Evaluated articles

eLife assessment

This study addresses a pertinent and important topic related to prolonged delays in cervical cancer screening and the need to maintain routine and timely screening services in a large health maintenance network in Boston. The findings provide a solid, yet incomplete roadmap for implementing simple strategies to help patients return to essential health services.

eLife assessment

By recording simultaneously from premotor and primary motor cortical nuclei in singing birds, this paper provides compelling evidence that premotor activity covaries with primary activity with the temporal specificity necessary to promote learning and drive adaptive vocal variation. As the first study to record from two distant sites at once in singing birds, this study also provides exceptional evidence for temporally precise coordination between two motor areas in the service of vocal learning.

eLife assessment

This Pentz et al study potentially provides fundamental insight into the evolution of multicellularity by experimentally demonstrating that yeast strains that form clonal groups evolve stronger group traits than ones that aggregate into non-clonal groups. While the repeatability of their experiments, supported by genomic analyses and models is compelling, the experimental design may be inadequate and would need to be extended to better support the main claims.

eLife assessment

This study presents an important finding that high-sugar diet-induced behavioral changes can be transmitted to the offspring through the maternal germline. Using genetic and molecular biology approaches in the fruit fly model, the authors argue that this Lamarckian inheritance is mediated by germline-inherited chromatin and is regulated by the general activity of a histone methylase, and H3K27me3 modification plays a critical role in this transgenerational effect. The behavioral data are convincing, while the underlying molecular and neural mechanisms need to be strengthened. The work will be of great interest to behaviorists and epigeneticist.

eLife assessment

This valuable study describes the development of a new structure-based learning approach to predict transcription binding specificity and its application in the modeling of regulatory complexes in cis-regulatory modules. The authors developed a structure-based learning approach to predict TF binding features and model the regulatory complex(es) in cis-regulatory modules, integrating experimental knowledge of structures of TF-DNA complexes and high-throughput TF-DNA interactions. The validation presented by the authors is currently incomplete, with a large variability in the performance of the method on the different TF families tested.

eLife assessment

This manuscript investigates thalamocortical communication and cross-frequency coupling in humans and animal models under anesthesia and the effects of the serotonergic psychedelic compound 5-MeO-DMT. These findings are exciting because they put two different perturbations of brain functions - anesthesia and psychedelic stimulation - into a single modeling framework. The framework describes anesthesia and psychedelic stimulation as opposing perturbations from normal brain function that respectively reduce and enhance thalamocortical communication.

eLife assessment

This important study combines conditional mutagenesis with proximity labeling to evaluate alterations in a sub-cellular proteome upon a perturbing event. The approach is applied to the deletion of a kinase involved in trafficking of adhesins to the malaria parasite-infected erythrocyte surface and the evidence supporting the conclusions is compelling. The work will be of broad interest to cell biologists and biochemists.

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.