Evaluated articles

eLife assessment

This important study investigates, from Drosophila to mammals, the role of the Forkhead box O (FoxO) transcription factors in airway epithelial cells' response to stressors including hypoxia, temperature variations, and oxidative stress. The findings suggest a conserved role of FoxO in maintaining airway homeostasis across species. However, limitations in the specificity and concerns with the loss-of-function experiments render the evidence presented incomplete. Nonetheless, this study highlights FoxO's potential relevance in respiratory diseases like asthma and offers insights into potential therapeutic targets for conditions affecting airway health.

eLife assessment

This important study reveals how Drosophila may be used to investigate the role of missense variants in the gene PLCG1 related to human disease in case studies. The evidence that most of these variants have a gain-of-function effect in the fly is convincing and supportive of their pathogenic effect. With some additional control experiments to assess overexpression toxicity, this work would be of relevance to human and Drosophila geneticists alike.

eLife assessment

This fundamental study provides insights into how pathogens respond, on a systemic level including several gene targets and clusters, to selected antimicrobial molecules. Compelling evidence is provided, through multi-omics and functional approaches, that very similar molecules originally designed to target the same bacterial protein act differently within the context of the whole set of cellular transcripts, expressed proteins, and pre-lethal metabolic changes. Given the incredibly fast accumulation of omics data to date and the much slower capacity of extracting biologically relevant insights from big data, this work exemplifies how the development of sensitive data analysis is still a major necessity in modern research.

eLife assessment

In this work, the authors use a Drosophila adult ventral nerve cord injury model extending and confirming previous observations; this important study reveals key aspects of adult neural plasticity. Taking advantage of several genetic reporter and fate tracing tools, the authors provide solid evidence for different forms of glial plasticity, that are increased upon injury. The data on detected plasticity under physiologic conditions and especially the extent of cell divisions and cell fate changes upon injury would benefit from validation by additional markers. The experimental part would improve if strengthened and accompanied by a more comprehensive integration of results regarding glial reactivity in the adult CNS.

eLife assessment

This important work provides insights into the neural mechanisms regulating specific parental behaviors. By identifying a key role for oxytocin synthesizing cells in the paraventricular nucleus of the hypothalamus and their projections to the medial prefrontal cortex in promoting pup care and inhibiting infanticide, the study advances our understanding of the neurobiological basis of these contrasting behaviors in male and female mandarin voles. The evidence supporting the authors' conclusions is solid but lacks some critical methodological detail. The work should be of interest to researchers studying neuropeptide control of social behaviors in the brain.

eLife assessment

This useful study reports the behavioural and physiological effects of the longitudinal activation of neurons associated with negative experiences. The main claims of the paper are supported by solid experimental evidence, but the specificity of the long-term manipulation requires additional validation. This study will be of interest to neuroscientists working on memory.

eLife assessment

This method paper proposes a valuable Oscillation Component Analysis (OCA) approach, in analogy to Independent Component Analysis (ICA), in which source separation is achieved through biophysically inspired generative modeling of neural oscillations. The empirical evidence justifying the approach's advantage is incomplete. This work will be of interest to cognitive neuroscience, neural oscillation, and MEG/EEG.

eLife assessment

This important study provides previously unappreciated insights into the functions of protist eIF4E 5'mRNA cap-binding protein family members, thereby contributing to a better understanding of translation regulation in these organisms. The authors provide solid evidence to support the major conclusions of the article. However, the study may further benefit from establishing whether all of the eIF4E family members are indeed involved in translation and more direct evidence for the selectivity of their binding.

eLife assessment

This study uses ex vivo live imaging of the uterus, uterotubal junction, and oviduct post-mating to test the role of the sperm hook in the house mouse (Mus musculus) in sperm movement which could be interesting to evolutionary biologists. The work is useful as their live imaging revealed sperm behaviors in the female tract that have not been previously reported. However, the strength of evidence is incomplete since the limited quantification of the data is insufficient and the extensive speculation on the functions of these sperm behaviors is not supported by sufficient experimental evidence to support their conclusions.

eLife assessment

This study provides valuable information on the mechanism of PepT2 through enhanced-sampling molecular dynamics, backed by cell-based assays, highlighting the importance of protonation of selected residues for the function of a proton-coupled oligopeptide transporter (hsPepT2). The molecular dynamics approaches are convincing, but with limitations that could be addressed in the manuscript, including lack of incorporation of a protonation coordinate in the free energy landscape, possibility of protonation of the substrate, errors with the chosen constant pH MD method for membrane proteins, dismissal of hysteresis emerging from the MEMENTO method, and the likelihood of other residues being affected by peptide binding. Some changes to the presentation could be considered, including a better description of pKa calculations and the inclusion of error bars in all PMFs. Overall, the findings will appeal to structural biologists, biochemists, and biophysicists studying membrane transporters.

