- Apr 2023
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www.biorxiv.org www.biorxiv.org
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eLife assessment<br /> <br /> Within this paper, the authors describe a rapid and easy-to-implement CRISPR/Cas9-mediated knock-in approach to precisely insert large transgenes in the African turquoise killifish. The established method will be instrumental for many researchers working with unusual model species, and, in particular, will expand the killifish community toolbox. It will revolutionize the field and bring the killifish, an emerging animal model in aging biology and disease modeling in vertebrates, into the spotlight even more.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study addresses the anticipated but poorly understood interconnections between ER proteostasis and lipid metabolism. The authors discovered key metabolic enzymes required for integration of ER stress and lipid synthesis and followed up with several direct experiments that provide solid evidence for a broad conservation of the described interactions.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
Motivated by previous demonstrations that cognitive modulation of heart beat evoked responses (HER) might distinguish minimally consciousness state and unresponsive wakefulness syndrome patients, the present work sought to determine whether contextual processing of auditory regularities (local-global paradigm) differentially affects HER in these patient groups. The results provide preliminary evidence for the usefulness of EEG and oddball paradigms in informing diagnosis of the state of consciousness. This paper will be of interest to those researchers studying signs of consciousness in post-comatose patients and more broadly to those studying brain-body interactions. However, some aspects of the study design and data analysis need to be clarified, particularly as these affect the conclusions that can be drawn.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Hernandez-Perez et al. perform a detailed analysis of Kazrin, a widely expressed protein that appears to be involved in many diverse cellular processes, but whose exact function is unknown. The authors employ mouse embryonic fibroblasts and biochemistry to investigate the function of Kazrin and determine that Kazrin promotes the dynein/dynactin-dependent transport of early endosomes. These findings are valuable to those in the field of intracellular transport, but the story will benefit from additional experiments to prove the main claims, or from textual modifications.
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eLife assessment
In the current study, Mondoloni and colleagues reveal how a selective nicotine receptor in the interpeduncular nucleus is involved in nicotine consumption, which is an important contribution to the understanding of individual differences in drug addiction. However, the preferred hypothesis would benefit from testing in additional experimental models, metabolic assessment, and cell-type specificity.
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eLife assessment
The cerebellum plays a critical role in motor learning, but exactly which forms of synaptic plasticity contribute to learning, as well as the underlying molecular mechanisms, remain poorly understood. In this study, Wang and colleagues show that presynaptic long-term potentiation at the parallel fiber to Purkinje cell synapse is required for one form of motor learning, and involves a previously-unknown signaling cascade, where EPAC activation leads to PKCε-dependent threonine phosphorylation of RIM1α. This study provides new insights into the underlying mechanisms and functional consequences of presynaptic LTP.
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eLife assessment
This paper expands on prior work by using whole-brain calcium imaging in Drosophila to examine how spontaneous and forced walking and turning affect neural activity in the brain. The measurements presented will serve as a valuable resource for the fly systems neuroscience community and suggest many testable hypotheses that may serve as the basis for future studies. Analyses of the data are solid, but conclusions drawn should be presented with more caveats. This article will be of interest to neuroscientists engaged with the central problem of how behavior modulates neural activity.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper provides valuable new information on the mechanisms by which Vibrio cholerae integrates and responds to environmental signals. While the strength of the evidence provided in the paper in support of the conclusions made and the model proposed is solid, there are several issues that if addressed will strengthen the study further. The work is relevant for a broad audience of microbiologists interested in the mechanisms by which bacteria sense their environment.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is a valuable study on DNA gyrase that provides further evidence for its mode of action via a double-stranded DNA break and against a recently-proposed alternative mechanism. The evidence presented is solid and is derived from state-of-the-art techniques. The work casts new light on the interactions that occur between gyrase molecules and will be of interest to biochemists and cell biologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study makes a valuable contribution to our functional understanding of the atypical amino-acid transporter SLC6A177 at nerve cell synapses and the role of SLC6A17 variants in certain forms of intellectual disability. The reported evidence that disease-linked SLC6A17 variants cause behavioral abnormalities is convincing. However, corresponding molecular underpinnings, i.e. the molecular role of SLC6A17 in synapses and the functional molecular consequences of disease-related SLC6A17 variations, remain unclear because corresponding informative experimental approaches are missing - most importantly direct measurements of the transport activity of SLC6A17 in the various genetic contexts studied. This limits the robustness and validity of key mechanistic conclusions drawn from the present work.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable work in human subjects reports that sounds that were associated with specific memories during waking behaviors can trigger the reactivation of these memory representations during REM sleep. However, the evidence supporting the conclusions is currently incomplete. Still, the work has the potential to expand our understanding of memory processing during sleep.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
Using a novel multi-depth plan display, this study reveals a valuable finding regarding crowding - it decreases with small depth differences between the target and flankers but increases with larger depth differences. The evidence supporting this finding is convincing, although the explanation of the findings is somewhat speculative. This paper will be of interest to visual scientists, neuroscientists, and ophthalmologists, especially those working on visual crowding and depth perception.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents useful findings on an important question in cognitive neuroscience - whether the brain can form sensory predictions during sleep. The paradigm used is compelling but evidence supporting the claims of the authors is incomplete. Major issues pertaining to large differences between the pattern of brain responses observed here relative to effects reported in the literature previously, and some evidence that the study might be underpowered to make strong conclusions about certain aspects of the data.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors ask if brain regions change based on the functional constraints or developmental constraints. To address this, they introduce an automated method for brain segmentation based on the zebrafish tool to study brain evolution in Astyanax. A caveat is that it is difficult to test the functional constraint hypothesis using this method, though it works well for testing developmental constraints.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Antimicrobial peptides (AMP) are a class of antibiotics that are inspired by natural components of innate immunity, which raises the specter of bacteria becoming resistant to both. The author this important study test this idea and find compelling evidence that a plasmid that encodes resistance to the AMP colistin also increases resistance to AMPS produced by humans, pigs, and chickens, enables the bacteria to grow better in low levels of AMP, and increases bacterial virulence in an insect model of infection. The study will be of interest to both evolutionary biologists and microbiologists focused on antimicrobial therapy and suggests that the evolution of resistance to these compounds can have collateral effects on immune evasion as well.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study provides compelling observations of the organization and architecture of haptomonads, a distinct and poorly understood developmental form of Leishmania found in sand fly vectors at later stages of infection. The authors used 3D electron microscopy techniques, including serial block face scanning electron microscopy and electron tomography, to visualize the colonization sand fly by haptomonads in impressive detail.
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eLife assessment:
Sampaio and colleagues utilize an elegant approach to manipulate fluid dynamics in zebrafish Kupffer's vesicle to ask if fluid movement or something in the fluid governs the break in symmetry. These valuable results support a role for fluid movement and detection as important in breaking symmetry in a ciliated left-right organizer and help set a time window when fluid flow is critical for this process. However, as the fluid extraction experiments affect both chemical and physical features, the authors need to provide further convincing evidence to support their mechanosensory hypothesis or temper the claims.
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eLife assessment
In this important study, the role of NBR1 in the degradation of photodamaged chloroplasts is analyzed, advancing our knowledge of chloroplast homeostasis in response to environmental stress. The evidence presented is convincing, in some parts even compelling, and the results are valuable for the plant and the autophagy research community.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable manuscript presents resources for genome-wide genetic perturbation in the fruitfly, Drosophila. The evidence for the usefulness is solid, with the authors demonstrating that they can identify novel genes that affect an important pathway, the mTOR pathway, which plays key roles in cell proliferation and cell death. The genetic resources are significant for their availability to colleagues in the Drosophila community seeking to to identify genes with important cellular functions.
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eLife assessment<br /> <br /> Descovich et al examine the important decision between proliferative (planar) and differentiation (perpendicular) divisions in the basal layers of the skin and find a key promoter of perpendicular divisions is inhibited by its paralog to specify planar divisions. The authors use sophisticated mouse genetics and imaging and discover that LGN and its paralog AGS3 function antagonistically in determining perpendicular vs. planar divisions. Some statements need to be tamed or further backed up, but overall this study provides a significant advance in the field.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important study on the role of a bacterial cell wall component, D-alanylated lipoteichoic acid, as a bacteria cue in Drosophila melanogaster-microbiome interactions. Overall, the evidence supporting the conclusions is compelling, with a solid approach combining crystallography with biochemical and cellular assays, that take advantage of both fly and bacterial mutants, to demonstrate a physiological role in juvenile growth promotion. The work will be of broad interest to those studying host-microbe interactions, especially as it is related to immunology and metabolism mediated by the microbiome.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The manuscript describes a fundamental study of the atypical MAPK, ERK3, in the activation of RhoGTPase Cdc42 and the formation of actin-rich protrusions and cell migration. The results show that ERK3 is required for the motility of tumor cells in vivo, providing a new target for fighting metastasis.
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- Mar 2023
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www.biorxiv.org www.biorxiv.org
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eLife assessment
These are important findings that show that pupil size is not only governed by the locus coeruleus but also by other neuromodulatory subcortical systems. Furthermore, the authors demonstrate that using a standard hemodynamic response kernel is not appropriate for capturing the activity of these systems, at least at rest. Thus, this paper presents compelling evidence against two prevalent working assumptions among researchers in the field.
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eLife assessment
This important work utilizes a model organism, zebrafish, to explore changes to the proteome and the role of KLHL40, a component of the ubiquitin-proteasome system, in the development of skeletal muscle disease. Using mass spectrometry, the authors demonstrate a major and selective role for proteome remodeling in development. They identify a specific role for KLHL40 deletion in regulating the expression of Sar1 - a key component of biosynthetic secretion, where the resulting elevated levels of Sar1 expression potentially lead to collagen secretion defects in the disease state. The findings are incomplete as further experimental characterization of the overall morphological changes and secretion defects, in particular ones derived from the deregulation of Sar1 levels, is required.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this useful study, a GWAS-type analysis is applied to clinical Mycobacterium tuberculosis isolates to discover genetic polymorphisms linked to poor tuberculosis outcomes. The evidence for the detected associations is still incomplete, as the corresponding polymorphisms are not adequate to power a prediction model for infection outcome, although key host factors - including patient age, sex, and duration of diagnostic delay (which have stronger predictive value) - appear to enhance predictive capacity.
