Evaluated articles

eLife Assessment

This important work describes systematic computational and experimental approaches to turn a moderately stable α-helical bundle into a very stable fold. The authors advance our understanding of α-helix stabilization providing a convenient framework that has general implications for the protein design field. The main claims have convincing support through a sound methodology, with strong specific conclusions for designing mechanically, thermally, and chemically stable α-helical bundles.

eLife Assessment

This work describes a useful computational tool for automated morphometry of dynamic organelles from microscope images. However, the supporting evidence and novelty of the manuscript as presented are incomplete and could be improved. The work will be of interest to microscopists and bioimage analysts who are non-experts but wish to improve quantitative analysis of cellular structures.

eLife Assessment

This important study examines how mismatched light and temperature cycles shape Drosophila locomotor timing and temperature-dependent timeless splicing, and leverages long-term early/late selection lines to probe evolutionary plasticity. The strength of evidence is incomplete at present, mainly because startle/masking under step cues could confound the behavioural readouts, and tim's involvement remains correlative. The authors should address masking in the behaviour analyses and provide causal support for tim's role.

eLife Assessment

This useful paper describes a software tool, "DrosoMating", which allows automated, high-throughput quantification of 6 common metrics of courtship and mating behaviors in Drosophila melanogaster. The validity of the tool is quite convincingly demonstrated by comparing expert human assessments with those made by DrosoMating. The work, however, does not address how DrosoMating compares with or advances on other existing tools for exactly the same purpose, whether it can be used for studies of other Drosophila species, and/or whether finer aspects of courtship response timing - which depend on proximal female signals to the male - could be extracted with more detailed analyses. Some additional statistical analyses would also help further strengthen the authors' current conclusions.

eLife Assessment

The authors investigate how dominance hierarchy shapes defensive strategies in mice under two naturalistic threats: a transient visual looming stimulus and a sustained live rat. This study provides important insights into how social context and dominance hierarchy modulate innate defensive behaviors across distinct naturalistic threats. The strength of evidence is convincing, with detailed classification and analysis of behaviors.

eLife Assessment

This work represents a valuable finding of how single-trial functional connectivity may be used to infer different cognitive states involved in speech perception and production. Although the data and analyses are overall convincing, the theoretical advance and novelty of the finding are less clear. With a clearer idea of the functional significance of the connectivity data, the paper would be of interest to those interested in brain networks and communication.

eLife Assessment

Muetter et al. provide an important argument that luminescence is a reliable, high-throughput alternative to colony-forming units (CFU) for super-MIC investigations, particularly when the quantity of interest is biomass. By examining 20 antimicrobials spanning 11 classes, the work shows that discrepancies between CFU and luminescence are often biological (filamentation, Viable But Not Culturable). The work provides a compelling view of how these three common measurements (luminescence, optical density, and CFU) relate to one another across a range of drug treatments, although testing on clinical isolates could be of further benefit.

eLife Assessment

This study provides valuable findings on how the activity of the E3 ubiquitin ligase Highwire (Hiw/Phr1) is regulated and its impact on synaptic growth. The authors propose that impaired endocytosis leads to condensation of Hiw, resulting in increased synaptic growth. They also integrate such a mechanism within the known JNK (c-JUN N-terminal Kinase) and BMP (Bone Morphogenetic Protein) signalling pathways involved in synapse regulation. While the work raises an interesting mechanistic framework, several aspects of the experimental design and methodology are incomplete, and key conclusions, particularly those regarding the liquid-liquid phase separation of the E3 ubiquitin ligase, are not fully supported by the presented data.

eLife Assessment

This valuable study uses a computer vision pipeline to infer the motor control of cephalopod skin, revealing that individual chromatophores exhibit anisotropic deformations and can be associated with multiple putative motor units. The evidence supporting these claims is convincing, and the authors present some limited electrophysiological validation of the findings from their computational analysis. This work will be of significant interest to biologists studying cephalopod behavior and motor control.

eLife Assessment

This study presents a valuable and well-documented computational pipeline for the scalable analysis and spike sorting of large extracellular electrophysiology datasets, with particular relevance for high-density recordings such as Neuropixels. The authors demonstrate the pipeline's utility for benchmarking spike sorter performance and evaluating the effects of data compression, supported by thorough testing, clear figures, and openly available code. The workflow is reproducible, portable, and practical, providing concrete guidance on computational cost and runtime. Overall, the evidence supporting the pipeline's performance and output quality is compelling, and this work will be of broad interest to the systems neuroscience community.

