Evaluated articles

eLife assessment

Moises and Harel generate an important set of novel molecular tools in African turquoise killifish, an innovative model to study aging biology. The new solid tools described in this paper can boost this buddying model system for broad biotechnological applications. The authors showcase the efficacy of their tools in the context of peptide hormones involved in growth and gonad development. The killifish community will greatly benefit from these novel tools and the relevance of the developed methods will likely go beyond the killifish community.

eLife assessment

This study addresses an important question in the field of antimicrobial chemotherapy: whether combinations of enzyme inhibitors that select for mutations that confer resistance to one inhibitor and at the same time increased sensitization to the other inhibitor can provide a path towards mitigating resistance risks. The authors here investigated one such combination of inhibitors of Plasmodium falciparum DHODH (dihydroorotate dehydrogenase), finding that despite "collateral sensitivity", it was still possible to select a mutation that mediated resistance to both inhibitors without any change in parasite fitness. Additional cross-susceptibility and structural modeling strengthen this study, which is performed to a high technical standard and presents a convincing body of data.

eLife assessment

The valuable study by Dumeaux et al examines the transcriptional response to antifungal treatment in the major opportunistic human fungal pathogen Candida albicans. Using solid methodology, including a novel droplet-based single cell transcriptomics platform, the authors report that fungal cells exhibit heterogeneity in their transcriptional response to antifungal drug treatment. The ability to study the trajectories of individual cells in a high-throughput manner provides a novel perspective on studying the emergence of drug tolerance and resistance in fungal pathogens.

eLife assessment

This manuscript addresses the important issue of hemodynamic response function (HRF) variability across brain areas and will be valuable to researchers who use fMRI and other types of functional imaging that rely on neurovascular coupling. Using simulations and experiments, the authors provide solid evidence that differences in the HRF can impact spectrum-based metrics such as ALFF and fALFF. A better understanding of the variability of the HRF is critical for the proper interpretation of activation onset times and of differences observed in clinical populations where both neural and vascular alterations can be expected.

eLife assessment

This valuable study shows that Rab12 is required for LRRK2 activation. However, while some of the data are compelling, some claims, especially the ones related to LRRK2's membrane association are not supported. Addressing discrepancies between figures (pointed out by reviewers) and re-writing certain sections will greatly improve this manuscript.

eLife assessment

This exceptional work substantially advances our understanding of the mechanics of the Reissner's fibre (RF) by performing in-vivo experiments that track and analyze the behavior of the RF when it is cut and the behavior of ciliated cells touching the RF when contact is interrupted. The data is valuable and the conclusions are compelling. The work will be of broad interest to many research communities including developmental neuroscience and cilia biology.

eLife assessment

This manuscript reports the fundamental finding that an oligomeric protein kinase, CaMKII, can be phosphorylated by another molecule of the holoenzyme in a manner that does not involve subunit exchange. The evidence for the main conclusion is compelling, supported by several independent experiments. If independently confirmed in future, the study will stand as having provided a novel regulatory mechanism for the autophosphorylation of this kinase. The work will be of broad interest to molecular and cellular neuroscientists as well as biochemists.

eLife assessment

This is an important analysis of two sleep datasets in children and adolescents that contributes to our understanding of sleep spindle and slow oscillation dynamics during development and is expected to be of interest to interdisciplinary fields including development and sleep. The analyses are solid and adequately complex to capture the changes in sleep spindle to slow oscillation coupling between the age groups. However, the paper would be strengthened by performing the same analyses in an adult sample to sufficiently characterize the maturation of sleep spindles and their coupling to slow oscillations.

eLife assessment

This study presents a valuable finding on the associations and causal relationship between second primary cancers and the initial diagnosis of a primary cancer via using a large database. The evidence supporting the claims of the authors is solid. The work will be of interest to cancer clinicians.

eLife assessment

This important study combines engineered mesenchymal stem cells together with mouse models of kidney injury to determine the ability of these cells to reduce kidney damage upon acute kidney injury. The evidence supporting the claims is solid, although the inclusion of more than one type of stem cell and the use of male mice which are more prone to acute kidney injury, would strengthen the study. This work will be of interest to both basic scientists and clinicians working on mechanisms of kidney injury and repair.

eLife assessment

This important study identifies the functional consequence of myelination of interneuronal axons on circuit function by showing that 4.1B deletion leads to altered myelination in a subset of interneurons and altered intrinsic and synaptic physiological parameters. The authors' conclusions about how myelination of inhibitory axons affects physiological properties are based on solid evidence using a combination of imaging and electrophysiological approaches.