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eLife Assessment:
The manuscript by Godoy and colleagues is an important contribution to the understanding of how lung endothelial regeneration progresses following endothelial ablation. The novelty and elegance of this study are rooted in the regional and specific ablation of lung endothelial cells using diphtheria toxin without the massive inflammatory activation that is seen with lung injury induced by bacterial infections, viral infections, or lipopolysaccharide. The data convincingly demonstrate that there is an emergence of a highly proliferative lung endothelial subpopulation that drives endothelial regeneration. The translational implications of the study include the identification of potential therapeutic targets to augment endothelial regeneration as a treatment for ALI/ARDS. This study will be of interest to vascular biologists, lung biologists, and researchers studying adult tissue regeneration.
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eLife assessment
This is an important contribution to colorectal cancer research to understand how we can predict high-risk patients for recurrence. The strength of the evidence is solid and looks at a novel approach but an approach that still has opportunities to improve.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This study provides an important demonstration that loneliness is associated with smaller hippocampal volume, reduced cortical thickness, and worse cognition in healthy older adults. This has theoretical or practical implications beyond a single subfield. The strength of evidence is solid given the cross-sectional and longitudinal design with a few weaknesses. With the analytical and interpretational part strengthened, this paper would be of interest to gerontologists, and dementia/cognitive aging researchers.
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eLife assessment
This paper provides strong evidence for the important point that microtubule function is required for the proper localization of Glut4 glucose transporters in an insulin responsive compartment. This membrane localization is required in turn for effective translocation of Glut4 to the muscle cell surface in response to the hormone.
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eLife assessment
This paper deals with an important unsolved problem in developmental biology of how cells execute their dynamics at the right time. The study combines compelling quantitative single cell and single transcript experiments with genetic perturbations and computational modelling and provides important insights into how the timing of transcription is regulated. The work would be strengthened by better integration of modeling and data.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This important study uses two well-established colorectal cancer models to estimate the potential impact of disruptions in screening caused by the COVID-19 pandemic. By dividing the population into separate cohorts based on age and pre-pandemic screening status, the authors provide convincing evidence for the adverse impact of delays in screening, switching regimens, and screening discontinuation. The finding that discontinuation has a much greater impact on screening-associated gains in life expectancy than shorter-term delays or switching of regimens suggests that access-related barriers to screening resumption may lead to the worsening of current disparities.
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eLife assessment
This is an interesting study investigating the propagation dynamics of ripples recorded from the dorsal hippocampus of mice using an open-access dataset. Findings may have theoretical and practical implications for the study and manipulation of sharp-wave ripples, a main oscillatory event underlying memory consolidation. While the strength of evidence is solid and claims broadly supported, there are some points requiring additional analysis to clarify issues regarding the anatomical axes involved and to reinforce mechanistic insights.
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eLife assessment<br /> <br /> This study presents valuable findings on how the ectopic expression of the Lck protein tyrosine kinase in Chronic Lymphocytic Leukemias (CLL) contributes to malignant transformation. The evidence supporting the claims of the authors is solid, although the use of gene editing to directly explore the functions unique to LCK in a CLL model would increase the appeal of the work.
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eLife assessment
This study provides valuable insight into the diversity within the NRAMP superfamily of transporters. Evidence of divalent metal ion transport and the structure (obtained without added metal ions) are convincing. However, molecular insight into Al3+ recognition and transport is incomplete, and the work would be strengthened by the determination of a metal-bound structure or additional experiments (such as molecular dynamics simulations or quantitative Al3+ binding/transport assays) to support the proposed Al3+ binding site. The work will be of interest to structural biologists and biophysicists studying NRAMP transporters.
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eLife assessment
The authors use data from 3 cross-sectional age-stratified serosurveys on Enterovirus D68 from England between 2006 and 2017 to examine the transmission dynamics of this pathogen in this setting. Understanding these dynamics, including how it changes over time, may help uncover potential changes in the transmissibility of the virus. While the topic is relevant, interpretation of the results challenging largely due to the great uncertainty around how to interpret the serological (serostatus) data, and the impact this has on the inferences made. We ask the authors to perform some additional analyses and to provide more intuition to understand some of the key findings of this analysis.
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eLife assessment
In this manuscript, a method to test a large number of drug combinations in a single cell culture sample is presented. The strength of the evidence lies in their multiple experiments with different combinations of agents. The paper suggests that results from this application are feasible and the methodology could be applied in other laboratories to use drug combinations for defined outcomes.
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eLife assessment
The authors' finding that Btk kinase activation relies on specific interactions with the Grb2 scaffold protein, including for recruitment into signaling clusters on membranes, is an unexpected finding that will potentially be of broad interest. The authors make a case for reinterpretation of the "Saraste dimer" of Btk as a signaling entity and assign roles to the component domains in the Src module in Btk activation, but the data provided are not yet fully convincing for this scenario.
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eLife assessment
This is a very interesting and important study that convincingly demonstrates a descending pathway for the control of nociception in non-mammalian organisms.
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eLife assessment
By combining electrophysiological analysis of mutant channels and molecular dynamics simulations, this important study identifies a common binding site for two structurally distinct activators of KCNQ1-KCNE1 channels. The findings represent an important advance for the field, with convincing functional data to support it. The simulations are still partially incomplete and would benefit from additional data and discussion. The work will be of interest to those studying the binding of small molecule drugs to membrane protein complexes.
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eLife assessment
This is a valuable study that shows the involvement of phosphoinositide 3-kinase (PI3K) signaling downstream of platelet-derived growth factor receptor alpha in latero-medial migration of cardiomyocytes during the formation of the early heart tube during zebrafish development. The authors provide convincing evidence using multiple drugs and expression of a dominant negative PI3K subunit, to inhibit the pathway, approaches that show the strong alignment of phenotypes, and which are quantified using live imaging. The demonstration of cardiomyocyte protrusions biased in the direction of migration, and randomised after PI3K inhibition, is a promising area for future exploration.
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eLife assessment
The study integrates experiments and data of various kinds to address the important biomedical problem of carbapenems resistance in Klebsiella. The authors present compelling evidence for loci that are sufficient for carbapenem resistance in this strain, with further evidence of their fitness cost. This study will be of interest to those across multiple audiences, including the microbial evolution community, and those interested in the biomedical problem of antibiotic resistance.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors describe the first full-length crystal structure and solution conformation of the GAC protein from Toxoplasma gondii. The data are convincing and support a model in which GAC uses multiple conformations and lipid-binding surfaces. This paper presents an important contribution to our understanding of the molecular machinery involved in host cell invasion, but questions remain about how this protein links to the cytoskeleton and functions during the invasion process.
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eLife assessment
This study explored practitioners' assessments of the impact of the pandemic on cervical cancer screening and follow-up. This is a very important topic that could continue to have implications for how this screening process is delivered now, after the pandemic. The authors need to more fully describe their methodology and temper conclusions to fit within those limitations.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study discovers that zinc ions can activate some OTOP proton channels, identifying a pharmacological tool for research, and further establishing that OTOP channels gate. The data presented provide convincing support for the conclusions made by the authors, and the study is expected to be of considerable interest to physiologists investigating OTOP and other proton channels.
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eLife assessment
This study provides important evidence regarding the development of concept representations, using functional brain imaging to compare concept structure in people with different amounts of language experience. The analyses, which are overall solid, suggest that representations in the left lateral anterior temporal lobe differ as a function of childhood language experience.
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eLife assessment
This useful paper describes a sensitive method for identifying the contributions of different behavioral and stimulus parameters to neural activity. The method has been convincingly validated using simulated data and applied to example state of the art data sets from mouse and zebrafish. The method could be productively applied to a wide range of experiments in behavioral and systems neuroscience, but it remained unclear how it relates to or improves on similar, existing methods.
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eLife assessment
The authors present an important contribution to the field of deep brain stimulation (DBS) for depression by providing further evidence for the validity of the lateral habenula as a DBS target. The evidence provided is compelling and particularly strong in its use of fMRI to delineate target subregions best corresponding both to clinical and downstream fMRI response. This study provides information relevant to both surgical targeting and the mechanism of action for this DBS target.
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eLife assessment
This important paper provides new insight into the effect of extra-copies of a chromosome, thus aneuploidy, on body metabolisms in mammals. The authors used various solid analyses on the metabolisms and physiology of the transgenic mouse with most of human chromosome 21 and presented convincing results to support the authors' claims. The work would be of interest to researchers who work on the physiology and biochemistry of body metabolisms in mammals.
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eLife assessment
The authors present a novel and precise method for determining boundaries of cortical layers from multi-electrode recordings in marmosets and macaques. Their method requires less data than current approaches to finding a systematic relationship between slow local field potentials and spiking across cortical columns. This approach may be broadly useful to those doing electrophysiological recordings in the primate brain.
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eLife assessment
In this important study, Di et al., examine the mechanism by which potassium channels are activated prior to NLRP3 inflammasome activation. The main strength of the study is that it uses a combination of cell culture work and a mouse model to address the cell biology of inflammasome activation. However, certain aspects of the study including the characterization of inflammasome activation and the evidence to support the role of Rab11a in the translocation of TWIK2 are incomplete.
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eLife assessment
This paper will be of interest to sensory and computational neuroscientists. In it, the authors find maximally informative dimensions for primate retinal ganglion cells and use models based on these analyses to examine features of early visual processing that impact predictive coding of visual motion.
