Evaluated articles

eLife Assessment

The present manuscript by Cordeiro et al., shows convincing evidence that α-mangostin, a xanthone obtained from the fruit of the Garcinia mangostana tree, behaves as a strong activator of the large-conductance (BK) potassium channels. The authors suggest that α-mangostin activation of the BK channel is state-independent, and molecular docking and mutagenesis suggest that α-mangostin binds to a site in the internal cavity. Additionally, the authors show that α-mangostin can relax arteries, further suggesting the plausibility of the proposed effects of this compound. These are valuable findings that should be of interest to channel biophysicists and physiologists alike.

eLife Assessment

The study curated a set of Liver X receptor ligands that may guide the design of future drugs that activate the Liver X receptor as potential therapeutics for cardiovascular disease, Alzheimer's and type 2 diabetes, without inducing mechanisms that promote fat/lipid production. The authors also present improved multiplexed precision CRT (coregulator TR-FRET) and cellular assays which allows measurement of ligand potencies to displace corepressors in the presence of coactivators, which cannot be achieved in a regular CRT assay. This makes the evidence presented compelling as it stretches beyond the current state-of-the-art, and these important findings are expected to have practical implications in many sub-fields and remain of interest to scientists working in cell and molecular biology, drug discovery, medicinal chemistry and pharmacology.

eLife Assessment

This important study presents convincing evidence that uncovers a novel signaling axis impacting the post-mating response in females of the brown planthopper. The findings open several avenues for testing the molecular and neurobiological mechanisms of mating behavior in insects, and in the revised version the authors provide further evidence supporting their conclusions.

eLife Assessment

This important study reports on the relationships between cerebral haemodynamics and a number of factors that relate to genetics, lifestyle, and medical history using data from a large cohort. Compelling evidence suggests that brief arterial spin labelling MRI acquisition can lead to both expected observations about brain health, as manifested in cerebral blood flow, and biomarkers for use in diagnosis and treatment monitoring. The results can be used as a starting point for hypothesis generation and further evaluation of conditions expected to affect haemodynamics in the brain.

eLife Assessment

This manuscript describes a valuable screening approach to identifying nanobodies with the potential to modulate gene expression via epigenetic regulators. While the concept is of interest and the screening strategy is well designed, the current evidence supporting mechanistic specificity remains incomplete.

eLife Assessment

This valuable study addresses a critical question regarding the role of a subpopulation of cortical interneurons (Chrna2-expressing Martinotti cells) in motor learning and cortical dynamics. However, despite the inclusion of interesting behavioral and imaging data, significant limitations remain, even after revision, in the design of the motor learning task and the associated data analyses. As a result, the presented data are incomplete to support the central conclusions.

eLife Assessment

This important study shows that regions of the human auditory cortex that respond strongly to human voices are also sensitive to vocalizations from closely related primate species. The evidence is convincing and methodologically strong. The work offers significant insight into the evolutionary continuity of voice processing and would be of interest to researchers studying auditory processing and evolutionary neuroscience in general.

eLife Assessment

This study presents a valuable RNA velocity solution which integrates cell differentiation and gene regulation, with a balance between neuralODE and raw gene space. The evidence supporting the claims of the authors is solid, although inclusion of discussion on the challenges in capturing cell cycle transitions would have strengthened the study. The work will be of interest to scientists working in the field of computational biology and gene regulation.

eLife Assessment

This fundamental study presents experimental evidence on how geomagnetic and visual cues are integrated in a nocturnally migrating insect. The evidence supporting the conclusions is compelling. The work will be of broad interest to researchers studying animal migration and navigation.

eLife Assessment

This valuable study investigates the role of P-bodies in yeast proliferation and mRNA regulation within the phyllosphere, proposing that P-body assembly contributes to methanol metabolism and stress adaptation. The findings are of interest to researchers studying post-transcriptional gene regulation and microbial ecology in plants. However, the evidence is incomplete, as most experiments were performed under artificial conditions, relied on limited genetic validation, and were supported primarily by qualitative or low-resolution imaging.

