Shin J, Patel A, Lou XA
… +8 more, Catoiu EA, Krishnan J, Hefner Y, Szubin R, Sung J, Son HF, Zielinski DC, Palsson BØ
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42384677
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encounters chemically diverse carbon sources, and the observed outputs of its transcriptional regulatory network (TRN) vary with substrate chemistry, metabolic entry route, and growth physiology. Here, we compiled PRECIS...encounters chemically diverse carbon sources, and the observed outputs of its transcriptional regulatory network (TRN) vary with substrate chemistry, metabolic entry route, and growth physiology. Here, we compiled PRECISE-NP881, an 881-condition transcriptome compendium comprising 346 RNA-seq profiles generated for this study during growth on 43 individual carbon sources, and used independent component analysis to quantify condition-specific activities of 137 iModulons, defined here as statistically independent gene-expression modules. We identified 25 carbon-catabolism iModulons and summarized their activity patterns across the 43 substrates into four activity-defined substrate groups. These activity patterns were associated with measured growth rates, substrate chemical classes, central-metabolic entry routes, carbon-normalized stoichiometric yield, and model-estimated proteome allocation. Faster-growing sugar conditions showed low CRP-linked iModulon activity, whereas slower-growing conditions showed elevated, condition-specific activity of CRP-linked and substrate-specific catabolic iModulons. TCA-entry and amino acid-associated conditions were linked with NtrC-1 and Propionate iModulon activities, with targeted knock-out assays supporting the conditional physiological relevance of selected propionyl-CoA-associated genes. A subset of nitrogen-containing, slower-growth conditions with predicted ammonium release induced the cryptic prophage-associated SgcABCEQX iModulon. Projection of an independent glucose starvation/refeeding time-course dataset revealed overlapping dynamics among selected carbon-catabolism iModulons and coordinated changes in growth- and stress-associated TRN outputs. Together, these results provide a systems-level atlas of observed carbon-responsive transcriptional states and systematize carbon physiology at scale.
Liu C, Goût TL, Hu Y
… +8 more, Li W, An S, Zhou Z, Cai S, Zhao H, Ni J, De Yoreo JJ, DePaolo DJ
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42384676
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Isotopic fractionation is a unique indicator of the mechanisms of mineral precipitation from aqueous solutions, but existing theory does not account for nucleation effects or nonclassical growth mechanisms. Here, using b...Isotopic fractionation is a unique indicator of the mechanisms of mineral precipitation from aqueous solutions, but existing theory does not account for nucleation effects or nonclassical growth mechanisms. Here, using barite (BaSO) as a model crystal, we provide an experimental measurement of isotope fractionation associated with nucleation. We isolated nucleation effects by precipitating crystals on an organic film, where cation enrichment creates a highly supersaturated microenvironment so nucleation dominates over crystal growth. In a single batch experiment, we retrieved nanocrystals (~1.5 nm) from the organic substrate and large microcrystals in bulk solution where growth dominates. The Ba/Ba isotopic fractionation of -0.6 to -0.8‰ for the microcrystals match those expected for classical ion-by-ion growth from a moderately supersaturated solution, whereas the fractionation for the nucleation-dominated nanocrystals is about -0.1‰, falling within the reported equilibrium fractionation range between barite and aqueous Ba. These results demonstrate that cation isotopic fractionation in sparingly soluble salts like barite and calcite is not a single-valued function of saturation indices (SI) and precipitation rate as predicted with current theory, with the fractionation factor (∆Ba = δBa - δBa) increasing in magnitude with increasing SI. Instead, the shifting precipitation mechanism(s) at high SI cause the fractionation factor to return to near-equilibrium values. This finding may be critical for understanding isotopic fractionation in localized extreme environments in nature, including for Ba isotopes during biomineralization.
