Evaluated articles

eLife Assessment

Gating of mechanosensitive channels has been explained by the force-from-lipids model in which mechanical coupling of the channel protein to the plasma membrane transfers force from membrane tension to open the channel. In this important manuscript, the authors provide evidence for this mechanism in two different mechanically gated channels. The experiments were carried out in the same membranes, but the evidence is incomplete without a clear explanation of the relationship between measured mechanical parameters and membrane interfacial tension.

eLife Assessment

This is a valuable study that presents convincing evidence on the genesis of the CPSF6 condensates that form upon HIV-1 infection and the specific molecular determinants involved in their formation, as well as their interactions with SRRM. The study could be strengthened by assessing the relevance of their findings to infection, and in particular, with reverse transcription and gene expression

eLife Assessment

This valuable descriptive manuscript builds on prior research showing that the elimination of Origin Recognition Complex (ORC) subunits does not halt DNA replication. The authors obtain solid data using various methods to genetically remove one or two ORC subunits from specific tissues and still observe replication. The replication appears to be primarily endoreduplication, indicating that ORC-independent replication may promote genome reduplication without mitosis. The mechanism behind this ORC-independent replication remains to be elucidated. The study and mutants described herein lay the groundwork for future research to explore how cells compensate for the absence of ORC and to develop functional approaches to investigate this process. The reviewers suggested the observations could be supported by additional experiments. This work will be of interest to those studying genome duplication and replication.

eLife Assessment

This fundamental work demonstrates that compartmentalized cellular metabolism is a dominant input into cell size control in a variety of mammalian cell types and in Drosophila. The authors show that increased pyruvate import into the mitochondria in liver-like cells and in primary hepatocytes drives gluconeogenesis but reduces cellular amino acid production, suppressing protein synthesis. The evidence supporting the conclusions is compelling, with a variety of genetic and pharmacologic assays rigorously testing each step of the proposed mechanism. This work will be of interest to cell biologists, physiologists, and researchers interested in cell metabolism, and is significant because stem cells and many cancers exhibit metabolic rewiring of pyruvate metabolism.

eLife Assessment

This manuscript provides potentially important findings examining in 2D and 3D models in MYC liver cancer cells changes in DNA repair genes and programs in response to hypoxia. The authors use convincing methodology in most cases, but there is some concern that the analysis is incomplete.

eLife Assessment

This fundamental study identified a novel role of NOLC1 in regulating p53 nuclear transcriptional activity and p53-mediated ferroptosis in gastric cancer. After major revisions, the evidence supporting the conclusions is solid. However, some new experiments are needed to draw more robust conclusions regarding the ferroptosis-associated studies.

eLife Assessment

This work is of fundamental significance and has an exceptional level of evidence for the role of a mutant p53 in regulation of tumorigenesis using an in vivo mouse model. The study is well-conducted and will be of interest to a broad audience including those interested in p53, transcription factors and cancer biology.

eLife Assessment

This study presents useful findings on the application of HPV cfDNA as a marker for monitoring treatment response and prognosis in patients with recurrent or metastatic cervical cancer. The evidence supporting the claims of the authors is solid, although inclusion of a larger number of patient samples would have strengthened the study. The work will be of interest to medics and biologists working on cervical cancer.

eLife Assessment

This important work advances our understanding of how the SARS-CoV-2 Nsp16 protein is regulated by host E3 ligases to promote viral mRNA capping. Support for the overall claims in the revised manuscript is convincing . This work will be of interest to those working in host-viral interactions and the role of the ubiquitin-proteasome system in viral replication.

eLife Assessment

This important work examines how microexons contribute to brain activity, structure, and behavior. The authors find that loss of microexon sequences generally has subtle impacts on these metrics in larval zebrafish, with few exceptions. The evidence is convincing, using modern high-throughput phenotyping methodology in zebrafish. Overall, this work will be of interest to neuroscientists and generate further studies of interest to the field.

