Evaluated articles

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. The methods and results are robust providing solid evidence of the effects of old age on nut cracking behaviour at this field site. 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 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 invaluable and will be of interest to the community, particularly those studying dopamine. The model simulations provide convincing evidence for differences between dorsal and ventral striatum dopamine concentrations, while evidence for differential tracking of dopamine changes by D1 vs D2 receptors is solid.

eLife Assessment

The study reports valuable findings from a very rich EEG-fMRI dataset, including 107 participants, which was collected during nocturnal naps. Using overall solid methods, 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 (spindles and slow oscillations) in non-rapid eye movement sleep. This work will be of broad interest to sleep and memory researchers and beyond.

eLife Assessment

This study by Lapao et al. uncovers a novel role for the Rab27A effector SYTL5 in regulating mitochondrial function and mitophagy under hypoxic conditions. Using a range of imaging and functional assays, the authors demonstrate that SYTL5 localizes to mitochondria in a Rab27A-dependent manner and impacts mitochondrial respiration and metabolic reprogramming. While the findings are solid and valuable in the area of cancer biology, further mechanistic clarity and improved imaging would strengthen the conclusions.

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. After revision, both reviewers found that these findings are important and that the data supporting these findings are convincing. Furthermore, these findings likely have significant implications for the treatment of AMKL with PRMT1 overexpression in the future.

eLife Assessment

This important study explores the mechanisms underlying the maintenance of cell surface protein levels. The authors present solid evidence to support their claims, though the addition of certain validation experiments could have further strengthened the conclusions. This work will be of particular interest to cell biologists focused 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. The findings are convincing and advance our understanding of RNA-binding protein-mediated miRNA sorting, providing deeper insights into miRNA dynamics.

eLife Assessment

The manuscript is an important study which aims to demonstrate the conserved and crucial role of IgM in both systemic and mucosal antiviral immunity in teleost, challenging the established differential roles of IgT and IgM. The strength of the evidence is solid and supported by a combination of in vivo studies, viral infection models, and complementary in vitro assays. In the current version, authors validate the MoAb against IgM

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 fundamental study characterizes the mechanics and stability of bolalipids from archaeal membranes using a minimalist, physics-based computational model. The authors present a robust mesoscale model of bolalipids-containing membranes, systematically evaluating it across diverse membrane configurations. The results are compelling, demonstrating that the incorporation of bolalipids and regular bilayer lipids in archaeal membranes significantly enhances membrane fluidity and structural 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. Reviewers were unconvinced by the presented evidence for the claim that distinct populations of mPFC neurons participate in non-local ensemble representations during SWR and non-SWR periods, and were unconvinced by the presented evidence for a previously unrecognized anatomical distinction between these populations. Further analyses might strengthen the incomplete evidence for some conclusions, and some of the strong claims of the paper should likely be moderated.

eLife Assessment

This manuscript describes a novel approach for assessing cognitive function in freely moving mice in their home-cage, without human involvement. The authors provide convincing evidence in support of the tasks they developed to capture a variety of complex behaviors and demonstrate the utility of a machine learning approach to expedite the acquisition of task demands. This work is important given its potential utility for other investigators interested in studying mouse cognition.

eLife Assessment

This study provides valuable findings on the effects of mating experience on sweet taste perception. The data as presented provide convincing evidence that the dopaminergic signaling-mediated reward system underlies this mating state-dependent behavioral modulation. The work will interest neuroscientists and particularly biologists working on neuromodulation and the effects of internal states on sensory perception.

eLife Assessment

This study demonstrates that conditional knockout of afadin disrupts retinal laminar organization and reduces the number of photoreceptors, while preserving certain aspects of retinal ganglion cell structure and light responsiveness. The work is valuable and well-supported by revised figures and comprehensive data on retinal cell types, lamination patterns, and visual functio. The findings are solid and intriguing, and the study provides insights into the relationship between retinal lamination and neural circuit function.

eLife Assessment

This useful study presents a virtual reality-based contextual fear conditioning paradigm for head-fixed mice. Solid evidence supports the claim that the reported methods provide a reliable paradigm for studying contextual fear conditioning in head-fixed mice. The approach provides a way to perform multiphoton imaging of neural circuits, and other techniques that are typically performed in head-fixed animals, during behaviors that have traditionally been studied in freely moving animals.

eLife Assessment

This multimodal neuroimaging study leverages fMRI, PET, and deep learning to predict memory performance. The authors introduce the brain-cognition gap to link these different imaging modalities to cognition and evaluate their results in two independent cohorts. The results are a valuable addition to the literature and will be of interest to neuroscientists working at the interface of cognition, neuroimaging, and computational modeling. However, the evidence supporting the conclusions remains incomplete.

eLife Assessment

This is a well-written important paper on the recovery of fauna and flora following the end-Permian extinction event in several continental sites in northern China. The convincing conclusion, a rapid recovery in tropical riparian ecosystems following a short phase of hostile environments and depauperate biota, is supported by an impressive amount of data from sedimentology, body fossils of animals and plants, and especially trace fossils.

eLife Assessment

The Twin Domain model proposed by Lui and Wang proposing that twin supercoiling domains of DNA emerge during transcription were first described decades ago, but direct experimental evidence has been challenging to obtain. Here, the authors make a fundamental contribution by directly measuring DNA torsion in cells using a photoactivatable intrastrand cross-linker compared to controls. They gather compelling data using this clever method, which provides direct evidence in support of the twin-supercoiled domain model, for torsional effects at transcription start and end sites, and thereby uncover novel features of higher order structure of chromatin in yeast. These data are exciting, and the tools will be of interest to anyone studying chromosome structure and gene regulation.