Evaluated articles

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.

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 machine learning-based image analysis pipelines for the automated segmentation of micronuclei and the detection and sorting of micronuclei-containing cells. These are powerful new tools for researchers who study micronuclei and their physiologic consequences. The analysis of the new tools and their benchmarking is rigorous and convincing; applications and remaining limitations are well explained in the paper.

eLife Assessment

This valuable study investigated the role of PLECTIN, a cytoskeletal crosslinker protein, in hepatocellular carcinoma development and progression. Using a liver-specific Plectin knockout mouse model, the authors showed solid evidence that PLECTIN is critical for hepatocarcinogenesis, since inhibition of PLECTIN suppressed tumor formation in multiple models. They also show that PLECTIN is key for HCC invasion and metastasis. They show a correlation between PLECTIN inhibition and attenuated FAK, MAPK/ERK, and PI3K/AKT signaling.

eLife Assessment

The research presents valuable findings on the impact of FRMD8 loss on tumor progression and resistance to tamoxifen therapy. Through a series of convincing and systematic experiments, the author thoroughly investigates the role of FRMD8 in breast cancer and its underlying regulatory mechanisms. The study confirms that FRMD8 holds potential as a therapeutic target for reversing tamoxifen resistance, offering helpful insights for future treatment strategies.

eLife Assessment

This important study describes how a single effector of the Type Six Secretion System (T6SS) has two distinct functions, which may contribute to bacterial survival and the development of novel antibacterials. The authors utilized various methods in biochemistry, microbiology, and microscopy to produce convincing data supporting their claims about the protein's function; however, they could clarify the implications for non-experts to enhance the accessibility of this work. This manuscript is of interest to those studying T6SS, particularly those interested in effectors and bacterial enzymes.

eLife Assessment

The article presents important 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 convincing analysis of temporal trends in phenology and range limit and their potential drivers.

eLife Assessment

In this 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 major contribution from membrane mechanics to the supercomplex formation and revealed interesting differences in structural and dynamical features of the protein components upon complex formation. Upon revision, the analysis is considered solid, although the magnitude of estimated membrane deformation energies seem somewhat large. Overall, the study is thorough, creative and the impact on the field of bioenergetics is expected to be significant.

eLife Assessment

This work provides an important framework for understanding the primary causes of disease. While the theoretical results rely on strong assumptions about the underlying causal mechanisms, the authors provide solid empirical evidence that the framework is robust to modest violations of these assumptions.

eLife Assessment

This important study provides the first putative evidence that alteration of the Hox code in neck lateral plate mesoderm is sufficient to induce ectopic development of forelimb buds at neck level. The authors use both gain-of-function (GOF) and loss-of-function (LOF) approaches in chick embryos to test the roles of Hox paralogy group (PG) 4-7 genes in limb development. The GOF data provide strong evidence that overexpression of Hox PG6/7 genes are sufficient to induce forelimb buds at neck level. However, the experiments using dominant negative constructs are lacking some key controls that are needed to demonstrate the specificity of the LOF effect rendering the work as a whole incomplete.

eLife Assessment

This important study provides insights into the role of maternal behavior in the learning and ontogeny of vocalization. It finds evidence that the maternal behavior of sac-winged bats (Saccopteryx bilineata) can influence the learned territorial songs of their pups. The behavioral analyses are convincing, using longitudinal acoustic recordings and behavioral monitoring of individual mother-pup pairs across development and multiple wild bat colonies. The work will be relevant to a broad audience interested in the evolution and development of social behavior as well as sensory-motor learning.

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 analyses are needed to clarify how the observed results relate to the relevant theoretical claims.

eLife Assessment

This is an important study demonstrating that cholecystokinin is a key modulator of auditory thalamocortical plasticity during development and in young adult but not aged mice, though 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. 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 useful study reveals that as C. elegans, a poikilothermic ("cold-blooded") animal, adapt to cold (4ºC), they display a drastic reduction in translation (assessed by polysome profiling and SUNSET). The remaining translation (by ribo-seq) correlates with mRNA levels (by RNA-seq), and the changes in gene expression at least partially require IRE-1, an established endoplasmic reticulum stress sensor. The reviewers consider the data assessing global translation and RNA expression upon cold exposure and the data demonstrating the requirement of ire-1 to be solid, but the conclusion that "transcription" is the major regulatory step and "lipid changes" can be a signal for IRE-1 activation in cold adapted worms needs substantially more evidence. Overall, this study demonstrated a good correlation between translation and RNA levels and yielded an inventory of gene changes as C. elegans adapt to cold, and will be of general interest to researchers interested in stress response and cold adaptation.

eLife Assessment

In this important study, the authors reconstruct the evolutionary history of a large and widespread group of freshwater fishes (Nemacheilidae) across Eurasia since the early Eocene, based on molecular phylogenetic analysis with very comprehensive samplings including 471 specimens belonging to 250 living species. The authors convincingly infer that range expansions of the family were facilitated by tectonic connections, favorable climatic conditions, and orogenic processes, adding to our understanding of the effects of climatic change on biodiversity during the Cenozoic. This work is of interest to evolutionary biologists, ichthyologists, paleontologists, and general readers.

eLife Assessment

This important study highlights the key role of the gut-liver axis mediated by LPS in causing hepatic steatosis. The authors provide solid evidence, in vivo, in vitro, and in silico, for the role of acyloxyacyl hydrolase in mediating this effect using KO mice subjected to MASD-inducing diets. The findings are significant for the liver research community and others interested in the gut-liver axis.