eLife Assessment

This study presents a valuable finding on the intersection between tuberculosis and diabetes and the impact on immune responses, notably T cell and myeloid cell responses. The single-cell data collected and analyzed are convincing and provide a rich dataset to develop a more detailed understanding of cellular responses during Mtb infection of diabetic mice. Some of the mechanistic claims are incomplete, as there are no experiments performed to clearly define a role for IL-16 or IL-17 in disease. Inclusion of analysis of human samples would have strengthened the conclusions in the paper for translational impact, as well as the inclusion of a DM group alone in addition to DM-TB vs TB in some of the experiments.

eLife Assessment

This valuable study reports the conservation of sperm-egg envelope binding by demonstrating successful recognition of the micropyle in fish eggs by the mouse sperm. However, the evidence supporting the conclusions drawn remains incomplete. In particular, the proposed specific role of CatSper in micropyle recognition and passage is not fully demonstrated. This study will be of interest to reproductive biologists and clinicians studying the biology of fertilization and fertility.

eLife Assessment

This fundamental study explores a novel cellular mechanism underlying the degeneration of locus coeruleus neurons during chronic restraint stress. The evidence supporting the overexpression of LC neurons after chronic stress is compelling. However, to fully support the broad implications for LC degeneration and Alzheimer's disease, the study would benefit from stronger causal integration and validation in age-relevant models.

eLife Assessment

This useful study describes a physical mechanism for the emergence of spiral patterns in the outer epithelial layer of the mammalian cornea independent of pre-patterning or guidance cues, using an agent-based model of self-propelled particles with alignment. The model is well constructed, however the central premise of the manuscript, that the spiral patterning of epithelial corneal cells occurs without guidance cues, is incomplete and not fully supported. Several significant questions remain unanswered, such as the role of the corneal curvature or the importance of topological defects. Furthermore, comparison between the model and data are qualitative at best for the moment.

eLife Assessment

This study demonstrates the application of END-seq, originally developed to study genome-wide DNA double-strand breaks, to telomere biology; the work packs a punch, concisely demonstrating the utility of this approach and the new insights that can be gained. The authors confirm that telomeres in telomerase-positive cells terminate with 5'-ATC in a Pot1-dependent manner, and demonstrate that this principle holds true in telomerase-negative ALT cells as well; S1-END-seq is similarly developed for telomeres, showing that ALT cells harbor several regions of ssDNA. The study is well-executed, the new insights are fundamental and compelling, and the optimized END-seq approaches will be widely utilized. The interest of the paper could be heightened by deepening the discussion of potential biases in telomere representation, the origin of the ssDNA captured in ALT cells, and the occurrence of variant telomere repeats in the cell lines studied.

eLife Assessment

This important study provides evidence for asymptomatic Bordetella pertussis carriage among mothers in a longitudinal cohort in Zambia, significantly advancing understanding of transmission dynamics. The evidence presented is convincing, with strengths including routine sampling irrespective of symptoms and rigorous qPCR methodology, although confirmatory diagnostics would further strengthen the claims. Overall, the study represents an influential contribution to the field of infectious disease epidemiology.

eLife Assessment

Cardiac Ca2+/Na+ exchange is mediated by the NCX1 antiporter, whose activity is tightly regulated. This important manuscript describes the structural basis of activation by the lipid DiC8-PIP2 and inhibition by binding of a small molecule to NCX1. These results provide convincing insights into NCX1 regulation and the structural basis of cellular Ca2+ signaling.

eLife Assessment

This study presents valuable findings with practical and theoretical implications for drug discovery, particularly in the context of repurposing cipargamin CIP for the treatment of Babesia spp. The evidence is solid with the methods, data, and analyses broadly supporting the claims. The paper will be of great interest to scientists in drug discovery, computational biology, and microbiology.

eLife Assessment

This study provides important insights as to how interacting brain areas produce movement during the execution of a skilled multi-directional reaching task. Using a combination of single neuron and neural population analysis, optogenetic stimulation, and computational models, the authors provide convincing evidence of an asymmetrical influence between mouse premotor and motor cortex during the execution of a well-practiced behaviour. This asymmetry can only be captured by some but not all population analysis methods, which is a key lesson to the field in and of itself. Analyzing how activity that is shared and private to these areas relates to different aspects of movements, and why different methods provide different outcomes regarding the nature of inter-area interactions would further strengthen this work.

eLife Assessment

This study provides valuable findings that MK2 inhibitor CMPD1 can inhibit the growth, migration and invasion of breast cancer cells both in vitro and in vivo. The evidence supporting the claims of the authors is solid, although the detailed molecular mechanism and additional animal experiments would strengthen the paper. This study will be of interest to the breast cancer field.

eLife Assessment

This manuscript makes a valuable contribution to the field by uncovering a molecular mechanism for miRNA intracellular retention, mediated by the interaction of PCBP2, SYNCRIP, and specific miRNA motifs. Overall, the findings are convincing and advance our understanding of RNA-binding protein-mediated miRNA sorting, providing deeper insights into miRNA dynamics.

eLife Assessment

The manuscript by Hawes et al. provides important findings on how striatal projection neurons regulate spontaneous locomotion speed in the context of implicit motivation and distinct contextual valence. Overall, the evidence for the findings is solid, although evidence for the claim that striatonigral projections from the matrix and patches have functionally opposing roles is incomplete. This work will be of broad interest to neuroscientists in the basal ganglia, movement control, and cognition fields.

eLife Assessment

This manuscript provides fundamental new insight into the mechanisms linking photoperiod, reproduction function, and feeding activity, using medaka, a genetic model that itself exhibits photoperiodic responses. As well as identifying key neuropeptide genes that are regulated by photoperiod and involved in regulating feeding activity, the authors establish a knockout line for agrp1 using CRISPR Cas9 - based approach, profiting from the extensive use and development on this methodology in medaka. The combination of the RNAseq and quantitative in situ hybridization analysis with the knockout results as well as the study of ovariectomized fish provides compelling evidence implicating agrp1 in feeding regulation in response to photoperiod and reproductive status.

eLife Assessment

This valuable work formulates an individual-based model to understand the evolution of division of labor in vertebrates, in particular, to examine the role of indirect versus direct fitness benefits. The evidence supporting the main conclusions is incomplete at this stage, with key details of simulation assumptions not adequately described and exploration of alternative assumptions and parameter space lacking.

