eLife assessment

This work explores the role of one the most abundant circRNAs, circHIPK3, in bladder cancer cells, showing with convincing data that circHIPK3 depletion affects thousands of genes and that those downregulated (including STAT3) share an 11-mer motif with circHIPK3, corresponding to a binding site for IGF2BP2. The experiments demonstrate that circHIPK3 can compete with the downregulated mRNAs targets for IGF2BP2 binding and that IGF2BP2 depletion antagonizes the effect of circHIPK3 depletion by upregulating the genes containing the 11-mer. These important findings contribute to the growing recognition of the complexity of cancer signaling regulation and highlight the intricate interplay between circRNAs and protein-coding genes in tumorigenesis.

eLife assessment

The authors aim to develop a CRISPR system that can be activated upon sensing an RNA. As an initial step to this goal, they describe RNA-sensing guide RNAs for controlled activation of CRISPR modification. Many of the data look convincing and while several steps remain to achieve the stated goal in an in vivo setting and for robust activation by endogenous RNAs, the current work will be important for many in the field.

eLife assessment

This study presents valuable findings describing how two brain regions, the midbrain periaqueductal gray matter and basolateral amygdala, communicate when a predator threat is detected. Though the periaqueductal gray is usually viewed as a downstream effector, this work contributes to a growing body of literature from this lab showing that the periaqueductal gray produces effects by acting on the basolateral amygdala. The experimental design, data collection and analysis methods provide solid evidence for the main claims. Although anatomical and immediately early gene results suggest the paraventricular nucleus of the thalamus may serve as a mediator of dorsolateral periaqueductal gray to basolateral amygdala neurotransmission, this finding would benefit from a functional assessment. This study will appeal to a broad audience, including basic scientists interested in neural circuits, basic and clinical researchers interested in fear, and behavioral ecologists interested in foraging.

eLife assessment

This valuable work describes a new protein factor that is required for filamentous phage assembly. Convincing evidence is provided for the binding of PSB15 to the packaging signal of the single-stranded DNA, Trx, and cardiolipin, and a mechanism for how the phage DNA is targeted to the assembly site in the bacterial inner membrane is presented. The work will be of interest to microbiologists.

eLife assessment

This study presents important data describing cell states of olfactory ensheathing cells, and how these cell states may relate to repair after spinal cord injury. While the overall framework used for characterizing these cells is solid, the quantification and contextualization of results are incomplete, given that measurements, significance statistics, and discussion of both previous work and experimental methods that would be necessary to support several claims are not provided. With more thorough quantification and discussion, this work will be of interest to stem cell biologists and spinal cord injury researchers.

eLife assessment

This study presents valuable research comparing three different species of extant cartilaginous fishes and describes new data on ratfish. The methods are convincing although the reviewers noted that standardized methods are essential when comparing numerical datasets. This study would be of interest to skeletal biologists working on the evolution of chondrichthyan skeletons.

eLife assessment

This useful study reports that epididymal proteins are required for embryogenesis after fertilization. The data presented are generally convincing, but the study is incomplete because it does not investigate in detail how those proteins cause DNA fragmentation and compromised embryonic development. This work will be of interest to reproductive biologists and andrologists.

eLife assessment

This important work advances our understanding of how brains flexibly gate actions in different contexts, a topic of great interest to the broader field of systems neuroscience. Recording neural activity from several sensory and motor cortical areas along a sensorimotor pathway, the authors found that preparatory activity in motor cortical areas of the mouse depends on the context in which an action will be carried out, consistent with previous theoretical and experimental work. Furthermore, the authors provide causal evidence that these changes support flexible gating of actions. The carefully carried out experiments were analyzed using state-of-the-art methodology and provide convincing conclusions.

eLife assessment

This fundamental study provides insights into the interplay of endogenous orienting and the planning of goal-directed gaze shifts (saccades). Using an elegant experimental protocol and detailed analyses of the time course of saccadic choices, the authors provide compelling evidence for independent mechanisms that guide early, reflexive eye movements and later, voluntary gaze shifts. This work will be of interest to neuroscientists and psychologists working on vision and motor control and to those researching decision-making across disciplines.

eLife assessment

This important study provides evidence for a combination of the latest generation of Oxford Nanopore Technology long reads with state-of-the art variant callers enabling bacterial variant discovery at accuracy that matches or exceeds the current "gold standard" with short reads. The evidence supporting the claims of the authors is convincing, although the inclusion of a larger number of reference genomes would further strengthen the study. The work will be of interest to anyone performing sequencing for outbreak investigations, bacterial epidemiology, or similar studies.

eLife assessment

The study, from the group that pioneered migrasome, describes a novel vaccine platform derived from this newly discovered organelle. Using these cleverly engineered migrasomes – that behave like natural migrasomes – as a novel vaccine platform has the potential to overcome obstacles such as cold chain issues for vaccines like messenger RNA. Although the findings are important with practical implications for the vaccine technology, and the evidence, based on appropriate and validated methodology is convincing and is in line with current state-of-the-art, there are some critical issues that need to be addressed. These include a head-to-head comparison with proven vaccine platforms, for example, a SARS-CoV-2 mRNA vaccine or an adjuvanted recombinant spike protein.

eLife assessment

This important study reports the deep evolutionary conservation of a core genetic program regulating spermatogenesis in flies, mice, and humans. The data presented are supportive of the main conclusion and generally convincing. This work will be of interest to evolutionary and reproductive biologists.

eLife assessment

This important study reports the developmental dynamics and molecular markers of the rete ovarii during ovarian development. However, the data supporting the main conclusions remain incomplete. This study will be of interest to developmental and reproductive biologists.

eLife assessment

The authors combined human genetic analysis with zebrafish experiments to produce evidence that alleles that impair the function of EPHA4 cause idiopathic scoliosis (IS), a common spinal deformity. The significance of the findings is important because the cellular and molecular mechanisms that contribute to IS remain poorly understood. The human genetic data are quite convincing whereas the zebrafish data, although supportive, are incomplete.

eLife assessment

This useful manuscript describes the second earliest known winged ovule without a capule in the Famennian of Late Devonian. Using solid mathematical analysis, the authors demonstrate that three-winged seeds are more adapted to wind dispersal than one-, two- and four-winged seeds. The manuscript will help the scientific community to understand the origin and early evolutionary history of wind dispersal strategy of early land plants.

eLife assessment

This work is important because it attempts to elucidate how immune cells migrate across the blood brain barrier. The authors developed a convincing framework to visualize, recognize and track the movement of different immune cells across primary human and mouse brain microvascular endothelial cells without the need for fluorescence-based imaging using microfluidic devices. The data gathered are solid, and this work will be of interest to the cancer biology, immunology and medical therapeutics fields.

