Evaluated articles

eLife assessment

This important study develops a new technical advancement in ex vivo live imaging of hematopoietic tissues to monitor blood cells in their native microenvironment. The new method for live imaging and tracking is compelling, and the strength and breadth of hematopoietic analysis are convincing. This work provides a very useful new system for immunologists and cell biologists, which will supply new perspectives on the system-level mechanisms of cell differentiation and innate immunity.

eLife assessment

This paper is of interest to immunologists conducting single-cell analyses of T-cell recognition. It provides a means of curating datasets to ensure T cell-antigen pairs are identified. The data generated through this method often suffers from a relatively high background, so the authors present a computational approach to enhance the signal-to-noise of this type of analysis. At this stage, it is unclear if the thresholds and filtering steps described by the authors can be generally applied to other datasets of different qualities than the one used here.

eLife assessment

This study presents a valuable mathematical model for the adaptive dynamics of cancer evolution in response to immune recognition. The mathematical analysis is rigorous and convincing, and overall the framework presented could be used in the future as a solid base for analytically tracking tumor evasion strategies. However additional discussion is needed to clarify certain gaps between the theory and cancer evolution in real systems. The work will be of interest to evolutionary cancer biologists and potentially it may also have implications for the design of clinical interventions.

eLife assessment

This study presents a valuable finding on the critical features and patterns of m1A modification and in neurons and OGD/R-treated neurons. Moreover, the authors identified m1A modifications on different RNAs and explored the possible effects of m1A modification on the functions of different RNAs via an integrated approach of omics and bioinformatics. The evidence supporting the claims of the authors is solid, although inclusion of more in-depth studies to analyze the transcription factors for the upstream regulation would have strengthened the study. The work will be of interest to neurobiologist and scientists in the field of RNAs.

eLife assessment

Scott et al use Drosophila as a model to study the sialylation pathway and its role in nervous system function. Surprisingly, they find that the critical substrate for sialylation, CMP-Neu5Ac, is 'outsourced' to glia. This significant study presents a new twist in mechanisms underlying protein glycosylation and uncovers a new layer in the complex interplay of neurons and glia.

eLife assessment

This study links chromatin remodeling with antifungal drug resistance in Cryptococcus neoformans. The work is important because it reveals a new facet of how drug resistance can emerge and associates. The work presented is well done but the story is incomplete since there are questions about methods and association that need to be addressed. Establishing a link between chromatin remodeling and antifungal resistance is a finding that would be of interest to infectious disease researchers, cell biologists, and drug developers.

eLife assessment

This study uses a combination of compelling biochemical and genetic approaches to identify a highly mutagenic DNA polymerase, which drives a wide spectrum of mutations when overexpressed. The important findings advance the understanding of mutagenesis in mycobacteria. The work will be of interest to bacteriologists interested in mutagenesis and the emergence of drug resistance.

eLife assessment

There are many strengths in this paper that examines patterns of epididymal blood and lymphatic vasculature, supported by quantitative methods, and well-conducted 3D imaging studies (graphics and videos). Minor weaknesses include the lack of higher magnification images and the organization of image panels in some figures. Overall, this is a very important contribution to the epididymis research field.

eLife assessment

This study, of interest to population geneticists and evolutionary biologists alike, aims at investigating temporal variation in patterns of germline mutation during the evolution of human populations. The authors suggest that shifts in mutation spectra occur frequently, over a few thousands of generations, possibly as a consequence of changes in environmental exposure, or of genetic modifiers. There are several important aspects of methodology that need to be clarified, and several additional tests have to be done to confirm that the reported observations are not the result of methodological artifacts. The paper also overstates certain weaknesses of previously published papers on mutation spectrum evolution as well as the generation time hypothesis; correcting these oversimplifications would more accurately capture what the paper's new analyses add to the state of knowledge in these areas.

eLife assessment

This manuscript provides compelling evidence that macrophages transfer mitochondria to cancer cells and that transferred mitochondria stimulate proliferation in recipient cells. The usage an array of clever cell biology-based tools provides compelling evidence for these claims despite the difficulties associated with studying a relatively low probability event. Solid evidence supports the proposed model that transferred mitochondria induce proliferation by stimulating ERK signaling in a ROS dependent manner, although at present some aspects of the proposed model are incomplete. The work has broad significance for both mitochondrial biology and cancer biology as the authors show clear evidence of mitochondrial transfer in mouse models of human tumors.