eLife Assessment

This work details the finding that in at least one of the subunits of the heterohexameric chaperone complex Pfdn5 has additional functions beyond its contribution to cytoskeletal protein folding in Drosophila. The authors provide convincing evidence that it is a hitherto unknown microtubule associated protein in addition to regulating microtubule organization and levels of tubulin monomers. The important findings show that Pfdn5 loss exaggerates pathological manifestations of mutant human Tau bearing FTDP-17 linked mutations in Drosophila, while its overexpression suppresses them, suggesting that the latter may constitute a future therapeutic approach.

eLife Assessment

This important work examines how microexons contribute to brain activity, structure, and behavior. The authors find that loss of microexon sequences generally has subtle impacts on these metrics in larval zebrafish, with few exceptions. The evidence is solid, using modern high-throughput phenotyping methodology in zebrafish. Overall, this work will be of interest to neuroscientists and generate further studies of interest to the field.

eLife Assessment

This valuable study explores the role of spatial genome organization in oncogenic transformation, addressing an ambitious and significant topic. The authors have assembled comprehensive datasets from various subtypes of localized and lung-metastatic breast cancer cells, as well as from healthy and cancerous lung cells. They identified switching patterns in the 3D genome organization of lung-metastatic breast cancer cells, revealing a reconfiguration of genome architecture that resembles that of lung cells. This provides solid evidence with significant biomedical implications for epigenetic regulation in both normal physiology and disease.

eLife Assessment

This study reports important findings about the nature of feedback to primary visual cortex (V1) during object recognition. The state-of-the-art functional MRI evidence for the main claims is solid, and the combination of high-resolution fMRI with MEG yields significant insight into neural mechanisms. The findings presented here are relevant to a number of scientific fields such as object recognition, categorisation and predictive coding.

eLife Assessment

This study presents the state-dependent role of serotonin for the protein and sugar intake of Drosophila by expressing a dominant-negative serotonin transporter in subsets of serotoninergic neurons. This paper is valuable for neuroscientists working on neuromodulation and the effects of internal states such as hunger, however the characterization of behavioral and neuroanatomical data is incomplete.

eLife Assessment

This valuable study relating brain anatomy to reading ability in children studied longitudinally finds that a difference in sulcal anatomy is more predictive of reading ability than cognitive measures. The evidence that this anatomical difference is predictive and confers some benefit in the connectivity between brain areas is based on careful analyses and is solid. The findings would be of interest to researchers studying brain and cognitive development.

eLife Assessment

This paper provides a valuable contribution to our understanding of how adenosine acts as a signal of nutrient insufficiency and extends this idea to suggest that adenosine is released by metabolically active cells in proportion to the activity of methylation events. Convincing data supports this idea. The authors use metabolic tracing approaches to identify the biochemical pathways that contribute to the regulation of adenosine levels and the S-adenosylmethionine cycle in Drosophila larval hemocytes in response to wasp egg infection.

eLife Assessment

This fundamental study investigates the role of polyunsaturated fatty acids (PUFAs) in physiology and membrane biology, using a unique model to perform a thorough genetic screen that demonstrates that PUFA synthesis defects cannot be compensated for by mutations in other pathways. These findings are supported by compelling evidence from a high quality genetic screen, functional validation of their hits, and lipid analyses. This study will appeal to researchers in membrane biology, lipid metabolism, and C. elegans genetics.

eLife Assessment

This study explores how heterozygosity for specific neurodevelopmental disorder-associated TRIO variants affects brain function in mice. The authors conducted thorough analyses on mouse lines harboring TRIO-variants associated with autism spectrum disorder, schizophrenia, and bipolar disorder, and the results provide compelling evidence demonstrating unique alterations of each variant in synaptic functions and behavior. These findings highlight a fundamental aspect of TRIO variants contributing to brain functions and neuropsychiatric disorders.