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Oscillatory and aperiodic neural dynamics shape temporal perception and weighting of perceptual priors in ADHD profiles

Attention-deficit/hyperactivity disorder (ADHD) is characterized by an atypically compressed sense of time, yet the neural mechanisms underlying this atypical temporal perception remain poorly understood. Temporal perception depends on the brain's ability to organize sensory input into coherent experiences, ensuring perceptual stability despite uncertainty. Oscillations in the alpha band (8-13 Hz) and aperiodic 1/f dynamics have been proposed as key neural mechanisms through which the visual ...

— Marsicano, G., Deodato, M., Melcher, D. 2026-01-31 00:00:00

Dopamine shapes brain metastate dynamics

Dopamine's influence on large-scale network dynamics, especially on the default mode network (DMN), remains uncertain, as fMRI studies have produced mixed results. One likely contributor to these discrepancies is reliance on traditional functional connectivity analyses, which typically derive a single metric (e.g., the Pearson correlation coefficient) from the entire time series and thus fail to capture network dynamics. To address this issue, we combined a dopaminergic challenge (mazindol, a...

— Matsuyoshi, D., Kimura, Y., Takahata, K., Ikoma, Y., Seki, C., Zhang, M.-R., Higuchi, M., Suhara, T., Yamada, M. 2026-01-31 00:00:00

The richness of little voices: using artificial intelligence to understand early language development

How informative are preschoolers' speech vocalizations? Preschoolers' speech is often imprecise, highly variable and hard to interpret by humans and machines; consequently, its predictive value for later developmental outcomes remains quite underexplored. Here, we analyzed 6.595 brief vocalizations (0.5-5s) from 127 preschoolers aged 3-4 years, including 74 children with diagnosed language delay, recorded in naturalistic environments. The vocalization models robustly distinguished children wi...

— Petrache, M., Carvallo, A., Silva, V., Barcelo, P., Pena, M. 2026-01-31 00:00:00

Neural representations of speech production in neocortical and cerebellar regions

Speech production depends on the precise temporal integration of articulatory movements with phonation. While ventral primary motor cortex is known to encode articulatory features, how phonatory timing, and its coordination with articulation, is represented across cortical and cerebellar circuits remains poorly understood. Using 7T functional MRI, we examined neural representations during overt syllable production varying in place of articulation and voice onset time. Multivariate analyses re...

— Jossinger, S., Arafat, B., Diedrichsen, J. 2026-01-31 00:00:00

Topographical differences during motion processing in autistic and dyslexic children

Atypical motion processing has been reported in multiple developmental conditions, including autism and dyslexia, and taken as support for a general developmental vulnerability in the dorsal stream. Yet by uncovering dynamically unfolding processes, electroencephalography can determine the extent to which motion processing signatures are shared or distinct across different developmental conditions. Here we used pre-registered topographical analyses across the whole high-density electrode arra...

— Sallard, E., Esenther, A., Scerif, G., Matusz, P. J., Manning, C. 2026-01-31 00:00:00

The progression of sex differences in brain networks across the lifespan

Sex differences in brain connectivity are well documented, yet how these differences evolve across the human lifespan remains poorly understood. Rigorously assessing sex-dependent trajectories of brain network organization is challenging due to difficulty in acquiring, processing, and modeling high-dimensional connectomes. Here, we analyzed 15 types of functional and structural connectivity networks from 1286 healthy individuals aged 8-100+ years, using our new AI-based Krakencoder to derive ...

— Huang, K., Jamison, K. W., Jacobs, E. G., Miolane, N., Kuceyeski, A. 2026-01-31 00:00:00

Counting apples - How does the prefrontal region support early numerical understanding in preschool children?

Because early maths skills strongly predict later outcomes, it is crucial to understand the mechanisms that shape early learning in children. The recent years have seen an increase in studying the neural correlates that support the acquisition of maths skills. However, existing work in early childhood has primarily focused on core number-processing regions in the parietal regions, with comparatively little attention to the supportive role of prefrontal regions. In this study, we examined the ...

