Evaluated articles

eLife assessment

This work is relevant to understanding how people represent uncertain events in the world around them and make decisions, with broad applications to economic behavior. It addresses a long-standing empirical puzzle from a novel perspective, where the authors propose that sequential effects in perceptual decisions may emerge from rational choices under cognitive resource constraints rather than adjustments to changing environments. Two new computational models have been constructed to predict behavior under two different constraints, among which the one assuming higher cost for more precise beliefs is better supported by new experimental data. The conclusion may be further strengthened by comparison with alternative models and (optionally) evidence from additional data.

eLife assessment

This manuscript describes a valuable new circuit mapping and profiling technique called Multiplexed projEction neuRons retrograde barcodE (MERGEseq) that combines transcriptome and projectome data at a single-cell resolution. The authors provide solid evidence that MERGEseq can be used to identify projection targets and cell type/layer/transcriptome differences of projection neurons in the mouse prefrontal cortex, and validation experiments are rigorous. While this report is a proof-of-principle that MERGEseq is useful for circuit mapping and profiling and many potential details will influence conclusions, this technique could easily be adapted to other regions with known projection targets and adds to a growing arsenal of combinatorial circuit mapping and profiling tools.

eLife assessment

This valuable work extends previous studies showing that the striatum multiplexes various aspects of locomotion, including velocity and movement transitions, by demonstrating that striatal neurons also encode single-limb gait. The authors present solid evidence to show that gait deficits induced by severe unilateral dopamine depletion are associated with an imbalance in the gait modulation of striatal firing. Although the source and function of this gait modulation remain unclear, this manuscript uncovers a role of striatal activity in gait, which may have implications for understanding gait disturbances in Parkinson's Disease.

eLife assessment

This important work shows compelling data that significantly advances our understanding of the regulation of neurotransmitter and hormone secretion by exploring the mechanisms of how the protein complexin 2 (Cplx2) interacts with the calcium sensor synaptotagmin. The function of mammalian Cplx2 is studied using chromaffin cells derived from Cplx2 knock out mice as a system to overexpress and functionally characterize mutant Cplx2 forms and the interaction between Cplx2 and synaptotagmin. The authors identify structural requirements within the protein for Cplx's dual role in preventing premature vesicle exocytosis and enhancing evoked exocytosis. The findings are of broad interest to neuroscientists and cell biologists.

eLife assessment

This important study proposes a new method for tracking neurons recorded with Neuropixel electrodes across days. The methods and the strength of the evidence are convincing, but the authors do not address whether their approach can be generalized to other brain areas, species, behaviors, or tools. Overall, this method will be potentially of interest to many neuroscientists who want to study long-term activity changes of individual neurons in the brain.

eLife Assessment

This work reports an important new method for activity-dependent neuronal labeling in Drosophila using in situ hybridization, with the potential to establish a new standard in the field. The authors demonstrate the method's applicability by generating compelling evidence of the function of male-specific neurons in both aggression and courtship behaviors. These results and the new method will be of great interest to the neuroscience community.

eLife assessment

The large-conductance Ca2+ activated K+ channel BKCa has been reported to promote breast cancer progression. The present study presents convincing evidence that an intracellular subpopulation of this channel reprograms breast cancer cells towards the Warburg phenotype, one of the metabolic hallmarks of cancer. This important finding advances the field of cancer cell metabolism and has potential therapeutic implications.

eLife assessment

The current version of the study presents important findings on how the RelA/Stat3-dependent gene program in the liver influences intestinal homeostasis. The evidence supporting the conclusions is solid, with new data added compared to an earlier version of the study. The work will be of interest to scientists in gastrointestinal research fields.

eLife Assessment

The authors of this manuscript study the transcriptional regulators that allow macrophages to assume different functional phenotypes in response to immune stimuli. They generate a computational map of the gene regulatory networks involved in determining macrophage phenotypes and experimentally validate the role of putative regulatory factors in a myeloid cell line. This study represents a valuable approach to understanding how gene regulation impacts macrophage polarization and their conclusions are supported by solid computational and experimental evidence. The revision has clarified that the focus is the identification of the regulatory barcodes in a myeloid cell line. Future studies in primary cells and in vivo will be required to assess the roles of these regulators in a broader context.

