Evaluated articles

eLife assessment

This manuscript probes the ways in which a protein tag might influence the structure, dynamics and stability of a covalently-attached substrate protein. Such findings are of important significance to several fields, particularly in understanding how these influences control the abundance of proteins within a cell. The evidence provided to support the authors' conclusions are, however, incomplete and further control experiments are necessary to fully support the proposed model.

eLife Assessment

This valuable study reports on electrophysiological recording of the spiking activity of single neurons in the entopeduncular nucleus (EPN) in freely-moving mice performing an auditory discrimination task. The data show that the activity of single EPN neurons is modulated by reward and movement kinematics, with the latter further affected by task contexts (e.g. movement toward or away from a reward location). The results provide solid evidence for the conclusions. There is some ambiguity as to whether the data contain the population of EPN neurons characterized in previous studies that obtained different results. Investigations separating confounding factors would be of benefit. Nonetheless, the work is overall of interest to those who study how the basal ganglia, particularly the EPN, contribute to behavior.

eLife assessment

This important paper shows that the anti-gremlin-1 (GREM1) antibody is not effective at treating liver inflammation or fibrosis. Critically, the evidence also challenges existing data on the detection of GREM1 by ELISA in serum or plasma by demonstrating that high-affinity binding of GREM1 to heparin would lead to localisation of GREM1 in the ECM or at the plasma membrane of cells. The conclusions are supported by a convincing, well-controlled set of experiments.

eLife assessment

This fundamental state-of-the-art modeling study explores neural mechanisms underlying walking control in cats, demonstrating the probability of three different states of operation of the spinal circuitry generating locomotion at different speeds. The authors' biophysical modeling sufficiently reproduces and provides explanations for experimental data on how the locomotor cycle and phase durations depend on treadmill walking speed and points to new principles of circuit functional architecture and operating regimes underlying how spinal circuits interact with supraspinal signals and limb sensory feedback signals to produce different locomotor behaviors at different speeds, which are major unresolved problems in the field. The modeling evidence is compelling, especially in advancing our understanding of locomotion control mechanisms and will interest neuroscientists studying the neural control of movement.

eLife Assessment

This important study is an advancement towards the understanding of animal nervous system organization and evolution by providing an exceptional, high-quality and detailed description of the entire connectome of the 3-day larva of the marine annelid Platynereis dumerilii. It provides a wealth of data on cell type diversity and the modules that interconnect them. Its strength is the massive amount of high-quality data, although this is also partly a weakness as it can make the work difficult to read and digest scientifically. This work lays the foundations for studies on cell type diversity, segmental vs. intersegmental connectivity, and mushroom bodies, but will certainly also be of use to scientists interested in other nervous systems parts, their functions, and evolution.

eLife Assessment

This study presents a valuable methodological advancement in quantifying thoughts over time. A novel multi-dimensional experience-sampling approach is presented, identifying data-driven patterns that the authors use to interrogate fMRI data collected during naturalistic movie-watching. The experimentation is inventive and the analyses carried out and results presented are convincing.

eLife Assessment

This important study provides new insights into the mechanisms that underlie perceptual and attentional impairments of conscious access. The paper presents convincing evidence of a dissociation between the early stages of low-level perception, which are impermeable to perceptual or attentional impairments, and subsequent stages of visual integration which are susceptible to perceptual impairment but resilient to attentional manipulations. This study will be of interest to scientists working on visual perception and consciousness.

eLife Assessment

This valuable study investigates how biologically plausible learning mechanisms can support assembly formation that encodes statistics of the environment, by enabling neural sampling that is based on within-assembly connectivity strength. It convincingly shows that assembly formation can emerge from predictive plasticity in excitatory synapses, while two types of plasticity in inhibitory synapses are required: inhibitory homeostatic (predictive) plasticity and inhibitory competitive (anti-predictive) plasticity.

eLife Assessment

This valuable study reports machine learning models derived from large-scale data to predict the risk of post-stroke epilepsy. The evidence supporting the conclusions is convincing, although there are some validation issues (lack of cross-validation, possible bias in external validation results). The study may be of interest in the field of clinical neurology

eLife Assessment

This study reveals a neural signature of a common behavioural phenomenon: serial dependence, whereby estimates of a visual feature (here motion direction) are attracted towards the recent history of encoded and reported stimuli. The study provides solid evidence that this phenomenon arises primarily during working memory maintenance. The pervasiveness of serial dependencies across modalities and species makes these findings important for researchers interested in perceptual decision-making across subfields.

