- Dec 2023
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents useful observations about how the human brain uses long-term priors (acquired during our lifetime of listening) to make predictions about expected sounds - an open question in the field of predictive processing. However, the evidence as currently presented is incomplete. Both the theoretical background and analysis approach should be strengthened.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Overall, this is a significant study, and it is able to highlight mast cells in amphibians and their putative capability to respond to and combat fungal infections. Therefore, this study is important for the field. However, the manuscript is incomplete from the standpoint that there is functional data lacking on how these mast cells are activated and their precise functional properties. Such experiments would add substantial impact and rigor and fully support the conclusions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study applies voltage clamp fluorometry to provide new information about the function of serotonin-gated ion channels 5-HT3AR. The authors convincingly investigate structural changes inside and outside the orthosteric site elicited by agonists, partial agonists, and antagonists, helping to annotate existing cryo-EM structures. This work confirms that the activation of 5-HT3 receptors is similar to other members of this well-studied receptor superfamily. The work will be of interest to scientists working on channel biophysics but also drug development targeting ligand-gated ion channels.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors present a comprehensive set of tools to compactly characterize the time-frequency interactions across a network. The utility of the toolbox is compelling and demonstrated through a series of exemplar brain imaging datasets. This fundamental work adds to the repertoire of techniques that can be used to study high-dimensional data.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This work uses an interdisciplinary approach combining microfluidics, structural biology, and genetic analyses to provide valuable findings that show that pathogenic enteric bacteria exhibit taxis toward human serum. The data are solid and show that the behavior utilizes the bacterial chemotaxis system and the chemoreceptor Tsr, which senses the amino acid L-serine. The work provides an ecological context for the role of serine as a bacterial chemoattractant and could have clinical implications for bacterial bloodstream invasion during episodes of gastrointestinal bleeding.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study contributes insights into the regulatory mechanisms of a protein governing cell migration at the membrane. The integration of approaches revealing protein structure and dynamics provides convincing data for a model of regulation and suggests a new allosteric role for a solubilized phospholipid headgroup. The work will be interesting to researchers focusing on signaling mechanisms, cell motility, and cancer metathesis.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this valuable manuscript, Yao et al. describe new methods for assessing the intracellular itinerary of Botulinum neurotoxin A (BoNT/A), a potent toxin used in clinical and cosmetic applications. The current manuscript challenges previously held views on how the catalytic portion of the toxin makes its way from the endocytic compartment to the cytosol, to meet its substrates. The approach taken is deemed innovative and the experiments are carefully performed, however, they are somewhat incomplete with respect to the drawn conclusions, as it is possible that the scope of their findings could be restricted to the specific neuron model and molecular tools that were used. This paper could be of interest to both cell biologists and physicians.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this study, camera trapping and species distribution models are used to show that human disturbance in mountain forests in the eastern Himalayas pushes medium-sized and large mammal species into narrower habitat space, thus increasing their co-occurrence. While the collected data provide a useful basis for further work, the study presents incomplete evidence to support the claim that increased co-occurrence may indicate positive interactions between species.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental study addresses a long-standing mystery in splicing regulation: does splicing occur co- or post-transcriptionally? The authors provide compelling evidence demonstrating that splicing can occur post-transcriptionally at a transcription site proximal zone, changing the way we think about splicing.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important study using 3D mapping of neuronal activation throughout the brain after pair-bonding in the monogamous vole, which can be broadly applied to other species and behaviors. The authors provide compelling evidence that there is some synchrony between male and female partners that have formed a pair bond, the strength of which is based on the number of ejaculations received by the female. Same-sex pairs also form a pair bond and were found to have activation in the same brain regions as mixed sex couples. An overall low level of sex differences in the degree and location of brain activation was observed, which was unexpected. This work will be of interest to those interested in social behavior and its neural mechanisms, or brain systems or behavior more broadly.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study reports on an improved deep-learning-based method for predicting TCR specificity. The evidence supporting the overall method is compelling, although the inclusion of real-world applications and clear comparisons with the previous version would have further strengthened the study. This work will be of broad interest to immunologists and computational biologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Studies of synaptic development and plasticity in the nematode C. elegans have been limited by the difficulty of rapid, accurate assessments of synaptic structure. Here, with a series of convincing studies, the authors introduce and validate a valuable computational pipeline, "WormPsyQi," that allows rapid, reproducible quantitation of fluorescent synaptic puncta while minimizing human error and bias. The authors also describe a new set of strains carrying synaptic markers. Together, these tools should provide groups studying this model system with the ability to quantitatively characterize chemical and electrical synapses, even in densely packed regions in 3D space such as the nerve ring.
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eLife assessment
The study is of importance for the cardiac modeling field by developing a novel mathematical model with sex difference. The data are compelling, and the model is helpful for mechanistic understanding, and thus is also important for experimental physiology. The model is based on experimental data and validated against some experimental data.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The important work by Aballay et al. significantly advances our understanding of how G protein-coupled receptors (GPCRs) regulate immunity and pathogen avoidance. The authors provide convincing evidence for the GPCR NPR-15 to mediate immunity by altering the activity of several key transcription factors. This work will be of broad interest to immunologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
BMP signaling plays a vital role in skeletal tissues, and the importance of its role in microtia prevention is novel and promising. This important study will shed light on the role of BMP signaling in preventing microtia in the ear. Solid data broadly support the claims with only minor weaknesses.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The study has added value to what we have already known in the potential pharmacological immunomodulatory therapies in LPS-induced sepsis, and especially the use of oral leucine might be of great interest to the readers engaged in this field. We believe this study is important and provides solid evidence on the potential use of leucine in sepsis.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study presents a novel method to analyze the correlation between the degree of pigmentation, and the gene expression profile of human-induced pluripotent stem cell-derived Retinal Pigmented Epithelial (iPSC-RPE) cells at the single cell level, trying to establish if this parameter might be of use as a guide for transplantation. The presented evidence is incomplete: pigmentation was not an indicator of functionality or maturity and the data, although obtained from a pertinent approach, is limited to in vitro conditions; further, this approach is not complete since no attempts were made to graft iPSC-RPE.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study introduces a simple mechanical model of C. elegans locomotion that captures aspects of the worm's behavioral repertoire beyond forward crawling. While the kinetic model (ElegansBot) provides a useful compromise and starting point to help understand the mechanical components of C. elegans behavior, the claim that this work improves on extant mechanical models is incomplete. In addition, the results of the application of the model to previously unstudied behaviors are primarily qualitative and do not produce new predictions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable finding on developing a state-of-the-art generative model of brain electrophysiological signals to explain temporal decoding matrices widely used in cognitive neuroscience. The evidence supporting the authors' claims is convincing. The results will be strengthened by providing more clear mappings between neurobiological mechanisms and signal generators in the model. The work will be of interest to cognitive neuroscientists using electrophysiological recordings.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this important paper, Blin and colleagues develop a high-throughput behavioral assay to test spontaneous swimming and olfactory preference in individual Mexican cavefish larvae. The authors present compelling evidence that the surface and cave morphs of the fish show different olfactory preferences and odor sensitivities and that individual fish show substantial variability in their spontaneous activity that is relevant for olfactory behaviour. The paper will be of interest to neurobiologists working on the evolution of behaviour, olfaction, and the individuality of behaviour.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study by Chiu and colleagues is a valuable contribution to the study of the circuitry of aggressive behaviours and of mechanisms that generate persistent behavioural states. The authors find that activation of two interconnected sets of neurons results in an increase in female aggression. The data ruling out recurrent connectivity between these clusters underlying this persistent state are convincing.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study reports on a new method for the fabrication and the analysis of the transport through nuclear pore complexes mimic. Methods, data and analyses are convincing and show a clear correlation between the size of the nuclear pore complex mimic and its transport selectivity. This work will be of high interest to biologists and biophysicists working on the mechanosensitivity of nucleocytoplasmic transport.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study analyzes a large cohort of Adolescent Idiopathic Scoliosis (AIS) patients, identifying an association with a variant in COL11A1 (Pro1335Leu). Experimental testing of this potentially pathogenic variant in vitro suggests a connection between Pax1, Col11a1, Mmp3, and estrogen signaling, thus providing solid support for the proposed link between hormonal and matrix components in the development of AIS.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study applies solid and previously validated methodology to identify archaically introgressed genes involved in high altitude adaptation. However, to test the robustness of the approach, this study would benefit from using at least one other method to detect adaptive introgression, and clarification on how the authors scored the networks in the signet analysis. With these parts strengthened, this paper would be of interest to population geneticists, anthropologists, and scientists interested in the genetic basis underlying high-altitude adaptation in Tibet.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study reports on the genome evolution of a poorly studied fungal group. By combining long-read sequencing and various bioinformatics approaches, the authors show that the giant genome of Entomophthora muscae expanded due to extensive transposable element activity. The strength of evidence is largely solid, but some analyses are only partially supported due to different methodologies used to analyze the genomes that are being compared. This paper will be of relevance to fungal biologists as well as to evolutionary biologists interested in the study of genome size dynamics.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The manuscript describes important findings supported by convincing data. The authors present persuasive genetic and biochemical evidence that supports the biological mechanism for optimal nodulation in soybean presented in this study. The results are of relevance to understanding the signaling pathway underpinning beneficial rhizobia symbiosis, while repressing the immune response. With the discussion part strengthened this paper would be of broad interest to plant biologists working on cell signaling and plant-microbe interactions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript investigates how chloroplasts are broken down during light-limiting conditions as plants reorganize their energy-producing organelles during carbon limitation. The authors provide convincing live-cell imaging data of plastids, documenting that buds form on the surface of chloroplasts and pinch away, then associate with the vacuole via a mechanism that depends on autophagy machinery, but not plastid division machinery. However, the absence of quantitative analyses makes the work incomplete at the current stage. The manuscript nevertheless provides important groundwork for other scientists studying the regulation and breakdown of energy-producing organelles, including chloroplasts and mitochondria.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides useful information by identifying the cell type (macrophages) in synovial tissues involved in the pathogenesis of post-traumatic osteoarthritis (OA) and clarifying distinct transcriptomic signatures that may be a good therapeutic target for OA. However, the analysis performed so far is incomplete, with a main weakness being the lack of data to confirm the authors' speculation about the underlying mechanisms.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study presents a new way to selectively activate a cell signaling pathway in a specific cell type by designer ligands that link signaling co-receptors to a marker specific to the target cells. Convincing experimental results demonstrate that the agonist molecules activate Wnt signaling in target cells expressing the marker as intended. More broadly, this concept could be used to induce Wnt signaling or another pathway initiated by co-receptor association in a cell type-specific manner. In vitro results in this study could be further strengthened by assessing the biological consequences of Wnt activation in target cells.
