Evaluated articles

eLife Assessment

This important study presents a technically rigorous and carefully controlled analysis of the signalling potential of cancer-associated gain-of-function Notch alleles. The work is clearly presented, and the experiments are robust, comprehensive, and well-controlled. While some data primarily establish the system or report negative findings, the comparative approach in a well-characterized model provides convincing mechanistic evidence for how these Notch variants function. This study will be of interest to researchers in both developmental and cancer biology.

eLife Assessment

This important study reports the development of the first tankyrase degrader and demonstrates its enhanced ability to inhibit β-catenin signaling compared to conventional tankyrase inhibitors. The evidence supporting the conclusions is comprehensive and convincing, based on rigorous biochemical and cellular analyses. The findings will be of broad interest to researchers studying Wnt signaling, protein degradation, and cancer biology.

eLife Assessment

This important study provides a theoretical framework for quantifying privacy risk from publicly shared genome-wide association summary statistics. The findings reveal the conditions under which genotype reconstruction may become feasible, challenging long-held assumptions about personal data safety. While the evidence is solid, supported by clear mathematical derivations and simulations, validation on large empirical datasets would further strengthen the claims.

eLife Assessment

This important study provides a theoretical framework for quantifying privacy risk from publicly shared genome-wide association summary statistics. The findings reveal the conditions under which genotype reconstruction may become feasible, challenging long-held assumptions about personal data safety. While the evidence is solid, supported by clear mathematical derivations and simulations, validation on large empirical datasets would further strengthen the claims.

eLife Assessment

The revised manuscript by Shukla et al. provides important mechanistic insights into kinesin-1 autoinhibition and cargo-mediated activation. Through a convincing integration of protein engineering, computational modeling, biophysical assays, HDX-MS, and electron microscopy, the study delineates how cargo binding induces an allosteric transition that propagates along the coiled-coil stalk to the motor domains, enhancing MAP7 engagement. The revisions substantially improve clarity, figure annotation, and methodological transparency, leaving the remaining limitations, primarily those inherent to conformational heterogeneity and resolution, appropriately acknowledged. Overall, the updated manuscript presents a coherent mechanism for kinesin-1 activation that will be of broad interest to the motor protein, structural biology, and cell biology communities.

eLife Assessment

Mitochondrial DNA (mtDNA) exhibits a degree of resistance to mutagenesis under genotoxic stress, and this study on the mitochondrial Transcription Factor A (TFAM) presents important data concerning the possible mechanisms involved. The presented data are solid, technically rigorous, and consistent with established literature findings. The experiments are well-executed, providing convincing evidence on the change of TFAM-DNA interactions following UVC irradiation.

eLife Assessment

This important study presents a compelling link between nutrient signaling and chromosome regulation, demonstrating that reduced activity in a central nutrient-sensing pathway improves chromosome stability and alters gene expression through effects on cohesin. The convincing evidence from a combination of genetic, biochemical and cell biological approaches supports a model in which TORC1-dependent phosphorylation of Mis4 and the cohesin subunit Psm1/Smc1 can modulate cohesin loading to enhance faithful chromosome transmission. While the underlying mechanisms and biological importance of this newly described circuit are not yet fully known, the overall body of evidence is strong and supports the main conclusions.

eLife Assessment

This study investigates the folding and unfolding behavior of the doubly knotted protein TrmD-Tm1570, providing insight into the molecular mechanisms underlying protein knotting. The findings reveal multiple unfolding pathways and suggest that the formation of double knots may require chaperone assistance, offering valuable insights into topologically complex proteins. The evidence is convincing, supported by consistent agreement between simulation and experiment, though some aspects of the presentation and experimental scope could be clarified or expanded.

eLife Assessment

This valuable work provides new insights into the role of lysine acetylation of alpha-synuclein, the protein involved in Parkinson's Disease. The evidence is mostly solid, but the claims around the potential disease relevance based on seeding assays and structural work need to be toned down, or else supported by additional experimental evidence. Overall, the work will be of interest to researchers in the fields of protein biophysics and post-translational modifications, as well as Parkinson's Disease.

eLife Assessment

Davis and colleagues describe findings that are fundamental to the understanding of pressure mechanosensation in lymphatic vessels and are of significant importance to other areas of mechanosensory physiology. Based on many different knockout mouse models and rigorous state-of-the-art pressure myography recordings, they present compelling evidence that mechano-activation of GNAQ/GNA11-coupled GPCRs generates IP3, which induces Ca2+ release from internal stores through IP3R1 and drives depolarization through the activation of ANO1 Cl- channels to induce lymphatic vessel contractility. Nevertheless, some aspects of the manuscript are incomplete. The specific identity of the GPCR(s) involved remains to be uncovered, as evidence of frequency-pressure impairment is only demonstrated with abolition of GNAQ/GNA11action, not the receptors per se.

