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    1. eLife assessment

      This study aims to explore the diabetes-bone paradox using the Mendelian Randomization approach. That diabetes itself is not the direct cause, but rather the complications or associated risk factors increase the risk of fracture, constitutes a valuable insight. Mendelian randomization to explain the relationship of two complex conditions is solid and conducted properly; however, the efforts to reconcile the discrepancies between the Mendelian Randomization analysis and observational studies are incomplete.

    1. eLife assessment

      This is an important paper as it is the first to use a reconstituted translation system to study competition among mRNAs for the initiation machinery. Understanding the principles of the biochemistry of mRNA competition for initiation factors cannot be achieved without such a system. The authors provide compelling evidence that Ded1 is required for efficient initiation of highly structured mRNAs. The findings are significant and validate the in vitro reconstituted system by recapitulating the effects of in-vivo perturbations of translation initiation by Ded1 mutants.

    1. eLife assessment

      This important study identifies the mitotic localization mechanism for Aurora B and INCENP (parts of the chromosomal passenger complex, CPC) in Trypanosoma brucei. The mechanism differs from that in the more commonly studied opisthokonts and is compellingly supported by RNAi and imaging experiments, targeted mutations, immunoprecipitations with crosslinking/mass spec, and AlphaFold interaction predictions. The findings will be of interest to cell biologists working on cell division, parasitologists, and those interested in the evolution of mitotic mechanisms.

    1. eLife assessment

      This fundamental study advances our understanding of the cell specific treatment of cone photoreceptor degeneration by Txnip. The evidence supporting the conclusions is compelling with rigorous genetic manipulation of Txnip mutations. The work will be of broad interest to vision researchers, cell biologists and biochemists.

    1. eLife assessment

      This valuable study on the molecular and cellular mechanisms of ingestion avoidance of high salt in insects is focused in scope, but the authors present convincing evidence that a specific subset of gustatory receptors in a pair of pharyngeal taste neurons are necessary and sufficient for avoiding ingestion of high salt during feeding. This work will be of interest to Drosophila neuroscientists interested in taste coding and feeding behavior.

    1. eLife assessment

      This valuable paper provides convincing evidence that loss of the tumor suppressor TMEM127 causes disorganization of plasma membrane lipid domains, alters clathrin assembly, and inhibits endocytosis of a variety of cell surface receptors, leading to increased cell surface levels of signaling proteins including RET and other transmembrane receptor tyrosine kinases. The results are significant for understanding how RET127 loss contributes to pheochromocytoma, although the evidence is indirect owing to the lack of human pheochromocytoma cell lines. The results will be of interest for researchers studying pheochromocytoma and endocytosis mechanisms.

    1. eLife assessment

      This fundamental study advances our understanding of how Notch signaling activates transcription by analyzing dynamics of the Mastermind transcriptional co-activator and its role in the activation complex. The evidence is compelling and based on state of the art methods with precise quantitative measurements.

    1. eLife assessment

      This useful study describes expression profiling by scRNA-seq of thousands of cells of recombinant yeast genotypes from a system that models natural genetic variation. The rigorous new method presented here holds promise for improving the efficiency of genotype-to-phenotype mapping in yeast, providing convincing evidence for its efficacy. This manuscript focuses on overcoming technical challenges with this approach. It currently offers somewhat limited new biological insights to place the work within the broader context of the field. Doing so would broaden the interest of the work for all geneticists and evolutionary biologists.

    1. eLife assessment

      This important study presents a new quantitative imaging pipeline that describes with high temporal precision and throughput the movements of late-stage Drosophila embryos, a critical moment when motion first appears. A new approach is used to explore the role of miRNAs in motion onset and presents solid evidence that shows a role for miR-2b-1 and its target Janus in embryonic motion. The data are well supported but do not provide mechanistic insight into the emergence of movement while the writing inflates the importance of the conclusions. The authors must change the name of Janus which is already used in Drosophila genetics.

    1. eLife assessment

      This study presents valuable findings on two distinct modes of endosomal fusion and the roles of actin dynamics in this process. The evidence supporting the authors' claims is solid, although the underlying molecular mechanisms and whether the proposed fusion modes are applicable in other cell types remain unclear. The work will be of interest to cell biologists and biophysicists working on the cytoskeleton and organelles.

    1. eLife assessment

      This important study addresses the mechanisms by which mutations in the PURA protein, a regulator of gene transcription and mRNA transport and translation, cause the neurodevelopmental PURA syndrome. Based on convincing evidence from structural biology, molecular dynamics simulation, biochemical, and cell biological analyses, the authors show that the PURA structure is very dynamic, rendering it generally sensitive to structure-altering mutations that affect its folding, DNA-unwinding activity, RNA binding, dimerization, and partitioning into processing bodies. These findings are of substantial importance to cell biology, neurogenetics, and neurology alike, because they provide first insights into how very diverse PURA mutations can cause similar and penetrant molecular, cellular, and clinical defects.

    1. eLife assessment

      This study by Sheng and colleagues provides valuable insights into the mechanism of competitive inhibitors of P2X receptors. The structural and functional evidence supporting the subtype specificity of pyridoxal-5'-phosphate derivatives is compelling and provides information for designing drugs that selectively target different subtypes of P2X receptor channels. The work will be of interest to biochemists, structural biologists, and pharmacologists.

    1. eLife assessment

      This important study used Voltage Sensitive Dye Imaging (VSDI) to measure neural activity in the primary visual cortex of monkeys trained to detect an oriented grating target that was presented either alone or against an oriented mask. The authors show convincingly that the initial effect of the mask ran counter to the behavioral effects of the mask, a pattern that reversed in the latter phase of the response. They interpret these results in terms of influences from the receptive field center, and although an alternative view that emphasizes the role of the receptive field surround also seems reasonable, this study stands as an interesting contribution to our understanding of mechanisms of visual perception.

    1. eLife assessment

      In this manuscript, the authors investigate the properties of prokaryotic NADPH oxidases (NOX) and discuss the implications for NOX regulation and function. The structure of the S. pneumoniae Nox protein is an important step forward in our understanding of procaryotic NOX enzymes and the characterization and interpretation are convincing. The results will be of interest to structural biologists as well as biochemists focusing on enzymatic functions.

    1. eLife assessment

      This study presents a deep learning-based inter-protein contact prediction method named PLMGraph-Inter which combines protein language models and geometric graphs. The evidence supporting the claims of the authors is solid. The authors show that their approach may be useful in cases where AlphaFold-Multimer performs poorly. This work will be of interest to researchers working on protein complex structure prediction, particularly when accurate experimental structures are available for one or both of the monomers in isolation.

    1. eLife assessment

      This important study identifies the gene mamo as a new regulator of pigmentation in the silkworm Bombyx mori, a function that was previously unsuspected based on extensive work on Drosophila where the mamo gene is involved in gamete production. The evidence supporting the role of Bm-nano in pigmentation is convincing, including high-resolution linkage mapping of two mutant strains, expression profiling, and reproduction of the mutant phenotypes with state-of-the-art RNAi and CRISPR knock-out assays. The work will be of interest to evolutionary biologists and geneticists studying color patterns and evolution of gene networks.

    1. Editors Assessment:

      MPDSCOVID-19 has been developed as a one-stop solution for drug discovery research for COVID-19, running on the Molecular Property Diagnostic Suite (MPDS) platform. This is built upon the open-source Galaxy workflow system, integrating many modules and data specific to COVID-19. Data integrated includes SARS-CoV-2 targets, genes and their pathway information; information on repurposed drugs against various targets of SARS-CoV-2, mutational variants, polypharmacology for COVID-19, drug-drug interaction information, Protein-Protein Interaction (PPI), host protein information, epidemiology, and inhibitors databases. After improvements to the technical description of the platform, testing helped demonstrate the potential to drive open-source computational drug discovery with the platform.

      This evaluation refers to version 1 of the preprint

    1. Editors Assessment:

      This Data Release paper presents an updated genome assembly of the doubled haploid perennial ryegrass (Lolium perenne L.) genotype Kyuss (Kyuss v2.0). To correct for structural the authors de novo assembled the genome again with ONT long-reads and generated 50-fold coverage high-throughput chromosome conformation capture (Hi-C) data to assist pseudo-chromosome construction. After being asked for some more improvements to gene and repeat annotation the authors now demonstrate the new assembly is more contiguous, more complete, and more accurate than Kyuss v1.0 and shows the correct pseudo-chromosome structure. This more accurate data have great potential for downstream genomic applications, such as read mapping, variant calling, genome-wide association studies, comparative genomics, and evolutionary biology. These future analyses being able to benefit forage and turf grass research and breeding.

      This evaluation refers to version 1 of the preprint

    1. eLife assessment

      This paper investigates how the EWS::FLI1 fusion protein organizes chromatin topology and regulates gene expression in an aggressive pediatric bone cancer known as Ewing sarcoma. The authors used the most recent genomics methodologies to provide a solid base of evidence for the role of a short alpha helix in the DNA binding domain of FLI1 in modulating binding to GGAA microsatellites and promoting enhancer activity. The study provides valuable insight into the underlying oncogenic mechanisms in Ewing sarcoma, but is limited to a single cell line and would benefit from consolidation of the main conclusions using additional techniques.

    1. eLife assessment

      This valuable study addresses the role of Rho-associated coiled-coil kinase (ROCK) and the cytoskeleton in the initiation and growth of the calcified endoskeleton of sea urchin embryos. Perturbation by two independent approaches (a morpholino and a selective inhibitor) provides convincing evidence that ROCK participates both in actomyosin regulation and in the gene regulatory network that controls skeletogenesis. Exciting areas of future work will be to elucidate the mechanisms by which ROCK influences gene expression and to further dissect the role of the cytoskeleton in mineralization.

    1. eLife assessment

      This useful work provides insight into agonist binding to nicotinic acetylcholine receptors, which is the stimulus for channel activation that regulates muscle contraction at the neuromuscular junction. The authors use in silico methods to explore the transient conformational change from a low to high affinity agonist-bound conformation as occurs during channel opening, but for which structural information is lacking owing to its transient nature. The evidence supporting the main conclusion that ligands flip ~180 degrees in the binding site as it transitions from a low to high affinity bound conformation is incomplete because little support is available for the starting low affinity docked conformations, and the rather approximate methods for computing binding free energies differ significantly from experimental measures for two of the four tested ligands. Nonetheless, this work presents an intriguing possibility for the nature of a transient conformational change at the agonist binding site correlated with channel opening. If the ligand flip observed in these simulations can be reproduced or verified by other studies, then this work would stand as a significant advance in our knowledge of nicotinic receptor gating.

    1. eLife assessment

      The manuscript reports on an important comparison of a range of approved clinical inhibitors for BTK used for the treatment of chronic lymphocytic leukemia (CLL). The authors provide solid evidence for their claims, using a combination of HDX-MS and NMR spectroscopy. The novelty is that this study also seeks to evaluate resistance mutation bias. The scope of the study is highly exciting but would benefit from a clear link of the biophysical studies to the functional assays - specifically nucleotide binding.

