eLife Assessment

This is a valuable study of the effects of selective or broadband amyloid deposition in medial septum (MS) cholinergic neurons on neuropathology, cognition, sleep, and hyperexcitability in aging mice carrying risk factors for Alzheimer's disease (AD). The investigation is still incomplete, with some weaknesses related to conceptualization and methodology that need to be addressed.

eLife Assessment

This important study investigates how viral macrodomains in dual-host viruses functionally contribute to their infection in the vector, which was previously understudied. The findings that chikungunya virus (CHIKV) macrodomain mutants have unique impacts on virus replication in mammalian cells and in live mosquitoes are convincing and significant; however, the study can be strengthened by further investigating the role of ADP-ribose binding and potential other compensatory mutations. The work will be of interest to virologists and biologists who study macrodomains and ADP-ribosylation.

eLife Assessment

This important study identifies and characterizes a set of amino acid states that can rescue protein function in the presence of substantially deleterious mutations. Some of these super-compensatory substitutions also confer substantial mutational robustness, with broader implications for understanding epistasis, protein evolution, and protein engineering. The evidence is convincing, supported by a creative reanalysis of a large deep-mutational-scanning dataset, statistically rigorous treatment of anticipated error rates, experimental validation, and analyses of additional proteins, although clearer presentation and deeper investigation of the evolutionary implications and structural mechanisms would further strengthen the study.

eLife Assessment

This important study investigated whether the adoption of different explicit strategies influences implicit recalibration during visuomotor adaptation. Through a series of increasingly controlled experiments, the authors demonstrated that implicit recalibration is relatively insensitive to the specific type of explicit strategy employed but is influenced by the variability of strategic motor plans. However, the evidence supporting these conclusions is currently incomplete. The findings will be of interest to cognitive scientists studying motor control and its relationship to higher-level cognitive processes, provided that the key claims are supported by more rigorous analyses and experimental approaches.

eLife Assessment

This study presents valuable findings implicating Xkr and its newly identified binding partners in regulating the exposure of apoptotic signal for phagocytosis, suggesting that Xkr might facilitate phosphatidylserine transfer at the ER-plasma membrane contact sites. However, several conclusions, including caspase-independent activity of Xkr and its role at the ER-PM contact sites, are not well supported by experimental data. Furthermore, some key controls are missing, and in numerous places the authors' discussion has extended far beyond what the data support. The findings presented are currently incomplete and do not fully support key mechanistic claims of the study.

eLife Assessment

Shin et al present significant new observations highlighting a novel oscillatory window during REM sleep that impacts neuronal dynamics and cross-regional communication and could have implications for our understanding of sleep's role in memory consolidation. This important study identifies and characterizes high-frequency oscillations (HFOs) in the prefrontal cortex (PFC) during REM sleep, reporting their temporal dynamics and coordination with hippocampal area CA1, and an intriguing dissociation between activation of CA1 neurons during REM HFOs and non-REM ripples that may impact sleep-dependent firing rate decreases. The main claims are supported with convincing evidence including an impressive range of analyses.

eLife Assessment

This study presents a useful combined analysis of human behavior, pupillometry and EEG measures to probe differences in ambiguity assessment between individuals during value-based decision-making. Using computational models, the authors aim to test for distinct groups of participants that differ in the relationship between evidence accumulation, arousal, and neural decision-making computations. However, at present, the evidence for group differences in the physiological, neural, and behavioral profile of decision-making under uncertainty is incomplete, lacking an appropriate statistical test for group differences, and a more complete assessment of the modeling results on evidence accumulation in decision-making in this study is required to robustly characterize and interpret the results.

eLife Assessment

This study presents valuable evidence that activating a lysosomal signaling pathway lowers blood glucose in diabetic mice, pointing to a potential new strategy for treating metabolic disease. However, the evidence for the proposed mechanism is inadequate: the glucose transporter's movement and glucose uptake were not measured in the physiologically relevant tissue, and the measurement that was performed used an unconventional technique. As a result, whether this transporter-dependent pathway explains the glucose-lowering effect has not yet been established.

eLife Assessment

This valuable study advances our understanding of the physiological conditions that promote the formation of mitochondrial-derived compartments (MDCs). The genetically amenable yeast system allowed the authors to generate convincing data showing the rapid formation of MDCs under physiologically relevant conditions where the mitochondrial proteome needs to be expanded during metabolic remodeling. The identification of a key role for a yeast AMPK-related protein called Snf1 will be of interest for cell biologists and biochemists.

eLife Assessment

This important study uses dual-color super-resolution microscopy, quantitative clustering analyses and simulations, as well as biochemical approaches to investigate the nanoscale organization of mucins and trans-sialidases on the surface of Trypanosoma cruzi, the causative agent of Chagas disease. The evidence supporting a non-uniform distribution of these molecules into segregated nanoclusters and a more ordered non-clustered population is solid. Overall, this work provides a generalizable analytical framework that can help understand how parasite surface proteins are spatially organized. The main remaining limitations concern the mechanistic basis of the proposed organization and the need to exclude possible effects of sample preparation before fixation.

eLife Assessment

A regulated cell death pathway that intentionally causes ferroptosis has not been previously described. The authors describe a useful finding that the ferroptosis inducers ML162 and erastin induce caspase-5-mediated cleavage of GSDME in mesenchymal-like ovarian cancer cells, resulting in pore formation. The data supporting the main claims are incomplete. This work will be of interest to researchers who study regulated cell death.

eLife Assessment

This study presents an important empirical analysis of the acoustic space of vocal repertoires across primates and humans, providing new data that challenge the widely held hypothesis that the expansion of the human vocal space, driven by modifications of the vocal tract, was a key prerequisite for the evolution of spoken language. The evidence is convincing in its technical implementation and acoustic measurements, offering helpful comparative insights into voiced vocalizations. However, the theoretical framing and interpretation would benefit from further discussion.

eLife Assessment

The ability to measure autophagic flux in vivo in response to physiological stresses remains a challenge for investigators in the field; the novel mouse model present in this work is significant and should prove valuable to investigators in addressing shortcomings of existing models. In addition, the development of the microplate reader approach to permit semi-high-throughput analysis of samples is convincing and a significant advance. The application of these approaches to measuring autophagy in multiple tissues is appreciated but raises some questions that need to be answered and highlighted, including what new biological insight has been generated for tissues under study, how overall autophagy versus rates of flux are determined, and how the sex of the animal affects outcomes. The neuronal populations under study should be reassessed.

eLife Assessment

This manuscript presents valuable experimental results describing the localisation and regulation of casein kinase CK1δ during the cell cycle. During the G2 phase of the cell cycle, the autophosphorylation of the C-terminal tail stabilises and inhibits the kinase which might protect CK1δ in the subsequent G1 phase. The results may be of interest to researchers working on casein kinase function and regulation but due to lack of some controls remain incomplete.

