eLife Assessment
The authors present an important approach to identify imported P. falciparum malaria cases, combining genetic and epidemiological/travel data. This tool has the potential to be expanded to other contexts. The data was analyzed using convincing methods, including a novel statistical model. This study may be of interest to researchers in public health and infectious diseases beyond malaria.
eLife Assessment
This study presents an important finding that has identified 27 differentially methylated regions as a signature for non-invasive early cancer detection and predicting prognosis for colorectal cancer. The findings demonstrate promising clinical potential, particularly for improving cancer screening and patient monitoring. In general, the evidence supporting the claims of the authors is solid. A larger sample size will be key to further improving this work in the future. The work will be of interest to researchers interested in cancer diagnosis or colorectal cancer monitoring.
eLife Assessment
This important study demonstrates that in Drosophila melanogaster, tachykinin (Tk) expression is regulated by the microbiota. The authors present convincing evidence that axenic flies raised with no microbiota are longer-lived than conventionally reared animals, and that Tk expression and Tk receptors in the nervous system are required for this effect. They further test individual bacterial strains for their role in these effects and connect the effect to loss of lipid stores and suggest that FOXO may be involved in the phenotype, results that are of interest to the fields of environmental perception, host microbiome interactions, and geroscience.
[Editors' note: this paper was reviewed by Review Commons.]
eLife Assessment
This study identifies the uncharacterised protein FAM53C as a novel, potential regulator of the G1/S cell cycle transition, linking its function to the DYRK1A kinase and the RB/p53 pathways. The work is valuable and of interest to the cell cycle field, leveraging a strong computational screen to identify a new candidate. The findings are solid, although confidence in the siRNA depletion phenotypes would have been higher with rescue experiments using an siRNA-resistant cDNA and more robust quantification of some immunoassay data.
[Editors' note: this paper was reviewed by Review Commons.]
eLife Assessment
This fundamental work examines how tRNA modifications influence antibiotic tolerance, providing novel insights that may have therapeutic uses. The evidence supporting the conclusions is convincing. Strengths of the manuscript include the mechanism of tRNA modification influencing antibiotic tolerance and the precise measurement techniques used throughout. Further analysis of growth rate impacts and specific identification of the proteins responsible for the effect would further strengthen the manuscript.
eLife Assessment
This valuable study examines how mammals descend effectively and securely along vertical substrates. The conclusions from comparative analyses based on behavioral data and morphological measurements collected from 21 species across a wide range of taxa are convincing, making the work of interest to all biologists studying animal locomotion.
eLife Assessment
This valuable study identifies asymmetric dimethylarginine (ADMA) modification of histones as a potential key determinant of the initial genomic binding of Rhino, a Drosophila-specific chromatin protein essential for piRNA cluster specification. The authors provide correlative genomic and imaging data to support their model, although functional validation of the proposed mechanism remains incomplete. Testing the redundancy between dART4 and dART1, which together could affect the prominent piRNA loci, in addition to the minor ones investigated in the manuscript, may change our assessment.
eLife Assessment
This useful study presents the potentially interesting idea that LRRK2 regulates cellular BMP levels and their release via extracellular vesicles, with GCase activity further modulating this process in mutant LRRK2-expressing cells. However, some of the evidence supporting these conclusions remains incomplete, and additional work is suggested under certain conditions. Overall, the study will be of interest to cell biologists working on Parkinson's disease.
eLife Assessment
This study presents important findings describing the early assembly of vascular basement membrane and how vascular cells switch from responding to cues provided by the external environment to those provided by self-assembled basement membrane. The evidence supporting the claims of the authors is convincing, with state-of-the-art microscopy and several different culture conditions examined. The work will be of interest to cell biologists studying the ECM, vascular development, as well as medical scientists focused on diseases that depend on vascular growth.
eLife Assessment
Amyotrophic lateral sclerosis (ALS) affects nerve cells in the brain and spinal cord. The authors' approach to use genetic code expansion to tag two ALS proteins associated with stress granules has value and should be useful in the ALS field. Parts of the work are well done, but there are concerns that the evidence is incomplete overall, and additional controls would strengthen the study.
eLife Assessment
This study proposes a potentially useful improvement on a popular fMRI method for quantifying representational similarity in brain measurements by focusing on representational strength at the single trial level and adding linear mixed effects modeling for group-level inference. The manuscript provides solid evidence of increased sensitivity with no loss of precision compared to more classic versions of the method. However, several assumptions are insufficiently motivated, and it is unclear to what extent the approach would generalize to other paradigms.
eLife Assessment
This important study uses the delay line axon model in the chick brainstem auditory circuit to examine the interactions between oligodendrocytes and axons in the formation of internodal distances. This is a significant and actively studied topic, and the authors have used this preparation to support the hypothesis that regional heterogeneity in oligodendrocytes underlies the observed variation in internodal length. In a solid series of experiments, the authors have used enhanced tetanus neurotoxin light chains, a genetically encoded silencing tool, to inhibit vesicular release from axons and support the hypothesis that regional heterogeneity among oligodendrocytes may underlie the biased nodal spacing pattern in the sound localization circuit.
[Editors' note: this paper was reviewed by Review Commons.]
eLife Assessment
This is a valuable study that combines biophysical and evolutionary approaches to understand why particular mutations in the SARS-CoV-2 protein N arose during the COVID-19 pandemic. The evidence is solid and supports the conclusions.
eLife Assessment
Glioblastoma is among the most aggressive cancers without a cure, and its cells are characterized by high mitochondrial membrane potential. This manuscript provides convincing evidence that glioblastoma tumorigenesis is closely linked to mitochondrial stress. The study makes a valuable contribution to the field by advancing our understanding of the metabolic mechanisms driving glioblastoma and highlighting potential therapeutic targets.
eLife Assessment
Weindel et al examine behavioural and EEG data in an innovative contrast comparison paradigm where they vary mean contrast widely while keeping contrast difference constant. As intended, this allowed an elegant decomposition of processing stages: while sensory encoding shortened with increasing contrast in keeping with Pieron's law, the period of decision formation lengthened, in keeping with Fechner's law, which was applied to drift rates in a diffusion model of that period. This is an important demonstration of how these two laws apply in concert, to two distinct processing levels, and the multivariate topography parsing, mixed effect models and diffusion models are convincing.
eLife Assessment
This Review Article provides a thorough overview of whole-brain activity changes induced by brain stimulation and summarizes the current state of the field. However, it lacks integration across spatial and mechanistic scales, which limits the reader's ability to understand how the different findings relate to one another. In addition, several key concepts are not explained in sufficient depth for non-expert readers. The manuscript would benefit from the development of a cohesive conceptual framework to more clearly synthesize the existing literature.
eLife Assessment
This study offers valuable insights into the anatomical and physiological features of cold-selective lamina I spinal projection neurons. The evidence supporting the authors' claims is convincing, although including a larger sample size and more quantification would have strengthened the study, and the claims of monosynaptic connectivity would benefit from being stated more cautiously. The work will interest those in the field of somatosensory biology, especially researchers studying spinal cord dorsal horn circuits and projection neuron cell types.
eLife Assessment
This potentially valuable cross-sectional longitudinal study leverages high-definition transcranial direct current stimulation to the left dorsolateral prefrontal cortex to examine its effect on procrastination behavior over an extended time span. Support for the conclusions is incomplete owing to missing information about the analyses, the nature of the procrastination tasks, and the derived dependent measures.
eLife Assessment
In this Review Article, the authors survey the literature describing how correlated dynamical states relate to various cognitive states, including anesthesia and sleep. While the topic is significant and the coverage broad, the manuscript does not yet provide a synthesis that connects the many available findings or highlights converging themes across studies. Additionally, many of the disparate concepts are not introduced at the level of first principles. As a result, the Review remains difficult to access for readers outside the immediate subfield. Developing a clearer integrative perspective would help make the article informative to a wider audience.
eLife Assessment
This important work combines theoretical analysis with precise experimental perturbation to demonstrate a previously unappreciated quantitative characteristic of the Wnt signaling pathway, which is anti-resonance, or a suppression of pathway output at intermediate activation frequencies. This effect is demonstrated experimentally with compelling evidence from optogenetic stimulation in multiple cell types, alongside modeling results that corroborate the phenomenon. While the demonstration of this phenomenon has yet to be extended to fully physiological situations, its clear existence within optogenetically stimulated systems shows that it is likely a significant factor that contributes to the behavior of this central signaling pathway.
eLife Assessment
Following retinal injury, zebrafish Müller glia reenter the cell cycle and generate replacement cells; this potentially valuable study proposes that injury induces a cxcl18b+ transitional state in Müller cells, which then express nitric oxide, inhibiting Notch signaling and allowing Müller glial cells to reenter the cell cycle. However, the evidence supporting the claims is incomplete, and the authors have made interpretations and conclusions that are not supported by the data. Questions of the temporal expression and function of cxcl18b, as well as the source of potential inflammatory cues before cxcl18b expression, remain unanswered and technical limitations and data inconsistencies raise concerns. Using larval animals complicates the analysis since the retina is still forming, and distinguishing between injury-induced regeneration and ongoing development is complex. With more rigorous testing of the signaling pathways proposed and a clear demonstration of their interdependence, the link between nitric oxide signaling and Notch activity, particularly, would interest those investigating retinal regeneration.
eLife Assessment
This important study focuses on the molecular mechanisms underlying the generation of neuronal diversity. Taking advantage of a well-defined neuroblast lineage in Drosophila, the authors provide convincing evidence that two transcription factors of the conserved forkhead box (FOX) family provide a mechanistic link between transient spatial cues that initially specify neuroblast identity and terminal selector genes that define post-mitotic neuron identity. The findings will be of interest to developmental neurobiologists.
eLife Assessment
This study presents a valuable open-source and cost-effective method for automating the quantification of male aggression and courtship in Drosophila melanogaster. The work as presented provides solid evidence that the use of the behavioral setup that the authors designed - using readily available laboratory equipment and standardised high-performing classifiers they developed using existing software packages - accurately and reliably characterises social behavior in Drosophila. The work will be of interest to Drosophila neurobiologists and particularly to those working on male social behaviors.
eLife Assessment
This important study presents a compelling theoretical framework for understanding condensation or phase separation of membrane-bound proteins, with a focus on the organization of tight junction components. By incorporating non-dilute binding effects into thermodynamic models and validating the model's predictions with in vitro experiments on the tight junction protein ZO-1, the authors provide a quantitative tool that combines theory and experiments and will help researchers in the field quantitatively interpret their findings. Given that phase separation of membrane bound molecules is becoming key in signaling, spanning from immune signaling to cell-cell adhesion, this work will be of broad interest for cell biologists and biophysicists.
