PLoS Biology最新文献

Bacteriophage-host interactions play a fundamental role in shaping microbial ecosystems. While extensively studied on Earth, their behavior in microgravity remains largely unexplored. Here, we report the dynamics between T7 bacteriophage and Escherichia coli in microgravity aboard the International Space Station (ISS). Phage activity was initially delayed in microgravity but ultimately successful. We identified de novo mutations in both phage and bacteria that enhanced fitness in microgravity. Deep mutational scanning of the phage receptor binding domain revealed striking differences in the number, position, and mutational preferences between terrestrial and microgravity conditions, reflecting underlying differences in bacterial adaptation. Combinatorial libraries informed by microgravity selections yielded T7 variants capable of productively infecting uropathogenic E. coli resistant to wild-type T7 under terrestrial conditions. These findings help lay the foundation for future research on the impact of microgravity on phage-host interactions and microbial communities and the terrestrial benefits of this research.

In early postnatal brain, the prefrontal cortex (PFC) remains immature and highly plastic, particularly for the intratelencephalic (IT) neurons. However, the spatiotemporal molecular and cellular dynamics of PFC during this period remain poorly characterized. Here, we performed spatiotemporal single-cell RNA analysis on mouse PFC during different postnatal time points and systematically delineated the molecular and cellular dynamics of mouse PFC during early postnatal development, among which IT neurons exhibit most dramatic alterations. Based on these comprehensive spatiotemporal atlases of PFC, we deciphered the time-specific molecular and cellular characteristics during the maturation process of IT neurons in PFC, particularly the dynamic expression programs of genes regulating axon development and synaptic formation, and the risk genes of neurological developmental diseases. Furthermore, we revealed the dynamic neuron-glia interaction patterns and the underlying signaling pathways during early postnatal period. Our study provided a comprehensive resource and important insights for PFC development and PFC-associated neurological diseases.

Brown adipose tissue (BAT) functions as a metabolic sink, efficiently processing fatty acids (FAs), glucose, and amino acids, playing a pivotal role in metabolic regulation and energy homeostasis. However, the metabolic adaptations enabling BAT to respond to fasting and refeeding cycles are not well understood. Using mass spectrometry techniques-Liquid Chromatography (LC), Capillary Electrophoresis (CE), and Spatially Resolved Imaging-we demonstrate that BAT exhibits a unique free fatty acid (FFA) and lipid-bound FA profile, with enrichment of very long-chain polyunsaturated fatty acids (VLC-PUFAs) and C13-C14 FAs compared to white adipose tissue (WAT) in male C57BL/6 mice. Alternate-day fasting (ADF) triggered a dynamic change of these FFAs in BAT, accompanied by selective alterations of upper glycolysis, glyceroneogenesis, and triglyceride synthesis, a shift less pronounced in WAT. Additionally, several BAT lipid species, including glycerolipids, glycerophospholipids, and sphingolipids, transitioned from highly unsaturated to more saturated lipids upon refeeding, alongside significant spatial and dynamic reprogramming. Mechanistically, periodic fasting and refeeding activated mTORC1, and genetic inactivation of mTORC1 in BAT diminished ADF-induced lipid saturation, storage, and redistribution in the C57BL/6 background. These findings reveal that while BAT generally prefers unsaturated fats, it undergoes substantial lipid saturation and spatially dynamic reprogramming in response to fasting and refeeding, offering new insights into BAT's adaptive role in metabolic homeostasis.

Synaptic convergence is fundamental to neuronal circuit function, underpinning computations such as coincidence detection and signal integration. Across sensory systems, convergence architecture and synaptic input strengths are key for extracting stimulus features and processing of sensory information. In the cochlear nucleus, globular bushy cells (GBCs) receive convergent inputs from multiple auditory nerve fibers via large endbulb of Held terminals. While these inputs vary considerably in size, even among those targeting the same cell, the functional consequences of this variation for sound encoding remain unclear. Here, we investigated how synaptic input variation shapes sound encoding in GBCs of Mongolian gerbils using in vitro conductance-clamp recordings and computational modeling. By simulating synaptic inputs with variable strength distributions, we found that increasing input variation enhances rate coding at the expense of temporal precision. These findings suggest that endbulb strength heterogeneity allows the GBC population to operate along a functional continuum, generating diverse information streams to downstream targets.

Metabolic rewiring of immune cells has broad impacts on immune responses and disease outcomes. Systems biology approaches, such as multi-omics profiling and perturbation screening, could uncover new actionable targets and therapeutic avenues to explore.

