Evaluated articles

eLife Assessment

The manuscript by Guo and colleagues reports valuable findings about 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 added clarity and a few targeted refinements and justifications of analytical choices. Results 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 important study identifies the "H-state" as a potential conformational marker distinguishing amyloidogenic from non-amyloidogenic light chains, addressing a critical problem in protein misfolding and amyloidosis. By combining advanced techniques such as small-angle X-ray scattering, molecular dynamics simulations, and H-D exchange mass spectrometry, the authors provide convincing evidence for their novel findings. However, incomplete experimental descriptions, limitations in SAXS data interpretation, and the way HDX MS data is presented affect the strength and generalizability of the conclusions. Strengthening these aspects would enhance the impact of this work for researchers in amyloidosis and protein misfolding.

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 TB field.

eLife Assessment

This well-written report uses functional neuroimaging in human observers to provide convincing 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 in its present form will be valuable to those examining attention, perception, learning and prediction, but with a few additional analyses could more informatively rule out potential alternative hypotheses. Further discussion of the mechanistic implications could clarify further the broad extent of its significance.

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 mostly convincing, although including additional experiments and discussions would further strengthen the study. 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 measured morphological changes remains unclear.

eLife Assessment

This important study identifies species- and sex-specific neuronal cell types and gene expression in the medial preoptic area (MPOA) to help understand the evolutionary divergence of social behaviors. The evidence from single-nucleus RNA sequencing and immunostaining is convincing and suggests that cellular differences in the MPOA 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 on 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 evidence supporting the claims of the authors is somewhat incomplete and some data are rather questionable; the authors should clarify the relations between ferroptosis-related genes in immune cells and those genes applied in a risk factor analysis in tumor cells. Moreover, the authors should provide experimental validation for the risk score model based on ferroptosis-related genes. The work will be of interest to scientists or clinical scientists working in the field of breast cancer.

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. However, the evidence presented for learning-dependent encoding of visual information is incomplete and it is possible that the surprisingly short-latency increases in activity are actually motor-related signals. Demonstrating that they really are visual responses is necessary in order to draw definitive conclusions from this study.

eLife Assessment

The presented evidence is compelling given a range of complementary and mutually supportive studies. Experiments are generally robustly conducted and well-presented, supporting the claims regarding miRNA mechanisms converging on EMC10 overexpression with 22q11 Del. This is an important study that works to establish a novel antisense oligonucleotide-based approach to treating 22q11.2 deletion syndrome; the findings are likely to advance therapeutic efforts. The authors provide evidence both in vitro in patient-derived iPSCs and in vivo in a 22q11 Del mouse supporting the knockdown (KD) of EMC10 as an effective strategy for the amelioration of neuronal and behavioral deficits.

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 but the evidence presented to support the conclusions drawn is incomplete and other interpretations are possible. 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. While the results are solid, more details about the mechanisms and methods are needed to strengthen the study's conclusions.

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 solid to support an interaction between NRL and the DHX9 helicase. However, the evidence for an interaction between the NRL transcription factor and R-loops is less conclusive. The significance of the study could be enhanced by examining the functional role of NRL interactions with R-loops in the developing retina, which would offer new insights into the gene regulatory networks.

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.

eLife Assessment

This manuscript describes valuable new material of small, unusually preserved fossils from deep in the Cambrian of China and argues they represent very early bilaterian animals such as annelids or panarthropods. The authors present convincing evidence of the fossilisation of specimens as microbial pseudomorphs, however, the fossils show few details and it is difficult to assess their affinity. The broader claims made about the timing and nature of the Cambrian explosion are inadequately supported by the material, given that bilaterians were already known to exist during that period.