eLife Assessment
This useful study raises interesting questions but provides inadequate evidence of an association between atovaquone-proguanil use (as well as toxoplasmosis seropositivity) and reduced Alzheimer's dementia risk. The findings are intriguing but they are correlative and hypothesis-generating with the strong possibility of residual confounding.
eLife Assessment
This important study shows that orientation tuning of V1 neurons is suppressed during a continuous flash suppression paradigm, especially when the neurons have a binocular receptive field. However, the evidence presented is incomplete and, in particular, does not distinguish whether this suppression is due to reduced contrast or due to masking.
eLife Assessment
In this important paper, Garcia et al seek to determine whether the superior frontal sulcus (SFS), an area previously implicated in evidence accumulation for perceptual decisions, plays a causal role in perceptual and/or value-based decisions. Through a combination of careful paradigm design, computational modelling, transcranial magnetic stimulation and fMRI analyses, the authors provide convincing evidence that the SFS supports perceptual but not value-based decisions and that its disruption leads to a lowering of decision boundaries.
eLife Assessment
Combining state-of-the-art in-situ cell-surface proteomics, functional genetic screening, and single-nucleus RNA sequencing, this fundamental work substantially advances our understanding of glial contributions to organismal lifespan. The evidence supporting the conclusions is compelling, although additional clarification, control experiments, and analysis would further strengthen the study. The work will be of broad interest to researchers studying aging biology, glia-neuron communication, and in vivo proteomic profiling.
for - planetary tipping points - social tipping points - positive tipping points
SRG Comment - 2025 summary of current state of tipping points - good summary of current state of planetary and social and positive tipping points - crossed our first tipping point - positive one - renewable energy - but it's still too slow, carbon emissions are still too high - comparison - irony - China will become world's first electrostate while the US doubles down as a leading petrostate
eLife Assessment
This important study presents novel data on temporal variation in sperm whale communication, contributing to a richer understanding of the social transmission of vocal styles across neighbouring clans. The evidence is solid, although some terminology limits comparisons to other taxa. This research will be of interest to bioacoustics and cetacean communication specialists, particularly those working on social learning and culture.
eLife Assessment
This manuscript uses adaptive-bandit simulations to describe the dynamics of the Pseudomonas-derived chephalosporinase PDC-3 β-lactamase and its mutants to better understand antibiotic resistance. The finding, that clinically observed mutations alter the flexibility of the Ω- and R2-loops, reshaping the cavity of the active site, is valuable to the field. The evidence is considered incomplete, however, with the need for analysis to demonstrate equilibrium weighting of adaptive trajectories and related measures of statistical significance.
eLife Assessment
This study makes a valuable contribution by elucidating the genetic determinants of growth and fitness across multiple clinical strains of Mycobacterium intracellulare, an understudied non-tuberculous mycobacterium. Using transposon sequencing (Tn-seq), the authors identify a core set of 131 genes essential for bacterial adaptation to hypoxia, providing a convincing foundation for anti-mycobacterial drug discovery.
eLife Assessment
This is an important study that utilized in vivo optical measurements of the cortical metabolic rate of O2 and blood flow, as well as measurements in isolated mitochondria to assess the uncoupling of the oxidative phosphorylation due to hypoxia-ischemia injury of the neonatal brain, and effects of the hypothermia treatment. The combination of state-of-the-art optical measurements, mitochondrial assays, and the use of various control experiments provides convincing evidence for the derived conclusions. This work will be of interest to those in the mitochrondrial metabolomics, brain injury and hypoxia fields.
eLife Assessment
This valuable study presents a well-designed set of experiments demonstrating how a planthopper salivary carbonic anhydrase can promote rice stripe virus infection by modulating callose deposition in the host plant. The authors provide solid data for the proposed protein-protein interactions, including strengthened evidence for the LssaCA-NP-OsTLP complex and clarified dynamics of LssaCA presence in planta. Overall, the work reveals a mechanistic link whereby a vector salivary protein enhances a plant β-1,3-glucanase to suppress callose-based defense, thereby facilitating early viral establishment.
eLife Assessment
The medicinal leech preparation is an amenable system in which to understand the neural basis of locomotion. Here a previously identified non-spiking neuron was studied in leech and found to alter the mean firing frequency of a crawl-related motoneuron, which fires during the contraction phase of crawling. The findings are valuable and the experiments were diligently done and considered solid. The results lay a foundation for additional studies in this system.
eLife Assessment
This important Research Advance builds on the authors' previous work delineating the roles of the rodent perirhinal cortex and the basolateral amygdala in first- and second-order learning. The convincing results show that serial exposure of non-motivationally relevant stimuli influences how those stimuli are encoded within the perirhinal cortex and basolateral amygdala when paired with a shock. This manuscript will be interesting for researchers in cognitive and behavioral neuroscience.
eLife Assessment
This study presents an important new approach to quantifying parsimony preferences in human inference. The work provides convincing evidence that humans are sensitive to specific formalizations of parsimony, such as the dimensionality of perceptual shapes. The work is considered timely, well-written, and technically sophisticated, effectively bridging concepts from statistical inference and human decision-making.
eLife Assessment
This valuable study successfully decoded visual representations of facial expressions and stereoscopic depth information from electroencephalogram (EEG) signals recorded in an immersive virtual reality (VR) environment. The evidence is solid in demonstrating the technical feasibility of integrating state-of-the-art EEG decoding and VR with eye tracking. This work will interest neuroscience researchers, as well as engineers developing brain-machine interfaces and/or virtual reality displays.
eLife Assessment
This important study reveals that mitotic release of an ER-microtubule tether is critical for normal mitotic progression. Manipulating CLIMP63 phosphorylation, the authors provide convincing evidence that persistent microtubule-ER contacts activate the spindle assembly checkpoint and, if mitosis is forced to proceed, drive severe micronucleation. While the study provides new mechanistic insights, some evidence is indirect, and additional experiments would further refine the model.
eLife Assessment
This study provides useful insights into addressing the question of whether the prevalence of autoimmune disease could be driven by sex differences in the T cell receptor (TCR) repertoire, correlating with higher rates of autoimmune disease in females. The authors compare male and female TCR repertoires using bulk RNA sequencing, from sorted thymocyte subpopulations in pediatric and adult human thymuses; however, the results do not provide sufficient analytical rigor and incompletely support the central claims.
eLife Assessment
The authors ask whether a simple whole-head spectral power analysis of human magnetoencephalography data recorded at rest in a large cohort of adults shows robust effects of age, and their results provide compelling evidence that it does. The relative simplicity of the analysis is a major strength of the paper, and the authors are careful to control for many different confounds - although perhaps highly correlated factors like brain anatomy still pose a slight issue. The paper provides a valuable power analysis framework that should inform researchers across the broader neuroimaging community
eLife Assessment
This study explores how exogenous attention operates at the finest spatial scale of vision, within the foveola - a topic that has not been previously explored. The question is important for understanding how attention shapes perception, and how it differs between the periphery and the central regions of highest visual acuity. The evidence is compelling, as shown by carefully designed experiments with state-of-the-art eye tracking to monitor attended locations just a few tens of minutes of arc away from the fixation target, but additional clarification regarding analyses and implications for vision and oculomotor control would broaden the impact of the study.
eLife Assessment
This valuable study provides solid evidence for deficits in aversive taste learning and taste coding in a mouse model of autism spectrum disorders. Specifically, the authors found that Shank3 knockout mice exhibit behavioral deficits in learning and extinction of conditioned taste aversion, and calcium imaging of the gustatory cortex identified impaired neuronal responses to taste stimuli. This paper will likely be of interest to researchers studying how learning and sensory processes are affected by genetic causes of autism spectrum disorders.
book review/ summary of [[Alone With You in The Ether by Olivie Blake]] that I picked up in Le Mans summer 2024, and haven't read yet. From a psychologists perspective.
However, I also believe that therapy should be about the client; there’s a line between self-disclosure and self-indulgent
when is it a conversation, when are you making it about yourself only?
Dr Yalom talks about this as well in the book and argues that self-disclosure can be useful to building connection, the thing that accounts for 80% of success in therapy.
Sessions also contain self-disclosure by Yalom, against therapeutic condition, but here positioned as way to connect. (and I think regular interaction between ppl.)
focusing on the ‘here and now’. Often, he picks up on the dynamic between him and the client and raises this with the client, linking it with the issue that brought them to him. Most of the time, this is effective.
Yalom makes the meeting between the original request and the current setting / dynamic in the conversational pair the thing to explore.
The book is a collection of stories of these one-off sessions, and they are fascinating to me as a psychologist. How effective can one hour of conversation be? It is true that Dr Yalom (or Irv, as he asks his clients to call him) does not promise to resolve his clients’ needs in one hour; in fact, every consultation is ended with him providing names of other clinicians and urging the client to continue with longer-term therapy.
Yalom during Covid engaged in 1 hour sessions. Not as self-contained therapy, but still self-contained one-off conversations.
[[Het uur van het hart by Irvin D. Yalom Benjamin Yalom]] review/summary .
https://web.archive.org/web/20251207114722/https://sobrief.com/books/hour-of-the-heart
[[Het uur van het hart by Irvin D. Yalom Benjamin Yalom]] gift from E, #2025/12
Another summary of [[Essentialism by Greg McKeown]] the 2014 version
https://web.archive.org/web/20251207094605/https://nielsbohrmann.com/essentialism-book-summary/
summary of [[Essentialism by Greg McKeown]], 2014 book. There's a 2024 2nd edition.
eLife Assessment
This important study shows that different forms and mixtures of cardenolide toxins in tropical milkweed, especially nitrogen- and sulfur-containing types, change how monarch caterpillars eat, grow, and store these chemicals under laboratory conditions. It provides solid evidence to demonstrate that chemical diversity within a single group of plant toxins (cardenolides) can have combined effects on even highly specialized herbivores that are different from what one would expect from each toxin alone. However, as all experiments used leaf-disc assays with fixed "natural" toxin ratios and only one adapted herbivore species, tests on living plants, other mixture designs, and non-adapted herbivores would make the broader conclusions stronger.
eLife Assessment
This study provides a useful advance in generating mouse oligodendrocytes by direct lineage conversion from cortical astrocytes. The authors demonstrate that Sox10 converts astrocytes to MBP+ oligodendrocytes, whereas Olig2 expression converts astrocytes to PDFRalpha+ oligodendrocyte progenitor cells. The data supporting the conclusions are solid, but there are concerns regarding select figures and the absence of functional validation.
eLife Assessment
In this valuable study, Wandler et al. provide convincing theoretical evidence for alternate mechanisms of rhythm generation by CPGs. Their model shows that cell-type-specific connectivity and an inhibitory drive could underlie rhythm generation. Excitatory input could act to enhance the frequency range of these rhythms. This modeling study could motivate further experimental investigation of these mechanisms to understand CPG rhythmogenesis.