Kraus F, He Y, Jiang Y
… +9 more, Li D, Ambaw YA, Gasparoli FM, Paulo JA, Walther TC, Farese RV, Gygi SP, Wilfling F, Harper JW
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42384675
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Lysosomes maintain cellular homeostasis by degrading proteins delivered via endocytosis and autophagy and by recycling building blocks for organelle biogenesis. Lysosomal storage disorders (LSDs) comprise a group of dise...Lysosomes maintain cellular homeostasis by degrading proteins delivered via endocytosis and autophagy and by recycling building blocks for organelle biogenesis. Lysosomal storage disorders (LSDs) comprise a group of diseases affecting diverse lysosomal functions. To facilitate molecular phenotyping across diverse LSD gene classes, we are developing a library of human embryonic stem cells engineered to lack individual LSD genes as a resource for the field. Here, we report our initial stem cell toolkit lacking one of 23 LSD genes, including the majority of genes associated with sphingolipidoses and neuronal ceroid lipofuscinoses, and its use in the generation of a proteomic resource for induced cortical-like and midbrain dopaminergic-like neurons. In-depth abundance and correlation profiling across organelles and suborganelle components revealed potential vulnerabilities that reflect distinct patterns of proteome alterations across both genotypes and neuronal cell types. We characterize alterations in the mitochondrial proteome associated with GBA1 and ASAH1 deficiency and identify synaptic and mitochondrial defects in induced neurons that correlate with defects in neuronal firing rates. Moreover, we developed an informatic pipeline for proteome-wide identification of individual protein-protein interactions and protein complexes that may be disrupted as a result of LSD gene deficiency. Finally, we visualized structural alterations of -deficient endolysosomes in situ using cryoelectron tomography, revealing swollen organelles that were largely devoid of dense internal membranes characteristic of wild-type cells, but containing numerous intralumenal vesicle compartments. This toolkit and associated proteomic landscapes provide a resource for defining molecular signatures associated with LSD gene dysfunction and organelle vulnerability.
Tsakiri E, Campos-Marques C, Ploumi C
… +16 more, Skourti K, Roussos A, Mytilinaiou E, Vamvaka Iakovou A, Ferreira IL, Dioli C, Gianniou DD, Samiotaki M, Campos J, Waites C, Sousa N, Trougakos IP, Silva JM, Rego AC, Sotiropoulos I, Palikaras K
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378301
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Mitochondrial damage is a shared hallmark of brain aging and neurodegeneration. While pathological Tau mutations disrupt mitochondrial dynamics and function, the physiological role of wild-type (WT) Tau in the maintenanc...Mitochondrial damage is a shared hallmark of brain aging and neurodegeneration. While pathological Tau mutations disrupt mitochondrial dynamics and function, the physiological role of wild-type (WT) Tau in the maintenance of mitochondrial homeostasis remains poorly understood. Here, using and mice lacking PTL-1, the nematode Tau-like homolog, and Tau respectively, we demonstrate that Tau deficiency promotes a shift toward a pro-fusion mitochondrial state associated with enhanced mitochondrial function and stress resistance. In both models, loss of Tau leads to increased mitochondrial activity and altered redox homeostasis, while it enhances resistance to heat and mitochondrial stress in . Strikingly, loss of FZO-1, the mitofusin homolog, abolishes the beneficial phenotypes, whereas its overexpression phenocopies key aspects of Tau/PTL-1 deficiency. Together, our findings uncover a conserved role for WT Tau in restraining mitochondrial fusion and functional adaptation, highlighting its contribution to mitochondrial homeostasis and cellular stress responses.
