Evaluated articles

eLife Assessment

This study provides valuable information on the impact of Lamin A/C knockdown on gene expression using RNA-Seq analysis, as well as on telomere dynamics through live cell imaging. However, the conclusions remain inadequately supported by the current data, and several of the major technical concerns raised in the first round have not yet been fully resolved.

eLife Assessment

In this important study, the authors conducted atomistic molecular dynamics simulations to probe the interactions between IRE and unfolded peptides. The results help reconcile contradicting experimental findings in the literature and offer mechanistic insights into the activation of the unfolded protein response. The level of evidence is considered solid, although the use of enhanced sampling and more quantitative analysis would further strengthen the conclusions.

eLife Assessment

This study investigates whether heavy metal stress can induce maize-like phenotypic and molecular responses in teosinte and whether these responses overlap with genomic regions implicated in domestication. By combining copper and cadmium treatments with quantitative phenotyping, gene-expression analyses, and expanded assessments of nucleotide diversity across a key chromosome 5 interval, the authors provide an integrated view of how abiotic stress responses intersect with domestication-related traits. The significance of the findings is valuable, as the work offers meaningful insights for the subfield of maize evolution and stress biology by extending heavy-metal response analyses to teosinte and linking them to domestication-associated loci, although the evolutionary implications remain indirect. The strength of evidence is solid, with appropriately designed and quantitatively supported experiments that broadly support the claims, but do not yet establish a causal or historical role for heavy metal stress in domestication.

eLife Assessment

This study introduces a valuable new metric-phenological lag-to help partition the drivers of observed versus expected shifts in spring phenology under climate warming. The conceptual framework is clearly presented and supported by an extensive dataset, and the revisions have improved the manuscript, though some concerns-particularly regarding uncertainty quantification, spatial analysis, and modeling assumptions-remain only partially addressed. The strength of evidence is generally solid, but further analysis would help to validate the study's conclusions.

eLife Assessment

This is a potentially important study that explores the relevant range of parameter values for calibration and validation of cardiac electromechanics in ventricular models. Although much of the work presented is solid, the evidence provided to support the authors' key scientific claims is incomplete, especially as it relates to the emphasis on standardized validation and verification approaches. Notably, the level of model personalization presented in this work falls short of the threshold for what could reasonably be called a "digital twin", even by the relatively relaxed standards that have emerged in computational physiology and related fields in recent years.

eLife Assessment

Inspired by bee's visual behavior, the goal of the manuscript is to develop a model of visual scanning, visual processing and learning to recognize visual patterns. In this model, pre-training with natural images leads to the formation of spatiotemporal receptive fields that can support associative learning. Due to an incomplete test of the necessity and sufficiency of the features included in the model, it cannot be concluded that the model is either the "minimal circuit" or the most biologically plausible circuit of this system. With a more in-depth analysis, the work has the potential of being important and very valuable to both experimental and computational neurobiologists.

eLife Assessment

This study presents significant and novel insights into the roles of zinc in mammalian meiosis/fertilization events. These findings are useful to our understanding of these processes. The evidence presented is solid, with experiments being well-designed, carefully described, and interpreted with appropriate rigor. The authors acknowledge the lack of mechanistic insight which represents the main limitation of the study.

eLife Assessment

This valuable manuscript describes cryo-EM structures of archaeal proteasomes that reveal insights into how occupancy of binding pockets on the 20S proteasome regulates proteasome gating. The evidence supporting these claims is convincing, although the extrapolation of these findings to the more complex eukaryotic proteasome may prove challenging. This work will be of high interest to researchers interested in proteasome structure and regulation.

eLife Assessment

This fundamental work by Yamamoto and colleagues advances our understanding of how positional information is coordinated between axes during limb outgrowth and patterning. They provide convincing evidence that the dorsal-ventral axis feeds into anterior-posterior signaling, and identify the responsible molecules by combining transplantations with molecular manipulations. This work will be of broad interest to regeneration, tissue engineering, and evolutionary biologists.

eLife Assessment

This valuable study investigates how stochastic and deterministic factors are integrated during cellular decision-making, particularly in situations where cells differentiate into distinct fates despite being exposed to the same environmental conditions. The authors present convincing evidence that gene expression variability contributes to the robustness of cell fate decisions in D. discoideum, which sheds light into the role of stochasticity during cell differentiation.

eLife assessment

This valuable study examines the role of E2 ubiquitin enzyme, Uev1a in tissue resistance to oncogenic RasV12 in Drosophila melanogaster polyploid germline cells and human cancer cell lines. The incomplete evidence suggests that Uev1a works with the E3 ligase APC/C to degrade Cyclin A, and the strength of evidence could be increased by addressing the expression of CycA in the ovaries and the uev1a loss of function in human cancer cells. This work would be of interest to researchers in germline biology and cancer.

