Molecular Biology

eLife assessment

This study provides useful data substantiating a role of long noncoding RNAs in liver metabolism and organismal physiology. With murine knockout and knockin models, the authors invoke a previously unidentified role for the lncRNA Snhg3 in fatty liver. While certain findings are backed by solid evidence, other conclusions require more support and should be consolidated with existing paradigms in the field.

eLife assessment

This useful study reports on the impact of antibiotic pressure on the genomic stability of the mc2155 strain of Mycobacterium smegmatis, a model for Mycobacterium tuberculosis. The study concludes that exposure to antibiotics did not lead to the emergence of new adaptive mutations in laboratory settings, contradicting the prevailing theory of antibiotic resistance development through drug-induced microevolution. While the genomic analysis provided detailed insights into the stability of M. smegmatis following exposure to standard TB treatment antibiotics, the evidence presented for antibiotic pressure not contributing to the occurrence of new adaptive mutations is still incomplete.

eLife assessment

This study reports some useful information on the mechanisms by which a high-fat diet induces arrhythmias in the model organism Drosophila. Specifically, the authors propose that adipokinetic hormone (Akh) secretion is increased with this diet, and through binding of Akh to its receptor on cardiac neurons, arrhythmia is induced. The presented data, however, incompletely support the conclusions, with a number of concerns identified, such as the need for editorial clarifications, issues with experimental design (including additional control experiments), and over or misinterpretation of some of the experimental data. Nonetheless, some of the data will be helpful to those who wish to extend the research to a more complex model system, such as the mouse.

eLife assessment

This valuable study reports a chemogenetic screen for resistance and sensitivity towards three compounds that inhibit cell cycle progression: camptothecin, colchicine, and palbociclib. Following up on the palbociclib results, the authors provide solid evidence that knockdown of the PRC2.1 complex, likely through increasing D-type cyclin expression, confers resistance to palbociclib. The generality of the results would be improved by demonstrating the effect of PRC2.1 on cyclin expression and cell cycle progression in more than one cell line.

eLife assessment

In this manuscript the authors present high-speed atomic force microscopy (HSAFM) to analyze real-time structural changes in actin filaments induced by cofilin binding. This important study enhances our understanding of actin dynamics which plays a crucial role in a broad spectrum of cellular activities. However, some technical questions remain, making the data interpretation incomplete.

eLife assessment

This study presents important new insights linking obesity to kidney disease using a Drosophila model. A series of compelling experiments demonstrated that a high-fat diet induces the excretion of a leptin-like JAK-STAT ligand from the fat body, driving the adipose-nephrocyte axis through activated JAK-STAT signaling and subsequently causing a functional defect in nephrocytes. While the combination of genetic tools and pharmacological intervention provides solid data and confirms the mechanistic link, the phenotypic analysis is restricted to tracer endocytosis and would benefit from immunofluorescence studies and higher animal numbers.

eLife assessment

This manuscript reports important data on the interaction of Rev7 with the Rad50-Mre11-Xrs2 complex in budding yeast providing evidence that a 42 amino acid region of Rev7 is necessary and sufficient for interaction. Rev7 is found to inhibit the Rad50 ATPase and the Mre11 nuclease activities, with the exception of the ssDNA exonuclease activity. Overall, the study is incomplete: controls are lacking, there is little evidence to support the conclusion about DSB repair pathway usage, and the work on the role of Mre11 in G4 metabolism is underdeveloped.

eLife assessment

This important study provides previously unappreciated insights into the functions of protist eIF4E 5'mRNA cap-binding protein family members, thereby contributing to a better understanding of translation regulation in these organisms. The authors provide solid evidence to support the major conclusions of the article. However, the study may further benefit from establishing whether all of the eIF4E family members are indeed involved in translation and more direct evidence for the selectivity of their binding.

eLife assessment

In this paper, the male sex-lethal (MSL) complex of proteins and RNA is studied through a domain analysis of one of its components, MSL1, and its interaction with others. While these results could be useful to researchers in the field, several studies have shown that the view that the MSL complex mediates dosage compensation is no longer considered tenable. Since there are many ways to alter viability, claims based on sex-specific viability as a reflection of dosage compensation should be viewed with much caution, and the evidence is currently considered inadequate to support the claims.

eLife assessment

This study is valuable in that it aims to demonstrate that genomic insertion of a G4-containing sequence can be sufficient to induce chromosome loops and alter gene expression. However, the evidence remains incomplete because it has not been shown yet that the inserted sequence indeed forms G4 structures in cells and that the observed effects are caused by these structures and not by other elements present in the inserted sequence. Testing of different G4 sequences and other loci would be required to generalize the findings.