— Ivanova, E., Farran, E. K., Soltanlou, M. 2026-01-31 00:00:00

Individual Differences in Dopaminergic Modulation of Exploration-Exploitation Behaviour

Dopamine (DA) has been implicated in exploration-exploitation behaviour, i.e., exploring novel, potentiallybetter options vs. exploiting known, previously rewarding options. Impairments in this trade-off occur inpsychiatric disorders involving DAergic dysfunction, including addiction and schizophrenia. Pharmacologicalstudies revealed a contribution of DA to exploration, but inconsistent findings suggest that interindividualvariability in baseline DA may modulate effects. To address this, we i...

— Smith, E., Theis, H., van Eimeren, T., Knauth, K. H. K., Tuzsus, D., Mathar, D., Peters, J. 2026-01-31 00:00:00

Alpha oscillations are dysrhythmic in Fragile X syndrome

Background: Alpha oscillations are dominant rhythms in the human brain, supporting inhibitory control and coordination of neural activity. Altered alpha dynamics are observed across many neuropsychiatric and neurodevelopmental disorders, including Fragile X syndrome (FXS), the most common monogenic cause of autism and intellectual disability. FXS exhibits paradoxical alpha power: elevated absolute but reduced relative power. To resolve this incongruity, we considered that conventional power m...

— Siekierski, P., Liu, Y., Westerkamp, G., Elmaghraby, R., ElSayed, Z., Gilbert, D., Erickson, C., Pedapati, E. 2026-01-31 00:00:00

Motor implementation of control and reward-based urgency regulation across impulsivity

Everyday decisions unfold dynamically, with commitment shaped by a growing sense of urgency that can, when excessive, contribute to impulsive choices. Here we aimed at dissociating two modes of urgency regulation, control-driven (accuracy-oriented) and reward-driven (motivation-based), and asked whether their relative influence varies across individuals differing in impulsivity. We further investigated how these regulatory modes are implemented in the motor system, focusing on two modulatory ...

— Fumery, T., Chaise, F., Soille Hambye, A., Fievez, F., Lambert, J., Vassiliadis, P., Derosiere, G., Duque, J. 2026-01-31 00:00:00

Higher-order intrinsic routes support flexible task-evoked communication

Flexible task-evoked communication requires the brain to transiently establish functional interactions that are not evident during rest, yet the network mechanisms supporting these newly formed connections remain unresolved. Using whole-brain functional MRI from 92 participants performing six cognitive tasks, we show that task-evoked communication is implemented within a constrained intrinsic network architecture rather than through large-scale rewiring. Across tasks, we found that approximat...

— Dang, S., Bargujar, G., Singh, S. 2026-01-30 00:00:00

Reducing haystacks to needles - ViralClust: A Nextflow pipeline to cluster viral sequences

The rapid accumulation of viral genome sequences presents major challenges for downstream analysis tools, including tools for multiple sequence alignments, phylogeny, and genome/alignment visualization, due to computational constraints and sampling biases caused by outbreak-driven over- representation. Selecting representative genomes through clustering offers a principled alternative to random subsampling, yet choosing appropriate clustering strategies remains non-trivial and context depende...

— Triebel, S., Lamkiewicz, K., Marz, M. 2026-01-30 00:00:00

The biophysical basis of enterocyte homeostasis

We present an approach to analysing cell homeostasis using a 'bond graph' modelling approach that ensures that the conservation laws of physics (conservation of mass, charge, and energy, respectively) are satisfied for the interdependent biochemical, electrical, mechanical, and thermal energy storage mechanisms operating within the cell. We apply the bond graph approach to several cell membrane transport mechanisms and then consider how physics constrains intracellular electrolyte homeostasis...

— Hunter, P. J., Dowrick, J. M., Ai, W., Nickerson, D. P., Shafieizadegan, M. H., Argus, F. 2026-01-30 00:00:00

CACNA2D4 variants are associated with exertional heat stroke susceptibility

Exertional Heat Stroke (EHS) is a life-threatening disease defined by severe hyperthermia, with a body temperature above 40{degrees}C, associated with a sudden neurological dysfunction, observed in healthy individuals exposed to intensive physical exercise. EHS shares many clinical and biological similarities with Malignant Hyperthermia (MH), a pharmacogenetic disorder associated with mutations in the RYR1, CACNA1S and STAC3 genes involved in calcium release required for skeletal muscle contr...