eLife Assessment
This global study compares environmental niche model outputs of avian influenza pathogen niche constructed for two distinct periods, and uses differences between those outputs to suggest that the changed case numbers and distribution relate to intensification of chicken and duck farming, and extensive cultivation. While a useful update to existing niche models of highly pathogenic avian influenza, the justification for the use of environmental niche models to explore land cover change as a driver of changed case epidemiology is incomplete.
eLife Assessment
Davis and colleagues describe findings that are fundamental to the understanding of pressure mechanosensation in lymphatic vessels and are of significant importance to other areas of mechanosensory physiology. Based on many different knockout mouse models and rigorous state-of-the-art pressure myography recordings, they present compelling evidence that mechano-activation of GNAQ/GNA11-coupled GPCRs generates IP3, which induces Ca2+ release from internal stores through IP3R1 and drives depolarization through the activation of ANO1 Cl- channels to induce lymphatic vessel contractility. Nevertheless, some aspects of the manuscript are incomplete. The specific identity of the GPCR(s) involved remains to be uncovered, as evidence of frequency-pressure impairment is only demonstrated with abolition of GNAQ/GNA11action, not the receptors per se.
eLife Assessment
This study offers important insights into how outer membrane vesicles (OMVs) secreted by Serratia marcescens, which carry various virulence factors, contribute to pathogenicity. The experiments provide solid preliminary support for OMV-mediated pathogenic effects, with a critical role for the metalloprotease virulence factor PrtA. However, the evidence remains incomplete, and the current level of validation limits confidence in the strength of the conclusions.
eLife Assessment
This valuable study presents an analysis of the gene regulatory networks that contribute to tumour heterogeneity and tumor plasticity in Ewing sarcoma, with key implications for other fusion-driven sarcomas. The authors convincingly employed orthogonal approaches, including single-cell sequencing and xenografts, to reveal the existence and plasticity of specific gene regulatory networks (e.g., TGF-beta signaling) within Ewing sarcoma, as well as significant differences that exist between cell lines and patient tumors.
eLife Assessment
This study tested the specific hypothesis that age-related changes to hearing involve a partial loss of synapse connections between sensory cells in the ear and the nerve fibers that carry information about sounds to the brain, and that this interferes with the ability to discriminate rapid temporal fluctuations in sounds. Physiological, behavioral, and histological analyses provide a powerful combination to test this hypothesis in gerbils. Contrary to previous suggestions, it was found that chemically-induced isolated synaptopathy (at similar levels as observed in aged gerbils) did not result in worse performance on a behavioral task measuring sensitivity to temporal fine-structure, nor did it produce degradations in auditory-nerve fiber encoding of fine structure. Aged gerbils showed degraded behavior and stronger than normal envelope responses, but temporal fine-structure coding was not affected; interpreted by the authors as suggesting central processing contributions to aging effects on discrimination. These findings are important for advancing our knowledge of the mechanistic bases for age-related changes to hearing, and the evidence provided is solid with the results largely supporting the claims made and minor limitations related to possible confounds discussed in reasonable depth.
eLife Assessment
This valuable study presents a theoretical model of how punctuated mutations influence multistep adaptation, supported by empirical evidence from some TCGA cancer cohorts. This solid model points to the case of possible punctuated evolution rather than gradual genomic change. There was some disagreement amongst the reviewers in terms of how closely the theoretical results apply to the phenomena examined empirically, and alternative explanations should be considered in the future.
eLife Assessment
This important study by Jeong and Choi studied neural activity in the medial prefrontal cortex (mPFC) while rats performed a foraging paradigm in which rats forage for rewards in the absence or presence of a threatening object (Lobsterbot). The authors present interesting observations suggesting that the mPFC population activity switches between distinct functional modes conveying distinct task variables- such as the distance to the reward location and types of threat-avoidance behaviors-depending on the location of the animal. The reviewers thought that the results are overall convincing, appreciated the value of studying neural coding in naturalistic settings, and felt that this work offers significant insights into how the mPFC operates during foraging behavior involving reward-threat conflict.
eLife Assessment
This important study investigates nerve-injury-induced allodynia by studying the role of a subpopulation of excitatory dorsal horn CCK+ neurons that express the estrogen receptor GPR30 and potentially modulate nociceptive sensitivity via direct inputs from primary somatosensory cortex. In this revised version, the authors addressed many of the critiques raised through added analyses that convincingly support the notion that spinal GPR30 neurons are indeed an excitatory subpopulation of CCK+ neurons that contribute to neuropathic pain. While evidence of a direct functional corticospinal projection to CCK+/GPR30+neurons is not fully demonstrated, this work will be of broad interest to researchers interested in the neural circuitry of pain.
eLife Assessment
Cryptovaranoides, a Late Triassic animal (some 230 Ma old), was originally described as a possibly anguimorph squamate, i.e., more closely related to snakes and some extant lizards than to other extant lizards, making Squamata much older than previously thought and providing a new calibration date inside it. Following a rebuttal and a defense, this fourth important contribution to the debate makes a convincing argument that Cryptovaranoides is not a squamate. Further comparisons to potentially closely related animals such as early lepidosauromorphs would greatly benefit this study, and parts of the text require clarification.
eLife Assessment
This manuscript describes the identification and characterization of 12 specific phosphomimetic mutations in the recombinant full-length human tau protein that trigger tau to form fibrils. This fundamental study will allow in vitro mechanistic investigations. The presented evidence is convincing. This manuscript will be of interest to all scientists in the amyloid formation field.
eLife Assessment
The present study employed transcriptomics to investigate the impact of methionine restriction (MR) and cold exposure (CE) on liver and adipose tissues in mice. The authors demonstrate that responses to MR and CE are tissue-specific, while both MR and CE have a similar effect on beige adipose tissue. While these findings are somewhat descriptive, this work is considered important, as it provides a comprehensive resource for enhancing our understanding of these lifestyle interventions. The study is of high scientific quality, and the analyses are convincing.
eLife Assessment
This useful study demonstrates that microsaccade direction primarily indexes shifts rather than the maintenance of covert spatial attention, offering a focused interpretation that may help reconcile inconsistencies in the prior literature. However, the evidence remains incomplete due to limited engagement with the broader body of existing work and the absence of independent measures, single-trial analyses, and neutral-condition controls needed to substantiate the central claims. The work will be of broad interest to researchers investigating attention, eye movements, and visuomotor mechanisms.
eLife Assessment
This important work significantly advances our understanding of the role of human hippocampal theta oscillations in memory encoding and retrieval. The evidence supporting the conclusions is solid, using both scopolamine administration and intracranial EEG recordings. This work will be of broad interest to neuroscientists and has translational implications.
eLife Assessment
This potentially important study examines the consequences of manipulating the expression of thyroxine-binding and amyloidogenic hepatocyte secretory protein transthyretin (TTR). Solid in vivo evidence from two dietary models supports that TTR production exacerbates liver injury, whereas the evidence for a link between TTR production, uptake, and calcium dysregulation is incomplete. If the findings are confirmed, they would provide evidence for a novel cell biological pathway of liver injury.
eLife Assessment
The authors attempt to use sequencing of nascent DNA (DNA linked to an RNA primer, "SNS-Seq") to localise DNA replication origins in Trypanosoma brucei, but they analyse the results for only part of the genome. There are also significant discrepancies between their results and those from other origin mapping methods which have not been addressed, meaning that SNS-seq has not been validated for origin mapping in T. brucei. For this reason, the evidence that origins are distributed as the authors claim - and not where previously mapped - is inadequate. This work will be of interest to those studying DNA replication.
eLife Assessment
This manuscript presents valuable findings which reveal an intricate pattern of memory expression following retrieval extinction at different intervals from retrieval-extinction to test. The novel advance is in the demonstration that, relative to a standard extinction procedure, the retrieval-extinction procedure more effectively suppresses responses to a conditioned threat stimulus when testing occurs just minutes after extinction. While the data provide solid evidence that the "short-term" suppression of responding involves engagement of the dorsolateral prefrontal cortex, there are inconsistencies in the analyses reported which obscure the interpretation and leave some of the claims with limited evidence.
eLife Assessment
This study offers valuable insights into how humans detect and adapt to regime shifts, highlighting distinct contributions of the frontoparietal network and ventromedial prefrontal cortex to sensitivity to signal diagnosticity and transition probabilities. The combination of an innovative task design, behavioral modeling, and model-based fMRI analyses provides a solid foundation for the conclusions; however, the neuroimaging results have several limitations, particularly a potential confound between the posterior probability of a switch and the passage of time that may not be fully controlled by including trial number as a regressor. The control experiments intended to address this issue also appear conceptually inconsistent and, at the behavioral level, while informing participants of conditional probabilities rather than requiring learning is theoretically elegant, such information is difficult to apply accurately, as shown by well-documented challenges with conditional reasoning and base-rate neglect. Expressing these probabilities as natural frequencies rather than percentages may have improved comprehension. Overall, the study advances understanding of belief updating under uncertainty but would benefit from more intuitive probabilistic framing and stronger control of temporal confounds in future work.
eLife Assessment
This study presents a fundamental discovery of how cerebellar climbing fibers modulate plastic changes in the somatosensory cortex by identifying both the responsible cortical circuit and the anatomical pathways. The evidence supporting the conclusions is convincing and well supported by modern neuroscience methodologies. Overall, this work represents a significant contribution that will be of broad interest to neuroscientists, especially those studying the long-distance cerebellar influence on non-motor brain functions.
eLife Assessment
This study presents important findings on the role of Slit-Robo signaling in cardiac innervation. The evidence supporting the main claims of the authors is convincing. The use of several mouse models including constitutive and cell type specific knockout models make the findings more robust. The scope of the presented studies is fitting, as they primarily focus on evaluating the phenotypic changes in cardiac innervation following the loss of various Slit or Robo genes
eLife Assessment
The study introduces a valuable dataset for investigating the relationship between vision and language in the brain. The authors provide convincing evidence that decoders trained on brain responses to both images and captions outperform those trained on responses to a single modality. The dataset and decoder results will be of interest to communities studying brain and machine decoding.
eLife Assessment
This study presents a large, systematically curated catalog of non-canonical open reading frames (ncORFs) in human and mouse by reanalyzing nearly 400 Ribo-seq datasets using a standardized pipeline; the resulting atlas consolidates ncORF annotations across tissues and provides a valuable reference for understanding non-canonical translation and ORF emergence. The main conclusions are supported by consistent data processing and multiple computational measures of translation and conservation. While the pipeline is transparent and robust, several downstream analyses are descriptive, and some evolutionary interpretations remain correlative; dataset heterogeneity, uneven tissue representation, and limited experimental validation also constrain the strength of a subset of the findings. Overall, the evidence is solid, and the resource will be broadly used by the community.
