Evaluated articles

eLife Assessment

This important study developed a novel theory to account for various aspects of dopamine signals, particularly dopamine ramps. The authors propose that dopamine reward prediction error (RPE) signals are generated by a dual-process learning system in which values inferred by a model-based system enter the RPE asymmetrically into the update target but not the prediction. The results are well-presented and convincing, and make a contribution that is of importance to the field. This work will be of interest to those studying dopamine specifically or brain learning computations and systems more broadly.

eLife Assessment

This study reports important findings by showing that two classes of kinase inhibitors, which stabilise the LRRK2 enzyme in either an active (Type I) or inactive state (Type II), have distinct effects on the formation of LRRK2 filaments and their association with cellular structures. Using correlative light microscopy, cryo-electron tomography and sub-tomogram averaging, the authors provide convincing evidence that a Type I inhibitor leads to the extensive decoration of microtubules with LRRK2 in a closed-kinase conformation, and that such decoration is not seen for a type-II inhibitor. The conclusions are consistent with previous work, although the physiological relevance of the work remains somewhat limited due to reliance on overexpression and the use of a rare mutation in a single cell type.

eLife Assessment

In this valuable study, de Vries and colleagues aim to determine how the perception of biological motion is organized at the neural level, specifically testing whether this process rests on hierarchical predictive processing by extending a methodological framework that the authors previously published. The evidence is solid for the empirical claim that neural representations of body motion systematically lead the stimulus in time, with simulations validating the regression approach and consistent effects on both peak magnitude and peak latency. Support for the stronger theoretical interpretation that these signatures specifically reflect active hierarchical predictive inference requires further substantiation, since the design and analysis do not distinguish such inference from cached associative retrieval or from nonlinear temporal integration of slowly varying features.

eLife Assessment

This study characterizes the heterogeneity and developmental origins of macrophages in the thymus and offers tantalizing evidence of their potential involvement in the first step of T cell selection. The macrophage characterisation is interesting, although the evidence for the specific involvement of macrophages in beta-selection is incomplete, as alternative explanations have not been ruled out. These results provide an important advance that further our understanding of thymus biology, especially in view of the contribution of heterogenous thymic macrophage subpopulations.

eLife Assessment

In this important theoretical contribution, the authors study the evolution of large microbial populations competing for resources in the challenging and relevant regime of overlapping ecological and evolutionary timescales. The modeling approach is overall convincing, anlthough its presentation would benefit from clarifications, e.g. on assumptions and approximations. The results will be of broad interest to researchers in evolutionary biology, ecology and microbiology.

eLife Assessment

This valuable study demonstrates that the inner membrane protease YME1 contributes to the formation of mitochondrial-derived compartments in yeast through the modulation of both the lipid transporter UPS2 and the MICOS complex. The evidence supporting this model is solid, although this manuscript could be improved by providing additional evidence supporting the independent roles for UPS2 and MICOS regulation in this process. This work will be of interest to cell biologists, biochemists, and geneticists interested in understanding the molecular basis of mitochondrial regulation and function.

eLife Assessment

This study presents a valuable contribution to comparative cognitive neuroscience by directly mapping functional homologues of the human multiple-demand network in macaques using a matched spatial maze task. However, the evidence is incomplete due to methodological asymmetries in task design and preprocessing parameters that warrant careful consideration. The work will be of interest to researchers studying the evolution of cognitive control and cross-species neuroimaging.

eLife Assessment

This important study investigates how distinct honey bee viruses differentially alter flight performance through interactions with octopamine signaling pathways. The combination of behavioral flight assays, pharmacological perturbation, and transcriptomic analyses provides solid evidence that virus-specific effects on flight are associated with octopamine signaling. However, some of the stronger mechanistic conclusions regarding direct regulation of octopamine signaling remain incomplete without more specific validation of receptor-level effects and direct quantification of octopamine levels or signaling activity.

eLife Assessment

In this study, the authors propose a role for the Huntingtin protein in the organization of the Golgi apparatus and examine the effect of polyQ aggregates at the Golgi. The observations are interesting and potentially important for the field; however, the key claim that polyQ HTT functionally disrupts the Golgi (Golgipathy) is incompletely supported by the data.

eLife Assessment

This paper addresses a key question regarding the molecular mechanisms underlying GABA and glutamate release from co-releasing neurons projecting from the entopeduncular nucleus (EPN) to the lateral habenula (LHb) in mice. The authors conclude that the two neurotransmitters are released from separate vesicle pools and rely on distinct molecular machinery; these conclusions contrast with previous functional studies at the same synapse, suggesting that GABA and glutamate are co-packaged within the same vesicles. The study employs useful electrophysiological and imaging approaches, however, a key limitation is the use of Cre lines that also label a purely glutamatergic EPN population projecting to the LHb. This inadequate methodology complicates the interpretation of the data and weakens the central conclusions regarding neurotransmitter co-release mechanisms.