eLife assessment

This important study reports the formation of a new organelle, called giant unilocular vacuole (GUVac), in mammary epithelial cells through a macropinocytosis-like process. The evidence supporting conclusions is solid, using state-of-the-art cell biology techniques. This work will be of interest to cell biologists and contribute to the understanding of cell survival mechanisms against anoikis.

eLife assessment

The manuscript presents a useful model for the field of endosome maturation, providing perspective on the role of the deubiquitinating enzyme UPS-50/USP8 in the process. The evidence presented in the paper is clear, incorporating well-designed experiments that suggest the dual actions of UPS-50 and USP8 in the conversion of early endosomes into late endosomes. Overall, the work is solid and centers on an intriguing subject.

eLife assessment

This fundamental study offers new structural insights into the form and functions of the ribosome-translocon complex. Through a combination of in vitro translation, cryoEM imaging, and comprehensive AlphaFold comparative modeling, the authors offer convincing support for the lateral gate model of co-translational ER protein biogenesis, including the location of RAMP4 near the Sec61 lateral gate and the plausible role of helix 59 of the 28S ribosomal RNA as a determinant of the positive-inside rule. While the reviewers identified minor limitations, such as the need to validate RAMP4 presence with orthogonal measures, these results will be broadly impactful.

eLife assessment

In this valuable study, Kumar et al., provide evidence suggesting that the p130Cas drives the formation of condensates that sprout from focal adhesions to cytoplasm and suppress translation. Pending further substantiation, this study was found to be likely to provide previously unappreciated insights into the mechanisms linking focal adhesions to the regulation of protein synthesis and was thus considered to be of broad general interest. However, the evidence supporting the proposed model was incomplete; additional evidence is warranted to substantiate the relationship between p130Cas condensates and mRNA translation and establish corresponding functional consequences.

eLife assessment

This study provides a useful strategy for treating mouse cutaneous squamous cell carcinoma (mCSCC) with serum derived from mCSCC-exposed mice. The exploration of serum-derived antibodies as a potential therapy for curing cancer is particularly promising but the study provides inadequate evidence for specific effects of mCSCC-binding serum antibodies. This study will be of interest to scientists seeking a novel immunotherapic strategy in cancer therapy.

eLife assessment

This study presents useful findings on an unresolved question of cerebellar physiology: Do synapses between Purkinje cells and granule cells, made by the ascending part of the granule cells' axon, have different properties than those made by parallel fibers? The authors conducted patch-clamp recordings on rat cerebellar slices and found a new type of plasticity in the synapses of the ascending part of granule cell axons. While the finding may contribute to a better understanding of cerebellar function, the results are still incomplete because the shift in the baseline recording may have influenced the readout of long-term plasticity.

eLife assessment

This important study demonstrated that ablation of astrocytes in the lumbar spinal cord not only reduced neuropathic pain but also caused microglia activation. The findings presented add considerable value to the current understanding of the role of astrocyte elimination in neuropathic pain, offering convincing evidence that supports existing hypotheses and insights into the interactions between astrocytes and microglial cells, likely through IFN-mediated mechanisms. This study may also offer a new therapeutic strategy for the treatment of debilitating neuropathic pain in patients with SCI.

eLife assessment

This important study reports the use of a surveillance approach in identifying emerging diseases, monitoring disease trends, and informing evidence-based interventions in the control and prevention of livestock abortions, as it relates to their public health implications. The data support the convincing finding that abortion incidence is higher during the dry season, and occurs more in cross-bred and exotic livestock breeds. Aetiological and epidemiological data can be generated through established protocols for sample collection and laboratory diagnosis. These findings are of potential interest to the fields of veterinary medicine, public health, and epidemiology.

eLife assessment

This study reports useful data suggesting the critical roles of two ancient proteins, XAP5 and XAP5L, in controlling the transcriptional program of ciliogenesis during mouse spermatogenesis. However, this study is considered incomplete because the data only partially support the conclusion. This work will be of interest to biomedical researchers who work on ciliogenesis and reproduction.

eLife assessment

In this paper, the male sex-lethal (MSL) complex of proteins and RNA is studied through a domain analysis of one of its components, MSL1, and its interaction with others. While these results could be useful to researchers in the field, several studies have shown that the view that the MSL complex mediates dosage compensation is no longer considered tenable. Since there are many ways to alter viability, claims based on sex-specific viability as a reflection of dosage compensation should be viewed with much caution, and the evidence is currently considered inadequate to support the claims.