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Individual differences in speech monitoring: Functional and structural correlates of delayed auditory feedback
Sensory feedback is essential for the fine-tuning of motor actions, and speech production is no exception. It depends on continuous self-monitoring to ensure that produced sounds match intended targets. Delaying auditory feedback (DAF) disrupts this alignment and impairs fluency, providing a powerful tool to investigate sensorimotor control. We combined functional and diffusion-weighted MRI in 31 participants performing a word-production task under delayed (DAF) and immediate (no-DAF) auditory feedback. While all participants slowed their speech under DAF, the extent of this effect varied across individuals and was quantified using a susceptibility index. At the group level, DAF > no-DAF elicited increased activation in a right-lateralized network encompassing the superior temporal gyrus, supramarginal gyrus, inferior frontal gyrus, supplementary motor area, and left cerebellum. Incorporating individual differences revealed that higher susceptibility was associated with greater activation in left-hemisphere speech motor homologues and larger volume of the right long segment of the arcuate fasciculus, a whitematter pathway connecting auditory and motor speech regions. This pattern suggests that susceptibility reflects increased recruitment of neural resources and a stronger reliance on auditory-motor coupling. In contrast, resilience was associated with greater engagement of the bilateral angular gyrus and higher fiber density in the right posterior AF, which connects auditory and somatosensory speech regions. This finding indicates that resilience is supported by a posterior temporo-parietal circuit that efficiently integrates multimodal sensory feedback. Together, these findings link functional dynamics with underlying structural connectivity to reveal how a right-lateralized network supports speech control, while accounting for individual differences in susceptibility to fluency disruption.
Daily briefing: How to brew a climate-friendly coffee
High-severity fire now dominant in California forests
Fire severity exerts crucial ecological controls in many forests globally. In California, where annual forest-fire area has increased dramatically in recent decades, understanding how burn severity is changing is essential for informing environmental policy and management. We developed remotely sensed high-resolution maps of severity for 4,391 forest fires to assess trends and drivers of burn severity across California’s forests from 1985–2024. We observed that historically dominant low-severity and ecologically restorative fire was increasingly replaced by high-severity stand-replacing fire, which became the most common severity class beginning in 2012. This regime shift indicates that forested areas are increasingly burning at severity levels they are unlikely to survive. Redistribution toward high-severity fire was strongest in high-biomass forests, implicating heavy fuel loads due to fire exclusion as an amplifier of tree mortality. Importantly, California’s forests provide a vast array of ecosystem services, including the regulation of climate and the water cycle, biodiversity support, and timber and recreation revenue. Thus, the growing dominance of high-severity forest fire is likely to impose significant socioeconomic costs on California.
Hepatitis B virus genome packaging and replication are coordinated by a polymerase-responsive RNA switch in the RNA element epsilon
Hepatitis B virus (HBV), a major human pathogen, replicates its DNA genome by protein-primed reverse transcription of a pregenomic RNA (pgRNA). This process is directed by the pgRNA-borne epsilon (ε) element, which provides the origin for minus-strand DNA synthesis and mediates coencapsidation of pgRNA with the viral polymerase (P protein) into nucleocapsids. ε adopts a thermodynamically stable hairpin structure that is remodeled upon formation of functional ε-P complexes, but the nature of the rearranged RNA structure and its implication for pgRNA encapsidation has remained elusive. Guided by in silico analyses of ε-like elements from distantly related nackednaviruses, we identify a distinct conformation of HBVε whose defining feature is a cryptic stem-loop (cSL), masked within the upper stem of ε. The P-dependent cSL conformation reorganizes key sequences into a compact structural unit that enables initiation of DNA synthesis and packaging of the viral pgRNA-P complex. RNAs engineered to favor cSL formation exhibit increased P protein affinity and strongly enhanced priming activity in vitro while maintaining replication competence in cells. Mutational analyses identify the cSL and its immediate vicinity, but not the remaining upper stem sequence, as the dominant determinants of ε function. Genetic variation in cSL-forming potential across hepadnaviruses links in vitro priming competence to the energetic accessibility of this alternative fold. Together, our findings reveal ε as a P protein-dependent RNA switch that tightly couples pregenome encapsidation to reverse transcription competence. This regulatory mechanism advances our understanding of HBV replication and could be exploited for antiviral intervention.
