Evaluated articles

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 but lacked in vivo support. Despite its elegant design and many strengths, the evidence supporting the claims of the authors is incomplete, particularly regarding whether Caspase-3 expression can really be isolated to synapses vs locally dying cells, whether microglia direct or instruct synapse elimination, and whether astrocytes are also involved. The work will be of interest to investigators studying cell death pathways, neurodevelopment, and neurodegenerative disease.

eLife Assessment

This valuable 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 provide 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 potential roles of the master regulator of X chromosome inactivation, the Xist long non-coding RNA, in autosomal gene regulation. 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, complementing recently published results from humans. While the evidence from individual genes is suggestive, shortcomings in the data and statistical analyses leave the evidence currently incomplete. The work would be of interest to anyone studying gene regulation and noncoding RNAA

eLife Assessment

This 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. While the study provides structural insights into the broad substrate specificity of these enzymes, the incomplete structural models, lack of key data such as Mn²⁺ binding confirmation, and reliance on basic docking methods diminish the overall impact. Although the work is useful for specialists in carbohydrate-active enzymes, additional data, and more rigorous analysis are required to present a complete study.

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 although the evidence shown is solid, suggestions by the two reviewers will strengthen the message. The work presented will be of interest to cancer biologists and more broadly to those interested in NSCLC translational studies.

eLife Assessment

The manuscript by Kolbeck and co-workers is an important contribution to understanding the physical mechanism that controls a key step in the retroviral infectious cycle. The authors employ a wide range of experimental techniques, complemented with Montecarlo simulations, that result in convincing evidence of compaction of HIV DNA by the viral integrase. This manuscript would benefit from in-depth discussion and analysis of the biophysical implications of the results.

eLife Assessment

This valuable paper reports image analysis pipelines for the automated segmentation of micronuclei and the detection and sorting of micronuclei-containing cells, which could be powerful tools for researchers studying micronuclei. While the development of the pipelines is solid, a proof-of-principle experiment is not entirely conclusive and leaves open the possibility that additional refinements are required, which would be facilitated by a more detailed explanation of the methods used.

eLife Assessment

This study presents a valuable finding in understanding the role of plectin in the development and progression of hepatocellular carcinoma (HCC). The evidence supporting the conclusions is convincing because multiple orthogonal ways were used to demonstrate the requirement of this target in liver cancer models. However, the study is incomplete as the downstream molecular activities of plectin that mediate the cancer phenotypes were not fully evaluated.

eLife Assessment

This manuscript presents a valuable finding on the impact of FRMD8 loss on tumor progression and the resistance to tamoxifen therapy. The author conducted systematic experiments to explore the role of FRMD8 in breast cancer and its potential regulatory mechanisms, confirming that FRMD8 affects tamoxifen resistance and convincingly validating this hypothesis through a series of experiments.

eLife Assessment

This valuable study describes how a single effector of the Type Six Secretion System (T6SS) has two distinct enzymatic functions that together may contribute to bacterial survival and dynamics in a community and provide potential for developing new antimicrobial compounds. The authors have deployed a range of methods in biochemistry, microbiology, and microscopy, generating solid data that support the main assertions. While the manuscript could benefit from additional clarifying experiments and a more detailed discussion of the methods, it will appeal to those studying T6SS, particularly those interested in effectors and bacterial enzymes.

eLife Assessment

This article presents valuable findings on the impact of climate change on odonates, integrating phenological and range shifts to broaden our understanding of biodiversity change. The study leverages extensive natural history data, offering a combined analysis of temporal trends in phenology and distribution and their potential drivers. The support for the findings is solid, though additional clarification regarding the methods and alternative sensitivity analyses could make the conclusions stronger.

eLife Assessment

In this potentially important study, the authors conducted extensive atomistic and coarse-grained simulations as well as a lattice Monte Carlo analysis to probe the driving force and functional impact of supercomplex formation in the inner mitochondrial membrane. The study highlighted the importance of membrane mechanics to the supercomplex formation and revealed differences in structural and dynamical features of the protein components upon complex formation. In its current form, the analysis is considered incomplete, especially concerning the contributions of membrane mechanics and allosteric coupling of key regions.

eLife Assessment

This work provides a potentially valuable framework for understanding the primary causes of disease. However, the evidence supporting the utility of the approach is incomplete given the reliance on strong assumptions about the underlying causal mechanisms.

eLife Assessment

This study investigates the role of Hox genes in determining the position of the forelimb bud using experimental loss- and gain-of-function approaches in chicken embryos, concluding that Hox4 and Hox5 provide permissive signals for forelimb formation throughout the neck region, while the final forelimb position is determined by the instructive signals of Hox6/7 in the lateral plate mesoderm. These results could potentially be fundamental to our understanding of Hox patterning. However, the evidence supporting these conclusions is incomplete; while the gain-of-function experiments are well supported, the loss-of-function experiments using dominant-negative constructs lack sufficient controls, and could be the result of an experimental artifact.

eLife Assessment

This important study provides insights into the role of maternal behavior in the learning and ontogeny of vocalization, finding evidence that the maternal behavior of sac-winged bats (Saccopteryx bilineata) can influence the learned territorial songs of their pups. The behavioral analyses are solid, although a more comprehensive and quantitative description of the babblings and the female displays would have strengthened the study. The work will interest biologists and neuroscientists studying vocal learning and its evolution.

eLife Assessment

These are valuable findings for those interested in how neural signals reflect auditory speech streams, and in understanding the roles of prediction, attention, and eye movements in this tracking. However, the evidence as it stands is incomplete. Further details are needed on how the observed quantities relate to the relevant theoretical claims and mathematical models. Moreover, additional motivation is required for several analytical choices.

eLife Assessment

This is an important study demonstrating that cholecystokinin is a key modulator of auditory thalamocortical plasticity during development and in young adults but not aged mice, though the cortical application of this neuropeptide in older animals appears to go some way to restoring this age-dependent loss in plasticity. A strength of this work is the use of multiple experimental approaches, which together provide convincing support for the proposed involvement of cholecystokinin. Nevertheless, the specificity of the electrical and optical stimulation experiments requires further validation and some key details are missing in the presentation and discussion of these findings. This work is likely to be influential in opening up a new avenue of investigation into the roles of neuropeptides in sensory plasticity.

eLife Assessment

This study uses C. elegans, a poikilothermic ("cold-blooded") animal, to investigate the interesting question of how cells and organisms adapt to prolonged exposure to cold temperature. The study employed ribosome profiling and RNAseq analyses and provides a useful inventory of genes changed in cold adapted nematodes. However, the overall conclusions that 1) translation is ongoing at a low rate and 2) IRE mediated transcriptional changes play a significant role in cold adaptation are incompletely supported by the evidence provided. The authors are encouraged to conduct additional bioinformatic analyses and rewrite the manuscript to more accurately reflect the evidence provided.