Evaluated articles

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.

eLife assessment

This study presents useful findings regarding the role of formin-like 2 in mouse oocyte meiosis. Some of the data are supported by incomplete methodological details and analyses, and several conclusions are overstated. This paper would be of interest to reproductive biologists.

eLife assessment

This valuable study reports that miR-199b-5p is elevated in human osteoarthritis patients. There is solid evidence for the finding that inhibiting miR-199b-5p alleviates symptoms in mice with knee osteoarthritis. Additionally, potential targets of miR-199b-5p are identified but whether miR-199b-5p truly functions through Fzd6 and/or Gcnt2 requires further investigation.

eLife assessment

This important study provides new insights into the development and function of medullary thymus epithelial cells (mTEC). The authors provide compelling evidence to support their claims as to the differentiation and lineage outcomes of CCL21+ mTEC progenitors, which further our understanding of how central tolerance of T cells is enforced within the thymus.

eLife assessment

Building on on the observation of an increase in miR-182-5p in diabetic patients, the authors investigated the role of miR-182-5p and its target gene LRP6 in dysregulated glucose tolerance and fatty acid metabolism in obese type 2 diabetics. The use of human livers complemented by supporting data in mice and cells are strengths, but the evidence presented remains incomplete. The findings provide valuable insights into the role of miRNAs in the regulation of liver metabolism and insulin sensitivity in individuals with diabetes and fatty liver disease.

eLife assessment

This valuable study seeks to disentangle the different selective forces shaping the evolutionary dynamics of transposable elements (TEs) in the wild grass Brachypodium distachyon. Using haplotype-length metrics, and genetic and environmental differentiation tests, the authors present convincing evidence that positive selection on TE polymorphisms is rare and that the distribution of TE ages points to purifying selection being the main force acting on TE evolution in this species. This study will be relevant for anyone interested in the role of TEs in evolution and adaptation.