Evaluated articles

eLife assessment:

In this important work, the authors describe a recombinant CRISPR/Cas9 construct, CRISPR-nuPin, that has the reported capacity to rapidly tether DNA to the inner nuclear membrane of cells. They then evaluate the effect of this construct on Herpes Simplex virus type 1 infection, identifying different phases of viral replication susceptible to inner nuclear membrane tethering. This work provides convincing evidence for the effects of intranuclear DNA localization on viral gene expression and replication, using a method applicable to nonviral genes as well.

eLife assessment:

In this fundamental manuscript, the authors provide compelling evidence that a housekeeping ATPase is required for heme utilization in the important pathogen Staphylococcus aureus through its interaction with the canonical heme transporter in this organism. The authors convincingly show that this complex associates with functional membrane microdomains and thus establishes a new paradigm for regional localization of the heme transport system in the staphylococci. The work will be of interest to microbiologists, particularly those studying transport for macromolecules.

eLife assessment

This paper is of potential interest to scientists within the field of drug-induced liver injury. The concept of the study is interesting by generating mitochondrial genotype-specific liver cell lines to evaluate idiosyncratic hepatotoxicity. While the proof-of-concept is clearly presented, the current data do not yet allow to draw broad conclusions about the significance of the study in terms of drug effects.

eLife assessment

The precise cellular and molecular mechanisms and signaling mediators underpinning the development of cardiomyopathy and heart failure in diabetes still remains unclear. In-depth investigations of the cardiac heterogeneity and cell-to-cell interactions could be of use to reveal the pathogenesis of diabetic myocardial fibrosis and thereby identify potential targets for the treatment of cardiac myopathy and heart failure. Utilizing a mouse model as well as in-vitro studies, this manuscript demonstrates cardiac cell mapping that provides novel insights into novel drivers of intercellular communication contributing to pathological extracellular matrix remodeling during diabetic myocardial fibrosis. The work provides compelling and convincing evidence to improve the understanding the cellular and molecular mechanisms of diabetes-induced cardiac pathology.

eLife assessment

Leptin is a fat-derived hormone that curbs appetite, and mutation of leptin causes obesity and diabetes. This manuscript investigates leptin-responsive neural circuits, revealing a key inhibitory connection from leptin-sensitive neurons in the arcuate nucleus of the hypothalamus (AGRP neurons) to neurons in the dorsomedial hypothalamus. Toggling this inhibitory connection impacted leptin effects on feeding and metabolism. The study contains valuable data, including several interesting molecular genetic systems and the demonstration of GABA signaling in the DMH for the control of food intake, however, there is inadequate information about experimental design, including a lack of quantification and controls, and unjustified assumptions.

eLife assessment

This fundamental study by Rose and colleagues addresses key challenges in demographic inference in non-model systems with an innovative approach to model parameter calibration based on known historical events. Using this approach, they convincingly show that human specialization in Ae. aegypti mosquitoes likely evolved due to a past climate event around 5,000 years ago, and that recent rapid urbanization has continued to fuel its spread in West Africa in the past 20-40 years. This work will be of broad interest to population geneticists working on demographic inference, and to mosquito biologists working on the monitoring and control of this important vector species.

eLife assessment

This manuscript presents a series of important findings about the roles of the BAR-domain containing protein SNX32 in endosomal cargo sorting and in neurite outgrowth. The authors provide convincing evidence for their claims, which will be of interest for those working not only in membrane trafficking but also for cell biologists in general with interest in neurobiology.

eLife assessment

The fundamental work represents an important contribution to our understanding of the diversity of photosynthetic mechanisms across the branches of phototrophic life, with the first high-resolution structure (2.9 Å) of a photosynthetic complex from a primitive green alga. This is a valuable resource for understanding function and evolution of light-harvesting antennas. The evidence is convincing in suggesting that the mechanism found here is distinct from the classical antenna state transitions seen in other organisms studied thus far.

eLife assessment

Sanz Perl and colleagues provide important insights regarding the application of computational brain models from neurodegenerative diseases to evaluate brain stimulation protocols in silico. Solid evidence is provided for the disease-specificity of the framework, however, the real-world impact of such stimulation protocols to alleviate psychiatric and neurological symptoms remains to be evaluated.

eLife assessment

This study uses single cell sequencing to characterize transcriptional profiles of cells in a brain region called the PVT that plays many roles in brain function. The authors combine these data with dataset of neuronal connectivity and conclude there are transcriptomically distinguishable populations of neurons in the PVT with different function. These data deepen our understanding of an important brain region.

