Evaluated articles

eLife Assessment

The authors identify the Bearded-type small protein E(spl)m4 as a physical and genetic interactor of TRAF4 in the Drosophila wing disc. These valuable findings with potential biomedical relevance are, however, supported by incomplete evidence based largely on overexpression studies that lack quantification, limited molecular support for their model, and issues with Bearded family protein specificity. The work could be of interest to researchers in the fields of cell signaling and developmental biology.

eLife Assessment

This manuscript makes a valuable contribution to the concept of fragility of meta-analyses via the so-called 'ellipse of insignificance for meta-analyses' (EOIMETA). The strength of evidence is solid, supported primarily by an example of the fragility of meta-analyses in the association between Vitamin D supplementation and cancer mortality, but the approach could be applied in other meta-analytic contexts. The significance of the work could be enhanced with a more thorough assessment of the impact of between-study heterogeneity, additional case studies, and improved contextualization of the proposed approach in relation to other methods.

eLife Assessment

This study presents a useful overview of the taxonomic composition of the microbiome associated with Dactylorhiza traunsteineri, a widely distributed orchid species in Central Europe. The evidence supporting the claims of the authors is incomplete, especially when it comes to the (secondary) metabolic pathways found in the metagenome assembled genomes, and requires more substantial analysis to be able to claim that these pathways play a key role in microbiome-orchid symbiosis.

eLife Assessment

The authors aim to understand why Kupffer cells (KCs) die in metabolic-associated steatotic liver disease (MASLD). This is a useful study using in vitro studies and an in vivo genetic mouse model, suggesting that increased glycolysis contributes to KC death in MASLD. However, the data presented are incomplete as some inconsistencies in the results presented are identified in the characterisation of KCs. This work will be of interest to researchers in the immunology and metabolism fields.

eLife Assessment

This is a useful study that examines the relationship between neuropeptide signaling and the precision of vocal motor output using the songbird as a model system. The study presents evidence based on differential expression patterns and genetic or pharmacological inhibition of various neuropeptide genes for a causal role in song performance; however, this evidence is incomplete.

eLife Assessment

This study examines the role of the fungal pathogen Candida albicans in the progression of colorectal cancer, a relevant and urgent topic given the global incidence of colon cancer. While the findings are useful and provide solid experimental work and insight into how Candida may contribute to tumor progression, the small patient sample size, reliance on in vitro models, and absence of in vivo validation may limit its impact. This work will interest scientists studying cancer progression and the role played by pathogens.

eLife Assessment

The present manuscript by Cordeiro et al., shows convincing evidence that α-mangostin, a xanthone obtained from the fruit of the Garcinia mangostana tree, behaves as a strong activator of the large-conductance (BK) potassium channels; macroscopic currents and single-channel experiments show that α-mangostin produces an increase in the probability of opening, without affecting the single-channel conductance. The authors put forward that α-mangostin activation of the BK channel is state-independent, and molecular docking and mutagenesis suggest that α-mangostin binds to a site in the internal cavity. Additionally, the authors show that α-mangostin can relax arteries, further suggesting the plausibility of the proposed effects of this compound. These are valuable findings that should be of interest to channel biophysicists and physiologists alike.

eLife Assessment

The study highlights development of a multiplex coregulator TR-FRET (CRT) assay that detects ligands with theoretical full agonist, partial agonist, antagonist, and inverse agonist signatures within the same chemical series. The findings are valuable and will have theoretical and practical implications in the subfield, with respect to guiding the design of non-lipogenic liver X receptor (LXR) agonists. The strength of the evidence is solid, whereby the methods, data, and analyses broadly support the claims with only minor weaknesses that can be dealt with through improvements in the data analysis and the discussion. This study will be of interest to experts working in the areas of pharmacology, medicinal chemistry, and drug discovery in Alzheimer's diseases and dementias.

eLife Assessment

The one-carbon tetrahydrofolate metabolism plays a crucial role in producing essential metabolic intermediates. In this study, the authors employ a genetics-based approach to demonstrate that three different metabolic pathways are essential for synthesizing 1C-tetrahydrofolates (1C-THF). Disrupting any of these pathways impairs both growth and virulence. Although the work presented is valuable, the experimental evidence remains incomplete without direct quantification of folate intermediates.

