eLife Assessment

This manuscript provides an important biochemical analysis of p53 isoforms, highlighting their aggregation propensity, interaction with chaperones, and dominant-negative effects on p53 family members. The authors have substantially strengthened the original manuscript by incorporating new mass spectrometry data and clarifying isoform-specific oligomerization behavior. Although the use of high expression levels limits direct physiological interpretation, the work is carefully framed as an investigation of protein misfolding and stability. Overall, this study offers convincing insights into p53 isoform biophysics with broad implications for cancer biology.

eLife Assessment

This study presents an advance in efforts to use histone post-translational modification (PTM) data to model gene expression and to predict epigenetic editing activity. Such models are broadly useful to the research community, especially ones that can model and predict epigenetic editing activity, which is novel; additionally, the authors have nicely integrated datasets across cell types into their model. The work is mostly solid, but it would be strengthened by performing further comparisons to existing methods that predict gene expression from PTM data and from more comprehensive functional validation of model-predicted epigenome editing outcomes beyond dCas9-p300 based perturbations. This work will be of interest to the epigenetics and computational modeling communities.

eLife Assessment

This is a very important study in which the authors have modified ChIP-seq and 4C-seq with a urea step, which drastically changes the pattern of chromatin interactions observed for SATB1, but not other proteins (including CTCF). The study highlights that the urea protocols provide a complementary view of protein-chromatin interactions for some proteins, which can uncover previously hidden, functionally important layers of chromatin organization. If applied more widely, these protocols may significantly further our understanding of chromatin organization. The study's findings are supported by a wealth of controls, making the evidence compelling.

eLife Assessment

This study, which includes additional experiments in response to the reviewer comments, presents valuable findings illustrating the role of PI3Kα in heterotopic ossification in FOP model mice. The methods, data, and analyses are solid and generally support the claims although as noted by one of the reviewers, there is no data demonstrating the effect of BYL79 on cell growth, and it remains unclear whether BYL79 also inhibits the Smad2/3 pathway. While this study provides new insights into the role of the PI3Kα pathway as a therapeutic target for FOP, questions about the mechanism of BYL79 still exist.

eLife Assessment

Using a unique cerebellar disruption approach in non-human primates, this study provides valuable new insight into how cerebellar inputs to the motor cortex contribute to reaching. The findings convincingly demonstrate that reaching movements following cerebellar disruption slow down because of both an acute deficit in producing muscle activity as well as a progressive decline in compensating for limb dynamics. This work will be of interest to neuroscientists and clinicians interested in cerebellar function and pathology.

eLife Assessment

The authors present a computational pipeline for the identification of endogenous allosteric modulators of GPCRs, with experimental validation performed in a yeast system. This approach is valuable for a broad audience, including GPCR structural biologists, molecular pharmacologists, and computational biophysicists. However, the rigor of the computational methods needs to be strengthened to provide more convincing evidence for the study's conclusions. The authors should justify their methodological choices and provide greater detail and clarity regarding each computational layer of the pipeline.

eLife Assessment

By using sparse Cre-dependent deletion of GluN1 subunit, in vitro quadruple patch clamp recordings, and pharmacological interventions, the authors show that spike timing dependent plasticity at between L5 synapses in the mouse visual cortex is: (i) dependent on presynaptic NMDA receptors; (ii) mediated by non-ionotropic NMDA receptor signaling, and (iii) reliant on presynaptic JNK2/Syntaxin-1a interactions. These fundamental findings advance our understanding of the molecular mechanisms underlying spike time dependent plasticity. The data are compelling and are supported by the elegant application of sophisticated experimental approaches.

eLife Assessment

This study presents valuable findings that advance our understanding of mural cell dynamics and vascular pathology in a zebrafish model of cerebral small vessel disease. The authors provide compelling evidence that partial loss of foxf2 function leads to progressive, cell-intrinsic defects in pericytes and associated endothelial abnormalities across the lifespan, leveraging powerful in vivo imaging and genetic tools. The strength of evidence could be further improved by additional mechanistic insight and quantitative or lineage-tracing analyses to clarify how pericyte number and identity are affected in the mutant model.

eLife Assessment

This study identifies 53BP1 as an interaction partner of GMCL1 (a likely CUL3 substrate receptor). The study seeks to link this finding to regulation of the mitotic surveillance pathway and paclitaxel resistance in cancer. The evidence for these claims is currently inadequate; concerns include the use of cell lines that have been reported to lack the mitotic surveillance pathway, insufficient consideration of paclitaxel mechanisms of action, and an overinterpretation of correlative results.

eLife Assessment

This valuable study expands the inventory of polyadenylated RNAs cleaved by the double-stranded RNA endonuclease Rnt1 in budding yeast, using solid methodology based on high-throughput sequencing. Previous studies had anecdotally discovered mRNA substrates, and this global characterization is comprehensive with multiple complementary controls. However, the study would be stronger with a deeper investigation into the biological function of Rnt1, as well as experiments directly probing the interaction between Rnt1 and its putative substrates.

eLife Assessment

Complex traits are influenced by genes and the environment, but especially the latter is difficult to pin down. This important study uses C. elegans to demonstrate that non-genetic differences in gene expression, partly influenced by the environment, correlate with individual differences in two reproductive traits. This supports the use of gene expression data as a key intermediate for understanding complex traits. The clever study design makes for compelling evidence, which is further strengthened by experimental confirmation that identified differentially expressed genes indeed influence these traits.

eLife Assessment

This useful study presents the potentially interesting concept that LRRK2 regulates cellular BMP levels and their release via extracellular vesicles, with GCase activity further modulating this process in mutant LRRK2-expressing cells. However, the evidence supporting the conclusions remains incomplete, and certain statistical analyses are inadequate. This work would be of interest to cell biologists working on Parkinson's disease.

eLife Assessment

This fundamental study advances our understanding of the role that energy metabolism, specifically anaerobic glycolysis, plays during retinal development. Convincing in vitro genetic and pharmacological evidence demonstrates that glycolytic flux controls retinal progenitor cell proliferation rates and the timing of photoreceptor maturation. Interesting evidence suggests potential downstream roles for intracellular pH and Wnt/β-catenin signaling; however, more direct evidence is needed to show they are the key mechanisms through which glycolytic flux regulates retinogenesis in vivo. This work is expected to stimulate broad interest and possible future studies investigating the link between metabolism and development in other tissue systems.

