Evaluated articles

eLife Assessment

This important study identifies species- and sex-specific neuronal cell types and gene expression in the preoptic area (POA) to help understand the evolutionary divergence of social behaviors. The evidence from single-nucleus RNA sequencing and immunostaining is compelling and suggests that cellular differences in the POA may contribute to behavioral variations such as mating and parental care that are apparent in two closely related deer mouse species. These rich observations provide an entry point for future hypothesis-driven experiments to demonstrate a causal role for these populations in sex- or species-variable behaviors in vertebrates. These data will be a resource that is of value to behavioral neuroscientists.

eLife Assessment

In this potentially valuable computational study, the authors conducted extensive atomistic and coarse-grained simulations to probe the temperature-dependent phase behaviors of ELF3, a disordered component of the evening complex in plant. The results aim to highlight the role of polyQ tracts in modulating temperature-responsive structural and condensation behavior. Despite considerable improvements in the revised manuscript, the level of evidence is considered incomplete, since several of the supplementary observables introduced to support the revised claim indicate that the variants studied are not statistically distinguishable within the reported replicate uncertainty.

eLife Assessment

This study presents a useful finding for the ferroptosis-mediated tumor microenvironment (TME) in triple-negative breast cancer (TNBC) using public single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data. The data were collected and analyzed using solid and validated methodology and can be used as a starting point for functional studies of TME in TNBC. The work will be of interest to medical biologists working in the field of TNBC.

eLife Assessment

This useful study employs AlphaFold2 to predict interactions among 20 nuage proteins, identifying five novel interaction candidates, three of which are validated experimentally through co-immunoprecipitation. Expanding the analysis to 430 oogenesis-related proteins and screening ~12,000 Drosophila proteins for interactions with Piwi, the study identifies 164 potential binding partners, demonstrating how computational predictions can streamline experimental validation. This study provides a solid basis for further investigations into eukaryotic protein interaction networks.

eLife Assessment

This is an important study that aims to investigate the behavioral relevance of multisensory responses recorded in the auditory cortex. The experiments are elegant and well-designed and are supported by appropriate analyses of the data. Although solid evidence is presented that is consistent with learning-dependent encoding of visual information in auditory cortex, further work is needed to establish the origin and nature of these non-auditory signals and to definitively rule out any effects of movement-related activity.

eLife Assessment

This is an important study that establishes how anti-sense oligonucleotides degrading a specific target protein called EMC10 can rescue neuronal function in models of chromosome 22.11.2 deletions. The authors use human iPSC-derived neurons and a mouse model to provide compelling data for the rescue of cellular and cognitive features of 22.11.2 phenotypes upon ASO regulation of EMC10. These pre-clinical data are of interest because they support reduction of ECM10 as a promising therapeutic strategy.

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 regulates the functions in macrophages have not yet been established.

eLife Assessment

This important work advances our understanding of DNA methylation and its consequences for susceptibility to DNA damage. This work presents evidence that DNA methylation can accentuate the genomic damage propagated by DNA damaging agents as well as potentially being an independent source of such damage. The experimental results reported are sound. The evidence presented to support the conclusions drawn is convincing and alternative interpretations are considered. The work will be of broad interest to biochemists, cell and genome biologists.

eLife Assessment

Zhang et al. present important findings that reveal a new role for TET2 in controlling glucose production in the liver, showing that both fasting and a high-fat diet increase TET2 levels, while its absence reduces glucose production. TET2 works with HNF4α to activate the FBP1 gene upon glucagon stimulation, while metformin disrupts TET2-HNF4α interaction, lowering FBP1 levels and improving glucose homeostasis. The results are convincing and expand our understanding of gluconeogenesis regulation.

eLife Assessment

This important study employed multiple orthogonal techniques and tissue samples to investigate the interaction between the NRL transcription factor and RNA-binding proteins in the retina. The findings are convincing to support an interaction between NRL and the DHX9 helicase. The significance of the study could be enhanced with functional experiments of NRL-R-loop interactions in the developing retina and their potential role in photoreceptor health and gene regulation.

