Evaluated articles

eLife assessment

This paper presents important computational modeling work that provides a mechanistic account for how memory representations become integrated or differentiated (i.e., having distinct neural representations despite being similar in content). The authors provide convincing evidence that simple unsupervised learning in a neural network model, which critically weakens connections of units that are moderately activated by multiple memories, can account for three empirical findings of differentiation in the literature. The paper also provides insightful discussion on the factors contributing to differentiation as opposed to integration, and makes new predictions for future empirical work.

eLife assessment

Drosophila is a powerful model organism for understanding the molecular and neural regulation of sleep. However, methodological limitations exist that would appear to limit the relevance of work done in the fly to our understanding of mammalian sleep. In this important work, the authors provide physiological, behavioral, and molecular evidence for the existence of two potential sleep stages in Drosophila. The experiments are generally well conducted and the authors' interpretations of their results are solid overall. Although technically innovative and conceptually provocative, there are aspects of the approaches used and results obtained that leave the central conclusions open to interpretation.

eLife assessment

The authors provide a fundamental resource, detailing genetic variation of nutrient-responsive islet calcium regulation in mice through the lens of proteomics. The evidence for the mechanisms identified using this resource is compelling and strongly supported by integration with results from genome-wide association studies in humans. The construction of a streamlined and searchable web interface for the data will maximize their accessibility and utilization by the community.

eLife assessment

The authors investigate the mechanism of amyloid nucleation in a cellular system using novel ratiometric measurements, providing fundamental insight into the role of polyglutamine length and the sequence features of glutamine-rich regions in amyloid formation. The problem addressed by this study is very significant and the ability to assess nucleation in cells is of considerable value. The data, as presented and analyzed, are mostly convincing.

eLife assessment

Secondary cell walls support vascular plants and conduct water throughout the plant body, and are crucial resources for lignocellulosic feedstocks. Here the authors present convincing genetic and biochemical evidence that secondary cell wall synthesis, known already to be under complex transcriptional control, is also controlled post-transcriptionally by MUSASHI-like RNA-binding proteins. These important results point to a new mechanism for control of secondary cell wall synthesis, which will be interesting to cell biologists and biochemists studying and attempting to manipulate plant biomass.

eLife assessment

This is an important study that contributes to our understanding of the role of beta-arrestins in endosomal activation of the vasopressin type 2 receptors. While the use of a minigene as a tool is a weakness, the evidence is overall convincing and makes for significant findings whose theoretical and practical implications extend to other GPCRs.

eLife assessment

This fundamental study advances the analytic toolset and understanding of long-term series of biological (freshwater) communities, and the impact of humans on these. The authors highlight the value of including not only spatiotemporal scales in biodiversity assessments but also some of the possible drivers of biodiversity loss. Analyzing their joint contribution as environmental stressors, the authors provide compelling evidence that ecosystem assessment methods currently used by environmental regulators throughout Europe are not fit-for-purpose, and they identify several alternatives, more robust indicators of freshwater ecosystem health. The work is timely and will be of interest to ecologists, modelers and global warming scientists in general.

eLife assessment

This useful manuscript presents an intriguing potential refinement of models for adult SVZ neurogenesis, and highlights the role of RNA splicing at specific stages in the lineage. Unfortunately, the evidence does not fully support the claims, leaving it currently incomplete. The proposed role of RNA splicing in neuronal differentiation, though interesting, remains unexplored and would benefit significantly from targeted gene manipulation studies.

eLife assessment

This study presents a useful inventory of the joint effects of genetic and environmental factors on psychotic-like experiences and identifies cognitive ability as a potential underlying mediating pathway. The data were analyzed using a solid and validated methodology based on a large, multi-center dataset. The claim that these findings are of relevance to psychosis risk and have implications for policy changes is partially supported by the results.

eLife assessment

This important study examined the mechanisms underlying reduced excitability of ventral tegmental area dopamine neurons in mice that underwent a chronic mild unpredictable stress treatment. The authors identify NALCN and TRPC6 channels as key mechanisms that regulate spontaneous firing of ventral tegmental area dopamine neurons and examined their roles in reduced firing in mice that underwent a chronic mild unpredictable stress treatment. The authors' conclusions on neurophysiological data are supported by multiple approaches and are convincing, although the relevance of the behavioral results to human depression remains unclear.

