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Basic reproduction number varies markedly between closely related pandemic Escherichia coli clones
Abstract Extra-intestinal pathogenic Escherichia coli ubiquitously colonize the human gut and represent clinically the most significant bacterial species causing urinary tract infections and bacteremia. During the last two decades clades of the ST131 lineage have spread globally, but it remains unknown how their transmission dynamics compare to the basic reproduction numbers ( R 0 ) for viral pandemics. We develop a compartmental model for asymptomatic gut colonization and onward transmission coupled with an epidemiological observation model and fit it on the major ST131 clades. Our results indicate that the ST131-A transmission potential ( R 0 = 1.47) can be comparable to pandemic influenza viruses, while the significantly lower transmissibility of ST131-C1 ( R 0 = 1.18) and ST131-C2 ( R 0 = 1.13) suggests that their dissemination has been aided by antibiotic selection pressure and healthcare facilities. Our results provide an advance in understanding the relative transmissibility of these opportunistic pathogens.
Conformational transitions enabling interkingdom transfer of effector multitudes
Entropy-driven strategy stabilizes photoactive halide perovskites for inverted solar cells
Reply to Singer: Strike paper mills at the root
Early Oldowan technology thrived during Pliocene environmental change in the Turkana Basin, Kenya
Abstract Approximately 2.75 million years ago, the Turkana Basin in Kenya experienced environmental changes, including increased aridity and environmental variability. Namorotukunan is a newly discovered archaeological site which provides a window into hominin behavioral adaptations. This site lies within the upper Tulu Bor and lower Burgi members of the Koobi Fora Formation (Marsabit District, Kenya), presently a poorly understood time interval due to large-scale erosional events. Moreover, this locale represents the earliest known evidence of Oldowan technology within the Koobi Fora Formation. Oldowan sites, older than 2.6 million years ago, are rare, and these typically represent insights from narrow windows of time. In contrast, Namorotukunan provides evidence of tool-making behaviors spanning hundreds of thousands of years, offering a unique temporal perspective on technological stability. The site comprises three distinct archaeological horizons spanning approximately 300,000 years (2.75 − 2.44 Ma). Our findings suggest continuity in tool-making practices over time, with evidence of systematic selection of rock types. Geological descriptions and chronological data, provide robust age control and contextualize the archaeological finds. We employ multiple paleoenvironmental proxies, to reconstruct past ecological conditions. Our study highlights the interplay between environmental shifts and technological innovations, shedding light on pivotal factors in the trajectory of human evolution.
A fiber array architecture for atom quantum computing
Abstract Arrays of single atoms trapped in optical tweezers are increasingly recognized as a promising platform for scalable quantum computing. In both the fault-tolerant and NISQ eras, the ability to individually control qubits is essential for the efficient execution of quantum circuits. Time-division multiplexed control schemes based on atom shuttling or beam scanning have been employed to build programmable neutral atom quantum processors, but achieving high-rate, highly parallel gate operations remains a challenge. Here, we propose a fiber array architecture for atom quantum computing capable of fully independent control of individual atoms. The trapping and addressing lasers for each individual atom are emitted from the same optical waveguide, enabling robust control through common-mode suppression of beam pointing noise. Using a fiber array, we experimentally demonstrate the trapping and independent control of ten single atoms in two-dimensional optical tweezers, achieving individually addressed single-qubit gates with an average fidelity of 0.9966(3). More significantly, we perform simultaneous arbitrary single-qubit gates on four randomly selected qubits, resulting in an average fidelity of 0.9961(4). Our work paves the way for time-efficient execution of quantum algorithms on neutral atom quantum computers.
An optical meta-image-processor for enhanced imaging through strongly scattering media
Precise temporal dynamics of ripple events support order memory in human hippocampal–cortical circuits
Serial order memory, a key type of episodic representation, requires the encoding of map–like context information (interitem relationships) to facilitate recall. In rodent models, both spatial and nonspatial order memory depend heavily on the hippocampus. However, in humans, lesional and neurophysiological data also implicate extrahippocampal areas, especially the orbital frontal cortex and medial parietal regions, in these mnemonic abilities. To investigate the neurophysiological mechanisms of order information in human memory, we used direct brain recordings from hippocampal–cortical circuits as neurosurgical patients performed a serial recall task. Our unique dataset included simultaneous acquisition of data from the hippocampus, orbitofrontal cortex, and posterior cingulate regions. Focusing on ripple events, we demonstrate distinct interregional dynamics during successful order memory encoding using temporally precise, simultaneous recordings across these circuits. The relative timing of co-rippling events implicates theta oscillations in cross-regional integration, particularly between the hippocampus and PCC, and we show that ripple rate, but not ripple duration, is correlated with the quantity of encoded order information. Notably, we find evidence for theta phase coding of serial position for early list items. We link our findings with computational and anatomical models of episodic memory processing as well as general theories of temporal binding facilitated by co-rippling events. These results point toward complementary mechanisms for order representation across hippocampal circuits and suggest the potential of anatomically specific approaches for neuromodulation that alter mnemonic neurophysiology.