Shelf-invading low-oxygen waters control Cenozoic organic carbon burial rates
The thermostatic mechanisms of Earth’s persistent habitability remain unresolved. High-resolution Cenozoic C isotope records, P accumulation, and coarse-fraction I/Ca allow recalculation and assessment of controls on the global proportion of total carbon buried as organic carbon ( f org ), a regulator of atmospheric CO 2 and O 2 . f org was suppressed during the Eocene hothouse, coincident with an oxygenated water column and low water-column phosphate. With decreased sea level, the area for efficient organic carbon and phosphate sedimentary burial diminished, leading increasingly to greater water-column phosphate, higher primary productivity, and emergent water column deoxygenation. The sea-level influence on the areal extent of high sedimentation in shelf regions acts as a control on phosphate availability for new production, respiratory demand, and ocean oxygenation, as proposed by hypsographic models [C. J. Bjerrum, J. Bendtsen, J. J. F. Legarth, Geochem. Geophys. Geosys. 7 , 1–24 (2006)]. During intermediate sea-level highs of the Neogene, pulses of enhanced organic carbon burial prevailed for multimillion years, in response to the redox recycling of phosphate when oxygen minimum zones with O 2 < 90 µmol/kg were present. We propose the existence of a self-limiting intermediate sea-level sweet spot with peak C org burial due to redox recycling of phosphate, whereby oxygen minimum zones (OMZ) with O 2 < 90 µmol/kg impinge on the most C org rich continental shelf sediments. Such a sweet spot has narrowed over Earth history due to deepening OMZs, stabilizing both atmospheric O 2 and CO 2 . Continental marine inundation controls on phosphate availability, and the sedimentary carbon flux, provide a positive-feedback and rectifier to perturbations during inception of the icehouse world.
Physiology is a hidden dimension of diversity in the radiation of woodland salamanders
Morphological evolution can be explosive, producing visually spectacular adaptive radiations like Caribbean anoles, Malagasy vangas, and African Rift Lake cichlids. Yet morphological stasis, the long-term retention of a conserved body plan, is often observed across evolutionary radiations. Woodland salamanders ( Plethodon ) are a classic example of such “nonadaptive” radiation, characterized by prolific speciation alongside morphological stasis (i.e., limited morphological divergence), often attributed to phylogenetic conservatism in their climatic and microhabitat niches. However, the multidimensional nature of phenotypes and the niche means that adaptive evolution in less apparent traits can occur even when morphology appears static. We investigated whether woodland salamanders exhibit adaptive divergence in a less conspicuous phenotypic axis—specifically, physiology—and compared patterns and rates of trait evolution to those of morphological traits. We found that most physiological traits are associated with climatic variation and exhibit elevated rates of evolution, high trait disparity, and more frequent shifts in adaptive optima than morphological traits. In particular, skin resistance to water loss, metabolic rate, and cold tolerance exhibit evolutionary signatures of adaptive radiation. Notably, morphology is not entirely static: Some traits show climatic associations, several exhibit localized shifts, and evolutionary rates exceed those of slower evolving physiological traits, such as heat tolerance. Biological systems, as evidenced by woodland salamanders, are not exclusively “conserved” or “labile” in their evolution, and this system illustrates how the same features that limit morphological divergence may also facilitate physiological evolution. Woodland salamanders exemplify how adaptive radiation can proceed despite outward similarity.
