Evaluated articles

eLife Assessment

This valuable study leverages innovative high-dimensional imaging strategies to interrogate pancreatic immune cell profiles and distributions throughout stages of type 1 diabetes (T1D). Despite a notable limitation in the number of donor samples analyzed, the authors identify a series of intriguing "immune signatures" and histopathological features that collectively constitute a solid foundation for future investigations into immunological processes underpinning the pathogenesis of T1D. Accordingly, the work will be of considerable interest to the community of T1D researchers and clinicians.

eLife Assessment

The study presents a valuable finding on the role of cholesterol-binding sites on GLP-1 receptors although the clinical ramifications are unclear and not eminent at this point. Based on the detailed and persuasive responses provided by authors to the concerns raised by reviewers, the revised manuscript is improved substantially and is convincing enough in its scientific merit. The study is a good addition to the scientific community working on receptor biology and drug development for GLP-1 R.

eLife Assessment

This is an important paper that reports in vivo physiological abnormalities in the hippocampus of a rat model of traumatic brain injury (TBI). In this study, authors focused on changes in theta-gamma phase coupling and action potential entrainment to theta, phenomena hypothesized to be critical for cognition. The authors provide convincing evidence of deficits in both features post-TBI and contributes new understanding to how disruptions in oscillatory coordination and spike timing may relate to cognitive impairment.

eLife assessment

This valuable contribution follows past descriptions of ciliation defects, potentially linked to cholinergic neuronal dysfunction, associated with mutated G2019S Lrrk2 expression. The strength of evidence is considered solid and broadly supportive of the claims concerning well-characterized cilia changes in cholinergic neurons over time in the model; however, additional work may be required to define the specificity of the pRab12 antibody in the IHC technique, dependence on LRRK2, and clarification of the cilia phenotype in sporadic PD brains that exists (for the moment) only in a non-peer-reviewed pre-print, despite the prominence of these (preliminary) results highlighted in the abstract and text of the current manuscript. It is hoped that the authors will begin to address the feedback provided by the expert reviewers to help provide a more mechanistic basis for the audience interested in cholinergic defects associated with Parkinson's disease.

eLife Assessment

This important work by Malita et al. describes a mechanism by which an intestinal infection causes an increase in daytime sleep through signaling from the gut to the blood-brain barrier. Their findings suggest that cytokines upd3 and upd2 produced by the intestine following infection act on glia of the blood brain barrier to regulate sleep by modulating Allatostatin A signaling. The evidence is compelling and elegantly performed using the ample Drosophila genetic toolbox, making this work appealing for a broad group of neuroscience researchers interested in sleep and gut-brain interactions.

eLife Assessment

This important study by Wong et al. addresses a longstanding question in the field of associative learning regarding how a motivationally relevant event can be inferred from prior learning based on neutral stimulus-stimulus associations. The research provides convincing behavioral and neurophysiological evidence to address this question. The manuscript will be interesting for researchers in behavioral and cognitive neuroscience.

eLife Assessment

This important work combines theory and experiment to demonstrate convincingly how humans make decisions about sequences of pairs of correlated observations. The proposed model for evidence integration in correlated environments will be of use for the study of decision-making.

eLife Assessment

In this manuscript, Griesius et al analyze the dendritic integration properties of NDNF and OLM interneurons, and suggest that the supralinear NMDA receptor-dependent synaptic integration may be associated with dendritic calcium transients only in NDNF interneurons. These findings are important because they suggest there might be functional heterogeneities in the mechanisms underlying synaptic integration in different classes of interneurons of the mouse neocortex and hippocampus. The revised work remains incomplete due to remaining concerns about experimental methodology, cell health, and lack of dendritic Na-spikes which have been recorded in previous works.

eLife Assessment

This important study shows that a very slow (infraslow) oscillation occurs in voltage recordings from the dentate gyrus of the adult mouse. The authors suggest that it is related to sleep stage and serotonin acting at one type of serotonin receptor in the dentate gyrus. The results are significant because they suggest new insight into how a slow oscillation affects memory through serotonin receptors in the dentate gyrus. Convincing data are provided to support the claims.

