼4,500–6,000 tree species. Very few species are shared among the African, American, and the Indo-Pacific regions. We provide a methodological framework for estimating species richness in trees that may help refine species richness estimates of tree-dependent taxa.Despite decades of biological inventories worldwide, we still do not know how many species exist and how they are distributed (1). Although global patterns of estimated vascular plant species richness and distribution have become more clear (2–5), no previous study has focused on trees as a distinct growth form. As a consequence, our estimation of the number of tree species in tropical forests still depends on untested expert opinions (6–8) rather than on an appropriate methodological framework and data set.Given the importance of trees as key structural components of forest ecosystems, sources of timber and nontimber products, and providers of vital ecosystem services (9, 10), the lack of reliable estimates of the total number of tropical tree species represents a critical knowledge gap that has direct consequences for estimating the diversity of other tree-dependent taxa (11). A classic example is Erwin’s (6) estimate of the existence of 30 million arthropod species, which was based on observed host specificities of arthropods with individual tropical tree species combined with an estimate of the total number of tropical tree species. Global arthropod richness has subsequently been revised downward (7, 11), but current estimates still suffer from the lack of information on the number of tropical tree species.In recent decades, the number of tree inventory plots across the tropics has grown to such an extent that species richness estimation at the continental and pantropical scale can now be addressed using standardized species lists with abundance data. Prior estimates of plant richness at such broad scales have mostly been based on analyses of incidence data obtained from herbarium collections and flora treatments (2–5). However, these methods are highly sensitive to collecting biases and ignore valuable information on species’ abundances (12). Abundance data enable extrapolation of richness from local to global scales using diversity estimators that fit the observed species rank abundance data (13–15).     

From the Cover: Dark-field computed tomography reaches the human scale

X-ray computed tomography (CT) is one of the most commonly used three-dimensional medical imaging modalities today. It has been refined over several decades, with the most recent innovations including dual-energy and spectral photon-counting technologies. Nevertheless, it has been discovered that wave-optical contrast mechanisms—beyond the presently used X-ray attenuation—offer the potential of complementary information, particularly on otherwise unresolved tissue microstructure. One such approach is dark-field imaging, which has recently been introduced and already demonstrated significantly improved radiological benefit in small-animal models, especially for lung diseases. Until now, however, dark-field CT could not yet be translated to the human scale and has been restricted to benchtop and small-animal systems, with scan durations of several minutes or more. This is mainly because the adaption and upscaling to the mechanical complexity, speed, and size of a human CT scanner so far remained an unsolved challenge. Here, we now report the successful integration of a Talbot–Lau interferometer into a clinical CT gantry and present dark-field CT results of a human-sized anthropomorphic body phantom, reconstructed from a single rotation scan performed in 1 s. Moreover, we present our key hardware and software solutions to the previously unsolved roadblocks, which so far have kept dark-field CT from being translated from the optical bench into a rapidly rotating CT gantry, with all its associated challenges like vibrations, continuous rotation, and large field of view. This development enables clinical dark-field CT studies with human patients in the near future.

