Evaluated articles

eLife Assessment

This is a valuable study of changes in host genome histone methylation and transcription changes associated with Chlamydia infection. The data presented are solid but further analysis would strengthen the authors overall conclusions.

eLife Assessment

This important study identifies a non-canonical essential role for acyl carrier protein in maintaining apicoplast metabolism and blood-stage survival in Plasmodium falciparum. The main conclusions are largely supported by strong genetic and biochemical evidence, although some claims regarding the dispensability of fatty acid synthesis pathways remain incomplete. The work provides novel mechanistic insight into ACP-mediated stabilization of pyruvate kinase II and will be of broad interest to the malaria and apicoplast biology communities.

eLife Assessment

This study presents a fundamental methodological advance that enables measurements of single-channel gating behavior of CRAC channels whose unitary currents are too small to be resolved electrically. By combining a channel-tethered calcium-sensitive dye (JF646-BAPTA) with voltage-clamp TIRF imaging, the authors discovered new kinetic behaviors of CRAC channels and further identified a dye-blinking artifact with implications that are of importance for optical single-channel studies. Although the work is convincing and the findings have biological relevance, some quantitative aspects of the study can be strengthened by additional analysis.

eLife Assessment

This important study advances methods for improved analyses of wide-field optical imaging of mice expressing the genetically encoded calcium indicator GCaMP6f in different neocortical layers through registering to layer-specific cortical atlases and deconvolution to account for depth-dependent light scattering. However, the key underlying assumption of the work, that widefield signals originate in somata, and not in their superficial axonal and dendritic compartments, remains untested. Similarly, other signal sources like intrinsic optical signals and hemodynamic occlusion are incompletely considered. This study is likely to be of interest to neuroscientists carrying out wide-field optical imaging of the mouse neocortex.

eLife Assessment

Using a genetic screen in C. elegans, Benbow et al., identify mutations in alpha-tubulin genes that suppress Tau-induced neurodegenerative phenotypes. The results provide solid support the authors' claim that the tubulin mutants protect against neurodegeneration without altering tau aggregation and hyperphosphorylation. While precise mechanisms of protection by tubulin mutants remain to be established, the results are valuable for understanding the underlying cellular mechanisms of Tauopathies and for the development of therapeutic interventions.

eLife Assessment

This important work uses a sophisticated combination of neuromodulator imaging, optogenetics, and two-photon calcium imaging to examine how locus coeruleus-mediated norepinephrine signaling influences distinct hippocampal cell types. The evidence is solid and provides novel insights into cell type-specific responses to norepinephrine release. However, the conclusions would be strengthened by a more thorough analysis of the differences between locomotion-associated activity and optogenetic stimulation of the locus coeruleus.

eLife Assessment

This study presents a valuable finding that perception of a material's properties and hardness during brief touches can be altered using only vibrotactile feedback. The user studies show that vibration energy can influence judgements of material hardness, but the evidence is incomplete to support the broader claim made by the authors that spectral energy is the dominant feature governing hardness perception.

eLife Assessment

This study adds important data on the transcriptional identity of the motor neurons innervating eye muscles in larval zebrafish, and shows how disruption to a specific gene, sim1a, impairs the movements of the eye. The evidence supporting the claims is convincing, with bulk and single-cell RNA sequencing as well as functional testing of the vestibulo-ocular reflex. This work will be of interest to developmental biologists and eye movement specialists.

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.