Publications in Proceedings of the National Academy of Sciences of the United States of America

In the 1970s, physicist Richard Feynman turned lunch with a friend into a math problem—how to optimize dish selection over multiple meals—but his handwritten notes remained a mystery for decades. Here we present the fully deciphered problem and solution, prove its optimality, generalize it to related problems, and compare the results to human behavior. The optimal policy specifies decreasing thresholds for switching from exploring new dishes to exploiting the best, with thresholds varying based on the distribution of the quality of dishes. We connect these results to the existing psychological literature on optimal stopping problems, which has explored close variants on Feynman’s problem, and use our generalization of the solution to explore how the underlying distribution of the quality of the options influences people’s choices. A preregistered experiment with 2,520 participants shows that people adopt thresholds that decrease linearly with the proportion of trials remaining, consistent with the observation of linear thresholds in other optimal stopping problems. However, we show that people tend to explore more than predicted by linear thresholds, and that different distributions of quality result in thresholds with the same slope but different intercepts. These results indicate that people adapt linear thresholds used in optimal stopping tasks in a way that is sensitive to the underlying distribution—a simple strategy that we show is nearly as effective as Feynman’s solution.

Political emotions are widely acknowledged as key drivers of political participation and polarization. Yet while it is well established that political emotions matter, far less is known about how they are felt and represented in the body. Across a preregistered, nationally representative study (N = 992), we introduce an embodied approach to political emotion using the validated emBODY-tool, which allows participants to map where in the body they experience sensations when feeling canonical emotions (e.g., anger) and their political counterparts (e.g., “political anger”). Specifically, we address three questions: 1) how political emotions are embodied and differ from their nonpolitical counterparts, 2) whether political dispositions influence how these political emotions are embodied, and 3) how their embodied experience interacts with political dispositions in explaining political attitudes and behavior. Pixelwise bodily sensation maps and aggregated “embodied impact” metrics show that political anger, anxiety, depression, disgust, and hope do not merely mirror their canonical forms, but take on distinct bodily patterns. Political ideology, but not political sophistication, modulates these bodily experiences, with Democrat-leaning participants reporting more intense sensations for negative political emotions, suggesting the presence of “ideological bodies.” Crucially, political participation is not explained by how intensely people report feeling emotions, but is instead closely linked to how strongly these emotions are embodied in the body. Together, our findings underscore the body’s central role in democratic engagement by showing how political contexts shape embodied emotional experience and how these embodied experiences shape politics and democracy.

Epigenetic and transcriptional dysregulation plays a fundamental role in tumor lineage plasticity (LP). However, the underlying mechanisms, especially for the initial events of LP development, are still poorly understood. Here, we report that in progression of prostate cancer from adenocarcinoma to treatment-induced neuroendocrine prostate cancer (t-NEPC), anti-androgen receptor (AR) signaling inhibitors (ARSIs) reprogram the function of circadian regulator/nuclear receptor REV-ERBα by switching its target gene programs from kinase signaling and metabolic programs to programs of LP, which includes neurogenesis, stem cell, and epithelial–mesenchymal transition as well as over fifteen LP drivers including POU3F2/BRN2, ASCL1, FOXA2, ONECUT2, and MYCN. Unexpectedly, REV-ERBα facilitates the chromatin occupancy of BRN2, ASCL1, and FOXA1 in their activation of LP programs, thus functioning as a master regulator of ARSI-induced LP driver network. Mechanistically, REV-ERBα induces chromatin accessibility and H3K27ac modification at promoters of LP genes through its recruitment of BRD4 and p300. Overexpression of REV-ERBα alone is sufficient to induce LP and neuroendocrine phenotype and confers resistance to ARSI in adenocarcinoma cells. Loss of REV-ERBα potently inhibits NEPC cell growth and abolishes the expression of LP drivers and gene programs. Pharmacological inhibition of REV-ERBα exhibits high potency in blocking the growth of NEPC tumors including patient-derived xenografts. Our findings reveal that therapy-induced LP development entails a coordinated induction of a network of LP drivers and that REV-ERBα is an unexpected master regulator of the network and a promising therapeutic target for treatment of advanced prostate cancer such as NEPC.

