Evaluated articles

eLife assessment

The study represents an impressive effort to use atomistic simulations to probe cryptic binding sites in the envelope of six flaviviruses. Moreover, using constant pH simulations, the authors suggest that a cluster of ionizable residues contribute to the pH dependent conformational rearrangements required in the infection process. Therefore, the study provides new mechanistic insights that can be helpful in future efforts to develop drugs that target flaviviruses.

eLife assessment

This is an important study that investigates the impact of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia. Through a combination of pre-clinical in vivo measurements, clinical data, and computational modeling, the authors present solid evidence regarding the heterogeneous effects of TKIs in patients and how the response to treatment may be improved. With the assumptions about differences between normal and leukemic cells addressed, this study would be of interest to those working in the fields of mathematical oncology and cancer biology.

eLife assessment

The authors revisit fundamentals of synaptic transmission using a combination of advanced optical methods capable of visualizing calcium influx and neurotransmitter release at single release sites. By doing so, the authors present evidence for silencing of neurotransmitter release at single release sites as a function of external calcium. The data have relevance to a wide range of phenomena including neural plasticity and inhibitory modulation of synaptic communication.

eLife assessment

This important study presents a machine learning-based classifier that can accurately determine the geographic origin of a Salmonella enterica sample from its whole-genome sequencing data in under five minutes leading to actionable public health insights. Applying the method to 2,313 whole genome sequences collected in the United Kingdom and several external validation datasets, the authors provide convincing evidence that Salmonella genomic data can be used to identify the likely geographic source of a food-borne outbreak and, in most cases, correctly identify the country of origin of an infection acquired overseas. The work presents an excellent case for the potential utility of routine genomics coupled with machine learning for public health microbiology and the methods are likely to be applicable to other pathogens besides Salmonella enterica.

eLife assessment

The findings in this study are important as they establish a rat model of a classic form of early-onset osteoporosis and demonstrate that osteoporosis medications are effective in the model. The evidence supporting the authors' claims is compelling.

eLife assessment

This important landmark paper identifies three distinct stellate ganglion nerve cell subtypes stratifiable in terms of their neuropeptide Y expression correlating these with gene expression and electrophysiological properties. Their innovative use of viral tracing techniques compellingly established their conclusions. This major contribution to cardiac sympathetic excitation is relevant to a wide scientific and clinical audience.

eLife assessment

This important work demonstrates a significant asymmetry between the connectivity statistics of the left and right hemispheres of the Drosophila larva brain. The evidence supporting the conclusions is compelling and represents a first step toward the development of statistical tests for comparing pairs of connectomes more generally. This work will therefore be of interest to the broad neuroscience community.

eLife assessment

This paper will be of interest to scientists involved in understanding the function of long non-coding RNAs. The authors found two genes previously reported as lincRNAs in early studies encode micropeptides in zebrafish. Zebrafish mutants lacking these micro-peptides show altered gene regulatory networks that preferentially affect oligodendrocytes and cerebellar cells in the embryonic brain. The data presented in the study are solid and present convincing additional evidence for the versatile functions of micro-peptides.

eLife assessment

This study is an important contribution to the understanding of Buruli ulcer transmission in Australia. The authors provide compelling evidence that the carriage of Mycobacterium ulcerans by possums, within their small home range, can predict cases of Buruli ulcer disease in individuals who visit those areas. While not directly relevant to the transmission of Buruli ulcer in West and Central Africa, the work will be of great interest to those studying the transmission of opportunistic environmental pathogens.

eLife assessment

This study employs live imaging to investigate the movement of mesodermal cells in early mouse embryos. By examining the dynamics of cell behavior in normal and mutant embryos, the authors propose that apical constriction of cells results from pulsed contraction guided by crumbs2 signals. The paper presents beautiful images and adds to the molecular understanding of cell migration during early development.