eLife Assessment

This important study presents convincing evidence that uncovers a novel signaling axis impacting the post-mating response in females of the brown planthopper. The findings open several avenues for testing the molecular and neurobiological mechanisms of mating behavior in insects, although broad concerns remain about the relevance of some claims.

eLife Assessment

This important study reports on the relationships between cerebral haemodynamics and a number of factors that relate to genetics, lifestyle, and medical history using data from a large cohort. Compelling evidence suggests that brief arterial spin labelling MRI acquisition can lead to both expected observations about brain health, as manifested in cerebral blood flow, and biomarkers for use in diagnosis and treatment monitoring. The results can be used as a starting point for hypothesis generation and further evaluation of conditions expected to affect haemodynamics in the brain.

eLife Assessment

This manuscript describes a valuable screening approach to identifying nanobodies with the potential to modulate gene expression via epigenetic regulators. While the concept is of interest and the screening strategy is well designed, the current evidence supporting mechanistic specificity remains incomplete.

eLife Assessment

This valuable study addresses a critical and timely question regarding the role of a subpopulation of cortical interneurons (Chrna2-expressing Martinotti cells) in motor learning and cortical dynamics. However, while some of the behavior and imaging data are impressive, the small sample sizes and incomplete behavioral and activity analyses make interpretation difficult; therefore, they are insufficient to support the central conclusions. The study may be of interest to neuroscientists studying cortical neural circuits, motor learning, and motor control.

eLife Assessment

This valuable study shows that regions of the human auditory cortex that respond strongly to voices are also sensitive to vocalizations from closely related primate species. The study is methodologically solid, though additional analyses - particularly those isolating the acoustic features that differentiate chimpanzee from bonobo calls - would further strengthen the conclusions. With additional analyses and discussions, the work has the potential to offer key insights into the evolutionary continuity of voice processing and would be of interest to researchers studying auditory processing and evolutionary neuroscience in general.

eLife Assessment

This study presents a valuable tool named TSvelo, a computational framework for RNA velocity inference that models transcriptional regulation and gene-specific splicing. The evidence supporting the claims of the authors is solid, although elaboration of the computational benchmark and datasets would have strengthened the study. The work will be of interest to computational scientists working in the field of RNA biology.

eLife Assessment

This fundamental study presents experimental evidence on how geomagnetic and visual cues are integrated in a nocturnally migrating insect. The evidence supporting the conclusions is compelling. The work will be of broad interest to researchers studying animal migration and navigation.

eLife Assessment

This valuable study investigates the role of P-bodies in yeast proliferation and mRNA regulation within the phyllosphere, proposing that P-body assembly contributes to methanol metabolism and stress adaptation. The findings are of interest to researchers studying post-transcriptional gene regulation and microbial ecology in plants. However, the evidence is incomplete, as most experiments were performed under artificial conditions, relied on limited genetic validation, and were supported primarily by qualitative or low-resolution imaging.

eLife Assessment

This important work introduces a family of interpretable Gaussian process models that allows us to learn and model sequence-function relationships in biomolecules. These models are applied to three recent empirical fitness landscapes, providing convincing evidence of their predictive power. The findings should be of interest to the community working on the sequence-function relationship, on epistasis, and on fitness landscapes.

eLife Assessment

This valuable study demonstrates that self-motion strongly affects neural responses to visual stimuli, comparing humans moving through a virtual environment to passive viewing. However, evidence that the modulation is due to prediction is incomplete as it stands, since participants may come to expect visual freezes over the course of the experiment. This study bridges human and rodent studies on the role of prediction in sensory processing, and is therefore expected to be of interest to a large community of neuroscientists.

eLife Assessment

The authors analyzed spectral properties of neural activity recorded using laminar probes while mice engaged in a global/local visual oddball paradigm. They found solid evidence for an increase in gamma (and theta in some cases) for unpredictable versus predictable stimuli, and a reduction in alpha/beta, which they consider evidence towards a "predictive routing" scheme. The study is overall important because it addresses the basis of predictive processing in the cortex, but some of the analytical choices could be better motivated, and overall, the manuscript can be improved by performing additional analyses.