Evaluated articles

eLife Assessment

Jung et al. present valuable work on the relationship between gamma-aminobutyric acid (GABA) levels within the anterior temporal lobes (ATL) to semantic memory while accounting for inter-individual differences. They provide solid evidence suggesting that inhibitory continuous theta burst transcranial magnetic stimulation (cTBS TMS) increased GABA concentration and decreased the blood-oxygen dependent signal (BOLD) during a semantic task. The results will be of interest to researchers studying the neurobiology of semantic cognition.

eLife Assessment

This important paper reports the discovery of calcarins, a protein family that seems to be involved in calcification in the calcareous sponge Sycon ciliatum, significantly enhancing our understanding of the molecular and cellular mechanisms underlying spicule formation in sponges and the evolution of carbonate biomineralization. The conclusions are supported by compelling evidence based on an integrated analysis that combines transcriptomics, genomics, proteomics, and precise in situ hybridization. These findings will be of broad interest to cell biologists, biochemists, and evolutionary biologists.

eLife Assessment

The authors present an important set of data implicating ETFDH as an epigenetically suppressed gene in cancer with tumor suppressive functions. The evidence is convincing, with the authors demonstrating that suppression of ETFDH activity results in accumulation of amino acids that impact metabolism via hyperactive mTORC1.

eLife Assessment

This study offers valuable insights into the role of post-translational modifiers, specifically SUMO2ylation at K81 in p66Shc, and its impact on endothelial function through reactive oxygen species. A series of compelling experiments demonstrated that lysine 81 of p66Shc is the site of SUMO2 conjugation, which is crucial for mitochondrial localization and essential for S36 phosphorylation, leading to specific pathological effects. The combination of cell overexpression and animal studies provides solid data supporting this mechanistic link.

eLife Assessment

This study provides important insights into the regulation of neuroblast lifespan and proliferation in the Drosophila mushroom body, identifying Krüppel (Kr) as a key transcription factor promoting timely termination of these neuroblasts by repressing Imp expression, and proposes an antagonistic role of Krüppel homolog 1 (Kr-h1), whose overexpression leads to prolonged mushroom body neuroblast proliferation and tumor-like expansion. The findings are impactful for researchers interested in temporal patterning and neural development, and the methods and data analysis are solid, however, the precise regulatory interactions between Kr and Kr-h1 and their modes of action remain incompletely tested. Further experiments would be required to fully elucidate the mechanistic interplay between the factors involved.

eLife Assessment

The findings in this manuscript are important because they demonstrate the key role of metabolism in insect development. The data were collected and analyzed using solid and validated methodologies, but the evidence is incomplete, as the extent of the involvement of AOX activity in vivo and in physiological conditions is not addressed. This manuscript will be of interest for the fields of mitochondrial bioenergetics, metabolism and development.

eLife Assessment

This important study advances our understanding of vertebrate forelimb development, specifically the contribution of Hox genes to zebrafish pectoral fin formation. The authors have employed a robust and extensive genetic approach to tackle a key and unresolved question. The findings are overall convincing and will be of broad interest to developmental and evolutionary biologists.

eLife Assessment

This valuable study aims to advance the toolkit of small molecules used for approaches to targeted protein degradation for research and therapeutic applications. The authors provide solid data demonstrating the use of a high-throughput screen of small molecules to target a specific E3 ligase, KLHDC2 (Kelch-like homology domain containing protein 2); the resulting compounds then form the basis for new PROTAC (proteolysis targeting chimera) reagents. The strength of the work lies in expanding the PROTAC reagent inventory. The current work would be strengthened further by confirming that the PROTAC's activity is dependent on KLHDC2 and by a more thorough examination of off-target effects in cellular applications.

eLife Assessment

This study presents the important finding that lysosomal damage triggers inflammatory signaling through ubiquitination and the TAB-TAK1-IKK-NF-kB axis. The data obtained from the unbiased transcriptomic and proteomic analyses are convincing and provide invaluable information to the field. Although further experiments will be required to clarify how TAB2/3 are recruited after various types of lysosome damage, this work will be of interest to researchers in the fields of organelle biology and inflammation.

eLife Assessment

Antibodies that selectively bind distinct amyloid-beta variants are vital tools for Alzheimer's disease research. This valuable manuscript aims to delineate the epitope specificity in a panel of anti-amyloid-beta antibodies, including some with clinical relevance. The experiments were rigorously conducted, employing an interesting combination of established and state-of-the-art methodologies, yielding convincing findings.

eLife Assessment

This study presents important findings on the role of Slit-Robo signaling in cardiac innervation. The evidence supporting the main claims of the authors is convincing. The use of several mouse models including constitutive and cell type specific knockout models make the findings more robust. The scope of the presented studies is fitting, as they primarily focus on evaluating the phenotypic changes in cardiac innervation following the loss of various Slit or Robo genes

eLife Assessment

This important study examines the role of map3k1, a MAP3K family member that has both kinase and ubiquitin ligase domains, in the differentiation of progenitors in the flatworm Planaria. The convincing analyses demonstrate that map3k1 acts within progenitors to restrict their premature differentiation and to prevent formation of teratomas. This work would be of interest to researchers in the fields of regeneration, developmental biology, and aging.

eLife Assessment

This study demonstrates the application of END-seq, originally developed to study genomewide DNA double-strand breaks, to telomere biology; the work packs a punch, concisely demonstrating the utility of this approach and the new insights that can be gained. The authors confirm that telomeres in telomerase-positive cells terminate with 5'-ATC in a Pot1-dependent manner, and demonstrate that this principle holds true in telomerase-negative ALT cells as well. S1-END-seq is similarly developed for telomeres, showing that ALT cells harbor several regions of ssDNA. The study is well-executed and convincing, the new insights are fundamental and compelling, and the optimized END-seq approaches will be widely utilized. The work will prompt additional studies that the reviewers look forward to, including combining telomeric END-seq with long-read sequencing to address the distribution and origin of variant telomere repeats and ssDNA along telomeres in ALT and telomerase-positive settings.

eLife Assessment

This important study describes newly identified light-gated ion channel homologs (channelrhodopsins, ChRs) in several protist species, with a primary focus on the biophysical characterization of ChRs of ancyromonads. The authors employed a powerful combination of bioinformatics, manual and automated patch-clamp electrophysiology, absorption spectroscopy, and flash photolysis. Additionally, they evaluated the applicability of the newly discovered anion-conducting ChRs in cortical neurons of mouse brain slices and in living C. elegans worms. The evidence supporting most of the claims is compelling, and this work will be of interest to the microbial rhodopsin community and neuro- and cardioscientists utilizing optogenetics in their research.

eLife Assessment

This valuable study employs transition-metal FRET (tmFRET) and time-correlated single-photon counting to investigate allosteric conformational changes in both isolated cyclic nucleotide-binding domains (CNBDs) and full-length bacterial CNG channels, demonstrating that transmembrane domains stabilize CNBDs in their active state. By comparing isolated CNBD constructs with full-length channels, the authors reveal how allosteric networks couple domain movements to gating energetics, providing insights into ion channel regulation mechanisms. The rigorous methodology and compelling quantitative analysis establish a framework for applying tmFRET to study conformational dynamics in diverse protein systems.

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.