eLife Assessment
This study provides valuable evidence that glycogen phosphorylase is unlikely to represent an effective insecticidal target in Plutella xylostella and that diflubenzuron does not directly inhibit this enzyme. The combination of biochemical, molecular and physiological approaches provides convincing data to support these conclusions, although the proposed metabolic compensation mechanism is supported primarily by indirect evidence and would benefit from direct demonstration.
eLife Assessment
This important study provides convincing evidence that envelope-carrying Ty3/gypsy retrotransposons (errantiviruses) are ancient and widespread across nearly all major animal phyla, with distribution in many lineages that are consistent with recent or ongoing genomic expansion. Using comprehensive phylogenetic and AlphaFold2-based structural analyses, together with new host-taxonomy concordance tests, the authors show that these elements independently acquired membrane fusion proteins early in metazoan evolution, likely predating the bilaterian-non-bilaterian split. The work offers significant insights into the deep evolutionary roots of retroelement-envelope associations and the origins of retroviruses.
eLife Assessment
In this important study, the authors have performed a zebrafish drug screen to identify suppressors of atherogenic lipoproteins. They utilize a well-established LipoGlo assay to find molecules that modulate these lipoproteins, identifying 49 potential hits and they perform validation experiments, including studies linking enoxolone to its likely inhibitory effect on a specific transcription factor, HNF4alpha. Overall, the results are convincing and robust, and will open up new areas of exploration for those investigators interested in in vivo lipid biology.
eLife Assessment
This study provides important insights into how researchers can use perceptual metamers to formally explore the limits of visual representations at different processing stages. The framework is compelling and the data support the claims.
eLife Assessment
This is an important study establishing the mechanistic principles how NUP98-KDM5A phase separates together with H3K4me3 chromatin in leukemia. Methods are sound and results are convincing, providing a framework to understand gene expression changes in leukemia patients.
eLife Assessment
In this important study, the authors describe the mechanisms by which CDK4/6 overexpression mediates resistance to Osimertinib in EGFR mutant lung cancer models. Their data show that CD4/6 overexpressing cells had increased replicative stress and genomic instability. The evidence is solid, but inclusion of some additional experiments would make this stronger.
eLife Assessment
This study presents a potentially important structure-interaction model describing recognition of polymyxin antibiotics by the human transporter hPepT2 and applies these insights to guide the rational design of potent polymyxin B analogues with reduced nephrotoxicity. The conclusions are supported by compelling evidence, integrating molecular dynamics simulations, transporter mutagenesis, uptake assays, protein expression analyses, antibacterial testing, and mouse nephrotoxicity studies, although some mechanistic interpretations remain limited by altered transporter expression and the absence of direct structural validation.
With knowledge and understanding of African American English, educators have a greater appreciation for the communication patterns and rich linguistic heritages of their African American English–speaking students. Linguistically informed educators are also better equipped to instruct African-American-English–speaking students in ways that enable them to recognize and value the rules, norms, and conventions of standardized English while also recognizing and valuing the language patterns they bring with them from home. As such, the linguistic path to justice for African Americans begins.
possible conclusion
When students who speak nonstandardized varieties of English perceive that their language is devalued in school and that they are not receiving appropriate feedback from educators, they may feel discouraged from continuing their education. They may also perceive that their own culture, family, friends, and even they themselves are being devalued. In turn, they may lose confidence in school and in their educators. They may even resist feeling like their language and culture are devalued in academic settings by disengaging from the standardized-English-speaking school culture and climate altogether.
possible evidence for topic/subtopic
Language varieties hold inherent value as markers of culture and identity. As a result, some speakers of African American English, including students, may feel shame, insecurity, and embarrassment when they operate within a society that expects them to speak standardized English. Educators who teach African-American-English–speaking students have a special role to play in understanding these students’ personal and cultural experiences and in helping them navigate comfortably between African American English and standardized English.
possible topic/subtopic
eLife Assessment
This valuable study provides solid evidence that N6 methylation of A74 by METTL3 is required for efficient translation directed by the SARS-CoV-2 5′UTR in uninfected cells, likely by limiting access of protein factors to the 5′UTR that are necessary for efficient translation. These findings advance our understanding of the role of RNA modification in coronavirus replication and m6A-mediated regulation of gene expression more broadly, while further supporting METTL3 as a potential anticoronaviral therapeutic target. However, the evidence that m6A acts by destabilizing the third stem-loop (SL3) of the 5′UTR remains incomplete. The impact of the study would be strengthened by biochemical analyses directly assessing structural changes in the 5′UTR induced by A74 methylation.
Even after the Civil War and the all-too-brief period of Reconstruction, most writings by African Americans continued to be chiefly in SE, not in AAVE. In fact, European-American Southerners were more likely than African Americans to use a form of AAVE, typically through nostalgic stories of the good old days of plantation slavery. Typically, these narratives used highly stereotyped written representations of the phonics and syntax of AAVE, intended to portray the speakers as not only poorly educated but also unintelligent.
By the late 1700s, it was illegal for enslaved people to be taught to read or write in most of the states where slavery remained legal. The penalties for violating these laws were harsh, so very few African Americans learned to read or write. During this time, for the vast majority of African Americans, their literary traditions were oral, not written. Their rich literature was passed along from person to person and generation to generation through the oral tradition.
Most African Americans were living in the south as slaves in what is the U.S. now, around the late 1700's slaves could not learn to read or write because of harsh laws. Most of the African American literary traditions became oral and not written around that time. Their literature started to get past down to many people, and generations using the oral tradition.
eLife assessment
In this manuscript, Rademacher and colleagues examined the effect of a chemogenetic approach on the integrity of the dopamine system in mice with chronically stimulating dopamine neurons. These findings are important: (1) This approach led to an axon-first degeneration over a time course (2–4 weeks) that is suitable for experimental investigation; (2) The finding that direct excitation of dopaminergic neurons causes differential degeneration sheds light on dopaminergic neuron selective vulnerability mechanisms. Overall, the strength of the evidence is solid, but the behavior experiments that do not include a CNO control provide incomplete support for the findings.
eLife Assessment
This study addresses an important gap in drug discovery by delivering a rigorous, large-scale evaluation of widely used co-folding methods for predicting ligand-bound protein complexes and virtual screening. A key strength is the comprehensive benchmarking framework, which leverages structures and chemical compounds that were absent from the AI models training set, thereby providing particularly compelling and unbiased evidence of co-folding performance. The findings clearly delineate the complementary roles of deep learning-based co-folding and physics-based docking, offering practical guidance for their rational integration into drug discovery workflows. Overall, the conclusions are well supported by thorough analyses across a representative set of cases.
eLife Assessment
This study identifies apoptotic retinal ganglion cells as a potential source of ATP-mediated activation of PANX1 channels that initiates developmental retinal Ca²⁺ waves and coordinates microglial activation and vascular outgrowth during postnatal maturation. The work is important because it proposes an integrative framework linking programmed cell death, spontaneous neural activity, immune responses, and angiogenesis into a self-regulating developmental loop. Although the mechanistic conclusions would benefit from complementary genetic validation, the study provides a convincing foundation for future investigations into the coordination of neural circuit development and tissue remodeling.
eLife Assessment
This convincing contribution addresses a question of practical importance: when collecting tilt-series data, what is the optimal angular step size between successive tilt images? The work provides valuable practical insights into cryo-ET data acquisition by demonstrating that balancing two competing demands - sufficient dose per individual tilt image and fine angular sampling - is essential to achieve high-quality tomographic reconstructions. They demonstrate that tilt-series acquired with finer increments (1-3 degrees) yield superior alignment accuracy and improved template-matching performance.
eLife Assessment
This is a valuable study on the metabolic adaptations upon succinate dehydrogenase loss in cancer cells. If confirmed, this study will offer some therapeutic vulnerabilities in treating SDH-deficient cancer. However, the evidence supporting the authors' claim is incomplete and would benefit from additional experimental evidence. This study will be of broad interest for cancer biologists focusing on metabolism.
eLife Assessment
This valuable study documents, for the first time, the degree of preference for contralateral versus ipsilateral forelimb movements in the motor cortex of mice, revealing subtly distinct profiles across cortical areas, with the orofacial region showing comparatively little limb selectivity relative to the forelimb motor areas. The experiments and analyses are, in general, solid and well-designed, and the data support the paper's conclusions.
eLife Assessment
This manuscript employs cryo-EM, mutational analysis, and biochemical assays to explore the molecular basis by which glutamine promotes filamentation and regulates the activity of human glutamine synthetase (hGS) by stabilizing interactions between hGS decamers. The combined structural and biochemical data supporting the proposed mechanism are solid, although the evidence for a higher-order filamentous architecture and the precise assignment of the interface density would benefit from additional support. This work will be of particular interest and useful to groups interested in understanding the molecular basis of nutrient sensing, cellular metabolism, and structural regulation of enzyme activity.
eLife Assessment
This work presents important findings on quantifying gene coexpression from spatial omics. These quantification methods have been applied to gastruloid to describe how genes are spatialised. The description of the quantifying tools is characterized by exceptional evidence after a thorough revision.
eLife Assessment
This multimodal neuroimaging study leverages fMRI, PET, and deep learning to predict memory performance. The authors introduce the brain-cognition gap to link these different imaging modalities to cognition and evaluate their results in two independent cohorts. The results are solid and provide an important contribution to the literature and will be of interest to neuroscientists working at the interface of cognition, neuroimaging.
eLife Assessment
This study explores how complement protein C3 and its signalling may modulate immune training in alveolar macrophages. The findings are an important contribution to the field of trained immunity. The findings are convincingly supported by in vivo and ex vivo experiments, encompassing both pharmacological and genetic-based approaches.
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 employed compelling 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.
There is empirically based evidence of teacher bias against black students
Bias can cause students who speak Black English to be though of as less intelligent, when they aren't
This will occur most readily as educators atall levels strongly promote both intercultural standards and a meaningful approach to"making it" in American society.
Teachers need to make sure to respect others' cultures and dialects and prepare students for the real world by teaching Standard English.
upward mobilityis the fountainhead from which most societal successes flow.
Getting farther in society means that you have to speak the way that other, "dominant" people do.
. And we must further examine how standard language ideology manifestsitself in individuals, classrooms, colleges and universities, and other public spaces
We should change the way standard English is being taught in schools so that it focuses more on diversity.
discourse, especially at the expense of their home languages, discourses, and identities.
