Biochemistry

Reduction of DNA Topoisomerase Top2 reprograms the epigenetic landscape and extends health and life span across species

1. Man Zhu
2. Meng Ma
3. Lunan Luo
4. Feiyang Li
5. Jiashun Zhang
6. Yan Pan
7. Lu Yang
8. Ying Xiao
9. Ziyan Wang
10. Bo Xian
11. Yi Zheng
12. Hao Li
13. Jing Yang

• Curated by eLife

  eLife Assessment

  Building on earlier evidence that Topoisomerase 2 depletion can extend yeast lifespan, the authors present convincing data demonstrating that reduced Top2 levels confer significant longevity benefits in C. elegans and mice. They show that these benefits encompass not only extended survival but also improved healthspan and mitigation of aging phenotypes, supported by robust transcriptomic, epigenetic, and histological analyses. While the exact mechanistic underpinnings-such as the potential connection to classical aging pathways and the selective down-regulation of genes with active promoters-remain to be fully elucidated, the breadth of these important findings strongly indicates a conserved role for Top2 in aging regulation.

Reviewed by eLife

Alzheimer-mutant γ-secretase complexes stall amyloid β-peptide production

1. Parnian Arafi
2. Sujan Devkota
3. Emily Williams
4. Masato Maesako
5. Michael S Wolfe

• Curated by eLife

  eLife Assessment

  This manuscript provides fundamental studies to gain insight into the mutations in the presenilin-1 (PSEN1) gene on proteolytic processing of the amyloid precursor protein (APP). The authors provide compelling evidence using mutations in PSEN to understand what drives alternative substrate turnover with convincing data and rigorous analysis. This deep mechanistic study provides a framework towards the development of small molecule inhibitors to treat AD.

Reviewed by eLife

Interaction hierarchy among Cdv proteins drives recruitment to membrane necks

1. Nicola De Franceschi
2. Alberto Blanch-Jover
3. Cees Dekker

• Curated by eLife

  eLife Assessment

  This valuable study investigates how the proteins of the Cdv division system in Metallosphaera sedula archaea sequentially interact with curved membranes in vitro, extending our understanding of this reduced ESCRT-like machinery. While the data support key aspects of protein recruitment and membrane remodeling, missing controls and statistical analysis information, unaddressed discrepancies, and limitations in recapitulating native geometry leave the data incomplete to fully support the proposed conclusions. The work will be of interest to evolutionary and synthetic biologists as membrane biophysicists but would benefit from additional experiments and a more cautious interpretation of results.

Reviewed by eLife

Membrane mimetic thermal proteome profiling (MM-TPP) towards mapping membrane protein-ligand dynamics

1. Rupinder Singh Jandu
2. Mohammed Al-Seragi
3. Hiroyuki Aoki
4. Mohan Babu
5. Franck Duong van Hoa

• Curated by eLife

  eLife Assessment

  This useful study introduces the peptidisc-TPP approach as a promising solution to challenges in membrane proteomics, enabling thermal proteome profiling in a detergent-free system. While the concept is innovative and holds significant potential, the demonstration of its utility and validation remains incomplete. The method presents a strong foundation for broader applications in identifying physiologically and pharmacologically relevant membrane protein-ligand interactions.

Reviewed by eLife

Elevated Ubiquitin Phosphorylation by PINK1 Contributes to Proteasomal Impairment and Promotes Neurodegeneration

1. Cong Chen
2. Tong-Yao Gao
3. Hua-Wei Yi
4. Yi Zhang
5. Tong Wang
6. Zhi-Lin Lou
7. Tao-Feng Wei
8. Yun-Bi Lu
9. Ting-Ting Li
10. Chun Tang
11. Wei-Ping Zhang

• Curated by eLife

  eLife Assessment

  The useful manuscript presents interesting findings in the field of neurodegenerative diseases by highlighting the dual role of phosphorylated ubiquitin (pUb) in cellular proteostasis and neurotoxicity. However, some claims for discovery are supported by unconvincing and incomplete evidence that requires further validation. The poor quality of key immunofluorescent images and questionable quantification analysis raise technical concerns.

Reviewed by eLife

Enzymatic access to the rare ΔUA (1→4) Glc 3, 6, N-sulfated heparin disaccharide, implications for heparin quality control

1. T. K. Kandola
2. C. J. Mycroft-West
3. M. L. Andrade De Lima
4. A. Turner
5. C. Gardini
6. E. Urso
7. G.J. Miller
8. A. Bisio
9. E. A. Yates
10. M. Guerrini
11. L. Wu
12. M. A. Skidmore

Reviewed by preLights

Curcuma longa Essential Oil Topically Mitigates Inflammatory Markers in Acetone-Induced Atopic Dermatitis in Wistar Albino Rats

1. Nathiim Namale
2. Deusdedit Tusubira
3. Kenneth Male
4. Angela Mumbua Musyoka
5. Patrick Maduabuchi Aja

Reviewed by Arcadia Science

Paradoxical dominant negative activity of an immunodeficiency-associated activating PIK3R1 variant

1. Patsy R Tomlinson
2. Rachel G Knox
3. Olga Perisic
4. Helen Su
5. Gemma V Brierley
6. Roger L Williams
7. Robert K Semple

• Curated by eLife

  eLife Assessment

  This important study reports on PI3KR mutations and a paradoxical mechanism of PI3KR signaling. The strength of evidence for the study is mostly convincing, as conclusions are supported by a variety of mutational strategies and cellular systems to look at interactions among signaling pathways.

Reviewed by eLife

The conserved biochemical activity and function of an early metazoan phosphatidylinositol 5 phosphate 4-kinase regulates growth and development

1. Harini Krishnan
2. Suhail Muzaffar
3. Sanjeev Sharma
4. Visvanathan Ramya
5. Avishek Ghosh
6. Ramanathan Sowdhamini
7. Padinjat Raghu

Reviewed by Review Commons

Scaling down for efficiency: Medium-sized protein language models perform well at transfer learning on realistic datasets

1. Luiz C. Vieira
2. Morgan L. Handojo
3. Claus O. Wilke

Reviewed by Arcadia Science