Evaluated articles

eLife Assessment

This study provides important insights into the mechanistic basis of neurological manifestations of RNA polymerase III-related disease by creating a mutant mouse to dissect transcriptional changes. The data provide compelling evidence for disease progression initiated by a global reduction in tRNA levels leading to integrated stress and innate immune responses and neuronal loss. The work will be of interest to those engaged in the study of chromosome biology, developmental biology and neurodegeneration.

eLife Assessment

This manuscript describes an AI-automated microscopy-based approach to characterize both bacterial and host cell responses associated with Shigella infection of epithelial cells. The methodology is compelling and should be helpful for investigators studying a variety of intracellular pathogens. The authors have acquired important findings regarding host and bacterial responses in the context of infection, which should be followed up with further mechanistic-based studies.

eLife assessment

The authors have presented an interesting set of results showing that female sex peptide signaling adversely affects late-life neurodegeneration after early-life exposure to repetitive mild head injury in Drosophila. This fundamental work substantially advances our understanding of how sex-dependent response to TBI occurs by identifying the Sex Peptide and the immune system as modulators of sex differences. The evidence supporting the conclusions is compelling with rigorous inclusion of controls and appropriate statistics.

eLife Assessment

This important article describes a meticulously-developed improved strategy for generation of functionally null mutants in Leishmania spp. via cytosine base editing, with reduced background toxicity and enhanced efficiency relative to a previously-described method. The authors show use of the strategy in a small-scale loss-of-function screen, providing compelling evidence that large-scale screens will be possible. The newly developed tools will be of great interest to researchers working with Leishmania and beyond.

eLife Assessment

This valuable biomechanical analysis of kangaroo kinematics and kinetics across a range of hopping speeds and masses is a step towards understanding a long-standing problem in locomotion biomechanics: the mechanism for how kangaroos, unlike other mammals, can increase hopping speed without a concomitant increase in metabolic cost. The authors convincingly demonstrate that changes in kangaroo posture with speed increase tendon stress/strain and hence elastic energy storage/return. This greater tendon elastic energy storage/return may counteract the increased cost of generating muscular force at faster speeds and thus allows for the invariance in metabolic cost. This methodologically impressive study sets the stage for further work to investigate the relation of hopping speed to metabolic cost more definitively.

eLife assessment

This useful article provides evidence of the potential neuropathogenicity of Bacillus cereus serovar anthracis in wild chimpanzees. The authors provide an extensive characterization of four chimpanzees that died acutely from anthrax. The study provides incomplete traditional histopathologic evidence of neuroinvasion since the meninges could not be evaluated, which weakens the authors' conclusions. The work will be of interest to infectious disease researchers.

eLife Assessment

This is an important study suggesting that neuron-specific loss of function of the RNA splicing factor Ptbp1 in striatal neurons induces dopaminergic markers and alleviates motor defects in a 6-hydroxydopamine (6-OHDA) mouse model of Parkinson's Disease. The evidence supporting the rescue of motor deficits following Ptbp1 manipulation is solid, and, while additional characterization of dopaminergic neuronal identity may be required in future studies, these results have clear implications for Parkinson's disease therapeutics. The study also addresses recent controversial literature on cell reprogramming in Parkinson's Disease and will be of interest to researchers with a focus on the application of gene therapy to rescue neurodegeneration.

eLife Assessment

Manley and Vaziri introduce an important new method for brain-wide imaging of cellular activity in zebrafish and provide evidence for the applicability of this technique. They use this method to explore the question of how neural variability gives rise to variability in behavior. The analyses used are mostly convincing, although questions regarding spatial and temporal imaging resolution and their effects on the study's interpretations and conclusions suggest only partial support for some of the central results.

eLife Assessment

This is an overall compelling set of findings on the role of centrally produced estrogens in the control of behaviors in male medaka. The significance of the findings rests on the revealed potential mechanism between brain derived estrogens modulating social behaviors in males , supported by the analysis of multiple transgenic lines. The evidence for the broader claim is incomplete since it has not been extended to female medaka, and further experimentation would be necessary to fully validate the conclusions on the role of brain-derived estrogens. Nonetheless, the findings have led to important hypotheses on the hormonal control of behaviors in teleosts that can be tested further.

