Evaluated articles

eLife Assessment

This revision of important work is a versatile addition to the chemical protein modifications and bioconjugation toolbox in synthetic biology. The technology developed cleverly uses Connectase to irreversibly fuse proteins of interest together so they can be studied in their native context, with compelling well-controlled data showing the technique works for various protein partners. This work will help multiple fields to explore multi-function constructs in basic synthetic biology. This work will also be of interest to those studying fusion oncoproteins commonly expressed in various human pathologies.

eLife Assessment

This valuable study provides quantitative data and analysis to reveal that variations in Dorsal (Dl ) nuclear dynamics along the Dorso-ventral axis in the early Drosophila embryo are governed by Dl-Cactus nuclear interactions. The solid evidence partially supports a mechanism where nuclear localized Cactus contributes to the fraction of Dl that binds to DNA, but additional work will be necessary to confirm the claims and the biological significance of these findings.

eLife Assessment

This study investigated mitochondrial dysfunction and the impairment of the ciliary Sonic Hedgehog signaling in Lowe syndrome (LS), a timely topic given the limited research in this area. The data obtained from patient-derived iPSC neurons and a mouse model are solid. Although the main claims of the study are only partially supported by the current evidence, it provides a useful starting point for future functional studies investigating the link between mitochondrial defects and primary cilia in neural development.

eLife Assessment

This valuable study proposes a theoretical model of clathrin coat formation based on membrane elasticity that seeks to determine whether this process occurs by increasing the area of a protein-coated patch with constant curvature, or by increasing the curvature of a protein-coated patch that forms in an initially flat conformation (so called constant curvature or constant area models). Identifying energetically favorable pathways and comparing the obtained shapes with experiments provides solid support to the constant-area pathway. This work will be of interest for biologists and biophysicists interested in membrane remodelling and endocytosis. It provides an innovative approach to tackle the question of constant curvature vs. constant area coat protein formation, although some of the model's assumption are only partially supported by experimental evidence.

eLife Assessment

The study presents a fundamental advance in antiviral RNA research by adapting SHAPE-Map to chart the secondary structure of the Porcine Epidemic Diarrhoea Virus (PEDV) genome in infected cells and pinpointing structurally conserved, accessible RNA elements as therapeutic targets. A broad, well-documented integration of biochemical probing, computational analysis, and functional validation provides convincing evidence that these regions are both biologically relevant and druggable. Beyond PEDV, the work offers a generalizable framework for RNA-guided antiviral discovery that will interest researchers in RNA therapeutics and viral genome biology.

eLife Assessment

This study investigates the neural basis of causal inference of illness, suggesting that it relies on semantic networks specific to living things in the absence of a generalized representation of causal inference across domains. The main hypothesis is compelling, and is supported by solid methods and data analysis. Overall, the findings make a valuable contribution to understanding the role of domain-specific semantic networks, particularly the precuneus, in implicit causal inference about illness.

eLife Assessment

This manuscript describes a fundamental investigation of the functioning of Cas9 and in particular on how variant xCas9 expands DNA targeting ability by an increase-flexibility mechanism. The authors provide compelling evidence to support their mechanistic models and the relevance of flexibility and entropy in recognition. This work can be of interest to a broad community of structural biophysicists, computational biologists, chemists, and biochemists.

eLife Assessment

This important study presents a meta-analysis confirming a statistically significant association between slow oscillation-spindle coupling and memory formation, although the reported effects are limited (~0.5% of variance). The evidence is overall convincing, but the statistical methods may be difficult to follow for readers unfamiliar with advanced techniques. This work will be of particular interest to neuroscientists studying the neural mechanisms of sleep and memory.

eLife Assessment

This important study introduces an experimental approach for studying Drosophila oviposition rhythms and identifies the subset of circadian clock neurons that mediate the circadian control of oviposition. The authors resolve an inherently noisy rhythm to provide convincing evidence by using statistical averaging techniques, which help reduce this noise but at the cost of variation across individual rhythms. This paper will be of interest to anyone interested in insect ovarian physiology, circadian biology, and reproductive fitness.

eLife Assessment

This useful work identifies a key role for Tachykinin-1 parasubthalamic neurons in avoidance learning. At present, the evidence for the conclusions regarding fiber photometry, viral transfection, reporting of behavioral outcomes, and pathway-specificity is incomplete. This work will be of interest to neuroscientists studying neural mechanisms for avoidance and aversion.

eLife Assessment

This important study demonstrates the ability for high-throughput recording and categorization of unconstrained and stimulus-based behaviors across a very large population of marmosets (n = 120 animals across 36 family units). The authors implement an analytical approach to identify "outlier" behavior that could be key in the development of next-generation precision psychiatry. While the strength of evidence appears solid overall, many key methodological details are incomplete.

eLife Assessment

The findings in this paper provide solid support for a hypothesis that has valuable implications at the intersection of value-based and social decision-making. The findings suggest that the brain processes rewards received for effort differently when they are earned for themselves versus someone else.

eLife Assessment

This important study reports solid evidence for the significant role of mother-child neural synchronization and relationship quality in the development of Theory of Mind (ToM) and social cognition. The findings effectively bridge brain development with children's behavior and parenting practices, and will be of interest to researchers studying brain development and social cognition, as well as the general public.

eLife Assessment

This important study is of relevance for the fields of predictive processing, perception and learning, with a well-designed paradigm allowing the authors to avoid several common confounds in investigating predictions, such as adaptation. Using a state-of-the-art multivariate EEG approach, the authors test the opposing process theory and find evidence in support of it. Overall, the empirical evidence is solid, however, some conclusions rest on limited evidence and need further work to reconcile the present results with previous studies.

eLife Assessment

NeuroSC is an accessible and interactive tool for streamlined observation of neuronal morphology, membrane contact, and synaptic connectivity across developmental stages in the nematode C. elegans. This important tool relies on solid electron microscopy datasets. This resource will be of high interest to C. elegans researchers interested in nervous system wiring and circuit function.

eLife Assessment

This study presents important findings on the activity of two compounds, BKC and IBC, isolated from Psoralea corylifolia, which act synergistically to inhibit cancer cell proliferation. Using a spectrum of methods, the authors characterized the mechanisms of action of both drugs, providing convincing evidence that BKC targets DNA polymerases and IBC selectively inhibits CHK2. The study opens the possibility of improving the effectiveness of the combination of BKC and other damaging agents with IBC in cancer treatment.

[Editors' note: this paper was reviewed by Review Commons.]

eLife Assessment

This paper presents the fundamental discovery that lipid metabolic imbalance induced by Snail, an EMT-related transcription factor, contributes to the acquisition of chemoresistance in cancer cells. The evidence, supported by a wide range of methods and adequate quantification, provides a convincing mechanistic explanation of how Snail drives ectopic expression of the cholesterol- and drug-efflux transporter ABCA1. This work, which introduces a novel therapeutic concept targeting invasive cancer, will be of broad interest to researchers in cancer biology, lipid metabolism, and cell biology.

eLife Assessment

The authors use deep mutational scanning to assess the effect of ~6,600 protein-coding variants in MC4R, a G protein coupled receptor associated with obesity. They develop new, more precise approaches to deep mutational scanning, enabling them to probe molecular phenotypes directly relevant to the development of drugs that target this receptor. In this important work, the authors provide compelling evidence that variants impact signaling through MC4R in different ways, that some defective variants are amenable to a corrector drug and that deep mutational scanning data could guide compound optimization.