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www.biorxiv.org www.biorxiv.org
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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 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.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study represents a valuable mechanistic contribution towards understanding how ribosomal RNA is processed during ribosome biogenesis. The biochemical evidence supporting the major conclusions is convincing. This work will be of interest to cell biologists and biochemists working on ribosome biogenesis.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents valuable findings on the potential of short-movie viewing fMRI protocol to explore the functional and topographical organization of the visual system in awake infants and toddlers. Although the data are compelling given the difficulty of studying this population, the evidence presented is incomplete and would be strengthened by additional analyses to support the authors' claims. This study will be of interest to cognitive neuroscientists and developmental psychologists, especially those interested in using fMRI to investigate brain organisation in pediatric and clinical populations with limited fMRI tolerance.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study draws attention to the importance of a previously overlooked structural motif in kinase regulation. While the data presented are intriguing and mostly solid, further analysis and additional experiments will be needed in the future to support the authors' hypothesis. The work will be of interest to protein biochemists and enzymologists with an interest in kinases and allostery.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The reviewers were generally enthusiastic about this study, noting that it reports new tools that could be valuable to the community. However, the results in follow-up experiments testing specific tools are often inconsistent with those in the literature, and some conclusions are overstated. More details are needed for both sections, the tool generation and the testing of the CNMa peptide. While the evidence for the tool development was solid, evidence demonstrating the validity of the tools was deemed incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study combines disease-associated genetic variation with a massively parallel reporter assay and different cellular perturbations to identify context-specific genetic regulatory effects. The methods and analyses are solid and the proposed functional variants will be helpful for experimental and quantitative geneticists studying a wide range of complex traits.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this manuscript, the authors investigate whether the effects of the BCG vaccine on immunity to Mtb infection could be improved by inhibiting amidation of the peptidoglycan sidechains to allow for recognition by NOD-1. This is a very important area and an interesting new approach to improve vaccination for TB. The authors find that CRISPRi knockdown of murT-gatD causes rather dramatic cell wall defects, more accessible cell wall labeling, and results in attenuated growth in macrophages and mice. This forms a foundation for further study of whether an approach like that which is presented herein would improve vaccination responses in TB.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this study, deep learning methods are deployed in the context of a group hunting scenario wherein two predators pursue a single prey. Through deep learning, the two predators achieve higher predation success than occurs with single predators. Much of the evidence in this important study is solid, with implications for future work on the ethology and simulation of cooperative behaviors.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides a valuable investigation into whether phenotypic variance due to interactions between genetic variants can be measured using genome-wide association summary statistics. The authors present a method, i-LDSC, that uses statistics on the correlations between genotypes at different loci (linkage disequilibrium) to estimate the phenotypic variance explained by both additive genetic effects and pairwise interactions. While the authors present extensive simulations on the performance of their method and empirical results indicating the presence of epistasis (as they define epistasis) it is unclear how their method and results relate to the traditional definitions of additive and non-additive genetic effects, which are different from the authors' definitions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents valuable findings regarding inter-individual variability in the neural and behavioral effects of ketamine. The methodological approach used to characterize this variability is compelling, but the evidence to support the specificity of the changes and their genetic correlates is incomplete. The study would benefit from a more thorough examination of the specificity of the pharmacological and genetic results.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a useful 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, although it could have information leakage between training and test sets, and although more emphasis should be given to predictions starting from unbound monomer structures. The authors show that their approach may be useful in some 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.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The bacterial neurotransmitter:sodium symporter homoglogue LeuT is an well-established model system for understanding the fundamental basis for how human monoamine transporters, such as the dopamine and serotonin, couple ions with neurotransmitter uptake. Here the authors provide convincing data to show that K+ binding on the intraceullular side catalyses the return step of the transport cycle in LeuT by binding to one of the two sodium sites. The mechansitic consequences of K+ binding could either facilitate LeuT re-setting and/or prevent the rebinding and possible efflux of Na+ and substrate.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper reports the fundamental discovery of adrenergic modulation of spontaneous firing through the inhibition of the Na+ leak channel NALCN in cartwheel cells in the dorsal cochlear nucleus. This study provides unequivocal evidence that the activation of alpha-2 adrenergic or GABA-B receptors inhibit NALCN currents to reduce neuronal excitability. The evidence supporting the conclusions is exceptional, the electrophysiological data is high quality and the experimental design is rigorous.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors pair single-cell sequencing technology with the LoopSeq synthetic long-read method to examine samples of hepatocellular carcinoma and benign liver, with the goal of identifying mutations and fusion transcripts specific to cancer cells. The authors present a valuable resource and the overall support for the major claims is solid.
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eLife assessment
This important study explores infants' attention patterns in real-world settings using advanced protocols and cutting-edge methods. The presented evidence for the role of EEG theta power in infants' attention is currently incomplete. The study will be of interest to researchers working on the development and control of attention.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this important study, chromatin is simulated as a polymer at the scale of genes, and the 3D organization of chromatin is analyzed at nucleosome resolution. There is convincing evidence for the emergence of chromatin microdomains due to the action of transcription factors, based on the simulation incorporating well-known biophysical properties of DNA, of nucleosomes, of linker histones, and of the transcription factor pair Myc:Max, as well as considering how the 3D organization of chromatin results from bending and looping of DNA. The work greatly improves our understanding of how the joint action of transcription factors and chromatin features affects chromatin structure and accessibility, which is of interest to anyone studying gene regulation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper, offering insights into the mechanisms of neuronal cell type diversification, provides important findings that have theoretical or practical implications beyond a single subfield. The data are compelling and provide evidence that features methods, data and analyses that are more rigorous than the current state-of-the-art.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper explores how Notch activity acts together with homeodomain transcription Bsh factors to establish distinct cell fates (L4 vs L5) in the visual system of Drosophila. The findings are important and have theoretical or practical implications beyond a single subfield. The methods, data, and analyses are compelling and support the claims with only minor weaknesses.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study presents a possible solution for a significant problem - that of draining vein sensitivity in functional MRI, which complicates the interpretability of laminar-fMRI results. The addition of a low diffusion-weighted gradient is presented to remove the draining vein signal and obtain functional responses with higher spatial fidelity. However, the strength of the evidence is inadequate, most tests appear to have been done only in a single subject. Significance thresholds in presented maps are very low and most cortical depth-dependent response profiles do not differ from baseline, even in the BOLD data shown as reference. Curiously, even BOLD group data fails to replicate the well-known pattern of draining towards the cortical surface.
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www.biorxiv.org www.biorxiv.org
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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 solid, but the theoretical and mechanistic interpretation of results and experimental approaches need to be strengthened. The work will be of broad interest to perceptual and cognitive neuroscience.
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eLife assessment
This important study presents a detailed investigation of the early development of cardiac and respiratory interoceptive sensitivity in infants aged 3, 9, and 18 months. The evidence supporting the conclusions are solid and based on convincing statistical analyses, despite the limited sample size for the younger and older age groups. This study will be of significant interest to developmental psychologists and neuroscientists working on interoception and its influence on socio-cognitive development.
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eLife assessment
This study presents a valuable framework and findings for our understanding of the brain as a fractal object, by observing the stability of its shape property within 11 primate species. Although the framework is well-detailed, the evidence presented is incomplete and would be strengthened by additional analyses to support the authors' claims, particularly on the effects of aging and on the interpretation of links between brain shape and the underlying anatomy. This study will be of interest to neuroscientists interested in brain morphology, and to physicists and mathematicians interested in modeling the shapes of complex objects.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In the last 15 years, large-scale association studies (GWAS) have served to estimate the association between genome-wide common variants and a large number of disparate traits and diseases in humans. This valuable method provides a new way to find correlations between the genetic component of a phenotype of interest, and all this wealth of genetic information. This software adds as a new tool to investigate genetic correlation between traits, and to generate new mechanistic hypotheses and dissect the role of the observed associations in disease heterogeneity. The results of the application of their method are solid and generally agree with what others have seen using similar AD and UKB data.
