Evaluated articles

eLife assessment

This valuable prospective study develops a new tool to accelerate pharmacological studies by using neural networks to emulate the human ventricular cardiomyocyte action potential. The evidence supporting the conclusions is convincing, based on using a large and high-quality dataset to train the neural network emulator. There are nevertheless a few areas in which the article may be improved through validating the neural network emulators against extensive experimental data. In addition, the article may be improved through delineating the exact speed-up achieved and the scope for acceleration. The work will be of broad interest to scientists working in cardiac simulation and quantitative system pharmacology.

eLife assessment

This valuable paper presents a new protocol for quantifying tRNA aminoacylation levels by deep sequencing. The improved methods for discrimination of aminoacyl-tRNAs from non-acylated tRNAs, more efficient splint-assisted ligation to modify the tRNAs' ends for the following RT-PCR reaction, along with the use of an error-tolerating mapping algorithm to map the tRNA sequencing reads provide new tools for anyone interested in tRNA concentrations and functional states in different cells and organisms. The results and conclusions are solid, with well-designed tests to optimize the protocol under different conditions.

eLife assessment

In an important study that will be of interest to the mechanistic membrane transport community, the authors capture the first cryo-EM structure of the inward facing melbiose transporter MelB, a well-studied model transporter from the major facilitator (MFS) superfamily. Cryo-EM experiments and supporting biophysical experiments provide solid evidence for transporter conformational changes.

eLife assessment

This work explores the role of one the most abundant circRNAs, circHIPK3, in bladder cancer cells, showing with convincing data that circHIPK3 depletion affects thousands of genes and that those downregulated (including STAT3) share an 11-mer motif with circHIPK3, corresponding to a binding site for IGF2BP2. The experiments demonstrate that circHIPK3 can compete with the downregulated mRNAs targets for IGF2BP2 binding and that IGF2BP2 depletion antagonizes the effect of circHIPK3 depletion by upregulating the genes containing the 11-mer. These important findings contribute to the growing recognition of the complexity of cancer signaling regulation and highlight the intricate interplay between circRNAs and protein-coding genes in tumorigenesis.

eLife assessment

This study reports a comparative biochemical and structural analysis of two PLP decarboxylase enzymes from plants. The work is useful because of the potential application of these enzymes in industrial theanine production. The structure provides a solid basis for understanding substrate specificity but some aspects of the work are incomplete. The paper will be of interest to enzymologists studying PLP enzymes and those working on enzyme engineering in plants.

eLife assessment

This manuscript provides important insights into the degradation of the host tRNA modification enzyme TRMT1 by the SARS-CoV-2 protease Nsp5 (nonstructural protein 5 or MPro). The data convincingly support the main conclusions of the paper. These results will be of interest to virologists studying the alterations in tRNA modifications, host methyltransferases, and viral infections.

eLife Assessment

This valuable study significantly enhances our understanding of how various ligands and receptors interact within the Notch signaling pathway. By developing novel cell-based assay systems, the authors systematically analyzed the effects of different ligand-receptor combinations on pathway activation. The convincing data reveal intriguing and unexpected differences and provide a foundation for interpreting Notch signalling in both normal and disease-related contexts.

eLife Assessment

This important study describes the function of Laminin y1-dependent basement membranes in development of the olfactory placode, including morphogenesis of the placode, boundary formation, and olfactory axonal pathfinding. The study uses elegant live imaging approaches and extensive quantitative analyses, combined with detailed mutant analyses to provide a compelling description of the role of Laminin in olfactory placode development. In addition to the contributions this study makes to understanding olfactory placode development, it will also be of broader interest to individuals studying extracellular matrix regulation of tissue morphogenesis, and neural development including neuronal pathfinding.

eLife assessment

This comprehensive study provides valuable information on the cooperation of Ikaros with Foxp3 to establish and regulate a major portion of the epigenome and transcriptome of T-regulatory cells. While the data are compelling, the evidence that these features are solely intrinsic, independent of the micro-environment, could be strengthened.

eLife Assessment

This manuscript provides important structural insights into the recognition and degradation of the host tRNA methyltransferase TRMT1 by SARS-CoV-2 protease nsp5 (Mpro). The data provide compelling support for the main conclusions of the authors. These results will be of interest to researchers studying structures, substrate recognition and specificity of viral proteases and their action on cellular targets.

