Evaluated articles

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 and computational data to support the claims. The work will be of interest to those studying the binding of small molecule drugs to membrane protein complexes.

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.

eLife assessment

This valuable manuscript attempts to identify the brain regions and cell types involved in habituation to dark flash stimuli in larval zebrafish. Habituation being a form of learning widespread in the animal kingdom, the investigation of neural mechanisms underlying it is a worthwhile endeavor. The authors use a combination of behavioral analysis, neural activity imaging, and pharmacological manipulation to investigate brain-wide mechanisms of habituation. While the data presented are solid, the authors conclude that there is no simple relationship between pharmacological intervention, neural activity patterns, and behavioral outcomes, and a robust causative link can therefore not be established.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

eLife assessment

Boyle et al identify Npy-expressing dorsal horn neurons as powerfully inhibiting pain and itch under normal and pathological conditions. The valuable data are convincing, and the effect sizes are robust and directly challenge previous work.

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. This paper is of interest to a broad and growing community of biologists, biophysicists, and engineers interested in cell-geometry interactions.

eLife assessment

This important study uses genomically-engineered glypican alleles (Dally and Dally-like) to determine the role of these proteins on the Dpp/BMP morphogen gradient in the wing disc of Drosophila melanogaster. The new glypican null and tagged add-back alleles, as well as a Dpp mutant that cannot bind heparin sulfate moieties in glypicans, provide solid results that support the model in which Dally but not Dally-like stabilizes Dpp on the cell surface by counteracting receptor-mediated Dpp internalization. This paper would be of interest to developmental biologists working on morphogens.

eLife assessment

This paper reports the fundamental discovery of a new function of neutrophil in specifically clearing apoptotic hepatocytes by penetrating the cells rather than engulfing them without causing inflammation as a part of tissue homeostasis. This solid study transforms the way we think about role of neutrophil in pathogenesis of autoimmune liver disease.

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.