eLife assessment

This important study of mouse genetic variation in atrial septum formation, a trait correlated with the patent foramen ovale (PFO) cardiac defect, provides convincing evidence for 37 quantitative trait loci (QTL) affecting this trait, combining genetic mapping with transcriptome analysis to zero in on relevant pathways and candidate genes within the QTL, and validating the role of one gene in tissue culture. The paper provides an important resource for hypothesis generation and future studies, which could lead to novel diagnostic or therapeutic approaches that target atrial septal defects in common congenital heart disease.

eLife assessment

In this study, neurons were recorded and combined across the parahippocampal area while rats performed a memory-guided spatial navigation task. Sophisticated analytical tools were used to provide convincing evidence that neuronal populations in these areas show behavior-related changes that might indicate the encoding of errors by the system. The valuable results suggest that rate remapping is a likely mechanism to support changes in representations that support memory-guided behavior in these regions, most interestingly in neurons that code head direction.

eLife assessment

This important paper advances our understanding of the role of lipid peroxidation in loss of muscle mass and force-generating capacity during aging and hind-limb suspension. The evidence is in general solid, drawing from experiments in vivo and cell culture using multiple types of manipulations of the formation of lipid peroxides although some weaknesses were identified. The results should be of interest to those who study the molecular basis for sarcopenia and disuse atrophy of skeletal muscle.

eLife assessment

In this manuscript, the authors investigate the role of histone deacetylases in the spatial epigenetic control of zygotic gene expression in early gastrulation. They discover HDAC1 binding is maternally-controlled and that inhibition of histone acetylation blocks gastrulation and disrupts cell lineage integrity, tied to both positive and negative regulatory effects on gene transcription in space and time. The study contributes to a growing body of evidence that highlights a central role of histone acetylation-deacetylation dynamics in epigenetic regulation of gene expression and cell fating in early tissue patterning of the embryo.

eLife assessment:

This study provides valuable insight into the molecular mechanism of ion selectivity in the broader family of ATP-gated P2X receptors. The experimental data are of high quality, the evidence supporting the conclusions is convincing, and the work will be of broad interest to biophysicists working on ion channel selectivity.

eLife assessment

This important study aimed to identify rhythms linked to primary symptoms of Parkinson's disease such as involuntary shaking of the limbs and slowness. The evidence supporting the conclusions is solid, although validating their behavioural measures and considering the relationship between signatures from different brain regions would have strengthened the study. The work will be of broad interest to movement control, movement disorders, and brain stimulation fields.

eLife assessment

When a neuron is born it correlates with where it targets in the neuropil and this has been best demonstrated in the olfactory lobe of Drosophila. This important study uses sophisticated genetics and advanced live imaging to provide a compelling description of how neuronal dendrites explore the targeting field, eliminate excessive branches, and assort into the correct region during development. In the process, it develops valuable tools. It brings us closer to a comprehensive understanding of how the birth order of a neuron translates to dendrite patterning within the Drosophila antennal lobe circuit

eLife assessment

Black et al., provide evidence that levels of Paternally Expressed Gene 10 (PEG10) protein are regulated by Ubqln2 and that proteolytic fragments from PEG10 cleavage induce changes in gene expression, in particular genes that encode proteins involved in axon biology. Based on these data and the finding of an increase in PEG10 levels and alterations of proteins regulated by PEG10 in the spinal cord of ALS patients, they propose that abnormal induction of PEG10-regulated genes is involved in ALS. However, the evidence for these claims and PEG10 involvement could be strengthened, and the rigor of the work could be enhanced in places.

eLife assessment

This important study provides a provocative potential challenge to explain sensitivity across the visual field by using cortical magnification factors. The evidence supporting this theoretical challenge is solid in general, although the inclusion of subject-specific measurements of cortical magnification factors would have strengthened the study. The work will be of interest to vision researchers of both basic and medical science.

eLife assessment

This valuable study by Pasquereau and Turner examined the activity neurons in the subthalamic nucleus (STN) while monkeys performed a task in which they had to withhold their response during a delay period whose length was defined by a specific cue. The results indicate that the activity of STN neurons was modulated by reward size and delay. The results are potentially important for understanding how STN regulates behavior such as self-control, but the reviewers thought that the study is incomplete as the analyses, at least in the presented forms, have some potential problems and some analyses require clarification.