[Editors’ note: Primary data for this manuscript are not available due to a corrupted hard drive that occurred during the course of peer review. However, preprocessed data are available.]

eLife Assessment

This landmark study describes the structure of the human RAD51 filament with a recombination intermediate called the displacement loop (D-loop). Using cryogenic structural, biochemical, and single-molecule analyses, the authors provide compelling evidence on how the RAD51 filament promotes strand exchange between single-stranded and double-stranded DNAs. The work will be of interest to the community of homologous recombination and DNA repair, as well as genome stability more generally.

eLife Assessment

This important study by Lee et al. investigates the heterogeneous response of non-growing bacteria to the antimicrobial peptide (AMP) tachyplesin. In this response, a subpopulation of bacteria limits the accumulation of a fluorescent analog of the AMP, avoiding lethal damage. The study provides compelling evidence of the reduced susceptibility to the antimicrobial peptide antibiotic tachyplesin in a subpopulation of cells characterized by reduced drug accumulation. The evidence on the underlying molecular mechanisms is solid.

eLife Assessment

This is a well-written important paper on the recovery of fauna and flora following the end-Permian extinction event in several continental sites in northern China. The convincing conclusion, a rapid recovery in tropical riparian ecosystems following a short phase of hostile environments and depauperate biota, is supported by an impressive amount of data from sedimentology, body fossils of animals and plants, and especially trace fossils.

eLife Assessment

This study provides a comprehensive exploration of the role of hypothermia of mitigating IL1beta induction and NETosis in the context of lung injury induced by mechanical ventilation. The data are convincing, and the study is important for the field.

eLife Assessment

This important work advances our understanding of CHMP5's role in regulating osteogenesis through its impact on cellular senescence. The evidence supporting the conclusion is convincing and the revised manuscript is largely improved. This paper holds potential interest for skeletal biologists who study the pathogenesis of age-associated skeletal disorders.

eLife Assessment

This manuscript introduces a useful protein-stability-based fitness model for simulating protein evolution and unifying non-neutral models of molecular evolution with phylogenetic models. The model is applied to four viral proteins that are of structural and functional importance. The justification of some hypotheses regarding fitness is incomplete, as well as the evidence for the model's predictive power, since it shows little improvement over neutral models in predicting protein evolution.

eLife Assessment

This study presents a valuable assessment of increased similarity in visual appearance combined with an increased chemical difference between two butterfly species in sympatry compared with differences between three populations of one of the two species in allopatry. While the evidence is solid, its interpretation in terms of evolutionary responses to shared predators (visual signals) and avoiding between-species mating (chemical signals) is overstated due to the lack of direct experimental evidence.

eLife Assessment

This study presents a valuable advance for the analysis of gene expression variation at the level of individual cells by introducing a novel reference-free framework that can detect splicing, fusion, editing, immune-receptor diversity and repeated elements in sequencing data. The evidence supporting these claims is solid, with rigorous validation on simulated datasets and extensive analysis of full-length single-cell sequencing data demonstrating improved performance over existing methods. This work will be of particular interest to researchers developing methods for high-resolution transcriptome analysis and to those studying cellular heterogeneity in health and disease.

eLife Assessment

This important study applies an innovative multi-model strategy to implicate the ribosomal protein (RP) encoding genes as candidates causing Hypoplastic Left Heart Syndrome. The evidence from the screen in stem cell-derived cardiomyocytes and whole genome sequencing of human patients, followed by functional analyses of RP genes in fly and fish models, is convincing and supports the authors' claims. This work and methodology applied would be of broad interest to medical biologists working on congenital heart diseases.

eLife Assessment

This study presents an important finding on the role of GATA4 in aging and OA-associated cartilage pathology. The evidence supporting the conclusions is compelling, with rigorous in vitro and in vivo data. The work will be of broad interest to cell biologists and orthopedic clinicians.

eLife Assessment

This important study investigated whether the nuclear receptor Nur77 is regulated by a non-canonical mechanism of ligand-induced disruption of its interaction with RXRg, similar to the family member Nurr1. The overall evidence is solid, but additional mechanisms that have not been fully explored in this study might contribute as well. This manuscript will be of interest to scientists focusing on mechanisms of transcriptional regulation.

eLife Assessment

This study clarifies that stalled RNA pol II is not sufficient for AID targeting, which is important to the field. The authors provide solid experimental evidence that RNA poll II stalling is not the driving mechanism for AID targeting, and even though the results are generally "negative", they are highly relevant to our current understanding of SHM. The authors propose premature transcription termination as a possible mechanism to determine V gene mutability, but the study does not experimentally address such possibilities. This paper makes investigators rethink the model with which AID finds single-strand DNA in the genome.

eLife Assessment

This fundamental study demonstrates how a left-right bias in the relationship between numerical magnitude and space depends on brain lateralization. The evidence is compelling, and the manuscript could be strengthened by improving its contextualization, presentation, and discussion. The results will be of interest to researchers studying numerical cognition, brain lateralization, and cognitive brain development more broadly.

eLife Assessment

This useful study presents a biologically realistic, large-scale cortical model of the rat's non-barrel somatosensory cortex, investigating synaptic plasticity of excitatory connections under varying patterns of external activations and characterizing relations between network architecture and plasticity outcomes. The model offers an impressive level of biological detail, addressing many aspects of the cellular and network anatomy and properties, and investigating their relationships to the biologically plausible plasticity. The numerical simulations appear to be well executed and documented, providing an excellent resource to the community. The evidence supporting the main conclusions is solid with results being more observational in nature, and minor weaknesses relating to the lack of explanatory power of causal relationships and mechanisms.

eLife Assessment

This study presents a valuable description of the cellular and transcriptional landscape of the tumor microenvironment in 27 gastric cancer (GC) patients based on their H. pylori status (HpGC, ex-HpGC, non-HpGC). The single-cell RNA sequencing dataset and computational analysis are convincing and provide a starting point that is of value for understanding H pylori-associated GC cell type composition, cell transitions, and mechanisms of response to therapy. The section correlating immunotherapy outcomes with GC cell type compositions from bulk RNAseq would have been strengthened by further comparing H. pylori GC versus non H. pylori GC.

eLife Assessment

This study provides important insights into the role of polyUbiquitination in neurodegenerative diseases, elucidating how pUb promotes neurodegeneration by affecting proteasomal function. The findings not only offer a new perspective on the pathophysiology of neurodegenerative diseases but also provide potential targets for developing new therapeutic strategies. The experiments in the revised submission provide solid evidence to support the conclusions.