eLife Assessment
Recent studies have shown that mRNA can be acetylated (ac4c), altering mRNA stability and translation efficiency; however, the role of mRNA acetylation in the brain remains unexplored. In this valuable study, the authors demonstrate that ac4c occurs in synaptically localised mRNAs, mediated by NAT10. Conditional reduction of NAT10 protein levels led to decreases in ac4c of mRNAs and deficits in synaptic plasticity and memory. These solid results suggest that mRNA acetylation may play a role in memory consolidation.
eLife Assessment
This is a valuable study that investigates peptidoglycan (PG) recycling in Caulobacter crescentus, demonstrating its importance for β-lactam resistance, cell morphology, and cell division. The findings are compelling, although limited complementation somewhat constrains the interpretation of specific gene functions.
eLife Assessment
This is a valuable study of the physiological mechanisms promoting network activity during fever in the mouse neocortex. The supporting evidence is solid, and has improved with revision, along with increased clarity of presentation.
eLife Assessment
This study provides a useful investigation of human-AI interaction and decision-making, using both behavioral and electrophysiological measures. However, the theoretical framework and experimental design are incomplete, with an unclear task structure and feedback implementation limiting interpretability. With these issues addressed, the work could make a significant contribution to understanding human-AI collaboration.
eLife Assessment
This important study provides convincing evidence that envelope-carrying Ty3/gypsy retrotransposons (errantiviruses) are ancient, widespread, and actively expanding across nearly all major animal phyla. Using comprehensive phylogenetic and AlphaFold2-based structural analyses, the authors show that these elements independently acquired membrane fusion proteins early in metazoan evolution, likely predating the bilaterian-non-bilaterian split. While some aspects could be more clearly contextualized and explained better, the work offers insights into the deep evolutionary roots of retroelement-envelope associations and the origins of retroviruses.
eLife Assessment
This important study provides convincing evidence that glucosylceramide synthase (GlcT), a rate-limiting enzyme for glycosphingolipid (GSL) production, plays a role in the differentiation of intestinal cells. Mutations in GlcT compromise Notch signaling in the Drosophila intestinal stem cell lineage, resulting in the formation of enteroendocrine tumors. Further data suggest that a homolog of glucosylceramide synthase also influences Notch signaling in the mammalian intestine. While the outstanding strengths of the initial genetic and downstream pathway analyses are noted, there are minor weaknesses in the data regarding the potential role of this pathway in Delta trafficking. Nevertheless, this study opens the way for future mechanistic studies addressing how specific lipids modulate Notch signalling activity.
eLife Assessment
This paper reports a valuable finding that gastric fluid DNA content can be used as a potential biomarker for human gastric cancer. The evidence supporting the claims of the authors is solid, although an inclusion of explanations for the methodological limitations, moderate diagnostic performance, and the unexpected survival correlation would have strengthened the study. The work will be of interest to medical biologists working in the field of gastric cancer.
eLife Assessment
This study concerns how macaque visual cortical area MT represents stimuli composed of more than one speed of motion. The study is valuable because little is known about how the visual pathway segments and preserves information about multiple stimuli, and the study involves perceptual reports from both humans and one monkey regarding whether there are one or two speeds in the stimulus. The study presents compelling evidence that (on average) MT neurons shift from faster-speed-takes-all at low speeds to representing the average of the two speeds at higher speeds. Ultimately, this study raises intriguing questions about how exactly the response patterns in visual cortical area MT might preserve information about each speed, since such information could potentially be lost in an average response as described here, depending on assumptions about how MT activity is evaluated by other visual areas.
eLife Assessment
This paper presents the fundamental discovery that lipid metabolic imbalance induced by Snail, an EMT-related transcription factor, contributes to the acquisition of chemoresistance in cancer cells. The evidence, supported by a wide range of methods and adequate quantification, provides a convincing mechanistic explanation of how Snail drives ectopic expression of the cholesterol- and drug-efflux transporter ABCA1. This work, which introduces a novel therapeutic concept targeting invasive cancer, will be of broad interest to researchers in cancer biology, lipid metabolism, and cell biology.
eLife Assessment
This study reports the important development and characterization of next-generation analogs of the molecule AA263, which was previously identified for its ability to promote adaptive ER proteostasis remodeling. The evidence supporting the conclusions is convincing, with rigorous assays used to benchmark the changes in potency and efficacy of the AA263 analogs as well as AA263 targets. The ability of AA263 analogs to restore the loss of function associated with disease-associated proteins prone to misfolding will be of interest to pharmacologists, chemical biologists, and cell biologists, as well as those working on protein misfolding disorders.
eLife Assessment
This useful study develops an individual-based model to investigate the evolution of division of labor in vertebrates, comparing the contributions of group augmentation and kin selection. The model incorporates several biologically relevant features, including age-dependent task switching and separate manipulation of relatedness and group-size benefits. However, the evidence remains incomplete to support the authors' central claim that group augmentation is the primary driver of vertebrate division of labor. Key modelling assumptions, such as limited opportunities for task synergy, the structure of helper and floater dynamics, and the relatively narrow parameter space explored, continue to restrict the potential for kin selection to produce division of labor, thereby limiting the generality of the conclusions.
eLife Assessment
The authors identify the Bearded-type small protein E(spl)m4 as a physical and genetic interactor of TRAF4 in the Drosophila wing disc. These valuable findings with potential biomedical relevance are, however, supported by incomplete evidence based largely on overexpression studies that lack quantification, limited molecular support for their model, and issues with Bearded family protein specificity. The work could be of interest to researchers in the fields of cell signaling and developmental biology.
eLife Assessment
This important study applies an innovative multi-model strategy to implicate the ribosomal protein (RP) encoding genes as candidates causing Hypoplastic Left Heart Syndrome. The evidence from the screen in stem cell-derived cardiomyocytes and whole genome sequencing of human patients, followed by functional analyses of RP genes in fly and fish models, is convincing and supports the authors' claims. This work and methodology applied would be of broad interest to medical biologists working on congenital heart diseases.
eLife Assessment
This valuable work substantially advances our understanding of prognostic value of total gfDNA in gastric cancer. The evidence supporting the conclusions is solid, supported by a large, well-classified patient cohort and controlled clinical variables. The work will be of broad interest to scientists and clinical pathologist working in the field of gastric cancer.
Editors Assessment:
Coded and written up as part of the African Society for Bioinformatics and Computational Biology (ASBCB) Omicscodeathons, EMImR is a novel Shiny application for transcriptomic and epigenomic change identification and correlation wrapped up using a combination of Bioconductor and CRAN packages. Case studies are on publicly available GEO data corresponding to sequencing data of human blood cell samples of multiple sclerosis patients to demonstrate how the tool works. And a documentation and videos are provided. Peer review and the study highlighting the usefulness of the developed tool for analyzing transcriptomic and epigenomic data.
This evaluation refers to version 1 of the preprint
eLife Assessment
This study presents a valuable finding on whether executive resources mediate the impact of language predictability in reading in the context of aging. The evidence is solid in the investigation of prediction in reading, with one caveat that the text materials used could be biased against the aging population. The work will be of interest to cognitive neuroscientists working on reading, language comprehension, and executive control.
eLife Assessment
M proteins are essential group A streptococci virulence factors that bind to numerous human proteins; a small subset of M proteins, such as M3, have been reported to bind collagen, which is thought to promote tissue adherence. In this important paper, the authors provide a solid characterization of M3 interactions with collagen. The work raises significant questions regarding the specificity of the structure and its interactions with different collagens, with implications for the variable actions of M protein collagen interactions on biofilm formation.
eLife Assessment
This important study introduces the Life Identification Number (LIN) coding system as a powerful and versatile approach for classifying Neisseria gonorrhoeae lineages. The authors show that LIN codes capture both previously defined lineages and their relationships in a way that aligns with the species' phylogenetic structure. The compelling evidence presented, together with its integration into the PubMLST platform, underscores its strong potential to enhance epidemiological surveillance and advance our understanding of gonococcal population biology.
eLife Assessment
This valuable study uses zebrafish as a model to reveal a role for the cell cycle protein kinase CDK2 as a negative regulator of type I interferon signaling. The evidence supporting the authors' claims is convincing, including both in vivo and in vitro investigative approaches that corroborate a role for CDK2 in regulating TBK1 degradation. In this latest version, the authors included data addressing a concern raised by the reviewer in the previous peer review round. This work will interest cell biologists, immunologists, and virologists.
eLife Assessment
The authors investigated the potential role of IgG N-glycosylation in Haemorrhagic Fever with Renal Syndrome (HFRS), which may offer significant insights for understanding molecular mechanisms and for the development of therapeutic strategies for this infectious disease. The findings are valuable to the field and the strength of evidence to support the findings is solid.
eLife Assessment
This study presents a useful overview of the taxonomic composition of the microbiome associated with Dactylorhiza traunsteineri, a widely distributed orchid species in Central Europe. The evidence supporting the claims of the authors is incomplete, especially when it comes to the (secondary) metabolic pathways found in the metagenome assembled genomes, and requires more substantial analysis to be able to claim that these pathways play a key role in microbiome-orchid symbiosis.
eLife Assessment
This manuscript makes a valuable contribution to the concept of fragility of meta-analyses via the so-called 'ellipse of insignificance for meta-analyses' (EOIMETA). The strength of evidence is solid, supported primarily by an example of the fragility of meta-analyses in the association between Vitamin D supplementation and cancer mortality, but the approach could be applied in other meta-analytic contexts. The significance of the work could be enhanced with a more thorough assessment of the impact of between-study heterogeneity, additional case studies, and improved contextualization of the proposed approach in relation to other methods.
eLife Assessment
In the gram-positive model organism Bacillus subtilis, the membrane associated ParA family member MinD, concentrates the division inhibitor MinC at cell poles where it prevents aberrant division events. This important study presents compelling data suggesting that polar localization of MinCD is largely due to differences in diffusion rates between monomeric and dimeric MinD. This finding is exciting as it negates the necessity for a third, localization determinant, in this system as has been proposed by previous investigations.
eLife Assessment
This study, from the group that pioneered migrasome, describes a novel vaccine platform of engineered migrasomes that behave like natural migrasomes. Importantly, this platform has the potential to overcome obstacles associated with cold chain issues for vaccines such as mRNA. In the revised version, the authors have addressed previous concerns and the results from additional experiments provide compelling evidence that features methods, data, and analyses more rigorous than the current state-of-the-art. Although the findings are important with practical implications for the vaccine technology, results from additional experiments would make this an outstanding study.
eLife Assessment
This paper reports the fundamental finding of how Raman spectral patterns correlate with proteome profiles using Raman spectra of E. coli cells from different physiological conditions and found global stoichiometric regulation on proteomes. The authors' findings provide compelling evidence that stoichiometric regulation of proteomes is general through analysis of both bacterial and human cells. In the future, similar methodology can be applied on various tissue types and microbial species for studying proteome composition with Raman spectral patterns.
