Evaluated articles

eLife Assessment

This valuable study introduces a new framework for improving the automated sorting of extracellular action potentials. However, the evidence is incomplete; the biophysical model used for simulation is based on one simulation that does not necessarily reflect real experimental data, the test datasets are insufficiently diverse, and essential algorithmic details are currently missing. This work will be of interest to neuroscientists using high-density multichannel electrophysiology.

eLife Assessment

This useful study addresses the interesting question of how immune cells recognise infected erythrocytes in malaria. It proposes the parasite protein PfGBP-130 as an interaction partner of the human cell surface protein LFA 1, which could help explain how NK cells recognize infected erythrocytes. The conclusions are partially supported by pull-down and cell-based activation data. However, the overall evidence of direct interaction at the cell-cell interface and downstream effects is incomplete; stronger evidence is required to demonstrate surface exposure of PfGBP-130, as well as a direct role of this antigen in killing.

eLife Assessment

This important study addresses a discrepancy between population-level growth laws and single-cell correlations. It shows, for flagellar and synthetic genes in E. coli, that while gene expression of certain genes reduces population-average growth, expression levels positively correlate with growth at the single-cell level. The measurements are mostly convincing, and the proposed mechanism-inheritance of growth factors such as ribosomes during asymmetric division- explains this observation. The theoretical analysis would benefit from clearer explanations and robustness checks.

eLife Assessment

This study addresses an important question about how large-scale brain networks interact, and specifically how the default mode network exchanges information with the sensory cortex. The analyses are sophisticated, but at present provide incomplete evidence for the claims made in the paper.

eLife Assessment

The valuable study aims to differentiate between foveal and peripheral attentional mechanisms in visual and frontal brain regions in monkeys engaged in a free-gaze visual search task. The authors interpret differences in responses between target and nontarget conditions as feature-based attention; however, this may not be the correct interpretation. The authors do not provide enough information on how they distinguish foveal and peripheral RFs. Consequently, the study provides only incomplete evidence that does not support the authors' conclusions, and the significance of the findings is not strong.

eLife Assessment

In this manuscript, based on electron microscopy observations of C. elegans embryos, the authors make the bold claim that the plasma membrane ruptures during cell division and that closure of this opening by membrane extension contributes to cytokinesis. Although the findings are potentially valuable, the evidence in support of the authors' claims is inadequate.

eLife Assessment

This fundamental work substantially advances our understanding of short-term plasticity mechanisms by providing evidence for release-independent low-frequency synaptic depression that reflects a redistribution of vesicles within the readily releasable pool, via a reduction in docking site occupancy due to vesicle undocking. The evidence supporting this model is convincing, with rigorous electrophysiological and computational analysis. The work will be of broad interest to cellular neuroscientists and synaptic physiologists.

eLife Assessment

The authors previously identified SLAP as a key suppressor of the Src tyrosine kinase and a tumor suppressor. In this important study, the authors show SLAP functions in a cell-autonomous fashion in colon stem cells and propose solid evidence that SLAP reduces tumorigenesis by inhibiting an EphB2-SRC axis.

eLife Assessment

This valuable study addresses a timely question regarding the contribution of transposable elements to splice isoform diversity in the Drosophila brain, directly engaging with recent conflicting findings in the field. The work provides convincing evidence that TE-gene chimeric transcripts are detectable and that prior discrepancies largely arise from methodological differences in computational pipelines and experimental design. The combination of reanalysis, methodological clarification, and targeted validation represents a technical contribution that will be of interest to researchers studying transcriptome complexity and transposable elements. However, the strength of evidence would be further enhanced by increased methodological transparency, more rigorous experimental controls, and a more cautious interpretation of functional implications.

eLife Assessment

This important study deepens our understanding of how populations of a given species may diverge in their molecular and physiological patterns as a result of adaptation to different thermal regimes. By approaching this question from multiple directions, the authors provide solid evidence for adaptive changes in three strains of the diamondback moth after only three years of experimental evolution, and support the causal involvement of the PxSODC gene in thermal adaptation to both cold and hot temperatures. This work would benefit from more sophisticated phylogenetic analyses, better statistical support, and a more detailed discussion of the differences in the three strains at the pathway level.

eLife Assessment

This is a potentially important work on the organization of visual information in the rodent superior colliculus. It reports that the selectivity of neurons to line orientation and motion in the visual image is largely governed by the sensitivities of retinal neurons and their ordered projection to the superior colliculus. If confirmed, these conclusions could substantially revise prior thinking in this field. However, in the present state, the methods and analysis are incomplete and cannot justify all the claims.