eLife assessment

This is an important study that uses chromatin accessibility as a measure to determine the impact of neuronal activity on the state of chromatin regulatory elements in striatal neurons. The authors provide convincing evidence of how Pdyn gene expression is highly dependent on a distal regulatory genomic region both at basal and upon neuronal activation in this particular system, a mechanism conserved as well in human neuronal cells. Although the basic idea of accessibility changes have been studied before, this paper ties previous findings all together in one place and uses the analysis to identify a functionally relevant and conserved enhancer for the prodynorphin gene with potential relevance for neuropsychiatric disorders beyond basic cellular neuroscience. The study will be of interest to neuroscientists studying the striatum, neuronal plasticity, or related neuropsychiatric disorders.

eLife assessment

This study characterized the activity of optogenetically identified dopaminergic and GABAergic neurons in the ventral tegmental area in mice performing a memory-guided T-maze task, and shows that subpopulations of dopaminergic and GABAergic neurons exhibited choice-related activity during the delay period, consistent with some previous studies (e.g. Morris et al., 2006, Parker et al., 2016). The authors demonstrate that these delay-period activities were enhanced when the task requires short-term memory. The results are convincing and this study provides important results regarding the nature of delay-period activity in the task.

eLife assessment

This study proposes a deep learning-based segmentation pipeline of fetal brain MRI, with parcellation based on a newly implemented atlas. This represents an important contribution to the field of developmental neuroscience and pediatric neuroimaging, especially as the pipeline and atlas are publicly available. The evidence for the pipeline robustness and atlas relevance is convincing given the extensive validations provided and the very high-quality ground truth dataset. Although beyond the state of the art, the study would benefit from further comparisons with existing methods and additional evaluations of the framework generalizability according to image quality, subject age or brain abnormalities.

eLife assessment

The authors provide a valuable analysis of what neural circuit mechanisms enable varying the speed of retrieval of sequences, which is needed in situations such as reproducing motor patterns. Their use of heterogeneous plasticity rules to allow external currents to control speed of sequence recall is a novel alternative to other mechanisms proposed in the literature. They perform a convincing characterization of relevant properties of recall via simulations and theory, though a better mapping to biologically plausible mechanisms is left for future work.

eLife assessment

This paper identifies a subset of neurons within adult mouse myenteric ganglia that are not labeled via canonical neural-crest labeling, and argues, based on extensive lineage tracing, imaging and genomic data that these neurons are derived from mesoderm. There is convincing evidence for the existence of an unusual cell type in the gut that expresses neuronal markers, but which is derived from cells expressing markers of the mesoderm rather than the expected neural crest, which is an intriguing and important observation. While the data do not definitively establish the molecular taxonomy of this lineage, there is sufficient evidence to support the provocative and paradigm-shifting hypothesis of the non-ectodermal origin for enteric neurons to warrant further deeper investigation.

eLife assessment

This solid study addresses the unresolved question of why many thousands of small-effect loci contribute more to the heritability of a trait than the large-effect lead variants. The authors explore resource competition within the transcriptional machinery as one possible explanation with a simple theoretical model, concluding that the effects of resource competition would be too small to explain the heritability effects. The topic and approximation of the problem are important and offer an intuitive way to think about polygenic variation, but there are concerns on the derivation of the equations with respect to dropping vs. including certain terms that deal inherently with small numbers.

eLife assessment

This is a useful study of the connection between the ubiquitin ligase protein deltex and the wingless signaling pathway. Two different links are inferred from genetic interactions in vivo between loss-of-function mutations and overexpression. While the genetic data are solid, the precise mechanism underlying either effect remains to be established.

eLife assessment

This study provides an important cell type atlas of the gill of the mussel Gigantidas platifrons using a single nucleus RNA-seq dataset, a resource for the community of scientists studying deep sea physiology and metabolism and intracellular host-symbiont relationships. The evidence supporting the conclusions is convincing with high-quality single-nucleus RNA sequencing and transplant experiments. This work will be of broad relevance for scientists interested in host-symbiont relationships across ecosystems.

eLife assessment

This study presents a valuable dataset and tool that can aid in arthropathies' assessment, potentially enabling such evaluation to be done outside the lab. There is solid evidence supporting the comparison between the force plate and insole data, which can be strengthened by improvements in cross-validation, but the evidence for distinguishing disease signatures and elimination of walking speed as a factor is inconclusive and would need further analysis. This work will be of interest to physical therapists, clinicians, and researchers in the field of ankle/knee/hip osteoporosis and other lower limb joint diseases.