eLife assessment

This fundamental study provides a modeling regime that provides new insight into the energy-preservation parameters among schooling fish. The strength of the evidence supporting observations such as distilled dynamics between leading and lagging schooling fish which are derived from emergent properties is convincing. Overall, the study provides exciting insights into energetic coupling with respect to group swimming dynamics. Some potential improvements to strengthen the study include clarification regarding degrees of freedom and parameter ranges in the model.

eLife assessment

This is a valuable study that describes the effects of T. pallidum on neural development by applying single-cell RNA sequencing to an iPSC-derived brain organoid model. The evidence supporting the claims of the authors is solid, although further evidence to understand the differences in infection rates would strengthen the conclusions of the study. In particular, the conclusions would be strengthened by validating infection efficiency as this can impact the interpretation of single-cell sequencing results, and how these metrics affect organoid size as well as comparison with additional infectious agents. Furthermore, additional functional validations of downstream effectors could be insightful.

eLife assessment

This fundamental study reports differential expression of key genes in full-term placenta between Tibetans and Han Chinese at high elevations, which are more pronounced in the placenta of male fetus than in female fetus. The gene expression data were collected and analyzed using solid and validated methodology, although there is limited support for hypoxia-specific responses due to a lack of low-altitude samples. Several of the placental genes found in this study have been previously reported to show signatures of positive selection in Tibetans, pointing to a potential mechanism of how human populations adapt to high elevation by mitigating the negative effects of low oxygen on fetal growth. The work will be of interest to evolutionary and population geneticists as well as researchers working on human hypoxic response.

eLife assessment

This study aggregates across five fMRI datasets and reports that a network of brain areas previously associated with response inhibition processes, including several in the basal ganglia, are more active on failed stop than successful stop trials. This study is valuable as a well-powered investigation of fMRI measures of stopping. However, evidence for the authors' conclusions regarding the role of subcortical nodes in stopping is incomplete, due to the limitations in the fMRI analysis.

eLife assessment

This important study provides a new perspective on why preparatory activity occurs before the onset of movement. The authors report that when there is a cost on the inputs, the optimal inputs should start before the desired network output for a wide variety of recurrent networks. The authors present convincing evidence by combining mathematically tractable analyses in linear networks and numerical simulation in nonlinear networks.

eLife assessment

The valuable findings by Dasgupta et al demonstrate the role of Sema7a in fine tuning the morphology of the microcircuit between afferent axons and sensory hair cells in the lateral line organ. The loss and gain of function evidence provides solid support for a role for Sema7a in this process. Additional work is needed to determine the role for different isoforms in Sema7a-mediated synapse formation and chemoattraction as well as cell type specificity.

eLife assessment

This important work provides convincing data on neuronal heterogeneity in the dorsal raphe nucleus (DRN), focusing on their electrophysiological properties, morphology, and susceptibility to the neurodegeneration of noradrenaline and dopamine systems in the Parkinsonian state. These findings suggest a significant interplay between catecholaminergic systems in healthy and parkinsonian conditions, as well as neuronal structure and function. Such findings provide a strong foundation for basic scientists as well as pre-clinical researchers interested in the role of dorsal raphe neurons in Parkinson's disease.

eLife assessment

The authors use point light displays to measure biological motion (BM) perception in children (mean = 9 years) with and without ADHD, and relate it to IQ, social responsiveness scale (SRS) scores and age. They report that children with ADHD were worse at all three BM tasks, but that those tasks loading more heavily on local processing relate to social interaction skills and those loading on global processing relate to age. There are still some elements of the results that are unclear, but nevertheless, the important and solid findings extend our limited knowledge of BM perception in ADHD, as well as biological motion processing mechanisms in general.

eLife assessment

This fundamental study significantly advances our understanding of the role of water influx and swelling on neutrophil migration in response to chemoattractant. The evidence supporting the conclusions, based on a genome-wide CRISPR screen and high quality cellular observations, is compelling. This paper will be of interest to cell biologists and biophysicists working on cell migration.

eLife assessment

Despite the well-known facilitatory effect that integration across the senses has on behavioural measures, standard neuroimaging approaches have not yet produced reliable and precise neural correlates. In this paper, Buhman et al. harness the decoding of EEG responses, beyond univariate approaches, to capture these correlates in a robust, clear fashion. If confirmed, this approach could be important for estimating multisensory integration in humans across a wide range of different domains. However, the strength of evidence to support these claims is still incomplete because of the potentially confounding factor of eye movements, which the authors themselves identify in their data, and because of the discrepancies between the behavioural and EEG data.

eLife assessment

Following synaptic vesicle fusion events at release sites, vesicle remnants will need to be cleared in order to allow new rounds of vesicle docking and fusion. This fundamental study of Mahapatra and Takahashi examines the role of release site clearance in synaptic transmission during repetitive activity in two types of central synapses, the giant calyx of Held and hippocampal CA1 synapses. The study uses pharmacological approaches to interfere with release site clearance by blocking membrane retrieval (endocytosis). The results also show how pharmacological inhibition of scaffold proteins affects short-term plasticity. The data presented make a compelling case for fast endocytosis as necessary for rapid site clearance and vesicle recruitment to active zones. The data reveal an unexpected, fast role for local site clearance in counteracting synaptic depression.

eLife assessment

This paper provides valuable insights into the neural substrates of human working memory. Through clever experimental design and rigorous analyses, the paper provides compelling evidence that the working memory representation of stimulus orientation is a reformatted version of the presented stimulus, though more work is needed to establish more generally that visual working memories are abstractions of percepts. This work will be of broad interest to cognitive neuroscientists working on the neural bases of visual perception and memory.

eLife assessment

This useful experiment seeks to better understand how memory interacts with incoming visual information to effectively guide human behavior. Using several methods, the authors report two distinct pathways relating visual processing to the default mode network: one that emphasizes "semantic" cognition, and the other, spatial cognition. Despite the impressive array of methods employed, the evidence supporting a clear distinction is currently incomplete.

eLife assessment

The study presents a useful investigation of the relation between pupil size and saccade decision in human observers. Based on the premise that pupil size is a reliable proxy of "effort", the authors conclude that less costly saccade targets are preferred. The data were collected and analyzed using solid and validated methodology, but the evidence supporting the claim that effort drives saccade target selection is incomplete and alternative explanations are not ruled out.

