Proceedings of the National Academy of Sciences of the United States of America最新文献

Quantitative studies of cultural evolution and gene-culture coevolution (henceforth "CE" and "GCC") emerged in the 1970s, in the aftermath of the "race and intelligence quotient (IQ)" and "human sociobiology" debates, as a counter to extreme hereditarian positions. These studies incorporated cultural transmission and its interaction with genetics in contributing to patterns of human variation. Neither CE nor GCC results were consistent with racist claims of ubiquitous genetic differences between socially defined races. We summarize how genetic data refute the notion of racial substructure for human populations and address naive interpretations of race across the biological sciences, including those related to ancestry, health, and intelligence, that help to perpetuate racist ideas. A GCC perspective can refute reductionist and determinist claims while providing a more inclusive multidisciplinary framework in which to interpret human variation.

Dry eye disease (DED) is characterized by a dysfunctional tear film in which the corneal epithelium and its abundant nerves are affected by ocular desiccation and inflammation. Although adaptive immunity and specifically CD4⁺ T cells play a role in DED pathogenesis, the exact contribution of these cells to corneal epithelial and neural damage remains undetermined. To address this, we explored the progression of a surgical DED model in wild-type (WT) and T cell-deficient mice. We observed that adaptive immune-deficient mice developed all aspects of DED comparably to WT mice except for the absence of functional and morphological corneal nerve changes, nerve damage-associated transcriptomic signature in the trigeminal ganglia, and sustained tear cytokine levels. Adoptive transfer of CD4⁺ T cells from WT DED mice to T cell-deficient mice reproduced corneal nerve damage but not epitheliopathy. Conversely, T cell-deficient mice reconstituted solely with naïve CD4⁺ T cells developed corneal nerve impairment and epitheliopathy upon DED induction, thus replicating the WT DED phenotype. Collectively, our data show that while corneal neuropathy is driven by CD4⁺ T cells in DED, corneal epithelial damage develops independently of the adaptive immune response. These findings have implications for T cell-targeting therapies currently in use for DED.

Biological mixtures, such as the cellular cytoplasm, are composed of a large number of different components. From this heterogeneity, ordered mesoscopic structures emerge, such as liquid phases with controlled composition. The competition of these structures for the same components raises several questions: what types of interactions allow the retrieval of multiple ordered mesoscopic structures, and what are the physical limitations for the retrieval of said structures. In this work, we develop an analytically tractable model for multicomponent liquids capable of retrieving states with target compositions. We name this model the liquid Hopfield model in reference to corresponding work in the theory of associative neural networks. In this model, we show that nonlinear repulsive interactions are a general requirement for retrieval of target structures. We demonstrate that this is because liquid mixtures at low temperatures tend to transition to phases with few components, a phenomenon that we term localization. Taken together, our results reveal a trade-off between retrieval and localization phenomena in liquid mixtures, and pave the way for other connections between the phenomenologies of neural computation and liquid mixtures.

The goal of this paper is predicting the conformational distributions of ligand binding sites using the AlphaFold2 (AF2) protein structure prediction program with stochastic subsampling of the multiple sequence alignment (MSA). We explored the opening of cryptic ligand binding sites in 16 proteins, where the closed and open conformations define the expected extreme points of the conformational variation. Due to the many structures of these proteins in the Protein Data Bank (PDB), we were able to study whether the distribution of X-ray structures affects the distribution of AF2 models. We have found that AF2 generates both a cluster of open and a cluster of closed models for proteins that have comparable numbers of open and closed structures in the PDB and not too many other conformations. This was observed even with default MSA parameters, thus without further subsampling. In contrast, with the exception of a single protein, AF2 did not yield multiple clusters of conformations for proteins that had imbalanced numbers of open and closed structures in the PDB, or had substantial numbers of other structures. Subsampling improved the results only for a single protein, but very shallow MSA led to incorrect structures. The ability of generating both open and closed conformations for six out of the 16 proteins agrees with the success rates of similar studies reported in the literature. However, we showed that this partial success is due to AF2 "remembering" the conformational distributions in the PDB and that the approach fails to predict rarely seen conformations.

Cultural evolutionary processes can often lead to a statistical association between neutral and adaptive traits during episodes of population dispersal and the introduction of a beneficial technology in a geographic region. Here, we examine such cultural hitchhiking processes using an individual-based model that portrays the cultural interaction between a migrant and an incumbent population. Our model is loosely based on the interaction between farming and foraging populations during the initial stages of the adoption and diffusion of agricultural practices. The two populations are characterized by different variants for their neutral and adaptive cultural traits, with the latter set providing a reproductive advantage for the migrant communities over the incumbent ones. We explore how the neutral traits of the migrant population spread and how this process is conditioned by the following factors: 1) the possibility of transmission of the adaptive traits; 2) the extent of the increased reproductive advantage provided by the adaptive variants of the migrant population; 3) postmarital residence rules; and 4) how and when neutral traits are transmitted. Our results reveal a diverse range of outputs, highlighting the relevance of factors such as the nature of postmarital resocialization and the specific combination of postmarital residence rules and sex-biased transmission.

