Evaluated articles

eLife Assessment

Ruppert et al. investigated how activation of thermogenesis by cold exposure (CE) and methionine restriction (MetR) impacts health and leads to weight loss in mice. The authors provided valuable datasets showing that the responses to MR and CE are tissue-specific, while MR and CE affect beige adipose similarly. Although the study is descriptive, the data analyses are solid, with well-supported conclusions drawn from the findings.

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 a valuable finding regarding the need for prior inhibitory training to recruit the infralimbic cortex in extinction learning. The multiple clever behavioral designs supply converging lines of evidence in a compelling manner, but several issues, such as the group sizes and appropriate analysis of data, render the overall strength of support incomplete. With these issues resolved, this manuscript will be of interest to behavioral neuroscientists, especially those interested in learning & memory and/or cortical function.

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 is a valuable methodological contribution towards accurate characterization of viral genetic diversity using long-read sequencing and unique molecular identifiers (UMIs). However, the methods are currently incomplete and the sensitivity is not rigorously demonstrated. Addressing these gaps would strengthen the manuscript and make it a key addition to the field.

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 putative iron and zinc 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 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.

eLife Assessment

This valuable study presents a theoretical model of how punctuated mutations influence multistep adaptation, supported by empirical evidence from some TCGA cancer cohorts. This solid model is noteworthy for cancer researchers as it points to the case for possible punctuated evolution rather than gradual genomic change. However, the parametrization and systematic evaluation of the theoretical framework in the context of tumor evolution remain incomplete, and alternative explanations for the empirical observations are still plausible.

eLife Assessment

This important work fills a gap in the characterization of motor architecture and chemical coupling of the male reproductive system, crucial to understanding male reproduction and fertility. The convincing analysis reveals two distinct types of glutamatergic neurons that co-release either serotonin or octopamine. While serotonergic neurons are required for male fertility, octopaminergic neurons are dispensable, indicating a division of labour. This work lays the foundations for future investigations into the conserved key principles by which multi-transmitter systems control coordinated motor outputs.