Evaluated articles

eLife Assessment

This important contribution to the field demonstrates the role of a single transcription factor with cell-autonomous functions in the differentiation of two distinct neuronal populations in regulating the interactions between those cells in a non-autonomous manner to generate their final organized projection pattern. There are additional quantifications and controls that would enhance the study and would improve the strength of the evidence from incomplete if they were performed.

eLife Assessment

This paper provides an important proposal for why learning can be much faster and more accurate if synapses have a fast component that immediately corrects errors, as well as a slower component that corrects behavior averaged over a longer timescale. It is convincingly shown that integrating these two learning timescales improves performance compared to classical strategies, particularly in terms of robustness and generalization when learning new target signals. However, the biological plausibility and justification for the proposed rapid learning mechanism require further elaboration and supporting mechanistic examples.

eLife Assessment

This important study aims to understand the role of endothelial cell differentiation into pericytes in the restoration of blood-brain barrier function after ischemic stroke. Identification of pericytes derived from endothelial cells and the involvement of myeloid cell-derived TGFβ1 signaling are compelling new findings, but future studies will be needed to validate the origin and nature of these pericytes. The work will be of interest to blood-brain barrier and basic and translational stroke researchers.

eLife Assessment

This manuscript introduces Opto-PKCε, an optogenetic tool that enabled important findings derived from interactome and phosphoproteome studies. Light-dependent recruitment of Opto-PKCε to the plasma membrane revealed the specific phosphorylation of the insulin receptor at Thr 1160. In turn, recruitment to mitochondria led to phosphorylation of the complex I subunit NDUFS4, correlating with reduced spare respiratory capacity. The evidence supporting these conclusions is solid, although additional clarification on data analysis would further enhance readability.

eLife Assessment

This work presents an important genetic toolkit for Drosophila neurobiologists to access and manipulate neuronal lineages during development and adulthood. The evidence supporting the fidelity of this toolkit after revision is compelling. This work will interest Drosophila neurobiologists in general, and some of the genetic tools may be used outside the nervous system. The conceptual approaches used in this paper are likely transferable to other fields as comparable data and genomic methods are obtained.

eLife Assessment

Kin selection and inclusive fitness have generated significant controversy. This paper reconsiders the general form of Hamilton's rule in which benefits and costs are defined as regression coefficients, with higher-order coefficients being added to accommodate non-linear interactions. The paper is a landmark contribution to the field with compelling, systematic analysis, giving clarity to long-standing debates.

eLife Assessment

This study introduces a valuable toolkit for zebrafish transgenesis, significantly enhancing the flexibility and efficiency of transgene generation for immunological applications. The authors provide convincing evidence through well-designed experiments, demonstrating the toolkit's utility in generating diverse and functional transgenic lines.

eLife Assessment

This paper reports the fundamental finding of how Raman spectral patterns correlate with proteome profiles using Raman spectra of E. coli cells from different physiological conditions and found global stoichiometric regulation on proteomes. The authors' findings provide compelling evidence that stoichiometric regulation of proteomes is general through analysis of both bacterial and human cells. In the future, similar methodology can be applied on various tissue types and microbial species for studying proteome composition with Raman spectral patterns.

eLife Assessment

The study reports valuable findings on the nature of genotype-by-climate interaction, parameterised in a framework that allows integrating genetics and ecophysiological variation in switchgrass. The evidence provided is solid overall but the analysis could be improved to better support some of the claims.

eLife Assessment

This important manuscript investigates the role of olfactory cues in Pieris brassicae larvae, focusing on their interactions with the host plant Brassica oleracea and the parasitoid wasp Cotesia glomerata. The authors' demonstration that impaired olfactory perception reduces caterpillar performance and increases susceptibility to parasitism is convincing. These findings highlight the ecological significance of olfaction in mediating feeding behavior and predator avoidance in herbivorous insects.

eLife Assessment

This study presents a valuable open-source and cost-effective method for automating the quantification of male aggression and courtship in Drosophila melanogaster. The work as presented provides solid evidence that the use of the behavioral setup that the authors designed - using readily available laboratory equipment and standardised high-performing classifiers they developed using existing software packages - accurately and reliably characterises social behavior in Drosophila. The work will be of interest to Drosophila neurobiologists and particularly to those working on male social behaviors.

