Evaluated articles

eLife Assessment

Whole-brain imaging of neuronal activity in freely behaving animals holds great promise for neuroscience, but numerous technical challenges limit its use. In this important study, the authors describe a new set of deep learning-based tools to track and identify the activity of head neurons in freely moving nematodes (C. elegans) and jellyfish (Clytia hemisphaerica). While the tools convincingly enable high tracking speed and accuracy in the settings in which the authors have evaluated them, the claim that these tools should be easily generalizable to a wide variety of datasets is incompletely supported.

eLife Assessment

This valuable study presents a theoretical model of how punctuated mutations influence multistep adaptation, supported by empirical evidence from some TCGA cancer cohorts. This solid model is noteworthy for cancer researchers as it points to the case for possible punctuated evolution rather than gradual genomic change. However, the parametrization and systematic evaluation of the theoretical framework in the context of tumor evolution remain incomplete, and alternative explanations for the empirical observations are still plausible.

eLife Assessment

This important work fills a gap in the characterization of motor architecture and chemical coupling of the male reproductive system, crucial to understanding male reproduction and fertility. The convincing analysis reveals two distinct types of glutamatergic neurons that co-release either serotonin or octopamine. While serotonergic neurons are required for male fertility, octopaminergic neurons are dispensable, indicating a division of labour. This work lays the foundations for future investigations into the conserved key principles by which multi-transmitter systems control coordinated motor outputs.

eLife Assessment

This useful study uses creative scalp EEG decoding methods to attempt to demonstrate that two forms of learned associations in a Stroop task are dissociable, despite sharing similar temporal dynamics. However, the evidence supporting the conclusions is incomplete due to concerns with the experimental design and methodology. This paper would be of interest to researchers studying cognitive control and adaptive behavior, if the concerns raised in the reviews can be addressed satisfactorily.

eLife Assessment

This paper presents important new findings about the impact of the TAK-003 vaccine against dengue based on a convincing reanalysis of trial data. The results corroborate those of the original trial analyses, but with reduced uncertainty about the estimates of the impact of the vaccine. The findings will be of interest to clinicians, infectious disease epidemiologists, trial statisticians and policymakers seeking to understand the vaccine's efficacy profile and associated uncertainties.

eLife Assessment

This study makes a valuable contribution by separating two timescales of adaptation: rapid, within block reductions in learning rate, and slower, location specific, meta-learned adjustments. Behavioural data and computational modeling converge to support both processes. The evidence is solid with neuroimaging results suggesting that meta-learned learning rates are encoded in the orbitofrontal cortex, while prediction errors are represented in a distributed network including the ventral striatum and are modulated by expected error magnitude, though the specificity of these effects requires further contextualization. The manuscript is timely and clearly written; its main limitation is the weak linkage between neural signals and behavior, leaving uncertainty over whether the reported signals play a mechanistic role in learning.

eLife Assessment

This important study investigates why the 13-lined ground squirrel (13LGS) retina is unusually rich in cone photoreceptors, the cells responsible for color and daylight vision. The authors perform deep transcriptomic and epigenetic comparisons between the mouse and the 13-lined ground squirrel (13LGS) to provide convincing evidence that identifies mechanisms that drive rod vs cone-rich retina development. Overall, this key question is investigated using an impressive collection of new data, cross-species analysis, and subsequent in vivo experiments. However, the functional analysis showing the sufficiency and necessity of Zic3 and Mef2C remains incomplete, and further analyses are needed to support the claim that these enhancers are newly evolved in 13LGS.

eLife Assessment

This important study used five metrics to compare the cost-effectiveness of intramural and extramural research funded by the National Institutes of Health in the United States between 2009 and 2019. They found that each type of research had its own set of strengths: extramural research was more cost-effective in terms of publications, whereas intramural research was more cost-effective in terms of influencing clinical work. The evidence supporting these findings is mostly solid, but there are a number of questions about the methods and data - notably about indirect cost recovery and other non-NIH sources of funding - that need to be answered.

eLife Assessment

The authors make an important advance in enzyme annotation by fusing biochemical knowledge with language‑model-based learning to predict catalytic residues from sequence alone. Squidly, a new ML method, outperforms existing tools on standard benchmarks and on the CataloDB dataset. The work has solid support, yet clarifications on dataset biases, ablation analyses, and uncertainty filtering would strengthen its efficiency claims.

