Evaluated articles

eLife assessment

In this valuable study, the authors investigate the transcriptional landscape of tuberculous meningitis. They reveal potentially significant molecular differences contributed by HIV co-infection, and derive a prognostic model to predict mortality combining a gene expression signature with clinical parameters. Whilst some of the evidence presented is compelling, the bioinformatics analysis remains limited and cannot be used to make causal inferences and conclusions about immunopathogenesis for tuberculous meningitis. The work will be of broad interest to the infectious disease community however, further validation of the findings is critical for future utility.

eLife assessment

This important study examines the extent to which distinct developmental pathways that result in alternative morphs correlate with transcriptome differences in a marine annelid, Streblospio benedicti. The strengths of the study include the experimental design and dense temporal sampling, which together provide convincing evidence that the two morphs can be clearly distinguished at the transcriptome level, despite relatively modest overall differences. The work will be of particular interest to students of the evolution of development.

eLife assessment

This study presents the valuable finding that TFIIIC interacts with MYCN to regulate RNA polymerase II dynamics by dissecting its impact on 3D chromatin architecture. Authors provide convincing evidence that MYCN and TFIIIC show long-range chromatin contacts, and that the expression of each protein limits the function of the other. The notion emerges that TFIIIC helps MYCN to maintain output at promoters while decreasing less productive associations at larger more extensively connected chromatin hubs. The paper is of interest to molecular biologists working on MYCN-dependent regulation of gene expression.

eLife Assessment

This useful study aimed to examine the relationship of spatial frequency selectivity of single macaque inferotemporal (IT) neurons to category selectivity. Interesting findings in this report suggest a shift in preferred spatial frequency during the response, from low to high spatial frequencies. This agrees with a coarse-to-fine processing strategy, which is in line with multiple studies in the early visual cortex. Some of the findings were difficult to evaluate because the methods are incomplete. The conclusion that single-unit spatial frequency selectivity can predict object coding requires further evidence to confirm.

eLife assessment

This important work substantially advances our understanding of osteoblast migration to the sites of bone formation and regeneration. The evidence supporting the conclusion is compelling, with rigorous in vitro assays for cellular and biochemical aspects and with appropriate in vivo models. The work will be of broad interest to developmental biologists and bone biologists.

eLife assessment

This study represents a useful description of a third interaction site between melanophilin and myosin-5a which has a role in regulating the distribution of pigment granules in melanocytes. While much of the data forms a solid case for this interaction, the inclusion of controls for the cellular studies and measurement of interaction affinities would have been helpful.

eLife assessment

This fundamental work substantially advances our understanding of the role of calcium-binding proteins 1 and 2 (CaBP1 and CaBP2) for generating sustained calcium currents in mouse inner hair cells and their capacity for indefatigable exocytosis. The evidence supporting the conclusions is compelling, with rigorous in vitro and in vivo physiological experiments and state-of-the-art microscopy. The work will be of broad interest to synaptic physiologists, cellular biochemists, and hearing researchers.

eLife Assessment

Given a great need for novel human model systems to study small cell lung cancer (SCLC), the authors describe an important pre-clinical model with broad potential for the study of how genetic perturbations or drug treatments alter SCLC tumor growth, metastasis, and response to therapy. For the major finding, the authors provide convincing evidence that RB/TP53 suppression coupled with MYC overexpression in an ES cell-derived model system results in aggressive and metastatic SCLC. However, the impact of the work would have been increased with the inclusion of a broader set of genetic perturbations, such as over-expression of MYCL, to better model major SCLC phenotypes. The new model described will be of significant interest to researchers studying lung cancer.

eLife assessment

To investigate the evolutionary relationship between the RNAi pathway and innate immunity, this valuable study uses biochemistry and structural biology to investigate the trimeric complex of Dicer-1, DRH-1 (a RIGI homologue), and RDE-4, which exists in C. elegans. The results described include rigorous kinetic analysis of the enzymatic activity of the complex and a moderate resolution cryo-EM structure. The results are convincing and add to the broader understanding of the evolution of antiviral defense.

eLife Assessment

Axon growth is essential to formation of neural connections. This manuscript presents a useful presentation of a new method for assessing the adhesion strength of axons with the use of a laser-induced shock wave. However, the strength of the evidence is incomplete as critical controls for calibration and time course are lacking.

