The impact of a poverty reduction intervention on infant brain activity

Early childhood poverty is a risk factor for lower school achievement, reduced earnings, and poorer health, and has been associated with differences in brain structure and function. Whether poverty causes differences in neurodevelopment, or is merely associated with factors that cause such differences, remains unclear. Here, we report estimates of the causal impact of a poverty reduction intervention on brain activity in the first year of life. We draw data from a subsample of the Baby’s First Years study, which recruited 1,000 diverse low-income mother–infant dyads. Shortly after giving birth, mothers were randomized to receive either a large or nominal monthly unconditional cash gift. Infant brain activity was assessed at approximately 1 y of age in the child’s home, using resting electroencephalography (EEG; n = 435). We hypothesized that infants in the high-cash gift group would have greater EEG power in the mid- to high-frequency bands and reduced power in a low-frequency band compared with infants in the low-cash gift group. Indeed, infants in the high-cash gift group showed more power in high-frequency bands. Effect sizes were similar in magnitude to many scalable education interventions, although the significance of estimates varied with the analytic specification. In sum, using a rigorous randomized design, we provide evidence that giving monthly unconditional cash transfers to mothers experiencing poverty in the first year of their children’s lives may change infant brain activity. Such changes reflect neuroplasticity and environmental adaptation and display a pattern that has been associated with the development of subsequent cognitive skills.

Early childhood poverty has long been associated with lower school achievement, educational attainment, and adult earnings (1–4). Moreover, from early childhood through adolescence, higher family income tends to be associated with higher scores on assessments of language, memory, self-regulation, and social-emotional processing (5–8). Furthermore, poverty has been correlated with the structural development and functional activity of brain regions that support these skills. For example, higher family income is associated with a larger surface area of the cerebral cortex, particularly in regions that support children’s language and executive functioning (9, 10). This association is strongest among the most economically disadvantaged families (9), suggesting that a given increase in family income may be linked with greater differences in brain structure among economically disadvantaged children compared with more advantaged peers (11).Economic disadvantage has also been associated with differences in electrical brain activity, a key aspect of brain function that is measured by electroencephalography (EEG) (12–16). EEG measures brain activity along two primary dimensions: frequency and power. “Frequency” refers to oscillatory brain activity that occurs throughout the brain at different rates. Neuroscientists traditionally divide the continuous frequency spectrum into bands. Some of these bands represent lower-frequency (slower) oscillations (e.g., the theta-band), and some represent higher-frequency (faster) brain activity in the mid to high portions of the frequency spectrum (e.g., the alpha-, beta-, and gamma-bands). All individuals have brain activity across the frequency spectrum throughout the brain. “Power” refers to the amount of brain activity in a certain band measured across the scalp, broadly reflecting the electrical activity of the underlying brain. Power varies across frequency bands and between people. “Absolute power” refers to the amount of brain activity measured at a certain frequency (or within a certain frequency band). “Relative power” expresses absolute power as a fraction of power summed across all frequency bands.Childhood EEG-based brain activity demonstrates a specific developmental pattern. As children mature from the neonatal period through middle childhood, they tend to show a decrease in brain power in the low-frequency portion of the frequency spectrum, as well an increase in brain power in the mid- to high-frequency portions of the frequency spectrum (17–20). Individual differences in this pattern, particularly in absolute power, have been associated with children’s cognitive and behavioral outcomes. For example, more absolute power in mid- to high- (i.e., alpha, beta, and gamma) frequency bands has been associated with higher language (21–24), cognitive (21, 25), and social-emotional (26) scores, whereas more absolute or relative low-frequency (i.e., theta) power has been associated with the development of behavioral, attention, or learning problems (27–29).At birth, family income appears to be unrelated to brain activity, as measured by EEG (23). However, some studies find that family income quickly begins to predict differences in the neurodevelopmental patterns described above. Specifically, several studies with small sample sizes have suggested that within the first several years of life, children from lower-income families average more low-frequency (i.e., theta) EEG band power, and less mid- to high-frequency (i.e., alpha, beta, and gamma) band power compared with children from higher-income homes (13–15, 30). Similar patterns of more low-frequency band power and less mid- to high-frequency band power have also been found among children facing other forms of early adversity (31–33) and, in some of these studies, these differences appear to persist throughout childhood and early adolescence (13, 14, 34–36). Of course, these general patterns conceal considerable heterogeneity; not all children facing poverty or other forms of adversity will show evidence of these neurodevelopmental differences.Neuroplasticity, or the concept that children’s brains adapt to their environmental contexts, is one path through which these differences are thought to emerge. That is, the structure and function of the developing brain adapt in response to different experiences. Brain activity may thus be one mechanism by which early adverse experiences shape subsequent child developmental outcomes.Despite the correlational evidence linking income to early childhood cognitive development, it is unclear whether poverty causes developmental differences early in life (37). Support for a causal role comes from rigorous quasiexperimental studies that have linked increases in family income to higher school achievement and educational attainment, as well as to better physical and mental health (38). On the other hand, many other characteristics of individuals and their environments have been linked to these kinds of child outcomes (39). A careful experimental manipulation is needed to differentiate between these alternate interpretations.The Baby’s First Years study (BFY; https://www.babysfirstyears.com) is the first randomized control trial of poverty reduction in early childhood, and was designed to address whether poverty reduction causes changes in children’s brain development (40). Based on prior economic research showing that relatively modest differences in early childhood family income are associated with better school achievement (41–43), BFY randomized 1,000 low-income mothers living in four geographically diverse United States metropolitan areas to receive either a large cash gift of $333 per month (termed the “high-cash gift group”) or a nominal cash gift of $20 per month (the “low-cash gift group”) for the first several years of their children’s lives. These cash gifts took the form of unconditional cash transfers provided on a debit card; participating mothers were told that the money could be used in any way they wished, with no restrictions. The $313/mo difference between the amount received by the high-cash and low-cash gift groups amounted to $3,756 per year. Here we report the differential impacts of these unconditional cash transfers on infant brain activity at 1 y of age. We preregistered our analytic plan and hypothesized that infants of mothers randomized to the high-cash gift group would show greater mid- to high-frequency (i.e., alpha, beta, gamma) power and decreased low-frequency (i.e., theta) power when compared with infants of mothers randomized to the low-cash gift group.     

Effects of childhood poverty and chronic stress on emotion regulatory brain function in adulthood