eLife Assessment
The authors analyzed spectral properties of neural activity recorded using laminar probes while mice engaged in a global/local visual oddball paradigm. They found solid evidence for an increase in gamma (and theta in some cases) for unpredictable versus predictable stimuli, and a reduction in alpha/beta, which they consider evidence towards a "predictive routing" scheme. The study is overall important because it addresses the basis of predictive processing in the cortex, but some of the analytical choices could be better motivated, and overall, the manuscript can be improved by performing additional analyses.
eLife Assessment
Mark and colleagues developed and validated a valuable method for examining subspace generalization in fMRI data and applied it to understand whether the entorhinal cortex uses abstract representations that generalize across different environments with the same structure. The manuscript presents convincing evidence for the conclusion that abstract entorhinal representations of hexagonal associative structures generalize across different stimulus sets.
eLife Assessment
This important study advances our understanding of population-level immune responses to influenza in both children and adults. The strength of the evidence supporting the conclusions is compelling, with high-throughput profiling assays and mathematical modeling. The work will be of interest to immunologists, virologists, vaccine developers, and those working on mathematical modeling of infectious diseases.
eLife Assessment
This is a useful study that examines the relationship between neuropeptide signaling and the precision of vocal motor output using the songbird as a model system. The study presents evidence based on differential expression patterns and genetic or pharmacological inhibition of various neuropeptide genes for a causal role in song performance; however, this evidence is incomplete.
eLife Assessment
The authors aim to understand why Kupffer cells (KCs) die in metabolic-associated steatotic liver disease (MASLD). This is a useful study using in vitro studies and an in vivo genetic mouse model, suggesting that increased glycolysis contributes to KC death in MASLD. However, the data presented are incomplete as some inconsistencies in the results presented are identified in the characterisation of KCs. This work will be of interest to researchers in the immunology and metabolism fields.
eLife Assessment
This study examines the role of the fungal pathogen Candida albicans in the progression of colorectal cancer, a relevant and urgent topic given the global incidence of colon cancer. While the findings are useful and provide solid experimental work and insight into how Candida may contribute to tumor progression, the small patient sample size, reliance on in vitro models, and absence of in vivo validation may limit its impact. This work will interest scientists studying cancer progression and the role played by pathogens.
eLife Assessment
This is a valuable study describing transcriptome-based pheochromocytoma and paraganglioma (PPGL) subtypes and exploring the mutations, immune correlates and disease progression of cases in each subtype. The cohort is a reasonable size and a second cohort is included from the Cancer Genome Atlas (TCGA). One of the key premises of the study is that identification of driver mutations in PPGL is not complete and that compromises characterisation for prognostic purposes. This is a solid starting point on which to base characterisation using different methods.
eLife Assessment
This important series of studies provides converging results from complementary neuroimaging and behavioral experiments to identify human brain regions involved in representing regular geometric shapes and their core features. Geometric shape concepts are present across diverse human cultures and possibly involved in human capabilities such as numerical cognition and mathematical reasoning. Identifying the brain networks involved in geometric shape representation is of broad interest to researchers studying human visual perception, reasoning, and cognition. The evidence supporting the presence of representation of geometric shape regularity in dorsal parietal and prefrontal cortex is solid, but does not directly demonstrate that these circuits overlap with those involved in mathematical reasoning. Furthermore, the links to defining features of geometric objects and with mathematical and symbolic reasoning would benefit from stronger evidence from more fine-tuned experimental tasks varying the stimuli and experience.
eLife Assessment
The authors present valuable empirical and modelling evidence that statistical learning in speech perception may contain sub-processes. While the evidence for statistical learning effects is solid, the link between the pattern of effects (both empirical and simulated) and the theoretical concepts of the sub-processes (e.g., segmentation, anticipation) could be further developed. This work is of broad interest to researchers working on, or with, statistical learning, and to any researcher interested in the challenges of how data and models adjudicate between competing theoretical constructs.
eLife Assessment
This study presents an important finding that ant nest structure and digging behavior depend on ant age demographics for a ground-dwelling ant species (Camponotus fellah). By asking whether ants employ age-polyethism in excavation, the authors address a long-standing question about how individuals in collectives determine the overall state of the task they must perform. The experimental evidence that the age of the ants and the group composition affect the digging of tunnels is convincing, and their model is able to replicate the colony's excavation dynamics qualitatively, results that may prove to be a key consideration for interpreting results from other studies in the field of social insect behavior.
eLife Assessment
The present manuscript by Cordeiro et al., shows convincing evidence that α-mangostin, a xanthone obtained from the fruit of the Garcinia mangostana tree, behaves as a strong activator of the large-conductance (BK) potassium channels; macroscopic currents and single-channel experiments show that α-mangostin produces an increase in the probability of opening, without affecting the single-channel conductance. The authors put forward that α-mangostin activation of the BK channel is state-independent, and molecular docking and mutagenesis suggest that α-mangostin binds to a site in the internal cavity. Additionally, the authors show that α-mangostin can relax arteries, further suggesting the plausibility of the proposed effects of this compound. These are valuable findings that should be of interest to channel biophysicists and physiologists alike.
eLife Assessment
The one-carbon tetrahydrofolate metabolism plays a crucial role in producing essential metabolic intermediates. In this study, the authors employ a genetics-based approach to demonstrate that three different metabolic pathways are essential for synthesizing 1C-tetrahydrofolates (1C-THF). Disrupting any of these pathways impairs both growth and virulence. Although the work presented is valuable, the experimental evidence remains incomplete without direct quantification of folate intermediates.
eLife Assessment
The study highlights development of a multiplex coregulator TR-FRET (CRT) assay that detects ligands with theoretical full agonist, partial agonist, antagonist, and inverse agonist signatures within the same chemical series. The findings are valuable and will have theoretical and practical implications in the subfield, with respect to guiding the design of non-lipogenic liver X receptor (LXR) agonists. The strength of the evidence is solid, whereby the methods, data, and analyses broadly support the claims with only minor weaknesses that can be dealt with through improvements in the data analysis and the discussion. This study will be of interest to experts working in the areas of pharmacology, medicinal chemistry, and drug discovery in Alzheimer's diseases and dementias.
eLife Assessment
This manuscript describes a valuable screening approach to identifying nanobodies with the potential to modulate gene expression via epigenetic regulators. While the concept is of interest and the screening strategy is well designed, the current evidence supporting mechanistic specificity remains incomplete.
eLife Assessment
This important study reports on the relationships between cerebral haemodynamics and a number of factors that relate to genetics, lifestyle, and medical history using data from a large cohort. Compelling evidence suggests that brief arterial spin labelling MRI acquisition can lead to both expected observations about brain health, as manifested in cerebral blood flow, and biomarkers for use in diagnosis and treatment monitoring. The results can be used as a starting point for hypothesis generation and further evaluation of conditions expected to affect haemodynamics in the brain.
eLife Assessment
This important study presents convincing evidence that uncovers a novel signaling axis impacting the post-mating response in females of the brown planthopper. The findings open several avenues for testing the molecular and neurobiological mechanisms of mating behavior in insects, although broad concerns remain about the relevance of some claims.
eLife Assessment
This valuable study addresses a critical and timely question regarding the role of a subpopulation of cortical interneurons (Chrna2-expressing Martinotti cells) in motor learning and cortical dynamics. However, while some of the behavior and imaging data are impressive, the small sample sizes and incomplete behavioral and activity analyses make interpretation difficult; therefore, they are insufficient to support the central conclusions. The study may be of interest to neuroscientists studying cortical neural circuits, motor learning, and motor control.
eLife Assessment
This valuable study shows that regions of the human auditory cortex that respond strongly to voices are also sensitive to vocalizations from closely related primate species. The study is methodologically solid, though additional analyses - particularly those isolating the acoustic features that differentiate chimpanzee from bonobo calls - would further strengthen the conclusions. With additional analyses and discussions, the work has the potential to offer key insights into the evolutionary continuity of voice processing and would be of interest to researchers studying auditory processing and evolutionary neuroscience in general.
eLife Assessment
This valuable simulation study proposes a new coarse-grained model to explain the effects of CpG methylation on nucleosome wrapping energy. The model accurately reproduces the all-atom molecular dynamics simulation data, and the evidence to support the claims in the paper is solid. This work will be of interest to researchers working on gene regulation, mechanisms of DNA methylation and effects of DNA methylation on nucleosome positioning.
eLife Assessment
This useful study identifies knowledge of letter shape as a distinct component of letter knowledge and shows that children acquire it even before formal reading instruction and without knowing the corresponding letter sounds. However, the evidence supporting the main conclusions is incomplete at the current stage. With additional analyses examining the relationships among the underlying variables and/or revising interpretations, the work would be of broad interest to researchers studying language and vision.
eLife Assessment
This important work develops a new protocol to experimentally perturb target genes across a quantitative range of expression levels in cell lines. The evidence supporting their new perturbation approach is convincing, and we propose that focusing on single modality (activation or inhibition) would be sufficient to draw their conclusions. The study will be of broad interest to scientists in the fields of functional genomics and biotechnology.
eLife Assessment
This study presents a valuable tool named TSvelo, a computational framework for RNA velocity inference that models transcriptional regulation and gene-specific splicing. The evidence supporting the claims of the authors is solid, although elaboration of the computational benchmark and datasets would have strengthened the study. The work will be of interest to computational scientists working in the field of RNA biology.
eLife Assessment
This valuable study investigates the role of P-bodies in yeast proliferation and mRNA regulation within the phyllosphere, proposing that P-body assembly contributes to methanol metabolism and stress adaptation. The findings are of interest to researchers studying post-transcriptional gene regulation and microbial ecology in plants. However, the evidence is incomplete, as most experiments were performed under artificial conditions, relied on limited genetic validation, and were supported primarily by qualitative or low-resolution imaging.
eLife Assessment
This fundamental study presents experimental evidence on how geomagnetic and visual cues are integrated in a nocturnally migrating insect. The evidence supporting the conclusions is compelling. The work will be of broad interest to researchers studying animal migration and navigation.
eLife Assessment
This important work introduces a family of interpretable Gaussian process models that allows us to learn and model sequence-function relationships in biomolecules. These models are applied to three recent empirical fitness landscapes, providing convincing evidence of their predictive power. The findings should be of interest to the community working on the sequence-function relationship, on epistasis, and on fitness landscapes.
eLife Assessment
This important study describes a novel Bayesian psychophysical approach that efficiently measures how well humans can discriminate between colors across the entire isoluminant plane. The evidence was considered compelling, as it included successful model validation against hold-out data and published datasets. This approach could prove to be of use to color vision scientists, as well as to those who use computational psychophysics and attempt to model perceptual stimulus fields with smooth variations over coordinate spaces.
