Evaluated articles

eLife Assessment

In light of the diverse functions associated with the Dorsal Raphe Nucleus across vertebrate species, this important study presents findings on the role of serotonin in promoting behavioral quiescence through the regulation of neuromotor populations. Combining optogenetics with brain-wide activity analyses, the study provides convincing evidence of interest to researchers in neuromodulation and translational medicine fields.

eLife Assessment

This study presents important findings for the understanding of central brain circuits that underlie nociception-induced escape. Using a laser-based nociception assay, chronic neuronal silencing, trans-Tango anatomical tracing, and reference to connectomic data, the authors propose that nociceptive signals (from painless- and trpA1-expressing neurons) converge on a subset of dopaminergic neurons (subsets of PPL1 and PAM), which in turn engage mushroom body output neurons (MBONs) to shape escape latency. However, methods and controls fall short of fully supporting the findings, rendering the evidence incomplete. This study will be of interest to scientists studying nociception and learning and memory circuits.

eLife Assessment

This valuable work identifies a subpopulation of neurons in the larval zebrafish pallium that responds differentially to varying threat levels, potentially mediating the categorization of negative valence. The evidence supporting these claims is solid; however, the study would be strengthened by more sophisticated analyses of functional imaging results, behavioral confirmation of stimulus valence, and further evidence linking the functionally distinct clusters to their molecular identity. This work will be of interest to systems neuroscientists investigating the circuit-level encoding of emotion and defensive behavior.

eLife Assessment

This manuscript presents important findings that challenge traditional models of speech processing by demonstrating that theta-gamma phase-amplitude coupling in the auditory cortex is primarily a stimulus-driven alignment to external acoustic structures rather than an intrinsic neural oscillatory mechanism. The evidence supporting these claims is convincing, grounded in a robust cross-linguistic acoustic analysis and high-fidelity, time-resolved intracranial recordings.

eLife Assessment

This is a potentially important study comparing infants (8 months) and adults with respect to rhythmic EEG response properties during periodic and aperiodic visual stimulation. The results provide solid evidence for a ~4 Hz EEG response in infants that emerges independently of stimulation frequency. At this stage, additional work will be required to conclusively establish that this theta-band effect reflects genuine neural resonance rather than oculomotor processes.

eLife Assessment

This work presents a valuable new open-source tool for wirelessly controlling optogenetic stimulation in neuroscience experiments in behaving rodents. Evidence for its potential usefulness in different types of optogenetic experiments is solid, although some details and concerns were viewed as lacking or overlooked (e.g., system latency, battery weight). The work is expected to interest neuroscientists working with optogenetics and neuroengineers developing small-sized integrated devices for rodent experiments.

eLife Assessment

This valuable study presents a plastic recurrent spiking network model that spontaneously generates repeating neuronal sequences under unstructured inputs. The authors provide solid evidence that, while the global weight distribution stabilizes, individual synaptic connections undergo constant turnover with strength-dependent timescales, supporting sequence generation. However, the study is purely simulation-based and phenomenological, lacking both a mechanistic explanation for sequence emergence and explicit experimental predictions, and robustness to alternative, more biologically realistic plasticity rules remains to be demonstrated. The work will be of interest to theoretical and experimental neuroscientists working on synaptic plasticity and neural sequence generation.

eLife Assessment

Shin et al present important new observations regarding novel REM-specific cortical high-frequency oscillations. The evidence demonstrating the presence of a novel rhythm is convincing. However, the data presented is incomplete to demonstrate claims of a) brain-state-specific effects of these events, b) clear structured reactivation, and c) the specific degree of linkage to memory consolidation.

eLife Assessment

This study is useful and unique, since hagfish brains are of phylogenetic importance and can reveal features ancestral to all vertebrates. The manuscript is, however, incomplete and would benefit from contextualization with the current literature; comparisons with the recent amphioxus study are suggested, plus an increased focus on the specific, unique features of the hagfish brain. One significant concern is the apparent absence of Datx2 expression, given that the riboprobe was synthesized from cDNA derived from whole-brain RNA extracts. Ideally, the authors should identify a tissue in which Datx2 is known to be strongly expressed and then apply the probe as a positive control.

eLife Assessment

This study provides important insights into how species-specific variation in oxytocin receptor regulatory architecture contributes to diversity in brain expression patterns and social behaviors. By generating multiple BAC transgenic mouse lines carrying the prairie vole oxytocin receptor locus and combining anatomical, molecular, behavioral, and chromatin-structure analyses, the authors present convincing evidence that distal regulatory elements constrain peripheral expression while permitting brain expression aligned with behavior. This study provides an experimental framework and a resource that are of value for dissecting how regulatory variation in neuromodulatory systems contributes to species differences in social behavior. This work will be of interest to those interested in social behavior, oxytocin, neuromodulation, and related conditions.