eLife Assessment

This study presents an important practical modification of the orthogonal hybridization chain reaction (HCR) technique, a promising yet underutilized method with broad potential for future applications across various fields. The authors advance this technique by integrating peptide ligation technology and nanobody-based antibody mimetics - cost-effective and scalable alternatives to conventional antibodies - into a DNA-immunoassay framework, which convincingly merges oligonucleotide-based detection with immunoassay methodologies.

eLife Assessment

This important study demonstrates that interferon beta stimulation induces WTAP transition from aggregates to liquid droplets, coordinating m6A modification of a subset of mRNAs that encode interferon-stimulated genes and restricting their expression. The evidence presented is solid, supported by microscopy, immunoprecipitations, m6A sequencing, and ChIP, to show that WTAP phosphorylation controls phase transition and its interaction with STAT1 and the methyltransferase complex.

eLife Assessment

TDP-43 mislocalization is a key feature of some neurodegenerative diseases, but cellular models are lacking. The authors endogenously-tagged TDP-43 with a C-terminal GFP tag in human iPSCs, followed by expression of an intrabody-NES that targeted GFP to the cytosol. They convincingly report physical mislocalization and functional depletion of TDP-43, as measured by microscopy and RNAseq. This method will be valuable to investigators studying the biological consequences of TDP-43 mislocalization and the methodology is in line with the current state-of-the-art.

eLife Assessment

This paper reports on an important study that aims to move beyond current experimental approaches in speech production by (1) investigating speech in the context of a fully interactive task and (2) employing advanced methodology to record intracranial brain activity. Together these allow for examination of the unfolding temporal dynamics of brain-behaviour relationships during interactive speech. This approach and the analyses presented in support of the authors' claims pose convincing evidence.

eLife Assessment

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

eLife Assessment

These are valuable findings for those interested in how neural signals reflect auditory speech streams, and in understanding the roles of prediction, attention, and eye movements in this tracking. However, the evidence as it stands is incomplete. Further analyses are needed to clarify how the observed results relate to the relevant theoretical claims.

eLife Assessment

The authors analyses describe a novel mechanism by which a retrotransposon-derived LTR may be involved in genomic imprinting and demonstrate imprinting of the ZDBF2 locus in rabbits and Rhesus macaques using allele-specific expression analysis. This imprinting of the ZDBF2 locus correlates with transcription of GPR1-AS orthologs. The accompanying genomic analysis is very well executed allowing for the conclusions reached in the manuscript. The revisions made at the request of the reviewers in this important manuscript strengthen the evidence from the genomic analyses, and as a result, the evidence is now convincing and will be informative to the genomics and developmental biology communities.

eLife Assessment

The ExA-SPIM methodology developed here and characterized and supported by convincing evidence is an important development for the field of light sheet microscopy as the new technology provides an impressive field of view making it possible to image the entire expanded mouse brain at cellular and subcellular resolution.

eLife Assessment

This comprehensive study presents important findings that delineate how specific dopaminergic neurons (DANs) instruct aversive learning in Drosophila larvae exposed to high salt through an integration of behavioral experiments, imaging, and connectomic analysis. The work reveals how a numerically minimal circuit achieves remarkable functional complexity, with redundancies and synergies within the DL1 cluster that challenge our understanding of how few neurons generate learning behaviors. By establishing a framework for sensory-driven learning pathways, the study makes a compelling and substantial contribution to understanding associative conditioning while demonstrating conservation of learning mechanisms across Drosophila developmental stages.

eLife Assessment

This study provides an important understanding of the contribution of different striatal subregions, the anterior Dorsal Lateral Striatum (aDLS) and the posterior Ventrolateral Striatum (pVLS), to auditory discrimination learning. The authors have included robust behavior combined with multiple observational and perturbation techniques. The data provided are convincing of the relevance of task-related activity in these two subregions during learning.

eLife Assessment

This study presents a valuable meta-analysis of two independent genome-wide association studies (GWASs) elucidating the role of plasma proteins as biomarkers for improving early detection of prostate cancer (PCa). The evidence supporting novel protein biomarkers of PCa risk is solid, although exploration of how these markers may also be shared with other prostate diseases would have strengthened the study. The work will be of interest to the field for elucidating novel variants of prostate cancer risk.

eLife Assessment

This study presents a valuable meta-analysis that highlights low and highly variable breast cancer survival rates across Africa, emphasizing the pressing need for public health in Africa. The evidence supporting the claims of the authors is solid, although a clarification of the crude 5-year survival rates would have strengthened the study. The work will be of interest to scientists working in the field of public health and breast cancer.

eLife Assessment

This valuable study provides a conceptual advance in our understanding of how membrane geometry modulates the balance between specific and non-specific molecular interactions, reversing multiphase morphologies in postsynaptic protein assemblies. Using a mesoscale simulation framework grounded in experimental binding affinities, the authors successfully recapitulate key experimental observations in both solution and membrane-associated systems, providing novel mechanistic insight into how spatial constraints regulate postsynaptic condensate organization. While the evidence supporting the conclusions is largely solid, a few aspects of the analysis and model proposed remain incomplete.

eLife Assessment

This work presents an important technical advancement with the release of MorphoNet 2.0, a user-friendly, standalone platform for 3D+T segmentation and analysis in biological imaging. The authors provide convincing evidence of the tool's capabilities through illustrative use cases, though broader validation against current state-of-the-art tools would strengthen its position. The software's accessibility and versatility make it a resource that will be of value for the bioimaging community, particularly in specialized subfields.

eLife Assessment

Thick multicellular plant samples provide unique challenges when it comes to cryo-preservation, which has resulted in limited successful examples for structural studies using in situ cryo-electron tomography. To address this deficiency, this important study describes procedures for high-pressure-freezing, focused ion-beam milling, and cryo-electron tomography imaging of certain plant types. The results described in the paper provide solid evidence for the usefulness of the methods described, although some reservations remain about the applicability of the methods to a wider range of plant cell types.

eLife Assessment

This study provides a valuable extension of credibility-based learning research by showing how feedback reliability can distort reward-learning biases in a disinformation-like bandit task. Although the paradigm is well controlled and the computational modelling rigorous, the evidential support is incomplete: key claims about learning from 50 %-credible feedback and heightened positivity bias at low credibility hinge on a single dataset, specific parameter definitions, and modelling assumptions not fully validated across studies. Clearer reporting of the discovery-study null result, behavioural tests of positivity bias, and standard information-criterion model comparisons are needed to solidify the conclusions and enhance generalizability.

eLife Assessment

This important study of the inhibitory complex amacrines (CAM) in the vertical lobe of Octopus vulgaris delivers a solid standard for the structural characterization of an anatomical region likely to be key for memory processing in this unconventional but complex organism, as well as a helpful classification of CAM subtypes. This work will be of broad relevance to the fields of memory and evolutionary neuroscience.