Structural insights into antagonist recognition by the vasopressin V2 receptor
Geochronology of the Early Triassic based on coupled Bayesian zircon eruption age and Bayesian age–depth models
Precise and accurate geochronology is essential for reconstructing Earth’s history and coeval life evolution. The Early Triassic was a critical time interval following the greatest Phanerozoic mass extinction, recording remarkable biotic changes and a series of environmental and climatic upheavals. Its geochronology remains, however, rather poorly constrained and highly debated. Here, we present high-precision zircon U-Pb dates for four ash beds from the Induan in South China, along with carbon isotope data. We use coupled Bayesian eruption age and Bayesian age–depth models to estimate the ages of our ash beds and to reinterpret the published ages of 25 ash beds from other four sections in South China, as well as to construct new age–depth models for each section. Our new age–depth models, integrated with biostratigraphic data, yield new age estimates for the following boundaries: Permian–Triassic (~251.867 Ma), Griesbachian–Dienerian (~251.562 Ma), Induan–Olenekian (~250.626 Ma), Smithian–Spathian (~249.236 Ma), and Olenekian–Anisian (~246.979 Ma). Calibration of the Early Triassic carbon isotopic record using the new age model reveals highly variable rates of individual carbon isotope excursions. For instance, the negative excursion across the Permian–Triassic boundary exhibits a rate of approximately −11.7‰ per 100 kyr—nearly seven times faster than the early Smithian negative excursion rate of approximately −1.7‰ per 100 kyr. This refined age model also provides a robust temporal framework to evaluate the tempo of biotic evolution in the aftermath of the Permian–Triassic mass extinction.
The Salmonella pathogenicity island 1 injectisome reprograms host cell translation to evade the inflammatory response
Abstract During bacterial infection both the host cell and its invader must rapidly divert resources to synthesize specific proteins. For the host, these factors may be needed for innate immune responses, including programmed cell death, and in the bacteria newly synthesized proteins may include survival factors that counteract host defences. Salmonella is an important bacterial pathogen that invades and multiplies within host cells. It is well established that epithelial cell invasion is dependent upon the Salmonella pathogenicity island 1 (SPI-1) type III injectisome, a biological needle that penetrates host cells and injects effectors that promote bacterial internalization. However, the importance of the SPI-1 injectisome in infection of professional phagocytes such as macrophages, the predominant host cell type supporting systemic infection, is less clear. Through time-resolved parallel transcriptomic and translatomic studies of macrophage infection, we reveal SPI-1 injectisome-dependent infection of macrophages triggers rapid translation of transcription factors, including Early Growth Response 1 (EGR1). Despite EGR1’s short half-life, its swift synthesis, driven by untranslated regions of its mRNA, is sufficient to inhibit the transcription of pro-inflammatory genes; this restrains inflammation and macrophage death which would otherwise abort systemic infection. This demonstrates the importance of translational activation in host–pathogen dynamics during bacterial infection.
Characterization of endothelin-converting enzyme 1 as a key enzyme in the multienzyme Aβ degradation pathway
Altered β-amyloid (Aβ) homeostasis is a critical event triggering the shift from healthy aging to Alzheimer disease (AD) through the overproduction and impaired clearance of Aβ peptides. The Aβ-degrading enzymes (ADEs) are a collective group of proteases that normally promote clearance to counteract Aβ-induced neurodegeneration. We previously discovered that the beta-site amyloid precursor protein cleaving enzyme 1 is an atypical ADE that produces the nontoxic fragment Aβ34 by recognizing 40- or 42-residue-long Aβ peptides as substrates in vitro and in vivo. Here, we examined other known ADEs for their potential roles in degrading Aβ34, Aβ40, and Aβ42. By genetic, cellular, and pharmacological approaches, we identified and characterized endothelin-converting enzyme 1 (ECE1) in a human neuroblastoma cell line, human brain vascular pericytes, and primary rat cortical cultures as a major enzyme degrading Aβ34 but not Aβ40 or Aβ42. Notably, we found that ECE1 cleaves Aβ34, an indicator of amyloid clearance, to a unique and unusually stable Aβ20-34 fragment that has the potential to serve as a measurable biomarker. Biocomputational analyses from non-AD controls and individuals with AD pathology showed that the highest messenger ribonucleic acid (mRNA) levels of ECE1 expression were found in pericytes (i.e., cells within the brain microvasculature that are known to produce Aβ34) compared to other cell types. Given Aβ34 is an indicator for prodromal AD, we postulate that our collective findings (i.e., generation of Aβ34 and Aβ20-34 intermediates within the “amyloidolytic” degradation pathway) will generate a set of biomarkers to detect amyloid clearance activity in vivo.