Laser ablation microscopy reveals apical notch, apical dominance, and meristem regeneration dynamics in <i>Marchantia polymorpha</i>
Meristems are the growth centers of plants and fundamental in understanding plant development, morphogenesis, and vegetative propagation. Across all plant groups, the phytohormone auxin controls meristem maintenance, represses the emergence of new meristems (apical dominance), and mediates cellular reprogramming when new meristems regenerate following removal of existing meristems. The liverwort Marchantia produces clonal propagules (gemmae) featuring two apical notches that develop into functional meristems. This presents a tractable experimental system to study meristem developmental biology. I used laser ablation microscopy to precisely disrupt cells in and around the developing premeristem in the apical notches of germinating gemma, finding that the first cell row is indispensable. Within this layer, a contiguous quorum of stem cells is required for activity. Apical notches reorientate in response to damage, demonstrating that the apical notch stem cells act as a communicating population. Feedback from the stem cell population is necessary to maintain notch activity and generate the notch apex. These experiments show communication between notches and regenerating meristems. The apical dominance signal represses cell division and requires both sources and sinks, features of auxin-mediated communication. Central regions of the gemma could transmit these apical dominance signals, but the tissues of the gemma periphery could not. I present a model of Marchantia gemma and apical notch organization, involving intra-, inter-, and extranotch communication. This provides a framework for further study of meristem formation, communication, and maintenance in Marchantia and improving knowledge of plant meristems more generally.
Transient pores account for cell-penetrating peptide and homeoprotein translocation
Homeoproteins (HPs) and cell-penetrating peptides (CPPs) enter cells by endocytosis and direct membrane crossing (translocation). However, unlike endocytosis, translocation remains globally unknown. Here, we developed an electrophysiological approach to assess the internalization of CPPs (Tat, R 9 , penetratin and R 6 W 3 ) and the HPs Otx2 and En2 though single-cell unitary transient currents in mammalian cells. At resting membrane potential, CPPs or HPs lead to submillisecond transient pores, faster than any endocytosis event, which reveal the rapid passage of the peptide across the membrane i.e., by translocation. We evidenced that expression of specific membrane glycosaminoglycans is mandatory for translocation-induced transient pores. Associated transient currents are supralinearly enhanced by hyperpolarization and poorly affected by depolarization. Moreover, a CPP-conjugated bioactive cargo similarly translocates into cytosol. Finally, we show similar HPs-evoked transient pores in brain cortical pyramidal cells, showing the physiological relevance of translocation, with crucial biotechnological and therapeutical consequences for cell delivery purposes.
Differentiation drives the erosion of positivity on social media
Most people believe that social media discourse is negative and divisive. Here we show how this negativity can evolve even when users are not motivated to be negative. We propose that social media users seek to differentiate themselves from other users, and it is easier to differentiate oneself through negativity than positivity because negative information is more heterogeneous and counternormative than positive information. This makes users increasingly likely to post negative comments as a conversation unfolds and it becomes more challenging to make unique contributions. Analyzing 2.05 billion comments from 2,150 Reddit communities shows that comments become more negative over time, both within threads and community histories. This trend toward negativity is mediated by the semantic uniqueness of comments, suggesting that it arises from users differentiating themselves. This trend is strongest when initial dialogue is positive, making negative comments highly counternormative. We replicate these patterns in an experiment simulating social media dialogue ( n = 3,685). Participants become more negative over time, but only when incentivized to be unique, and especially when dialogue begins positively. These findings suggest that the structure of social media platforms interacts with human motivation to foster a drift toward negativity over time in online discourse.
Horseshoe bats foraging in the wild adjust sensing to separate prey echoes from background clutter
How animals handle immense incoming sensory information and regulate sensing is difficult to study under natural conditions. Using miniature GPS tags with microphones we monitored the sensing of freely foraging greater horseshoe bats. Bats stayed in acoustic contact with the environment and caught insects while commuting and in short flights from a perch. Bats adjusted their call frequency to maintain the highest-frequency echoes from background in a forward-directed, spatially limited sector at a constant maximal frequency. This Doppler-shift-compensation strategy guaranteed that echoes of insects flying in front of the bats were received at the sensitive center of their auditory fovea while masking background echoes were received at lower frequencies. Our results reveal an active sensing strategy allowing segregation of signals from background input under natural conditions.
