Evaluated articles

eLife Assessment

This manuscript describes a resource detailing the econstitution of Holothuria glaberrima gut following self-evisceration in response to a potassium chloride injection, using scRNAseq and fluorescent RNA localization in situ. It provides some new findings about organ regeneration, as well as the origins of pluripotent cells, and places these findings in the context of regeneration across species. The paper's schematic model and HCR images are a valuable foundation for future work. The authors provide convincing RNA localization images to validate their data and to provide spatial context. These validation experiments are of good quality but remain challenging to connect to the complex spatial organization of complex tissues. This resource will be of interest to the field of regeneration, particularly in invertebrates, but also in comparative studies in other species, including evolutionary studies.

eLife Assessment

This important study uses optogenetics in combination with single cell recordings to selectively activate sensory input channels within the olfactory bulb, providing direct evidence for activity-dependent and distance-independent enhancement of stimulus-evoked gamma oscillations via lateral interactions between input channels, most likely via granule cells. The article presents solid evidence to support the main conclusions.

eLife Assessment

This important study substantially advances our understanding of noncoding somatic mutations by identifying a novel class of mutations that affect 3'UTR polyadenylation signals enriched in tumor suppressor genes in cancer. The evidence supporting the conclusions is convincing, with rigorous statistical analyses. The work will be of broad interest to cancer researchers.

eLife Assessment

In this manuscript, the authors sought to elucidate mechanistic intricacies of inflammatory responses, with emphasis on T cell dysfunction, to S. aureus-induced pneumonia in the context of aging process using Terc deficient mice. Conceptually, the study is very interesting with a set of useful findings. Although some experimental approaches are appropriate, the work as shown in the revised manuscript remains significantly underpowered and the absence of rigorous controls make this study incomplete in support of its claims.

eLife Assessment

This important study examines the role of endothelin signaling in nerve regeneration, providing convincing evidence that it functions as a default brake on axon regrowth. Inhibiting endothelin signaling with Bosentan promotes regeneration and counteracts the decline in regenerative potential caused by aging. Since Bosentan is an FDA-approved drug, these findings could have therapeutic value in clinical settings where peripheral nerve regeneration is not adequate or seriously impaired, as is often the case in older individuals.

eLife Assessment

This important revised report describes the control of the activity of the RNA-activated protein kinase, PKR, by the Vaccinia virus K3 protein. A strength of the manuscript is the powerful combination of a classic yeast-based assay with high-throughput sequencing and its convincing experimental use to characterize large numbers of PKR variants, now with improved controls for potential biases. A minor current limitation that the authors may address in the future is the scope of the screen in terms of the segments of PKR included.

eLife Assessment

This work introduces a new Python package, Avian Vocalization Analysis (AVN) that provides several key analysis pipelines for birdsong research. This tool is likely to prove useful to researchers in neuroscience and beyond, as demonstrated by convincing experiments using a wide range of publicly available birdsong data.

eLife Assessment

NAD deficiency perturbs embryonic development resulting in multiple congenital malformations, collectively termed Congenital NAD Deficiency Disorder (CNDD). The authors report fundamental findings demonstrating that extra-embryonic visceral yolk sac endoderm is critical for NAD de novo synthesis during early organogenesis and perturbations of this pathway may underlie CNDD. The authors combine gene expression with metabolic assays to provide solid evidence of an essential role of the extra-embryonic visceral yolk sac in both mouse and human embryos.

eLife Assessment

The authors provide a solid set of data supporting the safety of transcutaneous auricular vagal nerve stimulation on cardiovascular parameters in the acute setting of critically ill patients presenting with subarachnoid hemorrhage. This important study also suggests a promising effect on autonomic balance.

eLife Assessment

The authors have developed a biosensor for programmed cell death. They use this biosensor to provide cell death measurements in a specific early development time. The findings useful in a specific context; however, the application of this biosensor is incomplete as it does not take into account existing literature and is missing controls.

eLife Assessment

This work presents important findings that the human frontal cortex is involved in a flexible, dual role in both maintaining information in short-term memory, and controlling this memory content to guide adaptive behavior and decisions. The evidence supporting the conclusions is compelling, with a well-designed task, best-practice decoding methods, and careful control analyses. The work will be of broad interest to cognitive neuroscience researchers working on working memory and cognitive control.

eLife assessment

The intrinsic chirality of actin filaments (F-actin) is implicated in the chiral arrangement and movement of cellular structures, but it was unknown how opposite chiralities can arise when the chirality of F-actin is invariant. Kwong et al. present evidence that two actin filament-based cytoskeletal structures, transverse actin arcs and radial stress fibers, drive clockwise and anti-clockwise rotation, respectively. This fundamental work, which has broad implications for cell biology, is supported by compelling data.

eLife Assessment

Transient receptor potential mucolipin 1 (TRPML1) functions as a lysosomal ion channel whose variants are associated with lysosomal storage disorder mucolipidosis type IV. This important report describes local and global structural changes driven by binding of regulatory phospholipids and by mutations that allosterically cause gain or loss of channel function. Most of the claims related to the allosteric regulation of TRPML1 are convincingly supported by two new cryo-EM structures which are evaluated within the context of previously reported TRPML1 structures, and a proposed allosteric gating mechanism is partially supported by functional electrophysiology results.

eLife Assessment

This important study presents work on the molecular mechanism driving asymmetric cell division and fate decisions during embryonic development of echinoids. The evidence supporting the claims of the authors is convincing. The work will be of interest to developmental biologists and cell biologists working in the field of self-renewal.

eLife Assessment

This study provides a valuable approach to image and analyze in vivo metabolic flux through glucose turnover kinetics in glioblastoma tumor microenvironments. The evidence for the method's validity is convincing, which establishes the dynamic Deuterium Metabolic Imaging technique as an effective tool enabling non-invasive exploration of various tumors.

eLife Assessment

This study explores the mechanistic link between glycosylation at the N162 site of the Fc gamma receptor FcγRIIIa and the modulation of NK cell-mediated antibody-dependent cytotoxicity. Using innovative isotope labeling strategies and advanced NMR spectroscopy techniques, the authors provide compelling evidence of how glycan composition influences receptor stability and immune function. These findings offer fundamental insights that may contribute to the development of more effective therapeutic antibodies. The manuscript will be of significant interest to immunologists and researchers focused on therapeutic antibody design.

eLife Assessment

This work presents valuable data demonstrating that a camelid single-domain antibody can selectively inhibit a key glycolytic enzyme in trypanosomes via an allosteric mechanism. The claim that this information can be exploited for the design of novel chemotherapeutics is solid but limited by the modest effects on parasite growth, as well as the lack of evidence for cellular target engagement in vivo.

eLife Assessment

MGPfactXMBD is a novel computational method for investigating cell evolutionary trajectory for scRNA-seq samples. It is important, with several potential future applications. The authors benchmarked this method using synthetic and real-world samples and showed superior performance for some of the tasks in cell trajectory analysis compared to other methods with compelling evidence.

eLife Assessment

This important study investigates the role of Drp1 in early embryo development. The authors have addressed most of the original comments and the work now presents convincing evidence on how this protein influences mitochondrial localization and partitioning during the first embryonic divisions. The research employs the Trim-Away technique to eliminate Drp1 in zygotes, revealing critical insights into mitochondrial clustering, spindle formation, and embryonic development.