Evaluated articles

eLife assessment

This convincing study advances our understanding of the physiological consequences of the strong overexpression of non-toxic proteins in baker's yeast. The findings suggest that a massive protein burden results in nitrogen starvation and a shift in metabolism likely regulated via the TORC1 pathway, as well as defects in ribosome biogenesis in the nucleolus. The study presents findings and tools that are important for the cell biology and protein homeostasis fields.

eLife Assessment

Kan et al. report the discovery of a Bacillus amyloliquifaciens strain that kills Nerisseria gonorrhoeae via oxydifficidin which targets ribosomal proteins. Resistance occurred via mutation in the DedA flippase to influence oxydifficidin uptake. The overall mechanism of action is well described making this an important study with implications for combating clinical antibiotic resistance. The evidence presented is convincing due to rigour employed in the methodological approach. The authors should consider performing a more comprehensive genetic analyses of DedA and RpIL in this clinically relevant strain. This work will be of broad interest to microbiologists and synthetic biologists.

eLife Assessment

This revised manuscript presents an important characterization of mouse auditory cortex receptive field organization, utilizing two-photon imaging of specific subpopulations. They demonstrate a degradation of tonotopic organization from the input to the output neurons. The strength of the evidence is convincing.

eLife Assessment

This study resolves a cryo-EM structure of the GPCR, human GPR30, which responds to bicarbonate and regulates cellular responses to pH and ion homeostasis. Understanding the ligand and the mechanism of activation is important to the field of receptor signaling and potentially facilitates drug development targeting this receptor. Structures and functional assays provide solid evidence for a potential bicarbonate binding site.

eLife Assessment

This study provides new single-cell multi-omics datasets that may be useful in the study of early cardiac lineages. However, the authors' conclusions regarding the mutual regulation of key regulators for cardiac specification and new cardiac lineage trajectories are inadequately supported by persuasive analysis and do not align with prior published studies. If revised to address the serious caveats adequately, the findings may be of interest to researchers in the field of cardiac development and congenital heart disease.

eLife Assessment

This study presents a valuable finding on predator threat detection in C. elegans and the role of neuropeptide systems in defensive behavioral strategies. The evidence supporting the conclusions is solid, although additional analyses and control experiments would strengthen the claims of the study. Overall, the work is of interest to the C. elegans community as well as neuroethologists and ecologists studying predator-prey interactions.

eLife Assessment

This important and well-executed study describes how deleting the autism spectrum disorder risk gene CNTNAP2 in mice increases dorsolateral striatal projection neuron excitability and promotes repetitive behaviors and cognitive inflexibility. The evidence supporting this claim is convincing. The study provides a potential cellular explanation for the repetitive and inflexible behavior in Cntnap2 knockout mice and CNTNAP2 disorder in humans, which would interest both basic and translational neuroscientists.

eLife Assessment

This important study utilizes humanized mice, in which human immune cells are introduced into immune-deficient mice, to provide convincing evidence that two helper CD4 T-cell subsets, T-follicular helper (Tfh) and T-peripheral helper (Tph) cells, are able to drive both autoantibody production and induction of autoimmunity. The work will be of broad interest to medical scientists engaged in deciphering how human immune cells mediate immune responses and contribute to the development of autoimmune diseases.

eLife Assessment

This study offers a valuable treatment of how the population of excitatory and inhibitory neurons integrates principles of energy efficiency in their coding strategies. The convincing analysis provides a comprehensive characterisation of the model, highlighting the structured connectivity between excitatory and inhibitory neurons. The role of the many free parameters are discussed and studied in depth.

eLife Assessment

The study describes a valuable new technology in the field of targeted protein degradation that allows identification of E3-ubiquitin ligases that target a protein of interest. The presented data are convincing, however, additional work will be needed to optimize for high-throughput evaluation. This technology will therefore serve the community in the initial stages of developing targeted protein degraders.

eLife Assessment

Lloyd et al. used an evolutionary comparative approach to study DNA damage repair associated with low sleep duration in Astyanax mexicanus, highlighting how the cavefish population has evolved a reduced DNA damage response. The results presented here have important implications. Their results are generally solid however, the evidence suggesting that sleep differences are linked to DNA damage response is missing and this hypothesis remains to be fully tested.

