Evaluated articles

eLife Assessment

This is an important study describing 'SPEx', a broadly accessible method that combines cell expansion, laser microdissection, and mass spectrometry to enable subcellular proteomic profiling. The authors provide convincing evidence that this flexible integration of established techniques provides a robust and practical approach for compartment-resolved spatial proteomics. The authors support their main claims with appropriate validation across multiple subcellular compartments and show that the method can recover known markers while also identifying previously uncharacterized components. Overall, the work is likely to be of broad interest to cell and molecular biologists, particularly those seeking scalable and cost-effective strategies for mapping organelle composition.

eLife Assessment

By using a combination of patch clamp recordings, calcium imaging and computer modeling, the authors analyze the spatial distribution of voltage gated calcium channels at glutamatergic synapses formed between layer 5 pyramidal neurons (L5PNs) and between layer 2/3 and L5PNs in the prefrontal cortex (PFC) and primary somatosensory cortex (S1); they conclude that the calcium channel-vesicle coupling is looser in the PFC compared to S1, although additional experiments are needed to determine how the distinct functional characteristics of these synapses in different brain regions might affect data interpretation. Overall, these findings are important because they have implications for shaping synaptic plasticity and neural circuit function across brain regions. They are solid because they are based on the use of a multi-pronged approach, although the presentation would benefit from stronger integration of the current findings with the existing literature and a more explicit discussion of potential limitations and confounding factors for data interpretation.

eLife Assessment

This study reports the relative importance of Tie1 and Tie2 signaling for atrial versus ventricular trabeculation. It is an important study and is one of the few works to date that have carefully and simultaneously analyzed these two processes. In line with a previous study in zebrafish, the authors demonstrate key differences between atrial and ventricular trabeculation. While the imaging and quantitative data were conducted with solid and validated methodology throughout the manuscript, the work would benefit from more rigourous approaches where Tie1/2 signaling is disrupted prior to the onset of atrial/ventricular trabeculation, to allow for a more direct comparison.

eLife Assessment

This study reports a novel function for syntaxin 11, a specialized SNARE protein critical for the immune system whose mutations cause familial hemophagocytic lymphohistiocytosis type 4. The data convincingly show that depletion of STX11 impairs store-operated calcium entry in Jurkat T cells and that this defect is recapitulated in primary cells from a patient suffering from the disease; the authors further show that the syntaxin interacts with the pore subunit of the ORAI1 channel and propose that it primes the channel by promoting the assembly of multimers before activation by its endogenous ligand, the ER Ca2+ sensing protein STIM1. This is a conceptually important claim that challenges the prevailing view that all structural transitions in ORAI1 are STIM-driven. The data are high-quality and broadly consistent with the interpretation, but alternative mechanisms for the defects are not considered; additional work should rule out vesicular trafficking, discuss other mechanisms, and address methodological issues.

eLife Assessment

This important study provides detailed insights into the metabolic states of hemocyte populations across developmental stages and in both physiological and pathological contexts, including during immune challenge. The study provides convincing evidence by comparing the relative utilization of glycolysis and oxidative phosphorylation in Drosophila larval immune cells, and can have implications for metabolic programs that shape immune function in health and disease.

eLife Assessment

This valuable study demonstrates that a multi-step differentiation programme in bacteria combining a bistable switch with two quorum-sensing systems is capable of generating autonomous and self-organized spatial patterns. The evidence for the core engineering system supporting patterning across several conditions is convincing, albeit incomplete for the stronger differentiation/maturation claims because the irreversibility of the proposed states is not consistently established, and some modelling and conceptual interpretation details require further clarification.

eLife Assessment

This important study combines single-molecule imaging and CUT&TAG to address the molecular mechanism underlying the differentiation process that initiates the formation of red blood cells in the bone marrow. The authors provide evidence that the transcription factor GATA2 transiently associates with a new set of genomic loci early in the differentiation process before it is replaced by GATA1. Together, the experiments across three biological systems are solid, but they could benefit from additional details and controls to strengthen the conclusions.

eLife Assessment

This study provides fundamental insights by demonstrating that the Nanog mRNA coding sequence (CDS) and 3′UTR domains are spatially segregated and functionally distinct in pluripotent stem cells and blastocysts, with 3′UTR-enriched border cells primarily influencing morphogenesis and CDS-enriched inner cells largely regulating transcription and epigenetic programs. The work opens a novel conceptual avenue for understanding how separable mRNA domains can differentially control cell behavior and differentiation. However, the evidence is incomplete, as key aspects of the molecular nature, biogenesis, and precise characterization of the separated 3′UTR and CDS RNA species, as well as causal links between their perturbation and the observed phenotypes (e.g., via rescue and deeper characterization of 3′UTR elements), remain to be fully established.