Childhood poverty has pervasive negative physical and psychological health sequelae in adulthood. Exposure to chronic stressors may be one underlying mechanism for childhood poverty−health relations by influencing emotion regulatory systems. Animal work and human cross-sectional studies both suggest that chronic stressor exposure is associated with amygdala and prefrontal cortex regions important for emotion regulation. In this longitudinal functional magnetic resonance imaging study of 49 participants, we examined associations between childhood poverty at age 9 and adult neural circuitry activation during emotion regulation at age 24. To test developmental timing, concurrent, adult income was included as a covariate. Adults with lower family income at age 9 exhibited reduced ventrolateral and dorsolateral prefrontal cortex activity and failure to suppress amygdala activation during effortful regulation of negative emotion at age 24. In contrast to childhood income, concurrent adult income was not associated with neural activity during emotion regulation. Furthermore, chronic stressor exposure across childhood (at age 9, 13, and 17) mediated the relations between family income at age 9 and ventrolateral and dorsolateral prefrontal cortex activity at age 24. The findings demonstrate the significance of childhood chronic stress exposures in predicting neural outcomes during emotion regulation in adults who grew up in poverty.Childhood poverty is related to increased risk of psychopathology (1–3) and physical illness in adulthood (4, 5). Furthermore, childhood poverty predicts adult morbidity irrespective of adult poverty (5–7). One possible mechanism to explain the far-reaching effects of childhood poverty on health is chronic stress (8). Chronic exposure to stressors associated with living in low-income families has long-term negative effects on physiological stress regulatory systems (9–12), eventually resulting in pathology (13, 14). Growing evidence suggests exposure to chronic stress and socioeconomic adversity produces lasting neurobiological changes (15, 16). However, little is known about whether childhood poverty is prospectively associated with central nervous system mechanisms involved in emotion regulation. Such knowledge may provide insights into identifying neural patterns for emotion regulatory dysfunction among adults who grew up in childhood poverty.The amygdala and prefrontal cortex (PFC) play a critical role for stress and emotion regulation. The amygdala detects and responds to threats from the environment, activating physiological stress responses (17). The PFC is widely considered as a top-down region that regulates the amygdala (18, 19). More specifically, the ventrolateral PFC (VLPFC), dorsolateral PFC (DLPFC), and medial PFC (mPFC) implement cognitive strategies such as cognitive reappraisal involved in emotion regulation (18–20). During reappraisal of negative stimuli, increased activity in the VLPFC, DLPFC, and mPFC regions is associated with diminished amygdala reactivity to negative stimuli as well as decreased perceived negative affect (21). Amygdala and PFC dysregulation has also been observed in populations with mood dysregulation, including depression (22), anxiety disorders (23, 24) including posttraumatic stress disorder (25), impulsive aggression (26), and substance abuse (27). Aberrant amygdala reactivity and inefficient or blunted PFC regulatory function are considered a neurobiological mechanism involved in impaired emotion regulation in these psychiatric disorders.Amygdala and PFC functions have also been shown to be affected by socioeconomic disparities (28, 29). In children, low socioeconomic status (SES) has been related to greater amygdala volume (30) and reduced PFC activity during cognitive tasks (31). In adults, retrospective reports of childhood SES were associated with elevated amygdala activity while processing negative facial expressions independently of adult SES (32) and reduced VLPFC activity while experiencing social exclusion (33). However, whether the amygdala and PFC functions associated with childhood poverty are directly related to effortful emotion regulation has never been examined.At present, little is known about underlying mechanisms that account for the relation between childhood SES and neural functioning. Chronic stress is one hypothetical mediator of the negative link between childhood poverty and adult health outcomes (8, 10). For example, children living in poverty are more likely to be exposed to multiple chronic stressors including violence, family turmoil, separation from family members, and substandard living environments (34, 35). In our previous studies, poverty exposure at age 9 prospectively predicted physiological stress dysregulation (34) and emotion dysregulation (36, 37) in adolescence when concurrent levels of poverty exposure were controlled. In these studies, poverty exposure at age 9 was concurrently and prospectively associated with chronic stress exposure at age 9, 13, and 17 (37–39), and elevated chronic stress, in turn, mediated the association between childhood poverty and later outcomes. Furthermore, animal studies and recent human brain imaging studies demonstrate that repeated exposure to chronic stress impacts amygdala and PFC development, potentially leading to impaired emotion regulation (40–43).Therefore, in this longitudinal study, we investigated whether childhood family income was associated prospectively with adult neural activity in the amygdala and PFC during emotion regulation. We also examined a stress pathway linking childhood poverty and the subsequent neural functions for emotion regulation. The current study used family income assessed at age 9 as a direct measure of childhood poverty exposure. To investigate the developmental timing of poverty and neural functioning, we examined the link between childhood poverty and adult neural functioning after controlling for adult income levels. We used a well-established emotion regulation functional magnetic resonance imaging (fMRI) paradigm (18, 44), in which participants are instructed to experience the natural emotional state (Maintain) or to decrease the intensity of their negative affect by using cognitive reappraisal (Reappraisal) while viewing negative images. We hypothesized that, in the contrast of Reappraisal vs. Maintain conditions, low family income at age 9 would be associated with increased amygdala and decreased PFC activation. The amygdala and PFC activation may also be associated with self-reports of emotion regulation (Materials and Methods). Furthermore, we assessed chronic stress by averaging exposure to multiple physical (i.e., substandard housing, crowding, and noise) and social (i.e., family turmoil, violence, and child–family separation) risk factors across ages 9–17. We hypothesized that the influence of childhood income on amygdala and PFC activity would be mediated by chronic stress exposure throughout childhood.     

Sustainable-use protected areas catalyze enhanced livelihoods in rural Amazonia

Finding new pathways for reconciling socioeconomic well-being and nature sustainability is critically important for contemporary societies, especially in tropical developing countries where sustaining local livelihoods often clashes with biodiversity conservation. Many projects aimed at reconciling the goals of biodiversity conservation and social aspirations within protected areas (PAs) have failed on one or both counts. Here, we investigate the social consequences of living either inside or outside sustainable-use PAs in the Brazilian Amazon, using data from more than 100 local communities along a 2,000-km section of a major Amazonian river. The PAs in this region are now widely viewed as conservation triumphs, having implemented community comanagement of fisheries and recovery of overexploited wildlife populations. We document clear differences in social welfare in communities inside and outside PAs. Specifically, communities inside PAs enjoy better access to health care, education, electricity, basic sanitation, and communication infrastructure. Moreover, living within a PA was the strongest predictor of household wealth, followed by cash-transfer programs and the number of people per household. These collective cobenefits clearly influence life satisfaction, with only 5% of all adult residents inside PAs aspiring to move to urban centers, compared with 58% of adults in unprotected areas. Our results clearly demonstrate that large-scale “win–win” conservation solutions are possible in tropical countries with limited financial and human resources and reinforce the need to genuinely empower local people in integrated conservation-development programs.

Tropical deforestation worldwide is a major contributor to the loss of biodiversity, ecosystem services, and livelihoods (1, 2). Human activities, such as agricultural development, industrial logging, overhunting, and overfishing, have catalyzed rapid tropical forest degradation (3). Contemporary societies now face the intractable challenge of establishing new development pathways that align biodiversity conservation with enhanced local welfare. This is especially important in developing countries, which support most of the world’s biota (4) and ethnocultural diversity but frequently suffer from high levels of poverty and social inequality (1).Protected areas (PAs) arguably represent the most effective conservation policy tool for a more sustainable world (5). Although the primary goal of PAs is to maintain biodiversity, ecological processes and ecosystem services (6, 7), the ways in which PAs are created, managed and regulated continue to evolve (8). In tropical developing countries — where rural poverty is often a critical constraint — sustainable-use PAs are increasingly charged with the additional challenge of integrating mounting social aspirations (9, 10). The complex challenge of fulfilling seemingly opposing conservation and social goals has created an apparent conservation dilemma (11, 12), yet reconciling these two legitimate demands within human-occupied PAs remains largely unresolved (12).There is considerable evidence that local people incur opportunity costs when a PA is established, including physical displacement and restricted access to natural resources (13–15). This can in turn lead to higher levels of poverty (13) and local resentment, if not social unrest (16). Nevertheless, depending on when, where and how PAs are implemented, they can also generate important benefits for local livelihoods. Most studies are focused on economic indicators (17) but PAs also catalyze wider improvements in well-being outcomes, including cultural maintenance, emotional and mental health, strengthening of local governance, ensuring social rights, land tenure, increased access to natural resources and greater food security and sovereignty for disenfranchised communities (17–20).Global society has committed to decelerate biodiversity loss, increase PA coverage and halve rural poverty by 2030 through the Aichi Biodiversity targets and Sustainable Development Goals (21). Since PAs can have either negative or positive impacts on livelihoods, meeting these commitments will mean identifying scalable strategies that successfully reconcile conservation and social aspirations. Many studies have focused on the linkages between human well-being and ecosystem services to demonstrate the potential of PAs to provide positive social outcomes (6, 22). One such cultural service is tourism development within PAs, which has been shown to contribute to poverty alleviation in different countries (23, 24). Nevertheless, tourism is not always a viable option, and other attempts to integrate nature conservation and local welfare in PAs have received far less attention. Empirical assessments of other mechanisms that can ensure the long-term goals of PAs, including the development of biodiversity value-chains and cultural practices, are thus urgently required to support conservation policy and practice (20, 25).Community-based conservation initiatives within Amazonian sustainable-use PAs represent a promising window of opportunity to assess the degree to which biodiversity protection is compatible with local aspirations. In these arrangements, local communities are empowered to protect their own territories against illegal fishers, loggers, and poachers. Concomitantly, socioeconomic benefits can be obtained through biodiversity-based value chains, including Açaí palm fruits (Euterpe precatoria and Euterpe oleracea), Brazil nuts (Bertholletia excelsa), and wild-caught fish (19, 26–28). These schemes are often built by multiple partners under polycentric arrangements, including rural communities, local associations, nonprofit organizations, private companies, and government agencies (29), in which each partner makes a specific role to the same target but shares autonomous decision-making at different scales (27, 30). Although not a panacea, these participatory models represent a transformative approach in sustainable resource management accruing positive outcomes for both local welfare and biodiversity (30).Here, we evaluate different elements of human well-being and their enablers both inside and outside a system of sustainable-use PAs in Brazilian Amazonia underpinned by strong local governance. This study covers more than 100 rural communities stretched across ∼2,000 km of the Juruá River, a major tributary of the Amazon River. Communities within PAs in our study area have been participating in a set of remarkably successful community-based conservation initiatives to sustainably manage commercially valuable aquatic and terrestrial resources, which have resulted in the population recovery of other wild species (19, 31, 32). We hypothesize that PAs create a wide range of opportunities that can induce local social changes resulting in enhanced socioeconomic profiles. We also discuss the role of sustainable-use PAs in megadiverse countries, arguing that some mechanisms ensuring social and ecological outcomes inside PAs can be largely rolled out beyond PA boundaries, thereby decentralizing biodiversity conservation and spreading transformative livelihood gains and biodiversity conservation at much larger scales.     

