Evaluated articles

eLife Assessment

This paper addresses the significant question of quantifying epistasis patterns, which affect the predictability of evolution, by reanalyzing a recently published combinatorial deep mutational scan experiment. The findings are useful, showing that epistasis is fluid, i.e. strongly background dependent, but that fitness effects of mutations are statistically predictable based on the background fitness. While the general approach appears solid, some claims remain incompletely supported by the analysis, as arbitrary cutoffs are used and the description of methods lacks specifics. This analysis should be of interest to the community working on fitness landscapes.

eLife Assessment

This study makes a valuable contribution to understanding Bayesian inference in dynamic environments by demonstrating how humans integrate prior beliefs with sensory evidence, revealing an overestimation of environmental volatility while accurately tracking noise. The evidence is solid, supported by robust model fitting and principled factorial model set analyses, though limitations in sample size and inconclusive findings on memory capacity tradeoffs reduce the overall impact. Future work should expand validation across datasets, enhance model comparisons, and explore the generalizability of reduced Bayesian frameworks to strengthen the conclusions and broader relevance of the study.

eLife Assessment

This important study uses diffusion magnetic resonance imaging to non-invasively map the white matter fibres connecting the zona incerta and cortex in humans. The authors present convincing evidence to indicate that these connections are organized along a rostro-caudal axis. The findings will be of interest to researchers interested in neuroanatomy and cortico-subcortical connectivity.

eLife Assessment

This manuscript presents a useful mean-field model for a network of Hodgkin-Huxley neurons retaining the equations for ion exchange between the intracellular and extracellular space. The mean-field model derived in this work relies on approximations and heuristic arguments that, on the one hand, allow a closed-form derivation of the mean-field equations, but also raise questions about their justifications and the degree to which the results agree with experiments as well as direct numerical simulations. Therefore, the evidence for the utility of this approach is at present incomplete.

eLife Assessment

This important study provides compelling data from in vitro models and patient-derived samples to demonstrate how modulation of GSK3 activity can reprogram macrophages, revealing potential therapeutic applications in inflammatory diseases such as severe COVID-19. The study stands out for its clear and systematic presentation, convincing experimental approach, and the relevance of its findings to the field of immunology.

eLife Assessment

This valuable study presents a mouse gastruloid system to generate successive waves of hematopoietic progenitors that in vivo would emerge during embryonic development. Although this newly revised manuscript has addressed some of the concerns raised during the first round of review, the study is still considered incomplete, as the claims are only partially supported. In particular, the claim of definitive wave hematopoietic progenitors being produced in the gastruloids, and their engraftment after transplantation, would benefit from further validation.

eLife Assessment

The study conducted by Hurtado et al. offers important insights and solid evidence regarding the prediction of drug combinations for cancer treatment. By leveraging disease-specific drug response profiles and single-cell transcriptional signatures, this research not only demonstrates a novel and effective approach to identifying potential drug synergies but it also enhances our understanding of the underlying mechanisms of drug response prediction.

eLife Assessment

This important study provides insights into the role of the cerebellum in fear conditioning, addressing a key gap in the literature. The evidence presented is solid overall, although the theoretical framing and clarity of the results can be improved and some concerns remain about the reliability of results based on small numbers of trials. This work will be of interest to both the extinction learning and cerebellar research communities.

eLife Assessment

This important study provides information on the TMEM16 family of membrane proteins, which play roles in lipid scrambling and ion transport. By simulating 27 structures representing five distinct family members, the authors captured hundreds of lipid scrambling events, offering insights into the mechanisms of lipid translocation and the specific protein regions involved in these processes. While the data on comparison of scrambling competence is compelling, the evidence for outside-the-groove scramblase activity without experimental validation is missing and is based on a limited set of observed events.

eLife Assessment

This work defines the response dynamics in forepaw-related cortical circuits of S1 and M1 following stimulation of peripheral mechanoreceptors in the mouse. In this revised version, the authors have addressed the reviewers' prior concerns. The results are convincing and present a valuable comparison to previously published work. This study has implications for understanding the interactions between primary somatosensory and motor cortex, required for active sensing, and will be of interest to scientists seeking to better understand the functions of somatosensory and motor circuits.

eLife Assessment

This study examined the important question of how neurons code temporal information across the hippocampus, dorsal striatum, and orbitofrontal cortex. Using a behavioral task in the rat that requires discrimination between short and long time intervals, the authors conclude that time intervals are represented in all three regions and that synchronized activity of time-coding cells across the brain regions is coordinated by theta rhythms. However, several weaknesses are noted, and in its current form, the study provides incomplete evidence for understanding how temporal information is processed and coordinated throughout these brain networks.

