Evaluated articles

eLife assessment

Drug-resistant tuberculosis (TB) is a growing threat to global public health. By analysing a large database of clinical Mycobacterium tuberculosis isolates, the authors of this study identify previously unrecognized genetic mutations that might be implicated in improved mycobacterial survival under antibiotic treatment. Using laboratory and experimental infection models, they present evidence that these mutations should be considered potential genetic markers of reduced antibiotic efficacy and accelerated acquisition of TB drug resistance.

eLife assessment

This important study defines new functions for the ER-resident protein HSP47 in the quality control of multi-pass membrane receptor proteins. The evidence supporting the conclusions is solid, with rigorous biochemical assays employed in appropriate models. However, additional consideration regarding the mechanism of HSP47-dependent regulation of membrane protein quality control would have strengthened the study. This work will be of broad interest to cell biologists and biochemists interested in the fields of proteostasis membrane protein quality control, and neuroreceptor signaling.

eLife assessment

This fundamental study is important and carefully executed, providing important insights into the allosteric regulation of GPCRs with exceptional strength of evidence. This work will be of interest to a wide audience in drug discovery and receptor biology. The major strengths are the comprehensive structural and pharmacological characterization with only minor weaknesses, most notably a concern regarding the approach used to quantify efficacy.

eLife assessment

The authors have developed a useful model for how proteins that mediate a connection between invariant components of the T cell antigen receptor and leukaemic cells antigens, called bispecific engagers (BiTEs), mediate immunological synapse formation and impact T cell search for tumour cells in vivo. The model was compared against the in vitro experiments and in vivo data following a solid approach. The developed framework could provide a direction for employing computational mechanistic models for evaluating various strategies for BiTE treatments.

eLife assessment

This important study uses state-of-the-art methods to explore the evolution of dosage compensation between two closely related nematode species. The evidence supporting the rapid evolution of the recognition motifs on the X chromosome, despite a general conservation of the mechanism, is compelling. Provided the discussion on the evolutionary aspect of the findings is improved, this work will be of broad interest to cell biologists and evolutionary biologists.

eLife assessment

This potentially important article identifies an apparent oligogenic architecture for an ecologically relevant trait, the circalunar reproduction of marine midges, which contributes to assortative mating, is likely under divergent selection, and supports reproductive isolation in sympathy. A claim for a causal role of chromosomal inversions in this system is made, but the support for this claim is incomplete.

eLife assessment

This study presents a careful evaluation of the distribution of monocytes and dendritic cells in the the blood and nasopharyngeal aspirates of patients with mild respiratory tract infections. There are some interesting differences between monocytes and dendritic cells and variations with patient age. This is an important contribution to understanding monocyte and DC subset specific functions in dependency on the tissue microenvironment.

eLife assessment

This work provides valuable new insights into the mechanisms by which 25-hydroxycholesterol (which is known to be rapidly produced in macrophages and other cells during acute infections) acts to protect cells and animals from microbial infection. The authors provide compelling evidence that the cholesterol-esterifying enzyme acylCoA:cholesterol acyltransferase (ACAT) that is induced by 25-hydroxycholesterol promotes the depletion of an accessible pool of plasma membrane cholesterol, producing anti-microbial effects.

eLife assessment

This manuscript provides important findings that have practical implications for reproductive medicine and would be of interest to IVF specialists. Based on the compelling strength of evidence, the authors present significant results on improving the predictive value of the live birth model based on blastocyst evaluation and clinical features. However, some methodological information should be added to improve the reproducibility of the study results.

eLife assessment

The authors report the results of three experiments assessing how one or both eyes open under a patch influence resting EEG activity, contrast sensitivity, and binocular balance in normally sighted subjects. Their results suggest that the state of eye opening temporarily, but significantly, influences shifts in ocular dominance with relevance for treatment of binocular visual disorders such as amblyopia that are treated with periodic monocular occlusion. The evidence supporting their conclusions is solid and the findings are important for the field.

eLife assessment

This study highlights a significant concept whereby a retained memory of disease during stem cell reprogramming (likely via epigenetic modifications) affects the chondrogenic differentiation potential of osteoarthritis (OA)-iMSCs. The evidence supporting the conclusions is compelling, with rigorous RNAseq analysis of genes and signaling pathways. The relevance of this research is highlighted by the valuable role of iPSCs as a potential cell source for regenerative medicine. The work will be of broad interest to skeletal stem cell biologists working on osteoarthritis and cartilage regeneration.

