Evaluated articles

eLife assessment

This manuscript by Combe et al. presents the role of cholinergic modulation in the spike rate adaptation in pyramidal place cells. Using combined electrophysiology, pharmacological, and multi-compartment computational modeling, the authors identify the downstream pathway (e.g. activation of TRPM4 channel) that shapes the firing pattern under the triangular-shaped ramps. The study demonstrates solid evidence, and the findings are important for bridging pyramidal neurons' molecular/channel properties to behavior-level implications (place field firing).

eLife assessment

This important work studies the spontaneous contractions (SC) of the Hydra body wall and presents a mathematical model of nutrient transport to hypothesize the role of SC on maintaining the microbiota. The solid evidence presented yields insights on the functional implications of the SC and the increased nutrient update obtained from mixing the local fluid environment through body wall contractions. The main result represents an important observation about the role of hydrodynamics on organism behavior and its relation to diffusive chemical transport processes.

eLife assessment

The manuscript by Brunetti et al. represents an important contribution where SARS-CoV-2 infection of T-helper cells is implicated and found to be mediated by CD4. The work progressed through a computationally driven hypothesis, by analyzing the interaction partners of SARS-CoV-2 spike glycoprotein (as initially modelled through similar SARS-CoV-1), followed by experimental validations, and further computational and experimental insights on the mechanism of binding. The study identifies the interaction between spike RBD domain and N Terminal domain of CD4 molecule as the specific viral attachment strategy. The evidence supporting the claims of the authors is solid, the results look significant and the data is clear and enough for understanding the manuscript. It also provides a potential usefulness of their approach in future work in understanding how viruses mediate infection of T cells. The work will be of interest to medical biologists working on SARS-CoV-2.

eLife assessment

This fundamental work advances our understanding of the effects of metformin on bone healing in hyperglycemic conditions. The evidence supporting the conclusion is convincing, using three different types of bone fracture models in type-2 diabetes (T2D) mice. This paper is of potential interest to skeletal biologists, orthopaedic surgeons, and endocrinologists who study the effects of metformin on fracture healing.

eLife assessment

In their current study, Detraux D and colleagues provide some evidence suggesting a role for heme biosynthesis on FGF-ERK and TGF beta signalling and exit from naïve pluripotency, and in controlling the 2-cell-like cell state. The observations provided by the authors are interesting and potentially relevant in the field of pluripotent cell state transitions.

eLife assessment

Dhekne et al report a novel pathway for activation of the multi-domain LRRK2 protein kinase by Rab12 GTPase. LRRK2, which is mutated in Parkinson's Disease phosphorylates a subset of Rab proteins involved in intracellular trafficking, and Parkinson's disease-linked mutations increase this phosphorylation. This work adds an important new layer of understanding of this highly complex pathway by revealing that LRRK2's binding to Rab12 enhances its ability to phosphorylate Rab10. This conclusion is supported by compelling evidence from a wide array of rigorous approaches.

eLife assessment

This valuable study reports on the role of transposable elements in gene expression variation in rice and how TE-associated expression changes could have been selected during domestication. The combination of evidence from linkage studies and selection scans for a subset of insertions is convincing, although it is difficult to know in how many cases linkage of TE insertions to other regulatory variants is responsible for altered gene expression and in how many cases the TE insertions themselves are the bona fide cause of altered gene expression. The work will be of interest to colleagues working on the role of transposable elements in adaptation and to biologists working on domestication.

eLife assessment

This important study identifies and characterizes a broad peptidergic network that coordinates nutrient-specific consumption needs for food or water. Using state-of-the-art methodology the authors combine a well-balanced set of exploratory anatomical analyses with rigorous functional experimental approaches to examine how ingestion is regulated based on internal needs. These significant and convincing new findings are of broad interest to the neuroscience field.

eLife assessment

This important study makes use of AlphaFold2 to predict the models of tens of cohesin subcomplexes from different species. The models, which are in most cases consistent with published cohesin variants with compromised in vitro and in vivo cohesin activity, provide convincing evidence that leads to testable hypotheses of cohesin dynamics and regulation. More broadly, this study serves as an example of how to use AlphaFold2 to build models of protein complexes that involve the docking of flexible regions to globular domains.

eLife assessment

This important study describes a high performance computational approach to interrogate how microscopic epistasis and clonal interference affect evolutionary dynamics in a spin glass model of microbial evolution. The study offers several insights that can aid in our understanding of the forces that operate in adaptive evolution. The evidence provided is compelling, with its rigorous use of models and analytical descriptions of how these forces manifest in evolution.

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.