Browse Articles

Author Correction: Acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand management of acute disease

The exocyst subunits OsEXO70L2 and OsSEC3A regulate root development through modulating OsPIN1a/b-mediated auxin distribution in rice

Exocyst complex–mediated vesicle trafficking is essential for plant growth and development, yet its roles in crop root development remain poorly understood. Previously, we showed that mutation of the exocyst subunit encoded gene OsEXO70L2 leads to reduced root length in the short-root 1 ( sr1 ) mutant, but the underlying mechanism was unclear. Here, we demonstrate that OsEXO70L2 interacts with another exocyst subunit, OsSEC3A. The OsSEC3A knockout mutant sec3a-1 exhibits shortened roots, a reduced root apical meristem, and vesicle trafficking defects, with phenotypes weaker than those of sr1 . The sr1 sec3a-1 double mutant resembles sr1 , indicating that OsEXO70L2 and OsSEC3A act in the same pathway. Both sr1 and sec3a-1 show reduced sensitivity to exogenous indole-3-acetic acid and the auxin transport inhibitor 1-naphthylphthalamic acid, accompanied by disrupted auxin distribution in the root tips. OsEXO70L2 and OsSEC3A regulate the plasma membrane abundance and localization of the auxin efflux carriers OsPIN1a/b. Consistently, the ospin1a ospin1b double mutant displays more severe short-root phenotypes and auxin distribution defects, confirming OsPIN1a/b as downstream targets. This study elucidates that OsEXO70L2 and OsSEC3A control root length by regulating vesicle trafficking-dependent OsPIN1a/b localization and auxin distribution in the root tips.

Effect of porosity on catalytic performance of HKUST-1 in Knoevenagel condensation

Abstract Hierarchically porous HKUST-1 materials ( A and B ) were synthesized via a cooperative template-directed strategy enabling controlled introduction of mesoporosity while preserving the characteristic original framework ( 1 ). Structural, spectroscopic, and textural characterization confirmed retention of the intrinsic HKUST-1 structure together with high specific surface areas of 1788, 1554, and 1690 m 2 g − 1 for activated 1’ , A’ , and B’ , respectively. The hierarchical materials exhibited pore size distributions extending from intrinsic micropores to mesopores. The catalytic performance was evaluated in the Knoevenagel condensation of benzaldehyde derivatives with malononitrile. Under optimized conditions (toluene, 80°C, 50 mg catalyst, 60 min), conversions of 93% and 98% were achieved for A’ and B’ , respectively. Arrhenius analysis yielded a lower effective activation energy for B’ (43.9 ± 5.2 kJ mol − 1 ) compared to A’ (53.6 ± 3.1 kJ mol − 1 ), indicating more favorable reaction kinetics. High conversions (~ 96–98%) were obtained for electron-withdrawing substituents, whereas bulky alkyl-substituted substrates showed lower conversions (~ 6–16% for B’ , ~ 5–11% for A’ ), confirming diffusion limitations. Recyclability tests showed only moderate activity loss after five cycles (17% for A’ , 15% for B’ ). Post-catalysis analysis confirmed preserved framework structure and crystallinity, while infrared and thermogravimetric analyses indicate residual species in the pores.

How should I respond to race-based exclusion in my lab?

Migratory jackpot individuals fuel rapid ecotype shifts in Galaxias fishes

Structure of Human adenovirus 7 virus-like particles, a platform for developing nanotherapeutics and studying capsid assembly

Adenoviridae family members routinely infect humans, exhibit significant genetic diversity, and are associated with a variety of illnesses. Types 4 and 7 frequently circulate in the United States and are major causes of respiratory disease. Infections can result in hospitalization and, in severe cases, death. Although a live wild-type-virus vaccine targeting these two types exists, its use is restricted to military personnel due to concerns about viral-shedding and potential for genetic recombination. To overcome these limitations, we recently developed a virus-like particle (VLP) platform as an alternative vaccination strategy. These VLPs are stable, lack genomic material, and elicit a potent humoral immune response in mice, effectively neutralizing adenoviral infection. Here, we describe the cryo-EM structure of adenovirus 7 (AdV-7) VLPs. Structural insights are essential to ensure that neutralizing antigens displayed on the VLPs accurately mimic those of the virion, guide the design of particles with improved stability and efficacy, and enable engineering of VLPs with antigenic properties targeting multiple adenovirus types. The structure shows that hexon, penton, pIIIa, pVI, pVIII, and IX assemble comparable to AdV-5, hexon and penton neutralizing epitopes are appropriately displayed for antibody recognition, penton insertion into the hexon shell promotes cement protein pIIIa to increase its interaction with the peripentonal hexons, and presence of the core-genome is associated with increased interaction between cement protein pVIII and hexon. Finally, limited proteolysis and mass spectrometry demonstrate that VLP incorporated hexons digest more readily than virion incorporated hexons, indicating the greater dynamic nature of the VLP.

