Evaluated articles

eLife Assessment

The manuscript by Russell et al. investigates an important problem: the current lack of methods for early and accurate N. fowleri diagnosis, which is >95% fatal. The authors provide solid evidence that a small RNA secreted by N. fowleri is detectable in biological fluids like blood and urine in a mouse model, and is present in cerebrospinal fluid and blood for a limited number of patient samples. This could potentially help with earlier diagnosis, which could save lives.

eLife Assessment

This important work describes a set of parameters that give a robust description of shape features of cells in tissues. The evidence for the usefulness of these parameters is solid. The work should be of interest for anybody analyzing epithelial dynamics, but more details about the analysis of experimental images are necessary and some streamlining of the text would increase the accessibility of the material for non-specialists.

eLife Assessment

In this manuscript, the authors analyse the nanoscale localisation of α5β1 and αVβ3 integrins in integrin adhesion complexes (IAC) by dual-colour STORM and assess the spatial organisation at the nano and mesoscale of their main adaptors (paxillin, talin and vinculin). This is an important work that provides detailed analyses that reveal how elements of these complex structures are really organised at the nanoscale, an essential perspective for a better understanding of how IACs function and regulate mechanotransduction processes. The evidence presented is solid, with super-resolution imaging experiments conducted using a single, validated methodology and subsequent computational modelling that enabled a quantitative assessment of the resulting data.

eLife Assessment

This valuable study determines the functional requirements for localization and activity of S. cerevisiae septin-associated kinases using in vivo imaging, in vitro and in vivo protein-protein interaction assays, and an instructive in vivo "tethering" approach. In addition to confirming previous results, the study offers evidence that the septin-associated kinases may directly interact with the contractile ring machinery. Although the experiments appear to have been conducted correctly, the quantitative analysis of some experiments is incomplete and should be improved to strengthen the conclusions.

eLife Assessment

This important study presents single-unit activity collected during model-based (MB) and model-free (MF) reinforcement learning in non-human primates. The dataset was carefully collected, and the statistical analyses, including the modeling, are rigorous. The evidence convincingly supports different roles for particular cortical and subcortical areas in representing key variables during reinforcement learning.

eLife Assessment

This important study presents an alternative platform for nanobody discovery using phage-displayed synthetic libraries. The evidence supporting the platform, which is used to isolate and validate nanobodies targeting Drosophila secreted proteins, is compelling. By making the library openly accessible, this provides an excellent resource to the wider scientific community. The paper presents a detailed protocol for nanobody screening; as this protocol is refined and optimized over time, this will increase the success rate for discovering nanobodies with improved properties using this alternative platform.

eLife Assessment

This manuscript applies state-of-the-art techniques to define the cellular composition of the dorsal vagal complex in two rodent species (mice and rats). The result is a fundamental resource that substantially advances our understanding of the dorsal vagal complex's role in the regulation of feeding and metabolism while also highlighting key differences between species. The analyses of single-cell profiling experiments in the manuscript provide compelling insight into the cellular architecture of the dorsal vagal complex, with potential implications for obesity therapeutics.

eLife Assessment

This study makes an important contribution to the molecular mechanisms of neural circuit formation. The data convincingly show that the transcription factor Sp1 regulates ephrin-mediated axon guidance in the spinal cord. Although the authors show that Sp1 and its co-activators p300 and CBP are required to induce ephrin expression, additional discussion and/or experiments are needed to support the claims that Sp1 regulates cis-binding of Epha receptors, or that Sp1 controls ephrin expression in relevant motor neuron populations. The study will be of broad interest to developmental neurobiologists.

eLife Assessment

This important study uses the delay line axon model in the chick brainstem auditory circuit to examine the interactions between oligodendrocytes and axons in the formation of internodal distances. This is a significant and actively studied topic, and the authors have used this preparation to support the hypothesis that regional heterogeneity in oligodendrocytes underlies the observed variation in internodal length. In a solid series of experiments, the authors have used enhanced tetanus neurotoxin light chains, a genetically encoded silencing tool, to inhibit vesicular release from axons and support the hypothesis that regional heterogeneity among oligodendrocytes may underlie the biased nodal spacing pattern in the sound localization circuit.

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

eLife Assessment

This study offers valuable insights into the role of miR-283 in ventral-lateral neurons (LNvs) and its impact on senescence, cardiac function, and aging in the Drosophila melanogaster model. However, the evidence supporting some of the conclusions remains incomplete, and further mechanistic studies are needed to clarify how miR-283 affects normal aging and influences exercise adaptations. Nonetheless, the work can be of interest to cell biologists studying miRNA biology, aging, and age-related diseases.

eLife Assessment

This study presents useful findings on the role of AFD thermosensory neurons in locomotory behaviours. The study appears solid with respect to parsing out the non-thermosensory role of AFD and also brings to light the role of AFD and AIB (linked through electrical synapses) in tactile-dependent locomotory modulation.

eLife Assessment

This important study provides a description of how single-neuron firing rates in the human medial temporal lobe and frontal cortex are modulated by theta-burst stimulation of the basolateral amydala. The results are supported by convincing evidence obtained from a rigorous task design and analysis of an incredibly rare dataset. The results may help guide future studies incorporating amygdala stimulation to improve patient health.

eLife Assessment

This paper uses a new computational method that integrates bulk sequencing and single-cell sequencing data to provide refined gene expression datasets for 52 neuron classes in C. elegans. The paper's findings are convincing, presenting an approach that alleviates a key shortcoming of single-cell RNA sequencing. While the datasets have some limitations that the authors acknowledge, the new methodology and refined datasets will be important resources for those interested in understanding how gene expression shapes neuronal morphology and physiology.

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 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.)