Evaluated articles

eLife Assessment

This study presents a valuable theoretical exploration on the electrophysiological mechanisms of ionic currents via gap junctions in hippocampal CA1 pyramidal-cell models, and their potential contribution to local field potentials (LFPs) that is different from the contribution of chemical synapses. The biophysical argument regarding electric dipoles appears solid, but the evidence would be stronger if their predictions are tested against experiments. A shortage of model validation and strictly comparable parameters used in the comparisons between chemical vs. junctional inputs makes the modeling approach incomplete; once strengthened, the finding can be of broad interest to electrophysiologists, who often make recordings from regions of neurons interconnected with gap junctions.

eLife Assessment

NCX1 is an important cardiac Ca2+/Na+ exchanger whose activity is tightly regulated. This manuscript describes the structural basis of activation by the lipid PIP2 and inhibition by binding of a small molecule to NCX1. These results provide key insights into NCX1 regulation and cellular Ca2+ signaling, but the evidence presented is still incomplete.

eLife Assessment

This study highlights ITCH as a regulator of SARS-CoV-2 replication by promoting K63-linked ubiquitination of M and E proteins. While the findings are potentially useful, the approaches are overly reliant on ectopic expression models and lack direct mechanistic evidence that ubiquitination of M and E has functional relevance. Accordingly, the strength of evidence is incomplete, as further experiments are needed to validate the findings and address potential confounding factors.

eLife Assessment

This useful study integrates experimental methods from materials science with psychophysical methods to investigate how frictional stabilities influence tactile surface discrimination. The authors argue that force fluctuations arising from transitions between frictional sliding conditions facilitate the discrimination of surfaces with similar friction coefficients. However, the reliance on friction data obtained from an artificial finger, together with the ambiguous correlative analyses relating these measurements to human psychophysics, renders the findings incomplete.

eLife Assessment

This study maps the genotype-phenotype landscapes of three E. coli transcription factors and the topographical features of these landscapes. It shows that ruggedness and epistasis do not hinder the evolution of strong transcription factor binding sites. These convincing findings contribute valuable insights into fitness landscape theories and highlight the role of chance, contingency, and evolutionary biases in gene regulation. The authors then study the topographical features of these landscapes, especially the number and distribution of local maxima, as well as the statistical properties of evolutionary paths on these landscapes.

eLife Assessment

This study presents important insights into the regulation of left-right organ formation. By combining genetic perturbation of all three Meteorin genes in zebrafish and timelapse imaging, the authors identify an essential role for this protein family in the establishment of left-right patterning. They provide convincing evidence that Meteorins are required for the morphogenesis of dorsal forerunner cells, the precursors of the left-right organizer (also named Kupffer's vesicle) in zebrafish. In line with this, Meteorins were shown to genetically interact with integrins ItgaV and Itgb1b to regulate dorsal forerunner cell clustering.

eLife Assessment

This manuscript reports an important new statistical method for calculating the significance of correlations between two time-series, which provides more accuracy than other methods when the data has few replicates. The proposed method solves a real-life problem that is frequently encountered and is broadly applicable to many realistic datasets in many experimental contexts. The technique is supported with compelling mathematical derivations as well as analysis of both computer-generated and previously published experimental data.

eLife Assessment

This important study characterizes and validates a new activity marker - fast labelling of engram neurons (FLEN) - which is transiently active and driven by cFos, allowing the monitoring of intrinsic and synaptic properties of engram neurons shortly after the learning experience. The results convincingly demonstrate the utility of this novel viral tool for studying early changes in the properties of engram cells. However, the study would benefit from exploring how accurately FLEN reflects endogenous cFos activity, how this labelling technique compares to previous versions, and from careful consideration of alternative explanations such as changes in release probability.

eLife Assessment

This study provides important evidence that the postmating behavioral switch in male mice is mediated by distinct stages of synaptic plasticity within the medial amygdala-MPOA-BSTrh pathway. The findings are convincing, supported by rigorous behavioral characterization and electrophysiological approaches that disentangle the contributions of mating, cohabitation, and parental experience to neural circuit changes. While some methodological details and statistical reporting require clarification, the study significantly advances our understanding of the neural mechanisms underlying paternal behavior.

eLife Assessment

This is a valuable study that tests the functional role of food-washing behavior in removing tooth-damaging sand and grit in long-tailed macaques and whether dominance rank predicts level of investment in the behavior. The evidence that food-washing is deliberate is compelling and the evidence that individual investment in the behavior varies is solid. Overall, the paper should be of interest to researchers interested in foraging behavior, cognition, and primate evolution.