    1. eLife assessment

      In this interesting study, Drożdżyk and colleagues analyze the ability of placental CALHM orthologs to form stable complexes, identifying that CALHM2 and CALHM4 form heterooligomeric channels. The authors then determine cryo-EM structures of heterooligomeric CALHM2 and CALHM4 that reveal a distinct arrangement in which the two orthologs can interact, but preferentially segregate in the channel. This is an important study; the data provide compelling support for the interpretations and overall, the work is clearly described.

    1. eLife assessment

      In this important study, the authors report a novel measurement of the Escherichia coli chemotactic response and demonstrate that these bacteria display an attractant response to potassium, which is connected to intracellular pH level. Whilst the experiments are mostly convincing, there are some confounders regards pH changes and fluorescent proteins that remain to be addressed.

    1. eLife assessment

      This important study describes how PhoP regulates cyclic-AMP production in the human pathogen Mycobacterium tuberculosis. The authors provide convincing evidence that PhoP acts as a repressor of the cyclic-AMP-specific phosphodiesterase, Rv0805, which can degrade cyclic-AMP. The work will be of interest to bacteriologists and whilst the revised manuscript has been substantively improved, there are some outstanding points that could improve clarity and presentation.

    1. eLife assessment

      This important manuscript details the characterization of ClpL from L. monocytogenes as an effective and autonomous AAA+ disaggregase that provides enhanced heat resistance to this food-borne pathogen. The authors compellingly demonstrate that ClpL has DnaK-independent disaggregase activity towards a variety of aggregated model substrates, which is more potent than that observed with the endogenous canonical DnaK/ClpB bi-chaperone system. The work will be of broad interest to microbiologists and biochemists.

    1. eLife assessment

      Morphological characteristics and phenotypes of mutations in key developmental genes suggest that head, trunk, and tail development are regulated by discernible modules. Gdf11 signalling plays a crucial role in orchestrating the transition from trunk to tail tissues in vertebrate embryos. This important study presents convincing evidence that Tgfbr1 acts upstream of Isl1 (a pivotal effector of Gdf11 signalling) and regulates blood vessels, the lateral plate mesoderm, and the endoderm associated with the trunk-to-tail transition. Together with the previous studies, this work identifies a key signal that acts as the pivot of the trunk-to-tail transition.

    1. eLife assessment

      This study presents a valuable finding and developed ME3BP-7 as a novel microencapsulated form of 3BP targeting MCT1 overexpressing PDAC cells, demonstrating its specificity and efficacy in vitro and in PDAC mouse models with significant anti-tumor effects and improved serum stability. The evidence supporting the claims of the authors is solid; however, the study calls for additional comparative in vivo data to enhance its translational significance.

    1. eLife assessment

      This is an important study on the biochemical and biophysical analysis of a transcriptional riboswitch, detailing how Mg2+ and guanidine regulate RNA conformations. The study provides compelling evidence, developing Position-specific labeling of RNA (PLOR) and single-molecule FRET (smFRET) microscopy that are well suited to investigate the conformational dynamics of RNA structure formation. The study would have been strengthened by using a bacterial instead of phage protein to better recapitulate the physiology of the process. The work is of broad interest to those interested in RNA functional architecture and regulation.

    1. eLife assessment

      This is an important study that demonstrates that RNA intermediates arising from improper splicing are exported out of the nucleus via the canonical mRNA export machinery and the nuclear pore basket. The authors provide convincing evidence that the role of the nuclear basket rather than retaining the transcripts is stimulating their export, putting into question the current model of the role of the basket. The conclusions are in line with recent studies in mammalian cells that suggest that the basket's role in mRNA export and quality control has to be revised.

    1. eLife assessment

      The formation of the Z-ring at the time of bacterial cell division interests researchers working towards understanding cell division across all domains of life. The manuscript by Jasnin et al reports the cryoET structure of toroid assembly formation of FtsZ filaments driven by ZapD as the cross linker. The findings are important and have the potential to open a new dimension in the field, but the evidence to support these exciting claims is currently inadequate.

    1. eLife assessment

      The Hippo signaling pathway plays a crucial role in controlling organ size, cell proliferation, and apoptosis, though its role in endocrine pancreas development has remained unclear. In this useful work, the authors study the function of the Tead1 transcription factor, a Hippo effector, specifically in pancreatic beta cells. They provide solid evidence, using multiple different conditional knockout models to reveal Tead1's regulatory functions in insulin secretion and beta cell proliferation. However, deeper exploration of their data and incorporating findings from existing literature on this topic would provide a clearer understanding of Tead1's role in β-cell function, within or beyond the Hippo pathway.

    1. eLife assessment

      The main finding in this paper is that EGFR can be a novel substrate of the membrane ZNRF3/RNF43 E3 ligases. This is significant as the prevailing understanding posits that the Wnt receptors Frizzled and LRP5/6 exclusively served as substrates for these ligases. Given the frequent occurrence of mutations in ZNRF3/RNF43 or compromised expression levels in human cancers, the new evidence that aberrant EGFR expression and signaling may also contribute to the tumorigenic effects of ZNRF3/RNF43 mutations in cancer is important. The conclusions of the manuscript are supported by solid data, but some aspects of the mechanism presented need to be reinforced to fully support the claims made by the authors.

    1. eLife assessment

      This compelling study reports the to-date most comprehensive neurotransmitter atlas of any organism, using fluorescent knock-in reporter lines. It represents an extremely useful tool for a broad audience of scientists interested in neuronal cell type differentiation and function.

    1. eLife assessment

      Dong et al. investigate the role of the small Ras-like GTPase Rab10 in the exocytosis of DCVs in mouse hippocampal neurons, showing that Rab10 depletion hinders DCV exocytosis independently of its effects on neurite outgrowth. Their findings are convincing and provide evidence that Rab10 depletion leads to altered ER morphology, impaired ER-based calcium buffering, and decreased ribosomal protein expression, which collectively contributes to defective DCV secretion. The study comes to the important conclusion that Rab10 is critical for DCV release by ensuring ER calcium homeostasis.

    1. eLife assessment

      Overall, the reviewers found the significance of the work valuable to the field of visual neuroscience, particularly given the large data set and strength of the method used that allowed for spatial analysis of neuronal responses in macaque V1. The evidence was deemed compelling, owing in part to the consistency of responses across animals and the fitness of modeling. The authors have addressed the major comments from reviewers and improved the manuscript through relation to prior literature and addressing specific limitations of the method used.

    1. eLife assessment

      Sisigano et al. report findings about the role of sphingolipids using lipidomics with machine learning in paclitaxel-induced peripheral neuropathy and preliminary translation of the impact of SA1P in cultured neuronal cells. This study presents a valuable finding on the increased activity of two well-studied signal transduction pathways in a subtype of breast cancer. The strength of evidence is incomplete with some support for the main claims with some limitations.

    1. eLife assessment

      This study presents important insights into the dynamical process whereby sensory information is converted from stimulus-driven activity to a working memory representation from which the information can be recalled later. The evidence supporting the claims is convincing, using detailed fits and model-comparison techniques applied to new and existing psychophysical data sets to evaluate a wide variety of potential mechanisms. The overall conclusion, that iconic memory and working memory are not distinct mechanisms but rather two slightly different regimes of the same circuitry, will be of interest to neuroscientists and psychologists studying sensory systems and/or working memory.

    1. eLife assessment

      This valuable study has practical implications for understanding rhythm perception and production in human cognition. The evidence for individual frequency preferences and a deterioration in frequency adaptation with age is solid. These findings may inform existing models of rhythm perception and production, and the reported effects of age may have clinical implications.

    1. eLife assessment

      This manuscript represents a cleanly designed experiment for assessing biological motion processing in children (mean age = 9) with and without ADHD. The group differences concerning accuracy in global and local motion processing abilities are solid, but the analyses suggesting dissociable relationships between global and local processing and social skills, age, and IQ are inconclusive. The results are useful in terms of understanding ADHD and the ontogenesis of different components of the processing of biological motion.

    1. eLife assessment

      This important modeling work demonstrates out-of-distribution generalization using a grid cell coding scheme combined with an attentional mechanism that operates over these representations (Determinantal Point Process Attention). The simulations provide compelling evidence that the model can improve generalization performance for analogies, addition, and multiplication. The paper is significant in demonstrating how neural grid codes can support human-like generalization capabilities in analogy and arithmetic tasks, which has been a challenge for prior models.

    1. eLife assessment

      This study provides solid evidence for differences in habit-learning in obsessive-compulsive disorder versus controls. Contrary to previous studies that employed a single laboratory session to study habit-learning, here a smartphone app delivered motor-sequence tasks daily for a month. These results have important implications for our understanding of goal-directed versus habit learning in obsessive-compulsive disorder.

    1. eLife assessment

      In this work, Huerlimann and colleagues suggest an intertalk between the thyroid and corticosteroid axis in regulating grouper metamorphosis. The work provides valuable genomic resources to address the endocrine control of a life cycle transition in the Malabar grouper fish. The evidence is still incomplete and it does not fully support an interaction between the thyroid and corticosteroid axis.

    1. eLife assessment

      This important study details the development of 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 4-5 years of age. Although the evidence supporting some conclusions is solid, the relevance of the results would be improved by defining clearer hypotheses regarding the developmental changes expected for the different connections, and by discussing the unexpected findings on early negative connectivity and connectivity decreases. Considering more advanced analytical approaches would allow the authors to deal with longitudinal data and integrate mediation links, even if the study might be underpowered to link adverse conditions such as undernutrition and later cognitive development. This study will be of interest to neuroscientists, psychologists, and neuroimaging researchers working on infant development in relation to environmental factors.

    1. eLife assessment

      This important study combined fMRI, TMS and computational modelling of behaviour to investigate the functional role of the left superior frontal sulcus (SFS) in both perceptual and value-based decisions. Based on sophisticated analyses, the results provide solid evidence that downregulating left SFS activity through TMS selectively alters perceptual decision accuracy but does not influence value-based decisions. The work will be of interest to cognitive neuroscientists investigating the neural correlates of decision-making and may have implications for computational psychiatry.

    1. eLife assessment

      This work provides a valuable characterization of neural activity in the anterior insular cortex during fear. The data were collected using behavior, single unit recording, and optogenetic control of neural activity. The study is a great starting point on the path to testing hypotheses about bidirectional control of behavior via segregated, anatomically defined output populations, since the authors recorded true neural activity, as opposed to bulk calcium flux, which is often used in this kind of experiment. However, the link between spiking, anatomy, and behavior is incomplete, and additional controls are necessary to support the claim for associative learning.