eLife Assessment

This important study investigates the peptide-binding principles of promiscuous chicken MHC molecules. The data from crystallography, mass spectrometry, and modeling are convincing. However, the presentation would benefit from streamlining and clear links between data and conclusions. This paper will be of broad interest to immunologists and those interested in vaccine development.

eLife Assessment

The authors have presented a study which addresses a recognised gap in the literature, the emergence of the neural correlates of cognitive and affective empathy in children; they introduce a task for measuring both positive and negative empathy in a relatively large group of children aged 3-5. The task was combined with functional near-infrared spectroscopy to examine brain regions involved in the task. The findings are interpreted as providing evidence for the earlier emergence of cognitive than affective empathy. The study represents a valuable contribution to understanding the development of cognitive function, but in its current form, the strength of support for the conclusion is incomplete due to limited support for the comparison to the adult literature and a need to more clearly justify the pre-selected brain regions, their links to empathy and the justification of the hypotheses.

eLife Assessment

This is an important study that applies a new chromatin profiling technique to the study of cellular responses to low oxygen. The authors provide convincing evidence for distinct kinetic phases of the response and identify many new putative regulators of the response. This work will be of broad interest to those studying low oxygen responses and transcriptional regulation.

eLife Assessment

This study presents a valuable finding that the Par polarity complex, but not Crumbs or Scrib, regulates morphological remodeling during the naive-to-primed transition of pluripotent stem cells, with later effects on differentiation and neural tube organoid lumen formation. The evidence is incomplete, as the developmental significance of the PAR KO phenotype requires clearer framing and deeper characterization, and the proposed signaling pathway is currently presented more strongly than the data support. The work will be of interest to developmental and stem cell biologists studying polarity, pluripotent-state transitions, epithelialization, and lumen formation.

eLife Assessment

This study presents fundamental results on the presence of the Entner-Doudoroff pathway in cyanobacteria. In contrast to an earlier study, compelling evidence is given that Synechocystis PCC 6803 lacks both an Entner-Doudoroff pathway and a related bypass but contains a promiscuous aldolase. This study successfully reconciles data from different studies and lessons learned from a previous misconception.

eLife Assessment

This important work introduces an integrated open-source platform for behavioral acquisition and pose estimation that substantially improves the accessibility and speed of real-time animal tracking workflows. The evidence supporting the utility and usability of SqueakPose Studio is compelling, particularly the substantial inference speed gains, intuitive graphical interface, flexible pose configuration, and successful testing on independent datasets, although the evidence supporting broader benchmarking claims and the hardware ecosystem surrounding MouseHouse and SqueakView remains somewhat incomplete. The study will be of broad interest to neuroscientists and behavioural researchers seeking scalable and user-friendly approaches for real-time behavioral analysis, and the work would be further strengthened by more rigorous benchmarking, expanded installation and hardware documentation, formal software release practices, and clearer delineation between demonstrated capabilities and future applications.

eLife Assessment

This is a fundamental study that clarifies the cellular mechanism of sound localization in the horizontal plane. The analysis of medial superior olivary neurons provides experimental and computational evidence for a new mechanism in which a range of asymmetric dendritic delays permits individual MSO neurons to represent the full range of biologically relevant ITDs. Using elegant 2-photon guided simultaneous recordings from distal dendrites and soma, along with compartmental modeling on anatomically reconstructed neurons, the authors provide compelling evidence that this mechanism contributes to microsecond-level tuning.

eLife Assessment

This manuscript provides a valuable perspective on microbial community diversity and how this is shaped by the presence of cheaters. The evidence provided is solid, and the methods used to assess the research question are convincing. However, a major weakness is the general framing (or lack of embedding in recent literature), reducing the usefulness of the paper for a broad audience.

eLife Assessment

GPR52 is an orphan receptor implicated in neuropsychiatric disorders, and this study addresses the lack of real-time monitoring tools by developing GPR52-1.0, a genetically encoded fluorescent sensor built on the GRAB platform. The design of the sensor is elegant and the validation is thorough. The authors also utilized the sensor to discover that striatal neuron excitation may activate the sensor, providing exciting new biological insights into GPR52 functional mechanisms. The work could be useful to the field if presented in the correct context, but as it stands, the work remains incomplete as it overlooks GPR52's well-documented high constitutive activity (PMID: 32076264, PMID: 26384023), which raises major questions about the sensor's physiological relevance.

eLife Assessment

This valuable study combines multiscale molecular simulations with supporting biophysical experiments to investigate how the myristoylated VP4 peptide of non-enveloped viruses interacts with host membranes during viral entry. The authors show that myristoylation facilitates VP4 membrane anchoring, condensate formation, and membrane remodeling events linked to early stages of membrane breaching. The work provides a convincing biophysical framework for understanding myristoylation-dependence in membrane-penetrating proteins.