Kirigami-based metastructures with programmable multistability

Multistability plays an important role in advanced engineering applications such as metastructures, deployable structures, and reconfigurable robotics. However, most existing multistability design is based on the two-dimensional (2D)/3D series or parallel combinations of bistable unit cells, which are derived from snap-through instability, nonrigid foldable origami structures, and compliant mechanism, due to the lack of a generic multistable unit cell. Here, we develop a tristable kirigami cuboid by creating a set of elastic joints only effective in a specific motion range which integrates the elastic sheets and switchable hinge axes inspired by the kinematic behaviors of a kirigami cuboid with thick facets. The energy barriers between the stable states can be programmed by the geometric design parameters and material properties of the elastic joints. Taking the tristable cuboid as a unit cell, we construct a family of metastructures with multiple stable states. The number of stable states, the combination of unit stable states, and their transform sequences can be programmed by the number of unit cells, unit design parameters, and loading modes and loading sequences. We also apply this tristable cuboid to the design of frequency reconfigurable antenna with three programmable working frequencies, which demonstrates that such versatile multistability and structural diversity facilitate the development of multifunctional materials and devices.

Multistability is a characteristic of structures with more than one stable equilibrium configuration, which can realize the rapid structural reconfiguration to meet certain functional requirements. Recently, multistable structures have been used to design mechanical structural materials with shape reconfiguration (1–3) and negative stiffness (4) for trapping elastic strain energy (5), energy absorption (6–8), and ternary logic operation (9); robots (10–14) for simplifying actuators, reducing power consumption, and improving the locomotion speed and motion integration; soft media (15) and mechanical diodes (16, 17) for the propagation of mechanical signals; devices for mechanical memory storage (18); deployable structures for self-locked configuration (19, 20) and rapid deployment (21); and other potential applications (22).However, most existing multistability is based on the two-dimensional (2D)/3D series or parallel combinations of bistable unit cells, which are derived from snap-through instability (1, 8, 17, 23–27), nonrigid foldable origami structures (28–32), and compliant mechanisms including rigid origami (33–37). Among them, the snap-through instable beam or structure is the most commonly used fundamental unit in construction with planer motifs or spatial topologies to form 1D, 2D, and 3D multistable structures with unidirectional (1, 24), bidirectional, and multidirectional multistability (2, 4, 6, 9), such as the multistable 1D cylindrical structures, 2D square lattices, and 3D cubic/octahedral lattices (9). Recently, nonrigid origami structure is an emerging resource for designing bistable units based on the elastic deformation of origami facets, such as the Kresling pattern (11, 18, 20, 38) and the hypar pattern (30, 39). Multiple Kresling units can be assembled in series to construct multistable structures (18, 31), and multiple hypar-origami units can be tessellated in plane to be a multistable metasurface (30). Meanwhile, compliant mechanisms derived from mechanisms by introducing spring hinges with compliant segments (34, 36) or torsional springs (40) to store energy have been used to propose bistable unit cells, such as four-bar developable mechanisms (37), Sarrus linkages (41), twisting and rotational mechanisms (42, 43), rotating polygon embedded magnets (44–46), the waterbomb unit (34), and the Miura-ori unit (47, 48). The Miura-ori units have been stacked to be multilayer multistable structures (16, 33, 47).Besides few tristable units with nonzero energy stable states (32, 41), there is no generic tristable or multistable structure which itself is a basic unit rather than constructing with bistable units. On the other hand, most of the bistable unit cells are accompanied by large deformation on beams or facets, while few are derived from the design of joints. One such example is quadrastable overconstrained spatial Sarrus mechanisms with compliant joints (41), whose stable states are also nonzero energy ones, except the initial fabrication state. Therefore, in this paper, we are aiming to develop a generic tristable kirigami cuboid with a set of specially designed elastic joints based on its kinematic behaviors. By combining the tristable kirigami cuboid in series, multistable structures with programmable stable configurations, transformation sequence, and stiffness are constructed. This work paves the way to design multistable metastructures, which facilitates the development of functional materials and devices.     

Testing the efficacy of three informational interventions for reducing misperceptions of the Black–White wealth gap

Americans remain unaware of the magnitude of economic inequality in the nation and the degree to which it is patterned by race. We exposed a community sample of respondents to one of three interventions designed to promote a more realistic understanding of the Black–White wealth gap. The interventions conformed to recommendations in messaging about racial inequality drawn from the social sciences yet differed in how they highlighted data-based trends in Black–White wealth inequality, a single personal narrative, or both. Data interventions were more effective than the narrative in both shifting how people talk about racial wealth inequality—eliciting less speech about personal achievement—and, critically, lowering estimates of Black–White wealth equality for at least 18 mo following baseline, which aligned more with federal estimates of the Black–White wealth gap. Findings from this study highlight how data, along with current recommendations in the social sciences, can be leveraged to promote more accurate understandings of the magnitude of racial inequality in society, laying the necessary groundwork for messaging about equity-enhancing policy.

In a recent study, a nationally representative sample of survey respondents estimated that, on average, Black families had $90 US in wealth relative to the $100 of US White families in the United States (1, 2). The mean estimates generated by respondents in this and other studies were between 40 and 80 percentage points higher for Black family wealth than median statistics collected using the federal government’s Survey of Consumer Finances (SCF), where at the time of this writing, Black families hold $12.81 US in wealth relative to White families (3). The magnitude of this misperception is vast (4, 5). Reducing this perceptual gap, with the larger aim of reducing racial inequality through policy, is the focus of this research.In this study, we sought to better understand how to promote more realistic perceptions of racial inequality in the United States. We conducted a laboratory-based intervention on people’s estimates of the Black–White wealth gap—an inequality that Americans, on average, are shockingly ignorant of (1, 2). We then followed respondents who completed the intervention for up to 18 mo to determine if any changes in understandings of the wealth gap would persist. Our central prediction was that information communicating the magnitude of the Black–White wealth gap with data, versus exposure to a narrative featuring the hardships and lived experiences of a single family contending with obstacles that stem from the Black–White wealth gap, would be necessary to increase the perceived magnitude of Black–White wealth inequality in society.We focus on wealth inequality in this study because it is the single most consequential economic indicator of the ability to absorb unanticipated financial shocks (1). The process for how Americans develop and sustain such a large gap between perception of the Black–White wealth gap and its reality is multifaceted. One barrier to a more accurate understanding of racial wealth inequality is a failure to reckon with the specific relationship between wealth accrual and societal racism, both past and present (6). The capacity to accrue wealth has been unequal for Black and White Americans since before the founding of the United States (when Black Americans constituted wealth) to the recent past, when policies like redlining and the GI Bill largely excluded Black Americans from their wealth-accruing benefits (6–8). Contemporary practices also create racially unequal capacities for Black and White Americans to accrue wealth. For instance, Black Americans need to take on significantly more student loan debt (8), are more likely to be incarcerated, earn lower wages, and live in neighborhoods with lower property values relative to Whites (8, 10).The magnitude of Black–White wealth inequality can be startling for many people who learn of it for the first time, and yet many never learn about it at all. Some of the reasons for this lack of learning include the aversion to numeracy that leads people to avoid population statistics (11). A second barrier is misinformation about the Black–White wealth gap propagated by prevailing narratives about the exceptional and meritocratic nature of American life (12, 13). The narrative of racial progress is one such narrative that shapes our understanding of the Black–White wealth gap (14, 15). This narrative minimizes contemporary societal racial inequality, preferring instead to highlight the capacity for individual achievement regardless of race and to consider racial inequality as something that is rapidly, and perhaps naturally, decreasing over time (16, 17). As long as this narrative governs perceptions of societal racial equity, the magnitude of the Black–White wealth gap will remain an inconvenient truth that must be ignored.Evidence suggests that people adhere to the narrative of racial progress, and that motivational processes supporting that narrative drive misperceptions of racial inequality in society (18–20). For instance, belief in a just world predicts the extent that Americans underestimate racial inequality (5). In more recent experimental work, efforts to incentivize accuracy through monetary compensation were successful in eliciting more accurate perceptions of racial wealth inequality (4), suggesting that these misperceptions are, at least in part, motivated by a desire to uphold beliefs in contemporary racial equality (21). In the following section, we compare the ability of different messaging strategies, based on personal narratives or data, to elicit more realistic perceptions of the Black–White wealth gap.     

miR-182 targeting reprograms tumor-associated macrophages and limits breast cancer progression

The protumor roles of alternatively activated (M2) tumor-associated macrophages (TAMs) have been well established, and macrophage reprogramming is an important therapeutic goal. However, the mechanisms of TAM polarization remain incompletely understood, and effective strategies for macrophage targeting are lacking. Here, we show that miR-182 in macrophages mediates tumor-induced M2 polarization and can be targeted for therapeutic macrophage reprogramming. Constitutive miR-182 knockout in host mice and conditional knockout in macrophages impair M2-like TAMs and breast tumor development. Targeted depletion of macrophages in mice blocks the effect of miR-182 deficiency in tumor progression while reconstitution of miR-182-expressing macrophages promotes tumor growth. Mechanistically, cancer cells induce miR-182 expression in macrophages by TGFβ signaling, and miR-182 directly suppresses TLR4, leading to NFκb inactivation and M2 polarization of TAMs. Importantly, therapeutic delivery of antagomiR-182 with cationized mannan-modified extracellular vesicles effectively targets macrophages, leading to miR-182 inhibition, macrophage reprogramming, and tumor suppression in multiple breast cancer models of mice. Overall, our findings reveal a crucial TGFβ/miR-182/TLR4 axis for TAM polarization and provide rationale for RNA-based therapeutics of TAM targeting in cancer.