    1. eLife assessment

      This paper describes the structure and connectivity of brain neurons that send descending connections to motor neurons and muscle in the fruit fly nerve cord, using a synapse-resolution connectome. This valuable work provides a wealth of hypotheses and predictions for future experimentation and modelling. Using state-of-the-art methods, the authors provide solid evidence for their conclusions. Some conclusions however could be qualified to acknowledge currently unavoidable ambiguities associated with current methodologies.

    1. eLife assessment

      This important study reports the first results on the effects of subthreshold kilohertz sinusoidal transcranial magnetic stimulation (TMS) on the brain. Stimulation at fields of 2V/m and 3.5kHz enhances cortical motor excitability as measured by motor-evoked potentials elicited by single-pulse TMS. The evidence in support of this claim is compelling. This result is of importance to the field of non-invasive brain stimulation and to cognitive neuroscience as a whole.

    1. eLife assessment

      This study presents a valuable finding on a potential signaling pathway responsible for the direct effects of nicotine on intestinal stem cell growth and tumorigenesis. However, the evidence supporting the authors' claims remains incomplete. Additional analysis on how stem cells uniquely respond to nicotine could provide more definitive evidence and strengthen the study. This research will be of interest to medical biologists specializing in intestinal tumors.

    1. eLife assessment

      This valuable study advances our understanding of how leaf and soil microbes separately affect the performance of an invasive plant, Ageratina adenophora. The conclusions regarding the roles of litter microbes in regulating the A. adenophora population are currently supported only by incomplete evidence owing to limitations in experimental design and statistical analyses, as well as uncertainties associated with the presentation. The work will be of interest to invasion biologists.

    1. eLife assessment:

      This study reports compelling data supporting the role of beta-catenin on intercellular communication occurring via extracellular vesicles, with implications for immune evasion in hepatocellular carcinoma (HCC). This fundamental insight sheds light on the underlying biology of HCC at a time when an increasing number of treatment options, including targeted small molecular inhibitors and immuno-oncologic drugs are being used to treat patients in the absence of validated predictive biomarkers. This work will be of special interest to researchers investigating the basic biology of liver function and HCC, and also to readers investigating novel pathways for therapeutic targeting of HCC.

    1. Evaluation statement (8 March 2024)

      Seljeset et al. investigate the mechanism by which NMDA receptors are activated by co-agonists glutamate and glycine. By mutating residue Asp732 in the glycine-binding site, they generate receptors activated by glutamate, and not glycine, but inhibited by glycine antagonists. Conventional and unnatural amino acid mutagenesis reveals that Asp732 interacts with nearby residues to influence channel gating as well as ligand binding. Furthermore, a homomeric receptor from Trichoplax adhaerens, which has a tyrosine in the homologous position, displays constitutive activity that becomes glycine-dependent when the tyrosine is mutated to aspartate. The study is valuable because it reveals the importance of position 732 for controlling ligand potency and channel activity in glutamate receptors, which should lead to a better understanding of how these receptors are primed for channel opening.

      Biophysics Colab recommends this study to scientists interested in the structure and function of glutamate receptors

      Biophysics Colab has evaluated this study as one that meets the following criteria:

      • Rigorous methodology
      • Transparent reporting
      • Appropriate interpretation

      (This evaluation refers to version 2 of this preprint, which has been revised in response to peer review of version 1.)

    1. eLife assessment

      Using unbiased transcriptional profiling, the study reports a fundamental discovery of a novel hepatic lncRNA, FincoR, which regulates FXR. The convincing findings have therapeutic implications in the treatment of MASH. The authors use state-of-the-art methodology and use unbiased transcriptomic profiling and epigenetic profiling, including validation in mouse models and human samples.

    1. eLife assessment

      This study represents a step towards integrating human and non-human primate research towards a broader understanding of the neural control of motor strategies. It could offer valuable insights into how humans and non-human primates (Rhesus monkeys) manage visuomotor tasks, such as stabilizing an unstable virtual system, potentially leading to discoveries in neural behaviour mechanisms. While the evidence is mostly solid, some results, particularly from the binary classification of control strategies for non instructed behaviour, require further validation before it could be conclusively interpreted.

    1. eLife assessment

      In this important study, the authors set out to investigate the biogenesis of extracellular vesicles in mycobacteria and provide several observations to link VirR with vesiculogenesis, PG metabolism, lipid metabolism, and cell wall permeability. Whilst some of the evidence provided is convincing, data to support the proposed mechanism are somewhat incomplete. The work will be of interest to bacteriologists.

    1. eLife assessment

      This study addresses the long-standing question as to how different functional pools of synaptic vesicles are organized in presynaptic terminals to mediate different modes of neurotransmitter release. Based on imaging of active synapses with recycling synaptic vesicles labeled by FM-styryl dyes, the authors provide data that are compatible with the hypothesis that two separate reserve pools of vesicles – slowly vs. rapidly mobilizing – feed two distinct releasable pools – reluctantly vs. rapidly releasing. Overall, this study represents a valuable contribution to the field of synapse biology, specifically to presynaptic dynamics and plasticity. The authors' methodological approach of using bulk FM-styryl dye destaining as a readout of precise vesicle arrangements and pools in a population of functionally very diverse synapses has limitations. Consequently, the evidence that directly supports the authors' two-pool-interpretation of their data is incomplete, and alternative interpretations of the data remain possible.

    1. eLife assessment

      This important paper sheds light on the role of expectations in perceptual decision-making. Sophisticated analyses of human EEG data provide convincing evidence that both motor preparation and sensory processing were affected by expectations, albeit with different time courses. These findings will be of interest to scientists interested in perception and decision-making.

    1. eLife assessment

      This work advances our understanding of transcriptional regulation of virulence and metabolic pathways in plant pathogenic bacteria. Solid evidence for the claims is provided by computational analysis of the newly generated data on the genome-wide binding of 170 transcription factors to their target genes, together with experimental validation of the biological functions of some of these transcription factors. The findings and resources from this study will be valuable to researchers in the fields of systems biology, bacteriology, and plant-microbe interactions.

    1. eLife assessment

      The methods presented in this work provide modest yet consistent accuracy improvements for data classification tasks where certain data are missing. The authors also present a way to use quantum computers for this task. The methodology and results for the classical (non-quantum) case are solid, although evidence for the practical quantum advantage via their approach in 'next generation' quantum computers remains incomplete. The results are valuable and should interest data scientists, life scientists and anyone working in quantum computing.

    1. eLife assessment

      This study provides valuable new insights into the trade-offs associated with the evolution of drug resistance. The authors use a solid approach to evolve and phenotype hundreds of independent strains. They identify distinct phenotypic clusters based on growth across defined conditions that suggest that tradeoffs are diverse but at the same time could be limited to a few classes based on the underlying resistance mechanisms. The methodologies used align with the current state-of-the-art, and the data and analysis are solid as they broadly support the claims, with only minor weaknesses. This work will interest molecular biologists working on the evolution of new phenotypes and microbiologists studying multi-drug therapy.

    1. eLife assessment

      The authors provide useful information, confirming previous observations that heterologous sequecnes affect crossing-over frequency. Surprisingly, they conclude that heterozygous introgressed regions, with greater levels of heterology, have greater noncrossover levels than non-introgressed regions with much lower levels of heterology. As the evidence for this conclusion is incomplete and potentially biased, the significance of these findings relative to previous knowledge in the field remains to be determined.

    1. eLife assessment

      In this important study, the authors manually assessed randomly selected images published in eLife between 2012 and 2020 to determine whether they were accessible for readers with deuteranopia, the most common form of color vision deficiency. They then developed an automated tool designed to classify figures and images as either "friendly" or "unfriendly" for people with deuteranopia. While such a tool could be used by publishers, editors or researchers to monitor accessibility in the research literature, the evidence supporting the tools' utility was incomplete. The tool would benefit from training on an expanded dataset that includes different image and figure types from many journals, and using more rigorous approaches when training the tool and assessing performance. The authors also provide code that readers can download and run to test their own images. This may be of most use for testing the tool, as there are already several free, user-friendly recoloring programs that allow users to see how images would look to a person with different forms of color vision deficiency. Automated classifications are of most use for assessing many images, when the user does not have the time or resources to assess each image individually.

    1. eLife assessment

      This useful manuscript presents an intriguing potential refinement of models for adult SVZ neurogenesis, and highlights the role of RNA splicing at specific stages in the lineage. Unfortunately, the evidence does not fully support the claims, leaving it currently incomplete. The proposed role of RNA splicing in neuronal differentiation, though interesting, remains unexplored and would benefit significantly from targeted gene manipulation studies.

    1. eLife assessment

      This manuscript is an important advance in the study of Histone H1s, finding distinct distributions of various H1 variants in the genome. The controls presented by the authors provide convincing evidence to demonstrate a heterogenous distribution of H1 which might reflect functional regulation of chromatin accessibility by linker histones. This work will be of interest to the genome organization field, and could additionally provide a framework for understanding H1 mis-regulation observed in cancer cells.

    1. eLife assessment

      This valuable work extends previous studies showing that the striatum multiplexes various aspects of locomotion, including velocity and movement transitions, by demonstrating that striatal neurons also encode single-limb gait. The authors present solid evidence to show that gait deficits induced by severe unilateral dopamine depletion are associated with an imbalance in the gait modulation of striatal firing. Although the source and function of this gait modulation remain unclear, this manuscript uncovers a role of striatal activity in gait, which may have implications for understanding gait disturbances in Parkinson's Disease.

    1. eLife assessment

      The manuscript by Jingsong Zhou and colleagues tries to uncover the reasons for the resistance of extraocular muscles (EOMs) to degenerative changes induced by amyotrophic lateral sclerosis (ALS). The findings of the study offer valuable information that EOMs are spared in ALS because they produce protective factors for the NMJ and, more specifically, factors secreted by EOM-derived satellite cells. While most of the experimental approaches are convincing, the use of sodium butyrate (NaBu) in this study needs further investigation, as NaBu might have a variety of biological effects. Overall, this work may help develop future therapeutic interventions for patients with ALS.

    1. eLife assessment

      This useful study uses a chemoinformatics pipeline to identify a list of candidate mosquito repellants that may be pleasant to smell and safe for humans. The computational methodology is solid, but insufficiently benchmarked against other leading models. At the high concentrations tested, there may also be off-target effects of the repellents on the mosquitoes that are not considered. This paper may be of interest to specialists interested in the discovery of new mosquito repellents.

    1. eLife assessment

      This study reports a potentially important discovery that testosterone-induced metabolic changes in seminal vesicle epithelial cells lead to the production of oleic acids in seminal plasma to enhance sperm fertility. The evidence to support metabolic changes in seminal vesicles and the identification of oleic acid as a key factor in seminal plasma is solid. However, the evidence for how oleic acids support enhanced sperm fertility in vivo is not well supported, thus currently remains incomplete, and requires further study.