eLife Assessment

This valuable study reports on the critical role of ANKRD5 (ANKEF1) in sperm motility and male fertility. However, the supporting data remain incomplete. This work will be of interest to biomedical researchers working in sperm biology and andrologists.

eLife Assessment

This study demonstrates the critical role of Afadin on the generation and maintenance of complex cellular layers in the mouse retina. The data are solid, which provides important insights into how cell-adhesion molecules contribute to retinal organization. However, further investigations are needed to clarify the mechanisms underlying the cellular disorganization phenotype in the retina and axonal projection to the brain.

eLife Assessment

This important study reports a detailed computational analysis of the CFTR ion channel's permeation mechanism, advancing our understanding of its structure-function relationship. The conclusions are based on extensive molecular dynamics simulations and thorough analysis, but the use of an approximate chloride ion model, known to underestimate key ion-protein interactions, leaves them incomplete without experimental or alternative computational validation. The work will be of interest to biophysicists working on CFTR and cystic fibrosis.

eLife Assessment

This study presents a potentially fundamental analysis of the original color of a fossil feather from the crest of a 125-million-year-old enantiornithine bird, using sophisticated 3D microscopic and numerical methods to conclude that the feather was iridescent and brightly colored, possibly indicating that this was a male bird that used its crest in sexual displays. At present, the strength of evidence supporting the authors' conclusions is considered incomplete based on methodological incompleteness and questions about taphonomy.

eLife Assessment

The authors developed a methodology to graph antigenic surface loops on influenza virus neuraminidases. The hybrid proteins retained the structure of the neuraminidase scaffold and the antigenicity of the grafted loops. This fundamental work should help in developing novel neuraminidase constructs for use in influenza virus vaccines. The paper presents compelling evidence supporting the conclusions arrived at by the authors.

eLife Assessment

This study presents valuable findings by using Fmr1 knockout mice as a model to investigate the role of Fmr1 in sleep regulation. These mice exhibited clear evidence of sleep and circadian disturbances, including abnormal retinal innervation of the SCN, which may provide a potential mechanistic explanation for the observed behavioral deficits. Interestingly, the results suggest that a scheduled feeding approach could improve sleep and circadian rhythms while enhancing social interactions and reducing repetitive behaviors in a mouse model of Fragile X syndrome. The topic is both intriguing and highly significant; however, while the evidence supporting the authors' claims is solid, several issues hinder the manuscript's clarity and impact.

eLife Assessment

This study presents an important discovery regarding the diversity and evolution of gall-forming microbial effectors. Supported by convincing computational structural predictions and analyses, the research provides insights into the unique mechanisms by which gall-forming microbes exert their pathogenicity in plants. This study also offers guidance that is of value for future studies on pathogen effector function and co-evolution with host plants.

eLife Assessment

This fundamental manuscript comprehensively examines the roles of nine structural proteins in herpes simplex virus 1 (HSV-1) assembly and nuclear egress. By integrating cryo-light microscopy and soft X-ray tomography, the study presents an innovative approach to investigating viral assembly within cells. The research is thoroughly executed, yielding compelling data that explain previously unknown functions of these structural proteins. This work is of broad interest to virologists, cellular biologists, and structural biologists, offering a robust, contextually rich methodology for studying large protein complex assembly within the cellular environment, serving as an excellent starting point for high-resolution techniques.

eLife Assessment

Rennert et al. developed a valuable thermodynamic framework to study the force response of branched actin networks from the crucial and unexplored perspective of energetic cost. They used the fact that the entropy production rate must be positive to derive inequalities that set limits on the maximum force produced by branched actin networks, and speculate that the dissipative cost beyond that required to move the load may be necessary to maintain an adaptive steady state. This work is highly innovative, but remains incomplete until the hypotheses of the model are better justified and the conclusions about the dissipative cost of the system are better established.

eLife Assessment

These useful findings assigned a novel functional implication of histone acylation, crotonylation. Although the mechanistic insights have been provided in great detail regarding the role of the YEATS2-GCDH axis in modulating EMT in HNC, the strength of evidence for the manuscript is incomplete. The patient cohort is very small, with just 10 patients; to establish a significant result the cohort size should be increased. Furthermore, the functional implication of p300 is also to be looked into.