Evaluated articles

eLife assessment

This study addresses several gaps that are evident with regards to cancer cell invasion in tissue. The approaches taken by this group encompassing mathematical modeling and experimental procedures are for the most part rigorous. The study is deemed as of high potential impact.

eLife assessment

This manuscript provides a solid and valuable analysis of the advantages and potential pitfalls of the application of Granger Causality to calcium imaging data that should be of interest to a wide range of neuroscience researchers. Granger Causality is a key tool in assessing the temporal relationships between variables, but one that is susceptible to many types of artifacts. The rigor of the authors' application of the methodology to calcium imaging data in particular leads to a more robust understanding of the effects of measurement artifacts and analysis choices on the results. There was some concern, however, about whether all of the findings would apply outside feedforward neural circuits and it was unclear how some of the results relate to others that currently exist in the literature.

eLife assessment

This paper presents a single-molecule polarization microscopy study aimed at monitoring the arginine/agmatine antiporter AdiC as it transiently exchanges between conformational states. This approach measures how a bis-TMR fluorophore anchored onto helix 6a changes its orientation in the microscope, and the authors identify four states that they propose correspond to the key steps in the transport cycle (inward-open, inward occluded, outward occluded and outward open). This is a cutting-edge and challenging approach that sets the stage for direct measurements of conformational equilibria and will thus be of interest to anyone studying transport mechanisms. However, additional investigation is required to validate the robustness of the post-processing of the single-molecule data to yield the four-state model compared to alternate models, to test the robustness of the data with transport mutants/conditions that would slow or eliminate states, and to consolidate transitions that are observed that conflict with previous observations of obligatory coupling in AdiC.

eLife assessment

The manuscript reports a new structure of the small conductance mechanosensitive channel MscS from E. coli in the open state, together with coarse-grained and atomistic molecular dynamics simulations of MscS and the related channel MSL1 of plant mitochondria in closed and open states. The important finding is that the surrounding lipid bilayer is severely distorted in the closed state only, with the protein inducing high curvature in the inner leaflet due to the membrane protruding into the cytoplasm. The authors argue convincingly that the role of membrane tension is to increase the energy of the protein-membrane system in this closed state compared to the relatively flat-membrane open state, in contrast to the previous proposal that tension-induced gating is driven by expansion of the in-plane area of the protein. The finding may be relevant for the understanding of ion channel mechano-sensation more generally, including of the PIEZO1 channel.

eLife assessment

This article presents a model that uses spike timing-dependent plasticity and theta phase precession of spiking neurons to generate representations similar to those learned by temporal difference learning to form successor representations. This work is important for bridging between biologically detailed mechanisms shown in experimental data and the more abstract models in the reinforcement framework literature. The simulations are compelling, but several aspects may rely on unrealistic assumptions, so further work is necessary to determine whether such a learning process could actually occur in the brain.

eLife assessment

This manuscript describes cell types in the head of the squid, Loligo vulgaris, through expression patterns of key genes identified in single cell transcriptomics. This topic is generally of great comparative interest. It will contribute to a better understanding of the cephalopod nervous and sensory systems, providing a basis for future comparative and evolutionary research.

eLife assessment

This study provides valuable findings about how brain machine interfaces cope with changes in context, an important consideration for deploying such devices in the real world. The evidence supporting the claims is solid although increasing the number and range of contexts investigated would have strengthened the study. The work will be of interest to motor neuroscientists and engineers developing brain machine interfaces and will be useful for future development of such devices.

eLife assessment

This is an important and methodologically compelling paper that reports the first application of optogenetics to inner hair cell ribbon exocytosis mechanisms in the inner ear and rapid flash-and-freeze techniques to a ribbon synapse. The conclusions of the paper are mostly well supported by the data and it will capture the interests of a broad audience of neurobiologists and sensory physiologists. Paired recordings of inner hair cells and afferents validate the optogenetic protocols of stimulation. A surprising finding is the nearly complete absence of docked vesicles at rest and after stimulation, but upon stimulation vesicles rapidly associate with the ribbon. The reviewers agreed that this is a high-quality study, but that some additional work is needed to address certain pitfalls of the methods used and to rule out alternative explanations of the data.

eLife assessment

This manuscript provides a successful model to study the ultrafast brain oscillation-mediated brain circuitry and cellular mechanisms in sensory processing. Utilizing this model, the authors studied potential cellular mechanisms that generate ultrafast oscillations (250-600Hz) in the cortex. These oscillations correlate with sensory stimulation and might be relevant for perceiving relevant sensory inputs. The data reasonably support most of the claims by the authors in this manuscript.

