eLife assessment

The paper reports rare compound heterozygous deletion variants that affect the kinase domains of non-receptor tyrosine kinases TNK and ACK1 in families with human systemic lupus erythematosus (SLE). Using a mouse experimental model and human induced pluripotent stem cell (hiPSC)-derived macrophages, the study provides solid evidence that clarifies cause-effect relationships and that suggests a potential cellular mechanism underlying the resultant nephritis. With the identification of novel SLE-related genes, this manuscript provides an important basis for understanding the molecular and cellular basis of SLE pathogenesis.

eLife assessment

This study demonstrates mRNA-specific regulation of translation by subunits of the eukaryotic initiation factor complex 3 (eIF3) using convincing methods, data, and analyses. The investigations have generated important information that will be of interest to biologists studying translation regulation. However, the physiological significance of the gene expression changes that were observed is not clear.

eLife assessment:

In flies defective for axonal transport of mitochondria, the authors report the upregulation of one subunit, the beta subunit, of the heterotrimeric eIF2 complex via mass spectroscopy proteome analysis. Neuronal overexpression of eIF2β phenocopied aspects of neuronal dysfunction observed when axonal transport of mitochondria was compromised. Conversely, lowering eIF2β expression suppressed aspects of neuronal dysfunction. While these are intriguing observations that are potentially useful, several technical weaknesses limit the interpretation and mean the evidence supporting the current claims is incomplete.

eLife assessment

This important study combines a range of biophysical techniques to carry out a series of compelling experiments to explore whether glutamine binding protein binds glutamine via an induced fit or a conformational selection process. The evidence supporting the major conclusion of the work is convincing, although it may not be generalized to other protein-ligand or protein-protein systems. The work will be of broad interest to biochemists and biophysicists.

eLife assessment

The demonstration that the PARG dePARylation enzyme is required in S phase to remove polyADP-ribose (PAR) protein adducts that are generated in response to the presence of unligated Okazaki fragments is potentially valuable, but the evidence is incomplete, and identification of relevant PARylated PARG substrates in S-phase is needed to understand the role of PARP1-mediated PARylation and PARG-catalyzed dePARylation in S-phase progression.

eLife assessment

This paper provides a useful analysis of the variation of the burden of strokes across geographic regions, finding differences in the relationship between strokes and their comorbidities. This dataset and the correlations found within will be a resource for directing the focus of future investigations. The statistical analyses are incomplete.

eLife assessment

This study provides valuable information on how Arg-II participates in cardiac aging. Although the phenotypic data appear robust, the study is incomplete in elucidating the mechanisms, particularly in explaining how Arg II influences IL-1b and affects cardiac aging. It would be beneficial to investigate the possibility of NO involvement in this mice model. A co-culture system may be required to understand the non-cell-autonomous functions of macrophages. Lastly, the MI mouse model may not be directly linked to cardiac aging.

eLife assessment

This useful paper looks for correlations between immunophenotypic markers and several measures of HIV reservoir volume in cross-sectional cohorts of people living with HIV on ART using several bioinformatic and machine-learning tools. The level of evidence linking these variables is incomplete given possible confounding variables, lack of directionality & effect size, and mechanistic basis.

eLife assessment

This paper reports a valuable platform for cardiac tissue cultivation. The throughput, consistency of the tissue, and the potential integration of high-throughput automation are an advantage over other approaches. The tissues and the platform are validated using appropriate methodology to provide convincing evidence of the tissue cultivation capability.

eLife assessment

This fundamental study provides evidence that de novo beige adipogenesis from Pdgfra+ adipocyte progenitor cells is blocked during early aging in subcutaneous fat. The depth of the data at early ages is compelling, with rigorous cell tracing methodology employed. The study will aid in identifying new approaches to switch dormant adipocytes into an active thermogenic phenotype, and should be of interest to cell biologists at large.

eLife assessment

This study includes fundamental findings on protein evolution, namely that changes in function are largely attributable to pairwise rather than higher-order interactions, and that epistasis potentiates rather than constrains evolutionary paths. Compelling evidence supporting the conclusions is provided by applying a new model to a previously generated experimental dataset on deep mutational scanning of the DNA-binding domain (DBD) of steroid hormone receptor. The implications of this work are of considerable interest to protein biochemistry, evolutionary biology, and numerous other fields.