eLife Assessment

This work provides a simple, rapid and valuable protocol for the isolation of small extracellular vesicles from small volumes of plasma, using two well-known methodologies, in tandem: size exclusion chromatography (SEC) and density gradient ultracentrifugation (DGUC). The authors exhaustively test these methodologies separately and in combination, showing superior results for the SEC-DGUC in terms of purity and yield. The results obtained in this work are convincing, using multiple state-of-art methodologies for the characterization of the isolates that support their conclusions.

eLife assessment

This is an important paper as it is the first to use a reconstituted translation system to study competition among mRNAs for the initiation machinery. Understanding the principles of the biochemistry of mRNA competition for initiation factors cannot be achieved without such a system. The authors provide compelling evidence that Ded1 is required for efficient initiation of highly structured mRNAs. The findings are significant and validate the in vitro reconstituted system by recapitulating the effects of in-vivo perturbations of translation initiation by Ded1 mutants.

eLife Assessment

This valuable study shows that eliminating a large portion of the principal neurons in the mammalian olfactory bulb does not affect the initial establishment of the circuit but has an impact on its maintenance. The strength of the paper is that the anatomical changes induced by genetic ablation of neurons are clear-cut. There is solid support for the findings, with a description of the structural and behavioral effects of ablating the majority of M/T neurons.

eLife Assessment

This important study presents a method to visualize the location of the cell types discovered through single-cell RNA sequencing. The data allowed the authors to build spatial tissue atlases of the fly head and body, and to identify the location of previously unknown cell types. The data are convincing and appropriate, and the authors validate the methodology in line with the current state-of-the-art.

eLife Assessment

This important study by Jeong and Choi studied neural activity in the medial prefrontal cortex (mPFC) while rats performed a foraging paradigm in which rats forage for rewards in the absence or presence of a threatening object (Lobsterbot). The authors present interesting observations suggesting that the mPFC population activity switches between distinct functional modes conveying distinct task variables- such as the distance to the reward location and types of threat-avoidance behaviors-depending on the location of the animal. The reviewers thought that the results are overall convincing, appreciated the value of studying neural coding in naturalistic settings, and felt that this work offers significant insights into how the mPFC operates during foraging behavior involving reward-threat conflict.

eLife assessment

The authors develop a novel genetic strategy for specific and comprehensive labeling of axo-axonic cells, also referred to as chandelier cells, in the mouse brain. The approach and analysis are rigorous such that the data convincingly support the key conclusions, including the expanded distribution of axo-axonic cells throughout the brain. This study provides important new information about the distribution of a significant neuronal cell type, as well as new tools for future studies. This work will be of broad interest to neuroscientists who work on the anatomical and functional organization of neural circuits.

eLife assessment

This fundamental study reports compelling findings that intermediate states exist in epithelial-mesenchymal transition (EMT) during natural development and differentiation of mammalian neural crest cells, similar to recent reports in cancer. The authors determined that there were at least two paths to delamination and migration - one that occurs during S-phase of cell cycle and another during G2/M phase, and that the process of delamination is not restricted to cell fate. Finally, the authors showed that expression of Dlc1 may be used to identify cells in an intermediate state of EMT as well as their spatial location in the mouse embryo. The work will be of interest to developmental biologists, neurobiologists and cancer researchers.

eLife assessment

The reprocessing and reanalysis of archived samples can yield further insights from past experiments. Here, a useful procedure to perform tissue clearing and immunolabeling on large-scale formalin-fixed paraffin-embedded brain specimens is convincingly evaluated on a set of archival pathology specimens, and its applicability to further such samples is analyzed. This method will be of interest to both neuroscientists and pathologists.

eLife assessment

This valuable study presents convincing evidence for an association between PARP-1 and H4K20me1 in transcriptional regulation, supported by biochemical and ChIP-seq analyses. The work contributes significantly to our understanding of how Parp1 associates with target genes to regulate their expression.

eLife assessment

This important study describes how PhoP regulates cyclic-AMP production in the human pathogen Mycobacterium tuberculosis. The authors provide convincing evidence that PhoP acts as a repressor of the cyclic-AMP-specific phosphodiesterase, Rv0805, which can degrade cyclic-AMP. The revised manuscript has addressed all outstanding comments and the work will be of interest to bacteriologists.