Evaluated articles

eLife Assessment

In this important study, the authors advance our understanding of copper uptake by chalkophores and their targeted metalloproteins in Mycobacterium tuberculosis. These convincing data demonstrate that chalkophore-acquired copper is solely incorporated into the Mtb bcc:aa3 copper-iron respiratory oxidase under low copper conditions, and that chalkophore-mediated protection of the respiratory chain is critical to Mtb virulence. These findings may be leveraged for drug discovery and will be of broad interest to those studying bacterial pathogenesis.

eLife Assessment

This study provides evidence that single-cell multi-omics profiling can reveal key regulators of HIV-1 persistence and early immune dysregulation, particularly implicating KLF2 and Th17 cells as major players in viral reservoir dynamics. The findings are solid, supported by rigorous integration of scRNA-seq and scATAC-seq data, but are limited by sample size and lack of validation with external datasets. Overall, this work makes a valuable contribution to understanding HIV-1 immune evasion and highlights potential therapeutic targets for reservoir eradication.

eLife Assessment

The authors utilize a valuable computational approach to exploring the mechanisms of memory-dependent klinotaxis, with a hypothesis that is both plausible and testable. Although they provide a solid hypothesis of circuit function based on an established model, the model's lack of integration of newer experimental findings, its reliance on predefined synaptic states, and oversimplified sensory dynamics, make the investigation incomplete for both memory and internal-state modulation of taxis.

eLife Assessment

This valuable work presents how PRDM16 plays a critical role during colloid plexus development, through regulating BMP signaling. Solid evidence supports the context-dependent gene regulatory mechanisms both in vivo and in vitro. The work will be of broad interest to researchers working on growth factor signaling mechanisms and vertebrate development.

eLife Assessment

This important study examines the role of pericytes in patterning the zebrafish blood-brain barrier (BBB) and controlling its permeability. Using pdgfrb mutant zebrafish models lacking brain pericytes, the authors report that pericyte-deficient cerebrovasculatures are ill-patterned, yet display unaltered restrictive BBB permeability properties at larval and juvenile stages. More severe phenotypes are detected in adults, with focal leakage sites associated with hemorrhages and aneurysms. Using solid and beautifully documented imaging, the authors suggest that, contrary to the situation described in rodent models, pdgfrb-dependent pericytes are not required to maintain the BBB in the zebrafish brain; these unexpected and intriguing findings reshape our understanding of BBB permeability regulation in vertebrates.

eLife Assessment

Birdsong production depends on precise neural sequences in a vocal motor nucleus HVC. In this useful biophysical model, Daou and colleagues identify specific biophysical parameters that result in sparse neural sequences observed in vivo. While the model is presently incomplete because it is overfit to produce sequences and therefore not robust to real biological variation, the model has the potential to address some outstanding issues in HVC function.

eLife Assessment

This important study seeks to examine the relationship between pupil size and information gain, showing opposite effects dependent upon whether the average uncertainty increases or decreases across trials. Given the broad implications for learning and perception, the findings will be of broad interest to researchers in cognitive neuroscience, decision-making, and computational modelling. Nevertheless, the evidence in support of the particular conclusion is at present incomplete - the conclusions would be strengthened if the authors could both clarify the differences between model-updating and prediction error in their account and clarify the patterns in the data.

eLife Assessment

This important manuscript proposes a new strategy for the identification of new mechanisms of drug resistance based on SAturated Transposon Analysis in Yeast (SATAY), a powerful transposon sequencing method in Saccharomyces cerevisiae. This method allows us to uncover loss- and gain-of-function mutations conferring resistance to 20 different antifungal compounds. The method is convincing, allowing the authors to identify a novel interaction of chitosan with the cell wall mannosylphosphate, and show that the transporter Hol1 concentrates the novel antifungal ATI-2307 within yeast.

eLife Assessment

This manuscript presents a clever and powerful approach to examining differential roles of Nav1.2 and Nav1.6 channels in excitability of neocortical pyramidal neurons, by engineering mice in which a sulfonamide inhibitor of both channels has reduced affinity for one or the other channels. Overall, the results in the manuscript are compelling and give important information about differential roles of Nav1.6 and Nav1.2 channels. Activity-dependent inactivation of NaV1.6 was also found to attenuate seizure-like activity in cells, demonstrating the promise of activity-dependent NaV1.6-specific pharmacotherapy for epilepsy.

