Evaluated articles

eLife assessment

This paper provides important evidence for the impact of the COVID-19 pandemic on cancer screening for breast, cervix, and colorectal cancer in Italy. The authors compared Invitation and examination coverage, as well as conducted telephone interviews, investigated the population screening test coverage, before and during the pandemic, according to educational attainment, perceived economic difficulties and citizenship. Their findings convincingly show that the lockdown and pandemic restrictions caused delays in screening activities but particularly increased the pre-existing individual and geographical inequalities in access.

eLife assessment

The paper describes an online tool, CausalCell, intended for the analysis of causal links in single-cell datasets. Regarding its significance, this work is timely and important, with potentially broad applications as a generally useful tool. However, there are major concerns about the suitability of the tool for its intended purpose, and the extent of validation in the current manuscript is incomplete.

eLife assessment

This paper provides valuable evidence for a weakening of the association between cognitive ability and height from 1957 to 2018 in the UK. The authors find the strength of the association declined over this time frame. These associations were further attenuated after accounting for proxy measures of social class. This paper is a solid contribution to debates about how genetic, environmental, and social factors have affected the joint distribution of height and cognitive ability over the last 60 years.

eLife assessment:

This study by Li et al describes an interesting attempt to predict the functional status of the p53 tumor suppressor in tumors where no DNA mutations in p53 could be identified. To this end, the authors employed SVM models to train the algorithm for the detection of 'p53 inactivation' features contrasting normal and tumor tissues. The approach could be a valuable tool for attributing tumors with unknown p53 status. The authors provide solid evidence supporting their findings and the concept of the study is solid, but in its current formulation, some of the bioinformatic analyses are incomplete, particularly related to the selection of associated genes and the potential mechanism(s).

eLife assessment

NOX2 is the most well-studied member of the NADPH oxidase family, membrane enzymes that produce reactive oxygen species (ROS), and the proper function of NOX2 is critical for innate immunity against pathogens in mammals. This study reports a high-resolution structure of the NOX2-p22 complex, providing valuable information for a mechanistic understanding of NOX2 activation at the molecular level.

eLife assessment

In this study, Hung et al. address the biology and therapy of chondrosarcoma. The authors provided high-quality data that uncovered a new signaling axis, EZH2/hSULF1/c-Met, that promotes chondrosarcoma growth and progress. The authors also reported evidence showing that c-Met inhibition may be a plausible treatment option for chondrosarcoma. The findings are novel and translational and are of interest to cancer biologists and oncologists.

eLife assessment

Sodium selenate reduced seizures when administered after initiation of epilepsy, complementing earlier work showing efficacy if administered before initiation. The novelty of the results is not much more than the earlier study. Sodium selenate reduced phospho-tau and increased PP2A protein expression, and reversed TLE-associated telomere-shortening. However, whether these effects were critical to the reduced seizures is not clear. Finally, proteome and metabolome data from the animal model of epilepsy is discussed and provide initial insights into the effects of sodium selenate treatment on molecular pathology, however, the data are not well developed so revisions along these lines will be important so conclusions can be made.

eLife Assessment:

Predicting the effect of mutations on protein stability is important both for protein engineering and for helping to decipher the effects of genetic and clinical mutations. The machine learning methodology introduce here is timely in view of the millions of AlphaFold model structures that are now becoming available, which could hypothetically be examined through approaches such as this one. The methodology presented is valuable, but the manuscript would benefit from a substantial amount of comparative data to provide more compelling evidence for the validity of the methods.

eLife assessment

This manuscript addresses the mechanism of ligand specificity of odorant receptors (OR) through mutational analyses and structure prediction. The authors identify a single amino acid substitution that switches ligand specificity between two olfactory receptors. Obtaining structures of OR complexes has been challenging, so such an approach is valuable and will be of interest to scientists within the fields of chemical ecology and sensory neuroscience.

eLife assessment

The manuscript makes an important contribution to understanding the roles of the bee host and microbiome in degrading amygdalin, a dietary secondary metabolite. Several bacterial strains and their enzymes responsible for the deglycosylation of amygdalin are identified. Conclusions are reached convincingly through a comprehensive combination of in vitro and in vivo experiments including gene-expression analysis, proteomics, HPLC-MS, and the use of recombinant E. coli to test enzyme function. As the consequences of microbial-derived amygdalin metabolisation on host health remain uncertain from the experiments conducted, the manuscript could be improved through a clearer discussion of future work needed and in parts more careful wording to not prematurely suggest benefits to the host.