eLife Assessment

This is an important study introducing a stimulus-computable model of multisensory perception that extends an existing framework to accept raw, stimulus-level inputs (i.e., image- and soundscape-computable). The author demonstrates how low-level correlation detection can drive both illusions and cue integration, and the model bridges diverse stimuli, behaviors, and species. The model and evidence provided are deemed generally convincing and of broad applicability, potentially impacting areas across neuroscience, psychology, and computational cognitive science. There are, however, certain aspects of the work considered incomplete, particularly as they relate to explaining details pertinent to model fitting.

eLife Assessment

The study conducted by Hurtado et al. offers important insights and solid evidence regarding the prediction of drug combinations for cancer treatment. By leveraging disease-specific drug response profiles and single-cell transcriptional signatures, this research not only demonstrates a novel and effective approach to identifying potential drug synergies but it also enhances our understanding of the underlying mechanisms of drug response prediction.

eLife Assessment

This manuscript presents a valuable minimal model of habituation which is quantified by information theoretic measures. The results here could be of use in interpreting habituation behavior in a range of biological systems. The evidence presented is solid, and uses simulations of the minimal model to recapitulate several hallmarks of habituation from a simple model.

eLife Assessment

This study presents an important set of new tools to facilitate Cre or Dre-mediated recombination in mice. The characterization of these new tools was done using solid and validated methodology. The work convincingly demonstrates the efficient gene knockout capability of these models and will progress the field.

eLife Assessment

This analysis of the formation of the oral-aboral body axis in cnidarians, the sister group of bilaterians, is a significant and fundamental contribution to the field of Wnt signalling and planar cell polarity, particularly in or understanding in gradient formation, non-canonical Wnt signalling and Wnt-Frizzled interactions in cnidarians. The evidence supporting the conclusions is compelling and has the potential to contribute to a deeper understanding of the origin and evolution of Wnt signalling in cnidarians and metazoans in general. These findings, which are presented in a thoughtful and scholarly manner, will be of broad interest to developmental and evolutionary biologists.

eLife Assessment

This paper provides a compelling and rigorous quantitative analysis of the turnover and maintenance of CD4+ tissue-resident memory T cell clones, in the skin and the lamina propria. It provides a fundamental advance in our understanding of CD4 T cell regulation. Interestingly, in both tissues, maintenance involves an influx from progenitors on the time scale of months. The evidence that is based on fate mapping and mathematical inference is strong, although open questions on the interpretation of the Ki67-based fate mapping remain.

eLife Assessment

This important study addresses an essential morphogenetic process-epithelial fusion-by identifying the transcription factor Hamlet as a potential master regulator. Using a combination of genetic, cell biological, and omics approaches, including a comprehensive RNAi screen and high-quality imaging, the authors provide compelling evidence for Hamlet's role in coordinating cell fate and differentiation. The findings are robust and of broad interest to developmental biologists and geneticists.

eLife Assessment

This important study reports on a basis for neurabin-mediated specification of substrate choice by protein phosphatase-1. The data from the comprehensive approach using structural, biochemical, and computational methods are compelling. This paper is broadly relevant to those investigating various cellular signaling cascades that entail phosphorylation as the main mechanism.

eLife assessment

This study offers a useful discussion of the well-accepted abundance-occupancy relationship in macroecology. While using the ebird large dataset to revisit the theme is interesting, multiple unresolved confounding factors exist, leaving the results inadequate to overturn the repeatedly confirmed abundancy-occupancy relationship.

eLife Assessment

This important theoretical study shows that active hexatic topological defects in epithelia play a crucial role in enabling collective cell flows. While the use of coarse-grained hydrodynamic models to describe cell-scale behavior has limitations, the study provides solid evidence supporting its claims. These findings will interest both biophysicists studying collective cell behaviors and biologists investigating epithelial flows during development.

eLife Assessment

This important study addresses the question of how large-scale events such as the COVID-19 pandemic can change people's beliefs and their updates. Using a well-validated task, the authors find that belief updating becomes less optimistically biased during COVID-19 compared to before it. In this revision, due to the addition of more model-based analyses and power calculations, they have generated convincing evidence for their primary claim that the pandemic significantly impacted people's belief updating away from optimistic belief updating. As with many manipulations outside the experimenters' control, it remains unclear which psychological factor impacted by the pandemic drives the group differences, and sample sizes are, by necessity, on the smaller side as data cannot readily be acquired. However, the authors are commended for doing power analyses, showing their sensitivity, and recognizing the limitations of their study.

eLife Assessment

Jung et al. present valuable work on the relationship between gamma-aminobutyric acid (GABA) levels within the anterior temporal lobes (ATL) to semantic memory while accounting for inter-individual differences. They provide solid evidence suggesting that inhibitory continuous theta burst transcranial magnetic stimulation (cTBS TMS) increased GABA concentration and decreased the blood-oxygen dependent signal (BOLD) during a semantic task. The results will be of interest to researchers studying the neurobiology of semantic cognition.

eLife assessment

Using an elegant and thorough experimental design, Thomazeau et al show that, in the developing mouse visual cortex, presynaptic NMDA receptors at layer 5 neocortical synapses mediate spike-timing dependent LTD via JNK2, non-ionotropic signaling. These fundamental findings shed light on how NMDA receptors can tune synaptic function without acting as coincidence detectors. The experiments are supported by compelling evidence, gathered through mouse transgenics and quadruple patch clamp recordings from cortical slices.

eLife Assessment

This study offers valuable insights into the role of post-translational modifiers, specifically SUMO2ylation at K81 in p66Shc, and its impact on endothelial function through reactive oxygen species. A series of compelling experiments demonstrated that lysine 81 of p66Shc is the site of SUMO2 conjugation, which is crucial for mitochondrial localization and essential for S36 phosphorylation, leading to specific pathological effects. The combination of cell overexpression and animal studies provides solid data supporting this mechanistic link.

eLife Assessment

This valuable paper shows image correlation spectroscopy (ICS) as a new tool to analyze the clustering of proteins involved in DNA damage response (DDR). The convincing evidence presented demonstrates that ICS is more sensitive than traditional foci counting. This new method provides an alternative tool to quantify immunostained foci for researchers in the fields of DDR and cell biology.

eLife Assessment

This study presents a useful finding for the ferroptosis-mediated tumor microenvironment (TME) in triple-negative breast cancer (TNBC) using public single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data. The data were collected and analyzed using solid and validated methodology and can be used as a starting point for functional studies of TME in TNBC. The work will be of interest to medical biologists working in the field of TNBC.

