Evaluated articles

eLife assessment

The ability to estimate the force of infection for Plasmodium falciparum from other more directly measurable epidemiological quantities is a useful contribution 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. While the simulations are sophisticated, the real-world application of the method is incomplete in its analysis and would benefit from clearer articulation of the assumptions being made. Given the lack of clarity in the methods and presentation of results, it is difficult to fully assess the performance of their proposed estimation procedure.

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 work, which represents a fundamental advance, 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 work will likely influence the field substantially and may inform future clinical applications.

eLife assessment

Saijilafu et al. describe that MLCK and MLCP bidirectionally regulate NMII phosphorylation ultimately impinging on axonal growth during regeneration in the central and peripheral nervous systems. However, the evidence is in most cases incomplete, since some key controls are missing, some major claims are too broad to be supported by data and some claims and evidence present internal contradictions. In sum, this knowledge is potentially useful for the field due to the relevance of identifying mechanisms that regulate axonal regeneration, providing some claims inconsistencies are better supported and properly discussed.

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

In this important study, the findings have theoretical and practical implications beyond a single subfield; the 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, using appropriate and validated methodology in line with the current state-of-the-art; 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 but also to developmental biologists.

eLife assessment

This 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 seeks to expand the understanding of insulin and glucose responses in the brain, specifically by implicating a family of protein kinases responsive to insulin. The significance of the study to the field is valuable. The evidence supporting the conclusions about brain glucose utilization is convincing, although there are several aspects that could benefit from additional validation to strengthen the claims.

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 incomplete and would benefit from additional experiments. 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 methods and interpretation of the data are solid, but the study can be further strengthened with some additional studies and controls.

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 addressed several discrepancies relating to their earlier work, and 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.

eLife assessment

Examination of (a)periodic brain activity has gained particular interest in the last few years in the neuroscience fields relating to cognition, disorders, and brain states. Using large EEG/MEG datasets from younger and older adults, the current study provides compelling evidence that age-related differences in aperiodic EEG/MEG signals can be driven by cardiac rather than brain activity. Their findings have important implications for all future research that aims to assess aperiodic neural activity, suggesting control for the influence of cardiac signals is essential.

eLife assessment

This study demonstrates the potential role of 17α-estradiol in modulating neuronal gene expression in the aged hypothalamus of male rats, identifying key pathways and neuron subtypes affected by the drug. While the findings are useful and provide a foundation for future research, the strength of supporting evidence is incomplete due to the lack of female comparison, a young male control group, unclear link to 17α-estradiol lifespan extension in rats, demonstration of physiological effects of the treatment, and insufficient analysis of glial cells and cellular senescence in CRH neurons.

eLife assessment

This study provides important computational insights into the dynamics of PROTAC-induced degradation complexes. The findings are solid and hold significant implications for advancing cancer treatments, particularly for breast and prostate cancers. However, the major conclusions of the work could be strengthened with a more thorough analysis. This work will be of broad interest to both biochemists and biophysicists.

eLife assessment

Bonnifet et al. present data on the expression and interacting partners of the transposable element L1 in the mammalian brain. The work includes important findings addressing the potential role of L1 in aging and neurodegenerative disease. However, several aspects of experimental evidence presented are preliminary and the study remains incomplete in its current form.

eLife assessment

This study presents a valuable finding on the role of the Inferior Colliculus in sensory prediction, cognitive decision-making, and reward prediction. The evidence supporting the claims of the authors is solid. The work will be of interest to neurobiologists working on auditory processing.

eLife assessment

This work presents a valuable new approach for self-supervised segmentation for fluorescence microscopy data, which could eliminate time-consuming data labeling and speed up quantitative analysis. The experimental evidence supplied is currently incomplete as the comparison with other methods is only done on a single dataset, lacks common metrics, and could not be easily reproduced for other sample data listed in the manuscript.

eLife assessment

The fruit fly brain hosts neurosecretory neurons (Insulin Producing Cells or IPCs) that integrate many inputs and release insulin directly into the hemolymph. In this fundamental study, the population of IPCs are shown to be heterogeneous in their receptor diversity, exhibiting a range of responses to neuromodulation. The authors convincingly demonstrate, using a battery of experimental techniques and relying on the mapped whole brain connectome, how the heterogeneity in the responses across individual IPCs occur simultaneously and together modulate insulin release to maintain metabolic homeostasis. This work will be of interest to neuroscientists and physiologists, in particular for how cellular diversity results in a better control of homeostasis in short time scales.

eLife assessment

In this report, the authors present valuable findings identifying a novel worm-specific protein (sdg-1) that is induced upon loss of dsRNA import via SID-1, but is not required to mediate SID-1 RNA regulatory effects. The genetic and genomic approaches are well-executed. The existing data are solid, but the study would benefit from additional supporting evidence. The manuscript's central findings could also be refined to avoid overstating the results. These findings will be of interest to those working in the germline epigenetic inheritance field.