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eLife assessment
This study presents important findings on the different polymorphs of alpha-synuclein filaments that form at various pH's during in vitro assembly reactions with purified recombinant protein. Of particular note is the discovery of two new polymorphs (1M and 5A) that form in PBS buffer at pH 7. The strength of the evidence presented is solid, but the addition of replicate experiments with re-purified proteins at pH 5.8 and pH 7 would further strengthen the conclusions. The work will be of interest to biochemists and biophysicists working on protein aggregation and amyloids.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable manuscript demonstrates that the glycosyltransferase UGGT slows the degradation of endoplasmic reticulum (ER)-associated degradation substrates through a mechanism involving re-glucosylation of asparagine-linked glycans following release from the calnexin/calreticulin lectins. The evidence supporting this conclusion is solid using genetically-deficient cell models and biochemical methods to monitor the degradation of trafficking-incompetent ER-associated degradation substrates, although the manuscript could be improved through additional studies directed towards defining potential functional differences between UGGT1 and UGGT2 and additional insights into the impact of UGGT on the nature of substrate glycosylation within the ER. This work will be of specific interest to those interested in mechanistic aspects of ER protein quality control and protein secretion.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
The study provides valuable insights into OCD patients' acquisition of automaticity, skill learning, and the impact of intrinsic rewards on action sequence completion. The data provide incomplete evidence for the main claims as it is not clear that the participants' performance on the task meets the criteria for habitual behaviour.
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eLife assessment
In this study, Ger and colleagues present a valuable new technique that uses recurrent neural networks to distinguish between model misspecification and behavioral stochasticity when interpreting cognitive-behavioral model fits. Evidence for the usefulness of this technique, which is currently based primarily on a relatively simple toy problem, is considered incomplete but could be improved via comparisons to existing approaches and/or applications to other problems. This technique addresses a long-standing problem that is likely to be of interest to researchers pushing the limits of cognitive computational modeling.
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eLife assessment
This important study evaluates a model for multisensory correlation detection, focusing on the detection of correlated transients in visual and auditory stimuli. Overall, the experimental design is sound and the evidence is compelling. The synergy between the experimental and theoretical aspects of the paper is strong. The work will be of interest to neuroscientists and psychologists working in the domain of sensory processing and perception.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study advances our understanding of the brain nuclei involved in rapid-eye movement (REM) sleep regulation. Using a combination of imaging, electrophysiology, and optogenetic tools, the study provides convincing evidence that inhibitory neurons in the preoptic area of the hypothalamus influence REM sleep. This work will be of interest to neurobiologists working on sleep and/or brain circuitry.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study seeks to advance the current understanding of intergenerational olfactory changes associated with odor-induced fear conditioning in mice. Whilst the overall approach employed by the authors is appropriate and the evidence presented in support of claims is solid, there is general agreement that specific points - particularly the lack of effect in the F1 generation - deserve further attention.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study explores how archerfish adapt their shooting behavior to environmental changes, particularly airflow perturbations. It will be of interest to experts interested in mechanisms for motor learning. While the evidence for an internal model for adaptation is solid, evidence for adaptation to light refraction, as initially hypothesized, is inconclusive. As such, the evidence supporting an egocentric representation might be caused by alternative mechanisms to airflow perturbations.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study uses a novel experimental design to elegantly demonstrate how we exploit stimulus structure to overcome working memory capacity limits. While the behavioural evidence is convincing, the neural evidence is incomplete, as it only provides partial support for the proposed information compression mechanism. This study will be of interest to cognitive neuroscientists studying structure learning and memory.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important theoretical study providing insight into how fluctuations in excitability can contribute to gradual changes in the mapping between population activity and stimulus, commonly referred to as representational drift. The authors provide convincing evidence that fluctuations can contribute to drift. Overall, this is a well-presented study that explores the question of how changes in intrinsic excitability can influence distinct memory representations.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides important findings based on convincing evidence demonstrating that females and males have different strategies to regulate energy consumption in the brain in the context of low energy intake. While food deprivation reduces energy consumption and visual processing performance in the visual cortex of males, the female cortex is unaffected, likely at the expense of other functions. This study is relevant for scientists interested in body metabolism and neuroscience.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Zhang et al. deliver an important transcriptomic atlas of the human spinal cord, combining single-cell and spatial transcriptomics to unveil molecular insights. While convincingly overcoming Visium limitations using snRNA-seq, the manuscript is criticized for its largely observational approach and lack of quantitative analysis, especially in supporting claims about sex differences in motor neurons and DRG-spinal cord neuronal interactions.
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www.biorxiv.org www.biorxiv.org
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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 a valuable contribution to this branch of meta-research, and while the evidence in support of the findings is solid, the interpretation and presentation of the results (especially the figures) needs to be improved.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents findings on the structure and dynamics of the Type I ABC importer and bacterial osmolarity regulator OpuA, addressing the question of whether the substrate binding domains physically interact in a salt-dependent manner. Based on a collective assessment of the single-molecule fluorescence resonance energy transfer and cryogenic electron microscopy data, the researchers convincingly conclude that the substrate domains directly interact. These findings are valuable and it will be interesting to see if future studies can provide further evidence of this direct interaction and define it in further detail.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors propose that the asymmetric segregation of the NuRD complex in C. elegans is regulated in a V-ATPase-dependent manner, that this plays a crucial role in determining the differential expression of the apoptosis activator egl-1 and that it is therefore critical for the life/death fate decision in this species. The proposed model is interesting and the work could be important if proven correct. However, the current evidence is inadequate to support the major claims.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The identification of existing and new agents for the treatment of T-cell leukemias is clearly significant to the field of cancer biology and experimental therapeutics. This manuscript identifies an important role of Cannabis based derivatives in the treatment of T-ALL in disease-relevant cell-based and in vivo models of the disease. The work has provided new mechanistic insights into how these drugs are working, with convincing evidence. However, further work to define the exact molecular target of these drugs and expanding the work beyond a limited number of cell lines would strengthen the conclusions and impact of this work.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable finding on how the GAP DLC1, a deactivator of the small GTPase RhoA, regulates RhoA activity globally as well as at Focal Adhesions. Using a new acute optogenetic system coupled to a RhoA activity biosensor, the authors present solid evidence that DLC1 amplifies local Rho activity at Focal Adhesions. Nevertheless, the proposed mechanism could be further supported by a deeper analysis of the data.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This study presents valuable 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.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This work reports a valuable finding on glucocorticoid signaling in male and female germ cells in mice, pointing out sexual dimorphism in transcriptomic responsiveness. The convincing evidence provided supports an inert GR signaling despite the presence of GR in the female germline and GR-mediated alternative splicing in response to dexamethasone treatment in the male germline. The work may interest basic researchers and physician-scientists working on reproduction and stress-related disease conditions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This solid study presents a useful dataset regarding chromatin remodeling by the BAF complex in the context of meiotic sex chromosome inactivation. Using knockouts of the BAF complex subunit ARID1A, there appears to be pachynema arrest and a failure to repress sex-linked genes, which is supported by an increase in chromatin accessibility, as assessed by ATAC-seq.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript describes rigorous experiments that provide a wealth of virologic, respiratory physiology, and particle aerodynamic data pertaining to aerosol transmission of SARS-CoV-2 between infected Syrian hamsters. The significance of the paper is fundamental because infection is compared between alpha and delta variants, and because viral load is assessed via numerous assays (gRNA, sgRNA, TCID) and in tissues as well as the ambient environment of the cage. The strength of evidence is compelling.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study follows the career trajectories of the winners of an early-career funding award in the United States, and finds that researchers with greater mobility, men, and those hired at well-funded institutions experience greater subsequent funding success. Using data on K99/R00 awards from the National Institutes of Health's grants management database, the authors provide compelling evidence documenting the inequalities that shape faculty funding opportunities and career pathways, and show that these inequalities disproportionately impact women and faculty working at particular institutions, including historically black colleges and universities. Overall, the article is an important addition to the literature examining inequality in biomedical research in the United States.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable finding on the mechanisms underlying general anesthesia, with a focus on microglial regulation. The evidence supporting the claims of the authors is solid, although some of the novelty of these findings may be reduced based on the recent publication of a similar study. The work will be of interest to medical biologists working on mechanisms of anesthesia, microglia, and neuron-microglia interaction.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Urtecho et al. use genome-integrated massively parallel reporter assays to catalog and characterize promoters throughout the Escherichia coli genome. The result is a state-of-the-art atlas of promoters, coupled with information on their regulation, that is readily accessible through the website http://ecolipromoterdb.com. This compelling work provides an important resource for researchers studying bacterial transcriptional regulation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper reports the development of SCA-seq, a new method derived from PORE-C for simultaneously measuring chromatin accessibility, genome 3D and CpG DNA methylation. Most of the conclusions are supported by convincing data. SCA-seq has the potential to become a useful tool to the scientific communities to interrogate genome structure-function relationships.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The paper addresses the important 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. However, the logic of the channel concept as employed here, as well as the claims regarding a sensorimotor basis for these channels, is incomplete and thus requires clarification and/or modification.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The study by Chardon et al. is fundamental to advancing our understanding of presynaptic control of motor neuron output. Large-scale computer simulations were performed using well-established single motor neuron models to provide compelling evidence regarding the time-varying patterns of inputs that control motor neuron ensembles. The work will interest the community of motor control, motor unit physiology, neural engineering, and computational neuroscience.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The manuscript presents valuable evidence of temporal correlations during specific oscillatory activity between the prefrontal cortex, thalamic nucleus reuniens, and the hippocampus, in naturally sleeping animals. Such correlations represent solid evidence to support the notion that the thalamic nucleus reuniens participates in the hippocampal and prefrontal cortex dialogue subserving memory processes.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The study used slice physiology and modeling to investigate neurotransmitter release at the cerebellar parallel fiber-to-molecular layer interneuron synapse, revealing that each docking site can accommodate up to two synaptic vesicles simultaneously. The evidence presented is convincing. These important findings validate a two-step docking model and shed light on the mechanisms underlying short-term synaptic plasticity and strategies for achieving synaptic reliability, which plays a critical role in information processing in the brain.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study combines electrophysiology and neuroanatomy with pharmacological and optogenetic manipulation in the Drosophila genetic model system to pinpoint the neural substrate that is influenced by altered activity during a critical period (CP) of larval locomotor circuit development. Increasing activity during the CP causes permanent network changes, manifesting in increased recovery times from seizures and altered intersegmental coordination during locomotion, thus indicating that a setpoint of network excitability is determined during the CP. Next, compelling experiments demonstrate that this goes along with increased excitation/inhibition ratios to single identified motoneurons and most importantly, for excitability setpoint determination during the CP excitatory and inhibitory inputs are integrated such that the effect of CP hyperexcitation is rescued by the stimulation of endogenous inhibitory inputs to the motoneurons. This provides novel insight into how developing neural network excitability is tuned and how it can be entrained during the CP.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable manuscript reveals sex differences in bi-conditioning Pavlovian learning and conditional behavior. Males learn hierarchical context-cue-outcome associations more quickly, but females show more stable and robust task performance. These sex differences are related to cellular activation in the orbitofrontal cortex. Although the evidence for the claims is solid, the claim of sex differences in context-dependent discrimination behaviour is not fully supported by the data. Nevertheless, the results will be of interest to many behavioural neuroscientists, particularly those who investigate sex-specific behaviours.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Identifying chromatin interactions with high sensitivity and resolution remains technically challenging using genome-wide approaches. This study presents findings using the refined MNase-based proximity ligation method called MChIP-C, which allows for the measurement of chromatin interactions at single-nucleosome resolution on a genome-wide scale. Overall, the evidence in this manuscript is solid, and the technological advances will be valuable for the study of 3D genome structure.
