Evaluated articles

eLife assessment

This important multicenter study provides convincing evidence that the auditory noise emitted during online transcranial ultrasound stimulation (TUS) protocols can pose a considerable confound and is able to explain corticospinal excitability changes as measured with Motor Evoked Potentials (MEP). The findings lay the ground for future studies optimising protocols and control conditions to leverage TUS as a meaningful experimental and clinical tool. A clear strength of the study is the multitude of control conditions (i.e., control sites, acoustic masking, acoustic stimulation). These findings will be of interest to neuroscience researchers using brain stimulation approaches.

eLife assessment

This important paper addresses the process by which cryptic splice sites that occur randomly in exons are ignored by the splicing machinery. Integrating state-of- the-art genome-wide approaches such as CLIP-seq with the study of individual examples, this study convincingly implicates members of RBMX family of RNA binding proteins in such cryptic splice site suppression and showcases its importance for the fidelity of expression of genes with very large exons.

eLife assessment

This manuscript describes a deep mutational scanning study of the kinase domain of the MET receptor tyrosine kinase. The study yields an important catalog of essentially all possible deleterious mutations in this portion of the receptor., with convincing evidence. The manuscript will be of interest to researchers working in the field of receptor tyrosine kinases.

eLife assessment

This study presents useful findings for how sevoflurane anesthesia modulates the activity of corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus and how manipulation of such PVHCRH neurons influences anesthesia and post-anesthesia responses. The technical approaches are solid and the data presented is largely clear. Whether PVHCRH neurons are critical for the mechanisms of sevoflurane anesthesia is a direction for the future.

eLife assessment

This important study provides convincing evidence of the criticality of estradiol – estrogen receptor-mediated upregulation of kisspeptin within neurons of the preoptic area to generate an ovulation-inducing luteinizing hormone surge. The use of in vivo CRIPSR-Cas9 is novel in this system and provides a road map for future studies in reproductive neuroendocrinology. This paper will be of interest to reproductive neuroscientists and endocrinologists.

eLife assessment

This important manuscript focuses on the mechanisms by which food signals and food ingestion modulate animal foraging. The authors provide convincing support for the interesting idea that chemosensory and interoceptive signals converge on transcriptional regulation of the TGF-beta ligand DAF-7 in a single pair of C. elegans chemosensory neurons (ASJ) to regulate behavior. Their studies implicate a conserved signaling molecule, ALK, in this regulation, suggesting a conserved link between food cues and the neuroendocrine control of foraging behavior.

eLife assessment

This paper explores how Notch activity acts together with homeodomain transcription Bsh factors to establish distinct cell fates (L4 vs L5) in the visual system of Drosophila. The findings are important and have theoretical or practical implications beyond a single subfield. The methods, data, and analyses are compelling and support the claims with only minor weaknesses.

eLife assessment

The manuscript introduces an important and innovative non-AI computational method for segmenting noisy grayscale images, with a particular focus on identifying immunostained potassium ion channel clusters. This method significantly enhances accuracy over basic threshold-based techniques while remaining user-friendly and accessible, even for researchers with limited computational backgrounds. The evidence supporting the method's efficacy is convincing. Its practical application and ease of use make it a tool that will benefit a wide range of laboratories.

eLife assessment

This fundamental study identifies the homeodomain transcription factor Meis2 as a transcriptional regulator of maturation and end-organ innervation of low-threshold mechanoreceptors (LTMRs) in the dorsal root ganglia (DRG) of mice. The authors use histology, behavioral tests, RNA-sequencing, and electrophysiological recordings to provide evidence that conditional deletion of Meis2 in postmitotic DRG neurons causes gene expression changes together with targeting errors and altered sensory neuron responses, ultimately resulting in reduced sensitivity to light touch in mutant animals. The data presented are convincing, the discussion comprehensive, and the conclusions drawn justified.