eLife Assessment

This study provides valuable data on the role of Hsd17b7, a gene involved in cholesterol biosynthesis, as a potential regulator of mechanosensory hair cell function. The authors used both zebrafish and the HEI cell line to examine the effects of deletion of Hsd17b7 on hair cell function and survival. While the study presents convincing evidence, the effect sizes observed across several experiments, including functional readouts such as the acoustic startle response, are modest, which raises questions about the biological significance of the proposed mechanism.

eLife Assessment

This manuscript reports on the application of ribosome profiling (EZRA-seq and eRF1-seq) and massively parallel reporter assays (MPRA) to identify and characterize sequence elements that regulate translation termination. The authors conclude that a GA-rich element upstream of stop codons is associated with ribosome pausing during translation termination; in contrast, C-rich sequences upstream of stop codons abolish termination pausing. While the overall findings of this study are useful and the identification of GA-rich elements upstream of stop codons is compelling, support for several other claims remains incomplete. Specifically, the evidence that the MPRA results mirror the ribosome profiling, that a C-rich sequence preceding the stop codon promotes termination slippage in cellular mRNAs, and that Rps26 interferes with mRNA interactions to regulate translation termination would benefit from further support.

eLife Assessment

This manuscript provides evidence that mouse germline cysts develop an asymmetric Golgi, ER, and microtubule-associated structure that resembles the fusome in Drosophila germline cysts. This fundamental study provides new evidence that fusome-like structures exist in germ cell cysts across species. Overall, the data are convincing and represent a significant advance in our understanding of germ cell biology.

eLife Assessment

The authors combine experiments and mathematical modeling to determine how the infectivity of human cytomegalovirus scales with the viral concentration in the inoculum, i.e., considering the multiplicity of infection (MOI). They propose and test different model assumptions to explain a mechanism termed "apparent cooperativity" of virions based on an observed super-linear increase of the number of infected cells with increasing inocula. The authors present a solid study showing valuable findings for virologists and quantitative scientists working on the analysis and interpretation of viral infection dynamics for which quantitative knowledge of MOI is needed.

eLife Assessment

This study presents a role for heparin sulfate in SARS-CoV-2 entry that runs counter to prevailing data in the field. If the conclusions were firmly supported by the data, the work would be a significant contribution to the field. While the use of diverse cellular models, virological tools, and robust microscopy approaches constitutes a useful data set, the proposed model remains incomplete and requires clarification of entry mechanisms, host factors, and viral variant-specific fusion pathways to substantiate it against established entry models.

eLife Assessment

The authors investigated the epigenetic mechanisms regulating the differentiation of circulating monocytes that infiltrate the CNS and adopt microglia-like characteristics. The work is useful to the field, as the contribution of circulating myeloid cell-derived microglia remains controversial. However, the evidence presented is inadequate as the analyses are based on a very limited set of genes, which does not sufficiently support the authors' central claims.

eLife Assessment

This important study reports that EEG recordings of the earliest stage of information processing in human visual cortex can be used to predict subsequent choice responses. The findings provide novel, convincing evidence for integrative processing in low-level sensory cortices at the level of scalp-recorded potentials, with the exact nature of the neural signals at the single cell level to be determined. The paper is likely to be of interest to neuroscientists interested in the contribution of early sensory signals to decision making.

eLife Assessment

This study presents data suggesting that excitatory cholecystokinin (CCK)-expressing neurons in hippocampal area CA3 influence hippocampal-dependent memory using multiple methods to manipulate excitatory CCK-expressing CA3 neurons. The study is valuable, particularly considering that most past studies of CCK-expressing neurons have focused on those neurons that co-express CCK and GABA. Currently, the strength of evidence is incomplete, but it would improve if evidence of specificity was provided and other concerns were addressed. If this is not possible, the conclusions, particularly those requiring evidence of specific targeting of excitatory neurons, should be modified accordingly.

eLife Assessment

Zebra finches are a prominent model system for vocal learning and auditory system function, yet little is known about the functional development of the auditory system. Here, the authors convincingly show that newly hatched zebra finches lack detectable auditory brainstem responses and that auditory neural signals emerge only days after hatching, challenging influential claims of prenatal acoustic communication in altricial birds. This important work clarifies the developmental timeline for auditory communication and highlights the value of neuroscientific methods for validating and complementing behavioral ecological studies of animal perception.

eLife Assessment

This study integrates large-scale behavioral, genetic, and molecular analyses in animal models to investigate morphine response. Utilizing high-quality, time-series Quantitative Trait Loci (QTL) mapping, the work provides compelling evidential support for novel, time-dependent genetic interactions (epistasis). A fundamental result of this rigorous analysis is the discovery of a novel Oprm1-Fgf12-MAPK signaling pathway, which offers new insights into the mechanisms of opioid sensitivity.