eLife Assessment

This important manuscript sets out to identify sleep/arousal phenotypes in larval zebrafish carrying mutations in Alzheimer's disease (AD)-associated genes. The authors provide detailed phenotypic data for F0 knockouts of each of 7 AD-associated genes and then compare the resulting behavioral fingerprints to those obtained from a large-scale chemical screen to generate new hypotheses about underlying molecular mechanisms. The data presented are solid, although extensive interpretation of pharmacological screen data does not necessarily reflect the limited mechanistic data. Nonetheless, the authors address most reviewer concerns in their revised version, providing invaluable new analyses. Phenotypic characterization presented is comprehensive, and the authors develop a well-designed behavioral analysis pipeline that will provide considerable value for zebrafish neuroscientists.

eLife assessment

The identification of NCS1 as a distal appendage protein that captures preciliary vesicles has important implications for understanding the early steps of ciliary assembly. Furthermore, the work has important implications for the broader understanding of NCS1, which prior to this work was focused on roles in neurotransmission, but now must be considered in a broader context. The investigators used a variety of state-of-the-art methodologies, and the conclusions are convincingly supported by the experimental data. This work will be of interest to cell biologists studying ciliary assembly, human geneticists exploring the pathology of cilia as well as neurobiologists studying NCS1.

eLife assessment

This important and detailed study presents the most comprehensive view of the functional organization and requirements for a mother centriole's distal appendage in primary cilia assembly published to date. Crispr-knockouts and super-resolution microscopy analysis of the distal appendage proteins provides convincing evidence to support the claims of the authors. This work will be of high value to cell biologists and biophysicists working on the structure and function of the centrosome as well as human geneticists exploring ciliary pathology.

eLife Assessment

This important paper explores the impact of early life stress (ELS) on adult brain and behavior. The significance of the convincing findings are that they implicate regulation of non-neuronal cells in the development of brain and behavioral dysfunction associated with ELS. With an elegant combination of behavioral models, morphological and functional assessments using immunostaining, electrophysiology, and viral-mediated loss-of-function approaches, the authors report that astrocyte dysfunction plays a role in ELS responses. The work is of interest to a broad behavioral and cellular neuroscience audience.

eLife Assessment

This important study combines the use of Fisher Kernels with Hidden Markov models aiming to improve brain-behaviour prediction. The evidence supporting the authors' conclusions is compelling, comparing brain-behaviour prediction accuracies across a range of different traits, including out of sample assessment. This work is timely and will be of interest to neuroscientists working on functional connectivity for brain-behaviour association.

eLife Assessment

This important modeling study alters a previous model of the intact cat spinal locomotor network to simulate a lateral hemi-section of the spinal cord. The modeling and experimental work described provide convincing evidence that this model is capable of qualitatively predicting alterations to the swing and stance phase durations during locomotion at different speeds on intact or split-belt treadmills. This paper will interest neuroscientists studying vertebrate motor systems, including researchers working on motor dysfunction after spinal cord injury.

eLife Assessment

This valuable study revealed numerous distinct lineages that evolved within a local human population in Alberta, Canada, leading to persistent cases of E. coli O157:H7 infections for over a decade and highlighting the ongoing involvement of local cattle in disease transmission, as well as the possibility of intermediate hosts and environmental reservoirs. This study also showed a shift towards more virulent stx2a-only strains becoming predominant in the local lineages. The evidence supporting the role played by cattle in the transmission system of human cases of E. coli O157:H7 in Alberta is solid.

eLife Assessment

This work models reinforcement-learning experiments using a recurrent neural network. It examines if the detailed credit assignment necessary for back-propagation through time can be replaced with random feedback. In this useful study the authors show that it yields a satisfactory approximation but the evidence to support that it holds in general is incomplete. As only short temporal delays are used and the examples simulated are overly simple, the approximation would need to be tested on more complex task and with larger networks.

eLife Assessment

The current human tissue-based study provides convincing evidence correlating hippocampal expressions of RNA guanine-rich G-quadruplexes with aging and with Alzheimer's Disease presence and severity. The results are important and hold promise for deeper understanding of AD's pathogenesis and potential new therapeutic strategies.

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

eLife Assessment

In this valuable study the authors use electrophysiology in brain slices and computer modeling and suggest that layer 2/3 pyramidal neurons of the mouse cortex have functional HCN channels on the proximal apical dendrite which allows distinct processing of input at that location from the input to distal apical dendrites. The revisions improved the solid paper but some of the concerns were not addressed sufficiently and many of these concerns could be addressed by further revision.

eLife Assessment

This study proposes a new model that could solve some long-standing puzzles about inversion polymorphisms in Drosophila melanogaster by invoking sexually antagonism and negative frequency-dependent selection. While the idea developed here is a valuable contribution to the field, the experiment only addresses one element of the hypothesis, so that the empirical evidence in support of the model remains incomplete.

eLife Assessment

The revised report provides valuable findings for the field, suggesting a relationship between CRF1 receptors, sociability deficits in morphine-treated male mice yet not females, and a potential mechanism involving oxytocin neurons in the paraventricular nucleus of the hypothalamus. Generally, the strength of evidence is solid in terms of the methods, data, and analyses. This work will be of interest to those interested in social behavior and addiction.

eLife Assessment

This fundamental study illuminates the dynamics of BRAF in its monomeric and dimeric forms, both in the absence and presence of inhibitors, through a convincing combination of traditional experiments and sophisticated computational analyses. By revealing novel insights into the selectivity and cooperative processes of BRAF inhibitors, it holds significant promise for the development of future therapeutics, particularly against mutant isoforms in cancer. Overall, these findings will be of great interest to structural biologists, medicinal chemists, and pharmacologists.

eLife Assessment

This study presents valuable evidence of sex differences in oxycodone relapse-related behavior in rats and provides insight into associated synaptic plasticity in the paraventricular thalamus to the nucleus accumbens shell (PVT-NAcSh) circuit. The report reveals that females show heightened cue-induced oxycodone seeking compared to males after 14 days – but not 1 day – of abstinence; however, an increase in synaptic strength from the PVT inputs to the NAcSh was observed in both males and females at 14 days of abstinence. Therefore, whereas the behavioral data and much of the electrophysiology data are solid, the link between them is incomplete. Further investigation of the functional role of the PVT-NAcSh pathway in the observed sex differences in oxycodone relapse and examination of input and cell-type specificity of synaptic alterations would greatly strengthen this study.

eLife Assessment

Although others have proposed that OHC electromotility subserves cochlear amplification by acting as a "fluid pump", and evidence for this has been found using electrical stimulation of excised cochleae, this important study substantially advances our understanding of cochlear homeostasis. This is the first report to test the pumping effect in vivo and consider its implications for cochlear homeostasis and drug delivery. The manuscript provides convincing evidence for OHC-based fluid flow within the cochlea.