eLife Assessment

Using advanced CryoEM and mass spectrometry, the authors provide compelling evidence of how tubule formation occurs in an oxygen-dependent manner. These fundamental findings offer a novel mechanism by which rubrerythrin tubules encapsulate encapsulin to prevent oxidative stress in Pyrococcus furiosus. However, there are a few reasonable concerns about biochemical validations and the lack of adequate description of results and methodology.

eLife Assessment

This study provides new and interesting findings that SCoR2 acts as a denitrosylase to control cardioprotective metabolic reprogramming and prevent injury following ischemia/reperfusion. The compelling evidence is supported by a novel multi-omics approach, but questions remain regarding the stability and human relevance of BDH1 as well as the sufficiency of SCoR2. Overall, the work will be of interest to cardiovascular researchers and provides valuable information to the field, though some mechanistic aspects require further clarification.

eLife Assessment

This manuscript focuses on developing a structural model of how the multidomain ECM protein SVEP1 enables Angiopoietin (ANG) binding to the orphan receptor TIE1, resulting in downstream receptor phosphorylation and signaling. This is a potentially important study, however, it currently lacks key controls and is therefore incomplete. The data will be of interest to scientists working in vascular biology and RTK signaling.

eLife Assessment

This fundamental study advances our understanding of population-level immune responses to influenza in both children and adults. The strength of the evidence supporting the conclusions is compelling, with high-throughput profiling assays and mathematical modeling. The work will be of interest to immunologists, virologists, vaccine developers, and those working on mathematical modeling of infectious diseases.

eLife Assessment

This study presents a useful finding on the effects of arginine vasopressin (AVP) on islet cells in pancreatic tissue slices, using technically sophisticated spatio-temporal calcium recordings to confirm that AVP influences α and β cells differently depending on glucose concentrations. While the study’s methods – particularly the calcium imaging techniques and peptide ligand design targeting V1b receptors – are strong, the reviewers were concerned about several aspects of the experimental design. The results on β-cell responses are incomplete and insufficient to support the manuscript’s claims, especially due to the high variability of islet responses and lack of mechanistic and functional (hormone release) data. There are also concerns about the possibility of off-target effects and suboptimal receptor specificity: the study would be significantly strengthened by inclusion of signaling pathway interrogation, hormone output assays, genetic validation (e.g., β cell-specific deletion of V1br), and receptor localization. The work will still be of interest to researchers studying islet physiology in the context of health and diabetes.

eLife Assessment

By performing a chemical screen of an FDA-approved library of small molecules against a leucine-dependent Mtb strain, this work discovered that semapimod inhibits Mtb growth by impairing leucine import. The work is useful because it connects leucine uptake with the cell wall lipids in Mtb; however, it remains incomplete as the evidence supporting semapimod's ability to target leucine uptake needs more substantial proof. The work requires significant experimental evidence to identify leucine transporter(s) and determine how PDIM participates in leucine uptake.

eLife Assessment

This study presents an alternative to conventional and UV-based tetramers, which are easy to use and reliable for the identification of antigen-specific CD8 T cells. The authors demonstrate that tetramers for HLA alleles A0301, A1101, B0702, and C0702 can be subjected to specific temperatures that facilitate peptide exchange, whilst maintaining structural integrity. Whilst the strength of the evidence is currently incomplete, further development and validation of this approach is likely to provide a useful alternative to generating reagents for examining T cell specificities.

eLife Assessment

This useful study shows a protective role of type 1 IFN during Mycobacterium tuberculosis infection. It shows that the type 1 IFN response in human skin TST inversely correlates with TB severity, suggesting its protective role. Considering that type I IFN is usually shown to be pro-pathogenic, the higher vulnerability of zebrafish larvae lacking stat2 to M marinum infection is a strong result. However, the conclusion that IFN-I is protective during mycobacterial infection remains indirect and incomplete; the study requires additional mechanistic insights and validation.

eLife Assessment

Engineering of adeno-associated virus (AAV) replication proteins may provide new insights into Parvoviral replication. The authors created a useful collection of Rep protein variants with changes that alter the amino acid sequence, but these did not lead to clear improvements in how the virus worked. Instead, their screen showed that changes that do not alter the protein ("synonymous" mutations) and changes to the promoter were more common. As it stands the results are incomplete due to potential issues with the screening design. We encourage a more complete characterization, which may enhance the translational potential of the approach.