eLife assessment

This study represents a valuable finding on the neuron-glia communication and glial responses to traumatic brain injury (TBI). The data supporting the authors' conclusions on TBI analysis, RNA-seq on FACS sorted astrocytes, genetic analyses on Pvr-JNK/MMP1 are solid. However, cellular aspects of the response to TBI, statistical analysis, and molecular links between Pvr-AP1 are incomplete, which could be further strengthened in the future by more rigorous analyses.

eLife assessment

This important work advances our understanding of TLR7 signaling at epithelial surfaces that drives monocytes expansion and its impact on viral responses. The evidence supporting this conclusion is solid, particularly data demonstrating TLR7 stimulation and the requirement for TLR7 in the monocyte expansion. The work will be of interest to immunologists and virologists.

eLife assessment

In this work, the authors provide important mechanistic insights into how the intracellular effector protein Calcineurin B homologous protein 3 (CHP3) can be regulated in a calcium-independent manner to expose its lipid binding site. Compelling evidence demonstrates a binding partner protein (NHE1) triggers a conformation change and exposure of the myristoyl group in CHP3 resulting in membrane association. This provides mechanistic insight into the signalling mechanisms achieved by CHP3 in a target-dependent manner, which will be of broad scientific interest.

eLife assessment

Although largely descriptive, this meta-analysis of 13,000 published Typhi genomes is hugely important to public health. The dataset and presented analysis represents the first wholesale analysis of all available Typhi genomes from the last 21 years. The findings are of great significance to tracking the emergence and maintenance of AMR in Typhi and include novel insights into XDR strain emergence in Pakistan as well as the relationship between MDR maintenance and chromosomal integration.

eLife assessment

The authors describe a sophisticated method to follow enhancer activity in both live embryos and fixed embryos in Tribolium and present important data about the function of a number of enhancers in early development. They show that some of the enhancers are "dynamic" and others are "static" and use this to provide support for the "enhancer-switching" model of gene regulation suggested by some of these authors in the past. However, the evidence they provide is incomplete and although it is consistent with the model, it does not directly support it.

eLife assessment

This study presents findings that are important for understanding plant-soil feedbacks in agriculture. The authors use a large-scale agricultural field experiment to demonstrate the role of root-emitted secondary metabolites in enhancing the yield of the next crop. By using a benzoxazinoid-deficient maize genotype, the authors provide compelling evidence that biomass production and grain yield of several wheat varieties can be increased when grown in soil conditioned by maize plants able to release benzoxazinoids.

eLife assessment

This valuable work investigates the fundamental concept of how the energy of agonist binding is converted into the energy of the conformational change that opens the pore of a ligand-gated ion channel. The conclusions are based on analysis of solid data in terms of a mechanistic model, but adequate statistical analysis is lacking and the uniqueness of the proposed model is not discussed. The findings will be interesting to biophysicists working on ligand-gated ion channels and, more generally, to enzymologists focused on allosteric enzyme regulation.

eLife assessment

This valuable study examines the distribution of four states of brain activity across a variety of cognitive conditions, linking systems neuroscience with cognition and behavior. The work is convincing, using null models and replication in independent datasets to support their findings.

eLife assessment

This important work shows how a transcription factor, fruitless isoform C, fine-tunes the expression of stemness genes to maintain proper stem-cell identity during neurogenesis in Drosophila. The rationale of the work is well-thought-out, conclusions are supported by compelling evidence, and experiments are performed in a rigorous manner, although additional statistics would improve the conclusions. Overall, this work will be of interest to those working on chromatin regulation, transcription regulation, and stem-cell biology.

eLife assessment

This work presents a fundamental meta-analysis on the causes of glucocorticoid variations in birds and mammals. It provides convincing evidence that an increase in metabolic rates increases glucocorticoid concentrations. The work will be of broad interest to animal physiologists.