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378300
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Prion diseases represent a unique biological paradigm with mechanistic parallels to other neurodegenerative conditions like Alzheimer's and Parkinson's diseases. However, the study of human prion pathobiology and the dev...Prion diseases represent a unique biological paradigm with mechanistic parallels to other neurodegenerative conditions like Alzheimer's and Parkinson's diseases. However, the study of human prion pathobiology and the development of effective therapeutics has been severely constrained by the inability to propagate human prions in dividing cells-forcing reliance on costly and slow animal bioassays. Here, we report the generation of EKV cells-a humanized cell model which supports the robust, indefinite propagation of sporadic Creutzfeldt-Jakob disease (sCJD) prions. We demonstrate that these cells replicate bona fide human prion infectivity in culture-cell lysates induce lethal neurodegeneration in humanized mice that is clinically and neuropathologically indistinguishable from inoculation with sCJD-infected brain tissue. We use EKV cells to develop the Human Prion Assay (HPA), which quantifies sCJD infectivity with sensitivity comparable to gold-standard mouse bioassay, while reducing the experimental timeline from years to weeks. Furthermore, we demonstrate that established sCJD infection can be cured by an anti-prion protein antibody, validating the system as a high-throughput platform for drug discovery. This model bridges a critical translational gap, offering a renewable alternative to animal bioassays, a paradigm to dissect the biology of human sCJD prion disease and screen for therapeutic agents.
Ziaei H, Zhang M, Guo T
… +6 more, Feng J, Meng L, Araujo-Villalba A, Jing J, Ho TV, Chai Y
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378299
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Sensory innervation of developing organs is influenced by molecular cues secreted from surrounding tissues, yet the mechanisms coordinating this tissue-tissue communication are not well understood. Tooth innervation duri...Sensory innervation of developing organs is influenced by molecular cues secreted from surrounding tissues, yet the mechanisms coordinating this tissue-tissue communication are not well understood. Tooth innervation during root development provides a valuable model to investigate how local mesenchymal cues regulate axonal growth under physiological conditions, as innervation begins and progresses alongside tooth root formation. Here we identify the histone demethylase KDM6B, expressed in cranial neural crest-derived dental mesenchyme, as a critical extrinsic regulator of tooth sensory innervation. Loss of in dental mesenchyme severely impairs trigeminal axon entry and branching into the dental pulp, leading to tooth root development defects. Mechanistically, loss of reduces the expression of bone morphogenetic protein (BMP) pathway antagonist in the dental mesenchyme by modulating H3K27me3 chromatin marks, causing overactivation of BMP signaling, which then directly suppresses the expression of nerve growth factor (). Compromised NGF activity thereby diminishes mesenchymal support for sensory axon extension during tooth root development. Haploinsufficiency of which antagonizes , or a key BMP receptor, partially rescues expression, sensory innervation, and tooth root development defects in mutants. Together, these findings reveal that epigenetic regulation within mesenchymal cells governs sensory innervation during organogenesis, uncovering important regulatory mechanisms that may inform future strategies for restoring innervation in tissue regenerative approaches.
Wang J, Marshall N, Han Z
… +9 more, Wang K, Sprague R, Yi Z, Yu W, Xu X, He Z, Wang DW, Scully MO, Sokolov AV
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378298
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Vibrational microspectroscopy, including both Raman-based and infrared-based techniques, can map the chemical distribution of samples based on molecular vibrations without labeling. However, imaging fast dynamics in livi...Vibrational microspectroscopy, including both Raman-based and infrared-based techniques, can map the chemical distribution of samples based on molecular vibrations without labeling. However, imaging fast dynamics in living organisms remains challenging. To address this, we propose a wide-field infrared microspectroscopy capable of single-shot imaging, where each image is captured with a single pair of laser pulses lasting approximately one picosecond. It minimizes motion blur and allows observing fast dynamic processes at frame rates up to the laser repetition rate. This approach is based on the infrared-resonant third-order sum-frequency process, which converts infrared light to visible signals. We demonstrate the capability through single-shot in vivo imaging of alive worms in water, achieving a spatial resolution of approximately 400 nm. Additionally, 1,000 Hz single-shot videos of moving worms are shown by using a kHz laser system. This approach opens more possibilities for imaging chemicals involved in fast dynamic processes, offering diverse applications in both chemistry and biology.
