Evaluated articles

eLife Assessment

This study provides valuable new insight into the role of Fgf signalling in SUFU mutation-linked cerebellar tumors and indicates novel therapeutic interventions via inhibition of Fgf signalling. The potential impact of this work is therefore very high and it is supported by solid evidence. However, due to current limitations in the full identification of the cell types secreting FGF5, and issues with robustness of evaluation of genetically engineered animals, the validation of some interpretations awaits future experiments.

eLife Assessment

This valuable study investigates the immune system's role in pre-eclampsia. The authors map the immune cell landscape of the human placenta and find an increase in macrophages and Th17 cells in patients with pre-eclampsia. Following mouse studies, the authors suggest that the IGF1-IGF1R pathway might play a role in how macrophages influence T cells, potentially driving the pathology of pre-eclampsia. There is convincing evidence in this study that will be of interest to immunologists and developmental biologists.

eLife Assessment

This study presents a valuable finding that the biomechanical force of heart contractility is required for robust endocardial id2b expression, which in return promotes valve development and myocardial function through upregulation of Neuregulin 1. The data were collected and analyzed using solid methodology and can be used as a starting point for deeper mechanistic insights into the genetic programs regulating endocardial-myocardial crosstalk during heart development.

eLife Assessment

This important study offers a powerful empirical test of a highly influential hypothesis in population genetics. It incorporates a large number of animal genomes spanning a broad phylogenetic spectrum and treats them in a rigorous unified pipeline, providing the convincing negative result that effective population size scales neither with the content of transposable elements nor with overall genome size. These observations demonstrate that there is still no simple, global hypothesis that can explain the observed variation in transposable element content and genome size in animals.

eLife Assessment

This study presents valuable findings with practical and theoretical implications for drug discovery, particularly in the context of repurposing cipargamin CIP for the treatment of Babesia spp. The evidence is solid with the methods, data, and analyses broadly supporting the claims. The paper will be of great interest to scientists in drug discovery, computational biology, and microbiology.

eLife Assessment

This is an important account of replay as recency-weighted context-guided memory reactivation that explains a number of empirical findings across human and rodent memory literatures. The evidence is compelling and the work is likely to inspire further adaptions to incorporate additional biological and cognitive features.

eLife Assessment

This important study provides convincing data suggesting that subcellular localization of the spatial regulator of cell division, MinD, is an intrinsic feature of the protein's ability to associate with the membrane as both a dimer and a monomer. These findings distinguish the behavior of MinD in B. subtilis from its counterpart in E. coli and suggest that there is not a need to invoke additional localization factors. The reviewers felt that the revisions, particularly the additional experiments and changes to the text to make the experimental design and conclusions clearer, improve the quality of the manuscript.

eLife Assessment

In the gram-positive model organism Bacillus subtilis, the membrane associated ParA family member MinD, concentrates the division inhibitor MinC at cell poles where it prevents aberrant division events. This important study presents compelling data suggesting that polar localization of MinCD is largely due to differences in diffusion rates between monomeric and dimeric MinD. This finding is exciting as it negates the necessity for a third, localization determinant, in this system as has been proposed by previous investigations.

eLife Assessment

The ability to estimate the force of infection for Plasmodium falciparum from other more directly measurable epidemiological quantities would contribute to malaria epidemiology. The authors propose a method to accomplish this using genetic data from the var genes of the Pf genome and novel applications of existing methods from queueing theory. After revising the manuscript, this is a useful contribution to the field and the authors provide solid evidence to support it.

eLife Assessment

The study presents compelling evidence that the melanocortin system originating in the arcuate nucleus of the hypothalamus plays a crucial role in puberty onset, representing a significant advance in our understanding of reproductive biology. The research employs innovative approaches and benefits from the combined expertise of two respected laboratories, enhancing the robustness of the findings. Given the potential impact on human health and the strength of the evidence presented, this fundamental work will likely influence the field substantially and may inform future clinical applications.

