Evaluated articles

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 results do show a reduction in hair cells in the lateral line neuromasts of Hsd17b7 mutant fish, the reduction was limited. The findings are considered incomplete, with additional experiments required to confirm the conclusions.

eLife Assessment

This manuscript reports on the application of ribosome profiling (EZRA-seq and eRF1-seq) combined with massively parallel reporter assays to identify and characterize a GA-rich element associated with ribosome pausing during translation termination. While the development of eRF1-seq is useful and the identification of GA-rich elements upstream of stop codons is convincing, the level of support for other claims is inadequate. Specifically, the evidence that GA-rich sequences upstream of stop codons can base-pair with the 3′ end of 18S rRNA to prolong ribosome dwell time, and the evidence that Rps26 interferes with this interaction to regulate translation termination, are not adequate.

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 in 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. Some of the presented aspects would benefit from additional clarification.

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 valuable study reports that EEG recordings of the earliest stage of information processing in the human visual cortex can be used to predict subsequent choice responses. The findings provide novel, solid evidence for integrative processing in low-level sensory cortices, though the exact nature of the neural signals measured here requires some clarification. While some conceptual issues need to be addressed, 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 shows that excitatory cholecystokinin (CCK)-expressing neurons in hippocampal area CA3 influence hippocampal-dependent memory using multiple methods to manipulate excitatory CCK-expressing CA3 neurons selectively. The work is valuable because 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; however, if additional evidence were to be presented that the methods were selective, the evaluation would potentially be higher.

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.

eLife Assessment

This important work characterizes layers of neuropeptidergic modulations that collectively regulate the intake of sugar in a hunger state-dependent manner. Combinations of genetic, physiological, and behavioral approaches present convincing evidence that neurons that release Hugin and Allatostatin A are in an active state in sated flies, leading to suppression of sugar feeding behavior by reducing the sensitivity of sugar-sensitive gustatory neurons that express Gr5a. They also demonstrate that neurons that release Neuromedin U, a vertebrate homolog of Hugin, have common physiological properties as the fly Hugin neurons, revealing a similar function of evolutionarily conserved peptides across animal phyla.

eLife Assessment

This study investigates how people adapt their speech when auditory feedback is altered. The analyses are rigorous and the work makes a valuable contribution by extending methods from limb motor control to speech. However, because the paradigm does not directly measure sensory error, the evidence for the proposed mechanism of sensorimotor learning is incomplete. The findings are best viewed as evidence for how prior motor adjustments influence subsequent behaviour, highlighting the need for future studies to more precisely separate sensory and motor contributions to adaptation.

eLife Assessment

This study extends prior work on head bristle mechanosensation by delivering a synaptic-resolution map of second-order partners that preserves somatotopy and highlights a cholinergic pathway linking sensory input to grooming circuits, providing a valuable resource for the field. The reconstructions and quantitative connectivity analyses provide solid support the main anatomical claims, while causal sufficiency for the behavioral sequence remains inferential and could be strengthened by a simple rank-order test relating wiring to the known grooming hierarchy.

eLife Assessment

This timely and fundamental study introduces a human iPSC-based co-culture system that models Kupffer cell-hepatocyte interactions and aims to recapitulate liver-specific immune-parenchymal dynamics. Direct contact between iMacs and iHeps promotes mutual tissue-specific maturation, with iHeps downregulating fetal genes while iMacs acquire a Kupffer cell-like profile. This convincing in vitro model holds significant promise and is a leap forward; future experimental understanding will enhance its translational impact.

eLife Assessment

The results in this study are useful because they begin to establish a causal link between physical activity and the cellular mechanisms of regeneration. The evidence presented is largely solid, supporting the conclusion that exercise-induced changes in the extracellular matrix disrupt regeneration; however, some claims are incomplete, requiring additional controls and a clearer distinction between the effects of mechanical loading and mechanical injury to the blastema. The work will be of interest to researchers in regenerative medicine.

eLife Assessment

This study is useful because it challenges the widely accepted notion that muscle stem cell numbers decline with aging, providing novel insights into population heterogeneity and the identification of new surface markers for geriatric MuSCs. However, the evidence is considered incomplete due to insufficient quantitative comparisons of absolute cell numbers, limited analysis of age groups (particularly the lack of "aged" mice as opposed to geriatric), and the need for further functional and mechanistic validation of key subpopulations. Additional concerns that require clarification include the lack of statistical rigor in some experiments, the presentation of supporting data not being complete, and the overextension of claims relating to senescence and new marker validation. Overall, while the findings advance understanding of MuSC aging, the conclusions drawn by the authors should be strengthened with expanded experiments and more rigorous data analysis.

eLife Assessment

This study provides valuable insights into the role of the NF-kB and IKK signaling pathways in γδ T cell development and survival, using robust genetic mouse models. While the research is methodologically sound, some conclusions require further evidence, with incomplete analyses, particularly regarding cell-intrinsic effects and mechanistic details. Overall, the findings are significant for immunologists interested in innate-like T cell biology and advancing the understanding of γδ T cell differentiation and maintenance.

eLife Assessment

This study provides a valuable insight into how the medial and lateral entorhinal cortices interact through distinct excitatory and inhibitory pathways. Using anatomical tracing, optogenetics, and electrophysiology, the authors show that glutamatergic medial entorhinal neurons provide broad excitatory input to lateral entorhinal, while long-range SST+ interneurons deliver selective inhibition to layer I. These findings reveal a novel layer- and cell-type-specific organization of medial to lateral entorhinal connectivity with implications for spatial and episodic memory. The work is solid, but validation of injection specificity and viral spread is needed to fully confirm the anatomical interpretations; with these clarifications, this will be a significant contribution to understanding entorhinal-hippocampal circuit organization.

eLife Assessment

The use of DNA tethers is an important advance for studying how motor proteins respond to load. The authors use a convincing methodology to investigate the detachment and reattachment kinetics of kinesin-1, 2, and 3 motors against loads oriented parallel to the microtubule. As the manuscript stands, the conclusions drawn from the experiments, as well as the overall interpretation of the results, are incompletely supported by the presented data, and the novelty over previous reports appears less clear.

eLife Assessment

The mechanistic basis for the potential health benefits of NAD⁺ precursors remains incompletely understood. This manuscript provides a useful assessment of the role of SIRT1 in mediating the effects of NMN in mice fed a high-fat diet. The study addresses a key question, though some of the conclusions appear only partially supported by the presented data.