eLife Assessment

This important work shows the biological processes and detailed mechanisms involving testosterone's influence on seminal plasma metabolites in mice. Evidence supporting the up regulation of metabolic enzymes and the role of ACLY is solid, though the precise contributions of fatty acids to sperm motility requires further elucidation.

eLife Assessment

This useful manuscript provides a newly curated database (termed AACDB) of antibody-antigens structural information, alongside annotations that are either taken and from the PDB, or added de-novo. Sequences, structures, and annotations can be easily downloaded from the AACDB website, speeding up the development of structure-based algorithms and analysis pipelines to characterize antibody-antigen interactions. The methodology presented for this data curation is solid. The curated dataset will be of broad interest and value to researchers interested in antibody-antigen interactions.

eLife Assessment

The authors present an important set of data implicating ETFDH as an epigenetically suppressed gene in cancer with tumor suppressive functions. The evidence is solid, with the authors demonstrating that ETFDH suppression results in accumulation of amino acids that impact metabolism via hyperactive mTORC1.

eLife Assessment

This important paper reports the discovery of calcarins, a protein family that seems to be involved in calcification in the calcareous sponge Sycon ciliatum, significantly enhancing our understanding of the molecular and cellular mechanisms underlying spicule formation in sponges and the evolution of carbonate biomineralization. The conclusions are supported by compelling evidence based on an integrated analysis that combines transcriptomics, genomics, proteomics, and precise in situ hybridization. These findings will be of broad interest to cell biologists, biochemists, and evolutionary biologists.

eLife Assessment

This study provides important insights into the regulation of neuroblast lifespan and proliferation in the Drosophila mushroom body, identifying Krüppel (Kr) as a key transcription factor promoting timely termination of these neuroblasts by repressing Imp expression, and proposes an antagonistic role of Krüppel homolog 1 (Kr-h1), whose overexpression leads to prolonged mushroom body neuroblast proliferation and tumor-like expansion. The findings are impactful for researchers interested in temporal patterning and neural development, and the methods and data analysis are solid, however, the precise regulatory interactions between Kr and Kr-h1 and their modes of action remain incompletely tested. Further experiments would be required to fully elucidate the mechanistic interplay between the factors involved.

eLife Assessment

The findings in this manuscript are important because they demonstrate the key role of metabolism in insect development. The data were collected and analyzed using solid and validated methodologies, but the evidence is incomplete, as the extent of the involvement of AOX activity in vivo and in physiological conditions is not addressed. This manuscript will be of interest for the fields of mitochondrial bioenergetics, metabolism and development.

eLife Assessment

This important study advances our understanding of vertebrate forelimb development, specifically the contribution of Hox genes to zebrafish pectoral fin formation. While there are reservations about some of the descriptions and interpretations of the data, the results are mostly convincing. The authors have employed a robust and extensive genetic approach to tackle a key and unresolved question. The findings will be of broad interest to developmental and evolutionary biologists.

eLife Assessment

Antibodies that selectively bind distinct amyloid-beta variants are vital tools for Alzheimer's disease research. This valuable manuscript aims to delineate the epitope specificity in a panel of anti-amyloid-beta antibodies, including some with clinical relevance. The experiments were rigorously conducted, employing an interesting combination of established and state-of-the-art methodologies, yielding mostly robust findings. While the data regarding antibody sequence preferences for distinct amyloid-beta regions and aggregation states are convincing, a thorough revision of the manuscript would help to highlight the key results.

eLife Assessment

This valuable study aims to advance the toolkit of small molecules used for approaches to targeted protein degradation for research and therapeutic applications. The authors provide solid data demonstrating the use of a high-throughput screen of small molecules to target a specific E3 ligase, KLHDC2 (Kelch-like homology domain containing protein 2); the resulting compounds then form the basis for new PROTAC (proteolysis targeting chimera) reagents. The strength of the work lies in expanding the PROTAC reagent inventory. The current work would be strengthened further by confirming that the PROTAC's activity is dependent on KLHDC2 and by a more thorough examination of off-target effects in cellular applications.

eLife Assessment

This study presents a valuable finding on the role of Slit-Robo signaling in cardiac innervation. The evidence supporting the main claims of the authors is solid. The use of several mouse models including constitutive and cell type specific knockout models make the findings more robust. The scope of the presented studies is somewhat limited, as they primarily focus on evaluating the phenotypic changes in cardiac innervation following the loss of various Slit or Robo genes.

eLife Assessment

This study presents the important finding that lysosomal damage triggers inflammatory signaling through ubiquitination and the TAB-TAK1-IKK-NF-kB axis. The data obtained from the unbiased transcriptomic and proteomic analyses are convincing and provide invaluable information to the field. Although further experiments will be required to clarify how TAB2/3 are activated, this work will be of interest to researchers in the fields of organelle biology and inflammation.

eLife Assessment

This important study describes newly identified light-gated ion channel homologs (channelrhodopsins, ChRs) in several protist species, with a primary focus on the biophysical characterization of ChRs of ancyromonads. The authors employed a powerful combination of bioinformatics, manual and automated patch-clamp electrophysiology, absorption spectroscopy, and flash photolysis. Additionally, they evaluated the applicability of the newly discovered anion-conducting ChRs in cortical neurons of mouse brain slices and in living C. elegans worms. The evidence supporting most of the claims is convincing and this work will be of interest to the microbial rhodopsin community and neuro- and cardioscientists utilizing optogenetics in their research.

eLife Assessment

This valuable study examines the role of map3k1, a MAP3K family member that has both kinase and ubiquitin ligase domains, in the differentiation of progenitors in the flatworm Planaria. The convincing analyses demonstrate that map3k1 acts within progenitors to restrict their premature differentiation and to prevent formation of teratomas. This work would be of interest to researchers in the fields of regeneration, developmental biology, and aging.

eLife Assessment

This important study is a first report investigating the boundary formation between sensory and non-sensory tissues of the inner ear, which has broad relevance to the developmental field in general. All three reviewers thought the results and data analyses presented are solid. However, the causal relationship between the morphological evidence and the role of Lmx1a is not well supported by the results. The mechanism linking Lmx1a to ROCK is also incomplete, considering ROCK is involved in so many processes.

eLife Assessment

The first part of this manuscript describes an interdisciplinary approach to mine the human channelome and discover further ion channel orthologues across diverse organisms. Although the findings and data curation enabled by the new approach are valuable to the ion channel community, as well as to those interested in improved methods for mining sequence space for their protein of interest, this part of the work is incomplete because critical methodological information is missing. Further validation of the improvements this approach shows over others is needed. The second part of the manuscript utilizes the approach described in the first part to delineate co-conserved amino acid patterns in CALHM channels, but the evidence provided to support the role of the identified residues in channel gating is currently inadequate.