eLife Assessment

This important study provides insights and strategies for assessing laminar structure in vivo in the visual cortex of the macaque monkey with high-density linear electrode arrays. The paper provides convincing evidence demonstrating that signals in higher frequency bands, related to the discharge of action potentials, are of substantially better use for achieving well-resolved cortical layer identification than are signals in lower frequency bands typically associated with local field potentials and standard-practice Current Source Density (CSD) analyses. These findings are of interest to a wide range of neuroscientists making comparisons between cortical layers or recording with array electrodes.

eLife assessment

This important manuscript shows that axonal transport of Wnd is required for its normal degradation by the Hiw ubiquitin ligase pathway. In Hiw mutants, the Wnd protein accumulates in nerve terminals. In the absence of axonal transport, Wnd levels also rise and lead to excessive JNK signaling, disrupting neuronal function. These are interesting findings supported by convincing data. However, how Rab11 is involved in Golgi processing or axonal transport of Wnd is not resolved as it is clear that Rab11 is not travelling with Wnd to the axon.

eLife Assessment

This valuable simulation study proposes a new coarse-grained model to explain the effects of CpG methylation on nucleosome wrapping energy. The model accurately reproduces the all-atom molecular dynamics simulation data, and the evidence to support the claims in the paper is solid. This work will be of interest to researchers working on gene regulation, mechanisms of DNA methylation and effects of DNA methylation on nucleosome positioning.

eLife Assessment

This important study provides a comprehensive assessment of mitochondrial function across age and sex in mice. The strength of evidence supporting this resource is compelling, given the exhaustive number of tissues profiled and in-depth analyses performed.

eLife assessment

This study provides useful insights for anyone focusing on exonic regions when looking into the investigation of DNA fragmentation patterns (fragmentomics) for circulating tumor DNA (ctDNA) data for cancer detection. The method expands the DELFI method of Cristiano and colleagues (2019), but the datasets chosen are not ideal and the analysis remains incomplete.

eLife Assessment

This study provides a useful set of experiments showing the relative contribution of the Noradrenergic system in reversing the sedation induced by midazolam. The evidence supporting the claims of the authors is solid, although specificity issues in the pharmacology and neural-circuit investigations narrow down the strengths of the conclusions. Dealing with these limitations will make the paper attractive to medical biologists working on the neurobiology of anesthesia.

eLife Assessment

This useful manuscript presents an interesting multi-modal omics analysis of lung adenocarcinoma patients with distinct clinical clusters, mutation hotspots, and potential risk factors identified in cases linked to air pollution. The findings show potential for clinical and therapeutic impact. Some of the conclusions remain incomplete as they are based on correlative or suggestive findings, and would benefit from further functional investigation and validating approaches.

eLife Assessment

This useful study partially succeeds in providing solid evidence in support of the therapeutic potential of the plant-derived compound eugenol for ameliorating symptoms associated with STZ-induced oxidative stress, identifying Nuclear factor E2-related factor (Nrf2) as a mediator of the effects induced by eugenol. Although the study provides interesting data, there remain concerns associated with the STZ model and the rather superficial mechanistic assessment.

eLife assessment

This study presents important findings linking circHMGCS1 and miR-4521 in diabetes-induced vascular endothelial dysfunction. Overall, the evidence supporting the claims of the authors is convincing. The work will be of interest to biomedical scientists working with cardiovascular and/or RNA biology, particularly those studying diabetes.

eLife assessment

This study combines experimental and theoretical approaches to examine metabolites at the single-cell level in tea plants. The authors skilfully integrated various tools available for this type of research, and meticulously presented and illustrated every step of the survey. The overall quality of the work is convincing, and it represents an important contribution to our understanding of the compartmentalization of biosynthesis pathways.

eLife Assessment

This important manuscript sets out to identify sleep/arousal phenotypes in larval zebrafish carrying mutations in Alzheimer's disease (AD)-associated genes. The authors provide detailed phenotypic data for F0 knockouts of each of 7 AD-associated genes and then compare the resulting behavioral fingerprints to those obtained from a large-scale chemical screen to generate new hypotheses about underlying molecular mechanisms. The data presented are solid, although extensive interpretation of pharmacological screen data does not necessarily reflect the limited mechanistic data. Nonetheless, the authors address most reviewer concerns in their revised version, providing invaluable new analyses. Phenotypic characterization presented is comprehensive, and the authors develop a well-designed behavioral analysis pipeline that will provide considerable value for zebrafish neuroscientists.