Computed tomography (CT) provides high-resolution three-dimensional imaging with fast (subsecond) acquisition times for medical radiology (1). Its versatility allows for a wide variety of applications and thus, makes it an essential tool in diagnostic imaging. For example, just recently CT imaging proved to play a crucial role in clinical practice in the fight against COVID-19 (2). While very successful so far, present CT approaches [including the latest dual-energy and spectral approaches (3)] generate contrast solely based on attenuation differences in the tissue. As shown recently, significant additional diagnostic potential lies in also exploiting the complementary wave nature of X-rays, which results in refraction and small-angle scattering as complementary signal channels. A range of preclinical studies has proven that particularly the small-angle scattering (usually referred to as dark-field) signal is very valuable for the diagnosis and staging of lung diseases, such as chronic obstructive pulmonary disease (COPD) (4, 5), lung fibrosis (4, 6), pneumonia (7), and lung cancer (8). This is because the dark-field signal picks up complementary information on microstructural properties in lung parenchyma, which is beyond the resolution limit of presently used CT approaches (9, 10) and yet, does not require a higher dose than conventional CT.X-ray dark-field CT, based on a grating interferometer, was originally introduced at highly brilliant synchrotron sources (11) and was then successfully translated to more readily available medical X-ray tube sources (12, 13). There have been a number of important technical advances in fabrication of the required grating optics (14–18), and new data processing approaches were introduced (19–23). More recently, first clinical prototypes have been developed for two-dimensional radiographic grating–based X-ray imaging, again supporting strongly the significant benefit of diagnostic information, particularly for lung diseases (24–27). The implementation into a human-scale CT system for first clinical studies, however, could so far not be achieved. This is essentially due to the markedly increased technological challenges associated with the required large field of view for human scanning, the cylindrical interferometer geometry, and the rapidly and continuously rotating gantry. Moreover, the fast rotation times (subseconds), with all the associated vibrational instabilities, posed many so far unresolved algorithmic challenges, which have not at all been addressed with presently existing benchtop or small-animal systems featuring step and shoot acquisition and typical acquisition times of several minutes to hours (4, 26).Here, we now report on 1) a technological approach that enabled the construction of a dark-field CT system based on a compact, inverse, and cylindrically bent X-ray grating interferometer; 2) an associated algorithmic approach with a processing pipeline, which can compensate for inevitable vibrations in the fast-rotating CT system; and 3) results on a human-scale anthropomorphic thorax phantom acquired within a scan time of 1 s.     