eLife assessment

In this study, Ferling and colleagues provide convincing evidence demonstrating that myeloid cells exert distinct, cargo-dependent responses during and after phagocytosis. These important findings establish previously unrecognized insights into the function(s) of myeloid cells in immunosurveillance and are thus likely to be broadly impactful across the spectrum of biomedical disciplines including immunology and cell biology. Notwithstanding these clear strengths of the article, some minor issues were noted pertinent to the relative opaqueness of the mechanisms underpinning context-specific RhoA activation.

eLife Assessment

Utilizing transgenic lineage tracing techniques and tissue clearing-based advanced imaging and three-dimensional slices reconstruction, the authors comprehensively mapped the distribution atlas of NFATc1+ and PDGFR-α+ cells in dental and periodontal mesenchyme and tracked their in vivo fate trajectories. This important work extends our understanding of NFATc1+ and PDGFR-α+ cells in dental and periodontal mesenchyme homeostasis, and should provide impact on clinical application and investigation. The strength of this work is compelling in employing CRISPR/Cas9-mediated gene editing to generate two dual recombination systems, and mapped gNFATc1+ and PDGFR-α+cells residing in dental and periodontal mesenchyme, their capacity for progeny cell generation, and their inclusive, exclusive and hierarchical relations in homeostasis, generating a spatiotemporal atlas of these skeletal stem cell population.

eLife assessment

The authors made a useful finding that Zizyphi spinosi semen, a traditional Chinese medicine, has demonstrated excellent biological activity and potential therapeutic effects against Alzheimer's disease (AD). The researchers presented the effects, but the research evidence for the mechanism was incomplete. The main claims were only partially supported.

eLife Assessment

This study presents a fundamental finding on how levels of m6A levels are controlled, invoking a consolidated model where degradation of modified RNAs in the cytoplasm plays a primary role in shaping m6A patterns and dynamics, rather than needing active regulation by m6A erasers and other related processes. The evidence is compelling through its use of transcriptome-wide data and mechanistic modeling. Relevant for any reader with an interest in RNA metabolism, this new framework consolidates previous observations and highlights the importance of careful experimentation for evaluation m6A levels.

eLife Assessment

This important study represents a data processing pipeline to discover causal interactions from time-lapse imaging data, and convincingly illustrates it on a challenging application for the analysis of tumor-on-chip ecosystem data. The authors describe the raw data they used (imaging data), go through a step-by-step description on how to extract the features they are interested in from the raw data, and how to perform the causal discovery process. This paper tackles the problem of learning causal interactions from temporal data, which is applicable to many biological applications.

eLife assessment

This important study shows a significant role for Mushashi-2 (Msi2) in lung adenocarcinoma. The authors provided solid data that support the requirement for Msi2 in tumor growth and progression, although the study would have been strengthened by including more patient samples and additional evidence regarding Msi2+ cells being more responsive to transformation. These findings are of interest to both the lung cancer and the RNA binding protein fields.

eLife Assessment

This valuable study examines the variability in spacing and direction of entorhinal grid cells, providing convincing evidence that such variability helps disambiguate locations within an environment. This study will be of interest to neuroscientists working on spatial navigation and, more broadly, on neural coding.

eLife Assessment

This important study combines genetic analysis, biochemistry, and structural modeling to reveal new insights into how changes in protein-protein structure activate signal transduction as part of the bacterial general stress response. The data, which was collected using validated and standard methods, and its interpretations are convincing; however, to fully meet the title's promise, additional experimental evidence is needed to strengthen the proposed model and its potential application to other systems. This manuscript will be of broad interest to microbiologists, structural biologists, and cell biologists.

eLife Assessment

This important study developed a new sensor for TDP-43 activity that is sensitive and robust that should strongly impact the field's ability to monitor whether TDP-43 is functional or not. The evidence, though limited to cell culture, is compelling and is the first demonstration that a GFP on/off system can be used to assess genetic TDP-43 mutants as well as loss of soluble TDP-43.

eLife Assessment

The authors implement a valuable multi-tissue approach to dissect the physiologic consequences of JNK inhibition in parallel with dietary perturbation via sucrose. The conclusions of disrupted liver, muscle and adipose metabolism being central to these effects are solid, as they are supported by a combination of experimental dissection and network modeling approaches.

eLife Assessment

This manuscript presents a valuable new quantitative crosslinking mass spectrometry approach using novel isobaric crosslinkers. The data are solid and the method has potential for a broad application in structural biology if more isobaric crosslinking channels are available and the quantitative information of the approach is exploited in more depth.