Evaluated articles

eLife assessment

This important study elucidates the molecular divergence of caspase 3 and 7 in the vertebrate lineage. Convincing biochemical and mutational data provide evidence that in humans, caspase 7 has lost the ability to cleave gasdermin E due to changes in a key residue, S234. The diversification and specialization of gasdermins such as gasdermin E in humans compared to early vertebrates such as teleosts may enable each human gasdermin molecule to have more restricted and tightly regulated physiological functions in different cell death pathways.

eLife assessment

Host cell death is an effective strategy to protect against infection, and is believed to function primarily by the elimination of the intracellular niche for pathogen replication. Abele and colleagues address an important question: does the mode of cell death affect its effectiveness in pathogen clearance? Consistent with prior observations, the authors provide compelling new evidence that the answer can depend on the cell type and/or tissue involved.

eLife assessment

This work presents some valuable information regarding the molecular mechanisms controlling the regeneration of pancreatic beta cells following induced cell ablation in zebrafish. Specifically, the data suggest that Calcineurin is a regulator of beta cell regeneration. However, the study lacks the critical lineage tracing results to support the conclusion about the origin of the regenerated beta cells and thus is deemed incomplete.

eLife assessment

This manuscript provides a useful characterization of penumbral microvascular flow disturbances over the first hours after ischemia onset in a rat model of middle cerebral artery occlusion. This work suggests that there are microscopic changes (including directionality of capillary blood flow and formation of capillary stalls) during the peri-ischemic timeframe but the data are incomplete and not sufficient to support the claims.

eLife assessment

This important study investigated transcriptional profiles of midbrain dopamine neurons using single nucleus RNA (snRNA) sequencing. The authors found more nuanced subgroups of dopamine neurons than previous studies, and identified some genes that are preferentially expressed in subpopulations that are more vulnerable to neurochemical lesions using 6-hydroxydopamine (6OHDA). The results are convincing and provide critical information on the heterogeneity and vulnerability of dopamine neurons which will be a foundation for future studies.

eLife assessment

This valuable study from Zaman et al. demonstrates that the cKit-Kit ligand complex is necessary for the formation and/or maintenance of molecular layer interneuron synapses in cerebellar Purkinje cells. The evidence presented is convincing; in particular, the use of cell-type specific knockout of cKit in molecular layer interneurons and knockout of Kit ligand in Purkinje cells provides robust evidence. This work will be of particular relevance to those interested in inhibitory synapse formation or the role of inhibition in Purkinje cell behavior.

eLife Assessment

This valuable modeling study explores how biophysical properties of different interneuron subtypes in the basolateral amygdala (BLA) enable production of oscillations that facilitate functions such as spike-timing-dependent plasticity. Simulated networks provide solid evidence that highlights the importance of interactions between interneurons for some forms of spike-timing dependent plasticity. This work will likely be of interest to investigators studying interactions among interneurons, rhythms in the amygdala, and mechanisms of plasticity thought to underlie associative learning.

eLife assessment

This study addresses how protein synthesis in activated lymphocytes keeps up with their rapid division, with important findings that are of significance to cell biologists and immunologists endeavouring to understand the 'economy' of the immune system. The work is supported by solid data. Because it proposes non-conventional mechanisms, the study sets the scene for further work in this area.

eLife assessment

This manuscript introduces two valuable new metrics - "variant vulnerability" and "drug applicability" - that would be of use to identify candidate drugs for treating infections while considering longer-term, evolution-based treatment outcomes. Despite the intuitive appeal of the metrics and their potential, the study remains incomplete, as it fails to demonstrate the generality of the approach. The work could be improved by analysing a broader range of data in a systematic way and directly tying the metrics to outcomes, which would make it possible to better assess their impact and utility.

eLife assessment

This study presents valuable observations on a potential role of creatine (Cr) as a novel neurotransmitter. While the data provide compelling evidence that Cr is present in synaptic vesicles, the evidence that Cr is synaptically released and binds to a post-synaptic receptor is incomplete, as no receptor is described. With further evidence, these results will be of wide interest to the field of neuroscience.

eLife assessment

The humanized model of EAE represents a valuable model in which to evaluate mechanisms that may drive EAE-like processes in vivo. The data are solid given the revisions and expansion of numbers of mice to yield more statistical rigor. This model will be used by the greater community studying EAE.

eLife assessment

This study presents an important dataset that captures the transition from epiblast to amnion using a novel in vitro model of human amnion formation. The supporting evidence for the authors' claims is convincing. Key strengths of the study include the efficiency and purity of the cell populations produced, a high degree of synchrony in the differentiation process, comprehensive benchmarking with single-cell data and immunocytochemistry from primate embryos, and the identification of critical markers for specific differentiation phases. A notable limitation, however, is the model's exclusion of other embryonic tissues.

eLife assessment

This study describes CLEVER, an improved method for fast and efficient rescue and mutagenesis of SARS-CoV2. While the principle of this method is not new, this work significantly improves upon existing protocols, providing an important advancement in the field of viral infectious clones. Convincing proof-of-concept experiments were performed that demonstrate the utility and efficiency of the method.

eLife Assessment

The paper presents valuable computational findings on how growth feedback affects the performance of synthetic gene circuits designed for adaptive responses. By systematically analyzing over four hundred circuit topologies, the authors provide solid evidence for their conclusions on failure mechanisms and design features that enhance robustness against growth dynamics. While the study's significance and rigor are somewhat constrained by its reliance on previously published network topologies, these results are highly relevant for advancing the engineering of gene circuits in various applications.

eLife assessment

In this valuable study, the authors use deep learning models to provide solid evidence that epithelial wounding triggers bursts of cell division at a characteristic distance away from the wound. The documentation provided by the authors should allow other scientists to readily apply these methods, which are particularly appropriate where unsupervised machine-learning algorithms have difficulties.

eLife assessment

The authors aim to develop a CRISPR system that can be activated upon sensing an RNA. As an initial step to this goal, they describe RNA-sensing guide RNAs for controlled activation of CRISPR modification. Many of the data look convincing and while several steps remain to achieve the stated goal in an in vivo setting and for robust activation by endogenous RNAs, the current work will be important for many in the field.

eLife assessment

This manuscript is an important contribution toward understanding the mechanisms of transcriptional bursting. The evidence is considered solid. Questions regarding the broader advance, details of the analysis, and the models used in the analysis were addressed by the authors.

eLife Assessment

This paper shows that it is possible to optogenetically activate single retinal ganglion cells in vivo in monkeys. This is an important step towards towards causal tests of the role of specific ganglion cell types in visual perception. The paper presents convincing evidence for the promise of the approach but further work will be needed to full explore its limitations and specificity.

eLife assessment

This valuable study focuses on the role of the Gr28 family of insect chemoreceptors. Using the Drosophila larva, the authors show that taste neurons expressing different members of this family of bitter taste receptors trigger opposite behavior – attraction and repulsion. They establish the minimal bitter taste receptor subunit composition needed in these neurons to mediate the repulsion of bitter tastants. The evidence presented is convincing, using well-validated and controlled tools and experiments.

eLife assessment

Using state-of-the-art single-nucleus RNA sequencing, Yao et al. investigate the transcriptomic features of neural stem cells (NSCs) in the human hippocampus to address how they vary across different age groups and stroke conditions. The authors report alterations in NSC subtype proportions and gene expression profiles after stroke. Although the study is valuable and the analysis is comprehensive, the significance is restricted by well-acknowledged technical limitations leading to incomplete evidence supporting some main conclusions.