eLife assessment

This study presents fundamental findings on the evolution of extremely elongated mandibular symphysis and tusks in longirostrine gomphotheres from the Early and Middle Miocene of northern China. The integration of multiple methods provides compelling results in the eco-morphology, behavioral ecology, and co-evolutionary biology of these taxa. In doing so, the authors elucidate the diversification of fossil proboscideans and their likely evolutionary responses to late Cenozoic global climatic changes.

eLife assessment

This important study advances our understanding of the biological significance of the DNA sequence adjacent to telomeres. The data presented convincingly demonstrate that subtelomeric repeats are non-essential and have a minimal, if any, role in maintaining telomere integrity of budding yeast. The work will be of interest to the telomere community specifically and the genome integrity community more broadly.

eLife assessment

In this study, the authors offer a theoretical explanation for the emergence of nematic bundles in the actin cortex, carrying implications for the assembly of actomyosin stress fibers. As such, the study is a valuable contribution to the field actomyosin organization in the actin cortex. While the theoretical work is solid, experimental evidence in support of the model assumptions remains incomplete. The presentation could be improved to enhance accessibility for readers without a strong background in hydrodynamic and nematic theories.

eLife assessment

This valuable study describes mRNA shortening during cellular stress and interestingly observes that this shortening is dependent on localization in stress granules. Surprisingly, this mRNA shortening does not appear to require the shortening of polyA tails. These are in principle novel findings, but the evidence for them is currently incomplete. Additional experiments would help bolster confidence in how the authors interpret their data.

eLife assessment

This is an important study on the regulation of chlorophyll biosynthesis in rice embryos. It provides insights into the genetic and molecular interactions that underlie chlorophyll accumulation, highlighting the inhibition of OsGLK1 by OsNF-YB7 and the broader implications for understanding chloroplast development and seed maturation in angiosperms. The results presented, including mutation analysis, gene expression profiles, and protein interaction studies, provide convincing evidence for the function of OsNF-YB7 as a repressor in the chlorophyll biosynthesis pathway.

eLife assessment

The authors report useful findings on novel function of apical ICAM1 in regulating bile duct homeostasis in the liver. The strength of evidence is solid using appropriate methodolgy with only minor weakness. The findings will be of interest to researchers in hepatology and membrane traffic biology.

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 supported by compelling 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.

eLife assessment

This valuable paper presents a new approach for association testing, using the output of neural networks that have been trained to predict functional changes from DNA sequences. As such, the approach is an interesting addition to statistical genetics, and the evidence for the presented method being able to identify trait-associations in regions where GWASs are typically underpowered is solid. A limitation is, however, that it is unclear how the quality of these associations compares to those detected using conventional methods. Additional work assessing this method's power and characterizing false positives / false negative regions would be critical to ensure that the method is broadly adopted by the field.

eLife assessment

Using state-of-the-art single-nucleus RNA sequencing, Yao et al. investigate the transcriptomic features of neural stem cells (NSCs) in the human hippocampus to address how they vary across different age groups and stroke conditions. The authors report alterations in NSC subtype proportions and gene expression profiles after stroke. Although the study is valuable and the analysis is comprehensive, the significance is restricted by well-acknowledged technical limitations leading to incomplete evidence supporting some main conclusions.

eLife assessment

This manuscript supports the intriguing idea that some aspects of novel learning can occur during sleep and outside of awareness. The authors provide solid evidence that presenting participants with novel words and their translations during sleep, especially during slow oscillation troughs, leads to the ability to categorize the semantic meaning of those words during awake testing 36 hours later. These findings represent a valuable contribution to the literature on unconscious processing and learning during sleep, although the claim that the results reflect episodic memory formation, in particular, deviates from the typical use of this term in the literature.

