Evaluated articles

eLife Assessment

Lu and colleagues developed an important imaging protocol that combines expansion microscopy, light-sheet microscopy, and image segmentation for use with the planarian Schmidtea mediterranea, a powerful model system for regeneration. This represents a substantial improvement on current standards and enables more rapid data acquisition. The utility of this solid protocol is demonstrated by quantifying several aspects of this flatworm's neural anatomy and musculature during homeostasis and regeneration. This work will be of interest to researchers looking to implement more systematic approaches towards imaging and quantifying intact specimens.

eLife Assessment

The study provides valuable insight into the biological significance of SARS-CoV-2 by using a series of computational analyses of viral proteins. While the evidence is solid, the reviewers noted a lack of clarity about the objectives of the analyses. While impactful for the field, the manuscript would benefit from improved presentation.

eLife Assessment

This valuable work explores the timely idea that aperiodic activity in human electrophysiology recordings is dynamically modulated in response to task events in a manner that may be relevant for behavioral performance. Moreover, the authors present solid evidence that, in some circumstances, these aperiodic changes might be misinterpreted as oscillatory changes.

eLife Assessment

This important work advances our understanding of parabrachial CGRP threat function. The evidence supporting CGRP aversive outcome signaling is solid, while the evidence for cue signaling and fear behavior generation is incomplete. The work will be of interest to neuroscientists studying defensive behaviors.

eLife Assessment

This study presents a valuable finding on the identification of a complex consisting of NHE1, hERG1, β1/integrin and NaV1.5 on the membrane of breast cancer cells. The evidence supporting the claims of the authors is somewhat incomplete. The inclusion of clarification of some experimental design and the amendment of cropping Western blot data would have strengthened the study. The work will be of interest to scientists working on breast cancer.

eLife Assessment

SGLT2 inhibitors (SGLT2i) have assumed important roles in reducing cardiovascular risk, particularly in those with diabetes. It has become appreciated that its protective effects are likely beyond their ability to lower blood sugar levels. This research presents a novel approach to studying the SGLT2i mechanism of action which is yet to be fully elucidated.

eLife Assessment

This important work addresses the role of Marcks/Markcksl during spinal cord development and regeneration. The study is exceptional in combining molecular approaches to understand the mechanisms of tissue regeneration with behavioural assays, which is not commonly employed in the field. The data presented is convincing and comprehensive, using many complementary methodologies.

eLife Assessment

This important work advances our understanding of factors influencing early childhood development. The large sample size and methodology applied make the findings of this study convincing; however, support for some of the claims made by the authors is incomplete. The work will be of interest to researchers in developmental science and early childhood pediatrics.

eLife Assessment

This study provides a valuable new perspective on how motor learning occurring in one state generalizes to new states (for example, a different limb posture). The proposed model improves upon previous theories in its ability to predict patterns of generalization, but evidence supporting this specific proposed model over possible alternatives is incomplete. The newly proposed theory appears promising but would be more convincing if its conceptual and theoretical basis were clearer and more rigorously derived.

eLife Assessment

This important work describes results from a set of simulation and empirical studies of a set-up assessing exploratory behavior in a potentially rewarding environment that contains danger. The core idea is that an instrumental agent can be helped to be both effective and safe, thus avoiding excessive danger, during exploratory behavior, if the influence of an independent Pavlovian fear is flexibly gated based on uncertainty. This work is grounded in previous foundational work on Pavlovian control of instrumental choice, and significantly extends prior work showing that the impact of Pavlovian reward biases can be flexibly gated. The conclusion that safe but effective exploration can be achieved based on a flexibly weighted combination of a Pavlovian and an instrumental agent is convincing.

eLife Assessment

In this important manuscript, the authors reveal novel findings on the role of exosomes in regulating filopodia formation. Filopodia are crucial for various cellular processes, including migration, polarization, directional sensing, and the formation of neuronal synapses. The authors convincingly demonstrate that exosomes, particularly those enriched with the protein THSD7A, play a significant role in promoting filopodia formation in both cancer cells and neurons.

