Evaluated articles

eLife assessment

This manuscript presents valuable and significant data on how lipids may accumulate in the tubulointerstitial compartment of the diseased kidney, but the work is largely descriptive, using methods that are inadequate for quantification (colorimetric assays versus mass spec), thus rendering data interpretation not very convincing. Therefore, while a major strength is the presentation of innovative ideas, additional experiments would be needed to support the main conclusions.

eLife assessment

This important work will be of interest to neuroscientists working on synaptic transmission and modulation of ion channel activity. This work provides solid evidence of how modulation of Nav1.2 channels by SUMOYLation alters the function of layer 5 pyramidal neurons, using convincing methodology that includes the use of a mouse engineered to eliminate the SUMOYLation site on Nav1.2. Some aspects need to be revised to strengthen data analysis and interpretation.

eLife assessment

This paper will be of interest to immunologists and infectious disease experts, as it reports the investigation of a novel treatment of invasive pneumococcal diseases using complement-activating monoclonal antibodies. Using a combination of in vitro and in vivo methods, the authors demonstrate convincingly that the introduction of specific mutations in human monoclonal antibodies that target the surface of pneumococcus bacteria can result in enhanced complement activation after these antibodies bind to the bacterial surface.

eLife assessment

This study shows that cis H3 tail acetylation promotes nucleosome accessibility to H3K4 methyl readers and writers such as MLL1. The findings provide a molecular basis for the long-standing connection between H3 acetylation and H3K4 methylation. Additional evidence is required to fully support the conclusions.

eLife assessment

Authors investigated the role of dopamine (DA) release via GRABDA in the dorsal bed nucleus of the stria terminalis (dBNST) in sign and goal tracking behavior, in response to systemic fentanyl, and to fentanyl self-administration. The behavioral experiments were well-conducted and provide novel information about BNST DA in theories of learning and reinforcement. Identified limitations had to do with acknowledgment and discussion of divergent sources of DA innervation, the low sample size in fentanyl experiments with the exclusion of a large number of animals, and a need for additional analyses of the photometry data and/or control recordings to rule out spontaneous transients in this region.

eLife assessment

The manuscript by Yanis Zekri et al identifies the direct T3 target genes that are important in thyroid hormone signaling in brown adipose tissue (BAT). The findings reported in this manuscript are significant and fundamental to our understanding of thyroid hormone action in response to environmental changes. The strength of the evidence presented with the novel methodological approaches used makes the manuscript exceptional in the area of BAT biology and T3 regulation of adaptive thermogenesis.

eLife assessment

This manuscript examines the inhibition of transmitter release induced by the activation of opioid receptors, both MOR and DOR, using a novel imaging method. The authors specifically examine how the inhibition of transmitter release is changed following prolonged exposure to saturating concentrations of agonists. They showed convincingly that there is a depletion of plasma membrane-associated receptors and suggest that the decline in receptors at the plasma membrane underlies presynaptic tolerance. This work addresses a long-standing question about how tolerance develops at the presynaptic level and indicates that the location of receptors is critically important in the development of tolerance. This work is fundamental and a game changer in the understanding of tolerance at the cellular level.

eLife assessment

This paper will be of interest to neuroscientists who study visual processing or are interested in dendritic integration. The authors used calcium imaging, pharmacology, and electrophysiology to investigate how a large, loom-sensitive neuron in grasshoppers integrates visual input to respond to both light and dark looming objects. These experiments support the finding that the integration is done by two distinct arbors of the neuronal dendritic tree, one of which loses retinotopic information. The authors suggest potential advantages of this dendritic arrangement.

eLife assessment

The complex mechanisms through which diet impact Parkinson's Disease are unclear, limiting the ability to guide patients to an optimal diet. Here, researchers use a mouse model to test the impact of dietary fiber, revealing changes in gut microbes and immune cells in the brain. This study raises intriguing hypotheses about how diet-induced changes in the microbiome could lead to changes in brain function.

eLife assessment

Sanderson developed novel interactive software for visualizing phylogenetic trees representing millions of sequences. This is a fundamental advance over previous software that is typically limited to trees with a few thousand tips. Taxonium has been used intensively by the virus evolution community over the past months and has thus already proven its utility and performance.

eLife assessment

This manuscript examines the functional relationship between neural activities in several cortical areas (such as the primary and secondary motor cortex and the medial prefrontal cortex) and the different sleep states or under anesthesia. The quality of the recordings in infant rats is excellent. Results are important in the field of research into the role of active sleep in the neuronal and circuit mechanisms of early cortical development. Some of the findings presented and hypothesis developed are novel, but the overall demonstration remains incomplete and further in-depth analysis and additional experiments are required to fully support the authors' claims.

