Evaluated articles

eLife assessment

This valuable study reveals that patient-derived organoids recapitulate similar genomic signatures as that of the parental tissue, which could be a useful model to evaluate chromosome instability, drug sensitivity, and intratumoral heterogeneity. However, whereas some of the sequencing data are compelling, the theoretical analysis is incomplete and would benefit from a more rigorous definition. With the theoretical part strengthened, the work will be of interest to medical biologists working on ovarian carcinoma.

eLife assessment

Only few species of Leishmania, an important human pathogen, have an RNAi machinery, alternative methods are needed for genetic screens. The authors resent and validate a valuable method, based on the introduction of premature stop codons, that can be used for several different species. The results are very convincing, the data are solid, and the approach will be of interest to researchers studying any eukaryote that lacks the RNAi machinery.

eLife assessment

This convincing work reviews and synthesizes evidence of the impact of the COVID-19 pandemic on a variety of cancer outcomes. The results have potentially useful implications for various fields of cancer research as they review evidence spanning from cancer prevention efforts to changes in diagnoses and cancer treatment modalities.

eLife Assessment:

Mutations in a variety of intermediate filament proteins and their regulators lead to abnormal development, reduced lifetime, and increased stress sensitivity. This manuscript rigorously demonstrates that such defects result from inappropriate assembly of intermediate filament networks, as mutations in a central intermediate filament protein prevent assembly of both the normal network and these inappropriate assemblages and largely rescue most of the defects. This has important implications for our understanding of the assembly of intermediate filament structures and for understanding and potentially treating diseases resulting from mutations in intermediate filament protein genes.

eLife assessment

This important study in the protozoan parasite Toxoplasma gondii significantly advances our understanding of calcium signaling mediated by the kinase CDPK1 in this species. The authors' conclusions are supported by convincing evidence, with rigorous biochemical experiments and microscopy analysis. The work will be of broad interest to researchers in the fields of signal transduction and protozoan biology.

eLife assessment

This is an important study that asks why odors smell similar even though their chemical structures appear quite different. The authors use machine-learning to make a compelling case to map the odor-relatedness of compounds to their place in metabolic pathways and propose that this is a general feature of odor perception across the animal kingdom. The conclusions could be strengthened by considering published physiological data.

eLife assessment

Antibodies perform a critical function in host defense against viruses and have emerged as major therapeutic tools in modern medicine, as evidenced by the large scale use antibody-based therapies during the COVID-19 pandemic. This paper describes the characterization of human antibodies to hantaviruses that have the potential to create devastating epidemics. The results teach us about the viral structures that are targets for neutralization and the results are relevant for vaccine development and antibody therapeutic design.

eLife assessment

This study uses behavioral monitoring and cutting-edge calcium imaging approaches to track the activity of cholinergic and noradrenergic axons in cortex of head-fixed mice, and correlate activity with behavioral state. While the evidence that behaviorally related signals are broadly broadcasted to the dorsal cortex is clear from the data, the conclusion that there is also heterogeneity across axons and areas is of less certain significance and might be undermined by methodological artifacts.

eLife assessment

In this work Frantz et al. assess transcriptomic states of melanocyte stem cells that are recruited to differentiate during the process of melanocyte regeneration in zebrafish and they analyze roles for Kit signaling in this process. The analyses are nicely done, and the paper requires only relatively minor modifications and clarifications. The study will provide new insights into melanocyte stem cell biology that should be of interest to those studying pigmentation, regeneration, and melanoma biology using zebrafish and other systems.

eLife assessment

This important study employs auxin-induced degradation to show that the TATA-binding protein (TBP) is not required for ongoing RNA polymerase II transcription nor heat-shock or retinoic acid-induced transcription, but that TBP is essential for RNA polymerase III transcription, with TBP-independent TFIID complexes being assembled and present at the transcription start sites of polymerase II-transcribed promoters. The evidence for the major claims is currently incomplete.

eLife assessment

The authors have developed a useful and user-friendly software to analyse gene expression data from four datasets representing premalignant lung lesions. This software would be of interest to those working in lung cancer and specifically the pre-malignant space. The major strength is the ease of use while the major limitation is the inability for the user to integrate other datasets.

