Evaluated articles

eLife Assessment

Arecchi et al. demonstrate that polarized second-harmonic generation microscopy can be used to probe the ON/OFF states of myosin in both permeabilized and intact muscle, making this key measurement accessible to a greater number of labs. This has the potential to help with the study of disease-causing mutations and our understanding of drug function. The methodology is well defined, and the results are important; however, whilst this is overall a convincing study, there are some limitations to the interpretation of the data.

eLife Assessment

This study reports the important development and characterization of next-generation analogs of the molecule AA263, which was previously identified for its ability to promote adaptive ER proteostasis remodeling. The evidence supporting the conclusions is convincing, with rigorous assays used to benchmark the changes in potency and efficacy of the AA263 analogs as well as AA263 targets. The ability of AA263 analogs to restore the loss of function associated with disease-associated proteins prone to misfolding will be of interest to pharmacologists, chemical biologists, and cell biologists, as well as those working on protein misfolding disorders.

eLife Assessment

This study provides valuable insight into stress biology by showing that yeast populations can rapidly evolve a trehalose producing resting state that substantially improves survival and rapid regrowth after freeze-thaw. This finding is consistent with the role of trehalose metabolism as a biophysical adaptation that is broadly relevant to the community working on environmental resilience and dormancy. The evidence is convincing: the authors integrate experimental evolution, cell-level biophysical measurements, and modelling in a mutually reinforcing manner.

eLife Assessment

This important study presents a well-constructed multiscale simulation framework to investigate ATP-driven DNA translocation by prokaryotic SMC complexes, supporting a segment-capture mechanism. The strength of evidence is convincing, highlighting the necessity of a precise balance between electrostatic interactions and hydrogen bonding, as well as the critical role of kleisin asymmetry in ensuring unidirectional movement.

eLife Assessment

This useful study employs optogenetics, genetically-encoded dopamine and serotonin sensors, and patch-clamp electrophysiology to investigate modulations of neurotransmitter release between striatal dopamine and serotonin neurons - a topic of interest to neuroscientists studying the basal ganglia. The results suggest that the dopamine and serotonin systems operate largely in parallel, with the activation of serotonin neurons resulting in a small, transient dopamine release. The authors suggest that this interaction occurs via glutamate release in the ventral tegmental area, findings that are closely related to previous work. Some conclusions are incomplete requiring larger samples-sizes and controls.

eLife Assessment

This important work introduces a splitGFP-based labeling tool with an analysis pipeline for the synaptic scaffold protein bruchpilot, with tests in the adult Drosophila mushroom bodies, a learning center in the Drosophila brain. The evidence supporting the conclusions is convincing.

eLife Assessment

This article presents valuable findings on how the timing of cooling affects autumn bud set in European beech saplings. The study leverages extensive experimental data and provides an interesting conceptual framework for the various ways in which warming can affect bud set timing. The statistical analysis is very well considered, while indicating some factors that may temper the authors' claims. The factorial experiments offer solid support.

eLife Assessment

In this manuscript, Park et al. developed a multiplexed CRISPR construct to genetically ablate the GABA transporter GAT3 in the mouse visual cortex, with effects on population-level neuronal activity. This work is important, as it sheds light on how GAT3 controls the processing of visual information. The findings are compelling, leveraging state-of-the-art gene CRISPR/Cas9, in vivo two-photon laser scanning microscopy, and advanced statistical modeling.

eLife Assessment

This study identifies astrocyte-intrinsic mechanisms by which the LRRK2 G2019S, a mutation linked to familial Parkinson's disease, disrupts synaptic integrity in the anterior cingulate cortex. The findings are convincing, as they rely on a comprehensive set of in vivo and in vitro genetic, biochemical, proteomic, and electrophysiological approaches. They are important because of their translational value, being validated in both mouse models and post-mortem human samples.

eLife Assessment

The authors present a solid study in the unique conditions of weightlessness providing evidence that movements carried out in 0g are underactuated. They further provide a thorough discussion based on computational modelling to address the question as to whether the CNS underestimates mass when programming movements in weightlessness. In all cases, the persistence of the observed effects in weightlessness has important implications for theories of motor adaptation.