eLife assessment

This is a fundamental study that advances our understanding of the contribution of somatic variations in microglia that may contribute to the onset or progression of neurodegenerative disease. Specifically, during Alzheimer's disease, somatic mutations were identified in the MAPK pathway genes. The findings presented here are backed by compelling evidence drawn from a patient cohort, along with mechanistic proof-of-concept studies. Collectively, this research will be of interest to a wide audience, particularly those involved in the study of somatic mutations, neurodegeneration, immunology, and cell signalling.

eLife assessment

This study could pose an important step forward in understanding brain network embedding of beta oscillations, advancing our circuit-level understanding of the pathophysiology associated with frontal beta or dopaminergic alterations in psychiatric or neurological disorders. The study provides compelling evidence that beta oscillations across the neocortex and basal ganglia map onto shared functional and structural networks that show significant positive correlations with dopamine receptors.

eLife assessment

This study employed a comprehensive approach to examining how the MT+ region integrates into a complex cognition system in mediating human visuo-spatial intelligence. While the findings are useful, the experimental evidence is incomplete and the study design, hypothesis, analyses, writing, and presentation need to be improved. The work will be of interest to researchers in psychology, cognitive science, and neuroscience.

eLife assessment

This study offers a valuable description of the layer-and sublayer specific outputs of the somatosensory cortex based on convincing evidence obtained with modern tools for the analysis of brain connectivity, together with functional validation of the connectivity using optogenetic approaches in vivo. Beyond bridging together, in one dataset, the results of disparate studies, this effort brings new insights on layer specific outputs, and on differences between primary and secondary somatosensory areas. This study will be of interest to neuroanatomists and neurophysiologists.

eLife assessment

Abbasi and colleagues use Granger causality to explore the cortico-subcortical dynamics during speaking and listening. They find valuable evidence for bi-directional connectivity in distinct frequency bands as a function of behaviour, but currently offer incomplete support for the validity of their analyses and the predictive coding interpretation of their results.

eLife assessment

This a useful study that reports a genetic regulatory network that accounts for altered lipid metabolism in response to two different bacterial diets of C. elegans. The proposed mechanism, linking vitamin B12, S-adenosyl methionine (SAM), phosphatidylcholine (PC), and neutral lipid levels, is solid but has been previously demonstrated by other studies using similar assays. The evidence to support a new layer of regulation, via the production of phospho-choline by ASM-3/acid sphingomyelinase, requires further substantiation.

Editors Assessment:

This work is part of a series of papers from the Hong Kong Biodiversity Genomics Consortium sequencing the rich biodiversity of species in Hong Kong. This example presents the genome of the golden birdwing butterfly Troides aeacus (Lepidoptera, Papilionidae). A notable and popular species in Asia that faces habitat loss due to urbanization and human activities. The lack of genomic resources impedes conservation efforts based on genetic markers, as well as better understanding of its biology. Using PacBio HiFi long reads and Omni-C a 351Mb genome was assembled genome anchored to 30 pseudo-molecules. After reviewers requested more information on the genome quality it seems there was high sequence continuity with contig length N50 = 11.67 Mb and L50 = 14, and scaffold length N50 = 12.2 Mb and L50 = 13. Allowing a total of 24,946 protein-coding genes were predicted. This study presents the first chromosomal-level genome assembly of the golden birdwing T. aeacus, a potentially useful resource for further phylogenomic studies of birdwing butterfly species in terms of species diversification and conservation. This evaluation refers to version 1 of the preprint

Editors Assessment:

This work is part of a series of papers from the Hong Kong Biodiversity Genomics Consortium sequencing the rich biodiversity of species in Hong Kong. This example assembles the genome of the common chiton, Liolophura japonica (Lischke, 1873). Chitons are marine molluscs that can be found worldwide from cold waters to the tropics that play important ecological roles in the environment, but to date are lacking in genomes with only a few assemblies available. This data was produced using PacBio HiFi reads and Omni-C sequencing data, the resulting genome assembly being around 609 Mb in size. From this 28,010 protein-coding genes were predicted. After review improved the methodological details the quality metrics look near chromosome-level, having a scaffold N50 length of 37.34 Mb and 96.1% BUSCO score. This high-quality genome should hopefully be a valuable resource for gaining new insights into the environmental adaptations of L. japonica in residing the intertidal zones and for future investigations in the evolutionary biology in Polyplacophorans and other molluscs.

This evaluation refers to version 1 of the preprint

Editors Assessment:

This work is part of a series of papers from the Hong Kong Biodiversity Genomics Consortium sequencing the rich biodiversity of species in Hong Kong. This example assembles the genome of the long-spined sea urchin Diadema setosum (Leske, 1778). Using PacBio HiFi long-reads and Omni-C data the assembled genome size was 886 Mb, consistent to the size of other sea urchin genomes. The assembly anchored to 22 pseudo-molecules/chromosomes, and a total of 27,478 genes including 23,030 protein-coding genes were annotated. Peer review added more to the conclusion and future perspectives. The data hopefully providing a valuable resource and foundation for a better understanding of the ecology and evolution of sea urchins.

This evaluation refers to version 1 of the preprint

eLife assessment

This, in principle, useful study suggests that the G-protein subunit Gng13 is required for limiting injury and inflammation following H1N1 influenza infection via anti-inflammatory effects from ectopic tuft cells. While support for Gng13 helping to limit influenza injury in the transgenic mouse models used here is solid, evidence for these effects being mediated by normal tuft cells remains incomplete, giving conflicting data from mice that lack tuft cells entirely.

eLife assessment

This fundamental study elucidates the function of the cohesin subunit SCC3 in maintaining homologous chromosome pairing and synapsis during meiosis. The observation of sterility in the SCC3 weak mutant prompted an investigation of abnormal chromosome behavior during anaphase I, and the discovery that SCC3's loading onto meiotic chromosomes is REC8-dependent. The convincing evidence presented in this study contributes to our understanding of meiosis in rice and attracts cell biologists, reproductive biologists, and plant geneticists.

eLife assessment

This study represents a useful description of a third interaction site between melanophilin and myosin-5a which has a role in regulating the distribution of pigment granules in melanocytes. While much of the data forms a solid case for this interaction, the inclusion of controls for the cellular studies and measurement of interaction affinities would have been helpful.

eLife assessment

This important study contributes insights into the regulatory mechanisms of a protein governing cell migration at the membrane. The integration of approaches revealing protein structure and dynamics provides convincing data for a model of regulation and suggests a new allosteric role for a solubilized phospholipid headgroup. The work will be interesting to researchers focusing on signaling mechanisms, cell motility, and cancer metathesis.

