Evaluated articles

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 study presents a comprehensive multi-approach and functional investigation of RBMX2 as a host factor involved in Mycobacterium bovis pathogenesis and its potential role in promoting epithelial-mesenchymal transition and lung cancer progression. The findings are valuable since the possible connection between M. bovis and lung cancer and the underlying mechanisms provides a promising direction for future research. The evidence is solid with methods, data, and analyses broadly supporting the claims, albeit with minor weaknesses that, if addressed, will make the evidence stronger. The study remains of great interest to microbiology, oncology, and drug discovery scientists.

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 was solid, although the sample size was small for the intervention.

eLife Assessment

This valuable study explores changes in remote memory impairment in an amyloid pathology mouse model, demonstrating that progressive deficits coincide with inhibitory interneuron alterations. While the findings shed light on circuit remodeling in this model, the mechanistic links between heightened inhibition and memory loss are currently incomplete. Additional data and deeper analysis may be needed to fully substantiate the authors' interpretations.

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 identifies a novel Legionella effector, Lfat1, which binds F-actin via a coiled-coil domain and structurally resembles the RID toxin, with cryo-EM revealing key interactions mediated by a hydrophobic helical hairpin. While the study is mostly complete and has compelling data, a few minor changes are recommended.

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. However, it is incomplete due to limited comparison with ground truth data from optogenetically identified interneuron subtypes and with existing spike sorting pipelines available to users.

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.

eLife Assessment

This important study provides a novel approach for delineating subcortical-cortical white matter bundles. The authors provide convincing evidence by harnessing state-of-the-art methods and cross-species data. Together, this effort will be of interest to scientists across multiple subfields.

eLife Assessment

This useful study attempts to place an ancient maize sample from Bolivia, dated to the end of the Incan empire, in genetic and geographical context. The analyses show that this sample is most closely related to ancient Peruvian maize, but the data are inadequate to determine the direction of dispersal. There are additional deficiencies in the statistical analyses and selection inferences. The topic of the study would appeal to researchers studying maize dispersal and adaptation.

eLife Assessment

This important study demonstrates the significance of incorporating biological constraints in training neural networks to develop models that make accurate predictions under novel conditions. By comparing standard sigmoid recurrent neural networks (RNNs) with biologically constrained RNNs, the manuscript offers compelling evidence that biologically grounded inductive biases enhance generalization to perturbed conditions. This manuscript will appeal to a wide audience in systems and computational neuroscience.

eLife Assessment

The findings represent an important contribution to understanding whether BMI influences head and neck cancer (HNC) risk after accounting for tobacco use. Within the context of the Mendelian Randomization (MR) field, the strength of evidence appears convincing, supported by rigorous methods and a thorough exploration of multiple genetic models of adiposity using diverse MR approaches. Limitations include the absence of associations in sensitivity models designed to better account for pleiotropy, which prevents evaluation of whether incorporating an instrumental variable for tobacco use would alter the findings. Additionally, the lack of a formal power assessment for detecting associations with the instrumental variables employed limits the interpretability and reach of the results.

eLife Assessment

This study identifies novel approaches to improving transgene expression in the injured mammalian myocardium through a combination of a tissue regeneration enhancer element and engineered AAVs - specifically, a liver-detargeting capsid, AAV.cc84, and an in vivo library screen-selected AAV-IR41. The evidence is convincing, and the AAV vectors are of fundamental value to the field of cardiac gene therapy. Future research exploring how to combine the features of AAV.cc84 and AAV-IR41 could yield an even more promising vector for therapeutic use.

eLife Assessment

This valuable study concerns a model for transgenerational epigenetic inheritance, the learned avoidance by C. elegans of the PA14 pathogenic strain of Pseudomonas aeruginosa. A recent study questioned whether transgenerational inheritance in this paradigm lacks robustness. The authors of this study have worked independently of the group that reported the original phenomenon and also independently of the group that challenged the original report. With solid data, this study independently validates findings previously reported by the Murphy group, confirming that the paradigm is reproducible elsewhere. The present study is therefore of broad interest to anyone studying genetics, epigenetics, or learned behavior.