From the Cover: Father's brain is sensitive to childcare experiences

Although contemporary socio-cultural changes dramatically increased fathers'' involvement in childrearing, little is known about the brain basis of human fatherhood, its comparability with the maternal brain, and its sensitivity to caregiving experiences. We measured parental brain response to infant stimuli using functional MRI, oxytocin, and parenting behavior in three groups of parents (n = 89) raising their firstborn infant: heterosexual primary-caregiving mothers (PC-Mothers), heterosexual secondary-caregiving fathers (SC-Fathers), and primary-caregiving homosexual fathers (PC-Fathers) rearing infants without maternal involvement. Results revealed that parenting implemented a global “parental caregiving” neural network, mainly consistent across parents, which integrated functioning of two systems: the emotional processing network including subcortical and paralimbic structures associated with vigilance, salience, reward, and motivation, and mentalizing network involving frontopolar-medial-prefrontal and temporo-parietal circuits implicated in social understanding and cognitive empathy. These networks work in concert to imbue infant care with emotional salience, attune with the infant state, and plan adequate parenting. PC-Mothers showed greater activation in emotion processing structures, correlated with oxytocin and parent-infant synchrony, whereas SC-Fathers displayed greater activation in cortical circuits, associated with oxytocin and parenting. PC-Fathers exhibited high amygdala activation similar to PC-Mothers, alongside high activation of superior temporal sulcus (STS) comparable to SC-Fathers, and functional connectivity between amygdala and STS. Among all fathers, time spent in direct childcare was linked with the degree of amygdala-STS connectivity. Findings underscore the common neural basis of maternal and paternal care, chart brain–hormone–behavior pathways that support parenthood, and specify mechanisms of brain malleability with caregiving experiences in human fathers.Throughout human history and across cultures, women have typically assumed primary caregiving responsibility for infants (1, 2). Although humans are among the few mammalian species where some male parental caregiving is relatively common, father involvement varies considerably within and across cultures, adapting to ecological conditions (1, 3). Involved fathering has been linked with children''s long-term physiological and social development and with increases in mothers'' caregiving-related hormones such as oxytocin and prolactin (3–6). In addition, animal studies demonstrated structural brain alterations in caregiving fathers (7, 8). It has been suggested that, although maternal caregiving is triggered by neurobiological processes related to pregnancy and labor, the human father''s brain, similar to other biparental mammals, adapts to the parental role through active involvement in childcare (1–3). Despite growing childcare involvement of fathers (3, 5, 6), mechanisms for human fathers'' brain adaptation to caregiving experiences remain largely unknown, and no study to our knowledge has examined the brain basis of human fatherhood when fathers assume primary responsibility for infant care.For social species with lengthy periods of dependence, parental caregiving is key to survival and relies on brain structures that maximize survival (2, 9). Animal studies have demonstrated that mammalian mothering is supported by evolutionarily ancient structures implicated in emotional processing, vigilance, motivation, and reward, which are rich in oxytocin receptors, including the amygdala, hypothalamus, nucleus accumbens, and ventral tegmental area (VTA), and that these regions are sensitive to caregiving behavior (9, 10). Imaging studies of human mothers found activation in similar areas, combined with paralimbic insula-cingulate structures that imbue infants with affective salience, ground experience in the present moment and enable maternal simulation of infant states (11–13). These structures implicate a phylogenetically ancient network of emotional processing that rapidly detects motivationally salient and survival-related cues (14) and enables parents to automatically identify and immediately respond to infant distress, thereby maximizing survival. In humans, this emotional processing network is complemented by a cortical mentalizing network of frontopolar-medial-prefrontal-temporo-parietal structures involved in social understanding, theory of mind, and cognitive empathy, including the medial prefrontal cortex (mPFC), frontopolar cortex, superior temporal sulcus (STS), and temporal poles (15). The mentalizing network plays an important role in individuals'' ability to infer mental states from behavior, is already activated during the parents'' first weeks of parenting, and enables parents to cognitively represent infant states, predict infant needs, and plan future caregiving (11–13).The few studies examining the human father''s brain showed activation in similar areas, including the STS, lateral and medial frontal regions, VTA, inferior frontal gyrus (IFG), and orbitofrontal cortex (OFC) (16, 17). Only one study compared maternal and paternal brain response to infant cues, reporting mothers'' greater amygdala activation, fathers'' greater superior-temporal and medial-frontal activation, and maternal and paternal oxytocin''s different associations with amygdala vs. cortical activation (18). Oxytocin, a nine-amino acid neuropeptide that underpins the formation of affiliative bonds (19), supports the development of human parental caregiving (20). Research has shown that maternal and paternal oxytocin levels are associated with parent–infant synchrony, which is the parent''s careful adaptation of caregiving behavior to infant''s social signals (21). However, although oxytocin levels are similar in mothers and fathers, oxytocin is differentially linked with the parent-specific repertoire, for instance, with affectionate contact in mothers and stimulatory play in fathers (5, 20).Ethological perspectives emphasize the importance of studying the neurobiology of parenting in its natural habitat and of using a behavior-based approach to test parents'' brain adaptation to ecological pressures (22). Consistent with findings in other mammals (10), studies on brain–behavior associations in human mothers describe links between mother–infant synchrony and brain activation in the mother''s subcortical regions, including the amygdala, nucleus accumebens, and hippocampus (11, 13). In contrast, the one study testing human fathers'' brain–behavior associations showed correlations with cortical activation (17). Overall, these findings suggest that distinct brain–hormone–behavior pathways may underpin maternal and paternal care; therefore, oxytocin and parenting behavior may be associated with the emotional processing network in mothers but with the socio-cognitive circuit in fathers. Furthermore, animal studies indicate that active caregiving in biparental fathers leads to greater integration of multiple brain networks involved in nurturance, learning, and motivation (7). Hence, active involvement in caregiving may possibly facilitate integration of both parenting-related networks in human fathers, particularly among those who undertake the primary caregiver role.The present study sought to examine the brain basis of human fatherhood by using a “natural experiment,” afforded for the first time in human history, to our knowledge, by contemporary socio-cultural changes. Throughout history, infants without mothers were cared for by other women (2). Current social changes enable the formation of two-father families raising children with no maternal involvement since birth (3). Such a context provides a unique setting to assess changes in the paternal brain on assuming the traditionally maternal role. Moreover, understanding mechanisms of brain adaptation to caregiving experiences in primary-caregiving fathers may shed further light on processes that refine all fathers'' responses to childcare activities.We visited the homes of two-parent families rearing their firstborn child: heterosexual mother-father couples comprising primary-caregiving mothers (PC-Mothers) and secondary-caregiving fathers (SC-Fathers) and homosexual couples comprising two primary-caregiving fathers (PC-Fathers) (SI Materials and Methods). We videotaped parent–infant interaction in the natural habitat, measured parental oxytocin, and used the videotaped parent–child interactions as stimuli for functional MRI (fMRI) to test parental brain response to infant-related cues. Five hypotheses were proposed. First, we expected activation in both subcortical areas involved in vigilance and reward and cortical circuits implicated in social understanding in all parents raising a young infant. Second, we expected greater subcortical activation in mothers, particularly in the amygdala, which has been repeatedly linked with mammalian mothering (23, 24), and greater activation in cortical socio-cognitive circuits in fathers. Third, the brain–hormone–behavior constellation underpinning maternal care was expected to center around the emotional-processing network, whereas the brain–hormone–behavior links in fathers were expected to coalesce with the socio-cognitive network. Fourth, consistent with the context-specific evolution of human fathering (1), we expected greater variability in fathers'' brain response as mediated by actual caregiving experiences. Such variability would be particularly noted among the primary-caregiving fathers raising infants without mothers and may involve functional integration of the subcortical and cortical networks subserving parenting. Finally, we expected that the pathways leading from the parent''s primary caregiving role to greater parent–infant synchrony would be mediated by parental brain activation and oxytocin levels.     