    1. eLife assessment

      This work is potentially useful because it has generated a mineable yield of new candidate immune inhibitory receptors, which can serve both as drug targets and as subjects for further biological investigation. It is noted however that the work is rather incomplete, in that it does little to validate the putative new receptors, and instead makes a study of their putative distribution across cell types. Experimental follow-up to demonstrate the claimed properties for the proteins identified, or mining existing experimental data sources on gene expression across tissues to at least show that the pipeline correctly identified genes likely to be specific to immune cells, would make this work more complete.

    1. eLife assessment

      This study provides valuable new insights as to how two evolutionary conserved motifs in CD4 contribute to the CD4-mediated enhancement of TCR signaling independently of the CD4-LCK interaction. The data at hand are convincing, even if confined to a cell line model and not substantiated in vivo and with little new mechanistic insight provided regarding the domains of CD4 shown to have significant roles in the signaling process. Without the data from primary cells it is difficult to make statements about the quantitative contribution of LCK-dependent and independent functions of CD4 in TCR signaling.

  2. Mar 2024
    1. eLife assessment

      This solid study addresses the unresolved question of why many thousands of small-effect loci contribute more to the heritability of a trait than the large-effect lead variants. The authors explore resource competition within the transcriptional machinery as one possible explanation with a simple theoretical model, concluding that the effects of resource competition would be too small to explain the heritability effects. The topic and approximation of the problem are important and offer an intuitive way to think about polygenic variation, but there are concerns on the derivation of the equations with respect to dropping vs. including certain terms that deal inherently with small numbers.

    1. eLife assessment

      This important study examines the ancestral function of Hippo pathway kinases in contractility and cell density in the ameboid organism Capsaspora owczarzaki, a unicellular animal that is a close relative of multicellular animals. There is convincing evidence for Hippo kinases regulating contractility and cell density but not proliferation in C. owczarzaki. The work complements previous work on the Hippo effector Yorkie homolog in this species, although the unavailability of extensive genetic tools in this species precludes informative epistasis experiments. The work would be of interest to evolutionary and developmental biologists.

    1. eLife assessment

      This manuscript presents valuable findings that contribute to our understanding of how sphingolipids and membrane contact sites, formed by the tethering protein family tricalbins, are involved in regulating vacuolar morphology in S. cerevisiae. The evidence supporting the authors' claims is largely solid: while the reported correlation between sphingolipid levels and vacuole homeostasis is intriguing, the data do not completely substantiate the proposed mechanism. This study will be of interest to cell biologists focusing on intracellular organization and lipid metabolism.

    2. eLife assessment

      This manuscript presents valuable findings that contribute to our understanding of how sphingolipids and membrane contact sites, formed by the tethering protein family tricalbins, are involved in regulating vacuolar morphology in S. cerevisiae. The evidence supporting the authors' claims is largely solid. While the reported correlation between sphingolipid levels and vacuole homeostasis is interesting and intriguing, more work is needed to thoroughly substantiate the proposed mechanism. This study will be of interest to cell biologists focusing on intracellular organization and lipid metabolism.

    1. eLife assessment

      This manuscript presents a valuable approach to exploring CD4+ T-cell response in mice across stimuli and tissues through the analysis of their T-cell receptor repertoires. The authors use a transgenic mouse model with reduced diversity of the T-cell receptor repertoire to elicit more consistent T-cell responses across individuals, demonstrating challenge-specific and tissue-specific responses of regulatory T-cells. The evidence for the authors' conclusions is solid, and the work will be of interest to immunologists studying T cell responses.

    1. eLife assessment

      The study presents valuable findings on sexually dimorphic patterns of osteocytic transcriptomes and low calcium diet-induced osteocytic osteolysis in FNDC5-deficient mice. The authors present solid evidence for sex-specific changes in osteocyte morphology and gene expression under a calcium-demanding setting in this particular strain of mice, although the protective role of FNDC5-deficiency in lactation and low-calcium diet in female mice remains unclear due to lack of mechanistic studies. The study also lacks evidence that irisin, a proteolytically cleaved product of FNDC5, is responsible for the observed phenotypes, as irisin was not directly measured.

    1. eLife assessment

      In this potentially useful study, the authors use deep learning models to provide solid evidence that epithelial wounding triggers bursts of cell division at a characteristic distance away from the wound. The usefulness of the methods to the community will depend on documenting their robustness toward variability in temporal resolution and/or mitotic event duration, demonstrating their overall superiority over existing approaches and making the code possible to use by others.

    1. eLife assessment:

      This valuable work substantially advances our understanding of the organization of neural dynamics relative to behavioral outputs within recurrent neural networks, with implications for biological neural networks. Evidence supporting the conclusions is convincing, with rigorous analyses of neural variance and robustness to noise. The work will be of broad interest to neuroscientists studying computation through dynamics.

    1. eLife assessment

      This work presents a valuable data-driven method to extract the "true" synaptic plasticity rule (or learning rule) operating in a neural circuit from empirical measurements of neural activity. The approach aims to train a generative adversarial network (GAN) to match neural activity measurements in terms of statistics, learning them from the data, rather than being pre-determined by the experimenter. The main conclusion is that the extracted learning rules are not unique, but rather degenerate, meaning that multiple plasticity rules can produce the same neural activity. Although the paper presents a thorough investigation using one learning rule as a case study (the Oja rule), the evidence that the results can be inferred beyond the specific numerical experiments presented in the paper is incomplete.

    1. eLife assessment

      This valuable study presents convincing evidence for an association between PARP-1 and H4K20me1 in transcriptional regulation, supported by biochemical and ChIP-seq analyses. The work contributes significantly to our understanding of how Parp1 associates with target genes to regulate their expression.

    1. eLife assessment

      This paper presents useful results that extend our understanding of how the visual cortex encodes temporal structure, providing new information about sequence representations in superficial layers of the visual cortex. The evidence for prediction errors is solid, however, support for other claims regarding sparsification and simplification of activity following training is incomplete.

    1. eLife assessment

      The authors analyze the role of newborn astrocytes in the modulation of glial scar formation in a middle carotid artery occlusion (MCAO) hypoxia lesion model. The findings are valuable because they have implications for understanding the molecular and cellular processes contributing to brain repair in response to ischemia. The results are currently incomplete, in the absence of data showing: (i) cell-target specificity of molecular markers for newborn astrocytes; (ii) consistent phenomena across different rodent species.

    1. eLife assessment

      This work addresses an important biological question: what is the cellular basis of wound healing? Using the Drosophila pupal notum as a model, the paper provides an elegant, thorough, descriptive characterisation of syncytia-driven wound closure using state-of-the-art confocal live imaging of the pupal notum. The authors meticulously characterize the cell-cell fusion events during wound healing, but without any mechanisms to inhibit cell fusion, it is incomplete, since it remains unclear whether cell fusion is required or not for speeding wound healing and/ or increasing the level of actin resources at the leading edge.

    1. eLife assessment

      This valuable paper by Yao, Dai, and colleagues describes a viral gene drive against herpes simplex virus 1 in cell culture. The authors provided solid evidence that an engineered gene drive sequence, expressing either spCas9 or Un1Cas12f1 nuclease, could spread efficiently in the population of wild-type viruses and induce fewer drive-resistant mutations than spCas9. Limitations include a mechanistically inaccurate title, several methodologic flaws, and a paucity of descriptions of possible therapeutic applications.

    1. eLife assessment

      This fundamental work significantly advances our understanding of how FOG1 nuclear localization is regulated during erythropoiesis and megakaryopoiesis, including the role of EPO and MPL/TPO signaling in this process. The authors provide compelling evidence using both K562 and CD34+ cells that heat shock cognate B (HSCB) can promote the proteasomal degradation of TACC3 to regulate the nuclear localization of FOG1, and that this function is independent of its role in iron-sulfur cluster (ISC) biogenesis. The conclusions would be strengthened in the future by the use of in vivo model systems, however, as written, this work will be of broad interest to cell biologists.

    1. eLife assessment

      This study is an important contribution to our insights into the impact of heat stress on sexual reproduction in plants and provides information about how centromere integrity is affected by heat stress during male meiosis in Arabidopsis thaliana. The evidence supporting the claims, specifically the dynamics of tagged proteins in meiocytes by live cell imaging is solid, even though a deeper mechanistic understanding is still lacking.

    1. eLife assessment

      This manuscript provides important insights into the degradation of the host tRNA modification enzyme TRMT1 by the SARS-CoV-2 protease Nsp5 (nonstructural protein 5 or MPro). The data convincingly support the main conclusions of the paper. These results will be of interest to virologists studying the alterations in tRNA modifications, host methyltransferases, and viral infections.

    1. eLife assessment

      This article provides a review and test of image-analysis methods for bacteria growing in the 'mother-machine' microfluidic device, introducing also a new graphical user interface for the computational analysis of mother-machine movies based on the 'Napari' environment. The tool allows users to segment cells based on two previously published methods (classical image transformation and thresholding as well as UNet-based analysis), with solid evidence for their robust performance based on comparison with other methods and use of datasets from other labs. While it was difficult to assess the user-friendliness of the new GUI, it appears to be valuable and promising for the field.

    1. eLife assessment

      This valuable study informs on the regulation of metabolic flux between glycolysis and respiration in yeast, mediated by inorganic phosphate. The authors propose a novel mechanism involving Ubp3/Ubp10 that potentially mitigates the Crabtree effect, based on an array of assays that offer substantial insight into mitochondrial biogenesis under high glucose conditions. However, the evidence supporting the conclusions remains incomplete because of a limited number of replicates, particularly in protein blot analyses with insufficient normalization methods, which undermines the robustness of the findings. This work could influence the subfield significantly if the methodological weaknesses are addressed to provide more support for the proposed model.

    1. eLife assessment

      This valuable study examines the evolution of the pillars in the shell architecture of organo-phosphatic brachiopods. The phylogenetic implications of this shell structure in relation to other early Cambrian brachiopod families are interpreted based on solid evidence. As such, this paper with interesting ideas regarding the evolution of brachiopod shell structure contributes to our understanding of the ecology and evolution of brachiopods as a whole.

    1. eLife assessment

      This study investigated the factors related to understudied genes in biomedical research. It showed that understudied genes are largely abandoned at the writing stage, and it identified a number of biological and experimental factors that influence which genes are selected for investigation. The study is an important contribution to this branch of meta-research, and the evidence in support of the findings is solid.

    1. eLife assessment

      This study presents a valuable contribution towards understanding the protein target and mechanism of action of an herbicide, which could be applied to the development of herbicide-based technologies to improve crop yields. Evidence is gathered using a variety of technical approaches that enrich and support the findings, but the methodology and the presentation of the results are incomplete.

    1. eLife assessment

      This study provides a detailed evaluation of how HIV evades nascent immune pressure from people living with HIV followed nearly immediately after infection. There is convincing evidence that H173 mutations in the V2 loop was a key determinant of selection pressure and escape. These data are congruent with protection in the RV144 clinical trial, the only trial that showed protection from infection. Overall, this study is an important contribution to the field.