— Charpentier, C., Fall, A., De la Rosa Vazquez, J., Schreiber, J., Brocard, J., Meresse, P., Guergour, D., Benstaali, C., Bosson, C., Roux-Buisson, N., Allard, B., Lee, A., Marty, I., Faure, J. 2026-01-30 00:00:00

Barley (Hordeum vulgare L.) HvDEP1 alleles and their effect on agronomic and physical grain traits

The Dense and erect particle 1 (HvDEP1) gene, located on chromosome 5H in barley (Hordeum vulgare L.), encodes a heterotrimeric G-protein {gamma}-subunit that regulates grain size and stem elongation. Multiple alleles of HvDEP1 have been identified, including the widely utilized semi-dwarf allele HvDEP1.GP, caused by an insertion mutation, and a recently discovered variant, HvDEP1.V, characterized by two deletions in the putative cis-regulatory region. In this study, we evaluated the phenotyp...

— Vu, H. M., Coram, T. E., Able, J. A., Walter, J., Coventry, S. J., Tucker, M. R. 2026-01-30 00:00:00

Castling, a novel therapeutic concept for rewiring pathological gene-expression networks, enabled by the TRIPLE technology

Background Pathological conditions often arise from dysregulation of complex gene networks. MicroRNAs (miRNAs) are central modulators of these networks, with upregulation of disease-promoting miRNAs suppressing beneficial pathways, and downregulation of protective/therapeutic miRNAs normally restraining pathological programs. Because individual miRNAs coordinately regulate multiple genes, they represent powerful therapeutic targets. We hypothesized that pathology-associated gene expression im...

— Antony, D., Roman Azcona, M. S., Kalinski, H., Pultar, M., Adamsky, S., Nachum, S. A., Shalom, E., Rhiel, M., Tsouris, A., Diendorfer, A., Andrieux, G., Boerries, M., Hackl, M., Cornu, T. I., Zurr, D., Cathomen, T., Feinstein, E., Mussolino, C. 2026-01-30 00:00:00

Dynamic Regulation of CD300b, and CD300f on Myeloid Cells in Oral Immunotherapy

Introduction. Oral immunotherapy (OIT) induces desensitization in IgE-mediated food allergy, yet the role of myeloid cells in acquisition of tolerance is unclear. CD300 receptors regulate activation of myeloid cells, with CD300f acting as an inhibitory receptor and CD300b as an activating receptor. Their modulation during OIT may reflect effector cell reprogramming and serve as biomarkers of treatment response. Methods. Thirty-five patients undergoing OIT were prospectively enrolled. Peripher...

— Epstein-Rigbi, N., Itan, M., Avlas, S., Damari, E., Nachshon, L., Koren, Y., Levy, M., Goldberg, M. R., Elizur, A., Munitz, A. 2026-01-30 00:00:00

High-fidelity backpropagation through primate foveal cones

Primate vision has exceptionally high spatial acuity and contrast sensitivity. This performance originates in specialized photoreceptors of the fovea. These cones transduce light into electrical signals in the outer segment, and convey these signals to the presynaptic terminal for transmission. Backpropagating signals are also possible, as the terminal receives gap-junctional input from neighboring cones. Such signals could influence phototransduction itself. To test this idea, we recorded el...

— Wienbar, S. R., Bryman, G. S., Do, M. T. H. 2026-01-30 00:00:00

The schizophrenia associated protein DISC1 is a multivalent tetrameric hub of conserved ancient fold

DISC1 is a pleiotropic protein with essential roles in neuronal proliferation and migration, intracellular signalling and cargo transport. It associates with a diverse array of partner molecules in these contexts. Mutations at the DISC1 locus are strongly associated with a spectrum of mental illnesses such as schizophrenia and depression. Despite its clinical relevance, the molecular architecture and function of DISC1 have remained largely elusive. We present a cryo-EM structure of the entire...