eLife assessment

This study provides valuable insight into the role of miR-199a/b-5p in cartilage formation. The evidence supporting the significance of the identified miRNA and its target mRNA transcripts is convincing. This paper will likely primarily benefit scientists focused on diseases related to this biological process, such as osteoarthritis. Furthermore, researchers interested in miRNAs as a broader subject may find the computational model development methodology helpful.

eLife assessment

This study demonstrates that neurons receiving inputs from auditory cortex in the inferior colliculus widely encode the outcome of a sound detection task independant of the presence of auditory cortex. This valuable study based on imaging of transynaptically labelled neurons provides convincing evidence that auditory cortex is necessary neither for sound detection, nor to channel information related to behavioral outcome to the subcortical auditory system. This study will be of wide interest for sensory neuroscientists.

eLife assessment

This study provides valuable evidence that differentiated cells of the zebrafish skin form membrane protrusions called cytonemes, that contact and potentially transmit Notch signals to cells of the intermediate layer below. Evidence that periderm cells send out cytoneme-like protrusions is solid, and perturbations that affect cytoneme number clearly affect periderm structure and gene expression. However, evidence that these effects are directly due to cytoneme mediated-Notch signaling is incomplete.

eLife assessment

In this important study, Li and others identified cell membrane receptors for juvenile hormone (JH), a terpenoid hormone in insects that regulates their development and reproduction. While intracellular receptors for JH have been well characterized, membrane receptors for JH have remained elusive. Although the authors provide convincing evidence to indicate that the receptor tyrosine kinases they identified bind to JH in vitro and induce responses in cultured cells, their loss-of-function phenotypes are not consistent with known JH functions, leaving obscure the physiological roles of these receptors in mediating in vivo JH function.

eLife assessment

This important study identifies the TNXB-AKT pathway as a potential mechanism underlying hemophilia-associated cartilage degeneration. The evidence supporting the conclusions is convincing, with murine and human patient evidence as well as genome-wide DNA methylation analysis. This paper would be of interest to cell biologists and biochemists working on the field of musculoskeletal disorders.

Editors Assessment:

This work is part of a series of papers from the Hong Kong Biodiversity Genomics Consortium sequencing the rich biodiversity of species in Hong Kong. This example This work is part of a series of papers from the Hong Kong Biodiversity Genomics Consortium sequencing the rich biodiversity of species in Hong Kong. This example presenting the first whole genome assembly of Dacryopinax spathularia, an edible mushroom-forming fungus that is used in the food industry to produce natural preservatives. Using PacBio and Omni-C data a 29.2 Mb genome was assembled, with a scaffold N50 of 1.925 Mb and 92.0% BUSCO score demonstrating the quality (review pushing the authors to provide more detail and QC stats to help better convince on this). This data providing a useful resource for further phylogenomic studies in the family Dacrymycetaceae and investigations on the biosynthesis of glycolipids with potential applications in the food industry.

This evaluation refers to version 1 of the preprint

Editors Assessment:

This work is part of a series of papers from the Hong Kong Biodiversity Genomics Consortium sequencing the rich biodiversity of species in Hong Kong. This example assembles the genome of the milky mangrove Excoecaria agallocha, also known as blind-your-eye mangrove due to its toxic properties of its milky latex that can cause blindness when it comes into contact with the eyes. Living in the brackish water of tropical mangrove forests from India to Australia, they are an extremely important habitat for a diverse variety of aquatic species, including the mangrove jewel bug of which this tree is the sole food source for the larvae. Using PacBio HiFi long-reads and Omni-C technology a 1,332.45 Mb genome was assembled, with 1,402 scaffolds and a scaffold N50 of 58.95 Mb. After feedback the annotations were improved, predicting a very high number (73,740) protein coding genes. The data presented here provides a valuable resource for further investigation in the biosynthesis of phytochemical compounds in its milky latex with the potential of many medicinal and pharmacological properties. As well as increasing the understanding of biology and evolution in genome architecture in the Euphorbiaceae family and mangrove species adapted to high levels of salinity.

This evaluation refers to version 1 of the preprint

eLife assessment

Combining experimental and computation approaches, this manuscript provides solid evidence for a post-transcriptional mechanism that provides robust control over the protein expression level of RecB in E. coli. In addition to uncovering how DNA damage drives more efficient translation of RecB protein, this work also reveals important tenets for how broader mechanisms that suppress noise and underlie responsive tuning of protein levels can be achieved.

Editors Assessment:

The King Angelfish (Holacanthus passer) is a great example of a Holacanthus angelfish that are some of the most iconic marine fishes of the Tropical Eastern Pacific. However, very limited genomic resources currently exist for the genus and these authors have assembled and annotated the nuclear genome of the species, and used it examine the demographic history of the fish. Using nanopore long reads to assemble a compact 583 Mb reference with a contig N50 of 5.7 Mb, and 97.5% BUSCOs score. Scruitinising the data, the BUSCO score was high compared to the initial N50’s, providing some useful lessons learned on how to get the most out of ONT data. The analysis suggests that the demographic history in H. passer was likely shaped by historical events associated with the closure of the Isthmus of Panama, rather than by the more recent last glacial maximum. This data provides a genomic resource to improve our understanding of the evolution of Holacanthus angelfishes, and facilitating research into local adaptation, speciation, and introgression of marine fishes. In addition, this genome can help improve the understanding of the evolutionary history and population dynamics of marine species in the Tropical Eastern Pacific.

This evaluation refers to version 1 of the preprint

eLife assessment

This important bibliometric analysis shows that authors of scientific papers whose names suggest they are female or East Asian get quoted less often in news stories about their work. While caveats are inevitable in this type of study, the evidence for the authors' claims is convincing, with a rigorous, and importantly, reproducible analysis of over 20,000 articles from across 15 years. This paper will be of interest to science journalists and to researchers who study science communication.

eLife assessment

This study tackles a significant question: Does the brain apply spatial navigation systems to evaluate decision options in conceptual social spaces? The investigation is useful as it seeks to address this intriguing hypothesis. The findings offer partial support: a solid analysis revealed characteristic grid-like patterns associated with decision-making directions. However, it remains uncertain whether these effects are genuinely due to navigating a conceptual social space or potentially confounded by changes in visual stimuli. The experimental design may not be capable of definitively resolving this issue.

eLife assessment

This valuable study advances our understanding of why diabetes is a risk factor for more severe Covid-19 disease. The authors offer convincing evidence that cathepsin L is more active in diabetic individuals because of the presence of high glucose, where the main mechanism is increased cathepsin L maturation. This study should be of interest to researchers in diabetes, virology and immunology.

