Browse Articles

From retinotopic to ordinal coding: Dissecting the cortical stages of visual word recognition

Fluent reading requires the brain to precisely encode the positions of letters within words, distinguishing for instance FORM and FROM across variations in size, position, and font. Early visual areas, however, are known to encode retinotopic positions, and how these representations get transformed into a position-invariant neural code remains unclear. Building upon a computational model of reading, we used 7T functional MRI and magnetoencephalography (MEG) to reveal a cortical hierarchy in which early visual areas (V1–V4) predominantly encode retinotopic information, whereas higher-level regions, including the visual word form area, transition to an ordinal letter-position code. MEG analyses confirm that retinotopic encoding emerges early (60 to 200 ms), followed by a shift toward ordinal representations in later time windows (220 to 450 ms). Despite this transition, word position remained a dominant factor across all time points, suggesting a concurrent coding of both retinotopic and abstract positional information. These findings uncover the spatiotemporal dynamics by which the human brain transforms visual input into structured prelexical representations, shedding light on the cortical stages of reading and their developmental and clinical implications.

Modulatory effect of quercetin on premature ovarian insufficiency induced by cyclophosphamide via the PARP1 and GSK3β

Delayed fragmentation of methane induced by femtosecond laser pulses

We experimentally investigated the delayed fragmentation process of methane (CH4) molecules in a strong linearly polarized femtosecond laser field by cold target recoil-ion momentum spectroscopy. The prompt fragmentation and delayed fragmentation processes of the CH42+→H++CH3+ channel were unambiguously identified in the coincident photoion–photoion time-of-flight spectrum. By solving Newton’s equations, the survival times of long-lived methane dications have been obtained, with a corresponding statistical lifetime of 304 ± 9 ns. The branching ratios have also been evaluated, with the relative yield of delayed fragmentation being much lower than that of prompt fragmentation. Momentum distributions and kinetic energy release spectra have been obtained for both prompt and delayed processes. The possible formation mechanism of delayed fragmentation was also discussed.

Proteolytically activated antibacterial toxins inhibit the growth of diverse gram-positive bacteria

Many species of bacteria produce small-molecule antibiotics that enter and kill a wide range of competitor microbes. However, diffusible antibacterial proteins (ABPs) that share this broad-spectrum activity are not known to exist. Here, we report a family of proteins widespread in gram-positive bacteria that display potent antibacterial activity against a diverse range of target organisms. Upon entering susceptible cells, these ABPs enzymatically degrade essential cellular components including DNA, transfer ribonucleic acid (tRNA), and ribosomal ribonucleic acid (rRNA). Unlike previously characterized bactericidal proteins, which require a specific cell surface receptor and therefore display a narrow spectrum of activity, we find that ABPs act in a receptor-independent manner and consequently kill bacteria spanning multiple phyla. Target cell entry by ABPs requires proteolytic activation by a cognate, coexported serine protease, and the liberated toxin component of the cleaved ABP is driven across the target cell membrane by the proton motive force. By examining representative ABPs from diverse pathogenic, commensal, and environmental bacteria, we show that broad-spectrum antibacterial activity is a conserved property of this protein family. Collectively, our work demonstrates that secreted proteins can act as broad-spectrum antibiotics, suggesting that ABPs represent one of potentially many such families produced in nature.

Changes in proteome and protein carbonylation in potato (Solanum tuberosum L.) under single and combined abiotic stresses

Abstract Environmental stresses are one of the main factors limiting plant production. In the era of a changing climate, more crop areas are exposed to drought and heat. The potato is one of the key plants for ensuring food security in the world, but at the same time, it is susceptible to environmental stresses. Our research aimed to investigate the response of potato to drought, increased temperature, and a combination of these stresses at the proteomic level. We also examined physiological parameters such as relative water content, assimilation surface and yield, as well as biochemical parameters such as the content of carbonylated proteins or 20 S proteasome activity. Our results demonstrated that abiotic stressors significantly affected photosynthesis and carbohydrate metabolism in potato plants. All tested treatments activated a series of proteins involved in the stress response, many of which were associated with chloroplasts. The responses to drought, high temperature, and their combination were distinct. Among these factors, high temperature exhibited the least detrimental effect on potato metabolism, which correlated with the absence of significant yield loss. Furthermore, the response to the combined stress closely mirrored the response to drought alone, suggesting that drought was the primary stressor influencing metabolic changes.