eLife Assessment

This manuscript provides valuable mechanistic insight into NSCLC progression, both in terms of tumour metastasis and the development of chemoresistance. The authors draw upon a range of techniques and assays and the evidence shown is solid and has been strengthened by incorporation of suggestions by the two reviewers. The work presented will be of interest to cancer biologists and more broadly to those interested in NSCLC translational studies.

eLife Assessment

This study presents fundamental findings that could redefine the specificity and mechanism of action of the well-studied Ser/Thr kinase IKK2 (a subunit of inhibitor of nuclear factor kappa-B kinase (IkB) that propagates cellular response to inflammation). Solid evidence supports the claim that IKK2 exhibits dual specificity that allows tyrosine autophosphorylation and the authors further show that auto-phosphorylated IKK2 is involved in an unanticipated relay mechanism that transfers phosphate from an IKK2 tyrosine onto the IkBa substrate. The findings are a starting point for follow-up studies to confirm the unexpected mechanism and further pursue functional significance.

eLife Assessment

This manuscript addresses the role of alpha oscillations in sensory gain control. The authors use an attention-cuing task in an initial EEG study followed by a separate MEG replication study to demonstrate that whilst (occipital) alpha oscillations are increased when anticipating an auditory target, so is visual responsiveness as assessed with frequency tagging. The authors propose that their results demonstrate a general vigilance effect on sensory processing and offer a re-interpretation of the inhibitory role of the alpha rhythm. While some concerns remain about the interpretation of the alpha inhibition hypothesis, these results are valuable, and the provided evidence is solid.

eLife Assessment

In this work, the authors characterize the synaptic adhesion molecule RTN4RL2, demonstrating its critical involvement in the development and function of auditory synapses between inner hair cells and spiral ganglion neurons. This study is important because it offers potential insights into therapeutic strategies for hearing loss associated with synaptic dysfunction. The findings are solid, because they are supported by the use of multiple advanced techniques, including FISH and SBEM imaging.

eLife Assessment

This study provides an important contribution to our understanding of the mechanisms underlying the limited capacity to process rapid sequences of visual stimuli. It reports convincing evidence that the attentional blink affects neurally separable processes of visual detection and discrimination. The study will be of interest to neuroscientists and psychologists investigating perception and attention.

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 study presents a useful characterisation of the topographical organisation of the human pulvinar, an associative thalamic subregion crucial for visual perception and attention. The evidence supporting the conclusions is solid given the multimodal validation and replication across datasets, although even higher-resolution imaging data would have strengthened the study. In their revised manuscript, the authors elaborated further on the motivation for their study and conducted several robustness checks. Nevertheless, there remains an opportunity for a more fully integrated interpretation of the findings. The work would be of interest to neuroscientists, neurologists, and neuropsychiatrists working on pulvinar functioning in health and disease.

eLife Assessment

This useful study describes expression profiling by scRNA-seq of thousands of cells of recombinant yeast genotypes from a system that models natural genetic variation. The rigorous new method presented here shows promise for improving the efficiency of genotype-to-phenotype mapping in yeast, providing convincing evidence for its efficacy. This manuscript focuses on overcoming technical challenges with this approach and identifies several new biological insights that build upon the field of genotype-to-phenotype mapping, a central question of interest to geneticists and evolutionary biologists.

eLife Assessment

This paper presents a valuable software package, named "Virtual Brain Inference" (VBI), that enables faster and more efficient inference of parameters in dynamical system models of whole-brain activity, grounded in artificial network networks for Bayesian statistical inference. The authors have provided solid evidence, across several case studies, for the utility and validity of the methods using simulated data from several commonly used models, but more thorough benchmarking could be used to demonstrate the reliability, generalizability, and practical utility of the toolkit. This work will be of interest to computational neuroscientists interested in modelling large-scale brain dynamics.

eLife Assessment

This study presents valuable findings on the patterned loss of Purkinje cells in the mouse cerebellum during aging. Convincing evidence shows that Purkinje cell loss with aging occurs in a pattern of parasagittal stripes in relationship with the zebrin-II expression pattern. Further evidence supporting the Purkinje cell aging loss pattern as it relates to human cerebellar aging would strengthen the study.

eLife Assessment

This valuable work uses serial block face electron microscopy to reconstruct detailed morphologies of large populations of Drosophila sensory neurons to determine the degree of diversity both within and across distinct neuronal populations. The authors convincingly show that there is considerable morphological diversity even within classes, and develop testable hypotheses about how arbors are optimized for particular sensory function and physiology. This work will be of interest to biologists working in physiology, insect chemosensation, and neuroscience.

eLife Assessment

This study presents a valuable finding on how the locus coeruleus modulates the involvement of medial prefrontal cortex in set shifting using calcium imaging. The evidence supporting the claims was viewed as incomplete, although a more rigorous statistical comparison of intradimensional vs. extradimensional stages of the task, either in behavior or in the calcium imaging data, would help to address this concern. The work is of broad interest to those studying flexible cognition.

eLife Assessment

This valuable study found Gamma Knife SBRT combined with tislelizumab offers a safe and powerful later-line option for pMMR/MSS/MSI-L metastatic CRC patients who were unresponsive to the first and second-line chemotherapy. The authors implemented a well-structured experimental protocol and provide convincing evidence to substantiate the conclusions. This work would be of broad interest to oncologists working on colorectal cancer.

Evaluation Statement (30 January 2025)

Kay and Aminzare discuss a claim made in a prior publication that macromolecular condensation acts as a water buffering mechanism in cells to compensate for the effects of osmotic shock. The authors argue that, although such a buffer could temporarily maintain a transmembrane osmolality differential, this differential would drive water across the membrane to reach a steady-state in which osmolality within the cell equals osmolality outside the cell. Using the well-established pump-leak model for osmotic water transport, they further show that the timescale at which a water buffer could maintain a modest 10% osmolality differential across the membrane is at most one minute for a typical animal cell.

Biophysics Colab recommends this study to researchers working on membrane transport, intracellular water buffering, and condensate biology.

