Evaluated articles

eLife assessment

In this study, the authors develop a strategy for fluorophore-tagging endogenous proteins in human induced pluripotent stem cells (iPSCs) using a split mNeonGreen approach, and they conclude that the system will be appropriate for performing live imaging studies of highly dynamic cellular processes such as cytokinesis in iPSCs. Experimentally, the methods are solid, and the data presented support the authors' conclusions. Overall, these methodologies should be useful to a wide audience of cell biologists who want to study protein localization and dynamics at endogenous levels in iPSCs.

eLife Assessment

This study provides important insights into how researchers can use perceptual metamers to formally explore the limits of visual representations at different processing stages. The framework is compelling and the data largely support the claims, subject to minor caveats.

eLife assessment

This fundamental study provides an unprecedented understanding of the roles of different combinations of NaV channel isoforms in nociceptors' excitability, with relevance for the design of better strategies targeting NaV channels to treat pain. Although the experimental combination of electrophysiological, modeling, imaging, molecular biology, and behavioral data is convincing and supports the major claims of the work, some results remain inconclusive and need to be strengthened by further evidence. The work may be of broad interest to scientists working on pain, drug development, neuronal excitability, and ion channels.

eLife assessment

This study presents valuable findings on the mechanism of glucocorticoid-induced osteonecrosis of the femoral head. The data were collected and analyzed using solid, validated methodology and can be used as a starting point for functional studies of development of glucocorticoid-induced osteonecrosis. This paper would be of interest to cell biologists and biophysicists working on potential pharmacological treatments for glucocorticoid-induced osteonecrosis.

eLife assessment

Using a set of animal models, this valuable paper shows tumor suppressive function of the non-core regions of RAG1/2 recombinases. The conclusions are supported by solid evidence.

eLife Assessment

The findings of this valuable manuscript advance our understanding of the significance of Bestrophin isoform 4 (BEST4) in suppressing colorectal cancer (CRC) progression. The authors used appropriate and validated methodology, such as the knockout of BEST4 using CRISPR/Cas9 in CRC cells, to provide a solid foundation for elucidating the potential link between BEST4 and CRC progression.

eLife assessment

This important study reports on key characteristics of MYC-driven cancers: dysregulated pre-mRNA splicing and altered metabolism, with the data being overall solid. The manuscript should be of broad interest to cancer biologists due to its therapeutic implications.

eLife assessment

This is an important study for understanding the pathogenesis of ulcerative colitis. It convincingly demonstrates reduced levels of the vesicular trafficking protein Rab7 in ulcerative colitis and Crohn's disease, leading to altered levels of calcium-activated chloride channel regulator 1 (CLCA1) and subsequent mucin dysregulation, highlighting Rab7's significance in gut homeostasis maintenance. The manuscript advances the field as it provides insights into a novel regulatory pathway implicated in ulcerative colitis, potentially paving the way for the development of targeted therapeutic interventions.

eLife assessment

This study investigates the presence of DNA adenine methylation (6mA) and the associated function of TET enzyme, a DNA methylation mark eraser, in Drosophila. The study presents valuable findings on the scarcity of 6mA in the Drosophila genome and challenges previous findings regarding the role of TET in 6mA modification. The evidence supporting the claims is solid, and the paper has the potential to stimulate re-evaluations of the significance and regulatory mechanisms of 6mA DNA modifications in Drosophila.

eLife assessment

This fundamental study advances our understanding of how Notch signaling activates transcription by analyzing dynamics of the Mastermind transcriptional co-activator and its role in the activation complex. The evidence is compelling and based on state of the art methods with precise quantitative measurements.

eLife Assessment

This important study reports an endometrial organoid culture system mimicking the window of implantation. The evidence supporting the conclusion drawn is convincing. The data will be of interest to embryologists and investigators working on reproductive biology and medicine.

eLife assessment

The current manuscript presents a cryo-EM structure of a tripartite ATP-independent periplasmic (TRAP) transporter that contributes to Haemophilus influenzae virulence. Convincing biophysical and cryo-EM experiments yield a valuable molecular model, but the functional importance of some of the molecular features identified remains to be demonstrated.

eLife assessment

This important study reports the cryo-electron microscopy structure of a multi-protein complex that recognizes the 5'-end cap of mRNAs and plays a critical role in mRNA export. The structural and biochemical analyses in this study provide convincing evidence to support the major claims of the authors, with the inclusion of more functional characterizations in cell-based systems having corroborated the claims further and and thus strengthening the study. This paper would be of interest to structural biologists and RNA biologists working on mRNA metabolism.

eLife assessment

This manuscript used the sci-Plex system for screening compounds to improve the Ascl1-induced reprogramming from Müller glia to bipolar neurons in vitro, followed by in vivo characterization of two promising compounds in mice. The findings are valuable for future studies to develop cell replacement strategies for treatment of retinal degeneration. The strength of evidence is solid, featuring a scalable drug screening design, albeit with limited mechanistic insights.

eLife assessment

This manuscript reports a valuable computational study of the effects of axon de-myelination and re-myelination on action potential speed and propagation failure. The manuscript presents solid evidence for the effects of de- and re-myelination in different models of working memory, with potential implications in disorders such as multiple sclerosis. The exposition of the manuscript is targeted for researchers interested in biophysical models of cognitive deficits.

eLife assessment

This manuscript describes an important web resource for kinases connected to cytokines. The compelling information will be used by researchers across a number of fields including analysts, modelers, wet lab experimentalists and clinician-researchers, who are looking to improve our understanding of pathologies and means to correct them through modulating the immune response.

eLife assessment

The findings of this study are valuable as they provide new insights into the role of acetylcholine in modulating sensory processing in the auditory cortex. This paper reports a systematic measurement of cell activity in the auditory cortex before and after the microiontophoretic application of Ach during an oddball and cascade sequence of auditory stimuli. The evidence presented is convincing, as the study used a rigorous experimental design and statistical analysis. The manuscript will interest researchers in auditory neuroscience and neuromodulation, as well as clinicians and individuals with auditory processing disorders.

eLife assessment

This fundamental study explored the impact of migraine-related cortical spreading depression (CSD) on the firing of nerves innervating the coverings of the brain that are considered the putative source of migraine-related pain. Using convincing approaches they show that these responses are altered in response to mechanical deformation of the brain coverings. Given that migraine is characterized by worsening head pain in response to movement, the findings offer a potential mechanism that may explain this clinical phenomenon.

eLife Assessment:

This study presents valuable findings that add to our understanding of cortical astrocytes, which respond to synaptic activity with calcium release in subcellular domains that can proceed to larger calcium waves. The proposed concept of a spatial "threshold" is based on solid evidence from in vivo and ex vivo imaging data and the use of mutant mice. Details of the specific threshold must be taken with caution and are necessarily incomplete, but may be supported by additional experiments with higher resolution in space and time in the future.