    1. eLife assessment

      This study presents two valuable new mouse models that individually tag proteins from the SMAD family to identify distinct roles during early pregnancy. Convincing evidence is provided that SMAD1 and SMAD5 target many of the same genomic regions as each other and the progesterone receptor. Given the broad effect of these signaling pathways in multiple systems, these new tools will most likely interest readers across biological disciplines.

    1. eLife assessment

      In this useful study, Wang and colleagues investigate the potential probiotic effects of Bacillus velezensis to prevent colitis in a mouse model. They provide solid evidence that B. velezensis limits the growth of Salmonella typhimurium in lab culture and in mice, together with beneficial effects on the microbiota. The work will be of interest to infectious disease researchers and those studying the microbiome.

    1. eLife assessment

      This study addresses an important long-standing controversy in the field of reproductive biology. Using cutting-edge techniques the authors provide compelling evidence supporting a pivotal role of prolactin as the mediator of lactational infertility. Some methodological, technical, interpretive, stylistic, and typographical aspects of the paper need to be strengthened.

    1. eLife assessment

      Spermiogenesis is a complex process allowing the emergence of specific sperm organelle, including the acrosome, a sperm giant vesicle of secretion. This important study reports the key role of Cylicin-1 in acrosome biogenesis and identifies the molecular partners necessary for acrosome anchoring. The compelling demonstration is based on infertile patient samples and two animal models. Overall, this provides results that will be invaluable to the male reproduction community, including scientists and andrologists.

    1. eLife assessment

      This manuscript provides useful findings to further explore the heterogeneity of hematopoietic stem cells and myeloid-biased hematopoiesis during aging. The results presented in this study are incomplete and additional data is needed to strengthen the conclusions. Some of the methods and data analyses, including the replicates and statistical robustness, remain inadequate to support the primary claims.

    1. eLife assessment

      This is a useful study that provides solid, yet confirmatory findings about the complex (FtsEX) that controls peptidoglycan remodeling during bacterial cell division. The authors capitalize on the finding that ATP binding stabilizes the FtsEX complex allowing structural characterization for this system. A model is then developed using biochemical approaches to explain ATP regulation. The resulting model would be strengthened were the authors to incorporate their structural findings as well as previously published work.

    1. eLife assessment

      This important study identifies a novel link between the early keratinocyte response to wounds and the subsequent regenerative capacity of local sensory neurons. The evidence supporting the claims of the authors is solid, although the inclusion of additional pharmacological and genetic manipulations might have strengthened the mechanistic aspects. The work will be of interest to cell and developmental biologists interested in tissue regeneration and cell interactions in a broader context.

    1. eLife assessment

      This study presents an important application of high-content image-based morphological profiling to quantitatively and systematically characterize induced pluripotent stem cell-derived mixed neural cultures cell type compositions. Convincing evidence through rigorous experimental and computational validations supports new potential applications of this cheap and simple assay.

    1. eLife assessment

      This work demonstrates an important regulatory role of the N-terminal disordered tail of small ubiquitin-like modifier (SUMO) proteins, which modulates the function of a variety of proteins in eukaryotic cells. The authors present convincing evidence that the N-terminal region of SUMO inhibits its own interaction with downstream effector proteins and SUMOylation targets. This new discovery significantly advances the field by providing a possible explanation of how SUMO paralogues select their effectors and SUMOylation targets.

    1. eLife assessment

      This manuscript reports important data on the stability of nucleosomes. Convincing evidence obtained by single-molecule FRET experiments shows that DNA unwrapping is found to be slower when a single CC base pair mismatch is introduced at three different positions. The work is carefully conducted and described clearly, but the biological significance and implications of the findings on cellular DNA metabolism remain unclear.

    1. eLife assessment

      This study reports an important finding highlighting the essential role of the putative ion channel, TMC7 (transmembrane channel-like 7) in male fertility, thereby significantly advancing our understanding of the function of the previously uncharacterized protein in sperm development. The evidence supporting TMC7's requirement in acrosome biogenesis during spermatogenesis is solid, and its function as an ion channel requires more study.

    1. eLife assessment

      This valuable study addresses how distinct cilia lengths of different cell types in zebrafish are regulated and proposed an interesting mechanism. While the quality of imaging and the resources generated in this study are excellent, key experimental information is not always provided and the strength of evidence to support the proposed hypothesis on ciliary length regulation is currently incomplete.

    1. eLife assessment

      The development of this mouse model is an important step to establish the role of the FSH Receptor in tissues beyond the reproductive system, and the data provided in this paper are convincing for a role for the FSH receptor in cell systems well beyond the classic reproductive tissues. Such model(s) have long been needed in this field and will provide expanded opportunities to better define FSH biology in vivo in these important target tissues. Ultimately, this model could shed light on FSH biology in women after menopause, when endogenous FSH levels rise dramatically, or in men with hypogonadism when FSH levels are high.

    1. eLife assessment

      This fundamental study employs a combination of cryo-electron microscopy, molecular dynamics, and mass spectrometry to elucidate the role of α-tubulin acetylation at the lumenal lysine 40 residue (αK40) within the cilium. Compelling evidence shows αK40 acetylation to impact the structure and stability of doublet microtubules in cilia by affecting the lateral rotational angle. The work will be of relevance to those interested in cytoskeleton and structural biology.

    1. eLife assessment

      The solid study addresses the role of extracellular matrix (ECM) in neuronal migration. The authors showed that the interaction between the ternary complex formed by tenascin-C, the chondroitin sulfate proteoglycan neurocan, and hyaluronic acid is important for the multipolar to bipolar transition in the intermediate zone (IZ) of the developing cortex

    1. eLife assessment

      This study provides an important insight into the mechanisms of cooperation between Hsp70 and its cochaperones during protein disaggregation. Based on compelling evidence, the authors demonstrate that Hsp110 increases Hsp70 recruitment to protein aggregates. This work is of broad interest to biochemists and cell biologists working in the protein homeostasis field.

    1. eLife assessment

      This manuscript highlights single-stranded DNA exo- and endo-nuclease activities of ExoIII as a potential caveat and an underestimated source of decreased efficiency in its use in biosensor assays. The data present convincing evidence for the ssDNA nuclease activity of ExoIII and identifies residues that contribute to it. The findings are useful, but the study remains incomplete as the effect on biosensor assays was not established.

    1. eLife assessment

      This valuable study presents findings that suggest the need for postoperative type 2 diabetes screening and that this should be prioritized in colorectal cancer survivors with overweight/obesity regardless of the type of colorectal cancer treatment applied. The evidence supporting the claims of the authors is solid and the authors use a population-based cohort study including all Danish colorectal patients who had undergone colorectal cancer surgery between 2001-2018. The work will be of interest to medical biologists, endocrinologists and oncologists working on colorectal cancer.

    1. eLife assessment

      This study presents a valuable inventory of immune signatures that are correlated with cancer treatment-related pneumonitis. The data were collected and analysed using validated methodology and can be used as a starting point for further prospective studies. The authors have provided a scRNA-Seq analysis with an HD baseline using publicly available dataset and the evidence for their claims is convincing.

    1. eLife assessment

      Pin1 as an essential prolyl cis/trans isomerase has attracted considerable attention because this enzyme family is implicated in cancer and neurodegenerative diseases. However, the requirement for its catalytic function remains a matter of dispute. The authors provide solid evidence that Pin1 modulates the activity of an important cell signaling kinase, Protein Kinase C, by a non-catalytic mechanism, acting as a chaperone to regulate the stability of this kinase.

    1. eLife assessment

      This computational study is a valuable empirical investigation into the common trait of neurons in brains and artificial neural networks: responding effectively to both objects and their mirror images and it focuses on uncovering conditions that lead to mirror symmetry in visual networks and the evidence convincingly demonstrates that learning contributes to expanding mirror symmetry tuning, given its presence in the data. Additionally, the paper delves into the transformation of face patches in primate visual hierarchy, shifting from view specificity to mirror symmetry to view invariance. It empirically analyzes factors behind similar effects in two network architectures, and key claims highlight the emergence of invariances in architectures with spatial pooling, driven by learning bilateral symmetry discrimination and importantly, these effects extend beyond faces, suggesting broader relevance. Despite strong experiments, some interpretations lack explicit support, and the paper overlooks pre-training emergence of mirror symmetry.

    1. eLife assessment

      This manuscript presents a detailed phenotyping of the role of dietary iron in a large number of genetically distinct mouse strains. There are exciting and convincing data that could be valuable in their impact on the fields of nutrition, iron metabolism and anemia.

    1. Myelin, a coating of fatty tissues around the axon of the neuron (Carlson, 2014).
      • insulates nerve and speeds up the impulses between cells while supporting the neural pathways
      • improves coordination, thought process and movement.
      • present in adolescents but most dramatic first years
    2. Synaptic Pruning, where neural connections are reduced thereby making those that are used much stronger
      • helps master our complex skills. experience will determine which connections are kept in our brains.
      • occurs during childhood and adolescence after blooming period
    1. eLife assessment

      This valuable study provides new insight into potential subtle dynamics in effector biology. The data presented generally support the claims, but in some cases controls are missing and so the overall work is currently incomplete. If the limitations can be addressed, this work should be of broad relevance for biologists interested in molecular plant-microbe interactions.

    1. eLife assessment

      This important study reveals the molecular basis of mutualism between a vector insect and a bacterium responsible for the most devastating disease in citrus agriculture worldwide. The evidence supporting the conclusions is compelling, with biochemical and gene expression analysis demonstrating the phenomenon. However, there are concerns related to the presentation, as well as lack of sufficient information about data analysis, both of which should be clarified and/or extended. With these matters addressed, this work will be of great interest to the fields of vector-borne disease control and host-pathogen interaction.

    1. eLife assessment

      This study presents valuable findings that expand our view of dopamine release in different brain regions and show that dopamine release in the lateral hypothalamus is related to the activity of orexin neurons. The evidence supporting the claims of the authors is solid, although inclusion of tests that directly assess causality of the noble pathways would have been even more conclusive. The work will be of interest of neuroscientists who study the neural basis of motivation.

    1. eLife assessment

      This manuscript claims to have found evidence for coordinated membrane potential oscillations in E. coli biofilms that can be linked to a putative K+ channel and that may serve to enhance photo-protection. The finding of waves of membrane potential would be of interest to a wide audience from molecular biology to microbiology and physical biology. Unfortunately, a major issue with the experimental technique affects the interpretation of the observations: the dye used has been previously shown not to report membrane potential, leaving the evidence inadequate.