Privacy-aware diabetic retinopathy grading and visual lesion-focused interpretability through mixture-of-experts federated deep learning with explainable AI

Structural mechanisms of drebrin-mediated F-actin network modulation

Abstract Drebrin modulates F-actin networks and links them to other intracellular components, regulating crucial processes including neuritogenesis, synaptic plasticity, virus internalisation and cancer invasion. Using single-particle cryo-EM we characterise drebrin’s interaction with F-actin through two separate conserved actin binding domains (ABD1 and ABD2), revealing structural bases for its F-actin-modulating properties. We describe a multimodal interaction where drebrin’s ABD1 can adopt two conformations and a long flexible loop connecting to ABD2 allows the two ABDs to occupy multiple relative positions along F-actin. The flexible loop connecting the two ABDs also confers some propensity to loosely bundle F-actin. Drebrin’s ABDs bind across multiple actin protomers and their subdomains and modify the longitudinal inter-protomer interface, explaining its F-actin stabilising properties. Furthermore, we show drebrin’s binding site on F-actin is shared with other critical actin-binding and regulatory proteins, explaining their competitive displacement.

Estimating the amount of computation done by a brain using population neural activity

Many dynamical systems, ranging from genetic circuits to the human brain to human social systems, are often characterized as computational. Although extensive research has explored their dynamics, the computations underlying often remain elusive. Even the fundamental task of quantifying the amount of computation underlying a dynamical system remains underinvestigated. In this study we introduce a task-independent framework to estimate the amount of computation implemented by an observed system based on empirical time-series of its dynamics. This framework works by forming a statistical reconstruction of that dynamics, and defining the amount of computation in terms of both the complexity and fidelity. We validate our framework by showing it appropriately distinguishes the relative amount of computation across different regimes of Lorenz dynamics and various computation classes of cellular automata. We then apply this framework to whole-brain neural recordings of Caenorhabditis elegans and large scale population recordings of the mouse cortex. We find that high and low amounts of computation underlie the neural dynamics of freely moving and immobile worms. Our analysis further sheds light on the amount of computation C. elegans performs in various locomotion states. When applied to large-scale electrophysiological recordings from the mouse cortex during a visual decision-making task, our framework recovers the ground-truth difficulty of the task, assigning higher amounts of computation to more difficult trials where sensory inputs are ambiguous. In sum, our study explores a powerful framework for quantifying the amount of computation performed by a system based on time-series data of its dynamics, and highlights neural computation in both simple and complex organisms.

Experiments with optimal model trees

Abstract Model trees provide an appealing way to perform interpretable machine learning for both classification and regression problems. In contrast to “classic” decision trees with constant values in their leaves, model trees can use linear combinations of predictor variables in their leaf nodes to form predictions, which can help achieve higher accuracy and smaller trees. Typical algorithms for learning model trees from training data work in a greedy fashion, growing the tree in a top-down manner by recursively splitting the data into smaller and smaller subsets. This yields a fast algorithm, but the selected splits are only locally optimal, potentially rendering the tree overly complex and less accurate than a tree whose structure is globally optimal for the training data. In this paper, we empirically investigate the effect of constructing globally optimal model trees for classification and regression. The trees we consider feature linear support vector machines at the leaf nodes and are learned using mixed-integer linear programming (MILP) formulations. We use benchmark datasets to compare them to model trees obtained using greedy and dynamic programming-based algorithms, evaluating both tree size and predictive accuracy. We also compare to classic optimal and greedily grown decision trees, random forests, and support vector machines. Our results show that MILP-based optimal model trees can achieve competitive accuracy with very small trees. We also investigate the effect on the accuracy of replacing axis-parallel splits with multivariate ones, foregoing interpretability while potentially obtaining greater accuracy.

Retraction Note: Sub-second periodicity in a fast radio burst

The metabolic vulnerability index predicts outcomes in patients with metabolic dysfunction associated steatotic liver disease

Computational design and cellular synthesis of two protein topological isomers: Solomon link vs. three-twist knot

Chemical topology has emerged as a unique dimension in protein engineering, motivating the pursuit of topologically nontrivial protein architectures for functional advantages, such as enhanced stability and rich dynamics. However, the structural diversity of artificial mechanically interlocked proteins remains limited. Here, we report the computational design and cellular synthesis of a pair of topological isomers via symmetric assembly of orthogonal entangling motifs. By fusing two C 2 symmetric entangling motifs, i.e., p53dim and HP0242, in specific arrangements, we programmed the formation of multiple crossings, which upon cyclization yielded a protein Solomon link and a protein three-twist knot. The fusion patterns and linker lengths were systematically optimized to direct the formation of the intended topologies. Their successful cellular synthesis was validated through biophysical and structural analyses, including sodium dodecyl sulfate-polyacrylamide gel electrophoresis, size exclusion chromatography, and liquid chromatography-mass spectrometry. Notably, we report the crystal structure of an artificial protein three-twist knot. Both the Solomon link and the three-twist knot displayed increased structural compactness and stability relative to their controls with lower topological complexity (e.g., Hopf link, trefoil knot, and linear forms), as evidenced by their superior thermal stability and resistance to chemical denaturation. This modular design strategy provides a rational and extensible route to diverse mechanically interlocked proteins and could be generalized to access even more complex architectures, such as protein chainmail-like nanocages and woven protein frameworks.

