Genetics

Inflammation-Induced Alternative Splicing in Human Endothelial Cells Reveals Genetic Mechanisms of Cardiovascular Disease Risk

1. Anna K. Golebiewski
2. Lindsey K. Stolze
3. Valentina D. Vazquez
4. Alhan Mehrabi Yazdi
5. Cecilia M. Careaga
6. Casey E. Romanoski

Reviewed by Arcadia Science

Life-history trade-offs explain local adaptation in Arabidopsis thaliana

1. Benjamin Brachi
2. Danièle L Filiault
3. Rahul Pisupati
4. Tal Dahan-Meir
5. Anna Igolkina
6. Alison Anastasio
7. Mathew S Box
8. Susan Duncan
9. Talia L Karasov
10. Envel Kerdaffrec
11. Laura Merwin
12. Timothy C Morton
13. Viktoria Nizhynska
14. Polina Yu Novikova
15. Fernando Rabanal
16. Takashi Tsuchimatsu
17. Torbjörn Säll
18. Caroline Dean
19. Svante Holm
20. Joy Bergelson
21. Magnus Nordborg

• Curated by eLife

  eLife Assessment

  This manuscript reports a large series of experiments to investigate specific aspects of plant adaptation, leveraging genetic and genomic resources of Arabidopsis thaliana. The study provides convincing evidence for local adaptation in this highly selfing plant. This is an important dataset contributing to the developing understanding of non-linear selection in plants and beyond.

Reviewed by eLife

Computer prediction and genetic analysis identifies retinoic acid modulation as a driver of conserved longevity pathways in genetically-diverse Caenorhabditis nematodes

1. Stephen A Banse
2. Christine A Sedore
3. Anna L Coleman-Hulbert
4. Erik Johnson
5. Brian Onken
6. David Hall
7. Erik Segerdell
8. E Grace Jones
9. Yuhua Song
10. Hadley Osman
11. Jian Xue
12. Elena Battistoni
13. Suzhen Guo
14. Anna C Foulger
15. Madhuri Achanta
16. Mustafa Sheikh
17. Theresa Fitzgibbon
18. John H Willis
19. Gavin C Woodruff
20. Monica Driscoll
21. Gordon J Lithgow
22. Patrick C Phillips

• Curated by eLife

  eLife Assessment

  This important study explores the power of computational methods to predict lifespan-extending small molecules, demonstrating that while these methods significantly increase hit rates, experimental validation remains essential. The study uses all-trans retinoic acid in Caenorhabditis elegans as a model, providing genetic and transcriptomic insights into its longevity effects. The data are compelling in describing a robust, computationally informed screening process for discovering compounds that extend lifespan in this species.

Reviewed by eLife

Borzoi-informed fine mapping improves causal variant prioritization in complex trait GWAS

1. Divyanshi Srivastava
2. Anya Korsakova
3. Qingbo Wang
4. Luong Ruiz
5. Han Yuan
6. David R Kelley

Reviewed by Arcadia Science

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 would benefit from a more robust genetic analysis and comprehensive presentation of human phenotypic data to clarify the modes of inheritance in the families, currently limited by loss of patient follow-up and addressing whether there is a reduction in bipolar cell number or decreased marker protein expression through cell counts or quantifiable, less saturated Western blots. The work will be of interest to ophthalmologists and researchers working on myopia

Reviewed by eLife

Identifying in vivo genetic dependencies of melanocyte and melanoma development

1. Sarah Perlee
2. Yilun Ma
3. Miranda V Hunter
4. Jacob B Swanson
5. Nelly M Cruz
6. Zhitao Ming
7. Julia Xia
8. Timothée Lionnet
9. Maura McGrail
10. Richard M White

• Curated by eLife

  eLife Assessment

  This important manuscript introduces a genetic tool utilizing mutant mitfa-Cas9 expressing zebrafish to knockout genes to analyze melanocyte function in development and tumorigenesis. The data are convincing and the authors cover potential caveats from their model that might impact its utility for future work. This work significantly adds to the existing approaches in the field, as the mitfa:Cas9 strategy taken here provides a roadmap for generating similar platforms for using other tissue-specific regulators and Cas proteins in the future.

Reviewed by eLife

Female-germline specific protein Sakura interacts with Otu and is crucial for germline stem cell renewal and differentiation and oogenesis

1. Azali Azlan
2. Li Zhu
3. Ryuya Fukunaga

• Curated by eLife

  eLife Assessment

  This valuable study reports the first characterization of the CG14545 gene in Drosophila melanogaster, which the authors name "Sakura." Acting during germline stem cell fate and differentiation, Sakura is required for both oogenesis and female fertility, although some mechanistic details require further investigation. This solid study presents a wide-ranging and well-controlled characterization of Sakura, and accordingly the findings and associated reagents described will be of use to scientists interested in oogenesis and early development.

Reviewed by eLife

Positive genetic interactions: high impact, but underrepresented in the literature

1. Mengyi Sun
2. David M. McCandlish

Reviewed by Arcadia Science

WRN and WRNIP1 ATPases impose high fidelity on translesion synthesis by Y-family DNA polymerases

1. Jung-Hoon Yoon
2. Karthi Sellamuthu
3. Louise Prakash
4. Satya Prakash

• Curated by eLife

  eLife Assessment

  This manuscript reports an important finding for understanding the molecular mechanisms of mutagenesis, carcinogenesis, and senescence. It follows a previous report showing that the Werner syndrome protein WRN and its interacting protein WRNIP1 are indispensable for translesion DNA synthesis (TLS) by Y-family DNA polymerases (Pols). The manuscript provides convincing evidence that WRN and WRNIP1 ATPases, in addition to the previously reported role of the WRN 3'>5' exonuclease activity, are essential for promoting the fidelity of replication through DNA lesions by Y-family Pols in human cells.

Reviewed by eLife

Independent Validation of Transgenerational Inheritance of Learned Pathogen Avoidance in Caenorhabditis elegans

1. Aalimah Akinosho
2. Joseph Alexander
3. Kyle Floyd
4. Andrés Vidal-Gadea

• Curated by eLife

  eLife Assessment

  This valuable study concerns a model for transgenerational epigenetic inheritance, the learned avoidance by C. elegans of the PA14 pathogenic strain of Pseudomonas aeruginosa. A recent study questioned whether transgenerational inheritance in this paradigm lacks robustness. The authors of this study have worked independently of the group that reported the original phenomenon and also independently of the group that challenged the original report. With solid data, this study independently validates findings previously reported by the Murphy group, confirming that the paradigm is reproducible elsewhere. The present study is therefore of broad interest to anyone studying genetics, epigenetics, or learned behavior.

Reviewed by eLife