Evaluated articles

eLife Assessment

This valuable study presents a mechanistic model of predictive coding by medial entorhinal cortex grid cells, implemented with biologically detailed conductance-based neurons. The evidence supporting the emergence of this coding scheme from specific membrane currents and the anatomical connectivity among inhibitory neurons is solid. However, the justification for the choice of connectivity patterns and other network parameters remains somewhat incomplete. This work will be of interest to neuroscientists working on spatial navigation, circuit dynamics, and neuronal coding.

eLife Assessment

Complementing previous work (Namiki et al, 2018), this study provides an important resource for the Drosophila community as it reports 500 lines targeting descending neurons (DN), in addition to compiling 306 existing DN lines from the literature. The compelling work characterizes 146 DNs and makes a critical link with the DNs identified in Electron microscopy (EM). The lines in this paper will be of interest to Drosophila neuroscientists who will be able to use the reported genetic drivers for further functional characterization of DNs and circuit mapping in conjunction with existing EM datasets.

eLife Assessment

Using single-cell transcriptomic data from mouse inner ear hair cells, the authors compare for the first time gene expression across the four recognized hair cell types in adults, generating information fundamental to understanding hair cell relationships between the ancient vestibular compartment and the more recent cochlea. Among observed differences, compelling evidence is provided for the expression in vestibular hair cells but not cochlear hair cells of certain ciliary motility-related genes, suggesting that the kinocilium of vestibular hair cells may function as an active force generator to increase sensitivity.

eLife Assessment

This useful study provides new insights into the liver stage antigen LSA3, its export to erythrocytes, and its role in liver stage development. While the functional importance of LSA3 is well-demonstrated, the data underlying conclusions about antibody specificity, liver stage localization, and phenotype remain incomplete. A key gain is the use of mosquito and humanized mouse models to access life cycle stages rarely studied in most laboratories.

eLife Assessment

This valuable study characterizes the emergence of the membrane-associated periodic cytoskeleton (MPS) in the axons of human motor neurons derived from induced pluripotent stem cells. Super-resolution imaging of beta-II spectrin provides convincing evidence for the patterned assembly of spectrin-poor gaps and spectrin-rich MPS in the medial region of the axons and its enhancement by the kinase inhibitor staurosporine. The data advocates against gap formation by axonal degeneration or cytoskeleton disassembly in a continuous MPS. Instead, a continuous MPS may result from nascent MPS patches and their maturation, a model that would benefit from live imaging for validation.

eLife Assessment

To evaluate phenotypic correlations between complex traits, this study aimed to measure the genetic overlap of traits by evaluating GWAS signals assisted by eQTL signals. They suggested an improved version of the previous Sherlock to integrate SNP-level signals into gene-level signals. Then they compared 59 human traits to identify known and novel genetic distance relationships. This work is valuable to the field, but still needs substantial improvement because many parts of the paper are incomplete.

eLife Assessment

This valuable study introduces a data augmentation approach based on generative unsupervised models to address data imbalance in immune receptor modeling. Support for the findings is solid, showing that the use of generated data increases the performance of downstream supervised prediction tasks, e.g., TCR-peptide interaction prediction. However, the validation, mainly relying on synthetic data, could be completed, especially regarding unseen epitopes, and given the exclusive focus on CDR3β. The results should be of interest to the communities working on immunology and biological sequence data analysis.

eLife Assessment

This important study combines microscopy and CRISPR screening to identify factors involved in global chromatin organisation, using centromere clustering as a proxy. The authors present solid evidence demonstrating that acute depletion of a range of mitotic regulators alters centromere distribution in interphase. The work will be of interest to researchers studying genome organisation, nuclear architecture, chromosome biology, and the mechanisms linking mitosis to interphase nuclear organisation.

eLife Assessment

The analysis of neural morphology across Heliconiini butterfly species revealed brain area-specific changes associated with new foraging behaviours. While the volume of the centre for learning and memory, the mushroom bodies, was known to vary widely across species, these new, valuable results show conservation of the volume of a center for navigation, the central complex, but with specific changes in neuropeptide expression in the noduli and in the numbers of ellipsoid body ring neurons. The presented evidence is convincing for both volumetric conservation in the central complex and fine neuroanatomical differences associated with pollen feeding, delivered by experimental approaches that are applicable to other insect species. This work will be of interest to evolutionary biologists, entomologists, and neuroscientists.

eLife Assessment

This study offers a valuable theoretical framework for quantifying molecular transport across interfaces between coexisting liquid phases, emphasizing interfacial resistance as a central factor governing transport kinetics. The mathematical derivations are solid. To enhance the paper's relevance and broaden its appeal, it would be helpful to clarify how the key equations connect to existing literature and to elucidate the physical mechanisms underlying scenarios that give rise to substantial interfacial resistance.