eLife Assessment

This valuable manuscript presents a thorough analysis of the evolution of Major Histocompatibility Complex gene families across Primates. A key strength of this analysis is the use of state-of-the-art phylogenetic methods to estimate rates of gene gain and loss, but estimates of gene loss may suffer from the issue of genes entirely or partially missing from genome assemblies represented in the public databases used, given the notorious difficulty to properly assemble MHC gene genomic regions. Overall the evidence provided is still convincing, but the manuscript may benefit from discussing approaches that can address the issue of entirely or partially missing genes, in particular how the use of long reads to completely re-assemble complex loci might improve the assessment of the complex evolutionary processes at play in MHC gene families.

eLife Assessment

The authors present new expression analysis software (TEKRABber) to help analyze expression correlations between transposable elements (TEs) and KRAB zinc finger (KRAB-ZNF) genes in experimentaly validated datasets. The authors use this method to decipher the regulatory networks of KRAB-ZNFs and TEs during human brain evolution and in Alzheimer's disease. The direction of the work is important, with potentially significant interest from others looking for a tool for correlative gene expression analysis across individual genomes and species. However, identified biases and shortcomings in the current analysis pipeline could lead to an unacceptable number of false positive and negative signals and thus impact the conclusions, leaving this work in its current form incomplete.

eLife Assessment

This study provides useful insights into the ways in which germinal center B cell metabolism, particularly lipid metabolism, affects cellular responses. The authors use sophisticated mouse models to demonstrate that ether lipids are relevant for B cell homeostasis and efficient humoral responses. Although the data were collected from in vitro and in vivo experiments and analyzed using solid and validated methodology, more careful experiments and extensive revision of the manuscript will be required to strengthen the authors' conclusions.

eLife Assessment

This study is important, advancing our understanding of how humans adapt to uncertainty in dynamic environments by investigating the interplay between two types of uncertainty-volatility (systematic changes in outcomes) and noise (random variability in outcomes). Using an innovative experimental task, reinforcement learning (RL) models, and Bayesian Observer Models (BOM), the authors demonstrate that humans exhibit approximate rationality, often misattributing noise as volatility and adopting suboptimal learning rates in noisy conditions. The evidence is compelling, supported by a well-designed experimental task that independently manipulates noise and volatility, robust behavioral data, and computational modeling; the inclusion of BOM lesioning and physiological validation through pupillometry provides a nuanced understanding of suboptimal human learning. While the study could benefit from expanding the model space (e.g., by including latent state models) and offering greater clarity in task instructions and raw behavioral data, these limitations do not undermine the strength of the findings.

eLife Assessment

This important study provides insights into the neurodevelopmental trajectories of structural and functional connectivity gradients in the human brain and their potential associations with behaviour and psychopathology. While certain aspects of the methodology are rigorous, the evidence supporting the findings is currently incomplete and would benefit from additional sensitivity analyses to evaluate methodological choices supporting the findings. This study will be of interest to neuroscientists interested in understanding functional connectivity across development.

eLife Assessment

This is a useful study that adds new data to how different DAG pools influence cellular signaling, and dissects how the enzyme Dip2 modulates the minor lipid signaling DAG pool, which is distinct from the DAG pool utilized in membrane biosynthesis. The paper presents solid evidence on how different DAG pools influence cellular signaling.

eLife Assessment

This manuscript describes valuable findings regarding the expression pattern of orexin receptors in the midbrain and how manipulating this system influences several behaviors, such as context-induced locomotor activity and exploration. The overall strength of evidence - which includes anatomical, viral manipulation studies, and brain imaging - is solid and broadly substantiates claims in the paper. However, there are several areas in which the conclusions are only partially supported by the combination of methods used. These results have implications for understanding the neural underpinnings of reward and will be of interest to neuroscientists and cognitive scientists with an interest in the neurobiology of reward.

eLife Assessment

This valuable study suggests that the dosage compensation complex and m6A act in a feedback loop in Drosophila melanogaster. The study provides integrated analyses of RNA sequencing and mapping data of the m6A RNA modification in the context of unbalanced genomes, which suggests that m6A modification status may influence H3K16Ac deposition through regulation of the acetyltransferase MOF. However, it is not clear whether this regulation is directly or indirectly related to m6A regulation. The evidence is considered incomplete due to technical concerns, as quantitative assessments were made using non-quantitative methods.

for - meaning crisis - 50 episodes - John Vervaeke - meaning crisis - summary table of 50 episodes

meaning crisis - summary table of the title of 50 episodes - 1: Introduction - 2: Flow, Metaphor, and the Axial Revolution - 3: Continuous Cosmos and Modern World Grammar - 4: Socrates and the Quest for Wisdom - 5: Plato and the Cave - 6:Aristotle, Kant, and Evolution - 7: Aristotle's World View and Erich Fromm - 8: The Buddha and "Mindfulness" - 9: Insight - 10: Consciousness - 11: Higher States of Consciousness, Part 1 - 12: Higher States of Consciousness, Part 2 - 13: Buddhism and Parasitic Processing - 14: Epicurians, Cynics, and Stoics - 15: Marcel Aurelius and Jesus - 16:Christianity and Agape - 17:Gnosis and Existential Inertia - 18: Plotinus and Neoplatonism - 19: Augustine and Aquinas - 20: Death of the Universe - 21: Martin Luther and Descartes - 22: Descartes vs. Hobbes - 23: Romanticism - 24: Hegel - 25: The Clash - 26: Cognitive Science - 27:Problem Formulation - 28: Convergence to Relevance Realization - 29: Getting to the Depths of Relevance Realization - 30: Relevance Realization Meets Dynamical Systems Theory - 31: Embodied-Embedded RR as Dynamical-Developmental GI - 32: in the Brain, Insight, and Consciousness - 33: The Spirituality of RR: Wonder/Awe/Mystery/Sacredness - 34: Sacredness: Horror, Music, and the Symbol - 35: The Symbol, Sacredness, and the Sacred - 36: Religio/Perennial Problems/Reverse Eng. Enlightenment - 37: Reverse Engineering Enlightenment: Part 2 - 38: Agape and 4E Cognitive Science - 39: The Religion of No Religion - 40: Wisdom and Rationality? - 41: What is Rationality? - 42: Intelligence, Rationality, and Wisdom - 43: Wisdom and Virtue - 44: Theories of Wisdom - 45: The Nature of Wisdom - 46: Conclusion and the Prophets of the Meaning Crisis - 47: Heidegger - 48: Corbin and the Divine Double - 49: Corbin and Jung - 50: Tillich and Barfield

eLife Assessment

This work presents important findings of a modulatory effect of yohimbine, an alpha2-adrenergic antagonist that raises noradrenaline levels, on the reconsolidation of emotionally neutral word-picture pairs, depending on the hippocampal and cortical reactivation during retrieval. The evidence supporting the main conclusions is convincing, with an elegant design combining fMRI and psychopharmacology. The work will be of broad interest to researchers working on memory.