eLife assessment

This paper reports on the transcriptional changes upon chloramphenicol-induced surface mobility of Bacillus subtilis, a phenomenon that can occur during co-incubation with Streptomyces venezuelae, a chloramphenicol producer. The work presented includes valuable and thorough transcriptomics data, which convincingly indicate that sub-lethal chloramphenicol triggers substantial changes in B. subtilis gene expression. There are, however, significant limitations and concerns whether the documented changes are causal for the phenotypes observed or simply correlated with these phenotypes; additionally, the notion that chloramphenicol triggers a 'division of labor' was incomplete and should be backed up experimentally.

eLife assessment

This valuable study describes mice with a knock out of the IQ motif-containing H (IQCH) gene, to model a human loss-of-function mutation in IQCH associated with male sterility. The infertility is reproduced in the mouse, making it a compelling model, but some of the mechanistic experiments provide only indirect and thus incomplete evidence for interaction between IQCH and potential RNA binding proteins. With more rigorous approaches, the paper should be of interest to cell biologists and male reproductive biologists working on the sperm flagellar cytoskeleton and mitochondrial structure.

eLife assessment

This important study indicates a role for linker Histone H1 in protecting heterochromatic regions from certain types of repression. The experiments and data analysis that support the model for the role of linker Histone H1are solid, although additional experiments could provide a deeper mechanistic understanding. The study will be of broad interest to those interested in the role of chromatin in eukaryotic gene expression.

eLife assessment

This study presents a valuable new behavioral apparatus aimed at differentiating the strategies animals use to orient themselves in an environment. The evidence supporting the claims is solid, with statistical modeling of animal behavior. Overall, this study will attract the interest of researchers exploring spatial learning and memory.

eLife assessment

This study investigates a dietary intervention that employs a smartphone app to promote meal regularity, which may be useful. Despite no observed changes in caloric intake, the authors report significant weight loss. While the concept is very interesting and deserves to be studied due to its potential clinical relevance, the study's rigor needs to be improved, and is currently considered inadequate, notably for its reliance on self-reported food intake, a highly unreliable way to assess food intake. Additionally, the study theorizes that the intervention resets the circadian clock, but the study needs more reliable methods for assessing circadian rhythms, such as actigraphy.

eLife assessment

This study provides important insights into the role of neurexins as regulators of synaptic strength and timing at the glycinergic synapse between neurons of the medial nucleus of the trapezoid body and the lateral superior olive, key components of the auditory brainstem circuit involved in computing sound source location from differences in the intensity of sounds arriving at the two ears. Through an elegant combination of genetic manipulation, fluorescence in-situ hybridization, ex vivo slice electrophysiology, pharmacology and optogenetics, the authors provide compelling and rigorous evidence to support their claims. While further work is needed to reveal the mechanistic basis by which neurexins influence glycinergic neurotransmission, this work will be of interest to both auditory and synaptic neuroscientists.

eLife assessment

This study provides important evidence supporting the ability of a new type of neuroimaging, OPM-MEG system, to measure beta-band oscillation in sensorimotor tasks in 2-14 years old children and to demonstrate the corresponding development changes, since neuroimaging methods with high spatiotemporal resolution that could be used on small children are quite limited. The evidence supporting the conclusion is compelling. This work will be of interest to the neuroimaging and developmental science communities.

eLife assessment

In this fundamental work, the authors demonstrated that maternal choline supplementation improved spatial memory, reduced hyperexcitability, and restored NeuN expression in a familial Alzheimer's disease mouse model. Interestingly, choline deficiency increased mortality, while paradoxically reduced hyperexcitability. Using behavior, electrophysiological, and histological measures, the authors present convincing evidence supporting the significant role of maternal choline supplementation in protecting hippocampal functions vulnerable to Alzheimer's disease.

eLife assessment

The gut microbiota influences many infectious diseases; however, its role Leptospirosis remains unclear. In this fundamental work, Xie et al. use a hamster model to show that Leptospira infection leads to gut pathology, an altered gut microbiota, and increased translocation. A combined use of antibiotics and LPS neutralization prolonged survival, providing a potential new therapeutic approach. This study utilizes compelling methods to provide new insights into this emerging disease, which could be dissected further in future studies aimed at gaining mechanistic insight and assessing the translational relevance of these discoveries.

eLife assessment

How the triplicate interaction between chemokines with both GAGs and G protein-coupled receptors (GPCR) works and how gradients are created and potentially maintained in vivo are poorly understood. The authors provide solid evidence to show phase separation can drive chemotactic gradient formation. The paper is a useful advance in the field of chemokine biology.

Editors Assessment: Marsupial species are invaluable for comparative studies due to their distinctive modes of reproduction and development, but there are a shortage of genomic resources to do these types of analyses. To help address that data gap multi-tissue transcriptomes and transcriptome assemblies have been sequenced and shared for the fat-tailed dunnart (Sminthopsis crassicaudata), a mouse-like marsupial that due to is ease of breeding is emerging as a useful lab model. Using ONT nanopore and Pacbio long-reads and illumina short reads 2,093,982 transcripts were sequenced and assembled, and functional annotation of the assembled transcripts was also carried out. Some addition work was required to provide more details on the QC metrics and access to the data but this was resolved during review. This work ultimately producing dunnart genome assembly measuring 3.23 Gb in length and organized into 1,848 scaffolds, with a scaffold N50 value of 72.64 Mb. These openly available resources hopefully provide novel insights into the unique genomic architecture of this unusual species and provide valuable tools for future comparative mammalian studies.

This evaluation refers to version 1 of the preprint

eLife assessment

This study presents an important finding on the anatomical connectivity and functional roles of the previously uncharacterized neuronal populations in the nucleus incertus. The evidence supporting the conclusions is convincing, with imaging and manipulations of the genetically targeted populations of neurons. The work presents a significant milestone for future mechanistic studies of the nucleus incertus.

eLife assessment

This study uses carefully designed experiments to generate a useful behavioural and neuroimaging dataset on visual cognition. The results provide solid evidence for the involvement of higher-order visual cortex in processing visual oddballs and asymmetry. However, the evidence provided for the very strong claims of homogeneity as a novel concept in vision science, separable from existing concepts such as target saliency, is inadequate.

eLife assessment

This important manuscript provides compelling experimental evidence of extended motivational signals encoded in the mouse anterior cingulate cortex (ACC) that are implemented by orbitofrontal cortex (OFC)-to-ACC signaling during learning. The experimental methods used were state-of-the-art. These results will be of interest to those interested in cortical function, learning, and/or motivation.