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arxiv.org arxiv.org
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eLife assessment
This manuscript is an important contribution, assessing the role of intraspecific consumer interference in maintaining diversity using a mathematical model. Consistent with long-standing ecological theory, the authors convincingly show that predator interference allows for the coexistence of multiple species on a single resource, beyond the competitive exclusion principle. The model matches observed rank-abundance curves in several natural ecosystems. However, a more detailed synthesis of relevant prior studies is needed to clarify the contribution of this manuscript in the context of existing knowledge.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental study substantially advances our physical understanding of the sharp increase and saturation of the viscosity of non-confluent tissues with increasing cell density. Through the analysis of a simplified model this study provides compelling evidence that polydispersity in cell size and the softness of cells together can lead to this phenomenon. The work will be of general interest to biologists and biophysicists working on development.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors present a valuable open-source tool for three-dimensional analysis of dissected slices of human brains including 3D reconstruction and high-resolution 3D segmentation. Convincing evidence is provided based on experiments on both real and synthetic data. This tool would be useful to researchers in the neuropathology and neuroimaging field.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work addresses an interesting question for the vertebrate olfactory community of whether mice can discriminate odorant intermittency to help them navigate the environment. The data were collected and analyzed using solid methodology, however, the paper seems to fall short in demonstrating that animal is actually sensitive to intermittency but not other flow parameters. The work will be of interest to researchers working on sensory neurobiology and animal behavior.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript describes a valuable new circuit mapping and profiling technique called Multiplexed projEction neuRons retrograde barcodE (MERGEseq) that combines transcriptome and projectome data at a single-cell resolution. The authors provide solid evidence that MERGEseq can be used to identify projection targets and cell type/layer/transcriptome differences of projection neurons in the mouse prefrontal cortex, and validation experiments are rigorous. While this report is a proof-of-principle that MERGEseq is useful for circuit mapping and profiling and many potential details will influence conclusions, this technique could easily be adapted to other regions with known projection targets and adds to a growing arsenal of combinatorial circuit mapping and profiling tools.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study describes an atypical role of the odorant binding protein Obp56g in mating plug formation in Drosophila melanogaster suggesting that Obps may play roles in reproduction in addition to their originally described roles in olfaction. Mutant males lacking Obp56g fail to induce the formation of a mating plug in the female reproductive tract-leading to ejaculate loss and reduced sperm storage. The evidence supporting the claims of the authors is solid and compelling. The work will be of interest to biologists studying Obps and seminal fluid protein function and their evolution.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This work is relevant to understanding how people represent uncertain events in the world around them and make decisions, with broad applications to economic behavior. It addresses a long-standing empirical puzzle from a novel perspective, where the authors propose that sequential effects in perceptual decisions may emerge from rational choices under cognitive resource constraints rather than adjustments to changing environments. Two new computational models have been constructed to predict behavior under two different constraints, among which the one assuming higher cost for more precise beliefs is better supported by new experimental data. The conclusion may be further strengthened by comparison with alternative models and (optionally) evidence from additional data.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important paper provides web based interface for cross-tissue analysis of omics datasets from – so far – two different human populations, with compelling evidence that the tool can be used to make meaningful scientific discoveries. Conceptually, these analyses are relevant for any systems biologist or bioinformatician who is interested in integrating large population datasets. Currently, the resource is already of use for scientists studying the HMDP or using GTEx data, and we hope to see updates in the coming years that incorporate more populations and more datatypes, which could make it a general tool for a wide community.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study investigates the presence of DNA adenine methylation (6mA) and the associated function of TET enzyme, a DNA methylation mark eraser, in Drosophila. The study presents valuable findings on the scarcity of 6mA in the Drosophila genome and challenges previous findings regarding the role of TET in 6mA modification. The evidence supporting the claims is solid, and the paper has the potential to stimulate re-evaluations of the significance and regulatory mechanisms of 6mA DNA modifications in Drosophila.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental work significantly advances our understanding of the regulation of neurotransmitter and hormone secretion by exploring the mechanisms by which the protein complexin interacts with the release machinery and the calcium sensor synaptotagmin. The authors identify structural requirements within the protein for complexin's dual role in preventing premature vesicle release and enhancing evoked exocytosis. The evidence supporting the author's conclusions is compelling and the findings are of broad interest to neuroscientists and cell biologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this manuscript, the authors recorded the activity of D1- and D2-MSNs in the dorsal striatum and analyzed their firing activity in relation to single-limb gait in normal and 6-OHDA lesioned mice. This important 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 pathways, however, the reviewers also point out that the evidence supporting the conclusion that striatal neurons encode single-limb gait is incomplete.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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eLife assessment
The work addresses an important methodological aspect by optimizing an activity-dependent labelling of neural circuits in behaving flies. The authors provide convincing evidence to support the broad applicability of this method. However, a more comprehensive description of the methodology would greatly enhance its dissemination and adoption. Additionally, the authors successfully implement the method, providing solid evidence for the activity-dependent labelling of P1 neurons during aggression and courtship.
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eLife assessment
This study provides valuable insights into how chromatin-bound PfMORC controls gene expression in the asexual blood stage of Plasmodium falciparum. By interacting with key nuclear proteins, PfMORC appears to affect expression of genes relating to host invasion and subtelomeric var genes. Correlating transcriptomic data with in vivo chromatin insights, the study provides solid evidence for the central role of PfMORC in epigenetic transcriptional regulation through modulation of chromatin compaction.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The findings presented by Huff and colleagues describe different motor patterns of swallowing following optogenetic activation of the Postinspiratory Complex (PiCo) in a group of mice exposed to Chronic Intermittent Hypoxia (CHI). The presented results are important, and the experimental procedures are rigorous and technically remarkable, but drawing meaningful conclusions is currently not obvious due to some bias in statistical comparisons that require consideration. The strength of the evidence is currently incomplete and would benefit from additional experiments. Overall this work would be of interest to the field of respiratory physiology and pathophysiology since a disruption of swallowing and possibly discoordination with breathing may be involved in diseases characterized by the presence of hypoxic conditions such as obstructive sleep apnea.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study provides convincing evidence of the criticality of estradiol – estrogen receptor-mediated upregulation of kisspeptin within neurons of the preoptic area to generate an ovulation-inducing luteinizing hormone surge. The use of in vivo CRIPSR-Cas9 is novel in this system and provides a road map for future studies in reproductive neuroendocrinology. This paper will be of interest to reproductive neuroscientists and endocrinologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important paper that revises the canonical model of how olfactory sensory neurons choose which odor receptor to express. The data presented in the paper are convincing and the model proposed is provocative and likely to enable future work.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors of this manuscript address the following question in the immunology field: what are the transcriptional regulators that allow macrophages to assume different functional phenotypes in response to immune stimuli? They generate a computational map of the gene regulatory networks involved in determining macrophage phenotypes and experimentally validate the role of putative regulatory factors in a myeloid cell line. This study represents a valuable approach to understanding how gene regulation impacts macrophage polarization but the analyses remain incomplete without further validation in primary cells or by examining the identified genes in the in vivo setting.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The large-conductance Ca2+ activated K+ channel has been reported to promote breast cancer progression. The present study presents convincing evidence that an intracellular subpopulation of this channel reprograms breast cancer cells towards the Warburg phenotype, one of the metabolic hallmarks of cancer. This important finding advances the field of cancer cell metabolism and has potential therapeutic implications. However, additional experiments are needed to ascribe the metabolic reprogramming to BK channels located in mitochondria.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study reveals the RelA/Stat3-dependent gene program in the liver influences intestinal homeostasis. The evidence supporting the conclusions is compelling, although some additional experiments will strengthen the study. The work will be of interest to scientists in gastrointestinal research fields.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this convincing study, the authors examine the interactions between stellate cells and PV+ interneurons in the medial entorhinal cortex, shedding light on the circuit mechanisms that underlie grid cell activity. Huang et al., focus on the spatial distribution of synaptic inputs and report that closely located neuron pairs receive common inputs, suggesting a structured functional organization in the entorhinal cortex. Advanced dual whole-cell patch recordings further reveal patterns of postsynaptic activation, indicating intensive interactions within clusters of these neurons, with weaker interactions between clusters. These important findings offer significant insights into the functional dynamics of the entorhinal cortex.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides important new insights into how multisensory information is processed in the lateral cortex of the inferior colliculus, a poorly understood part of the auditory midbrain. By developing new imaging techniques that provide the first optical access to the lateral cortex in a living animal, the authors provide convincing in vivo evidence that this region contains separate subregions that can be distinguished by their sensory inputs and neurochemical profiles, as suggested by previous anatomical and in vitro studies. Additional information and analyses are needed, however, to allow readers to fully appreciate what was done, and the comparison of multisensory interactions between awake and anesthetized mice would benefit from being explored in more detail.
