Pathology

PKR activation-induced mitochondrial dysfunction in HIV-transgenic mice with nephropathy

1. Teruhiko Yoshida
2. Khun Zaw Latt
3. Avi Z Rosenberg
4. Briana A Santo
5. Komuraiah Myakala
6. Yu Ishimoto
7. Yongmei Zhao
8. Shashi Shrivastav
9. Bryce A Jones
10. Xiaoping Yang
11. Xiaoxin X Wang
12. Vincent M Tutino
13. Pinaki Sarder
14. Moshe Levi
15. Koji Okamoto
16. Cheryl A Winkler
17. Jeffrey B Kopp

• Curated by eLife

  eLife assessment

  This study presents valuable new insights into a HIV-associated nephropathy (HIVAN) kidney phenotype in the Tg26 transgenic mouse model, and delineates the kidney cell types that express HIV genes and are injured in these HIV-transgenic mice. A series of compelling experiments demonstrated that PKR inhibition can ameliorate HIVAN with reversal of mitochondrial dysfunction (mainly confined to endothelial cells), a prominent feature shared in other kidney diseases. The data support that inhibition of PKR and mitochondrial dysfunction has potential clinical significance for HIVAN.

Reviewed by eLife

Drosophila model to clarify the pathological significance of OPA1 in autosomal dominant optic atrophy

1. Yohei Nitta
2. Jiro Osaka
3. Ryuto Maki
4. Satoko Hakeda-Suzuki
5. Emiko Suzuki
6. Satoshi Ueki
7. Takashi Suzuki
8. Atsushi Sugie

• Curated by eLife

  eLife assessment

  This study provides valuable insights into the complex genetics of dominant optic atrophy. Leveraging a fly model, the investigators provide solid evidence, albeit with small effect sizes, for a dominant negative mechanism of certain pathogenic variants that tend to cause more severe phenotypes, a long held hypothesis in the field. The work is of high interest to those in the optic atrophy and degeneration fields.

Reviewed by eLife

Evaluation of Gremlin-1 as a therapeutic target in metabolic dysfunction-associated steatohepatitis

1. Paul Horn
2. Jenny Norlin
3. Kasper Almholt
4. Birgitte M Viuff
5. Elisabeth D Galsgaard
6. Andreas Hald
7. Franziska Zosel
8. Helle Demuth
9. Svend Poulsen
10. Peder L Norby
11. Morten G Rasch
12. Mogens Vyberg
13. Jan Fleckner
14. Mikkel Parsberg Werge
15. Lise Lotte Gluud
16. Marco R Rink
17. Emma Shepherd
18. Ellie Northall
19. Patricia F Lalor
20. Chris J Weston
21. Morten Fog-Tonnesen
22. Philip N Newsome

• Curated by eLife

  eLife assessment

  This important paper shows that the anti-gremlin-1 (GREM1) antibody is not effective at treating liver inflammation or fibrosis. Critically, the evidence also challenges existing data on the detection of GREM1 by ELISA in serum or plasma by demonstrating that high-affinity binding of GREM1 to heparin would lead to localisation of GREM1 in the ECM or at the plasma membrane of cells. The conclusions are supported by a convincing, well-controlled set of experiments.

Reviewed by eLife

Protective Role of RIPK1 Scaffolding against HDV-Induced Hepatocyte cell death and the Significance of Cytokines in Mice

1. Gracián Camps
2. Sheila Maestro
3. Laura Torella
4. Carla Usai
5. Ana Aldaz
6. Cristina Olagüe
7. Africa Vales
8. Anne Montfort
9. Bruno Ségui
10. Lester Suarez
11. Rafael Aldabe
12. Gloria Gonzalez-Aseguinolaza

Reviewed by Rapid Reviews Infectious Diseases

Cbfβ regulates Wnt/β-catenin, Hippo/Yap, and Tgfβ signaling pathways in articular cartilage homeostasis and protects from ACLT surgery-induced osteoarthritis

1. Wei Chen
2. Yun Lu
3. Yan Zhang
4. Jinjin Wu
5. Abigail McVicar
6. Yilin Chen
7. Siyu Zhu
8. Guochun Zhu
9. You Lu
10. Jiayang Zhang
11. Matthew McConnell
12. Yi-Ping Li

• Curated by eLife

  eLife assessment

  This fundamental work advances our understanding of the role of Cbfβ in maintaining articular cartilage homeostasis and the underlying mechanisms. The evidence supporting the conclusion is mostly convincing, although including additional experiments and discussions would have strengthened the study. This paper is of potential interest to skeletal biologists and orthopaedic surgeons who study the pathogenesis and the therapeutics of osteoarthritis.

