Evaluated articles

eLife Assessment

This valuable paper provides refined gene expression datasets for 52 neuron classes in C. elegans using a new method that takes advantage of the complementary strengths of bulk sequencing of flow-sorted cells and single-cell sequencing. In general, support for the paper's findings is convincing. However, more rigorous consideration of some of the method's statistical assumptions and validation of the predicted gene sets would improve the work.

eLife Assessment

This study presents valuable findings on the role of specific dopamine neurons for aversive learning and modulation of innate behavior in Drosophila larvae. The authors present solid evidence backed up by detailed behavioral quantification and rigorous testing. Their data confirms previous findings and will be of interest to the learning and memory community.

eLife Assessment

This translational study presents a direct cross-species comparison (between mice, rats, and humans) of choice behavior in the same perceptual decision-making task. The study is rare in opening a window on the evolution of decision-making, and the results will be important for many disciplines including behavioral sciences, psychology, neuroscience, and psychiatry. While the strength of the evidence presented is solid, the manuscript would benefit from additional information and analyses to strengthen and clarify its main conclusions.

eLife Assessment

In this important study, the authors use computational modeling to explore how rapid learning can be reconciled with the accumulation of stable memories in the olfactory bulb, where adult neurogenesis is prominent. They focus on the "flexibility-stability dilemma" and how it is resolved through local mechanisms within the olfactory bulb. These compelling results present a coherent picture of a neurogenesis-dependent learning process that aligns with diverse experimental observations and may serve as a foundation for further experimental and computational studies.

eLife Assessment

This fundamental work significantly enhances our understanding of how structural variants influence human phenotypes. The conclusion is convincingly supported by rigorous analyses of long-read sequencing data. If the raw data are made publicly available, these high-quality datasets and findings will further advance our knowledge of genetic variation in the human population.

eLife Assessment

Pannexin (Panx) channels are a family of poorly understood large-pore channels that mediate the release of substrates like ATP from cells, yet the physiological stimuli that activate these channels remain poorly understood. The study by Henze et al. describes an elegant approach wherein activity-guided fractionation of mouse liver led to the discovery that lysophospholipids (LPCs) activate Panx1 and Panx2 channels expressed in cells or reconstituted into liposomes. The authors provide compelling evidence that LPC-mediated activation of Panx1 is involved in joint pain and that Panx1 channels are required for the established effects of LPC on inflammasome activation in monocytes, suggesting that Panx channels play a role in inflammatory pathways. Overall, this important study reports a previously unanticipated mechanism wherein LPCs directly activate Panx channels. The work will be of interest to scientists investigating phospholipids, Panx channels, purinergic signalling and inflammation.

[Editors' note: this paper was reviewed and curated by Biophysics Colab]

Evaluation Statement (5 February 2025)

Pannexin (Panx) channels are a family of poorly understood large-pore channels that mediate the release of substrates like ATP from cells, yet the physiological stimuli that activate these channels remain poorly understood. The preprint by Henze et al. describes an elegant approach wherein activity-guided fractionation of mouse liver led to the discovery that lysophospholipids (LPCs) activate Panx1 and Panx2 channels expressed in cells or reconstituted into liposomes. The authors provide evidence that LPC-mediated activation of Panx1 is involved in joint pain and that Panx1 channels are required for the established effects of LPC on inflammasome activation in monocytes, suggesting that Panx channels play a role in inflammatory pathways. Overall, this important study reports a previously unanticipated mechanism wherein LPCs directly activate Panx channels.

Biophysics Colab recommends this study to scientists investigating phospholipids, Panx channels, purinergic signalling and inflammation.

Biophysics Colab has evaluated this study as one that meets the following criteria:

• Rigorous methodology
• Transparent reporting
• Appropriate interpretation

(This evaluation refers to version 3 of this preprint, which has been revised in response to peer review of versions 1 and 2.)

eLife Assessment

Xenacoelomorpha is an enigmatic phylum, displaying various presumably simple or ancestral bilaterian features. This valuable study characterises the reproductive life history of Hofstenia miamia, a member of class Acoela in this phylum. The authors describe the morphology and development of the reproductive system, its changes upon degrowth and regeneration, and the animals' egg-laying behaviour. The evidence is convincing, with fluorescent microscopy and quantitative measurements as a considerable improvement to historical reports based mostly on histology and qualitative observations.

eLife Assessment

This useful study presents a hierarchical computational model that integrates locomotion, navigation, and learning in Drosophila larvae. The evidence supporting the model is solid, as it qualitatively replicates empirical behavioral data, but the experimental data is incomplete. While some simplifications in neuromechanical representation and sensory-motor integration are limiting factors, the study could be of use to researchers interested in computational modeling of biological movement and adaptive behavior.

eLife Assessment

The authors provide valuable insights into the candidate upstream transcriptional regulatory factors that control the spatiotemporal expression of selector genes and their targets for GABAergic vs glutamatergic neuron fate in the anterior brainstem. The computational analysis of single-cell RNA-seq and single-cell ATAC-seq datasets to predict TF binding combined with cut and tag-seq to find TF binding represents a solid approach to support the findings in the study, although the display and discussion of the datasets could be strengthened. This study will be of interest to neurobiologists who study transcriptional mechanisms of neuronal differentiation.

eLife Assessment

In Plasmodium male gametocytes, rapid nuclear division occurs with an intact nuclear envelope, requiring precise coordination between nuclear and cytoplasmic events to ensure proper packaging of each nucleus into a developing gamete. This valuable study characterizes two proteins involved in the formation of Plasmodium berghei male gametes. By integrating live-cell imaging, ultrastructural expansion microscopy, and proteomics, this study convincingly identifies SUN1 and its interaction partner ALLAN as crucial nuclear envelope components in male gametogenesis. A role for SUN1 in membrane dynamics and lipid metabolism is less well supported. The results are of interest for general cell biologists working on unusual mitosis pathways.

