Evaluated articles

eLife assessment

This study uses top-notch spatial profiling methods to present a valuable account of the number of different neuron types in the central nucleus of the amygdala of the mouse. The approaches and evidence presented are compelling, but the analysis is incomplete and would benefit from increases in sample size. With this aspect strengthened, this paper would be of interest to neuroscientists investigating the function of the central amygdala.

eLife assessment

Here, Morgan and colleagues report a novel synthetic lethal interaction between nucleoporin inhibition and KRAS-driven hepatocyte hyperproliferation. The authors show that nucleoporin inhibitor treatment or heterozygosity of nucleoporin genes (ahctf1 and/or ranbp2) suppresses KRAS-driven zebrafish larval liver overgrowth, providing impetus for developing Nup inhibitors as hepatocellular carcinoma treatment. Their data provide insights into the consequences of nucleoporin inhibition in cancer, demonstrating that disrupting ahctf1 decreases proliferation and promotes apoptosis by impairing nuclear pore formation and mitotic spindle assembly through a mechanism that may be at least partially dependent on tp53.

eLife assessment

This study addresses whether the composition of the microbiota influences the intestinal colonization of encapsulated vs unencapsulated Bacteroides thetaiotaomicron, a resident micro-organism of the colon. This is an important question because factors determining the colonization of gut bacteria remain a critical barrier in translating microbiome research into new bacterial cell-based therapies. To answer the question, the authors develop an innovative method to quantify B. theta population bottlenecks during intestinal colonization in the setting of different microbiota. Their main finding that the colonization defect of an acapsular mutant is dependent on the composition of the microbiota is valuable and this observation suggests that interactions between gut bacteria explains why the mutant has a colonization defect. The evidence supporting this claim is currently insufficient. Additionally, some of the analyses and claims are compromised because the authors do not fully explain their data and the number of animals is sometimes very small.

eLife assessment

There is an urgent need to improve prognostication of diabetic kidney disease in different diverse populations so this study is valuable in identifying specific predictive factors in a cohort of South East Asian populations whose baseline risk is higher. There are some limitations: the assumptions the authors make and the methods would benefit from some more investigation/validation.

eLife assessment

This is an important study that shows how Snf1/AMP Kinase fine-tunes TORC1 signaling in response to glucose starvation. Their observation that Snf1 phosphorylation of the TORC regulator Pib1 and the TORC effector kinase Sch9 provides new mechanistic information on this important pathway involved in cell growth. The combination of phosphoproteomics, genetic, biochemical, and physiological experiments is generally convincing, although the results with the Pib2 SA and SE mutants are somewhat inconsistent.

eLife assessment

This fundamental study presents solid evidence for T1r (sweet /umami) taste receptors as chloride (Cl-) receptors, based on a combination of state-of-the-art techniques to demonstrate that T1r receptors from Medaka fish bind chloride and that this binding induces a conformational change in the heteromeric receptor. This conformational change leads to low-concentration chloride-specific action potential firing in nerves from neurons containing these receptors in mice, results that represent an important advance in our understanding of the logic of taste perception.

Endorsement statement (17 November 2022)

The preprint by Atsumi et al. describes how chloride binding to sweet- and umami-sensing proteins (T1R taste receptors) can evoke taste sensation. The authors use an elegant combination of structural, biophysical and electrophysiological approaches to locate a chloride binding site in the ligand-binding domain of medaka fish T1r2a/3 receptors. They convincingly show that low mM concentrations of chloride induce conformational changes and, using single fiber recordings, establish that mouse chorda tympani nerves are activated by chloride in a T1R-dependent manner. This suggests that chloride binding to sweet receptors could mediate the commonly reported sweet taste sensation following ingestion of low concentrations of table salt. The findings will be of broad relevance to those studying taste sensation and ligand recognition in GPCRs.

(This endorsement by Biophysics Colab refers to version 2 of this preprint, which has been revised in response to peer review of version 1.)

eLife assessment

This valuable study presents a potentially interesting contribution on animal caching behaviour. At present, evidence that the flying squirrels themselves modified the nuts is incomplete, but there are clear video observations of them associating with the nuts. Either way, the images of the modified nuts and the detailed descriptions of the caching behaviour describe a new technique for storing nuts in a tropical rainforest.

eLife Assessment

This important manuscript presents a thorough analysis of trans-specific polymorphism (TSP) in Major Histocompatibility Complex gene families across primates. The analysis makes the most of currently available genomic data and methods to substantially increase the amount and evolutionary time that TSPs can be observed. Both false negative TSPs due to missing genes at the assembly and/or annotation level, as well as false positives due to read mismapping with missing paralogs, are well assessed and discussed. Overall the evidence provided is compelling, and the manuscript clearly delineates the path for future progress on the topic.

eLife assessment

This valuable study substantially advances our understanding of the phenotypic divergence of the plague-causing bacterium, Yersinia pestis, from a closely related species, Yersinia pseudotuberculosis, which causes much milder disease. The authors provide convincing evidence that a frameshift mutation in the Y. pestis rcsD gene changes a signaling pathway that contributes to the flea-mammal transmission of plague. The work shows how small genetic differences can alter pathogenicity and stress survival.

