Evaluated articles

eLife Assessment

Cav2 voltage-gated calcium channels play key roles in regulating synaptic strength and plasticity. In contrast to mammals, invertebrates like Drosophila encode a single Cav2 channel, raising questions on how diversity in Cav2 is achieved from a single gene. Here, the authors present solid evidence that two alternatively spliced Cac isoforms enable important changes in Cav2 expression, localization, and function in synaptic transmission and plasticity at the Drosophila neuromuscular junction. How the isoforms affect synaptic calcium channel levels remains less clear. This study provides insights into the roles of voltage-gated calcium channel splice isoforms in synaptic transmission.

eLife Assessment

This study describes the impact of mycobacterial genetic diversity on host-infection phenotypes by assessing the effect of different M. tuberculosis lineages on granulomatous inflammation using a 3D in vitro granuloma model. Despite being descriptive and showing mostly correlative relationships, the findings are useful and provide some solid support regarding the functional impact of M. tuberculosis's natural diversity on host-pathogen interactions. The study will interest researchers working on mycobacteria and motivate future studies to understand how genetic diversity influences virulence and immunity outcomes.

eLife Assessment

The study is a valuable contribution to the question of evolutionary shifts in neuronal proliferation patterns and the timing of developmental progressions. The authors present convincing data which confirm the presence of type-II NB lineages in beetle with the same molecular characteristics as the Drosophila counterparts but differing in lineage size and number. The data lay the foundation for future analysis of the role and molecular characteristics of individual lineages and of whether differences in the identity, proliferation pattern and timing of developmental progression can be linked to differences in the development of functionality of the central complex.

eLife Assessment

This important manuscript describes a creative approach using dual-component gRNAs to create a new class of molecular proximity sensors for genome editing. The authors demonstrate that this tool can be coupled with several different gene editing effectors, showing convincingly that the tool functions as intended. This study not only introduces a first-of-its kind approach, but through careful measurements also enables future further development of the technology.

eLife Assessment

This is an important study providing compelling evidence that the Mediator kinase module mediates an elevated inflammatory response, manifested by heightened cytokine levels, associated with Downs syndrome (DS) via transcriptional changes impacting cell signaling and metabolism that involve mobilization of nuclear receptors by altered lipid metabolites, which has significance for the treatment of DS and other chronic inflammatory conditions. Particular strengths of the study include the combined experimental approaches of transcriptomics, untargeted metabolomics and cytokine screens and the use of sibling matched cell lines (trisomy 21 vs disomy 21) from various donors. Evidence is also provided implicating the Mediator kinase module in controlling mRNA splicing and mitochondrial function that should stimulate new research to elucidate the mechanistic bases for these novel functions.

eLife Assessment

This is an important study that provides CCR7-APEX2 proximity labelling mass spectrometry data that is expected to provide new insights into CCR7 signaling partners and pathways. The study is technically easy to follow and the data is convincing. It will be interesting in the future to have complementary studies in lymphocytes/dendritic cells that endogenously express CCR7. This is of value to the community, and there are likely multiple opportunities to use the APEX2 data set to extend these findings, strengthen some claims, and even explore a new pathway identified in the APEX2 data set.

eLife Assessment

This important study reports findings on the GnRH pulse generator's role in androgen-exposed mouse models, providing further insights into PCOS pathophysiology and advancing the field of reproductive endocrinology. The experimental data were collected using cutting-edge methodologies and are solid. The findings, while interesting, are primarily applicable to mouse models, and their translation to human physiology requires cautious interpretation and further validation. This work will be of interest to endocrinologists and reproductive biologists.

eLife assessment

This important study provides novel evidence that navigational experiences can shape perceptual scene representations. The evidence presented is incomplete and would benefit from clearer explanations of the experiment design and careful discussion of alternative interpretations such as contextual associations or familiarity. The work will be of interest to cognitive psychologists and neuroscientists working on perception and navigation.