Machine learning on frontier orbital energy of atomically precise gold nanoclusters

The highly promising application of atomically precise gold nanoclusters (Au NCs, protected by organic ligands such as thiolate, phosphate, etc.) in electrochemical and photochemical catalysis has highlighted the importance of accurately predicting their electronic states, which has been challenging because of the high experimental and computational cost. In this study, a machine learning model based on interpretable automated feature engineering was developed. Starting with the 99 data points of Au NCs, 227 candidate parameters were first screened by a bi-directional stepwise regression, associated with the Kolmogorov–Arnold network model, to improve the prediction performance. With this suite of codes and using only 79 data points as the training set and 4 key descriptors, the mean average error (MAE) of the HOMO, LUMO, and HOMO–LUMO gap of the testing set (20 data points) reaches 0.17, 0.27, and 0.16 eV, respectively. The model could also be used to generalize the oxidation potential (OP) of the target clusters, with an MAE of 0.20 V. In particular, four dominant physicochemical parameters for HOMO/LUMO/HOMO–LUMO gap/OP were identified. The number of cluster charges (NC) and average Au–Au coordination numbers (CNAu–Au) are consistently present in the four filtered features, indicating that these parameters are critical for determining the electronic structure of Au NCs. Overall, the present study demonstrates that a small set of key structural descriptors could enable a cost-efficient strategy to accurately predict the electronic structure of Au NCs.

Physical activity is directly associated with total energy expenditure without evidence of constraint or compensation

The prevailing linear model of physical activity (PA) and total energy expenditure (TEE) has been challenged by models that predict an upper limit of TEE linked to a compensatory reduction elsewhere in the energy budget in response to increased PA. We determined the equation of best fit between PA and TEE and explored relationships between PA and behavioral and physiological compensation. Using linear and nonlinear modeling, we observed a positive linear relationship between PA and TEE either without or after adjustment for fat-free mass (R 2 = 0.3492, TEE = 0.00685*PA + 7.124: R 2 =0.3667, TEE_ADJ(FFM) = 0.00511*PA + 8.598). Higher PA was associated with lower sedentary time (R 2 = 0.7207, %SPA= −0.0211*X + 91.261). There was no association between PA, TEE, or resting metabolic rate and adjusted biomarkers of immune, reproductive, or thyroid function after Bonferroni correction. The findings of this observational study do not support the constrained/compensated model but affirm the conventional additive relationship between PA and TEE across a broad range of PA levels.

Patient-specific hiPSC-Podocytes as an in vitro model of genetic FSGS

Abstract Mutations in podocyte-specific genes are associated with genetic focal segmental glomerulosclerosis (FSGS), yet the potential for targeted treatments remains uncertain. Therefore, patient-specific models are essential for understanding cellular phenotypes, identifying personalized therapies, and avoiding ineffective treatments. This study utilized patient-specific human induced pluripotent stem cell (hiPSC)-Podocytes to investigate cellular phenotypic and functional alterations associated with genetic FSGS in vitro. HiPSC-Podocytes were generated from a patient with a mutation in the inverted formin 2 ( INF2 ) gene, who showed a partial clinical response to steroid treatment. Compared to healthy donor-derived hiPSC-Podocytes, the patient-specific hiPSC-Podocytes exhibited decreased protrusion length, reduced levels of actin-associated markers, and alterations in INF2 protein levels. Additionally, actin filaments were disrupted, characterized by increased actin depolymerization. Next to the actin-modulating agent Bis-T-23, the steroid Solu-Decortin H (SDH) improved the actin cytoskeleton in the patient-specific cells, which aligned with the patient’s partial response to steroids. This underscores the importance of personalized treatment strategies based on specific cellular responses in genetic FSGS.