eLife Assessment
This valuable study demonstrates that self-motion strongly affects neural responses to visual stimuli, comparing humans moving through a virtual environment to passive viewing. However, evidence that the modulation is due to prediction is incomplete as it stands, since participants may come to expect visual freezes over the course of the experiment. This study bridges human and rodent studies on the role of prediction in sensory processing, and is therefore expected to be of interest to a large community of neuroscientists.
eLife assessment
This meta-analysis provides a fundamental synthesis of evidence demonstrating that transcranial magnetic stimulation targeting the hippocampal-cortical network reliably enhances episodic memory performance across diverse study designs. The evidence is convincing, with rigorous methodology and consistent effects observed despite modest sample sizes and some heterogeneity in stimulation approaches. The work highlights the specificity of memory improvements to hippocampal-dependent memories and identifies key methodological factors-such as individualized targeting-that influence efficacy. Overall, this study offers a timely and integrative framework that will inform both basic memory research and the design of future clinical trials for cognitive enhancement.
eLife Assessment
This useful study provides a well-constructed computational investigation of how intermittent theta-burst stimulation (iTBS) influences synaptic plasticity within the corticothalamic circuit, improving our mechanistic understanding of how stimulation parameters interact with intrinsic brain oscillations. The authors build a corticothalamic population model that generates individual alpha rhythms with a calcium-dependent metaplasticity rule, and provide solid evidence that aligning stimulation frequencies to brain-intrinsic oscillatory subharmonics enhances plasticity effects. This insight could open a route toward personalized, more effective stimulation protocols.
eLife Assessment
This study is an important contribution to the field of viral sequencing, providing methods for more accurate characterization of viral genetic diversity using long-read sequencing and unique molecular identifiers (UMIs). Although it is a small pilot study, it shows promise as a convincing, validated methodology with broad applicability.
eLife Assessment
This study presents a useful method based on flow cytometry to study partitioning noise during cell division. The methods, data and analysis support the claims of the authors is convincing. This work will be of interest to cell biologists and biophysicists working on asymmetric partitioning during cell division.
THE VHS TAPES waited inside a small pull-out cabinet. Thin adhesive panels on the cabinet’s sides gave the chipboardthe appearance of polished, solid wood. The heavy inner drawer rolled smoothly on its track to reveal the row of tapes,each with a hand-lettered label—some in my mother’s careful italics but many in the large block letters of my father’shand. As a long-haul truck driver in the pre-GPS early ’90s, my father was responsible for manually logging his trips inan oversize ledger when he got home. Those block letters spelled out maps like secret codes: I-77 S PICK UP, 460 E, I 77But his writing on these tapes looked very different:N DETROIT. FRANKENSTEIN. DRACULA. THE MUMMY. THEWOLF MAN.
To Taylor the VHS tapes are like a secret world. She ties the horror movies to a connection with her father and they foreshadow themes of this work.
eLife Assessment
This important study combines brain stimulation with fMRI and behavioural modelling to probe the role of the left superior frontal sulcus in perceptual and value-based decision making. The evidence that the left SFS plays a key role in perceptual decision making is convincing; the results also suggest that the value-based decision process was largely unaffected by the stimulation, despite a change in response times.
eLife Assessment
This important study presents a cross-species and cross-disciplinary analysis of cortical folding. The authors use a combination of physical gel models, computational simulations, and morphometric analysis, extending prior work in human brain development to macaques and ferrets. The findings support the hypothesis that mechanical forces driven by differential growth can account for major aspects of gyrification. The evidence presented is overall strong and convincingly supports the central claims; the findings will be of broad interest in developmental neuroscience.
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. The evidence supporting the findings is solid. This study will be of interest to neuroscientists interested in understanding functional connectivity across development.
eLife Assessment
In this valuable technical report, Verma et al. provide convincing evidence that endogenously tagged dynein and dynactin form processive motor complexes that move along microtubules in living cells. Using quantitative fluorescence microscopy, they directly compare the stoichiometry and motility of these complexes to kinesin-1, revealing distinct transport behaviors and regulatory properties. This study offers key methodological and conceptual advance for understanding the dynamics of native motor proteins within the cellular environment and will be of interest to the cell biology community.
eLife Assessment
This valuable manuscript presents a potentially novel mechanism by which the phospholipid scramblase, PLSCR1, defends against influenza A virus infection. The strength of the paper rests on solid findings involving knockout and lung specific over-expressing Plscr1 mice, airway tissue expression and mechanistic studies to show Plscr1 enhances type III interferon-mediated viral clearance.
eLife Assessment
This important study combines a comprehensive range of biophysical, kinetic, and thermodynamic techniques, together with high-quality experimental and computational analysis, to carry out a series of well-designed experiments to explore whether glutamine-binding protein binds glutamine via an induced fit or a conformational selection process. The evidence supporting the major conclusion of the work is compelling. The work will be of broad interest to biochemists and biophysicists.
eLife Assessment
This study presents an important finding linking the bacterial metabolite trimethylamine and its receptor to circadian rhythms and olfaction. The current evidence supporting the claims of the authors is compelling. This work will be of broad interest to researchers interested in nutrition, microbial metabolism, circadian rhythms, and host-microbiome interactions.
eLife Assessment
This important study uses innovative microfluidics-based single-cell imaging to monitor replicative lifespan, protein localization, and intracellular iron levels in aging yeast cells. The evidence for the proposed role of Ssd1 and reduced nutrients for lifespan through limiting iron uptake is convincing, even though some mechanistic details remain unclear. This work will be of interest to cell biologists working on aging and iron metabolism.
eLife Assessment
This valuable study investigates how perceptual and semantic features of maternal behavior adapt to infants' attention during naturalistic play, providing new insights into the bidirectional and hierarchical organization of early social interaction. The methodology is innovative and overall solid, supported by comprehensive multimodal analyses and advanced information-theoretic methods, though some developmental claims warrant further tests of directionality and age effects. The work will be of interest to psychologists, cognitive scientists, and developmental researchers studying early communication, social learning, and methodological innovation in quantifying naturalistic behavior.
eLife Assessment
This valuable study focuses on a unique morphogenetic module, the junction-based lamellipodia (JBL). It provides a biomechanical understanding of how JBLs control endothelial cell-cell junctional remodelling to generate lumenised, multicellular blood vessels. The manuscript represents a robust, thoughtfully executed, and convincing study that uses high-resolution time-lapse imaging combined with pharmacological treatments to advance our understanding of lumen formation in vascular development.
eLife Assessment
The authors of this manuscript study the transcriptional regulators that allow macrophages to assume different functional phenotypes in response to immune stimuli. They generate a computational map of the gene regulatory networks involved in determining macrophage phenotypes and experimentally validate the role of putative regulatory factors in a myeloid cell line. This study represents a valuable approach to understanding how gene regulation impacts macrophage polarization and their conclusions are supported by solid computational and experimental evidence. The revision has clarified that the focus is the identification of the regulatory barcodes in a myeloid cell line. Future studies in primary cells and in vivo will be required to assess the roles of these regulators in a broader context.
eLife Assessment
This important study explored a number of issues related to citations in the peer review process. An analysis of more than 37000 peer reviews at four journals found that: i) during the first round of review, reviewers were less likely to recommend acceptance if the article under review cited the reviewer's own articles; ii) during the second and subsequent rounds of review, reviewers were more likely to recommend acceptance if the article cited the reviewer's own articles; iii) during all rounds of review, reviewers who asked authors to cite the reviewer's own articles (a practice known as 'coercive citation') were less likely to recommend acceptance. However, when an author agreed to cite work by the reviewer, the reviewer was more likely to recommend acceptance of the revised article. The evidence to support these claims is convincing.
eLife Assessment
This important study substantially advances our understanding of pediatric Crohn's disease, mapping the cellular make-up of this disease and how patients respond to treatment. The evidence supporting the conclusions is compelling, with thorough bioinformatic analyses, underpinned by rigorous methodology and data integration. The work will be of broad interest to pediatric clinicians, immunologists and bioinformaticians.
eLife Assessment
This important study provides solid evidence to support the anti-tumor potential of citalopram, originally an anti-depression drug, in hepatocellular carcinoma (HCC). In addition to their previous report on directly targeting tumor cells via glucose transporter 1 (GLUT1), the authors tried to uncover additional working mechanisms of citalopram in HCC treatment in the current study. The data here suggests that citalopram may regulate the phagocytotic function of TAM via C5aR1 or CD8+T cell function to suppress HCC growth in vivo.
eLife Assessment
This functional MRI study critically tests the hypothesis that poor face recognition in developmental prosopagnosia in humans is driven by reduced spatial integration and smaller receptive fields in face-selective brain regions. The evidence provided is compelling as it is well-powered, uses state-of-the-art functional brain imaging, eye tracking, and computational analyses. The observed lack of difference in population receptive field sizes between face-selective brain regions of individuals with and without prosopagnosia, though a null result, has important implications for the field, and specifically, for theories of face recognition.
eLife Assessment
This manuscript makes a valuable contribution to understanding learning in multidimensional environments with spurious associations, which is critical for understanding learning in the real world. The evidence is based on model simulations and a preregistered human behavioral study, but remains incomplete because of inconclusive empirical results and insufficiencies in the modeling. Moreover, there are open questions about the nature and extent to which the behavioral task induced semantic congruency.
eLife Assessment
AGC kinases, such as PKN1, are regulated by activation loop phosphorylation. This paper reports that exposing cells to high concentrations of monovalent cations induces rapid activation loop dephosphorylation, with rapid re-phosphorylation when physiological salt is restored. Re-phosphorylation is apparently independent of ATP or candidate kinases, and the paper presents an extraordinary and unconventional mechanism involving phosphate exchange between the activation loop and an unknown acceptor molecule. The findings are intriguing and the approach is logical, but the evidence is incomplete and the significance unclear until the biochemical mechanism is identified.
eLife Assessment
This important study uncovers a previously unrecognized light-responsive pathway in C. elegans, centred on ZIP-2/CEBP-2 and the cytochrome P450 enzyme CYP-14A5. The pathway operates independently of known photoreceptors, modulates long-term memory, and can be harnessed as a low-cost light-inducible expression system, opening new directions for sensory biology and genetic engineering in worms. The strength of evidence is compelling if a bacterially derived stimulus is ruled out. Multiple genetic, transcriptional, and behavioural assays support the pathway's role, but a decisive test showing that the initiating light cue is worm-intrinsic rather than mediated by changes in the bacterial food source is still needed.
eLife Assessment
This important study describes a deep learning framework that analyzes single-cell RNA data to identify a tumor-agnostic gene signature associated with brain metastases. The identified signature uncovers key molecular mechanisms, highlights potential therapeutic targets, and demonstrates a metastasis-specific transcriptional signal in circulating platelets, suggesting its promise for non-invasive diagnostics through liquid biopsy. The evidence supporting the findings is solid, utilizing interpretable deep learning methodologies and large-scale datasets across multiple cancer types, though some aspects may benefit from additional analysis and validation.
