Evaluated articles

eLife assessment

This paper will be of interest to those studying retinal angiogenesis and endothelial cell biology. The authors performed rigorous data analysis and presented a logical, well-written report. The key conclusions of the manuscript are supported by the data and uncover a novel factor for retinal endothelial cell growth.

eLife assessment

This study takes a fresh view of the hypothesis that right inferior frontal gyrus is critical in inhibitory control in humans, as assessed by the widely-used stop signal task. It applies recent development in modeling and EEG measures in patients with focal brain damage, yielding causal insights. It will be of interest to neuroscientists and clinical researchers who study the brain basis of response control. Reviewers found this to be a strong, hypothesis-driven study that makes new progress on an important topic.

eLife assessment

This manuscript reports data consistent with a new and unanticipated phenomenon: that Cre or its mRNA may be transmitted between tissues in the mouse and that the male reproductive tract (epididymis) appears to be the most common target of such transported molecules. The data serve as a timely warning to mouse researchers about an unexpected complication of Cre-mediated gene manipulation.

eLife assessment

Type II topoisomerases are essential players in virtually every aspect of genome organization and function of all organisms. The in vitro data presented here clearly demonstrate that eukaryotic type II topoisomerases phase separate under physiological conditions, forming liquid-liquid condensates, and that the outcomes of type topoisomerase II activity on DNA are altered in these condensates. The experiments and methods are sound, clearly described, and fully support the insightful and carefully formulated interpretation of the data. This work has broad implications for dissecting and delineating the myriad fundamental roles of this centrally important molecule.

eLife assessment

This study reports an interesting analysis of evolutionary variation in forelimb/hand bone shapes in relation to functional and developmental variation along the proximo-distal axis. The authors found expected and compelling patterns of evolutionary shape variation along the proximo-distal axis but less expected, yet equally compelling, patterns of shape integration. This paper will be of interest to researchers working on macroevolutionary patterns and sources of morphological diversity.

eLife assessment

This study builds upon previous results of the authors to study the neural computations within the basal ganglia that support behavioral proactive inhibition. Here, the authors identify features of neural activity in the SNr that correlate with proactive inhibition, including changes in firing rate and neural variability, and how both of these variables are influenced by an animal's outcome history. The analyses are rigorous and provide important insights into the neural dynamics in the basal ganglia that support proactive inhibition.

eLife assessment

This paper by Einarsson and colleagues presents a comprehensive analysis on how human genetic variability impacts both gene expression and promoter. Using a new resource of CAGE data in lymphoblastoid cell lines from 108 individuals, they uncover a series of features that distinguish promoters with highly variable expression across individuals from those exhibiting low variability. The authors propose various explanations for the observed results. A few additional analyses and a more pragmatic interpretation of their data may help consolidate or refine the models proposed.

eLife assessment

Seipin is a multifunctional Endoplasmic Reticulum localised protein associated with seemingly unrelated human diseases. Here the authors establish a correlation between the expression of a particular mutant form of Seipin associated in humans with motor neuron disease and altered intracellular calcium dynamics and allied proteotoxic stress. The paper is noted for the clues it provides into how these cellular defects arise and for offering a plausible, but yet unproven hypothesis for the cellular pathology that may account for the human disease phenotype.

eLife assessment

Dingus et al. have developed an innovative approach for improving the intracellular stability of nanobodies. Working with a set of 75 nanobodies, the authors have identified key amino acid changes that can improve the stability of nanobodies expressed within the cell that might be generalized to other nanobodies.

eLife assessment

The replication protein A (RPA) plays a critical role in DNA replication, DNA repair, and recombination by interacting with various proteins. This paper describes the structure of an N-terminus OB-fold of the 70kD subunit of human replication protein A (RPA70N or DNA-binding domain-F) bound to peptides from five different proteins, HELB, ATRIP, BLM, RMI1, and WRN. This paper provides useful knowledge regarding the structural flexibility of RPA70N in the binding to the different interacting peptides. The structural and biochemical analyses of the interaction of RPA70N with the different peptides provide solid evidence for the presented conclusion. The work will be of interest to those studying DNA replication, recombination and repair.

eLife assessment

This study provides new experimental data and detailed modeling of the partitioning of low copy plasmids under the control of the ParABS system in bacteria. The dynamics of the partition complex is tracked over many generations, providing useful data to constrain the models. The authors propose a model which can manifest either regular positioning or oscillations depending on the model parameters. The research will be of interest to biologists and biophysicists interested in cellular dynamics and internal organization in bacteria.