— Zhou, J. C., Kratochvil, J., Ye, F., el Omari, K., Kukura, P., Zhang, M., Seiradake, E. 2026-01-30 00:00:00

An adaptive multi-strategy metaheuristic for robust model calibration in large-scale systems biology

Parameter estimation is a central challenge in systems biology, particularly for large dynamic models described by nonlinear ordinary differential equations (ODEs). These global optimization problems exhibit landscapes which are topologically heterogeneous, often exhibiting a pathological mixture of stiff, smooth valleys and rugged, noisy plateaus, making single-strategy hybrids ineffective. While methods like enhanced Scatter Search (eSS) represent the current state-of-the-art, their rigid i...

— Polo-Rodriguez, A., Penas, D. R., Banga, J. R. 2026-01-30 00:00:00

Structural Optimization of CHI3L1 Inhibitors with Improved Pharmacokinetics and Functional Activity in 3D Glioblastoma Models

Chitinase-3-like protein 1 (CHI3L1) is a key driver of glioblastoma (GBM) progression and an emerging therapeutic target. Building on the CHI3L1 inhibitor 11g, we optimized the scaffold through medicinal chemistry to assess structure-property relationships and improve pharmacokinetics. Using microscale thermophoresis (MST) and computational studies, we validated 10p, which exhibits a CHI31 binding affinity (Kd) of 13.22 M. Notably, 10p overcomes previous developability hurdles by achieving a ...

— Kaur, B., Nada, H., Gabr, M. 2026-01-30 00:00:00

Structural mechanism of Necrocide 1 activation of human TRPM4 that triggers necrosis by sodium overload

The small molecule Necrocide 1 (NC1) constitutively activates human TRPM4, triggering Na influx and leading to necrotic cell death, a process termed Necrosis by Sodium Overload (NECSO). NC1 activation is specific to human TRPM4 and does not affect most of the other mammalian TRPM4 orthologs. Here, we elucidate the molecular mechanism underlying NC1 activation and its species-specific selectivity for human TRPM4 using a combination of single-particle cryo-EM, electrophysiology, and cell death ...

— Teixeira-Duarte, C. M., Fu, W., Zeng, W. M., Wang, J., Jiang, X., Zhao, Z., Zhong, Q., Jiang, Y. 2026-01-30 00:00:00

Ubiquitous low-energy RNA fluctuations and energetic coupling measured by chemical probing

RNA function is governed by RNA folding, but strategies for measuring RNA folding thermodynamics are limited, and fundamental questions such as the energy of base pair opening remain debated. Here we introduce Probing-Resolved Inference of Molecular Energetics (PRIME) to extract nucleotide-resolution RNA structural energetics from scalable chemical probing experiments. Applying PRIME to diverse RNAs, we find that RNA base pairs and tertiary interactions dynamically open with free energies of ...

— Choi, E. K., Bose, R., Mathews, D. H., Mustoe, A. M., Lucks, J. B. 2026-01-30 00:00:00

A Carboxylate Switch Point Controls Long-Range Energy Transduction in Respiratory Complex I

Complex I is a highly intricate membrane-bound protein that powers the cellular energy metabolism by a long-range (>300 [A]) proton-coupled electron transfer (PCET) reaction. Here, we investigate the unknown coupling mechanism of Complex I by probing the charge transfer reaction along its functionally central carboxylate pathway (E-channel). By combining biophysical and site-directed mutagenesis experiments with high-resolution (2.6-2.7 [A]) cryo-electron microscopy (cryo-EM) and multiscale s...

— Beghiah, A., Saura, P., Kovalova, T., Hoeser, F., Friedrich, T., Kaila, V. R. I. 2026-01-30 00:00:00

Deep learning-enabled speckle reduction for cleared-sample coherent scattering tomography

Clearing Assisted Scattering Tomography (CAST) extends coherent scattering tomography to whole-brain imaging, enabling visualization of fine-scale brain-wide connectivity. As a coherent optical tomography modality, CAST is inherently affected by speckle noise, which degrades image quality and limits quantitative analysis. However, existing speckle reduction methods developed for optical coherence tomography (OCT) are not directly transferable to CAST images due to differences in sample and no...