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

eLife Assessment

This important study identifies a non-canonical essential role for acyl carrier protein in maintaining apicoplast metabolism and blood-stage survival in Plasmodium falciparum. The main conclusions are compelling, and supported by strong genetic and biochemical evidence, while function of fatty acid synthesis pathways in low-lipid conditions will require future studies to fully resolve. The work provides novel mechanistic insight into ACP-mediated stabilization of pyruvate kinase II and will be of broad interest to the malaria and apicoplast biology communities.

eLife Assessment

This important work identifies phlda2 as a specific marker for primordial cardiomyocytes in the adult zebrafish heart and demonstrates their essential role in myocardial morphogenesis and coronary vascularization, but not in heart regeneration. The conclusions are well supported by single-cell transcriptomics, new genetic tools, and cell-specific ablation experiments. The revised version strengthens these findings with analyses of the epicardium, long-term time points showing that the developmental defects persist, and a control confirming that loss of primordial cardiomyocytes alone does not trigger a regenerative response. Overall, the evidence is solid and provides insight into the difference between developmental and regenerative cardiac programs, and this work will be of interest for those studying cardiac development and regeneration.

eLife Assessment

This important study identifies PRRT2 as an auxiliary regulator of Nav channel slow inactivation in vitro and in vivo, demonstrating 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

The authors describe the results of a longitudinal study of pertussis infection in mother/infant dyads in Lusaka, Zambia. This work represents an important contribution to our understanding of the global burden of pertussis. The evidence presented is compelling, with strengths including routine sampling irrespective of symptoms and rigorous qPCR methodology. The study is a significant and much-needed contribution, which sheds light on an often-overlooked dimension of pertussis transmission and opens avenues for future research and policy consideration.

eLife Assessment

This study provides a useful single-cell atlas of the Clytia hemisphaerica planula, complemented by an updated medusa dataset, ultrastructural analyses and in situ validation of expression patterns. The cross-stage comparison and cluster-similarity framework offer a promising basis for investigating cellular diversification across the life cycle. The evidence has the potential to be convincing, but is currently incomplete due to documentation deficits and insufficient cross-referencing with prior work. It should be relatively easy to address these issues, which should make this a valued resource for cnidarian researchers and for colleagues studying cell-type evolution.

eLife Assessment

This study offers valuable insights into the genetic and evolutionary basis of the starvation response by confirming the hypothesis about the mito-nuclear etiology of this trait. The level of evidence is currently incomplete but could be improved if controls were designed better, particularly by including analysis of variation in the initial, common population prior to all treatments. Overall, this work would be interesting to a broad audience, beyond the Drosophila community, if the analysis of the candidate genes against Human ortholog loci were to be conducted with more careful controls.

eLife Assessment

This valuable study combines a chromosome-level genome assembly with population resequencing and demographic modelling to reassess the status of the Formosan landlocked salmon, a critically endangered salmonid at the southern edge of the genus. The assembly and the evidence for extensive lineage-specific chromosomal fusions are genuinely well done, and the discovery of an overlooked, genetically distinct population in Hehuan Creek is sound and of clear management relevance. Evidence for the headline claims is incomplete: species rank is asserted but nowhere argued, and gene flow is excluded using a coalescent model that contains no migration parameter. Support for the population-viability conclusions is also not complete, as the demographic mechanisms invoked in the discussion are not borne out by the supplementary tables.

eLife Assessment

This important study combines cryo-EM, biochemical, and cell-based assays to examine how Gβγ interacts with and potentiates PLCβ3. The authors present evidence for multiple Gβγ interaction surfaces and argue that Gβγ primarily enhances PLCβ3 activity after membrane recruitment rather than serving mainly as a membrane-recruitment factor. Following additional experimental support, the evidence in support of their conclusions is convincing.

eLife Assessment

This fundamental work uncovers an unexpected lysosomal function for NINJ2 and links it to ferroptosis and cancer biology. The evidence supporting the conclusions appears to be convincing. This work will be of general interest to the community of ferroptosis and cancer biology.

eLife Assessment

This valuable study uses genetic, behavioural, neuronal activity and cell-based assays to show that the Drosophila ionotropic receptor IR20a contributes to the detection of arginine and low-sodium salt, and suggests that peripheral receptor combinations may help integrate these nutrient cues. The evidence for a role for IR20a and associated co-receptors in these responses is solid, but the evidence that distinct receptor assemblies mediate receptor-level multimodal integration is incomplete, as this central model is inferred from functional data and leaves some discrepancies between behaviour, physiology and prior work unresolved. The study will be of interest to sensory neuroscientists and chemosensory biologists.

eLife Assessment

This Review delineates postmenopausal age-related lobular involution (ARLI) in the breast that remains only partially resolved. In contrast to the conventional view of persistent lobules as passive residual structures, this work defines them as an actively maintained senescence-immune reserve niche. Inclusion of operational definitions for the reserve state in human breast tissue would strengthen the article. The work will be of interest to scientists working in the fields of breast disorders.

eLife Assessment

This important study provides new insights into the regulation of cell organization and division in Trypanosoma brucei through the phosphorylation-dependent control of a kinesin motor protein by a polo-like kinase. The authors present convincing evidence, combining rigorous biochemical, cell biological, and imaging analyses, demonstrating that phosphorylation modulates kinesin localization and function, thereby influencing cellular organization and cytokinesis. The findings advance our understanding of the molecular mechanisms governing trypanosome cell division and will be of broad interest to researchers studying trypanosomes, cytoskeletal regulation, and eukaryotic cell division.

eLife Assessment

This study provides an important contribution to retinal regeneration research by using overexpression of pro-neural factors to reprogram fetal human RPE cells into retinal neurons. The authors provide solid evidence of fetal RPE reprogramming into neural and photoreceptor-like states using scRNA-seq and imaging validation; however, there are concerns regarding comparisons between the effectiveness of different combinatorial transcription factor codes.

eLife Assessment

This important study presents an ultrastructural atlas of extracellular vesicles and non-vesicular particles in Drosophila olfactory sensilla, using cryofixation-based serial block-face electron microscopy to catalogue roughly 7,800 particles across four antennal regions. The evidence is compelling: the cryofixation minimizes fixation artifacts, and the rigorous, well-validated methodology and morphometric analyses provide strong support for the structural classifications and spatial distributions, though some conclusions require moderation or additional evidence. The work provides a potentially foundational resource for researchers studying extracellular-particle signaling in sensory organs.

eLife Assessment

This study addresses a valuable question with implications for the development of EEG-based neurofeedback interventions for pain. However, the strength of evidence is incomplete because the principal conclusions rely on post hoc responder analyses and methodological ambiguities that weaken the support for the claimed causal relationship between gamma modulation and pain reduction.