It is well known that the nonmalignant stromal components in tumors play pivotal roles in tumor progression and therapeutic responses (1, 2). Macrophages are a major component of tumor microenvironment and display considerable phenotypic plasticity in their effects toward tumor progression (3–5). Classically activated (M1) macrophages often exert direct tumor cytotoxic effects or induce antitumor immune responses by helping present tumor-related antigens (6, 7). In contrast, tumoral cues can polarize macrophages toward alternative activation with immunosuppressive M2 properties (6–8). Numerous studies have firmly established the protumor effects of M2-like tumor-associated macrophages (TAMs) and the association of TAMs with poor prognosis of human cancer (9–11). However, how tumors induce the coordinated molecular and phenotypic changes in TAMs for M2 polarization remains incompletely understood, impeding the designing of TAM-targeting strategies for cancer intervention. In addition, drug delivery also represents a hurdle for therapeutic macrophage reprogramming.Noncoding RNAs, including microRNAs, have been shown to play vital roles in various pathological processes of cancer (12). The microRNA miR-182 has been implicated in various developmental processes and disease conditions (13–15). Particularly, it receives extensive attention in cancer studies. Prevalent chromosomal amplification of miR-182 locus and up-regulation of its expression in tumors have been observed in numerous cancer types including breast cancer, gastric cancer, lung adenocarcinoma, colorectal adenocarcinoma, ovarian carcinoma, and melanoma (16–21). miR-182 expression is also linked to higher risk of metastasis and shorter survival of patients (20, 22–24). Functional studies showed that miR-182 expression in cancer cells plays vital roles in various aspects of cancer malignancy, including tumor proliferation (25–29), migration (30, 31), invasion (16, 32, 33), epithelial-mesenchymal transition (34–36), metastasis (21, 37, 38), stemness (30, 39, 40), and therapy resistance (41, 42). A number of target genes, including FOXO1/3 (18, 21, 43–45), CYLD (46), CADM1 (47), BRCA1 (27, 48), MTSS1 (34), PDK4 (49), and SMAD7 (35), were reported to be suppressed by miR-182 in cancer cells. Our previous work also proved that tumoral miR-182 regulates lipogenesis in lung adenocarcinoma and promotes metastasis of breast cancer (34, 35, 49). Although miR-182 was established as an important regulator of cancer cell malignancy, previous studies were limited, with analyses of miR-182 in cultured cancer cells and transplanted tumors. Thus, the consequences of miR-182 regulation in physiologically relevant tumor models, such as genetically modified mice, have not been shown. More importantly, whether miR-182 also plays a role in tumor microenvironmental cell components is unknown.In this study, we show that miR-182 expression in macrophages can be induced by breast cancer cells and regulates TAM polarization in various tumor models of mice. In addition, miR-182 inhibition with TAM-targeting exosomes demonstrates promising efficacy for cancer treatment.     

Combining pressure and electrochemistry to synthesize superhydrides

Recently, superhydrides have been computationally identified and subsequently synthesized with a variety of metals at very high pressures. In this work, we evaluate the possibility of synthesizing superhydrides by uniquely combining electrochemistry and applied pressure. We perform computational searches using density functional theory and particle swarm optimization calculations over a broad range of pressures and electrode potentials. Using a thermodynamic analysis, we construct pressure–potential phase diagrams and provide an alternate synthesis concept, pressure–potential (P2), to access phases having high hydrogen content. Palladium–hydrogen is a widely studied material system with the highest hydride phase being Pd₃H₄. Most strikingly for this system, at potentials above hydrogen evolution and ∼ 300 MPa pressure, we find the possibility to make palladium superhydrides (e.g., PdH₁₀). We predict the generalizability of this approach for La-H, Y-H, and Mg-H with 10- to 100-fold reduction in required pressure for stabilizing phases. In addition, the P2 strategy allows stabilizing additional phases that cannot be done purely by either pressure or potential and is a general approach that is likely to work for synthesizing other hydrides at modest pressures.

Hydrides are a large class of materials containing hydrogen, the lightest and most abundant element in the universe. They have attracted much research interest due to their scientific significance and numerous applications. As important hydrogen storage media (1), they are able to store hydrogen at densities higher than that of liquid hydrogen (2). They also find applications in hydrogen compressors (3), refrigeration (4), heat storage (5), thermal engines (6), batteries (7), fuel cells (8), actuators (9), gas sensors (10), smart windows (11), H₂ purification (12), isotope separation (13), alloy processing (14), catalysis (15), semiconductors (16), neutron moderators (17), low-energy nuclear reactions (18), and recently possible high-temperature superconductors with a critical superconducting temperature T_c in the vicinity of room temperature in hydrogen-rich materials under pressure (19–38).In the late 1960s, Neil Ashcroft (19) and Vitaly Ginzburg (20) independently considered the possibility of high-temperature superconductivity in metallic solid hydrogen at high pressure. Later, the idea of chemical precompression was proposed in which chemical “pressure” is exerted to form hydrogen dominant metal hydrides stable at lower pressures (21). Following the successful prediction (22, 23) and confirmation (24) of very high T_c superconductivity in H₃S, near–room-temperature superconductivity was predicted (25, 26), synthesized (27), and discovered (28) in the superhydrides (defined as MH_n, for n > 6) in the La-H system. Later, comparable T_c values were observed experimentally for other La-H (29), Y-H (30–32), and La-Y-H (33) superhydrides, and room-temperature superconductivity was also reported in the C-S-H system (34). In addition, even higher T_c s have been theoretically predicted, such as Li₂MgH₁₆ with T_c as high as ∼ 470 K at 250 GPa (35).High pressures are needed to synthesize superhydrides (38). One major reason is that at lower pressures, the thermodynamic stability of superhydrides is weakened or no longer exists. To overcome such a challenge, it is obvious that more processing variables need to be introduced in addition to chemical composition and pressure. A processing variable that has been largely hidden is the electrical potential when utilizing electrochemistry for synthesis, which has been used in synthesizing palladium hydride at ambient pressure (39). In the present work we show that the synergetic use of pressure and electrical potential can dramatically extend the thermodynamic stability regime of superhydrides to modest pressures, an approach we term P2. This approach opens more opportunities for the creation of superhydrides and other materials by combining pressure and electrochemical loading techniques. We begin by outlining the general thermodynamic framework. We then apply the approach to the Pd-H system, where we also present density functional theory (DFT) predictions of palladium hydrides under pressure. This is followed by predictions for other metal hydride systems and then a discussion of the broad implications.     

The spontaneous emergence of conventions: An experimental study of cultural evolution

How do shared conventions emerge in complex decentralized social systems? This question engages fields as diverse as linguistics, sociology, and cognitive science. Previous empirical attempts to solve this puzzle all presuppose that formal or informal institutions, such as incentives for global agreement, coordinated leadership, or aggregated information about the population, are needed to facilitate a solution. Evolutionary theories of social conventions, by contrast, hypothesize that such institutions are not necessary in order for social conventions to form. However, empirical tests of this hypothesis have been hindered by the difficulties of evaluating the real-time creation of new collective behaviors in large decentralized populations. Here, we present experimental results—replicated at several scales—that demonstrate the spontaneous creation of universally adopted social conventions and show how simple changes in a population’s network structure can direct the dynamics of norm formation, driving human populations with no ambition for large scale coordination to rapidly evolve shared social conventions.Social conventions are the foundation for social and economic life (1–7), However, it remains a central question in the social, behavioral, and cognitive sciences to understand how these patterns of collective behavior can emerge from seemingly arbitrary initial conditions (2–4, 8, 9). Large populations frequently manage to coordinate on shared conventions despite a continuously evolving stream of alternatives to choose from and no a priori differences in the expected value of the options (1, 3, 4, 10). For instance, populations are able to produce linguistic conventions on accepted names for children and pets (11), on common names for colors (12), and on popular terms for novel cultural artifacts, such as referring to junk email as “SPAM” (13, 14). Similarly, economic conventions, such as bartering systems (2), beliefs about fairness (3), and consensus regarding the exchangeability of goods and services (15), emerge with clear and widespread agreement within economic communities yet vary broadly across them (3, 16).Prominent theories of social conventions suggest that institutional mechanisms—such as centralized authority (14), incentives for collective agreement (15), social leadership (16), or aggregated information (17)—can explain global coordination. However, these theories do not explain whether, or how, it is possible for conventions to emerge when social institutions are not already in place to guide the process. A compelling alternative approach comes from theories of social evolution (2, 18–20). Social evolutionary theories maintain that networks of locally interacting individuals can spontaneously self-organize to produce global coordination (21, 22). Although there is widespread interest in this approach to social norms (6, 7, 14, 18, 23–26), the complexity of the social process has prevented systematic empirical insight into the thesis that these local dynamics are sufficient to explain universally adopted conventions (27, 28).Several difficulties have limited prior empirical research in this area. The most notable of these limitations is scale. Although compelling experiments have successfully shown the creation of new social conventions in dyadic and small group interactions (29–31), the results in small group settings can be qualitatively different from the dynamics in larger groups (Model), indicating that small group experiments are insufficient for demonstrating whether or how new conventions endogenously form in larger populations (32, 33). Important progress on this issue has been made using network-based laboratory experiments on larger groups (15, 24). However, this research has been restricted to studying coordination among players presented with two or three options with known payoffs. Natural convention formation, by contrast, is significantly complicated by the capacity of individuals to continuously innovate, which endogenously expands the “ecology” of alternatives under evaluation (23, 29, 31). Moreover, prior experimental studies have typically assumed the existence of either an explicit reward for universal coordination (15) or a mechanism that aggregates and reports the collective state of the population (17, 24), which has made it impossible to evaluate the hypothesis that global coordination is the result of purely local incentives.More recently, data science approaches to studying norms have addressed many of these issues by analyzing behavior change in large online networks (34). However, these observational studies are limited by familiar problems of identification that arise from the inability to eliminate the confounding influences of institutional mechanisms. As a result, previous empirical research has been unable to identify the collective dynamics through which social conventions can spontaneously emerge (8, 34–36).We addressed these issues by adopting a web-based experimental approach. We studied the effects of social network structure on the spontaneous evolution of social conventions in populations without any resources to facilitate global coordination (9, 37). Participants in our study were rewarded for coordinating locally, however they had neither incentives nor information for achieving large scale agreement. Further, to eliminate any preexisting bias in the evolutionary process, we studied the emergence of arbitrary linguistic conventions, in which none of the options had any a priori value or advantage over the others (3, 23). In particular, we considered the prototypical problem of whether purely local interactions can trigger the emergence of a universal naming convention (38, 39).     