Requiring standardized English makes it harder for some people to get education, jobs, and talk to people in conversations and actively telling students to not use their home language at school.
eLife Assessment
This manuscript reports an important new statistical method for calculating the significance of correlations between two time-series, which provides more accuracy than other methods when the data has few replicates. The proposed method solves a real-life problem that is frequently encountered and is broadly applicable to many realistic datasets in many experimental contexts. The technique is supported with compelling mathematical derivations as well as analysis of both computer-generated and previously published experimental data.
eLife Assessment
This important study by Otgonbaatar and colleagues employs advanced live microscopy, optogenetics, and an endogenous fluorescent timer system to investigate short- and long-term stabilization dynamics of β-catenin/Armadillo (Arm) during Drosophila development. The authors identify an unexpected and functionally relevant enrichment of stabilized junctional Arm in leading-edge cells during dorsal closure, providing evidence for a stabilization mechanism that appears independent of canonical Wingless signaling. These findings are significant because they expand current understanding of β-catenin/Arm beyond its canonical signaling functions and suggest a role in tissue mechanics and force transmission during dorsal closure. The proposed model represents a key advance in the field, but the strength of evidence is currently incomplete: the main conclusions regarding Wingless independence, JNK-mediated regulation, and the mechanical role of stabilized Arm are only partially supported by the available data and would benefit from further experimental testing and corroboration.
eLife Assessment
This study presents a valuable RNA velocity solution which integrates cell differentiation and gene regulation, with a balance between neuralODE and raw gene space. The evidence supporting the claims of the authors is solid, although inclusion of discussion on the challenges in capturing cell cycle transitions would have strengthened the study. The work will be of interest to scientists working in the field of computational biology and gene regulation.
eLife Assessment
This study demonstrates that endothelial toll-like receptor 4 is a central regulator of leptomeningeal inflammation in neonatal E. coli meningitis. The data are derived from cell-type-specific gene knockouts in mice and cultured endothelial cells and are convincing. This work is important as it advances our understanding of host cellular processes and molecular pathways underlying meningitis pathogenesis and specifically expands the knowledge of how breakdown of the blood brain barrier contributes to the pathogenesis.
eLife Assessment
This important study addresses how the molecular identity of a single neuron specifies its hard-wired synaptic connectivity, using repeated single-cell RNA sequencing of identified Drosophila sensory neurons together with functional perturbation of candidate cell-surface molecules. It demonstrates remarkably low transcriptomic variability across animals for the same identified neuron, defines a tractable set of differentially expressed cell-surface molecules that distinguish mechanosensory from chemosensory neurons, and links several of these molecules to axonal targeting and circuit function. The evidence is solid, with the single-neuron transcriptomic datasets and Dscam isoform repertoires offering a lasting resource for the field, though clearer articulation of the experimental logic, additional controls in the RNAi screen, and a more complete characterization of the neuronal re-wiring would further strengthen the central claims.
eLife Assessment
This study addresses an important question in liver biology: how zonal hepatocytes balance survival and proliferation following injury? The authors propose that a mid-zone Atf4-Chop axis to Btg2 program temporarily suppresses proliferation to promote survival after a variety of chemical and surgical liver injury models. The authors provide evidence that some zones mount tailored stress responses, which ultimately promote regeneration and liver healing; however, the "mid-zone" changes with different injury models, making it difficult to conclude that the ATF4-CHOP response is specific to this zone in all injury contexts. In addition, it is possible that Atf4 and Btg2 overexpression could lead to Cyp2e1 suppression, which could reduce the extent of injury after CCl4 or APAP. To some extent, these points make the strength of the evidence incomplete, but do not entirely detract from the significance of the study, which is underscored by the helpful observation that there are zone-specific stress responses that mediate liver regeneration and survival.
eLife Assessment
This study investigates the role of Interleukin-2-inducible T cell kinase (ITK) deficiency in autoimmune lung injury using a pristane-induced pulmonary hemorrhage (PH) model, suggesting that ITK-deficient regulatory T cells (Tregs) restrict severe tissue pathology. The work represents a valuable addition to the fields of autoimmunity, inflammation, and T-cell biology in the lung. However, the experimental evidence supporting the underlying cellular and molecular mechanisms and the integration of foundational background literature to provide the necessary context are incomplete.
eLife assessment
The authors present a valuable open-source tool for three-dimensional analysis of dissected slices of human brains including 3D reconstruction and high-resolution 3D segmentation. Convincing evidence is provided based on experiments on both real and synthetic data. This tool would be of use to researchers in the neuropathology and neuroimaging field.
eLife assessment
The study presents a tool for searching molecular dynamics simulation data, making such data sets accessible for open science. The authors provide convincing evidence that it is possible to identify noteworthy molecular dynamics simulation data sets and their analysis can produce valuable information.
eLife Assessment
This valuable manuscript by Alonso-Caraballo et al is a novel piece of work that examines the impact of oxycodone self-administration on neural plasticity within paraventricular thalamic (PVT) to nucleus accumbens shell (Shell) pathway - two regions shown to play a key role in cue-induced drug seeking on their own - and whether this plasticity varies based on abstinence period and biological sex. Data show that a clinically relevant long-access model of self-administration promotes dependence in both male and female rats and provide compelling data that when compared to current literature indicate that craving-induced relapse for opioids may develop faster and may be more pronounced in females compared to males. In addition to these behavioral findings, the authors provide the first evidence that glutamate signaling within the PVT-to-Shell pathway is selectively strengthened at the output medium spiny neurons by opioids following protracted, but not acute abstinence. These data highlight a potential role for these adaptations in relapse behavior and identify a potential therapeutic target during abstinence to reduce relapse risk in abstaining individuals.
eLife Assessment
This important study addresses the role of sphingolipid metabolism in maintaining endolysosomal membrane integrity and its impact on tau pathology in Caenorhabditis elegans and human cell culture models. The findings are convincing, and the proposed mechanisms are conceivable. The experimental evidence supports the conclusions of the study. The work will be of broad interest to cell biologists and biologists working on Alzheimer's disease and related proteinopathies.
eLife Assessment
This study presents a fundamental finding that the JAK-STAT pathway (JSP) exerts context-dependent roles across distinct cellular compartments within the breast cancer microenvironment. The conclusions are supported by convincing evidence from multi-omics analyses. This study may inspire future studies to explore specific factors that selectively modulate JAK-STAT activity in immune cells to achieve favorable therapeutic outcomes.
eLife Assessment
In this valuable study, the authors performed cell-specific ribosome pulldown to identify gene expression (translatome) differences in the anterior (NT1) vs middle & posterior (NT2-9) cells of the C. elegans intestine, under fed, starved, or refeeding conditions. The data generated will be very helpful to the C. elegans community, and the evidence supporting the conclusions of the study is assessed to be solid. Some methodological caveats remain and are discussed.
eLife Assessment
This study investigated mitochondrial dysfunction and the impairment of the ciliary Sonic Hedgehog signaling in Lowe syndrome (LS), a timely topic given the limited research in this area. The data obtained from patient-derived iPSC neurons and a mouse model are solid. Although the main claims of the study are only partially supported by the current evidence, it provides a useful starting point for future functional studies investigating the link between mitochondrial defects and primary cilia in neural development.
eLife Assessment
This study introduces an artificial-intelligence tool that estimates fat in skull bone marrow from routine brain scans, enabling large studies that were previously impractical. The evidence for the method's repeatability and for identifying genetic links is convincing overall. The authors identify genes, diseases, and other biological characteristics that are linked to skull marrow fat, which represents an important advance. The work will be of most interest to researchers using large imaging biobanks and those studying ageing-related changes across bone, blood, and brain.
eLife Assessment
This work presents valuable new data on the role of D-Serine and how it competes with its stereoisomer L-Serine to influence metabolism. The work presents a variety of convincing experimental data combined with simulated results to investigate the mechanisms focused on one-carbon metabolism, which is relevant for several research fields. However, some claims are only partially supported by data, and critical areas comparing L- vs D-Serine and further mechanistic studies are required. Furthermore, while the work has potential for various fields, the work has only been studied in a limited cell type and context.
eLife Assessment
This useful study investigates how plasticity and homeostatic adaptation can lead to the emergence of synchronization patterns associated with different sleep phases. The ideas are novel and interesting, but the evidence at present remains incomplete. Further work is needed to determine whether the reported states persist for larger system sizes, longer integration times, and how robust the results are to different initial conditions.
eLife Assessment
This important study introduces a non-perturbative pulse-labeling strategy for yeast nuclear pore complexes (NPCs), employing a nanobody-based approach in order to selectively capture Nup84-containing complexes for imaging and biochemical analysis. The data convincingly demonstrate that a short induction period (20 minutes to 1 hour) yields a strong and sustained signal, enabling affinity purification that faithfully recapitulates the endogenous Nup84 interactome. This tool offers a powerful framework for investigating NPC dynamics and associated interactomes through both imaging and biochemical assays.
eLife Assessment
This valuable study presents a comparative analysis of the transcriptomic features underlying C. elegans longevity, providing insights into how different changes in gene expression can promote longevity. The authors present solid evidence with analysis and selected functional validation showing that some long-lived animals share common changes while others appear to use opposing strategies. The datasets and analyses contained within and the user-friendly website developed will be of interest to researchers interested in complicated transcriptomic analyses and/or the biology of aging.
[Editors' note: this paper was reviewed by Review Commons.]
eLife Assessment
This valuable study provides insights into the role of MATR3 in oocyte maturation and folliculogenesis, using conditional knockout mice and in vitro follicle culture systems to show that MATR3 is required for oocyte growth and gene transcription, with downstream effects on follicle development. The evidence is solid, but some minor inadequacies in replication of key methods and independent validation reduce confidence in the conclusions. The work will be of interest to researchers in reproductive biology and fertility.
eLife Assessment
This study reports important and invaluable findings that advance understanding of how attention is distributed between what we look at directly and what lies outside the center of gaze during active visual search. The evidence supporting the main claims is solid, with a large and rich dataset spanning multiple brain areas, although some aspects of the interpretation would benefit from additional controls and clearer separation of attention from eye-movement planning. The work will be of particular interest to researchers studying attention, visual perception, and eye movements behavior.
eLife Assessment
One-carbon tetrahydrofolate metabolism plays a crucial role in producing essential metabolic intermediates. In this valuable study, the authors employ a solid genetics-based approach to demonstrate that three distinct metabolic pathways are essential for synthesising 1C-tetrahydrofolates (1C-THF). Disrupting any of these pathways impairs both growth and virulence.
eLife Assessment
This is a detailed and well-designed simulation study of the utility of replication metrics in animal-to-human study translations in bridging the gap between laboratory discoveries and health practice, a critical consideration in turning laboratory scientific research findings into tangible, real-world applications, to directly help human health. The study approaches are convincing, and the findings are important, as they offer insights into clinical research translations to advance health decision-making.
eLife Assessment
This fundamental study uses simultaneous EEG and fMRI recordings to shed light on the relationship between alpha and gamma oscillations and specific cortical layers. The sophisticated methodology provides compelling evidence for correlations between oscillatory power and the strength and contents of fMRI signals in different cortical layers. This paper will be of interest to neuroscientists studying the role and mechanisms of alpha and gamma oscillations.
eLife Assessment
The report by Liu and colleagues provides a valuable analysis of environmental adaptation across diverse lineages of the grass Phragmites australis differing by their level of ploidy. The analysis reports solid evidence that lineages with distinct levels of ploidy occupy different climate niches. The use in tandem of regional survey and common garden experiment represents a convincing approach to suggest a correlation between ploidy and climate adaptation. This manuscript will be of interest to a broad community of ecological genomicists interested in how structural variation in gene dosage potentially affects the pattern of adaptation.
eLife Assessment
This work presents a software and hardware suite for targeted photostimulation that can be used in vivo. The package is a well-designed and documented hardware/software suite with a comprehensive build guide. This tool will likely promote important neuroscience advances through targeted real-time perturbation of the cerebral cortex. Overall, this manuscript makes a compelling case on how to design and make available power tools for the research community.