eLife Assessment

This study provides important evidence that crickets use bat-associated odors as cues of predation risk, extending the classic bat-insect arms race beyond its traditional acoustic framework. The authors combine fecal metabarcoding, behavioral assays, electrophysiology, chemical analyses, and field observations to show that Loxoblemmus equestris avoids the odor of the insectivorous bat Scotophilus kuhlii, and that synthetic limonene can elicit antennal responses, avoidance in the laboratory, and reduced calling activity in the field. Together, the multidisciplinary results provide a coherent and convincing chain of evidence for an olfactory component of predator detection in this bat-insect system. The work will be of broad interest to researchers in sensory ecology, chemical ecology, predator-prey interactions, and bat-insect coevolution.

eLife Assessment

This important study systematically investigates repeat expansion in the plant Arabidopsis thaliana using a new k-mer-based method, expanding on previous smaller studies, to comprehensively identify cis- and trans-acting loci associated with repeat dynamics. The approach is methodologically sound, and the exploration of different k-mer lengths and use of a more complete reference assembly strengthen confidence in the analysis while clarifying its limitations and the method is broadly applicable to large-scale short-read datasets for assessing copy-number variation and genomic repeat content. The findings are convincing in their scope and novelty for A. thaliana. It will be of interest to learn in future how the approach generalizes to species with substantially greater or lower repeat content.

eLife Assessment

This important study presents an innovative combination of experimental evolution and CRISPR screening to study the genetic basis of a polygenic trait, resistance against octanoic acid in Drosophila. The evidence supporting the authors claims is solid. The work will be of interest to the Drosophila community and researchers interested in functional testing of polygenic traits.

eLife Assessment

This study presents valuable findings on the functional consequences of nuclear envelope rupture caused by the depletion of nuclear pore complex subunits on the behaviour and organisation of chromosomes during mitosis in C. elegans embryos. The experiments are generally well-designed and executed; however, the evidence for some of the main conclusions is incomplete. This work is of potential interest to cell biologists working on cell division.

eLife Assessment

This useful study employs an innovative chemoproteomic and multi-modal experimental approach to support VDAC2 as a key functional mediator of STX effects on mitochondrial bioenergetics. However, concerns remain regarding the physiological and disease relevance, including the reliance on cell lines, lack of loss-of-function validation, unresolved binding specificity, and limited justification for focusing on POMC neurons in the context of Alzheimer's disease. As a result, the evidence is incomplete for a link between VDAC2 and Alzheimer's pathogenesis, and aspects of the binding data raise alternative interpretations, including a potential role for other VDAC isoforms.

eLife Assessment

This revised study offers valuable insights into how nuclear export influences protein condensates and TDP-43 phase behaviour. The findings are solid and highlight several noteworthy observations for the field, such as RNA-dependent stabilisation of TDP-43 condensates and the inhibition of nuclear export in an ALS organoid model. The work suggests a possible mechanistic link between nuclear export and TDP-43 aggregation in ALS/FTD; however, the exact mechanistic connection remains unclear, as much of the evidence is based on indirect observations within sensitised model systems. Although the authors carefully acknowledge these limitations and moderate their conclusions, further validation in more physiologically relevant models will be necessary to demonstrate a direct causal role of nuclear export in regulating pathological TDP-43 aggregation.

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. The system's robustness is exhibited by its applicability to nanoluc, an ubiquitous protein and to more challenging proteins like vimentin and the active restriction endonuclease Bsal. The evidence is convincing and supports the main claims on efficiency backed up by investigations on the mechanisms. The paper will be of interest to scientists in cell and molecular biology, microbiology, biotechnology and protein synthesis.

eLife Assessment

This is an important study that comprehensively determines the consequences of DNMT3A mutations on human neuronal development in culture. The data derived from multiple different mutations in iPSC and hESC derived neurons and organoids are convincing and well controlled. This work will be of interest to researchers who study chromatin mechanisms of brain development and to those interested in DMNT3A mutations in Tatton-Brown-Rahman Syndrome.

eLife Assessment

This important work presents a novel computational framework for modeling macroscopic traveling waves in the mouse cortex by integrating open-source connectomic and transcriptomic data into a spiking network model. This approach allows the computational model to assign excitatory/inhibitory connections based on neurotransmitter profiles and extends simulations to the 3D domain. The authors present results that demonstrate how spatiotemporal dynamics such as slow oscillations (0.5-4 Hz) emerge and self-organize at the whole-brain scale. This study provides convincing initial insights into the structural basis of traveling waves at the whole-brain scale, and allows future links between connectome-driven spiking neural networks and whole-hemisphere imaging in the mouse.

eLife Assessment

This study shows that combining forced cell cycle re-entry with Rbpj deletion enhances Müller glia dedifferentiation and promotes their conversion into retinal neuron-like cells in the uninjured mouse retina. It provides a valuable strategy for improving Müller glia-mediated neurogenesis and advancing regenerative potential in the mammalian retina. Overall, the data are convincing. The authors have also addressed concerns regarding Müller glia function, cell survival, and the limitations of neuronal maturation and integration, further strengthening the conclusions of the study.

eLife Assessment

This study investigates the role of the Z-disc protein Zasp52 in Drosophila flight muscles and provides evidence that an intrinsically disordered region (IDR) helps to stabilize and promote the localization of the protein to the Z-disc. Overall, this represents an important study that provides insights into Z-disc function and maintenance. The data are convincing, supported by strong genetic evidence and behavioral tests, well-controlled experiments, and detailed statistical analyses. Characterization of a new actin-binding motif mutant and FRAP analysis further support the functional importance of the Zasp52 IDR.

eLife Assessment

This study reports important findings regarding social influence on charitable donations, showing that giving is shaped by the statistical properties of others' donations in a manner that can be captured by a reinforcement learning model. The evidence for the conclusions is solid, although the computational modelling could be better motivated and described, the individual differences analyses could be more robust, and some design choices could be better motivated. Overall, the core effect appears robust and is supported by multiple well-designed experiments, but the conclusions that rely upon computational modelling and individual differences may require further support.

eLife Assessment

In this important study, Lau et al. identify non-conserved nucleotides within the common binding motifs of BLIMP1 and IRF4 that provide a molecular mechanism for their distinct roles as crucial transcription factors during the antibody-secreting cell differentiation. The major strength of this manuscript is the solid and detailed characterization of human in vitro plasma cell differentiation. However, several overstatements exist, therefore requiring careful revision to improve the manuscript.