From the Cover: Condensing water vapor to droplets generates hydrogen peroxide

It was previously shown [J. K. Lee et al., Proc. Natl. Acad. Sci. U.S.A., 116, 19294–19298 (2019)] that hydrogen peroxide (H₂O₂) is spontaneously produced in micrometer-sized water droplets (microdroplets), which are generated by atomizing bulk water using nebulization without the application of an external electric field. Here we report that H₂O₂ is spontaneously produced in water microdroplets formed by dropwise condensation of water vapor on low-temperature substrates. Because peroxide formation is induced by a strong electric field formed at the water–air interface of microdroplets, no catalysts or external electrical bias, as well as precursor chemicals, are necessary. Time-course observations of the H₂O₂ production in condensate microdroplets showed that H₂O₂ was generated from microdroplets with sizes typically less than ∼10 µm. The spontaneous production of H₂O₂ was commonly observed on various different substrates, including silicon, plastic, glass, and metal. Studies with substrates with different surface conditions showed that the nucleation and the growth processes of condensate water microdroplets govern H₂O₂ generation. We also found that the H₂O₂ production yield strongly depends on environmental conditions, including relative humidity and substrate temperature. These results show that the production of H₂O₂ occurs in water microdroplets formed by not only atomizing bulk water but also condensing water vapor, suggesting that spontaneous water oxidation to form H₂O₂ from water microdroplets is a general phenomenon. These findings provide innovative opportunities for green chemistry at heterogeneous interfaces, self-cleaning of surfaces, and safe and effective disinfection. They also may have important implications for prebiotic chemistry.