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eLife Assessment:
This study is fundamental to understanding the intrinsic driving forces of gene losses during mammalian genome evolution, linking the propensity for gene losses to the local genomic features such as mutation rate and spatially restricted expression. In general, the study is methodologically convincing because independent gene losses in at least two mammalian lineages were identified as "elusive human genes". However, additional (comparative genomics and statistical) analyses would make the current study more rigorous. This manuscript will appeal to readers interested in the evolutionary fates of genes across the phylogenetic tree.
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eLife assessment
This important study uses genomically-engineered glypican alleles to demonstrate convincingly that Dally (not Dally-like protein [Dlp]) is the key contributor to formation of the Dpp/BMP morphogen gradient in the wing disc of Drosophila. The authors provide solid genetic evidence that, surprisingly, the core domain of Dally appears to suffice to trap Dpp at the cell surface. They conclude with a model according to which Dally modulates the range of Dpp signaling by interfering with Dpp's internalization by the Dpp receptor Thickveins.
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eLife assessment
The authors address the function of dorsal horn inhibitory neurons that express neuropeptide Y in adulthood. They find relevant functions in pain and itch control that should be of broad interest to people working in the field. This valuable study changes the view of this cell class and the authors provide compelling data that goes beyond the current state of research.
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eLife assessment
This paper presents important findings into the response of epithelial monolayers to the combined effects of surface curvature and hydraulic stress, offering insights into how these cues contribute to epithelial cell extrusion. Most of the evidence is convincing, relying mainly on a combination of imaging-based techniques, though some parts would benefit from a more rigorous analysis and some claims require more evidence to be justified. This paper is of interest to a broad and growing community of biologists, biophysicists, and engineers interested in cell-geometry interactions.
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eLife assessment
This important report provides solid evidence that neutrophils can remove apoptotic hepatocytes in vivo and in vitro by burrowing into apoptotic hepatocytes. The findings could have profound implications with respect to the role of neutrophils and the etiology of autoimmune liver disease. The findings are of broad interest in medicine and in particular in hepatology.
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eLife assessment
This manuscript will be of interest to scientists who study cardiomyocyte homeostasis and contraction. It assesses the functional consequences of cardiomyocyte-specific knockout of Palladin, leading to the identification of a compensation mechanism when Palladin is deleted in embryogenesis, but not in adulthood. In addition, the authors identified new Palladin interactors, revealing a role for Palladin in the maintenance of intercalated disc structure.
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eLife assessment
This is a valuable study that quantifies CD8 T cell movement in different tissue environments and concludes that T cells display more confined movement in the inflamed lung than in lymph nodes or intestinal villi. The evidence supporting conclusions is solid with well-defined measurements and sufficient statistical analysis. The work will stimulate further efforts to understand the mechanisms behind the different behaviour of T cells that are important in host defence against intracellular pathogens and cancer.
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eLife assessment
This valuable study reports improvements in methods and tools for curating complex pathogen-host interactions. A compelling framework is described, using rigorous approaches and to considerable extent validated by the biocuration community. The developed ontologies and controlled vocabularies could be extended beyond host pathogens, e.g. ecological contexts with multi-species and multilevel interactions.
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eLife assessment
This work presents a multimodal approach to ascertain links between risk and resilience to depression and Alzheimer's disease in a large pediatric sample. The authors find two latent imaging variables that may be associated with resilience to adverse life events and disease risk, which show some spatial overlap with disease relevant gene-expression patterns and neurotransmitter expression. Such findings could be important for understanding mechanisms underlying resilience in neurological disorders, however, the analyses are inadequate for fully supporting the interpretation of the variables involved in these models, or for supporting some of the overall conclusions of the work.
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eLife assessment
The manuscript by Eyraud and colleagues examines the role of interactions between fibrocytes and CD8 cells as drivers of disease progression in COPD (chronic obstructive pulmonary disease). The findings that there exist bidirectional interactions between CD8 cells and fibrocytes are supported by solid evidence that combines histology of clinical lung samples, in vitro studies obtained from circulating blood fibrocytes and CD8 cells, as well as a computational model that predicts how bidirectional interactions could promote disease progression over the course of 20 years. The study, which is based on patient samples, thus provides fundamental insights on COPD progression.
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eLife assessment
This useful study uses untargeted metabolomics to help us understand how some herbivores are able to be generalists, rather than specializing in the metabolism of specific plant species. This is an important area, since little is known about how generalist insect species metabolize their food. In its current form, the study lacks ecological relevance due to the exclusive use of refined sampling procedures, and the metabolomic analysis is incomplete.
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eLife assessment
This important study should be of interest to vision scientists and those seeking to model naturalistic image processing for humans in simulated or real navigational [walking] situations. The experiments aim to provide information about the statistics of "retinal" motion patterns generated by human participants physically walking a straight path in real terrains that differ in "smoothness". State-of-the-art eye, head, and body tracking allowed simultaneous assessment of eye movements, head movements, and gait, with convincing evidence for an asymmetrical gradient of flow speeds during walking, tied predominantly to vertical gaze angle, together with a radial motion direction distribution tied most critically on horizontal gaze angle. While not a major weakness per se, additional details on analytical methods used and estimations of variance across observers would strengthen these results and clarify the basis of the global claims made about visual motion information across the visual field in walking humans.
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iiraorg.com iiraorg.com
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The central question of the Anthropocene, why did behaviorally modern humans gain the unprecedented capacity to change an entire planet, cannot be answered by genetic changes in human behavior. To explain why human societies scaled up to become a global force capable of changing the Earth and why there are so many different forms of human societies and ecologies shaped by them, explanations must be sought beyond the theories of biology, chemistry or physics. Here I introduce a new evolutionary theory, sociocultural niche construction, aimed at explaining the origins of human capacity to transform the Earth 3. As will be seen, this theory also explains why behaviorally modern human societies came to transform ecology in so many different ways over the past 50,000 years as they expanded across the Earth.
//Summary* - The central question of the Anthropocene: - why did behaviorally modern humans gain the unprecedented capacity to change an entire planet? - cannot be answered by genetic changes in human behavior. - To explain why human societies scaled up to become a global force capable of changing the Earth and why there are so many different forms of human societies and ecologies shaped by them, - explanations must be sought beyond the theories of - biology, - chemistry or - physics. - Here I introduce a new evolutionary theory, sociocultural niche construction, - aimed at explaining the origins of human capacity to transform the Earth . - As will be seen, this theory also explains why - behaviorally modern human societies came to - transform ecology in so many different ways over the past 50,000 years as they expanded across the Earth. //
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eLife assessment
This valuable study provides solid results on the molecular signaling mechanisms of CaM kinase kinase-1 (CKK-1) in the context of the nociceptive behaviors of C. elegans. The authors report previously undescribed elements that control the nuclear/cytoplasmic shuttling of CKK-1, suggesting a complex interplay of multiple nuclear localization and export sequences. Therefore, the work will be of broad interest to scientists studying behavior, neuronal signaling, and signal transduction in general.
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eLife assessment
This important study proposes a phenomenologically motivated theoretical framework to explain observed patterns of the temperature dependence of microbial diversity. The methodology is overall convincing, but the explanations of approximations and assumptions, and of their regime of validity, are incomplete. The manuscript should be of interest to microbial ecologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this study, the authors made important progress in understanding bone metabolic defects of T2D. They have established a valuable model that could mimic some aspects of T2D in mice. Particularly, the study provided important evidence showing bone turnover and metabolism were in defects, and changes in glycolysis would rescue bone defects in T2D. Overall, the authors provide compelling evidence from dynamic histomorphometry, C13 isotype labeling in vivo, scRNA-seq, and metabolic assays to demonstrate that the defective glucose metabolism causes osteopenia associated with T2D.
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eLife assessment
The current study provides important, mechanistic insight into the potential contribution of antisense C4G2 expanded RNA to disease in C9orf72-associated ALS/FTD. The authors convincingly demonstrate that expression of this RNA species activates the PKR/eIF2α-dependent integrated stress response. They further provide evidence that this can contribute to disease phenotypes using multiple models and post-mortem patient samples.
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eLife assessment
This important study reports a unique N-terminal motif of Staphylococcus aureus GpsB and the co-crystal structure of GpsB with the C-terminus of PBP4. It provides convincing evidence demonstrating the interactions of GpsB with PBP4 and FtsZ, shedding light on the role of GpsB in the pathogen's cell division. However, the functional characterization of GpsB's new motif caused and the structural characterization of GpsB and FtsZ's interaction is incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental work shows the absence of links between striatal dopamine synthesis capacity and working memory capacity, spontaneous eye-blink rate, and trait impulsivity. The evidence supporting the conclusions is compelling, with rigorous PET investigations and state-of-the-art cognitive assessments in a large sample. Given the high interest in the role of dopamine, the work will be of very broad interest to basic neuroscientists, clinical neuroscientists, and clinicians including neurologists and psychiatrists.
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eLife assessment
This important manuscript describes a series of cellular phenotypes associated with the depletion of TANGO2, a poorly characterized gene product but relevant to neurological and muscular disorders. The authors present solid data indicating that TANGO2 associates with membrane-bound organelles, mainly mitochondria, impacting lipid metabolism and the accumulation of reactive-oxygen species. A few additional experiments would help to understand the link between the lipid changes reported and the cellular phenotype.
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eLife assessment
The paper is of interest to neuroscientists, developmental biologists, and those interested in mechanisms that underlie intellectual disability. The study is well executed and brings new insight into the role of WDR62 and its role in causing microcephaly. The key claims of the manuscript require additional data.
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eLife assessment<br /> <br /> This work provides a valuable allele-specific gene editing therapeutic approach to selectively target the human RHO-T17M mutation, one of the most frequent genetic causes of autosomal dominant retinitis pigmentosa. However, the current data are incomplete. Further validation of gene editing efficiency in rods at cellular level in vivo and use of Rho-T17M mice will strengthen the conclusion.
