Evaluated articles

eLife Assessment

This study provides valuable mechanistic insight into the mutually exclusive distributions of the histone variant H2A.Z and DNA methylation by testing two hypotheses: (i) that DNA methylation destabilizes H2A.Z nucleosomes, thereby preventing H2A.Z retention, and (ii) that DNA methylation suppresses H2A.Z deposition by ATP-dependent chromatin remodelling complexes. Through a series of well-designed and carefully executed experiments, findings are presented in support of both hypotheses. However, the evidence in support of either hypothesis is incomplete, so that the proposed mechanisms underlying the enrichment of H2A.Z on unmethylated DNA remain somewhat speculative.

eLife Assessment

This is an important work implementing data mining methods on IMC data to discover spatial protein patterns related to the triple-negative breast cancer patients' chemotherapy response. The evidence supporting the claims of the authors is solid, although more detailed methodology clarification and validation are needed. While the accuracy of the methods is not very high, the work shows potential for translational application.

eLife Assessment

This study investigates low-affinity Ca2+ binding by WT calreticulin and mutant calreticulin associated with type I myeloproliferative neoplasms, as well as the impact on Ca2+ fluxes in suspension cultures of megakaryocyte-like cells in vitro in response to ER Ca2+ ATPase inhibitors that deplete endoplasmic reticulum (ER) Ca2+ store and open plasma membrane Ca2+ channels through STIM1-Orai interactions. The results are important in that they show that Ca2+ binding by calreticulin and store-operated Ca2+ entry are not fundamentally impacted by the type I deletion mutation in calreticulin, which rules out a direct effect of the calreticulin mutation on its own low-affinity Ca2+ binding and any broad impact on ER Ca2+ regulation. The strength of the data and methods used ranges from solid to convincing, although the use of suspension-based flow cytometric assays to investigate ER Ca2+ levels and Ca2+ entry can be challenged. High-affinity Ca2+ binding sites could be further considered, and possible confounding effects of Abl kinase activity in the megakaryocyte-like cell lines could be offset.

eLife Assessment

This important study combines a two-person joint hand-reaching paradigm with game-theoretical modeling to examine whether, and how, one's reflexive visuomotor responses are modulated by a partner's control policy and cost structure. The study provides a solid and novel set of behavioral findings suggesting that involuntary visuomotor feedback is indeed modulated in the context of interpersonal coordination. The work will be of interest to cognitive scientists studying the motoric and social aspects of action control.

eLife Assessment

This important study addresses a classic debate in visual processing, using a strong method applied to a rare clinical population to evaluate hierarchical models of visual object perception. The paper finds only partial support for the hierarchical model: as expected, neural responses in ventral visual cortex show increased representational selectivity for faces along the posterior-anterior axes, but the onsets of the signals do not show a temporal hierarchy, indicating more parallel processing. The iEEG dataset is impressive, but the evidence for lack of temporal hierarchy is incomplete: essential quality checks need to be performed, and statistical analyses adapted to ensure that the data and analyses would be able to reveal temporal hierarchy if it were present in the data.

eLife Assessment

This article reports an algorithm for inferring the presence of synaptic connection between neurons based on naturally occurring spiking activity of a neuronal network. One key improvement is to combine self-supervised and synthetic approaches to learn to focus on features that generalize to the conditions of the observed network. This valuable contribution is currently supported by incomplete evidence.

eLife Assessment

This valuable study provides a practical computational framework for inferring latent neural states directly from calcium fluorescence recordings, bypassing the traditional need for a separate spike deconvolution step. The evidence supporting the method is solid, featuring rigorous validation across multiple latent variable model families (including HMM, GPFA, and LFADS) using both simulated and experimental data. However, the assessment of the method's generality would be further strengthened by application to a broader range of experimental datasets, such as recordings from different brain regions or using different calcium indicators.

eLife Assessment

Insects can act as vectors of plant diseases, hence the study of insect-pathogen interactions is relevant for agriculture. This important study identifies in Diaphorina citri a dopamine receptor responsive to 'Candidatus Liberibacter asiaticus' infection, demonstrate direct regulation of this receptor by a microRNA, and integrate dopamine signaling into an established insect reproductive hormone framework. Multiple complementary experimental approaches convincingly support the findings, but key conclusions rely on correlative data and the mechanistic evidence for the proposed linear signaling cascade is incomplete. This work will be of interest for insect physiology and vector-pathogen biology, and more broadly for citrus agriculture.

eLife Assessment

The authors address a hard question and propose a pipeline for using Large Language Models to reconstruct signalling networks as well as to benchmark future models. The findings are valuable for a defined subfield, as the proposed framework allows for assessing such approaches systematically. The overall support is solid, although the present evaluation remains limited in scope and would benefit from a wider range of networks and performance metrics.

eLife Assessment

This manuscript presents a valuable study of the activity and functional relevance of different circuits in the dentate gyrus of mice performing a pattern separation task. The study is likely to be of interest to those studying the subregional organization and cell type-specific functions of the dentate gyrus. However, the strength of evidence for the study's conclusions is currently incomplete.

