eLife Assessment

This important study presents an impressive large-scale effort to assess the reproducibility of published findings in the field of Drosophila immunity. The authors analyse 400 papers published between 1959 and 2011, and assess how many of the claims in these papers have been tested in subsequent publications. In a companion article they report the results of experiments to test a subset of the claims that, according to the literature, have not been tested. The present article also explores if various factors related to authors, institutions and journals influence reproducibility in this field. The evidence supporting the claims is solid, but there is considerable scope for strengthening and extending the analysis. The limitations inherent to evaluating reproducibility based on the published literature should also be acknowledged.

eLife Assessment

This study introduces an important approach using selection linked integration (SLI) to generate Plasmodium falciparum lines expressing single, specific surface adhesins PfEMP1 variants, enabling precise study of PfEMP1 trafficking, receptor binding, and cytoadhesion. By moving the system to different parasite strains and introducing an advanced SLI2 system for additional genomic edits, this work provides compelling evidence for an innovative and rigorous platform to explore PfEMP1 biology and identify novel proteins essential for malaria pathogenesis including immune evasion.

eLife Assessment

This study resolves a cryo-EM structure of the GPCR, human GPR30, which responds to bicarbonate and regulates cellular responses to pH and ion homeostasis. Understanding the ligand and the mechanism of activation is important to the field of receptor signaling and potentially facilitates drug development targeting this receptor. Structures and functional assays provide solid evidence for a potential bicarbonate binding site.

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 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 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 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 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 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.

when is it a conversation, when are you making it about yourself only?

Sessions also contain self-disclosure by Yalom, against therapeutic condition, but here positioned as way to connect. (and I think regular interaction between ppl.)

Yalom makes the meeting between the original request and the current setting / dynamic in the conversational pair the thing to explore.

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

https://web.archive.org/web/20251207101419/https://ericsandroni.com/book-summary-essentialism-by-greg-mckeown/

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

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 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.