eLife Assessment
This important study combines peptide engineering, molecular docking, and functional assays to define the molecular basis of ligand recognition and activation of the human Y4 receptor and to identify three novel small-molecule agonists. The evidence supporting the conclusions is convincing, with complementary experimental and computational approaches providing strong support for the proposed receptor-ligand interactions. While concentration-response analyses of the small-molecule agonists and additional structural or mutagenesis studies would further strengthen the work, these are not essential to support the main conclusions. The work will be of interest to researchers studying GPCR pharmacology, structural biology, and ligand discovery.
eLife Assessment
This study presents a valuable metagenomic analysis of the gut microbiome in sickle cell disease (SCD) patients, revealing associations between bacteriophage, host immunity, and SCD pathophysiology. While these data are interesting and helpful for hypothesis generation, they are deemed incomplete; additional experiments would be needed to test causality and to provide mechanistic insight. Despite these limitations, this work will be of broad interest to researchers studying SCD, immunology, phage biology, and the microbiome, adding to the small but growing literature suggesting a microbial component to SCD.
eLife Assessment
This is an important study that applies a new chromatin profiling technique to the study of cellular responses to low oxygen. The authors provide convincing evidence for distinct kinetic phases of the response and identify many new putative regulators of the response. This work will be of broad interest to those studying low oxygen responses and transcriptional regulation.
eLife Assessment
The manuscript concerns a fundamental and controversial question in Trypanosoma brucei biology and the parasite life cycle, whether or not dividing slender bloodstream forms must transition to growth-arrested stumpy forms before differentiating to the procyclic form in the Tsetse midgut. The authors provide further evidence that slender bloodstream forms can infect Tsetse flies, and that although their differentiation is considerably delayed, they do not become classical stumpy forms during the process. The study is solid in design and execution, and addresses several criticisms made of the authors' earlier work, although discrepancies with results from other laboratories remain.
eLife Assessment
This important study reports the development of the first tankyrase degrader and demonstrates its enhanced ability to inhibit β-catenin signaling compared to conventional tankyrase inhibitors. The evidence supporting the conclusions is comprehensive and convincing, based on rigorous biochemical and cellular analyses. The findings will be of broad interest to researchers studying Wnt signaling, protein degradation, and cancer biology.
eLife Assessment
This manuscript presents openretina, an open-source platform that integrates retinal datasets, model training, benchmarking, and in silico analysis tools within a unified framework. The resource is valuable because it addresses long-standing challenges in reproducibility, accessibility, and cross-study comparison in computational retina research, while providing a foundation for community-driven model development and evaluation. The supporting evidence is solid, with the authors demonstrating a functional and well-documented platform across multiple datasets and species, although a clearer discussion of model interpretability, current performance limitations, and data quality standards would strengthen the resource.
eLife Assessment
In this manuscript, the authors describe a cell-specific mechanism by which glutamate transporters regulate the fidelity with which T-stellate cells in the mouse ventral cochlear nucleus relay information from auditory nerve inputs. The study is supported by solid electrophysiological data. It provides valuable insights into how the rapid binding of glutamate to transporters shapes auditory information processing at specific synapses.
eLife Assessment
This manuscript describes an important development of several variants of optogenetic tools to control endogenous p53 activity. They are based on peptides competing with Mdm2/MdmX for binding to p53, thus releasing p53 from its negative regulators and stabilizing its cellular levels. In principle, the data are convincing but should be complemented by investigations of p53 target genes at endogenous levels (instead of only reporter constructs). The study therefore remains incomplete but will be of interest to scientists working on optogenetics as well as the p53 field.
eLife Assessment
Verma and colleagues interrogate the mechanisms of phagosome maturation arrest during Mycobacterium tuberculosis infection. While cellular events that culminate in this arrest have been largely elucidated, involvement of other organelles, such as mitochondria, has not been highlighted mechanistically. In this valuable study, elements of mitochondrial quality control, such as mitophagy and mitochondrial-derived vesicles involvement, are shown to be paramount in the host-pathogen tussle. The evidence supporting the main conclusions is solid, based on multiple complementary approaches and appropriate controls, although some central mechanistic aspects of the proposed pathway remain only partially resolved.
eLife Assessment
This valuable study provides a cross-species single-cell transcriptomic resource for early female gonadal development in mammals. The data supporting the main conclusion remain incomplete, and experimental validation is needed to strengthen the conclusions. The work will be of interest to reproductive biologists and developmental biologists.
eLife Assessment
The Review Article by Bal and co-workers presents an overview of skeletal muscle physiology, focusing on Sarcoplasmic Reticulum and Mitochondria-Associated Membranes (MAMs) in relation to calcium handling, ROS, and signaling. It provides a foundation based on the current literature but could have gone further by identifying future research directions and potential avenues for therapeutic intervention.
eLife Assessment
This study investigates the cellular mechanisms underlying theta-nested gamma oscillations in the medial entorhinal cortex; the experiments are rigorous, and the analyses and modeling provide potentially useful insights into cell-type-dependent circuit dynamics. However, the evidence supporting several key conclusions remains incomplete. The study is limited by conceptual constraints in the experimental design and a modeling approach that does not fully address underlying physiological mechanisms. Overall, this is a careful study that addresses how distinct neuronal populations in superficial MEC participate in theta-gamma coordination and provides new data linking cell-type-specific activity patterns to oscillatory network structure.
eLife Assessment
This study makes a solid and valuable contribution to elucidating the intricate relationship between mitochondrial calcium and neuronal survival. Well-controlled experiments show that homeostatic mitochondrial calcium correlates with the most resilient neuronal subtypes after optic nerve injury. However, altering mitochondrial calcium levels does not affect neuronal survival as initially predicted by this correlation.
eLife Assessment
This article describes the comprehensive metabolic phenotype of a mouse model of Down Syndrome, together with supporting transcriptomic, metabolomic, and biochemical data. The evidence presented is compelling and highlights several core phenotypes including insulin resistance, dyslipidemia, and tissue signatures indicating inflammatory and cellular stress pathways. Similarities and differences in male and female mice are highlighted. This important study provides essential groundwork for the further genetic dissection of dosage-sensitive genes causing metabolic dysregulation in Down Syndrome.
eLife Assessment
This study presents an important large-scale behavioral and transcriptomic analysis of Drosophila that are heterozygous for putative loss-of-function alleles of homologs of human genes that have been linked to autism spectrum disorders. The authors consider 48 genes as hits from their screen, which show significant behavioral alterations in sleep, basal activity, and/or social behavior, and significant sexual dimorphism. The authors then focus on the domino/SRCAP gene as a candidate regulator of sleep, social behavior, transcriptional programs, and RNA splicing. The work generates a solid dataset and applies quantitative analytical approaches that will be of interest to researchers in the field, yet the evidence presented remains incomplete because issues of genetic background need to be further addressed.
eLife Assessment
In this useful Tools & Resources article, the authors describe a new cryogenic light microscopy design and characterize its temperature and spatial stability. This compelling system avoids the challenges associated with vacuum-based designs, particularly vacuum transfer systems, which are difficult to engineer. A key advantage of the system is that it reduces ice contamination and drift, which are the primary challenges in open cryostat systems.
eLife Assessment
This manuscript describes a valuable study of the mechanism by which acetylation on the histone H3 core domain regulates RNA polymerase II transcription passing through nucleosomes. The authors provide convincing evidence that acetylation influences transcription in a context-specific fashion. Some questions relating to the static nucleosome structures and the polymerase passage remain, but this manuscript will be of considerable interest to researchers in the chromatin and transcription fields.
eLife Assessment
This important study provides a mechanistic view of how antibody affinity maturation can reshape encounter-state landscapes and association pathways, with implications for understanding HIV antibody maturation and vaccine design. The results are solid, supported by a coherent integration of adaptive molecular dynamics, Markov state modeling, SPR kinetics, mutagenesis, and double-mutant cycle analysis, although aspects of the kinetic validation, MSM-state robustness, and causal interpretation would benefit from further support. The work will be of interest to immunologists, structural biologists, and computational biophysicists.
eLife Assessment
Muetter et al. provide an important argument that luminescence is a reliable, high-throughput alternative to colony-forming units (CFU) for super-MIC investigations, particularly when the quantity of interest is biomass. By examining 20 antimicrobials spanning 11 classes, the work shows that discrepancies between CFU and luminescence are often biological (filamentation, Viable But Not Culturable). The work provides a convincing view of how these three common measurements (luminescence, optical density, and CFU) relate to one another across a range of drug treatments, although testing on clinical isolates could be of further benefit.
eLife Assessment
This valuable study introduces MULTI i<sup>2</sup>, a robust and high-throughput method to measure Plasmodium falciparum viability in the presence of drugs. This new assay offers significant time savings over the traditional Parasite Reduction Rate (PRR) assay and should enable faster screening of drug combinations, which is urgently needed in the field. The assay is well validated, with convincing data showing it can reproduce known drug interactions and identify new interaction patterns.
eLife Assessment
This important study combines anatomical tracing, tissue clearing, and functional manipulations to demonstrate lateralized brainstem control of hepatic glucose metabolism and identify a site of sympathetic nerve crossover supplying the liver. The evidence supporting the anatomical organization of hepatic sympathetic innervation is compelling, and the functional studies provide solid support for a role of asymmetric sympathetic outflow in regulating glucose homeostasis. While some uncertainty remains regarding the contribution of sensory innervation and the extent to which these findings generalize beyond mice, the work provides an invaluable advance in understanding neural regulation of liver metabolism.
eLife Assessment
This valuable study demonstrates that self-motion strongly affects neural responses to visual stimuli, comparing humans moving through a virtual environment to passive viewing. The evidence for visuomotor mismatch responses is solid, although the interpretation in terms of prediction remains somewhat preliminary. This study bridges human and rodent studies on the role of prediction in sensory processing, and is therefore expected to be of interest to a large community of neuroscientists.
eLife Assessment
This study presents a key finding: self-generated mechanical stresses enable collective protocell proliferation without dedicated division machinery, offering insight into primitive life's population growth. While quantitative imaging, membrane tension measurements, and computational modeling support the mechanism, establishing causal links between deformation and division and testing sensitivity assumptions would strengthen the work. Overall, the work reports important findings, and although the evidence in support of the conclusions is largely solid, some incomplete elements need to be addressed.
eLife Assessment
This important study combines experimental evidence with computational modeling to suggest that neurons in the frontal eye field form two overlapping topographical maps, one for visual inputs and the other for eye movement directions. The experiments leverage the smooth cortex of the marmoset to provide solid evidence that two maps exist at different scales. The modelling work provides a potential mechanistic insight into how these patterns may be used for flexible visuomotor transformations.
eLife Assessment
In this valuable study, Bhojappa et al. investigate the function of four septin-associated kinases (Elm1p, Gin4p, Hsl1p and Kcc4p) in controlling septin ring stability, actomyosin ring organization and constriction, and cytokinesis in budding yeast. The evidence supporting the conclusions is convincing. The results are a meaningful addition to previously published work and provide a clearer picture of a complex mechanism involving proteins of partially redundant functions.