Active topolectrical circuits

The transfer of topological concepts from the quantum world to classical mechanical and electronic systems has opened fundamentally different approaches to protected information transmission and wave guidance. A particularly promising emergent technology is based on recently discovered topolectrical circuits that achieve robust electric signal transduction by mimicking edge currents in quantum Hall systems. In parallel, modern active matter research has shown how autonomous units driven by internal energy reservoirs can spontaneously self-organize into collective coherent dynamics. Here, we unify key ideas from these two previously disparate fields to develop design principles for active topolectrical circuits (ATCs) that can self-excite topologically protected global signal patterns. Realizing autonomous active units through nonlinear Chua diode circuits, we theoretically predict and experimentally confirm the emergence of self-organized protected edge oscillations in one- and two-dimensional ATCs. The close agreement between theory, simulations, and experiments implies that nonlinear ATCs provide a robust and versatile platform for developing high-dimensional autonomous electrical circuits with topologically protected functionalities.

Information transfer and storage in natural and man-made active systems, from sensory organs (1–3) to the internet, rely on the robust exchange of electrical signals between a large number of autonomous units that balance local energy uptake and dissipation (4, 5). Major advances in the understanding of photonic (6–9), acoustic (10–12), and mechanical (13–16) metamaterials have shown that topological protection (17–24) enables the stabilization and localization of signal propagation in passive and active (25–27) dynamical systems that violate time-reversal and/or other symmetries. Recent studies have successfully applied these ideas to realize topolectrical circuits (28) in the passive linear (29–34) and passive nonlinear (35, 36) regimes. However, despite substantial progress in the development of topological wave guides (37), lasers (38, 39), and transmission lines (40–43), the transfer of these concepts to active (44, 45) nonlinear circuits made from autonomously acting units still poses an unsolved challenge. From a broader perspective, not only does harnessing topological protection in nonlinear active circuits promise a new generation of autonomous devices, but also understanding their design and self-organization principles may offer insights into information storage and processing mechanisms in living systems, which integrate cellular activity, electrical signaling, and nonlinear feedback to coordinate essential biological functions (46, 47).Exploiting a mathematical analogy with active Brownian particle systems (26), we theoretically develop and experimentally demonstrate general design principles for active topolectrical circuits (ATCs) that achieve self-organized, self-sustained, topologically protected electric current patterns. The main building blocks of ATCs are nonlinear dissipative elements that exhibit an effectively negative resistance over a certain voltage range. Negative resistances can be realized using van der Pol (vdP) circuits (48), tunnel diodes, unijunction transistors, solid-state thyristors (49), or operational amplifiers set as negative impedance converters through current inversion (50), and the design principles described below are applicable to all these systems. Indeed, we expect them to apply to an even broader class of nonlinear systems, as similar dynamics also describe electromagnetic resonators with Kerr-type nonlinearities (51–53).     

Wealth redistribution promotes happiness

How much happiness could be gained if the world’s wealth were distributed more equally? Despite decades of research investigating the relationship between money and happiness, no experimental work has quantified this effect for people across the global economic spectrum. We estimated the total gain in happiness generated when a pair of high-net-worth donors redistributed US$2 million of their wealth in $10,000 cash transfers to 200 people. Our preregistered analyses offer causal evidence that cash transfers substantially increase happiness among economically diverse individuals around the world. Recipients in lower-income countries exhibited happiness gains three times larger than those in higher-income countries. Still, the cash provided detectable benefits for people with household incomes up to $123,000.

A core goal of economic systems is to improve human well-being by allocating scarce resources. Yet, the world’s richest 10% owns three-quarters of global wealth, while the poorest half owns only 2% (1). Prominent scholars across disciplines have argued that extreme income inequality may vastly undermine the potential happiness of the world’s population (2–4). How much happiness could be gained if the wealthy few redistributed money to a broader swath of the world’s population? To estimate this effect, we examined the total happiness gained when two high-net-worth donors redistributed 2 million US dollars ($2M) of their wealth to 200 individuals around the world.A great deal of research suggests that individuals earning higher incomes are happier than those earning lower incomes (for a review, see ref. 5), with the strength of this relationship diminishing as income increases (6). Although a few studies have examined the effect of naturally occurring income shocks using longitudinal panel data (7–10), most scholarly work has relied on correlational analyses, which cannot isolate the causal impact of money on happiness. Indeed, people with higher incomes tend to have better health, education, and other advantages linked to greater happiness (11, 12), and being happy may even lead to greater wealth: Happier high-schoolers earn higher incomes a decade later (13).In recent years, a separate line of research has emerged using randomized controlled trials to test the impact of cash transfers as a form of aid to ameliorate poverty in lower-income nations (see ref. 14 for a review). In this line of work, cash is provided directly to the poor in place of traditional forms of aid, like food or clothing. While these studies broadly support the finding that money provides happiness (15), they have focused on samples living in poverty in lower-income countries, so it is unclear whether the benefits of receiving cash extend beyond the world’s poorest individuals.Would receiving an influx of cash substantially improve the happiness of individuals in higher-income nations? To address this pressing question, numerous pilot projects examining the effects of cash transfers have been launched in the United States, Canada, Finland, and other countries (see ref. 16 for a review). To the best of our knowledge, only two projects have been completed so far. In Finland, the government provided 560 Euros per month to 2,000 unemployed residents and reported that this program increased their happiness (17). In Canada, 50 homeless individuals received a one-time cash transfer of 7,500 Canadian dollars each, but did not exhibit substantial increases in happiness (18). Another prominent study is currently underway, providing $500 per month for 2 y to 125 low-income households in Stockton, CA. Preliminary results from the first year of the study point to improvements in positive mood (19). Given that these unpublished studies have examined relatively narrow samples, it remains an open question whether providing cash transfers could improve happiness among the broader population.In this study, we took advantage of a unique experiment, in which two wealthy donors partnered with the organization TED to give away $2M to an economically diverse global sample. Three hundred participants were recruited from three lower-income countries and four higher-income countries and randomly assigned to receive a single cash transfer of $10,000 ($10k) (or not). We assessed participants’ happiness by measuring the three core components of subjective well-being (SWB): satisfaction with life, positive affect, and negative affect (see ref. 5 for an overview). Going beyond previous work, this study allows us to assess the causal impact of cash transfers on happiness across a large and economically diverse sample.     

Conditions for metachronal coordination in arrays of model cilia

On surfaces with many motile cilia, beats of the individual cilia coordinate to form metachronal waves. We present a theoretical framework that connects the dynamics of an individual cilium to the collective dynamics of a ciliary carpet via systematic coarse graining. We uncover the criteria that control the selection of frequency and wave vector of stable metachronal waves of the cilia and examine how they depend on the geometric and dynamical characteristics of a single cilium, as well as the geometric properties of the array. We perform agent-based numerical simulations of arrays of cilia with hydrodynamic interactions and find quantitative agreement with the predictions of the analytical framework. Our work sheds light on the question of how the collective properties of beating cilia can be determined using information about the individual units and, as such, exemplifies a bottom-up study of a rich active matter system.