eLife assessment

This manuscript will be of interest to researchers within the fields of haematological and bone oncology. It reveals a novel effect of FABP5 inhibition to reduce myeloma growth both in vitro and in vivo, with convincing supporting associations between FABP5 expression and survival in patients with myeloma.

eLife assessment

In their paper, Rao, Li et al. explore the mechanisms by which the microtubule-associated protein, doublecortin (DCX), functions in regulating retrograde transport in neurons. They find that DCX affects the dynein-microtubule interaction to perturb its motion. Impressively, they reconstitute a dynein-dynactin-JIP3 complex, validating JIP3 as a bona fide adaptor, and show that DCX disrupts the transport of this processive complex. This mechanism will be useful in understanding how mutations in DCX cause lissencephaly and this paper will be of interest to those in the cytoskeletal and neurobiology fields.

eLife assessment

The work by Kim et al., used synthetic constructs in Drosophila to examine the relationship between regulators (activator/repressor) and transcription initiation. By measuring regulator concentrations and the corresponding RNA polymerase initiation rates in different synthetic constructs and using a thermodynamic model, the authors concluded that that higher-order cooperativities between the repressor on adjacent binding sites, and that between the repressor and RNA polymerase are needed to explain the observed response curves in RNA polymerase loading rate. This work targets a challenging question in eukaryotic transcription regulation, where higher-order cooperativity between different molecular components, in addition to simple transcription factor binding and unbinding, is often necessary to account for observed promoter behaviors when multiple elements (repressors, mediators, activators) exist.

eLife assessment

This paper will be of interest to cell biologists, structural biologists, and biophysicists studying programmed cell death, membrane transport, and protein-lipid interactions. The simulation data presented offers atomistic detail of how gasdermin-D N-terminal domains assemble on the plasma membrane and trigger the formation of membrane pores which lead to pyroptosis. The study is well designed and the resulting data are rigorously analyzed; however, some clarifications and additional data are required to fully justify the conclusions.

eLife assessment

This manuscript reports a novel role of Mcm2 licensing factor and helicase subunit of the Mcm2-Mcm7 complex in the differentiation of embryonic stem cells into neuronal lineages. A series of compelling experimental manipulations dissect the abnormalities in the formation of heterochromatin at pluripotent genes and the resolution of bivalent chromatin domains at lineage-specific genes in differentiation in response to mutation of the histone binding domain of Mcm2. These findings provide new insights into the replication-independent roles of Mcm2. This paper will be of interest to scientists working on development and embryonal cell differentiation.

eLife assessment

Understanding the integration and contribution of different combinations of environmental cues to the synchronization of the daily oscillator is important, because it provides insight into how organisms might be able to distinguish (and weight) between irregular (or in the tidal zone highly complex) versus regular individual daily changes of light and temperature. The study, which is thoroughly conducted and provides an impressive amount of experimental and analytical work, dissects the effects of sensory conflict on behavior and gene expression rhythms.

eLife assessment

The ability of organisms to cope with environmental stressors can be modified by their physiological conditions as well as life experience. Here, taking advantage of the tractability of the nematode C. elegans, the authors find that exposure to elevated temperatures enhances defenses against peroxides, agents whose toxicity is enhanced by temperature. The finding that a key thermosensory neuron is required for this phenomenon is an important advance in understanding the underlying mechanism; further, the authors' proposal that this is an "enhancer sensing" phenomenon is interesting and thought-provoking. The multidisciplinary approach and mechanistic detail revealed by this work will make it of interest to readers in the fields of sensory biology, signal transduction, and physiology.

eLife assessment

This manuscript provides an improved version of the little skate genome, which will be of great interest to the field of comparative genomics and evolutionary biology. The authors use the genome to compare gene expression and chromatin accessibility profiles in motor neurons of the little skate and other species (mouse, chicken), aiming to predict conserved and divergent gene regulatory mechanisms underlying motor neuron development. While the manuscript contributes a valuable resource to the field, more rigorous analyses and experimental validation are needed to support the major claims of this study.

eLife assessment

This study provides a valuable analysis of the splicing landscape in colon cancer cells that have properties intermediate between those typically found in primary cancers ("epithelial") and those that are spreading by metastasis ("mesenchymal"). The strength of evidence provided is wide ranging and convincing, and supports current ideas that changes in the way that RNA from particular genes is processed plays a key role in cancer spread.