eLife Assessment
This useful study provides new insights into the liver-stage antigen LSA3, its export to erythrocytes, and its role in liver-stage development. While the functional importance of LSA3 is well demonstrated, the data underlying the conclusions regarding antibody specificity, liver-stage localization, and phenotype remain incomplete. A key strength of the study is the use of mosquito and humanized mouse models to access life-cycle stages that are rarely studied in most laboratories.
eLife Assessment
This study offers an important set of literature-based parameter ranges for calibrating cardiac electromechanical models. The key scientific claims are largely supported by convincing evidence and carefully-documented methodologies, but a few specific issues remain only partially supported, in particular relating to the locking-free formulation, reporting of adequate details regarding the electrophysiological model (Eikonal approach), and the fact that physiological accuracy is predominantly achieved in a single chamber (the LV).
eLife Assessment
The study presents important findings from a very rich EEG-fMRI dataset including 107 participants, which was collected during nocturnal naps. Using overall solid methods, the authors link activity in memory related brain regions (e.g., hippocampus, thalamus, and medial prefrontal cortex), as well as their functional connectivity, to the occurrence of canonical sleep rhythms (spindles and slow oscillations) during non-rapid eye movement (NREM) sleep. This work will be of broad interest to researchers studying sleep, memory, and related domains.
eLife Assessment
By mining the Logan assemblage of the Sequence Read Archive to reveal substantial papillomavirus diversity, this valuable study establishes a framework for integrating viral discovery with host, geographic, and ecological metadata. The evidence for identifying novel papillomavirus sequences is convincing, supported by large-scale sequence searches, established L1-based typing criteria, phylogenetic analyses, protein annotation, and structural comparisons. The broader host-association and ecological conclusions are more tenuous due to heterogeneous public metadata and uneven sampling, and would benefit from clearer discussion of potential biases, contamination, endogenous viral elements, and alternative explanations. The work should be of interest to a broad range of colleagues in the areas of microbiome research, virology, and viral evolution.
eLife Assessment
This valuable study reports that ALDH-abundant cells exhibit stem cell properties and may play a key role in endometrial epithelial development in mice. The data support the main conclusion and are convincing. This work will be of great interest to reproductive biologists and biomedical researchers working on women's reproductive health.
eLife Assessment
The authors use solid high resolution microscopy techniques to present a model in which SARS-CoV-2 attachment and endocytosis are mediated by heparan sulfate, whereas ACE2 only functions downstream of these early processes. These findings serve as a potentially valuable starting point to examine SARS-CoV-2 entry models that challenge current paradigms. However, examination of the model in a clean heparan sulfate deficient background and in the context of TMPRSS2-dependent plasma membrane fusion are lacking. Thus, the broader impact remains uncertain in the absence of additional controls and orthogonal approaches.
eLife Assessment
This important study investigates the mechanisms by which Mycobacterium tuberculosis suppresses protective Th17 differentiation during infection. Using ESX-1- and PDIM-deficient mutants of M. tuberculosis, which lack functional eccC1 and fadD28 respectively, the authors demonstrate that these virulence factors actively restrict IL-17 responses via a T-bet-dependent pathway, independent of overall bacterial attenuation or infection duration. While the precise molecular interactions by which ESX-1 and PDIM modulate Th17 differentiation warrant further elucidation, the experiments are rigorously designed, the findings are clearly presented, and the evidence is solid for a specific role for these factors in limiting protective IL-17 immunity in M. tuberculosis infection.
eLife Assessment
This useful study reports findings that support the use of the Open Field Test in Drosophila as a model to study "emotion-like states", which are behavioral responses to several stressful or aversive treatments, and resilience upon their subsequent removal. Behavioral data, by employing established stress-causing treatments and genetic manipulations, are solid. The main advance of this work over previous Drosophila work using a similar experimental setup is systematic analysis of various stressors.
eLife Assessment
This important study addresses a timely issue at the intersection of mitochondrial and telomere biology by focusing on the relationship between naturally occurring variants in the mitochondrial genome and telomere length. This work thereby provides a conceptual and experimental framework for investigating communication between mitochondria and telomeres. Using an innovative transmitochondrial cybrid approach, the authors provide evidence that mitochondrial DNA variants influence telomere maintenance through effects on mitochondrial function, reactive oxygen species, and NAD⁺-dependent repair processes. The evidence supporting the central conclusion that mitochondrial genotype influences telomere-associated phenotypes is convincing and is strengthened by the use of complementary functional and rescue experiments. However, some of the mechanistic interpretations and broader conclusions regarding telomere length inheritance in humans would benefit from additional donors and longitudinal analyses following cybrid generation, or more cautious framing.
eLife Assessment
This fundamental manuscript describes a key role for the integrated stress response-regulated transcription factor CHOP in regulating liver biology in response to endoplasmic reticulum stress through both the downregulation of transcription factors involved in regulating hepatic identity and altering the capacity for integrated stress response and unfolded protein response signaling to induce protective signaling. The data supporting this model is convincing, but including some additional discussion on the mechanism and importance of the work in the context of the published literature would be helpful to better define the complex importance of CHOP signaling. This work will be of interest to a wide range of biologists interested in liver biology, stress-responsive signaling, and ER stress.
eLife Assessment
This important study combines behavioural analysis, voltage imaging and electrophysiology to advance our understanding of muscle coordination at the cell-to-cell level, in Caenorhabditis elegans. The evidence supporting the conclusions is convincing; however, the use of correlation in some aspects of data interpretation is a relative weakness. The technically sophisticated optogenetic voltage clamp approach introduced here can be applied to other small, transparent animals, making these findings of broad interest to researchers studying electrical coupling between cells or utilising optical electrophysiology techniques.
eLife Assessment
This important study describes how selective lesions of key cortical and subcortical motor areas affect reaching actions in macaque monkeys. The results will be of interest to both basic and clinical researchers studying the neural control of movement. Kinematic analysis of movement quality is solid but could be improved by considering other metrics, especially those that relate to grasping. Evidence for the general claims related to the role of specific motor areas is incomplete because the lesions did not fully eliminate any single area while simultaneously involving neighbouring areas.
eLife Assessment
The framework of this potentially important study – with the integration of multiple levels of analysis, glymphatic MRI, transcriptomics, functional MRI, and public amyloid maps, in one framework – is clever. The assertion that regional amyloid vulnerability may depend not just on neural activity alone, but on whether clearance is appropriately matched to activity, is an interesting and novel concept. However, the chosen approach to imaging glymphatic clearance relies on indirect inferences from a small subgroup. In its current form, the main conclusions of this study are therefore incompletely supported.
eLife Assessment
The OpenApePose dataset presented in this manuscript represents an important contribution to the field of primate behaviour and computer-vision science with methodological applications that are sure to be applicable for a wide variety of taxa. The analysis supporting the utility of this database is solid and compelling but would benefit from some additional clarity, particularly with regards to the annotation of landmarks, model parameters and division of the dataset for training, validation and testing.
eLife Assessment
This study addresses an important question in aging biology by combining metabolomics, transcriptomics, molecular genetics, and functional analyses to examine how cytosolic acetyl-CoA metabolism influences late-life fitness in replicatively aging yeast. The evidence supporting the roles of AMPK activation, mitochondrial acetyl-CoA utilization, and fatty acid synthesis in preserving fitness during aging is convincing overall, and the engineered A2A strain provides an elegant demonstration that coordinated modulation of distinct acetyl-CoA metabolic branches can increase the proportion of aged cells with a low-senescence phenotype. The study provides significant insight into mechanisms that allow aging cells to maintain fitness without extending replicative lifespan.
eLife Assessment
This study offers important insight into the pathogenic basis of intragenic frameshift deletions in the carboxy-terminal domain of MECP2, which account for some Rett syndrome cases, yet similar variants also appear in unaffected individuals. Using base editing and mouse models, the authors present convincing evidence supporting the pathogenicity of select deletion variants, with potential implications for therapeutic development.
eLife Assessment
This valuable study presents a comprehensive exploration of c-di-GMP-associated protein interaction networks in Pseudomonas fluorescens, with a particular focus on biofilm-related phenotypes. The evidence is convincing, supported by a genome-wide yeast two-hybrid screen, phenotypic analyses, and experimental validation. The work identifies multiple interaction hubs and provides a resource that will be of use to the biofilm and c-di-GMP communities, while additional mechanistic exploration would further enhance its impact by clarifying the biological roles of many of the identified interactions.
eLife Assessment
This important study conducted by Hall and colleagues advances our understanding of host-pathogen co-evolution by providing an elegant multi-omic comparative framework that uncovers a profound, pathogen-directed epigenomic reprogramming of bovine alveolar macrophages uniquely driven by host-adapted Mycobacterium bovis. Convincing evidence supports these findings and draws on robust, multi-layered high-throughput sequencing data integrated with large-scale cattle GWAS metadata to prioritize actionable genetic variants linked to disease susceptibility and to highlight key immune response genes/pathways upregulated in response to infection and pathogen-specific host adaptation mechanisms.
eLife Assessment
This important study investigates how verbal and nonverbal working-memory processing is distributed across large-scale functional networks in the human brain using precision fMRI. By leveraging extensive within-subject data and individualized network mapping, the authors provide solid evidence that hemispheric specialization for verbal versus nonverbal information extends across multiple association networks and is reproducible across independent datasets. The use of state-of-the-art precision neuroimaging approaches reveals fine-grained laterality patterns that are likely obscured in conventional group analyses.
eLife Assessment
Murrell et al. describe a high-throughput method, the Feeding Experimentation Device (FED3), to study food foraging strategies in mice. The authors provide solid evidence about key sex differences in foraging strategies, specifically the finding of greater male win-stay behavior. Further consideration of how sex differences could be uniquely influenced by FED3 testing conditions (e.g., single-housing, hormones) and task demands (e.g., 100-0 vs. 80-20) would be helpful. Given this open source FED3 platform, the authors provide valuable findings that have utility to the field of behavioral neuroscience, specifically to those interested in studying reward-related behavior.
eLife Assessment
This study sets out to show that the directionality of bacterial transport in confined environments is affected by a salt gradient. Using Pseudomonas putida in microfluidics devices, the authors hypothesize that salt-induced diffusiophoresis acts as a steering mechanism to guide microbial movement. However, the evidence to support this hypothesis is incomplete, because the underlying reorientation process is not directly demonstrated, and the necessary controls to rule out alternative hypotheses are not presented.
eLife Assessment
This important manuscript presents a way to understand allostery and allostery-inspired mechanical systems. It presents a mechanochemical model of an ATPase-like molecular machine in which geometric constraints and mechanically coupled linkages generate negative allostery, yielding a large stochastic reaction network that captures productive and futile cycling behavior. The work presents an interesting framework for bridging concepts from molecular motors and allostery. It provides a compelling, intuitive physical mechanism for mechanochemical transduction and reveals nontrivial tradeoffs that emerge from geometry-induced constraints.
eLife Assessment
This study presents a useful application of trans-omic network analyses to existing human brain datasets, generating systems-level insights into metabolic dysregulation in Alzheimer's disease. Overall, the authors' analytical choices are solid, with appropriate use of existing data and methods, and with many of their results confirming previous findings. However, some of the authors' key claims, related to previously unknown details of regulatory relationships, are only partially supported due to limitations in dataset cell-type resolution and network robustness, as well as a lack of functional validation. This work will be of interest to cellular or systems neurobiologists studying Alzheimer's disease and could serve as a helpful starting point for future work.