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eLife assessment
The present manuscript addresses the controversial issue of the regeneration potential of cerebellar Purkinje cells in zebrafish and their integration into functional circuits. The authors use interesting genetic models to induce Purkinje cell-specific ablation to demonstrate regeneration of Purkinje cells can occur until adulthood and is accomplished by ptf1a+ progenitors. They further show that regenerated neurons reestablish electrophysiological properties and support appropriate behavior. These are important results that may help understand why mammalian neurons do not have similar properties and fail to regenerate. The conclusions on the source of regenerated neurons will however need additional experimental support.
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eLife assessment
In this manuscript, Gonzalez et al investigated the dynamics of dopamine signals in the lateral shell of the nucleus accumbens (LNAc) in response to different types of carefully defined visual stimuli. Contrary to reigning theories of dopamine signaling, the authors presented convincing evidence that LNAcc dopamine transients tracked visual sensory transitions rather than any immediately apparent motivational variable. These important findings based on compelling evidence point to a potentially new role for dopamine signaling in the ventral striatum.
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eLife assessment
Based on the Cryo-EM structure of human ETB in complex with the vasoconstricting peptide ET-1 and the inhibitory G-protein (Gi), this valuable study presents convincing data on how agonist binding is coupled to Gi-protein binding. The complex structure is solid and will appeal to the GPCR and pharmacology communities.
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eLife assessment
Nearly all organisms require a ribonucleotide reductase (RNR) to convert ribonucleotides to their deoxyribonucleotide counterparts. In this important study, the reader learns how the model organism Escherichia coli can adapt to survive without any of its three RNRs. Compelling microbiology experiments to develop this model and analysis of compensatory mutations reveals patterns that are conserved in the few known pathogens that have also eliminated their dependence on an RNR. The manuscript will be of interest to microbiologists, biochemists, and those who work on the evolution of microbial metabolism.
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eLife assessment
This work provides a promising first pass at providing an integrative model for how decisions arise from neural circuits. The approach is novel but lacks a more rigorous vetting against alternative model formulations to be able to determine its true significance. More stringent evaluations of the model in the context of existing work, as well as a clearer description of the goals and implementation of the approach, would help to address these concerns.
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eLife assessment
The study represents an impressive effort to use atomistic simulations to probe cryptic binding sites in the envelope of six flaviviruses. Moreover, using constant pH simulations, the authors suggest that a cluster of ionizable residues contribute to the pH dependent conformational rearrangements required in the infection process. Therefore, the study provides new mechanistic insights that can be helpful in future efforts to develop drugs that target flaviviruses.
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eLife assessment
This is an important study that investigates the impact of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia. Through a combination of pre-clinical in vivo measurements, clinical data, and computational modeling, the authors present solid evidence regarding the heterogeneous effects of TKIs in patients and how the response to treatment may be improved. With the assumptions about differences between normal and leukemic cells addressed, this study would be of interest to those working in the fields of mathematical oncology and cancer biology.
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eLife assessment
The authors revisit fundamentals of synaptic transmission using a combination of advanced optical methods capable of visualizing calcium influx and neurotransmitter release at single release sites. By doing so, the authors present evidence for silencing of neurotransmitter release at single release sites as a function of external calcium. The data have relevance to a wide range of phenomena including neural plasticity and inhibitory modulation of synaptic communication.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This important study presents a machine learning-based classifier that can accurately determine the geographic origin of a Salmonella enterica sample from its whole-genome sequencing data in under five minutes leading to actionable public health insights. Applying the method to 2,313 whole genome sequences collected in the United Kingdom and several external validation datasets, the authors provide convincing evidence that Salmonella genomic data can be used to identify the likely geographic source of a food-borne outbreak and, in most cases, correctly identify the country of origin of an infection acquired overseas. The work presents an excellent case for the potential utility of routine genomics coupled with machine learning for public health microbiology and the methods are likely to be applicable to other pathogens besides Salmonella enterica.
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eLife assessment
The findings in this study are important as they establish a rat model of a classic form of early-onset osteoporosis and demonstrate that osteoporosis medications are effective in the model. The evidence supporting the authors' claims is compelling.
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eLife assessment
This important landmark paper identifies three distinct stellate ganglion nerve cell subtypes stratifiable in terms of their neuropeptide Y expression correlating these with gene expression and electrophysiological properties. Their innovative use of viral tracing techniques compellingly established their conclusions. This major contribution to cardiac sympathetic excitation is relevant to a wide scientific and clinical audience.
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eLife assessment
This important work demonstrates a significant asymmetry between the connectivity statistics of the left and right hemispheres of the Drosophila larva brain. The evidence supporting the conclusions is compelling and represents a first step toward the development of statistical tests for comparing pairs of connectomes more generally. This work will therefore be of interest to the broad neuroscience community.
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eLife assessment
This paper will be of interest to scientists involved in understanding the function of long non-coding RNAs. The authors found two genes previously reported as lincRNAs in early studies encode micropeptides in zebrafish. Zebrafish mutants lacking these micro-peptides show altered gene regulatory networks that preferentially affect oligodendrocytes and cerebellar cells in the embryonic brain. The data presented in the study are solid and present convincing additional evidence for the versatile functions of micro-peptides.
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eLife assessment
This study is an important contribution to the understanding of Buruli ulcer transmission in Australia. The authors provide compelling evidence that the carriage of Mycobacterium ulcerans by possums, within their small home range, can predict cases of Buruli ulcer disease in individuals who visit those areas. While not directly relevant to the transmission of Buruli ulcer in West and Central Africa, the work will be of great interest to those studying the transmission of opportunistic environmental pathogens.
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eLife assessment
This study employs live imaging to investigate the movement of mesodermal cells in early mouse embryos. By examining the dynamics of cell behavior in normal and mutant embryos, the authors propose that apical constriction of cells results from pulsed contraction guided by crumbs2 signals. The paper presents beautiful images and adds to the molecular understanding of cell migration during early development.
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eLife assessment
In this Tools and Resources article, Sapiro et al. overcome the technical burden of low Borrelia burgdorferi numbers during infection by physically enriching for spirochetes prior to RNA-sequencing/mass spectrometry. This work is important as it provides technical advances for the study of global transcriptomic changes of B. burgdorferi during tick feeding and builds on the knowledge already collected by the field. The evidence presented is compelling, and the strategy described here could benefit researchers in the field and possibly support broader applications.
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eLife assessment
This important work reports the identification of a list of proteins that may participate in the clearance of paternal mitochondria during fertilization, which is known as essential for normal fertilization and embryonic and fetal development. While the main method used is state of the art and the supporting data are solid, the vigor of the biochemical assays and function validation is inadequate. This work will be of interest to developmental and reproductive biologists working on fertilization.
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eLife assessment
This study provides valuable insights into the role of two under-researched sperm-specific proteins (Cylicin 1 and Cylicin 2). The authors provide convincing evidence that they have an essential role in sperm head structure during spermatogenesis, and that their loss leads to subfertility or infertility, with a dose-dependent phenotype. The authors identify infertile males with mutations in both Cylicin1 and Cylicin2: thus the findings from the mouse models might be applicable to understanding human male infertility with similar structural defects.
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eLife assessment
Gordon-Fennell et al. present a low-cost, open-source platform for measuring action elicitation and consummatory behavior in head-fixed animals. The findings are important because they allow animals to perform a truly voluntary action whilst their head is held still, and the evidence supporting them is both comprehensive and compelling (in some cases even exceptional). The results have the potential to have a broad impact in the field as many labs start to move towards measuring head-fixed behavior effectively, although this is said with the caveat that such behavior will never be an ideal replication of naturalistic behavior.
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eLife assessment
This manuscript describes an approach to creating fat tissue in culture for food applications. Specifically, the efforts of growing cultivated meat focus mostly on growing skeletal muscle. However, the taste component of such artificial meat would be determined by fat content. There is a significant desire and motivation to cultivate fat tissues in vitro for the purpose of the replacement of animal products. This paper provides new technological approaches to expand adipocytes and aggregate them into structures that resemble fat.
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eLife assessment
This important manuscript employs a rigorous and multi-pronged comparative genomics approach to unravel how lifestyle modulates the acquisition and domestication of viral genetic elements in the genomes of hymenopteran insects. Using an extensive dataset of over 120 hymenopteran genomes, the authors provide convincing evidence that endoparasitism (where parasite development occurs within hosts) facilitates the uptake and domestication of double-stranded DNA viral elements.
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eLife assessment
This valuable paper examines the effect of deiodinase polymorphism on thyroid hormone signaling in the brain by employing a transgenic animal model and then switching to studying T3 axonal transport using microfluid devices. Although methodologically extensive this paper has several claims that are not convincingly supported by the current experiments and furthermore some disjoint is observed between the two halves of the study. The therapeutic implications of understanding T3 signaling in the brain makes it a potentially important manuscript.
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eLife assessment
The authors use analytic calculations and numerical simulations to convincingly show that the purported benefits of nonlinear decay in morphogen gradients may be marginal in some cases and completely reversed in others (far from the concentration source). This is a valuable contribution to the field, as it questions common assumptions about the biological function of non-linear morphogen decays during development.
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eLife assessment
This important study presents valuable findings on the dissemination of plasmids. In an analysis of five major Enterobacterales genera, the authors convincingly demonstrate that similar plasmids are shared between genera, species, and clones, both within and between ecological niches. Given the size of the dataset and the very detailed level of analysis this study importantly contributes to insights into to the flow of plasmids, including those carrying antimicrobial resistance genes, across niches.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors characterize an H3N2 influenza A virus that jumped from birds into dogs in 2006. Through its evolutionary adaptation to dogs, the virus is now gaining properties that are increasingly consistent with the potential to infect humans. Using experiments with canine H3N2 influenza isolates, the authors found that more recent viruses have acquired receptor specificity for both avian- and human-like receptors, enhanced low-pH stability and in vitro growth, as well as improved replication and transmission in the dog and ferret models.