Biophysics Colab has evaluated this study as one that meets the following criteria:

• Rigorous methodology
• Transparent reporting
• Appropriate interpretation

eLife Assessment

This study provides important information on the ultrastructural organization of layer 1 of the human neocortex. The quantitative assessment of various synaptic parameters, astrocytic coverage and mitochondrial morphology is based on convincing experimental approaches. These data provide new information on the detailed morphology of human neocortical tissue that will be of interest to neuroscientists working on different network functions.

eLife Assessment

In this valuable study, the authors report on an innovative chemostat propagation system to reduce eukaryotic viruses while retaining phages in mixtures used for FVTs (fecal virome transplant). The authors hypothesized that chemostat-propagated viromes could modulate the gut microbiota and reduce necrotizing enterocolitis (NEC) lesions while avoiding potential side effects, such as earlier onset of diarrhea. The study is solid in that it integrates in vitro fermentation, high-resolution metagenomics, immunogenicity assays, and in vivo validation, demonstrating the potential of FVT using eukaryotic-free virome-based therapeutics. However, the study overall has some conceptual and technical limitations.

eLife Assessment

Mackie and colleagues present a valuable comparison of lateralized gustation in two well-studied nematodes. Their results present convincing evidence that ASEL/R lateralization exists and is achieved by different means in P. pacificus compared to C. elegans. This work will be of interest to neurobiologists interested in how small nervous systems make sense of the environment, and how evolution can take multiple paths to asymmetry within a neuron class.

eLife Assessment

This study provides an important and timely analysis of invasive and non-invasive Streptococcus pyogenes emm89 isolates, which have become a dominant serotype in the past decade. Using genome sequencing of 311 strains from Japan and comparing them with 666 global strains, the authors present compelling evidence in support of the identification of genetic factors linked to the invasive phenotype of emm89. The findings are both theoretically and practically significant in medical microbiology.

eLife Assessment

This valuable study presents a deep learning framework for predicting synergistic drug combinations for cancer treatment in the AstraZeneca-Sanger (AZS) DREAM Challenge dataset. The level of evidence seems solid, although performance on some datasets seems unconvincing and further validation would be required to demonstrate the generalizability of the model and, in turn, its clinical relevance. The reported tool, DIPx, could be of use for personalized drug synergy prediction and exploring the activated pathways related to the effects of drug combinations.

eLife Assessment

This is valuable work with theoretical implications for possible mediation by MMP12 in the link between atherosclerosis and intracranial aneurysms, using Mendelian Randomization for causal inference. Additional analysis would be required to verify the claims, which currently have incomplete support in terms of the strength of evidence. Given that most of the identified causal associations do not hold after correcting for multiple tests, the conclusions should be carefully reviewed in order to be fully supported by the results.

eLife Assessment

The reported cryo-EM imaging of a pentameric ligand-gated ion channel in liposomes as opposed to nanodiscs has both broad implications and contributes valuable methodological advances to the structural investigation of membrane receptors. The comparison of structures assigned to distinct functional states in liposomes versus nanodiscs is convincing, and will aid membrane protein structural biologists in selection of functionally relevant membrane reconstitution environments. This work could be strengthened by a more quantitative presentation of the pore dimension profile leading to the proposed 9' desensitization gate with discussion of the additional apparent constriction at 2' in the desensitized structure, and by a more thorough description of the biochemistry methods for which core parts are not described and/or discussed in sufficient detail.

eLife Assessment

This valuable study highlights the potential of combining immunotherapy for pMMR CRC by selecting suitable cases and demonstrating that Gamma Knife SBRT with tislelizumab provides a safe and effective later-line treatment option for patients with pMMR/MSS/MSI-L mCRC unresponsive to standard chemotherapy. The authors employed a robust experimental design and rigorous statistical analyses to ensure the reliability of their findings. Their results offer convincing evidence to support the clinical value of this combined therapeutic approach.

eLife Assessment

This important work supports the role of breast carcinoma amplified sequence 2 (Bcas2) in positively regulating primitive wave hematopoiesis through amplification of beta-catenin-dependent (canonical) Wnt signaling. The study is convincing: it uses appropriate and validated methodology in line with the current state-of-the-art, and there is a first-rate analysis of a strong phenotype with highly supportive mechanistic data. The findings shed light on the controversial question of whether, when, and how canonical Wnt signaling may be involved in hematopoietic development. The work will be of interest to hematologists and developmental biologists.

eLife Assessment

How misfolded proteins are segregated and cleared is a significant question in cell biology, since clearance of these aggregates can protect against pathologies that may otherwise arise. The authors discover a cell cycle stage-dependent clearing mechanism that involves the ER chaperone BiP, the proteosome, and CDK inactivation, but is curiously independent of the anaphase promoting complex (APC). These are valuable and interesting new observations, and the evidence supporting these claims is solid.

eLife Assessment

This useful study uses brain stimulation and electroencephalography to study speech-gesture integration. It investigates the role of frontotemporal regions in integrating linguistic and extra-linguistic information during communication, focusing on the inferior frontal gyrus and posterior middle temporal gyrus. Reliance on activation patterns of tightly-coupled brain regions over short timescales leads to incomplete support for the study's conclusions due to conceptual and methodological limitations.

eLife Assessment

The study presents a fundamental advance in antiviral RNA research by adapting SHAPE-Map to chart the secondary structure of the Porcine Epidemic Diarrhoea Virus (PEDV) genome in infected cells and pinpointing structurally conserved, accessible RNA elements as therapeutic targets. A broad, well-documented integration of biochemical probing, computational analysis, and functional validation provides convincing evidence that these regions are both biologically relevant and druggable. Beyond PEDV, the work offers a generalizable framework for RNA-guided antiviral discovery that will interest researchers in RNA therapeutics and viral genome biology.

eLife Assessment

This paper presents valuable findings on the processing of sound mixtures in the auditory cortex of ferrets, a species widely used for studies of auditory processing. Using the convenient and relatively high-resolution method of functional ultrasound imaging, the authors provide solid evidence that background noise invariance emerges across the auditory cortical processing hierarchy. However, differences between this and other methods limit the comparisons that can be made across different species, and additional controls are needed to fully substantiate the paper's claims. This work will nonetheless be of interest to researchers studying the auditory cortex and the neural mechanisms underlying auditory scene analysis and hearing in noise.

eLife Assessment

This work presents an important genetic toolkit for Drosophila neurobiologists to access and manipulate neuronal lineages during development and adulthood. The evidence supporting the fidelity of this toolkit after revision is compelling. This work will interest Drosophila neurobiologists in general, and some of the genetic tools may be used outside the nervous system. The conceptual approaches used in this paper are likely transferable to other fields as comparable data and genomic methods are obtained.

eLife Assessment

Oor and colleagues report the potentially independent effects of the spatial and feature-based selection history on visuomotor choices. They outline compelling evidence, tracking the dynamic history effects based on their extremely clever experimental design (urgent version of the search task). Their finding is of fundamental significance, broadening the framework to identify variables contributing to choice behavior and their neural correlates in future studies.

eLife Assessment

This is a well-written important paper on the recovery of fauna and flora following the end-Permian extinction event in several continental sites in northern China. The convincing conclusion, a rapid recovery in tropical riparian ecosystems following a short phase of hostile environments and depauperate biota, is supported by an impressive amount of data from sedimentology, body fossils of animals and plants, and especially trace fossils.