[Editors' note: this paper was reviewed by Review Commons.]
eLife Assessment
The authors propose a pipeline using large language models (LLMs) to benchmark experimentally well validated computational models of signaling networks. The findings are important, with available methods that guide testing future models and find new molecular interactions. Furthermore, the work shows how general-purpose LLMs can generate up to 91% of reactions of a bacterial metabolic network. The support is convincing and offers a number of performance metrics.
eLife Assessment
The study presents important findings revealing previously unresolved conformational dynamics of the heterodimeric type IV ABC transporter TmrAB using single-molecule FRET. The evidence presented is convincing, integrating careful experimental design with computational approaches to uncover states that are typically masked and difficult to detect. The work will be of interest to scientists studying the molecular mechanisms of primary active transport processes.
eLife Assessment
This important study addresses a classic debate in visual processing, using a strong method applied to an impressive dataset obtained from a rare clinical population to evaluate hierarchical models of visual object perception. The paper provides compelling evidence that the hierarchical model is only partly supported: as expected, neural responses in ventral visual cortex show increased representational selectivity for faces along the posterior-anterior axes, but the onsets of the signals do not show a temporal hierarchy, indicating more parallel processing.
eLife Assessment
This important study provides convincing evidence for our understanding of HIV transmission dynamics by age and sex in Zambia during the PopART trial. By combining phylogenetic and individual-based mathematical modelling (IBM), it adds depth to the epidemiological literature and may inform more strategic allocation of HIV prevention resources in sub-Saharan Africa. The authors employ two complementary and well-established methodologies (phylogenetics and IBM), and this dual approach is a notable strength.
eLife Assessment
This valuable study describes PXGS, a poly-transgene expression system that exploits the mutually exclusive splicing of Dscam variable exon 4 to enable conditional, simultaneous expression of up to 12 transgenes in Drosophila, addressing a longstanding limitation in which conditional co-expression has been restricted to a handful of genes. The approach is conceptually elegant and technically accessible, with potential applications spanning neuroscience, synthetic biology, and biomanufacturing across arthropod species. The evidence that Dscam exon 4 splicing is preserved in a UAS vector and that individual alternates can be replaced with functional transgenes is solid, and the in vivo axonal re-wiring application provides a convincing proof of principle. Quantitative characterization of expression levels, a direct demonstration of expression across all twelve positions, and additional imaging controls would further substantiate the system's utility and scope.
eLife Assessment
This study presents a valuable finding on linking the frequency of neural activity to cortical depths of blood flow in a naturalistic setting of participants listening to music. The presentation of evidence in the version of the original submission is incomplete, as further clarifications in methods and results, as well as performing additional analyses, would strengthen the study. The work will be of interest to cognitive neuroscientists working on multimodal recordings, auditory perception and music.
eLife Assessment
This study provides a useful anatomical resource by mapping the expression of four putative chemoreceptors in spinal cerebrospinal fluid-contacting neurons (CSF-cNs) of larval zebrafish. These descriptive findings offer an interesting entry point to explore how the nervous system senses signals within the spinal fluid microenvironment. The evidence supporting the spatial expression patterns of these receptors is convincing, utilizing high-resolution hybridization chain reaction (HCR) to validate previous transcriptomic data. However, the evidence remains incomplete regarding the actual functional roles of these receptors, as the study lacks protein-level validation, evidence of ligand availability in the CSF, or functional assays to demonstrate active chemoreception.
eLife Assessment
This work provides a reassessment of VBIT-4, a compound previously proposed to inhibit oligomerization of the crucial protein known as the mitochondrial voltage-dependent anion channel. Combining complementary experimental approaches with molecular dynamics simulations, the authors provide compelling evidence that VBIT-4 primarily disrupts lipid membranes and induces channel-independent cytotoxicity. The study has important implications for interpreting previous work using VBIT-4 as a probe of channel function and highlights the need to consider membrane-disruptive effects when evaluating drug mechanisms.
eLife Assessment
This valuable study investigates the mechanisms underlying inter-item biases in visual working memory. By experimentally manipulating the relative noise levels of target and non-target items, the authors report bias patterns that are broadly consistent with predictions of their previously proposed normative demixing theory. However, the supporting evidence remains incomplete, as the manuscript lacks a sufficient description of the underlying theory, key assumptions, and a quantitative link between the model and behavioral data. The manuscript would be substantially strengthened by clearer exposition and stronger tests, including analyses of the full error distributions and comparisons with alternative models, which would increase its potential interest to the cognitive neuroscience and computational cognitive science communities.
eLife Assessment
This useful study reports on lifespan extension in C. elegans males that carry a mutation in a gene for an insulin receptor; while the observations are striking, the strength of evidence is currently incomplete. The central claim of male-specificity is undermined by the absence of direct hermaphrodite healthspan comparisons, and the reliance on a single mutant allele leaves open the possibility that background mutations, rather than daf-2 loss-of-function, drive the phenotype. Methodological details critical for reproducibility are also lacking, particularly regarding male housing density, censoring of plate-leaving animals, and the adequacy of replication for the key epistasis experiment. The work could be substantially strengthened by a targeted set of additional experiments and fuller engagement with the existing literature on sex-specific aging in C. elegans.
eLife Assessment
This valuable study provides novel evidence that congenital aphantasia is associated with structural differences in frontotemporal and cingulate systems, with relative sparing of early visual regions and major visual pathways. The multimodal structural imaging approach is carefully implemented and will be of interest to researchers studying mental imagery and aphantasia. However, the strength of evidence is incomplete because the data cannot adjudicate between alternative cognitive interpretations, and the multiple discovery streams make the findings better viewed as key exploratory evidence, rather than as establishing a definitive structural phenotype of aphantasia.
eLife Assessment
This valuable study identifies Gcn5 as a regulator of blood cell development in the Drosophila lymph gland, with links to autophagy and nutrient-sensing mTORC1 signalling. The evidence is solid that altering Gcn5, autophagy genes and mTORC1 activity perturbs blood cell homeostasis, and the revised manuscript adds helpful genetic and quantitative analyses. However, the evidence for a clean linear Gcn5-mTORC1-TFEB/autophagy pathway is insufficient, because several cell-type-specific phenotypes remain difficult to reconcile and the pathway logic relies on different genetic tools, cell populations and pharmacological perturbations.
eLife Assessment
This study uses convincing modeling methods and analyses of rich behavioral datasets to investigate the role of attention in value-based decision making; for instance, as when choosing between two snacks. The results are important, as they challenge existing theories that assume that paying attention to an available option biases the eventual choice toward that option. The results suggest that the correlation between attention and decision-making is formed largely after rather than before the (internal) choice process has terminated, a finding that offers an intuitively appealing rethinking of how attention and decision-making processes interact during value-based choices.
eLife Assessment
This important study measures single-unit activity in area MT of awake-behaving monkeys to test the idea that sensory adaptation contributes to flexible evidence accumulation during decision making. The authors provide compelling evidence that adaptation to different temporal contexts shapes both perceptual judgements and neural responses. Although the precise computational mechanisms underlying these effects remain uncertain, the results support the conclusion that recent sensory history influences the temporal dynamics of decision formation. This work will be of interest to researchers studying visual perception, sensory adaptation, and decision making.
eLife Assessment
By investigating spine nanostructure and dynamics across multiple genetic mouse models for neurodevelopmental disorders, this important study has the potential to uncover convergent or divergent synaptic phenotypes that may be specifically associated with autism versus schizophrenia risk. The imaging and overall breadth of the methods are convincing. The purely in vitro nature of the study slightly limits the generalisability of the findings, though these limitations are acknowledged and discussed in the manuscript.
eLife Assessment
This useful study combines experiments and mathematical modeling to show that antibiotic protection provided by resistant cells can extend across both surface-associated and freely growing bacterial populations. Notably, they show that treatment efficacy depends on population composition and density. The evidence supporting the main conclusions is incomplete, primarily because the biofilm context is not adequately characterized and demonstrated, raising the concern that it might represent only an aggregate of cells on the surface (rather than a biofilm) under the studied experimental conditions.
eLife Assessment
This important study provides the first in vivo evidence that nonsense-mediated mRNA decay (NMD) in mature astrocytes regulates astrocyte function, synaptic plasticity, and anxiety-related behavior. Using a broad range of approaches, the authors show that conditional deletion of Upf2 alters astrocyte morphology and calcium signaling while impairing synaptic transmission and plasticity, providing solid support for the central conclusion that astrocytic NMD influences neural circuit function. Some key mechanistic claims remain incompletely supported, including whether phenotypes reflect astrocyte remodeling versus loss, the interpretation of synaptic engulfment data, the link between NMD targets and calcium signaling, and the extent to which calcium dysregulation explains the observed synaptic and behavioral effects.
eLife Assessment
This is a valuable paper looking at nanoscale organization of the membrane associated periodic cytoskeleton in mouse sciatic nerve axons. Despite previous studies, the precise organisation of the structure remains unclear, especially in vivo, and this manuscript significantly adds to this knowledge with solid data. An unexpected observation is the presence of discrete nanoscale clusters, regularly distributed around sections of axons. However, the paper misses a description of these clusters along the longitudinal axis of the axons.
eLife Assessment
This valuable study shows the impact of the metabolic state of bacteria on phage infection. The experimental results, based on various phages infecting E. coli, are convincing and consistent with a two-step adsorption mathematical model. This study should be of interest to the communities working on cell metabolism and on host-pathogen interactions.
eLife Assessment
This study makes a valuable contribution by broadening the range of eukaryotic model systems and establishing Blastocystis, the most prevalent microeukaryote in the human gut, tractable for reverse-genetics investigations. The presented imaging data are convincing and informative, although confirmation by molecular methods would further strengthen the study. The work should interest readers studying host-microbe interactions in the human gut, as well as those developing new systems for eukaryotic research.
eLife Assessment
This important study explores whether complex structures that are lost during evolution can re-evolve, which is a long-standing debate in evolutionary and developmental biology. The authors demonstrate that re-evolution can occur if the gene regulatory network that underlies the development of complex traits is maintained. The evidence supporting its conclusions is convincing and the work will be of interest to those studying the evolution and development of complex traits.
eLife Assessment
Building on earlier studies, this manuscript reports a role for pol kappa in cisplatin resistance in the very specific scenarios of head and neck squamous cell carcinoma, providing evidence that the PIP box of Pol kappa is critical for cisplatin resistance in these cells. The findings are of a highly focused relevance and will be useful in the field, but the conclusions are limited to very specific cancer cells. Conclusions cannot be generalized to all cisplatin resistance mechanisms and cell types and are based on incomplete evidence that presents uncertainties and discrepancies that need to be resolved.
eLife Assessment
This is a potentially important study comparing LTP mechanisms between primates and rodents. The experimental methods have some possible confounds, and the power (replicates) and design of the statistical methods could be strengthened, hence the support for the central claims of species differences is currently incomplete.
eLife Assessment
This important study assessed the replicability of a selection of lab-based biomedical experiments in papers published by authors based in Brazil. The study adds a unique perspective to the literature on replication, and provides rich data on the approach taken, the outcomes, and the challenges involved in conducting large-scale crowd-sourced research. The evidence supporting the claims is convincing, but there is scope for clarifying the presentation of the results and extending the discussion section.
