Evaluated articles

eLife Assessment

This important study identifies inhibitory cerebellar nuclei neurons as drivers of dystonic crisis and shows that their modulation can both induce and alleviate severe motor symptoms, proposing a cerebello-thalamic circuit mechanism with clear therapeutic relevance. The evidence is convincing, supported by rigorous bidirectional optogenetic manipulations, iCNN-to-CL thalamic monosynaptic tracing, and deep brain stimulation experiments, although the specificity of the genetic strategy remains to be fully resolved. The study will be of broad interest to neuroscientists and clinicians working on movement disorders and circuit-based therapies.

eLife Assessment

This valuable study rigorously examines how motor learning is influenced by the feedback response to a previous movement error. Using a series of well-conducted experiments, the authors provide solid evidence that the learning response following a cursor jump does not depend on the timing of the perturbation and is influenced by the tonic component of the feedback responses. Further work is needed to determine whether this generalizes to other perturbation paradigms and to more fully understand the relationship between learning and the tonic and phasic components of the feedback response.

eLife Assessment

This study leverages publicly available datasets to confirm, validate and extend the knowledge of the transcriptional profile of beta cells that resist destruction in Type 1 diabetes. The significance of the findings is considered valuable as they could be used for engineering stem cell-derived islets and for identifying therapeutic targets to preserve beta cell survival. The strength of the evidence is solid, in that the findings are supported by a sophisticated bioinformatic analysis pipeline and are largely consistent with and extend the existing literature.

eLife Assessment

This important study uses a feedback-driven recurrent neural network framework to explore the dynamics underlying learning of BCI decoder perturbations. With convincing evidence, the authors demonstrate that behavioral learning trajectories that match those of primates learning within-manifold and outside-manifold perturbations are likely tied to the dynamical controllability of the network and input-driven learning. This work is likely to motivate a new generation of BCI and learning experiments combining large-scale neural recordings with latent dynamical systems analyses.

eLife Assessment

This study provides conditionally useful evidence that amino acid starvation and other stresses induce RNF25-dependent ubiquitination of RPS27A/eS31, extending this pathway beyond A-site-trapping conditions and implicating GCN1. However, incomplete and largely indirect evidence was provided to support key mechanistic claims-notably competition between RNF25 and GCN2 for GCN1 and a role in resolving ribosome collisions. Additional direct and orthogonal evidence is required to substantiate these conclusions.

eLife Assessment

This study presents a valuable finding that coordinated changes in epigenetic modifications and three-dimensional chromatin architecture may drive primary trastuzumab resistance in HER2+ breast cancer. Moreover, this manuscript identifies SGK1 as a potential therapeutic target. The evidence supporting the claims of the authors is solid, although the inclusion of a more direct validation of the key findings using tumor samples from patients with clinical trastuzumab resistance would have strengthened the study. The work will be of interest to scientists or clinicians working in the field of BCs.

eLife Assessment

This manuscript provides a timely and important statistical re-evaluation of a paper by Epp et al., on the discordance of BOLD and CMRO2 measures. The authors present a convincing case based on rigorous re-analysis of the data that these previous results arise predominantly from uncertainty in measurement, rather than physiological features. These findings have implications that are of importance to all studies of brain function using BOLD FMRI.

eLife Assessment

This valuable paper uses a mathematical model applied to a dataset of E coli / ESBL carriage and transmission to infer drivers of drug resistance in France. The strength of support for the study findings is incomplete. While the research question is of importance, and the mathematical model has structural and methodological integrity, numerous issues are noted: insufficient description of the data, lack of included equations and code, definitions of antibiotic use that are not complete, low sensitivity of assays for carriage, technical issues with statistical prior selection and parameter identification, and application of non-regional ECDC surveillance data to France.

eLife Assessment

This potentially valuable study describes the development of protein binders targeting DELE1, a protein involved in activating the integrated stress response when mitochondria are perturbed (the mitoISR pathway. The strategy appears to be successful, as several designed proteins were shown to bind DELE1, disrupt DELE1 oligomerization, and attenuate ISR activation. However, the demonstration of the utility of these inhibitory binders is incomplete, particularly given the limited biological outcomes examined in the current study, thus limiting the significance of the paper in its current form.

eLife Assessment

This useful study employs longitudinal widefield cortical imaging to investigate how bilateral vision loss reshapes spontaneous activity across the mouse cortex over time, revealing a state-dependent alteration in the locomotion-related modulation of visual cortical activity. The work provides solid support for its main findings and offers a thorough characterization of the large-scale reorganization of cortical dynamics following adult vision loss. However, the mechanistic interpretation remains limited, as the conclusions are based on a single abrupt and irreversible manipulation without sham controls and on a recording approach that cannot resolve the cell-type-specific mechanisms invoked in the discussion.

eLife Assessment

This is a valuable paper that compares various deep learning models, trained with different objective functions, on their ability to predict fMRI data collected during naturalistic video gameplay. The data and analysis provide solid within-distribution evidence that models trained with PPO and imitation learning outperform untrained models and standard convolutional networks. However, the evidence for brittleness in out-of-distribution encoding remains incomplete, as the claim that this stems from the networks' training rather than from alternative causes-like overfitting of ridge regression parameters-is not yet fully supported.

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.