Evaluated articles

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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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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.

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.

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.

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.

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.

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.

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.