Magermans L, Kim J, Chacon R
… +4 more, Leray A, Atherton TJ, Gacoin T, Kim J
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378297
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Liquid crystals (LC) represent topological soft matter that spontaneously form assemblies of constituents and mesoscale textures to minimize free energy. Depending on boundary conditions, they exhibit transformable topol...Liquid crystals (LC) represent topological soft matter that spontaneously form assemblies of constituents and mesoscale textures to minimize free energy. Depending on boundary conditions, they exhibit transformable topological defects, whose study provides fundamental insights applicable to a wide array of disciplines. However, their three-dimensional (3D) structures and dynamics remain largely unexplored due to the subdiffraction limit length scales and submillisecond time scales characteristic of conventional molecular LCs. Here, we report a morphogenesis from conventional nematic tactoids to a unique flower-shaped morphology using a colloidal LC composed of Eu-doped LaPO nanorods. We demonstrate 3D orientational tomography based on polarized photoluminescence spectroscopy of the Eu dopants, revealing dramatic topological and topographical modulations. We find that this morphogenesis is driven by a theoretically unexpected vertical anchoring of the nanorods on the substrate, which exerts conflicting boundary conditions and leads to a competition between elastic energy and relatively weak surface tension. Our results provide valuable insights into how energy balance in topological matter can be modulated by tuning physicochemical properties of its building blocks.
Tyllis TS, Norton TS, Abbott C
… +8 more, McPeake DJ, Fenix KA, Wilson JJ, Kara EE, Good-Jacobson KL, Alsharifi M, McColl SR, Comerford I
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378296
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Chemotactic receptors involved in generation of ectopic pulmonary germinal centers (GCs) within inducible bronchus-associated lymphoid tissue (iBALT) are poorly defined. Here, using CIBER -reporter mice, we demonstrate t...Chemotactic receptors involved in generation of ectopic pulmonary germinal centers (GCs) within inducible bronchus-associated lymphoid tissue (iBALT) are poorly defined. Here, using CIBER -reporter mice, we demonstrate that the prototypical type 1 inflammatory chemokine receptor CXCR3 is highly induced in influenza A virus (IAV)-reactive B cells in the mediastinal lymph node, spleen, lung, peripheral blood, and airways following intranasal infection. Notably, elevated was observed in ectopic pulmonary germinal center B (GCB) cells in iBALT relative to their contemporaneous counterparts in secondary lymphoid organs across the timecourse of the response to IAV infection. Mice with a B cell-specific deletion of displayed a 50 to 60% reduction in the frequency and number of ectopic GCB cells in the lungs at the peak of the response following IAV infection, relative to controls. Furthermore, in cotransfers, -deficient B cells were substantially outcompeted by their -sufficient counterparts for ectopic pulmonary GC participation, but were not impacted with respect to GCB cell frequencies in other compartments. Thus, the data elucidate the requirement of B cell-intrinsic CXCR3 expression for efficient generation of ectopic pulmonary GCB cell responses in iBALT following respiratory viral infection with IAV, a finding that broadens understanding of the molecular cues underpinning this key component of local protective humoral immunity to IAV.
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378295
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Photosynthetic organisms must continuously balance efficient light harvesting with protection against excess excitation energy, a challenge met by nonphotochemical quenching (NPQ). Although the molecular components invol...Photosynthetic organisms must continuously balance efficient light harvesting with protection against excess excitation energy, a challenge met by nonphotochemical quenching (NPQ). Although the molecular components involved in NPQ have been extensively studied, how the essential energy-quenching site is assembled remains poorly understood, particularly in marine diatoms. Here, we show that in the centric diatom , which belongs to one of the most abundant and diverse genera in marine phytoplankton, the light-harvesting complex (LHC) protein Lhcf2 is required for energy-dependent quenching (qE). Targeted knockout of Lhcf2 abolished qE by preventing the stable accumulation of Lhcx1, a core component of the NPQ effectors in this species. Lhcf2 localizes to the peripheral antenna system and associates with Lhcx1 in a higher-order complex suggested by biochemical and functional analyses. In contrast, other established NPQ-related factors, including the trans-thylakoid proton gradient and the accumulation of diatoxanthin, were not affected by the loss of Lhcf2. These results identify a non-Lhcx-type LHC protein as an essential structural component for qE-NPQ and establish a general design principle for the cooperative assembly of photoprotective energy-quenching sites in eukaryotic photosynthesis, with implications for marine carbon fixation.
