Evaluated articles

eLife assessment

This important study unravels the interaction between effort cost, pupil-indexed brain state, and movement (saccadic) vigor during foraging decisions in marmoset monkeys. Based on a normative computational model, the authors derive the prediction that anticipated effort should affect both decisions and movement vigor during foraging; and then provide solid behavioural and pupillometric evidence for this prediction in a foraging task. This paper will be of interest to decision and motor neuroscience as well as to all researchers studying animal behavior.

eLife assessment

This is an important paper that links distinctive stinging behavior of two related anemones occupying different ecological niches to varying inactivation properties of voltage-gated calcium channels conferred by auxiliary Cavβ subunits. Further convincing evidence is provided that these differences are mediated by alternative splicing of Cavβ subunit of the calcium channel. The study will be of interest to scientists studying Ca2+ signaling, ion channel biophysicists, and marine biologists.

eLife assessment

This important paper uses a genome-wide, massively parallel reporter assay to determine how CpG methylation affects regulatory sequences that control the expression of human genes. The authors provide compelling evidence that methylation not only influences baseline activity of regulatory sequences but also the magnitude of acute responses to environmental stimuli. The findings are of broad interest, and the extensive data set will likely become a key resource for the community.

eLife assessment

This study describes important findings on how a core component of the circadian clock impacts the effect of dietary restriction (DR) on longevity and fecundity in Drosophila, which lead the authors to postulate rhythmic control of proteostasis in the fat body as a critical aspect of DR effects. The evidence presented is still incomplete, not fully supporting the conclusions of the study, as alternative hypotheses/explanations have not yet been systematically explored. The work will nevertheless be of substantial interest to researchers working in circadian and cell biology, metabolism, and aging, with an interesting hypothesis to be explored further.

eLife assessment

In this valuable study, advanced simulation methodologies are used to extract the mechanisms of inactivation for the potassium ion channel KcsA. The string method approach provides solid evidence that reveal features associated with the interplay between gate size and collapse of the selectivity filter, as well as remarkable differences between different force fields. While this manuscript does not address recent discoveries in K channel inactivation involving dilated selectivity filter structures obtained by Xray and cryo-EM, it does help us understand the KcsA constriction process. With added descriptions and analysis of collective variables, improved reproducibility of results, consistency between string method free energies and unbiased simulations, and improved transition rate calculation, this manuscript will be of interest to the ion channel field.

eLife assessment

The primary goal of this paper is to examine microtubule detyrosination as a potential therapeutic target for axon regeneration. The valuable findings of this study provide convincing evidence for mechanistic links between microtubule detyrosination and neurite outgrowth in vitro and some evidence for axon regeneration in vivo.

eLife Assessment

This important study uses machine learning-based network analysis on transcriptomic data from different tissue cell types to identify a small set of conserved (pan-tissue) genes associated with changes in cell mechanics. The new method, which provides a new type of approach for mechanobiology, is accessible, compelling, and well-validated using in silico and experimental approaches. The study provides motivation for researchers to test hypotheses concerning the identified five-gene network, and the method will be strengthened over time with expanded sets of validations, such as testing genes with hitherto unknown roles and different perturbation techniques.

eLife Assessment

This important study combines virology experiments and mathematical modeling to determine the nuclear export rate of each of the eight RNA segments of the influenza A virus, leading to the proposal that a specific retention of mRNA within the nucleus delays the expression of antigenic viral proteins. The proposed model for explaining the differential rate of export is compelling, going beyond the state of the art, but the experimental setup is only in partial support and further studies will be needed to confirm the proposed mechanism.

eLife assessment

This study presents the valuable finding that sustained calcium signaling in induced-Treg (iTreg) cells can lead to the loss of Foxp3 expression and iTreg identity by altering the chromatin landscape. The evidence supporting the claims of the authors is convincing. The work will be of interest to immunologists working on Treg cell therapy.