eLife assessment

This important paper provides a convincing mechanism for relative binding specificity of Type II inhibitors to kinases. The combination of a sequence-derived Potts-model with experimental dissociation constants and calculated free energies of binding to the DFG-out state is highly compelling and goes beyond the current state of the art. Given the importance of kinases in pathophysiological processes, the results will be of interest to a broad audience and, in addition, the combination of computational methods can be applicable to a wide variety of other biophysical processes that involve conformational rearrangements.

eLife assessment

This paper reports a useful set of results that uses a reduced network model based on a previously published large-scale network model to explain the generation of theta-gamma rhythms in the hippocampus. Combining the detailed and reduced models and comparing their results is a powerful approach. However, the evidence for the main claim that CCK+ basket cells play a key role in theta-gamma coupling in the hippocampus is currently incomplete.

eLife assessment

This fundamental work addresses the role of the mitotic kinase PLK-1 in meiosis, using C. elegans as a model system. The valuable findings are convincing and combine beautiful cell biology and biochemical assays. The work will be of broad interest to people working on Plk1 and/or in meiosis in many different systems.

eLife assessment

Powers and colleagues reveal that commonly used "genetic markers" (selectable cassettes that allow for genome modification) may lead to unintended consequences and unanticipated phenotypes. These consequences arise from cryptic expression directed from within the cassettes into adjacent genomic regions. In this work, they identify a particularly strong example of marker interference with a neighboring gene's expression and develop and test next-generation tools that circumvent the problem. The work will be primarily of interest to yeast biologists using these types of tools and interpreting these types of data.

eLife assessment

Powers and colleagues reveal that commonly used "genetic markers" (selectable cassettes that allow for genome modification) may lead to unintended consequences and unanticipated phenotypes. These consequences arise from cryptic expression directed from within the cassettes into adjacent genomic regions. In this work, they identify a particularly strong example of marker interference with a neighboring gene's expression and develop and test next-generation tools that circumvent the problem. The work will be primarily of interest to yeast biologists using these types of tools and interpreting these types of data.

eLife assessment

This manuscript provides compelling evidence that in response to calcium, the C-lobe of calmodulin changes its interaction with the C-terminal domain of an SK2 small-conductance calcium-activated potassium channel. These findings will be of interest to those in the field of ion channels and calcium signaling as they are valuable to understanding the molecular mechanics by which calcium activates SK2 channels, which are important for a wide variety of physiological signaling processes.

eLife assessment

This is an extremely thorough investigation of the role of cadherins in generating a functional motor circuit. The presented data support a model whereby combinations of redundant adhesion molecules create a code to wire the breathing circuit. This study advances understanding of the molecular basis of circuit wiring in the brain.

eLife assessment

This study models the predictions a listener makes in music in two ways: how different model algorithms compare in their performance at predicting the upcoming notes in a melody, and how well they predict listeners' brain responses to these notes. The study will be valuable to the field as it implements three contemporary models of music prediction. In a set of solid analyses, the authors find that musical melodies are best predicted by models taking into account long-term experience of musical melodies, whereas brain responses are best predicted by applying these models to only a few most recent notes.

eLife assessment

This fundamental study employs a publicly available dataset to examine the role of gamma oscillations in the coding of olfactory information in the mouse piriform cortex. The authors convincingly show that gamma originates in the piriform cortex, is driven by feedback inhibition, and that the time course of odour decoding is most accurate when gamma oscillations are strongest. This work is relevant to a wide audience interested in the mechanisms and role of oscillations in the brain, and nicely demonstrates the benefits of well-curated, publicly available datasets.

eLife assessment

This work would be of interest to global health scientists, particularly in low- and middle-income countries where childhood stunting is an ongoing challenge, and to statisticians interested in building clinical prediction rules. The authors leveraged large, rich datasets from multi-center studies to build and validate predictive models. But by using change in growth, rather than absolute growth, as the only outcome, it may be missing children of concern who are already experiencing growth failure and require intervention but have reached a growth faltering floor.

eLife assessment

This is a very interesting manuscript that will be of interest to the field of stress neurobiology and neuropsychiatry. Claims about the interactions between stress and medial prefrontal cortex NPAS4 on anhedonia and motivation remain to be firmly established, yet clear evidence is provided for NPAS4 function on medial prefrontal cortex pyramidal neuron dendritic morphology and gene expression.