Evaluated articles

eLife Assessment

In this manuscript Taujale et al describe an interdisciplinary approach to mine the human channelome and further discover orthologues across diverse organisms. Further, this work provides evidence that supports a role for conserved residues in CALHM channel gating. Overall this important work presents findings that can be helpful to the ion channel community, as well as to those interested in improved methods for mining sequence space for their protein of interest. However, further validation of the improvements their approach shows over previous approaches is needed, making this a solid contribution to the literature in this field.

eLife Assessment

This useful study describes a physical mechanism for the emergence of spiral patterns in the outer epithelial layer of the mammalian cornea independent of pre-patterning or guidance cues, using an agent-based model of self-propelled particles with alignment. The model is well constructed, however the central premise of the manuscript, that the spiral patterning of epithelial corneal cells occurs without guidance cues, is incomplete and not fully supported. Several significant questions remain unanswered, such as the role of the corneal curvature or the importance of topological defects. Furthermore, comparison between the model and data are qualitative at best for the moment.

eLife Assessment

This is an important study describing the morphological changes during boundary formation between sensory and non-sensory tissues of the inner ear. The authors provided solid evidence that a transcription factor, Lmx1a and ROCK-dependent actinomyosin are key for border formation in the inner ear. However, future studies will be needed to investigate the direct relationships among boundary formation, Lmx1a and ROCK. This work will be of interest to developmental biologists interested in boundary formation.

eLife Assessment

This manuscript presents a fundamental advance in our understanding of nuclear receptor pharmacology by expanding on previous work demonstrating dual ligand occupancy in the peroxisome proliferator-activated receptor-gamma (PPARγ). Using a compelling combination of biophysical, biochemical, and cellular approaches, the authors show that covalent inverse agonists with enhanced efficacy shift the receptor conformation toward a transcriptionally repressive state that limits orthosteric ligand co-binding more effectively. This revised manuscript further strengthens support for a proximal, bidirectional allosteric model of dual ligand occupancy by sharpening the distinction between prior and new findings, adding clear conceptual figures, and strengthening statistical rigor.

eLife Assessment

This is a fundamental discovery revealing two independent IFNγ-induced pathways that restrict bacterial motility: one GBP1-dependent and the other GVIN1-dependent. The findings are supported by compelling evidence. While the paper is already very strong, there are a few points that could be addressed editorially or through the addition of a few key experiments.

eLife Assessment

This valuable study presents an analysis of evolutionary conservation in intrinsically disordered regions, identified as key drivers of phase separation, leveraging a protein language model. The strength of evidence presented is convincing overall, though the theoretical grounding could benefit from further development.

eLife Assessment

In this valuable study, the authors demonstrate that TCF7L2 plays a role in the pathogenesis of cachexia in a mouse model of GI cancer. The results are solid, although future studies will need further mechanistic analyses. These data will be interesting to cancer biologists, especially those trying to understand late-stage complications such as cachexia and wasting, a major cause of cancer morbidity and mortality.

eLife Assessment

This study exploring the role of TRPV1 signaling in recruiting macrophages and promoting angiogenesis during tympanic membrane wound healing presents useful findings. However, the strength of evidence supporting the central claims is incomplete, as the mechanistic links between TRPV1 activation and immune cell recruitment remain largely correlative and rely heavily on previously published datasets without sufficient functional validation. The work will be of interest to researchers studying wound healing and sensory-immune interactions, though substantial revisions are needed to support its broader significance.

eLife Assessment

This high-N, multi-task study offers a comprehensive examination of rhythmicity in behavioral performance during listening. It presents a valuable set of findings that reveal task- and ear-specific effects, challenging the notion of a universal rhythmicity in auditory perception. The evidence is solid and the work is likely to be of significant interest to behavioral and cognitive scientists focused on perception and neural oscillations.

eLife Assessment

This revised manuscript provides fundamental findings on how the mouse barrel cortex connects to the dorsolateral striatum, uncovering that inputs from discrete whisker cortical columns are convergent and SPN-specific, but topographically organized at the population level. The evidence supporting this claim is compelling, demonstrating that SPNs uniquely integrate sparse input from variable stretches across the barrel cortex. The study would be of interest to basal ganglia and sensory-motor integration researchers.