eLife assessment

Determination of the biomechanical forces and downstream pathways that direct heart valve morphogenesis is an important area of research. In the current study, potential functions of localized Yap signaling in cardiac valve morphogenesis were examined. However, the evidence for Yap pathway activation and localization relative to areas of the valve subject to different mechanical stresses is not convincing.

eLife assessment

This is a well-explained and potentially useful study that describes the generation and use of pYtags, recombinant proteins that, if properly used, should allow spatiotemporal monitoring of the activation of different receptor tyrosine kinases in living cells. Although this study has generated new tools to evaluate receptor localization and activation in different cells, the broad concept showing that different receptor dimers generate specific stimuli, and downstream signaling pathways, is quite limited in terms of novelty. Although it is felt that the study is technologically innovative, the analysis of receptor spatial signaling is incomplete and should be improved.

eLife assessment

This fundamental study substantially advances our understanding of the process of ribosome maturation. The authors have purified and determined the structures of several nucleolar ribosome assembly intermediates in yeast using cryo-electron microscopy (cryo-EM). The study combines genetic, biochemical, and structural analysis to provide compelling support for the conclusions the authors wish to draw. The work will be of broad interest to cell biologists, biochemists, and structural biologists.

eLife assessment

This is an intriguing study investigating the molecular mechanisms of neural circuit developmental organization. Using a defined hippocampal circuit, the authors find that ectopic expression of an adhesion G protein-receptor leads to axon mistargeting. This work defines new mechanisms of axon target specificity.

eLife assessment

Russel et al. study and reveal compelling evidence for potential sequence-based factors that may drive VDJ trimming, a mechanism involved in VDJ recombination that shapes adaptive immune repertoire generation. The work is based on a rigorous statistical comparison of logistic regression models to reveal the role and function of cutting enzymes in shaping T- and B-cell receptor diversity. It could provide fundamental new insights into these processes with some claims being currently incomplete.

eLife assessment

This study investigates the spatiotemporal characteristics of human brain activities during object recognition under noisy and ambiguous conditions. By using state-of-the-art data analysis and model-driven fusion of MEG and 7T, this work demonstrates distinct representational profiles in ventral and dorsal pathways, contributing new perspectives to our understanding of the neural implementation of object recognition under uncertainty.

eLife assessment

Siglec-1 (CD169), a plasma membrane-associated sialic acid-binding lectin, has been implicated in the capture of HIV and other viruses by dendritic cells and macrophages. However, the molecular details of how HIV particles are captured by Siglec-1 are poorly understood. In this paper, the authors use advanced imaging methods to analyse the cell surface distribution of Siglec-1 on immature and mature dendritic cells to study the regulation of Siglec-1 distribution by actin and regulators of actin polymerization and to understand how virus-Siglec-1 engagement leads to virus sequestration within so-called virus containing compartments. These types of analyses have only recently become feasible with the implementation of super-resolution imaging and as yet few virus-host cell systems have been examined in detail. Thus, this study has relevance for researchers studying the engagement of HIV and many other viruses with cells, as well as researchers interested in the mechanisms regulating receptor distribution and function on cells.

eLife assessment

Poison frogs sequester alkaloids to make themselves toxic or unpalatable to predators, but how this sequestration occurs is not well understood. This valuable study identifies an alkaloid-binding protein in the plasma of poison frogs, which may help explain how these animals are able to sequester a diversity of alkaloids with different target sites. The supporting evidence is solid and the study adds to our understanding of how toxic animals resist the effects of their own defenses.

eLife assessment

Elbaz-Hayoun et al. investigate the role of macrophages in the gliotic response of retinal Müller glia and photoreceptor cell death. The authors find that macrophages play a role in inducing retinal damage. A role for the muller glia expressed, C-C chemokine receptor axis was identified as a causative factor in promoting retinal degeneration. These important data identify a new link between cells of the immune system and those within the retina which contribute to the progression of retinal degeneration.