eLife Assessment
This valuable manuscript provides solid evidence regarding the role of alpha oscillations in sensory gain control. The authors use an attention-cuing task in an initial EEG study followed by a separate MEG replication study to demonstrate that whilst (occipital) alpha oscillations are increased when anticipating an auditory target, so is visual responsiveness as assessed with frequency tagging. The authors propose that their results demonstrate a general vigilance effect on sensory processing and offer a re-interpretation of the inhibitory role of the alpha rhythm.
eLife Assessment
This valuable study presents the first detailed and comprehensive description of brain sulcus anatomy of a range of carnivoran species based on a robust manual labeling model allowing species comparisons. The database and method for reconstructing cortical surfaces are compelling, and the evidence supporting the conclusions is solid. Despite the additional specimen, the evaluation of intra-species variations remains limited, but an insight into the inter-individual variability is now available for certain species. Exploring the associations between sulcal length and behavioral characteristics further suggests the potential of sulci as a proxy of functional organization. Setting an instructive foundation for comparative anatomy, this study will be of interest to neuroscientists and neuroimaging researchers interested in that field, as well as in brain morphology and sulcal patterns, their phylogeny and ontogeny in relation to functional development and behaviour.
eLife Assessment
This valuable study examines the role of IL17-producing Ly6G PMNs as a reservoir for Mycobacterium tuberculosis to evade host killing activated by BCG immunisation. The authors provide solid data reporting that IL17-producing polymorphonuclear neutrophils harbour a significant bacterial load in both wild-type and IFNg-/- mice and that targeting IL17 and Cox2 improved disease outcomes whilst enhancing BCG efficacy. The specific contribution of neutrophil-derived IL-17 to disease pathogenesis remains to be definitively established through direct demonstration of IL-17 production by neutrophils and targeted depletion studies.
eLife Assessment
This important study provides new insights into the neuronal dynamics of the locus coeruleus in relation to hippocampal sharp-wave ripples. Using high-temporal-resolution, multi-site electrophysiological recordings in rats, the authors present solid evidence supporting their main claims. Nonetheless, some aspects of the evidence remain incomplete, and several points in the data presentation would benefit from clarification. Overall, the work will be of interest to neuroscientists studying large-scale brain coordination and memory processes.
eLife Assessment
Using a combination of connectomics, optogenetics, behavioral analysis and modeling, this study provides important findings on the role of inhibitory neurons in the generation of leg grooming movements in Drosophila. The data as presented provide convincing evidence that the identified neuronal populations are key in the generation of rhythmic leg movements. Based on reconstructions from ventral nerve cord electron microscopy data, the authors uncover distinct pathways to the motor neurons, which they propose inhibit and disinhibit antagonistic sets of motor neurons. This results in an alternation of flexion and extension. By analyzing limb kinematics upon silencing of specific populations of premotor inhibitory neurons and using computational modelling, they show the potential role of these neurons in rhythmic leg movement. The work will interest neuroscientists and particularly those working on motor control.
eLife Assessment
This manuscript provides important information on the neurodynamics of emotional processing while participants were watching movie clips. This work provides convincing results in deciphering the temporal-spatial dynamics of emotional processing. This work will be of interest to affective neuroscientists and fMRI researchers in general.
eLife Assessment
The conclusions of this work are based on valuable simulations of a detailed model of striatal dopamine dynamics. Establishing that lower dopamine uptake rate can lead to a "tonic" level of dopamine in the ventral but not dorsal striatum, and that dopamine concentration changes at short delays can be tracked by D1 but not D2 receptor activation, is invaluable and will be of interest to the community, particularly those studying dopamine. The model simulations provide convincing evidence for differences between dorsal and ventral striatum dopamine concentrations, while evidence for differential tracking of dopamine changes by D1 vs D2 receptors is solid.
eLife Assessment
In this useful study, the authors utilize published scRNA-seq data to highlight the potential importance of mast cells (MCs) in TB granulomas, presenting a solid comparative assessment of chymase- and tryptase-expressing MCs in the lungs of Mycobacterium tuberculosis-infected individuals and non-human primates. While the authors appropriately discussed the inconsistencies across models, adoptive transfer experiments in MC-deficient mice would substantially strengthen the causal link between MCs and TB outcomes, providing more direct functional validation of the proposed role of MCs in TB pathogenesis.
eLife Assessment
This important study demonstrates a reduction in airway hyperresponsiveness (one of the mechanisms of allergic asthma) in the absence of IgM in a house dust mite-induced mouse model of allergic asthma. While this result suggests a new mechanistic role for IgM, the proposed new function is not as yet robustly supported by the current experiments and thus the evidence remains incomplete. A connection between the findings and human disease is not established so far, but the study will be interest to clinical immunologists.
eLife Assessment
This study used deep neural networks (DNN) to reconstruct voice information (viz., speaker identity), from fMRI responses in the auditory cortex and temporal voice areas, and assessed the representational content in these areas with decoding. A DNN-derived feature space approximated the neural representation of speaker identity-related information. The findings are valuable and the approach solid, yielding insight into how a specific model architecture can be used to relate the latent spaces of neural data and auditory stimuli to each other.
eLife Assessment
This study makes a valuable contribution by elucidating the genetic determinants of growth and fitness across multiple clinical strains of Mycobacterium intracellulare, an understudied non-tuberculous mycobacterium. Using transposon sequencing (Tn-seq), the authors identify a core set of 131 genes essential for bacterial adaptation to hypoxia, providing a convincing foundation for anti-mycobacterial drug discovery. Minor concerns remain regarding the presentation of Fig. 8C and the interpretation of data related to hypoxia.
eLife Assessment
This work offers important insights into the protein CHD4's function in chromatin remodeling and gene regulation in embryonic stem cells, supported by extensive biochemical, genomic, and imaging data. The use of an inducible degron system allows precise functional analysis, and the datasets generated represent a key resource for the field. While some interpretations of complex data could be more strongly substantiated, the study overall provides compelling evidence and makes a significant contribution to understanding CHD4's role in epigenetic regulation. This work will be of interest to the epigenetics and stem biology fields.
eLife Assessment
Dong et al. present a valuable analysis of mutant phenotypes of the Rab GTPases Rab5, Rab7, and Rab11 in Drosophila second-order olfactory neuron development. This is a solid characterization and comparison of the different Rab mutants on projection neuron development, with clear differences for the three Rabs, and by inference for the early, late, and recycling endosomal functions executed by each.
eLife Assessment
This valuable study uses mathematical modeling and analysis to address the question of how neural circuits generate distinct low-dimensional, sequential neural dynamics that can change on fast, behaviorally relevant timescales. The authors propose a circuit model in which spatially heterogeneous inhibition constrains network dynamics to sequential activity on distinct neural subspaces and allows top-down sequence selection on fast timescales. The study convincingly demonstrates how this mechanism could operate and makes predictions about connectivity patterns and dynamics.
eLife Assessment
This manuscript presents a valuable antiviral approach using an engineered ACE2-Fc fusion protein that demonstrates broad-spectrum neutralization capacity against SARS-CoV-2 variants and achieves significant prophylactic protection in animal models through a novel Fc-mediated phagocytosis mechanism. The study provides convincing evidence for protective efficacy through rigorous in vivo validation in mice, mechanistic characterization via biodistribution studies and macrophage depletion assays, and demonstration of antibody-dependent cellular phagocytosis as the primary clearance mechanism. However, there are some gaps that require attention, including the need for comparison with a previously reported ACE2 decamer, inclusion of control molecules, insufficient discussion of potential limitations such as off-target binding and immunogenicity risks, and lack of clarity regarding certain methodological aspects.
eLife Assessment
This report provides useful evidence that EABR mRNA is at least as effective as standard S mRNA vaccines for the SARS-CoV-2 booster vaccine. Although the methodology and the experimental approaches are solid, the inconsistent statistical significance throughout the study presents limitations in interpreting the results. Also, the absence of results showing possible mechanisms underlying the lack of benefit with EABR in the pre-immune makes the findings mostly observational.
eLife Assessment
This is an important study on how dissociable emotions of shame and guilt emerge from cognitive processes and guide behavioral responses. The task is well designed and yields compelling behavioral, computational, and neural evidence elucidating the cognitive link between emotions and compensatory decisions. The work has broad theoretical and practical implications across a range of disciplines concerned with human behavior, including psychology, neuroscience, economics, public policy, and psychiatry.
eLife Assessment
This Review Article provides a timely review of how the extracellular matrix (ECM), particularly the vascular basement membrane, regulates leukocyte extravasation, migration, and downstream immune function, with a focus on monocytes/macrophages. It integrates molecular, mechanical, and spatial aspects of ECM biology in the context of inflammation, drawing from recent advances.
eLife Assessment
This important study explored a number of issues related to citations in the peer review process. An analysis of more than 37000 peer reviews at four journals found that: i) during the first round of review, reviewers were less likely to recommend acceptance if the article under review cited the reviewer's own articles; ii) during the second and subsequent rounds of review, reviewers were more likely to recommend acceptance if the article cited the reviewer's own articles; iii) during all rounds of review, reviewers who asked authors to cite the reviewer's own articles (a practice known as 'coercive citation') were less likely to recommend acceptance. However, when an author agreed to cite work by the reviewer, the reviewer was more likely to recommend acceptance of the revised article. The evidence is convincing, and while the revisions made by the author have addressed most of the concerns the reviewers had about the original version, a small number of concerns remain.