Water molecules in liquid water are considered stable and inert. We and other investigators have reported that water molecules become electrochemically active and catalytic for various reactions when bulk water is formed into micrometer-sized droplets (microdroplets). Reaction rates for various chemical reactions are accelerated in microdroplets by factors of 10² or more compared to bulk solution (1). The microdroplet environment provides conditions for a lowered entropic barrier, which allows thermodynamically unfavorable reactions to proceed in microdroplets at room temperature (2, 3). We also have shown that water microdroplets induce spontaneous charge exchanges between solutes and water molecules to induce the spontaneous reduction of organic molecules and metal ions as well as the formation of nanostructures without any added reducing agent or template (4, 5). Moreover, we have reported that water molecules undergo spontaneous oxidation to form reactive oxygen species, including hydroxyl radicals (OH) and hydrogen peroxide (H₂O₂) (6–8). Recent investigations attributed the origin of these unique physicochemical properties observed in microdroplets to the enrichment of reactants at the interface (9–11), restricted molecular rotations (12), partial solvation at the water surface (1, 13), and a strong interfacial electric field at the surface of the water microdroplet (14).Microdroplets can be formed either by atomizing bulk water (top down) with various methods such as high-pressure gas nebulization (15), ultrasonic nebulization (16), vibrating micromesh nebulization (17), and piezoelectric nebulization (18), or by condensing vapor-phase molecules (bottom up) (19). A question may be asked whether those unique properties of microdroplets arise only in microdroplets formed by atomization of bulk water. In addition, it may be wondered whether the spontaneous oxidation of water to form H₂O₂ in microdroplets (6) was caused by the atomizing process involving friction or vibration. These questions motivated us to investigate whether H₂O₂ becomes spontaneously generated in water microdroplets formed by the condensation of water vapor in air on cold surfaces, and how universal might this process be. We have paid special attention to the influence of different surface properties, including hydrophilicity and surface roughness, as well as environmental factors, including relative humidity and surface temperature.     

From the Cover: Quantum teleportation between remote atomic-ensemble quantum memories

Quantum teleportation and quantum memory are two crucial elements for large-scale quantum networks. With the help of prior distributed entanglement as a “quantum channel,” quantum teleportation provides an intriguing means to faithfully transfer quantum states among distant locations without actual transmission of the physical carriers [Bennett CH, et al. (1993) Phys Rev Lett 70(13):1895–1899]. Quantum memory enables controlled storage and retrieval of fast-flying photonic quantum bits with stationary matter systems, which is essential to achieve the scalability required for large-scale quantum networks. Combining these two capabilities, here we realize quantum teleportation between two remote atomic-ensemble quantum memory nodes, each composed of ∼10⁸ rubidium atoms and connected by a 150-m optical fiber. The spin wave state of one atomic ensemble is mapped to a propagating photon and subjected to Bell state measurements with another single photon that is entangled with the spin wave state of the other ensemble. Two-photon detection events herald the success of teleportation with an average fidelity of 88(7)%. Besides its fundamental interest as a teleportation between two remote macroscopic objects, our technique may be useful for quantum information transfer between different nodes in quantum networks and distributed quantum computing.     

From the Cover: Phosphorylation of protocadherin proteins by the receptor tyrosine kinase Ret

The clustered protocadherins (Pcdhs) are a large family of cadherin-like transmembrane proteins expressed in the nervous system. Stochastic expression of Pcdh genes and alternative splicing of their pre-mRNAs have the potential to generate enormous protein diversity at the cell surface of neurons. At present, the regulation and function of Pcdh proteins are largely unknown. Here, we show that Pcdhs form a heteromeric signaling complex(es), consisting of multiple Pcdh isoforms, receptor tyrosine kinases, phosphatases, and cell adhesion molecules. In particular, we find that the receptor tyrosine kinase rearranged during transformation (Ret) binds to Pcdhs in differentiated neuroblastoma cells and is required for stabilization and differentiation-induced phosphorylation of Pcdh proteins. In addition, the Ret ligand glial cell line-derived neurotrophic factor induces phosphorylation of Pcdhγ in motor neurons and phosphorylation of Pcdhα and Pcdhγ in sympathetic neurons. Conversely, Pcdh proteins are also required for the stabilization of activated Ret in neuroblastoma cells and sympathetic ganglia. Thus, Pcdhs and Ret are functional components of a phosphorylation-dependent signaling complex.     