eLife Assessment

This fundamental study demonstrates that lipid binding can regulate the dimerization state of the SARS-CoV2 Orf9b protein. The data from biophysical and cellular experiments along with mathematical modeling are compelling. This paper is broadly relevant to those studying coupled equilibria across all aspects of biology.

eLife Assessment

This study provides important insights into the evolution of pesticide resistance, demonstrating that resistance can arise rapidly and repeatedly, which complements prior work on parallel evolution across species. The combination of extensive temporal sampling in the field, experimental evolution, and genomics makes for compelling findings. The authors are to be commended for acknowledging the main limitations of their study in the Discussion. Framing the work in a broader context of resistance beyond arthropod pests would further increase the appeal of the study, which is of relevance for both agronomic practitioners and evolutionary biologists.

eLife Assessment

IL-10 balances protective and deleterious immune functions in mice and humans, but if IL-10 also controls avian intestinal homeostasis remains unclear. Generating genetic knockouts, Meunier et al. established that a complete lack of IL-10 strengthened immunity against enteric bacteria in chickens, while also aggravating infection-inflicted inflammatory tissue damage and dysbiosis upon parasite infection, but unlike mouse models, IL-10 deficiency did not provoke spontaneous colitis in chickens. The findings presented are valuable, and the strength of evidence is convincing. The observation may have implications for the livestock industry and additional studies involving genetic knockouts may further unravel conserved and distinct avian IL-10 controls.

eLife Assessment

This paper addresses a valuable research question on the modest heritability of the brain's response to movie watching, and how heritability varies under different parameters such as regional spatial hyperalignment and BOLD frequency bands. The topic of this paper is of interest to fMRI methodological experts, and potentially to a broader cognitive neuroscience audience, and those with an interest in understanding the heritable sources of individual differences in brain function. Although some of the conclusions could be strengthened by future cross validation studies in independent and larger family-based samples, and through complementary twin/family and SNP-based models, taken altogether, the analyses and results provide convincing evidence for the overall conclusions.

eLife Assessment

This manuscript characterizes a mutated clone of RNA polymerase I in yeast, referred to as SuperPol, to understand the mechanisms of RNA polymerase I elongation and termination. The authors present convincing evidence that demonstrates the existence of premature termination in Pol I transcription. Overall, the characterization of this RNA pol I offers important insights into the regulation of ribosomal RNA transcription and its potential application in cancer pharmacology.

[Editors' note: this paper was reviewed by Review Commons.]

eLife Assessment

This valuable study provides insights into a key question in comparative neuroanatomy and development. The authors provide evidence of the role for a particular micro-RNA in regulating the development of key transcription factors that control forebrain development. The study rests on clear but incomplete results.

eLife Assessment

The open-source software Chromas tracks and analyses cephalopod chromatophore dynamics. The software features a user-friendly interface alongside detailed instructions for its application, with compelling exemplary applications to two widely divergent cephalopod species, a squid and a cuttlefish, over time periods large enough to encompass new chromatophore development among existing ones. It demonstrates accurate tracking of the position and identity of each chromatophore. The software and methods outlined therein will become an important tool for scientists tracking dynamic signaling in animals.

eLife Assessment

This useful study explores the role of RAP2A in asymmetric cell division (ACD) regulation in glioblastoma stem cells (GSCs), drawing parallels to Drosophila ACD mechanisms and proposing that an imbalance toward symmetric divisions drives tumor progression. While findings on RAP2A's role in GSC expansion are promising, and the reviewers found the study innovative and technically solid, the study relies on neurosphere models without in vivo confirmation and will therefore need to be further validated in the future.

eLife Assessment

This important resource paper presents a library of cell-type-specific genetic driver lines that label wing-related motor and premotor neurons in the ventral nerve cord of the fruit fly, Drosophila. The toolkit is systematically validated with compelling anatomical and behavioral evidence and will provide a resource for future studies of Drosophila flight and courtship.

eLife Assessment

This valuable study shows that targeted mutations in specific cassava eIF4E-family genes can reduce infection and disease symptoms caused by cassava brown streak viruses. Through systematic knockouts across the eIF4E gene family, the authors provide convincing evidence that certain double mutants show resistance-associated outcomes. Overall, the work supports practical routes to engineer cassava with improved resistance and clarifies which host factors are relevant for this disease.