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

In their important manuscript, Chen et al. investigate the phospho-regulation of the C. elegans kinesin-2 motor protein OSM-3, revealing that the kinase, NEKL-3, phosphorylates a serine/threonine patch at the hinge region of the motor to mediate autoinhibition until it reaches the ciliary middle segment. The findings are supported by robust genetic data, in vivo imaging, and motility assays with wild-type and mutant motors. Overall, the study provides a compelling contribution to understanding the regulation of OSM-3 kinesin activity both on the molecular and cellular levels.

eLife Assessment

The authors use a multidisciplinary approach to provide a link between Beta-alanine and S. Typhimurium (STM) infection and virulence. This valuable work shows how Beta-alanine synthesis mediates zinc homeostasis regulation, possibly contributing to virulence. The work is convincing as it adds to the existing knowledge of metabolic flexibility displayed by STM during infection.

eLife Assessment

African (or Salivarian) trypanosomes are significant pathogens of humans and domestic animals. For many decades is was accepted that only the "stumpy" non-proliferative form was capable of infecting the Tsetse-fly vector, but recent work challenged this, suggesting that the proliferative "slender" form is also infective. The current paper provides important and convincing laboratory evidence that the original concept is probably correct for most infections: the slender form was not infective for adult Tsetse, and was only able to infect young, less immunocompetent flies if N-acetyl glucosamine was added to the feed.

eLife Assessment

This manuscript provides a single-cell transcriptomic atlas for AML (222 samples comprising 748,679 cells) integrating data from multiple studies. They use this dataset to investigate t(8;21) AML, and they reconstruct the Gene Regulatory Network and enhancer Gene Regulatory Network, which allowed identification of interesting targets. This aggregation is useful and can help infer differences in genetic regulatory modules based on the age of disease onset, which may help explain age-related variations in prognosis and disease development. However, result interpretations and the motivation and critical analysis of the applied computational methods are incomplete, and the statistical analyses lack control experiments and should be improved to avoid potential selection bias in the later analyses.

eLife Assessment

This important work substantially advances our understanding of the molecular mechanisms underlying the timing of the initiation of metamorphosis of the Ciona ascidian tadpole larva. Through the combination of gene knockdown experiments and fluorescent molecular reporters the authors provide compelling evidence about a crosstalk between different G protein mediated signalling pathways and are able to place different signalling molecules within a signalling network. The work will be of interest to molecular, developmental and marine biologists and to scientists working on animal metamorphosis.

eLife Assessment

The study evaluates the feasibility, safety, and tolerability of neoadjuvant radiotherapy followed by a CDK4/6 inhibitor (dalpiciclib) and hormonal therapy in treatment-naive patients with unilateral early-stage HR+/HER2- breast cancer. The findings are convincing, with a strong scientific rationale supported by integrated correlative studies. The trial is considered to be important as the outcomes could inform the design of larger, future studies. The limitations of the study have been acknowledged and outlined in this manuscript, which include only a small cohort of patients (n=12), which was not adequately powered to definitively assess the efficacy or safety of this combinatorial treatment approach.

**Editors Assessment: ** Sinocyclocheilus are a genus of freshwater cavefish fish that are endemic to the Karst regions of Southwest China. Having diverse traits in morphology, behavior, and physiology typical of cavefish, that make them interesting models for studying cave adaptation and phylogenetic evolution. The manuscript assembled chromosomal-level genomes of five Sinocyclocheilus species, and conducted allotetraploid origin analysis on these species. Assembling S. grahami (the golden-line barbel), using PacBio and Hi-C sequencing technologies, a final chromosome-level genome assembly was 1.6 Gb in size with a contig N50 of 738.5 kb and a scaffold N50 of 30.7 Mb. With 93.1% of the assembled genome sequences and 93.8% of the predicted genes anchored onto 48 chromosomes. Subsequently the authors conducted a homologous comparison to obtain chromosome-level genome assemblies for four other Sinocyclocheilus species: S. maitianheensis, S. rhinocerous, S. anshuiensis, and S. Anophthalmus. With over 82% of the genome sequences anchored on these constructed chromosomes. Peer review provided clarification on the assembly strategy and provided more benchmarking. This data having the potential to contribute to species conservation and the exploitation of potential economic and ecological values of diverse Sinocyclocheilus members.

This evaluation refers to version 1 of the preprint

eLife Assessment

The ability to estimate the force of infection for Plasmodium falciparum from other more directly measurable epidemiological quantities would contribute to malaria epidemiology. The authors propose a method to accomplish this using genetic data from the var genes of the Pf genome and novel applications of existing methods from queueing theory. After revising the manuscript, this is a useful contribution to the field, and the authors provide solid evidence to support it.

eLife Assessment

It is well established that cellulose synthesis in higher plants requires three different but related catalytic subunits known as CESA proteins. Here the authors provide cryo electron microscopy structural information on soybean CESA1, CESA3, and CESA6 and find substantial differences between the structure of these CESA homotrimers and the previously-resolved secondary cell wall CESAs. They present an important model with convincing evidence in which the multi-subunit cellulose synthase complexes are made of multiple homotrimers.

eLife Assessment

This important study aims to understand the role of endothelial cell differentiation into pericytes in the restoration of blood-brain barrier function after ischemic stroke. Identification of pericytes derived from endothelial cells and the involvement of myeloid cell-derived TGFβ1 signaling are compelling new findings, but future studies will be needed to validate the origin and nature of these pericytes. The work will be of interest to blood-brain barrier and basic and translational stroke researchers.

eLife Assessment

This paper provides a useful systematic quantification of the relationship between electrophysiological response properties of single neurons with their position in the brain. The quality of the classification setup is high and the methodology is solid.

eLife Assessment

This valuable study provides strong evidence for the development of a penetration ring during Magnaporthe oryzae infection and, supported by knockout and expression studies, shows that Ppe1 is involved in the virulence of the fungus. Although the authors demonstrated the close association of Ppe1 with the host plasma membrane, the work fell short in providing direct evidence for its role at the host-pathogen interface and the precise molecular function of the penetration ring. Therefore, the study presented strong structural and phenotypic characterization but remains incomplete regarding mechanistic insights of Ppe1.