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eLife assessment
This study reports useful findings on the influence of acute stress on prosocial behavior and its neural correlates. The approach is solid, combining neuroimaging and neuroendocrine measures with computational cognitive modeling. The results will be of interest to researchers seeking to better characterize the influence of stress on neural computations mediating complex social behavior.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study by Nandy and colleagues examined relationships between behavioral state, neural activity, and trial-by-trial variability in the ability to detect weak visual stimuli. They present useful findings indicating that certain changes in arousal and eye-position stability, along with patterns of synchrony in the activity of neurons in different layers of cortical area V4, can show modest correspondences to changes in the ability to correctly detect a stimulus. At present, however, the findings are based on data and analyses that are somewhat incomplete but could be improved with further revisions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The study by Zhu et al. provides important insights into cell-specific genome-wide histone modifications in the frontal cortex of individuals with schizophrenia, as well as shedding light on the role of age and antipsychotic treatment in these associations. The evidence supporting the conclusions is solid, although more details regarding methodology would be helpful, and the integration of additional data could further enhance the novelty of the study.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study combines experiments and fluid mechanics modeling to determine the mechanism of the ultrafast ejection of the polar tube of the Microsporidia parasite and of transport through this tube. The methods and the analysis, based on the variation of the viscosity of the external medium, are compelling and allow for the first time to discriminate among proposed ejection mechanisms. This approach where simple physical principles are used for distinguishing between mechanisms when the precise geometry is inaccessible through imaging is potentially applicable to other systems in microbiology.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This interesting and important manuscript combines in vitro and in vivo experiments to investigate the reciprocal regulation between mitochondria-associated membranes and Notch signaling in skeletal muscle atrophy, with implications beyond the single subfield of muscle atrophy. The methods, data, and analyses are solid and broadly support the claims.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study reports the identification of a new amino acid sequence motif (i.e., "internal beta-signal") on outer membrane proteins, which is recognized by beta-assembly machinery in gram-negative bacteria. The authors carried out rigorous experiments, providing compelling evidence in support of their conclusions. This work significantly advances our understanding of the biogenesis of outer membrane proteins.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study examines the effects of prenatal alcohol exposure and maternal diet on offspring DNA methylation, revealing that alcohol can alter epigenetic patterns and impact brain and organ development in the fetus, with some changes preventable by a diet rich in folate and choline. The work identifies several differentially methylated regions linked to adverse health outcomes from alcohol exposure, but the evidence is somewhat incomplete, as the paper currently lacks comprehensive methodological details and sensitivity analyses. Further analysis of the functional relevance of these DNA methylation changes, particularly addressing the current technical and statistical shortcomings, would increase the study's novelty and significance.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents valuable insights into the epigenetic landscape in adult kidney podocytes. A series of solid experiments demonstrate that genes that are regulated by a key kidney transcription factor, Mafb, are essential for H3K4me3 methylation and recruitment of Wt1 to Nphs1 and Nphs2. This new information provides insights into the potential relationship and coordination of transcription factors in regulating target genes in podocytes in glomerular diseases, although the conclusion that MafB is generally required for Wt1 to bind to podocyte-specific promoters is incomplete and should be extended beyond two or three genes.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study seeks to address the importance of physical interaction between proteins in higher-order complexes for covariation of evolutionary rates at different sites in these interacting proteins. Following up on a previous analysis with a smaller dataset, the authors provide solid evidence that the exact contribution of physical interactions, if any, remains difficult to quantify. A weakness of the study is that alternative hypotheses, specifically the importance of similar expression levels and patterns of genes that encode interacting proteins -- for which there is already substantial evidence in the literature -- are not sufficiently considered. The work will be of relevance to anyone interested in protein evolution.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides a valuable resource that documents the protein-protein interactions (PPI) network for alpha-arrestins in both human and Drosophila based on affinity purification/mass spectrometry and the SAINTexpress method followed by a series of bioinformatic and functional assessments. Through these, the authors confirmed the roles of known and novel interactions, including proteins involved in RNA splicing and helicase, GTPase-activating proteins, and ATP synthase. This study represents a convincing example of how to adopt comparative molecular interactions and how to interpret the functional implications.
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www.biorxiv.org www.biorxiv.org
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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 is different from that in the more commonly studied opisthokonts and there is solid support from RNAi and imaging experiments, targeted mutations, immunoprecipitations with crosslinking/mass spec, and AlphaFold interaction predictions. The results could be strengthened by biochemically testing proposed direct interactions and demonstrating that the targeting protein KIN-A is a motor. The findings will be of interest to parasitology researchers as well as cell biologists working on mitosis and cell division, and those interested in the evolution of the CPC.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a useful characterization of mechanisms underlying glycosuria-mediated increase in compensatory glucose production in Glut2 knockout mice. The strength of support is incomplete but the data represent a starting point for further studies regarding the role of the HPA axis and acute phase proteins in regulating blood glucose during glycosuria.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study enhances our understanding of the relationship between metabolic syndrome (MetS) and brain health from two large-scale datasets and crosses different scales of investigation. The results range from solid to inadequate, with the overall effects of MetS on the brain well supported, but the claimed inference of non-fasting blood glucose reflecting insulin resistance and suggestions of causative link to cognitive function need to be revised or tempered. Overall this study will be of great interest to researchers and clinicians seeking to understand metabolic syndrome.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript provides a useful reconstruction of the structure of the sirtuin-class histone deacetylase Sirt6 bound to a nucleosome based on cryo-EM observations, and additional characterization of the flexibility of the histone tails in the complex based on molecular dynamics simulations. While similar structures have recently been published, this solid study supports the conclusions of those papers and also includes new insights into the potential dynamics of Sirt6 bound to a nucleosome, insights that help explain its substrate specificity. Unfortunately, the authors do not mention the other recent publications until the end of their Discussion, and therefore provide little opportunity for comparison or context for the results presented.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript describes valuable new findings on the impact of chromatin context on the outcomes of microhomology-mediated end joining of DNA double-strand breaks (DSBs), specifically a preference for DSB-proximal microhomologies in repair within a heterochromatic compared to a euchromatic locus. The authors develop the Drosophila spermatogonia as a model for repair at induced DSBs in a mitotically-active tissue and leverage this system to provide convincing evidence that the local environment impacts the preference for repair mechanism and outcome. The work could be strengthened by the use of additional euchromatin insertion(s) to robustly validate the findings.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study combines experiments and mathematical modelling to enhance our understanding of the interplay between the two flight muscles in birds during slow flight. The evidence for the findings is compelling, derived from new methods for measuring wing shape and force production combined with previously validated methods in muscle physiology. This work will be of broad interest to comparative biomechanists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study shows that the yeast transcription factor Sfp1 binds to a subset of its target gene mRNAs, increases their half-lives, and affects RNA polymerase II backtracking. These, and other related findings, provide important new insights into mechanisms by which a transcription factor can affect post-transcriptional steps in gene regulation. The main claims are partially backed by the evidence presented. However, the evidence remains incomplete as the methods used to estimate RNA degradation rates and the biochemistry of Sfp1-RNA complexes require further validation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This in principle useful study suggests that the G-protein subunit Gng13 is required for limiting injury and inflammation following H1N1 influenza infection via anti-inflammatory effects from ectopic tuft cells. There appears to be support for Gng13 helping to limit influenza injury in the transgenic mouse models used here, but evidence for these effects being mediated by tuft cells is incomplete, giving conflicting data from mice that lack tuft cells entirely.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper presents what could be a useful approach for association testing, using the output of neural networks that have been trained to predict functional changes from DNA sequences. The approach presented by the author is an interesting addition to statistical genetics. It is, however, unclear whether the method not only detects more associations but also whether the quality of these associations (i.e., the likelihood that they are causal associations) is as good or better than what one finds with conventional methods. The enrichment analyses are encouraging but without rigorous assessment of statistical power and a better understanding of the pitfalls of the method, the evidence for this being an advance that will find application in the field remains incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study uses a combination of computational modeling and glutamate imaging to show how a particular synaptic organization referred to as space-time wiring contributes minimally to a dendritic computation that occurs in the retina. The evidence supporting the claims of the authors is compelling, incorporating new findings regarding dynamic receptive field properties, an improvement over previous modeling and experimental results based on static visual stimuli. The work will be of interest to retinal neurobiologists and neurophysiologists interested in dendritic computations.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The work shows that the experimental application of serotonin to locust antennal lobes induces an increased feeding-related response to some odorants (even in food-satiated animals). To explain how the odorant-specific effects are seen despite similar consequences of 5-HT modulation on all projection neuronal types analyses by electrophysiology, the authors propose a simple quantitative model built around PNs with different downstream connections. These convincing observations are useful to guide further studies of serotonin and other modulatory mechanisms in the olfactory system.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript provides solid evidence for the involvement of membrane actin, and its regulatory proteins, mDia1/3, RhoA, and Rac1 in the mechanism of synaptic vesicle re-uptake (endocytosis). These valuable data fill a gap in the understanding of how the regulation of actin dynamics and endocytosis are linked. The manuscript will be of interest to all scientists working on cellular trafficking and membrane remodeling
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important paper on the role of engrams and relevant conditions that influence memory and forgetting. The variety of methods used, namely, behavioural, labeling, interrogation, immunohistochemistry, microscopy, pharmacology, and computational, are exemplary and provide solid evidence for the role of engrams in the dentate gyrus in memory retrieval and forgetting. This examination will be of interest broadly across behavioural and neural science.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study shows that, in mice, fresh cat saliva elicits a greater defensive response compared to old cat saliva. Additionally, the authors implicate the vomeronasal organ (VNO) and ventromedial hypothalamus (VMH) as part of a circuit that underlies this process. While the study has potential, the results are somewhat preliminary, and as such the evidence presented is incomplete.