eLife Assessment

This important study provides new insights into how Staphylococcus aureus adapts to disulfide stress through the redox-sensitive regulator Spx, which coordinates nutrient uptake, cysteine import, redox homeostasis, and bacterial growth. While the authors present compelling evidence supporting the central role of Spx in managing disulfide stress, several aspects require further clarification. In particular, the precise mechanisms regulating cysteine uptake and the proposed link between disulfide stress responses and iron limitation would benefit from additional explanation and experimental or conceptual justification.

eLife Assessment

In this valuable study, the authors performed cell-specific ribosome pulldown to identify gene expression (translatome) differences in the anterior (NT1) vs middle & posterior (NT2-9) cells of the C. elegans intestine, under fed, starved, or refeeding conditions. The data generated will be very helpful to the C. elegans community, and the evidence supporting the conclusions of the study is assessed to be solid. Some methodological caveats remain and are discussed.

eLife Assessment

In this useful paper, the authors present a comprehensive method for the purification of recombinant Snake Venom Metalloproteinases (SVMPs) using the MultiBac expression system, explain the self-activation of the enzymes by Zn2+ incubation, and establish high-throughput screening (HTS) techniques. The authors addressed a key problem: producing a substantial amount of pure and enzymatically active SVMPs required for structural and functional studies. Altogether, this work builds a solid foundation for the large-scale production of active SVMPs for future biochemical and structural characterization as well as for drug discovery, albeit leaving certain caveats about the universal applicability of the described methodology for the production of any recombinant SVMPs.

eLife Assessment

This study presents a valuable human stem cell-derived organoid model that captures key morphological and cellular features of spinal cord development and provides evidence for a YAP-dependent mechanism of lumen formation relevant to secondary neurulation. Overall, the evidence is convincing, using strong and validated approaches consistent with the current state of the art, including systematic protocol optimisation across multiple cell lines and quantitative analysis of tissue architecture. However, some claims regarding precise anterior-posterior and dorsoventral spinal cord identity, as well as several novelty claims, are at times overstated and would benefit from more direct validation and more careful positioning. The work will be of interest to developmental biologists and researchers studying neural tube defects.

eLife Assessment

The authors used genetic mutations in VANGL2 to study cell morphological changes during differentiation of hPSCs and understand the mechanisms underlying neural tube closure defects. The findings are important as they establish a quantitative, reproducible 2D human iPSC-to-neural-progenitor platform for analyzing cell-shape dynamics during differentiation. The convincing evidence provided, combined with the relative simplicity of the model and its tractability as a patient-specific and reverse genetic platform, make it attractive.

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

eLife Assessment

This valuable paper advances understanding of the role of the HGF receptor, MET, in cancer cell invasion by demonstrating HGF-induced coordinated trafficking of MET and metalloprotease MT1-MMP into invadopodia. The results are generally solid, but there are concerns about the cell biology and whether the trafficking mechanism is clinically relevant. It's also unclear whether this is a general mechanism or specific to triple-negative breast cancer cells. The paper will be of interest to cancer cell biologists.

eLife Assessment

This study reports insights into how the caspase Dcp-1, best known for cell death, can also promote tissue growth in Drosophila, extending the authors' earlier work by identifying regulatory factors that shape this non-lethal activity. The valuable findings identify new Dcp-1-interacting proteins Sirt1, Fkbp59, Debcl, Buffy, Atg2, and Atg8a, and help broaden understanding of how growth and death pathways intersect. The evidence is solid, but some conclusions would be strengthened by additional studies, particularly regarding the nature of the cell death observed and the involvement of autophagy.

eLife Assessment

This study presents a valuable advance by enabling functional mapping of Ca²⁺ responses in live human pancreatic tissue slices, providing new opportunities to study islet heterogeneity and diabetes-related dysfunction in an intact tissue context. The evidence supporting the main conclusions is solid, based on reproducible methodology and functional validation across multiple human donor samples. Key revisions needed include clearer quantification of transduction efficiency and tissue viability, and improved clarification of how CaMPARI2 signals should be interpreted.

eLife Assessment

This paper addresses valuable questions about the evolution of recombination landscape under domestication by examining recombination maps in domesticated chickens and their wild ancestor. However, despite employing a state-of-the-art deep learning method for recombination map inference, the lack of systematic benchmarking and presence of some unexpected patterns raise concerns about the reliability of the inferred maps, thus providing incomplete support for rapid evolution of recombination landscapes. Additionally, due to methodological limitations in testing for intra-genome correlations between evolutionary processes, the current evidence is inadequate to support the associations of recombination with selection and/or introgression in domesticated chickens.

eLife Assessment

Koch et al. describe a valuable novel methodology, SynSAC, to synchronise cells to analyse meiosis I or meiosis II or mitotic metaphase in budding yeast. The authors present convincing data to validate abscisic acid-induced dimerisation to induce a synthetic spindle assembly checkpoint (SAC) arrest that will be of particular importance to analyse meiosis II. The authors use their approach to determine the composition and phosphorylation of kinetochores from meiotic metaphase I and metaphase II that will be of interest to the broader meiosis research community.

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