eLife Assessment

This important study provides convincing evidence that glucosylceramide synthase (GlcT), a rate-limiting enzyme for glycosphingolipid (GSL) production, plays a role in the differentiation of intestinal cells. Mutations in GlcT compromise Notch signaling in the Drosophila intestinal stem cell lineage, resulting in the formation of enteroendocrine tumors. Further data suggest that a homolog of glucosylceramide synthase also influences Notch signaling in the mammalian intestine. While the outstanding strengths of the initial genetic and downstream pathway analyses are noted, there are minor weaknesses in the data regarding the potential role of this pathway in Delta trafficking. Nevertheless, this study opens the way for future mechanistic studies addressing how specific lipids modulate Notch signalling activity.

eLife Assessment

TrASPr is an important contribution that leverages transformer models focused on regulatory regions to enhance predictions of tissue-specific splicing events. The revisions strengthen the manuscript by clarifying methodology and expanding analyses across exon and intron sizes, and the evidence supporting TrASPr's predictive performance is compelling. This work will be of interest to researchers in computational genomics and RNA biology, offering an improved model for splicing prediction and a promising approach to RNA sequence design.

eLife Assessment

Fleming et al sought to better understand DNAJC7's function in motor neurons as mutations in this gene have been associated with amyotrophic lateral sclerosis (ALS). Using iPSC-derived motor neurons, interactome, and transcriptomic data, they provide solid evidence that loss-of-function mutations in DNAJC7 disrupt RNA binding proteins and resistance to proteasomal stress. These important findings advance our understanding of DNAJC7 in motor neurons while providing clues to how its loss may be causal for ALS; nonetheless, the experiments were performed with a single iPSC line, while at least 3 are deemed to be required to validate the results. Furthermore, the mechanistic evidence is still incomplete with respect to how DNAJC7 mutations lead to HSF1 impaired activity, and whether it is direct or not.

eLife Assessment

This study presents valuable findings on the regulation of survival and maintenance of brain-resident immune cells called microglia. Using compelling and sophisticated genetic tools, the authors demonstrate a gene dosage-dependent mechanism using which microglia are eliminated. This research on cell competition and survival will be of broad interest to the cell biology community.

eLife assessment

Using intracellular in vitro and in vivo recordings and a deep learning approach, this study shows that mouse dentate gyrus mossy cells (MCs) and CA3 pyramidal cells process information from an important electrophysiological hall mark of hippocampus, sharp wave-ripples (SWRs). The innovative use of deep learning to predict SWR waveforms from MC membrane potentials represents an interesting methodological advance. While the key findings are potentially fundamental, some of the evidence is currently incomplete and should be revised to better support the findings.

eLife Assessment

The authors make an important contribution to comparative functional genomics by developing a semi-automated computational pipeline that integrates classification and marker-based cluster annotation to identify orthologous cell types. Using a single-cell RNA-seq dataset of induced pluripotent stem cells and derived embryonic bodies from four primate species: humans, orangutans, cynomolgus macaques, and rhesus macaques, the authors provide convincing evidence that cell type-specific marker genes are substantially less transferable across species than broadly expressed genes, with transferability declining as phylogenetic distance increases. This study establishes a key framework and reference dataset for comparative single-cell analyses and encourages more rigorous evaluation of marker gene transferability across species.

eLife Assessment

This study provides a valuable contribution to spatial transcriptomics by introducing MerQuaCo, a computational tool for standardizing quality control in image-based spatial transcriptomics datasets. The tool addresses the lack of consensus in the field and provides robust metrics to identify and quantify common imperfections in datasets. The work is supported by an impressive dataset and compelling analyses, and will be of significant interest to researchers focused on data reproducibility and downstream analysis reliability in spatial transcriptomics.

eLife Assessment

This study provides an important method to model the statistical biases of hypermutations during the affinity maturation of antibodies. The authors show convincingly that their model outperforms previous methods with fewer parameters; this is made possible by the use of machine learning to expand the context dependence of the mutation bias. They also show that models learned from nonsynonymous mutations and from out-of-frame sequences are different, prompting new questions about germinal center function. Strengths of the study include an open-access tool for using the model, a careful curation of existing datasets, and a rigorous benchmark; it is also shown that current machine-learning methods are currently limited by the availability of data, which explains the only modest gain in model performance afforded by modern machine learning.

eLife Assessment

Using an unbiased approach, this important study discovered a role of Ezh2 in the differentiation of granule neuron precursors, the cell of origin for Shh group of medulloblastoma. Furthermore, the authors also provided solid evidence that combined inhibition of Ezh2 and CDK4/6 likely represents a promising strategy for the treatment of this subgroup of MB. Validation of these findings using the FDA-approved Ezh2 inhibitor is needed to further strengthen this preclinical study.