Evaluated articles

eLife assessment

This important study shows the sexually dimorphic dynamics of the components of meiosis-specific chromosome structure and the gene-dosage effect of the components on meiotic recombination. The experimental evidence in the paper is solid with cytological analysis with Fluorescence Recovery After Photobleaching (FRAP). The work will be of interest to researchers working on meiosis and chromosome dynamics.

eLife assessment

Rossi et al. carry out a valuable characterization of the molecular circuitry connecting the immunomodulatory cytokine BAFF (B-cell activating factor) in the context of cellular senescence. They present solid evidence that BAFF is upregulated in response to senescence, and that this upregulation is partially driven by the immune response-regulating transcription factor (TF) IRF1, with potential cell type-specific effects during senescence. Ultimately, these results strongly suggest that BAFF plays a senomorphic role in senescence, modulating downstream senescence-associated phenotypes, and may be an interesting candidate for senomorphic therapy.

eLife assessment

This important work provides new insights into the structure and function of respiratory complex I. The cryoEM data are convincing but the assignment of different conformations of the enzyme complex to specific functional states has not yet been conclusively determined. This work will be of interest to researchers studying the molecular basis of energy metabolism, the evolution of respiratory enzyme complexes, and mitochondrial diseases.

eLife assessment

This manuscript provides an important advance in our understanding of burn-associated T-cell responses. The evidence is convincing and the techniques are using the latest single-cell RNA-seq approaches in a rigorous manner. The studies are done directly on human skin so are highly clinically relevant.

eLife assessment

The work by Lindmark et al. provides us with an important natural experiment on fish that challenges current literature on relationships between temperature, growth rate, and size. The strength of their results is compelling, as Lindmark et al. mixed a unique warming setup with a large battery of models and statistics. The work will be of interest to ecologists and physiologists interested in the impacts of global warming on natural communities.

eLife assessment

The findings of this article provide valuable information on the spatial dynamics of the human oral mucosa in chronic inflammatory disease. The strength of evidence presented is solid and should yield a better understanding of common mucosal diseases in humans.

eLife assessment

This study presents an application of a deep learning approach (adult-trained variational autoencoder) to describe the development of the functional brain connectome in human fetuses and neonates. The results suggest that this may lead to a better characterization of the complex patterns of brain maturation during this period. The evidence is convincing but the impact of other confounding factors in addition to maturation on the results could be explored and further analysis should be considered to highlight how this method can account for non-linear patterns of development, as well as the biological plausibility of the observed brain states. This work is of potential methodological interest to researchers exploring functional brain networks and brain development notably with deep learning.

eLife assessment

The function of specific proteins made by SARS-CoV-1 and SARS-CoV-2 is under debate, with diverging claims previously published regarding the ability of Orf3a proteins from either virus to form ion channels. The authors undertook a thorough characterization of Orf3a from CoV-1 and CoV-2 by combining data from a range of different structural and functional experiments, arguably providing the most compelling evidence to date that Orf3a from viruses is not an ion channel. Instead, the orthologue-specific interaction with a component of a larger protein complex suggests a role of one of the two membrane proteins in the endo-lysosomal pathway. The work is significant from a fundamental science perspective, for its implications for COVID antiviral development strategies, and also for establishing guidelines for future identification of true viral ion channels.

eLife assessment

The manuscript by Abramson and colleagues is a new analysis of previously published data from experiments in which rats ran on a treadmill in either fixed-time or fixed-distance trials. The valuable results provide solid evidence to demonstrate that time and distance cells are more common in fixed-time and fixed-distance trials, respectively. These findings suggest that the hippocampus flexibly shifts between representing variables depending on their relevance.

