Evaluated articles

eLife assessment

We believe this study has the potential to be fundamental for the field of microbial communication and compelling evidence with the chance of changing the current state-of-the-art in this area has been presented. This is will be of natural interest to the field of parasitology, but scientists in the general area of cell-to-cell communication will certainly benefit from this contribution too. A major strength of this manuscript is the clear demonstration of the role of cytoneme-like structures and extracellular vesicles in parasite communication using the Trichomonas vaginalis model. Given the potential of these findings, the authors could deepen their discussion and perspectives for other areas.

eLife assessment

This study reports a cutting-edge set of experiments examining evolutionary models of paralog function differentiation for the mammalian ribosomal proteins eS27 and eS27L. No differentiated roles were identified for either paralog, but the paralogs are differentially expressed, and they preferentially associate with different transcript classes. Reciprocal switching of their coding sequences yielded no detectable phenotypes, but loss of either paralog resulted in lethality at different developmental stages, suggesting that subfunctionalized expression patterns underlie the retention of these paralogs. The work will be of interest to colleagues studying the evolution and diversification of ribosomes.

eLife assessment

The authors show that tunneling nanotubes or TNTs are used by cells to transfer full-length mRNAs. The data show that as much as 1% of the endogenous mRNA are passed between cells by this procedure. The transferred mRNA affect the transcriptome of the acceptor cells thus highlighting the significance of this nanotube mediated trafficking of mRNA between cells. We appreciate the difficulty of this exercise. The strength of the presented evidence could be questioned based on technical limitations.

eLife assessment

After mating, animals show a repertoire of behavioural changes. In flies, this includes an increase in egg-laying, salt, and food (particularly protein) consumption, and a concomitant decrease in sexual receptivity. This valuable study compellingly shows that flies also have an increased sugar appetite and they identify the central brain circuitry that controls this increase in the mated condition.

eLife assessment

The large genetic association studies conducted in East Africa have shown that the Dantu blood group provides substantial protection against severe malaria since it increases the surface tension of red blood cells making it harder for malaria parasites to invade. In this important work, the authors show that parasite growth is indeed restricted in vivo by testing this hypothesis in adult Kenyan volunteers infected with P. falciparium under careful monitoring. They were able to show convincingly that indeed, parasite growth was reduced amongst Dantu adults.

eLife assessment

Seelbinder et al. describe a new method for perturbing chromatin in living cells by local heating. Employing this approach, the authors uncover interesting behaviors that underscore the variability in the mechanical response of subnuclear domains and structures. The study is timely, and if some conceptual and technical aspects are improved, it should be of broad interest to both the cell biophysics and cell biology communities, in particular since the method can also be applied to study mechanical relationships of subcellular compartments in other cellular and multicellular systems.

eLife assessment

This study presents a useful inventory of chromatin modifications and genes that are up- and down-regulated during cerebellar development in vivo and in primary culture. The main claims were incomplete and would benefit from further analysis and/or additional experiments. The work will be of interest to biologists working on brain development.

eLife assessment

This study presents important findings regarding the quantification of dynamics in fish communities in changing ecosystems by combining a large-scale environmental DNA metabarcoding time series with novel statistical approaches. The methods are convincing, with controlled experiments, thorough statistical analyses, and a substantial dataset covering two years of detailed observation, which can provide sufficient power to detect fine-scale ecological interactions. This work is relevant for informing future research on assessing community stability under climate change.

eLife assessment

The authors use a combination of structural and MD simulation approaches to characterize phospholipid interactions with the pentameric ligand-gated ion channel, GLIC. The general agreement between structures and simulations increases confidence in the description of the lipid interaction poses and provides a solid basis for the prediction of a state-dependent interaction site where lipids could dynamically modulate channel gating. The results will be very useful to understand the nature of phospholipid interactions with pentameric ligand-gated ion channels, although the functional or structural significance of these lipid interactions remains to be verified.

eLife assessment

This study reports the important finding that there appears to be a timer that monitors the repair of DNA after damage and regulates whether cells are subsequently able to enter mitosis. The authors identify proteins important for this decision and propose a mechanism supported by solid but not conclusive data. This study will be of interest to researchers in the fields of DNA damage repair and cell cycle control.