eLife Assessment
This valuable paper uses a mathematical model applied to a dataset of E coli / ESBL carriage and transmission to infer drivers of drug resistance in France. The strength of support for the study findings is incomplete. While the research question is of importance, and the mathematical model has structural and methodological integrity, numerous issues are noted: insufficient description of the data, lack of included equations and code, definitions of antibiotic use that are not complete, low sensitivity of assays for carriage, technical issues with statistical prior selection and parameter identification, and application of non-regional ECDC surveillance data to France.
eLife Assessment
This study presents an important finding regarding the effect of Yoda molecules on PIEZO2 function, challenging the assumption that they selectively activate PIEZO1. The evidence supporting this claim is solid, but several methodological and conceptual issues need to be addressed. Overall, this work will be of broad interest to researchers working with PIEZO channels across various biological scales.
eLife Assessment
In this manuscript, the authors describe a new member of the KCNE auxiliary subunits of potassium channels from a lamprey. This new subunit represents an early evolutionary member which confers new properties when expressed along with KCNQ channels. The authors present convincing evidence from several experimental approaches. The contents of this manuscript are important and should be relevant to understanding both the mechanism of modulation of KCNQ channels by KCNE subunits and the evolutionary history of these subunits, which this manuscript now extends to the divergence of early vertebrates.
eLife Assessment
In this important study, Boudjema et al. use cell culture models and high quality advanced microscopic imaging to provide detailed analyses of the cellular processes underlying centriole amplification, apical migration, and assembly of hundreds of motile cilia in multi-ciliated cells. The authors present convincing evidence showing that in these cells all the molecular and cellular steps controlling centriole biogenesis that in cycling cells extend over almost two cell cycles, occur within a single cell cycle variant. This work provides a better understanding of the regulation and order of these processes and is of interest to all cell biologists and in particular researchers studying centrioles and cilia.
eLife Assessment
This manuscript provides valuable insight into how genome organization changes as cells progress through the cell cycle after mitotic exit, identifying two sharp genome remodeling events at G1-S and to a lesser extent, at S-G2 transitions. The conclusions are supported by solid, rigorous data, including sequencing and orthogonal imaging data. The use of sorted unsynchronized cells rather than cells treated with drugs is a particular strength.
eLife Assessment
This important study identifies PRRT2 as an auxiliary regulator of Nav channel slow inactivation in vitro and in vivo, proposing that PRRT2 facilitates entry into, and delays recovery from, the slow-inactivated state. The revised manuscript has been substantially strengthened, providing compelling evidence that PRRT2 is relevant to normal brain physiology and disease pathophysiology, providing a mechanistic link between PRRT2 mutations and episodic neurological phenotypes. Overall, this study will be of interest to ion channel biophysicists and neurophysiologists, particularly those studying channelopathies.
eLife Assessment
This important study investigates how surface stickiness shapes whisker mechanics and peripheral neural responses during active touch. The biomechanical evidence that surface stickiness alters whisker mechanics and stick-slip dynamics is compelling, supported by a large and high-quality 3D dataset, while the electrophysiological evidence is solid but limited by a small sample size and insufficient validation of the sticky stimuli. The work will be of broad interest to sensory neuroscientists studying active touch.
eLife Assessment
This study presents a useful compendium of triangulated single-cell eQTLs, Mendelian randomisation and colocalization of genetic signals in prostate cancer datasets. Biological interpretation in the context of the aging prostate gland, the tumour microenvironment and immune cell specificity is incomplete, so this study is a starting point for further study, and would require validation of the resulting putative causal genes.
eLife Assessment
This useful study explores how macrophage cell-cycle state may influence endocytosis, Mycobacterium tuberculosis uptake, and the intracellular stress experienced by bacteria. While the question is interesting and the experimental approach has promise, the evidence for the central claim that endocytic capacity is specifically regulated by cell-cycle stage is incomplete. The main concern is that fluorescence-based sorting and total-fluorescence measurements likely covary with cell size, so the reported phenotypes could reflect biomass accumulation or other cell-cycle-associated changes rather than endocytic capacity as the causal determinant. As a result, whilst the study raises a hypothesis that is of importance, additional controls are required before the proposed mechanism can be considered well supported.
eLife Assessment
This important submission from Ambler and colleagues brings new insights into how torpor conditions may confer resilience in cases of cardioprotection. It has novelty, which can be enhanced by additional in vivo support. The study is backed by solid evidence, and represents a unique interoceptive mechanism of interest.
eLife Assessment
This study addresses a recent discovery by others that electroconvulsive therapy (ECT) generates seizure activity and spreading depolarization (SD), reflected in large increases in calcium, which can be followed by imaging calcium fluctuations in neurons. This work is useful. However, the evidence to show that SD, rather than seizures, confers the neuroplastic and other therapeutic effects of ECT is incomplete.
eLife Assessment
This important study establishes a robust live-imaging toolkit to characterize excitatory and inhibitory synaptic dynamics during neuronal development, advancing our mechanistic understanding of synaptic homeostasis and neural circuit maturation. The core findings clarify how stable E/I balance is maintained despite persistent synaptic turnover, with broad implications for developmental neurobiology and neurodevelopmental disorders. The methodology and quantitative data are convincing and well validated, and this work represents a significant advance that will be of significant interest to researchers in synaptic biology, cell imaging and neuroscience.
eLife Assessment
This important study shows that regions of the human auditory cortex that respond strongly to human voices are also sensitive to vocalizations from closely related primate species. The evidence is convincing and methodologically strong. The work offers significant insight into the evolutionary continuity of voice processing and would be of interest to researchers studying auditory processing and evolutionary neuroscience in general.
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 potentially valuable study aims to investigate neural correlates of spatial attention in whisker somatosensory cortex (S1) in mice, finding increased sensory-evoked spiking when the mice appear to be attending to the contralateral whiskers. Although some of the results appear to be robust despite relatively small effect sizes, overall the findings are incompletely supported, because attentional modulation is insufficiently distinguished from learning of stimulus-response contingencies, and because the analyses do not adequately consider orofacial movements that may contribute key confounds.
eLife Assessment
This valuable study compares hippocampal-cortical functional connectivity to various other brain measures and examines their development across youth. It uses sophisticated analyses replicated in multiple datasets, but provides incomplete evidence to support the primary claim that hippocampal-cortical connectivity relates to cognitive maturation. The manuscript would benefit from a more nuanced consideration of the biological basis of some of the derived imaging measures and the limitations of the cross-sectional design. This work will be of interest to neuroimaging specialists and cognitive neuroscientists.
eLife Assessment
This valuable manuscript investigates how Drosophila larvae make foraging decisions in patchy environments with controlled resource density and valence; using movement tracking in bounded arenas, the authors show that larvae's patch residence time (PRT) differs depending on resource type, environmental context, and prior experience. A drift-diffusion model is used to describe patch-leaving behaviour, suggesting that an integration process may underlie stay-leave decisions during foraging. The strength of the evidence is mostly solid, but the interpretation and use of PRT needs further investigation, as PRT could be a direct effect of resource concentration on locomotion. Explicit reports of PRT statistical tests are needed for rigorous interpretation.
eLife Assessment
This useful study investigates noise-robust and energy-efficient circuit mechanisms for working memory by optimizing connectivity and reports that the resulting networks exhibit rotational dynamics and better match aspects of PFC population recording. However, the supporting evidence remains incomplete, given the restricted linear, task-specific training and analysis, and limited comparisons with other prominent models. The manuscript would be strengthened by extending the analysis to nonlinear dynamics, providing more rigorous comparisons with alternative models, and establishing a stronger link to prior theoretical and experimental work.
eLife Assessment
This important study provides a detailed characterization of individual sarcomeres' contractility and of their synchrony in spontaneously beating cardiomyocytes derived from human induced pluripotent stem cells. The combination of high-resolution tracking, statistical analysis and mesoscopic modeling leads to compelling evidence that sarcomeres operate as dynamically unstable units, leading to stochastic heterogeneities in their contraction-elongation cycles depending on substrate stiffness. The work will be relevant to scientists interested in muscle biophysics, nonlinear dynamics and synchronization phenomena in biological systems.
eLife Assessment
The authors developed a new Agbl5 KO allele, extending the deletion to the N-terminus of CCP5 to explore its function in mouse ependymal cells and trachea. They show that the KO mice exhibit severe hydrocephalus due to mislocated basal bodies and impaired ciliary beating. The findings are valuable with implications in the subfield of cell biology. The evidence is solid in that the methods, data and analyses largely support the claims with only a few remaining weaknesses.
eLife Assessment
This paper addresses a valuable research question on the modest heritability of the brain's response to movie watching, and how heritability varies under different parameters such as regional spatial hyperalignment and BOLD frequency bands. The topic of this paper is of interest to fMRI methodological experts, and potentially to a broader cognitive neuroscience audience, and those with an interest in understanding the heritable sources of individual differences in brain function. Although some of the conclusions could be strengthened by future cross validation studies in independent and larger family-based samples, and through complementary twin/family and SNP-based models, taken altogether, the analyses and results provide convincing evidence for the overall conclusions.
eLife Assessment
This study presents important findings by identifying small molecules that can stabilize and refold missense-mutated VHL tumor suppressor protein, offering a potential therapeutic approach for clear cell renal cell carcinoma. The computational design approach is well-executed, but the evidence is incomplete due to insufficient demonstration that HIF2 downregulation occurs through on-target VHL rescue rather than off-target effects. Additional experiments with appropriate controls are needed to establish the specificity of the mechanism.
eLife Assessment
This important study advances our understanding of the biomechanics of seed processing in birds by providing a comprehensive 3D kinematic analysis of coordinated bill and tongue movements across two species with contrasting biting forces. The evidence is convincing, combining high-speed XROMM with Bayesian statistical modeling in a rigorous and technically innovative framework that advances the understanding of avian feeding kinematics. Strengthening the statistical validation of qualitative claims, particularly for tongue-seed velocity relationships, and improving the accessibility of the probabilistic modeling framework would further solidify the conclusions.
eLife Assessment
This valuable study investigates the neural basis for recovery of complex wheel running behaviour following a unilateral spinal cord injury in mice. By combining behavioural analyses, whole-brain mapping, and tracing techniques, the authors provide incomplete evidence that new cortico-medullary connections can drive effective motor recovery. The paper could be strengthened with manipulations to establish causality, a more fine-grained analysis of the behaviour, and some reorganisation of how the data are presented and discussed.
eLife Assessment
The worldwide decline in the health of coral reefs is well documented, and overgrowth by microbial consortia can be a contributing factor. Kelman and colleagues used metagenomic analysis to interrogate potential changes in phage-associated genes predicted to be involved in central carbon metabolism. The study addresses the hypothesis that metabolic genes associated with carbon metabolism that are encoded by viruses reflect the health of the corals. The study contributes a valuable perspective on the potential role of phages in coral health, although limitations of the data and analyses offer an exploratory examination rather than a definitive result. Overall, the evidence supporting the major findings is incomplete, in part because the conceptual model relies on qualitative assumptions rather than empirical data.
