Evaluated articles

eLife assessment

Hearing is mediated by hair cells in the cochlea, which synapse onto the primary dendrites of the auditory nerve. This study shows how deletion of a postsynaptic glutamate receptor subtype strongly influences inner hair cell-spiral ganglion cell synapse formation. Thus pre- and post-synaptic changes are dynamically intertwined, providing insights into how pathological outcomes arise from synaptic perturbations.

eLife assessment

This paper should be of broad interest to developmental biologists who seek to understand spatiotemporal control of myosin-based force generation during tissue morphogenesis during early development. The central conclusions are well-grounded in rigorous quantitative data analysis and modeling. The results challenge current views of how gene expression patterns control myosin II anisotropies and provide new testable hypotheses on the role and importance of tissue geometry.

eLife assessment

The authors identify co-deletion of the mitochondrial AAA+ ATPase ATAD1 with the tumor suppressor PTEN as a factor modifying cancer prognosis, based on a new mechanism of increasing sensitivity to proteotoxic stress induced by proteasome inhibition. The authors also identify the mitochondrial E3 ubiquitin ligase MARCH5 as a gene whose deletion is synthetically lethal with ATAD1. These findings suggest that the use of proteasome-targeting agents may be useful in patients with tumors dually deleted for ATAD1 and PTEN. The study is based on convincing evidence, and makes an innovative contribution to the understanding of the biology of tumors with 10q23 deletions.

eLife assessment

The authors provided strong evidence that the Fusarium oxysporum effector protein FolSpv1 enhances virulence by targeting tomato SlPR1 and preventing the generation of the SlPR1-derived phytocytokine CAPE1, which otherwise positively regulates disease resistance in tomato plants. Strikingly, they show that FolSpv1 translocates SlPR1 from the apoplast back into the nucleus of tomato cell, suggesting a previously unknown mechanism employed by pathogenic microbes.

eLife assessment

This well-presented and sophisticated study provides significant proof-of-concept for the application of the ForensOMICS approach as a new pathway for forensic taphonomy with great promise to advance future research. The solid foundation of the research combining metabolomics, proteomics, and lipidomics is considered very exciting, strong, and expands the boundaries of forensics research.

eLife assessment

The transcription factor DUX4 is emerging as a key molecule in early mammalian development and in diverse pathologies including muscular dystrophy and solid tumors. While DUX4 has been linked to immune evasion, the mechanisms have not been delineated. In this study, the authors demonstrate that DUX4 functions as a negative regulator of interferon signaling by inhibiting STAT1, thereby suppressing interferon-stimulated gene induction. These studies provide a critical mechanistic link between DUX4 expression and the modulation of immune signaling pathways.

eLife assessment

This manuscript contains fundamental work on hormonal and neurobiological processing of social experience in humans. It sheds compelling new light on potential mechanisms underlying how humans place social experiences in context, demonstrating how oxytocin and cortisol might interact to modulate higher-level processing and contextualizing of familiar vs. stranger encounters.

eLife assessment

In this important manuscript the authors use a powerful cross-specifies approach and cutting-edge experimental methods to examine possible shifts in the excitatory and inhibitory balance in both an animal model of Parkinsonism and in human patients with Parkinson's disease. Their solid findings support such a shift, wherein untreated Parkinson's disease is characterized by excessive activity in the subthalamic nucleus. While a strong paper, there are concerns with some of the methodological choices and their implications.

eLife assessment

In this important study, the authors examine transport and synaptic activity in the corticostriatal circuit in both microfluidic devices and in mice. They convincingly show that the Huntingtin protein regulates the anterograde transport of synaptic vesicle precursors in coordination with the molecular motor KIF1A. Activated Huntingtin recruits KIF1A, accelerates synaptic vesicle precursor's transport, modifies synaptic transmission and motor skill learning in mice. This work sheds new light on the role of axonal transport in synaptic function under physiological and pathological conditions related to Huntington's disease.