eLife Assessment

This study presents analyses of single neuron activity in the subthalamic nucleus (STN) of monkeys performing a decision-making task that manipulates both perceptual evidence and reward. The study shows convincing evidence of distinct subpopulations of neurons in STN that differ in their representations of key quantities related to decision formation. These findings reveal important functional heterogeneity within the STN that helps provide new insights into its contributions to decision processing.

eLife Assessment

This manuscript presents a novel investigation of organizational principles governing brain activity at both global and local scales during naturalistic viewing paradigms, an important advance for theoretical neuroscience, functional neuroimaging, and neurology. The authors demonstrate that brain activity during naturalistic viewing is dominated by two anti-correlated states that toggle between each other with a third transitional state mediating between them. The evidence supporting this finding is compelling, with the successful replication across three independent datasets (StudyForrest, NarrattenTion, and CamCAN) a particular strength.

eLife Assessment

This valuable study examined how sensory adaptation supports visual perception in the presence of noise. The authors used a combination of human psychophysics, electroencephalography (EEG), and deep neural networks to show that adaptation to noise can improve perception. The results are solid but are, at present, weakened by a number of concerns, including some related to the experimental design and some regarding the interpretation of the results in terms of particular mechanisms. With these concerns adequately addressed, the study and conclusions would be likely to be of broad interest to the neuroscience community.

eLife Assessment

This manuscript describes a series of studies using four different Go/No Go task variants in combination with fast-scan cyclic voltammetry to determine the role of dopamine release in the ventromedial striatum in action selection, controllability of reward pursuit, effort, and reward approach. The authors conclude that dopamine signals in the ventromedial striatum integrate the invigoration of action initiation with continuous estimation of spatial, but not temporal, proximity to rewards. There are, however, a number of concerns regarding methodology that could affect the interpretation of the results. Thus, while the findings are useful, they are considered incomplete, with the primary claims only partially supported.

eLife Assessment

This valuable study investigates whether the activity of an ABC transporter, BmrA, can be modulated by mechanical stimuli. The authors develop a single-molecule experimental system to address this question, although aspects of the methodological framework are incomplete. This work also develops a convincing theoretical model to explain the effect of membrane curvature on the conformational transitions observed during the activity cycle of this membrane protein. This study is of interest to the fields of membrane biophysics and membrane transport.

eLife Assessment

In this important work, it is demonstrated that certain high-resolution cryo-EM structures can be obtained by using concentrated cell extracts without purification. The compelling results with the mammalian ribosomes demonstrate the utility of this approach for this molecule and complexes with elongation factor 2. Moreover, this work also demonstrates the utility of 2D template matching for particle picking for structure determination by single-particle averaging pipelines.

eLife Assessment

The study proposed hemogenic endothelium in adult BM using lineage tracing. Though the study is potentially valuable, the data is incomplete due to the lack of control and insufficient analysis. There is potential for the study to be improved by further revision.

eLife Assessment

This useful study by Palo et al proposes that FRG1 functions as a negative regulator of Nonsense-Mediated mRNA decay (NMD) by associating with the exon junction complex (EJC) and destabilizing UPF1 independently of DUX4. The authors present solid evidence to dissect the relationship between FRG1 and DUX4 in NMD. However, the evidence to support the claim that FRG1 is a component of the EJC or the NMD machinery is incomplete.

eLife Assessment

This study presents a valuable finding on maternal SETDB1 as a key chromatin repressor that shuts down the 2C gene program and enables normal mouse embryonic development. The evidence supporting the claims of the authors is solid, although the inclusion of a causality test, a mechanistic understanding of SETDB1 targeting, and phenotypic quantification would have greatly strengthened the study. The work will be of broad interest to biologists working on embryonic development, stem cells and gene regulation.

eLife Assessment

This manuscript provides valuable insight into how genome organization changes as cells progress through the cell cycle after mitotic exit. The conclusions are supported by solid, rigorous data, and the use of sorted unsynchronized cells rather than cells treated with drugs is a particular strength. Two sharp genome remodeling events are identified at G1-S and to a lesser extent, at S-G2 transitions. A discussion on the limitations of Hi-C and a broader interpretation of results in the context of other mechanistic models would strengthen the overall rigor.