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eLife assessment
This valuable study reveals that patient-derived organoids recapitulate similar genomic signatures as that of the parental tissue, which could be a useful model to evaluate chromosome instability, drug sensitivity, and intratumoral heterogeneity. However, whereas some of the sequencing data are compelling, the theoretical analysis is incomplete and would benefit from a more rigorous definition. With the theoretical part strengthened, the work will be of interest to medical biologists working on ovarian carcinoma.
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eLife assessment
Only few species of Leishmania, an important human pathogen, have an RNAi machinery, alternative methods are needed for genetic screens. The authors resent and validate a valuable method, based on the introduction of premature stop codons, that can be used for several different species. The results are very convincing, the data are solid, and the approach will be of interest to researchers studying any eukaryote that lacks the RNAi machinery.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This convincing work reviews and synthesizes evidence of the impact of the COVID-19 pandemic on a variety of cancer outcomes. The results have potentially useful implications for various fields of cancer research as they review evidence spanning from cancer prevention efforts to changes in diagnoses and cancer treatment modalities.
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eLife Assessment:
Mutations in a variety of intermediate filament proteins and their regulators lead to abnormal development, reduced lifetime, and increased stress sensitivity. This manuscript rigorously demonstrates that such defects result from inappropriate assembly of intermediate filament networks, as mutations in a central intermediate filament protein prevent assembly of both the normal network and these inappropriate assemblages and largely rescue most of the defects. This has important implications for our understanding of the assembly of intermediate filament structures and for understanding and potentially treating diseases resulting from mutations in intermediate filament protein genes.
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eLife assessment
This important study significantly advances our understanding of the calcium signaling pathway mediated by the kinase CDPK1, in the protozoan parasite Toxoplasma gondii. The evidence supporting the authors' conclusions is in many parts convincing, with rigorous biochemical and microscopy analysis. The work will be of broad interest to researchers in the field of signal transduction and protozoan biology.
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eLife assessment
This is an important study that asks why odors smell similar even though their chemical structures appear quite different. The authors use machine-learning to make a compelling case to map the odor-relatedness of compounds to their place in metabolic pathways and propose that this is a general feature of odor perception across the animal kingdom. The conclusions could be strengthened by considering published physiological data.
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eLife assessment
Antibodies perform a critical function in host defense against viruses and have emerged as major therapeutic tools in modern medicine, as evidenced by the large scale use antibody-based therapies during the COVID-19 pandemic. This paper describes the characterization of human antibodies to hantaviruses that have the potential to create devastating epidemics. The results teach us about the viral structures that are targets for neutralization and the results are relevant for vaccine development and antibody therapeutic design.
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eLife assessment
This study uses behavioral monitoring and cutting-edge calcium imaging approaches to track the activity of cholinergic and noradrenergic axons in cortex of head-fixed mice, and correlate activity with behavioral state. While the evidence that behaviorally related signals are broadly broadcasted to the dorsal cortex is clear from the data, the conclusion that there is also heterogeneity across axons and areas is of less certain significance and might be undermined by methodological artifacts.
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eLife assessment
In this work Frantz et al. assess transcriptomic states of melanocyte stem cells that are recruited to differentiate during the process of melanocyte regeneration in zebrafish and they analyze roles for Kit signaling in this process. The analyses are nicely done, and the paper requires only relatively minor modifications and clarifications. The study will provide new insights into melanocyte stem cell biology that should be of interest to those studying pigmentation, regeneration, and melanoma biology using zebrafish and other systems.
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eLife assessment
This important study employs auxin-induced degradation to show that the TATA-binding protein (TBP) is not required for ongoing RNA polymerase II transcription nor heat-shock or retinoic acid-induced transcription, but that TBP is essential for RNA polymerase III transcription, with TBP-independent TFIID complexes being assembled and present at the transcription start sites of polymerase II-transcribed promoters. The evidence for the major claims is currently incomplete.
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eLife assessment
The authors have developed a useful and user-friendly software to analyse gene expression data from four datasets representing premalignant lung lesions. This software would be of interest to those working in lung cancer and specifically the pre-malignant space. The major strength is the ease of use while the major limitation is the inability for the user to integrate other datasets.
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eLife assessment
Determination of the biomechanical forces and downstream pathways that direct heart valve morphogenesis is an important area of research. In the current study, potential functions of localized Yap signaling in cardiac valve morphogenesis were examined. However, the evidence for Yap pathway activation and localization relative to areas of the valve subject to different mechanical stresses is not convincing.
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eLife assessment
This is a well-explained and potentially useful study that describes the generation and use of pYtags, recombinant proteins that, if properly used, should allow spatiotemporal monitoring of the activation of different receptor tyrosine kinases in living cells. Although this study has generated new tools to evaluate receptor localization and activation in different cells, the broad concept showing that different receptor dimers generate specific stimuli, and downstream signaling pathways, is quite limited in terms of novelty. Although it is felt that the study is technologically innovative, the analysis of receptor spatial signaling is incomplete and should be improved.
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eLife assessment
This fundamental study substantially advances our understanding of the process of ribosome maturation. The authors have purified and determined the structures of several nucleolar ribosome assembly intermediates in yeast using cryo-electron microscopy (cryo-EM). The study combines genetic, biochemical, and structural analysis to provide compelling support for the conclusions the authors wish to draw. The work will be of broad interest to cell biologists, biochemists, and structural biologists.
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eLife assessment
This is an intriguing study investigating the molecular mechanisms of neural circuit developmental organization. Using a defined hippocampal circuit, the authors find that ectopic expression of an adhesion G protein-receptor leads to axon mistargeting. This work defines new mechanisms of axon target specificity.
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eLife assessment
Russel et al. study and reveal compelling evidence for potential sequence-based factors that may drive VDJ trimming, a mechanism involved in VDJ recombination that shapes adaptive immune repertoire generation. The work is based on a rigorous statistical comparison of logistic regression models to reveal the role and function of cutting enzymes in shaping T- and B-cell receptor diversity. It could provide fundamental new insights into these processes with some claims being currently incomplete.
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eLife assessment
This study investigates the spatiotemporal characteristics of human brain activities during object recognition under noisy and ambiguous conditions. By using state-of-the-art data analysis and model-driven fusion of MEG and 7T, this work demonstrates distinct representational profiles in ventral and dorsal pathways, contributing new perspectives to our understanding of the neural implementation of object recognition under uncertainty.
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eLife assessment
Siglec-1 (CD169), a plasma membrane-associated sialic acid-binding lectin, has been implicated in the capture of HIV and other viruses by dendritic cells and macrophages. However, the molecular details of how HIV particles are captured by Siglec-1 are poorly understood. In this paper, the authors use advanced imaging methods to analyse the cell surface distribution of Siglec-1 on immature and mature dendritic cells to study the regulation of Siglec-1 distribution by actin and regulators of actin polymerization and to understand how virus-Siglec-1 engagement leads to virus sequestration within so-called virus containing compartments. These types of analyses have only recently become feasible with the implementation of super-resolution imaging and as yet few virus-host cell systems have been examined in detail. Thus, this study has relevance for researchers studying the engagement of HIV and many other viruses with cells, as well as researchers interested in the mechanisms regulating receptor distribution and function on cells.
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eLife assessment
Poison frogs sequester alkaloids to make themselves toxic or unpalatable to predators, but how this sequestration occurs is not well understood. This valuable study identifies an alkaloid-binding protein in the plasma of poison frogs, which may help explain how these animals are able to sequester a diversity of alkaloids with different target sites. The supporting evidence is solid and the study adds to our understanding of how toxic animals resist the effects of their own defenses.
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eLife assessment
Elbaz-Hayoun et al. investigate the role of macrophages in the gliotic response of retinal Müller glia and photoreceptor cell death. The authors find that macrophages play a role in inducing retinal damage. A role for the muller glia expressed, C-C chemokine receptor axis was identified as a causative factor in promoting retinal degeneration. These important data identify a new link between cells of the immune system and those within the retina which contribute to the progression of retinal degeneration.
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eLife assessment:
In this important work, the authors describe a recombinant CRISPR/Cas9 construct, CRISPR-nuPin, that has the reported capacity to rapidly tether DNA to the inner nuclear membrane of cells. They then evaluate the effect of this construct on Herpes Simplex virus type 1 infection, identifying different phases of viral replication susceptible to inner nuclear membrane tethering. This work provides convincing evidence for the effects of intranuclear DNA localization on viral gene expression and replication, using a method applicable to nonviral genes as well.
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eLife assessment:
In this fundamental manuscript, the authors provide compelling evidence that a housekeeping ATPase is required for heme utilization in the important pathogen Staphylococcus aureus through its interaction with the canonical heme transporter in this organism. The authors convincingly show that this complex associates with functional membrane microdomains and thus establishes a new paradigm for regional localization of the heme transport system in the staphylococci. The work will be of interest to microbiologists, particularly those studying transport for macromolecules.
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eLife assessment
This paper is of potential interest to scientists within the field of drug-induced liver injury. The concept of the study is interesting by generating mitochondrial genotype-specific liver cell lines to evaluate idiosyncratic hepatotoxicity. While the proof-of-concept is clearly presented, the current data do not yet allow to draw broad conclusions about the significance of the study in terms of drug effects.
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eLife assessment
The precise cellular and molecular mechanisms and signaling mediators underpinning the development of cardiomyopathy and heart failure in diabetes still remains unclear. In-depth investigations of the cardiac heterogeneity and cell-to-cell interactions could be of use to reveal the pathogenesis of diabetic myocardial fibrosis and thereby identify potential targets for the treatment of cardiac myopathy and heart failure. Utilizing a mouse model as well as in-vitro studies, this manuscript demonstrates cardiac cell mapping that provides novel insights into novel drivers of intercellular communication contributing to pathological extracellular matrix remodeling during diabetic myocardial fibrosis. The work provides compelling and convincing evidence to improve the understanding the cellular and molecular mechanisms of diabetes-induced cardiac pathology.