eLife Assessment

This valuable study provides a novel framework for leveraging longitudinal field observations to examine the effects of aging on stone tool use behaviour in wild chimpanzees. However, the analysis and interpretation are currently incomplete and would benefit from a more robust consideration of additional sources of variance for the data (e.g., foraging ecology, nut and tool properties, etc.). Despite the low sample size of five individuals, this study is of broad interest to ethologists, primatologists, archaeologists, and psychologists.

eLife Assessment

The conclusions of this work are based on valuable simulations of a detailed model of striatal dopamine dynamics. Establishing that a lower dopamine uptake rate can lead to a 'tonic' level of dopamine in the ventral but not dorsal striatum, and that dopamine concentration changes at short delays can be tracked by D1 but not D2 receptor activation, is of value and will be of interest to dopamine aficionados. However, the simulations are incomplete, providing only partial support for the key claims. Several things can be done to strengthen the conclusions, including, for example, but not exclusively, a demonstration of how the results would change as a function of changes in D2 affinity.

eLife Assessment

The study reports valuable findings from a very rich EEG-fMRI dataset including 107 participants, which was collected during nocturnal naps. The authors link activity in memory-related brain regions (e.g., hippocampus, thalamus, and medial prefrontal cortex), and their functional connectivity, to the occurrence of canonical sleep rhythms, namely spindles and slow oscillations in non-rapid eye movement sleep. This work could contribute to further understanding of sleep neural dynamics, although the evidence for some of the main claims is incomplete at present.

eLife Assessment

This study presents valuable insights into the role of two proteins, Rab27A and SYTL5, which control vesicle transport and delivery. While the data is clear, the overall evidence is somewhat incomplete. Strengthening the mechanistic aspect would enhance the study, making it of greater interest to cell biologists studying membrane trafficking and mitochondria.

eLife Assessment

This study reveals that PRMT1 overexpression drives tumorigenesis of acute megakaryocytic leukemia (AMKL) and that targeting PRMT1 is a viable approach for treating AMKL. While the evidence, based largely on one cell line, is convincing, further validations in additional experiment settings will solidify the conclusion. These findings have important implications for the treatment of AMKL with PRMT1 over expression in the future.

eLife Assessment

This important study explores the commander-independent function of COMMD3-Arf1 in endosomal recycling. The evidence supporting the authors' claims is solid; however, the inclusion of additional validation experiments and control conditions would have further strengthened the study. The findings will be of significant interest to cell biologists working on membrane trafficking.

eLife Assessment

This manuscript makes a valuable contribution to the field by uncovering a molecular mechanism for miRNA intracellular retention, mediated by the interaction of PCBP2, SYNCRIP, and specific miRNA motifs. These findings advance our understanding of RNA-binding protein-mediated miRNA sorting and provide deeper insights into miRNA dynamics. While the conclusions are supported by solid experimental evidence, additional controls and clarification of the precise intracellular interactions would further strengthen the study.

eLife Assessment

This important study explores the conserved role of IgM in both systemic and mucosal antiviral immunity in teleosts, challenging established views on the differential roles of IgT and IgM. The findings have theoretical and practical implications for immunology and aquaculture. However, the strength of the evidence is incomplete due to insufficient validation of the monoclonal antibodies used to deplete IgM, which limits confidence in the main claims. Addressing these methodological weaknesses would significantly enhance the study's impact.

eLife Assessment

This valuable study provides convincing evidence that specific proteins on the surface of cancer cells undergo a particular form of recycling and are redirected toward the cell-cell contact with T cells, a type of immune cell. However, the characterization of the consequences of T cell activation resulting from perturbing the recycling pathway is incomplete. Furthermore, relevant literature has not been sufficiently cited.

eLife Assessment

This important study characterizes the mechanics and stability of bolalipids from archaeal membranes using molecular dynamics simulations. A mesoscale model of bolalipids is presented and evaluated across a series of membrane configurations. The evidence supporting the conclusions is convincing, demonstrating that mixtures of bolalipids and regular bilayer lipids in archaeal membranes enhance fluidity and stability.

eLife Assessment

This useful study reports analyses of Neuropixel recordings in the medial prefrontal cortex and hippocampus of rats in a spatial navigation trial, focusing on classifying prefrontal neurons based on SWR modulation and anatomical location. However, the evidence for claims of a clear link between SWR modulation and neuronal encoding, and the evidence for anatomical organization, is currently incomplete. Further analyses might strengthen the evidence for some conclusions, and some of the strong claims of the paper should likely be moderated.