Reviewed by eLife

Membrane-bound O-acyltransferase 7 (MBOAT7) shapes lysosomal lipid homeostasis and function to control alcohol-associated liver injury

1. Venkateshwari Varadharajan
2. Iyappan Ramachandiran
3. William J Massey
4. Raghav Jain
5. Rakhee Banerjee
6. Anthony J Horak
7. Megan R McMullen
8. Emily Huang
9. Annette Bellar
10. Shuhui W Lorkowski
11. Kailash Gulshan
12. Robert N Helsley
13. Isabella James
14. Vai Pathak
15. Jaividhya Dasarathy
16. Nicole Welch
17. Srinivasan Dasarathy
18. David Streem
19. Ofer Reizes
20. Daniela S Allende
21. Jonathan D Smith
22. Judith Simcox
23. Laura E Nagy
24. J Mark Brown

• Curated by eLife

  eLife assessment

  Varadharajan et al. explore the mechanistic basis of MBOAT7 SNP association with steatotic liver disease and link its function in LPI acylation to altered lipidomics of endosomal/lysosomal system and impaired TFEB mediated lysosomal biogenesis. The findings are important with theoretical and practical implications in MAFLD, alcohol-induced hepatic steatosis, and lysosomal diseases. The strength of evidence is convincing using methodology in line with current state-of-the-art.

Reviewed by eLife

Open-top Bessel beam two-photon light sheet microscopy for three-dimensional pathology

1. Won Yeong Park
2. Jieun Yun
3. Jinho Shin
4. Byung Ho Oh
5. Gilsuk Yoon
6. Seung-Mo Hong
7. Ki Hean Kim

• Curated by eLife

  eLife assessment

  This important work by Park et al. demonstrates an open-top two-photon light sheet microscopy (OT-TP-LSM) for lesser invasive evaluation of intraoperative 3D pathology. The authors provide convincing evidence for the effectiveness of this technique investigating various human cancer cells. This article will be of broad interest to biologists and, specifically, pathologists utilizing 3D optical microscopy.

Reviewed by eLife

The intricate relationship of G-Quadruplexes and bacterial pathogenicity islands

1. Bo Lyu
2. Qisheng Song

• Curated by eLife

  eLife assessment

  This fundamental study explores the relationship between guanine-quadruplex structures and pathogenicity islands in 89 bacterial strains representing a range of pathogens. Guanine-quadruplex structures were found to be non-randomly distributed within pathogenicity islands and conserved within the same strains. These compelling findings shed light on the molecular mechanisms of Guanine-quadruplex structure-pathogenicity island interactions and will be of interest to all microbiologists.

Reviewed by eLife

β-catenin inhibition disrupts the homeostasis of osteogenic/adipogenic differentiation leading to the development of glucocorticoid-induced osteonecrosis of the femoral head

1. Chenjie Xia
2. Huihui Xu
3. Liang Fang
4. Jiali Chen
5. Wenhua Yuan
6. Danqing Fu
7. Xucheng Wang
8. Bangjian He
9. Luwei Xiao
10. Chengliang Wu
11. Peijian Tong
12. Di Chen
13. Pinger Wang
14. Hongting Jin

• Curated by eLife

  eLife assessment

  This study presents valuable findings on the mechanism of glucocorticoid-induced osteonecrosis of the femoral head. The data were collected and analyzed using solid, validated methodology and can be used as a starting point for functional studies of development of glucocorticoid-induced osteonecrosis. This paper would be of interest to cell biologists and biophysicists working on potential pharmacological treatments for glucocorticoid-induced osteonecrosis.

Reviewed by eLife

Activin A marks a novel progenitor cell population during fracture healing and reveals a therapeutic strategy

1. Lutian Yao
2. Jiawei Lu
3. Leilei Zhong
4. Yulong Wei
5. Tao Gui
6. Luqiang Wang
7. Jaimo Ahn
8. Joel D Boerckel
9. Danielle Rux
10. Christina Mundy
11. Ling Qin
12. Maurizio Pacifici

• Curated by eLife

  eLife assessment

  This work is a valuable presentation of sharp-wave-ripple reactivation of hippocampal neural ensemble activity recorded as animals explored two different environments. It attempts to use the fact that the ensemble code remaps between the two mazes to identify the best replay-detection procedures for analyzing this type of data. The reviewers found the evidence for a prescriptive conclusion inadequate, while still appreciating the concept of comparing maze-identity discrimination with replay.

Reviewed by eLife