Browse Articles

Correction: Impact of rehabilitation on quality of life in patients with degenerative cerebellar ataxias using structural equation modeling

Research on the main controlling factors of low permeability coal seam under the action of high-pressure water jetting

Adrenomedullin production by adult cardiac fibroblasts via NF-κB/STAT6 signaling enhances post-infarction lymphangiogenesis and cardiac repair

Organic photovoltaic prediction model based on Bayesian optimization and explainable AI

Abstract Over the decades, as industrialization progressed, energy has been a critical topic for scientists and engineers. Particularly, photovoltaic technology has drawn great attention in the renewable energy industry as an environmentally clean technology for converting sunlight into electricity. However, the complexity of energy chemistry and the need for novel materials to improve solar cell efficiency and cost-effectiveness have led to challenges in establishing rules beyond empirical observations. Machine learning models are being developed to streamline the prediction process and efficiently predict photovoltaic parameters. This paper proposes a novel hybrid-optimized multi-objective predictive model to predict the photovoltaic parameters: open-circuit voltage (Voc), current density (Jsc), fill factor (FF), and power conversion efficiency (PCE). The proposed model is based on Bayesian Optimization (BO) with the ensemble Bootstrap Aggregating (Bagging) decision tree. The proposed model integrates with the Explainable Artificial Intelligence (XAI) using the SHAP (Shapley Additive Explanations) values to introduce feature importance analysis that provides valuable insights into the impact of individual features on prediction outputs. The proposed model, named BO-Bagging, achieves high prediction accuracy, with an average high correlation coefficient of r = 0.92, a coefficient of determination of R2 = 0.82, and a Mean Square Error (MSE) of 0.00172. In terms of complexity, the BO-Bagging model has a short processing time that is indicated with an average training time of 182.7 s and an average inference time averaging 0.00062 s. Also, the number of predicted observations per second is measured by prediction speed, which results in good prediction accuracy with an average of 2188.4 and model size with an average of 10,740.4 KB. Finally, the proposed model’s primary critical operations across each phase, from training to predicting the final outputs, are represented by 108 floating-point operations per second (FLOPS). All of these results demonstrate the proposed model’s accuracy and high efficiency in intelligent chemical applications.

Correction: Young adults’ circulating FGF23 and α-klotho and their relationship with habitual dietary acid load and phosphorus intake during growth

Differences in eye movement characteristics between expert and non-expert eSports players: a systematic review and meta-analysis

A nature-based conservation framework that aligns opportunities for bird biodiversity, climate mitigation, and human equity

<i>Salmonella</i> produces sulfide to compete with <i>Escherichia coli</i> in the gut lumen

Hydrogen sulfide production is a characteristic that distinguishes Salmonella serovars from closely related species, such as Escherichia coli , but its biological significance remains obscure. Here, we show that PhsABC and AsrABC-mediated hydrogen sulfide production by Salmonella enterica serovar ( S. ) Typhimurium was linked to an increased abundance of Deltaproteobacteria and inhibition of cytochrome bd oxidase-mediated aerobic respiration of Escherichia coli in the murine large intestine. Functional phsABC and asrABC operons provided a growth benefit to S. Typhimurium in the cecum of Enterobacterales- free conventional mice only upon inoculation with commensal E. coli. In gnotobiotic mice engrafted with a defined community of 17 human Clostridia isolates, S. Typhimurium infection inhibited cytochrome bd oxidase-mediated aerobic respiration in E. coli only in the presence of Desulfovibrio piger , a sulfide-producing representative of the Deltaproteobacteria. A S. Typhimurium strain deficient for hydrogen sulfide production ( phsA asrA mutant) did not inhibit cytochrome bd oxidase-mediated aerobic respiration in E. coli , even when D. piger was present. Collectively, these data suggest that the phsABC and asrABC operons of Salmonella serovars provide a benefit during competition with closely related bacteria, such as E. coli , by inhibiting cytochrome bd oxidase-mediated aerobic respiration of the commensal.