From the Cover: Behavioral assessment of sensitivity to intracortical microstimulation of primate somatosensory cortex

Intracortical microstimulation (ICMS) is a powerful tool to investigate the functional role of neural circuits and may provide a means to restore sensation for patients for whom peripheral stimulation is not an option. In a series of psychophysical experiments with nonhuman primates, we investigate how stimulation parameters affect behavioral sensitivity to ICMS. Specifically, we deliver ICMS to primary somatosensory cortex through chronically implanted electrode arrays across a wide range of stimulation regimes. First, we investigate how the detectability of ICMS depends on stimulation parameters, including pulse width, frequency, amplitude, and pulse train duration. Then, we characterize the degree to which ICMS pulse trains that differ in amplitude lead to discriminable percepts across the range of perceptible and safe amplitudes. We also investigate how discriminability of pulse amplitude is modulated by other stimulation parameters—namely, frequency and duration. Perceptual judgments obtained across these various conditions will inform the design of stimulation regimes for neuroscience and neuroengineering applications.Intracortical microstimulation (ICMS) is an important tool to investigate the functional role of neural circuits (1, 2). In a famous example, microstimulation of neurons in the middle temporal area was found to bias the perceived direction of visual motion stimuli, causally implicating these neurons in the computation of visual motion direction (3). Experiments with ICMS of somatosensory cortex showed that changing the frequency of stimulation elicited discriminable percepts, demonstrating that temporal patterning of cortical responses has perceptual correlates (4). Building on the success of these and other studies, ICMS has been proposed as an approach to restore perception in individuals who have lost it, for example in visual neuroprostheses for the blind (5, 6) or somatosensory neuroprostheses for tetraplegic patients (7–11). In the present study, we sought to characterize the psychometric properties of ICMS delivered to primary somatosensory cortex (S1) across a wide range of stimulation regimes. In psychophysical experiments with Rhesus macaques, we first measured the detectability of ICMS pulse trains and assessed its dependence on a variety of stimulation parameters. We then measured the degree to which animals could discriminate pairs of ICMS pulse trains that differed in amplitude. In both the detection and discrimination experiments, ICMS parameters—amplitude, pulse width, pulse train duration, and pulse train frequency—spanned the range that is detectable and has been typically deemed safe (12–14). Results from the present experiments will inform the design of future studies involving ICMS as well as the development of sensory encoding algorithms for neuroprostheses.     

From the Cover: Training conquers multitasking costs by dividing task representations in the frontoparietal-subcortical system