eLife Assessment

This useful manuscript addresses some key molecular mechanisms on the neuroprotective roles of soluble TREM2 in neurodegenerative diseases. The study will advance our understanding of TREM2 mutations, particularly on the damaging effect of known TREM2 mutations, and also provides solid evidence why soluble TREM2 can antagonize Aβ aggregation.

eLife Assessment

This valuable study investigates how the size of an LLM may influence its ability to model the human neural response to language recorded by ECoG. Overall, solid evidence is provided that larger language models can better predict the human ECoG response. Further discussion would be beneficial as to how the results can inform us about the brain or LLMs, especially about the new message that can be learned from this ECoG study beyond previous fMRI studies on the same topic. This study will be of interest to both neuroscientists and psychologists who work on language comprehension and computer scientists working on LLMs.

eLife Assessment

This study presents an important finding on the involvement of a Caspase 3-dependent pathway in the elimination of synapses for retinogeniculate circuit refinement and eye-specific territory segregation. This work fits well with the concept of "synaptosis" which has been proposed in the past. The evidence supporting the claims of the authors is convincing, demonstrating that caspase-3 activation is essential for microglial elimination of synapses during both brain development and neurodegeneration. The work will be of interest to investigators studying cell death pathways, neurodevelopment, and neurodegenerative disease.

eLife Assessment

This important paper provides an unbiased landscape for the cerebellar cortical outputs to the brainstem nuclei. By conducting anatomical and physiological analyses of the axonal terminals of Purkinje cells, the data provides convincing evidence that Purkinje cells innervate brainstem nuclei directly. The results show that in addition to previously known inputs to vestibular and parabrachial nuclei, Purkinje cells synapse onto the pontine central grey nucleus but have little effect on the locus coeruleus and mesencephalic trigeminal neurons.

eLife Assessment

This valuable study addresses the potential roles of the master regulator of X chromosome inactivation, the Xist long non-coding RNA, in the regulation of autosomal genes. Using data from mouse cells, the authors propose that Xist can coat specific autosomal promoters, which in turn leads to the attenuation of their transcriptional activity. The evidence from individual genes is interesting, and the model aligns with recently published results from humans. However, despite some improvements during revision, the data and statistical analyses in the current study are not yet strong enough to allow for conclusive inferences, leaving the evidence for mouse cells behaving like human cells incomplete. The topic of the work is of broad interest, in particular to colleagues studying gene regulation and noncoding RNAs.

eLife Assessment

This useful manuscript reports on the crystal structures of two glycosaminoglycan (GAG) lyases from the PL35 family, along with in vitro enzyme activity assays and comprehensive structure-guided mutagenesis. The authors have addressed key concerns by incorporating additional docking analyses, validating the role of His188 in alginate degradation, and providing ICP-MS data to examine Mn²⁺ binding. While these improvements enhance the study, the study is incomplete due to the lack of enzyme-substrate complex structures and reliance on modeling which still limit mechanistic insight. Nonetheless, the revised manuscript presents a more complete analysis that will be of interest to specialists in carbohydrate-active enzymes.

eLife Assessment

In this valuable manuscript, the authors propose that the lysosomal protein LAPTM4B plays a role in suppressing the TGF-β/SMAD signaling pathway and suggest that enhancing LAPTM4B function could be a potential therapeutic strategy for alleviating bleomycin-induced lung fibrosis. The findings will be of interest to the lung disease field, and the data presented to support the authors' conclusions is solid. However, it remains unclear whether the suppressive effect of LAPTM4b on idiopathic pulmonary fibrosis is mediated by Nedd4l.

eLife Assessment

This manuscript provides valuable mechanistic insight into NSCLC progression, both in terms of tumour metastasis and the development of chemoresistance. The authors draw upon a range of techniques and assays and the evidence shown is solid and has been strengthened by incorporation of suggestions by the two reviewers. The work presented will be of interest to cancer biologists and more broadly to those interested in NSCLC translational studies.