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378294
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Cannibalism is among the most widespread taboos in human societies, yet archaeological, ethnographic, and historical evidence indicates that it has repeatedly emerged across human populations. This coexistence of recurre...Cannibalism is among the most widespread taboos in human societies, yet archaeological, ethnographic, and historical evidence indicates that it has repeatedly emerged across human populations. This coexistence of recurrent practice and persistent prohibition raises a fundamental question: when does cannibalism become adaptive, and what mechanisms lead to its suppression? We address this problem using a formal model that treats cannibalism as a potential food source subject to energetic benefits and multiple sources of cost. Nutritional gains are modeled using a saturating function of caloric intake, while costs arise from acquisition, digestion, and infection. Infection costs are represented as a stochastic process whose mean increases with the length of the trophic transmission chain, capturing the risks associated with repeated within-species consumption. Analyzing the expected energetic balance across levels of food availability and cannibalism order reveals narrow ecological conditions in which cannibalism yields a positive expected balance and broader conditions in which it is strongly disfavored. The model provides a framework for interpreting archaeological and ethnographic findings by specifying boundary conditions and identifying the most probable ecological scenarios under which different forms of cannibalism are expected to occur. The results predict that cannibalism is most likely to emerge under extreme resource scarcity, when acquisition costs are low and infection risks are constrained, while sustained cannibalism rapidly becomes unviable due to escalating infection costs. Overall, the findings suggest that cannibalism is best understood as a conditional trade-off rather than a behavioral anomaly, with cultural taboos functioning as adaptive responses to nonlinear epidemiological risks.
Cheng S, Das D, Barchuk M
… +4 more, Armstrong R, Klingbeil MM, Thomases B, Zhou S
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378293
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In the pathogenic parasite , a laterally attached flagellum drives rapid deformation of the complex cell body, producing puzzling dynamics. High-speed defocusing imaging reveals that surface points trace flower-like patt...In the pathogenic parasite , a laterally attached flagellum drives rapid deformation of the complex cell body, producing puzzling dynamics. High-speed defocusing imaging reveals that surface points trace flower-like patterns in transverse planes. The petals arise from clockwise flagellar beating, which generates a right-handed helical wave propagating from the anterior tip along the body, advancing the cell like a twisted corkscrew. The central lobes result from slower counterclockwise body rotation required to balance the active torque. The bent cell shape underneath the flagellum superimposes these two chiral motions at different radial distances, producing the observed patterns. Three-dimensional hydrodynamic simulations using the method of regularized Stokeslets reproduce these dynamics and show that bent cell shape enhances swimming, suggesting an adaptive advantage of 's morphology.
Pan Y, Li H, Liao M
… +14 more, Wang T, Rao X, Wang Q, Hu P, Zheng D, Jiao Y, Chen L, Shi YS, Zhao Y, Zhang X, Li Z, Bao L, Wu L, Wang B
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378292
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Intellectual disability (ID) is a highly prevalent condition affecting approximately 200 millions of people worldwide, characterized by impaired cognitive function. Dynactin complex consists of multiple protein subunits...Intellectual disability (ID) is a highly prevalent condition affecting approximately 200 millions of people worldwide, characterized by impaired cognitive function. Dynactin complex consists of multiple protein subunits and is required for intracellular trafficking and synaptic homeostasis in developing and mature neurons. Here, we identify deleterious variants of dynactin subunit 4 (DCTN4) in ID pedigrees. DCTN4 ablation in mice results in altered neuronal positioning and apoptosis in neural progenitor cells. Notably, mice carrying the ID-linked variant exhibit cognitive deficits with impaired dendritic development. Cortical neurons with DCTN4 deficiency or variant show reduced levels of various dynactin subunits, suggesting that deficits in dynactin complex affects synaptic function. Furthermore, disruption of the DCTN4-JIP3 complex impairs lysosomal transport and dendritic development as well as synaptic development. Importantly, we showed that damaging variants in another dynactin subunit DCTN2 also disrupt neuronal positioning, reinforcing the critical role of dynactin complex in neurodevelopment and ID pathogenesis. These findings illustrate dysfunctional dynactin complex as a previously unrecognized disease mechanism of ID.