Plant species invasions and community composition processes
Lipopolysaccharide biosynthetic locus as a source of clonal variation in Legionella pneumophila isolates associated with the outbreak in Japan
Abstract Some genomic subtypes of Legionella pneumophila exist in the environment that cause outbreaks. We examined how the clonal strains diverged through changes in their genomic structures using isolates associated with similar Pulsed-field gel electrophoresis patterns reported in the previous outbreak, serogroup (SG) 1 and SG13. The complete genomes for eight L. pneumophila SG1 and SG13 isolates were determined, and their genome structures were compared. A comparison of the complete genomes showed that these isolates had highly similar sequences, except for the region containing the lipopolysaccharide (LPS) biosynthetic locus, and IS 1182 elements were present at both ends of the LPS biosynthetic locus in the SG1 isolates. We deduced that the SG13 isolates transformed into the SG1 isolates through recombination at the LPS biosynthetic locus involving IS 1182 elements. It is important to consider the possibility that isolates associated with an outbreak of Legionella bacteria, despite having differing SGs, might be genetically related.
Hydrologic connectivity amplifies riverine N <sub>2</sub> O emission hot spots and hot moments across the contiguous United States
Riverine nitrous oxide (N 2 O) emissions constitute a significant yet uncertain component of global greenhouse gas budgets. Integrating approximately 3,600 observations across the contiguous United States (CONUS), we present a monthly resolved, national-scale estimate of riverine N 2 O emissions (60.7 Gg N 2 O-N y −1 ; 95% CI: 41.9 to 71.2) using a machine-learning framework. Our analysis reveals that enhanced hydrologic connectivity strongly regulates nitrogen and N 2 O delivery to streams, driving emission hot moments during high-flow periods, especially in nutrient-rich low-order streams. The Midwest Corn Belt is identified as a major emission hot spot, where seasonal increases in connectivity (e.g., late-winter thaws and postharvest rainfall) amplify riverine emissions relative to direct soil emissions. Our watershed-specific EF 5r (0.0005 to 0.029) exceeds the IPCC default (0.0026) by more than twofold on average and up to 10-fold in intensively managed watersheds. These findings highlight the importance of incorporating hydrologic connectivity and nitrogen transport into climate models and watershed nitrogen management strategies.
Intelligent adaptive frequency regulation of interconnected power networks under renewable uncertainty and time delays
Abstract This paper proposes a novel adaptive control framework for load frequency regulation (LFC) in modern power systems with renewable energy integration and communication delays. A Single Perceptron Proportional–Integral (SPPI) controller optimized using Harmony Search (HS) is designed for single-area systems, while a cascaded SPPI–PID structure is developed for two-area networks. Unlike conventional fixed-parameter controllers, the proposed approach adapts online to varying operating conditions and disturbances. Simulation studies under step load changes, random load variations, and wind power fluctuations demonstrate superior performance of the proposed controllers. For single-area systems, the SPPI controller achieves overshoot as low as $$\:1.28\times\:{10}^{-5}$$ , settling times between 9 and 21 s, and IAE ranging from 0.00176 to 0.312. In two-area systems, the cascaded SPPI–PID controller reduces peak-to-peak deviations to $$\:1.47\times\:{10}^{-4}$$ , with settling times from 3 to 109 s and IAE values between 0.00115 and 0.1854. A sensitivity analysis with ± 20% variations in inertia, load damping, and governor speed regulation confirms the robustness of the proposed approach. A frequency-domain robustness analysis using Bode plots further verifies satisfactory stability margins. In addition, a real-time validation has been performed to further confirm the practical applicability and real-world performance of the proposed control framework under realistic operating conditions. These results indicate that the HS-optimized SPPI and cascaded SPPI–PID controllers provide an effective, reliable, and robust solution for frequency regulation in modern interconnected power systems.
