Genetics

A mathematical model that predicts human biological age from physiological traits identifies environmental and genetic factors that influence aging

1. Sergiy Libert
2. Alex Chekholko
3. Cynthia Kenyon

• Curated by eLife

  eLife Assessment

  This important study developed a mathematical model to predict biological age by leveraging physiological traits across multiple organ systems. The results presented are convincing, utilizing comprehensive data-driven approaches. However, additional external validation could further strengthen its generalizability. The model provides a way to identify environmental and genetic factors impacting aging and lifespan, revealing new factors potentially affecting aging. It also shows promise for evaluating therapeutics aimed at prolonging a healthy lifespan.

Reviewed by eLife

The robust, high-throughput, and temporally regulated roxCre and loxCre reporting systems for genetic modifications in vivo

1. Mengyang Shi
2. Jie Li
3. Xiuxiu Liu
4. Kuo Liu
5. Lingjuan He
6. Wenjuan Pu
7. Wendong Weng
8. Shaohua Zhang
9. Huan Zhao
10. Kathy O Lui
11. Bin Zhou

• Curated by eLife

  eLife Assessment

  This study presents an important set of new tools to facilitate Cre or Dre-mediated recombination in mice. The characterization of these new tools was done using solid and validated methodology. The work convincingly demonstrates the efficient gene knockout capability of these models and will progress the field.

Reviewed by eLife

ZC3H11A mutations cause high myopia by triggering PI3K-AKT and NF-κB mediated signaling pathway in humans and mice

1. Chong Chen
2. Qian Liu
3. Cheng Tang
4. Yu Rong
5. Xinyi Zhao
6. Dandan Li
7. Fan Lu
8. Jia Qu
9. Xinting Liu

• Curated by eLife

  eLife Assessment

  This work investigates ZC3H11A as a cause of high myopia through the analysis of human data and experiments with genetic knockout of Zc3h11a in mouse, providing a useful model of myopia. The evidence supporting the conclusion is still incomplete in the revised manuscript as the concerns raised in the previous review were not fully addressed. The article will benefit from further strengthening the genetic analysis, full presentation of human phenotypic data, and explaining the reasons why there was no increased axial length in mice with myopia. The work will be of interest to ophthalmologists and researchers working on myopia.

Reviewed by eLife

DNA replication in primary hepatocytes without the six-subunit ORC

1. Róża K Przanowska
2. Yuechuan Chen
3. Takayuki-Okano Uchida
4. Etsuko Shibata
5. Xiaoxiao Hao
6. Isaac Segura Rueda
7. Kate Jensen
8. Piotr Przanowski
9. Anthony Trimboli
10. Yoshiyuki Shibata
11. Gustavo Leone
12. Anindya Dutta

• Curated by eLife

  eLife Assessment

  This valuable descriptive manuscript builds on prior research showing that the elimination of Origin Recognition Complex (ORC) subunits does not halt DNA replication. The authors obtain solid data using various methods to genetically remove one or two ORC subunits from specific tissues and still observe replication. The replication appears to be primarily endoreduplication, indicating that ORC-independent replication may promote genome reduplication without mitosis. The mechanism behind this ORC-independent replication remains to be elucidated. The study and mutants described herein lay the groundwork for future research to explore how cells compensate for the absence of ORC and to develop functional approaches to investigate this process. The reviewers suggested the observations could be supported by additional experiments. This work will be of interest to those studying genome duplication and replication.

Reviewed by eLife, Review Commons

Proteostasis modulates gene dosage evolution in antibiotic-resistant bacteria

1. Chinmaya Jena
2. Saillesh Chinnaraj
3. Soham Deolankar
4. Nishad Matange

• Curated by eLife

  eLife Assessment

  This important study explores the interplay between gene dosage and gene mutations in the evolution of antibiotic resistance. The authors provide compelling evidence connecting proteostasis with gene duplication during experimental evolution in a model system. This paper is likely to be of interest to researchers studying antibiotic resistance, proteostasis, and bacterial evolution.

Reviewed by eLife

Neanderthal-derived variants shape craniofacial enhancer activity at a human disease locus

1. Kirsty Uttley
2. Hannah J Jüllig
3. Carlo De Angelis
4. Julia MT Auer
5. Ewa Ozga
6. Hemant Bengani
7. Hannah K Long

Reviewed by Review Commons

A genome-wide association study implicates the olfactory system in Drosophila melanogaster diapause-associated lifespan extension and fecundity

1. Sreesankar Easwaran
2. Denise J Montell

• Curated by eLife

  eLife Assessment

  This important study shows how genetic variation is associated with fecundity following a period of reproductive diapause in female Drosophila. The work identifies the olfactory system as central to successful diapause with associated changes in longevity and fecundity. While the methods used are convincing, a limitation of the study, as of any other laboratory-based investigation is the challenge of demonstrating how well measures for fitness related to diapause and its recovery correlates with realities encountered during development in the wild.

Reviewed by eLife

UBR-1 deficiency leads to ivermectin resistance in Caenorhabditis elegans

1. Yi Li
2. Long Gong
3. Jing Wu
4. Wesley Hung
5. Mei Zhen
6. Shangbang Gao

• Curated by eLife

  eLife Assessment

  This important study allows for a better understanding of anthelmintic drug resistance in nematodes. The authors provide a detailed analysis of the role of UBR-1 and its underlying mechanism in ivermectin resistance using convincing behavioural and genetic experiments with C. elegans. Although the authors have addressed the concerns of the reviewers, it would be prudent for the authors to disclose the Dyf phenotype in ubr-1 mutants. The authors should at the very least report the Dyf phenotype and the experiment on which they base the argument that the Dyf phenotype does not affect their conclusions.

Reviewed by eLife

Becker muscular dystrophy mice showed site-specific decay of type IIa fibers with capillary change in skeletal muscle

1. Daigo Miyazaki
2. Mitsuto Sato
3. Naoko Shiba
4. Takahiro Yoshizawa
5. Akinori Nakamura

• Curated by eLife

  eLife Assessment

  The authors present three transgenic models carrying three representative exon deletions of the dystrophin gene. The findings presented are valuable to the field of muscle diseases, particularly muscular dystrophies. The evidence provided in the manuscript is convincing, with rigorous biochemical assays and state-of-the-art microscopy methods.

Reviewed by eLife

Regeneration following tissue necrosis is mediated by non-apoptotic caspase activity

1. Jacob W Klemm
2. Chloe Van Hazel
3. Robin E Harris

• Curated by eLife

  eLife Assessment

  This manuscript reports fundamental discoveries on how necrotic cells contribute to organ regeneration through apoptotic signalling to produce cells with non-lethal apoptotic caspase activity that contribute to the regenerated tissue. These findings will be of broad interest to those who study wound repair and tissue regeneration. The strength of the evidence is solid and has been improved in the revised version.

Reviewed by eLife