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, and the work will be of interest to biologists studying skeletal muscle stem cell biology in the context of skeletal muscle regeneration.
eLife Assessment
This study presents significant and novel insights into the roles of zinc in mammalian meiosis/fertilization events. These findings are useful to our understanding of these processes. The evidence presented is solid, with experiments being well-designed, carefully described, and interpreted with appropriate rigor. The authors acknowledge the lack of mechanistic insight which represents the main limitation of the study.
eLife Assessment
This important study addresses a topic that is frequently discussed in the literature but is under-assessed, namely correlations among genome size, repeat content, and pathogenicity in fungi. Contrary to previous assertions, the authors found that repeat content is not associated with pathogenicity. Rather, pathogenic lifestyle was found to be better explained by the number of protein-coding genes, with other genomic features associated with insect association status. The results are considered solid, although there remain concerns about potential biases stemming from the underlying data quality of the analyzed genomes.
eLife Assessment
This potentially valuable work aimed at a better understanding of the mechanisms of response and resistance to androgen deprivation therapy in prostate cancer using genetically engineered mouse models. A key observation relates to the timing of TNF blockage therapy and the concept of a "TNF switch." The solid data were collected using conventional approaches and the conclusions are mostly justified, particularly with the inclusion of more detailed statistics in the revision. The work will be of interest to the prostate cancer research community.
eLife Assessment
This useful study uses a combination of experimental and modeling approaches to investigate the role of actomyosin in epithelial invagination during Ciona siphon tube morphogenesis. Several types of solid quantitative analyses are presented, yet the evidence supporting the central claim of bidirectional translocation of actomyosin remains incomplete. Since epithelial invagination contributes to the morphogenesis of many developing organs, this work has the potential to appeal to both cell biologists and developmental biologists.
eLife Assessment
This important study presents a technically rigorous and carefully controlled analysis of the signalling potential of cancer-associated gain-of-function Notch alleles. The work is clearly presented, and the experiments are robust, comprehensive, and well-controlled. While some data primarily establish the system or report negative findings, the comparative approach in a well-characterized model provides convincing mechanistic evidence for how these Notch variants function. This study will be of interest to researchers in both developmental and cancer biology.
eLife Assessment
This study investigates the influence of genomic information and timing of vaccine strain selection on the accuracy of influenza A/H3N2 forecasting. The authors utilised appropriate statistical methods and have provided convincing evidence, which amounts to an important contribution to the evidence base. Substantial revisions have been made to the manuscript and issues of concern have been clarified, with the necessary study limitations appropriately discussed.
eLife Assessment
This manuscript reports on an FLIM-based calcium biosensor, G-CaFLITS. It represents an important contribution to the field of genetically-encoded fluorescent biosensors, and will serve as a practical tool for the FLIM imaging community. The paper provides convincing evidence of G-CaFLITS's photophysical properties and its advantages over previous biosensors such as Tq-Ca-FLITS. Although the benefits of G-Ca-FLITS over Tq-Ca-FLITS are limited by the relatively small wavelength shift, it presents some advantages in terms of compatibility with available instrumentation and brightness consistency.
eLife Assessment
The manuscript by Mancl et al. provides important mechanistic insights into the conformational dynamics of Insulin Degrading Enzyme (IDE), a zinc metalloprotease involved in the clearance of amyloid peptides. In the revised version, the authors have substantially expanded their analysis by incorporating time-resolved cryo-EM and coarse-grained molecular dynamics simulations, which reveal an insulin-induced allosteric transition and transient β-sheet interactions underlying IDE's unfoldase activity. Supported by a convincing combination of cryo-EM, SEC-SAXS, enzymatic assays, and both all-atom and coarse-grained simulations, this work refines our understanding of IDE's functional cycle and offers a structural framework for developing substrate-selective modulators of M16 metalloproteases.
eLife Assessment
This study represents a valuable addition to the catalog of mitochondrial proteins. With the use of methodology based on the bi-genomic split-GFP technology, the authors generate convincing data, including dually localized proteins and topological information, under various growth conditions in yeast. The study represents a key basis for further functional and/or mechanistic studies on mitochondrial protein biogenesis.
eLife Assessment
During the development of the unicellular eukaryote Dictyostelium discoideum, cells aggregate into mounds, forming protrusions or tips, which then become the front of migrating slugs and the top of fruiting bodies. This valuable study identifies adenosine deaminase-related growth factor (ADGF) as a key regulator of tip formation and convincingly shows that ADGF catalyses the conversion of adenosine to ammonia, allowing ammonia to initiate tip formation, and then elucidates pathways upstream and downstream of ADGF. The authors discuss the intriguing possibility that mammalian ADGF may also similarly regulate development.
eLife Assessment
This valuable study describes an interesting infection phenotype that differs between adult male and female zebrafish. The authors present data indicating that male-biased expression of Cyp17a2 mediates viral infection through STING and USP8 activity regulation. The authors present solid evidence linking this factor to direct and indirect antiviral outcomes through ubiquitination pathways. These findings raise interesting questions about immune mechanisms that underlie sex dimorphism and the selective pressures that might shape it.
eLife Assessment
This important study reports the development of the first tankyrase degrader and demonstrates its enhanced ability to inhibit β-catenin signaling compared to conventional tankyrase inhibitors. The evidence supporting the conclusions is comprehensive and convincing, based on rigorous biochemical and cellular analyses. The findings will be of broad interest to researchers studying Wnt signaling, protein degradation, and cancer biology.
eLife Assessment
This important study provides a theoretical framework for quantifying privacy risk from publicly shared genome-wide association summary statistics. The findings reveal the conditions under which genotype reconstruction may become feasible, challenging long-held assumptions about personal data safety. While the evidence is solid, supported by clear mathematical derivations and simulations, validation on large empirical datasets would further strengthen the claims.
eLife Assessment
The manuscript by Shukla et al. provides important mechanistic insights into kinesin-1 autoinhibition and cargo-mediated activation. Using a convincing combination of protein engineering, computational modeling, biophysical assays, HDX-MS, and electron microscopy, the authors reveal how cargo binding induces an allosteric transition that propagates to the motor domains and enhances MAP7 binding. Despite limitations arising from conformational heterogeneity and structural resolution, the study presents a unified mechanism for kinesin-1 activation that will be of broad interest to the motor protein, structural biology, and cell biology communities.
eLife Assessment
This important study describes a new link between nutrient signaling and chromosome regulation, providing compelling evidence that reduced activity in the central nutrient-sensing pathway governed by TORC1 improves chromosome stability and alters gene expression in S. pombe through effects on cohesin. While the biological importance of this newly described circuit is not yet fully known, and some data would benefit from further clarification, the overall body of evidence supports the main conclusions.
eLife Assessment
Mitochondrial DNA (mtDNA) exhibits a degree of resistance to mutagenesis under genotoxic stress, and this study on the mitochondrial Transcription Factor A (TFAM) presents valuable data concerning the possible mechanisms involved. The presented data are solid, technically rigorous, and consistent with established literature findings. The experiments are well-executed, providing reliable evidence on the change of TFAM-DNA interactions following UVC irradiation. However, the evidence is inadequate to support the primary claims.
eLife Assessment
This study investigates the folding and unfolding behavior of the doubly knotted protein TrmD-Tm1570, providing insight into the molecular mechanisms underlying protein knotting. The findings reveal multiple unfolding pathways and suggest that the formation of double knots may require chaperone assistance, offering valuable insights into topologically complex proteins. The evidence is solid, supported by consistent agreement between simulation and experiment, though some aspects of the presentation and experimental scope could be clarified or expanded.
eLife Assessment
This study used a conditional knockout mouse line to remove Ptbp1 in retinal progenitors and demonstrated that its deletion has no effect on retinal neurogenesis or cell fate specification, thereby challenging the prevailing view of Ptbp1 as a master regulator of neuronal fate. The data are convincing, supported by transcriptomic analysis, histology, and proliferation assays. This study is important, and the broader implications for other CNS regions warrant further investigation.
eLife Assessment
This study demonstrates the cartilage-protective effects of osteoactivin in inflammatory experimental models. The work offers valuable insights advancing current knowledge regarding regulation of joint inflammation and tissue degeneration. The evidence provided is compelling and suggests that osteoactivin may serve as a promising therapeutic target for inflammatory joint diseases.
eLife Assessment
This important work provides mechanistic insights into the development of cardiac arrhythmia and establishes a new experimental use case for optogenetics in studying cardiac electrophysiology. The agreement between computational models and experimental observations provides a convincing level of evidence that wave train-induced pacemaker activity can originate in continuously depolarized tissue, with the limitation that there may be differences between depolarization arising from constant optogenetic stimulation, as opposed to pathophysiological tissue depolarization. Future experiments in vivo and in other tissue preparations would extend the generality of these findings.
eLife Assessment
The authors investigate arrestin2-mediated CCR5 endocytosis in the context of clathrin and AP2 contributions. Using an extensive set of NMR experiments, and supported by microscopy and other biophysical assays, the authors provide compelling data on the roles of AP2 and clathrin in CCR5 endocytosis. This important work will appeal to an audience beyond those studying chemokine receptors, including those studying GPCR regulation and trafficking. The distinct role of AP2 and not clathrin will be of particular interest to those studying GPCR internalization mechanisms.
eLife Assessment
In this manuscript Taujale et al describe an interdisciplinary approach to mine the human channelome and further discover orthologues across diverse organisms. Further, this work provides evidence that supports a role for conserved residues in CALHM channel gating. Overall this important work presents findings that can be helpful to the ion channel community, as well as to those interested in improved methods for mining sequence space for their protein of interest. However, further validation of the improvements their approach shows over previous approaches is needed, making this a solid contribution to the literature in this field.
eLife Assessment
Antibodies that selectively bind distinct amyloid-beta variants are vital tools for Alzheimer's disease research. This valuable manuscript aims to delineate the epitope specificity in a panel of anti-amyloid-beta antibodies, including some with clinical relevance. The experiments were rigorously conducted, employing an interesting combination of established and state-of-the-art methodologies, yielding convincing findings.
eLife Assessment
This valuable work provides new insights into the role of lysine acetylation of alpha-synuclein, the protein involved in Parkinson's Disease. The evidence is mostly solid, but the claims around the potential disease relevance based on seeding assays and structural work need to be toned down, or else supported by additional experimental evidence. Overall, the work will be of interest to researchers in the fields of protein biophysics and post-translational modifications, as well as Parkinson's Disease.
eLife Assessment
This study seeks to expand the understanding of insulin and glucose responses in the brain, specifically by implicating a family of protein kinases responsive to insulin. The significance of the study to the field is valuable, given this study is very emblematic of the new field of interoception (Brain-Body physiology). The evidence supporting the conclusions about brain glucose utilization is convincing and is relevant to many age-related diseases, such as Alzheimer's disorder.
eLife Assessment
This study provides valuable data on the role of Hsd17b7, a gene involved in cholesterol biosynthesis, as a potential regulator of mechanosensory hair cell function. The authors used both zebrafish and the HEI cell line to examine the effects of deletion of Hsd17b7 on hair cell function and survival. While the results do show a reduction in hair cells in the lateral line neuromasts of Hsd17b7 mutant fish, the reduction was limited. The findings are considered incomplete, with additional experiments required to confirm the conclusions.
eLife Assessment
Zebra finches are a prominent model system for vocal learning and auditory system function, yet little is known about the functional development of the auditory system. Here, the authors convincingly show that newly hatched zebra finches lack detectable auditory brainstem responses and that auditory neural signals emerge only days after hatching, challenging influential claims of prenatal acoustic communication in altricial birds. This important work clarifies the developmental timeline for auditory communication and highlights the value of neuroscientific methods for validating and complementing behavioral ecological studies of animal perception.
eLife Assessment
This study provides evidence for distinct neurotransmitter release modalities between two subclasses of dopaminergic neurons in the olfactory bulb. Specifically, it demonstrates dendritic neurotransmitter release in anaxonic neurons and axonal release in axon-bearing neurons. The presence of GABAergic self-inhibition in anaxonic neurons further underscores the functional divergence between these subtypes. Overall, the manuscript presents solid evidence and offers biologically important insights into the organization and function of dopaminergic circuits within the olfactory bulb.