Motile cilia are hair-like organelles that beat with a whip-like stroke that breaks time-reversal symmetry to create fluid flow or propel swimming microorganisms under low Reynolds number conditions (1–3). The beat is actuated by many dynein motors, which generate forces between microtubules that cause the cilium to bend in a robust cyclic manner with moderate fluctuations (4, 5). On surfaces with many cilia, the actuating organelles can coordinate with each other and collectively beat in the form of metachronal waves, where neighboring cilia beat sequentially (i.e., with a phase lag) rather than synchronously (6). The flows created from this coordinated beating are important for breaking symmetry in embryonic development (7, 8), creation of complex and dynamic flow patterns for the cerebrospinal fluid in the brain (9, 10), and providing access to nutrients (11). In microorganisms such as Paramecium and Volvox, the metachronal beating of cilia provides propulsion strategies in viscous environments (12, 13). It has been shown that depending on the parameters, beating ciliary carpets can exhibit globally ordered and turbulent flow patterns (14), which can be stable even with a moderate amount of quenched disorder (15), and that metachronal coordination optimizes the efficiency of fluid pumping (16, 17). Natural cilia have inspired various designs of artificial cilia (18–22), which may be used for pumping fluid (23, 24) and mixing (25), or fabrication of microswimmers (26).Hydrodynamic interactions have been shown to play a key role in coordinated beating of cilia (27, 28) and mediating cell polarity control (29). To achieve synchronization between two cilia via hydrodynamic interactions, it is necessary to break the permutation symmetry between them [e.g., by exploiting the dependence of the drag coefficient on the distance from a surface (30), flexibility of the anchoring of the cilia (31), nonuniform beat patterns (32, 33), or any combination of these effects (34)]. In addition to the hydrodynamic interactions, the basal coupling between cilia can also facilitate the coordination (35–37).How can we predict the collective behavior of arrays of many cilia coordinated by hydrodynamic interactions, and in particular, the properties of the emerging metachronal waves, from the single-cilium characteristics? Extensive numerical simulations using explicitly resolved beating filaments (16, 17, 27, 38–40) and simplified spherical rotors (13, 14, 41, 42) have demonstrated that metachronal coordination emerges from hydrodynamic interactions. However, insight into this complex many-body dynamical system at the level that has been achieved in studies of two cilia is still lacking. Here, we propose a theoretical framework for understanding the physical conditions for coordination of many independently beating cilia, which are arranged on a substrate in the form of a two-dimensional (2D) array immersed in a three-dimensional (3D) fluid. We uncover the physical conditions for the emergence of stable metachronal waves and predict the properties of the wave in terms of single-cilium geometric and dynamic characteristics.     

From the Cover: Self-control forecasts better psychosocial outcomes but faster epigenetic aging in low-SES youth

There are persistent socioeconomic disparities in many aspects of child development in America. Relative to their affluent peers, children of low socioeconomic status (SES) complete fewer years of education, have a higher prevalence of health problems, and are convicted of more criminal offenses. Based on research indicating that low self-control underlies some of these disparities, policymakers have begun incorporating character-skills training into school curricula and social services. However, emerging data suggest that for low-SES youth, self-control may act as a “double-edged sword,” facilitating academic success and psychosocial adjustment, while at the same time undermining physical health. Here, we examine this hypothesis in a five-wave study of 292 African American teenagers from rural Georgia. From ages 17 to 20 y, we assessed SES and self-control annually, along with depressive symptoms, substance use, aggressive behavior, and internalizing problems. At age 22 y, we obtained DNA methylation profiles of subjects’ peripheral blood mononuclear cells. These data were used to measure epigenetic aging, a methylation-derived biomarker reflecting the disparity between biological and chronological aging. Among high-SES youth, better mid-adolescent self-control presaged favorable psychological and methylation outcomes. However, among low-SES youth, self-control had divergent associations with these outcomes. Self-control forecasted lower rates of depressive symptoms, substance use, aggressive behavior, and internalizing problems but faster epigenetic aging. These patterns suggest that for low-SES youth, resilience is a “skin-deep” phenomenon, wherein outward indicators of success can mask emerging problems with health. These findings have conceptual implications for models of resilience, and practical implications for interventions aimed at ameliorating social and racial disparities.Self-control is a powerful determinant of success across the lifespan. Defined as the capacity to regulate one’s thoughts, feelings, and actions (1), self-control helps people to resolve motivational conflicts between concrete, proximal goals and abstract, distal goals (2). People with good self-control resist temptations that otherwise would impede progress toward valued long-term goals. At the same, these individuals more easily initiate and sustain behaviors that facilitate attainment of those goals. In prospective studies that follow children into adulthood, self-control consistently presages favorable life outcomes. Youth who exhibit greater self-control go on to perform better in school, earn higher salaries, remain stably employed, and save more money. These youth are less likely to use drugs, be arrested for and convicted of crimes, and develop psychiatric disorders. In early adulthood, these youth also show better physical health (3–8). These associations are generally independent of confounds like demographic characteristics, general intelligence, and psychiatric history.In the United States, there are persistent socioeconomic disparities in many aspects of child development (9, 10). Relative to their affluent peers, children of lower socioeconomic status (SES) experience more academic difficulties, complete less education, have a higher prevalence of physical health problems, teenage pregnancies, and activity-limiting conditions and are more likely to be convicted of, and incarcerated for, criminal offenses (11–13). Recognizing that disparities in self-control partly underlie these trends (3), scholars are increasingly advocating for programs that provide low-SES youth with character-skills training, which along with self-control, includes traits like “grit,” optimism, and persistence (14–17). These efforts have gained momentum among policymakers. For example, the US government’s Administration for Children and Families is developing behavioral interventions to enhance the outcomes of social-service programs that it offers to low-income American families. Self-control is a major target of these interventions.As interest in character-skills development has surged, a parallel literature has been developing, which suggests that self-control may have unforeseen health consequences, particularly for low-SES children from minority backgrounds. Brody et al. (18) followed rural African American children over 8 y, many of whom were living below the federal poverty threshold. Teachers made annual ratings of children’s self-control from ages 11 to 13 y, which were used to forecast young adult outcomes; when assessed at age 19 y, children with better self-control went on to display what psychologists call resilience. Despite being low-SES, these children had fewer depressive symptoms and less substance use, rule breaking, and aggressive behavior as young adults. In analyses of health status, however, the opposite pattern emerged. To the extent that they had better self-control, low-SES children went on to experience greater cardiometabolic risk as young adults, as reflected on a composite of obesity, blood pressure, and the stress hormones cortisol, epinephrine, and norepinephrine. Similar conclusions emerged in a subsequent analysis of the same cohort, which mapped the trajectories of a subgroup of participants who would normatively be viewed as resilient. These individuals had achieved sustained academic success—they had graduated from high school and were now attending college—despite living in challenging neighborhoods with concentrated poverty. Compared with other participants, this cohort had lower rates of cigarette, alcohol, and marijuana use at age 20 y. However, this resilience was only “skin deep.” Despite academic success and healthy lifestyles, these youth showed relatively poor cardiometabolic health at age 20 y, as reflected in obesity, blood pressure, and stress hormones (19).These findings suggest that self-control may act as a “double-edged sword” in low-SES youth, facilitating academic success and psychosocial adjustment, while at the same time undermining cardiometabolic health. What could explain these divergent outcomes? Research shows that for low-SES youth, particularly those of African American descent, achieving normatively favorable outcomes poses intense self-regulatory demands (20–22). Because such demands result in sustained activation of stress hormone systems (18, 19, 23–25), we reasoned they would prematurely age bodily tissue through a process known as weathering (26). Here, we test this hypothesis in a new sample of rural African American youth, who were followed across the transition from adolescence to adulthood. To clarify the mechanisms by which skin-deep resilience develops, we focus on aging of immune cells, using an epigenetic biomarker derived from DNA methylation. This epigenetic clock has been validated in cells from over a dozen tissues and reflects the disparity between biological and chronological age. Using this metric, faster aging rates have been documented in tumor-derived cells from over 20 cancers, as well as liver biopsies from obese patients (27–29). Faster epigenetic aging also presages higher risks for all-cause mortality (30).     

Dynamics of thin precursor film in wetting of nanopatterned surfaces

The spreading of a liquid droplet on flat surfaces is a well-understood phenomenon, but little is known about how liquids spread on a rough surface. When the surface roughness is of the nanoscopic length scale, the capillary forces dominate and the liquid droplet spreads by wetting the nanoscale textures that act as capillaries. Here, using a combination of advanced nanofabrication and liquid-phase transmission electron microscopy, we image the wetting of a surface patterned with a dense array of nanopillars of varying heights. Our real-time, high-speed observations reveal that water wets the surface in two stages: 1) an ultrathin precursor water film forms on the surface, and then 2) the capillary action by nanopillars pulls the water, increasing the overall thickness of water film. These direct nanoscale observations capture the previously elusive precursor film, which is a critical intermediate step in wetting of rough surfaces.