eLife Assessment

This important study shows that cave-adapted Astyanax mexicanus have shifted from avoiding alarm and decay odors to being attracted by them, alongside sex-specific responses to social odors. The evidence for the behavioral and heritability claims is convincing, supported by analyses of different cave populations and F2 hybrids, as well as starvation-induced plasticity experiments. Whole-brain pERK mapping offers suggestive mechanistic insight, although uncertainties in anatomical assignments and aspects of statistical and ethogram reporting temper the strength of the neurobiological conclusions. The work will be of interest to anyone working on the evolution of behavior.

eLife Assessment

Using sci-L3-Strand-seq, this study shows genome-wide, single-cell evidence that DSBs triggered by CRISPR/Cas9 are frequently resolved through sister chromatid exchange (SCE), which is undetectable with conventional whole-genome sequencing approaches. This important work provides helpful metrics quantifying the occurrence of SCE events at targeted and repetitive genomic loci that are of particular interest to those working in gene editing, DNA repair, genome instability, or repetitive genomic loci. However, the evidence supporting the proposed involvement of under-replicated region/replication-termination-zone resolution and TRAIP/URR-like pathways is currently incomplete and could be strengthened with an increased number of reciprocal daughter-cell pairs and by genetic or molecular perturbation, or alternatively, this can be addressed by changing the discussion.

eLife Assessment

This valuable study provides insights into the developmental regulation of the unusual form of holometabolous metamorphosis that occurs in the black soldier fly, in which a distinct prepupal stage is interposed between the final larval instar and pupation. This type of life history strategy is similar to what is seen in insects at the hemimetabolous-holometabolous boundary, but, given the phylogenetic position of dipterans, it is likely to be a derived trait. The combination of developmental characterization, gene expression profiling, and RNAi-mediated functional analyses provides solid evidence supporting the authors' conclusions and will be of interest to researchers studying insect development and the evolution of metamorphosis.

eLife Assessment

What can a neural network trained to imitate animal behavior tell us about biology? This valuable work uses deep reinforcement learning to train an artificial neural network to transform the dynamics of a recurrent neural network based on the C. elegans connectome into an adult Drosophila walking program in a physical model of the fly body, demonstrating that achieving plausible output dynamics does not in and of itself imply biologically meaningful simulation. Evidence for this basic claim is solid, but more extensive analyses, better methodological description, and a discussion of deeper challenges in the undertaking of biological brain modeling would strengthen the study. This result demands the attention of the practitioners of the growing field of connectome simulation for the purpose of gaining mechanistic understanding of nervous system function.

eLife Assessment

This study provides valuable insights into the role of the bile acid receptor TGR5 in regulating bone marrow adipose tissue. This revised manuscript has additional characterization of TGR5 expression in hematopoietic and stromal populations, and phenotypic differences observed between sexes, during aging, and under high-fat diet conditions. Although the scope of the study has expanded, the mechanism of how TGR5 in the microenvironment regulates hematopoietic recovery is still incomplete.

eLife Assessment

This important study partially fills the gap in the knowledge of olfaction at the level of the Anterior Olfactory Nucleus (AON) and Piriform Cortex with functional magnetic resonance imaging, electrophysiology, and modeling. The methods used are convincing. Some of the findings confirm ongoing hypotheses, such as the behavioral importance of AON for odor source discrimination, while other results shed light on the dynamics of the connection between the olfactory system and the rest of the brain. However, the lack of access to raw data hampers the assessment of data quality.

eLife Assessment

This valuable study addresses two debates about how confidence is computed: whether it continues the accumulation process that produced the initial choice or reflects a separate one, and whether that accumulation stops at a time limit or an evidence boundary. The evidence is solid, combining systematic model comparison with an independent neural marker of evidence accumulation to adjudicate between models that behaviour alone cannot separate. Support for the boundary-based stopping rule is stronger than for the single-process account, as the neural comparison is qualitative rather than quantified and the alternatives tested cover only a narrow range of plausible two-stage architectures. The work will be of interest to researchers studying decision-making and metacognition.

eLife Assessment

The work presented represents important new evidence linking the cascade of neural processes triggered by memory-based prediction errors. The study uses an impressive collection of approaches and methods to characterize and measure cognitive control, arousal, and memory changes as a function of memory-based violations. Analyses are technically sophisticated and rigorous and, taken together, provide solid evidence that there are multiple processes accompanying prediction errors, and that they differentially relate to successful encoding.

eLife Assessment

This valuable study uses the Cntnap2 mouse model of autism to investigate how reduced activity in the dorsal CA1 region of the hippocampus contributes to impaired temporal binding and memory flexibility. The authors combined trace conditioning and radial maze assays with fibre photometry, optogenetic rescue, and brain-wide c-Fos mapping to provide solid evidence that dorsal CA1 hypoactivity limits the retention of temporally separated associations and biases learning towards less flexible strategies. The work advances understanding of hippocampal contributions to cognitive alterations associated with autism and will be of broad interest to researchers studying memory, hippocampal function, and neurodevelopmental disorders.

eLife Assessment

This fundamental study reveals a new downstream mechanism that mediates mTOR's effect on lifespan in C. elegans. Using a combination of genetic, genomic, and functional analyses, the authors uncovered that a bile acid-like hormone, dafachronic acid (DA), acts downstream of mTOR to modulate lifespan. The reviewers found the evidence provided to be compelling.

eLife Assessment

This important study combines crystallographic fragment-based screening with fluorescence-polarization competition assays to demonstrate that the SARS-CoV-2 accessory protein ORF9b, and its interface with the mitochondrial import receptor TOM70, is accessible to small-molecule binding. This is a result with practical implications beyond coronavirus biology for efforts to restore interferon signalling and the antiviral response. The structural evidence is convincing, resting on an unusually large body of ligand-bound crystal structures whose fragment hotspots are independently corroborated by orthogonal biophysical approaches including fluorescence polarization and SPR. This work would benefit from additional information regarding the use of CHAI-1 and other attempts to determine the interactions between hit compounds and Tom70.

eLife Assessment

This important manuscript proposes a dual behavioral/computational approach to assess emotional regulation in humans. The authors present convincing evidence for the idea that emotional distancing (as routinely used in clinical interventions for e.g. mood and anxiety disorders) enhances emotional control.

Editors Assessment:

Here is a Data Release article sharing the reference genome of the Pacific herring (Clupea pallasii), a species with broad ecological, economic, and cultural importance. This specimen coming from the eastern Bering Sea which are genetically quite different from those from the Gulf of Alaska. This high-quality chromosome-scale reference was built from Hi-C and PacBio Hifi reads, creating a 795MB assembly anchoring to 26 chromosomes. There was initially a mixup with the data availability but after review this was resolved and all data is publicly available. This data allows study of cryptic diversity in Clupea and its evolutionary history in the subarctic.

