Evaluated articles

eLife assessment

This important study advances our understanding of the potential mechanisms of deep-sea adaptation and sheds light on the evolutionary history of hadal snailfish. Through comparative genomic analysis, the authors provide convincing evidence and propose hypotheses on the timing of trench colonization, population structure, and adaptations to the hadal snailfish genome in response to their environment.

eLife assessment

This, in principle, useful study suggests that the G-protein subunit Gng13 is required for limiting injury and inflammation following H1N1 influenza infection via anti-inflammatory effects from ectopic tuft cells. While support for Gng13 helping to limit influenza injury in the transgenic mouse models used here is solid, evidence for these effects being mediated by normal tuft cells remains incomplete, giving conflicting data from mice that lack tuft cells entirely.

eLife assessment

This important manuscript follows up on previous findings from the same lab supporting the idea that deficits in learning due to enhanced synaptic plasticity are due to saturation effects. Compelling evidence is presented that behavioral learning deficits associated with enhanced synaptic plasticity in a transgenic mouse model can be rescued by manipulations designed to reverse the saturation of synaptic plasticity. In particular, the finding that a previously FDA-approved therapeutic can rescue learning could provide new insights for biologists, psychologists, and others studying learning and neurodevelopment.

eLife assessment

This important study reports that a transcription factor stimulating mRNA synthesis can stabilize its target transcripts. The convincing results demonstrate, with multiple independent approaches, co-transcriptional binding, stabilization of a family of mRNAs, and cytoplasmic activities of the transcription factor Sfp1. The results lead to the conclusion that the co-transcriptional association of Sfp1 with specific transcripts is a critical step in the stabilization of such transcripts in the cytoplasm.

eLife assessment

This useful work shows that the experimental application of serotonin to locust antennal lobes induces an increased feeding-related response to some odorants (even in food-satiated animals). To explain how the odorant-specific effects are seen despite similar consequences of 5-HT modulation on all projection neuronal types, the authors propose a simple quantitative model built around projection with different downstream connections. While they are consistent with the authors' conclusions, the current panel of experiments is incomplete and additional future work will be required to fully support the conclusions the authors currently draw from their observations.

eLife assessment

This valuable paper presents a new approach for association testing, using the output of neural networks that have been trained to predict functional changes from DNA sequences. As such, the approach is an interesting addition to statistical genetics, and the evidence for the presented method being able to identify trait-associations in regions where GWASs are typically underpowered is solid. A limitation is, however, that it is unclear how the quality of these associations compares to those detected using conventional methods. Additional work assessing this method's power and characterizing false positives / false negative regions would be critical to ensure that the method is broadly adopted by the field.

eLife assessment

This manuscript describes valuable new findings on the impact of chromatin context on the outcomes of microhomology-mediated end joining of DNA double-strand breaks (DSBs), specifically a preference for DSB-proximal microhomologies in repair within a heterochromatic compared to a euchromatic locus. The authors develop the Drosophila spermatogonia as a model for repair at induced DSBs in a mitotically-active tissue and leverage this system to provide convincing evidence that the local environment impacts the preference for repair mechanism and outcome. The work could be strengthened by the use of additional euchromatin insertion(s) to robustly validate the findings.

eLife assessment

This manuscript provides convincing evidence for the involvement of membrane actin, and its regulatory proteins, mDia1/3, RhoA, and Rac1 in the mechanism of synaptic vesicle re-uptake (endocytosis). These important data fill a gap in the understanding of how the regulation of actin dynamics and endocytosis are linked. The manuscript will be of interest to all scientists working on cellular trafficking and membrane remodeling.

eLife assessment

This study reports a novel substrate and a mediator of oncogenesis downstream of mTORC1, a fundamental advance in our understanding of the mechanistic basis of mTORC1-regulated cap-dependent translation and protein synthesis. Using an array of biochemical, proteomic and functional assays, the authors provide compelling evidence for a novel mTORC1/S6K1-IBTK-eIF4A1 signaling axis that promotes cancer pathogenic translation. This work is of broad interest and significance, given the importance of aberrant protein synthesis in cancer.