eLife Assessment

This study provides compelling evidence for functional subpopulations of β-cells responsible for Ca2+ signal initiation and maintenance using novel three-dimensional light sheet microscopy imaging and analysis of pancreatic islets. The findings are important as they help decode mechanistic underpinnings of islet calcium oscillations and the resulting pulsatile insulin secretion. The work will be of general interest to cell biologists and particular interest to islet biologists.

eLife Assessment

This important work presents the development of a novel inhibitor for SARS-CoV-2 Mac1 that has potential utility both as an antiviral therapeutic and as a tool for probing the molecular mechanisms by which infection-induced ADP-ribosylation triggers robust host antiviral responses. The evidence supporting the claims is generally convincing but could be improved if the authors expanded the phenotypic characterization of the compound and its potential effects on both viral and host targets.

eLife Assessment

This important work substantially advances our understanding of episodic memory by proposing a biologically plausible mechanism through which hippocampal barcode activity enables efficient memory binding and flexible recall. The evidence supporting the conclusions is convincing, with rigorously validated computational models and alignment with experimental findings. The work will be of broad interest to neuroscientists and computational modelers studying memory and hippocampal function.

eLife Assessment

This valuable study uses dynamic metabolic models to compare perturbation responses in a bacterial system, analyzing whether they return to their steady state or amplify beyond the initial perturbation. The evidence supporting the emergent properties of perturbed metabolic systems to network topology and sensitivity to specific metabolites is solid, although the authors do not explain the origin of some significant inconsistencies between models.

eLife Assessment

This study presents an important application of high-content image-based morphological profiling to quantitatively and systematically characterize induced pluripotent stem cell-derived mixed neural cultures cell type compositions. Exceptional evidence through rigorous experimental and computational validations support new potential applications of this cheap and simple assay.

eLife Assessment

This important study reveals a new mechanism for gene regulation in neurons by an RNA binding protein called RBM20 previously studied in the heart. The methods used are compelling, including the generation of new mouse knockout strains and leading edge sequencing methods for identification of gene regulatory mechanisms. The study shows that neuronal RBM20 governs long pre-mRNAs encoding synaptic proteins in specific neuronal cell types, but the functional consequences of this regulation remain questions for the future.

eLife Assessment

This valuable study shows a surprising scale-invariance of the covariance spectrum of large-scale recordings in the zebrafish brain in vivo. A solid analysis demonstrates that a Euclidean random matrix model of the covariance matrix recapitulates these properties. The results provide several new and insightful approaches for probing large-scale neural recordings.

eLife Assessment

The authors use a range of techniques to examine the role of Aurora Kinase A (AurA) in trained immunity. The study is hypothesis driven, it uses solid experimental approaches, and the data are presented in a logical manner. The findings are valuable to the trained immunity field because they provide an in-depth look at a common inducer of trained immunity, beta-glucan.

This evaluation refers to version 1 of the preprint

This work presents the genome of Cardamine chenopodiifolia, an amphicarpic plant (developing two fruit types, one above and another below ground) in the mustard (Brassicaceae) family. Cardamines also known as bittercresses and toothworts. As an octoploid species it has been challenging to create a genome reference for this species, and in this case the authors finally managed to achieve this using PacBio HiFi long-reads and Omni-C technology to assemble a fully phased, chromosome-level genome. Obtaining a 597Mb genome assembled into 32 phased chromosomes (plus mitochondrial and plastid genomes), and only having one gap in the centromeric region of chromosome 9. Peer review asked for additional QC and benchmarking, helping demonstrate the genome quality was very high, with only one gap and a N50 of 18.80Mb. The data presented here potentially helping to develop this species as an emerging model organism in the Brassicaceae for studying the development and evolution of amphicarpy by allopolyploidy.

This evaluation refers to version 1 of the preprint

Editors Assessment:

Among hot topics in coral reef research, the difference between anemonefish and other damselfish is currently a popular area of research. In this study the authors provide a new high-quality non-anemonefish genome, which will be of high relevance to further the depth of such analyses. In this case of the sapphire damselfish Chrysiptera cyanea, a widely distributed damselfish in the Indo-Pacific area, often studied to elucidate the roles of various environmental controls on their reproduction, and investigate related hormonal processes To further the potential of biomolecular analyses based on this species, this study generated the first genome of a Chrysiptera fish from a male individual collected in Okinawa, Japan. Using PacBio and HiFI long-read sequencing with 94.5x coverage, a chromosome-scale genome was assembled and 28,173 genes identified and annotated. Peer review gathered more parameters and details on the quality, and the final assembly comprised of 896 Mb pairs across 91 contigs, and a BUSCO completeness of 97.6%. This reference genome should therefore be of high value for future genetic-based approaches, from population structure to gene expression analyses.

This evaluation refers to version 1 of the preprint

eLife assessment

This paper makes a valuable contribution to the area of balancing selection at the Major histocompatibility complex (MHC), including trans-species polymorphism between humans and other primates, by incorporating a large evolutionary range of species and genes and by using newer methodological approaches to characterize the depth and extent of the trans-species polymorphism across an expanded range of primate taxa. While the presented results solidly support the authors' conclusions, additional analyses would be needed to firmly exclude modes of evolution that could mimic trans-specific polymorphism.

eLife Assessment

The useful manuscript presents interesting findings in the field of neurodegenerative diseases by highlighting the dual role of phosphorylated ubiquitin (pUb) in cellular proteostasis and neurotoxicity. However, some claims for discovery are supported by unconvincing and incomplete evidence that requires further validation. The poor quality of key immunofluorescent images and questionable quantification analysis raise technical concerns.

eLife Assessment

This valuable study reports multi-scale molecular dynamics simulations to investigate a class of highly potent antibodies that simultaneously engage with the HIV-1 Envelope trimer and the viral membrane. The work provides insights into how broadly neutralizing antibodies associate with lipids proximal to membrane-associated epitopes to drive neutralization. After extensive revision, the level of evidence is considered solid, although a quantitative assessment of the underlying energetics remain difficult to obtain.

eLife Assessment

This valuable study presents findings on the mode of action of MOTS-c (mitochondrial open reading frame from the twelve S rRNA type-c), and its impact on monocyte-derived macrophages. The authors present solid evidence for its increased expression in stimulated monocytes/macrophages, its direct bactericidal functions, as well as its role in the modulation of monocyte differentiation into macrophages. Since most of the data were generated from a cell line (THP1), future work is required to validate observations in primary cells and to further support the claims of this work.

