Evaluated articles

eLife assessment

This study presents a valuable finding on the mechanisms underlying general anesthesia, with a focus on microglial regulation. The evidence supporting the claims of the authors is solid, although some of the novelty of these findings may be reduced based on the recent publication of a similar study. The work will be of interest to medical biologists working on mechanisms of anesthesia, microglia, and neuron-microglia interaction.

eLife assessment

This study presents a useful deep learning-based inter-protein contact prediction method named PLMGraph-Inter which combines protein language models and geometric graphs. The evidence supporting the claims of the authors is solid. The authors show that their approach may be used in cases where AlphaFold-Multimer performs poorly. This work will be of interest to researchers working on protein complex structure prediction, particularly when accurate experimental structures are available for one or both of the monomers in isolation.

eLife assessment

Urtecho et al. use genome-integrated massively parallel reporter assays to catalog and characterize promoters throughout the Escherichia coli genome. The result is a state-of-the-art atlas of promoters, coupled with information on their regulation, that is readily accessible through the website http://ecolipromoterdb.com. This compelling work provides an important resource for researchers studying bacterial transcriptional regulation.

eLife assessment

This potentially important paper addresses the question of how numerical information is represented in the human brain. Experimental findings are interpreted as providing evidence for a sensorimotor mechanism that involves channels, each tuned to a particular numerical range. While this is an interesting application of methodologies used to identify the presence of channels, the evidence supporting the claim that these have a sensorimotor basis is incomplete.

eLife Assessment

The important manuscript presents convincing evidence of temporal correlations during specific oscillatory activity between the prefrontal cortex, thalamic nucleus reuniens, and the hippocampus, in naturally sleeping animals. Such correlations represent solid evidence to support the notion that the thalamic nucleus reuniens participates in the hippocampal and prefrontal cortex dialogue subserving memory processes.

eLife assessment

This valuable manuscript reveals sex differences in bi-conditional Pavlovian learning and conditional behavior. Males learn hierarchical context-cue-outcome associations more quickly, but females show more stable and robust task performance. These sex differences are related to cellular activation in the orbitofrontal cortex. Although the evidence supporting these claims is convincing, some assertions of sex differences in context-dependent discrimination behaviour may be slightly overstated yet have strong potential to guide future research to clarify the nature of these differences. The results will be of interest to many behavioural neuroscientists, particularly those who investigate sex-specific behaviours.

eLife Assessment

Identifying chromatin interactions with high sensitivity and resolution at the genome-wide scale continues to be technically challenging. This study introduces findings based on the improved MNase-based proximity ligation method, MChIP-C, which enables genome-wide measurement of chromatin interactions at single-nucleosome resolution. The evidence presented in this manuscript is convincing, and the technological advancements will be valuable for the study of 3D genome architecture.

eLife assessment

In the last 15 years, large-scale association studies (GWAS) have served to estimate the association between genome-wide common variants and a large number of disparate traits and diseases in humans. This valuable method provides a new way to find correlations between the genetic component of a phenotype of interest, and all this wealth of genetic information. This software adds as a new tool to investigate genetic correlation between traits, and to generate new mechanistic hypotheses and dissect the role of the observed associations in disease heterogeneity. The results of the application of their method are solid and generally agree with what others have seen using similar AD and UKB data.

eLife assessment

The authors of this study implemented an important toolset for 3D reconstruction and segmentation of dissection photographs, which could serve as an alternative for cadaveric and ex vivo MRIs. The tools were tested on synthetic and real data with compelling performance. This toolset could further contribute to the study of neuroimaging-neuropathological correlations.

eLife assessment

This important study describes an atypical role of the odorant binding protein Obp56g in mating plug formation in Drosophila melanogaster suggesting that Obps may play roles in reproduction in addition to their originally described roles in olfaction. Mutant males lacking Obp56g fail to induce the formation of a mating plug in the female reproductive tract-leading to ejaculate loss and reduced sperm storage. The evidence supporting the claims of the authors is solid and compelling. The work will be of interest to biologists studying Obps and seminal fluid protein function and their evolution.

eLife assessment

This important work addresses an interesting question for the vertebrate olfactory community of whether mice can discriminate odorant intermittency to help them navigate the environment. The data were collected and analyzed using solid methodology, however, the paper seems to fall short in demonstrating that animal is actually sensitive to intermittency but not other flow parameters. The work will be of interest to researchers working on sensory neurobiology and animal behavior.

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.