eLife assessment

This study shows compelling evidence that the less common D-serine stereoisomer is transported in the kidney by the neutral amino acid transporter ASCT2 and that it is a non-canonical substrate for sodium-coupled monocarboxylate transporter SMCTs. With a multi-hierarchical approach, this important study further shows that Ischemia-Reperfusion Injury in the kidney causes a specific increment in renal reabsorption carried out, in part, by ASCT2.

eLife Assessment

This valuable study investigates neural circuits mediating motor responses to cold in Drosophila larvae. Using a combination of behavioral analysis, genetic manipulations, EM connectomics, and reporters of calcium activity, the authors provide solid evidence that specific sensory and central neurons are required for cold-induced body contraction. This paper may be of interest to neuroscientists interested in how nervous systems sense and respond to cold.

eLife assessment

Using continuum theory of elastic solids the authors present evidence that periodic muscle contraction leads to elongation of C. elegans embryos by storing elastic energy that is subsequently released by extending the embryo's long axis. This important finding could apply to other developmental processes and be exploited in soft robotics. The presented evidence is convincing on the phenomenological level adopted in the work. How bending energy is converted into elongation on a more microscopic level remains to be worked out.

eLife assessment

This important study represents a follow-up of previous papers by Huff et al. (2023) in which the authors further investigate a specific medullary region named the Postinspiratory Complex (PiCo) involved in the control of swallow behaviour and its coordination with breathing. In the present work, they tested the impact of chronic intermittent hypoxia on the swallow motor pattern evoked by optogenetic stimulation of the same medullary area in transgenic mice. These solid results indicate that in chronic intermittent hypoxia-exposed mice PiCo stimulation triggers atypical swallow motor patterns. The experimental procedures are rigorous and technically remarkable. The work will be of interest in the field of respiratory physiology and pathophysiology since a disruption of swallowing and possibly discoordination with breathing may be involved in diseases characterized by the presence of hypoxic conditions such as obstructive sleep apnea.

eLife assessment

This manuscript provides a valuable demonstration that distractor effects in multi-attribute decision-making correlate with the form of attribute integration (additive vs. multiplicative). The evidence supporting the conclusions is convincing, but there are questions about how to interpret the findings. The manuscript will be interesting to decision-making researchers in neuroscience, psychology, and related fields.

eLife assessment

This valuable study uses convincing state-of-the-art neuroimaging analyses to characterise whole-brain networks during reward-based motor learning. This work motivates future research to dissociate why the observed changes in neural connectivity occur and how they support reward-based motor learning. The study is highly relevant for researchers at the intersection of decision-making and sensorimotor learning.

eLife assessment

This study by Ghafari et al. tackles a question relevant for the field of attention as it connects structural differences in subcortical regions with oscillatory modulations during attention allocation. Using a combination of Magnetoencephalography (MEG) and magnetic resonance imaging (MRI) data in human subjects, the valuable results show that inter-individual differences in the lateralisation of alpha oscillations are explained by asymmetry of subcortical brain regions. The strength of evidence is deemed convincing in line with current state-of-the-art.

eLife assessment

Miyano et al. study the impact of RIM-BP2 deletion at mossy fiber synapses, using direct electrophysiological recordings from mossy terminals and STED super-resolution microscopy. The paper addresses an important question in the field of synaptic transmission and provides compelling evidence demonstrating reduced calcium channel abundance in mossy terminals upon RIM-BP2 removal.

eLife assessment

The authors present a comprehensive set of tools to compactly characterize the time-frequency interactions across a network. The utility of the toolbox is compelling and demonstrated through a series of exemplar brain imaging datasets. This fundamental work adds to the repertoire of techniques that can be used to study high-dimensional data.

eLife assessment

This study presents important insights on the impact of SARS-CoV-2 variants on the binding and neutralization of a small library of nanobodies. The authors should be applauded for their comprehensive in vitro and in silico analyses of nanobody targeting of SARS-CoV-2 variants. The evidence supporting the claims of the authors is now convincing. This work will be of great interest to researchers in the fields of antibody/nanobody engineering and SARS-CoV-2 therapeutics.