Evaluated articles

eLife assessment

This is an important manuscript that provides support for the hypothesis that the relative increase in NIH funding matches the rate of overall inflation. The level of evidence is solid, and a clearer description of the analysis will further strengthen the manuscript. This paper should be of relevance to funders, investigators who are currently funded, and those who are seeking federal support.

eLife assessment

This paper will be of interest to developmental biologists who study the gene regulatory mechanisms necessary for neuronal identity and circuit assembly. The study presents important findings regarding the role of the LIM homeodomain transcription factor Isl2 in the development of spinal motor neurons. While the importance of Isl2 for the acquisition of axial and visceral motor neuron development was already described in the literature, the data convincingly describe an additional role in the differentiation of a subset of limb-innervating motor neurons.

eLife assessment

The authors demonstrate that patients with obesity-associated osteoarthritis and mice with the ApoE gene deficiency showed phenotypes of synovitis and enhanced macrophage infiltration in synovial tissues. Overall, this potentially important study is well-designed and carefully executed, although additional evidence is needed to fully support the authors' conclusions.

eLife assessment

This study reports an important new resource, MHC class I and MHC class II reporter mice, which provide a means to monitor MHC activation in vivo. The authors use these mice to study inflammatory demyelination in two mouse models of multiple sclerosis. The study provides a compelling demonstration of the new reporter lines as a valuable tool for analysis of inflammation and neurodegeneration.

eLife assessment

This manuscript presents a valuable new approach to modelling patterns of brain activity evoked by non-invasive brain stimulation, shedding light on how such stimulation drives neuronal dynamics. The performance of the model is impressive and its validity is supported by solid evidence. This work will be of interest to researchers working in computational neuroscience, neuroimaging, and non-invasive brain stimulation.

eLife assessment

This paper is valuable and of interest to scientists studying primary cilia/flagellar formation and regulation. It addresses how ciliary/flagellar length is controlled and whether calcium negatively regulates Intraflagellar transport (IFT) injection. The study convincingly demonstrates that calcium influx correlates with flagellar length, but calcium does not appear to work as a negative regulator of IFT injection, which challenges a previous model. The models and methods are generally sound, but some conclusions would be strengthened by additional experimental support.

eLife assessment

Why do fish school together? Energetic benefits have long been considered a key factor in motivating fish to swim together and tune their tail beat to exploit the whirling wake generated by conspecifics. This study clearly demonstrates that fish benefit from swimming in a two-dimensional vortical wake by locating their body in the vortical low-pressure zones that passively impart a net thrust force on their oscillating bodies. The behavioral and biofluid mechanical findings will interest comparative biomechanists, movement ecologists, evolutionary biologists, fluid mechanists, and bioinspired roboticists.

eLife assessment

This important study advances our understanding of respiratory complex I. The authors present convincing structural data for the enzyme from Drosophila melanogaster although the interpretation of conformational states is still not conclusively settled. This work will be of interest to researchers studying respiratory enzymes, the evolution of respiration, and mitochondrial diseases.

eLife assessment

This manuscript will be of interest to both developmental biologists and neuroscientists. The data suggest that most (but not all) neuronal types are present in both Drosophila sexes, and the existence of mostly shared scSeq clusters suggests that sex-specific versions of the transcription factor Fruitless can modify neural function in a sex-specific way without completely altering core neural identity. This cell type gene expression atlas should prove valuable in future efforts to understand mechanisms of sex-specific development, as well as the molecular and developmental-genetic basis of sex differences in behaviour.

eLife assessment

The author customises an alpha-fold multimer neural network to predict TCR-pMHC and applies this to the problem of identifying peptides from a limited library, that might engage TCR with a known sequence from a limited list of potential peptides. This is an important structural problem and a useful step that can be further improved through better metrics, comparison to existing approaches, and consideration of the sensitivity of the recognition processes to small changes in structure.

eLife assessment

The ABC transporter ABCG2 extrudes chemotherapy reagents and other xenobiotics from a number of different tissues. How ABCG2 operates at the molecular level has been largely derived from structures and dynamics carried out in non-physiological environments. The paper presents convincing cell-based evidence describing the relationship between structural changes of ABCG2 and substrate binding using flow cytometry, confocal microscopy, and fluorescence-correlation spectroscopy methods. Both the mechanistic conclusions and methodology employed offer important insights, which will be of general interest to the biochemistry and transport biology communities.