Negotiating the information-rich sensory world often requires the concurrent management of multiple tasks. Despite this requirement, humans are thought to be poor at multitasking because of the processing limitations of frontoparietal and subcortical (FP-SC) brain regions. Although training is known to improve multitasking performance, it is unknown how the FP-SC system functionally changes to support improved multitasking. To address this question, we characterized the FP-SC changes that predict training outcomes using an individual differences approach. Participants (n = 100) performed single and multiple tasks in pre- and posttraining magnetic resonance imaging (fMRI) sessions interspersed by either a multitasking or an active-control training regimen. Multivoxel pattern analyses (MVPA) revealed that training induced multitasking improvements were predicted by divergence in the FP-SC blood oxygen level-dependent (BOLD) response patterns to the trained tasks. Importantly, this finding was only observed for participants who completed training on the component (single) tasks and their combination (multitask) and not for the control group. Therefore, the FP-SC system supports multitasking behavior by segregating constituent task representations.It is thought that humans are poor at multitasking because frontoparietal and subcortical (FP-SC) brain regions both serve a broad range of mental functions (1, 2) and are limited information processors (3). Thus, performing multiple tasks concurrently exceeds the capability of the system, and performance impairments are incurred. Fortunately, these performance costs can be largely overcome with training: training improves multitasking ability (4) and typically leads to reduced activity in FP-SC brain regions (5, 6).One explanation for these effects is that training diverts task performance away from the capacity limited FP-SC system (5, 6), toward an unmediated sensory–motor association. According to this account, referred to here as the “redistribution account,” the FP-SC system contributes minimally to trained task performance. Therefore, after training, any task representations in this system should be dissociated from behavioral performance. A less considered alternative is that training differentiates the FP-SC response between trained tasks (7), thereby reducing intertask competition between neurons that were initially recruited by both tasks (2) and expanding the capacity for concurrent task processing. According to this framework, referred to here as the “divergence account,” the separation of task representations in these regions should predict training benefits. Thus, the “redistribution” and “divergence” theories make distinct predictions regarding the relationship between FP-SC task representations and improved multitasking abilities.We conducted a large-scale magnetic resonance imaging (MRI) study to test these opposing accounts, capitalizing on an underused information source: interindividual variability in the blood oxygen level-dependent (BOLD) signal. A key characteristic of multitasking is that large and meaningful individual differences have been observed for both the behavioral response to training (4) and the FP response to tasks typically used to study multitasking (8). Thus, analysis of interindividual variability may reveal hitherto unknown aspects of brain function that predict multitasking improvements. To ensure sufficient statistical power for the analysis of interindividual variability, sample sizes much larger than those typically used for fMRI studies (∼N = 16–32) (9) are required. To achieve 80% statistical power (10) to detect medium sized correlations between behavior and the BOLD signal within each group (r = 0.4), we recruited a total of 100 participants (training group, n = 50; control group, n = 50).Because each voxel potentially captures the activity of over a million neurons (11), the spatial resolution obtained by averaging BOLD activity across voxels is insufficient to assess task representations within brain regions. To examine how training alters task representations in FP-SC areas, we instead applied multivoxel pattern analysis (MVPA). This method uses a classification algorithm to decode the degree to which patterns of brain activity measured across voxel ensembles in a brain region carry task specific information, given that each voxel contains a nonuniform distribution of neural selectivity (12). Higher decoding accuracies reflect increased levels of task-relevant information being represented within a given brain area. Therefore, changes in task decoding accuracies from pre- to posttraining can provide insights into task representation changes in the FP-SC system. To preview the results, we observed that multitasking improvements were predicted by decoding accuracy increases in the FP-SC response to the constituent tasks. In support of the divergence account, this demonstrates that enhanced multitasking behavior is supported by the segregation of task-representations in the FP-SC system.     

From the Cover: Navigating transformations in governance of Chilean marine coastal resources

Marine ecosystems are in decline. New transformational changes in governance are urgently required to cope with overfishing, pollution, global changes, and other drivers of degradation. Here we explore social, political, and ecological aspects of a transformation in governance of Chile''s coastal marine resources, from 1980 to today. Critical elements in the initial preparatory phase of the transformation were (i) recognition of the depletion of resource stocks, (ii) scientific knowledge on the ecology and resilience of targeted species and their role in ecosystem dynamics, and (iii) demonstration-scale experimental trials, building on smaller-scale scientific experiments, which identified new management pathways. The trials improved cooperation among scientists and fishers, integrating knowledge and establishing trust. Political turbulence and resource stock collapse provided a window of opportunity that triggered the transformation, supported by new enabling legislation. Essential elements to navigate this transformation were the ability to network knowledge from the local level to influence the decision-making processes at the national level, and a preexisting social network of fishers that provided political leverage through a national confederation of artisanal fishing collectives. The resultant governance scheme includes a revolutionary national system of marine tenure that allocates user rights and responsibilities to fisher collectives. Although fine tuning is necessary to build resilience of this new regime, this transformation has improved the sustainability of the interconnected social–ecological system. Our analysis of how this transformation unfolded provides insights into how the Chilean system could be further developed and identifies generalized pathways for improved governance of marine resources around the world.     