eLife Assessment

This well-designed study offers important insights into the development of infants' responses to music based on the exploration of EEG neural auditory responses and video-based movement analysis. The compelling results revealed that evoked responses emerge between 3 and 12 months of age, but no age group demonstrated evidence of coordinated movements to music. This study will be of significant interest to developmental psychologists and neuroscientists, as well as researchers interested in music processing and in the translation of perception into action.

eLife Assessment

The authors proposed two hypotheses: first, that methamphetamine induces neuroinflammation, and second, that it alters neuronal stem cell differentiation. These are valuable hypotheses, and the authors provided in vivo observations of the methamphetamine response in mice. However, concerns about data interpretation, and the current evidence is incomplete, requiring further experimental validation.

eLife Assessment

This valuable study investigates the neural basis of bidirectional communication between the cortex and hippocampus during learning. The evidence supporting the identification of specific circuits and functional cell types involved is convincing. However, certain aspects of the behavioral analysis and statistical interpretation remain incomplete. Overall, the work will be of interest to neuroscientists studying learning and memory.

eLife Assessment

This study provides compelling evidence that action potential (AP) broadening is not a universal feature of homeostatic plasticity in response to chronic activity deprivation. By leveraging state-of-the-art methods across multiple brain regions and laboratories, the authors demonstrate that AP half-width remains largely stable, challenging previous assumptions in the field. These important findings help resolve longstanding inconsistencies in the literature and significantly advance our understanding of neuronal network homeostasis. The authors have clarified methodological differences with prior work and expanded the discussion of potential mechanisms, strengthening the interpretation of the findings without altering the central conclusions.

eLife Assessment

The authors investigated the potential role of IgG N-glycosylation in Haemorrhagic Fever with Renal Syndrome (HFRS), which may offer significant insights for understanding molecular mechanisms and for the development of therapeutic strategies for this infectious disease. The findings are valuable to the field and the strength of evidence to support the findings is solid.

eLife Assessment

This important work develops the C. elegans as a model organism for studying effort-based discounting by asking the worms to choose between patches of easy and hard to digest bacteria. The authors provide convincing evidence that the nematodes are effort discounting. They also provide solid evidence of involvement of dopamine in the food preference and that the finding is not restricted to lab-acclimated strains.

eLife Assessment

This important work investigates cooperative behaviors in adolescents using a repeated Prisoner's Dilemma game. The approach used in the study is solid. The impact of this work could be further enhanced with more rigorous modelling procedures and more modeling selection/comparison details, as well as by framing the findings in terms of the specific game-theoretic context, rather than general cooperation. Findings from this study will be of interest to developmental psychologists, economists, and social psychologists.

eLife Assessment

The findings of this important study substantially advance our understanding of the transcription factors that can induce hair cell-like cells from human pluripotent stem cells. The presented evidence supporting these findings is compelling, including rigorous characterization of the effects of hair cell induction using both single-cell RNA sequencing and electrophysiological assessments.

eLife Assessment

This study provides a fundamental advancement in our understanding of trabecular meshwork cell diversity and its role in eye pressure regulation and glaucoma using multimodal single-cell analysis, spatial validation, and functional testing that go beyond the current state-of-the-art. The study demonstrates that mitochondrial dysfunction, specifically in one of three distinct cell subtypes (TM3), contributes to elevated IOP in a genetic mouse model of glaucoma carrying a mutation in the transcription factor Lmx1b. While the identification of TM3 cells as metabolically specialized is compelling, there is somewhat limited evidence linking mitochondrial dysfunction to the Lmx1b mutation in TM3 cells.

eLife Assessment

This valuable study introduces a novel experimental and modeling framework to quantify passive joint torques in Drosophila, revealing that passive forces are insufficient to support body weight, contrary to prior assumptions based on larger insects. The approach is technically impressive, combining genetic silencing, kinematic tracking, and biomechanical modeling. However, the strength of evidence is incomplete, limited by concerns about the specificity of the genetic tools, simplifications in the mechanical model, and limited functional interpretation.