eLife assessment

This study introduces a useful deep learning-based algorithm that tracks animal postures with reduced drift by incorporating transformers for more robust keypoint detection. The efficacy of this new algorithm for single-animal pose estimation was demonstrated through comparisons with two popular algorithms. However, the analysis is incomplete and would benefit from comparisons with other state-of-the-art methods and consideration of multi-animal tracking.

eLife assessment

This study provides valuable insights into the mechanism of axonal directional changes, utilizing sLNv neurons as a model. The data were collected and analysed using solid methodology, although the conceptual framing of the work and contextualization of the results require revision and reassessment. The study holds potential interest for neurobiologists focusing on axonal growth and development.

eLife assessment

This important manuscript uses circuit mapping, chemogenetics, and optogenetics to demonstrate a novel hippocampal lateral septal circuit that regulates social novelty behaviours and shows that downstream of the hippocampal septal circuit, septal projections to the ventral tegmental area are necessary for general novelty discrimination. The strength of the evidence supporting the claims is convincing but would be strengthened by the inclusion of additional functional assays. The work will be of interest to systems and behavioural neuroscientists who are interested in the brain mechanisms of social behaviours.

eLife assessment

This study interrogates cell non-autonomous signaling between GABAergic neurons and somatic tissues in the nematode C. elegans. The authors report that mitochondrial stress in only GABAergic neurons extends lifespan and improves healthspan, phenotypes that are dependent on the transcription factor daf-16/FOXO3a. However, while the findings may be valuable to furthering our understanding of neuronal control of aging and health, the current evidence is incomplete and additional experiments are needed to support their claims.

eLife assessment

This study provides solid evidence of coordinated spiking activity of neurons in the anterior cingulate cortex (ACC), and correlated activity in the CA1 subregion of the hippocampus, during observational learning. The authors also show coordinated ACC-CA1 neural activity during rest periods prior to the performance of the observationally learned task. The important findings advance the field's understanding of neural mechanisms underlying social learning.

eLife assessment

This study presents valuable insight into a nuclear-encoded transcription factor network and the role of one transcription factor Clifford in mitochondrial biogenesis. The experimental design, data collection, and analyses are solid. Addressing a few points related to mitochondrial and ETC biogenesis will further strengthen the study.

eLife assessment

This study provides a methodological report on a modified adaptive sampling approach, multiple walker supervised molecular dynamics (mwSuMD), and its application to G protein-coupled receptors (GPCR), which are the most abundant membrane proteins and key targets for drugs. The mwSuMD approach assists in sampling complex binding processes, leading to some useful findings for GPCR activity, although results may be considered incomplete because the approach may have limited convergence to high-resolution structural data and is lacking other validation. The manuscript explores perhaps too many case studies at the expense of depth of description of methods, reference to existing computational literature, and deeper insight into GPCR activity.

eLife assessment

This important study, which presents novel data on variation in sperm whale communication, contributes to a richer understanding of the social transmission of vocal styles across neighbouring clans. The evidence is solid but could be further improved with some clarification of the specialized measurements and terms used, particularly for comparisons to other taxa. This research will be of interest for bioacoustics and animal communication specialists, particularly those working on social learning and culture.

eLife assessment

This important study highlights the role of SLAM-SAP signaling in shaping innate-like γδ T cell subsets, providing compelling evidence for the importance of SLAM-SAP in immune system regulation, and the potential implications of the findings for tumor surveillance and infectious disease management. The work will be of broad interest to immunologists.

eLife assessment

The study presents important findings on the role of MSI2-HOXA9 translocation in chronic myeloid leukemia. The authors provide convincing evidence supporting the role of this translocation in leukemogenesis by using elegant mouse modeling and in vitro mechanistic studies. Consistent with the reviews, the studies can be strengthened with further murine and cell line experiments.

eLife assessment

This study provides useful data substantiating a role of long noncoding RNAs in liver metabolism and organismal physiology. With murine knockout and knockin models, the authors invoke a previously unidentified role for the lncRNA Snhg3 in fatty liver. While certain findings are backed by solid evidence, other conclusions require more support and should be consolidated with existing paradigms in the field.

eLife assessment

This valuable study analyzes the role of the ciliary transition zone protein rpgrip1l in the development of the scoliotic phenotype in zebrafish. Through convincing proteomic and experimental validation in vivo, the authors demonstrated increased Annexin A2 expression in the brain and increased LCP1+ immune cell infiltration in scoliosis fish. These findings provide additional evidence for the previously proposed role of neuroinflammation in the development of idiopathic scoliosis in zebrafish.

eLife assessment

How misfolded proteins are segregated and cleared is a significant question in mechanistic cell biology, since clearance of these aggregates can protect against pathologies that may otherwise arise. The authors discover a cell cycle stage-dependent clearing mechanism that involves the ER chaperone BiP, the proteosome, and CDK inactivation, but is curiously independent of the APC. These are valuable and interesting new observations, but the evidence supporting these claims is incomplete, and needs to be strengthened and further validated.

eLife assessment

In this important study, Boudjema et al. use cell culture models and advanced microscopic imaging to provide detailed analyses of the cellular events underlying centriole amplification, apical migration, and assembly of hundreds of motile cilia in multi-ciliated cells. This largely descriptive work provides a better understanding of this process that is of interest to cell biologists studying centrioles and cilia. Most of the claims are supported by the data, but the study would benefit from additional analyses regarding the roles of microtubules, which are currently incomplete, and from text editing to improve accessibility and readability, especially for a wider audience.

eLife assessment

This work focuses on the role of Reactive Oxygen Species (ROS) signaling in cyst stem cells of the Drosophila testis. In particular, the authors suggest that ROS can act as signaling molecules between somatic and germ stem cells of the testis. The work is potentially useful, although the evidence that supports the authors' claims is incomplete.

eLife assessment

In their valuable study, Chen et al. investigate the neuronal role of HMMR, a microtubule-associated protein typically associated with cell division. Their findings indicate that HMMR is necessary for proper neuronal morphology and the generation of polymerizing microtubules within neurites, potentially by promoting the function of TPX2. This solid body of work is the first step in deciphering the influence of a mitotic microtubule-associated protein in organizing microtubules in neurons and will be of interest to the neurobiology and cytoskeleton fields.

eLife assessment

This work presents an important technological advance, in the form of a high throughput platform for Single Particle Tracking allowing us to measure millions of cells and thousands of compounds per day. Analysis of the diffusional behaviour of fluorescently-tagged targets permits the identification of, and differentiation between, small molecules that bind directly or affect the target indirectly. The methodology and metrics employed are compelling, leading to the identification of multiple compounds that effectively change the diffusive state of the estrogen receptor, the POC target of the study.