Posttranscriptional control of the B cell receptor by HuR is essential for innate B cell maintenance and function

Innate B-1 cells constitute a self-maintained layer of defense for early detection of bacteria, clearance of apoptotic cell debris, and removal of autoantigens driving autoimmunity. B-1 cells are originated from fetal tissues, but, as opposed to B-2 cells, the molecular mechanisms behind their development and homeostatic maintenance remain largely unknown. Here, we demonstrate that posttranscriptional regulation by the RNA binding protein HuR is essential for the homeostatic self-replenishment of innate B-1a cells, the expansion of B-1 cell clones targeting self-antigens, and the production of natural autoantibodies. HuR KO B-1 cells fail to express the high levels of surface B-cell receptor (BCR), TACI, and BAFFR required for tonic signaling and cell survival. At the molecular level, HuR promotes the translation of messenger RNAs encoding the IgM heavy chain and modules, in a direct or indirect manner, the expression of TACI and BAFFR. In summary, we reveal the need for posttranscriptional regulation in BCR expression, tonic signaling, and homeostatic maintenance of functional innate B-1 cells.

Disentanglement of prosodic meaning: Toward a framework for the analysis of nonverbal information in speech

We propose a theoretical framework and a cost-effective automated method for the interpretation of prosodic messages (e.g., chunking of information, emphasis, conversation action, emotion). At the core of the proposal is a hierarchy of layered prosodic messages that co-occur within the same intonation unit (0.5 to 2 s long). Motivated by this hierarchy, a procedure for the differential detection of three such co-occurring nonverbal messages is then described. In way of implementation, we produce a variant model of the WHISPER automatic speech recognition system that flags intonation unit boundaries, intonation unit prototypes, and emphases therein. The procedure required us to alter WHISPER’s token combinations and significantly adjust its prediction process. The variant model was tested on four datasets that contain spontaneous and read speech, and performs on a par with similar human annotation, and often better, using relatively modest training data. Several insights regarding this implementation, such as model size and encoding methods, are described as well. We believe that the proposed framework, coupled with the results of its application herein, can greatly improve the analysis of speech and language, integrating contextual information and speaker intentions into linguistic descriptions for a large array of purposes with modest means.

Urban water security and the historical pools of Jerusalem

Conflicting roles of cell geometry, microtubule deflection, and orientation-dependent dynamic instability in cortical array organization

The self-organization of cortical microtubule (MT) arrays within plant cells is an emergent phenomenon with important consequences for the synthesis of the cell wall, cell shape, and subsequently the structure of plants. Mathematical modeling and experiments have elucidated the underlying processes involved. There has been recent interest in the influence of geometric cues on array orientation, be it direct (cell shape) or indirect (tension in the membrane). However, the mechanical influence of membrane curvature on these elastic filaments has largely been ignored. A previous model was proposed to describe how the anchoring process may control the deflection of individual MTs seeking to minimize bending on a cylindrical cell. We incorporate this process into a model of interacting MTs and find the cell curvature influence to be significant: the array favors orientations parallel to the direction of elongation rather than the expected transverse direction. Even without elasticity, the geometry of large cells hinders robust MT organization. These results suggest the necessity of additional processes to overcome these factors. We propose an orientation-dependent catastrophe rate, hypothetically caused by cellulose microfibrils impeding MT polymerization. We find a combination of anchoring and impedance to be sufficient to generate transverse arrays despite the geometric influences.

Subtype-specific structural features of the hearing loss–associated human P2X2 receptor

The P2X2 receptor (P2X2R) is a slowly desensitizing adenosine triphosphate (ATP)-gated ion channel that is highly expressed in the cochlea. When mutated, the P2X2R exacerbates age- and noise-related hearing loss, but selective modulators of the receptor are lacking, and the molecular basis of activation and desensitization remains poorly understood. Here, we determine high-resolution cryoelectron microscopy structures of the full-length wild-type human P2X2R in an apo closed state and two distinct ATP-bound desensitized states. In the apo closed state structure, we observe features unique to the P2X2R and locate disease mutations within or near the transmembrane domain. In addition, our ATP-bound structures show how free anionic ATP forms subtype-specific interactions with the orthosteric binding site. We identify and characterize two different ATP-bound desensitized state structures, one similar to published models for other P2XR subtypes, and a second alternate conformation not previously observed. A loop adjacent to the orthosteric binding site between these two ATP-bound desensitized state structures undergoes significant conformational changes. These movements are supported by multireplicate, microsecond-scale molecular dynamics simulation studies and suggest a path by which ATP could enter or leave the orthosteric pocket. Together, our results provide structural insights into the P2X2R, facilitating structure-based drug development for this therapeutically important target.