eLife Assessment

This useful study examines patterns of diversity and divergence in two closely related sub-species of Zea mays, patterns that have bearings on local adaptation in maize and teosinte at intermediate geographic scales. The authors suggest that convergent evolution has been facilitated by both standing variation and gene flow, with independent selective sweeps in the two species. While the data themselves are solid, there are limitations concerning population sampling, false positive rates in sweep detection and integration of phenotypic data, which make it difficult to draw definitive conclusions. The work should in principle be of broad interest to colleagues studying the relationship between domesticated species and their progenitors, as well as those studying instances of parallel evolution.

eLife Assessment

This work presents important findings that the human frontal cortex is involved in a flexible, dual role in both maintaining information in short-term memory, and controlling this memory content to guide adaptive behavior and decisions. The evidence supporting the conclusions is compelling, with a well-designed task, best-practice decoding methods, and careful control analyses. The work will be of broad interest to cognitive neuroscience researchers working on working memory and cognitive control.

eLife Assessment

The authors provide solid evidence that the likelihood of looking behaviour is predicted by the expected information gain, hence constituting a valuable formal model and explanation of habituation. Such modelling can represent crucial advances in explanation, over-and-above less specified models that can be fitted post hoc to any empirical pattern, although contrast testing with other accounts are desired. The findings would be of interest to researchers studying cognitive development.

eLife Assessment

This manuscript describes the generation of a fused dorsal-ventral organoid system to model interactions between the cortex and striatum to study the onset and progression of Huntington's disease (HD) and other neurodegenerative disorders. While this approach is valuable, further methodological and analytical work is needed to fully support the interpretations and claims of the authors. Incomplete evidence suggests choroid plexus (ChP) abnormalities form a significant component of HD pathogenesis.

eLife Assessment

This valuable work explores how synaptic activity encodes information during memory tasks. All reviewers agree that the quality of the work is high. Although experimental data do support the possibility that phospholipase diacylglycerol signaling and synaptotagmin 7 (Syt7) dynamically regulate the vesicle pool required for presynaptic release, concerns remain that the central finding of paired pulse depression at very short intervals was more likely caused by Ca2+ channel inactivation than pool depletion. Overall, this is a solid study although the results warrant consideration of alternative interpretations.

eLife Assessment

This fundamental study reveals that aging in yeast leads to chromosome mis-segregation due to asymmetric partitioning of chromosomes, driven by disruption of the nuclear pore complex and pre-mRNA leakage. The findings are convincingly supported by carefully-designed experimental data with a combination of genetic, molecular biology and cell biology approaches.

eLife Assessment

Using highly sophisticated switching linear dynamical systems (SLDS) analyses applied to functional MRI data, this study provides important insights into network dynamics underlying threat processing. After identifying distinct neural network states associated with varying levels of threat proximity, the paper provides compelling evidence of intrinsically and extrinsically driven contributions to these within-state dynamics and between-state transitions. Although the findings could be made more biologically meaningful, this work will be of interest to a wider functional neuroimaging and systems neuroscience community.

https://taz.de/Folgen-der-Erderhitzung/!6057015/

Report: https://www.globalwater.online/globalwater/wp-content/uploads/2018/09/GWM-Report-2024.pdf

eLife Assessment

In this innovative study, Carpenet C et al explore the use of nanobody-based PET imaging to track proliferative cells after in vivo transplantation in mice, in a fully immunocompetent setting. The development of a unique set of PET tracers and mouse strains to track genetically-unmodified transplanted cells in vivo is an important novel asset that could potentially facilitate cell tracking. The evidence provided is compelling as the new method proposed might facilitate overcoming certain limitations of alternative approaches, such as full sized immunoglobulins and small molecules, while the specific claims would gain further support by additional experimentation and methodological details.

eLife Assessment

This systematic review presents valuable insights into CCR5 antagonist drugs for neuroprotection and stroke management. The strength of the evidence is convincing, and the review methods and reporting adhere to the expected standards. A sensitivity analysis based on the risk of bias assessment of the included studies would be beneficial, and a more focused/detailed acknowledgment of key limitations of the review would add value to the quality of the reporting and interpretations of the findings.

eLife Assessment

This Research Advance describes a valuable image analysis method to identify individual neurons within a ‎population of fluorescently labeled cells in the nematode C. elegans. The findings are solid and the method succeeds to identify cells with high precision. The method will be be of interest to the C. elegans research community.

eLife Assessment

This study provides valuable insights into the lesser-known effects of the sodium-potassium pump on how nerve cells process signals, particularly in highly active cells like those of weakly electric fish. The authors use a detailed mathematical model to show how the pump can shift a cell's normal firing patterns and disrupt the coordination of signals when inputs change quickly. The computational methods used to establish the claims in this work are solid and can be used as a starting point for further studies, yet the conclusions would be strengthened with experimental evidence or testable predictions regarding some of the proposed mechanisms across different cell types.

eLife Assessment

This important study presents a finding on the role of the Inferior Colliculus in sensory prediction, cognitive decision-making, and reward prediction. The evidence supporting the claims of the authors is convincing. The work will be of broad interest to sensory neuroscientists.

eLife Assessment

This valuable study describes how trains of mossy fiber stimulation control cerebellar unipolar brush cell discharges. The dissection of the contributions of relevant glutamate receptors to these transformations is convincing. Overall, the study broadens our understanding of temporal processing in the cerebellar cortex.

eLife Assessment

This important work advances our understanding of the contribution of tissue-resident immune cells to trained immunity phenotypes. The evidence supporting the claims is convincing, with results that will be of interest to immunologists and scientists studying the host-pathogen interface.

eLife Assessment

This work provides a valuable contribution to our understanding of the neurobiological mechanisms underlying spatial memory and learning, suggesting that dopamine plays a pivotal role in linking reward context and novelty to memory consolidation processes. The evidence presented to support the main conclusions is solid, although reviewers felt that the strength of evidence could have been further strengthened by more rigorous histological verification of the experimental conditions and the complexity of the experimental manipulations, increased sample sizes, and a more consistent approach to experimental dosing and timing, which will be crucial for confirming the reproducibility and reliability of the observed effects.

eLife Assessment

This important work uses an innovative approach to understand similarities between haemodynamic and electrophysiological activity of the human brain. The study provides incomplete evidence to indicate that while similar functional brain networks are used in both modalities, there is a tendency for these multi-modal networks to spatially converge at synchronous rather than asynchronous time points. This work will be of interest to neurophysiological and brain imaging researchers.

eLife Assessment

This important study offers insights into the function and connectivity patterns of a relatively unknown afferent input from the endopiriform to the CA1 subfield of the ventral hippocampus, suggesting a neural mechanism that suppresses the processing of familiar stimuli in favor of detecting memory guided novelty. The strength of evidence is convincing, with careful anatomical and electrophysiological circuit characterization. The work will be of broad interest to researchers studying the neural circuitry of behavior.