Biomechanical effects of endoscopic ULBD in a reduced‑stiffness lumbar spine model: focus on endplate stress and hypothesis‑generating risk indicators (a finite element analysis)

Daily briefing: NASA to launch satellite-rescue mission

Spatial analyses implicate high stromal tumour-infiltrating CD8+ lymphocytes as a negative predictive marker for chemotherapy in estrogen receptor-positive breast cancer

Abstract Female patients with ER + HER2 - breast cancer have a favourable prognosis for 5-10 years. Later relapses are, however, common, yet predictions of late recurrence risk are suboptimal, particularly for patients with intermediate risk determined by the Oncotype Dx Recurrence Score (RS, 16-25). Here, we analyse tissue samples from patients with ER + HER2 - breast cancer using spatial proteomics (multiplex immunofluorescence with 5 markers, n  = 440) and spatial transcriptomics ( n  = 359), and find decoupled immune states between stroma and epithelia. Moreover, inflamed stroma express genes linked to tissue remodelling, immune exhaustion, and inhibitory/checkpoint receptors ( CTLA4, TIGIT, CD96 ); inflamed epithelia similarly express genes associated with checkpoints ( CTLA4 ) and exhaustion ( CXCL13 ), but also genes attributed to antigen presentation. In our randomised, Intermediate RS cohort treated with chemotherapy we observe an association between higher stromal tumour-infiltrating CD8 + lymphocyte (sTIL CD8 + ) density and poor outcome (ΔLR-χ 2 : 6.79, p  = 0.009), which we validate using data from whole-resection specimens (ΔLR-χ 2 : 8.90, p  = 0.003). Our data thus provide insights into the immune states in ER + HER2 - breast cancer, and propose sTIL CD8 + density as candidate biomarker for treatment decisions.

An atlas of microtubule lattice parameters regulated through ligand binding to the microtubule-stabilizing sites

Microtubules are dynamic cytoskeletal polymers whose lattice architecture regulates force generation, nucleotide hydrolysis, and recognition by motor proteins and microtubule-associated proteins (MAPs). Microtubule-stabilizing agents (MSAs), including taxanes and laulimalide/peloruside-site ligands, suppress depolymerization by binding to defined lattice sites, yet stabilization is not structurally neutral. How ligand chemistry reshapes lattice organization and function remains unresolved. Here, we address three mechanistic questions. First, do distinct ligand classes induce defined lattice states? Using X-ray fiber diffraction, we show that MSAs selectively stabilize two preferred longitudinal conformations, a compact state (~4.06 nm monomer rise) and an expanded state (~4.17 nm), while modulating lateral organization reflected in shifts in mean MT radius. These axial spacings cluster around discrete values across chemotypes, indicating stabilization of preexisting conformational minima rather than continuous distortion. Second, are these states interconvertible upon changes in ligand occupancy? Time-resolved diffraction reveals that longitudinal transitions occur within seconds of ligand addition even at substoichiometric occupancy, whereas, lateral equilibration proceeds slower, consistent with redistribution within heterogeneous protofilament organizations. Third, do such structural states alter nucleotide hydrolysis and motor/MAP behavior? Expanded lattices are associated with reduced apparent GTP hydrolysis rates under steady-state assembly conditions and altered kinesin motility, whereas compact lattices preferentially promote tau binding and distinct motor interaction profiles. Together, these findings establish longitudinal lattice conformation as a regulatory parameter and position MSAs as chemical tools that bias a dynamic structural landscape with predictable catalytic and transport consequences.

DFT study of irradiation damage-defect correlations with mechanical properties in uranium nitride

Author Correction: Complete defluorination of PFASs via photocatalytic reduction in water

Wounding-induced redirection of sugar transport fuels tissue repair

Wounding triggers growth programs to restore damaged tissues, creating a local surge in metabolic demand. How resource recruitment is modified to meet this demand is unclear. Here, we show that regeneration of dissected root tips is dependent on photosynthetic sucrose in a dose-dependent manner, although sucrose itself is excluded from the injury site. High-resolution tracking of Glifon, a live glucose reporter, reveals that glucose accumulates near the cut. Glucose accumulation required the apoplasmic sugar transport components CELL WALL INVERTASE ( CWINV ) and SUGAR TRANSPORTER PROTEINS ( STP ), which were rapidly induced by wounding. Loss of CWINV or STP function compromised root repair, particularly under limited sucrose availability, whereas increased STP13 gene dosage enhanced repair rates. Similar sugar transport genes were activated in other wounding contexts and promoted wound-induced adventitious root initiation. We propose that injury elicits a proactive local shift in sugar flow to promote resource recruitment and sustain tissue repair.