eLife Assessment
This Review Article puts forth a normative theory for the grid cell representations found in the entorhinal cortex. It discusses a range of theoretical models and experimental findings, organizing them around a proposed framework in which grid cells are interpreted as biologically constrained, high-fidelity codes for path integration. This framing can be potentially interesting both for readers seeking a conceptual entry point into the grid cell literature and for those more generally interested in the promises and limitations of normative theories in neuroscience. Some logical gaps and points requiring conceptual or technical clarification were nonetheless identified. Moreover, the empirical support for the path-integration account is not yet as definitive as the manuscript's framing sometimes suggests. The review would thus be strengthened by clearer justification of key arguments and fuller discussion of biological complexities, model limitations, and competing interpretations. Some stylistic choices in how arguments and literature are sometimes rhetorically framed may lessen the review's appeal for key segments of its intended audience.
eLife Assessment
This study presents a valuable and well-documented computational pipeline for the scalable analysis and spike sorting of large extracellular electrophysiology datasets, with particular relevance for high-density recordings such as Neuropixels. The authors demonstrate the pipeline's utility for benchmarking spike sorter performance and evaluating the effects of data compression, supported by thorough testing, clear figures, and openly available code. The workflow is reproducible, portable, and practical, providing concrete guidance on computational cost and runtime. Overall, the evidence supporting the pipeline's performance and output quality is compelling, and this work will be of broad interest to the systems neuroscience community.
eLife Assessment
The authors describe a valuable finding that the Streptococcus pyogenes secreted protease SpeB is expressed in response to protease activity that degrades the Vfr repressor. Proteases can be released from host neutrophils (possibly by NETosis), as well as a positive feedback mechanism by SpeB itself. The authors utilize a dual fluorescent reporter system to simultaneously read speB and capsule gene expression, providing solid evidence that demonstrates that proteases can regulate Vfr; however, the data indicating that this is physiologically relevant and that extracellular traps themselves have a functional role are incomplete. This work will be of interest to microbiologists studying the regulation of virulence factors at the host-pathogen interface.
eLife Assessment
The study presents valuable findings of a new 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. It is interesting that the system's robustness is exhibited by its applicability to nanoluc, a protein that expresses readily in many systems, to more challenging proteins like the functional self-assembling vimentin and the active restriction endonuclease Bsal. Despite the study representing an advancement towards simplifying protein expression workflows, the evidence is solid and supports the main claims however minor weakness exists i.e. the efficiency claims about the new system needs to be supported by accurate comparisons with typical cell free expression systems, in addition, investigations into the mechanistic basis of the observations would provide more evidence. Despite this shortcoming, the paper remains of interest to scientists in cell and molecular biology, microbiology, biotechnology and protein synthesis.
eLife Assessment
The study presents important findings revealing previously unresolved conformational dynamics of the heterodimeric type IV ABC transporter TmrAB using single-molecule FRET. The evidence presented is convincing, integrating careful experimental design with computational approaches to uncover states that are typically masked and difficult to detect. The work will be of interest to scientists studying the molecular mechanisms of primary active transport processes.
eLife Assessment
The authors present important 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 compelling evidence that CROP1 and CROP2 regulate the trafficking of distinct subsets of cargoes; however, the cellular evidence for the existence of these distinct complexes is mostly inferred from immunoprecipitation analysis and would benefit from further validation.
eLife Assessment
This paper reports the findings of a neuroimaging experiment that tested the hypothesis that the cortex, specifically early visual areas, reinstates certain content from past episodic events. This is a useful study that highlights the role of early sensory cortices in supporting rapid, one-shot learning of location information for long-term memory. The strength of the evidence is solid, with the methods, data, and analyses broadly supporting the claims.
eLife Assessment
This fundamental study provides convincing evidence that distinct molecular mechanisms underlie AAV-associated retinal toxicity in retinal pigment epithelial cells and photoreceptors, advancing our understanding of gene therapy-related retinal injury. The authors employ a rigorous and comprehensive experimental approach, including multiple knockout mouse models, transcriptomic analyses, and genetic loss-of-function studies, which substantially strengthen the mechanistic conclusions. Some concerns remain regarding vector characterization, the absence of procedural injection controls, and the limited interpretation of adult versus neonatal studies; nevertheless, the study makes a substantial contribution to the field and provides a strong foundation for future translational investigations.
eLife Assessment
This study presents a useful methodological advance that better enables the simultaneous measurement of gene expression and chromatin accessibility in individual cells. The evidence supporting the improved detection of gene expression is solid. The method has the potential to be more broadly impactful if it were expanded to include orthogonal validation strategies. This method will be of interest to those studying transcription and gene regulation.
eLife Assessment
This important study shows that NPAS4, a gene that is switched on by neural activity, enhances the spatial and temporal precision of hippocampal neurons during navigation. These findings, based on selective and sparse gene deletion, are supported by convincing evidence. However, the experiments were performed entirely in animals exposed to long-term environmental enrichment, which leaves open the question of whether the same effects would emerge under standard housing conditions. This study will be of interest to neuroscientists studying neuronal circuits and spatial coding.
eLife Assessment
This revised study presents valuable findings implicating nuclear export in the regulation of protein condensate behaviour and TDP-43 phase behaviour, suggesting a link to pathogenic aggregation in ALS/FTD. The work contains several observations that will be of interest to the field; however, the underlying mechanistic links proposed by the authors remain insufficiently supported by the current data. The research relies extensively on synthetic, non-physiological protein variants and a homozygous disease model, with limited mechanistic validation, leaving many of the conclusions largely correlative. Thus, despite its technical strengths, the findings presented are currently incomplete, and while the results are invaluable to the field, these do not provide sufficient evidence to substantiate claims about the direct role of nuclear export in pathological protein aggregation and disease.
eLife Assessment
This study presents useful findings on the molecular mechanisms driving female-to-male sex reversal in the ricefield eel (Monopterus albus) during aging, which would be of interest to biologists studying sex determination. The manuscript describes an interesting mechanism potentially underlying sex differentiation in M. albus. However, the current data are incomplete and would benefit from more rigorous experimental approaches for Western blotting.
eLife Assessment
This study provides a valuable advance in understanding how disordered proteins interact with cell membranes by identifying the sequence rules that enable aromatic residues to penetrate deeply into the membrane interior. The integration of complementary computational approaches, including molecular simulations, large-scale sequence analysis, and the development of an online prediction server, makes the work potentially impactful for the membrane protein and intrinsically disordered protein communities. The evidence supporting the main conclusions is generally convincing, although its transferability across diverse membrane compositions and its validity as a prediction tool for real protein-membrane systems remain to be further established.
eLife Assessment
This important study combines chromatin accessibility and genomic DNA sequence conservation data from low-coverage genome sequencing of related species (without assembly), for the in silico identification of cis-regulatory elements in large genomes. The approach and results are compelling and well supported by the experimental validations. The work will be of interest to researchers working in the field of gene regulation and evolution, particularly because the methodology proposed can be applied to a large variety of experimental organisms.
eLife Assessment
This is an important study showing the interaction of the endoplasmic reticulum (ER)-resident tyrosine phosphatase PTP1B with the developing phagocytic cup in macrophages, and its role in inhibiting microbicidal superoxide production. The authors show convincing evidence that PTP1B interacts with Syk, a plasma membrane tyrosine kinase that plays an essential role in phagocytosis, and that ablation of PTP1B increases superoxide production and Syk phosphorylation without affecting phagocytosis. Further evidence suggests that PTP1B may inhibit a Syk/Shc1/NOX2 axis; however, robust demonstration of the proposed chain of events and of the actual role of ER-plasma membrane contact sites in the PTP1B-dependent downregulation of NOX2 activity will require additional experimental evidence. The integration of advanced imaging methods to study contact site formation with functional assays related to phagocytosis and signaling is inspiring.
eLife Assessment
This important study combined careful computational modeling, a large patient sample, and replication in an independent general population sample to provide convincing evidence in support of a computational account of a difference in risk-taking between people who have attempted suicide and those who have not. It is proposed that this difference reflects a general change in the approach to risky (high-reward) options and a lower emotional response to certain rewards. While the findings advance our understanding of cognitive mechanisms at the group level, the observation that computational phenotype is predictive of suicidal behavior only in the clinical sample and not in the online sample limits its applicability for individual prediction, early detection and prevention of suicidality.
eLife Assessment
In this important study, the authors present an interesting platform for digital twin construction of iPSC-CMs using an AI-based approach. The concept is timely and could have meaningful impact as the field continues to explore integration of computational and experimental models. The evidence is convincing overall, although additional attention to framing and calibration of claims would enhance clarity and better reflect the current level of validation.
eLife Assessment
This important study shows that long-range somatostatin-expressing neurons in the ventrolateral periaqueductal grey that project to the rostral ventromedial medulla selectively suppress pain responses during conditioned fear. The evidence supporting these conclusions is exceptional, with methods spanning a novel cued fear-conditioned analgesia paradigm, cell-type-specific optogenetic activation and inhibition, anatomical circuit tracing, and in vivo spinal cord electrophysiology. These results will be of broad interest to systems and behavioral neuroscientists studying fear, pain, and descending pain-control circuitry.
eLife Assessment
This important work challenges current models of merozoite surface protein function by showing that MSP2 is dispensable for parasite growth while modulating immune responses to AMA1, with implications for malaria vaccine design. The conclusions are supported by compelling experimental evidence, including state-of-the-art technologies and well-characterized monoclonal antibodies. These findings provide new insights into immune evasion and antigen targeting that will be of broad interest to parasitology, immunology, and vaccine researchers.
eLife Assessment
This important work addresses a very relevant biological question: what is the cellular basis of wound healing? Using the Drosophila pupal notum as a model, the paper provides an elegant, thorough, descriptive characterization of syncytia-driven wound closure using state-of-the-art confocal live imaging of the pupal notum. The authors meticulously characterize the cell-cell fusion events during wound healing and inhibit cell fusion to show to that it is necessary to speed wound closure. In addition, the study provides convincing evidence that cell fusion allows actin resources at be partitioned to the leading edge.
eLife Assessment
This study provides fundamental insights into the mechanisms of visual object categorization in primates through a scalable behavioral framework for assessing category learning and generalization in macaque monkeys. The evidence is compelling, based on extensive behavioral characterization, rigorous control experiments, and comprehensive comparisons with humans and computational models, although extending the model analyses to the secondary monkey experiments would further strengthen the conclusions.
eLife Assessment
This useful study presents the first application of engineered NK-92 cell-derived extracellular vesicles displaying CD19 scFv for the treatment of systemic lupus erythematosus (SLE). The concept of using targeted extracellular vesicles as a "cell-free" alternative to CAR-T/CAR-NK therapies is good. However, the current results are incomplete and do not provide strong support for the experimental hypothesis, particularly with respect to EV purification, characterization, mechanistic validation, and adherence to current EV field standards. Several major concerns should be addressed to strengthen the translational relevance, reproducibility, and biological interpretation of the study.
eLife Assessment
This study provides important findings regarding the efficacy of a chronotherapeutic protocol (termed LiFE), combining timed light, food, and exercise exposure in improving several physiological and health metrics in a rodent model. The evidence advanced in wild-type mice is solid but inconclusive and underpowered when applied to two transgenic mouse models of Alzheimer's Disease. Additionally, the potential of such protocols in clinical human studies is an open question. Overall, the study suggests that LiFE intervention may have positive effects on metabolic and brain health.
