Evaluated articles

eLife Assessment

The authors describe an interesting approach to studying the dynamics and function of membrane proteins in different lipid environments. The fundamental findings have theoretical and practical implications beyond the study of EGFR to all membrane signalling proteins. The evidence supporting the conclusions is compelling, based on the use of a nanodisk system to study membrane proteins in vitro, combined with state-of-the-art single-molecule FRET. The work will be of broad interest to cell biologists and biochemists.

eLife Assessment

This interesting study adapts machine learning tools to analyze movements of a chromatin locus in living cells in response to serum starvation. The machine learning approach developed is useful, the experiments are well controlled, and the data are solid. The study would be greatly strengthened by testing key predictions made using perturbation experiments. This work will be of interest to those studying chromosome biology and gene expression patterns.

eLife Assessment

The present study employed transcriptomics to investigate the impact of methionine restriction (MR) and cold exposure (CE) on liver and adipose tissues in mice. The authors demonstrate that responses to MR and CE are tissue-specific, while both MR and CE have a similar effect on beige adipose tissue. While these findings are somewhat descriptive, this work is considered important, as it provides a comprehensive resource for enhancing our understanding of these lifestyle interventions. The study is of high scientific quality, and the analyses are convincing.

eLife Assessment

This useful study investigates how intrinsically disordered domains can interact to dictate the sub-cellular localization of a major innate immune sensor termed cGAS. The data from various cellular and biochemical assays are mostly solid, but the main conclusions from these experiments need to be validated further. This paper is relevant to immunologists, especially those interested in cytosolic DNA-sensing pathways.

eLife Assessment

In this valuable study, through carefully executed and rigorously controlled experiments, the authors challenged a previously reported role of the Death Receptor 6 (DR6/Tnfrsf21) in Wallerian degeneration (WD). Using two DR6 knockout mouse lines and multiple WD assays, both in vitro and in vivo, the authors provided convincing evidence that loss of DR6 in mice does not protect peripheral axons from WD after injury. Questions remain about whether this conclusion is generalizable to CNS axonal degeneration in disease models such as ALS, AD, and prion diseases. In addition, the authors need to provide information about the sex, age, and genetic background of their animal studies to allow readers to better assess the basis for inconsistencies from previous reports on the protective effects of DR6.

eLife Assessment

In their study, Brown et. al. provide an important advance in understanding the architecture of the mycobacterial outer membrane. Using all-atom simulations of model mycomembranes, the work reports compelling structural insights into how α-mycolic acids and outer leaflet lipids (PDIM and PAT) shape membrane organisation. The work revealed membrane heterogeneity with ordered inner leaflets and disordered outer leaflets that provide a molecular explanation for the resilience of the mycobacterial envelope.

eLife Assessment

This useful study introduces a computational pipeline for designing RNA in situ fluorescence hybridization probes that could improve the sensitivity and specificity of RNA detection in cells. While the approach is novel and the preliminary data suggestive, the evidence supporting a clear advantage over existing probe design strategies is incomplete. The work will be of interest to researchers developing or using molecular tools for imaging RNA in cells.

eLife Assessment

This important study addresses the timely and interesting question of how itaconate generation emerged in evolution, using taxonomic analysis of the gene and enzyme cis-aconitate decarboxylase (CAD). The authors provide solid evidence identifying three CAD branches in metazoans and showing that the early metazoan paleo-form indeed generates aconitate and is already linked to innate immunity. They further provide limited evidence suggesting that taxonomic differences in subcellular localisation of this enzyme may allow for innate immune signalling without compromising cellular energetics. The implications of the study will be of high interest to the field of innate host defence and immunometabolism.

eLife Assessment

This set of experiments provides important knowledge for how the infralimbic cortex is recruited to inhibit behavior after extinction training. The evidence supporting the conclusions is convincing with multiple sophisticated behavioral designs providing converging lines of evidence, though reviewers note possible alternative interpretations and limitations of small group sizes in some cases. This work will be of interest to those interested in cortical function, learning and memory, aversive behavior, and/or related psychiatric factors.

eLife Assessment

This work provides a valuable comparison of sentence structure representations in the human brain and state-of-the-art Large Language Models (LLMs). Based on solid analysis of 7T fMRI data, it systematically identifies sentences in which LLMs underperform relative to models that explicitly code for syntactic structure. The study will be of significant interest to both cognitive neuroscientists and artificial intelligence researchers.

