eLife Assessment

This work provides a fundamental molecular mechanism of how a single enzyme can coordinate the ordered assembly of hyaluronan, a complex polysaccharide, from two different building blocks in an alternating pattern. The authors present compelling evidence by combining high-resolution structural data with rigorous biochemical validation to define the underlying process. Major strengths of the study include the clarity and coherence of the mechanistic insights and the complementary use of structural and functional approaches to address the research question.

eLife Assessment

This valuable study addresses a question related to how we achieve visual stability across saccadic eye movements. The authors' gaze-contingent fMRI design provides convincing evidence that peripherally presented visual stimuli are represented in foveal visual cortex prior to a saccade. The results will be of interest to vision scientists and behavioural neuroscientists.

eLife Assessment

The development of glmSMA represents a valuable advancement in spatial transcriptomics analysis, offering a mathematically robust regression-based approach that achieves higher-resolution mapping of single-cell RNA sequencing data to spatial locations than existing methods. The evidence is convincing, as the authors demonstrate the method's superiority by formulating it as a convex optimization problem that ensures stable solutions, coupled with successful validation across multiple biological systems. The rigorous mathematical framework and validation across diverse tissues enable precise spatial mapping of cellular heterogeneity at enhanced resolution.

eLife Assessment

This valuable study investigates the relationship between pupil dilation and information gain during associative learning, using two different tasks. A key strength of this study is its exploration of pupil dilation beyond the immediate response period, extending analysis to later time windows after feedback, and it provides convincing evidence that pupillary response to information gain may be context-dependent during associative learning. The interpretation remains limited by task heterogeneity and unresolved contextual factors influencing pupil dynamics, but a range of interesting ideas are discussed.

eLife Assessment

This study identifies 53BP1 as an interaction partner of GMCL1 (a likely CUL3 substrate receptor). The study proposes a novel mechanism by which cancer cells evade the mitotic surveillance pathway through GMCL1-mediated degradation of 53BP1, leading to reduced p53 activation and paclitaxel resistance. These data are the most useful aspect of the study, but the data supporting the authors' conclusions as to the clinical relevance of the study are inadequate. The authors have not taken relevant data about the clinical mechanism of taxanes into account.

eLife Assessment

This study presents a valuable advance in reconstructing naturalistic speech from intracranial ECoG data using a dual-pathway model. The evidence supporting the claims of the authors is solid, although the rationale for employing a smaller language model rather than a large language model (LLM) should be further clarified. This work will be of interest to cognitive neuroscientists and computer scientists/engineers working on speech reconstruction from neural data.

eLife Assessment

This fundamental study provides compelling evidence for the functional segregation of the sensorimotor cortex into precisely delineated areas, and highlights a rapid transition in functional properties at the boundaries between these areas. This result further confirms and extends recent work on the diversity of neural response specificities across cortical areas in the context of complex behavioral tasks. This work will be of interest to neuroscientists studying sensory-motor functions.

eLife Assessment

The authors present evidence for a WIPI2-Retriever complex (termed CROP2) that couples cargo selection to carrier fission at endosomes. CROP2 appears to function analogously to the previously described CROP1 complex, formed by WIPI1 and Retromer, with which it shares structural similarities. They provide convincing evidence that CROP1 and CROP2 regulate the trafficking of distinct subsets of cargoes; however, the cellular evidence for the existence of these distinct complexes remains incomplete. Overall, the findings are important and expand our understanding of how cargo selection by Retriever and Retromer is orchestrated at endosomes.

eLife Assessment

This study reports a valuable method to predict the capacity of a candidate probiotic bacterium to metabolically outcompete a bacterial pathogen in the ecological niche of the murine respiratory tract (niche exclusion) based on the overlap of used carbon sources in vitro. The in vivo confirmation of the in vitro/in silico predicted efficacy is, at this stage, incomplete and would require more persuasive experimental evidence for the elimination of alternative mechanisms of action.

eLife Assessment

This is an overall compelling set of findings on the role of centrally produced estrogens in the control of behaviors in male medaka. The significance of the findings rests on the revealed potential mechanism between brain derived estrogens modulating social behaviors in males , supported by the analysis of multiple transgenic lines. The evidence for the broader claim is incomplete since it has not been extended to female medaka, and further experimentation would be necessary to fully validate the conclusions on the role of brain-derived estrogens. Nonetheless, the findings have led to important hypotheses on the hormonal control of behaviors in teleosts that can be tested further.

eLife Assessment

This paper describes a useful Bayesian model to estimate the probabilities of access, use, and use given access of insecticide-treated bed nets (ITNs), by using sub-national cross-sectional survey data and the annual number of ITNs received at the country level. The authors provide convincing evidence to support their modeling approach, which could be enhanced by more validation and exploration of model assumptions.

eLife Assessment

The authors provide a useful integrated analytical approach to investigating MASLD focused on diverse multiomic integration methods. The strength of evidence for this new resource is solid, as analyses highlight the importance of previously-described pathophysiologic processes, as well as unveil several new mechanisms as key features of MASLD in obese patients.