eLife Assessment

This study presents valuable new insights into the patterns of organelle inheritance in the protozoan parasite Toxoplasma gondii. An innovative dual-labeling approach used in this study to track maternal-derived and de novo synthesized organelles provides a technical advance with potential to be more broadly applied. Solid evidence is provided that different organelles show distinct inheritance fates during cell replication; however, the data describing the residual body component in this process is incomplete.

eLife Assessment

In this manuscript, the authors used in vivo long-term tip recordings of the long trichoid sensilla of male hawkmoths to analyze spontaneous spiking activity indicative of the ORNs' endogenous membrane potential oscillations. The authors combine extracellular electrophysiology of the hawkmoth antennae with computational modeling to predict that Orco receptor neuron (ORN) activity is required for circadian, not ultradian, firing patterns. The work provides valuable support for the hypothesis that a posttranslational feedback loop regulates daily and ultradian rhythms in neuronal excitability. Nevertheless, the evidence reported provides only incomplete support for their conclusions, especially with regard to the biological implications of their assumption-heavy models.

eLife Assessment

This is a solid paper on intermittent fasting that will be of interest to readers. The data presented are certainly valuable as a resource. The findings of both shared and tissue-specific signatures, both at the proteomic and transcriptomic levels, align well with what has been established and bring new insight into metabolic adaptation and its consequences in muscle, cortex, and liver.

eLife Assessment

This study addresses an important question and shows how social navigation in homing pigeons can be explained by simple averaging, without requiring any complex cognitive abilities. The evidence, based on a rigorous and systematic comparison of seven models and data on how social routes can be generated from solitary routes, is compelling. The authors should be commended for their willingness to critically re-examine established interpretations.

eLife Assessment

This valuable study examines the cleavage of motor neuron nucleoporins by proteases 2A and 3C of enterovirus D68, a pathogen associated with acute flaccid myelitis. The evidence supporting the effects of EV-D68 proteases on nuclear import and export is solid and confirms previous results on the specific targeting of nucleoporins by proteases from other enteroviruses. However, the claim that cleavage of nucleoporins by EV-D68 2A is neurotoxic, though intriguing, is incomplete, as the evidence is largely indirect.

eLife Assessment

This valuable study tests whether prediction error or prediction uncertainty controls how the brain segments continuous experience into events. The paper uses validated models that predict human behavior to analyze multivariate neural pattern changes during naturalistic movie watching. The authors provide solid evidence that there are overlapping but partially distinct brain dynamics for each signal.

eLife Assessment

This important study provides evidence for our understanding of HIV transmission dynamics by age and sex in Zambia during the PopART trial; by combining phylogenetic and individual-based mathematical modelling (IBM), it adds depth to the epidemiological literature and may inform more strategic allocation of HIV prevention resources in sub-Saharan Africa. The authors employ two complementary and well-established methodologies (phylogenetics and IBM), and this dual approach is a notable strength. However, the evidence supporting key conclusions is incomplete, with several claims insufficiently substantiated by the data presented. Improvements in data presentation (e.g., quantification of qualitative statements, statistical estimates, and clearer description of results) would substantially strengthen the paper.

eLife Assessment

This useful study describes a mechanism of microbial modulation of anti-tumor immunity, which is of considerable interest in the field. However, the experimental supports for the key mechanistic claim, the interaction between RadD and NKp46, are not robust. Multiple experimental inconsistencies, especially in vivo, weaken the conclusions, making the strength of evidence incomplete. Additional controls, direct binding assays, and clarification of in vivo mechanistic relevance would strengthen the work.

eLife Assessment

This important study demonstrates that ocular organoids can generate both retina and lens through a non-canonical, "inside-out" morphogenetic route. The work is solid, with well-designed experiments combining imaging, molecular analyses, and transcriptomics to establish that lens formation in organoids follows conserved molecular programs despite an alternative morphogenesis. These findings expand our understanding of self-organization and developmental plasticity, and will be of broad interest to researchers working on eye development, organoids, and tissue engineering.

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

eLife Assessment

The study provides valuable insights into the role of thalamic nuclei in associative threat and extinction learning, supported by a large dataset and multipronged analyses. However, aspects of the evidence remain incomplete, particularly regarding the statistical methods, the claims of plasticity, and the network modeling framework. With this addressed, this manuscript will be of interest to those interested in learning and memory, fear, thalamic circuitry, and related mental heath conditions.

eLife Assessment

This important study concerns the propagation of waves in bacterial biofilms, bridging active matter physics and bacterial biophysics. While the experimental observations are solid, the theoretical interpretation and model validation are currently incomplete and require further refinement. This work will be of interest to microbiologists, biophysicists, and researchers studying collective behavior in biological systems.