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www.researchsquare.com www.researchsquare.com
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eLife assessment
This important study advances our understanding of the potential mechanisms of deep-sea adaptation and sheds light on the evolutionary history of hadal snailfish. Through comparative genomic analysis, the authors provide convincing evidence and propose hypotheses on the timing of trench colonization, population structure, and adaptations to the hadal snailfish genome in response to their environment.
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eLife assessment
This is an important study that addresses a significant question in microbiome research. The authors provide convincing evidence that certain bacterial groups within the fly microbiome have critical functions for host development. Additionally, dietary aspects such as microbial community progression in a natural food source are integrated into their host-microbe interaction analyses.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental study explores the relationship between guanine-quadruplex structures and pathogenicity islands in 89 pathogenic strains. Guanine-quadruplex structures were found to be non-randomly distributed within pathogenicity islands and conserved within the same strains. Positive correlations were observed between Guanine-quadruplex structures and GC content across various genomic features, suggesting a link between these structures and GC-rich regions. These compelling findings shed light on the molecular mechanisms of Guanine-quadruplex structure-pathogenicity island interactions and will be of interest to all microbiologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The findings in this fundamental study identify a novel substrate and mediator of oncogenesis downstream of mTORC1 and advance our understanding of the mechanistic basis of mTORC1-regulated cap-dependent translation and protein synthesis. The authors present convincing data using an array of biochemical, proteomic, and functional assays. These studies are of broad relevance to biochemists and cancer biologists and have potential translational relevance in cancer.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study explores the activation mechanisms of members of the kinesin-3 family, demonstrating common and unique regulation modes with solid evidence. The findings make for valuable contributions to the field of kinesin activation and regulation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study explores the activation mechanisms of members of the kinesin-3 family, demonstrating common and unique regulation modes with solid evidence. The findings make for valuable contributions to the field of kinesin activation and regulation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The manuscript investigates how the tandem reader domains in BPTF co-recognize two types of modifications present on histone tails, H3K4me3 and H3 acetylation. The authors interpret their results in the context of the conformational restriction of histone tails due to interactions with nucleosomal DNA. The findings contribute new insights into how the nucleosomal context regulates the recognition of multiple histone modifications by tandem reader domains and should be of interest to the broader chromatin field.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable paper examines the link between the neuropeptide cholecystokinin (CCK) and motor learning and neural plasticity in the motor cortex. While CCK was known to be involved in neural plasticity in other brain regions and behavioral contexts, this study is the first to provide evidence that CCK manipulation causes deficits in motor learning. However, the evidence for specific effects regarding behavior, activity, and pathways is currently incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this important study, the authors propose that lenacapavir inhibits HIV-1 replication by inducing "lethal hyperstabilization" of the capsid, based on experiments that clearly demonstrate such an effect at high drug concentrations. Data supporting the model are incomplete at low drug concentrations, and a firm correlation between the in vitro effects and therapeutic mechanism of action has not yet been established.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work presents a systematic survey of downstream target genes of the BMP pathway during body-axis establishment of the cnidarian Nematostella vectensis. BMP is a well-known developmental regulator, and this work identifies a previously unknown array of downstream targets. Combining genomic approaches and genetic manipulations, the authors present convincing evidence that Zswim4-6 acts as a negative feedback regulator of BMP activity in Nematostella. The authors also test a zebrafish homologue in over-expression assays and show solid evidence that it too dampens BMP signaling activity, leading to the suggestion that zswim4-6 is a conserved regulator of BMP signaling. This work will be of interest to researchers in the fields of both developmental biology and evo-devo.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents an important finding on the serial attentional resource allocation during parallel feature value tracking. The evidence supporting the claims of the authors is solid, although further clarification for high-/low-precision assigning, task effectivity of active tracking, and data analysis would have strengthened the study. The work will be of broad interest to psychology and cognitive science.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study provides a combination of experiment and theory to investigate the role of a key signalling pathway as a patterning guide for local and global mechanical properties in a developing tissue. It poses solid evidence that local dynamical effects are not necessarily predictive of global tissue mechanics, although it does not offer an alternative mechanistic explanation. This multidisciplinary work will likely have an impact on the fields of tissue mechanics and developmental biology.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The findings provided by Mohibi et al. are important to the field of lipid metabolism and cancer and provide insight for an in vivo role of FDX1. The evidence is solid, utilizing multiple modalities and both in vitro and in vivo lines of investigation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important initial study of cell type and spatially resolved gene expression in and around the locus coeruleus, the primary source of the neuromodulator norepinephrine in the human brain. The data are generated with cutting-edge techniques, and the work lays the foundation for future descriptive and experimental approaches to understand the contribution of the locus coeruleus to healthy brain function and disease. The empirical support for the main conclusions is solid. This paper, and the associated web application, will be of great interest to neuroscientists working on arousal-based behaviors and neurological and neuropsychiatric phenotypes.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The paper contains some useful analysis of existing data but there are concerns regarding the conclusion that there might be alternative mechanisms for determining the location of origins of DNA replication in human cells compared to the well known mechanism known from many eukaryotic systems, including yeast, Xenopus, C. elegans and Drosophila. The lack of overlap between binding sites for ORC1 and ORC2, which are known to form a complex in human cells, is a particular concern and points to the evidence for the accurate localization of their binding sites in the genome being incomplete.
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www.researchsquare.com www.researchsquare.com
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eLife assessment
This fundamental study presents a method to restore muscle innervations in ALS mouse models using optogenetics. It is convincing that embryonic stem cell derived motor neurons can be transplanted into and applied to reinnervate the muscles in an ALS mouse model. The work will be of broad interest to researchers and medical biologists to develop new strategies for the treatment of neurodegenerative disorders resulting from denervated skeletal muscles.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important article provides insights into the neural centers and hormonal modulations underlying seasonal changes associated with photoperiod-induced life-history states in birds. The physiological and transcriptomic analyses of the mediobasal hypothalamus and pituitary gland offer convincing evidence for a timing mechanism for measuring day length, which is relevant for the field of seasonal biology. The study's experiments and findings have the potential to captivate the attention of molecular and organismal endocrinologists and chronobiologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important study that provides new insights into the development and function of medullary thymus epithelial cells (mTEC). The authors provide compelling evidence to support their claims as to the differentiation and lineage outcomes of CCL21+ mTEC progenitors, which further our understanding of how central tolerance of T cells is enforced within the thymus.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This important study will provide evidence about a novel screen-triage-treat strategy for cervical cancer prevention. The trial will generate convincing evidence regarding the efficacy, effectiveness, cost-effectiveness, feasibility and acceptability in a range of geographically spread low-resource settings. The strategy should contribute to improving access to cervical cancer prevention to vulnerable women with low access to health care, and, therefore, at the highest risk of cervical cancer.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents useful findings regarding the role of formin-like 2 in mouse oocyte meiosis. The submitted data are supported by incomplete analyses, and in some cases, the conclusions are overstated. If these concerns are addressed, this paper would be of interest to reproductive biologists.