eLife Assessment

In this compelling study, the authors examine the interactions between stellate cells and PV+ interneurons in the medial entorhinal cortex. Huang et al. focus on the spatial distribution of synaptic inputs and demonstrate that closely located neuron pairs receive common inputs, suggesting a structured functional organization in the entorhinal cortex. Advanced dual whole-cell patch recordings further reveal patterns of postsynaptic activation, indicating intensive interactions within clusters of these neurons, with weaker interactions between clusters. These findings offer significant insights into the functional dynamics of the entorhinal cortex and the circuit mechanisms that shape grid cell activity. This study is important not only for the field of MEC and grid cells, but also for broader fields of continuous attractor networks and neural circuits.

eLife assessment

This study provides valuable new insights into how multisensory information is processed in the lateral cortex of the inferior colliculus, a poorly understood part of the auditory midbrain. By developing new imaging techniques that provide the first optical access to the lateral cortex in a living animal, the authors provide convincing in vivo evidence that this region contains separate subregions that can be distinguished by their sensory inputs and neurochemical profiles, as suggested by previous anatomical and in vitro studies. This work provides a foundation for future research exploring how this part of the auditory midbrain contributes to multisensory-based behavior.

eLife Assessment

This useful study by Nandy and colleagues examined relationships between behavioral state, neural activity in cortical area V4, and trial-by-trial variability in the ability to detect weak visual stimuli. They present solid evidence indicating that certain changes in arousal and eye-position stability, along with patterns of synchrony in the activity of neurons in different layers of V4, can show modest correspondences to changes in the ability to correctly detect a stimulus. These findings are likely to be of interest to those who seek a deeper understanding of circuit mechanisms that underlie perception.

eLife assessment

The study by Zhu et al. provides important insights into cell-specific genome-wide histone modifications in the frontal cortex of individuals with schizophrenia, as well as shedding light on the role of age and antipsychotic treatment in these associations. The evidence supporting the conclusions is solid.

eLife assessment

This useful study seeks to address the importance of physical interaction between proteins in higher-order complexes for covariation of evolutionary rates at different sites in these interacting proteins. Following up on a previous analysis with a smaller dataset, the authors provide compelling evidence that the exact contribution of physical interactions, if any, remains difficult to quantify. The work will be of relevance to anyone interested in protein evolution.

eLife assessment

This important study identifies the mitotic localization mechanism for Aurora B and INCENP (parts of the chromosomal passenger complex, CPC) in Trypanosoma brucei. The mechanism differs from that in the more commonly studied opisthokonts and is supported by compelling RNAi and imaging experiments, targeted mutations, immunoprecipitations with crosslinking/mass spec, and AlphaFold interaction predictions. The findings will be of interest to cell biologists working on cell division, parasitologists, and those interested in the evolution of mitotic mechanisms.

eLife assessment

This study presents valuable insights into the epigenetic landscape in adult kidney podocytes. A series of solid experiments demonstrate that genes that are regulated by a key kidney transcription factor, Mafb, are essential for H3K4me3 methylation and recruitment of Wt1 to Nphs1 and Nphs2. This new information provides insights into the potential relationship and coordination of transcription factors in regulating target genes in podocytes in glomerular diseases, although the conclusion that MafB is generally required for Wt1 to bind to podocyte-specific promoters is incomplete and should be extended beyond two or three genes.

eLife assessment

The study presents valuable findings on compensatory mechanisms in response to glycosuria. The evidence supporting the claims is solid, although a causal relationship is somewhat uncertain and the addition of a more clinically relevant model would have strengthened the findings. The work will be of interest to diabetes investigators.

eLife assessment

This important study unveils the significant impact of prenatal alcohol exposure on epigenetic patterns, offering new insights into its adverse health outcomes through solid evidence from both mouse models and human data. The findings, which reveal how a high-methyl diet can mitigate these epigenetic alterations, present a promising prenatal care strategy. Despite its solid data overall, the study's small sample size and unaccounted confounders suggest the need for further research to confirm these findings and explore their practical implications.

eLife assessment

This important work contributes to our understanding of the combined effects of metabolic syndrome on fronto-temporal gray matter morphology from two large-scale datasets. The evidence based on state-of-the art multivariate imaging analysis and detailed micro- and macrostructural contextualization analyses is convincing and provides an understanding of the neurological correlates of metabolic syndrome, although the study would have benefitted from the inclusion of longitudinal data.