eLife Assessment

This important study advances our understanding of the neural substrate of planning trajectories towards a goal by using recurrent neural networks. The manuscript provides solid evidence for most of the claims, but it remains unclear whether the dynamics do indeed bear the defining characteristics of attractors, and the interpretation and scope of some claims may need to be reassessed in light of prior work. The work will be of broad interest to theoretical and systems neuroscientists and to cognitive scientists.

eLife Assessment

This important study presents evidence that the Chromatin-linked adaptor for MSL complex proteins (CLAMP) GA-binding transcription factor (TF) regulates ~75% of HS-induced repression in Drosophila and suggests that CLAMP is the first known transcription factor to induce heat-stress-mediated repression of gene expression. While mechanistic details remain to be sorted out, this manuscript provides convincing evidence that novel pathways involving the CLAMP transcription factor repress gene expression during heat shock stress.

eLife Assessment

The study investigates how CD1c-restricted T cells respond to Mtb-infected APCs, leading to increased cytokine production and cytotoxic activity that may help control Mtb infection. While the work is important and will interest researchers in the field, the supporting evidence is incomplete and could be strengthened by additional experiments. Experiments would: (i) evaluate THP1-CD1c cells to determine whether MHC surface expression is reduced or entirely abolished, (ii) enhance confidence in the purity of the CD1c-specific T cell population isolated from blood, and (iii) suggest what additional signal THP1-CD1c cells treated with Mtb express that is absent from the untreated cells.

eLife Assessment

This is a detailed and well-designed simulation study of the utility of replication metrics in animal-to-human study translations in bridging the gap between laboratory discoveries and health practice, a critical consideration in turning laboratory scientific research findings into tangible, real-world applications, to directly help human health. The study approaches are solid, and the findings are important, as they offer insights into clinical research translations to advance health decision-making. There is some potential for the strength and applicability of the presented evidence to be improved upon revision.

eLife Assessment

This article describes the comprehensive metabolic phenotype of a mouse model of Down Syndrome, together with supporting transcriptomic, metabolomic, and biochemical data. While the work is largely descriptive, the evidence presented is convincing and highlights similarities and differences in male and female mice. This is a valuable study that provides essential groundwork for the further genetic dissection of dosage-sensitive genes causing metabolic dysregulation in Down Syndrome.

eLife Assessment

The nematode C. elegans is an ideal model in which to achieve the ambitious goal of a genome-wide atlas of protein expression and localization. In this paper, the authors explore the utility of a new and efficient method for labeling proteins with fluorescent tags, evaluating its potential to be the basis for a larger, genome-wide effort that is likely to be very useful for the community. While the evidence for the method itself is solid, carrying out this project at a large scale will require significant additional feasibility studies.

eLife Assessment

The authors provide valuable data linking NAD+ dependent HSD3b6 gene expression in the eyelid to a vicious cycle involving decreased steroidogenesis and AR signaling, pro-inflammatory cytokine release, inflammation, CD38 activation, and further NAD+ decline, which induces meibomian gland atrophy leading to dry eye disease. Overall, the presented work provides evidence for the pathologic relationship between a pro-inflammatory environment, intracrine activity, and the NAD+ cofactor. However, the current study does not clearly establish the proposed intracrine mechanism and may largely reflect systemic hormonal effects resulting from the global Had3b6 knockout, leading to an incomplete narrative.

eLife Assessment

This important study demonstrates the power of the UniDesign computational framework in prospectively engineering a PAM-relaxed Staphylococcus aureus Cas9 variant with editing performance comparable to evolution-derived counterparts. The authors provide convincing evidence through rigorous biochemical validation across multiple human cell types, comprehensive deep-sequencing analyses, and direct comparisons with established variants, providing mechanistic insights into PAM specificity remodeling and Cas9 optimization. By establishing computational design as a viable alternative to directed evolution for CRISPR systems, this work will be of broad interest to the protein engineering, genome engineering, synthetic biology, and computational protein design communities.

eLife Assessment

This study provides a valuable contribution to the field of zebrafish immunology by demonstrating that the two TNF paralogs tnfa and tnfb show distinct cellular sources and temporal expression patterns during inflammation. These findings are potentially significant because they suggest regulatory divergence and functional specialization within the TNF signaling system in teleosts. While the evidence supporting differential expression is convincing, the work remains largely observational and would benefit from functional experiments and deeper mechanistic insight to determine whether these differences translate into distinct roles in inflammatory signaling. This work will be of interest to immunologists interested in inflammatory cytokine evolution and immune regulation in vertebrates.