eLife assessment

This important work illuminates the dynamics of BRAF in both its monomeric and dimeric forms, with or without inhibitors, combining traditional techniques and sophisticated computational analyses. The evidence presented is convincing, though a more detailed description of the analyses could enhance reproducibility and the quality of the results. This study will interest structural biologists, medicinal chemists, and pharmacologists.

eLife assessment

This important paper compares cross-species cortical folding patterns in human and non-human primates, showing that most gyral peaks shared across species are in lower-order cortical regions. The supporting evidence is solid and multi-faceted, encompassing anatomy, connectivity and gene expression. This paper will be of interest to a broad readership within the neuroscience community, especially for those interested in cross-species correspondences in brain organisation.

eLife assessment

This study by Ghafari et al. tackles a question relevant for the field of attention as it connects structural differences in subcortical regions with oscillatory modulations during attention allocation. Using a combination of Magnetoencephalography (MEG) and magnetic resonance imaging (MRI) data in human subjects, the valuable results show that inter-individual differences in the lateralisation of alpha oscillations are explained by asymmetry of subcortical brain regions. The strength of evidence is deemed convincing in line with current state-of-the-art.

eLife assessment

Parkkinen et al. describe distinct biophysical profiles of brain-derived alpha-synuclein vs. in vitro-seeded synuclein fibrils. The findings are important and relevant to the emerging potential role of SAA as a biomarker of PD. The evidence is solid, using appropriate methodology and providing some support for the main claims with some limitations.

eLife assessment

Songbirds provide a tractable model system to study mechanisms of vocal production and sequencing, and past work showed that the lesions to LMAN, the output of a basal ganglia thalamocortical loop, reduced vocal variability, consistent with a role in motor exploration. In this fundamental work, the authors rigorously examined how lesions to an understudied neighboring region, MMAN, part of a parallel basal ganglia loop, affect singing in Bengalese finches, whose songs exhibit complex sequential transitions. The authors provide compelling evidence that MMAN lesions resulted in increased sequential variability but do not affect syllable acoustic structure, showing that distinct frontal systems can have distinct functions for producing and sequencing song syllables.

eLife assessment

These ingenious and thoughtful studies present important findings concerning how people can represent and generalise abstract patterns of sensory data. The issue of generalization is a core topic in neuroscience and psychology, relevant across a wide range of areas, and the findings will be of interest to researchers across areas in perception, learning and cognitive science. The findings are convincing in this setting, but future research must establish their generality and interrogate the precise nature of the underlying mechanism.

eLife assessment

The authors provide convincing experimental evidence of extended motivational signals encoded in the mouse anterior cingulate cortex (ACC) that are implemented by the orbitofrontal cortex (OFC)-to-ACC signaling during learning. The results are valuable to the field of motivation and cognition. The experimental methods used were state-of-the-art. The manuscript would further benefit from theory-driven analyses to inform a mechanistic understanding, particularly for the single-cell calcium imaging results. These results will be of interest to those interested in cortical function, learning, and/or motivation.

eLife assessment

This study presents important methodologies for repeated brain ultrasound localization microscopy (ULM) in awake mice and a set of results indicating that wakefulness reduces vascularity and blood flow velocity. The efficiency of the technique is however incompletely demonstrated, in particular regarding the reliability of longitudinal imaging. This study is relevant for scientists investigating vascular physiology in the brain.

eLife assessment

This valuable manuscript shows that the optogenetic stimulation of direct and indirect pathway spiny projection neurons (SPNs) in the dorsomedial versus the dorsolateral striatum has different consequences for locomotor activity, real-time place preference, and action selection, in a contextually mediated manner. The evidence in support of this conclusion is solid but would be further strengthened through deeper analysis of the effect and specificity of optogenetic manipulations on SPN activity. These findings will be of interest to neuroscientists, particularly behavioral neuroscientists.

eLife assessment

The authors of this study implemented an important toolset for 3D reconstruction and segmentation of dissection photographs, which could serve as an alternative for cadaveric and ex vivo MRIs. The tools were tested on synthetic and real data with compelling performance. This toolset could further contribute to the study of neuroimaging-neuropathological correlations.

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.

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. Supported by compelling evidence, the authors 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.