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www.researchsquare.com www.researchsquare.com
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eLife assessment
Both reviewers positively received the manuscript, in general. The agreement was that the manuscript presented valuable findings, using solid techniques and approaches, that shed additional light into how the canine distemper virus hemagglutinin might engage cellular receptors and how that engagement impacts host tropism. While both reviewers appreciated the X-ray crystallographic data, they also felt that the AFM experiments could have been performed at a higher standard and that the interpretation of the results ensuing from those AFM experiments could have been explained more thoroughly and in simpler terms. An additional missed opportunity of the current manuscript is the lack of comparison of the crystal structure to that of the already published cryo-EM structure, for context.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This important work employed global proteomic and phosphorylation site analysis to examine adipose tissue and skeletal muscle samples collected at baseline from a sample of 10 women, including those with and without PCOS, both before and after 5 weeks of electrical stimulation treatment. This work significantly enhances our knowledge by demonstrating that women with PCOS who exhibit protein hyperandrogenicity have elevated extramyocellular lipid levels and a decreased number of oxidative insulin-sensitive type I muscle fibers. The convincing evidence supporting these conclusions makes this research of broad interest not only to scientists but also to clinicians.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a potentially valuable discovery which indicates that activation of the P2RX7 pathway can reduce the lung fibrosis after its establishment by inflammatory damage. If confirmed, the study could clarify the role of specific immune networks in the establishment and progression of lung fibrosis. However, the presented data and analyses are incomplete as they primarily rely on limited pharmacological treatments with modest effect sizes.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The manuscript provides interesting evidence that miR-199b-5p regulates osteoarthritis and as such it may be considered as a potential therapeutic target. This finding may be useful to further advance the field. Although the study is considered potentially clinically relevant, the evidence provided was deemed insufficient and incomplete to support the conclusions drawn by the authors.
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- Nov 2023
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study uses cutting-edge miniature two-photon microscopy to follow the structural dynamics of microglia in the somatosensory cortex of freely-moving mice across the sleep/wake cycle. Solid evidence revealed the brain-state-dependent regulation of microglial activity, highlighting alterations in microglial morphology during REM and NREM sleep phases compared to wakefulness. Furthermore, this study provides evidence for a critical role of norepinephrine from the locus coeruleus as a modulator of microglial morphology through the β2-adrenergic receptor (b2AR). Overall, the article is an impressive technical feat to bridge a crucial gap in understanding sleep state-induced dynamics of microglia and its modulation by norepinephrine signaling.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Based on the observation of an increase in miR-182-5p in diabetic patients, the authors propose that miR-182-5p and its target gene LRP6 may play a role in dysregulated glucose tolerance and fatty acid metabolism in obese type 2 diabetics. The use of human livers complemented by supporting data in mice and cells are strengths, but the evidence presented remains incomplete. Nonetheless, the findings provide valuable insights into the role of miRNAs in the regulation of liver metabolism and insulin sensitivity in individuals with diabetes and fatty liver disease.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study identifies an Ephrin type-B Receptor 2 (EPHB2) interactor, MYCBP2, as a potential regulator of EPHB2 stability and function. In contrast to expectations, based on MYCBP2 function in the ubiquitin pathway, loss of function of MYCBP2 resulted in less EPHB2 receptor and defective EPHB2 function. The paper is supported by a largely convincing set of biochemical, cell culture and in vivo experiments.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study describes a method to decouple the mechanisms supporting pancreatic progenitor self-renewal and expansion from feed-forward mechanisms promoting their differentiation allowing in vitro expansion of hPSC-derived pancreatic progenitors. The strength of evidence is convincing in that the authors use appropriate and validated methodology in line with current state-of-the-art. The work will be of interest to the field of beta cell replacement therapy in diabetes.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study seeks to disentangle the different selective forces shaping the evolutionary dynamics of transposable elements (TEs) in the wild grass Brachypodium distachyon. Using haplotype-length metrics, and genetic and environmental differentiation tests, the authors present in large parts convincing evidence that positive selection on TE polymorphisms is rare, and that the distribution of TE ages points to purifying selection being the main force acting on TE evolution in this species. A caveat of this study, as of other studies that seek to assess TE insertion polymorphisms with short reads, is that the rates of false negatives and false positives are difficult to estimate, which may have major effects on the interpretation. This study will be relevant for anyone interested in the role of TEs in evolution and adaptation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The important study describes exhaustive deep mutational scanning (DMS) of the gonadotropin-releasing hormone wild-type receptor and for two single point mutations reported to impact its folding and structure, monitoring how plasma membrane expression levels are affected by mutations. This important work is pioneering in exploring the interaction between mutations (epistasis) in a membrane protein, with a potential for explaining membrane protein evolution and genetic diseases. The evidence provided for some mutations is convincing, but it remains incomplete and harder to interpret for others without further validation of folding and stability properties of the mutants.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study elucidates the role of a specific hemocyte subpopulation in oxidative damage response by establishing connections between DNA damage response and the JNK-JAK/STAT axis to regulate energy metabolism. The identification of this distinct hemocyte subpopulation through single-cell RNA sequencing analysis and the finding of hemocytes that respond to oxidative stress are important. The method for single-cell RNA sequencing and related analyses are convincing and experiments linking oxidative stress to DNA damage and energy expenditure are solid. The finding of stress-responsive immune cells capable of influencing whole-body metabolism adds insights for cell biologists and developmental biologists in the fields of immunology and metabolism.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript offers a valuable contribution to studying wildlife responses during and after COVID-19 lockdowns. It convincingly demonstrates that bird species in urban areas respond differently to human activity changes. What sets this study apart from others on avian responses to COVID-19 lockdowns is its use of passive acoustic monitoring. By concurrently measuring anthropogenic noise, a crucial reflection of changes in human activity due to COVID-19 lockdowns, this study reveals rare local-scale variations in bird responses to human activity. Only one study so far has used vocalization recordings to assess the effects of COVID-19 lockdowns on a bird species.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study combines experimental and computational data to address crucial aspects of RNA methylation by a vital RNA methyltransferase (MTase). The authors have provided compelling, strong evidence, utilizing well-established techniques, to elucidate aspects of the methyl transfer mechanism of methyltransferase-like protein 3 (METTL3), which is a part of the METTL3-14 complex. This work will be of broad interest to biochemists, biophysicists, and cell biologists alike.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides useful evidence that GIF/MT-3 harbors sulfane sulfur, which may play a role in zinc coordination. The study includes a variety of well-designed assays to support the authors' hypothesis, revealing that sulfane sulfur is released from MT-3. The analysis and conclusions could benefit from a more rigorous approach to analyzing sulfur and zinc content in recombinant MT3 protein, leaving the evidence in parts incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study investigates two secreted Mycobacterium tuberculosis proteins, ESAT-6 and CFP10, using biochemical assays, including a Biolayer Interferometry assay. Solid experimental evidence demonstrates that ESAT-6 forms a tight interaction with CFP10 as a heterodimer at neutral pH and that ESAT-6 also forms a homodimer at acidic pH. Additional, more definitive evidence is required to describe how these proteins disrupt the phagosomal membrane.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The study investigates the functional impact of cranial irradiation in mouse and proposes PAK3 as molecular element involved in radiation-induced cognitive decrement. The significance of the findings is useful for fields covering radiation, brain tumor and cognition. The strength of evidence is solid, although the referees expressed divergent views on the manuscript.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this important study, chromatin is simulated as a polymer at the scale of genes and 3D organization is analyzed at nucleosome resolution. There is convincing evidence for the emergence of microdomains due to the action of transcription factors, based on the simulation incorporating well-known biophysical properties of DNA, of nucleosomes, of linker histones, and of the transcription factor pair Myc:Max, as well as the 3D organization resulting from bending and looping of DNA. The work improves our knowledge of how the joint action of transcription factors and chromatin features affects chromatin structure and accessibility, which is of interest to anyone studying gene regulation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper provides useful information about how the ionome of Arabidopsis thaliana adapts to very high CO2-levels, backed up by solid evidence and carefully designed studies. However, the broader claims of the paper about climate change and food security - heavily emphasized in the abstract, introduction, and discussion - are inappropriate, as there is no direct link to the presented work.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study analyzes a large cohort of Adolescent Idiopathic Scoliosis (AIS) patients, identifying an association with a variant in COL11A1 (Pro1335Leu). Experimental testing of this potentially pathogenic variant in vitro suggests a connection between Pax1, Col11a1, Mmp3, and estrogen signaling, thus providing solid support for the proposed link between hormonal and matrix components in the development of AIS.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The effect of Vitamin D supplementation in reducing asthma via anti-inflammatory mechanisms is a topic of wide interest, with somewhat conflicting published data. Here, bioinformatic approaches help to identify a role of VDR in inducing the expression of the key regulator Ikzf3, which possibly suppresses the IL-2/STAT5 axis, consequently blunting the Th2 response and mitigating allergic airway inflammation. The evidence is solid and the findings are important for researchers in the field.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study aims to identify pioneer transcription factors - which are defined as transcription factors that compete with nucleosomes for DNA binding. The authors provide methods for identifying pioneer transcription factors on a cell type basis, using nucleosome positioning and motif information across different cell lines. The evidence to support the claims is largely solid. This work will be of interest to computational and molecular biologists working on transcription factors.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript introduces two valuable new metrics - "variant vulnerability" and "drug applicability" - that would be of use to identify candidate drugs for treating infections while considering longer-term, evolution-based treatment outcomes. Despite the intuitive appeal of the metrics and their potential, the study remains incomplete, as it fails to demonstrate the generality of the approach. The work could be improved by analysing a broader range of data in a systematic way and directly tying the metrics to outcomes, which would make it possible to better assess their impact and utility.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this valuable study, the discovery and subsequent design of the AF03-NL chimeric antibody yielded a tool for studying filoviruses and provides a possible blueprint for future therapeutics. However, the data are incomplete and not presented clearly, which obscures flaws in the analyses and leaves unexplained phenomena. The work will be of interest to virologists studying antibodies.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study employs a diverse array of techniques encompassing cell biological manipulations, biophysical measurements, and mouse models to elucidate the impact of target cell stiffness on CD8+ cytotoxic T cell activation, with a particular focus on the actin nucleator protein WASP. The finding that WASP is essential for the stiffness-dependent phosphorylation of ZAP70 in CD8 T cells is convincing. However, the data regarding the role of WASP in mechanosensing within CD8 T cell-mediated anti-tumor immunity is incomplete and would benefit from a more rigorous study design. This work would be of interest to cell biologists and investigators studying mechanosensing within the immune system.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This convincing study demonstrates a potentially important role for the factor Numb in skeletal muscle excitation-contraction coupling. Numb knockout reduced contractile force. The authors thus demonstrate a novel role for Numb in calcium release in skeletal muscle.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Perampalam and colleagues provide solid evidence that Netrin signaling drives survival of non-proliferating ovarian cancer cells and their dissemination. These valuable findings were thought to provide unique insights into the molecular underpinnings of ovarian cancer spread and thus to be of significant interest to cancer biologists. However, the incomplete evidence supporting the role of the described Netrin-dependent mechanism in cancer dormancy was found to be a major shortcoming of the study.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work by Park et al. introduces an open-top two-photon light sheet microscopy (OT-TP-LSM) for lesser invasive evaluation of intraoperative 3D pathology. The authors provide convincing evidence for the effectiveness of this technique in investigating various human cancer cells. The paper needs some minor corrections and has the potential to be of broad interest to biologists and, specifically, pathologists utilizing 3D optical microscopy.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This manuscript addresses an important question, that in countries endemic for P vivax the need to administer a primaquine (PQ) course adequate to prevent relapse in G6PD deficient persons poses a real dilemma. On one hand PQ will cause haemolysis; on the other hand, without PQ the chance of relapse is very high. As a result, out of fear of severe haemolysis, PQ has been under-used. This manuscript is convincing that regimen (1) can be used successfully to deliver within 3 weeks, under hospital conditions, the dose of PQ required to prevent P vivax relapse.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study, utilizing CITE-Seq to explore CML, is considered a useful contribution to our understanding of treatment response. However, the reviewers express concern about the incomplete evidence due to the small sample size and recommend addressing these limitations. Strengthening the study with additional patient samples and validation measures would enhance its significance.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This work describes a connection between inflammation and metabolism, in which itaconate stabilizes the mitochondrial fatty acid uptake enzyme Cpt1a to enhance fatty acid oxidation. The mechanism for itaconate action may be generalizable to other protein targets. This is an important advance, which is supported by solid experimental data.