The <i>Arabidopsis</i> TIRome informs the design of artificial TIR (Toll/interleukin-1 receptor) domain proteins

The TIR (Toll/interleukin-1 receptor) domain is an ancient protein module that functions in immune and cell death responses across the Tree of Life. TIR domains encoded by plants and prokaryotes function as enzymes to produce diverse small molecule immune signals. Plant genomes can encode hundreds of TIR-domain containing proteins—many of which confer important agricultural disease resistance as TIR-NLR (nucleotide-binding, leucine-rich repeat) immune receptors. Despite their importance, how natural variation influences TIR enzymatic output and immunity-associated cell death is largely unexplored. We assayed a complete collection of the TIR domains of Arabidopsis thaliana Col-0 (the “AtTIRome”) to explore variation in TIR metabolite production and cell death signaling. Roughly half of the AtTIRome triggered cell death in transient assays. Artificial TIR proteins designed based on consensus sequences of the AtTIRome’s cell death phenotypic classes revealed polymorphisms controlling variation in TIR cell death elicitation and metabolite production. Structure–function analyses of artificial TIRs revealed that natural variation in the “BB-loop”, a flexible region overlying the catalytic pocket, determines differences in function across Arabidopsis TIR-containing proteins. We further demonstrate that artificial TIRs are functional on an NLR chassis and that BB-loop variation can tune the activity of a natural TIR-NLR protein. These findings shed light on the diversity of TIR outputs and reveal methods to design and engineer TIR-based immune receptors.

In vivo Pirt-Marina voltage sensor imaging detects primary sensory neuron–specific voltage dynamics and neuronal plasticity changes

In vivo voltage imaging is a powerful tool for monitoring action potentials and dynamic electrical events in heterogeneous sensory neurons enabling the deciphering of rapid somatosensory information processing. Virus-driven expression of genetically encoded voltage indicator (GEVI) suffers from inconsistent expression levels and offers a limited time window for optimal voltage imaging. Here, we generated and characterized a knock-in mouse line with Pirt-driven expression of Marina, a positively tuned GEVI, in primary sensory neurons. Pirt-Marina mice enable optical reporting of touch, itch, and nociceptive sensations in vivo and distinct action potential patterns in the trigeminal and dorsal root ganglion neurons. Notably, Pirt-Marina mice display robust fluorescence signals in response to mechanical, thermal, or chemical stimuli, allowing visualization of transformations in sensory coding following inflammation and injury. This Pirt-Marina mouse line provides optical access to dynamic neuronal activity and plasticity in the peripheral nervous system (PNS) with high temporal accuracy, fidelity, and reliability.

The coherence of US cities

Diversified economies are critical for cities to sustain their growth and development, but they are also costly because diversification often requires expanding a city’s capability base. We analyze how cities manage this trade-off by measuring the coherence of the economic activities they support, defined as the technological distance between randomly sampled productive units in a city. We use this framework to study how the US urban system developed over almost two centuries, from 1850 to today. To do so, we rely on historical census data, covering over 600M individual records to describe the economic activities of cities between 1850 and 1940, as well as 8 million patent records and detailed occupational and industrial profiles of cities for more recent decades. Despite massive shifts in the economic geography of the United States over this 170-y period, average coherence in its urban system remains unchanged. Moreover, across different time periods, datasets, and relatedness measures, coherence falls with city size at the exact same rate, pointing to constraints to diversification that are governed by a city’s size in universal ways.