Summary: Defines segmentation as a tool for managing cognitive processing, supporting the claim that structure is necessary for the reader (consumer) to handle the flow of information.

This helps to simplify the approach for those learning a new language, and reduces cognitive load.

eLife Assessment

Argunşah et al. investigate the mechanisms underlying the differential response dynamics of barrel vs septa domains in shaping the responses to single vs multiple whiskers. Based on the observation of a higher density of SST+ interneurons in the septa, the authors investigate the hypothesis that Elfn1-dependent short-term plasticity shapes these responses. This important study is, however, supported by incomplete evidence; factors restricting the strength of evidence are the limited spatial resolution of the multi-unit activity, as well as the lack of a mechanistic explanation. This provocative and intellectually stimulating hypothesis provides a contribution to work on how different cell types shape cortical representation.

eLife Assessment

This important manuscript provides insights into the competition between Splicing Factor 1 (SF1) and Quaking (QKI) for binding at the ACUAA branch point sequence in a model intron, regulating exon inclusion. The study employs convincing, rigorous transcriptomic, proteomic, and reporter assays, with both mammalian cell culture and yeast models.

eLife Assessment

The study presents convincing quantitative evidence, supported by appropriate negative controls, for the presence of low-abundance glycine receptors (GlyRs) within inhibitory synapses in telencephalic regions of the mouse brain. Using sensitive single-molecule localization microscopy of endogenously tagged GlyRs, the authors reveal previously undetected populations of these receptors. Although the functional significance of these low-abundance GlyRs remains to be established, the findings offer valuable insights and methodologies that will be of interest to neuroscientists studying inhibitory synapse biology.

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

eLife Assessment

This important study characterizes with rigorous methodology anatomical and functional aspects of the peripheral innervation of the Drosophila male reproductive tract. The convincing analysis reveals two distinct types of glutamatergic neurons that co-release either serotonin or octopamine. While serotonergic neurons are required for male fertility, octopaminergic neurons are dispensable. The work is providing invaluable insight into neurochemical control of insemination, peripheral motor control and neuromodulation in the male reproductive tract.

eLife Assessment

The authors employ an unbiased, affinity-guided reagent to label P2X7 receptor and use super-resolution imaging to monitor P2X7 redistribution in response to inflammatory signaling. The evidence is convincing and the study will be valuable to those studying the dynamics of receptor distribution and clustering.

eLife Assessment

This fundamental manuscript provides compelling evidence that BK and CaV1.3 channels can co-localize as ensembles early in the biosynthetic pathway, including within the ER and Golgi. The findings, supported by a range of imaging and proximity assays, offer insights into channel organization in both heterologous and endogenous systems. The data substantiate the central claims, while highlighting intriguing mechanistic questions for future studies: the determinants of mRNA co-localization, the temporal dynamics of ensemble trafficking, and the physiological implications of pre-assembly for channel function at the plasma membrane.

eLife Assessment

This study investigates how the HIV inhibitor lenacapavir influences capsid mechanics and interactions with the nuclear pore complex. It provides important insights into how drug-induced hyperstabilization of the viral shell can compromise its structural integrity during nuclear entry. While the modeling is technically sophisticated and the results are promising, some mechanistic interpretations rely on assumptions embedded in the simulations, leaving parts of the evidence incomplete.