eLife assessment

This study presents an interesting set of findings that connects N-cadherin and glypican-4 to Slit signaling during the regulation of contact inhibition of locomotion of Schwann cells in culture. Solid evidence is provided showing that N-cadherin not only regulates cell recognition but also proper trafficking of Slit to the cell surface. An ex-vivo model demonstrates the importance of Slit signaling during cell migration but the molecular details of how N-cadherin traffics Slit to the surface and role of glypican are unclear. The data would have been strengthened with a similar interrogation of N-cadherin in this system. The work will be of interest to cell biologists studying the mechanisms behind peripheral nervous system regeneration.

eLife assessment

This important work addressed the identifcation of antimalarial drug resistance mutations that do not readily transmit to new human hosts, focusing on azithromycin resistance. The technically challenging analyses of azithromycin-resistant parasites as they traverse the mosquito host and human liver are conducted using state-of-the-art tools, including humanized mice. While the claim regarding the lack of transmission by atovaquone-resistant P. berghei is convincing, the evidence for the lack of transmission by atovaquone-resistant P. falciparum is insufficient. This work will appeal to biologists and biomedical scientists in parasitology and drug discovery, offering insights into combating antimalarial drug resistance and understanding the fitness costs associated with drug-resistant parasites.

eLife assessment

Tatekoshi et al. endeavored to utilize human-induced pluripotent stem cell-derived cardiomyocytes to create an in vitro model of Heart Failure with preserved Ejection Fraction (HFpEF) to investigate the impacts of inflammation, sera from HIV patients, and the application of cardioprotective and antiviral medications on cardiomyocyte relaxation as a proxy for diastolic function. Their investigations revealed that inflammatory cytokines lead to an increased decay in calcium transients, a process that could be alleviated through the use of SGLT2 inhibitors and mitochondrial antioxidants. These results indicate that inflammation might contribute to diastolic dysfunction and suggest that SGLT2 inhibitors and mitochondrial antioxidants could offer cardioprotective benefits by reducing inflammation in cardiomyocytes. These valuable, yet incomplete results, can be complemented by employing biomechanical and molecular analyses, alongside validation of the therapeutic duration and dosages.

eLife assessment

The study is solid and reports interesting findings on the sensitivity of different cell types to EDCs in vitro. The data are valuable but the manuscript requires more experimental details. Bioinformatic analyses need to be improved and the interpretation of results and conclusions adjusted to the results.

eLife assessment

The study by Long et al. presents valuable findings on the role of the SUL1 gene in yeast longevity, proposing that lifespan extension can occur through signaling pathways independent of its sulfate transport function, offering new insights into aging mechanisms with potential implications beyond yeast biology. However, the evidence supporting the uncoupling of SUL1's transport and signaling functions is inadequate, relying on limited lifespan analysis without measurements for nutrients and nutrient signaling status. This research is of particular interest to the aging research community, although additional experiments are needed to fully substantiate the claims.

eLife assessment

This study demonstrates mRNA-specific regulation of translation by subunits of the eukaryotic initiation factor complex 3 (eIF3) using convincing methods, data, and analyses. The investigations have generated important information that will be of interest to biologists studying translation regulation. However, the physiological significance of the gene expression changes that were observed is not clear.

eLife assessment

The Hippo signaling pathway plays a crucial role in controlling organ size, cell proliferation, and apoptosis, though its role in endocrine pancreas development has remained unclear. In this useful work, the authors study the function of the Tead1 transcription factor, a Hippo effector, specifically in pancreatic beta cells. They provide solid evidence, using multiple different conditional knockout models to reveal Tead1's regulatory functions in insulin secretion and beta cell proliferation. However, deeper exploration of their data and incorporating findings from existing literature on this topic would provide a clearer understanding of Tead1's role in β-cell function, within or beyond the Hippo pathway.

eLife assessment

This fundamental work significantly advances our understanding of how FOG1 nuclear localization is regulated during erythropoiesis and megakaryopoiesis, including the role of EPO and MPL/TPO signaling in this process. The authors provide compelling evidence using both K562 and CD34+ cells that heat shock cognate B (HSCB) can promote the proteasomal degradation of TACC3 to regulate the nuclear localization of FOG1, and that this function is independent of its role in iron-sulfur cluster (ISC) biogenesis. Together these data will be of interest to the fields of hematopoiesis and cell biology.

eLife assessment

This potentially useful study reports a new method for restoring sperm motility. Strengths are in the methodology being developed, but the conclusions require additional experimental support. The authors provide inadequate evidence for the success of the method or its mechanism.

eLife assessment

This valuable study advances our understanding of how the viral protease in a D-type retrovirus is activated and in particular how the exposure of the myristoyl group is required for processing of the Gag matrix precursor. The supporting evidence is convincing, but the work would benefit from additional data in support of the claims. This manuscript is of interest to retrovirologists and structural biologists.