3D pattern formation of a protein–membrane suspension

Many essential cellular processes, including cell division and the establishment of cell polarity during embryogenesis, are regulated by pattern-forming proteins. These proteins often need to bind to a substrate, such as the cell membrane, onto which they interact and form two-dimensional (2D) patterns. It is unclear how the membrane’s continuity and dimensionality impact pattern formation. Here, we address this gap using the MinDE system, a prototypical example of pattern-forming membrane proteins. We show that when the lipid substrate is fragmented into submicrometer-sized diffusive liposomes, adenosine triphosphate-driven protein–protein interactions generate three-dimensional (3D) spatially extended patterns, despite the complete loss of membrane continuity. Remarkably, these 3D patterns emerge at scales four orders of magnitude larger than the individual liposomes. By systematically varying protein concentration, liposome size, and density, we observed and characterized a variety of 3D dynamical patterns not seen on continuous 2D membranes, including traveling waves, dynamical spirals, and a coexistence phase. Simulations and linear stability analysis of a coarse-grained model revealed that the physical properties of the dispersed membrane effectively rescale both the protein–membrane binding rates and diffusion, two key parameters governing pattern formation and wavelength selection. These findings highlight the robustness of Min’s pattern-forming ability, suggesting that protein–membrane suspensions could serve as an adaptable template for studying out-of-equilibrium self-organization in 3D, beyond in vivo contexts.

Structural basis for Rad54- and Hed1-mediated regulation of Rad51 during the transition from mitotic to meiotic recombination

Rad51 catalyzes the DNA pairing reactions that take place during homologous recombination (HR), and HR must be tightly regulated to ensure physiologically appropriate outcomes. Rad54 is an ATP-dependent DNA motor protein that stimulates Rad51 activity during mitosis. In meiosis Rad51 is downregulated by the protein Hed1, which blocks Rad54 binding to Rad51, and allows Dmc1 to function as the active recombinase. We currently have a poor understanding of the regulatory interplay between Rad54, Hed1, Rad51, and Dmc1. Here, we identify a conserved Rad51 interaction motif within Rad54, and we solve a CryoEM structure of this motif bound to Rad51. We also identify a distinct Rad51 interaction motif within Hed1 and solve its structure bound to Rad51. These structures explain how Rad54 engages Rad51 to promote recombination between sister chromatids during mitosis and how Rad51 is downregulated by Hed1 upon entry into meiosis such that its meiosis-specific homolog Dmc1 can promote recombination between homologous chromosomes.

From simplicity to complexity: A path to innovation in science and art

Simple reductionist systems can serve as powerful catalysts for unlocking complex innovations in science and art. The evolution from simplicity to complexity is illustrated by the career journeys of the scientist Earl W. Sutherland, who discovered cyclic adenosine 3′-5′-monophosphate (cyclic AMP) and opened the field of cell signaling, and the artist Frank Stella, who pioneered geometrical patterns and shapes in both painting and sculpture. Their work profoundly influenced biomedical science and modern art. How one navigates the journey from simplicity to complexity is a fundamental challenge to scientists and artists who aim to identify fresh ideas that lead to insights with lasting impact.

Toughness enhancement by massive dislocation absorption at the crack front

Low-cost yet high-performance structural materials have been invariantly sought for modern engineering applications. However, due to the localized stress concentration induced by a high Peierls-Nabarro stress and limited dislocation mobility, increasing material strength usually comes at the expense of ductility and toughness, resulting in a trade-off between strength–ductility/strength–toughness. Here, we report an anomalous phenomenon of dislocation absorption at the crack front, which is unlike typically observed dislocation emission at the crack tip, in a heterogeneous “plain” steel consisting of tempered lath martensite embedded with stable carbon-enriched retained austenite. The continuous absorption of dislocations emitted from the tempered martensite into the tough austenite significantly alleviates the localized stress concentration, and as such retards crack propagation in the tempered martensite matrix. This allows the plain high-carbon low-alloyed steel subjected to simple quenching–partitioning–tempering processes to achieve remarkable properties comprising a multiplication of strength and elongation over 50 GPa·% with an exceptionally high fracture toughness over 130 MPa·m 1/2 . The toughening strategy based on this mechanism provides a promising route for developing cost-effective plain steels with ultrahigh strength, ductility, and toughness that is a persistent pursuit in the steel industry.