Evaluated articles

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.

eLife assessment

This study presents a valuable finding that the blood-brain barrier functionality changes with age and differs between males and females. The analysis is solid, comprising a large and racially diverse dataset, and utilizes a contrast-agent-free MRI method. Since limited work has been done in the MRI field on the blood-brain barrier using this method, this study is of great interest to neuroimaging researchers and clinicians.

eLife assessment

This work substantially advances our understanding of pharmacological inhibition of SWI/SNF as a therapeutic approach for cancer. The study is well-written and provides compelling evidence, including comprehensive datasets, compound screens, gene expression analysis, epigenetics, as well as animal studies. This study provides a fundamental advance for the uveal melanoma research field that might be exploited to target this deadly cancer and more generally for targeting transcriptional dependency in cancers.

eLife assessment

This useful study investigates the impact of disrupting the interaction of RAS with the PI3K subunit p110α in macrophage function in vitro and inflammatory responses in vivo. Solid data overall supports a role for RAS-p110α signalling in regulating macrophage activity and so inflammation, however for many of the readouts presented the magnitude of the phenotype is not particularly pronounced. Further analysis would be required to substantiate the claims that RAS-p110α signalling plays a key role in macrophage function. Of note, the molecular mechanisms of how exactly p110α regulating the functions in macrophage have not yet been established.

eLife assessment

This paper presents a valuable automated method to track individual mammalian cells as they progress through the cell cycle using the FUCCI system. The authors have developed a technique for analyzing cells that grow in suspension and used their method to look at different tumor cell lines that grow in suspension and determine the effect of drugs that directly affect the cell cycle. They show solid evidence that the method can be applied to both adherent and non-adherent cell lines. This paper will be of interest to cell biologists investigating cell cycle effects.

eLife assessment

The study is useful by attempting to present a new approach of combining two measurements (pHLA binding and pHLA-TCR binding) in order to refine predictions of which patient mutations are likely presented to and recognized by the immune system, but the evidence is incomplete. Whereas the novel methodology proposed is compelling, this article lacks a detailed explanation of the chosen model. The experimental validation confirming the computational predictions with actual immune responses is limited due to sample constraints.

eLife assessment

This is an important study that investigates how neural networks can learn to stochastically replay presented sequences of activity according to learned transition probabilities. The authors use error-based excitatory plasticity to minimize the difference between internally predicted activity and stimulus-driven activity, and inhibitory plasticity to maintain E-I balance. The approach is solid but the choice of learning rules and parameters is not always always justified, lacking a formal derivation and concrete experimental predictions.