eLife Assessment

This useful work employs transition-metal FRET (tmFRET) to study the cyclic nucleotide binding domain (CNBD) of a bacterial ion channel. The authors employ lifetime measurements of fluorescence to extend their own prior study and observe distance changes within the CNBD domains of a full-length channel; they base these measurements on changes in lifetimes due to tmFRET between a metal at an introduced chelator site and a fluorescent non-canonical amino acid at another site within the channel sequence. This allows the authors to show that coupling of the CNBDs to the rest of the channel stabilizes the CNBDs in their active state relative to an isolated CNBD construct. The data are compelling and of high quality, and support the authors' conclusions.

eLife Assessment

The fundamental findings reported here provide insight into how the viscoelasticity of the fingertip skin influences the activity of mechanoreceptive afferents and thus the neural coding of force in humans. The basic principle studied was whether and to what extent the previous applied force directions impact the firing of FA-1, SA-1 and SA-2 neurons during the current applied force directions. The data and analyses are compelling and will be helpful for modeling the neural representations of force in the context of object grasping and manipulation.

eLife Assessment

This fundamental work presents two clinically relevant BMP4 mutations that contribute to vertebrate development. The compelling evidence, both from wet lab and AI generated predictions, supports that the site-specific cleavage at the BMP4 pro-domain precisely regulates its function and provides mechanistic insight how homodimers and heterodimers behave differently. The work will be of broad interest to researchers working on growth factor signaling mechanisms and vertebrate development.

eLife Assessment

In their valuable study, Bracey et al. investigate how microtubule organization within pancreatic islet beta cells supports optimal insulin secretion. Using a combination of live imaging and photo-kinetic assays in an in vitro culture system, they provide convincing evidence that kinesin-1-mediated microtubule sliding, which plays critical roles in neurons and embryos, also plays a critical role in forming the sub-membranous microtubule band in response to glucose in beta cells. This work will be of interest to cell biologists studying cytoskeletal dynamics and organelle trafficking, as well as to translational biologists focused on diabetes.

eLife Assessment

This important study provides evidence of a deeply conserved role for the gene Mirror in providing positional identity in the posterior part of butterfly and fly wings, despite increased morphological complexity of butterfly wings. The findings are solid for the field of evo-devo. However, the tools in butterflies are more limited than in Drosophila and it is more difficult to determine which specific cells are mutant and whether the effect of mutation is cell-intrinsic. The work will be of interest to evolutionary and developmental biologists working on insect wing evolution and the evolution of patterning more generally.

eLife Assessment

This important study examines the neuronal mechanisms underlying visual perception of integrated face and body cues. The innovative paradigm, which employs monkey avatars in combination with electrophysiological recordings from fMRI-defined brain areas, provides compelling evidence on face and body integration. These results should be of wide interest to system and cognitive neuroscientists, psychologists, and behavioural biologists working on visual and social cognition.

for - book - Embracing Paradox, Evolving Language - book - review - Embracing Paradox, Evolving Language - adjacency - Lisa's conlanger - Deep Humanity BEing journeys - Indyweb - provenance - Deep Humanity - language BEing journey - author - Lisa E. Maroski - to - post - LinkedIn - Bayo Akomolafe - from 'belief' to 'apolief" - https://hyp.is/go?url=https%3A%2F%2Fwww.linkedin.com%2Fposts%2Fbayoakomolafe_i-am-against-worldview-the-term-seems-activity-7319799984663535616-fpVW%2F&group=world

new trailmark - summary to review - the word "review" may be a better trailmark word than "summary" - At this point, I will replace "summary" with "review" in the case of book or article reviews

review - Lisa's book is an insightful convergence of an important but ignored subject, the experiential intersection between language and consciousness. - Her understanding that language plays an important role in constructing our reality leads to a bold and novel proposal, especially salient at this time of global poly-meta-perma-meaning crisis. - She proposes that we individually and collectively experiment and explore creating new words and language structures that transcend the limitations of our existing language - If patterns of language usage traps us in outdated conceptual paradigms, then breaking out of these may be challenging, if not impossible, without the creation of new linguistic and language structures. - From a Stop Reset Go and Deep Humanity perpsective, Lisa's proposal for practical experimentation with constructing new languages to unleash new forms of expression is very aligned to Deep Humanity BEing journeys - As I read and annotate Lisa's book, any potential linguistic and language BEing journeys that her words inspired will be recorded for posterity

Addendum - note from journal - 2025, May 8 - reflections on Lisa's book - asynchronous communication is only one half of indyweb     - the other half is asynchronous REFLECTION AND SYNTHESIS - Effective timebinding requires both     - Annotation captures interpersonal shared ideas     - journalling captures ours own unique synthesis only emerges from asynchronous reflections of our existent associative network of ideas and the newly ingested interpersonal ones - Annotations capture the novel and newly inputted interpersonal ones     - but annotation currently only applies to hypothesis - it needs to expand to realtime meetings such as zoom calls, emails, socials media comments and socials media chats in order to be complete - Until now, there has not been a medium with sufficient set of affordances to unleash the affordances potential in language itself - While digital media has existed and rapidly developed for the past 5 decades,     - employing and leveraging it to unleash the full potential of language itself has not ever been conceived of until the concept of Indyweb arrived - Indeed, we could make the claim that the indyweb is a foundational human technology on the same order as language itself because it completes language, revealing its empty ( shunyata) quality, thereby     - uniting it with the universe itself -  From the unlimited potential of the tacit,     - the limited forms of words emerge, both are 2 sides off the same nondual coin     - and unleashing the full , unrealized potential of language - It is the provenance aspect of the indyweb that provides an automatic trail of all our learning journey, making both the     - individual and     - intertwingled collective evolution of ideas available as records for. timebinding posterity