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eLife assessment
Leptin is a fat-derived hormone that curbs appetite, and mutation of leptin causes obesity and diabetes. This manuscript investigates leptin-responsive neural circuits, revealing a key inhibitory connection from leptin-sensitive neurons in the arcuate nucleus of the hypothalamus (AGRP neurons) to neurons in the dorsomedial hypothalamus. Toggling this inhibitory connection impacted leptin effects on feeding and metabolism. The study contains valuable data, including several interesting molecular genetic systems and the demonstration of GABA signaling in the DMH for the control of food intake, however, there is inadequate information about experimental design, including a lack of quantification and controls, and unjustified assumptions.
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eLife assessment
This fundamental study by Rose and colleagues addresses key challenges in demographic inference in non-model systems with an innovative approach to model parameter calibration based on known historical events. Using this approach, they convincingly show that human specialization in Ae. aegypti mosquitoes likely evolved due to a past climate event around 5,000 years ago, and that recent rapid urbanization has continued to fuel its spread in West Africa in the past 20-40 years. This work will be of broad interest to population geneticists working on demographic inference, and to mosquito biologists working on the monitoring and control of this important vector species.
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eLife assessment
This manuscript presents a series of important findings about the roles of the BAR-domain containing protein SNX32 in endosomal cargo sorting and in neurite outgrowth. The authors provide convincing evidence for their claims, which will be of interest for those working not only in membrane trafficking but also for cell biologists in general with interest in neurobiology.
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eLife assessment
The fundamental work represents an important contribution to our understanding of the diversity of photosynthetic mechanisms across the branches of phototrophic life, with the first high-resolution structure (2.9 Å) of a photosynthetic complex from a primitive green alga. This is a valuable resource for understanding function and evolution of light-harvesting antennas. The evidence is convincing in suggesting that the mechanism found here is distinct from the classical antenna state transitions seen in other organisms studied thus far.
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eLife assessment
Sanz Perl and colleagues provide important insights regarding the application of computational brain models from neurodegenerative diseases to evaluate brain stimulation protocols in silico. Solid evidence is provided for the disease-specificity of the framework, however, the real-world impact of such stimulation protocols to alleviate psychiatric and neurological symptoms remains to be evaluated.
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eLife assessment
This study uses single cell sequencing to characterize transcriptional profiles of cells in a brain region called the PVT that plays many roles in brain function. The authors combine these data with dataset of neuronal connectivity and conclude there are transcriptomically distinguishable populations of neurons in the PVT with different function. These data deepen our understanding of an important brain region.
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eLife assessment
This important study of mouse genetic variation in atrial septum formation, a trait correlated with the patent foramen ovale (PFO) cardiac defect, provides convincing evidence for 37 quantitative trait loci (QTL) affecting this trait, combining genetic mapping with transcriptome analysis to zero in on relevant pathways and candidate genes within the QTL, and validating the role of one gene in tissue culture. The paper provides an important resource for hypothesis generation and future studies, which could lead to novel diagnostic or therapeutic approaches that target atrial septal defects in common congenital heart disease.
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eLife assessment
In this study, neurons were recorded and combined across the parahippocampal area while rats performed a memory-guided spatial navigation task. Sophisticated analytical tools were used to provide convincing evidence that neuronal populations in these areas show behavior-related changes that might indicate the encoding of errors by the system. The valuable results suggest that rate remapping is a likely mechanism to support changes in representations that support memory-guided behavior in these regions, most interestingly in neurons that code head direction.
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eLife assessment
This important paper advances our understanding of the role of lipid peroxidation in loss of muscle mass and force-generating capacity during aging and hind-limb suspension. The evidence is in general solid, drawing from experiments in vivo and cell culture using multiple types of manipulations of the formation of lipid peroxides although some weaknesses were identified. The results should be of interest to those who study the molecular basis for sarcopenia and disuse atrophy of skeletal muscle.
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eLife assessment
In this manuscript, the authors investigate the role of histone deacetylases in the spatial epigenetic control of zygotic gene expression in early gastrulation. They discover HDAC1 binding is maternally-controlled and that inhibition of histone acetylation blocks gastrulation and disrupts cell lineage integrity, tied to both positive and negative regulatory effects on gene transcription in space and time. The study contributes to a growing body of evidence that highlights a central role of histone acetylation-deacetylation dynamics in epigenetic regulation of gene expression and cell fating in early tissue patterning of the embryo.
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eLife assessment:
This study provides valuable insight into the molecular mechanism of ion selectivity in the broader family of ATP-gated P2X receptors. The experimental data are of high quality, the evidence supporting the conclusions is convincing, and the work will be of broad interest to biophysicists working on ion channel selectivity.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study aimed to identify rhythms linked to primary symptoms of Parkinson's disease such as involuntary shaking of the limbs and slowness. The evidence supporting the conclusions is solid, although validating their behavioural measures and considering the relationship between signatures from different brain regions would have strengthened the study. The work will be of broad interest to movement control, movement disorders, and brain stimulation fields.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
When a neuron is born it correlates with where it targets in the neuropil and this has been best demonstrated in the olfactory lobe of Drosophila. This important study uses sophisticated genetics and advanced live imaging to provide a compelling description of how neuronal dendrites explore the targeting field, eliminate excessive branches, and assort into the correct region during development. In the process, it develops valuable tools. It brings us closer to a comprehensive understanding of how the birth order of a neuron translates to dendrite patterning within the Drosophila antennal lobe circuit
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eLife assessment
Black et al., provide evidence that levels of Paternally Expressed Gene 10 (PEG10) protein are regulated by Ubqln2 and that proteolytic fragments from PEG10 cleavage induce changes in gene expression, in particular genes that encode proteins involved in axon biology. Based on these data and the finding of an increase in PEG10 levels and alterations of proteins regulated by PEG10 in the spinal cord of ALS patients, they propose that abnormal induction of PEG10-regulated genes is involved in ALS. However, the evidence for these claims and PEG10 involvement could be strengthened, and the rigor of the work could be enhanced in places.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study provides a provocative potential challenge to explain sensitivity across the visual field by using cortical magnification factors. The evidence supporting this theoretical challenge is solid in general, although the inclusion of subject-specific measurements of cortical magnification factors would have strengthened the study. The work will be of interest to vision researchers of both basic and medical science.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study by Pasquereau and Turner examined the activity neurons in the subthalamic nucleus (STN) while monkeys performed a task in which they had to withhold their response during a delay period whose length was defined by a specific cue. The results indicate that the activity of STN neurons was modulated by reward size and delay. The results are potentially important for understanding how STN regulates behavior such as self-control, but the reviewers thought that the study is incomplete as the analyses, at least in the presented forms, have some potential problems and some analyses require clarification.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript reports important findings regarding the evolution of snake venom proteins. The conclusions are convincing and are based on appropriate and validated methodology in line with the current state-of-the-art. The findings will be of interest to biologists and biochemists interested in the evolution of venoms as well as those generally interested in the evolution of molecular novelties.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this potentially important study, Mahbub and colleagues examine how the small GTPase ARL15 regulates ion transport. Using a complementary array of techniques, the authors gathered solid evidence for the binding of ARL15 to CNNM proteins, resulting in a proposal how this may affect the function of the TRPM7 channel. Additional experiments are required to fully substantiate the claims.
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learn-us-east-1-prod-fleet02-xythos.content.blackboardcdn.com learn-us-east-1-prod-fleet02-xythos.content.blackboardcdn.com
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this paragraph shows and explains the key diffrences and requirements of teachers and professors as college students we are adults and have to be treated as such.
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eLife assessment
These authors provide compelling evidence that gestational intermittent hypoxia, a component of sleep apnea during pregnancy, increases inflammation in the spinal cords of male mice. Increased inflammation is robustly linked to deficits in respiratory plasticity both biochemically and via functional depletion assays. These data are important given the fact that male infants have worse outcomes in the NICU and are at higher risk of sudden infant death syndrome.
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eLife assessment
Brodbeck et al. offer a timely and important contribution to how neural signals in response to continuous temporal modulations (as seen in speech and language processing) can be modelled effectively using temporal response functions. They offer a convincing new approach that includes a novel application of a boosting algorithm in addition to an accessible and didactically useful toolbox for analysis. With further comparison to existing toolboxes, or a more extensive comparison of boosting and ridge regression via simulation, this work will have a compelling impact on methods in speech and language neuroscience, as well as in cognitive neuroscience more broadly.
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eLife assessment:
This important study advances our understanding of host-derived lipid droplets' interaction with intracellular pathogens. The use of amoeba species Dictyostelium discoideum as a host for Legionella pneumophila infection is compelling and goes beyond the current state of the art, but the strength of evidence is incomplete, and the main claims are only partially supported by the data. With the experimental part strengthened, this paper would be of interest to cell biologists and microbiologists working on the interaction of microbes with host cells.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful work describes the establishment and characterization of new cell lines derived from specific tissues of the fruit fly Drosophila. The evidence supporting the claims of the authors is solid, although the characterization of the cell lines is incomplete and the genomic findings are not presented in a user-friendly manner. These lines could be a useful resource that complements in vivo Drosophila genetics, improving biochemistry and facilitating high-throughput screening.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This important study examines the association between SARS-CoV-2 infection and close contact among household members, measured using proximity sensors deployed after the first case was identified in the household. The authors provide solid evidence that transmission of SARS-CoV-2 within households is not dependent upon close contact, but the study suffers from a number of limitations that are fully acknowledged.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Regulation of gene expression in many biological systems occurs either through a binary mode where gene expression is either on or off (digital regulation), or through an analog mode leading to a graded modulation of gene expression. In this manuscript, the authors report how these two regulatory modes are integrated into a one-way switch pattern to control the expression of the Arabidopsis floral repressor gene FLOWERING LOCUS C (FLC). They suggest that an analog regulation in the autonomous pathway precedes a digital regulation conferred by Polycomb silencing before cold exposure, and this temporal switch correlates with the strength of transcription at the FLC locus in different genetic backgrounds.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study combines different approaches to unravel the genetic basis of a pigmentation polymorphism in natural populations of a fascinating study system with well-studied ecology. The paper has the potential to be of general interest to biologists curious about the genetic basis of adaptive variation, which is especially relevant to evolutionary biologists and ecologists. The study reports substantial data and makes a strong case for the contribution of a duplication-derived gene acquiring a morph-specific function. Further information is required to implicate valkea in pigmentation morph formation and for diagnosing the duplicated segment as a supergene (associated with low recombination).