eLife Assessment

This study provides important insights into the brain activity and connectivity underlying speech comprehension, revealing three brain states. The authors present compelling evidence by leveraging hidden Markov modeling of fMRI data to link brain state dynamics to comprehension scores, though the functional role of these states remains under-explored. These findings advance our understanding of how brain state transitions in narrative comprehension relate to stimulus-specific features.

eLife Assessment

This valuable study reports on electrophysiological recording of the spiking activity of single neurons in the entopeduncular nucleus (EPN) in freely-moving mice performing an auditory discrimination task. The data show that the activity of single EPN neurons is modulated by reward and movement kinematics, with the latter further affected by task contexts (e.g. movement toward or away from a reward location). The results provide solid evidence for the conclusions. There is some ambiguity as to whether the data contain the population of EPN neurons characterized in previous studies that obtained different results. Investigations separating confounding factors would be of benefit. Nonetheless, the work is overall of interest to those who study how the basal ganglia, particularly the EPN, contribute to behavior.

eLife Assessment

Kreeger et al. convincingly demonstrate that octopus cells in the mouse cochlear nucleus, previously thought to rely primarily on excitatory inputs for coincidence detection, also receive glycinergic inhibitory synaptic inputs that influence their synaptic integration. Using advanced techniques, including genetic mouse models, optogenetics, microscopy, slice physiology, and computational modeling, this important study reveals that inhibition can shunt synaptic currents and alter the timing of dendritic EPSPs, both of which are significant for auditory processing. This research broadens the understanding of octopus cells' roles in sensory processing, highlighting the importance of inhibitory inputs in shaping fast, high-frequency neural response capabilities.

eLife Assessment

In this manuscript, Abd El Hay and colleagues use an innovative behavioral assay and analysis method, together with standard calcium imaging experiments on cultured dorsal root ganglion (DRG) neurons, to evaluate the consequences of global knockout of TRPV1 and TRPM2, and overexpression of TRPV1, on warmth detection. Compelling evidence is provided for a role of TRPM2 channels in warmth avoidance behavior, but it remains unclear whether this involves channel activity in the periphery or in the brain. In contrast, TRPV1 is clearly implicated at the cellular level in warmth detection. These findings are important because there is substantial ongoing discussion regarding the contribution of TRP channels to different aspects of thermo-sensation.

eLife Assessment

This study presents valuable evidence concerning the potential for naturalistic movie-viewing fMRI experiments to reveal some features that are correlated with the functional and topographical organization of the developing visual system in awake infants and toddlers. The data are compelling given the difficulty of studying this population, the methodology is original and validated, and the evidence supporting the conclusions is convincing and in line with prior research using resting-state and awake task-based fMRI. This study will be of interest to cognitive neuroscientists and developmental psychologists, and in particular those interested in using fMRI to investigate brain organisation in pediatric and clinical populations with limited tolerance to fMRI.

eLife Assessment

In this article, Cheng et al present an important finding that advances the understanding of mitochondrial stress response(s). The authors employed mass spectrometry-based methods in conjunction with standard molecular and cellular biology techniques to provide compelling evidence that phosphatidylethanolamine-binding protein 1 (PEBP1) acts as a pivotal regulator of the mitochondrial component of integrated stress response. Notwithstanding that this discovery is likely to be of significant interest to researchers across a broad spectrum of disciplines ranging from cell biology to neuroscience, it was thought that further mechanistic dissection of the role of PEBP1 in modulating integrated stress response may further strengthen this study.

eLife Assessment

Using genomic data from ancient and modern samples, this important study investigates the genomic history of cattle in Iberia, focusing on the admixture between domestic cattle and their wild ancestors, aurochs. The authors present convincing evidence for interbreeding between domestic cattle and wild aurochs since the Neolithic period, although the evidence of sex-biased introgression is weak. The authors also show that the aurochs ancestry in cattle stabilized at ~20% since ~4000 years ago and continues into modern breeds; however, the aurochs ancestry is not heightened in a modern breed of Spanish fighting bulls that are bred for aggressiveness. The work will be of interest to evolutionary biologists and quantitative geneticists who seek to understand the genomic history and genetic basis of trait variation of domesticated animals.

eLife Assessment

This study reveals the important role of upstream open reading frames (uORFs) in limiting the translational variability of downstream coding sequences. Through a combination of computational simulations, comparative analyses of translation efficiency across different developmental stages in two closely related Drosophila species, and manipulative, experimental validation of translation buffering by an uORF for a gene, the authors provide convincing evidence supporting their conclusions. This work will be of broad interest to molecular biologists and geneticists.

eLife Assessment

This important study of regulatory elements and gene expression in the craniofacial region of the fat-tailed dunnart shows that, compared to placental mammals, marsupial craniofacial tissue develops in a precocious manner, with enhancer regulatory elements as primary driver of this difference. While the results are overall solid, addressing concerns regarding the liftover methods in the context of low conservation of alignable enhancers between dunnart and mouse would benefit the work, enhancing its value for uncovering mechanisms that drive heterochronic processes and as a reference for future mammalian evolution studies.

eLife Assessment

This study provides important insights into how a specific brain region controls innate responses to odors, showing that different parts of this region govern behaviors related to attraction and aversion. The findings are convincing and supported by a combination of well-executed experimental approaches, including genetic manipulations and neural activity mapping, though the evidence could be strengthened by addressing certain methodological concerns, such as clarifying the rationale for specific experimental choices and exploring alternative techniques.

eLife Assessment

This important manuscript presents a thorough analysis of trans-specific polymorphism (TSP) in Major Histocompatibility Complex gene families across primates. The analysis makes the most of currently available genomic data and methods to substantially increase the amount and evolutionary time that TSPs can be observed, but both false negative TSPs due to missing genes at the assembly and/or annotation level, as well as false positives due to read mismapping with missing paralogs, could be assessed and discussed more. Overall the evidence provided is convincing, and the manuscript may benefit from discussing the future use of more complete assemblies made from long reads to reduce the occurrence of both missing and false TSPs.

eLife Assessment

This valuable study presents a resource for researchers using Drosophila to study neural circuits, in the form of a collection of split-Gal4 lines with an online search engine, which will facilitate the mapping of neuronal circuits. The evidence is convincing to demonstrate the utility of these new tools, and of the search engine, for understanding expression patterns in adults and larvae, and differences between the sexes. These resources will be of broad interest to Drosophila researchers in the field of neurobiology.

eLife Assessment

This important study reports on PI3KR mutations and a paradoxical mechanism of PI3KR signaling. The strength of evidence for the study is mostly convincing, as conclusions are supported by a variety of mutational strategies and cellular systems to look at interactions among signaling pathways.

eLife Assessment

This important study provides insights into the physiological role of RIPK1 in liver physiology, particularly during short-term fasting. The discovery that RIPK1 deficiency sensitizes the liver to acute injury and hepatocyte apoptosis is based on convincing evidence, highlighting the importance of RIPK1 in maintaining liver homeostasis under metabolic stress. The work will be of relevance to anyone studying liver pathologies.

