Evaluated articles

eLife Assessment

This observational study from the UK Biobank provides an important investigation into the associations between menopausal hormone therapy and brain health in a large, population-based cohort of females in the UK. A convincing model of brain aging using an open source algorithm is used. While some modest adverse brain health characteristics were associated with current mHT use and older age at last use, the findings do not support a general neuroprotective effect of mHT nor severe adverse effects on the female brain. This work addresses a topic that is of grave importance since menopausal hormone therapy and its effect on the brain should be better understood in order to provide individualized effective medical support to women going through menopause.

eLife Assessment

The landmark significance of this manuscript is based on the mechanistic description of purine metabolism by Lactobacillus plantarum, which helps to alleviate hyperuricemia, which is a phenotype that underlies multiple disease symptoms. The evidence provided for L. plantarum's involvement in reducing hyperuricemia was exceptional, combining microbiomics, whole genomics, in vitro bacterial culture, gene knock-outs, and metabolomics. Collectively, the study shows a clear link between the gut microbiota and hyperuricemia, providing a pathway for modification to help alleviate this condition.

eLife Assessment

This study offers valuable information on how titin derived from different nuclei within the syncytium is organized and integrated during skeletal muscle development and remodeling. The authors developed a novel mCherry titin knock-in mice with the fluorophore mCherry inserted into titin's Z-disk region to track the titin during cell fusion. The approach using mcherry adds to understanding of the role and localization of titin in controlling stiffness of striated muscles and fine tuning contraction. The results demonstrate that the integration of titin into the sarcomere is tightly regulated, with its unexpected mobility aiding in the uniform distribution of titin post-cell fusion. Although the experimental approach is convincing, the work is very qualitative in its approaches, and the data needs rigorous statistical analysis. There is a need for some clarification concerning numbers of animals and control groups. Future studies will need more rigorous data analysis and interpretation.

eLife Assessment

This is a valuable study regarding the role of gasdesmin D in experimental psoriasis. The study contains solid evidence for such a role, involving neutrophils, from murine models of skin inflammation, as well as correlative data of elevated gasdermin D expression in human psoriatic skin. The findings will be of interest to researchers trying to unravel pathways of skin inflammation.

eLife Assessment

This study presents a valuable conceptual approach that cell lineage can be determined using methylation data. However, the evidence supporting the claims of the author remains incomplete after revision. If clarified further as described in the reviews, this approach could be of broad interest to neuroscientists and developmental biologists.

eLife Assessment

This manuscript provides fundamental new insight into the mechanisms linking photoperiod, reproduction function, and feeding activity, using medaka, a genetic model that itself exhibits photoperiodic responses. As well as identifying key neuropeptide genes that are regulated by photoperiod and involved in regulating feeding activity, the authors establish a knockout line for agrp1 using CRISPR Cas9 - based approach, profiting from the extensive use and development on this methodology in medaka. The combination of the RNAseq and quantitative in situ hybridization analysis with the knockout results as well as the study of ovariectomized fish provides compelling evidence implicating agrp1 in feeding regulation in response to photoperiod and reproductive status.

eLife Assessment

The paper presents a valuable theoretical treatment of the role of passage of time in optimal decision strategies in pursuit based tasks. The computational evidence and methodologies employed are novel, and the authors offer solid evidence for the majority of the claims.

eLife Assessment

This important study advances our understanding of maladaptive innate immune training. The experimental evidence supporting the conclusions is convincing and the expert reviewers strongly endorse the manuscript. The work will be of high interest to both researchers in the trained immunity field and clinician scientists.

eLife Assessment

This is a useful contribution to our understanding of taste perception. The idea that specific receptors function in the pharynx to mediate responses to carboxylic acids is interesting, although the expression analysis is incomplete. Reviewers also have a number of other suggestions for improvement, including the request that authors provide more details about the methodology used. In general, the claims are supported by solid evidence and add to a growing body of literature on this topic.