eLife assessment

In their manuscript, Dema et al. showcase an important tool to study the role of the microtubule end-binding protein, EB1. This important study is the first to locally inactivate EB1 in human neurons, and while the authors have previously published the effects of replacing endogenous EB1 with a light-sensitive variant, the novelty in this current study is that they use a one-step gene editing replacement method in addition to using human neurons derived from iPSCs. The data is of high quality and the evidence supporting the conclusions is solid, although including more controls are needed to strengthen the study. The findings of this work will be of interest to cell biologists and neurobiologists, while the methods utilized will have an even broader general interest.

eLife assessment

This study presents a valuable enhancer reporter of TGFb signaling in melanoma that has a conserved function in both human cell lines and zebrafish. The reporter data is solid and provides interesting insights into TGFb targets in melanoma. However, the model that macrophages preferentially phagocytose certain subsets of melanoma cells is still incomplete, and more data will be needed before this process is clearly understood.

eLife assessment

This important study advances our understanding of the molecular players downstream of the transcription factor Emx2 that establish planar cell polarity in hair cells of the mammalian inner ear. The conclusions, which are supported by compelling evidence, will be of interest to those studying the development and function of the vestibular system and mechanisms of planar cell polarity.

eLife assessment

This manuscript provides fundamental new insight into protein conformational transitions underlying the transport mechanism of Nramps, an important and widespread transporter family that facilitates the uptake and movement of essential transition metals. Eight new crystallographic structures of the prokaryotic homolog draNRMP in a variety of ligand-bound and conformational states, along with companion molecular dynamics simulations and metal binding and transport assays, provide compelling evidence supporting most of the conclusions. These findings will be of broad interest to scientists studying transport mechanisms and ligand recognition.

eLife assessment

This important work substantially advances our understanding of how human eye movements are shaped by social cues. Using clever experimental manipulations and innovative artificial intelligence analysis tools, the paper identifies distinctive patterns of saccadic eye movements tracking another person's gaze during dynamic video-scene viewing. This work will be of broad interest to psychologists, biologists, and neuroscientists interested in human social behavior.

eLife assessment

This study reports an important theoretical model with simulations of meiotic recombination hotspots and Prdm9 evolution. By integrating recently identified biological properties of Prdm9, the model provides compelling evidence for novel features of hotspots and Prdm9 evolution. Yet, the model, the different steps in implementing parameters, and the predictions are difficult to follow and would benefit from clarification.

eLife assessment

It is well established that valuation and value-based decision making is context-dependent, but the exact form of normalization has remained an open question. This study provides compelling evidence that values during reward learning are normalized based on the range of available values. These findings will be important for researchers interested in reward learning and decision-making.

eLife assessment

This important manuscript describes how methylation of a single arginine residue in a transcription factor, C/EBPα, can alter dynamics of cell fate transition. The study provides one of the most striking examples of the transcription factor regulation by methylation and is well-executed, with compelling evidence to support the authors' claims.

eLife assessment

This study convincingly demonstrates that the splicing factor SRSF1 can be solubilized in the presence of short RS or ER-containing peptides, and uses this discovery to determine the solution NMR structure of SRSF1, as well as to map its interactions with RS peptides. These findings are important in that SR proteins are key regulators of alternative splicing but their study has been greatly hampered by their low solubility. The development of a general method that allows the structural and biochemical analysis of SR proteins in solution will have broad applications.

eLife assessment

This landmark study uses compelling approaches such as quantitative and screening mass spectrometry to identify peptides from tuberculosis bacteria that are presented by macrophages infected with this pathogen. The authors provide convincing evidence that the presentation of these antigens depends on a specialist bacterial secretion system. The study will be of interest to infectious disease specialists and of particular value for future vaccine development.

eLife assessment

Lemerle et al utilize advanced correlative light and electron microscopy and molecular biology approaches to convincingly demonstrate the presence of the membrane-bending protein Bin1 and caveolae containing rings capable of membrane tubulation in developing muscle. The data is highly significant as it potentially advances our fundamental understanding of how transverse tubules are formed, a significant gap in our understanding of excitation-contraction coupling and muscle biology more broadly.