Evaluated articles

eLife Assessment

This paper examines selection on induced epigenetic variation ("Lamarckian evolution") in response to herbivory in Arabidopsis thaliana. The authors find weak evidence for such adaptation, which contrasts with a recently published study that reported extensive heritable variation induced by the environment. The authors convincingly demonstrate that the findings of the previous study were confounded by mix-ups of genetically distinct material, so that standing genetic variation was mistaken for acquired (epigenetic) variation. Given the controversy surrounding the influence of heritable epigenetic variation on phenotypic variation and adaptation, this study is an important, clarifying contribution; it serves as a timely reminder that sequence-based verification of genetic material should be prioritized when either genetic identity or divergence is of importance to the conclusions.

eLife Assessment

Using a combination of connectomics, optogenetics, behavioral analysis and modeling, this study provides important findings on the role of inhibitory neurons in the generation of leg grooming movements in Drosophila. The data as presented provide convincing evidence that the identified neuronal populations are key in the generation of rhythmic leg movements. Based on reconstructions from ventral nerve cord electron microscopy data, the authors uncover distinct pathways to the motor neurons, which they propose inhibit and disinhibit antagonistic sets of motor neurons. This results in an alternation of flexion and extension. By analyzing limb kinematics upon silencing of specific populations of premotor inhibitory neurons and using computational modelling, they show the potential role of these neurons in rhythmic leg movement. The work will interest neuroscientists and particularly those working on motor control.

eLife Assessment

This manuscript provides important information on the neurodynamics of emotional processing while participants were watching movie clips. This work provides convincing results in deciphering the temporal-spatial dynamics of emotional processing. This work will be of interest to affective neuroscientists and fMRI researchers in general.

eLife Assessment

Karimian et al. present a valuable new model to explain how gamma-band synchrony (30-80 Hz) can support human visual feature binding by selectively grouping image elements, countering recent criticisms that the stimulus dependence of gamma oscillations limits their functional role. Grounded in the theory of weakly coupled oscillators and informed by primate electrophysiology, the model captures behavioural patterns observed in human psychophysics, offering support for the potential role of synchrony-based mechanisms, but incomplete evidence for a specific role of gamma oscillations. This work could be strengthened by more direct evidence for the proposed mechanism, and expanding beyond figure-only model inputs with limited ecological validity.

eLife Assessment

This important study looks into the effect of exogenous CoA on the response of TLR4-activated macrophages. Specifically, CoA enhances the LPS response by examining metabolomics, 13C tracing, and assessments of transcription and acetylation. Together, these provide a compelling series of findings that show exogenous CoA is taken up by macrophages, and this facilitates histone acetylation and transcription associated with activation and antimicrobial activity.

eLife Assessment

This valuable manuscript investigates the localisation of nutrient receptors in bloodstream stage trypanosomes, with implications for both nutrient uptake and immune evasion. Results after direct fixation of the cells in culture medium provide convincing evidence that the amounts of receptors on the surface of the cell, as opposed to the flagellar pocket, have previously been severely underestimated. Some results were essentially confirmatory, and there are questions regarding the quantitation of ligand binding by transferring receptors.

eLife Assessment

The study is a timely and important contribution to our knowledge of the circuit mechanisms of fear analgesia. The novel cue-induced analgesia paradigm allowed a compelling identification of a brainstem circuit element, i.e., somatostatin-expressing neurons within the ventrolateral periaqueductal grey that project to the rostroventral medulla, in mediating fear analgesia. The vlPAG is a known region of pain modulation, and this study adds key insight to the circuit involved in fear-associated analgesia. This work will be of interest to systems and behavioral neuroscientists, especially those interested in emotional behavior, pain, and/or brainstem function.

eLife Assessment

The identification of RBMX2 as a novel regulator linking mycobacterial infection to Epithelial-Mesenchymal Transition and cancer progression are fundamental findings that advance our understanding of a major research question about the link between infectious and non-infectious diseases, microbiology and oncology. It does so by introducing RBMX2 as a novel host factor, a potential therapeutic target and biomarker for both TB and lung cancer. The evidence provided is convincing because it is appropriate and the validated multi-omics methodologies used are in line with the current state of the art. This study will be of interest to scientists working in the fields of drug discovery, microbiology and oncology.

eLife Assessment

The authors quantified intentions and knowledge gaps in scientists' use of sex as a biological variable in their work, and used a workshop intervention to show that while willingness was high, pressure points centered on statistical knowledge and perceived additional monetary costs to research. These important findings demonstrate the difficulty in changing understanding: while interventions can improve knowledge and decrease perceived barriers, the impact was small. The evidence for the findings is solid.

eLife Assessment

This study provides valuable insights into the mechanisms of remote memory impairment in an Alzheimer's disease mouse model. The evidence is compelling, with careful use of viral-TRAP labeling and patch-clamp electrophysiology to demonstrate altered inhibitory microcircuit function, though the mechanistic link to memory deficits remains correlative. Overall, the work advances understanding of early circuit-level changes in AD, while highlighting open questions regarding causality and broader network contributions.