eLife assessment

This study presents an atlas of glial cell morphology in Drosophila, from distinct locations at different periods of life. The authors integrate morphological information with the transcriptomic signatures of those cells and find that morphological diversity among glial cells of a given class is not a strong predictor of transcriptional identity. The study is of great value as connecting morphology with scRNA sequencing analysis is rarely done and is a necessary step for understanding the underlying biology of these cells. While the weak morphotype-transcriptomic link in many cases may be due to low sequencing resolution, nonetheless, the data are of very high quality and the study will be a very useful resource for the glial biology field.

eLife assessment

This manuscript proposes that metformin protects against elevated intraocular pressure and oxidative injury by regulating cytoskeleton remodeling through the integrin/ROCK pathway, thus providing a new direction for further exploration toward the treatment of primary open-angle glaucoma as well as investigation of oxidative injury in multiple settings.

eLife assessment

This work is of high relevance to developmental and quantitative biologists with an interest in morphogen-mediated position decoding. A general mathematical model formulation is presented that is nevertheless accessible to a broad audience. Model tests via perturbation experiments in the Drosophila wing disc look promising and inspire a new round of data generation.

eLife assessment

Using a heterologous model system of budding yeast, authors find that nuclear translocation of beta-catenin is mediated by Kap104, the ortholog of Transportin (TNPO)1/2. A TNPO1 binding motif was identified in the C-terminal region of beta-catenin, which serves as a nuclear localization signal, and mutation of the motif inhibits beta-catenin mediated transcription. The manuscript serves as a staring point to study how much this motif contributes to nuclear localization of full-length beta-catenin in mammalian cells and to assess whether inhibiting TNPO1 interaction can reduce hyperactivation of beta-catenin signaling.

eLife assessment

This manuscript puts forward a new idea that topography in neural networks helps to remove noise from inputs. The authors show that there is a critical level of topography that is needed for network to denoise inputs. At present, the analysis is limited to inputs that are constant in time.

eLife assessment

This is an important paper reporting that an adenosine methyltransferase in the model plant Arabidopsis functions to target a key RNA component of the spliceosome, as in fission yeast, and thereby contributes to intron recognition. By contrast, the authors report no major role for the methyltransferase in targeting mRNAs, as reported in previous studies in Arabidopsis. While some of the evidence is convincing, other evidence is incomplete. The conclusions that mRNAs are not a significant target and that specific intronic sequences define sensitivity to the methyltransferase require additional support.

eLife assessment

This study delineates the transcriptomics of lung neuroendocrine cells and provides important new information on the nature of these cells in normal mouse lungs and in a sample of a human lung carcinoid. It will inform future studies investing the roles of PNECs in health and disease.

eLife assessment

Dhurhandar and colleagues developed a computational method that predicts discriminability of odor mixtures based on chemical structures of component molecules. The model first transforms chemical structures into natural language descriptions of odor, and then perform Lasso regressions to obtain a compact transformation into discriminability. The results suggest that the model performs better compared to that without transformation to language descriptions, yet, there are some issues that need to be addressed to make strong conclusions.

eLife assessment

This study applies AlphaFold to the CHESS selection of transcripts with the goal of generating predicted 3D protein structures and a quality measure of folding, the pLDDT score. From these data, the authors build a database for result exploration, documented by several examples, including proteins, where the authors propose the pLDDT score as a measure of presumed superior biological functionality over other isoforms. These results will be highly relevant for anyone working with proteins that occur in different isoforms.

eLife assessment

This important study reveals the role of polygenic scores for four commonly diagnosed cancers with high genetic predisposition (breast, prostate, colorectal, and lung) in East Asian populations, which is developed in participants of European descent. The data is convincing that is derived from a prospective cohort including 21,694 Singaporean participants of East Asian descent. The work will be of interest and provide great help to disease specialists in the field.

eLife assessment

In learning to walk, infants must balance the need to explore their movement repertoire with the need to establish regular movement patterns. Using a longitudinal approach, this paper suggests that while young infants generate high variability from a small number of regular patterns ('primitives'), older infants use a greater number of primitives with less variability. These interesting conclusions are not currently fully supported by the small and somewhat selective sample of data, and some alternative explanations need to be considered more thoroughly.