This evaluation refers to version 1 of the preprint

eLife Assessment

This important study on multisensory learning examines the effect of integrating color vision and olfaction in the center for learning and memory (the mushroom body) in the fruit fly brain, and finds that memory performance is improved, with neurons otherwise selective for color being recruited into odor memories via interneuron interactions. The combination of carefully controlled behavioural experiments, neurogenetic manipulations of individual neurons and detailed analyses of synaptic connectivity in the fly brain connectome convincingly supports the findings. The circuit- and receptor-level demonstration of interactions across sensory modalities in memory performance will be of interest to the broader neuroscience field.

eLife Assessment

This valuable study provides key insights into the role of the G protein-coupled receptor GPR34 in an Alzheimer's disease (AD) model. Notably, its findings differ, at least in part, from those of previous studies, although the underlying reasons for these discrepancies are not investigated or discussed. The data show that GPR34 deficiency enhances the transcriptional disease-associated microglia signature in microglia and provide solid evidence that myelin is a GPR34 ligand, although the relevance of myelin engulfment in AD is unclear. This study would be of interest for neuro-immunologists and AD clinicians.

eLife Assessment

This is a fundamental study of individual variation and the contribution of learning to behavioural individuality. The experimental design of massively parallel behavioural phenotypes is outstanding and the conclusions are supported by a compelling and rigorous analysis across a large number of experiments in thousands of individuals across genotypes and conditions. The dataset further represents an advance in studying visual associative learning thanks to the ability to make longitudinal measurements of many behavioural decisions within the same animals. These results are a major contribution to the understanding of the sources of behavioural individuality.

eLife Assessment

This short report is an important study that visual acuity declines nonlinearly with cone dropout, while eye motion partially compensates by improving sampling from remaining cones. The method for experimentally simulating cone dropout is compelling, leveraging state-of-the-art imaging and testing in human subjects.

eLife Assessment

This important study provides evidence that plateau pikas, at moderate densities, can facilitate yak nutrition by suppressing a poisonous plant, offering a helpful perspective on reciprocal interactions between small mammal ecosystem engineers and large herbivores. The evidence is convincing, supported by a manipulative field experiment and appropriate measurements of intermediary ecological processes. The work will be of interest to ecologists, conservation biologists, and rangeland managers, particularly those studying grassland herbivore interactions and livestock management.

eLife Assessment

This important study provides new insights into the regulation of cell organization and division in Trypanosoma brucei through the phosphorylation-dependent control of a kinesin motor protein by a polo-like kinase. The authors present convincing evidence, combining rigorous biochemical, cell biological, and imaging analyses, demonstrating that phosphorylation modulates kinesin localization and function, thereby influencing cellular organization and cytokinesis. The findings advance our understanding of the molecular mechanisms governing trypanosome cell division and will be of broad interest to researchers studying trypanosomes, cytoskeletal regulation, and eukaryotic cell division.

eLife Assessment

This important study demonstrates that nutrient resorption efficiency in the widespread wetland grass Phragmites australis is largely canalized by phylogeographic lineage, ecotype and geographic origin, rather than responding plastically to short-term salt stress. The findings have implications beyond plant ecophysiology because they suggest that predictions of wetland nutrient cycling under increasing salinization should account for the genetic composition of plant populations. The evidence supporting the central conclusions is compelling, based on a well-designed common-garden experiment involving 110 genotypes, paired control and salinity treatments, and convergent metabolomic, ionomic and whole-plant evidence confirming that the treatment imposed substantial physiological stress. The interpretation is nevertheless limited to one growing season and a single, moderate salinity treatment, leaving open whether chronic, more severe or multigenerational exposure might induce plastic or transgenerational responses; further clarification of the relationships among phylogeographic lineage, ecotype and latitude, and a more cautious interpretation of the variance explained by latitude, would strengthen the manuscript.

eLife Assessment

This important study introduces an open-source software package that improves the computational efficiency of whole-brain modelling and facilitates individualised model fitting in large neuroimaging cohorts. The evidence is convincing for the main computational and practical claims, supported by evaluations across multiple optimisation strategies, speed benchmarks, and demonstrations using human neuroimaging data. Its modular design and documentation should make it a resource that is of value to researchers interested in scalable and individualised brain network modelling.

eLife Assessment

This is a valuable study addressing a debated question in brain repair research by testing whether NeuroD1 can convert brain immune cells into nerve cells using a virus-free genetic approach and live imaging. The solid evidence presented here supports that, under the conditions tested, NeuroD1-expressing cells do not become nerve cells and instead retain their original identity; however, some aspects of expression level, injury timing, and cell-type composition would benefit from further clarification. This work will be of interest to neuro-immunologists.

eLife Assessment

This study uses a technically challenging long-term in vivo recordings and computational modeling to investigate whether hawkmoth olfactory receptor neurons show circadian modulation of spontaneous firing. The study provides solid evidence that ORNs have a circadian pattern of spontaneous firing that is Orco-dependent and yet that Orco transcript abundance does express a circadian rhythmicity and that cAMP can modulate all Orco-dependent activity. Together with computational work, the work is valuable in proposing a provocative hypothesis that an Orco-centred post-translational feedback loop generates the circadian rhythm.

eLife Assessment

This fundamental work significantly advances our understanding of how contact-dependent antagonism enables keystone bacteria to establish and maintain their niche over time. The evidence obtained is convincing, supporting most of the conclusions drawn. This work will be of significant interest to the microbiome research community.

eLife Assessment

This study presents a valuable insight into the mechanism of action of With-No-lysine (K) kinases (WNK) in the insulin-dependent signaling in the context of learning and memory. The study uses solid methodological approaches that align with the current standards in the field. The revised manuscript, which includes diverse models ranging from mouse to cell systems assessed by a broad range of complementary techniques, convincingly argues that WNK signaling contributes to neuronal function in insulin-sensitive brain regions such as the hippocampus through its effects on GLUT4 trafficking.

eLife Assessment

This manuscript presents a valuable computational tool for identifying 3-5 gene regulatory network topologies capable of generating oscillatory dynamics. The application of Monte Carlo Tree Search to circuit design is novel and effectively expands the scale at which non-linear behaviours can be explored in silico. The efficiency of the proposed algorithm is convincing, and the work will be of interest to the systems and synthetic biology communities. While the generality of the identified circuit properties is constrained by the simplifying modelling assumptions and parameter choices, the methodological contribution represents a significant advance in the field.

eLife Assessment

This study reports the discovery of a new circuit mechanism for light-avoidance behavior in the marine annelid, Platynereis dumerilii. Using calcium imaging, molecular perturbations, behavioral measurements, and modeling, the authors provide compelling evidence that nitric oxide is released by postsynaptic neurons onto ciliary photoreceptors to prolong and enhance their response to ultraviolet light. The fundamental new role of nitric oxide described in this study may be conserved across animal phyla and thus will be of broad interests to neuroscientists and neuroendocrinologists.