eLife Assessment

This valuable paper explores the idea that transient modulations of neural gain promote switches between distinct perceptual interpretations of ambiguous stimuli. The authors provide solid evidence for this idea by pupillometry (an indirect proxy of neuromodulatory activity), fMRI, neural network modeling, and dynamical systems analyses. The highly integrative nature of this approach is rare in the field.

eLife Assessment

In this important study, Baniulyte and Wade provide convincing evidence that translation of a short ORF denoted toiL positioned upstream of the topAI-yjhQP operon is responsive to different ribosome-targeting antibiotics, consequently controlling translation of the TopAI toxin as well as Rho-dependent transcription termination. Strengths of the study include combining a genetic screen to identify 23S rRNA mutations that affect topA1 expression and a creative approach to map the different locations of ribosome stalling within toiL induced by different antibiotics, with ribosome profiling and RNA structure probing by SHAPE to examine consequences of different antibiotics on toiL-mediated regulation. The work leaves unanswered how bacteria benefit by activating expression of the genes using the proposed strategy and the mechanism underlying ToiL's sensing of structurally distinct antibiotics.

eLife Assessment

This valuable work provides solid evidence that a neuronal metallothionein, GIF/MT-3, incorporates metal-persulfide clusters. A variety of well-designed assays support the authors' hypothesis, revealing that sulfane sulfur is released from MT-3. However, the sufane sulfur content in the canonical induced MT-1 and MT-2 has not been demonstrated. Thus, the biological role of the persulfidated form is not yet clearly defined. There are caveats to the findings that limit the study, but the work will nevertheless prompt major follow-up work.

eLife Assessment

This valuable study demonstrates that the GSK-3 inhibitor AZD2858 inhibits the formation of TOPBP1 condensates and hence DNA damage responses in colorectal cancer cells. The evidence supporting the claims of the authors is convincing, although uncovering how this drug blocks bio-condensate formation would have strengthened the study. The work will be of interest to cancer researchers searching for synergistic drug combination strategies.

[Editors' note: this paper was reviewed by Review Commons.]

eLife Assessment

This valuable study focuses on defining how the HSP70 chaperone system utilizes J-domain proteins to regulate the heat shock response-associated transcription factor HSF1. Using a combination of orthogonal techniques in yeast, this manuscript provides compelling evidence that the J-domain protein Apj1 facilitates attenuation of HSF1 transcriptional activity through a mechanism involving its dissociation from heat shock gene promoter regions. This work improves our understanding of HSF1 regulation and will be of broad interest to cell biologists interested in proteostasis, chaperone networks, and stress-responsive signaling.

eLife Assessment

This important and creative study finds that the uplift of the Qinghai-Tibet Plateau-via its resultant monsoon system rather than solely its high elevation-has shifted avian migratory directions from a latitudinal to a longitudinal orientation. However, the main claims are incomplete and only partially supported, as the reliance on eBird data-which lacks the resolution to capture population-specific teleconnections-combined with a limited tracking dataset covering only seven species leaves key aspects of the argument underdetermined, and the critical assumption of niche conservatism is not sufficiently foregrounded in the manuscript. More clearly communicating these limitations would significantly enhance the interpretability of the results, ensuring that the major conclusions are presented in the context of these essential caveats.

eLife Assessment

This valuable study proposes a network implementation of the "re-aiming" learning strategy, which has been hypothesized to underlie brain-computer interface learning. Combining theoretical arguments, numerical simulations, and analysis of experimental data, the authors provide convincing evidence for their hypothesis. This paper will likely be of broad interest to the systems neuroscience community.

eLife Assessment

The authors investigated KLF Transcription Factor 16 (KLF16) as an inhibitor of osteogenic differentiation, which plays a critical role in bone development, metabolism and repair. The results of the study are valuable as they could help to facilitate future research on the regulation of osteogenesis in vitro and in vivo. However, the evidence overall is incomplete, as validation by knockout mouse models would help to strengthen the conclusions.

eLife Assessment

This important study combines an innovative experimental approach with mathematical modeling to demonstrate that genes separated by strong topological boundaries can exhibit coordinated transcriptional bursting, providing new insights into how regulatory information is transmitted across the genome. The evidence is solid within the studied locus, but the interpretation and generality of the findings would be strengthened by additional validation using simulated data and broader application beyond a single genomic region. This work will be of interest to cell biologists and biophysicists working on transcription and chromatin.

eLife Assessment

This study presents a valuable finding on the intersection between tuberculosis and diabetes and the impact on immune responses, notably T cell and myeloid cell responses. The single-cell data collected and analyzed are convincing and provide a rich dataset to develop a more detailed understanding of cellular responses during Mtb infection of diabetic mice. Some of the mechanistic claims are incomplete, as there are no experiments performed to clearly define a role for IL-16 or IL-17 in disease. Inclusion of analysis of human samples would have strengthened the conclusions in the paper for translational impact, as well as the inclusion of a DM group alone in addition to DM-TB vs TB in some of the experiments.

eLife Assessment

This valuable study reports the conservation of sperm-egg envelope binding by demonstrating successful recognition of the micropyle in fish eggs by the mouse sperm. However, the evidence supporting the conclusions drawn remains incomplete. In particular, the proposed specific role of CatSper in micropyle recognition and passage is not fully demonstrated. This study will be of interest to reproductive biologists and clinicians studying the biology of fertilization and fertility.

eLife Assessment

This fundamental study explores a novel cellular mechanism underlying the degeneration of locus coeruleus neurons during chronic restraint stress. The evidence supporting the overexpression of LC neurons after chronic stress is compelling. However, to fully support the broad implications for LC degeneration and Alzheimer's disease, the study would benefit from stronger causal integration and validation in age-relevant models.

eLife Assessment

This useful study describes a physical mechanism for the emergence of spiral patterns in the outer epithelial layer of the mammalian cornea independent of pre-patterning or guidance cues, using an agent-based model of self-propelled particles with alignment. The model is well constructed, however the central premise of the manuscript, that the spiral patterning of epithelial corneal cells occurs without guidance cues, is incomplete and not fully supported. Several significant questions remain unanswered, such as the role of the corneal curvature or the importance of topological defects. Furthermore, comparison between the model and data are qualitative at best for the moment.