eLife Assessment

This manuscript presents valuable findings which reveal an intricate pattern of memory expression following retrieval extinction at different intervals from retrieval-extinction to test. The novel advance is in the demonstration that, relative to a standard extinction procedure, the retrieval-extinction procedure more effectively suppresses responses to a conditioned threat stimulus when testing occurs just minutes after extinction. While the data provide solid evidence that the "short-term" suppression of responding involves engagement of the dorsolateral prefrontal cortex, there are inconsistencies in the analyses reported which obscure the interpretation and leave some of the claims with limited evidence.

eLife Assessment

Yonk and colleagues provide a valuable, timely, and in-depth study showcasing the role of thalamostriatal inputs in learning and action selection. After characterizing the synaptic properties of these inputs onto different striatal cell types in vitro, they provide solid evidence that posterior medial thalamic nucleus (POm) terminals in striatum are activated during reward expectation and arousal. The overall function of this pathway and the degree to which results are confounded by viral contamination of surrounding nuclei and movements remain open questions.

eLife Assessment

There is a growing interest in understanding the individuality of animal behaviours. In this important article, the authors build and use an impressive array of high throughput phenotyping paradigms to examine the 'stability' (consistency) of behavioural characteristics in a range of contexts and over time. The results show that certain behaviours are individualistic and persist robustly across external stimuli while others are less robust to these changing parameters. The data supporting their findings is extensive and convincing.

eLife assessment

This important study reports the discovery of a novel nucleotide ubiquitylation activity by the DTX3L E3 ligase. Solid evidence is presented for ubiquitin attachment to single-stranded oligonucleotides. This very interesting biochemical finding can be used as a starting point for studies to establish relevance in a physiological setting.

eLife Assessment

This valuable study reports the development of a novel organoid system for studying the emergence of autorhythmic gut peristaltic contractions through the interaction between interstitial cells of Cajal and smooth muscle cells. The authors further utilized the system to provide convincing evidence for a previously unappreciated potential role for smooth muscle cells in regulating the firing rate of interstitial cells of Cajal. The work will be of interest to those studying development and physiology of the gut.

eLife assessment

This work aimed at deconstructing how sebaceous gland differentiation is controlled in adult skin. Using monoclonal antibodies designed to inhibit specific Notch ligands or receptors, the authors present convincing evidence that the Jag2/Notch1 signaling axis is a crucial regulator of sebocyte progenitor proliferation and sebocyte differentiation. The valuable findings presented here contribute to the growing evidence that Notch signaling is not only key during the development of the skin and its appendages but also regulates cell fate in adult homeostatic tissues. From a translational perspective, it is intriguing that the effect of Jag2 or Notch1 inhibition, which leads to the accumulation of proliferative stem/progenitor cells in the sebaceous gland and prevents sebocyte differentiation, is reversible.

eLife Assessment

This valuable work presents an interesting strategy to interfere with the HBV infectious cycle as it identifies two previously unexplored HBc-Ag binding pockets. The experimental data is compelling and opens the door to generating and testing novel anti-HBV therapies.

eLife assessment

This valuable study presents the development of a single turnover stopped-flow fluorescence experiment to study the kinetics of substrate unfolding and translocation by the bacterial ClpB disaggregase. Using non-physiological nucleotides to bypass the physiological regulation mechanism of ClpB, the authors convincingly show that the ClpB disaggregase is a processive motor with a slow unfolding step preceding rapid translocation. The results of this analysis are of value for future mechanistic studies on energy-dependent unfolding, degradation, and disaggregation molecular machines.

eLife assessment

This study explores simple machine learning frameworks to distinguish between interacting and non-interacting protein pairs, offering solid computational results despite some concerns about dataset generation. The authors demonstrate a modest improvement in AlphaFold-multimers' ability to differentiate these pairs. Using a simple yet sound approach, this work is a valuable contribution to the challenging problem of reconstructing protein-protein interaction networks.

eLife Assessment

This study provides important insights into how the EBH domain of microtubule end-binding protein 1 (EB1) interacts with SxIP peptides derived from the MACF plus-end tracking protein. The revised manuscript includes convincing ITC and NMR experiments that clarify the role of flanking residues and address the influence of dimerization and cooperativity on binding. While some mechanistic aspects remain difficult to resolve experimentally, the data and analysis now more clearly justify the proposed "dock-and-lock" model and its interpretive value. This work will be of interest to structural biologists and biophysicists studying microtubule-associated protein interactions.