eLife Assessment
This valuable study establishes an improved long-term in vitro culture system for Schistosoma mansoni that enables progression of juvenile parasites to advanced developmental stages exhibiting sexual dimorphism. The work has significant implications for experimental studies of schistosome development and for reducing dependence on animal infection models. The evidence is compelling, supported by robust phenotypic characterization, and integrated molecular and metabolic analyses. The results show that host-derived culture conditions promote essential developmental programs associated with parasite maturation, although the system does not fully recapitulate reproductive development, as evidenced by low pairing frequencies and the lack of egg production.
eLife Assessment
This important study presents a computational framework inspired by cycleGAN that enables denoising and realistic simulation of cryo-electron tomography data, addressing central challenges in tomogram cleaning, simulation, and downstream annotation. The approach coherently links several key problems in the field and demonstrates strong performance across benchmark datasets, with additional benefits for particle detection and missing-wedge completion, indicating broad relevance across electron tomography. The evidence is solid, with appropriate quantitative benchmarks and applications to diverse datasets supporting the main claims, although validation on additional, more recent tomograms would further strengthen the conclusions.
eLife Assessment
This study presents a platform to implement closed-loop experiments in mice based on auditory feedback. The authors provide convincing evidence that their platform enables a variety of closed-loop experiments using neural or movement signals, indicating that it will be a valuable resource to the neuroscience community. The authors make this platform more accessible by complementing the paper with a detailed tutorial explaining how to implement the software and hardware.
eLife Assessment
The article presents important findings of a dissociation between phasic and tonic pain functions in adaptive behavior, combining immersive VR, computational modeling, skin conductance, and EEG data. The methodology used is convincing. Its ecological design and sophisticated computational modeling are major strengths.
eLife Assessment
This important study clearly demonstrates that Sox17 is key for the formation and function of the Sertoli valve, a transition region between the rete testis and seminiferous tubules, which remains an understudied domain of testicular biology. The supporting data are generally convincing but remain incomplete. This work will be of interest to reproductive biologists and andrologists who work on male fertility and men's health.
eLife Assessment
The authors show that innate defensive behavior in mice is shaped by threat intensity, reward value, and social hierarchy, highlighting how value and social context influence instinctive decisions. The authors provide a valuable characterization of escape behavior which approximates naturalistic conditions. Despite minor methodological limitations, the work provides a solid foundation for future investigation of how reward and social context interact to influence behavior.
eLife Assessment
This valuable study draws on large-scale multimodal MRI measurements of human brain structure across the lifespan to offer a new perspective on visual cortex architecture. The data provide compelling evidence for two cortical architectural gradients that show distinct functional, cytoarchitectural, behavioural, and lifespan profiles. One gradient captures a broad early-to-higher-level visual cortical hierarchy in which cortical thickness tissue density covary; the other reflects more localised divergence from this relationship, notably predicting putative anterior temporal visual field representations that have not previously been described.
eLife Assessment
In this valuable manuscript, the authors tackle a highly relevant question in biology: how cells integrate attractive and repulsive cues to achieve directed migration. They present solid data demonstrating that two wunen genes act as negative regulators of Hedgehog signalling, thereby enabling efficient primordial germ cell (PGC) migration in Drosophila embryos. Beyond its immediate scope, this work has broader implications, particularly for understanding key mechanisms underlying complex processes such as cancer metastasis, where the coordinated interpretation of guidance cues is critical.
eLife Assessment
The focus of this manuscript is a computational procedure to reveal signatures of selection on transcription factor binding sites through assessing changes in predicted binding affinity, setting out to avoid biases inherent in previous tests. The general approach could become a valuable resource for the community that can also be used for a broader range of questions. However, in its current implementation, the methods are inadequate to sufficiently support the primary claims.
eLife Assessment
This paper presents important findings on how the shapes of leaves might be biased towards simpler shapes due to biases in how variation is generated by developmental processes rather than selection. The authors present solid evidence that combines image analysis of a herbarium dataset and computational analysis of a model of leaf development. The paper should be of interest to diverse researchers, ranging from plant development to the evolution of complexity more broadly.
eLife Assessment
This useful study introduces a statistical model and accompanying software for jointly analysing how an organism's own genotype, and those of its neighbors, shape its traits (assessing both direct and indirect genetic effects), based on simulations and three datasets from plants. The implementation and its behavior on simulated data are solid, but the evidence that the approach is more powerful, more interpretable, or more novel than established alternatives is incomplete, because the authors do not benchmark against existing methods, nor validate the candidate genes they identify, nor test realistic scenarios in which neighbor effects are weaker than direct effects. The work will be of interest to quantitative geneticists and plant breeders studying competition among neighboring genotypes.
eLife Assessment
This valuable study advances our understanding of genes contributing to Drosophila resistance to octanoic acid, a primary toxin present in Morinda fruit, which is the natural host plant for Drosophila sechellia, a species that has become a model for understanding evolutionary specialization. The authors provide solid results from an original combination of experimental evolution and cell-based CRISPR screens. This work will be of interest to the Drosophila community and researchers interested in the genetic basis of polygenic traits.
eLife Assessment
This important study systematically investigates parent-of-origin (POE) effects on gene expression using large trio-based data from the Framingham Heart Study, identifying thousands of potentially novel associations. However, the statistical support for classifying POE eQTLs is incomplete, and as a result, downstream analyses of the identified POE eQTLs are not fully supported.
eLife Assessment
The study presents a valuable conceptual framework by classifying pattern-forming gene subnetworks into three established categories. However, the supporting evidence remains incomplete, as the mathematical generalizations rely on simplified assumptions that may not hold in more complex or realistic scenarios.
eLife Assessment
This study presents an important finding that loss or blockade of key integrins unexpectedly enhances central nervous system accumulation of T-cell acute lymphoblastic leukemia cells and may increase their sensitivity to chemotherapy. The evidence is convincing, supported by well-designed in vivo models, CRISPR-based perturbations, competitive assays, imaging, and complementary therapeutic experiments. However, the mechanistic basis linking integrin loss, altered spatial distribution, and increased proliferation remains incompletely defined, and the translational implications would be strengthened by additional survival studies and validation in more clinically relevant models.
eLife Assessment
This study of BDNF signaling in heterogeneous spinal cord cultures provides a fundamental conceptual advance by demonstrating that cell identity and maturation state, rather than receptor stoichiometry alone, ultimately determine how a trophic message is interpreted, in a framework the authors call "prepared competence." The evidence is compelling, with the discrete subpopulation behavior, the maturation-dependent acquisition of signaling competence, and the dissociation between receptor abundance and signaling output emerging clearly from the high-dimensional dataset. This study will be of interest to neurobiologists as well as cell biologists who study the molecular basis of cell signaling.
eLife Assessment
This Review Article provides a scholarly, clear and well-structured review of intracranial research into the neural correlates of consciousness (NCCs). To our knowledge this is the first such review and is therefore likely to become a must-read for anyone working in the field of consciousness research. The authors discuss the difficulties that researchers must face when studying NCCs and how insights may emerge via intracranial recordings in humans. This no doubt reflects an in-depth, timely, and insightful contribution to the literature.
eLife Assessment
This useful study examines excitation/inhibition (E/I) balance in the CA3-CA1 circuit of the hippocampus. Experimental and computational modeling results are presented. The computational modeling results were viewed as a novel advance supported by solid evidence, but incomplete evidence was provided to support the paper's main experimental claims due to deficiencies in the experimental methodology and concerns about the neurobiological relevance of the experimental observations.
eLife Assessment
This study makes a valuable contribution to understanding how negative affect shapes food-choice decision making in bulimia nervosa by using a mechanistic drift diffusion model to quantify the weighting and temporal integration of tastiness and healthiness attributes. The approach is solid and has clear potential to advance understanding of the decision processes underlying pathological food choices. The evidence is strengthened by the randomised crossover design and appropriate statistical analyses. The results are consistent across different analytic approaches, increasing confidence in the robustness of the findings.
eLife Assessment
This important study investigates frequency-dependent effects of transcutaneous tibial nerve stimulation (TTNS) on bladder function in healthy humans and, through a computational model, shows that low-frequency stimulation accelerates, and high-frequency delays, the urge to void. The integration of experimental and modeling approaches provides a solid proof-of concept foundation for clinical trials targeting urinary retention. However, concerns were raised about over-interpretation of modest effects and the limited physiological validity of the computational model, and the need for replication in clinical populations. Some conclusions, particularly in the abstract, could be further tempered to better align with the strength of the available evidence.
eLife Assessment
This study reports important findings by showing that two classes of kinase inhibitors, which stabilise the LRRK2 enzyme in either an active (Type I) or inactive state (Type II), have distinct effects on the formation of LRRK2 filaments and their association with cellular structures. Using correlative light microscopy, cryo-electron tomography and sub-tomogram averaging, the authors provide convincing evidence that a Type I inhibitor leads to the extensive decoration of microtubules with LRRK2 in a closed-kinase conformation, and that such decoration is not seen for a type-II inhibitor. The conclusions are consistent with previous work, although the physiological relevance of the work remains somewhat limited due to reliance on overexpression and the use of a rare mutation in a single cell type.
eLife Assessment
This important study identifies inhibitory cerebellar nuclei neurons as drivers of dystonic crisis and shows that their modulation can both induce and alleviate severe motor symptoms, proposing a cerebello-thalamic circuit mechanism with clear therapeutic relevance. The evidence is convincing, supported by rigorous bidirectional optogenetic manipulations, iCNN-to-CL thalamic monosynaptic tracing, and deep brain stimulation experiments, although the specificity of the genetic strategy remains to be fully resolved. The study will be of broad interest to neuroscientists and clinicians working on movement disorders and circuit-based therapies.
eLife Assessment
This important study provides new insights into the neuronal dynamics of the locus coeruleus in relation to hippocampal sharp-wave ripples. Using high-temporal-resolution, multi-site electrophysiological recordings in rats, the authors present convincing evidence that ripples and locus coeruleus activity are inversely correlated to levels of arousal and noradrenaline tone is modulated by hippocampo-cortical coupling. Overall, the work will be of interest to neuroscientists studying large-scale brain coordination and memory processes.
eLife Assessment
This valuable study shows that macaque monkeys preferentially fixate regions in natural scenes that are classified as "meaningful" by a computational model - an earlier model that was developed to identify locations that are semantically informative to humans - suggesting that overt attention to structured visual content is shared across primates. However, support is incomplete for the stronger claim that macaques are guided by semantic meaning, which is confounded by lower-level visual features that co-vary with it and by methodological limitations that complicate interpretation. If the semantic interpretation were more reliably established, the significance of the findings would increase, as they would connect the human cognitive process of scene understanding to neural circuit mechanisms accessible in non-human primates.
eLife Assessment
This valuable study rigorously examines how motor learning is influenced by the feedback response to a previous movement error. Using a series of well-conducted experiments, the authors provide solid evidence that the learning response following a cursor jump does not depend on the timing of the perturbation and is influenced by the tonic component of the feedback responses. Further work is needed to determine whether this generalizes to other perturbation paradigms and to more fully understand the relationship between learning and the tonic and phasic components of the feedback response.