Tan YQ, Ren YY, Yang Y
… +7 more, Wang J, Yu B, Wang X, Zhang P, Zhao Y, Wang P, Wang YF
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378291
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Both Ca-independent kinase OPEN STOMATA 1 (OST1) and Ca-DEPENDENT PROTEIN KINASEs (CPKs) play important roles in ABA-induced stomatal closure. We recently reported that OST1-mediated phosphorylation and activation of Ca...Both Ca-independent kinase OPEN STOMATA 1 (OST1) and Ca-DEPENDENT PROTEIN KINASEs (CPKs) play important roles in ABA-induced stomatal closure. We recently reported that OST1-mediated phosphorylation and activation of Ca channels constituted mainly with CYCLIC NUCLEOTIDE-GATED CHANNEL 5 (CNGC5), 6, 9, and 12 (CNGC5/6/9/12) are required for ABA-induced stomatal closure in Arabidopsis. However, Ca-dependent protein kinases and underlying mechanisms that are involved in this Ca signaling pathway are still largely unknown. In this study, we identified CPK3, 8, and 10 (CPK3/8/10) as Ca-dependent CNGC-activating kinases with CPK3 as the main one, and a conserved serine site at CNGCs' C termini is revealed to be the main CPK3-target sites, differing from OST-target sites at CNGCs' N termini. Double S-to-D (2D) and S-to-A (2A) point mutations at OST1- and CPK3-target sites respectively coactivate and cosuppress CNGCs, but individual S-to-D activation is impaired by S-to-A mutation at the other site. Abscisic acid (ABA)-induced stomatal closure and Ca oscillations are impaired in Arabidopsis triple mutant , but are rescued fully by the CNGC6's 2D variant, largely by mixed A/D variant, and not by 2A variant. These results demonstrate that the cytosolic Ca elevation derived from OST1-CNGC modules-mediated external Ca influx activates CPK3 via Ca binding, the Ca-bound CPK3 evokes more massive external Ca influx through enhancing the activity of CNGCs by phosphorylation, and CPK3-evoked Ca influx is required for the encoding of ABA-induced cytosolic Ca signaling in Arabidopsis guard cells.
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378290
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A spacetime crystal is a phase of matter that spontaneously develops periodic order in both space and time. Spacetime crystals have been experimentally observed in microscopic quantum many-body systems and, very recently...A spacetime crystal is a phase of matter that spontaneously develops periodic order in both space and time. Spacetime crystals have been experimentally observed in microscopic quantum many-body systems and, very recently, in a mesoscopic nematic liquid crystal. However, the melting process of a spacetime crystal and its underlying physical mechanisms have not yet been experimentally reported. Here, we present a direct observation of a classical continuous spacetime crystal melting in a table-top experiment with macroscopic active granular disks in 2 + 1 spacetime dimensions. The spacetime crystal is characterized by the spontaneous formation of a coherent, rigid-body rotation of a 2D triangular lattice that persists for almost a day and remains remarkably robust to noise. By tuning the disk packing fraction, we observe a complex three-stage melting process involving a spatially hexatic phase and multiple coexistence regions. Importantly, we show that spatial and temporal crystalline orders melt separately through distinct mechanisms: Spatial order is destroyed by the proliferation of topological defects, while temporal order is lost through the decay of directional persistence caused by the progressive weakening of many-body interactions. Our results demonstrate that the spontaneous breaking of spatial and temporal translational symmetries can be decoupled, leading to the emergence of exotic out-of-equilibrium classical phases of matter.