Desert ants are known to rely heavily on vision while venturing for food and returning to the nest. During these foraging trips, ants memorize and recognize their visual surroundings, which enables them to recapitulate individually learned routes in a fast and effective manner. The compound eyes are crucial for such visual navigation; however, it remains unclear how information from both eyes are integrated and how ants cope with visual impairment. Here, we manipulated the ants' visual system by covering one of the two compound eyes and analyzed their ability to recognize familiar views. Monocular ants showed an immediate disruption of their ability to recapitulate their familiar route. However, they were able to compensate for this nonnatural impairment in a few hours by engaging in an extensive route-relearning ontogeny, composed of more learning walks than what naïve ants typically do. This relearning process with one eye forms novel memories, without erasing the previous memories acquired with two eyes. Additionally, ants having learned a route with one eye only are unable to recognize it with two eyes, even though more information is available. Together, this shows that visual memories are encoded and recalled in an egocentric and fundamentally binocular way, where the visual input as a whole must be matched to enable recognition. We show how this kind of visual processing fits with their neural circuitry.

Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disease with a poorly understood immunopathogenesis. Here, we report that HS lesional skin is characterized by the expansion of innate lymphocytes and T cells expressing CD2, an essential activation receptor and adhesion molecule. Lymphocytes expressing elevated CD2 predominated with unique spatial distribution throughout the epidermis and hypodermis in the HS lesion. CD2⁺ cells were mainly innate lymphocytes expressing the NK cell marker, CD56, and CD4⁺ T cells. Importantly, these CD2⁺ cells interacted with CD58 (LFA3) expressing epidermal keratinocytes and fibroblasts in the hypodermis. Granzyme A^bright NKT cells (CD2⁺CD3⁺CD56^bright) clustered with α-SMA expressing fibroblasts juxtaposed to epithelialized tunnels and fibrotic regions of the hypodermis. Whereas NK cells (CD2⁺CD56^dim) were perforin⁺, granzymes A⁺ and B⁺, and enriched adjacent to hyperplastic follicular epidermis and tunnels of HS showing presence of apoptotic cells. The cytokines IL-12, IL-15, and IL-18, which enhance NK cell maturation and function were significantly elevated in HS. Ex vivo HS skin explant cultures treated with CD2:CD58 interaction-blocking anti-CD2 monoclonal antibody attenuated secretion of inflammatory cytokines/chemokines and suppressed inflammatory gene signature. Additionally, CD2:CD58 blockade altered miRNAs involved in NK/NKT differentiation and/or function. In summary, we show that a cellular network of heterogenous NKT and NK cell populations drives inflammation and is critical in the pathobiology of HS, including tunnel formation and fibrosis. Finally, CD2 blockade is a viable immunotherapeutic approach for the effective management of HS.

The Bayesian confidence hypothesis (BCH), which postulates that confidence reflects the posterior probability that a decision is correct, is currently the most prominent theory of confidence. Although several recent studies have found evidence against it in the context of relatively complex tasks, BCH remains dominant for simpler tasks. The major alternative to BCH is the confidence in raw evidence space (CRES) hypothesis, according to which confidence is based directly on the raw sensory evidence without explicit probability computations. Here, we tested these competing hypotheses in the context of perceptual tasks that are assumed to induce Gaussian evidence distributions. We show that providing information about task difficulty gives rise to a basic behavioral signature that distinguishes BCH from CRES models even for simple 2-choice tasks. We examined this signature in three experiments and found that all experiments exhibited behavioral signatures in line with CRES computations but contrary to BCH ones. We further performed an extensive comparison of 16 models that implemented either BCH or CRES confidence computations and systematically differed in their auxiliary assumptions. These model comparisons provided overwhelming support for the CRES models over their BCH counterparts across all model variants and across all three experiments. These observations challenge BCH and instead suggest that humans may make confidence judgments by placing criteria directly in the space of the sensory evidence.

Emergence is a fundamental concept in biology and other disciplines, but whether emergent phenotypes evolve similarly to nonemergent phenotypes is unclear. The hypothesized process of emergent evolution posits that evolutionary change in at least some collective behaviors will differ from evolutionary change in the corresponding intrinsic behaviors of isolated individuals. As a result, collective behavior might evolve more rapidly and diversify more between populations compared to individual behavior. To test whether collective behavior evolves emergently, we conducted a large comparative study using 22 ant species and gathered over 1,500 behavioral rhythm time series from hundreds of colonies and isolated individuals, totaling over 1.5 y of behavioral data. We show that analogous traits measured at individual and collective levels exhibit distinct evolutionary patterns. The estimated rates of phenotypic evolution for the rhythmicity of activity in ant colonies were faster than the evolutionary rates of the same behavior measured in isolated individual ants, and total variation across species in collective behavior was higher than variation in individual behavior. We hypothesize that more rapid evolution and higher variation is a widespread feature of emergent phenotypes relative to lower-level phenotypes across complex biological systems.