The human brain makes abundant predictions in speech comprehension that, in real-world conversations, depend on conversational partners. Yet, tested models of predictive processing diverge on how such predictions are integrated with incoming speech: The brain may emphasise either expected information through sharpening or unexpected information through prediction error. We reconcile these views through direct neural evidence from electroencephalography showing that both mechanisms operate at different hierarchical levels during speech perception. Across multiple experiments, participants heard identical ambiguous speech in different speaker contexts. Using speech decoding, we show that listeners learn speaker-specific semantic priors, which sharpen sensory representations by pulling them toward expected acoustic signals. In contrast, encoding models leveraging pretrained transformers reveal that prediction errors emerge at higher linguistic levels. These findings support a unified model of predictive processing, wherein sharpening and prediction errors coexist at distinct hierarchical levels to facilitate both robust perception and adaptive world models.

The timed release of gametes is an important feature of marine organisms, and in hydrozoan jellyfish is usually controlled by light. A recent study in PLOS Biology reveals an emerging endogenous clock controlling rhythmic egg release in a novel hydrozoan species.

Repeated population bottlenecks influence the evolution and maintenance of cooperation. However, it remains unclear whether bottlenecks select all cooperative traits expressed by an organism or only a subset of them. Myxococcus xanthus, a social bacterium, displays multiple cooperative traits, including growth, predation, sporulation in multicellular fruiting bodies, and germination. Using laboratory evolution experiments, we investigated the effect of repeated stringent versus relaxed population bottlenecks on the evolution of these four cooperative traits when they were all under selection. We found that only fruiting body formation and growth were positively selected under the stringent regimen, while the other two traits were selected against. The pattern was reversed in the relaxed regimen. Populations propagated under the relaxed regimen also exhibited greater fitness across the entire life cycle and maintained higher trait variations, including coexistence of cooperative and exploitative strategies. Genomic analyses identified mutations in σ54 interacting protein and DNA binding response regulator protein associated with adaptations in stringent and relaxed regimens, respectively. Furthermore, similar trade-offs, for example, between sporulation and germination, are also seen among natural populations of M. xanthus. Overall, we demonstrate that different bottleneck sizes drive the evolution of cooperative life history traits in distinct ways, often via trade-offs that constrain their joint optimization.

For marine species that reproduce by external fertilization, spawning is precisely coordinated within a local population to maximize the chances of producing offspring. Gamete release is often synchronized with respect to the diel light changes at dawn and dusk. In the hydrozoan jellyfish Clytia hemisphaerica, spawning occurs when oocyte maturation and gamete release are induced by maturation-inducing hormone (MIH) neuropeptides released from opsin-expressing cells in the gonad, directly upon light stimulus. Here, we characterize the distinct spawning cycle of a previously undescribed species Clytia sp. IZ-D, identified on the Pacific coast of Japan, which releases gametes in the evening. Clytia sp. IZ-D jellyfish spawn 14 hours after a light stimulus under a 24-hour light cycle and exhibit autonomous and synchronized spawning cycles with a 20-hour interval under constant light. We find that the female spawning cycle reflects the oocyte growth and their acquisition of competence for maturation, such that each day a new batch of growing oocytes becomes responsive to MIH at a time that correlates with the timing of actual spawning. We propose that the synchronized evening spawning in this species is controlled by an atypical circadian timing mechanism based on the progressive development of gamete competence to MIH and modulation of the opsin-controlled MIH signaling pathway. This mechanism may provide resilience to light cycle instability due to local climate variation and ensure reproductive isolation from other Clytia species by shifting the gamete release timing.

During embryogenesis, cells self-organize into precise patterns that enable tissues and organs to acquire specialized functions. Despite its importance, the molecular choreography driving these collective cellular behaviors remains poorly understood, posing a major challenge in developmental biology and limiting progress in regenerative medicine. Here, we use the developing mouse hair follicle as a model mini-organ to investigate the early events of epithelial bud formation. We identify the Rho GTPase regulator ARHGEF3 as a critical upstream factor that restricts cell fate acquisition and establishes a radial gradient of P-cadherin across the placode during early hair follicle development. In Arhgef3 knockout embryos, placodes are enlarged and exhibit elevated P-cadherin levels at cell-cell junctions, disrupting gradient formation without affecting E-cadherin distribution. This defect correlates with aberrant epithelial organization and increased incidence of straight hair follicle downgrowth. Our findings position ARHGEF3 as a novel regulator of cadherin patterning and placode polarization, and suggest broader roles in the morphogenesis of other epithelial appendages governed by similar developmental programs.