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eLife assessment
This manuscript describes a valuable method to study the mechanism of action of essential genes and novel putative drug targets. Evidence for the effectiveness of the system, which is based on engineering pre-validated targets for RNA-mediated knockdown into genes of interest, is compelling, though some questions remain about the ease with which it can be put into general use.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents valuable findings from a study of identical twin pairs discordant and concordant for smoking to assess whether smoking has a direct effect on DNA methylation. The results are a valuable contribution as the study confirms the reported association between smoking and epigenetic profile is indeed due to the direct effects of constituents of tobacco smoke. The study design and methods applied by the authors are solid and provide a starting point for larger studies with rigorous laboratory approaches, as well as for assessing clinical impact. The work will be of broad interest to addiction researchers, genetic epidemiologists, and environmental scientists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an interesting and potentially significant study that adds important new information to our understanding of the mechanisms of lung epithelial repair after tissue injury. The authors have delineated a novel and non redundant role for the hippo pathway and the down stream regulators Yap/Taz in regulating repair of lung injury. These studies will inform future investigations into the mechanisms of repair of lung injury
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eLife assessment
This study presents important results on the predicted impact of cancer screening disruptions in Australia during the COVID-19 pandemic based on consultation with public health stakeholders. The evidence presented is solid, as simulations were based on several previously validated breast, cervical, and bowel cancer screening decision models, though the scenarios were based on hypothetical disruptions that do not always match experienced disruptions. The work will be of interest to local policy-makers, public health specialists, and cancer epidemiologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This work shows that higher socioeconomic status is associated with a higher risk of obesity, which should inform China's obesity public health programs and policies, and also be of interest to other countries and communities. The evidence supporting the conclusions is strong, but the data analysis is incomplete and would benefit from more rigorous approaches.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is important work that addresses a long-standing (but rarely acknowledged) question: given that multi-peaked tuning curves optimize Fisher information, why do early sensory areas typically have single-peaked tuning curves? This paper shows clearly, and convincingly, that multi-peaked tuning curves are likely to produce catastrophic errors at short times, so if speed is important, multi-peaked tuning curves should be avoided. This work should encourage neuroscientists to take into account the importance of stimulus encoding time in their formulations of models of neural coding.
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eLife assessment
Endothelial cells mediate the growth of the vascular system, but they also need to prevent vascular leakage, which involves interactions with neighboring endothelial cells through junctional protein complexes. This important study provides a full mechanistic insight into how Sun1 is achieving its function, which supports the concept that nuclear anchoring is critical for proper mechanosensing and junctional organization. Although the evidence supporting the claims of the authors is solid and there are several merits and strengths in this study, a weakness is that some important controls are missing. The work will be of broad interest to cell biologists and vascular biologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript presents a useful meta-analysis of genes with parent-specific expression from mouse published RNA-seq datasets, focusing on genes with weak allelic bias. A combination of systematic bioinformatic analysis and experimental validation convincingly shows that the number of parentally biased genes has been overestimated and the few novel ones lie at the periphery of known imprinted loci. The work will be of interest to genomicists with an interest in imprinting and its mechanisms.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study will be of interest to scientists within the field of hematopoiesis and ribosome biology. The paper provides evidence that haploinsufficiency of the mouse ribosomal protein gene Rps12 results in a number of phenotypes including defects in the production of specific blood cells and loss of hematopoietic stem cell quiescence. This work adds to the growing body of evidence that specific cell populations are particularly sensitive to disruption of mRNA translation machinery.
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eLife assessment
This important paper advances our ability to understand feeding behavior in fruit flies, and begins to address the challenging question of motivation. With innovative methods based on the detailed monitoring of interactions between foods of different qualities at different hunger states, they present compelling evidence for non-homeostatic feeding not driven by metabolic need.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript describes an approach for efficiently integrating diverse libraries into the C. elegans genome. The method is a valuable contribution for researchers carrying out experiments that would benefit from easy generation of such libraries, and the data for the effectiveness of the method is solid. The relative advantages of this approach in terms of ease and effectiveness relative to others with similar aims will emerge as they are put to more general use in addressing biological problems.
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eLife assessment
The study has some significance for the field of dementia research and neurodegenerative diseases more broadly. Using the brain-age paradigm, the main findings are that having an older-appearing brain is associated with more advanced stages of amyloid and tau pathology, higher white matter hyperintensities, higher plasma NfL and carrying the APOE 34 allele. Findings were broadly similar in cognitively normal people and people with mild cognitive impairment and the evidence for these findings is convincing. Although sex differences are emphasized, the evidence for this is generally incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents important new findings regarding prenatal thalamocortical development. The authors present convincing evidence to overcome substantial methodological challenges in charting prenatal brain development in vivo. This work will be of interest to pediatric and developmental neuroscientists and neuroradiologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors present valuable findings regarding the mechanism of high mannose induced cellular toxicity in cancer cells. The evidence supporting genomic instability as the anti-cancer activity of mannose is convincing with multiple orthogonal approaches showing consistent results, but the conclusions related to metabolic remodeling could be further strengthened by additional metabolomics data. While the findings are limited to genetically modified cancer cell lines cultured in vitro, this work will be of interest to cell biologists working on cancer metabolism.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This potentially important study examines brain age based on resting state functional connectivity (RSFC) following an 18-month lifestyle intervention. The design of the intervention study is generally solid; the randomized controlled trial includes three intervention groups and assessments at two-time points of numerous health markers, however, the methodology for brain age prediction appears somewhat incomplete and would benefit from more rigorous approaches. The lack of control groups also prevents firm conclusions about the extent to which the observed RSFC changes are linked to the intervention. With these parts strengthened, the paper would be of broad interest to neuroscientists and biologists working on obesity, lifestyle interventions, and brain health.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper reports a valuable new method for creating localized damage to candidate brain regions for functional and behavioral studies. The authors present solid support for their ability to create long-term local lesions with mm spatial resolution, although data supporting the extension to primates was incomplete. If the authors can demonstrate that the technique is applicable beyond the specific technical setup they employ, the paper is likely to be of broad interest to brain researchers working to establish causal links between neural circuits and behavior.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful work proposes a framework inspired by chemotaxis for understanding how the brain might implement behaviours related to navigating towards a goal. The evidence supporting the conceptual claim is convincing, but some technical aspects are incomplete. The manuscript proposes a hypothesis that would be of interest to the broad systems neuroscience community, but the reviewers noted the relationship to existing similar hypotheses was not made sufficiently clear.
