Evaluated articles

eLife assessment

In this study, Perez-Lopez and colleagues examine an important function of the chemokine CCL28 in mucosal host defenses against the gut bacterial pathogen Salmonella Typhimurium and lung pathogen Acinetobacter baumanii. They find that CCL28-CCR3 axis regulates neutrophil recruitment and function, and promotes bacterial clearance in one infectious context but exacerbates disease against the other pathogen. Therefore, CCL28 plays a critical role in mucosal immunity and neutrophil biology that differentially affects host defenses against pathogens.

eLife Assessment

The study explored the influence of magnesium on phenotypic antibiotic resistance in two strains of Vibrios: V. alginolyticus ATCC33787 and V. parahaemolyticus VP01. This research is fundamental for revealing the phenotypic antibiotic resistance mechanism utilized by the specified model bacteria in elevated levels of magnesium. The study produced convincing evidence indicating that in high concentrations of magnesium, the efficacy of selected antibiotics was diminished due to decreased biosynthesis of unsaturated fatty acids and PE, along with an increase in the biosynthesis of PG.

eLife Assessment

The study highlights adhesion G-protein-coupled receptor A3 (ADGRA3) as a potential target for activating adaptive thermogenesis in both white and brown adipose tissue. This finding offers valuable insights for researchers in the field of adipose tissue biology and metabolism. The authors have presented additional evidence to address the reviewers' comments, including experiments conducted on primary stromal vascular fractions from adipose tissues. However, the revised manuscript fails to address several reviewer concerns, such as the measurement of whole-body energy expenditure through indirect calorimetry and the assessment of food intake. Furthermore, the nanoparticle-mediated knockdown of Adgra3 did not adequately address the tissue selectivity of ADGRA in mice. As a result, the primary claims of the study are only partially supported by the available data, leading to the conclusion that the research is deemed incomplete.

eLife Assessment

In this potentially important study, the authors conducted atomistic simulations to probe the salt-dependent phase separation of the low-complexity domain of hnRN-PA1 (A1-LCD). The authors have identified both direct and indirect mechanisms of salt modulation, provided explanations for four distinct classes of salt dependence, and proposed a model for predicting protein properties from amino acid composition. There is a range of opinions regarding the strength of evidence, with some considering the evidence as incomplete due to the limitations in the length and statistical errors of the computationally intense atomistic MD simulations.

eLife Assessment

This study provides useful in vitro evidence to support a mechanism whereby dyslipidemia could accelerate renal functional decline through the activation of the AT1R/LOX1 complex by oxLDL and AngII. As such, it improves the knowledge regarding the complex interplay between dyslipidemia and renal disease and provides a solid basis for the discovery of novel therapeutic strategies for patients with lipid disorders. The methods, data, and analyses partly support the presented findings, although the observed variability and need for further in vivo validation require additional research in this key area.

eLife Assessment

The authors demonstrate the valuable discovery that human CD29+/CD56+ myogenic progenitors can differentiate into tendon through the TGFβ pathway, addressing mouse and human interspecies differences in regard to the potential of muscle stem cells. The in vivo transplantation experiments provide convincing evidence for the conclusion, as human CD29+/CD56+ myogenic progenitors contribute to tendon regeneration, resulting in functional recovery in mouse model. The authors' approach can be used for the development of cell therapy for tendon-injured patients.

eLife Assessment

This manuscript reports important findings on the impact of maternal obesity on offspring metabolism. It presents solid evidence that maternal obesity induces genomic methylation alterations in oocytes, which can be partly transmitted to F2 in females, and that melatonin is involved in regulating the hyper-methylation of high fat diet oocytes by increasing the expression of DNMTs via the cAMP/PKA/CREB pathway. This study would be of interest to biologists in the fields of epigenetics and metabolism.

eLife Assessment

In an important fMRI study with an elegant experimental design and rigorous cross-decoding analyses, this work shows a convincing dissociation between two parietal regions in visually processing actions. Specifically, aIPL is found to be sensitive to the causal effects of observed actions, while SPL is sensitive to the patterns of body motion involved in those actions. The work will be of broad interest to cognitive neuroscientists, particularly vision and action researchers.

eLife Assessment

The authors have reported an important study in which they use a double-blind design to explore pharmacological manipulations in the context of a behavioral task. While the sample size is small, the use of varied methodology, including electrophysiology, behavior, and pharmacology, makes this manuscript particularly notable. Overall, the findings are solid and motivate future explanations into the relationships between acetylcholine and motivation.

