Evaluated articles

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 conclusions, but the structural analyses lack the necessary rigor and depth to provide a clear mechanism. The work 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 strength of support being mostly convincing, and incomplete in some aspects. 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.

eLife Assessment

This fundamental study addresses the regulation of the MICAL-family of actin regulators by Rab GTPases, which play a key role in directing membrane trafficking within cells. The compelling evidence explains how Rab8 family members bind at two sites to allosterically regulate MICAL1, and relieve an auto-inhibited state unable to bind actin. This study lays the basis for further progress in understanding membrane trafficking and cytoskeleton dynamics in eukaryotic cells.

eLife Assessment

This valuable study examines how different exercise training intensities affect intestinal barrier function and gut microbiota composition over a 6-week period in mice. The evidence supporting the main claims about exercise-induced intestinal injury and microbiota changes is solid, featuring comprehensive histological analysis, molecular characterization, and metabolomic profiling, though key mechanistic insights and causal relationships remain to be established. The findings have practical implications for understanding exercise-induced gastrointestinal stress, particularly the observation that daily moderate exercise may be more damaging to intestinal integrity than vigorous exercise with rest days. Additional experimental validation would strengthen these conclusions.

eLife Assessment

This valuable study uses the analysis of connectomic and transcriptomic datasets to survey the anatomy and connectivity of neurosecretory cells in the Drosophila brain. While the connectivity analyses are convincing, the anatomical and functional data provided to verify cell type identity and paracrine signaling is incomplete. Once these aspects are improved, this study would be of interest to neuroscientists working on hormonal signaling in Drosophila and other animals.

eLife Assessment

The authors examined the evolution of hepatitis C virus (HCV) in a cohort of 14 subjects with recent HCV infections. They showed that viral fitness declines as the virus mutates to escape the immune response and can rebound later in infection as HCV accumulates additional mutations. The study contributes to an important aspect of viral evolution. The combination of approaches contributes to a convincing study.

eLife Assessment

This important study provides evidence for the role of neutrophil extracellular traps in chronic kidney damage (CKD) induced by chemotherapy and suggests a therapeutic approach to mitigate the kidney pathology caused by the NETs. The study utilizes a sound murine in vivo model of CKD with low-dose administration cisplatin and a genetic model for impairment of NET formation by deletion of the enzyme Pad4. In its current form, the study was seen as incomplete as there is not yet formal demonstration of NET production by neutrophils in the model of CKD used. Additionally, the accuracy and clarity of data presentation could be improved.

eLife Assessment

The manuscript by de La Forest Divonne et al. offers an important and detailed exploration of the immune cells in the oyster Crassostrea gigas, by correlating distinct hemocyte morphotypes with specific single-cell transcriptional profiles. The evidence supporting the conclusion is convincing, deriving from the comprehensive dataset that not only captures unicellular diversity but also associates these cells with distinct immune roles, making it an invaluable resource for the broader research community.

eLife Assessment

This is a valuable study of the physiological mechanisms promoting network activity during fever in the mouse neocortex. The supporting evidence is solid, and has improved with revision, along with increased clarity of presentation.

eLife Assessment

This study presents an important computational framework, FLiSimBA (Fluorescence Lifetime Simulation for Biological Applications), for modeling experimental limitations in Fluorescence Lifetime Imaging Microscopy (FLIM). FLiSimBA is readily available in MATLAB and Python, enables users to simulate effects of noise and varying sensor expression levels, and provides practical guidance for both lifetime imaging experiments and biosensor development. The analyses are robust, and the evidence supporting the tool's utility in distinguishing between multiple lifetime signals is compelling, indicating strong potential for multiplexed dynamic imaging. However, users should also consider that the tool's effectiveness depends on the suitability of a two-component discrete exponential model.

eLife Assessment

This valuable study describes how trains of mossy fiber stimulation control cerebellar unipolar brush cell discharges. The dissection of the contributions of relevant glutamate receptors to these transformations is convincing. Overall, the study broadens our understanding of temporal processing in the cerebellar cortex.

eLife Assessment

This study provides important observations about the role of Hebbian synapse rewiring (which predicts that correlated activity between neurons begets stronger synapses) on brain connectivity development, by examining a naturally emerging case where Hebbian predictions can be tested because neurons with differing activity undergo development under otherwise similar conditions (albino mouse lateral geniculate nucleus [LGN], where retinal ganglion cells [RGCs] from the contralateral retina form inappropriate projections alongside a majority of ipsilateral RGCs). The evidence supporting the conclusions is compelling, with combined confocal imaging and serial electron microscopy (EM) reconstructions showing complete synaptic isolation of aberrantly projecting RGCs onto LGN thalamocortical projection neurons, and mixed connectivity onto LGN local interneurons. The morphological descriptions of connectivity presented here will be of interest to researchers studying synaptic connectivity and plasticity during development.

eLife Assessment

The microbiome field is constantly providing insight on various health-related properties elicited by the commensals that inhabit their mammalian hosts. Harnessing the potential of these commensals for knowledge about host-microbe interactions, as well as properties with therapeutic implications, will likely remain a fruitful field for decades to come. In this valuable study, Wang et al use various methods, encompassing classic microbiology, genomics, chemical biology, and immunology, to identify a potent probiotic strain that protects nematode and murine hosts from Salmonella enterica infection. The authors provide compelling evidence identifying gut metabolites that are correlated with protection, and show that a single metabolite can recapitulate the effects of probiotic administration.