The wettability of surfaces plays an important role in many natural and industrial processes (1–3). Wetting of a smooth surface by a liquid is commonly described by the Young’s equation, which quantifies the wettability of a solid surface using the contact angle of a liquid droplet (4, 5). When the surfaces are rough, the spreading of a droplet is governed by contact angle and capillary effects, and the droplet spreads via hemiwicking (6, 7). The rough features of the surface act as capillaries, or wicks, that imbibe liquid from the droplet (8–10). Earlier studies show that modifying the surface roughness can be a powerful approach to tuning the surface wettability (11–18), and such surface modifications have been used for applications in biomedicine (19, 20), textile industry (21, 22), and water treatment (23, 24).Despite the recent progress in designing rough superhydrophilic surfaces (17, 24), the nanoscale details of the wicking process on rough surfaces remain unknown because these processes are extremely challenging to visualize. Current approaches to study wetting are based on optical methods (25–28), and, while providing valuable insights, these methods lack the spatial resolution needed to discern the nanoscale details of wetting. Alternative approaches based on scanning probe microscopy techniques provide high spatial resolution but lack temporal resolution and thus have been limited to study the adsorption of water (29) and wetting of smooth surfaces (30, 31). Recent advances in liquid-phase transmission electron microscopy (TEM) (32–36) and fast electron detection cameras (37, 38) enabled direct imaging of the nanoscale dynamics of liquids on surfaces with high temporal and spatial resolutions. Here, we used this liquid-phase TEM approach to study the wetting of patterned nanostructures at high speeds (200 to 300 frames per second [fps]).     

Mutant libraries reveal negative design shielding proteins from supramolecular self-assembly and relocalization in cells

Understanding the molecular consequences of mutations in proteins is essential to map genotypes to phenotypes and interpret the increasing wealth of genomic data. While mutations are known to disrupt protein structure and function, their potential to create new structures and localization phenotypes has not yet been mapped to a sequence space. To map this relationship, we employed two homo-oligomeric protein complexes in which the internal symmetry exacerbates the impact of mutations. We mutagenized three surface residues of each complex and monitored the mutations’ effect on localization and assembly phenotypes in yeast cells. While surface mutations are classically viewed as benign, our analysis of several hundred mutants revealed they often trigger three main phenotypes in these proteins: nuclear localization, the formation of puncta, and fibers. Strikingly, more than 50% of random mutants induced one of these phenotypes in both complexes. Analyzing the mutant’s sequences showed that surface stickiness and net charge are two key physicochemical properties associated with these changes. In one complex, more than 60% of mutants self-assembled into fibers. Such a high frequency is explained by negative design: charged residues shield the complex from self-interacting with copies of itself, and the sole removal of the charges induces its supramolecular self-assembly. A subsequent analysis of several other complexes targeted with alanine mutations suggested that such negative design is common. These results highlight that minimal perturbations in protein surfaces’ physicochemical properties can frequently drive assembly and localization changes in a cellular context.

Understanding genotype to phenotype relationships is crucial to predict the molecular consequences of mutations (1). At the protein level, alanine scans have revealed how individual residues contribute to protein function, stability, and binding affinity (2–4). More recently, systematic mappings have been widely used to connect sequence variability to changes in protein structure (5, 6), stability (7–9), solubility (10), and functionality (2, 11–14). Similar efforts have been made to map the impact of mutations in protein–ligand (15, 16) and protein–protein interactions (17–21).However, mutations can impact proteins beyond their stability, function, or existing interactions with specific partners or ligands. Sequences can also encode how proteins distribute spatially in cells, either by addressing them to membrane-bound compartments (22) or by inducing their self-assembly into large polymeric structures (23–27) and membraneless compartments (28, 29). While changes in protein self-assembly and localization can serve a functional purpose in adaptation (30–36), they can also lead to disease (37). For example, the supramolecular self-assembly of hemoglobin and γD-crystallin cause sickle-cell disease and cataracts, respectively (38, 39). The mislocalization of nuclear proteins TDP-43 and FUS in the cytosol is associated with amyotrophic lateral sclerosis disease (40, 41), and the mislocalization of Ataxin-3 to the nucleus has been implicated in spinocerebellar ataxia type 3 disease (42). It is therefore critical to characterize principles by which mutations can trigger such supramolecular self-assembly and mislocalization.Symmetry is frequent in proteins (37, 43) and is a crucial property promoting their self-assembly into high-order structures (44–50). Indeed, a strong enrichment in symmetric homo-oligomers among natural filament-forming proteins has been reported (37). Previous work has also shown that point mutations to two hydrophobic amino acids—leucine and tyrosine—frequently led symmetric homo-oligomers to assemble into high-order assemblies. However, whether other types of amino acids would display a similar potential, whether they would do so often, and whether additional phenotypes of assembly and localization could emerge upon mutation remains unknown.Here, we assess the potential of mutations to trigger such changes in protein assembly and localization in vivo. We targeted two homo-oligomeric protein complexes and randomly mutated three neighboring residues at the surface of each complex. We expressed the mutants fused to a fluorescent protein to track their spatial distribution in yeast cells. We found that a vast sequence space led to changes in protein assembly and localization in both proteins with three predominant phenotypes: nuclear localization, the formation of filaments, and the formation of puncta. Sequencing of the mutants revealed that increasing surface stickiness frequently promoted nuclear localization in one of the two proteins. Surprisingly, in the other protein, a loss of negatively charged residues was sufficient to trigger protein self-assembly, with fibers frequently forming regardless of the type of mutation, including to alanine and glycine. We also observed that four out of eight additional complexes analyzed underwent supramolecular self-assembly or a change in cellular localization when surface charges were mutated to alanine, implying that negative design against supramolecular self-assembly and mislocalization is common among symmetric homo-oligomers.     

Evolution in pecunia

The paper models evolution in pecunia—in the realm of finance. Financial markets are explored as evolving biological systems. Diverse investment strategies compete for the market capital invested in long-lived dividend-paying assets. Some strategies survive and some become extinct. The basis of our paper is that dividends are not exogenous but increase with the wealth invested in an asset, as is the case in a production economy. This might create a positive feedback loop in which more investment in some asset leads to higher dividends which in turn lead to higher investments. Nevertheless, we are able to identify a unique evolutionary stable investment strategy. The problem is studied in a framework combining stochastic dynamics and evolutionary game theory. The model proposed employs only objectively observable market data, in contrast with traditional settings relying upon unobservable investors’ characteristics (utilities and beliefs). Our method is analytical and based on mathematical reasoning. A numerical illustration of the main result is provided.

Despite bulls and bears adorning financial investors’ desks and the financial press and traders’ assurance that “it’s a jungle out there,” the emergence of evolutionary models in finance has been slow. However, as witnessed by the present special issue, the research on evolutionary finance (EF) is gaining traction.Evolutionary ideas have a long history in the social sciences going back to Malthus, who played an inspirational role for Darwin [see, e.g., Hodgson (1)]. Veblen (2) coined the term “evolutionary economics” and started a systematic use of the evolutionary approach in the social sciences (3). Schumpeter (4) laid the groundwork for evolutionary economics in the 20th century. A crucial role in the creation of this branch of economics was played by the works of Alchian (5), Boulding (6), Downie (7), D. Friedman (8, 9), M. Friedman (10), Hodgson (1, 11), Penrose (12), Nelson (13), and Nelson and Winter (14).Research in EF was started by the Santa Fe Institute, and the first time the term “evolutionary finance” appears is in one of its publications dating back to 1995 [LeBaron (15)]. In the seminal Santa Fe Institute working paper “Market Force, Ecology, and Evolution,” Farmer (16) argues that financial market models can benefit from reasoning analogous to models of biological evolution. In particular, it would be useful to make investment strategies and not investors the actors in the model. This shift parallels biological models in which the interaction of species and not that of individual organisms are considered. Indeed, in financial market models, one can write market demand for assets as the wealth-weighted average of investors’ demand. Alternatively, one can group all investors’ wealth following the same strategy into one entity and write market demand as the wealth-weighted average of investment strategies. While this is a trivial operation mathematically, it shifts the focus away from the intentions behind the investment strategies (e.g., utility maximization subject to expectations) toward the actions taken in financial markets.Many empirical studies [for example, the well-known Fama and French factor models (17, 18)] have shown that a few strategies are sufficient to understand the dynamics of thousands of assets. Equating aggregate demand with the supply of assets, asset prices are then the wealth-weighted average of a few investment strategies. Thus, in order to understand asset returns, which are the ratios of next period prices (plus eventual dividends) to current period prices, one needs to understand the evolution of wealth behind investment strategies. As Farmer (16) notes, this evolution of wealth models the market selection process acting on the financial species, i.e., the investment strategies. While the market selection force reduces the variety of species in the financial markets, Farmer (16) also points out that there is a countervailing force that innovates new strategies. In biological evolution this is mostly done by sexual reproduction along which genes are recombined. In financial evolution, there are other methods of innovation including rational and behavioral aspects, e.g., backtesting and forward performance testing (often akin to adaptive heuristics in game theory [cf. Hart (19)]).     