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

eLife Assessment

This important study provides solid evidence for new insights into the role of Type-1 nNOS interneurons in driving neuronal network activity and controlling vascular network dynamics in awake, head-fixed mice. The authors use an original strategy based on the ablation of Type-1 nNOS interneurons with local injection of saporin conjugated to a substance P analogue into the somatosensory cortex. They show that ablation of type I nNOS neurons has surprisingly little effect on neurovascular coupling, although it alters neural activity and vascular dynamics.

eLife Assessment

This study provides valuable findings on the role of site-specific DNA methylation changes during spermatogenesis and their contribution to paternal epigenetic inheritance. The study proposes that selective loss of DNA methylation at a subset of promoters is required for nucleosome retention and the establishment of epigenetic states that may influence embryonic gene regulation. The present study's conclusion is mostly supported by solid data.

eLife Assessment

This important study dissects the mathematical and biological assumptions underlying the commonly used Activity-by-Contact model of enhancer action in transcriptional regulation. The authors provide a convincing mathematical analysis that links this (mostly phenomenological) model to concrete molecular mechanisms of enhancer function. This work provides a strong foundation from which to analyze a broad swath of genome-wide data such as that generated by CRISPRi screens.

eLife Assessment

This useful study presents computational analyses of over 5,000 predicted extant and ancestral nitrogenase structures. While the data and some analyses are solid, the study remains incomplete in demonstrating that the metrics used for comparing nitrogenase structures are statistically rigorous. The data generated in this study provide a vast resource that can serve as a starting point for functional studies of reconstructed and extant nitrogenases.

eLife Assessment

This useful study provides incomplete evidence that TANGO2 homologs, including HRG-9 and HRG-10, are not heme chaperones but play a role in cellular bioenergetics and oxidative stress homeostasis. While outstanding strengths include the use of different model systems, genetic tools, and behavioral assays, there are weaknesses in the data presented for the conclusions drawn. Due to the differences in experimental protocols between this study and the previous work reported by Sun et al., it is insufficient to rule out the role of TANGO2 as a heme chaperone, and furthermore, the authors provide only indirect evidence for the role of TANGO2 in bioenergetic and oxidative stress pathways. Nevertheless, this study paves the way for future mechanistic studies addressing the mechanisms of how TANGO2 regulates oxidative stress independent of its previously demonstrated role as a heme chaperone.

eLife Assessment

The submission by Gopal and colleagues reports important findings describing the structure of genetic and colour variation in its native range for the globally invasive weed Lantana camara. Whilst the importance of the research question and the scale of the sampling is appreciated, the analysis, which is currently incomplete, requires further tests to support the claims made by the authors.

eLife assessment

Using an elegant and thorough experimental design, Thomazeau et al show that, in the developing mouse visual cortex, presynaptic NMDA receptors at layer 5 neocortical synapses mediate spike-timing dependent LTD via JNK2, non-ionotropic signaling. These fundamental findings shed light on how NMDA receptors can tune synaptic function without acting as coincidence detectors. The experiments are supported by compelling evidence, gathered through optogenetics and quadruple patch clamp recordings from cortical slices.

eLife Assessment

Shihabeddin et al utilized single-cell RNA-Seq analysis of adult P23H zebrafish animals to identify transcription factors (e2fs, Prdm1a, Sp1) expressed selectively in neural progenitors and immature rods, and validated their necessity for regeneration using morphant analysis. The finding is useful, and the evidence is convincing. The deeper mechanistic analysis could further strengthen the current work by (1) distinguishing developmental vs regenerative transcriptional factors, (2) the addition of matched scATAC-Seq data, and (3) integration with single-cell multiome data from developing retina.

eLife Assessment

This work presents an atlas of vasopressin (AVP) and its receptor AVPR1a in mouse brains using RNAscope to map single transcript expressions of Avp and Avpr1a across various brain regions in males and females. The findings are valuable in that they identify brain regions expressing Avpr1a mRNA transcript. The impact of findings is decreased by incomplete analysis of the data due to limited description of Avpr1a mRNA distribution within brain regions and limited statistical inference.

eLife Assessment

This study dissects the function of 3 outputs of a specific population of modulatory neurons, dorsal raphe dopamine neurons, in social and affective behavior. It provides valuable information that both confirms prior results and provides new insights. The strength of the evidence is convincing, based on cutting-edge approaches and analysis. This study will be of interest to behavioral and systems neuroscientists, especially those interested in social and emotional behavior.