eLife Assessment

This manuscript applies a theoretical analysis to two published datasets on yeast and bacterial evolution to compare different ways of quantifying fitness. It makes an important advance by clarifying how discrepancies can arise by using different approaches and provides recommendations for best practices. Overall, this is an impressive and highly beneficial study that is based on convincing evidence and has the potential of setting standards in this rapidly growing field.

eLife Assessment

The authors ask whether a simple whole-head spectral power analysis of human magnetoencephalography data recorded at rest in a large cohort of adults shows robust effects of age, and their results provide compelling evidence that it does. The relative simplicity of the analysis is a major strength of the paper, and the authors are careful to control for many different confounds - although perhaps highly correlated factors like brain anatomy still pose a slight issue. The paper provides a valuable power analysis framework that should inform researchers across the broader neuroimaging community.

eLife Assessment

This valuable study demonstrates how rhythmic inputs can shape sequential working memory. The study puts forward plausible dynamic mechanisms, but some of the central behavioral effects are small, so the evidence - at present - remains incomplete.

eLife Assessment

This important study provides new insight into how frontostriatal circuits encode elapsed time and exhibit decision-related dynamics during an auditory change-detection task. Analyses of simultaneously recorded neurons from the frontal orienting field (FOF) and anterior dorsal striatum (ADS) provide solid evidence that FOF and ADS show similar dynamics during evidence accumulation, but that FOF shows stronger movement-aligned reorganization near the time of the decision report. However, the mechanistic interpretation would be strengthened by clearer links between the population-level analyses, single-neuron activity, and relevant circuit anatomy. The work will be of broad interest to systems neuroscientists studying timing, decision-making, and frontostriatal dynamics.

eLife Assessment

This important study combines behavioral testing, fiber photometry recordings, and optogenetic manipulations to understand the role of CRH+ neurons in the PVN of the hypothalamus in social and non-social settings, while varying the degree of familiarity. The approaches used and the finding that these neurons respond to various social (and non-social) stimuli are strong; however, the conclusion that the activity of these neurons is driven solely by unfamiliar situations and the lack of dynamic analysis of fiber photometry data leaves the manuscript incomplete. This elegant study will likely be of interest to the field of social neuroscience and, if outstanding issues are addressed, would expand our understanding of the role of the PVN in behavior.

eLife Assessment

This important work provides new insights into the role of lysine acetylation of alpha-synuclein, the protein involved in Parkinson's Disease. The evidence is convincing and the work will be of interest to researchers in the fields of protein biophysics and post-translational modifications.

eLife Assessment

The authors propose the existence of an AQP4-positive tanycyte-associated canal system in the hippocampus based on histological, ultrastructural, immunohistochemical, and RNA-based approaches. There are serious concerns regarding the evidence, and the identification of the tanycyte-related structures can be questioned. At this stage, the evidence for the central claims of the manuscript has to be regarded as inadequate.

eLife Assessment

This work describes a valuable method for monitoring pathogens using an innovative, field-deployable device that attracts animals and collects saliva on filter paper in a non-invasive manner. While the strategy is effective at collecting samples and ensuring their preservation, support for some claims remains incomplete. This study will interest scientists in various fields, ranging from biodiversity, ecology, and conservation to infectious diseases and public health.

eLife Assessment

This study provides an important and biologically plausible account of how human perceptual judgments of heading direction are influenced by a specific pattern of motion in optic flow fields known as retinal curl. By combining psychophysical experiments and neural modeling, the authors demonstrate that what was previously considered an incidental, 'nuisance' signal actually serves as a functional control signal for estimating heading and steering toward a fixated target. The evidence supporting the role of curl signals is convincing and advances our understanding of vision-based navigation at the behavioral level. A particular strength of the work is the direct manipulation of curl within flow fields, demonstrating that it effectively cancels or reverses heading biases. This work provides an invaluable framework for future exploration into the neural mechanisms of steering control based on retinal curl.

eLife Assessment

This manuscript describes a series of studies using four different Go/No Go task variants in combination with fast-scan cyclic voltammetry to determine the role of dopamine release in the ventromedial striatum in action selection, controllability of reward pursuit, effort, and reward approach. The authors conclude that dopamine signals in the ventromedial striatum integrate the invigoration of action initiation with continuous estimation of spatial, but not temporal, proximity to rewards. There is solid support for the conclusions, and the findings are valuable, with theoretical implications for the role of dopamine in reward-driven behavior.

eLife Assessment

In their important manuscript, Gangadharan, Kober and Rice focus on how Stu2/XMAP215-family microtubule polymerases use their TOG domains to catalytically promote microtubule growth, testing whether their mechanism follows an enzyme-like kinetic model similar to that of actin polymerases. The authors integrate measurements including microtubule polymerization rates and TOG-tubulin binding kinetics to convincingly show that Stu2 follows an enzyme-like model where tight tubulin binding enables efficient polymerization, revealing a shared mechanism with actin polymerases despite their evolutionary divergence. This work will be of general interest to the cell biology and biophysics communities.

eLife Assessment

This valuable study explores changes in the Drosophila microbiome in response to environmental temperature over more than ten years. The evidence that temperature leads to diversification of bacterial clades is solid, despite the need for greater clarity in defining and tracking strain competition. The work will interest researchers working with microbiomes, microbial ecology, and evolutionary biology.

eLife Assessment

This manuscript focuses on developing a structural model of how the multidomain ECM protein SVEP1 enables Angiopoietin (ANG) binding to the orphan receptor TIE1, resulting in downstream receptor phosphorylation and signaling. This is an important study, based on solid data. The results will be of interest to scientists working in vascular biology and RTK signaling.

eLife Assessment

This useful study examines whether microsaccade direction primarily indexes shifts rather than the maintenance of covert spatial attention, offering a potentially informative account of inconsistencies in the prior literature. However, the evidence remains incomplete because the key effects are based on relatively sparse microsaccadic events, while concerns about event detection, fixation control, subject-level robustness, and the interpretation of gaze-density analyses remain unresolved. The correlational design and absence of a neutral condition or independent measure of attentional shifting further limit the central claim. The work will be of interest to researchers studying attention, eye movements, and visuomotor mechanisms.

eLife Assessment

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 work provides a valuable contribution by leveraging simulation-based inference to investigate candidate compensatory mechanisms in neuronal network models and offering new insights into how distinct pathological perturbations may require different interventions. The computational evidence is convincing and has been strengthened by additional reproducibility analyses, although some aspects of inference validation and the biological interpretation of posterior dependencies warrant further investigation. The study establishes a helpful computational framework for exploring disease-specific compensatory mechanisms and will be of broad interest to the computational and systems neuroscience communities.