eLife Assessment

The authors propose a "simplified" model for intrinsically bursting neurons with explicitly controllable parameterization of oscillatory dynamics. The evidence that the modeling approach is generally appropriate and practical for modeling rhythmic bursting neurons and neural circuits is currently incomplete. Based on what the authors present, this model appears to have limited neurobiological relevance and utility but may be useful as a controller for an artificial system, such as in neuro-robotics applications.

eLife Assessment

There is a need for better and safer dengue virus live attenuated vaccines. This manuscript describes important findings that could lead to the design of a strongly immunogenic, tetravalent live attenuated vaccine for dengue, without the risk of causing antibody-dependent enhancement. However, the experimental evidence presented is incomplete since only constructions of one serotype were tested to prove the principle.

eLife Assessment

This study presents potentially important findings linking peripheral inflammation to the remodeling of perinodal adipose tissue and draining lymph nodes, suggesting a mechanism by which local tissue inflammation can reshape LN structure and metabolism. The idea is solid and supported by observations. However, the evidence remains incomplete in parts, as several conclusions rely on correlative weight and cellularity measurements, and macrophage involvement requires further validation.

eLife Assessment

This is a useful study investigating the role of peristalsis in the elongation of the gut, using the chick ceca as a model. The work employs optogenetics together with embryological approaches to establish links between peristaltic muscle contractions and downstream cell behaviors that lead to tube elongation. However, the work is somewhat incomplete, limited in mechanistic insights that would extend beyond prior work in the literature, which has already suggested a role for smooth muscle contractility in avian gut elongation.

eLife Assessment

This is an important study that develops multiple human iPSC-based models to study the consequences of DNMT3A mutations in Tatton-Brown-Rahman Syndrome. Convincing evidence shows dysregulation of GABAergic interneuron development and function, and the authors identify some of the key signaling mechanisms underlying these changes. This study will be of interest for understanding the functions of DNMT3A in brain development and the causes of neurological dysfunction in Tatton-Brown-Rahman Syndrome.

eLife Assessment

This valuable study builds a novel auditory-motor paradigm to investigate how the brain learns associations between movements and their auditory consequences. Solid evidence is provided for early ERPs (50-100 ms latency) reflecting violations of established key-pitch mappings. The writing, however, could be streamlined to better emphasize the paper's key contribution, and some statistical analyses might be improved.

eLife Assessment

This useful study asked whether the behaviour of motor units from a hand muscle changed across the two mechanical actions it performs. The authors used high-density intramuscular electrodes to record the activity of several motor units and reported changes in motor unit recruitment order across tasks that were not dependent on motor unit properties, suggesting differential spinal contributions to the two actions. However, the evidence supporting their main claims is incomplete, and some of the conclusions are based on unsubstantiated assumptions: the authors should correct several key analyses and temper claims that are not directly backed up by their data.

eLife Assessment

The authors make the valuable observation that directional memory during epithelial cell migration is enhanced compared to single-cell migration. They attribute this effect to adherens junctions and vinculin dimerization. In the work, central measures should be defined more precisely, and the support for their claims about the roles of adherens junctions and vinculin dimerization in memory enhancement remains incomplete.

[Editors' note: this paper was previously reviewed by another journal.]

eLife Assessment

The study provides valuable findings suggesting that modifying the donor's diet improves the effectiveness of fecal transplant therapies for liver disease. Although the reported results are of value, the evidence supporting the overall conclusions is incomplete. In particular, causal inferences regarding the effects of microbiota composition, as well as caproic acid signaling on the phenotypes studied, need further confirmation.

eLife Assessment

This study addresses the mechanism of action of benzoylurea insecticides and explores the metabolic consequences of inhibiting glycogen breakdown in insects. Both reviewers identify major flaws with the premise of the work. The strength of the provided evidence is inadequate as the data do not, or poorly, support several central claims. The significance of the findings is considered marginal.

eLife Assessment

This manuscript proposes a valuable idea on how cortical networks may learn a helpful representation of sensory stimuli. The model implementing this idea is tested in multiple experimental paradigms. However, the evidence remains incomplete as to whether the method supports both invariance and equivariance and whether it can estimate the dynamics of the moving object.

eLife Assessment

This valuable study examines how the prelimbic cortex represents learned and generalized threat over time and identifies potentially distinct stable and dynamic subnetworks that may support these functions. The work is conceptually interesting and is strengthened by the longitudinal calcium imaging approach and the inclusion of key control groups. However, the evidence supporting the claims is incomplete, particularly because the interpretations regarding inference, time-dependent representational change, and the dissociation of neural activity from freezing behavior extend beyond what is currently established by the data.