eLife assessment

This paper, offering insights into the mechanisms of neuronal cell type diversification, provides important findings that have theoretical or practical implications beyond a single subfield. The data are compelling and provide evidence that features methods, data and analyses that are more rigorous than the current state-of-the-art.

eLife assessment

This study discloses important physiological function for TMEM63 in regulating postnatal growth in mice. The data supporting the impaired body growth and skeletal phenotype as well as disrupted growth hormone/insulin-like growth factor-I (GH/IGF-I) signaling in TMEM63 knockout mice are compelling. However, to establish that alteration of hepatic GH/IGF-I signaling is the cause for observed growth and skeletal phenotype in TMEM63 knockout mice would need additional work.

eLife assessment

This valuable study combines proteomics and a mouse model to reveal the importance of iron uptake in bacterial therapy for cancer. The evidence presented is convincing. Notably, the authors showed upregulation of iron uptake of bacteria significantly inhibits tumor growth in vivo. This paper will be of interest to a broad audience including researchers in cancer biology, cell biology, and microbiology.

eLife assessment

This study illuminates the effects of ultrasound-induced extracellular vesicle interactions with macrophages. It provides solid data offering insights that will be potentially useful in exploring therapeutic approaches to inflammation modulation, by suggesting that ultrasound-treated myotube vesicles can suppress macrophage inflammatory responses.

eLife assessment

This valuable manuscript systematically addresses the role of intracellular lipid transfer proteins on cellular lipid levels. It provides convincing evidence on the role of ORP9 and ORP11 in sphingolipid metabolism at the Golgi complex. This article will be of broad interest to cell biologists interested in lipid metabolism and membrane biology.

eLife assessment

This valuable study evaluates the effects of nifuroxazide on radiotherapy for the treatment of hepatocellular carcinoma. Solid evidence is provided to support the conclusion that nifuroxazide facilitates the downregulation of PD-L1 and may improve therapy outcomes when combined with radiotherapy, though the inclusion of additional cell lines and animal models would have strengthened the study. This work will be of interest to cancer biologists and those working in immuno-oncology.

eLife assessment

This study presents a valuable finding that serum androstenedione levels may provide a new biomarker for early detection and progression of glaucoma, although a single biomarker is unlikely to be singularly predictive due to the etiological heterogeneity of the disease. The strength of the evidence presented is solid, supported by multiple lines of evidence.

eLife assessment

This solid study presents valuable insights into the role of Cers1 on skeletal muscle function during aging, although further substantiation would help to fully establish the experimental assertions. It examines an unexplored aspect of muscle biology that is a relevant opening to future studies in this area of research.

eLife Assessment

This important study demonstrates a reduction in airway hyperresponsiveness (one of the mechanisms of allergic asthma) in the absence of IgM in a house dust mite-induced mouse model of allergic asthma. While this result suggests a new mechanistic role for IgM, the proposed new function is not as yet robustly supported by the current experiments and thus the evidence remains incomplete. A connection between the findings and human disease is not established so far, but the study will be interest to clinical immunologists.

eLife assessment

The demonstration that the PARG dePARylation enzyme is required in S phase to remove polyADP-ribose (PAR) protein adducts that are generated in response to the presence of unligated Okazaki fragments is potentially valuable, but the evidence is incomplete, and identification of relevant PARylated PARG substrates in S-phase is needed to understand the role of PARP1-mediated PARylation and PARG-catalyzed dePARylation in S-phase progression.

eLife assessment

The authors discuss an effect, "diffusive lensing", by which particles would accumulate in high-viscosity regions – for instance in the intracellular medium. To obtain these results, the authors rely on agent-based simulations using custom rules performed with the Ito stochastic calculus convention. The "lensing effect" discussed is a direct consequence of the choice of the Ito convention without spurious drift which has been discussed before and its adequacy for the intracellular medium is insufficiently discussed and relatively doubtful. Consequently, the relevance of the presented results for biology remain unclear and based on incomplete evidence.