eLife Assessment

This important work has the potential to expand the repertoire of transgenic animals for systems neuroscience investigations across multiple fields. The generation of new reagents has the potential to open new directions in experimental design, and the Cas9-based approach for generating mice may provide additional benefits compared to existing BAC transgenic mouse lines. However, whereas some of the imaging data are compelling, quantitative analysis of transgene fidelity is incomplete, as it relies on a qualitative description of reporter XFP expression at low magnification, with some electrophysiological characterization.

eLife Assessment

This important study presents convincing findings on creating an exhaustive library of new enhancer-AAVs targeting astrocytes and oligodendrocytes with high potential for both basic and translational work, which will be of value to a large and growing community. However, the outdated description of glial biology in the Introduction, the overstated claims of utility in the Conclusion, and the loose stringency in the criteria used to assemble the library diminish the strengths of the claims. The work will be of interest to neuroscientists working on glial cell biology.

eLife Assessment

This paper presents a collection of analyses relating structure and function in the whole-brain Drosophila EM connectome and whole-brain calcium imaging data. The linkage of detailed anatomical structure with population activity is of broad interest in circuit neuroscience in light of increasingly detailed brain maps, but the analysis methods used made the evidence incomplete. The conclusions are useful for specific network observations, but a more thorough analysis of the anatomical and functional data is needed to support the overall claims.

eLife Assessment

This study is an important contribution to the field of viral sequencing, providing methods for more accurate characterization of viral genetic diversity using long-read sequencing and unique molecular identifiers (UMIs). Although it is a small pilot study, it shows promise as a convincing, validated methodology with broad applicability.

eLife Assessment

This important study elucidates the role of the exocyst component EXOC6A at distinct stages of ciliogenesis, which advances our understanding of ciliary membrane remodeling and cilium formation. The authors provide solid evidence that EXOC6A interacts with myosin-Va and is dynamically recruited via dynein-, microtubule-, and actin-dependent mechanisms, to support proper formation of the ciliary membrane. The study will be of interest to cell biologists and other researchers interested in vesicular trafficking, organellar membrane dynamics, and ciliogenesis.

eLife Assessment

This valuable study identifies a brown adipose tissue-specific heat shock factor 1-alcohol dehydrogenase 5 (ADH5) molecular cascade as a regulator of systemic aging, showing that ADH5 deficiency contributes to BAT dysfunction and health decline in aged mice. While there is evidence to support this mechanism, the conclusions remain incomplete, particularly regarding statistical rigor and clarity in data presentation.

eLife Assessment

This modelling study tests several hypotheses describing how seasonality and migration drive the epidemiology of Rift Valley Fever Virus among transhumant cattle in The Gambia. The work is methodologically solid, and findings offer valuable insights into how the movement of cattle in and out of the Gambia River and Sahel ecoregions could lead to source-sink transmission dynamics among cattle subpopulations, sustaining endemic transmission.

eLife Assessment

This study presents a valuable finding regarding the role of oxytocin neurons in thermogenesis and behavioral thermoregulation. The use of numerous converging methods, including behavior, fiber photometry, optogenetics, thermal recordings, metabolic analyses, and more, produces a multi-dimensional dataset delivering findings that provide solid support for the conclusions. Conclusions would be strengthened with validation of the approaches, inclusion of a loss of function experiment, and further investigation of the social nature of the behavior. The maternal findings are, at present, somewhat disconnected from the conclusions. The findings are novel and open new doors for understanding the role of the PVT and oxytocin in thermoregulation work; the work will be of strong interest to the thermoregulation, social behavior, and oxytocin signaling communities.

eLife Assessment

This important study identifies a metal transporter in the plasma membrane of the obligate intracellular pathogen, Toxoplasma gondii. Using an array of different approaches, the authors convincingly demonstrate that this transporter mediates iron and zinc uptake and regulates diverse cellular processes, including parasite metabolism and differentiation. This work will be of broad interest to cell biologists and biochemists studying metal ion transport mechanisms.

eLife Assessment

Whole-brain imaging of neuronal activity in freely behaving animals holds great promise for neuroscience, but numerous technical challenges limit its use. In this important study, the authors describe a new set of deep learning-based tools to track and identify the activity of head neurons in freely moving nematodes (C. elegans) and jellyfish (Clytia hemisphaerica). While the tools convincingly enable high tracking speed and accuracy in the settings in which the authors have evaluated them, the claim that these tools should be easily generalizable to a wide variety of datasets is incompletely supported.