eLife Assessment

This is a useful revised manuscript that shows a set of data including the first cryo-EM structures of human PIEZO1 as well as structures of disease-related mutants in complex with the regulatory subunit MDFIC, which generate different inactivation phenotypes. The molecular basis of PIEZO channel inactivation is of great interest due to its association with several pathologies. This manuscript provides some structural insights that may help to ultimately build a molecular picture of PIEZO channel inactivation. While the structures are of use and clear conformational differences can be seen in the presence of the auxiliary subunit MDFIC, the strength of the evidence supporting the conclusions of the paper, especially the proposed role for pore lipids in inactivation, is incomplete.

eLife Assessment

This manuscript reports effects of a single dose of methamphetamine vs placebo on a probabilistic reversal learning task with different levels of noise, in a large group of young healthy volunteers. The paper is well written and the methods are rigorous. The findings are important and have theoretical or practical implications beyond a single a subfield. The strength of the evidence is convincing, with the methods, data, and analyses broadly supporting the claims in the paper, which are sufficiently qualified given the lack of a significant effect of the binary baseline performance variable, and the nonlinear effect of individual differences in baseline performance.

eLife Assessment

This valuable paper analyses the role of endogenous CNS hemoglobin in protecting mitochondrial homeostasis in hypoxic conditions. The work is solid and opens the doors to future work in this field. However, it leaves many questions open regarding CNS-specific ischemia/hypoxia that should be considered in future work. In particular, a whole-body hypoxia model may liberate exosomes from other hypoxic organs, which may contribute to the protective effect. Overall, this work has the potential to be of broad interest to the neuroscience and hypoxia communities.

eLife Assessment

This study presents a useful characterisation of the topographical organisation of the human pulvinar, an associative thalamic subregion crucial for visual perception and attention. The evidence supporting the conclusions is solid given the multimodal validation and replication across datasets, although even higher-resolution imaging data would have strengthened the study. In their revised manuscript, the authors elaborated further on the motivation for their study and conducted several robustness checks. Nevertheless, there remains an opportunity for a more fully integrated interpretation of the findings. The work would be of interest to neuroscientists, neurologists, and neuropsychiatrists working on pulvinar functioning in health and disease.

eLife Assessment

This important study uncovers a surprising link between two self-cleaving RNAs that belong to the same structural family. The evidence supporting the main conclusions is convincing and based on extensive biochemical and bioinformatic analysis. This research will be of broad interest to RNA molecular biologists and biochemists.

eLife Assessment

This important paper uses elegant models, including genetic knock outs, to demonstrate that FABP4 contributes to lipid accumulation in tumor-associated macrophages, which seems to increase breast cancer migration. While the work is of high interest, the strength of the evidence relating to some of the conclusions is incomplete and the paper would benefit from some refinement. The work will be of interest to those researchers trying to link metabolism, the immune system, and cancer.

eLife Assessment

This manuscript describes an important study of a new lipid-mediated regulation mechanism of adenylyl cyclases. The biochemical evidence provided is convincing and will trigger more research in this mechanism. This manuscript will be of interest to all scientists working on lipid regulation and adenylyl cyclases.

eLife Assessment

This important study reports the transcriptomic and proteomic landscapes of the oviducts at four different preimplantation stages during natural fertilization, pseudopregnancy, and superovulation. The supporting data are convincing. This work will be of interest to reproductive biologists and clinicians practicing reproductive medicine.

eLife Assessment

In this important study, the authors test the model that a type of vascular lesion caused by the inactivation of one gene in the cells that line blood vessels requires the activity of a second gene for the lesions to form. The evidence supporting the conclusions is solid.

eLife Assessment

In this important study, the authors used a zebrafish model and scRNAseq analysis to show that a subset of keratinocytes within melanoma microenvironment highly up-regulate Twist and undergo Epithelial-Mesenchymal Transition (EMT). Surprisingly, when overexpressing Twist in keratinocytes, the resulting alteration in keratinocytes is inhibitory for melanoma invasion in both zebrafish and human cell culture models. The results are supported by overall convincing experimental data that provide new insights into the interactions between melanoma cells and their environment.

eLife Assessment

Building on previous structural studies, this work provides valuable new insights into the architecture of the autophagy initiation complex, comprising ULK1, ATG13, and FIP200. The authors present their findings with solid supporting evidence, making this study a significant contribution to the autophagy field.