eLife assessment

The authors have uncovered a new target that may be exploited to selectively kill BRCA2 mutant cancer cells. Strengths of the study include the novel pathway uncovered (ROCK kinases) and the strong data in support of the findings. Weaknesses include limited detail regarding the mechanism of BRCA2-specific cell death by ROCK kinase inhibitors, limited information on why some ROCK kinase inhibitors are not effective, as well as whether the cell killing in BRCA2 wild-type cells by ROCK kinase inhibitors is the same mechanism but just attenuated. The work will be of interest to cancer biologists and colleagues studying kinases.

eLife assessment

This manuscript is of interest to readers in the field of neural development and neurodegeneration. The study is important as it examines two disease-causing mutations within the homeodomain transcription factor Cone-Rod Homeobox (CRX) that causes retinopathy in humans. The data are solid and the work contributes to our understanding of the underlying pathogenetic mechanisms.

eLife assessment

This study combines experiments in developing embryos and embryo extracts to investigate a fundamental relationship in biology - how the size of mitotic chromosomes scales with changes in cell size during development. By combining the unique tools available in the Xenopus system with modern genomic approaches, the authors convincingly demonstrate that mitotic chromosome scaling is mediated by differential loading of maternal chromatin remodeling factors during interphase. Although it remains unclear exactly how these factors impact chromosome size, the findings reported here will be of broad interest to the cell biology community and are likely to spawn new avenues of experimental inquiry aimed at understanding intracellular scaling relationships.

eLife assessment

This study provides important estimates from international cancer screening data repository about the impact of the COVID-pandemic related disruptions on cancer screening programs in selected low- and middle-income countries. The evidence supporting the study is solid and relies on national-level screening program attendee volumes and assessments of screen positives during 2019 (pre-pandemic) and 2020 (during the pandemic). The study provides real-world data estimates of proportions/volumes of missed screenings due to pandemic control measures (lockdowns and closures) and may contribute to future modelling efforts for measuring the impact on late/advanced stage detection and excess case burden and mortality.

eLife assessment

This paper addresses an important clinical concern which is how the antidepressant ketamine exerts its effects acts rapidly. The authors suggest the reason is that ketamine increases glutamatergic transmission in the hippocampus. The strengths are the data are mostly very good, and the limitations are a lack of compelling evidence that the hippocampus is the location where effects occur, as well as several other issues.

eLife assessment

This important study will be of interest to those working on mycobacterial signal transduction. A combination of experiments provides convincing evidence to show how universal stress proteins bind to cAMP and function by direct sequestration of the second messenger. Although the methods, data and analyses broadly support the conclusions, the main claims are only partially supported and can be strengthened through further analytic approaches.

eLife assessment

Villalobos-Cantor et. al. describe a new technique for cell-type specific in vivo labeling of nascent peptides, which they call POPPi. POPPi is based on sequence-independent incorporation of the puromycin analog OPP into an elongating peptide, which also simultaneously terminates the growing peptide. To achieve cell-type-specific labeling, the authors used an OPP derivative, PhAc-OPP, as the labeling substrate. The method is potentially interesting but needs further characterization to be able to assess its use.

eLife assessment

This important study combines a screen of known N6-methyladenine (m6A)-dependent RNA modifying factors to identify ALKBH5 as critical in crush injury response. They demonstrate through gain and loss of function an effect on ALKBH5 m6A-dependent Lpin2 mRNA stability during injury-induced axon regeneration in both dorsal root ganglia nerve and optic nerve regeneration. The results provide new insight into the role of RNA modification on neural injury. However, the limitations of the experimental design on the conclusions drawn require additional consideration. With additional control experiments and further consideration of the limitations, the paper will provide a link between N6-methyladenine and neurotrauma.

eLife assessment

This study describes important results and convincing evidence linking myofibroblast senescence in the aged heart with a pro-arrhythmogenic phenotype. This is in turn related to higher mortality after myocardial infarction in the aged rabbit heart. These constitute important empiric as opposed to detailed findings. They nevertheless will be of interest to clinician scientists studying cardiac function and disease.

eLife assessment

Non-communicable diseases (NCDs) are rising rapidly in urbanizing populations in many parts of the developing world, including in sub-Saharan Africa. Temba and colleagues show important evidence that healthy Tanzanians display a pro-inflammatory phenotype with enrichment of specific immune-metabolic pathways. Dood-derived metabolites were identified as an important driver of inflammation-related molecules. These findings provide solid evidence that the dietary transition that occurs in urbanizing areas in sub-Saharan Africa may contribute significantly to the increased incidence of non communicable diseases in this part of the world.