Evaluated articles

eLife assessment

The authors performed a useful RNAi screen to identify epigenetic regulators involved in oxygen-glucose deprivation (OGD)-induced neuronal injury. PRMT5 was identified as a negative regulator of neuronal cell survival after OGD. Solid in vitro and in vivo data suggest that PRMT5 could be a novel therapeutic target for the treatment of ischemic stroke.

eLife assessment

This study presents solid evidence to support the effectiveness of the novel eIF2B activator DNL343 in mitigating the integrated stress response (ISR) and reducing neurodegeneration associated with ISR activation in two mouse models. These important findings offer promise for the potential use of DNL343 in treating vanishing white matter disease (VWMD), a rare condition resulting from eIF2B loss of function, and in addressing other neurodegenerative disorders characterized by ISR involvement. The study also identified potential VWMD biomarkers, which hold significance for assessing disease progression and evaluating treatment responses.

eLife Assessment

This comprehensive study presents important findings that delineate how specific dopaminergic neurons (DANs) instruct aversive learning in Drosophila larvae exposed to high salt through an integration of behavioral experiments, imaging, and connectomic analysis. The work reveals how a numerically minimal circuit achieves remarkable functional complexity, with redundancies and synergies within the DL1 cluster that challenge our understanding of how few neurons generate learning behaviors. By establishing a framework for sensory-driven learning pathways, the study makes a compelling and substantial contribution to understanding associative conditioning while demonstrating conservation of learning mechanisms across Drosophila developmental stages.

eLife assessment

The valuable findings in this study show that subpopulations of peripheral sensory neurons display different capacities for regeneration after a similar injury. Nociceptor neurons have greater regeneration over mechanoreceptor, proprioceptors and motor neurons. This differential responsiveness of neuronal subtypes was traced to activation of different transcriptional programs, which were carefully analyzed and quantitated, resulting in solid evidence for the conclusions.

eLife assessment

This important paper sheds light on the role of expectations in perceptual decision-making. Sophisticated analyses of human EEG data provide convincing evidence that both motor preparation and sensory processing were affected by expectations, albeit with different time courses. These findings will be of interest to scientists interested in perception and decision-making.

eLife Assessment

This important study extends the previous interesting work of this group to address the potentially different control of movement and posture. Through experiments in which stroke participants used a robotic manipulandum, the authors provide solid evidence supporting a lack of a relation between the resting force postural bias they measure (closely related to the flexor synergy in stroke) and kinematic deficits during movement. Based on these results, the authors propose a conceptual framework that differentially weights the two main descending pathways (corticospinal tract and reticulospinal tract) for neurologically intact and stroke patients.

eLife assessment

This fundamental study has major implications that can be paradigm-shifting for our understanding of how the phage lambda DNA motor works and what the precise roles of the TerS and TerL proteins in the motor complex are. The experiments are exceptionally well done, providing compelling evidence for the conclusion of the authors.

eLife Assessment

O'Brien and co-authors addressed how statins reduce levels of aldosterone in humans and provide important data demonstrating that tissue-resident macrophages can exert physiological functions and influence endocrine systems. However, the strength of evidence, as of now, is incomplete, as the sole description of the phenotype of MARCO-deficient mice is insufficient to claim that MARCO in alveolar macrophages can negatively regulate ACE expression and aldosterone production at steady-state. The work will be of broad interest to cell biologists and immunologists.

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.