eLife Assessment

This useful study presents Altair-LSFM, a solid and well-documented implementation of a light-sheet fluorescence microscope (LSFM) designed for accessibility and cost reduction. While the approach offers strengths such as the use of custom-machined baseplates and detailed assembly instructions, its overall impact is limited by the lack of live-cell imaging capabilities and the absence of a clear, quantitative comparison to existing LSFM platforms. As such, although technically competent, the broader utility and uptake of this system by the community may be limited.

eLife Assessment

This important study by Zheng et al characterizes a novel Legionella pneumophila effector, Llfat1 (Lpg1387), which binds actin through a newly identified actin-binding domain. Data is convincing; structural analysis of the Llfat1 ABD-F-actin complex enabled the development of this domain as a probe for F-actin. Additionally, the authors show that Llfat1 functions as a lysine fatty acyltransferase targeting small GTPases, highlighting its importance in both bacterial pathogenesis and cytoskeletal biology.

eLife Assessment

The work provides important insights into how this lncRNA regulates gene expression via complex mechanisms, however, the biological relevance awaits validation in other models. This paper provides extensive and carefully analysed data that is of value in efforts to understand the role of the lncRNA EPB41L4A-AS1 in a human cell line. The data is generally convincing and supported by clever integrative analysis; however, the known extensive artefacts from individual Gapmer oligonucleotides cast some doubt over the interpretation of those experiments where only one targeting and one control Gapmer are used.

eLife Assessment

This paper reports on a correlation between diminished cardiolipin content and the severity of steatohepatitis in human subjects. This is supported further by experimental evidence from mice in which the gene encoding a key enzyme in cardiolipin synthesis has been compromised in the liver. The correlations established between lipidology, mitochondrial function, and the induction of respiration and oxidative stress are notable and will be useful to researchers in the field. However, given that the causal relationship between lipid perturbation and the progression of steatohepatitis implied in the title has not been tested experimentally, the evidence supporting the paper's key conclusion is incomplete.

eLife Assessment

Argunşah et al. investigate the mechanisms underlying the differential response dynamics of barrel vs septa domains in shaping the responses to single vs multiple whiskers. Based on the observation of a higher density of SST+ interneurons in the septa, the authors investigate the hypothesis that Elfn1-dependent short-term plasticity shapes these responses. This important study is, however, supported by incomplete evidence; factors restricting the strength of evidence are the limited spatial resolution of the multi-unit activity, as well as the lack of a mechanistic explanation. This provocative and intellectually stimulating hypothesis provides a contribution to work on how different cell types shape cortical representation.

eLife Assessment

This important study reports that the human posterior inferotemporal cortex (hPIT) functions as an attentional priority map, integrating both top-down and bottom-up attentional signals rather than serving solely as an object-processing region. The experiments and analyses are well conducted and provide convincing evidence that hPIT bridges dorsal and ventral attention networks and is robustly modulated by attention across diverse visual tasks. The study will be relevant for researchers investigating visual attention, high-level visual cortex, and the neural mechanisms that integrate endogenous and exogenous attentional control.

eLife Assessment

This study provides important findings on the neural circuits underlying dishabituation of the olfactory avoidance response in Drosophila. The data as presented provide solid evidence that the dishabituation involves distinct pathways from habituation. They show that reward-activated dopaminergic neurons provide input for within-modal dishabituation, while punishment-activated dopaminergic neurons provide input for cross-modal dishabituation. The work will interest neuroscientists, particularly behavioral neuroscientists working on habituation, neural circuits, and the dopaminergic system.

eLife Assessment

In this manuscript, the authors describe a software package for automatic differentiation of action potentials generated by excitatory and inhibitory neurons, acquired using high-density microelectrode arrays. The work is valuable as it offers a tool with the potential to automatically identify these neuron types in vitro. It is solid, as it provides a tool to identify putative excitatory and inhibitory neurons on high-density electrode arrays, which can be used in conjunction with other existing spike sorting pipelines.

eLife Assessment

This useful study reports findings that support the use of the Open Field Test in Drosophila as a model to study "emotion-like states", which are behavioral responses to several stressful or aversive treatments, and resilience upon their subsequent removal. Behavioral data, by employing established stress-causing treatments and genetic manipulations, are solid. While the results and conceptual framework of this work will be of interest to behaviorists regardless of animal models, the novelty of this work over previous studies could have been clearer.

eLife Assessment

This manuscript presents a valuable computational tool for identifying 3-5 gene regulatory network topologies capable of generating oscillatory dynamics. The application of Monte Carlo Tree Search to circuit design is novel and effectively expands the scale at which non-linear behaviours can be explored in silico. The efficiency of the proposed algorithm is convincing, and the work will be of interest to the systems and synthetic biology communities. While the evolutionary implications remain unclear, the methodological contribution represents a significant advance in the field.