Wodeyar A, Chinappen D, Kwon H
… +4 more, Shi W, Richardson RM, Kramer MA, Chu CJ
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378289
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The cross-regional interplay of slow oscillations, spindles, and ripples during sleep is believed to support systems memory consolidation but remains understudied in humans. Using a validated behavioral task and simultan...The cross-regional interplay of slow oscillations, spindles, and ripples during sleep is believed to support systems memory consolidation but remains understudied in humans. Using a validated behavioral task and simultaneous intracranial neural recordings from the orbitofrontal cortex, thalamus, and hippocampus in 19 patients with epilepsy, we examined the cross-regional interplay of sleep oscillations (slow oscillations, spindles, and ripples), alongside epileptic spikes, and their role in motor memory consolidation. Orbitofrontal slow oscillations robustly modulate spindle and ripple oscillations within and across regions during sleep. Although most combinations of oscillation rates positively predicted overnight performance change in a motor task, hippocampal ripple rate and coupled hippocampal-orbitofrontal ripple rates were the most reliable predictors across subjects. In contrast, rates of most sleep oscillations coupled to epileptic spikes were negative predictors of overnight motor performance change, with the rate of slow oscillations co-occurring with epileptic spikes the most reliable predictors of negative change across subjects. These findings provide direct evidence of a hierarchical cascade of sleep oscillations in human motor memory processing and reveal that epileptic spikes coupled to sleep oscillations interfere with this process in patients with epilepsy.
Ginosar Yaari S, Chentsova-Dutton Y, Riediger M
… +30 more, Rauers A, Kim MY, Miyamoto Y, Vishkin A, Freitag JA, Cieciuch J, Gurevich M, Padun M, Solak N, Wang X, Qiu J, Alvarez-Risco A, Rossi AA, Hanoch Y, Uchida Y, Torres CV, Nascimento TG, Afshar Jahanshahi A, Singh R, Singh B, Kamble SV, An S, Dzokoto V, Anum A, Mannarini S, Huerta-Carvajal MI, Galindo-Bello E, García Ibarra VJ, Dash A, Tamir M
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378288
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In many Western cultures, trying to make others feel better is considered critical for psychological health and social relationships. However, given that people think about emotions and relationships differently across c...In many Western cultures, trying to make others feel better is considered critical for psychological health and social relationships. However, given that people think about emotions and relationships differently across cultures, the desirability, means, and benefits of making others feel better may also vary by culture. In two multicountry survey studies (Study 1: = 3,154, 13 countries; Study 2: = 3,503, 17 countries) and in a daily dairy study (Study 3: = 243, 2 countries), we assessed motivation and strategies used for influencing others' and one's own emotions. To test whether potential cross-cultural differences in motivation and strategies in emotion regulation are unique to social interactions, we compared cultural differences in making others feel better to making oneself feel better. Across studies, cultural differences in influencing others' emotions were greater than those in influencing one's own emotions. Members of more individualist (vs. collectivist) cultures were more motivated to make others (but not themselves) feel better, were more likely to express care and less likely to encourage others to suppress their emotions or to ruminate. These patterns, in turn, were linked to an index of relationship closeness in an individualist (but not a collectivist) culture. These findings suggest that helping others feel better may not be equally desirable across cultures.
Dhingra Y, Landick R, Campbell EA
… +1 more, Darst SA
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378287
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The nucleotide addition cycle (NAC) of multisubunit DNA-dependent RNA polymerases (RNAPs) involves coordinated conformational changes in conserved active-site structural elements, including the trigger loop (TL). The TL...The nucleotide addition cycle (NAC) of multisubunit DNA-dependent RNA polymerases (RNAPs) involves coordinated conformational changes in conserved active-site structural elements, including the trigger loop (TL). The TL is open (unfolded) in most RNAP structures but can close (fold) in substrate-bound (post- or pretranslocated) states of the RNAP, promoting catalysis. TL closure has been associated with closure of another conserved structural element, the Rim-Helices/F-loop (RH-FL), but the role of the RH-FL in the NAC is unclear. Antibiotic leads CBR9379 and AAP-SO inhibit the and RNAPs, respectively, by binding in a pocket formed by the bridge helix and RH-FL. The precise mechanism of action for these inhibitors is yet to be defined. We present cryoelectron microscopy structures showing that both compounds inhibit the RNAP NAC by preventing RH-FL closure, thereby allosterically destabilizing the closed TL. This work reveals a conserved mechanistic principle of RNAP catalysis across all domains of life and provides insight for antibiotic design.
