Evaluated articles

eLife Assessment

This elegant study presents a valuable approach to probing the structural features of the full-length human Hv1 channel as a purified protein, supported by rigorous biochemical assays and spectral FRET analysis, which will interest biophysicists and physiologists studying Hv1 and other ion channels. Overall, the work introduces an interesting labeling strategy and provides methodological observations that are of value in investigating hHV1. However, the analysis appears incomplete, requiring additional structural interpretation and mechanistic insight.

eLife Assessment

Li et al. present an important and innovative study linking developmental changes in sleep to ecological context in Drosophila mojavensis, and propose that sleep at one stage of an animal's life might anticipate needs at a future stage. The results fit well with this model, but are correlative in nature. The work is convincing, scientifically rigorous, and effectively bridges sleep biology and evolutionary ecology, opening promising new directions for the field.

eLife Assessment

This study provides useful insights regarding the alterations of sleep architecture in a knock-in mouse model of Alzheimer's Disease (AD). These include age-related hyperactivity that is typically associated with increased arousal, a normal homeostatic response to sleep loss, and a stronger AD-like phenotype in females. Although the analyses are robust, evidence for the proposed mechanisms underlying abnormal sleep architecture is incomplete. Overall, the study may have a focused impact on the sleep and AD fields.

eLife Assessment

This manuscript describing the phenotypes associated with loss and gain of RVCL-S documents important findings that have practical implications. Although the data and methods are solid and support many claims, there remain some concerns about mechanisms.

eLife Assessment

This manuscript reports high-resolution cryo-EM structures of a trimethylamine N-oxide demethylase and advances the intriguing hypothesis that the enzyme is bifunctional, coupling TMAO demethylation to formaldehyde capture at a distal tetrahydrofolate-binding site via an enclosed intramolecular tunnel. Supported by biochemical assays and molecular dynamics simulations, the structural findings are valuable and potentially of broad interest, particularly the unusual oligomeric architecture and the proposed conduit for a reactive intermediate. However, the mechanistic framework is considered incomplete, raising substantial concerns regarding the proposed catalytic mechanism, metal/cofactor requirements, and the interpretation of biochemical data supporting formaldehyde channelling.

eLife Assessment

This important study provides a comprehensive comparison of the mechanisms through which different inhibitors affect the SARS-CoV-2 main protease, a pivotal antiviral drug target, and suggests a potentially broad-spectrum strategy to inhibit this critical viral enzyme by disrupting its dimerization states. However, whereas the biophysical analyses of the dimer stability are convincing, evidence supporting this new mode of mechanism to inhibit the main protease is incomplete and would benefit from a correlation of the biophysical observations with functional activity. With the functional validation part strengthened, this work would be of interest to biochemists and virologists working on anti-coronavirus drug discovery.

eLife Assessment

This study presents a potentially valuable exploration of the role of thalamic nuclei in language processing. The results will be of interest to researchers interested in the neurobiology of language. However, the evidence is incomplete to support robust conclusions at this point.

eLife Assessment

This study provides a useful contribution to understanding how wearable augmentation devices interact with human proprioception, using a longitudinal design over a single session. Results demonstrate that the perceptual representation of the biological finger and augmentation device changes across different phases of device exposure and use. The evidence supporting a representational change over time is solid, although it is still not clear whether these changes reflect three distinct phases of sensorimotor plasticity, as argued, versus 'washout' or adaptation effects. This work will be of interest to researchers studying body representation, sensorimotor learning, and human-technology interaction.

eLife Assessment

In this study, the authors identify EOLA1 as a novel mitochondrial protein required for mitochondrial translation and normal cardiac function. The characterization of the molecular role of EOLA1 is still incomplete, and additional controls will be necessary. Nevertheless, the identification of a novel factor critical for mitochondrial gene expression and oxidative phosphorylation will be useful for cell biologists working on mitochondrial dysfunction.

eLife Assessment

Stearns and Poletti present a technically impressive study that aims to uncover a deeper understanding of microsaccade function: their role in perceptual modulation and the associated temporal dynamics. The question is useful, and advances prior work by adding temporal granularity. However, the strength of the evidence is currently incomplete. Additional analysis is needed to control for the effects of endogenous attention and to demonstrate changes in perceptual performance.

