Evaluated articles

eLife assessment

The study has identified a cell type in muscle that is characterized as an adipogenic progenitor cell that is capable of promoting regeneration through the action of BDNF, a prominent growth factor regulated by GDNF in Schwann cells. These results represent an important cellular explanation for nerve regeneration. The revised analysis is solid but the work remains incomplete due to a lack of evidence that BDNF is produced during the process through the action of GDNF.

eLife assessment

This important research describes the sensory innervation of oral tumors, with potential implications for understanding cancer-induced alterations in motivation and anhedonia in a mouse model. These findings are solid and are supported by anatomical and transcriptional changes in the tumor that suggest sensory innervation, neural tracing, and neural activity measurements. While nerve innervation of the tumor and associated increase in brain activity is well-supported, future studies could enhance specificity by employing more targeted genetic and pharmacological tools to manipulate these circuits selectively.

eLife assessment

This important work provides interesting datasets of myofiber differentiation. The evidence supporting the involvement of SRF2 in selected biological processes is convincing, however, additional evidence to pin-point the major action of SRF2 during muscle differentiation is appreciated. The work will be of broad interest to developmental biologists in general and molecular biologists in the field of gene regulation.

eLife assessment

This work provides solid evidence that Transforming Growth Factor β Activated Kinase 1 (TAK1) regulates esophageal squamous cell carcinoma (ESCC) tumor proliferation and metastasis. The findings are valuable to the field of molecular tumor biology in general and to the understanding of ESCC tumor invasiveness and metastatic potential.

eLife Assessment

In this useful manuscript, the authors performed scRNA-seq on a diverse cohort of 15 early-stage cervical cancer patients. Correlative data is provided to support the possible establishment of an immunosuppressive microenvironment near SCL26A3+ cells, and an association of these cells with upstaging at time of surgery. However without more extensive validation, the evidence supporting the conclusions remains incomplete. Overall, this paper will provide a potentially helpful dataset for researchers studying cervical cancer.

eLife assessment

This valuable study characterized a new set of small molecules targeting the interaction between ELF3-MED23, with one of the reported compounds representing a promising novel therapeutic strategy, The evidence supporting the conclusions is convincing. This article will be of interest to medical and cell biologists working on cancer and, particularly, on HER2-overexpression cancers.

eLife Assessment

This important study employs an optogenetics approach aimed at activating oncogene (KRASG12V) expression in a single somatic cell, with a focus on following the progression of activated cell to examine tumourigenesis probabilities under altered tissue environments. Although the description of the methodologies applied is incomplete, the authors propose a mechanism whereby reactivation of re-programming factors correlates with the increased likelihood of a mutant cell undergoing malignant transformation. This work will be of interest to developmental and cancer biologists, especially in relation to the genetic tools described.

eLife Assessment

This study describes the application of machine learning and Markov state models to characterize the binding mechanism of alpha-Synuclein to the small molecule Fasudil. The results suggest that entropic expansion can explain such binding. However, the simulations and analyses in their present form are inadequate.

eLife assessment

This valuable study establishes a method for live-cell imaging, tracking, and quantification of Alu elements marking euchromatic regions of the nucleus. The method will help characterize the relationship between chromatin dynamics and transcriptional activity. While the findings are largely consistent with previous reports, characterization of the technique is incomplete and could benefit from additional controls.

eLife Assessment

This important chronobiological study in mice suggests that light modulated activity of Cdk5 activity on the PKA-CaMK-CREB signaling pathway provides missing molecular mechanistic details to understand light-induced circadian clock phase delays during the early night, but not for phase advances in the morning. The authors provide convincing evidence bridging from behavioral to molecular/cellular experiments to neural activity imaging.

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.