    1. eLife assessment:

      The study answers the important question of whether the conformational dynamics of proteins are slaved by the motion of solvent water or are intrinsic to the polypeptide. The results from neutron scattering experiments, involving isotopic labelling, carried out on a set of four structurally different proteins are convincing, showing that protein motions are not coupled to the solvent. A strength of this work is the study of a set of proteins using spectroscopy covering a range of resolutions, however, it suffers from some scholarly shortcomings and limited discussion of results. The work is of broad interest to researchers in the fields of protein biophysics and biochemistry.

    1. eLife assessment

      This is an important study examining the role of prediction error in state allocation of memories. The data are convincing and largely support the conclusion that a gradual change between acquisition and extinction maintains the memory state of acquisition and, thus, results in extinction that is resistant to restoration. This paper is of interest to behavioural and neuroscience researchers studying learning, memory, and the neural mechanisms of those processes, as well as to clinicians using extinction-based therapies in treating anxiety-based disorders.

    1. eLife assessment

      Wound infections are very common and can lead to delayed wound healing or poor wound healing which significantly impacts morbidity and overall quality of life for patients. This manuscript uses scRNA-Seq to try to understand the impact of infection on various cell types during wound healing in a mouse model. The methodology is solid and the results provide a valuable 'atlas' of the cellular changes associated with infected and uninfected wounds which will of interest to the field.

    1. eLife assessment

      The paper investigates a potential cause of a type of severe epilepsy that develops in early life because of a defect in a gene called KCNQ2. The significance is fundamental because it substantially advances our understanding of a major research question. The strength of the evidence is convincing because appropriate methods are used that are in line with the state-of-the art, although there are some revisions/corrections that would strengthen the evidence further.

    1. eLife assessment

      The findings in this manuscript are important and novel, and the genomic analyses are convincing. This study expands upon our understanding of the role of hnRNP proteins in lncRNA function and the evidence is compelling, suggesting shared mechanism(s) in the regulation of ASARs and Xist RNAs by RBPs that bind Cot1 sequences in these lncRNAs. This manuscript should be of interest to the noncoding RNA and chromatin biology communities.

    1. eLife assessment

      This valuable study provides insights into how the brain parses the syntactic structure of a spoken sentence. Convincing evidence is provided that distributive cortical networks are engaged for incremental parsing of a sentence, and neural activity recorded by MEG correlates with sentence structure measures extracted by a deep neural network language model, i.e., BERT. A contribution of the work is to use a deep neural network model to quantify how the mental representation of syntactic structure updates as a sentence unfolds in time.

    1. eLife assessment

      This study enhances our understanding of the relationship between cortico-hippocampal interactions and behavioral performance. Using an inter-areal coherence metric to gate trial initiation in real time, the authors provide solid evidence that links high hippocampal-prefrontal theta coherence to correct performance on spatial working memory and cue-guided decision-making tasks. Although reviewers agreed that the results do not demonstrate causality between hippocampal-prefrontal synchrony and behavioral performance, the findings are viewed as important given their potential implications for brain-machine interface applications in humans.

    1. eLife assessment

      The reprocessing and reanalysis of archived samples can yield further insights from past experiments. Here, a useful procedure to perform tissue clearing and immunolabeling on large-scale formalin-fixed paraffin-embedded brain specimens is convincingly evaluated on a set of archival pathology specimens, and its applicability to further such samples is analyzed. This method will be of interest to both neuroscientists and pathologists.

    1. eLife assessment

      This important study presents relevant information about the involvement of TOR pathway in aflatoxin production by Aspergillus flavus. However, some of the presentation is confusing, leaving the study in its current form is incomplete. The strength of the evidence could be augmented with additional experiments and reorganization of the manuscript aiming to fully understand and characterize the involvement of TOR pathway in A. flavus aflatoxin production.

    1. eLife assessment

      This useful study, which systematically addresses off-target effects of a commonly used chemotherapy drug on bone and bone marrow cells and which therefore is of potential interest to a broad readership, presents evidence that reducing systemic inflammation induced by doxorubicin limits bone loss to some extent. Although the work does not inform in detail on the underlying mechanisms of doxorubicin action, the demonstration of the effect of systemic inflammation on bone loss is convincing. While not a new finding, the work sets the scene for additional genetic and pharmacologic experiments and a deeper analysis of the bone phenotype presented here, which should speak to the mechanisms involved in doxorubicin-induced bone loss and which may substantiate the clinical relevance of targeting inflammation in order to limit the negative impact of chemotherapies on bone quality.

    1. eLife assessment

      The results from this study, which investigates the mechanisms necessary for initiating tissue invagination using a cellular Potts modelling approach, suggests that apical constriction is not sufficient to drive the process by itself. The study highlights how choices inherent to modelling - such as permitting straight or curved cell edges - may affect the outcome of simulations and, consequently, their biophysical interpretation. Despite incomplete evidence supporting their major claims due to a rather coarse-grained exploration of the model, this work is useful for biophysicists investigating complex tissue deformation through computational frameworks.

    1. eLife assessment

      This important study reports the generation of genetic tools for manipulating several tissues at the same time in Drosophila. The authors provide convincing evidence that this allows for the generation of LexA and QF2 driver lines, which will be of great utility for understanding inter-organ communication. Making the tools available through the Drosophila stock center and plasmid depository will ensure that they are easily accessed by many researchers.

    1. eLife assessment

      In this important manuscript, Abd El Hay and colleagues reveal a clear role of TRPV1 and TRPM2 receptors in warm temperature perception and present a technically unique experimental strategy to measure and analyze temperature preference behavior, which will have a lasting impact on the field. In addition to the behavioral data, which is strong, the study provides an analysis of cultured sensory neurons to controlled warmth stimuli - in this case, the evidence relating the activity of TRPM2 channels to the behavioral responses of animals is incomplete. Overall, the findings are of importance for neuroscientists, physiologists, and biophysicists, as there is still substantial discussion in the field regarding the contribution of TRP channels to different aspects of thermosensation.

    1. eLife assessment

      This work presents an important online platform designed to facilitate the exploration of genes and genetic pathways implicated in human aging. Leveraging a new inference methodology, the tool enables the identification and visualization of key genes and tissues impacted by aging, facilitating scientific discovery. The methods and analyses are convincing and will be broadly used by scientists aiming to mine human aging RNA-seq data.

    1. eLife assessment

      This work will be of interest to the motor control community as well as neuroAI researchers interested in how bodies constrain neural circuit function. The authors present "MotorNet", a useful software package to train artificial neural networks to control a biomechanical model of an effector. The manuscript provides solid evidence that MotorNet is easy to use and can reproduce past results in the field, both at the neural and behavioural levels. Validation is limited to planar arm-like plants or point-masses, so future work exploring three-dimensional movements and other types of plants would strengthen the impact of the tool.

    1. eLife assessment

      The authors address the function of keratin 17 (K17), a marker of the most aggressive pancreatic ductal adenocarcinomas (PDACs). While this potentially useful study addresses a significant area of pancreatic cancer research, the lack of evidence demonstrating nuclear localization of K17 in human PDAC and the excessive reliance on a single cell line reduce the significance of the work. Moreover, the weak phenotypes of K17 phosphosite mutants provide incomplete support for the authors' mechanistic model.

    1. eLife assessment

      This potentially important paper addresses the question of how numerical information is represented in the human brain. Experimental findings are interpreted as providing evidence for a sensorimotor mechanism that involves channels, each tuned to a particular numerical range. While this is an interesting application of methodologies used to identify the presence of channels, the evidence supporting the claim that these have a sensorimotor basis is incomplete.

    1. eLife assessment

      In this manuscript, the authors present a wealth of fMRI data at both 3T and 7T to identify a scene-selective region of the intraparietal gyrus ("PIGS") that appears to have some responsivity to characteristics of ego-motion. In a series of experiments, they delineate the anatomical location of PIGS and functionally differentiate it from nearby V6 and OPA. Evidence for these important findings is solid, but further investigations as to the role of this region in processing ego-motion will be needed to confirm this conclusion.

    1. eLife assessment

      This valuable study showed convincing evidence that archerfishes can adapt their shooting behaviors to airflow perturbations. The fish also exhibits adaptive behaviors indicative of an egocentric representation of the perturbation, though direct evidence is missing. Hence, this work will be of interest to those interested in cross-species comparisons for motor learning.

    1. eLife assessment

      This useful study addresses the brain correlates underlying technical reasoning by a set of fMRI experiments and locates it to PF. If confirmed, this study provides an intriguing framework for our understanding of different types of problem-solving processes. However, the current evidence supporting the claims is incomplete, due to the existence of alternative explanations for the main overlapping results and potential confounding variables across conditions.

    1. eLife assessment

      This important study advances our understanding of the mechanisms of neuronal large dense-core vesicle (LDCV) secretion, which mediates neuropeptide and neurotrophin release. It describes a negative regulatory process involving the interaction of the Rab3-effector Rabphilin-3A with the SNARE fusion protein SNAP25, which limits LDCV secretion and neurite growth. The evidence in support of the authors' claims is solid overall, but some conclusions, e.g regarding the exact synaptic localization of Rabphilin-3A, its association with large dense-core vesicles, or the role of Rabphilin-3A-controlled neurotrophin signaling in neurite growth, are incompletely supported. This study will be of interest to the fields of cell biology, cellular neuroscience, and neuroendocrinology.

    1. eLife assessment

      This study provides valuable insights into understanding bone fragility in T2D patients through the use of human skeletal tissue, reinforcing previous pre-clinical studies or observational studies using serum samples that the Wnt signaling pathway may play a critical role in T2D-related bone impairment. The methods are solid, but a limited number of subjects and a small set of genes with lack of data in terms of cellular properties of skeletal tissue are viewed as weaknesses.

    1. eLife assessment

      This valuable study combines the use of Fisher Kernels with Hidden Markov models aiming to improve brain-behaviour prediction. The evidence supporting the authors' conclusions is solid, comparing brain-behaviour prediction accuracies across a range of different traits. This work is timely and will be of interest to neuroscientists working on functional connectivity for brain-behaviour association.

    1. eLife assessment

      This valuable study presents findings characterising the genomic features of E. coli isolated from neonatal meningitis from seven countries, and documents bacterial persistence and reinfection in two case studies. The genomic analyses are solid, although the inclusion of a larger number of isolates from more diverse geographies would have strengthened the generalisability of findings. The work will be of interest to people involved in the management of neonatal meningitis patients, and those studying E. coli epidemiology, diversity, and pathogenesis.

    1. eLife assessment

      This valuable study uses a model to determine when catalytic self-replication of polymers can emerge from a random pool of replicating polymers. The model accounts for the folding and function of polymers in addition to abstract evolutionary dynamics, providing solid evidence for the claims of the authors. The work will be of relevance to those interested in the origin of life, artificial cells, and evolutionary dynamics.

    1. eLife assessment

      In this fundamental study, the authors analyzed associations between circulating immune cells and periodontitis. Convincing evidence identifies three immune cell types related to periodontitis, which substantially advances our understanding of periodontitis.