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arxiv.org arxiv.org
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eLife assessment
This paper represents important findings when identifying untargeted metabolomics and its differences between metabolomes of different biological samples. GromovMatcher is the fantasy name for the soft development. The main idea behind it is built on the assumption of featuring and matching complex datasets. Although the manuscript reflects a solid analysis, it remains incomplete for validation with putative non-curated datasets.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study describes a single set of label-chase mass spectrometry experiments to confirm the molecular function of YafK as a peptidoglycan hydrolase, and to describe the timing of its attachment to the peptidoglycan. Confirmation of the molecular function of YafK will be helpful in further studies to examine the function and regulation of the outer membrane-peptidoglycan link in bacteria. The evidence supporting the molecular function of YafK and that lpp molecules are shuffled on and off the peptidoglycan is solid, however, data supporting conclusions relating to the locations of lpp-peptidoglycan attachment are incomplete. The work will be of interest to microbiologists studying the bacterial cell wall.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important study that investigates the role of commensal microbes and molecules in the antigen presentation pathway affecting the development and phenotype of an unusual population of T lymphocytes. The authors provide compelling evidence to identify a population of unconventional T cells that exist in the small intestinal epithelium, which appear to depend on commensal microbes, and show that a single commensal microbe (that encodes an antigen capable of weakly stimulating these cells) is sufficient to maintain this T cell population.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Sulphur atoms derived from cysteine are thought to play significant roles in maintaining redox homeostasis in Mycobacterium tuberculosis, which encounters stresses associated with immune cell interactions. In this valuable manuscript, the authors provide solid evidence that the genes encoding cysteine biosynthetic enzymes (cysM and cysK2) are required to maintain full viability of M. tuberculosis under in vitro stress conditions, macrophage infections, and within the lung tissues of mice. The manuscript presents transcriptomic and metabolomic evidence to support the hypothesis that CysM and CysK2 play distinct roles in maintaining cysteine-derived metabolite pools under stress conditions. The work will be of interest to microbiologists in general.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable work develops a new approach to measure imaginal disc growth in Drosophila. With this approach, the roles of two protocadherins (Fat and Dachsous), in late larval development is explored, and there is novel data on the scaling of their protein gradients. The evidence supporting the authors' findings overall are solid, though the genetic analysis of Fat and Dachsous function is incomplete and would benefit from further experiments.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable contribution studies factors that impact molecular exchange between dense and dilute phases of biomolecular condensates through continuum models and coarse-grained simulations. The authors provide solid evidence that interfacial resistance can cause molecules to bounce off the interface and limit mixing. Results like these can inform how experimental results in the field of biological condensates are interpreted.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study identifies differential Orsay virus infection of C. elegans when animals are fed on different bacteria. The evidence for this is however, incomplete, as experiments to control for feeding rate and bacterial pathogenicity are needed as well as direct quantification of viral load.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful work argues that claims on travelling waves in the cortex must be backed up with more careful experimental and theoretical work. Through simulations and neural recordings, the authors provide solid evidence to show that differences in activation timings can superficially appear as a travelling wave. This work has implications for how the field might need to revisit how travelling waves are methodologically characterised.
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for: IEA 2023 report - exec summary - Fossil Fuel industry, IEA 2023 report - exec summary - Oil and Gas industry
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summary
- this is the IEA summary of the position of the Oil and Gas industry and what they must do in order to transition to a net zero world by 2050 and avert 1.5 Deg C global mean temperature.
- it contains a lot of useful information and statistics
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work provides a detailed analysis of the population dynamics of an important human bacterial pathogen, Neisseria gonorrhoeae, using a large global collection of genomes with geographic, temporal, and demographic metadata. A unique facet of this work is the focus on both importation and exportation of N. gonorrhoeae; whilst quantifying importation is important to national public health efforts, quantifying exportation is relevant on an international level. However, the evidence supporting the conclusions is incomplete, due to potential inaccuracies in the method used for phylogenetic analysis, which forms the basis of this work. With the phylogenetic analysis strengthened, this paper would be of interest to epidemiologists and public health officials working on N. gonorrhoeae epidemiology and interventions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important report that has implications for both the brain stimulation field and beyond. The strength of evidence provided is quite convincing. The major strength of this work is the recognize the importance of participant expectation in brain stimulation studies.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a useful method for the extraction of behaviour-related activity from neural population recordings based on a specific deep learning architecture - a variational autoencoder. However, the evidence supporting the scientific claims resulting from the application of this method is incomplete as the results may stem, in part, from its properties. The authors should: (1) improve how they benchmark their method, by comparing against additional relevant techniques, and (2) reframe their results considering what observations may be a byproduct of their method, and which do constitute new scientific observations.
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www.biorxiv.org www.biorxiv.org
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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 and demonstrating their overall superiority over existing approaches.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper investigates host and viral factors influencing transmission of alpha and delta SARS-CoV-2 variants in the Syrian hamster model and fundamentally increases knowledge regarding transmission of the virus via the aerosol route. The strength of evidence is solid and could be improved with a clearer presentation of the data.
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www.biorxiv.org www.biorxiv.org
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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.
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www.biorxiv.org www.biorxiv.org
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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. Inter alia, clarifications of controls and variability among EC responses would strengthen the interpretations of the study.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study provides an unprecedented overview of the subcellular organization of proliferative blood stage malaria parasites using expansion microscopy. The localization of multiple parasite organelles is comprehensively probed using three-dimensional super-resolution microscopy throughout the entire intraerythrocytic development cycle. This work provides a compelling framework to investigate in future more deeply the unconventional cell biology of malaria-causing parasites.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This work provides a valuable characterization of the chaotic dynamics of high-dimensional spiking networks in the presence of internally generated oscillations due to synaptic delays or externally generated oscillations due to external input. The authors provide convincing analytical and numerical calculations to support their claims, however, the paper suffers from heavy mathematical jargon that reduces its impact. The paper could be revised to provide interpretations of the results so that it can be accessible to a broader neuroscience audience. In its current form, findings will be of interest mostly to researchers working at the interface between theoretical neuroscience, applied mathematics, and physics.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study advances our understanding of how past and future information is jointly considered in visual working memory by studying gaze biases in a memory task that dissociates the locations during encoding and memory tests. The evidence supporting the conclusions is convincing, with state-of-the-art gaze analyses that build on a recent series of experiments introduced by the authors. This work, with further improvements incorporating the existing literature, will be of broad interest to vision scientists interested in the interplay of vision, eye movements, and memory.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important study that extends our understanding of how the medial prefrontal cortex regulates goal-directed action during threat. The authors provide convincing evidence that prefrontal cortex parvalbumin neurons suppress conditional freezing responses, permitting the initiation of active controlling responses over shock onset (termed 'avoidance'); also, this cell-type function does not generalize to appetitive situations or general locomotion. These findings are expected to be of great benefit to multiple neuroscience subfields interested in the mechanisms of adaptive behavior.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides an important contribution to understanding how parafoveal words are neurally processed. The study employs a state-of-the-art frequency tagging paradigm to study the MEG response to words during natural reading. It provides solid evidence that semantic information of parafoveal words can be extracted.
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