eLife assessment

This high-quality study characterizes a key enzyme in asexual red blood stages of the malaria parasites that is used to salvage lipid precursors needed for membrane biogenesis and parasite growth in red blood cells. A previously identified glycerophosphodiesterase (PfGDPD), is shown to mediate the hydrolysis of host lyso-phosphatidycholine to generate choline, which in turn is required for parasite de novo phosphatidylcholine synthesis. Extensive analysis of the localization, growth phenotype and lipidomic profiles of PfGDPD deficient parasites indicate that this salvage pathway is essential for lipid homeostasis and asexual parasite development.

eLife assessment

Jneid et al find that an entomopathogenic strain of B. thuringiensis and its Cry1A toxins, which are widely used to combat lepidopteran pests, disrupt intestinal epithelial homeostasis in Drosophila-an insect that is generally considered non-suceptible. They demonstrate that the Cry1A toxins act by altering E-cadherin-based adhesion between intestinal stem cells and their new progeny. The findings carry potential implications for unintended, broad effects of B. thuringiensis in agricultural settings.

eLife assessment

This work, which will be of interest to scientists in the field of hematology and ubiquitin biology, identifies previously unrecognized functions and regulatory mechanisms of an E3 ubiquitin ligase during erythrocyte progenitor maintenance and differentiation. This work has the potential to reveal that the exchange of scaffold proteins of a modular E3 ligase can have an effect on cell fate and reveal a novel mechanism of E2 enzyme regulation during differentiation. However, additional work is needed to support the major claims.

eLife assessment

This paper describes the anatomy of important fossil remains of the dwarf dinosaur Europasaurus, providing compelling evidence for precociality. Only a handful of papers provide detailed information on sauropod neuroanatomy - as such this paper will be of interest to a relatively wide range of researchers, in particular vertebrate palaeontologists, and comparative anatomists.

eLife assessment

The manuscript is of broad interest in the field of muscle physiology and structure. The authors developed nanobodies against different domains of the giant Drosophila proteins Sallimus and Projectin, which are titin homologs, and used them to define their organization along sarcomeres of distinct fly muscles. This is an important contribution to understand the functional architecture of the muscle; it suggests that in invertebrates two proteins fulfil the role of the vertebrate titin in bridging the A-band and the I-band.

This manuscript was co-submitted with: https://www.biorxiv.org/content/10.1101/2022.04.13.488177v1

eLife assessment

This work provides valuable knowledge to the ongoing research to establish an algorithm to shorten the duration of hepatitis C therapy with direct-acting antivirals. This is an important study that is a nice addition to previous reports evaluating the utility of response-guided therapy for shortening the duration of HCV treatment. Given the disease burden and the high costs of treatment, especially in low-income countries, this is a major goal that was also advocated by the WHO. Although the main objective (shortening therapy to 4 weeks) was not adequately achieved (<90% success rate), the study's results may suggest that re-treatment in case of failure is safe and efficient, although further studies with a larger number of patients are needed for confirmation.

eLife assessment

Igf2 and H19 are the two best-studied imprinted genes in mice. Taking advantage of the varying levels of H19 and Igf2 expression in three existing mouse models, the authors dissect the role of H19 and Igf2 in cardiac and placental development. Their findings suggest that an accurate dosage of both H19 and Igf2 is critical for normal embryonic development, especially the development of the heart and placenta. The work is of interest to colleagues studying imprinting as well as mammalian development.

eLife assessment

The authors find a significant and unexpected consequence of hypoxia in lung fibroblasts and smooth muscle cells - decreased lactate production - a finding that is important in the field of pulmonary hypertension. Additional orthogonal assessments of lactate production will strengthen the conclusions put forward.

eLife assessment

The purpose of the study was to evaluate the transcription factor NF-kB, a common transcription factor that is thought to mediate muscle atrophy, in the setting of a rotator cuff injury. The authors used gain of function and loss of function NF-kB inhibitors to show that, surprisingly, NF-kB does not seem to be a major mediator of muscle atrophy in this model (as compared to other atrophy models), but there are sex-related differences. They found that male mice were more likely to have atrophy regulated by autophagy, both of which are interesting, novel findings.