Evaluated articles

eLife assessment

This paper is an important contribution to the microglia field and will be of interest to a broad readership in the fields of neurobiology, cell biology and immunology. This work describes fundamental mechanisms of efferocytosis by microglia and uses impressive imaging in zebrafish, in combination with molecular manipulations, to provide compelling data of how centrosome movements synchronize with phagocytic cup formation during microglial efferocytosis of neuronal corpses in vivo.

eLife assessment

This paper is of interest for somatosensory neurobiologists studying how polymodality is achieved in peripheral sensory neurons. The work identifies roles in cold nociception and not mechanosensation in chloride transport for a number of ion channels.

eLife assessment

Wang, Carlson, and colleagues investigate sensory adaptations in the fruit pest Drosophila suzukii, which prefers ripe over overripe fruit. This study focuses on changes in sensory pathways for sugars and food texture, which may contribute to ecological shifts. Several interesting physiological and molecular adaptations are observed in D. suzukii, but it remains unclear whether these observed changes account for behavioral changes.

eLife assessment

The manuscript makes a fundamental contribution to our understanding of sugar release by symbiotic dinoflagellates, and is of broad interest for the fields of ecology, marine biology, and cell biology. The experiments, which combine algal culture with targeted metabolomics, transcriptomics and the application of inhibitors, provide substantial, though not entirely complete evidence for an acidic environment mimicking conditions reported for the intracellular organelle that hosts the symbiotic algae, leading to upregulation of algal cellulases, which in turn degrade the algal cell wall and thereby releasing glucose and galactose that can be used as a source of food by the coral host. This is a new idea and could significantly contribute to our understanding of photosymbiosis.

eLife assessment

Using a genetically controlled experimental setting, the authors find that the lack of Polycomb-dependent epigenetic programming in the oocyte and early embryo influences the developmental trajectory through gestation in the mouse. By showing a two-phase outcome of early growth restriction followed by enhancement, the authors address previous inconsistencies in the field. However, the link with placenta function and gene misregulation is not yet fully supported.

eLife assessment

This work addresses the mechanisms of action of the transmembrane proteins TMEM87A and TMEM87B, which are thought to play a role in protein transport, but have been implicated in other processes as well, such as signaling and acting as mechanosensitive ion channels. The study represents an important advance of the understanding of this poorly characterized family of proteins. While the structure is of low resolution, it is well interpreted, and authors take good advantage of AlphaFold2 to gain insights into potential function. The work is of interest to colleagues studying transporters and ion channels.

eLife assessment

This paper is of particular interest to researchers who plan to use focused-ion beam scanning electron microscopes (FIB-SEMs) and require fluorescent data to guide the milling process. The authors describe a valuable after-market upgrade that allows fluorescent data acquisition during FIB-milling without stage repositioning. Technical details of the fluorescent module upgrade together with the sample stage redesign are compellingly documented and will enhance the implementation of this important technology.

eLife assessment

This important paper uses advanced imaging approaches to explore how Piezo1 distributes on surface red blood cells. The study provides compelling evidence that this molecule 'reads' the membrane curvature and clear support for the force-through-membrane model of mechanosensation.

eLife assessment

SARS-CoV-2 nonstructural protein (Nsp1) has emerged as an attractive target as it plays an important role in modulating the host and viral gene expression. This study describes multiple druggable sites in Nsp1. A 1.1Å co-crystal structure of Nsp1 with a fragment, together with computational studies, provides a framework for the rational design of potential antiviral candidates. This important study is methodologically convincing and will be of interest to researchers in the fields of structural virology and rational drug design.

eLife assessment

Conditional deletion and reactivation of a gene in situ remain challenging, and this study therefore addresses a gap in the genetic tool box. The authors introduce a reversible conditional gene inactivation and reactivation method using sequential expression of recombinases, with doxycycline treatment terminating gene transcription, while doxycycline and tamoxifen addition restore gene expression.

eLife assessment

This manuscript will be of broad interest to those working in the genetics of complex diseases, with the results strongly supporting the author's primary claims. Overall, this is an important study that demonstrates the power of proteomics-based systems genetics studies in the mouse.

eLife assessment

This study addresses a fundamental question about the origin and evolution of selfish genetic elements, focusing on the paradoxical abundance of toxin-antidote elements in selfing Caenorhabditis species. The authors propose for the C. elegans peel-1 zeel-1 locus fitness advantages; if these the findings can be supported with additional data, they will be of considerable interest to the field due to their wider implications for the evolution of such systems.

eLife assessment

The authors report results from experiments and modeling that study the motions of molecules in the dense and dilute phases of biomolecular condensates, with the key finding that molecules in the dense phase of condensates formed by folded domains appear to switch between a confined state with low apparent diffusivity and a mobile state with a high apparent diffusivity that is comparable to that of molecules in the dilute phase. The study provides experimental evidence that is suggestive of phase separation coupled with percolation as the operative mechanism that gives rise to biomolecular condensates.

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.