eLife assessment

This study presents a useful description of RNA in extracellular vesicles (EV-RNAs) and highlights the potential to develop biomarkers for the early detection of colorectal cancer (CRC) and precancerous adenoma (AA). The data were analysed using overall solid methodology and would benefit from further validation of predicted lncRNAs and biomarker validation at each stage of CRC/AA to evaluate the potential application to early detection of CRC and AA.

eLife assessment

The study presents a potentially useful approach to genetically modify cells to produce extracellular matrices with altered compositions. The evidence supporting the authors' conclusions regarding the chondrogenicity of lyophilized constructs is considered incomplete, as the study does not adequately demonstrate the formation of a histologically identifiable cartilaginous matrix. The study also lacks several significant details and does not have sufficient power to support the conclusions.

eLife assessment

This is a valuable study in which the authors provide an expression profile of the human blood fluke, Schistosoma mansoni. A strength of this solid study is in its inclusion of in situ hybridisation to validate the predictions of the transcript analysis.

eLife assessment

The manuscript presents valuable findings, using solid techniques and approaches, that shed additional light into how the canine distemper virus (CDV) hemagglutinin might engage cellular receptors and how that engagement impacts host tropism. The structural data and their analysis were thorough and well-presented. The HS-AFM data, which indicate that homodimers may dissociate into monomers - and thus have significant implications for the model of fusion triggering - are very exciting, but require further validation, perhaps by alternate approaches, to bolster the current molecular model of the CDV fusion triggering.

eLife assessment

This study investigates the associations of four ICD-related genes in bladder cancer with increased immune cell infiltration and more prolonged survival. The study is valuable because it identifies a risk-scoring model, showing a correlation between high-risk scores based on four ICD-related genes and weak anti-tumour immune function. However, the evidence supporting the association of these genes and immunotherapy response is incomplete.

eLife assessment

This is a mechanistic study showing the effect of combining inhibition of autophagy (through ULK1/2) and KRAS (using sotorasib) on KRAS mutant NSCLC making the study valuable to cancer biologists and more broadly in a clinical setting. The evidence generated by GEM mouse models and cell lines is solid but could be further strengthened by increasing the mouse cohort size. This study holds translational relevance beyond NSCLC to other indications that carry KRAS mutations.

eLife assessment

This is an important work and provides a significant advance in our understanding of mechanosensation in the epidermis. The evidence presented is solid, however, additional work such as testing whether the activation time can be shorter, addressing the mechanism underlying endoplasmic reticulum calcium release, and improving the clarity of writing and rigor of analysis would strengthen the study. This work will be of broad interest to neurobiologists, epithelial cell biologists, and mechanobiologists.

eLife assessment

This fundamental paper reports a new biosensor to study G protein-coupled receptor activation by the pituitary adenylyl cyclase-activating polypeptide (PACAP) in cell culture, ex vivo (mouse brain slices), and in vivo (zebrafish). Convincing data are presented that show the new sensor works, albeit at very high (non-physiological) concentrations of exogenous PACAP. The sensor has not yet been used to detect endogenously released PACAP, raising questions about whether the sensor can be used for its intended purpose. While further work must be pursued to achieve broad in vivo applications under physiological conditions, the new tool will be of interest to cell biologists, especially those studying the large GPCR family.

Evaluation statement (17 January 2024)

The study by Bassetto Jr. et al. presents an elegant and pioneering technique to rapidly manipulate membrane temperature by up to 10 ºC in less than 1.5 ms, thereby enabling high temporal resolution of the temperature dependence of ion channel currents. The approach combines the cut-open oocyte voltage clamp technique with laser illumination to heat the sub-membrane melanosome layer. Temperature is quantified from observed changes in membrane capacitance. Recordings of Kir1.1, TRPM8, and TRPV1 channels are used to validate the effectiveness of the technique. A limitation is that, in its current form, the technique can be used only on melanosome-containing Xenopus oocyte membranes.

Biophysics Colab recommends this study to scientists working on the temperature dependence of ion channels and other membrane proteins.

Biophysics Colab has evaluated this study as one that meets the following criteria: - Rigorous methodology - Transparent reporting - Appropriate interpretation

(This evaluation refers to the version of record for this work, which is linked to and has been revised from the original preprint following peer review.)

eLife assessment

This useful study investigates two secreted Mycobacterium tuberculosis proteins, ESAT-6 and CFP10, using biochemical assays, including a Biolayer Interferometry assay. Solid experimental evidence demonstrates that ESAT-6 forms a tight interaction with CFP10 as a heterodimer at neutral pH and that ESAT-6 also forms a homodimer at acidic pH. Additional, more definitive evidence is required to describe how these proteins disrupt the phagosomal membrane. While improved compared to a previous version, the revised manuscript did not address these concerns adequately.

eLife assessment

This study represents a fundamental contribution to our understanding of how gene expression levels are controlled in bacteria. Through a series of compelling and careful experiments, relying on a mutant that blocks DNA replication but permits growth, and using various methods, the authors reveal how genome concentration rapidly becomes limiting for growth when replication is inhibited. This work contributes to our understanding of the contributions and limiting roles of DNA, mRNA, and ribosomes for growth in bacteria, and will be of considerable interest within both systems biology and microbial physiology.

eLife assessment

This important study could potential provide insight into mechanisms for vaccine-mediated protection, although the evidence for live Leptospira contributing to protection against a pathogenic serovar is still incomplete. The work will be of interest to the scientists interested in host-pathogen interactions and leptospirosis.

eLife assessment

This valuable study reports single-nucleus multiomics-based profiling of transcriptome and chromatin accessibility of mouse XX and XY primordial germ cells (PGCs). Solid data generally support the main conclusions. However, data presentation and interpretation need improvement for clarity and accuracy. The study will be of interest to developmental and reproductive biologists, as well as andrologists.

eLife assessment

This important manuscript provides new insights into the biophysics of the SARS-CoV-2 nucleocapsid. The evidence, which relies on a convincing combination of genetic and biophysical data, nicely supports the conclusions.

eLife assessment

In this fundamental study, the authors use innovative fine-scale motion capture technologies to study visual vigilance with high-acuity vision, to estimate the visual fixation of free-feeding pigeons. The authors present convincing evidence for use of the fovea to inspect predator cues, the behavioral state influencing the latency for fovea use, and the use of the fovea decreasing the latency to escape of both the focal individual and other flock members. The work will be of broad interest to behavioral ecologists.