eLife Assessment

This study demonstrates the application of END-seq, originally developed to study genome-wide DNA double-strand breaks, to telomere biology; the work packs a punch, concisely demonstrating the utility of this approach and the new insights that can be gained. The authors confirm that telomeres in telomerase-positive cells terminate with 5'-ATC in a Pot1-dependent manner, and demonstrate that this principle holds true in telomerase-negative ALT cells as well; S1-END-seq is similarly developed for telomeres, showing that ALT cells harbor several regions of ssDNA. The study is well-executed, the new insights are fundamental and compelling, and the optimized END-seq approaches will be widely utilized. The interest of the paper could be heightened by deepening the discussion of potential biases in telomere representation, the origin of the ssDNA captured in ALT cells, and the occurrence of variant telomere repeats in the cell lines studied.

eLife Assessment

This important study provides evidence for asymptomatic Bordetella pertussis carriage among mothers in a longitudinal cohort in Zambia, significantly advancing understanding of transmission dynamics. The evidence presented is convincing, with strengths including routine sampling irrespective of symptoms and rigorous qPCR methodology, although confirmatory diagnostics would further strengthen the claims. Overall, the study represents an influential contribution to the field of infectious disease epidemiology.

eLife Assessment

Cardiac Ca2+/Na+ exchange is mediated by the NCX1 antiporter, whose activity is tightly regulated. This important manuscript describes the structural basis of activation by the lipid DiC8-PIP2 and inhibition by binding of a small molecule to NCX1. These results provide convincing insights into NCX1 regulation and the structural basis of cellular Ca2+ signaling.

eLife Assessment

This study presents valuable findings with practical and theoretical implications for drug discovery, particularly in the context of repurposing cipargamin CIP for the treatment of Babesia spp. The evidence is solid with the methods, data, and analyses broadly supporting the claims. The paper will be of great interest to scientists in drug discovery, computational biology, and microbiology.

eLife Assessment

This study provides important insights as to how interacting brain areas produce movement during the execution of a skilled multi-directional reaching task. Using a combination of single neuron and neural population analysis, optogenetic stimulation, and computational models, the authors provide convincing evidence of an asymmetrical influence between mouse premotor and motor cortex during the execution of a well-practiced behaviour. This asymmetry can only be captured by some but not all population analysis methods, which is a key lesson to the field in and of itself. Analyzing how activity that is shared and private to these areas relates to different aspects of movements, and why different methods provide different outcomes regarding the nature of inter-area interactions would further strengthen this work.

eLife Assessment

This study provides valuable findings that MK2 inhibitor CMPD1 can inhibit the growth, migration and invasion of breast cancer cells both in vitro and in vivo. The evidence supporting the claims of the authors is solid, although the detailed molecular mechanism and additional animal experiments would strengthen the paper. This study will be of interest to the breast cancer field.

eLife Assessment

This manuscript makes a valuable contribution to the field by uncovering a molecular mechanism for miRNA intracellular retention, mediated by the interaction of PCBP2, SYNCRIP, and specific miRNA motifs. Overall, the findings are convincing and advance our understanding of RNA-binding protein-mediated miRNA sorting, providing deeper insights into miRNA dynamics.

eLife Assessment

The manuscript by Hawes et al. provides important findings on how striatal projection neurons regulate spontaneous locomotion speed in the context of implicit motivation and distinct contextual valence. Overall, the evidence for the findings is solid, although evidence for the claim that striatonigral projections from the matrix and patches have functionally opposing roles is incomplete. This work will be of broad interest to neuroscientists in the basal ganglia, movement control, and cognition fields.

eLife Assessment

This manuscript provides fundamental new insight into the mechanisms linking photoperiod, reproduction function, and feeding activity, using medaka, a genetic model that itself exhibits photoperiodic responses. As well as identifying key neuropeptide genes that are regulated by photoperiod and involved in regulating feeding activity, the authors establish a knockout line for agrp1 using CRISPR Cas9 - based approach, profiting from the extensive use and development on this methodology in medaka. The combination of the RNAseq and quantitative in situ hybridization analysis with the knockout results as well as the study of ovariectomized fish provides compelling evidence implicating agrp1 in feeding regulation in response to photoperiod and reproductive status.

eLife Assessment

This valuable work formulates an individual-based model to understand the evolution of division of labor in vertebrates, in particular, to examine the role of indirect versus direct fitness benefits. The evidence supporting the main conclusions is incomplete at this stage, with key details of simulation assumptions not adequately described and exploration of alternative assumptions and parameter space lacking.

eLife Assessment

This study presents an important practical modification of the orthogonal hybridization chain reaction (HCR) technique, a promising yet underutilized method with broad potential for future applications across various fields. The authors advance this technique by integrating peptide ligation technology and nanobody-based antibody mimetics - cost-effective and scalable alternatives to conventional antibodies - into a DNA-immunoassay framework, which convincingly merges oligonucleotide-based detection with immunoassay methodologies.

eLife Assessment

This important study demonstrates that interferon beta stimulation induces WTAP transition from aggregates to liquid droplets, coordinating m6A modification of a subset of mRNAs that encode interferon-stimulated genes and restricting their expression. The evidence presented is solid, supported by microscopy, immunoprecipitations, m6A sequencing, and ChIP, to show that WTAP phosphorylation controls phase transition and its interaction with STAT1 and the methyltransferase complex.

eLife Assessment

TDP-43 mislocalization is a key feature of some neurodegenerative diseases, but cellular models are lacking. The authors endogenously-tagged TDP-43 with a C-terminal GFP tag in human iPSCs, followed by expression of an intrabody-NES that targeted GFP to the cytosol. They convincingly report physical mislocalization and functional depletion of TDP-43, as measured by microscopy and RNAseq. This method will be valuable to investigators studying the biological consequences of TDP-43 mislocalization and the methodology is in line with the current state-of-the-art.

eLife Assessment

This paper reports on an important study that aims to move beyond current experimental approaches in speech production by (1) investigating speech in the context of a fully interactive task and (2) employing advanced methodology to record intracranial brain activity. Together these allow for examination of the unfolding temporal dynamics of brain-behaviour relationships during interactive speech. This approach and the analyses presented in support of the authors' claims pose convincing evidence.

eLife Assessment

This study reveals the important role of upstream open reading frames (uORFs) in limiting the translational variability of downstream coding sequences. Through a combination of computational simulations, comparative analyses of translation efficiency across different developmental stages in two closely related Drosophila species, and manipulative, experimental validation of translation buffering by an uORF for a gene, the authors provide convincing evidence supporting their conclusions. This work will be of broad interest to molecular biologists and geneticists.

eLife Assessment

These are valuable findings for those interested in how neural signals reflect auditory speech streams, and in understanding the roles of prediction, attention, and eye movements in this tracking. However, the evidence as it stands is incomplete. Further analyses are needed to clarify how the observed results relate to the relevant theoretical claims.