    1. eLife assessment

      This valuable study combines in vitro and in vivo experiments designed to test if a deoxycytidine kinase inhibitor provides therapeutic benefit during infection with Staphylococcus aureus. Several in vitro methods used to measure therapeutic efficacy are thorough and compelling with appropriate conclusions drawn, however, the overall analysis is incomplete and would benefit from a more rigorous study design. With a strengthened study design, and more nuanced considerations of the strengths and limitations of the study, this paper would be of interest to bacteriologists, immunologists, and those studying host-microbe interactions.

    1. eLife assessment

      This valuable study combines in vitro and in vivo experiments designed to test if a deoxycytidine kinase inhibitor provides therapeutic benefit during infection with Staphylococcus aureus. The authors provide compelling evidence that this putative host-directed therapy has good potential to promote natural clearance of infection without targeting the bacterium. This paper would be of interest to bacteriologists, immunologists, and those studying host-microbe interactions.

    1. Editors Assessment:

      This is a Data Release paper describing data sets derived from the Pomar Urbano project cataloging edible fruit-bearing plants in Brazil. Including data sourced from the citizen science iNaturalist app, tracking the distribution and monitoring of these plants within urban landscapes (Brazilian state capitals). The data was audited and peer reviewed and put into better context, and there is a companion commentary in GigaScience journal better explaining the rationale for the study. Demonstrating this data providing a platform for understanding the diversity of fruit-bearing plants in select Brazilian cities and contributing to many open research questions in the existing literature on urban foraging and ecosystem services in urban environments.

      This evaluation refers to version 1 of the preprint

    1. eLife assessment

      The authors provide solid evidence that any contribution of oligodendrocyte precursors to the developing cortex from the lateral ganglionic eminence is minimal in scope. The methods used support the conclusions, with some technical concerns that the authors can address with further experimentation. These are considered valuable additions to our understanding of the origins of oligodendrocytes in the forebrain during development.

    1. eLife assessment

      This useful study presents data regarding the presence of synaptic proteins in the extracellular vesicle pool present in the blood of Parkinson's patients and non-parkinson neurological outpatients, trying to correlate changes in such levels with the progression of Parkinson's symptoms. The results are semi-quantitative and preliminary, suggesting that these biomarkers could be used in the follow up of a specific group of Parkinson patients. The evidence is incomplete at this point, and more quantitative approaches are required to propose this correlation. The isolation of extracellular vesicles was appropriate as revealed by their sizes, but they are not exclusively from neuronal origin. The presented approach is not ready to be used in the clinical setting.

    1. eLife assessment

      This study unveils important mechanistic insights into postnatal lung development and bronchopulmonary dysplasia (BPD) pathology. Using two BPD models enhances our comprehension of the disease, utilizing compelling evidence from single-cell sequencing and flow cytometry, revealing a myofibroblast loss. Pharmacological and genetic approaches convincingly argue against the presumed increase in TGFb signaling causing alveolar simplification; instead, it appears to be a compensatory response. The identified weakness is the absence of validation in tissue, leaving the question unanswered regarding whether myofibroblast loss is due to a lack of myofibroblast proliferation or myofibroblast differentiation/specification.

    1. eLife assessment

      Herein, Xie and colleagues use a hamster model to show that Leptospira infection leads to gut pathology, an altered gut microbiota, and increased translocation. A combined use of antibiotics and LPS neutralization prolonged survival, providing a potential new therapeutic approach. This fundamental study uses compelling methods to provide new insights into this emerging disease, which could be dissected further in future studies aimed at gaining mechanistic insight and assessing the translational relevance of these discoveries.

    1. eLife assessment

      This manuscript provides potentially valuable information suggesting that the earliest appearing T-cells during ontogeny may have properties that are fundamentally distinct from those appearing later in life. At this stage, weaknesses in the experimental design and data interpretation provide inadequate support for the conclusions. With modifications, the paper should be of interest to those interested in T-cell development.

    1. eLife assessment

      This study characterizes the composition and immune diversity of the zebrafish kidney, the immune organ equivalent to human bone marrow, with convincing single-cell transcriptomic data of hematopoietic cells and immunocytes. The key findings suggest that zebrafish kidney is a secondary lymphatic organ, and that hematopoietic stem cells in zebrafish may exhibit trained immunity, which are the unique features of the fish immune system. This study provides new and valuable insights into the antiviral response in teleost fish, which will be of interest to biologists in general, and to immunologists and cancer researchers in particular.

    1. eLife assessment

      This work describes a valuable new technique involving proximity labelling to identify Drosophila proteins modified by GlcNAcylation in subsets of cells in vivo. A solid set of experiments shows that several ribosomal proteins are modified in the fly mushroom body. Consistent with a role for GlcNAcylation of ribosomal proteins in control of memory related translational control, the authors show that perturbation of GlcNAc modification in KCs prevents efficient consolidation of long-term memory.

    1. eLife assessment

      This important work substantially advances our understanding of how resistant leukemia can arise without changes in mutational patterns by displaying epigenetic changes. The evidence supporting the conclusions is compelling, with rigorous genomic assays done on primary samples. and state-of-the-art microscopy. The work will be of broad interest to hematologists and cancer biologists.

    1. eLife assessment

      This important study outlines how the agr quorum sensing system in Staphylococcus aureus confers long-lived protection against oxidative stress, thereby linking bacterial metabolism to virulence in this pathogen. While the findings, which are supported by solid data, seem at first glance to contradict earlier findings that show increased fitness of agr mutants under oxidative stress, the core conclusions of the study are well-substantiated. The authors should, however, re-evaluate their interpretations related to the impact of agr inactivation on bacterial metabolic and redox status following oxidative stress. The topic of the paper holds broad relevance to microbiologists, especially those focusing on host-pathogen interactions and bacterial responses to ROS.

    1. eLife assessment

      The report presents the cryo-EM structure of human vesicular monoamine transporter 2 (VMAT2) bound to tetrabenazine, a clinical drug. VMAT2 is critical for neurotransmission, and the study constitutes an important milestone in neurotransmitter transport research. The evidence presented in the report is convincing and provides new opportunities for developing improved therapeutic interventions and furthering our understanding of this vital protein's function.

    1. eLife assessment

      This study provides useful information regarding the role of Netrin-1 and Unc5c in developing dopaminergic axons. Several findings are solid. These include that Netrin-1 and UNC5c can guide dopaminergic innervation from the nucleus accumbens to the cortex during adolescence, that the onset of Unc5 expression is sexually dimorphic in mice, and that in Siberian hamsters environmental effects on development are also sexually dimorphic. While this work is novel and provides useful information, the reviewers unanimously agree that support for the main claims remains incomplete. Understanding developmental trajectories of adolescence, and how they can be impacted by environmental factors, is an understudied area of neuroscience that is highly relevant to understanding the onset of mental health disorders. These data will be of interest to those interested in these factors.

    1. eLife assessment

      This study provides valuable observations indicating that human pyramidal neurons propagate information as fast as rat pyramidal neurons despite their larger size. Solid evidence demonstrates that this property is due to several biophysical properties of human neurons. This study will be of interest to neurophysiologists.

    1. eLife assessment

      This study presents a valuable finding on the spontaneous emergence of structured activity in artificial neural networks endowed with specific connectivity profiles. The evidence supporting the claims of the authors is potentially solid but still incomplete at this stage, as it is important to demonstrate that similar properties are observed with more diverse inputs and in more complex environments. The work will be of interest to systems and computational neuroscientists.

    1. eLife assessment

      Varadharajan et al. explore the mechanistic basis of MBOAT7 SNP association with steatotic liver disease and link its function in LPI acylation to altered lipidomics of endosomal/lysosomal system and impaired TFEB mediated lysosomal biogenesis. The findings are important with theoretical and practical implications in MAFLD, alcohol-induced hepatic steatosis, and lysosomal diseases. The strength of evidence is convincing using methodology in line with current state-of-the-art.

    1. eLife assessment

      This important study follows up on previous work defining the anti-leukemic effects of a previously characterized cannabis extract on Notch-activated T cells and identifies several pathways that mediate its anti-cancer activity including the ER calcium and integrated stress response. The evidence is solid, but several concerns remain including the over reliance on a single cell line for the majority of the studies and lack of integration of the observations with existing literature

    1. eLife assessment

      The authors provide compelling evidence that MSP1 inhibition (leading to chromosomal instability in the cancer cells) increases phagocytosis and that tumors with chromosomal instability respond better to the current state-of-the-art macrophage therapeutics. In this important study, they demonstrate particularly impressive survival rates for mouse models of CIN B16 tumors treated with CD47 blockade and anti-Tyrp1 IgG.

    1. eLife assessment

      Using state-of-the-art fate-mapping models and genetic and pharmacological targeting approaches, this study provides important findings on the distinct functions exerted by resident and recruited macrophages during cardiac healing after myocardial ischemia. Evidence supporting the conclusions are solid with the use of the FIRE mouse model in combination with fate-mapping to target fetal-derived macrophages. This study will be of interest for the macrophage biologists working in the heart but also in others tissues in the context of inflammation.

    1. eLife assessment

      The study presents important findings regarding a transcription-independent component of the early recovery of proteasome activity from a short pulse of proteasome inhibitor treatment, which has not been appreciated before and which is independent of the DDI2-NRF2 axis. While the evidence is in principle solid, with recapitulation in several cell line models, the proposed alternative underlying mechanism, namely regulation at the level of proteasome assembly, lacks experimental support, and at this point remain speculative.

    1. eLife assessment

      The authors build upon prior data implicating the secreted peptidoglycan hydrolase SagA produced by Enterococcus faecium in immunotherapy. Leveraging new strains with sagA deletion/complementation constructs, the investigators reveal that sagA is non-essential, with sagA deletion leading to a marked growth defect due to impaired cell division, and sagA being necessary for the immunogenic and anti-tumor effects of E. faecium. In aggregate, the study utilizes compelling methods to provide both fundamental new insights into E. faecium biology and host interactions and a proof-of-concept for identifying the bacterial effectors of immunotherapy response.

    1. eLife assessment

      This study, which seeks to identify factors from the glial niche that support and maintain neural stem cells, unveils a novel role for ferritin in this process. Furthermore, the work shows that defects in larval brain development resulting from ferritin knockdown can be attributed to impaired Fe-S cluster activity and ATP production. These findings will be valuable to both oncologists and neurobiologists, though the supporting evidence is currently incomplete.

    1. eLife assessment

      This important work presents a new methodology for the statistical analysis of fiber photometry data, improving statistical power while avoiding the bias inherent in the choices that are necessarily made when summarizing photometry data. The reanalysis of two recent photometry data sets, the simulations, and the mathematical detail provide convincing evidence for the utility of the method and the main conclusions, however, the discussion of the re-analyzed data is incomplete and would be improved by a deeper consideration of the limitations of the original data. In addition, consideration of other data sets and photometry methodologies including non-linear analysis tools, as well as a discussion of the importance of the data normalization are needed.