eLife assessment

Exploiting the power of the Drosophila larva as a model, Liu et al.'s important study sheds light on the neuronal mechanisms of speed regulation during locomotion. The data obtained using a combination of functional and structural approaches are mostly rigorous and convincing, but there are concerns about the small number of animals analysed in some of the behavioural experiments.

eLife assessment

This important study offers compelling evidence, in the form of a rigorous and clear analysis of SARS-CoV-2 mutations observed within non-human animal hosts, of viral mutations that may provide an adaptive advantage within hosts. The authors could, however, improve the description of some elements of their methods and analysis approach, and they should cite additional relevant literature. The findings are relevant to those interested in the ecology of infectious disease, epidemiology, and specifically those who are interested in the genetic underpinnings of pandemic potential.

eLife assessment

This paper introduces a fundamentally new automated method for assigning cell types and distinguishing organs in electron microscope (EM) reconstructions, a process that was previously manual. The authors present compelling evidence that their approach works as well or better than human efforts, in at least one species. This new method can help avoid a known bottleneck in EM reconstructions, one that will otherwise limit the ability of EM to scale up to larger volumes and target additional animal species. The main limitation is that the method has only been tested on a single species, but if tests show similar performance on other animals, the method will likely become a mainstay of EM reconstruction efforts.

eLife assessment

This manuscript has a number of important findings in the interesting area of attempts to rescue neurodevelopmental phenotypes in the postnatal setting. Ameliorating some of the symptoms of Angelman syndrome at later stages is potentially of major clinical significance and this study provides support for that possibility. More generally, this study also shows that treatment of a syndrome like Angelman with antisense oligonucleotides to modulate allele-specific expression at later stages of life has potential.

eLife assessment

This manuscript presents a theory of generalization in neural population codes and proposes sample efficiency as a new normative principle distinct from efficient coding. The theory suggests that, with small numbers of training examples, generalization performance depends exclusively on the population code's 'kernel' (pairwise similarity between population activity patterns), and that sample-efficient learning depends on whether the task is aligned with the population's inductive bias (i.e., the top eigenfunctions of the kernel). The theory can be used to identify the set of 'easily learnable' stimulus-response mappings from neural data which makes strong behavioral predictions that can be easily evaluated.

eLife assessment

The authors present an important study of the effects of chronic hepatic FGF21 overexpression on the development of non-alcoholic steatohepatitis (NASH) in a model of obesity and dyslipidemia, i.e. ApoE3-Leiden CETP transgenic mice fed a western diet. NASH is a major global health problem and exogenous FGF21 treatment has been explored as a therapeutic strategy. The authors find that chronic overexpression of FGF21 blocks weight gain on the western diet, and even induces some weight loss compared to the control diet. The findings are convincing and methodologically sound.

eLife assessment

This manuscript provides a valuable resource for scientists who wish to manipulate second messengers in zebrafish using optogenetics. The authors provide solid evidence, based on behaviour, monitoring of heart beat and imaging, that several of the opsins tested can have an effect in larval fish. Opsins that lack an effect are also described. As the second messengers affected by the tools are found in multiple cell types, the results should be of interest of scientists working in a variety of areas.

eLife assessment

This work provides a potentially useful resource for scientists who wish to use optogenetics to manipulate GPCR signalling in larval zebrafish. It compares the physiological effects of different vertebrate and invertebrate rhodopsins expressed in either reticulospinal neurons or cardiomyocytes. The evidence for light-induced effects on behavior (either tail bending or heart beating) is solid, although only limited cell types and conditions are tested.

eLife assessment

In this important work, the authors develop a theory for the co-evolutionary dynamics of bacteria and phages, where the major evolutionary pressure comes from CRISPR-Cas adaptive immunity in bacteria. Through extensive stochastic numerical simulations and analytical calculations, the paper presents a compelling analysis of the emergent properties of immune interactions, in the regime of a single proto-spacer and a single spacer. Some of the trends highlighted by the model are recovered from experimental data. The main results concern how diversity in both phage and bacteria population are linked and are shaped by immunity, and should be of broad interest in immunology.

eLife assessment

This is a valuable paper that relates the function of Ephrin-B1 to diastolic dysfunction via its actions on maturation of cardiomyocytes. The mechanisms of diastolic heart failure remain poorly understood, and this work contributes to advancing our understanding. The hypothesis is novel and the manuscript is fairly extensive and well-illustrated. The data, methods and analyses are presented to the community in a solid manner. The work represents an interesting insight into potential mechanisms of diastolic dysfunction and heart failure with preserved ejection fraction.

eLife assessment

This manuscript is of interest to neuroimaging scientists and neurophysiologists studying the glymphatic system. Using a multi-modal approach including magnetic resonance and histological methods, this work provides substantial data interrogating the effect of removing of aquaporin-4 (AQP4) from the mouse brain parenchyma on the structural morphology and interstitial fluid dynamics stagnation. In particular, the authors provide evidence that deletion of AQP4 in mice results in increased interstitial volume, likely due to increased resistance to parenchymal CSF efflux.