Cr3+-doped TiNb2O7 nanorods for ultra-fast charging lithium-ion batteries: Enhanced through structural and electronic engineering

TiNb2O7 is regarded as an ideal anode candidate for next-generation lithium-ion batteries because of the high theoretical specific capacity and operating potential. However, poor multiplicity performance and low intrinsic conductivity hinder their application. We have designed one-dimensional Cr3+-doped titanium niobate nanorods (TNO-Cr) by combining the advantages of heteroatom doping and nanosizing in order to improve the electronic conductivity. The optimal Cr3+-doped TNO anode material (TNO-6.0%Cr) maintains a discharge capacity of 125.1 mAh g−1 after 2000 cycles at 5C and 104.5 mAh g−1 even after 1000 cycles at 10C. In addition, NCM811//TNO-6.0%Cr maintains a discharge capacity of 119 mAh g−1 at 100 cycles at full cell 1C. The great electrochemical performance is attributed to its one-dimensional nanostructure that shortens the lithium-ion diffusion distance and the successful substitution of Cr for Ti sites that narrows the bandgap width and improves the ionic conductivity. The materials can be used as promising anode materials for fast-charging lithium-ion batteries.

Neuronal plasticity at puberty in mouse hypothalamic <i>Kiss1</i> neurons that control fertility

Puberty is a critical transition period to achieve reproductive capacity in all mammalian species. At puberty, hypothalamic Kiss1 neurons release kisspeptin, stimulating gonadotropin-releasing hormone (GnRH) release and activating the hypothalamic–pituitary–gonadal (HPG) axis. Here, we show that Kiss1 neurons in the arcuate nucleus of the hypothalamus ( Kiss1 ARC ) of female mice undergo profound intrinsic plasticity at puberty. Kiss1 ARC neurons in brain slices from 3-wk-old mice, when depolarized, typically fire a short high-frequency burst of action potentials before falling silent. This would make them unsuitable for the sustained activity that is required to activate pulsatile GnRH secretion and the HPG axis. At 4 wk of age and after puberty, Kiss1 ARC neurons can fire a sustained train of action potentials. There is a concomitant hyperpolarization in action potential threshold and postspike minimum voltage and larger medium after-hyperpolarizations (mAHP) and hyperpolarization-induced voltage sags. Transcriptomic profiling showed significant changes in ion channel expression after puberty. Using quantitative PCR, we confirmed changes in genes encoding voltage-gated sodium, calcium, potassium, and cation channels. Blocking hyperpolarization-induced cation channels caused Kiss1 ARC neurons from postpuberty mice to fire less sustained trains of action potentials. Recordings from Kiss1 ARC neurons in mice after ovariectomy and 17β-estradiol replacement revealed a critical window of estrogen-dependent plasticity between 3 and 6 wk, which is essential for the maturation of Kiss1 ARC neurons and the development of their adult electrophysiological activity. This represents an example of sex steroid–dependent plasticity in the mammalian brain at puberty.

Meta transfer learning for brain tumor segmentation using nnUNet in meningioma and metastasis cases

Photodynamics of Renner–Teller rovibronic coupling within a mixed parallel–perpendicular polarization manifold

