Evaluated articles

eLife Assessment

This important study provides evidence for dynamic coupling between translation initiation and elongation that can help maintain low ribosome density and translational homeostasis. The authors combine single-molecule imaging with a new approach to analyze mRNA translation kinetics using Bayesian modeling. This work is overall solid and will be of interest to those studying translational regulation.

eLife Assessment

This valuable study provides convincing evidence that MgdE, a conserved mycobacterial nucleomodulin, downregulates inflammatory gene transcription by interacting with the histone methyltransferase COMPASS complex and altering histone H3 lysine methylation. This work will interest microbiologists as well as cell and cancer biologists.

eLife Assessment

This study describes a genetic screen to identify deubiquitinases (DUBs) that counteract the activity of small molecule degraders (PROTACs). The presented data is valuable, identifying OTUD6A and UCHL5 as DUBs that impact the efficacy and potency of PROTAC-mediated degradation in distinct subcellular compartments. While the conclusions are broadly supported and the methods employed are solid, the validation of OTUD6A and UCHL5 mechanisms requires additional study. Overall, these findings merit further evaluation by the targeted protein degradation community when developing and optimizing PROTACs and efforts to achieve compartment-specific degradation.

eLife Assessment

This important study identifies a plant-derived metabolite, betulin, as an effective natural insecticide against aphids and uncovers its specific molecular target. The evidence is compelling, combining greenhouse and field efficacy trials with rigorous molecular, genetic, and electrophysiological approaches that converge on a conserved binding site in the aphid GABA receptor. While additional work is needed to fully assess potential off-target effects and ecological safety, the study provides a strong mechanistic foundation. These findings will be of interest to researchers in plant biology, chemical ecology, and sustainable pest management.

eLife Assessment

This manuscript reports a high-quality genome assembly of the European cuttlefish, Sepia officinalis, a representative species of the Cephalopod lineage. This solid work relies on current best practices in genome sequencing and assembly, combining PacBio HiFi long reads and Hi-C chromatin conformation capture, and on state-of-the-art comparative genomic analyses, including chromosome number evolution and analyses of expanded gene families. The resulting genome will be a valuable resource for researchers interested in cuttlefish biology and comparative genomics in general.

eLife Assessment

This important study advances our understanding of how cellular quality control machinery influences cystic fibrosis (CF) drug responsiveness by systematically analyzing the effects of the chaperone calnexin on more than two hundreds of CFTR (cystic fibrosis transmembrane regulator) variants. The evidence supporting the conclusions is convincing, with a comprehensive deep mutational scanning methodology and rigorous quantitative analysis. The findings reveal that calnexin is critical for both CFTR protein expression and corrector drug efficacy in a variant-specific manner, providing invaluable insights that could guide the development of personalized CF therapies. This work will be of significant interest to researchers in protein folding, CF drug development, and genetic disease therapeutics.

eLife Assessment

In this important contribution, Yan and colleagues describe a powerful and compelling strategy to generate concatamers of the BK channel and their fusion constructs with the auxiliary gamma subunits, which allows exploring contributions of individual subunits of the tetrameric channel to its gating and the study of heteromeric channel complexes of defined composition. Distinct examples are presented, which illustrate great diversity in the stoichiometric control of BK channel gating, depending on the site and nature of molecular perturbations. The molecular approaches could be extended to other membrane proteins whose N and C termini face opposite sides of the membrane.

eLife Assessment

This is a valuable study that explores the role of the conserved transcription factor POU4-2 in the maintenance, regeneration, and function of planarian mechanosensory neurons. The authors present convincing evidence provided by gene expression and functional studies to demonstrate that POU4-2 is required for the maintenance and regeneration of mechanosensory neurons and mechanosensory function in planarians. Furthermore, the authors identify conserved genes associated with human auditory and rheosensory neurons as potential targets of this transcription factor.

eLife Assessment

This study demonstrates the cartilage-protective effects of osteoactivin in inflammatory experimental models. The work offers valuable insights advancing current knowledge regarding regulation of joint inflammation and tissue degeneration. The evidence provided is compelling and suggests that osteoactivin may serve as a promising therapeutic target for inflammatory joint diseases.