eLife assessment

This paper is of potential interest to neuroscientists expert in cortical circuitry and behavioral role of neuron types. The imaging technique used permitted to detect a specific group of cortical neurons known as vasoactive intestinal peptide (VIP)-expressing interneurons from several cortical regions with high temporal resolution. The main message conveyed by this manuscript is that many VIP-expressing interneurons respond to reward and punishment but also show regional differences. The conclusions drawn are generally supported by the data, but some claims and interpretations require further attention and clarification.

eLife assessment

The work, which examines how Advanced Glycation End-products (AGEs), commonly found in processed and other cooked foods, affect eating behavior and signaling in the nematode C. elegans, is in a fundamentally important area of research with clear translational potential for humans. Some aspects of the manuscript are compelling, including the well-characterized assays on food intake, while other aspects are still incomplete, such as the mechanistic work on the neural network responsible for the response to AGEs.

eLife assessment

This is an important and timely characterization of a diversity of behaviors male and female rats exhibit during the acquisition of Pavlovian fear conditioning in a conditioned suppression procedure. The data are compelling and provide an exhaustive analysis of behavior in a complex associative learning paradigm that blends aversive Pavlovian and appetitive instrumental elements. The generalizability of these findings to other paradigms could be enhanced, however, with the inclusion of tests of cue responses in a neutral environment. These findings are likely to be of interest to those who study fear conditioning and associative learning more broadly in rodents.

eLife assessment

This large-scale collaborative study is a timely contribution that will be of interest to researchers working in the fields of infectious disease forecasting and epidemic control. This paper provides a comprehensive evaluation of the predictive skills of real-time COVID-19 forecasting models in Europe. The conclusions of the paper are well supported by the data and are consistent with findings from studies in other countries.

eLife assessment

In this valuable contribution, the authors apply an artificial intelligence method to predict the three-dimensional structure of complexes of outer membrane proteins of the Gram-negative bacterium E. coli. Some of the cases presented are compelling, as they explain previously published biochemical data and/or reproduce existing structural data.

eLife assessment

Primates perceive and detect stimuli differently depending on the stimulus context in which they are embedded, and have a remarkable ability to understand the way in which objects and parts of objects are embedded in natural scenes (scene segmentation). An example of this is figure-ground segmentation, a well documented phenomenon resulting in a "pop-out" of a figure region and corresponding enhanced neural firing rates in visual areas. It is unknown whether mice show similar behavioral and neural signatures as primates. The present study suggests that mice show different segmentation behavior than primates, lacking texture-invariant segmentation of figures and corresponding neural correlates. This reveals a fundamental difference between primates and mice important for researchers working on these species and researchers studying scene segmentation. The findings are further interpreted in terms of neural network architectures (feedforward networks) and are relevant for this field too.

eLife assessment

This study modeled monkeys' behavior in a stimulus-response rule-learning task to show that animals can adopt mixed strategies involving inference for learning latent states and incremental updating for learning action-outcome associations. The task is cleverly designed, the modeling is rigorous, and importantly there are clear distinctions in the behavior generated by different models, which makes the authors' conclusions convincing. The study makes a strong contribution overall, however, there were aspects of the design that were unclear and some alternative accounts that were not considered.

eLife assessment

It's been widely known that the amino acid Glycine can work as a cytoprotectant and inhibit pyroptosis-associated plasma membrane rupture. However, a long-standing question has been: how does Glycine cytoprotection work? The authors observed that Glycine treatment phenocopied deficiency of NINJ1 (a recently reported cell surface molecule critical for plasma membrane rupture), and can inhibit aggregation of NINJ1. Understanding the intrinsic mechanism by which Glycine affects NINJ1 could provide a significant advance in the cell death field.

eLife assessment

The study by Kim et al. combines extracellular recordings from olfactory sensory neurons (OSNs) in locusts with computational modelling approaches to investigate the dynamics of odour responses. The authors demonstrate that OSN responses can be grouped into four distinct response motifs, with OSNs showing different motifs in an odour-dependent manner. Using computational modelling the authors provide some evidence that these diverse response motifs expand the coding space and could facilitate odour discrimination and navigation. This study can be of high relevance to both experimental and theoretical neuroscientists investigating odour coding and odour-driven behaviours such as navigation. In its present form, while the experimental data and analysis are of the highest quality, the modelling part needs to be expanded to fully support the experimental measurements.

eLife assessment

The interesting manuscript shows that breast cancer cells that are poorly migratory in culture can be more metastatic in mice. This is due, at least in part, to the secretion of extracellular vesicles containing the the crosslinking enzyme Transglutaminase-2, which can activate fibroblasts in the tumours. These fibroblasts can then promote metastatic phenotypes. This study demonstrates how cancer cells can manipulate the cells around them in order to disseminate.