eLife Assessment

This important work introduces a family of interpretable Gaussian process models that allows us to learn and model sequence-function relationships in biomolecules. These models are applied to three recent empirical fitness landscapes, providing convincing evidence of their predictive power. The findings should be of interest to the community working on the sequence-function relationship, on epistasis, and on fitness landscapes.

eLife Assessment

The authors analyzed spectral properties of neural activity recorded using laminar probes while mice engaged in a global/local visual oddball paradigm. They found solid evidence for an increase in gamma (and theta in some cases) for unpredictable versus predictable stimuli, and a reduction in alpha/beta, which they consider evidence towards a "predictive routing" scheme. The study is overall important because it addresses the basis of predictive processing in the cortex, but some of the analytical choices could be better motivated, and overall, the manuscript can be improved by performing additional analyses.

eLife Assessment

This important study describes a novel Bayesian psychophysical approach that efficiently measures how well humans can discriminate between colors across the entire isoluminant plane. The evidence was considered compelling, as it included successful model validation against hold-out data and published datasets. This approach could prove to be of use to color vision scientists, as well as to those who employ computational psychophysics and attempt to model perceptual stimulus fields with smooth variations over coordinate spaces.

eLife Assessment

This meta-analysis provides a fundamental synthesis of evidence demonstrating that transcranial magnetic stimulation targeting the hippocampal-cortical network reliably enhances episodic memory performance across diverse study designs. The evidence is convincing, with rigorous methodology and consistent effects observed despite modest sample sizes and some heterogeneity in stimulation approaches. The work highlights the specificity of memory improvements to hippocampal-dependent memories and identifies key methodological factors-such as individualized targeting-that influence efficacy. Overall, this study offers a timely and integrative framework that will inform both basic memory research and the design of future clinical trials for cognitive enhancement.

eLife Assessment

This useful study provides a well-constructed computational investigation of how intermittent theta-burst stimulation (iTBS) influences synaptic plasticity within the corticothalamic circuit, improving our mechanistic understanding of how stimulation parameters interact with intrinsic brain oscillations. The authors build a corticothalamic population model that generates individual alpha rhythms with a calcium-dependent metaplasticity rule, and provide solid evidence that aligning stimulation frequencies to brain-intrinsic oscillatory subharmonics enhances plasticity effects. This insight could open a route toward personalized, more effective stimulation protocols.

eLife Assessment

This functional MRI study critically tests the hypothesis that poor face recognition in developmental prosopagnosia in humans is driven by reduced spatial integration and smaller receptive fields in face-selective brain regions. The evidence provided is compelling as it is well-powered, uses state-of-the-art functional brain imaging, eye tracking, and computational analyses. The observed lack of difference in population receptive field sizes between face-selective brain regions of individuals with and without prosopagnosia, though a null result, has important implications for the field, and specifically, for theories of face recognition.

eLife Assessment

AGC kinases, such as PKN1, are regulated by activation loop phosphorylation. This paper reports that exposing cells to high concentrations of monovalent cations induces rapid activation loop dephosphorylation, with rapid re-phosphorylation when physiological salt is restored. Re-phosphorylation is apparently independent of ATP or candidate kinases, and the paper presents an extraordinary and unconventional mechanism involving phosphate exchange between the activation loop and an unknown acceptor molecule. The findings are intriguing and the approach is logical, but the evidence is incomplete and the significance unclear until the biochemical mechanism is identified.

eLife Assessment

This manuscript makes a valuable contribution to understanding learning in multidimensional environments with spurious associations, which is critical for understanding learning in the real world. The evidence is based on model simulations and a preregistered human behavioral study, but remains incomplete because of inconclusive empirical results and insufficiencies in the modeling. Moreover, there are open questions about the nature and extent to which the behavioral task induced semantic congruency.