eLife Assessment

This valuable work advances our understanding of the relationship between multimodal magnetic resonance imaging (MRI) measures, cognition, and mental health. Compelling use of statistical learning techniques in UK Biobank data shows that 48% of the variance between an 11-task derived g-factor and imaging data can be explained. Overall, this paper contributes to the study of brain-behaviour relations and will be of interest for both its methods and its findings on how much variance in g can be explained.

eLife Assessment

This important study investigates the self-assembly activity of all 109 human death-fold domains. The data collected using advanced microscopy and distributed amphifluoric FRET-based flow cytometry methods are compelling to support the "phase change battery" model that explains how signal amplification can occur without ATP consumption. This paper provides new insight into the thermodynamic control of protein phase behaviors within cells and will be of interest to those studying a variety of biological pathways involved in inflammatory responses and various forms of cell death.

eLife Assessment

This study in the Drosophila antennal lobe, which contains multiple non-equivalent sensory channels, provides valuable new insight into how early-life sensory experience can produce lasting, cell-type-specific changes in neural circuit function. The work convincingly demonstrates that glial-mediated pruning during a defined developmental window leads to persistent suppression of odor responses in one olfactory neuron type, while sparing another. The evidence is solid and supported by multiple complementary approaches, although some mechanistic interpretations remain speculative and would benefit from additional functional testing.

eLife Assessment

The authors used three genetically diverse mouse models to investigate the impact of genome diversity on metabolic disease outcomes, such as obesity and glucose tolerance. This study is important because it integrates comprehensive metabolic analyses and multi-tissue phenotyping across sexes to reveal pathways relevant to obesity and its complications; the data are convincing and uncover several pathways that advance understanding of disease etiology while suggesting potential therapeutic avenues to prevent obesity-related health risks. There are limitations, such as a limited number of mouse strains used in the work, the 9-week feeding regime may be too short to capture full metabolic remodeling, and the mechanisms by which the immune-adipose axis impacts the broader phenotype are not fully described. Overall, the study is compelling, but the manuscript could be improved by justifying the strain selection, addressing the concern about the feeding duration, and providing stronger mechanistic support or discussion.

eLife Assessment

This work provides an important resource identifying 72 proteins as novel candidates for plasma membrane and/or cell wall damage repair in budding yeast, and describes the temporal coordination of exocytosis and endocytosis during the repair process. The data are convincing; however, additional experimental validation will better support the claim that repair proteins shuttle between the bud tip and the damage site.

eLife Assessment

This study offers important insights into how entorhinal and hippocampal activity support human thinking in feature spaces. It replicates hexagonal symmetry in entorhinal cortex, reports a novel three-fold symmetry in both behavior and hippocampal signals, and links these findings with a computational model. The task and analyses are sophisticated, and the results appear convincing and of broad interest to neuroscientists.

eLife Assessment

This fundamental manuscript presents a novel application of the SANDI (Soma and Neurite Density Imaging) model to study microstructural alterations in the basal ganglia of individuals with Huntington's disease (HD). The compelling methods are, to our understanding, the first application of SANDI to neurodegenerative diseases, provide strong evidence for HD-related neurodegeneration in the striatum, account significantly for striatal atrophy, and correlate with motor impairments. The integration of novel diffusion acquisition and modelling methods with multimodal behavioural data are both of high value in their own right, and create a framework for future studies.

eLife Assessment

This manuscript presents useful insights into the molecular basis underlying the positive cooperativity between the co-transported substrates (galactoside sugar and sodium ion) in the melibiose transporter MelB. Building on years of previous studies, this convincing study improves on the resolution of previously published structures and reports the presence of a water molecule in the sugar binding site that would appear to be key for its recognition, introduces further structures bound to different substrates, and utilizes binding and transport assays, as well as HDX-MS and molecular dynamics simulations to further understand the positive cooperativity between sugar and the co-transported sodium cation. The work will be of interest to biologists and biochemists working on cation-coupled symporters, which mediate the transport of a wide range of solutes across cell membranes.

eLife Assessment

The study showcases a significant and important enhancement of the MAGIC transgenesis method, by extending it genome-wide to all chromosomes. The authors provide compelling evidence to demonstrate that the MAGIC mosaic clones can be generated for genes from all, including the 4th chromosome. With this toolkit extension, the method is set to complement the classical FRT/Flp recombination system for gene manipulation in flies.

eLife Assessment

This is a valuable study that presents human single nuclei RNA-seq and spatial transcriptomics data of the developing outflow tract and adult aortic valves that will facilitate research in this area. Data presented are solid, with bioinformatics analyses showing cell lineage and trajectory relationships, intriguingly suggesting persistence of embryonic signature in adult aortic valve cells. The latter results would be strengthened by experimental validation.