eLife Assessment

Saijilafu et al. describe valuable findings suggesting that MLCK and MLCP bidirectionally regulate NMII phosphorylation ultimately impinging on axonal growth during regeneration in the central and peripheral nervous systems. Solid evidence is collected from culture and in vivo models, and through pharmacologic and genetic loss-of-function approaches. However, how MLCK and MLCP regulates NMII activity is not fully addressed or discussed. In sum, this knowledge is of potential interest for the field due to the relevance of identifying mechanistic details that regulate axonal regeneration

eLife Assessment

Data presented in this useful report suggest a potentially new model for chemotaxis regulation in the gram-negative bacterium P. putida. Data supporting interactions between CheA and the copper-binding protein CsoR, reveal potential mechanisms for coordinating chemotaxis and copper resistance. There was, however, concern about the large number of CheA interactors identified in the initial screen and it was felt that the study was incomplete without a substantial number of additional experiments to test the model and bolster the authors' conclusions.

eLife Assessment

This important work supports the role of breast carcinoma amplified sequence 2 (Bcas2) in positively regulating primitive wave hematopoiesis through amplification of beta-catenin-dependent (canonical) Wnt signaling. The study is convincing: it uses appropriate and validated methodology in line with the current state-of-the-art, and there is a first-rate analysis of a strong phenotype with highly supportive mechanistic data. The findings shed light on the controversial question of whether, when, and how canonical Wnt signaling may be involved in hematopoietic development. The work will be of interest to hematologists and developmental biologists.

eLife Assessment

This fundamental work describes for the first time the combined gene expression and chromatin structure at the genome level in isolated chondrocytes and classical (cranial) and non-classical (notochordal) osteoblasts. In a compelling analysis of RNA-Seq and ATAC data, the authors characterize the two osteoblast populations relative to their associated chondrocyte cells and further proceed with a convincing analysis of the crucial entpd5a gene regulatory elements by investigating their respective transcriptional activity and specificity in developing zebrafish.

eLife Assessment

This study presents a valuable insight into the mechanism of action of With-No-lysine (K) kinases (WNK) in the insulin-dependent signaling in the context of learning and memory. The study uses solid methodological approaches that align with the current standards in the field. The revised manuscript, which includes diverse models ranging from mouse to cell systems assessed by a broad range of complementary techniques, convincingly argues that WNK signaling contributes to neuronal function in insulin-sensitive brain regions such as the hippocampus through its effects on GLUT4 trafficking.

eLife Assessment

This study presents a useful demonstration that a specific protein fragment may induce the loss of synapses in Alzheimer's disease. The evidence supporting the data is solid but only partially supports the conclusion and would benefit from additional discussion indicated by the literature from reviewer #1. The application of the findings is limited because blocking the formation of the protein fragment has not benefited patients in several clinical trials.

eLife Assessment

This manuscript describes the impact of modulating signaling by a key regulatory enzyme, Dual Leucine Zipper Kinase (DLK), on hippocampal neurons. The results are interesting and will be important for scientists interested in synapse formation, axon specification, and cell death. The authors have carefully addressed the comments made by the reviewers and the findings are convincing in large part due to the use of extensive mouse genetics, detailed gene expression of enriched genes, and recognition of neuron vulnerability.

eLife Assessment

This fundamental work demonstrates that ABHD6 regulates AMPAR gating kinetics in a TARP γ-2-dependent manner. The evidence in this study is compelling. This study will be of interest to readers in the field of synaptic transmission.

eLife Assessment

In this manuscript, Chen et al. used cryo-ET and in vitro reconstituted system to demonstrate that the autoinhibited form of LRRK2 can also assemble into filaments on the microtubule surface, with a new interface involving the N-terminal repeats that were disordered in the previous active-LRRK2 filament structure. The structure obtained in this study is the highest resolution of LRRK2 filaments done by subtomogram averaging, representing a major technical advance compared to the previous paper from the same group. This is an important study, especially considering the pharmacological implications of the effect of inhibitors of the protein. The strengths of the data are convincing, but the study would be considerably strengthened if the authors explored the physiological significance of the new interfaces and the incomplete decoration of microtubules described here.

eLife Assessment

The authors provide convincing data that identify a novel, non-opioid biologic from human birth tissue products with anti-nociceptive properties in a preclinical mouse model of surgical pain. This important study highlights the potential use of naturally derived biologics from human birth tissues as safe and sustainable pain treatment options that do not possess the adverse side effects associated with opioids and synthetic pharmaceuticals. Whether these results will translate to the clinic remains to be seen, nevertheless, these preclinical findings are promising.