eLife Assessment

Ferredoxins are ubiquitous electron transfer proteins that drive essential metabolic processes across all domains of life. This fundamental contribution to the field provides the first description of how specific amino acids, though a series of hydrogen bonds, control the ability of iron-sulfur clusters in ferrodoxins to accept and donate electrons. The evidence supporting the conclusions is compelling as is the combined use of neutron crystallography with X-ray crystallography and classical spectral/redox studies.

eLife Assessment

This manuscript describes valuable new material of small, unusually preserved fossils from deep in the Cambrian of China and argues they represent very early bilaterian animals such as annelids or panarthropods. The authors present convincing evidence of the fossilisation of specimens as microbial pseudomorphs, however, the fossils show few details and it is difficult to assess their affinity. The broader claims made about the timing and nature of the Cambrian explosion are inadequately supported by the material, given that bilaterians were already known to exist during that period.

eLife Assessment

This study offers valuable insights into the molecular mechanisms by which Osx influences osteocyte function, particularly through its regulation of Cx43. However, the evidence supporting the authors' claims is incomplete, necessitating additional experimental data and further investigation to fully substantiate these findings. While this study presents a new perspective on the complex role of Osx in bone biology, it also raises significant questions about the intricacies of its regulatory network.

eLife Assessment

This manuscript focuses on the identification of RNA crosslinks within the HIV RNA genome under different conditions i.e. in infected cells and in virions using a new method called HiCapR. These cross-links reveal long-range interactions that can be used to determine the structural arrangement of the viral RNA, providing valuable data that show differences in the genomic organization in different conditions. The data analysis, however, is incomplete and based on extensive computational analysis from a limited number of datasets.

eLife Assessment

This comprehensive scRNAseq atlas of the cranial region during neural induction, patterning, and morphogenesis provides a fundamental demonstration of how different cell fates are organized in specific spatial patterns along the anterior-posterior and medial-lateral axes within the developing neural tissue. The compelling data are analyzed with a rigorous computational approach, and the data revealed both known and novel genes differentially expressed along rostro-caudal and medio-lateral axes. This will be a helpful resource for researchers studying brain development.

eLife Assessment

This useful manuscript presents findings on Tom1p's interaction with Spt6p and its role in chromatin dynamics, supported by structural analysis through CryoEM. The evidence for the conclusions is currently incomplete, lacking key experiments including continuation in vivo interaction and orthogonal binding assays (e.g., SPR, MST, ITC) to fully support the proposed mechanism. While the results are promising, further validation is needed to strengthen the evidence and improve the manuscript's overall cohesion.

eLife Assessment

This important study by Bi and colleagues employed a clever genetics screen to uncover the role of the GidB rRNA methylase in translation fidelity, under certain conditions, in Mycobacterium smegmatis. The findings are solid, supporting the findings that the loss of GidB results in mistranslation. The work contributes to a more in-depth understanding of mycobacterial translation fidelity and will be of interest to microbiologists.

eLife Assessment

This is an important study demonstrating the importance of S100A4+ alveolar macrophages in the earlier stages of tumour development and suggesting a role in angiogenesis. As such this convincing study is of interest to cancer biologists focused on early tumour development and those interested in the development of therapeutics that may specifically target early cancers.

eLife Assessment

This study represents an important advance in our understanding of how certain inhibitors affect the behavior of voltage gated potassium channels. Robust molecular dynamics simulation and analysis methods lead to a new proposed inhibition mechanism with convincing strength of support. This study has considerable significance for the fields of ion channel physiology and pharmacology and could aid in development of selective inhibitors for protein targets.

eLife Assessment

This study presents important findings on cold tolerance shared between hibernating and non-hibernating mammals, identifying a key molecule, GPX4, through multi-species genome-wide CRISPR screens. The evidence supporting these conclusions is compelling, combining multi-species CRISPR screening with rigorous pharmacological assays. This work will be of significant interest to biologists studying hibernation physiology and medical researchers interested in cold tolerance.