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 compelling, although including a larger sample size and more quantification would have strengthened the study further, 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 important work advances our understanding of the single neuron coding types in the mouse gustatory cortex and the functional roles of these neurons for perceptual decision-making. The conclusions are based on compelling evidence from rigorous behavioral experiments, high-density electrophysiology, sophisticated data analysis, and neural network modeling with in silico perturbations of functionally-identified units. This work will be of broad interest to systems neuroscientists.

eLife Assessment

This valuable study leverages a large global dataset of tens of thousands of tuberculosis samples to place recurrent protein-coding mutations into their three-dimensional structural context, offering an expanded view of how antibiotic resistance emerges compared to traditional genetic analyses alone. The strength of evidence is convincing, supported by the scale and breadth of the dataset and the systematic structural analysis, although some of the assumptions made in the the modeling approach are only partially supported. Overall, the work will be of broad interest to researchers studying microbial evolution, antibiotic resistance, and structure-function relationships in pathogens.

eLife Assessment

This valuable study shows that combining reactivation-based training with anodal tDCS yields an unusually broad generalization of visual perceptual learning, while preserving robust learning gains and markedly reducing total training time. Although the empirical evidence is solid, the proposed mechanistic account, i.e., the GABA modulation, disrupted offline consolidation and reduced perceptual overfitting, remains insufficiently substantiated, as these assumptions lack direct neurochemical support, and several alternative behavioral explanations and necessary control comparisons have not been fully addressed. The work will be of broad interest to researchers investigating brain plasticity, perceptual learning, and rehabilitation training.

eLife Assessment

This important study establishes the first vertebrate models of DeSanto-Shinawi Syndrome, revealing conserved craniofacial and social and behavioral phenotypes across mouse and zebrafish that mirror key clinical features. The solid evidence is supported by behavioral, anatomical, and molecular analyses of Wac animal mutants that broadly support the authors' claims, though additional mechanistic investigation would strengthen the conclusions. This study sets a baseline for future mechanistic studies and reports a platform to test approaches to reverse phenotypes.

eLife Assessment

This fundamental study reports solid evidence for early verbal episodic memory formation. The findings demonstrate that speaker identity is a crucial feature, enabling episodic-like memories from birth, and will be of interest to cognitive neuroscientists working on brain development, memory, language learning and social cognition.

eLife Assessment

This study offers a valuable contribution to understanding how working memory (WM) shapes neural processing in extrastriate cortex. By applying spectral decomposition to LFP recordings from primate middle temporal area (MT) during a spatial WM task, the authors show that lower-frequency components (theta, alpha, and beta, but not gamma or high-gamma) correlate with trial-by-trial gain modulation of visually evoked responses. However, certain aspects of the gain-modulation and statistical analyses are incomplete. A clearer and more comprehensive description of these components would substantially strengthen the manuscript.

eLife Assessment

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

eLife Assessment

This paper presents fundamental research showing that the acquisition and expression of Pavlovian conditioned responding are lawfully related to temporal characteristics of an animal's conditioning experience. It showcases a rigorous experimental design, several different approaches to data analysis, careful consideration of prior literature, and a thorough introduction. The evidence supporting the conclusions is compelling. The paper will have a general appeal to those interested in the behavioral and neural analysis of Pavlovian conditioning.

eLife Assessment

The study presents valuable findings of an optimized E. coli cell-free protein synthesis (eCFPS) system that has been simplified by reducing the number of core components from 35 to 7; furthermore, the findings communicate a simplified 'fast lysate' preparation that eliminates the need for traditional runoff and dialysis steps. This study is an advance towards simplifying protein expression workflows, and the evidence provided is solid, starting with nanoluc, a protein that expresses readily in many systems, to applications to more challenging proteins like the functional self-assembling vimentin and the active restriction endonuclease Bsal. Data on the underlying mechanisms and efficiency of the presented system in terms of protein yield relative to other known cell-free systems would greatly enhance the findings' significance and the strength of the evidence. The paper remains of interest to scientists in microbiology, biotechnology and protein synthesis.

eLife Assessment

This study provides important evidence for the mechanism underlying KCNC1-related developmental and epileptic encephalopathy. The authors have generated and characterized a new knock-in mouse with a pathogenic mutation found in patients to determine the synaptic and circuit mechanisms contributing to KCNC1-associated epilepsy. They provide convincing evidence for reduced excitability of parvalbumin-positive fast-spiking interneurons, but not in neighboring excitatory neurons, and suggest that this may contribute to seizures and premature death in the mice.

eLife Assessment

This valuable study provides solid evidence that supports TANGO2 homologs, including HRG-9 and HRG-10, can play a role in cellular bioenergetics and oxidative stress homeostasis. It also challenges the previously reported role of TANGO in heme transport and paves the way for future mechanistic studies addressing the mechanisms of how TANGO2 regulates oxidative stress homeostasis. The strengths include the use of different model systems, genetic tools, behavioral assays and efforts by the authors in using the same reagents to reproduce results of other groups.

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.