Evaluated articles

eLife Assessment

In this important study, the authors use computational modeling to explore how fast learning can be reconciled with the accumulation of stable memories in the olfactory bulb, where adult neurogenesis is prominent. Their model demonstrates that changes in excitability, plasticity, and susceptibility to apoptosis during the maturation of adult-born granule cells can help resolve the flexibility-stability dilemma. These compelling results provide a coherent picture of a neurogenesis-dependent learning process that is consistent 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

This work is a important resource for hypothesis testing of 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. Extensive high-quality datasets were generated and state of the art computational methods were convincingly implemented to identify candidate regulatory elements. The work will be of interest to biologists working to understand neuronal gene regulatory networks.

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 valuable study presents computational analyses of over 5,000 predicted extant and ancestral nitrogenase structures. The data analyses are convincing, it offers unique insights into the relationship between structural evolution and environmental and biological phenotypes. The data generated in this study provide a vast resource that can serve as a starting point for studies of reconstructed and extant nitrogenases.

eLife Assessment

This valuable study provides solid evidence that supports TANGO2 homologs, including HRG-9 and HRG-10, can play a role in cellular bioenergetics and oxidative stress homeostasis. It also challenges the previously reported role of TANGO in heme transport and paves the way for future mechanistic studies addressing the mechanisms of how TANGO2 regulates oxidative stress homeostasis. The strengths include the use of different model systems, genetic tools, behavioral assays and efforts by the authors in using the same reagents to reproduce results of other groups.

eLife Assessment

The submission by Praveen 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

By using sparse Cre-dependent deletion of GluN1 subunit, in vitro quadruple patch clamp recordings, and pharmacological interventions, the authors show that spike timing dependent plasticity at between L5 synapses in the mouse visual cortex is: (i) dependent on presynaptic NMDA receptors; (ii) mediated by non-ionotropic NMDA receptor signaling, and (iii) reliant on presynaptic JNK2/Syntaxin-1a interactions. These fundamental findings advance our understanding of the molecular mechanisms underlying spike time dependent plasticity. The data are compelling and are supported by the elegant application of sophisticated experimental approaches.

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.

eLife Assessment

This valuable study investigates the computational role of top-down feedback -- a property that is found in biological circuits -- in Artificial Neural Network (ANN) models of the neocortex. Using hierarchical recurrent ANNs in an audiovisual integration task, the authors show a visual bias consistent with that observed in human perception, which mildly improves learning speed. While the study offers a tool that is of value for studying top-down feedback in cortical models, with the potential to inspire other fields (e.g. machine learning), the presented evidence for a general framework of deep learning architectures that predict behavior is incomplete, and the methods section lacks sufficient detail in terms of hyperparameter choice and network structures.

eLife Assessment

This study proposes a valuable and interpretable approach for predicting hematoma expansion in patients with spontaneous intracerebral hemorrhage from non-contrast computed tomography. The evidence supporting the proposed method is solid, including predictive performance evaluated through external validation. This quantitative approach has the potential to improve hematoma expansion prediction with better interpretability. The work will be of interest to medical biologists working on stroke and neuroimaging.

eLife Assessment

This important study provides a nuanced analysis of the impact of cues on cost/benefit decision-making deficits in male rats that could have translational relevance to many addictive disorders. The main findings are that cues paired with rewarded outcomes increase the proportion of risky outcomes, whereas risky choice is reduced when cues are paired with reward loss. The experimental data is convincing, but the computational analysis based on the optimisation of different Q-learning models is incomplete. The findings will be of interest to behavioural neuroscientists and clinicians with an interest in risk, decision making, and gambling disorders.