eLife Assessment

The authors analyses describe a novel mechanism by which a retrotransposon-derived LTR may be involved in genomic imprinting and demonstrate imprinting of the ZDBF2 locus in rabbits and Rhesus macaques using allele-specific expression analysis. This imprinting of the ZDBF2 locus correlates with transcription of GPR1-AS orthologs. The accompanying genomic analysis is very well executed allowing for the conclusions reached in the manuscript. The revisions made at the request of the reviewers in this important manuscript strengthen the evidence from the genomic analyses, and as a result, the evidence is now convincing and will be informative to the genomics and developmental biology communities.

eLife Assessment

The ExA-SPIM methodology developed here and characterized and supported by convincing evidence is an important development for the field of light sheet microscopy as the new technology provides an impressive field of view making it possible to image the entire expanded mouse brain at cellular and subcellular resolution.

eLife Assessment

This comprehensive study presents important findings that delineate how specific dopaminergic neurons (DANs) instruct aversive learning in Drosophila larvae exposed to high salt through an integration of behavioral experiments, imaging, and connectomic analysis. The work reveals how a numerically minimal circuit achieves remarkable functional complexity, with redundancies and synergies within the DL1 cluster that challenge our understanding of how few neurons generate learning behaviors. By establishing a framework for sensory-driven learning pathways, the study makes a compelling and substantial contribution to understanding associative conditioning while demonstrating conservation of learning mechanisms across Drosophila developmental stages.

eLife Assessment

This study provides an important understanding of the contribution of different striatal subregions, the anterior Dorsal Lateral Striatum (aDLS) and the posterior Ventrolateral Striatum (pVLS), to auditory discrimination learning. The authors have included robust behavior combined with multiple observational and perturbation techniques. The data provided are convincing of the relevance of task-related activity in these two subregions during learning.

eLife Assessment

This study presents a valuable meta-analysis of two independent genome-wide association studies (GWASs) elucidating the role of plasma proteins as biomarkers for improving early detection of prostate cancer (PCa). The evidence supporting novel protein biomarkers of PCa risk is solid, although exploration of how these markers may also be shared with other prostate diseases would have strengthened the study. The work will be of interest to the field for elucidating novel variants of prostate cancer risk.

eLife Assessment

This study presents a valuable meta-analysis that highlights low and highly variable breast cancer survival rates across Africa, emphasizing the pressing need for public health in Africa. The evidence supporting the claims of the authors is solid, although a clarification of the crude 5-year survival rates would have strengthened the study. The work will be of interest to scientists working in the field of public health and breast cancer.

eLife Assessment

This valuable study provides a conceptual advance in our understanding of how membrane geometry modulates the balance between specific and non-specific molecular interactions, reversing multiphase morphologies in postsynaptic protein assemblies. Using a mesoscale simulation framework grounded in experimental binding affinities, the authors successfully recapitulate key experimental observations in both solution and membrane-associated systems, providing novel mechanistic insight into how spatial constraints regulate postsynaptic condensate organization. While the evidence supporting the conclusions is largely solid, a few aspects of the analysis and model proposed remain incomplete.

eLife Assessment

This work presents an important technical advancement with the release of MorphoNet 2.0, a user-friendly, standalone platform for 3D+T segmentation and analysis in biological imaging. The authors provide convincing evidence of the tool's capabilities through illustrative use cases, though broader validation against current state-of-the-art tools would strengthen its position. The software's accessibility and versatility make it a resource that will be of value for the bioimaging community, particularly in specialized subfields.

eLife Assessment

Thick multicellular plant samples provide unique challenges when it comes to cryo-preservation, which has resulted in limited successful examples for structural studies using in situ cryo-electron tomography. To address this deficiency, this important study describes procedures for high-pressure-freezing, focused ion-beam milling, and cryo-electron tomography imaging of certain plant types. The results described in the paper provide solid evidence for the usefulness of the methods described, although some reservations remain about the applicability of the methods to a wider range of plant cell types.

eLife Assessment

This study provides a valuable extension of credibility-based learning research by showing how feedback reliability can distort reward-learning biases in a disinformation-like bandit task. Although the paradigm is well controlled and the computational modelling rigorous, the evidential support is incomplete: key claims about learning from 50 %-credible feedback and heightened positivity bias at low credibility hinge on a single dataset, specific parameter definitions, and modelling assumptions not fully validated across studies. Clearer reporting of the discovery-study null result, behavioural tests of positivity bias, and standard information-criterion model comparisons are needed to solidify the conclusions and enhance generalizability.

eLife Assessment

This important study of the inhibitory complex amacrines (CAM) in the vertical lobe of Octopus vulgaris delivers a solid standard for the structural characterization of an anatomical region likely to be key for memory processing in this unconventional but complex organism, as well as a helpful classification of CAM subtypes. This work will be of broad relevance to the fields of memory and evolutionary neuroscience.

eLife Assessment

This is an important study introducing a stimulus-computable model of multisensory perception that extends an existing framework to accept raw, stimulus-level inputs (i.e., image- and soundscape-computable). The author demonstrates how low-level correlation detection can drive both illusions and cue integration, and the model bridges diverse stimuli, behaviors, and species. The model and evidence provided are deemed generally convincing and of broad applicability, potentially impacting areas across neuroscience, psychology, and computational cognitive science. There are, however, certain aspects of the work considered incomplete, particularly as they relate to explaining details pertinent to model fitting.

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 manuscript presents a valuable minimal model of habituation which is quantified by information theoretic measures. The results here could be of use in interpreting habituation behavior in a range of biological systems. The evidence presented is solid, and uses simulations of the minimal model to recapitulate several hallmarks of habituation from a simple model.

eLife Assessment

This study presents an important set of new tools to facilitate Cre or Dre-mediated recombination in mice. The characterization of these new tools was done using solid and validated methodology. The work convincingly demonstrates the efficient gene knockout capability of these models and will progress the field.

eLife Assessment

This analysis of the formation of the oral-aboral body axis in cnidarians, the sister group of bilaterians, is a significant and fundamental contribution to the field of Wnt signalling and planar cell polarity, particularly in or understanding in gradient formation, non-canonical Wnt signalling and Wnt-Frizzled interactions in cnidarians. The evidence supporting the conclusions is compelling and has the potential to contribute to a deeper understanding of the origin and evolution of Wnt signalling in cnidarians and metazoans in general. These findings, which are presented in a thoughtful and scholarly manner, will be of broad interest to developmental and evolutionary biologists.