eLife assessment

Detailed electron-microscopy reconstructions of neurons, which are now available for a complete Drosophila central brain, raise the prospect of detailed models of their electrical properties. This manuscript uses a recently released dataset to model one particular neuron in an olfactory learning center of the fly brain. The model elucidates how this neuron responds to synaptic inputs that represent odor, suggesting how modification of these synapses might underlie olfactory memory. This work brings together electrophysiological recordings and neuroanatomical reconstructions from volume electron microscopy to model how a neuronal arbor integrates synaptic inputs. With the many ongoing connectome mapping projects world wide, the results here can illustrate an approach to interpretation of connectomes towards understanding neural circuit function. The rules of synaptic plasticity discussed here furthermore do not only shed light into the mechanisms of learning and memory in biological systems but also inspire the formulation of new approaches to adjusting connection weights in artificial neural networks.

eLife assessment

This study has looked at the 30-day mortality risk from COVID-19 in a large population of unvaccinated patients with and without cancer. Age and cancer were independent risk factors for death. In particular haematological malignancies and lung cancer presented the highest risk. These data add to the body of evidence regarding the risk of COVID-19 in patients with cancer. This manuscript is of broad interest to oncologists, internists, and infectious disease specialists in managing patients with COVID-19 and cancer.

eLife assessment

One must appreciate the challenges of antimicrobial stewardship in an immunocompromised population. This retrospective single-institution study provides support for the working hypothesis that initial procalcitonin levels might be used in cancer patients admitted with COVID-19 infection to omit, reduce, or de-escalate the need for empiric antimicrobial therapy. In the setting of a global pandemic, this is a common issue with COVID-19 patients in generally, but far more difficult in a cancer patient population. The results presented here support the authors' conclusions, however, future subgroup analysis of more specific scenarios among cancer patients with COVID-19 (e.g., neutropenia, active chemotherapy, and need for intensive care) are warranted.

eLife assessment

In this study, Diehl and Redish present a novel account of functional variability in the rodent medial prefrontal cortex. The authors report that, in general, the dorsal regions encode decision-related variables, whereas the ventral regions encode variables more linked to motivation, such as trial number in the session and amount of lingering time. Overall, the study is interesting, the experimental design is excellent, and the uniquely large neural data set is a strength. The suggestion of functional subdivisions in the prelimbic area is particularly provocative, and this conclusion, along with the data supporting it, will be of broad interest to those who study the anatomy and function of the rodent medial prefrontal cortex.

eLife assessment

The results of this work show a non-determinant effect of the COVID pandemic on the logistics of patient care from diagnosis to treatment modalities. The significance of this scoping review relates to the methodologic design of future outcome measures in cancer reporting that include time measurements between important clinical decision points or treatments in a standardized fashion. Without this standardization in reporting, comparisons to different length intervals are impossible and may have a significant impact on patient outcomes. The strength of the evidence is compelling, given the exhaustive nature of the literature review. This work should be seen by all oncologic units and research groups so that time benchmarks can be established that correlate to patient outcomes. These measurements require oncology society uptake and reporting to be effective.

eLife assessment

This useful theoretical and numerical study shows that evolution can stabilize predator and prey populations in a generalized Lotka-Volterra framework with high variance species-species interactions. It demonstrates an example of evolutionary bet hedging, rescuing species at risk of extinction due to destabilizing predator-prey interactions. The methodology is solid, but some modeling choices are quite specific, limiting direct applicability to concrete systems. The study should be useful to the community working on theoretical ecology and evolution, and the ecology-evolution coupling should resonate with a broader audience.

eLife assessment

This study confirms a role of traditional cardiovascular risk factors (age, sex, cholesterol levels, weight) and polygenetic risk scores when predicting coronary heart disease in a large prospective cohort. It further reports an independent effect of seropositivity from past infection with a commensal bacterium F. nucleatum as a risk factor. The work is based on solid data and methodology and constitutes an important contribution to the understanding of disease risk, but the role of infection needs independent replication.

eLife assessment

This important manuscript investigates the circuitry connecting the galactose utilization regulon of the human pathogen and model organism Candida albicans to the sensing of galactose. In the non-pathogenic model yeast Saccharomyces cerevisiae this circuit represents a textbook model that rivals the lac operon as a teaching tool. Using a broad array of mainly classical approaches, this study convincingly demonstrates the transcriptional activators that are required for galactose (and GlcNAc) responsive galactose metabolic genes in C. albicans. The recognition of just how different the regulation of the galactose pathway across fungal species represents an important advance in our understanding of the evolution of the regulatory control of these circuits, and would make a nice addition to the textbook version of eukaryotic gene regulation.

eLife assessment

Oxidation regulation of neuronal Kv7 channels contributes to the regulation of brain excitability. The manuscript concludes that this regulation is due to a disruption of the interaction between the S2S3 linker of Kv7 with the CaM EF3 site. The proposed mechanism is potentially important, but there are several weaknesses with the presentation and interpretation of the data that need to be addressed.