The Renner–Teller (RT) effect, arising from the breakdown of the Born–Oppenheimer approximation in linear molecules, couples degenerate electronic states with rovibrational motion, profoundly influencing molecular photodynamics. I present a rigorous time-dependent wavepacket formulation to describe RT rovibronic coupling between the 21A′ and 21A″ excited states of N2O within a mixed parallel–perpendicular polarization manifold. Using Jacobi coordinates, parity-adapted rovibronic basis functions, and Clebsch–Gordan expansions, I derive explicit expressions for initial wavepackets and propagate them on high-level multireference configuration interaction potential energy surfaces. This formulation captures state-specific decay and nuclear flux transfer between the coupled electronic surfaces, incorporating parity selection rules, angular momentum couplings, and symmetry-dependent dipole transitions. Application to N2O photodissociation reveals that RT coupling mediates Feshbach-type resonances, generates diffuse absorption features, and drives coupled bending–stretching dynamics that enhance low-energy spectral intensities. The methodology provides a broadly applicable framework for modeling RT-mediated rovibronic interactions in small polyatomic systems.

Adipose cullin 3 mediates the antiobesity effect of pan neddylation inhibitors

Cullin Ring E3 Ligases (CRLs) belong to the largest family of multisubunit ubiquitin E3 ligases. A cullin serves as the scaffold protein that recruits E3 ligases and substrate receptors in a CRL complex, whose activity requires cullin neddylation, a posttranslational modification that can be pharmacologically targeted by neddylation inhibitors. Elevated neddylation activity has been observed in the liver and adipose tissue of obese mice, implicating a pathogenic link between altered CRL activity and the development of metabolic disorders. Emerging evidence has also shown that neddylation inhibitors possess antiobesity and hypoglycemic property. However, the roles of cullin proteins in regulating adipocyte biology are still incompletely defined. Here, we report that pan neddylation inhibitor TAS4464 treatment reversed obesity and adipose inflammation, resulting in improved hepatic steatosis and insulin sensitivity in obese mice. Among all mammalian cullin proteins that were targeted by TAS4464, we identified that cullin 3 (Cul3) was required for adipogenesis and adipocyte hypertrophy. A complete absence of Cul3 in adipocytes caused severely inhibited adipose expansion associated with ectopic fat accumulation in the liver and brown adipose tissue and insulin resistance, while adipocyte-specific Cul3 haploinsufficiency attenuated obesity and improved overall metabolic homeostasis, which recapitulated the metabolic benefits of TAS4464. Mechanistically, we found that Cul3 inhibition caused adipose nuclear factor erythroid 2-related factor 2 (NRF2) stabilization, which contributed to impaired adipogenesis by inhibiting lipogenesis. Together, these findings demonstrate that Cul3 is required during adipogenesis and acts as a downstream mediator of the antiobesity effect of pan neddylation inhibitors.

Exploration of the roles of HLAs when predicting infection status by T cell receptors

Nudged-elastic band calculations of polymorph transitions and solid-state reactions in molecular crystals

The modeling of solid-state transformations, such as polymorphic transitions and chemical reactions in molecular crystals, is vital for many applications, including drug design and the development of new synthesis methods. However, a description via nudged-elastic band (NEB) calculations faces several crucial challenges. First, the automatic initial pathway generation based on a linear interpolation often fails for periodic systems, leading to unrealistic geometries and atomic collisions. Second, the necessary system sizes are typically beyond the scope of density functional theory (DFT) calculations in terms of computational cost, but the associated accuracy is vitally needed. To address these issues, we introduce a hybrid interpolation method that combines linear interpolation for cell parameters with spherical linear interpolation for molecular structures or intramolecular fragments, ensuring smooth and realistic transitions. Moreover, we train and benchmark machine-learned force fields (MLFFs) based on the SO3krates equivariant neural network architecture to accelerate NEB calculations while retaining near-DFT accuracy. We apply our approach to two polymorph transitions and a solid-state Diels–Alder reaction and show that our new interpolation method reliably produces viable initial pathways. The MLFFs are trained on PBE+MBD reference data and reproduce DFT lattice energies with a mean absolute error of 0.4 kJ mol−1 along the minimum-energy paths. These results highlight the potential of combining advanced interpolation techniques with MLFFs to enable automated, accurate, and efficient exploration of solid-state transformations in molecular crystals.