eLife assessment

In this Tools and Resources article, the authors overcome the challenge of low Borrelia burgdorferi numbers during infection for analyses such as RNA-sequencing or mass spectrometry. They do so by physically enriching for spirochetes, which is important, as it provides technical advances for the study of global transcriptomic changes of B. burgdorferi during tick feeding, helping to build on the knowledge already collected by the field. The evidence presented is compelling, and the strategy described here could benefit researchers in the field and possibly also support broader applications.

eLife assessment

This important work reports the identification of a list of proteins that may participate in the clearance of paternal mitochondria during fertilization, which is known as essential for normal fertilization and embryonic and fetal development. The main method used is state-of-the-art and the supporting data are solid. This work will be of interest to developmental and reproductive biologists working on fertilization.

eLife assessment

This study provides valuable insights into the role of two under-researched sperm-specific proteins (Cylicin 1 and Cylicin 2). The authors provide convincing evidence that they have an essential role in sperm head structure during spermatogenesis, and that their loss leads to subfertility or infertility, with a dose-dependent phenotype. Importantly, the authors identify infertile males with mutations in both Cylicin1 and Cylicin2. Thus, the findings from the mouse models might be applicable to understanding human male infertility with similar structural defects.

eLife assessment

Gordon-Fennell et al. present a low-cost, open-source platform for measuring action elicitation and consummatory behavior in head-fixed animals. The findings are important because they allow animals to perform a truly voluntary action whilst their head is held still, and the evidence supporting them is both comprehensive and compelling (in some cases even exceptional). The results have the potential to have a broad impact in the field as many labs start to move towards measuring head-fixed behavior effectively, although this is said with the caveat that such behavior will never be an ideal replication of naturalistic behavior.

eLife assessment

This manuscript describes an approach to creating fat tissue in culture for food applications. Specifically, the efforts of growing cultivated meat focus mostly on growing skeletal muscle. However, the taste component of such artificial meat would be determined by fat content. There is a significant desire and motivation to cultivate fat tissues in vitro for the purpose of the replacement of animal products. This paper provides new technological approaches to expand adipocytes and aggregate them into structures that resemble fat.

eLife assessment

This important manuscript employs a rigorous and multi-pronged comparative genomics approach to unravel how lifestyle modulates the acquisition and domestication of viral genetic elements in the genomes of hymenopteran insects. Using an extensive dataset of over 120 hymenopteran genomes, the authors provide convincing evidence that endoparasitism (where parasite development occurs within hosts) facilitates the uptake and domestication of double-stranded DNA viral elements.

eLife assessment

This valuable paper examines the effect of deiodinase polymorphism on thyroid hormone signaling in the brain by employing a transgenic animal model and then switching to studying T3 axonal transport using microfluid devices. Although methodologically extensive this paper has several claims that are not convincingly supported by the current experiments and furthermore some disjoint is observed between the two halves of the study. The therapeutic implications of understanding T3 signaling in the brain makes it a potentially important manuscript.

eLife assessment

The authors use analytic calculations and numerical simulations to convincingly show that the purported benefits of nonlinear decay in morphogen gradients may be marginal in some cases and completely reversed in others (far from the concentration source). This is a valuable contribution to the field, as it questions common assumptions about the biological function of non-linear morphogen decays during development.

eLife assessment

This important study presents valuable findings on the dissemination of plasmids. In an analysis of five major Enterobacterales genera, the authors convincingly demonstrate that similar plasmids are shared between genera, species, and clones, both within and between ecological niches. Given the size of the dataset and the very detailed level of analysis this study importantly contributes to insights into to the flow of plasmids, including those carrying antimicrobial resistance genes, across niches.

eLife assessment

The authors characterize an H3N2 influenza A virus that jumped from birds into dogs in 2006. Through its evolutionary adaptation to dogs, the virus is now gaining properties that are increasingly consistent with the potential to infect humans. Using experiments with canine H3N2 influenza isolates, the authors found that more recent viruses have acquired receptor specificity for both avian- and human-like receptors, enhanced low-pH stability and in vitro growth, as well as improved replication and transmission in the dog and ferret models.