eLife assessment

Sorkac et al. present a novel genetically encoded retrograde synaptic tracing method that has the potential for unbiased identification of presynaptically connected neurons. Retro-Tango is based on the previously developed anterograde method trans-Tango, promising high applicability and rendering the significance of this contribution important. The strength of the evidence is convincing.

eLife assessment

This manuscript presents an important mathematical analysis on metabolic "co-substrates" and how their cycling can affect metabolic fluxes. Through mathematical analysis of simple network motifs, it shows the impact on constraining metabolic fluxes and the applied mathematical modeling/simulation approaches and the statistical analysis to compare predictions with data from previous studies offer convincing support for the potential biological relevance of co-substrate cycling. The work will be of interest to researchers who study microbial metabolism and metabolic engineering. However, part of this analysis remains unclear and would benefit from clarification.

eLife assessment

This important analysis helps to shed light on the relationship between blood type and the occurrence of ICD-based phenotypes in a hospital setting. A particularly compelling strength is the analysis' reliance on a population-based patient registry. The results would be further strengthened by an exploration as to whether these phenotypes are driven by patient characteristics (e.g. ethnicity, SES) and not just blood type. Additionally, differences across blood types are driven, in part, by differences in prevalence, somewhat limiting the scope of the analytical findings.

eLife assessment

The study shows that human inflammasome-forming sensor CARD8 contains a specific motif that allows cleavage by the proteases of HIV-1 and its direct precursor infecting chimpanzees. In comparison, CARD8 proteins from non-human primates contain changes in this motif and seem largely resistant to proteolytic activation. The results are important, and the data on the cleavage of CARD8 in HEK293T cells are convincing, while effects on inflammasome stimulation and cell death in primary viral target cells are insufficiently supported.

eLife assessment

This work provides important new insights into the mutational pathways of SARS-CoV-2 to achieve antibody escape, as well as how these pathways are shaped by epistasis. The evidence supporting the conclusions is compelling based on rigorous analyses of data from a high-throughput binding assay. The study is important for evolutionary medicine and biology and relevant for human health.

eLife assessment

The current study employed NSCs derived from human induced pluripotent stem cells (iPSCs) together with NSC-derived exosomes extracted from NSCs to treat cerebral ischemia, and they made an important observation. Remarkably, NSC-derived exosomes could promote NSCs differentiation, reduce the oxidative stress and inflammation, and alleviate the formation of glial scars after ischemia and reperfusion, and as a result, could enhance the therapeutic effects of NSC transplantation, which is compelling. The solid experimental evidence strongly supports their major claims.

eLife assessment

Experimental models of simple cell-like compartments can help us to understand how biology operated early in its history. The authors convincingly show how the properties of coacervate droplets can be influenced by the activity of ribozymes inside them. This important result potentially provides a new route for biologists or chemists to establish cell mimics that support the evolution of biomolecules within.

eLife assessment

Through theoretical analysis, the authors argue that the proliferation of neurons in the outer subventricular zone, which is specific to humans, decreases the distance between neighboring sulci in the cerebral cortex and increases cell density in the ventricular zone. Though the exact mechanisms remain to be further elucidated, the compelling data and approach represent a valuable foundation for the study of cortical folding from the underpinning cellular level as well as the coupling role of mechanics and cellular biology. This study will be of particular interest to the large community of scientists studying the mechanisms of brain development and disorder and even possibly beyond.

eLife assessment

This fundamental work reports an analysis of microbial abundance similarities among individuals over time in a longitudinal wild baboon cohort from Amboseli, Kenya. The authors provide compelling evidence that there are remarkably consistent dynamic associations over time in microbial abundances between baboons, despite individual baboons having individualized microbial signatures. The authors further identify universal microbial associations that appear to go beyond the studied baboon cohort, extending to human microbiomes. This study adopts a novel powerful statistical approach to analyzing longitudinal microbial dynamics at the individual level, which will likely make this work become a key reference study in the field of microbial ecology.