eLife Assessment

This important study reports a novel phenomenon of maternal growth during pregnancy that is independent of growth hormone (GH), adding a new dimension to maternal biology of reproduction. The evidence is convincing and supported by state-of-the-art methodologies conducted in mice and persuasive observations in humans with hereditary isolated GH deficiency. Revised discussion should focus on possible mechanisms, including the role of IGF2, and on directions for future research.

eLife Assessment

In this valuable study, Zhang et al. investigated EEG neurofeedback as a method to modulate brain activity prior to painful stimulation and examined its effect on pain perception in a well-powered, double-blind study. Results showed that real, but not sham, feedback enabled learning-dependent enhancement of pre-stimulus α oscillations. However, the evidence for a neurofeedback-specific reduction in pain remains incomplete, as the current paradigm cannot distinguish between genuine neurofeedback effects and placebo effects. Nonetheless, this work is likely to be of interest to researchers in the fields of neurofeedback and pain.

eLife Assessment

This important study investigates whether perceived gender is represented in the brain in a category-invariant manner across faces, bodies, and objects, identifying the right middle temporal gyrus (rMTG) as a potential locus. The evidence is incomplete due to major conceptual concerns, weak statistical methods, and unaddressed low-level confounds like stimulus size and motion. This work will be of interest to psychology and social neuroscience researchers in face and person perception literature, provided the authors temper their claims regarding abstract representation.

eLife Assessment

This important study extends a model of cortical normalization (ORGaNICs) to interacting cortical areas and shows that communication through coherence and communication subspaces can arise from a single set of dynamics. The evidence is solid, showing analytically that contrast-dependent gamma dynamics and a low-dimensional inter-areal communication subspace arise from one parameter set, though the comparisons to data remain qualitative and the analytics rest on a linearization that is not checked against numerical simulation. The work will interest neuroscientists and theorists concerned with inter-areal communication, cortical oscillations, and divisive normalization.

eLife Assessment

This valuable descriptive study describes the expression of a developmentally relevant transcription factor in the adult Tribolium brain. The evidence supporting the claims is convincing and based on a very detailed and rigorous analysis of light microscopy data, which, however, lacks single-cell resolution. This neuroanatomical study is of interest to the field of insect neural development and neuroscience.

eLife Assessment

This paper describes a valuable tool for the detection and analysis of dentate spikes, network events in the dentate gyrus that are common yet understudied. This tool could help standardize dentate spike detection and analysis across labs and is therefore likely to be of interest to hippocampal neurophysiologists. However, the strength of evidence for its broad usefulness was viewed as incomplete, due to several identified bugs in the program and insufficient explanations of parameter selection and methods.

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

This valuable study characterizes how antibody responses converge on similar functional solutions despite diverse genetic backgrounds, providing a resource that is of importance in understanding immune responses and informing vaccine research. The evidence is solid, with extensive and well-executed analyses supporting the primary findings, although broader conclusions regarding vaccine design would benefit from more cautious interpretation and fuller discussion of the study's limitations. The work will be of interest to researchers studying antibody responses, viral evolution, and vaccine development.

eLife Assessment

This is an important study reporting a new phenotype for a gene cluster that has previously been associated with the responses of the Gram-negative opportunistic pathogen Pseudomonas aeruginosa to flow fluid. Expression of the froABCD gene cluster is induced by HOCl in vitro and by activated immune cells, which produce these types of reactive chlorine species and the evidence presented by the authors is in many places convincing. Overall, the authors have been responsive to the previous review, although the exact mechanism of fro-induction by HOCl remains unclear. The high cysteine- and methionine content of the anti-sigma factor FroI hints at a direct oxidative modification of this protein during activation of the operon and a corneal infection model shows that fro is upregulated in P. aeruginosa 20 h after infection, but the evidence that HOCl is the causative agent of fro upregulation under these conditions is at present circumstantial. This study is of interest to infection biologists interested in mechanisms of bacterial pathogenicity.

eLife Assessment

This study provides important insights into the neural mechanisms linking sleep and long-term memory consolidation. By combining behavioural, genetic, imaging, and connectomic approaches in Drosophila, it identifies a target neural circuit that will be of broad interest to researchers studying sleep, memory, and neural circuits. The evidence supporting the involvement of the identified circuit in the regulation of sleep and memory is solid and represents a substantial advance in the field. Nevertheless, there is limited evidence to support the mechanistic claim that this circuit directly links sleep and memory consolidation within the available data, and some results should therefore be interpreted with appropriate caution.

eLife Assessment

This important study introduces NoSeMaze, a semi-naturalistic platform for continuous, high-dimensional tracking of social and cognitive behaviors in group-housed mice, and uses it to show that individual social rank is stable across changing social contexts. By integrating automated dominance measures, proactive social behaviors, and reinforcement-learning-based profiles, the authors demonstrate a novel framework for examining how stable individual differences shape social structure. The findings provide compelling evidence that dominance traits are stable across changing social contexts and largely independent of non-social cognitive performance, supporting the view that social rank reflects an intrinsic dimension of individuality however, the broader functional significance of dominance in this paradigm remains somewhat ambiguous, including the extent to which the measured behaviors capture how dominance operates in more naturalistic social settings. This work will be of broad relevance for behavioral neuroscience and social behavior research.

eLife Assessment

This important study provides evidence that locus coeruleus activity is coordinated with heart rate during sleep, confirming previous work in mice and humans, with a possible role for sleep-dependent memory consolidation. The claims are supported by convincing evidence. This work will be of interest to neuroscientists focusing on sleep, memory, and autonomic functions.

eLife Assessment

This important study reveals distinct representations of task-related information in the dendrites and somata of cortical neurons during sensorimotor learning and behavioral adaptation. The evidence is compelling, combining imaging of dendritic and somatic activity during behavior to demonstrate compartment-specific encoding of sensory cues, motor actions, and corrective signals. The work will be of broad interest to neuroscientists studying dendritic computation, motor learning, and the cellular mechanisms underlying adaptive behavior.

eLife Assessment

This study provides a useful analysis of the effects of arginine vasopressin (AVP) on islet cells in pancreatic tissue slices, using sophisticated spatiotemporal calcium recordings to show that AVP affects α and β cells differently depending on glucose concentration. The calcium imaging, analytical approaches, and V1b receptor-targeted peptide ligands are strengths of the work. However, the reviewers were concerned that the proposed mechanistic model is not sufficiently supported by the data. Characterisation of β-cell responses remains incomplete, and potential off-target effects and limited receptor specificity raise alternative explanations, including indirect effects mediated through α cells. The study would have been strengthened by signalling pathway analyses, genetic validation (e.g. β-cell-specific V1bR deletion), or selective V1b receptor silencing. The RNAscope data included in the revision indicate broader expression patterns but do not clearly establish receptor localisation within specific endocrine populations.