    1. eLife assessment

      This manuscript presents a valuable, lightweight software package that aims to accelerate the implementation of experiment pipelines running on heterogeneous computer environments. The authors present solid evidence of the advantages of their chosen approach, including demonstrating the flexibility, ease of use, and practical utility of this new system. However, questions remain regarding the maturity of the project and its specific advantages in relation to existing widely adopted software packages.

    1. eLife assessment

      This important study investigated transcriptional profiles of midbrain dopamine neurons using single nucleus RNA (snRNA) sequencing. The authors found more nuanced subgroups of dopamine neurons than previous studies, and identified some genes that are preferentially expressed in subpopulations that are more vulnerable to neurochemical lesions using 6-hydroxydopamine (6OHDA). The results are convincing and provide critical information on the heterogeneity and vulnerability of dopamine neurons which will be a foundation for future studies.

    1. eLife assessment

      This work addresses the connectivity of giant excitatory neurons in a part of CA1 of the hippocampus. Recordings in rat brain slices provide new evidence that these cells excite bistratified and basket inhibitory neurons, and have weak inhibitory input from basket cells, as well as other findings. This circuitry gives these cells unique potential, making the work valuable, however the strength of the evidence is currently incomplete.

    1. eLife assessment

      In this important study, Xiong and colleagues studied PKA regulation in synaptic plasticity. They provide convincing evidence that dissociation of PKA catalytic subunits is essential for the proper function of the kinase. Experiments using a PKA regulatory-catalytic subunit fusion establish that dissociative activation is required for both structural long-term potentiation and basal priming of AMPA receptors.

    1. eLife assessment

      This useful manuscript reports on a new mouse model for LAMA2-MD, a rare but very severe congenital muscular dystrophy; the knockout mice were generated by removing exon3 in the Lama2 gene, which results in a frameshift in exon4 and a premature stop codon. These animals lack any laminin-alpha2 protein and confirm results from previous Lama2 knockout models. Additionally, this study includes transcriptomics data that might be a good resource for the field. However, the experimental evidence supporting the main claims of the manuscript is incomplete, citations of previous Lama2 null mice studies are lacking, and both data presentation and interpretation need improvement.

    1. eLife assessment

      This valuable study addresses one way in which animals identify predator-associated cues and respond in a manner that reflects the imminence of the potential threat. The report shows that, in mice, fresh saliva from a natural predator (cat) elicits a greater defensive response compared to old cat saliva and implicates the vomeronasal organ and ventromedial hypothalamus as part of a circuit that underlies this process. While the study has potential, the results are somewhat preliminary, and as such support for the primary conclusions is incomplete.

    1. eLife assessment

      This important study by Lee and colleagues examined how neural representations are transformed between the olfactory tubercle (OT) and the ventral pallidum (VP) using single neuron calcium imaging in head-fixed animals trained in classical conditioning. They show that the dimensionality of neural responses is lower in the VP than in the OT and suggest that VP responses represent values in a more abstract form while OT contains more odor information, potentially enhancing odor contrast. The reviewers found the results overall convincing although the nature of OT responses needs to be investigated further.

    1. eLife assessment

      This study addresses the role of FMRP in the migration of newborn neuroblasts in the postnatal brain. Through extensive and convincing analysis of living imaging videos, the authors showed that neurons with FMRP deletion migrate aberrantly and exhibit defects in nucleokinesis and centrokinesis. The study presents a valuable finding on the mechanism of neuroblast migration in the postnatal brain.

    1. eLife assessment

      The authors use reinforcement learning modeling to study the alterations following acute ketamine in macaques. The evidence supporting the conclusion that ketamine reduces the impact of losses vs. neutral/gains is solid. In this version of this valuable study, the authors make more measured interpretations about the relationship between the processing of losses and ketamine's antidepressant effects.

    1. eLife assessment

      This important study uses calcium imaging in mice to advance our understanding of the effect of antipsychotic drugs on neural functioning. The evidence supporting the conclusions is convincing, and this work will be of interest to neuroscientists working on visual processing and psychosis researchers.

    1. eLife assessment

      This is a fundamental resource of snRNA-seq and and chromatin accessibility data from human aortic endothelial cells (ECs), treated with relevant perturbations such as IL1b, TGFB2, or si-EGR. The authors show that ECs can be categorized by distinct subpopulations of differing plasticity. The support for the existence of these subpopulations is compelling, supported also by three publicly available scRNA-seq datasets, and differential enrichment of coronary artery disease associated SNPs in open chromatin in these subpopulations.

    1. eLife assessment

      In this valuable study, the discovery and subsequent design of the AF03-NL chimeric antibody led to a tool for studying filoviruses and provides a possible blueprint for future therapeutics. In general, the data presented are solid, although further improvements can be made in the overall presentation of the results. The work will be of interest to virologists studying antibodies.

    1. eLife assessment

      This study reports comparative biochemical and structural analysis of two PLP decarboxylase enzymes from plants. The work is useful because of the potential application of these enzymes in industrial theanine production. The results, particularly the x-ray crystal structures, provide a solid basis for understanding substrate specificity. The paper will be of interest to enzymologists studying PLP enzymes and those working on enzyme engineering in plants.

    1. eLife assessment

      This study presents valuable data on the antigenic properties of neuraminidase proteins of human A/H3N2 influenza viruses sampled between 2009 and 2017. The antigenic properties are found to be generally concordant with genetic groups. Additional analysis have strengthened the revised manuscript, and the evidence supporting the claims is solid.

    1. eLife assessment

      This important study reports comprehensive multi-omics data on the changes induced in young and aged male mouse tail fibroblasts after treatment with chemical reprogramming factors. The authors provide solid evidence to support their claim that chemical reprogramming factors induce changes consistent with a reduction of cellular 'biological' age (e.g., correlations with established aging markers in whole tissues).

    1. eLife assessment

      This solid study presents valuable insights into the role of Cers1 on skeletal muscle function during aging, although further substantiation would help to fully establish the experimental assertions. It examines an unexplored aspect of muscle biology that is a relevant opening to future studies in this area of research.

    1. eLife assessment

      This important study introduces a novel AI method for the analysis of published data, with practical implications for early cancer diagnosis. The results are supported by compelling evidence.

    1. eLife assessment

      This valuable paper examines the role of the WRNIP1 AAA+ ATPase in regulating R-loop formation, which induces a conflict with active replication forks and transcription. The authors provide convincing evidence to support a role of the ubiquitin-binding UBZ domain of WRNIP1 in R-loop suppression generated by this conflict. The work is of interest to researchers who work on genome stability/instability.

    1. eLife assessment

      Large scale cell movements occur during gastrulation in vertebrate embryos but their role in this major morphogenetic transition in formation of the body plan is poorly understood. Using the chick embryo model system, this study makes important advances using elegant methods to show that extension of the primitive streak during gastrulation, occurring through cell proliferation, polarisation and intercalation, and large-scale polonaise cell movements, can be uncoupled. Although the driving mechanism and precise role of these movements remains a mystery, the study provides convincing evidence for the uncoupling through independent approaches, the most creative of which are the effects shown after induction of a supernumerary primitive streak.

    1. eLife assessment

      This important study combines psychophysics, fMRI, and TMS to reveal a causal role of FEF in generating an attention-induced ocular dominance shift, with potential relevance for clinical applications. The evidence supporting the claims of the authors is convincing. The work will be of broad interest to perceptual and cognitive neuroscience.

    1. eLife assessment

      This valuable study advances our understanding that YAP/TAZ, as well as their target genes, play a prominent role in the formation of processing bodies (P-bodies). The evidence supporting the conclusions is convincing. The article could be improved through further analysis to elucidate the mechanistic link between P-body formation and oncogenesis. The work will be of broad interest to scientists working in the field of Hippo signaling and cancer biology.

    1. eLife assessment

      This important study identifies a role for triglycerides and lipid droplets in spermatogenesis, with data supporting relevance of this finding across phyla. The work shows with convincing data that a triglyceride lipase is required cell-autonomously for germline differentiation into meiotic stages and haploid spermatids and that an increase in triglycerides is detrimental to spermatogenesis. This paper would be of interest to developmental and cell biologists working on gametogenesis.

    1. eLife assessment

      This study presents valuable empirical work and simulations that are relevant for the evolution of genetic load linked to self-incompatibility alleles in Arabidopsis. The evidence supporting the findings is solid but could be improved by a more detailed quantitative assessment of the impacts of deleterious alleles and their dominance. The simulation results are somewhat incomplete, as details of the approach and code do not appear to be available, but this could be easily remedied. The work will be of relevance to geneticists interested in the evolution of allelic diversity in similar systems.

  3. Feb 2024
    1. eLife assessment

      This valuable study provides the detailed molecular mechanism of how OGT, an O-GlcNac transferase, promotes cancer progression. Using loss-of-function OGT models, the authors demonstrated that OGT cleaves HCF-1, a guardian of genomic stability. These solid findings can lead to some potential approaches to modulate anti-tumor immunity by targeting this process.

    1. eLife assessment

      This manuscript provides useful information about the lipid metabolite 15d-PGJ2 as a potential regulator of myoblast senescence. The authors provide experimental evidence that 15d-PGJ2 inhibits myoblast proliferation and differentiation by binding and regulating HRas. However, the manuscript is incomplete in its current form, as it lacks robust support from the data regarding the main conclusions related to senescence and technical concerns related to the senescence models used in this study.

    1. eLife assessment

      This study makes a valuable finding, a polyunsaturated fatty acid increases the conductance of a K+ channel by helping its K+ selectivity filter form a conductive state. Overall, support for this major claim is solid, though other claims remain speculative with incomplete support. These findings are expected to be of interest to researchers studying ion channel gating.

    1. eLife assessment

      In this useful study, the authors investigate the regulatory mechanisms related to toxin production and pathogenicity in Aspergillus flavus. Their observations indicate that the SntB protein regulates morphogenesis, aflatoxin biosynthesis, and the oxidative stress response, however, the data supporting these conclusions are incomplete. The work will be of interest to bacteriologists.

    1. eLife assessment

      How the triplicate interaction between chemokines with both GAGs and G protein-coupled receptors (GPCR) works and how gradients are created and potentially maintained in vivo are poorly understood. The authors provide solid evidence to show phase separation can drive chemotactic gradient formation. The paper is a useful advance in the field of chemokine biology.

    1. eLife assessment

      Yu and colleagues used two-sample MR to test the effect of PUFA on cerebral aneurysms. They found that genetically predicted omega-3 and DHA decreased the risk for Intracranial Aneurysm and Subarachnoid Haemorrhage. This work is useful, although the evidence is incomplete as it lacks a robust set of analyses to provide credibility to the findings.