Single-cell sequencing uncovers sensory neuron–mediated CGRP signaling as a driver of sarcoma progression

Bone pain is a presenting feature of bone cancers such as osteosarcoma (OS), relayed by skeletal-innervating peripheral afferent neurons. Potential functions of tumor-associated sensory neurons in bone cancers beyond pain sensation are unknown. To uncover neural regulatory functions, a chemical-genetic approach in mice with a knock-in allele for TrkA was used to functionally perturb sensory nerve innervation during OS growth and disease progression. TrkA inhibition in transgenic mice led to significant reductions in sarcoma-associated sensory innervation and vascularization, skewed tumor associated macrophage polarization, reduced tumor growth and metastasis, and prolonged overall survival. Single-cell transcriptomics revealed that sarcoma denervation was associated with phenotypic alterations in both OS tumor cells and cells within the tumor microenvironment, and with reduced calcitonin gene-related peptide (CGRP) and vascular endothelial growth factor (VEGF) signaling. Multimodal and multiomics analyses of human OS bone samples further implicated peripheral innervation and neurotrophin signaling in OS tumor biology. Next and in two parallel approaches to inhibit nerve ingrowth, we repurposed FDA-approved bupivacaine liposomes and separately blocked CGRP signaling using FDA-approved Rimegepant. Both strategies led to significant reductions in sarcoma growth, vascularity, and sarcoma-induced hyperalgesia. In sum, TrkA-expressing peripheral neurons positively regulate key aspects of OS progression and sensory neural inhibition disrupts CGRP signaling within the sarcoma microenvironment leading to significantly reduced tumor growth and improved survival. These data suggest that interventions to prevent pathological innervation of OS represent an adjunctive therapy to improve clinical outcomes and survival.

Effects of different intercropping systems on soil properties and tobacco yield and quality

Homotopy continuation method for solving Dyson equation fully self-consistently: Theory and application to NdNiO2

The solution of the Dyson equation for the small-gap systems can be plagued by large non-converging iterations. In addition to the convergence issues, due to a high non-linearity, the Dyson equation may have multiple solutions. We apply the homotopy continuation approach to control the behavior of iterations. We used the homotopy continuation to locate multiple fully self-consistent GW solutions for the NdNiO2 solid and to establish the corresponding Hartree–Fock limits. Some of the solutions found are qualitatively new and help to understand the nature of electron correlation in this material. We show that there are multiple low-energy charge-transfer solutions leading to the formation of charge-density waves. Our results qualitatively agree with the experimental conductivity measurements. To rationalize the structure of solutions, we compare the k-point occupations and generalize the concept of natural difference orbitals for correlated periodic solids.

Foot placement control underlies stable locomotion across species

Animals navigate their environment stably without inefficient course corrections despite unavoidable errors. In humans, this stability is achieved by modulating the placement of the foot on each step such that recent errors are corrected. However, it is unknown whether animals with diverse nervous systems and body mechanics use such foot placement control; foot trajectories of many-legged animals are considered to be stereotypical velocity-driven patterns, as opposed to error-driven. Here, we put forth a unified “feedforward-feedback” control structure for stable locomotion that combines velocity-driven and body state error-driven foot placement. We provide empirical support for this control structure across flies, mice, and humans by mining their natural locomotor variability, finding that a competing control structure with purely velocity-driven foot placement is not supported by the data. This work finds shared behavioral signatures of foot placement control in flies, mice, and humans. We find that key characteristics of these signatures, such as their urgency and centralization, vary with neuromechanical embodiment across species. For example, more inherently stable multilegged animals exhibit less urgent control with a lower control magnitude and a slower correction timescale compared to humans. Furthermore, many-legged animals display modular, direction-, and leg-specific control signatures, whereas humans exhibit common signatures across both legs. Overall, our findings provide insight into stable locomotion across species, revealing how species with diverse neuromechanics achieve a shared functional goal: foot placement control.

Context specific personality associations with political ideology are shaped by geographical variation