eLife Assessment

Kim et al. provide important findings explaining how T3SS assembly is regulated by a conserved genetic context. The evidence supporting the conclusions is compelling, with numerous experiments demonstrating the validity of the findings. The work will be of interest to molecular biologists, biochemists, and microbiologists working on secretion systems or similar complexes. Further studies revealing similar mechanisms in other systems would enhance the impact of the current study.

eLife Assessment

This important study combines cryo-EM, biochemical, and cell-based assays to examine how Gβγ interacts with and potentiates PLCβ3. The authors present evidence for multiple Gβγ interaction surfaces and argue that Gβγ primarily enhances PLCβ3 activity after membrane recruitment rather than serving mainly as a membrane-recruitment factor. The evidence is solid overall, although uncertainty remains about the physiological relevance and precise arrangement of the proposed interfaces because the structural model relies on engineered crosslinking.

eLife Assessment

This valuable study presents a comparative dataset on crab locomotion to examine the evolution of sideways walking. The evidence supporting the authors' claims is largely convincing. This work will be of interest to researchers in animal locomotion.

eLife Assessment

This study provides valuable insights into the role of MATR3 in oocyte maturation and folliculogenesis, using conditional knockout mice and in vitro follicle culture systems to show that MATR3 is required for oocyte growth and gene transcription, with downstream effects on follicle development. The strength of the evidence is incomplete, as key findings lack independent validation, methodological details are insufficient, and inconsistencies in data presentation reduce confidence in the conclusions. The work will be of interest to researchers in reproductive biology and fertility.

eLife Assessment

This valuable article provides a convincing and very detailed model of the process regulating the assembly of the spore coat in the model spore-forming bacterium Bacillus subtilis. It focuses on SafA, a morphogenetic coat protein involved in the assembly of the spore coat inner layer, deciphering the contributions of disulfide bond formation and crosslinking reactions catalyzed by a transglutaminase. The process had been studied with a combination of genetics and microscopy, but this is the first complete assessment incorporating detailed biochemical approaches.

eLife Assessment

This important paper substantially advances our understanding of how Molidustat may work, beyond its canonical role, by identifying its therapeutic targets in cancer. This study presents a compelling and well-structured investigation into the therapeutic vulnerabilities of APC-mutant colorectal cancer. This work will be of broad interest to the cancer community in studying small molecules and their therapeutic targets.

eLife Assessment

In this important study, the authors demonstrate that generative AI techniques (restricted Boltzmann machine) can be used effectively to design and characterize mutational pathways of WW domains with different binding specificities. The computational studies are complemented by experimental validations, and the results provide solid evidence supporting the idea that sequence landscape holds significance in understanding protein evolution from a transition path perspective. The minor weakness of the study in the current form concerns limited success in designing variants with smoothly varying binding specificities. Nevertheless, the work will likely have a major impact on research aimed at understanding how evolution navigates fitness landscapes as well as reconstructing ancestral sequences.

eLife Assessment

This study represents a useful finding on the social modulation of the complex repertoire of vocalizations made across a variety of strains of lab mice. The evidence supporting the claims is, at present, incomplete, as numerous concerns regarding the appropriate categorization of vocalizations, the averaging of data points with disparate levels of occurrence, the interpretation of the function of noisy calls, and a general lack of adequate analyses of experimental data were raised. With these issues addressed, the work will be of importance to scientists studying rodent vocal communication.

eLife Assessment

This manuscript uncovers the importance of Vinculin in the maintenance of junctional integrity during neural tube closure in regions of increased mechanical stress, by using sophisticated methods such as laser ablation and live imaging. The manuscript also reports a novel application of an established embryonic stem cell protocol to efficiently generate mutant and transgenic embryos for analysis. The findings are fundamental in nature, significantly improve our understanding of a major research question, and are backed by compelling evidence. Whilst there is much to appreciate in this work, exactly how Vinculin mediates neural fold elevation remains unclear, and addressing this lacuna will significantly improve the strength of the manuscript; in addition, some rewriting for better clarity (including technical/methodological details) and inclusion of possible consequences of the increased number of tight junction gaps in the vinculin mutant would be pertinent.

eLife Assessment

In this important study, a new multi-scale imaging workflow promises to accelerate and democratize comparative connectomics, with projectome-level data informing synapse-level connectivity. While the pipeline and time savings are convincing, the evidence for the segmentation methodology as a reusable community resource is incomplete, with key metrics like error rates, annotation times, and proof-reading times not reported. Furthermore, the evidence on the utility of projectome-level information for analysing brains appears misleading. By clarifying the findings and ensuring that the complete software pipeline is available in online open source repositories alongside precise documentation, the authors would deliver on their vision to enable any laboratory to map and analyse brain connectomes.