Self-assembly of alkynylplatinum(II) terpyridine amphiphiles into nanostructures via steric control and metal–metal interactions

A series of mono- and dinuclear alkynylplatinum(II) terpyridine complexes containing the hydrophilic oligo(para-phenylene ethynylene) with two 3,6,9-trioxadec-1-yloxy chains was designed and synthesized. The mononuclear alkynylplatinum(II) terpyridine complex was found to display a very strong tendency toward the formation of supramolecular structures. Interestingly, additional end-capping with another platinum(II) terpyridine moiety of various steric bulk at the terminal alkyne would lead to the formation of nanotubes or helical ribbons. These desirable nanostructures were found to be governed by the steric bulk on the platinum(II) terpyridine moieties, which modulates the directional metal−metal interactions and controls the formation of nanotubes or helical ribbons. Detailed analysis of temperature-dependent UV-visible absorption spectra of the nanostructured tubular aggregates also provided insights into the assembly mechanism and showed the role of metal−metal interactions in the cooperative supramolecular polymerization of the amphiphilic platinum(II) complexes.Square-planar d⁸ platinum(II) polypyridine complexes have long been known to exhibit intriguing spectroscopic and luminescence properties (1–54) as well as interesting solid-state polymorphism associated with metal−metal and π−π stacking interactions (1–14, 25). Earlier work by our group showed the first example, to our knowledge, of an alkynylplatinum(II) terpyridine system [Pt(tpy)(C ≡ CR)]⁺ that incorporates σ-donating and solubilizing alkynyl ligands together with the formation of Pt···Pt interactions to exhibit notable color changes and luminescence enhancements on solvent composition change (25) and polyelectrolyte addition (26). This approach has provided access to the alkynylplatinum(II) terpyridine and other related cyclometalated platinum(II) complexes, with functionalities that can self-assemble into metallogels (27–31), liquid crystals (32, 33), and other different molecular architectures, such as hairpin conformation (34), helices (35–38), nanostructures (39–45), and molecular tweezers (46, 47), as well as having a wide range of applications in molecular recognition (48–52), biomolecular labeling (48–52), and materials science (53, 54). Recently, metal-containing amphiphiles have also emerged as a building block for supramolecular architectures (42–44, 55–59). Their self-assembly has always been found to yield different molecular architectures with unprecedented complexity through the multiple noncovalent interactions on the introduction of external stimuli (42–44, 55–59).Helical architecture is one of the most exciting self-assembled morphologies because of the uniqueness for the functional and topological properties (60–69). Helical ribbons composed of amphiphiles, such as diacetylenic lipids, glutamates, and peptide-based amphiphiles, are often precursors for the growth of tubular structures on an increase in the width or the merging of the edges of ribbons (64, 65). Recently, the optimization of nanotube formation vs. helical nanostructures has aroused considerable interests and can be achieved through a fine interplay of the influence on the amphiphilic property of molecules (66), choice of counteranions (67, 68), or pH values of the media (69), which would govern the self-assembly of molecules into desirable aggregates of helical ribbons or nanotube scaffolds. However, a precise control of supramolecular morphology between helical ribbons and nanotubes remains challenging, particularly for the polycyclic aromatics in the field of molecular assembly (64–69). Oligo(para-phenylene ethynylene)s (OPEs) with solely π−π stacking interactions are well-recognized to self-assemble into supramolecular system of various nanostructures but rarely result in the formation of tubular scaffolds (70–73). In view of the rich photophysical properties of square-planar d⁸ platinum(II) systems and their propensity toward formation of directional Pt···Pt interactions in distinctive morphologies (27–31, 39–45), it is anticipated that such directional and noncovalent metal−metal interactions might be capable of directing or dictating molecular ordering and alignment to give desirable nanostructures of helical ribbons or nanotubes in a precise and controllable manner.Herein, we report the design and synthesis of mono- and dinuclear alkynylplatinum(II) terpyridine complexes containing hydrophilic OPEs with two 3,6,9-trioxadec-1-yloxy chains. The mononuclear alkynylplatinum(II) terpyridine complex with amphiphilic property is found to show a strong tendency toward the formation of supramolecular structures on diffusion of diethyl ether in dichloromethane or dimethyl sulfoxide (DMSO) solution. Interestingly, additional end-capping with another platinum(II) terpyridine moiety of various steric bulk at the terminal alkyne would result in nanotubes or helical ribbons in the self-assembly process. To the best of our knowledge, this finding represents the first example of the utilization of the steric bulk of the moieties, which modulates the formation of directional metal−metal interactions to precisely control the formation of nanotubes or helical ribbons in the self-assembly process. Application of the nucleation–elongation model into this assembly process by UV-visible (UV-vis) absorption spectroscopic studies has elucidated the nature of the molecular self-assembly, and more importantly, it has revealed the role of metal−metal interactions in the formation of these two types of nanostructures.     

Air-stable droplet interface bilayers on oil-infused surfaces

Droplet interface bilayers are versatile model membranes useful for synthetic biology and biosensing; however, to date they have always been confined to fluid reservoirs. Here, we demonstrate that when two or more water droplets collide on an oil-infused substrate, they exhibit noncoalescence due to the formation of a thin oil film that gets squeezed between the droplets from the bottom up. We show that when phospholipids are included in the water droplets, a stable droplet interface bilayer forms between the noncoalescing water droplets. As with traditional oil-submerged droplet interface bilayers, we were able to characterize ion channel transport by incorporating peptides into each droplet. Our findings reveal that droplet interface bilayers can function in ambient environments, which could potentially enable biosensing of airborne matter.Inspired by the pitcher plant (1), it was recently found that nano/microstructured hydrophobic substrates can be impregnated with lubricating fluids to create slippery surfaces for droplets (2–5). In contrast to dry, superomniphobic surfaces (6), lubricant-infused surfaces demonstrate stable liquid repellency at extreme pressures and temperatures (5, 7), are self-healing to mechanical damage (5), and their wettability and optical properties can be tuned (7, 8). A wide variety of applications are being explored for lubricant-infused surfaces, such as enhancing condensation heat transfer (9, 10), self-cleaning (11), fog harvesting (12), and omniphobic textiles (13), or minimizing ice nucleation (14, 15), ice adhesion (16, 17), and biofouling (18). Though previous studies have characterized the dynamics and possible wetting states of isolated droplets on lubricant-infused surfaces (5, 19–22), the interactive behavior of multiple droplets has not been reported.For the more traditional scenario of water droplets completely submerged in a reservoir of immiscible fluid, the physics of droplet–droplet interactions are well known. Water droplets submerged in crude oil can exhibit stable noncoalescence; this is because the crude oil contains surface-active components, such as resins and asphaltenes, which congregate at the droplet interfaces (23). When amphiphilic phospholipids are introduced into an oil reservoir containing water droplets, droplet interface bilayers (DIBs) can form between adjacent water droplets (24, 25). Recently, DIBs have emerged as an ideal model membrane system due to attractive features such as durability (26, 27), tunable size and curvature (28–30), deformability (31), facile electrical characterization of ion channels (32–35), the option to introduce asymmetry into the system (36), and droplet interchangeability (26, 32). In the absence of any stabilizing agents, water droplets colliding in an immiscible fluid will exhibit coalescence when their interaction time exceeds the time required to drain the film of fluid trapped between the droplets (37, 38). Droplet collision is typically controlled by applying a constant force (i.e., gravity) (39, 40), constant approach velocity (41, 42), or constant flow rate (43, 44). For experimental studies in pure oil baths, the time required for colliding water droplets to exhibit film rupture and coalesce typically ranges from 10⁻³ to 10² s, depending on parameters such as oil viscosity, droplet size, and the flow field (40, 42–44).Here, we show that water droplets in an ambient environment exhibit noncoalescence when colliding on an oil-infused surface, even in the absence of any surfactants. This phenomenon is due to the oil meniscus that surrounds each water droplet; when the oil menisci of neighboring droplets overlap, the menisci spontaneously merge together to minimize their surface energies and an oil film is squeezed upward to form a barrier between the colliding droplets. Though droplet coalescence will eventually occur due to film drainage, the time required for film rupture is several hours for moderate-viscosity [∼100 centistokes (cSt)] oils and is 1–3 orders of magnitude longer compared with droplets submerged in an oil bath (40, 42–44). These findings should refine the understanding of using oil-infused substrates for processes involving droplet–droplet interactions, such as condensation (9, 10) and fog harvesting (12).When incorporating amphiphilic phospholipids into the water droplets, we demonstrate that the thinning oil membrane between noncoalescing droplets gets replaced by a stable lipid bilayer, somewhat analogous to the formation of a black lipid membrane in an aperture painted with oil (45). To our knowledge, this is the first report of producing droplet interface bilayers in an ambient environment. We show that air-stable DIBs still allow for the robust electrical characterization of ion channels inserted in the lipid bilayer. Previously, it has been demonstrated that black lipid membranes or DIBs can be used for biosensing (46–50), light sensing (26), microscale biobatteries (26), electrical circuits (51, 52), and engineering tissue-like material (53). However, these suspended lipid bilayers have always been confined to fluid reservoirs (25, 45). We suggest that our air-stable DIBs will allow for an unprecedented degree of control regarding the fabrication, manipulation, transportation, and utilization of functional droplet networks.