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eLife assessment:
This important paper reports recent improvements and extensions to stdpopsim, a community-driven resource that is built on top of powerful software for performing simulations of population genomic data and provides a catalog of species with curated genomic parameters and demographic models. In addition to describing the new features and species in stdpopsim, the authors provide a set of simple guidelines for implementing realistic simulations. Overall, this convincing manuscript serves as an excellent overview of the utility, challenges, common pitfalls, and best practices of population genomic simulations. It will be of broad interest to population, evolutionary, and ecological geneticists studying humans, model organisms, or non-model organisms.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable combination of X-ray and cryo-EM structures of the bacterial adhesin PrgB, an atypical microbial cell surface-anchored polypeptide that binds DNA. There is convincing support for the claims regarding the overall function and importance of individual domains. The model for PrgB's binding of eDNA is thought-provoking, but the evidence for it based on low-resolution volumes of cryoEM data is incomplete. If additional experimental evidence for the model is produced, this work will be impactful in the field of bacterial adhesins, conjugation, and biofilm formation, and is particularly important as it focuses on a clinically important Gram-positive pathogen, whereas most work in the field has been focused on Gram-negative model systems.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper presents valuable information on the role of type I PRMTs in programming muscle stem cell identification. The evidence presented is mostly solid, with some weaknesses in the evidence regarding the proposed mechanism. The paper will be of particular interest to those who study skeletal muscle satellite cell biology.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
The authors have used an extensive database to study associations between biphosphanate use and COVID-19. Using careful statistical analyses biphosphonate use appeared strongly associated with a lower risk of COVID-19. If these findings are confirmed in well-designed prospective studies biphosphanate use could be an attractive drug to prevent COVID-19.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper provides a valuable systematic analysis of proteomic profiles associated with a particular murine Ryanodine receptor abnormality. Its analysis technique provides a solid and systematic set of data summarising the differences in different muscle types. The work emerges with insights into pathological mechanism of congenital muscle diseases linked to mutations in a range of other genes related to excitation contraction coupling in workers within the skeletal muscle field.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is a rigorous and compelling extension of previous normative modeling work that demonstrates that normative models incorporating lifespan trajectories of structural and functional connectivity provide a strong basis for brain imaging studies across a range of tasks including, univariate group difference assessment, classification, and building regression models. The work is important, rigorous and a valuable contribution to the field.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This study presents a useful identification of an herbal drug combination for the treatment of plasma cell mastitis (PCM), a breast inflammation with severe and intense clinical symptoms. The data were collected and analyzed using a solid and in clinical trial of 160 patients (NCT05530226) and can be used as a starting point for understanding how herbal drug combinations could be helpful in the management of PCM patients.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This paper presents an analysis of both contact tracing and whole-genome sequence data to track the elimination of dog-mediated rabies in Pemba Island, Tanzania. The work is a valuable contribution to the literature as it will have practical implications for the elimination of dog-mediated rabies in other regions/contexts. The main claims made are largely supported, but the strength of evidence for the cost-effectiveness is limited.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This important study presents the idea of "Skeletal Age", defined as the age of one's skeleton as a consequence of fragility fracture, as a potential new tool to raise awareness about the increased risk of mortality following a fracture (particularly hip fractures) and thus improve the medical management of osteoporosis. The evidence is convincing and is derived from a very large database from the Danish National Hospital Discharge Registry. The proposed approach might represent a starting point for making doctor-patient communication about the health risks of an osteoporotic fracture more intuitive and possibly more effective.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents an important finding on the cause of the widely reported disruption of the excitation to inhibition (E-I) ratio change in Autism Spectrum Disorder (ASD) mouse models. The evidence supporting the main conclusions is solid and well-sampled. These results can be a starting point for studies that assess the functional role of daily oscillations of the E-I ratio in the pathophysiology of ASD, and possibly, reshape our understanding of the nature of the E/I balance alterations that contribute to normal and diseased circuits.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Understanding specific tau-tau interactions that play key roles in Alzheimer's disease and tauopathies will enable the elucidation of the toxic tau species involved in the pathogenesis of these diseases and therapeutic development in this area. In this paper, the authors developed a series of NanoBiT complementation-based tau biosensors to monitor tau intramolecular and intermolecular interactions. This paper will be of high interest to a broad target audience including researchers in the field of biophysics, biochemistry, cell biology, neuroscience, neuropathology, and drug discovery as well as physicians.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study reveals that slow plasticity in the neocortex is essential to prevent memory interference. The method of artificially increasing plasticity in the prefrontal cortex of rats during learning and its effect on sleep physiology, when memories are believed to be reprocessed, is solid. The work will be of interest to neuroscientists interested in learning and memory.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Alamia and colleagues investigate the direction of traveling waves in the alpha frequency band during visual spatial attention. The authors' novel perspective adopted here is valuable to understanding the functional relevance of alpha oscillations for spatial attention. The observed pattern of results is consistent with distinct roles for travelling alpha waves in spatially opposite directions and makes a solid case for considering this new perspective on alpha rhythms in human cognitive function.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Silva and colleagues present useful findings related to the isolation of an anti-S2 antibody that recognizes a previously uncharacterized SARS-CoV2 Spike (S) epitope, adding to the growing repertoire of anti-S antibodies that broadly cross-react against human and zoonotic coronaviruses. The evidence supporting the claims of the authors is solid, although antibody effectiveness as a prophylactic or therapeutic reagent in an animal model would have strengthened the study. The work will be of interest to biologists working to develop pan-coronavirus therapies.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Germline inactivation of NPHP2, which encodes a protein that localizes to the transition zone at the base of the primary cilium, results in infantile kidney cysts and fibrosis. In this study, the authors provide solid evidence that increased cell proliferation and fibrosis precede cyst formation in Nphp-2 mouse models, that mutant renal epithelial cells are responsible for the phenotype, and that genetic inhibition of ciliogenesis in this model reduces disease severity. They also show that valproic acid, a drug that affects a number of cellular targets and is used to treat other human conditions, slows disease progression. One limitation of the study is that it provides limited insights into the mechanisms responsible for any of its interesting observations.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental work substantially advances our understanding of how neighboring genes on a chromosome can be separately controlled in time and space. The evidence supporting the conclusions is compelling, with state-of-the-art genetic perturbations and imaging. The work will be of broad interest to geneticists and cell biologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a useful tool called Phantasus, a web application to analyze gene expression data generated by microarray or RNA-seq technologies. The web application will help biologists end users, and non-bioinformatics experts to analyze new data or replicate transcriptomic studies. Local use of the Phantasus through its Bioconductor package reveals an incomplete functionality concerning the current best practices in analyzing bulk RNA-seq data.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this important work, the authors present a sequence-based approach using transfer learning and Restricted Boltzmann Machines to predict antigen immunogenicity and specificity. The evidence and methodology are compelling. This work should be of interest to immunologists, computational biologists, and biophysicists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study demonstrates a non-canonical, cancer-cell intrinsic role of the ectonucleotidase CD73 in the regulation of cancer cell metabolism. The evidence supporting the claims is solid, although further experimental details and conditions would strengthen the evidence provided.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study by Bonnet et al addresses the question of how AMPA receptor numbers at the synapse are regulated during basal conditions and during chemically induced Long Term Potentiation. Specifically, the study aims to determine the molecular mechanisms that contribute to the intracellular trafficking of AMPA receptors and determine their insertion into the synaptic plasma membrane. Using compelling methodology, the authors dissect the distinct roles of two proteins that bind to the C-terminal domain of the AMPA receptor subunit GluA1: 4.1N and SAP97. The findings will be of interest to anyone trying to understand molecular events contributing to synaptic plasticity in health and disease, and more broadly, the method could be adapted for tracking intracellular movements of a wide range of proteins.
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eLife assessment
This manuscript significantly advances our understanding of the development of drug resistance in the HIV-1 protease. The paper addresses the fundamental relationship between resistance mutations and inhibitor structure and will be useful in the design and development of the next generation of inhibitors.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This important study evaluates the immunogenicity of 3rd and 4th doses of SARS-CoV2 vaccinations in patients with cancer. Their study is notable in that neutralization of Omicron was absent in all patients after the third dose but increased to 33% after the fourth dose. With the definitions and patient population better described, this paper would be of interest to those studying the effects of repeated COVID boosters on Omicron immunity.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper proposes a new computational model for replay that is biologically realistic and accounts for a number of important phenomena in hippocampal replay. This is an important study with implications for multiple subfields. Whilst the majority of claims are convincingly supported by the data, simulation analyses for some crucial aspects of replay literature are currently incomplete.
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eLife assessment
The authors developed a two-photon fluorescence microscope coupled with adaptive optics (AO-2PFM), allowing in vivo imaging of the mouse retinal structure and function. This new imaging system will be important for exploring normal retinal physiology and pathological alterations in retinal disease models.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The overarching question of the manuscript is important and the findings inform the patterns and mechanisms of phage-mediated bacterial competition, with implications for microbial evolution and antimicrobial resistance. The evidence in the manuscript is, however, still incomplete and some of the conclusions made are not supported by the data. This manuscript would additionally be strengthened by a clearer narrative, to enable readers to more easily extract the key message this paper wants to convey.
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eLife assessment
This is a well-done study to understand how Rab27 and its effectors regulate insulin secretion. The present work examines the relative hierarchy of exophilin-8 and melanophilin using single vs double knockouts and rescue experiments to show that melanophilin functions downstream of and potentially redundantly from Exo8. Imaging and protein co-localization studies were done in a rigorous way. The data are solid, and some additional data will make the work fully compelling. Overall this is an important study that sheds new light on the regulation of insulin granule exocytosis.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable finding on the role and function of the Gaq axis on the inflammatory response during decidualization essential for early pregnancy. The evidence supporting the claims of the authors is solid, although some of the methodology and data interpretation require further clarification and justification. The work will be of interest to reproductive biologists and clinicians.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study reports Foxc2+ cells in the testis might be the true spermatogonial stem cells (SSCs). The data supporting this claim are solid and the finding, if proven true, would have a great impact on reproductive biology and stem cell biology as the genes responsible for maintaining the quiescent state of SSCs during spermatogenesis remain elusive.
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eLife assessment
This paper reports valuable data on a classic model for cell fate specification in the C. elegans gonad. The data, though extensive, provide so far incomplete support for the major claims of the paper, especially regarding the functional significance of their conclusions. The paper will be of interest to developmental biologists studying transcriptional control of cell fate specification in animals, especially once issues around the functional significance of the condensates are resolved.
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eLife assessment:
This manuscript describes development of a new algorithm for integrative analysis of multi-omics data. This work should be of potential interest to scientists performing bioinformatic pathway discovery in multi-omic datasets especially those that relate to signaling.
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eLife assessment
This manuscript presents valuable findings that bring together two important topics in cell biology: the function of membrane contact sites and cell migration. The authors describe a role of the ER tether protein VAP-A in focal adhesion dynamics and cell motility. Although the authors present solid evidence to support some of the main claims of the paper, some of the other claims would benefit from stronger experimental support. Nonetheless, this paper will be of interest to those cell biologists and biophysicists working on adhesion, migration, and membrane contact site biology.
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eLife assessment
This paper is of interest for skeletal biologists studying bone marrow stem/progenitor cells and bone remodeling. Using Adipoq-Cre-driven conditional deletion of Csf1 that encodes M-CSF and reanalyzing publicly available scRNAseq data, the authors recognize a subpopulation of bone marrow cells (i.e. AdipoQ-lineage progenitors) as an important source of M-CSF. The authors found that M-CSF production from these bone marrow cells influences the development of macrophages and osteoclasts as well as bone mass, including the bone loss associated with estrogen deficiency. This is a clearly written and nicely presented study that has potential to offer important new information regarding the source of M-CSF in the bone marrow.
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eLife assessment
This study provides a valuable data resource to study the systemic effects of severe COVID-19. It shows compelling evidence that the transcriptional response to COVID-19 is coordinated across the body, and it highlights cell interactions between macrophages and endothelial cells in COVID-19. This analysis and the associated resource will be valuable to understand the pathogenic mechanism of long-COVID.
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eLife assessment
This important study develops a new technical advancement in ex vivo live imaging of hematopoietic tissues to monitor blood cells in their native microenvironment. The new method for live imaging and tracking is compelling, and the strength and breadth of hematopoietic analysis are convincing. This work provides a very useful new system for immunologists and cell biologists, which will supply new perspectives on the system-level mechanisms of cell differentiation and innate immunity.
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