eLife Assessment

This valuable study presents a technically sophisticated intravital two-photon calcium imaging approach to characterize Ca²⁺ dynamics in distinct populations of meningeal macrophages in awake, freely behaving mice. These data are solid and suggest that meningeal macrophage calcium activity is tightly linked to anatomical sub-compartments, with potential implications for migraine and neuroinflammatory processes. Despite these strengths and broad relevance to neuroimmunology, several technical and interpretational issues limit the study, which could be addressed to strengthen this manuscript.

eLife Assessment

This study provides valuable evidence that hepatic DHHC7-dependent palmitoylation is a physiologically relevant regulator of systemic metabolism, and that loss of DHHC7 disrupts Gαi palmitoylation, activates cAMP-PKA-CREB signaling, and increases hepatic transcription and secretion of Prg4. The identification of Prg4 as a hepatokine that is elevated in vivo, together with some in vitro evidence for its interaction with GPR146, represents a conceptually novel contribution to the field. However, the evidence linking these mechanisms to systemic lipolysis, liver-adipose tissue crosstalk, and whole-body metabolic physiology remains incomplete, as the phenotypic analyses rely on a limited set of experiments and do not yet fully support claims regarding adipose tissue dysfunction or altered lipid flux.

eLife Assessment

This important study introduces a pulsed laser phase plate that generates stable phase contrast in electron microscopy, offering a practical alternative to continuous-wave designs that suffer from optical instabilities and diffraction artifacts. The experimental results demonstrate a controllable and stable electron phase shift, and the evidence supporting the feasibility of this approach for phase-contrast electron microscopy is convincing. Clarifying the agreement between experiment and theory and further elaborating on possible applications would strengthen the manuscript.

eLife assessment

The manuscript presents important findings with theoretical or practical implications beyond a single subfield. The work is overall solid, and the methods, data, and analyses broadly support the claims. Although the novelty of this study and the work put into it are appreciated, there are also clearly some weaknesses that should be addressed.

eLife Assessment

This study offers important methodological advances for CRISPR-based mutagenesis in mice, highlighting the potential of founder animals for early phenotypic characterization. The authors present convincing evidence, supported by rigorous experimental design, that "crispant" (F0) analysis in mice, despite prior concerns about genetic mosaicism, can be utilized to assess protein function.

eLife Assessment

This potentially important study explores the specificity of olfactory perceptual learning. In keeping with previous work, the authors found that learning to discriminate between two enantiomers does not generalize across the nostrils or to unrelated enantiomers, whereas learning to discriminate odor mixtures does generalize across the nostrils and to other odor mixtures, with this learning effect persisting over at least two weeks. While the evidence presented to support these findings is convincing, it remains unclear why the results differ for enantiomers and why training on odor mixtures generalizes to other odor mixtures.

eLife Assessment

This fundamental work substantially advances our understanding of OXT (oxytocin) neurons and OXTR (oxytocin receptor) expressions in mammalian brains using an advanced RNAscope at the single transcript level. The evidence supporting the conclusions is compelling using chromogenic assays and state-of-the-art microscopy. The work will be of broad interest to neuroscientists and endocrinologists.

eLife Assessment

This important study provides evidence, albeit still incomplete, that high-elevation species lose water at slower rates than low-elevation species. The findings imply that egg physiology may be a factor limiting the distributional range of bird species. While this work reinforces the need for all life stages to be considered when evaluating physiological adjustment to climate change, the analyses as presented by the authors do not clearly highlight the specific impact of species differences in influencing these adjustments.

eLife Assessment

In this manuscript, Jong et al. provide and validate a very useful resource for performing CRISPR screenings to study neutrophil differentiation and function by generating Hoxb8 cells that constitutively express Cas9. This library-screening approach has the potential to improve on the established lentiviral CRISPR-Cas9 editing of Hoxb8 cells. However, the technical advances provided are only incremental and the results presented in this study do not significantly further our understanding of these cells, but rather provide a good validation of their Cas9+ modified version.

eLife Assessment

In their study, Scherer and colleagues aim to use analyses of single-cell clones of murine granulocyte monocyte progenitors that are conditionally immortalized, and analyses of neutrophils derived from those clones to characterize an experimental system for studying neutrophil heterogeneity. The multi-omic and functional analyses reported are valuable but the strength of the evidence presented in support of them is incomplete because the study lacks a rigorous demonstration that the neutrophil-like cells that they derive are fully mature neutrophils.