Evaluated articles

eLife Assessment

This study presents an important finding that loss or blockade of key integrins unexpectedly enhances central nervous system accumulation of T-cell acute lymphoblastic leukemia cells and may increase their sensitivity to chemotherapy. The evidence is convincing, supported by well-designed in vivo models, CRISPR-based perturbations, competitive assays, imaging, and complementary therapeutic experiments. However, the mechanistic basis linking integrin loss, altered spatial distribution, and increased proliferation remains incompletely defined, and the translational implications would be strengthened by additional survival studies and validation in more clinically relevant models.

eLife Assessment

This study provides important findings regarding the efficacy of a chronotherapeutic protocol (termed LiFE), combining timed light, food, and exercise exposure in improving several physiological and health metrics in a rodent model. The evidence advanced in wild-type mice is solid but inconclusive and underpowered when applied to two transgenic mouse models of Alzheimer's Disease. Additionally, the potential of such protocols in clinical human studies is an open question. Overall, the study suggests that LiFE intervention may have positive effects on metabolic and brain health.

eLife Assessment

This valuable study shows that macaque monkeys preferentially fixate regions in natural scenes that are classified as "meaningful" by a computational model - an earlier model that was developed to identify locations that are semantically informative to humans - suggesting that overt attention to structured visual content is shared across primates. However, support is incomplete for the stronger claim that macaques are guided by semantic meaning, which is confounded by lower-level visual features that co-vary with it and by methodological limitations that complicate interpretation. If the semantic interpretation were more reliably established, the significance of the findings would increase, as they would connect the human cognitive process of scene understanding to neural circuit mechanisms accessible in non-human primates.

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.