eLife Assessment

In this important work, the authors develop methods to forecast epidemic growth from viral sequencing data alone. The evidence for the usefulness of the approach is solid, but some justifications and methodological details are incomplete. This study should be of broad interest to the community interested in viral dynamics and epidemiology.

eLife Assessment

The paper provides a valuable, foundational dataset that will undoubtedly provide substantial value to the cancer research community. The aggregation and harmonization of a broad, rich, multi-omic dataset is convincing and will potentially support further downstream research on GIST, which currently has poor supporting datasets. Support for the accompanying claims is more incomplete, however: the biological demonstration rests on a single gene tested by one approach, several analyses lack sample sizes and multiple-testing correction, the claims made for the LLM assistant are not backed by direct evaluation, and the curated data matrices would ideally be deposited independently of the web.

eLife Assessment

This important study presents the development of a model to quantify the dynamics of stress-induced volatile emissions in plants and identify biologically relevant differences in these responses. The model is based on a convincing methodology and represents a starting point for studies of similar responses in other plants or investigations of induced phenotypes in different biological systems.

eLife Assessment

This important study presents a cell-based screen for small-molecule activators of GCN2, an eIF2α kinase that regulates the Integrated Stress Response under diverse stress conditions. The authors identify a compound as a potent GCN2 activator with GCN1-independent activity under the tested conditions, providing a new pharmacological tool for probing GCN2 regulation. The revised manuscript provides compelling support for the central conclusions through a clearer description of the screening workflow, extended kinetic analyses, and demonstration that the identified compound causes a GCN2-dependent reduction in protein synthesis.

eLife Assessment

This important paper describes the role of the Pre-rRNA in meiotic sex chromosome inactivation in mouse spermatocytes. The cytological analyses of nucleolar components and the chemical inhibition of RNA polymerase I for rDNA transcription provided solid evidence, supporting the authors' conclusions. However, the results were not well described or explained in the text, making the logic difficult to follow. This paper will be of interest to researchers in meiotic chromosome structure and the nucleolus.

eLife Assessment

The authors addressed a significant biological question, namely the role of glutamine metabolism in humoral responses, and they obtained solid conclusions. The strength of this study is that the authors used state-of-the-art transgenic mouse models together with in vitro analysis, thereby providing important insights into the question posed. The manuscript has been further substantiated by adding more appropriate experimental controls and describing more in-depth functionality/physiological relevance.

eLife Assessment

This interesting study adapts machine learning tools to analyze movements of a chromatin locus in living cells in response to serum starvation. The machine learning approach developed is useful, the experiments are well controlled, and the data are solid. The study will benefit from future work testing predictions by perturbation experiments. This work will be of interest to those studying chromosome biology and gene expression patterns.

eLife Assessment

This important study reports insights into how the caspase Dcp-1, best known for cell death, can also promote tissue growth in Drosophila, extending the authors' earlier work by identifying regulatory factors that shape this non-lethal activity. The compelling findings identify a physical and functional interaction between Dcp-1 and Bruce, as well as new Dcp-1-interacting proteins that function in autophagy: Sirt1, Fkbp59, Debcl, Buffy, Atg2, and Atg8a. This work helps broaden the understanding of the non-lethal roles of Dcp-1.

eLife Assessment

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. In the revised version of the manuscript, 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

This useful study addresses a timely question about semantic prioritisation in visual working memory, using behavioural manipulations and drift-diffusion modelling. However, the strength of evidence is incomplete for the broader claims about working-memory representations because the main interpretation relies on indirect inferences from non-decision time, which cannot uniquely identify memory access or retrieval.

eLife Assessment

The manuscript by von Velsen et al. offers valuable structural insights into the mitogen-activated protein kinase (MAPK) pathway by providing cryo-EM structures of stabilized MEK1-ERK2 kinase-substrate complexes in inactive, active, and nucleotide-free states, complemented by HDX-MS, SAXS, ITC, crystallography, and molecular dynamics. The work provides solid evidence for the overall architecture of the complex and identifies interaction sites that help explain MAPK pathway specificity. However, some mechanistic conclusions are not yet fully supported, particularly the designation of one state as an active phosphoryl-transfer configuration, the claim that substrate binding releases the MEK1 catalytic machinery, the proposed link to processive phosphorylation, and the extrapolation to disease-associated mutations.

eLife Assessment

The authors use a novel patch-leaving task to reveal a reward-reset strategy when mice choose to leave a depleting resource, and find that accumulated step-like activity in the dorsomedial striatum is correlated with the timing of these decisions. These important behavioral and neural findings are supported by substantial and convincing data. Additional control analyses would strengthen the evidence that these signals are specifically related to timing and patch-leaving decisions, rather than alternative task-related processes.

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 uses longitudinal EEG to chart how neural tracking of syllables and word-level statistical structure develops over the first two years of life in infants at high and low likelihood for autism and links these measures to verbal outcomes at 18-20 months. The strength of evidence is convincing: the prospective longitudinal design, careful data-quality handling, and partial least squares analyses are appropriate and well executed, though some interpretations of the group differences in syllable tracking, along with the possible contributions of multilingual exposure and sleep state during recording, warrant caution. The work will be of interest to developmental cognitive neuroscientists studying language acquisition and early neural markers of neurodevelopmental conditions.

eLife Assessment

In this valuable study, the authors identified a rare population of Nestin-expressing cells within the external granule layer of the early postnatal mouse cerebellum. They demonstrated that these cells are distinct from Sox2+ progenitors and can give rise to medulloblastoma. Collectively, the findings provide convincing evidence that this unique Nestin+ population is susceptible to oncogenic transformation and may underlie the preferential emergence of Sonic hedgehog-driven medulloblastomas.

eLife Assessment

This manuscript presents important new findings showing that the transcription factor and regulator of lipid and glucose metabolism PPARγ is methylated by the enzyme SETD6. The data convincingly demonstrate that methylation of PPARγ by SETD6 regulates its function in controlling transcription of lipid storage and metabolism genes and thereby modulates lipid accumulation in liver cells. This work uncovers a new role for post-translational modulation by lysine methylation in controlling transcription factor activity and lipid metabolism in a relevant physiological context.

eLife Assessment

This study presents valuable data suggesting that ATP-induced modulation of alveolar macrophage (AM) functions is associated with NLRP3 inflammasome activation and enhanced phagocytic capacity. While the in vivo and in vitro data reveal an interesting phenotype, the evidence provided is incomplete and does not fully support the paper's conclusions. Additional investigations would be of value in complementing the data and strengthening the interpretation of the results. This study should be of interest to immunologists and the mucosal immunity community.