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A Consensus Statement on establishing causality, therapeutic applications and the use of preclinical models in microbiome research
The gut microbiome comprises trillions of microorganisms and profoundly influences human health by modulating metabolism, immune responses and neuronal functions. Disruption in gut microbiome composition is implicated in various inflammatory conditions, metabolic disorders and neurodegenerative diseases. However, determining the underlying mechanisms and establishing cause and effect is extremely difficult. Preclinical models offer crucial insights into the role of the gut microbiome in diseases and help identify potential therapeutic interventions. The Human Microbiome Action Consortium initiated a Delphi survey to assess the utility of preclinical models, including animal and cell-based models, in elucidating the causal role of the gut microbiome in these diseases. The Delphi survey aimed to address the complexity of selecting appropriate preclinical models to investigate disease causality and to study host–microbiome interactions effectively. We adopted a structured approach encompassing a literature review, expert workshops and the Delphi questionnaire to gather insights from a diverse range of stakeholders. Experts were requested to evaluate the strengths, limitations, and suitability of these models in addressing the causal relationship between the gut microbiome and disease pathogenesis. The resulting consensus statements and recommendations provide valuable insights for selecting preclinical models in future studies of gut microbiome-related diseases.
Informational ecosystems partially explain differences in socioenvironmental conceptual associations between U.S. American racial groups
Social groups represent a collective identity defined by a distinct consensus of concepts (e.g., ideas, values, and goals) whose structural relationship varies between groups. Here we set out to measure how a set of inter-concept semantic associations, comprising what we refer to as a concept graph, covaries between established social groups, based on racial identity, and how this effect is mediated by information ecosystems, contextualized as news sources. Group differences among racial identity (278 Black and 294 white Americans) and informational ecosystems (Left- and Right- leaning news sources) are present in subjective judgments of how the meaning of concepts such as healthcare, police, and voting relate to each other. These racial group differences in concept graphs were partially mediated by the bias of news sources that individuals get their information from. This supports the idea of groups being defined by common conceptual semantic relationships that partially arise from shared information ecosystems.
Pathogen stress heightens sensorimotor dimensions in the human collective semantic space
Infectious diseases have been major causes of death throughout human history and are assumed to broadly affect human psychology. However, whether and how conceptual processing, an internal world model central to various cognitive processes, adapts to such salient stress variables remains largely unknown. To address this, we conducted three studies examining the relationship between pathogen severity and semantic space, probed through the main neurocognitive semantic dimensions revealed by large-scale text analyses: one cross-cultural study (across 43 countries) and two historical studies (over the past 100 years). Across all three studies, we observed that increasing pathogen severity was associated with an enhancement of the sensory-motor dimension in the collective semantic space. These patterns remained robust after controlling for the effects of sociocultural variables, including economic wealth and societal norms of tightness. These results highlight the universal dynamic mechanisms of collective semantics, such that pathogen stress potentially drives sensorially oriented semantic processing.
A neurocognitive mechanism for increased cooperation during group formation
How do group size changes influence cooperation within groups? To examine this question, we performed a dynamic, network-based prisoner’s dilemma experiment with fMRI. Across 83 human participants, we observed increased cooperation as group size increased. However, our computational modeling analysis of behavior and fMRI revealed that groups size itself did not increase cooperation. Rather, interaction between (1) participants’ stable prosocial tendencies, and (2) dynamic reciprocal strategy weighed by memory confidence, underlies the group size-modulated increase in cooperation because the balance between them shifts towards the prosocial tendency with higher memory demands in larger groups. We found that memory confidence was encoded in fusiform gyrus and precuneus, whereas its integration with prosocial tendencies was reflected in the left DLPFC and dACC. Therefore, interaction between recall uncertainty during reciprocal interaction (i.e., forgetting) and one’s individual prosocial preference is a core pillar of emergent cooperation in more naturalistic and dynamic group formation.
Maternal effects in the model system Daphnia: the ecological past meets the epigenetic future
Maternal effects have been shown to play influential roles in many evolutionary and ecological processes. However, understanding how environmental stimuli induce within-generation responses that transverse across generations remains elusive, particularly when attempting to segregate confounding effects from offspring genotypes. This review synthesizes literature regarding resource- and predation-driven maternal effects in the model system Daphnia, detailing how the maternal generation responds to the environmental stimuli and the maternal effects seen in the offspring generation(s). Our goal is to demonstrate the value of Daphnia as a model system by showing how general principles of maternal effects emerge from studies on this system. By integrating the results across different types of biotic drivers of maternal effects, we identified broadly applicable shared characteristics: 1. Many, but not all, maternal effects involve offspring size, influencing resistance to starvation, infection, predation, and toxins. 2. Maternal effects manifest more strongly when the offspring’s environment is poor. 3. Strong within-generation responses are typically associated with strong across-generation responses. 4. The timing of the maternal stress matters and can raise or lower the magnitude of the effect on the offspring’s phenotype. 5. Embryonic exposure effects could be mistaken for maternal effects. We outline questions to prioritize for future research and discuss the possibilities for integration of ecologically relevant studies of maternal effects in natural populations with the molecular mechanisms that make them possible, specifically by addressing genetic variation and incorporating information on epigenetics. These small crustaceans can unravel how and why non-genetic information gets passed to future generations.
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