Hong X, Dalouchi F, Prom JC
… +14 more, Ponte ME, Hockey BL, Braun JL, Nies P, Stoltz A, Chakravarthi VP, Sinha M, Choi SY, Ronca AE, Alwood JS, Fajardo VA, Morris EM, Puukila S, Christenson LK
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378286
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Spaceflight presents unique gravitational, radiation, and isolation hazards for human exploration of the Moon, Mars, and beyond, yet its impact on the female reproductive system and successive generations has been largel...Spaceflight presents unique gravitational, radiation, and isolation hazards for human exploration of the Moon, Mars, and beyond, yet its impact on the female reproductive system and successive generations has been largely unassessed. In the NASA Rodent Research 20 mission, we examined the impact of a 42-d spaceflight on the female reproductive axis including ovulatory capacity, implantation rate, and fecundity as well as behavioral, metabolic, and functional outcomes in F1 and F2 offspring. Females bred 5 d after return to Earth became pregnant but only exhibited a slight decline in fecundity compared to ground controls. In contrast, F1 offspring from spaceflight dams exhibited marked growth, functional, and behavioral differences compared to F1 offspring from control dams. Moreover, F1 female offspring from spaceflight dams exhibited decreased ovarian reserves as evidenced by reduced anti-Mullerian hormone levels early in life (21 d of age) and premature ovarian failure or an early loss in fertility, as indicated by reduced numbers of litters and total number of pups born to females over a 9-mo period. Strikingly, transgenerational metabolic and reproductive disturbances were also observed in F2 pups of spaceflight granddams, including persistent reductions in ovarian reserve, suggesting germline-level effects. Together these findings reveal significant short- and long-term impacts of spaceflight on the female reproductive system and on their offspring across generations, demonstrating biological transmission of reproductive vulnerability following maternal spaceflight exposure, and raising concerns for space travelers and colonization missions.
Proc Natl Acad Sci U S A
· 2026 Jul · PMID 42378285
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Poetry condenses language into minimal forms, evoking emotion, imagery, and aesthetic judgment, yet the neural basis of such evaluations remains poorly understood. We investigated how the brain evaluates two structurally...Poetry condenses language into minimal forms, evoking emotion, imagery, and aesthetic judgment, yet the neural basis of such evaluations remains poorly understood. We investigated how the brain evaluates two structurally matched but thematically distinct poetic forms: nature-themed Haiku and emotion-themed Senryu. Participants read poems and rated them across five dimensions-aesthetic appeal, vivid imagery, being moved, originality, and creativity-while EEG was recorded. Using multiclass gradient-boosted tree models with SHapley Additive exPlanations, we predicted evaluative ratings from oscillatory neural features across temporal windows and scalp regions. Models outperformed linear baselines and showed limited cross-theme generalization, indicating content-specific neural encoding. Distinct processing patterns emerged: Senryu showed stronger beta-band contributions, whereas Haiku engaged more distributed multifrequency dynamics. Temporal profiles also differed, with Haiku showing sustained engagement across reading and contemplation phases and Senryu showing earlier evaluative resolution during reading. Prestimulus neural activity contributed to prediction of subsequent evaluations, suggesting a role for anticipatory brain states in aesthetic evaluation. Across poems, evaluative dimensions converged on a dominant shared axis that was reliably predicted from neural features. Together, these findings suggest that aesthetic evaluation of poetry reflects an interaction between anticipatory neural states, content-specific oscillatory dynamics, and dimension-specific processes organized around a shared evaluative axis. This work establishes poetry as a tractable model system for studying how the brain constructs meaning and value from minimal linguistic input.