— Chen, C., Huiru, W., Peilin, G., Xi, C., Ren, J. 2026-01-30 00:00:00

AI-enhanced cardiac digital twins extend drug proarrhythmic risk assessment through experimental data uncertainty propagation and overdose exploration: a loperamide case study

Drug-induced QT interval prolongation is a key biomarker of proarrhythmic risk and central to drug cardiac safety evaluation alongside in vitro assays and animal studies. Current preclinical frameworks, however, provide limited insight into how experimental uncertainty and extreme exposures translate into real-world arrhythmic risk, despite both factors critically modulating outcomes. To address this, we used sex-specific machine learning surrogate models trained on 3D cardiac digital twins--...

— Dominguez Gomez, P., Zingaro, A., Balzotti, C., Leitner, M., Jacobo-Piqueras, N., Vazquez, M., Rast, G., Aguado-Sierra, J. 2026-01-30 00:00:00

Catch-and-Display Immunoassay as an Accessible Platform for Digital Biomarker Detection

Digital immunoassays provide exceptional analytical sensitivity for detecting low-abundance biomarkers, but their broad adoption is limited by practical barriers. Commercial platforms are prohibitively expensive for routine use by individual laboratories, and laboratory-scale concepts typically describe specialized biosensors and sophisticated workflows. Here, we introduce a nanomembrane-based Catch-and-Display Immunoassay (CAD-IA) as an accessible digital immunoassay for common laboratory se...

— Liu, Y., Walker, S., Klaczko, M., Singer, B., Godin, M., Tabard-Cossa, V., Flax, J., McGrath, J. 2026-01-30 00:00:00

Engineering the Self-assembly of Bacterial Microcompartment Shell Proteins via Charged Mutations

Protein self-assembly is a fundamental biological process of great importance for the design and synthesis of biomaterials. Developing the ability to precisely manipulate protein assembly would greatly expand both our understanding of the process and our biotechnological capabilities. Within bacteria, proteins that self-organize to form bacterial microcompartments (MCPs) offer an excellent model system for studying protein self-assembly and advancing biomaterial design capabilities. MCPs cons...

— Gomez, A., Mehrafrooz, B., Waltmann, C., Mills, C., Kennedy, N., Miller, J., Tullman-Ercek, D., Olvera de la Cruz, M. 2026-01-30 00:00:00

Principles of in situ protein sequencing: expansion microscopy-adapted Edman degradation and amino acid recognition

The ability to map protein identity, with resolution sufficient to infer interactions, would support analysis of how proteins work together, or malfunction, in biological processes and diseases. Although several emerging technologies aim towards single-molecule protein sequencing, they require proteins to be removed from the nanoscale spatial context of cells and tissues. Expansion microscopy (ExM) has facilitated a diversity of chemical analyses by isotropically separating molecules througho...

— Mitchell, C. M., Tavana, S. Z., Peng, J., Wang, H., Shi, J., Zhang, C., Evgeniou, L., Domecillo, M., Wang, S., Estandian, D. M., Choueiri, A. G., Wong, E., Dohadwala, S., Polizzi, N., Kiessling, L. L., Boyden, E. S. 2026-01-30 00:00:00

DDX3X syndrome mutations lock DDX3X-RNA conformational states to drive persistent pathological condensation and neuronal death

DDX3X is a highly conserved RNA helicase associated with RNA metabolism, translation initiation, and deciding cell fate choices. Spontaneous mutations in DDX3X cause a rare genetic human disorder called DDX3X syndrome, showing a spectrum of neurodevelopmental and intellectual abnormalities. How missense mutations in DDX3X lead to aberrant cellular functions and pathological consequences is unclear. Here, we demonstrate that specific DDX3X syndrome missense mutations induce the formation of pe...

— Ghosh, P., Kapuganti, S. K., Gopal, S., Lamba, S., Rajyaguru, P. I., Kesavardhana, S. 2026-01-30 00:00:00