eLife assessment

The study provides useful data supporting prior findings that mitochondria in cultured cells maintain a temperature that is up to 15°C above the external temperature at which cultured cells are maintained. The evidence supporting the hypothesis is solid, although direct measures of temperature in isolated mitochondria or comparison with other cellular compartments would have strengthened the ability to interpret the relevance of the findings. Nevertheless, the bioenergetic implications of the work will be of interest to cell biologists, biochemists, and physiologists.

eLife assessment

This study provides useful findings regarding the capacity for mental state attribution on the Frith-Happé task in a highly social non-human primate species, the marmoset. The methods are solid, integrating validated brain imaging and eye-tracking techniques, however, the theoretical analysis is incomplete due to the omission of a "goal-directed condition." The inclusion of the goal-directed condition would enable a stronger interpretation of the findings and would be of broad interest to neuroscientists working in social and affective sciences.

eLife assessment

This study provides important new insights into how learning affects behavior in the Drosophila model. Using a combination of connectomics, neurophysiology, and behavioral analysis, a small group of neurons in the Drosophila brain that integrates learned odor valences and promotes odor tracking by driving upwind orientation and movement is described. The study's conclusion is supported by convincing evidence and rigorous quantitative analysis. Insights from the neural circuit mechanism that translates learning-induced plasticity into appropriate behavioral actions will be of broad interest to neuroscientists.

eLife assessment

This simulation work with open source code will be of interest to those developing visual prostheses and demonstrates useful improvements over past visual prosthesis simulations. While the authors provide compelling evidence to support the generation of individual phosphenes and integration into deep-learning algorithms, the assumptions beyond individual phosphenes and the overall validation process are inadequate to support the claim of fitting the needs of cortical neuroprosthetic vision development.

eLife assessment

This study provides useful information on the impact of the pandemic on the quantity of healthcare delivered to patients with pancreatic cancer in England. The authors showed that there was no difference in the number of diagnoses of pancreatic cancer during the pandemic compared to the preceding 5-year period, but a reduction in surgical resections by nearly 25%. They reported no difference in deaths between the two periods. They show no differences in rates of diagnosis, but the clinical relevance is incomplete as they have not compared survival from cancer between those time periods.

eLife assessment

This is an important study reanalysing previously published datasets to understand methylation changes during aging. The evidence supporting the conclusions is solid and sheds new light on features of aging in cells, highlighting the concept of cell-specific methylation changes and their relationship to other physiological changes such as inflammation that may impact methylation patterns. This work will be of broad interest to cell and molecular biologists.

eLife assessment

This important study reveals the genetic regulation of changes in cuticular hydrocarbon profiles in a Hymenopteran insect and links these changes with courtship behaviour and sexual attractiveness. It provides convincing empirical evidence, spanning genetic, chemical, and behavioural data. It adds valuable new perspectives on the mechanisms that underlie chemical recognition and communication systems in nature.

eLife assessment

The significance of this manuscript is that is provides useful information for the field of hepatology and endocrinology on the regulatory mechanisms of cholesterol homeostasis by melanocortin. The authors provide solid evidence utilizing both in vivo and in vitro molecular, cellular, and biochemical approaches to support their claims.

eLife assessment

This important work advances our understanding of the import of clonal heterogeneity in cancers in immune response to individual antigens. The evidence supporting the conclusions is convincing, and uses interesting tools, although the mechanistic basis of the observations is unclear. The work will be of broad interest to immunologists including cancer immunologists.

eLife assessment

This is an important study describing the mechanism of Spermidine modulation of Src kinase, identifying the interacting amino acids and the effect on indoleamine 2,3-dioxygenase 1 (IDO1) activation based on solid evidence. Considering the important role of IDO1 in the immune response this study could provide important information for the design of allosteric modulators capable of turning SRC on/off.

eLife assessment

This work examines a role for altered splicing in pancreatic tumorigenesis by interrogating effects of a specific mutation in the Sf3b splicing factor in pancreatic organoid and cell line growth primarily, with some in vivo work also performed. There is significant potential in the study but there is a concern about the lack of in vivo validation of claims that are most relevant to metastatic progression and the focus on one specific mechanism at the expense of other possible effects on splicing of factors important for disease progression.