• when we feel in a good state of health and wellbeing and absent of any disease
  • we feel when everything is within harmony in our temporary state of being alive
• Any disease shows us how the diseases-free state is so fragilely constructed
• disease-free is an and condition of many subsystems working together harmoniously -aspectualizing is creating
  • a perspective,
  • a word
  • an idea
• the greatest freedom of afforded when we are free of all perspectives
  • for that is when a new perspective can emerge
• When we cling to words and ideas, we cling to perspectives and aspects of the whole
• The teaching of one taste is the highest and most subtle teaching - equal taste - and easiest to be misinterpreted
  • because we are anchored in the world of many different tastes and of measurement and scale,
    • where some things are greater than others on our scale
• Bayo Akomolafe does some language construction - conlangering on his LinkedIn post on the derivation of the word "apolief" from "belief"

eLife Assessment

Some delayed rectifier currents in neurons are formed by the combination of Kv2 and silent subunits, KvS. However, we lack the tools to identify these heteromeric channels in vivo. In this important study by the Sack group, the authors identify a pharmacological tool that can reveal the presence of KvS subunits as components of the delayed rectifier potassium currents in selected neurons. The experimental evidence presented in the manuscript is compelling and represents a significant advance that should be of interest to a wide community of neuroscientists and channel physiologists.

eLife Assessment

The study presents compelling evidence that the melanocortin system originating in the arcuate nucleus of the hypothalamus plays a crucial role in puberty onset, representing a significant advance in our understanding of reproductive biology. The research employs innovative approaches and benefits from the combined expertise of two respected laboratories, enhancing the robustness of the findings. Given the potential impact on human health and the strength of the evidence presented, this fundamental work will likely influence the field substantially and may inform future clinical applications.

eLife Assessment

Combining experiments in microfluidic devices and computer simulation, this study provides a valuable analysis of the relevant parameters that determine the motility of (multicellular) magnetotactic bacteria in sediment-like environments. The study presents convincing evidence that there is an optimum in the biological parameters for motile life under such conditions.

eLife Assessment

This manuscript reports findings of fundamental significance on how bacteria might load helicase for DNA replication when normal DnaA-based loading pathway is defective. It provides convincing genetic and biochemical evidence that helicase loading at the E. coli oriC is not (as previously assumed) exclusively performed by the DnaA initiator protein but can also be executed by PriC (whether this occurs specifically at oriC has not been addressed in vivo). This is a significant step forward in our understanding of bacterial replication initiation.

eLife Assessment

This manuscript presents a fundamental advance in our understanding of nuclear receptor pharmacology by expanding on previous work demonstrating dual ligand occupancy in the peroxisome proliferator-activated receptor-gamma (PPARγ). Using a compelling combination of biophysical, structural, and cellular approaches, the authors show that covalent inhibitors with inverse agonist activities modulate receptor conformation to permit co-binding with additional ligands, leading to a finely tuned transcriptional response. The data support a model of proximal, bi-directional allostery that challenges traditional views of nuclear receptor regulation. These findings will be of broad interest to researchers in structural biology, transcriptional control, and drug discovery.

eLife Assessment

This important paper shows that the moment at which rats acquire an appetitive Pavlovian conditioned response is determined by the ratio of the reward rate during the Pavlovian cue to the overall reward rate in the context. The exact quantitative relationship between reward rate during the Pavlovian cue, reward rate in the context and acquisition of conditioned responding is very similar to that observed over 40 years ago in a pigeon auto-shaping procedure. This similarity suggests that the mathematical laws that determine acquisition of conditioned responding in different species may be perfectly general. Claims about the processes underlying learning and conditional behavior in rats are supported by convincing evidence. There is solid evidence for the claim that the same relationship describes data from pigeons by Gibbon and Balsam (1981) and the rats in this study. This study will be of interest to those interested in learning, motivated behavior, and related disease states and brain mechanisms.

eLife Assessment

This valuable study presents an analysis of evolutionary conservation in intrinsically disordered regions, identified as key drivers of phase separation, leveraging a protein language model. The strength of evidence is potentially compelling, but a clearer justification of the methods and analyses is needed to fully support the main claims.

eLife Assessment

In this valuable study, the authors demonstrate that TCF7L2 plays a role in the pathogenesis of cachexia in a mouse model of GI cancer. The results are solid, although future studies will need further mechanistic analyses. These data will be interesting to cancer biologists, especially those trying to understand late-stage complications such as cachexia and wasting, a major cause of cancer morbidity and mortality.

eLife Assessment

This is a fundamental discovery revealing two independent IFNγ-induced pathways that restrict bacterial motility: one GBP1-dependent and the other GVIN1-dependent. The findings are supported by compelling evidence. While the paper is already very strong, there are a few points that could be addressed editorially or through the addition of a few key experiments.

eLife Assessment

This study has fundamental findings that support the potential application of exogenous stem cell therapy as a viable therapeutic option for the management of intraocular pressure (IOP) and to increase outflow facility. The evidence supporting the clinical application of stem cells is compelling, using a combination of established in vivo and ex vivo experimental techniques. The work will be of interest to both basic stem cell biologists and clinical glaucoma specialists.

eLife Assessment

This important work combines self-report, neural and physiology data to examine the efficacy and mechanisms of counter conditioning versus extinction in reducing re-emergence of conditioned threat responses and show that this appears to rely on the nucleus accumbens rather than the ventromedial prefrontal cortex. These findings are supported by convincing evidence, though some areas could benefit from a few targeted refinements. The findings will be of interest to researchers across multiple subfields, including neuroscientists, cognitive theory researchers, and clinicians, particularly those with an interest in clinical applications in trauma therapies.

eLife Assessment

This study presents valuable findings on the relative cerebral blood volume of non-human primates that move us closer to uncovering the functional and architectonic principles that govern the interplay between neuronal and vascular networks. The evidence of areal variations and of vessel counting and laminar analysis is solid. The lack of a direct comparison of their approach against better-established MRI-based methods for measuring hemodynamics and vascular structure somewhat weakens the evidence provided in the current paper version, but the current work is an significant step forward. The work will be of interest to NHP imaging scientists.

eLife Assessment

This study explores how heterozygosity for specific neurodevelopmental disorder-associated TRIO variants affects brain function in mice. The authors conducted thorough analyses on mouse lines harboring TRIO-variants associated with autism spectrum disorder, schizophrenia, and bipolar disorder, and the results provide compelling evidence demonstrating unique alterations of each variant in synaptic functions and behavior. These findings highlight a fundamental aspect of TRIO variants contributing to brain functions and neuropsychiatric disorders.

eLife Assessment

This valuable study confirms the association between the human leukocyte antigen (HLA)-II region and tuberculosis (TB) susceptibility in genetically admixed South African populations, specifically identifying a near-genome-wide significant association in the HLA-DPB1 gene, which originates from KhoeSan ancestry. The evidence supporting the association between the HLA-II region and TB susceptibility is solid, and the work will be of interest to those studying the genetic basis of tuberculosis susceptibility/infection resistance.