eLife Assessment

This work presents important findings regarding the interaction of the monkeypox virus (MPXV) attachment H3 protein with the cellular receptor heparan sulfate and the use of this information to develop antivirals potentially effective against all orthopoxviruses. Using a combination of state-of-the art computational and wet experiments the authors present convincing evidence to sustain their claims. These results will interest those working on basic orthopoxviruses biology and antiviral development.

eLife assessment

This valuable study investigates the selectivity of neuronal responses in the primary visual cortex and the dorsal lateral geniculate nucleus to stimuli presented far outside their receptive fields. The evidence supporting the claims is incomplete, due to lack of clarity. This paper should be of interest to neurophysiologists interested in vision and contextual modulations.

eLife assessment

This study identified an innovative molecular mechanism linking diabetes to Alzheimer's disease (AD) risk, with important significance. The finding presents novel insights into AD pathogenesis and provides strong evidence about the mechanistic roles of Kallistatin, and the therapeutic potential of fenofibrate in AD. The experiments are well conducted, and the evidence is convincing.

eLife assessment

This important study examines E. coli growth and division, suggesting that inhomogeneous organization of ribosomes in the cytoplasm results in cell size-dependent growth rate perturbations. The work is conceptually appealing, but incomplete due to shortcomings in the experiments and modeling.

eLife Assessment

This important work proposes a neural network model of interactions between the prefrontal cortex and basal ganglia to implement adaptive resource allocation in working memory, where the gating strategies for storage are adjusted by reinforcement learning. Numerical simulations provide convincing evidence for the superiority of the model in improving effective capacity, optimizing resource management, and reducing error rates, as well as for its human-like performance. This work will be of broad interest to computational and cognitive neuroscientists, and may also interest machine-learning researchers who seek to develop brain-inspired machine-learning algorithms for memory.

eLife Assessment

Rachubinski and colleagues provide an important manuscript that includes two major advances in understanding immune dysregulation in a large cohort of individuals with Down syndrome. The work comprises compelling, comprehensive, and state-of-the-art clinical, immunological, and autoantibody assessment of autoimmune/inflammatory manifestations. Additionally, the authors report promising results from a clinical trial with the JAK inhibitor tofacitinib for individuals with dermatological autoimmune disease.

eLife assessment

The manuscript presents a machine-learning method to predict protein hotspot residues. The validation is incomplete, along with the misinterpretation of the results with other current methods like FTMap.

eLife assessment

Ctnnb1 encodes β-catenin, an essential component of the canonical Wnt signaling pathway. In this important study, the authors identify an upstream enhancer of Ctnnb1 responsible for the specific expression level of β-catenin in the gastrointestinal track. Deletion of this enhancer in mice and analyses of its association with human colorectal tumors provide compelling support that it controls the dosage of Wnt signaling critical to the homeostasis in intestinal epithelia and colorectal cancers.

eLife Assessment

This useful study examines the neural activity in the motor cortex as a monkey reaches to intercept moving targets, focusing on how tuned single neurons contribute to an interesting overall population geometry. The presented results and analyses are solid, though the investigation of this novel task could be strengthened by clarifying the assumptions behind the single neuron analyses, and further analyses of the neural population activity and its relation to different features of behaviour.

eLife Assessment

This valuable study presents a deep learning framework for predicting synergistic drug combinations for cancer treatment in the AstraZeneca-Sanger (AZS) DREAM Challenge dataset. However, the evidence on the generalizability of the model is incomplete, as part of the validation seems to be flawed by overfitting, and only a modest correlation between predictions and observations was observed in the second, more independent test set. The reported tool, DIPx, could be of use for personalized drug synergy prediction and exploring the activated pathways related to the effects of drug combinations.

eLife Assessment

This valuable study by Cui et al. investigates mechanisms generating sighs, which are crucial for respiratory function and linked to emotional states. Utilizing advanced methods in mice, they provide solid evidence that increased excitability in specific preBötzinger complex neuronal subpopulations expressing Neuromedin B receptors, gastrin-releasing peptide receptors, or somatostatin can induce sigh-like large amplitude inspirations. With additional technical clarifications and further elaboration of the limitations in terms of how the results are interpreted in the revised manuscript, the study will interest neuroscientists studying respiratory neurobiology and rhythmic motor systems.