Evaluated articles

eLife Assessment

This important study uses Mendelian Randomization to provide evidence that early-life reproductive phenotypes (i.e., age at onset of menarche and age at first birth) have a significant impact on numerous health outcomes later in life. The empirical evidence provided by the authors supporting the antagonistic pleiotropy theory is solid. Theories of aging should be empirically tested and this study provides a good first step in that direction.

eLife Assessment

This valuable study by Guo and colleagues reports the inhibitory activity of caffeic acid phenethyl ester (CAPE) against TcdB, a key toxin produced by Clostridioides difficile. C. difficile infections are a major public health concern, and this manuscript provides interesting data on toxin inhibition by CAPE, a potentially promising therapeutic alternative for this disease. The strength of the evidence to support the conclusions is solid, with some concerns about the moderate effects on the mouse infection model and direct binding assays of CAPE to the toxin.

eLife Assessment

This important work combines self-report, neural and physiology data to examine the efficacy and mechanisms of counter conditioning versus extinction in reducing re-emergence of conditioned threat responses and show that this appears to rely on the nucleus accumbens rather than the ventromedial prefrontal cortex. These findings are supported by convincing evidence, though some areas could benefit from a few targeted refinements. The findings will be of interest to researchers across multiple subfields, including neuroscientists, cognitive theory researchers, and clinicians, particularly those with an interest in clinical applications in trauma therapies.

eLife Assessment

This study addresses an important and longstanding question regarding the molecular mechanism of protein misfolding in Ig light chain (LC) amyloidosis (AL), a life-threatening condition. By combining advanced techniques, including small-angle X-ray scattering, molecular dynamics simulations, and hydrogen-deuterium exchange mass spectrometry, the authors provide convincing evidence that the "H state" distinguishes amyloidogenic from non-amyloidogenic LCs. These findings not only offer novel insights into LC structural dynamics but also hold promise for guiding therapeutic strategies in amyloidosis and will be of particular interest to structural biologists, biophysicists, and many others working on amyloid diseases.

eLife Assessment

This basic research study presents useful data concerning the menstrual fluid composition and its potential for endometriosis biomarker research. However, despite solid bioinformatics analyses, the choice of markers used to separate or identify the different cell types needs to be justified and the results better discussed in relation to current knowledge of the pathophysiology of endometriosis.

eLife Assessment

This study provides valuable insights into the host's variable susceptibility to Mycobacterium tuberculosis, using a novel collection of wild-derived inbred mouse lines from diverse geographic locations, along with immunological and single-cell transcriptomic analyses. While the data are convincing, a deeper mechanistic investigation into neutrophil subset functions would have further enhanced the study. This work will interest microbiologists and immunologists in the tuberculosis field.

eLife Assessment

This important and well-written study uses functional neuroimaging in human observers to provide compelling evidence that activity in the early visual cortex is suppressed at locations that are frequently occupied by a task-irrelevant but salient item. This suppression appears to be general to any kind of stimulus and also occurs in advance of any item actually appearing. The work will be of great interest to psychologists and neuroscientists examining attention, perception, learning and prediction.

eLife Assessment

This important work advances our understanding of CHMP5's role in regulating osteogenesis through its impact on cellular senescence. The evidence supporting the conclusion is convincing and the revised manuscript is largely improved. This paper holds potential interest for skeletal biologists who study the pathogenesis of age-associated skeletal disorders.

eLife Assessment

The study describes a useful tool for assessing microglia morphology in a variety of experimental conditions. The MorphoCellSorter provides a solid platform for ranking microglia to reflect their morphology continuum and may offer new insight into changes in morphology associated with injury or disease. While the study provides an alternative approach to existing methods for measuring microglia morphology, the functional significance of the measured morphological changes were not determined.

eLife Assessment

This important study identifies species- and sex-specific neuronal cell types and gene expression in the preoptic area (POA) to help understand the evolutionary divergence of social behaviors. The evidence from single-nucleus RNA sequencing and immunostaining is compelling and suggests that cellular differences in the POA may contribute to behavioral variations such as mating and parental care that are apparent in two closely related deer mouse species. These rich observations provide an entry point for future hypothesis-driven experiments to demonstrate a causal role for these populations in sex- or species-variable behaviors in vertebrates. These data will be a resource that is of value to behavioral neuroscientists.

