Evaluated articles

eLife assessment

This important study employs auxin-induced degradation to show that the TATA-binding protein (TBP) is not required for ongoing RNA polymerase II transcription nor heat-shock or retinoic acid-induced transcription, but that TBP is essential for RNA polymerase III transcription, with TBP-independent TFIID complexes being assembled and present at the transcription start sites of polymerase II-transcribed promoters. The evidence for the major claims is currently incomplete.

eLife assessment

The authors have developed a useful and user-friendly software to analyse gene expression data from four datasets representing premalignant lung lesions. This software would be of interest to those working in lung cancer and specifically the pre-malignant space. The major strength is the ease of use while the major limitation is the inability for the user to integrate other datasets.

eLife assessment

Determination of the biomechanical forces and downstream pathways that direct heart valve morphogenesis is an important area of research. In the current study, potential functions of localized Yap signaling in cardiac valve morphogenesis were examined. However, the evidence for Yap pathway activation and localization relative to areas of the valve subject to different mechanical stresses is not convincing.

eLife assessment

This is a well-explained and potentially useful study that describes the generation and use of pYtags, recombinant proteins that, if properly used, should allow spatiotemporal monitoring of the activation of different receptor tyrosine kinases in living cells. Although this study has generated new tools to evaluate receptor localization and activation in different cells, the broad concept showing that different receptor dimers generate specific stimuli, and downstream signaling pathways, is quite limited in terms of novelty. Although it is felt that the study is technologically innovative, the analysis of receptor spatial signaling is incomplete and should be improved.

eLife assessment

This fundamental study substantially advances our understanding of the process of ribosome maturation. The authors have purified and determined the structures of several nucleolar ribosome assembly intermediates in yeast using cryo-electron microscopy (cryo-EM). The study combines genetic, biochemical, and structural analysis to provide compelling support for the conclusions the authors wish to draw. The work will be of broad interest to cell biologists, biochemists, and structural biologists.

eLife assessment

This is an intriguing study investigating the molecular mechanisms of neural circuit developmental organization. Using a defined hippocampal circuit, the authors find that ectopic expression of an adhesion G protein-receptor leads to axon mistargeting. This work defines new mechanisms of axon target specificity.

eLife assessment

Russel et al. study and reveal compelling evidence for potential sequence-based factors that may drive VDJ trimming, a mechanism involved in VDJ recombination that shapes adaptive immune repertoire generation. The work is based on a rigorous statistical comparison of logistic regression models to reveal the role and function of cutting enzymes in shaping T- and B-cell receptor diversity. It could provide fundamental new insights into these processes with some claims being currently incomplete.

eLife assessment

This study investigates the spatiotemporal characteristics of human brain activities during object recognition under noisy and ambiguous conditions. By using state-of-the-art data analysis and model-driven fusion of MEG and 7T, this work demonstrates distinct representational profiles in ventral and dorsal pathways, contributing new perspectives to our understanding of the neural implementation of object recognition under uncertainty.

eLife assessment

Siglec-1 (CD169), a plasma membrane-associated sialic acid-binding lectin, has been implicated in the capture of HIV and other viruses by dendritic cells and macrophages. However, the molecular details of how HIV particles are captured by Siglec-1 are poorly understood. In this paper, the authors use advanced imaging methods to analyse the cell surface distribution of Siglec-1 on immature and mature dendritic cells to study the regulation of Siglec-1 distribution by actin and regulators of actin polymerization and to understand how virus-Siglec-1 engagement leads to virus sequestration within so-called virus containing compartments. These types of analyses have only recently become feasible with the implementation of super-resolution imaging and as yet few virus-host cell systems have been examined in detail. Thus, this study has relevance for researchers studying the engagement of HIV and many other viruses with cells, as well as researchers interested in the mechanisms regulating receptor distribution and function on cells.

eLife assessment

Poison frogs sequester alkaloids to make themselves toxic or unpalatable to predators, but how this sequestration occurs is not well understood. This valuable study identifies an alkaloid-binding protein in the plasma of poison frogs, which may help explain how these animals are able to sequester a diversity of alkaloids with different target sites. The supporting evidence is solid and the study adds to our understanding of how toxic animals resist the effects of their own defenses.

eLife assessment

Elbaz-Hayoun et al. investigate the role of macrophages in the gliotic response of retinal Müller glia and photoreceptor cell death. The authors find that macrophages play a role in inducing retinal damage. A role for the muller glia expressed, C-C chemokine receptor axis was identified as a causative factor in promoting retinal degeneration. These important data identify a new link between cells of the immune system and those within the retina which contribute to the progression of retinal degeneration.

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.