eLife Assessment

This important collection of over 800 new cell type-specific driver lines will be an invaluable resource for researchers studying associative learning in Drosophila. Thoroughly characterized and well documented, this collection will permit researchers to selectively target neurons that deliver information to, or receive it from, the memory center of the fly brain called the Mushroom Body. Given the wealth of new drivers and the genetic access they provide to over 300 cell types, this compelling work will be of interest not only to researchers studying the mechanisms of associative learning but more generally to those dissecting sensorimotor circuits in the fly nervous system.

eLife Assessment

This paper presents useful results that extend our understanding of how the visual cortex encodes temporal structure, providing new information about sequence representations in the upper layers of the visual cortex. The evidence for prediction errors is solid, however, support for other claims regarding sparsification and simplification of activity following training is incomplete. The main concerns pertain to the confounds associated with restricted ordering within blocks that does not allow for separate plasticity mechanisms operating on different time scales.

eLife Assessment

This paper addresses an important topic (normative trajectory modelling), seeking to provide a method aiming to accurately reflect the individual deviation of longitudinal/temporal change compared to the normal temporal change characterized based on a pre-trained population normative model. The evidence provided for the new methods is solid.

eLife Assessment

Yonk and colleagues provide a valuable, timely, and in-depth study showcasing the role of thalamostriatal inputs in learning and action selection. After characterizing the synaptic properties of these inputs onto different striatal cell types in vitro, they provide solid evidence that posterior medial thalamic nucleus (POm) terminals in striatum are activated during reward expectation and arousal. The overall function of this pathway and the degree to which results are confounded by viral contamination of surrounding nuclei and movements remain open questions.

eLife Assessment

Somatostatin-expressing neurons of the entopeduncular nucleus (EPNSst+) provide a limbic output of the basal ganglia and co-release GABA and Glutamate in their projection to the lateral habenula, a structure that is key for reward-based learning. Combining fiber photometry and computational modeling, the authors provide compelling evidence that EPNSst+ neural activity represents movement, choice direction and reward outcomes in a probabilistic switching task but, surprisingly, neither chronic genetic silencing of these neurons nor selectively elimination glutamate release affected behavioral performance in well-trained animals. This valuable study shows that despite its representation of key task variables, EPNSst+ neurons are dispensable for ongoing performance in a task requiring outcome monitoring to optimize reward. This work will be of interest to those interested in neural circuits, learning, and/or decision making.

eLife Assessment

Cav2 voltage-gated calcium channels play key roles in regulating synaptic strength and plasticity. In contrast to mammals, invertebrates like Drosophila encode a single Cav2 channel, raising questions on how diversity in Cav2 is achieved from a single gene. Here, the authors present solid evidence that two alternatively spliced Cac isoforms enable important changes in Cav2 expression, localization, and function in synaptic transmission and plasticity at the Drosophila neuromuscular junction. How the isoforms affect synaptic calcium channel levels remains less clear. This study provides insights into the roles of voltage-gated calcium channel splice isoforms in synaptic transmission.

eLife Assessment

This important study presents an evaluation of several tools used for detecting Identity-By-Descent (IBD) segments in highly recombining genomes, using simulated data to replicate the high recombination and low marker density of Plasmodium falciparum, the parasite responsible for malaria. Most of the evidence presented by the authors is solid demonstrating that users should be cautious calling IBD when SNP density is low and recombination rate is high. This study will be of interest to scientists working in the field of genome evolution and infectious diseases.

eLife Assessment

This useful observational study was conducted in Dar es Salaam, Tanzania, to investigate potential associations between genetic variation in Mycobacterium tuberculosis and human host vs. disease severity. The authors conclude that human genetic ancestry did not contribute to tuberculosis severity, but the evidence for this conclusion is currently incomplete, as the analysis did not fully leverage the genome-wide data available in a human-strain association study, and there was no comparison group from the general population (or household controls), to which the ancestry findings could be compared. The findings have significance for the understanding of the influence of host / bacillary genetics on tuberculosis disease.

eLife Assessment

This important study introduces a fully differentiable variant of the Gillespie algorithm as an approximate stochastic simulation scheme for complex chemical reaction networks, allowing kinetic parameters to be inferred from empirical measurements of network outputs using gradient descent. The concept and algorithm design are convincing and innovative. While the proofs of concept are promising, the determination of the range of applicability and of the errors is incomplete, leaving open some questions about implications for more complex systems that cannot be addressed by existing methods. This work has the potential to be of significant interest to a broad audience of quantitative and synthetic biologists.

eLife Assessment

This study presents a platform to implement closed-loop experiments in mice based on auditory feedback. The authors provide solid evidence that their platform enables a variety of closed-loop experiments using neural or movement signals, indicating that it will be a valuable resource to the neuroscience community. However, the demonstration experiments could be strengthened by increasing the sample size for several groups in the neurofeedback experiments, as well as a more thorough description of the results in the text.

eLife Assessment

This important study conducted experiments to quantify how changes in blood flow results in apparent fluorescence changes when imaging neural activity sensors using two-photon microscopy. While the study highlights the prevalence neural-activity independent artifacts in two-photon imaging, the evidence linking the observed signals to hemodynamic occlusion remains incomplete.

eLife Assessment

This study examined how multidimensional social relationships influence social attention in rhesus macaques, linking individual and group-level behaviors to attentional processes. The findings that oxytocin altered social attention and its relationship to both social tendencies and dyadic relationships are important, as recent technological advances allow for the exploration of neuronal activities and mechanisms in free-moving macaques. This work is convincing and will be of interest to those studying the interplay between social dynamics and information processing in primates.

eLife Assessment

This valuable study uses a novel method to record spine calcium responses without the confounds of backpropagating action potentials to study how the dendritic integration of large numbers of inputs generates the tuned output of cortical neurons. While the results are generally solid, the study would benefit from more details, characterizations, and quantifications, including better validation of the method to suppress backpropagating action potentials.

eLife Assessment

This study presents a valuable finding on a new role of glia in activity-dependent synaptic remodeling using the Drosophila NMJ as a model system. The evidence supporting the claims of the authors is solid. However, the unaddressed cell-type specific mechanisms of Shv secretion and regulation on the extracellular glutamate levels and lack of details on the methods for statistical analysis have hindered further evaluation of the claims. The work will be of interest to neuroscientists working on glia-neuron interaction and synaptic remodeling.

eLife Assessment

In this important manuscript, Ryan et al perform a genome-wide CRISPR based screen to identify genes that modulate TDP-43 levels in neurons. They identify a number of genes and pathways and highlight the BORC complex, which is required for anterograde lysosome transport as one such regulator of TDP-43 protein levels. Overall, this is a convincing study, which opens the door for additional future investigations on the regulation of TDP-43.