eLife Assessment

In this potentially valuable computational study, the authors conducted atomistic and coarse-grained simulations to probe the temperature-dependent phase behaviors of ELF3, a disordered component of the evening complex in plant. The results aim to highlight the role of polyQ tracts in modulating the temperature sensitivity. The level of evidence is considered incomplete, due to the lack of systematic calibration of the coarse-grained model and limited statistical uncertainty analysis, especially considering the relatively subtle nature of the differences due to temperature change.

eLife Assessment

This study presents a useful finding for the ferroptosis-mediated tumor microenvironment (TME) in triple-negative breast cancer (TNBC) using public single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data. The data were collected and analyzed using solid and validated methodology and can be used as a starting point for functional studies of TME in TNBC. The work will be of interest to medical biologists working in the field of TNBC.

eLife Assessment

This useful study employs AlphaFold2 to predict interactions among 20 nuage proteins, identifying five novel interaction candidates, three of which are validated experimentally through co-immunoprecipitation. Expanding the analysis to 430 oogenesis-related proteins and screening ~12,000 Drosophila proteins for interactions with Piwi, the study identifies 164 potential binding partners, demonstrating how computational predictions can streamline experimental validation. This study provides a solid basis for further investigations into eukaryotic protein interaction networks.

eLife Assessment

This is an important study that aims to investigate the behavioral relevance of multisensory responses recorded in the auditory cortex. The experiments are elegant and well-designed and are supported by appropriate analyses of the data. Although solid evidence is presented that is consistent with learning-dependent encoding of visual information in auditory cortex, further work is needed to establish the origin and nature of these non-auditory signals and to definitively rule out any effects of movement-related activity.

eLife Assessment

This is an important study that establishes how anti-sense oligonucleotides degrading a specific target protein called EMC10 can rescue neuronal function in models of chromosome 22.11.2 deletions. The authors use human iPSC-derived neurons and a mouse model to provide compelling data for the rescue of cellular and cognitive features of 22.11.2 phenotypes upon ASO regulation of EMC10. These pre-clinical data are of interest because they support reduction of ECM10 as a promising therapeutic strategy.

eLife Assessment

This useful study investigates the impact of disrupting the interaction of RAS with the PI3K subunit p110α in macrophage function in vitro and inflammatory responses in vivo. Solid data overall supports a role for RAS-p110α signalling in regulating macrophage activity and so inflammation, however for many of the readouts presented the magnitude of the phenotype is not particularly pronounced. Further analysis would be required to substantiate the claims that RAS-p110α signalling plays a key role in macrophage function. Of note, the molecular mechanisms of how exactly p110α regulates the functions in macrophages have not yet been established.

eLife Assessment

This important work advances our understanding of DNA methylation and its consequences for susceptibility to DNA damage. This work presents evidence that DNA methylation can accentuate the genomic damage propagated by DNA damaging agents as well as potentially being an independent source of such damage. The experimental results reported are sound. The evidence presented to support the conclusions drawn is convincing and alternative interpretations are considered. The work will be of broad interest to biochemists, cell and genome biologists.

eLife Assessment

Zhang et al. present important findings that reveal a new role for TET2 in controlling glucose production in the liver, showing that both fasting and a high-fat diet increase TET2 levels, while its absence reduces glucose production. TET2 works with HNF4α to activate the FBP1 gene upon glucagon stimulation, while metformin disrupts TET2-HNF4α interaction, lowering FBP1 levels and improving glucose homeostasis. The results are convincing and expand our understanding of gluconeogenesis regulation.

eLife Assessment

This important study employed multiple orthogonal techniques and tissue samples to investigate the interaction between the NRL transcription factor and RNA-binding proteins in the retina. The findings are convincing to support an interaction between NRL and the DHX9 helicase. The significance of the study could be enhanced with functional experiments of NRL-R-loop interactions in the developing retina and their potential role in photoreceptor health and gene regulation.

eLife Assessment

Ferredoxins are ubiquitous electron transfer proteins that drive essential metabolic processes across all domains of life. This fundamental contribution to the field provides the first description of how specific amino acids, though a series of hydrogen bonds, control the ability of iron-sulfur clusters in ferrodoxins to accept and donate electrons. The evidence supporting the conclusions is compelling as is the combined use of neutron crystallography with X-ray crystallography and classical spectral/redox studies.