eLife Assessment

This is an important study that demonstrates that blood pressure variability impairs myogenic tone and diminishes baroreceptor reflex. The study also provides evidence that blood pressure variability blunts functional hyperemia and contributes to cognitive decline. The evidence is compelling whereby the authors use appropriate and validated methodology in line with or more rigorous than the current state-of-the-art.

eLife Assessment

This important study provides new evidence on the role of norepinephrine (NE) release in the hippocampus in response to environmental transitions (event boundaries), providing a potential link between NE signaling and the segmentation of episodic memories. The work is solid, employing innovative techniques such as fiber photometry with the GRAB-NE sensor for NE measurement, the analysis of public electrophysiology hippocampal datasets, and well-controlled experiments. While further analysis could strengthen some claims, this work offers insights into memory, neuromodulation, and hippocampal function.

eLife Assessment

This is a convincing study of the morphological properties of Purkinje cell dendrites and dendritic spines in adult humans and mice, and the anatomical determinants of multi-innervation by climbing fibers. The data will provide an important resource for the field of cerebellar computation.

eLife Assessment

This important work advances our understanding of intraflagellar transport, ciliogenesis, and ciliary-based signaling, by identifying the interactions of IFT172 with IFT-A components, ubiquitin-binding, and ubiquitination, mediated by IFT172 C-terminus and its role in ciliogenesis and ciliary signaling. The results of the structural analysis of the IFT172 C-terminus and the evidence for the interaction between IFT172 and IFT-A components are convincing. However, the analysis of ubiquitin-binding and ubiquitination mediated by IFT172 is incomplete.

eLife Assessment

Combining experiments in microfluidic devices and computer simulation, this study provides a valuable analysis of the relevant parameters that determine the motility of (multicellular) magnetotactic bacteria in sediment-like environments. The study presents convincing evidence that there is an optimum in the biological parameters for motile life under such conditions.

eLife Assessment

Using several hundreds of samples and cutting-edge genomic methods, including BioNano, PacBio, HiFi, and advanced bioinformatic pipelines, the authors identify six large chromosomal inversions segregating in over 100 species of Lake Malawi cichlids. This important study provides compelling evidence for the presence of these six inversions, their differential distribution among populations, and the association of chromosome 10 inversion with a sex-determination locus. This work also provides a starting point for further investigating the role of these inversions with respect to local adaptation, speciation, sex determination, hybridization, and ILS in cichlids, which represent ~5% of the extant vertebrate species and are one of the most prominent examples of adaptive radiations.

eLife Assessment

This valuable study assesses epigenetic clocks across ancestries, including in the context of accelerated aging in Alzheimer's Disease patients. It provides convincing evidence for population differences in age estimation accuracy across a variety of epigenetic clocks, but the degree to which these differences reflect continuous variation in ancestry, and/or are confounded by environmental or power differences is not entirely clear; consequently, the evidence that reduced portability is rooted in genetics is incomplete. Given the accelerating use of epigenetic clocks across fields, this study is nevertheless likely to be of interest to researchers working on human genetic and epigenetic variation or who apply epigenetic clocks to diverse human populations.

eLife Assessment

This important study presents compelling observational data supporting a role for transcription and polysome accumulation in the separation of newly replicated bacterial chromosomes. Through a comprehensive and rigorous comparative analysis of the spatiotemporal dynamics of ribosomal accumulation, nucleoid segregation, and cell division, the authors develop a model that nucleoid segregation rates are determined at least in part by the accumulation of ribosomes in the center of the cell, exerting a steric force to drive nucleoid segregation prior to cell division. This model circumvents the need to invoke as yet unidentified active mechanisms (e.g. an equivalent to a eukaryotic spindle) as drivers of bacterial chromosome segregation and intrinsically couples this vital step in the cell cycle to cell growth.

eLife Assessment

This study presents an important finding that has identified 27 differentially methylated regions as a signature for non-invasive early cancer detection and predicting prognosis for colorectal cancer. The findings demonstrate promising clinical potential, particularly for improving cancer screening and patient monitoring. In general, the evidence supporting the claims of the authors is solid. A larger sample size will be key to further improving this work in the future. The work will be of interest to researchers interested in cancer diagnosis or colorectal cancer monitoring.