eLife Assessment

This valuable study addresses one way in which animals identify predator-associated cues and respond in a manner that reflects the imminence of the potential threat. The report shows that, in mice, fresh saliva from a natural predator (cat) elicits a greater defensive response compared to old cat saliva and implicates the vomeronasal organ and ventromedial hypothalamus as part of a circuit that underlies this process. The evidence supporting the main conclusions is solid. This study will be of interest to those interested in aversive behavior, its processes, and mechanisms.

eLife assessment

This fundamental study explores the relationship between guanine-quadruplex structures and pathogenicity islands in 89 bacterial strains representing a range of pathogens. Guanine-quadruplex structures were found to be non-randomly distributed within pathogenicity islands and conserved within the same strains. These compelling findings shed light on the molecular mechanisms of Guanine-quadruplex structure-pathogenicity island interactions and will be of interest to all microbiologists.

eLife assessment

This is an important paper on the role of engrams and relevant conditions that influence memory and forgetting. The variety of methods used, namely, behavioural, labeling, interrogation, immunohistochemistry, microscopy, pharmacology, computational, are exemplary and provide convincing evidence for the role of engrams in the dentate gyrus in memory retrieval and forgetting. This examination will be of interest broadly across behavioural and neural science communities.

eLife assessment

This valuable paper examines the link between the neuropeptide cholecystokinin (CCK) and motor learning and neural plasticity in the motor cortex. While CCK was known to be involved in neural plasticity in other brain regions and behavioral contexts, this study is the first to provide evidence that CCK manipulation causes deficits in motor learning. However, the evidence for specific effects regarding behavior, activity, and pathways is currently incomplete.

eLife assessment

In this important study, the authors propose that lenacapavir inhibits HIV-1 replication by inducing "lethal hyperstabilization" of the capsid, based on experiments that clearly demonstrate such an effect at high drug concentrations. Data supporting the model are incomplete at low drug concentrations, and a firm correlation between the in vitro effects and therapeutic mechanism of action has not yet been established.

eLife assessment

This important work presents a systematic survey of downstream target genes of the BMP pathway during body-axis establishment of the cnidarian Nematostella vectensis. BMP is a well-known developmental regulator, and this work identifies a previously unknown array of downstream targets. Combining genomic approaches and genetic manipulations, the authors present convincing evidence that Zswim4-6 acts as a negative feedback regulator of BMP activity in Nematostella. The authors also test a zebrafish homologue in over-expression assays and show solid evidence that it too dampens BMP signaling activity, leading to the suggestion that zswim4-6 is a conserved regulator of BMP signaling. This work will be of interest to researchers in the fields of both developmental biology and evo-devo.

eLife assessment

The manuscript investigates how the tandem reader domains in BPTF co-recognize two types of modifications present on histone tails, H3K4me3 and H3 acetylation. The authors interpret their results in the context of the conformational restriction of histone tails due to interactions with nucleosomal DNA. The findings contribute new insights into how the nucleosomal context regulates the recognition of multiple histone modifications by tandem reader domains and should be of interest to the broader chromatin field.

eLife assessment

This study presents an important finding on the serial attentional resource allocation during parallel feature value tracking. The evidence supporting the claims of the authors is solid, although further clarification for high-/low-precision assigning, task effectivity of active tracking, and data analysis would have strengthened the study. The work will be of broad interest to psychology and cognitive science.

eLife assessment

The findings provided by Mohibi et al. are important to the field of lipid metabolism and cancer and provide insight for an in vivo role of FDX1. The evidence is solid, utilizing multiple modalities and both in vitro and in vivo lines of investigation.

eLife assessment

This valuable study provides a combination of experiment and theory to investigate the role of a key signalling pathway as a patterning guide for local and global mechanical properties in a developing tissue. It poses solid evidence that local dynamical effects are not necessarily predictive of global tissue mechanics, although it does not offer an alternative mechanistic explanation. This multidisciplinary work will likely have an impact on the fields of tissue mechanics and developmental biology.

eLife assessment

The manuscript presents valuable findings, using solid techniques and approaches, that shed additional light into how the canine distemper virus (CDV) hemagglutinin might engage cellular receptors and how that engagement impacts host tropism. The structural data and their analysis were thorough and well-presented. The HS-AFM data, which indicate that homodimers may dissociate into monomers - and thus have significant implications for the model of fusion triggering - are very exciting, but require further validation, perhaps by alternate approaches, to bolster the current molecular model of the CDV fusion triggering.