eLife Assessment

This important work provides mechanistic insights into the development of cardiac arrhythmia and establishes a new experimental use case for optogenetics in studying cardiac electrophysiology. The agreement between computational models and experimental observations provides a convincing level of evidence that wave train-induced pacemaker activity can originate in continuously depolarized tissue, with the limitation that there may be differences between depolarization arising from constant optogenetic stimulation, as opposed to pathophysiological tissue depolarization. Future experiments in vivo and in other tissue preparations would extend the generality of these findings.

eLife Assessment

This study presents a valuable finding about how receptor-ligand binding pathways with multi-site phosphorylation can show non-monotonic responses to increasing ligand affinity and to kinase activity. The authors provide compelling evidence through a simple ordinary differential equation model of such signaling networks with the key new ingredient of ligand-induced receptor degradation. The work will be of interest to physicists and biologists working on signal transduction and biological information processing.

eLife Assessment

This study introduces an important method to estimate the probability of malaria importation with a new Bayesian approach that integrates epidemiological, travel reports, and genetic data. The authors provide convincing evidence for the value of this model in identifying the main sources of malaria transmission and risk factors. This work will be of interest to the area of genomic epidemiology and public health strategies aiming to eliminate malaria.

eLife Assessment

The findings are valuable, given that they highlight the flexible and future-oriented nature of working memory. However, the evidence for the claims about context/color generalization, behavioural relevance of context decoding, dimensionality reduction, neural geometry, the XOR representation, and the specific contribution of working memory is incomplete. The work could be reframed in terms of prospective remapping.

eLife Assessment

This study provides novel and convincing evidence that both dopamine D1 and D2 expressing neurons in the nucleus accumbens shell are crucial for the expression of cue-guided action selection, a core component of decision-making. The research is systematic and rigorous in using optogenetic inhibition of either D1- or D2-expressing medium spiny neurons in the NAc shell to reveal attenuation of sensory-specific Pavlovian-Instrumental transfer, while largely sparing value-based decision on an instrumental task. The important findings in this report build on prior research and resolve some conflicts in the literature regarding decision-making.

eLife Assessment

This study provides important findings on the understanding of circannual timing in mammals, for which iodothyronine deiodinases (DIOs) have been suggested to be of critical importance, yet functional genetic evidence has been missing. The authors convincingly implicate dio3, the major inactivator of the biologically active thyroid hormone T3, in circannual timing in Djungarian hamsters, using a combination of correlative and gene knock-out experiments; thus this provides key insights into the evolution and function of animal annual timing mechanisms.

eLife Assessment

These findings are among some of the first to identify a behavioral and neurobiological substrate that disentangles nonassociative from associative fear responses following stress, providing a fundamental push forward in the field. The evidence supporting this is compelling and uses a variety of conceptual and technological approaches. This investigation will be of interest to neuroscientists and behaviourists broadly, as well as clinicians for its relevance to post-traumatic stress disorder.

eLife Assessment

This valuable study presents a theoretical framework for building continuous attractor networks that integrate with a wide range of topologies, which are of increasing relevance to neuroscientists. While the work offers solid evidence for most claims, the evidence supporting biological plausibility and key claims - such as the existence of a continuum of stable states and robustness across geometries - is currently incomplete and would benefit from further analysis or discussion. The study will be of interest to computational and systems neuroscientists working on neural dynamics and network models of cognition.

eLife Assessment

Avoidance of UV and blue light by the nematode C. elegans is mediated by the unusual transmembrane protein LITE-1, a non-canonical photoreceptor. In this valuable work, the authors provide convincing evidence that LITE-1 function is also required for avoidance of very high concentrations of the food-associated cue diacetyl, suggesting that it may also function as a diacetyl chemoreceptor. While the evidence for this idea is incomplete, these intriguing findings suggest an unexpected complexity in the function of this unusual photoreceptor.

eLife Assessment

This study examines how the neuronal cytoskeleton contributes to the formation of the axonal membrane-associated periodic skeleton (MPS) in embryonic dorsal root ganglia (DRG) neurons, using STED imaging. Conclusions are supported by convincing methods, data, and analyses. This useful work confirms previous data and improves our understanding of the roles of microtubules and actin dynamics in the chronological recruitment of MPS components.