eLife assessment

This useful study aims to add fresh insights into the sharing of lymphoid and CDP (common DC precursor) lineage origin of plasmacytoid dendritic cells (pDCs). The evidence for a small subset of pDCs sharing its origin with B cell progenitors and depending on BCL11a expression is solid, although further functional characterization of the reported pDC subset would significantly enhance the significance of the study. The study will be of relevance to cellular immunologists interested in the ontogeny of plasmacytoid dendritic cells.

eLife assessment

This useful study identifies amino acid residues in the C. elegans RNA-binding protein NHL-2 that are required for RNA binding in vitro and NHL-2 function in vivo. The evidence in support of the authors' mechanistic model is currently incomplete, as data implicating specific NHL-2 amino acids in RNA binding per se in vivo are not presented. This manuscript will be of interest to scientists working in the area of gene regulation.

eLife assessment

This study presents a light-entrainable synthetic oscillator in bacteria, the optorepressilator. The authors develop a toolbox using optogenetics that makes the cellular oscillator easily controllable. This toolbox is valuable, contributing both to bioengineering and to the understanding of biological dynamical systems. The comparison with a mathematical model, population, and single-cell measurements demonstrate convincingly that the planned system was achieved and is suitable to control and study biological oscillators.

eLife assessment

This is a valuable contribution to the electric fish community, and to studies of active sensing, in that it provides evidence that a well-studied behavior (chirping) may serve in active sensing rather than communication. This is likely to stimulate follow-up behavioral and physiological studies to determine whether the active sensing component of the behavior is pre-eminent, or whether their major function is communication. For the most part, the evidence for increased chirping in more cluttered environments and the relationship between chirping and movement are convincing. However, the evidence used to argue that chirping does not vary with behavioral context is less so, and the arguments against a communicative function of chirps are not strong. The main conclusions are only supported by correlations and remain for now at the level of an interesting hypothesis to explore.

eLife assessment

The authors present an algorithm and workflow for the inference of developmental trajectories from single-cell data, including a mathematical approach to increase computational efficiency. While such efforts are in principle useful, the absence of benchmarking against synthetic data and a wide range of different single-cell data sets make this study incomplete. Based on what is presented, one can neither ultimately judge if this will be an advance over previous work nor whether the approach will be of general applicability.

eLife assessment

This important study introduces a biologically constrained model of telencephalic area of adult zebrafish to highlight the significance of precisely balanced memory networks in olfactory processing. The authors convincingly show that their model performs better in multiple situations (for e.g. in terms of network stability and shaping the geometry of representations), compared to traditional attractor networks and persistent activity. However the study lacks a mechanistic understanding of the results in terms of parameter sensitivity analysis. The work supports recent studies reporting functional E/I subnetworks in several sensory cortexes, and will be of interest to both theoretical and experimental neuroscientists studying network dynamics based on structured excitatory and inhibitory interactions.

eLife assessment

This important work presents a creative and thoughtful analysis of mouse foraging behavior and its dependence on body reference frame-based vs world reference frame-based cues. It convincingly demonstrates that a robust map capable of supporting taking novel shortcuts is learned based primarily on self-motion cues from a known starting location and this can be done in contexts where there is little reliance on distal visual landmarks; this may be a unique finding outside of the human literature. The discussion is rich with ideas about the role of the hippocampus in supporting the behavior that should be interesting to test in future analyses of brain recordings as mice perform the tasks considered by the study.

eLife assessment

This important study by Yogesh and Keller provides a set of results describing the response properties of cholinergic input and its functional impacts in the mouse visual cortex. They found that cholinergic inputs are elevated by locomotion in a binary manner regardless of locomotor speeds, and activation of cholinergic input differently modulated the activity of Later 2/3 and Layer 5 visual cortex neurons induced by bottom-up (visual stimuli) and top-down (visuomotor mismatch) inputs. The experiments are cutting-edge and well-executed, and the results are convincing.

eLife assessment

This important study has practical and theoretical implications for understanding rhythm perception and production in human cognition. The evidence for individual frequency preferences and a deterioration in frequency adaptation with age is convincing. These findings will inform existing models of rhythm perception and production, and the reported effects of age may have clinical implications.

eLife assessment

This magnetoencephalography study reports important new findings regarding the nature of memory reactivation during cued recall. It replicates previous work showing that such reactivation can be sequential or clustered, with sequential reactivation being more prevalent in low performers. It adds convincing evidence, even though based on limited amounts of data, that high memory performers tend to show simultaneous (i.e., clustered) reactivation, varying in strength with item distance in the learned graph structure. The study will be of interest to scientists studying memory replay.

eLife assessment

Chang et al. provide glutamate co-expression profiles in the central noradrenergic system and test the requirement of Vglut2-based glutamatergic release in respiratory and metabolic activity under physiologically relevant gas challenges. Their experiments provide compelling evidence that conditional deletion of vesicular glutamate transporters from noradrenergic neurons does not impact steady-state breathing or metabolic activity in room air, hypercapnia, or hypoxia. This study provides an important contribution to our understanding of how noradrenergic neurons regulate respiratory homeostasis in conscious adult mice.

eLife assessment

In this manuscript, the authors have identified Rapamycin, a common pharmacological tool, thought to only bind to the mTOR kinase, as an off-target modulator of the ion channel TRPM8, the main cold sensor in mammals. This is a valuable study, that presents solid evidence for its claims. The NMR methods employed need to be better validated in order to become a tool for the community.

eLife assessment

This study presents valuable observations indicating that the excitability of cultured sympathetic motor neurons increases in neurons cultured from aged mice, and is inversely correlated with the amplitude of KCNQ currents. The alterations in membrane excitability are relevant for aging-related changes in neuronal membrane properties. While the study documents interesting changes in membrane excitability in cultured neurons with aging, the mechanisms underlying these changes are not clear and physiological relevance of the results to the intact circuits is incomplete.

eLife assessment

In this important paper, Blin and colleagues develop a high-throughput behavioral assay to test spontaneous swimming and olfactory preference in individual Mexican cavefish larvae. The authors present compelling evidence that the surface and cave morphs of the fish show different olfactory preferences and odor sensitivities and that individual fish show substantial variability in their spontaneous activity that is relevant for olfactory behaviour. The paper will be of interest to neurobiologists working on the evolution of behaviour, olfaction, and the individuality of behaviour.

eLife assessment

This study provides valuable insights and allows for hypothesis generation around diet-microbe-host interactions in alcohol use disorder. The strength of the evidence is convincing: the work is done in a rigorous manner and includes well-characterized and described human samples. Limitations include the cross-sectional study design, and the authors should clarify their experimental groups and definitions.