SLC11A2 withholds divalent metals from <i>Salmonella</i> in the gut epithelium
There is a constant tug-of-war for transition metals at the pathogen–host interface. Vertebrate hosts modulate the availability of metals to pathogens in a process known as nutritional immunity, but pathogens have evolved numerous countermeasures to this host defense strategy. The bioavailability of trace metals therefore shapes the outcome of disease. In mammals, epithelial cells lining the intestine are a major site of metal absorption. Intestinal epithelial cells (IECs) are also a target for invading enteric pathogens but the contribution of epithelium-intrinsic factors toward nutritional immunity is unclear. Using Salmonella enterica serovar Typhimurium (STm) harboring genetically encoded fluorescent sensors for transition metals, we mapped the spatiotemporal nature of metal competition during enteric salmonellosis. In contrast to the metal replete lumen, a subpopulation of STm experience a temporal, cell-specific restriction of Fe 2+ and Zn 2+ (≤0.1 µM), and possibly Mn 2+ , in both IECs and cells of the lamina propria during the early stages of infection. We further studied the contribution of the broad specificity divalent metal transporter, SLC11A2, in IECs to nutritional immunity against STm. SLC11A2 was recruited to maturing Salmonella -containing vacuoles and knockout of SLC11A2 led to increased bacterial proliferation in IECs. Metal-responsive fluorescent reporters showed that vacuolar STm were less starved for Fe 2+ , and possibly Mn 2+ , but not Zn 2+ or Mg 2+ in the absence of SLC11A2 . STm counters SLC11A2-mediated growth restriction in IECs via the Mn 2+ /Fe 2+ transporter, MntH, and iron-binding siderophores. We conclude that SLC11A2-mediated sequestration of a subset of metals is an IEC innate defense mechanism against STm.
Entrepreneurial success across novice, serial and portfolio entrepreneurs
Genomic reconstruction of upland cotton domestication uncovers staged selection, gene flow, and flowering-time adaptation
Upland cotton ( Gossypium hirsutum L.) makes up about 90% of global cotton farming. Despite its importance, the origins and domestication history of upland cotton remain poorly understood. Here, we present a high-density pan-genome variation map constructed from 2,910 cotton accessions, including 440 newly sequenced G. hirsutum landraces. Our pan-genome analysis indicates that modern upland cotton most probably originated from a single domestication and underwent three major stages. We also identified several genomic signatures associated with agriculturally important traits, including photoperiod sensitivity, fiber properties, and seed yield, which map to candidate loci GhTOFD06 , GhFLD11, and GhSID05, respectively, through a genome-wide association study (GWAS) and VIGS knockdown. During the third domestication stage (D3), selective pressures favored genes, such as GhTOFD06, a homolog of Arabidopsis COP9 signalosome complex subunit 5b (CSN5B), that control photoperiod-regulated flowering, thereby accelerating cotton domestication and facilitating upland cotton’s latitudinal expansion. Notably, functional validation via gene silencing showed that knockdown of GhSID05 reduced single seed weight by 11.41%, confirming its pivotal role in seed yield regulation. Additionally, we revealed natural gene flow between G. hirsutum and G. barbadense , which has significantly enriched the genetic diversity of the G. hirsutum gene pool and may have contributed favorable alleles for improving modern upland cotton. Our study provides a comprehensive understanding of the genomic evolution of G. hirsutum and valuable genetic resources for future breeding programs.
Association of serum S100A8/A9 with sepsis-associated acute kidney injury and 28-day mortality: a hybrid cohort study
Nongenetic engineering nanozyme proximity labeling reveals subcellular in situ interactomes and trafficking pathways of nanoparticles
Elucidating the dynamic interactions between nanocarriers and cellular machinery is critical for advancing targeted nanomedicine. However, the optical microscopy imaging techniques can only provide a generalized view of nanomedicine localization. Proteomics approaches require cell lysis which disrupt native protein coronas during isolation, obscuring real-time intracellular trafficking mechanisms. Although proximity labeling enables in situ investigation of intracellular protein–protein interactions, it relies on genetically engineered enzyme fusion, thus limiting applicability across diverse systems. In this study, we report nanozyme proximity labeling (NPL), a genetic engineering-free strategy that harnesses the intrinsic peroxidase activity of Fe 3 O 4 nanoparticles (NPs) to biotinylate proximal proteins within live cells. NPL achieves rapid biotinylation of NP-interacting proteins during intracellular transit. Using streptavidin pulldown and LC–MS/MS, we mapped high-fidelity in situ interactomes and suggested distinct trafficking pathways for mitochondrial-targeted Fe 3 O 4 @TPP NPs and nontargeted Fe 3 O 4 NPs. Our NPL interrogates the native NP–protein corona–organelle interfaces, offering a generalizable platform to decipher subcellular targeting mechanisms and accelerate nanomedicine optimization.