eLife Assessment

This study exploring the role of TRPV1 signaling in recruiting macrophages and promoting angiogenesis during tympanic membrane wound healing presents useful findings. However, the strength of evidence supporting the central claims is incomplete, as the mechanistic links between TRPV1 activation and immune cell recruitment remain largely correlative and rely heavily on previously published datasets without sufficient functional validation. The work will be of interest to researchers studying wound healing and sensory-immune interactions, though substantial revisions are needed to support its broader significance.

eLife Assessment

This high-N, multi-task study offers a comprehensive examination of rhythmicity in behavioral performance during listening. It presents a valuable set of findings that reveal task- and ear-specific effects, challenging the notion of a universal rhythmicity in auditory perception. While the evidence is solid, the study would benefit from a stronger conceptual framework to contextualize and explain the observed patterns. Nonetheless, the work is likely to be of significant interest to behavioral and cognitive scientists focused on perception and neural oscillations.

eLife Assessment

This study provides valuable insights into the evolution of pesticide resistance, demonstrating that resistance can arise rapidly and repeatedly, which complements prior work on parallel evolution across species. The combination of extensive temporal sampling in the field, experimental evolution, and genomics makes for convincing findings. The authors are to be commended for acknowledging the main limitations of their study in the Discussion. Framing the work in a broader context of resistance beyond arthropod pests would further increase the appeal of the study, which is of relevance for both agronomic practitioners and evolutionary biologists.

eLife Assessment

This important study demonstrates that lipid binding can regulate the dimerization state of the SARS-CoV2 Orf9b protein. The data from biophysical and cellular experiments, along with mathematical modeling, are convincing. However, this study can further benefit from more rigorous quantitative analyses and from resolving the role of dimerization in viral infection and host innate responses. This paper is broadly relevant to those studying coupled equilibria across all aspects of biology.

eLife Assessment

Despite the conserved anti-inflammatory activity in birds, whether IL-10 also controls avian intestinal homeostasis remains unclear. Generating genetic knockouts, Meunier et al. firmly established that a complete lack of IL-10 strengthened immunity against enteric bacteria in chickens, while also aggravating infection-inflicted tissue damage upon parasite infection. The findings presented in this manuscript are valuable, and the strength of evidence is convincing; however, it is advised that the deficiencies and weaknesses pointed out by all the reviewers are meticulously addressed.

eLife Assessment

This work provides fundamental findings on how the mouse barrel cortex connects to the dorsolateral striatum, uncovering that inputs from discrete whisker cortical columns are convergent and SPN-specific, but topographically organized at the population level. The evidence supporting this claim is compelling, demonstrating that SPNs uniquely integrate sparse input from variable stretches across the barrel cortex. The study would be of interest to basal ganglia and sensory-motor integration researchers.

eLife Assessment

In this study, the authors investigated whether HIV-1 cell-to-cell transmission activates the CARD8 inflammasome in macrophages. The data convincingly support the idea that CARD8 is activated by the viral protease, promoting inflammation. The study's significance is further enhanced by including time-course analyses in primary T cells and macrophages and provides valuable insights into the role of CARD8 in HIV-induced inflammation.

eLife Assessment

This paper addresses a valuable research question on the heritability of the brain's response to movie watching, given various parameters such as regional spatial hyperalignment and BOLD frequency bands. The topic of this paper would be 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. However, the current findings provide incomplete support for the conclusions, since several key methodological concerns need to be addressed to ensure the validity of the analyses and results.

eLife Assessment

The authors report that chemogenetic methods targeting the ventral cervical spinal cord can be used to increase phrenic inspiratory motor output and subsequent diaphragm EMG activity and ventilation in rodents. These findings are important because they are a necessary first step towards using chemogenetic methods to drive inspiratory activity in disorders in which motor neurons are compromised, such as spinal injury and degenerative disease. The data are convincing, with rigorous assessments of phrenic inspiratory activity and its ability to drive the diaphragm and subsequent ventilation, as well as assessments of DREADD expression.

eLife Assessment

This important study uses single-cell transcriptomics to analyze syncytiotrophoblasts in two trophoblast organoid models compared to primary placental tissue, providing compelling insights into syncytialization and highlighting the utility of organoid models in placental research. It also serves as an invaluable resource for the field.

eLife Assessment

This manuscript characterizes a mutated clone of RNA polymerase I in yeast, referred to as SuperPol, to understand the mechanisms of RNA polymerase I elongation and termination. The authors present solid evidence that SuperPol has higher processivity during transcription elongation than wild-type RNA polymerase I. Notably, the study provides evidence that the transcriptional pause of RNA polymerase I may be a therapeutic vulnerability in cancers. Overall, the characterization of this RNA pol I is important as it provides insights into the regulation of ribosomal RNA transcription and its potential application in cancer pharmacology.

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

eLife Assessment

This valuable paper analyses the role of endogenous CNS hemoglobin in protecting mitochondrial homeostasis in hypoxic conditions. The work is solid and opens the doors to future work in this field. However, it leaves many questions open regarding CNS-specific ischemia/hypoxia that should be considered in future work. In particular, a whole-body hypoxia model may liberate exosomes from other hypoxic organs, which may contribute to the protective effect. Overall, this work has the potential to be of broad interest to the neuroscience and hypoxia communities.

eLife Assessment

This important study highlights the essential role of AARS2 in safeguarding cardiomyocytes against ischemic stress by modulating energy metabolism towards glycolysis via PKM2. This mechanism unveils a promising new therapeutic target for treating myocardial infarction. Convincing findings are underpinned by a comprehensive dataset, including cardiomyocyte-specific genetic modifications, functional assays, and ribosome profiling, all collectively providing strong evidence for the critical involvement of the AARS2-PKM2 signalling pathway in cardiac protection.

eLife Assessment

Manley and Vaziri introduce an important new method for brain-wide imaging of cellular activity in zebrafish and provide evidence for the applicability of this technique. They use this method to explore the question of how neural variability gives rise to variability in behavior. The analyses used are mostly convincing, although questions regarding spatial and temporal imaging resolution and their effects on the study's interpretations and conclusions suggest only partial support for some of the central results.

eLife Assessment

This manuscript describes methods and software, called SMARTR, to map neuronal networks using markers of neuronal activity. They illustrate their approach using tissue from mice that have undergone behavioral tasks. The reviewers considered the study important to the field and compelling in that the methods and analyses were an advance over current tools.

eLife Assessment

This valuable study provides insights into a key question in comparative neuroanatomy and development. The authors provide evidence of the role for a particular micro-RNA in regulating the development of key transcription factors that control forebrain development. The study rests on clear but incomplete results.