eLife Assessment

This valuable study by Cui et al. investigates mechanisms generating sighs, which are crucial for respiratory function and linked to emotional states. Utilizing advanced methods in mice, they provide solid evidence that increased excitability in specific preBötzinger complex neuronal subpopulations expressing Neuromedin B receptors, gastrin-releasing peptide receptors, or somatostatin can induce sigh-like large amplitude inspirations. With additional technical clarifications and further elaboration of the limitations in terms of how the results are interpreted in the revised manuscript, the study will interest neuroscientists studying respiratory neurobiology and rhythmic motor systems.

eLife Assessment

In this revised manuscript, Dong et al. investigate the role of the small Ras-like GTPase Rab10 in the exocytosis of DCVs in mouse hippocampal neurons, showing that Rab10 depletion hinders DCV exocytosis independently of its effects on neurite outgrowth. Upon revising their work, these findings provide compelling evidence that Rab10 depletion leads to altered ER morphology, impaired ER-based calcium buffering, and decreased ribosomal protein expression, which collectively contributes to defective DCV secretion. The study comes to the fundamental conclusion that Rab10 is critical for DCV release by ensuring ER calcium homeostasis.

eLife Assessment

This important study develops and exploits novel ideas in dendritic integration and implements these ideas in a neural network. Historically, dendritic plateau potentials were thought to exist primarily for maintaining neurons in a depolarized state for 100s of milliseconds, but this study presents a new perspective that dendritic plateau potentials are equally effective in much shorter integration windows. The computational evidence supporting the article's claims is compelling.

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, and following revisions provides solid evidence for its conclusions.

eLife Assessment

In this fundamental study, the authors describe ELF3 as a candidate driver of luminal progenitor transformation, such that its up-regulation during replicative stress conditions and in BRCA1 deficient cells may permit cell proliferation by suppressing genome instability. While the work is certainly of interest, the supporting data remain incomplete as luminal progenitor cells could not be isolated, which would be needed in order to definitively determine whether ELF3 is a driver of transformation in these cells. Overall this paper may offer insight into mechanisms by which BRCA1 deficiency fuels breast tumorigenesis.

eLife Assessment

This important work advances our understanding of factors influencing efficacy assessments and biomarker viability for complement-directed gene therapy against age-related macular degeneration. The data presented is convincing and offers insights and teachings for the design of gene therapy and complement-targeted therapeutics in the eye and more broadly for future ocular biomarker studies.

eLife Assessment

In this valuable study, the authors propose a model wherein the bacterial redox state plays a crucial role in the differentiation of Chlamydia trachomatis into elementary and reticulate bodies. They provide solid evidence to argue that a highly oxidising environment favours the formation of elementary bodies while a reducing condition slows down development. Overall, the study convincingly demonstrates that Chlamydial redox states play a role in differentiation, an observation that may have implications for the study of other bacterial systems.

eLife Assessment

This is a valuable study on the efficacy of a live attenuated vaccine that was tested in different animal models and the evidence is convincing. The study has been strengthened after revisions.

eLife Assessment

In this important study, the authors investigate the biogenesis of extracellular vesicles in mycobacteria and provide several observations to link VirR with vesiculogenesis, peptidoglycan metabolism, lipid metabolism, and cell wall permeability. The authors have done a commendable job of comprehensively examining the phenotypes associated with the VirR mutant using various techniques. The evidence presented in the revised manuscript is convincing and creates several avenues for further research.

eLife Assessment

The authors performed extensive coarse-grained molecular dynamics simulations of 140 different prion-like domain variants to interrogate how specific amino acid substitutions determine the driving forces for phase separation. The analyses are solid, and the derived predictive scaling laws can aid in identifying potential phase-separating regions in uncharacterized proteins. Overall, this is a valuable contribution to the field of biomolecular condensates. It exemplifies how data-driven methodologies can uncover new insights into complex biological phenomena.

eLife Assessment

The authors propose that positive biodiversity-ecosystem functioning relationships found in experiments have been exaggerated because commonly used statistical analyses are flawed. To remedy this, a new type of analysis based on a concept of "partial density monoculture yield" is proposed. However, the presented concept and analysis methods are not reproducibly described (how can partial density monoculture yield experimentally be assessed?), do not appear to be complete, and are inadequate for hypothesis testing. The reviewers found that the authors misinterpret current research in the field and made limited efforts to understand or address the reviewer comments about this study.

eLife Assessment

This neuroimaging and electrophysiology study in a small cohort of congenital cataract patients with sight recovery aims to characterize the effects of early visual deprivation on excitatory and inhibitory balance in visual cortex. While contrasting sight-recovery with visually intact controls suggested the existence of persistent alterations in Glx/GABA ratio and aperiodic EEG signals, it provided only incomplete evidence supporting claims about the effects of early deprivation itself. The reported data were considered valuable, given the rare study population. However, the small sample sizes, lack of a specific control cohort and multiple methodological limitations will likely restrict usefulness to scientists working in this particular subfield.

eLife Assessment

This valuable study provides insights into the structure and function of bacterial contractile injection systems that are present in the cytoplasm of many Streptomyces strains. A convincing high-resolution model of the structure of extended forms of the cytoplasmic contractile injection system assembly from Streptomyces coelicolor is presented, with some investigation of the membrane protein CisA in attachment of the extended assembly to the inner face of the cytoplasmic membrane and the firing of the system. The work expands the current understanding of these diverse bacterial nanomachines.

eLife Assessment

This is a valuable study and a promising development for the field of open-source microscopy for educational purposes. The strengths include the low cost of constructing the microscope, impressive performance and detailed resources including a dedicated website and YouTube channel. The claims are generally supported by solid evidence, however, the manuscript would be strengthened by inclusion of further details on standard performance metrics (e.g. signal to noise ratio etc.) compared to existing systems and further details and clarification on the microscope, construction and operation.

eLife Assessment

The work presented in this paper provides an important insight into how early life experience shapes adult behavior in fruit bats. The authors raised juvenile bats either in an impoverished or enriched environment and studied their foraging behaviors. The evidence is convincing that bats raised in enriched environments are more active, bold, and exploratory, although further exploration of the data and clarification of the analysis would strengthened the evidence. The work will be of interest to ethologists and developmental psychologists.

eLife Assessment

This valuable study presents findings linking prophage carriage to lifestyle regulation in the marine bacterium Shewanella fidelis, with potential implications for niche occupation within a host (Ciona robusta) and mediation of host immune responses. The study leverages a unique animal model system that offers distinct advantages in identifying select phenotypes to present generally solid evidence that supports findings relating to the impact of a prophage on host-microbe interaction. Understanding the role of integrated lysogenic phages in bacterial fitness, both within a host and in the environment, is a significant concept in bacterial eco-physiology, potentially contributing to the success of certain strains.