From the Cover: Geographically varying associations between personality and life satisfaction in the London metropolitan area

Residential location is thought to influence people’s well-being, but different individuals may value residential areas differently. We examined how life satisfaction and personality traits are geographically distributed within the UK London metropolitan area, and how the strength of associations between personality traits and life satisfaction vary by residential location (i.e., personality–neighborhood interactions). Residential area was recorded at the level of postal districts (216 districts, n = 56,019 participants). Results indicated that the strength of associations between personality traits and life satisfaction depended on neighborhood characteristics. Higher openness to experience was more positively associated with life satisfaction in postal districts characterized by higher average openness to experience, population density, and ethnic diversity. Higher agreeableness and conscientiousness were more strongly associated with life satisfaction in postal districts with lower overall levels of life satisfaction. The associations of extraversion and emotional stability were not modified by neighborhood characteristics. These findings suggest that people’s life satisfaction depends, in part, on the interaction between individual personality and particular features of the places they live.Where is the best place to live? Numerous “livability” rankings of cities and neighborhoods have been published in academic journals and newspapers (1–4). Such rankings tend to imply that all people would value the same residential areas equally. Places are often ranked by residents’ average happiness or life satisfaction—without considering how these places might match with specific dispositions of individuals. However, it seems likely that people’s life satisfaction depends on the interactions between neighborhood characteristics and individual dispositions (5, 6). For example, a location with high cultural diversity might enhance the lives of residents who are eager to explore new customs and cuisines, but increase the anxiety and discomfort of residents who prefer to live by their own social traditions.A growing number of studies have shown that personality traits are geographically clustered, and that these regional personality clusters are correlated with many sociocultural factors (6, 7). For example, the west coast of the United States is characterized by higher openness and emotional stability compared with the rest of the country, whereas the east coast has lower emotional stability and conscientiousness (7). One important question arising from these findings is whether the geographical clustering of personality represents adaptive patterns, so that people with certain personality traits are found in specific neighborhoods because these locations provide them higher levels of happiness for their personalities (6, 8–10). High extraversion, for instance, might be clustered in specific neighborhoods because these neighborhoods provide more opportunities of social interaction for individuals with high extraversion (11, 12). Thus, personality provides a psychological measure to test whether and how the people’s dispositions and neighborhood characteristics jointly influence life satisfaction.In the present study, we used data from more than 56,000 individuals living in the metropolitan area of London (United Kingdom) to examine the role of personality–neighborhood interactions in predicting life satisfaction. First, we examined how mean levels of life satisfaction and personality traits are spatially distributed across London. Although earlier studies have reported geographical differences in aggregated levels of personality and life satisfaction (6), these studies have not used the relevant spatial statistics to assess the geographical patterns. We used spatial analysis to quantify how strongly life satisfaction and different personality traits are geographically clustered. To further contextualize these geographical patterns, we assessed how the mean levels of life satisfaction and personality traits of neighborhoods were related to specific neighborhood characteristics, such as population density and crime rate.Second, we investigated whether personality traits correlate with life satisfaction differently depending on residential location. This analysis addressed the issue of personality–neighborhood interactions in determining people’s life satisfaction, because the focus was on geographically varying associations between personality traits and life satisfaction. The “person–environment fit” hypothesis postulates that a better match between person and environment leads to higher satisfaction, because the person’s behavior is better in line with the prevailing social norms, and the person’s needs are better fulfilled (13–15). To test how personality was differently related to life satisfaction in different neighborhoods, we fitted regression models that allowed personality traits to be differently associated with life satisfaction in different neighborhoods. To examine the specific neighborhood characteristics associated with higher or lower fit with personality traits, the neighborhood-specific regression slopes were then correlated with neighborhood characteristics and mean levels of personality. A positive correlation between the regression slope and mean personality level would indicate an adaptive spatial clustering of personality, so that people with high levels of the trait are living in neighborhoods where the trait is most strongly associated with higher life satisfaction.Most previous studies have examined psychological differences between relatively large geographical units, such as states and counties (7). To get more detailed measures of people’s residential locations and their surroundings, we determined neighborhoods at the finer resolution of postal districts. Life satisfaction was rated by the participants using the Satisfaction with Life Scale (16), and personality was self-reported by using the Big Five Inventory (17) that measures extraversion, neuroticism, agreeableness, conscientiousness, and openness to experience. Given the lack of previous research on the topic at the small-area spatial scale, we did not have predefined hypotheses of spatial patterns of life satisfaction or personality traits.