eLife Assessment

This study investigates the neural basis of causal inference of illness, suggesting that it relies on semantic networks specific to living things in the absence of a generalized representation of causal inference across domains. The main hypothesis is compelling, and is supported by solid methods and data analysis. Overall, the findings make a valuable contribution to understanding the role of domain-specific semantic networks, particularly the precuneus, in implicit causal inference about illness.

eLife Assessment

This important work investigates how orientation signals detected in higher brain areas may be transformed into motor responses in behaving animals. The authors characterize two types of descending neurons (DNs) that connect the brain to motor units and are involved in different aspects of turning control. They further show that orientation signals act by preferentially increasing relative stimulation onto left- or right-turn-inducing DNs. These compelling results, together with the independent work that they have inspired, represent significant progress in our understanding of mechanisms of animal navigation.

eLife Assessment

This study represents valuable findings on the asymmetric connectivity pattern of two different types of CA3 pyramidal cell types showing that while athorny cells receive strong inputs from all other cell types, thorny cells receive weaker inputs from athorny neurons. Computational modeling is used to evaluate the impact of this connectivity scheme on the sequential activation of different cell types during sharp wave ripples. The evidence combining experimental and computational modelling approaches convincingly supports the authors' claims regarding the network mechanisms underlying the temporal sequences of neuronal activity during sharp-waves.

eLife Assessment

This important study details changes in the brain functional connectivity in a longitudinal cohort of Gambian children assessed outside a lab setup with functional near-infrared spectroscopy (fNIRS) from age 5 to 24 months, in relation to early physical growth and cognitive flexibility capacities at preschool age. While evidence supporting conclusions on the evolution of brain connectivity are solid, the statistical power was insufficient to perform proper analyses of longitudinal data and link the connectivity trajectories with early adverse conditions such as undernutrition and later cognitive development. This study will be of significant interest to neuroscientists, psychologists and neuroimaging researchers working on infant development in relation to environmental factors.

eLife Assessment

This work defines the response dynamics in forepaw-related cortical circuits of S1 and M1 following stimulation of peripheral mechanoreceptors in the mouse. In this revised version, the authors have addressed the reviewers' prior concerns. The results are convincing and present a valuable comparison to previously published work. This study has implications for understanding the interactions between primary somatosensory and motor cortex, required for active sensing, and will be of interest to scientists seeking to better understand the functions of somatosensory and motor circuits.

eLife Assessment

The findings presented in this manuscript are fundamental, as they uncover MYL3, a member of the myosin family, as a potential entry receptor and therapeutic target for a virus that poses a major threat to aquaculture. The evidence is convincing, supported by robust in vitro and in vivo data. However, additional studies investigating the presence of MYL3 in NNV target tissues would further strengthen the authors' conclusions.

eLife Assessment

The microbiome field is constantly providing insight on various health-related properties elicited by the commensals that inhabit their mammalian hosts. Harnessing the potential of these commensals for knowledge about host-microbe interactions, as well as properties with therapeutic implications, will likely remain a fruitful field for decades to come. In this valuable study, Wang et al use various methods, encompassing classic microbiology, genomics, chemical biology, and immunology, to identify a potent probiotic strain that protects nematode and murine hosts from Salmonella enterica infection. The authors provide compelling evidence identifying gut metabolites that are correlated with protection, and show that a single metabolite can recapitulate the effects of probiotic administration.

eLife Assessment

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

eLife Assessment

The open-source software Chromas tracks and analyses cephalopod chromatophore dynamics. The software features a user-friendly interface alongside detailed instructions for its application, with compelling exemplary applications to two widely divergent cephalopod species, a squid and a cuttlefish, over time periods large enough to encompass new chromatophore development among existing ones. It demonstrates accurate tracking of the position and identity of each chromatophore. The software and methods outlined therein will become an important tool for scientists tracking dynamic signaling in animals.

eLife Assessment

This important resource paper presents a library of cell-type-specific genetic driver lines that label wing-related motor and premotor neurons in the ventral nerve cord of the fruit fly, Drosophila. The toolkit is systematically validated with compelling anatomical and behavioral evidence and will provide a resource for future studies of Drosophila flight and courtship.

eLife Assessment

This useful study explores the role of RAP2A in asymmetric cell division (ACD) regulation in glioblastoma stem cells (GSCs), drawing parallels to Drosophila ACD mechanisms and proposing that an imbalance toward symmetric divisions drives tumor progression. While findings on RAP2A's role in GSC expansion are promising, the study is nevertheless incomplete. Limitations include the lack of comprehensive GBM subtype analysis, insufficient mechanistic validation, and reliance on neurosphere models without in vivo confirmation. Addressing those gaps is necessary to substantiate the study's claims.

eLife Assessment

This important and well-executed study describes how deleting the autism spectrum disorder risk gene CNTNAP2 in mice increases dorsolateral striatal projection neuron excitability and promotes repetitive behaviors and cognitive inflexibility. The evidence supporting this claim is convincing. The study provides a potential cellular explanation for the repetitive and inflexible behavior in Cntnap2 knockout mice and CNTNAP2 disorder in humans, which would interest both basic and translational neuroscientists.

eLife Assessment

This important study identified a molecular mechanism linking diabetes to AD risk and the data presented are convincing. The authors investigated the role of kallistatin in metabolic abnormalities associated with AD and identified that Kallistatin is a key player that mediates Aβ accumulation and tau hyperphosphorylation in AD. This manuscript provides novel insights into the pathogenesis of AD, indicating that the hypolipidemic drug fenofibrate attenuates AD-like pathology in Kallistatin transgenic mice.

eLife Assessment

This study presents valuable research comparing three different species of extant cartilaginous fishes and describes new data on ratfish. The methods are convincing, although there remains a concern about the claim in the title about paedomorphosis. This study will be of interest to skeletal biologists working on the evolution of chondrichthyan skeletons.

eLife Assessment

This important contribution to the field evaluated the function of the cytoskeletal protein ABBA in mediating key aspects of mitosis of neuronal precursor cells. The authors provide compelling evidence that ABBA interactions with its signaling partners is related to the development of at least some cases of microcephaly-a developmental anomaly associated with intellectual disability and other neurological findings.

eLife Assessment

This important study uses C. elegans to provide new insights into the role of the conserved protein FLWR-1/Flower in synaptic transmission. Employing a variety of techniques, including calcium imaging, ultrastructural analysis, and electrophysiology, the paper provides convincing evidence that challenges some previous thinking about FLWR-1 function. This work will be of particular interest to neuroscientists studying synaptic physiology and plasticity.