Computational signatures of uncertainty are reflected in motor cortex excitatory neurochemistry
Abstract How individuals process and respond to uncertainty has important implications for cognition and mental health. Here, we use computational phenotyping to examine inter-individual differences in uncertainty processing in relation to neurometabolites and trait anxiety in humans. We introduce a categorical state-transition extension of the Hierarchical Gaussian Filter to model individuals’ evolving beliefs about transition probabilities in a four-choice probabilistic sensorimotor learning task with a reversal. Using 7-Tesla Magnetic Resonance Spectroscopy, we measure neurotransmitter levels in the primary motor cortex. Model-based results reveal dynamic belief updating in response to environmental changes. We further find region-specific relationships between baseline primary motor cortex glutamate+ glutamine levels and prediction errors and volatility beliefs. High trait anxiety is associated with faster post-reversal responses. This study establishes a direct neurochemical correlate of hierarchical belief updating, identifying motor cortex glutamate + glutamine as an important neural marker of inter-individual differences in uncertainty processing.
Learning expectations shape cognitive control allocation
Current models frame the allocation of cognitive control as a process of expected utility maximization. The benefits of a candidate control signal are weighed against its costs (e.g., opportunity costs). Recent theorizing has found that, despite promoting the counterintuitive behavior of longer deliberation, which is less rewarding in the short term, it is nevertheless normative to account for the value of learning when determining control allocation. Here, we sought to test this proposal by examining whether people were willing to allocate greater control and thereby expend greater effort (e.g., deliberate for longer) when they perceived a task to be learnable compared to when they did not. We found that participants’ proficiency and learning rate in the first block of a simple perceptual dot-motion task were able to predict their willingness to deliberate in a second block. These findings support the hypothesis that agents consider learnability when allocating cognitive control, and comply with a formal model of control allocation that considers the future discounted value of learning on reward.
Bennu and Ryugu constituents from samples IR analyses and potential source of terrestrial planets’ ingredients
Flagellar location determines the stability of bacterial surface entrapment
Surface interactions play a crucial role in shaping the motility patterns and ecological adaptations of swimming bacteria. Previous studies have primarily focused on peritrichous bacteria like Escherichia coli , whose multiple flagella form a bundle during swimming, allowing them to remain trapped at surfaces for extended periods. However, this surface entrapment phenomenon varies significantly among different bacterial species, despite all fitting into the simplified theoretical models of pusher-type bacteria, suggesting that key factors remain unidentified. Here, we demonstrate that flagellar location is a critical determinant of surface entrapment stability in pusher-type bacteria. Using fluorescently labeled Pseudomonas aeruginosa , we show that cells with a single lateral flagellum exhibit substantially longer surface residence times compared to those with a single polar flagellum, despite similar cell morphology and swimming speeds. Through direct visualization of bacterial orientation angles relative to surfaces, we reveal that this difference results from the distinct bending directions of the flagellar hook—the flexible joint connecting the rigid filament to the cell body. The hook-generated torque resists reorientation differently depending on flagellar location, facilitating surface escape for polar-flagellated bacteria while enhancing entrapment for lateral-flagellated bacteria. Our findings highlight the previously overlooked importance of flagellar placement in bacterial surface interactions, providing insights for understanding microbial ecology and designing biomimetic microswimmers.
Biomimetic supramolecular protein matrix restores structure and properties of human dental enamel
Abstract Tooth enamel is characterised by an intricate hierarchical organization of apatite nanocrystals that bestows high stiffness, hardness, and fracture toughness. However, enamel does not possess the ability to regenerate, and achieving the artificial restoration of its microstructure and mechanical properties in clinical settings has proven challenging. To tackle this issue, we engineer a tuneable and resilient supramolecular matrix based on elastin-like recombinamers (ELRs) that imitates the structure and function of the enamel-developing matrix. When applied as a coating on the surface of teeth exhibiting different levels of erosion, the matrix is stable and can trigger epitaxial growth of apatite nanocrystals, recreating the microarchitecture of the different anatomical regions of enamel and restoring the mechanical properties. The study demonstrates the translational potential of our mineralising technology for treating loss of enamel in clinical settings such as the treatment of enamel erosion and dental hypersensitivity.
Subgiants in NGC 188 reveal that rotationally induced mixing creates the main sequence Li-Dip
Abstract The Lithium-Dip is a severe lithium depletion observed in mid-F (6200-6650 K) dwarfs, which has puzzled astronomers since it was discovered in 1986. Proposed mechanisms include effects related to rotation, magnetic fields, diffusion, gravity waves, and mass loss. Which, if any, of these is realistic remains unclear. Here we show that mixing due to shear induced by stellar angular momentum loss is the unique mechanism driving the lithium depletion. Each mechanism leaves a different signature in the subsurface lithium distribution. The deepening surface convection zones of subgiants of NGC 188 evolving out of the Lithium-Dip dredge up the subsurface material and thus reveal the signature of the responsible mechanism, rotation. Subgiants can also be used more generally, thereby improving fundamental understanding of stellar evolution. Rotational mixing may be the dominant lithium-depleting mechanism in a wide range of solar-type stars, including in the Sun. Our results may further reconcile the cosmological lithium discrepancy.