Evaluated articles

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

The authors use solid high resolution microscopy techniques to present a model in which SARS-CoV-2 attachment and endocytosis are mediated by heparan sulfate, whereas ACE2 only functions downstream of these early processes. These findings serve as a potentially valuable starting point to examine SARS-CoV-2 entry models that challenge current paradigms. However, examination of the model in a clean heparan sulfate deficient background and in the context of TMPRSS2-dependent plasma membrane fusion are lacking. Thus, the broader impact remains uncertain in the absence of additional controls and orthogonal approaches.

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

This important study measures the development of hearing in the zebra finch and shows that two-day-old hatchlings have no detectable electrophysiological response to 95 dB SPL clicks. Because this stimulus carries energy across a broad range of sound frequencies and is some 60 dB louder than faint, high-pitched parental calls, the findings challenge prior proposals that such calls serve as a channel for heat-dependent prenatal developmental programming. Two reviewers found the evidence on the absence of auditory responses convincing, supported by auditory brainstem recordings using validated methods with appropriate controls and by a separate laser vibrometry experiment ruling out detection through egg vibration. A third reviewer disputed these findings and questioned whether absent physiological markers of hearing definitively establish deafness. On the evidence presented, embryonic hearing is unlikely to mediate the developmental effects reported for heat whistle playback. Whether those effects reflect some other pathway or require re-interrogation of the behavioral phenomenon is now the open question, alongside a need for auditory measurements more sensitive than the auditory brainstem response.

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 delineates layered glucose-responsive neuropeptidergic mechanisms that regulate sugar intake. Using a combination of genetic, physiological, and behavioral experiments, the authors convincingly show that Hugin- and Allatostatin A-releasing neurons suppress sugar feeding by reducing the sensitivity of Gr5a-expressing gustatory neurons. They further demonstrate that Neuromedin U neurons share key physiological properties with fly Hugin neurons, highlighting conserved peptide functions 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 important study provides a comprehensive map of how touch-sensitive neurons in the fly head connect to downstream circuits, revealing parallel pathways that preserve spatial organization and identifying a developmentally defined circuit linking sensory input to grooming behavior. The evidence is convincing, with detailed anatomical reconstruction and quantitative analysis supporting the main claims, while the link to behaviour remains based on prior functional work. The study will be of interest to neuroscientists studying sensory processing and motor control, and provides an invaluable resource for future functional investigations.

eLife Assessment

This timely and fundamental study presents an innovative iPSC based co-culture system to model Kupffer cell-hepatocyte interactions and hepatotoxicity, demonstrating reciprocal acquisition of tissue identity and enhanced hepatocyte maturation. The work is convincing, supported by well-executed methodology and functional validation, including physiologically relevant, concentration-dependent hepatotoxic responses. The research approach is promising and of broad interest, further clarification of experimental design and interpretation may strengthen its 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 provides valuable insights into aged muscle stem cell biology by revealing phenotypic and functional heterogeneity within the geriatric MuSC pool and proposing a VCam-low/negative subpopulation that may account for the reported decline in MuSC numbers with age. These findings have implications for understanding aging-related changes in stem cell maintenance and for improving strategies to isolate or rejuvenate aged MuSCs. However, the evidence supporting the main claims is incomplete, key analyses such as absolute MuSC quantification, fate assessment of VCam-low/negative cells, inclusion of standard aged cohorts, and validation of proposed surface markers are still needed to confirm that overall MuSC abundance is maintained and that a distinct subpopulation has been identified.

eLife Assessment

This study reports important findings regarding the role of the NF-kB signaling pathway in the development and long-term survival of gamma delta T cells. The authors report disparate roles of IKK-dependent NF-kB activation in the development and long-term survival of gamma delta T cell subsets. The approach and methodology employed is convincing. This work will be of great interest to immunologists interested in innate-like T cell biology and in T cell development.

eLife Assessment

This study provides an important 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 evidence for the paper's overall conclusions is convincing.

eLife Assessment

The authors use convincing methodology to investigate the detachment and reattachment kinetics of kinesin-1, 2 and 3 motors against loads oriented parallel to the microtubule. The conclusions drawn from the valuable experiments as well as the overall interpretation of the results are fully supported by the presented data.

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.

eLife Assessment

This work identifies a novel, conserved link between glycolysis and sulfur metabolism that governs fungal morphogenesis and virulence. The compelling evidence, integrating multiple approaches, provides an important conceptual advance. A future mechanistic dissection of how sulfur metabolites interface with known pathways is encouraged.