eLife assessment

Opioid-induced respiratory depression is one of the side effects of opioid drugs. Although opioid overdose deaths are highly prevalent, our knowledge of the neural circuits underlying respiratory depression in the brainstem is far from complete. The present study used a variety of sophisticated experimental techniques to convincingly reveal the identity of brainstem components that are part of the neural circuits involved in the mediation of opioid respiratory effects, together with defining potential synaptic underlying mechanisms. They focused on two regions of the brainstem, namely the Kolliker-Fuse and the preBötzinger Complex, and proposed a combination of three complementary processes at pre- and post-synaptic sites in both KF and preBötC regions to explain respiratory depression linked to opioid exposure. This study provides very important findings on the circuitry involved in opioid-induced respiratory depression, and the present results are of broad interest to the respiratory control research community, as well as medically relevant.

eLife assessment

Candida morphogenesis is important for virulence. This study provides important new information as to how C. albicans regulates the switch from budding to hyphal morphology. Their results identify transcription factors involved in the process of hyphal morphogenesis in the host. The results are convincing and will be interesting to scientists in the fields of medical mycology and cell biology.

eLife assessment

This manuscript analyzes large-scale Neuropixels recordings from visual areas and hippocampus of mice passively viewing repeated clips of a movie and reports that neurons respond with elevated firing activities to specific, continuous sequences of movie frames. The important results support a role of rodent hippocampal neurons in general episode encoding and advance understanding of visual information processing across different brain regions. The strength of evidence for the primary conclusion was found to be convincing.

eLife assessment

This work critically evaluates several widely-used assays of transcriptional responses to water limitation in Arabidopsis grown on defined agar-solidified media and, finding inconsistent responses in root transcriptome responses, introduces a new 'hard agar' assay with more consistent responses. The work is valuable as a simple and alternative experimental system that would enable high-throughput genetic screening (and GWAS) to assess the impacts of environmental perturbations on transcriptional responses in various genetic backgrounds. Within this scope, the work is solid, though the debate about whether field-level physiological inferences can be made from such assays remains.

eLife assessment

This study makes valuable observations about the representation of "value" in the mouse brain, by using a nice task design and recording from an impressive number of brain regions. The combination of state-of-the-art imaging and electrophysiology data offer solid support for the authors' conclusions. The paper will be of interest to a broad audience of neuroscientists interested in reward processing in the brain.

eLife assessment

This study examines the inflammatory and immune response to live E. coli bacterial infection in neonatal and juvenile mice. Important information is described on the roles of Class II MHC and interferon responsive genes in regulating the host response to infection. This study will inform future efforts to further elucidate the impact of bacterial infections on lung development.

eLife assessment

This is a valuable study showing that fast, but transient, modifications of the synaptic efficacies, alone, can support the integration of information over time. Convincing supportive evidence is provided by showing that feed-forward networks, when equipped with such short-term synaptic modulations, can successfully perform a variety of temporal integration tasks at a performance level comparable with that of recurrent networks. These results will be of interest to both neuroscientists and researchers in machine learning.

eLife assessment:

Bone marrow stromal cells (BMSCs) can differentiate into a variety of cell types such as osteoblasts, chondrocytes, and adipocytes. The authors of this important study provide compelling and strong evidence that ablating O-GlcNAc transferase (OGT) in BMSCs impairs bone formation but promotes marrow adiposity. The results show that the balance of osteogenic and adipogenic differentiation of BMSCs is controlled by reciprocal O-GlcNAc regulation of lineage-specifying transcription factors, and highlights the importance of an intracellular glycosylation process of specific proteins in bone formation and bone marrow adipocytes.

eLife assessment

This theoretical work deals with the problem of homeostasis of protein density within cells, relying on the Pump and Leak model. The model makes predictions both for growing and senescent cells, which they compare to experimental data on budding yeast. The work extends previous works and makes biologically-relevant predictions, which will be of interest to both theorists and experimentalists interested in cell physiology.

eLife assessment

The analysis of 89,000 independent somatic mtDNA mutations provides compelling evidence that allows the authors to refute the idea that reactive oxygen species (ROS) are a main driver of mtDNA mutagenesis, although ROS effects may still be tissue-dependent. These are fundamental results with convincing evidence, and they should appeal to a broad audience. The discovery of transversion mutations (C>A/G>T and C>G/G>C), which previously were assumed to be almost nonexistent, will nevertheless require additional validation.