eLife Assessment

In this valuable contribution, the authors present a novel and versatile probabilistic tool for classifying tracking behaviors and understanding parameters for different types of single-particle motion. The software package will be broadly applicable to single-particle tracking studies. The methodology has been convincingly tested by computational comparisons and experimental data, although the mathematical foundation for the hypothesis testing method can be further strengthened.

eLife Assessment

This valuable study uses high-field fMRI to test the hypothesized involvement of subcortical structures, particularly the striatum, in updating working memory. The study overcomes limitations of prior work by applying high-field imaging with a more precise definition of regions of interest in the brain. Thus, the empirical observations are of use to specialists interested in working memory gating or the reference back task specifically. The evidence is generally solid, but strong conclusions on dopaminergic contributions must await additional work using molecular imaging or related techniques.

eLife Assessment

This study provides valuable advances in our understanding of how inputs from multiple sources can impact the physiology of motor neurons during the process of multisensory integration. Specifically, the authors show how streams of auditory and principally visual information modulate the physiology of Mauthner neurons in goldfish, thus allowing the different senses to influence escape behavior. Supporting evidence is generally convincing, although material reporting the direct control of behavior is less representative of the data.

eLife assessment

This study represents an important contribution to the study of decision-making under risk, bringing an interdisciplinary approach spanning economic theory, behavioral neuroscience, and computational modeling to test how choice preference is influenced by rare and extreme events. The authors present evidence that rats are indeed sensitive to these rare and extreme events despite their infrequent occurrence, driven primarily by an almost complete avoidance of "Black Swans" - rare and extreme losses. The evidence for specific sensitivity to rare and extreme events however remains incomplete, owing in part to the difficulty of isolating the effect of these events beyond that arising from risk preferences more generally in both task design and in the computational modeling of the choice behavior. Given the approach here brings a relatively novel perspective, with a more detailed treatment of these confounds this paper will be of broad interest to those seeking to understand animal behavior through the lens of economic choice.

eLife assessment

This valuable study provides insights into how the brain learns to better detect a target by predicting when the target may appear. Overall, solid evidence is provided that the power fluctuations of alpha- and beta-band oscillations can reflect the predicted occurrence time of the target, but some conclusions, especially ones related to the neural-network model and temporal gain control account, need further consideration. The study highlights an advanced EEG analysis approach as well as a close combination of human EEG analysis and computational modeling using recurrent neural networks.

eLife Assessment

This study represents a valuable addition to the catalog of mitochondrial proteins. With the use of methodology based on the bi-genomic split-GFP technology, the authors generate convincing data, including dually localized proteins and topological information, under various growth conditions in yeast. The study represents a key basis for further functional and/or mechanistic studies on mitochondrial protein biogenesis.

eLife assessment

This study provides a valuable contribution to the development of small molecules that inhibit the aggregation of tau, a protein involved in several neurodegenerative diseases. The authors present convincing evidence that analogs of the plant alkaloid tryptanthrin can prevent the formation of larger aggregates by targeting the early stages of tau oligomerization. Nevertheless, further studies are needed to elucidate the precise mechanisms of action and to provide a detailed kinetic analysis. This work will be of interest to biochemists and biophysicists focused on designing small molecules to inhibit fibril formation.

eLife Assessment

This paper reports important findings on giant organelle complexes containing endosomes and lysosomes (termed endosomal-lysosomal organelles form assembly structures [ELYSAs]) present in mouse oocytes and 1- to 2-cell embryos. The data showing the localization and dynamics of ELYSAs during oocyte/embryo maturation are convincing. This work will be of interest to general cell biologists and developmental biologists.

eLife Assessment

A combination of molecular dynamics simulation and state-of-the-art statistical post-processing techniques provided valuable insight into GPCR-ligand dynamics. This manuscript provides solid evidence for differences in the binding/unbinding of classical cannabinoid drugs from new psychoactive substances. The results could aid in mitigating the public health threat these drugs pose.