eLife Assessment

This fundamental study examines infection of the liver and hepatocytes during Mycobacterium tuberculosis infection using different systems including aerosol infection of mice and guinea pigs to demonstrate appreciable infection of the liver as well as the lung. The authors present convincing evidence that hepatocyte infection leads to metabolic dysfunction that promotes M. tuberculosis growth, in part potentially mediated by a nuclear receptor called PPARg. Overall, this is an interesting paper on an area of tuberculosis research which has been understudied, representing a significant advancement in the field.

eLife Assessment

This important theoretical study examines the possibility of encoding genomic information in a collective of short overlapping strands (e.g., the Virtual Circular Genome (VCG) model). The study presents solid theoretical arguments, simulations and comparisons to experimental data to point at potential features and limitations of such distributed collective encoding of information. The work should be of relevance to colleagues interested in molecular information processing and to those interested in pre-Central Dogma or prebiotic models of self-replication.

eLife Assessment

This manuscript describes an important finding of the transcriptional control of a chimeric gene transfer agents (GTA) cluster in Bartonella by a processive anti-termination factor (BrrG). The evidence provided is solid. This manuscript will interest researchers working on transcriptional regulation, horizontal gene transfer, and phages.

eLife Assessment

Using a TN-seq based approach, the authors identified the genetic determinants of drug tolerance in M. abscessus. Since M. abscessus is resistant to multiple antibiotics, the study is valuable in generating new knowledge linking antibiotic tolerance with ROS in this non-tuberculosis mycobacterial (NTM) species. However, the study is incomplete due to a need for more validation of the Tn-seq data, inconsistency with the clinical strains, and insufficient experiments confirming the role of ROS detoxification in drug tolerance.

eLife Assessment

This work describes a valuable method, SICKO, for real-time longitudinal quantification of bacterial colonization in the gut of individual C. elegans. The authors present convincing evidence to support the validity of the approach. SICKO provides an experimental framework that will enable progress in our understanding of host-microbe interactions.

eLife Assessment

This useful paper systematically evaluates B-cell receptor (BCR) repertoires across tumors, tumor-draining lymph nodes, and peripheral blood in patients with melanoma, lung adenocarcinoma, and colorectal cancer. It investigates the interplay between the tumor microenvironment and immune responses, revealing differences in BCR clonotype maturity, hypermutation, and spatial distribution. The study highlights the heterogeneity in immune responses and provides solid insights into the potential of tumor-infiltrating B cells for therapeutic applications, despite limitations in patient cohort size and sequencing methodology.

eLife Assessment

The paper presents a streamlined new approach for functional validation of genes known to underlie fragile bone disorders in a relatively high throughput, using CRISPR-mediated knockouts and a number of phenotypic assessments in zebrafish. Convincing data demonstrate the feasibility and validity of this approach, which presents an important tool for rapid functional validation of candidate gene(s) associated with heritable bone diseases identified from genetic studies.

eLife Assessment

This manuscript describes important findings on a rhizobial effector, its cleavage, and legume receptors involved in symbiosis. The evidence supporting the main claims is solid, though some conclusions would benefit from additional investigation. The findings have potential implications beyond bacterial interactions with plants.

eLife Assessment

Given a great need for novel human model systems to study small cell lung cancer (SCLC), the authors describe an important pre-clinical model with broad potential for the study of how genetic perturbations or drug treatments alter SCLC tumor growth, metastasis, and response to therapy. For the major finding, the authors provide convincing evidence that RB/TP53 suppression coupled with MYC overexpression in an ES cell-derived model system results in aggressive and metastatic SCLC. However, the impact of the work would have been increased with the inclusion of a broader set of genetic perturbations, such as over-expression of MYCL, to better model major SCLC phenotypes. The new model described will be of significant interest to researchers studying lung cancer.

eLife Assessment

This study reports valuable insights into the interactome of the RNA-binding protein SERBP1 and possible links through PARylation to diverse processes, including splicing, cell division, and ribosome biogenesis. The diversity of processes SERBP1 may regulate means this work would be of very broad interest to the cell biology community. The proteomics data are solid, but the functional connection to downstream processes and the link to Alzheimer's disease, while compelling, still require further examination. These latter data currently rely on a very limited set of experiments and patient samples with questionable quality of preservation and methodology.

eLife Assessment

This work is a valuable study that presents a detailed analysis of translation, driven by the untranslated regions of the Japanese encephalitis virus. It reports a role for the RNA helicase DDX3 in promoting a cap-independent translation mechanism. The conclusions are based on generally solid evidence, although there are some weaknesses in the overall model based on suboptimal experimental approaches and over-interpretation of some of the data. Addressing deficiencies noted in peer review could elevate the impact of the study.

eLife Assessment

The authors demonstrated cellular heterogeneity of companion cells (CCs) and also suggested the CC subpopulation that highly expressed the florigen gene FT. Based on this finding, they further identified flowering time regulators acting in CCs, including small proteins and NITRATE-INDUCIBLE GARP-TYPE TRANSCRIPTIONAL REPRESSOR1 type proteins (NIGT1s). In particular, the authors propose the NIGT1-FT regulatory module, which may be involved in the response to nitrogen status. This important study advances our understanding of flowering time control at high spatial resolution. While we believe this work will be of broad interest to plant biologists, the supporting evidence remains in parts incomplete. In particular, the quality of the single-cell and bulk RNA-seq data needs to be addressed to solidify the conclusions.

eLife Assessment

The manuscript provides an important assessment of the number and distribution of different retrovirus env genes present in primate genomes in the form of ancient endogenous retroviruses (ERV loci) and the potential role that viral recombination played in the diversification of retrovirus env genes and their propagation in the primate germline over millions of years. The exploration of this process in this study is considered solid, ultimately representing a conceptual advance with potentially broad implications. However, issues of clarity in the text and figures of the current version of the manuscript, as noted by multiple reviewers, may limit the ultimate impact of the work if insufficiently unaddressed.

eLife Assessment

This study provides a valuable and timely analysis of invasive and non-invasive Streptococcus pyogenes emm89 isolates, which have become a dominant serotype in the past decade. Using genome sequencing of 311 strains from Japan and comparing them with 666 global strains, the authors present compelling evidence in support of the identification of genetic factors linked to the invasive phenotype of emm89. The findings are both theoretically and practically significant in medical microbiology.

eLife Assessment

This study presents a valuable finding regarding the role of Arp2/3 and the actin nucleators N-WASP and WAVE complexes in myoblast fusion. The data presented is convincing, but it is suggested to perform validation of the knock-down efficiency of the mouse model and making adjustments to some of the data interpretation. The work will be of interest to biologists studying skeletal muscle stem cell biology in the context of skeletal muscle regeneration.