[Editors’ note: A revised version of this work has been published in the Journal of Cognitive Neuroscience (DOI: https://doi.org/10.1162/JOCN.a.2409).]

eLife Assessment

These studies make a fundamental contribution to our understanding of axon-guidance mechanisms, focusing on the role of UNC-6/Netrin in the long-range growth and targeting of axons. Using state-of-the-art genetics and in vivo imaging, the authors provide compelling support for the finding that UNC-6/Netrin can act via both chemotaxis and haptotaxis. This work will be of interest to a wide variety of cell and developmental biologists and neuroscientists.

eLife Assessment

Kreeger et al. convincingly demonstrate that octopus cells in the mouse cochlear nucleus, previously thought to rely primarily on excitatory inputs for coincidence detection, also receive glycinergic inhibitory synaptic inputs that influence their synaptic integration. Using advanced techniques, including genetic mouse models, optogenetics, microscopy, slice physiology, and computational modeling, this important study reveals that inhibition can shunt synaptic currents and alter the timing of dendritic EPSPs, both of which are significant for auditory processing. This research broadens the understanding of octopus cells' roles in sensory processing, highlighting the importance of inhibitory inputs in shaping fast, high-frequency neural response capabilities.

eLife Assessment

This study provides an important understanding of the contribution of different striatal subregions, the anterior Dorsal Lateral Striatum (aDLS) and the posterior Ventrolateral Striatum (pVLS), to auditory discrimination learning. The authors have included robust behavior combined with multiple observational and perturbation techniques. The data provided are convincing of the relevance of task-related activity in these two subregions during learning.

eLife Assessment

This manuscript reports a detailed model of juvenile rat somatosensory cortex, consisting of 4.2 million morphologically and biophysically detailed neuron models, arranged in space and connected according to diverse experimental data - a valuable tool for the field. The construction of the model is based on a methodology with solid supporting evidence. It should be noted that, by necessity, such a large-scale model development involves many assumptions, interpolations, and decisions that could have compounding downstream effects on further analyses that may be difficult to disambiguate.

eLife assessment

This important study compared the brain development trajectories of humans and macaque monkeys to quantify different evolutionary effects of convergent and divergent neural pathways between the two species. The cross-species evidence is solid, based on brain age prediction models that were carefully developed by using public MRI datasets of both humans and macaque monkeys. The findings will be of interest to neuroscientists, developmental biologists, and evolutionary biologists.

eLife assessment

This important study explores and delineates multivariate mappings between brain structure and functional measures with latent dimensions of psychopathology. This work provides solid evidence for the existence of such mappings and charts the relationship between different neurobiological measures and distinct dimensions of psychopathology. This work will be of broad interest within the neuroscience field.

eLife assessment

This potentially important work presents a tool for performing phylogenetic taxonomic classification of DNA sequences. In terms of methodology, the work is compelling. The authors perform a benchmark experiment against current state-of-the-art tools using real and simulated datasets to demonstrate where the novel tool stands in the context of existing methods. However, the experimentation is still incomplete. It would benefit from a more thorough exploration of existing methods as well as data sets that better represent real-world use cases.

eLife assessment

This important work offers an experimental structural characterization of the Tramtrack-like BTB/POZ domains in insects, revealing that these domains form stable hexameric assemblies. The structural evidence is convincing, and validated by fold prediction and evolutionary pathway analyses. This paper would be of interest to structural and evolutionary biologists.

eLife assessment

In this study, Perez-Lopez and colleagues examine an important function of the chemokine CCL28 in mucosal host defenses against the gut bacterial pathogen Salmonella Typhimurium and lung pathogen Acinetobacter baumanii. They find that CCL28-CCR3 axis regulates neutrophil recruitment and function, and promotes bacterial clearance in one infectious context but exacerbates disease against the other pathogen. Therefore, CCL28 plays a critical role in mucosal immunity and neutrophil biology that differentially affects host defenses against pathogens.

eLife Assessment

The study explored the influence of magnesium on phenotypic antibiotic resistance in two strains of Vibrios: V. alginolyticus ATCC33787 and V. parahaemolyticus VP01. This research is fundamental for revealing the phenotypic antibiotic resistance mechanism utilized by the specified model bacteria in elevated levels of magnesium. The study produced convincing evidence indicating that in high concentrations of magnesium, the efficacy of selected antibiotics was diminished due to decreased biosynthesis of unsaturated fatty acids and PE, along with an increase in the biosynthesis of PG.

eLife Assessment

The study highlights adhesion G-protein-coupled receptor A3 (ADGRA3) as a potential target for activating adaptive thermogenesis in both white and brown adipose tissue. This finding offers valuable insights for researchers in the field of adipose tissue biology and metabolism. The authors have presented additional evidence to address the reviewers' comments, including experiments conducted on primary stromal vascular fractions from adipose tissues. However, the revised manuscript fails to address several reviewer concerns, such as the measurement of whole-body energy expenditure through indirect calorimetry and the assessment of food intake. Furthermore, the nanoparticle-mediated knockdown of Adgra3 did not adequately address the tissue selectivity of ADGRA in mice. As a result, the primary claims of the study are only partially supported by the available data, leading to the conclusion that the research is deemed incomplete.