We find evidence of belief in belief—intuitive preferences for religious belief over atheism, even among atheist participants—across eight comparatively secular countries. Religion is a cross-cultural human universal, yet explicit markers of religiosity have rapidly waned in large parts of the world in recent decades. We explored whether intuitive religious influence lingers, even among nonbelievers in largely secular societies. We adapted a classic experimental philosophy task to test for this intuitive belief in belief among people in eight comparatively nonreligious countries: Canada, China, Czechia, Japan, the Netherlands, Sweden, the United Kingdom, and Vietnam (total N = 3,804). Our analyses revealed strong evidence that 1) people intuitively favor religious belief over atheism and that 2) this pattern was not moderated by participants’ own self-reported atheism. Indeed, 3) even atheists in relatively secular societies intuitively prefer belief to atheism. These inferences were robust across different analytic strategies and across other measures of individual differences in religiosity and religious instruction. Although explicit religious belief has rapidly declined in these countries, it is possible that belief in belief may still persist. These results speak to the complex psychological and cultural dynamics of secularization.

Negative or antagonistic relationships are common in human social networks, but they are less often studied than positive or friendly relationships. The existence of a capacity to have and to track antagonistic ties raises the possibility that they may serve a useful function in human groups. Here, we analyze empirical data gathered from 24,770 and 22,513 individuals in 176 rural villages in Honduras in two survey waves 2.5 y apart in order to evaluate the possible relevance of antagonistic relationships for broader network phenomena. We find that the small-world effect is more significant in a positive world with negative ties compared to an otherwise similar hypothetical positive world without them. Additionally, we observe that nodes with more negative ties tend to be located near network bridges, with lower clustering coefficients, higher betweenness centralities, and shorter average distances to other nodes in the network. Positive connections tend to have a more localized distribution, while negative connections are more globally dispersed within the networks. Analysis of the possible impact of such negative ties on dynamic processes reveals that, remarkably, negative connections can facilitate the dissemination of information (including novel information experimentally introduced into these villages) to the same degree as positive connections, and that they can also play a role in mitigating idea polarization within village networks. Antagonistic ties hold considerable importance in shaping the structure and function of social networks.

A key feature of many developmental systems is their ability to self-organize spatial patterns of functionally distinct cell fates. To ensure proper biological function, such patterns must be established reproducibly, by controlling and even harnessing intrinsic and extrinsic fluctuations. While the relevant molecular processes are increasingly well understood, we lack a principled framework to quantify the performance of such stochastic self-organizing systems. To that end, we introduce an information-theoretic measure for self-organized fate specification during embryonic development. We show that the proposed measure assesses the total information content of fate patterns and decomposes it into interpretable contributions corresponding to the positional and correlational information. By optimizing the proposed measure, our framework provides a normative theory for developmental circuits, which we demonstrate on lateral inhibition, cell type proportioning, and reaction–diffusion models of self-organization. This paves a way toward a classification of developmental systems based on a common information-theoretic language, thereby organizing the zoo of implicated chemical and mechanical signaling processes.

Despite numerous female contraceptive options, nearly half of all pregnancies are unintended. Family planning choices for men are currently limited to unreliable condoms and invasive vasectomies with questionable reversibility. Here, we report the development of an oral contraceptive approach based on transcriptional disruption of cyclical gene expression patterns during spermatogenesis. Spermatogenesis involves a continuous series of self-renewal and differentiation programs of spermatogonial stem cells (SSCs) that is regulated by retinoic acid (RA)–dependent activation of receptors (RARs), which control target gene expression through association with corepressor proteins. We have found that the interaction between RAR and the corepressor silencing mediator of retinoid and thyroid hormone receptors (SMRT) is essential for spermatogenesis. In a genetically engineered mouse model that negates SMRT-RAR binding (SMRT^mRID mice), the synchronized, cyclic expression of RAR-dependent genes along the seminiferous tubules is disrupted. Notably, the presence of an RA-resistant SSC population that survives RAR de-repression suggests that the infertility attributed to the loss of SMRT-mediated repression is reversible. Supporting this notion, we show that inhibiting the action of the SMRT complex with chronic, low-dose oral administration of a histone deacetylase inhibitor reversibly blocks spermatogenesis and fertility without affecting libido. This demonstration validates pharmacologic targeting of the SMRT repressor complex for non-hormonal male contraception.