Results 91 to 100 of about 153,321 (216)

Pharmacological Inhibition of FKBP51 Mitigates Early Life Adversity‐Induced Social Deficits in Male Mice

Advanced Science, EarlyView.
Early life adversity triggers persistent social subordination and brain‐wide molecular dysregulation. Pharmacological inhibition of the stress‐mediator FKBP51 during the adversity period prevents these long‐term deficits and restores normative social hierarchy.
Joeri Bordes, Xiuqi Ji, Serena Gasperoni, Choham Sudre‐Chinsky, Amirali Kalbasi, Daniela Harbich, Cornelia Flachskamm, Paula Fontanet, Sowmya Narayan, Manfred Uhr, Christian Namendorf, Camilla Bellone, Alon Chen, Felix Hausch, Juan Pablo Lopez, Mathias V. Schmidt   +15 more
wiley   +1 more source

A Phase‐Resolved Geometric Deep Learning Framework Maps Structural Determinants of Disease‐Associated Protein Aggregation and Guides Suppressor Design

Advanced Science, EarlyView.
SKALE 2.0 maps disease‐associated protein aggregation as a phase‐resolved structural process, linking mutation‐induced geometric perturbations to nucleation, elongation, and suppressor design. Across neurodegenerative proteins, the framework reveals cryptic aggregation vulnerabilities, separates phase‐concordant and phase‐switching mutations, and ...
Jia Shen Sio, Wei Xuan Wilson Loo, Yan Shan Loo, Wen Xin Tan, Hui Xuan Lim, Huitao Liu, Chen Seng Ng   +6 more
wiley   +1 more source

TDP‐43 Aggregation: The Healthy‐Toxic Balance of the Prion‐Like Domain

Advanced Science, EarlyView.
TDP‐43 function relies on a delicate balance between reversible phase‐separated states and irreversible aggregation. Under physiological conditions, TDP‐43 forms dynamic droplets and oligomers that support normal cellular functions. In pathological contexts, this balance shifts toward aberrant aggregation, leading to toxic species.
Luca Zangrando, Emanuele Buratti, Francesca Paron   +2 more
wiley   +1 more source

Inhibition of KDEL Receptors Remodels the Tumor Microenvironment for T Cell Independent Tumor Regression

Advanced Science, EarlyView.
Inhibition of KDELR2 in a small fraction of tumor cells generates sustainable immunogenic cell death conditions within the tumor microenvironment. These conditions promote the regression of tumors in a T cell independent manner. During regression, macrophages prime T cells that subsequently provide systemic protection against recurrence. The potency of
Shakti P Pattanayak, Hong Wang, Belinda Willard, Timothy A. Chan, William C Merrick, Zheng‐Rong Lu, Boaz Tirosh   +6 more
wiley   +1 more source

Mitochondrial stress in advanced fibrosis and cirrhosis associated with chronic hepatitis B, chronic hepatitis C, or nonalcoholic steatohepatitis

Hepatology, EarlyView., 2022
Adaptive mitochondrial mechanisms allow mitochondrial resilience and prevent the worsening of fibrosis, while deregulation of these mechanisms promotes the progression from no/minimal‐mild (F0‐F2) fibrosis to advanced fibrosis and cirrhosis (F3‐F4). Abstract Background and Aims Hepatitis B virus (HBV) infection causes oxidative stress (OS) and alters ...
Dimitri Loureiro, Issam Tout, Stéphanie Narguet, Cheikh Mohamed Bed, Morgane Roinard, Ahmad Sleiman, Nathalie Boyer, Nathalie Pons‐Kerjean, Corinne Castelnau, Nathalie Giuly, Dorothy Tonui, Vassili Soumelis, Jamel El Benna, Patrick Soussan, Richard Moreau, Valérie Paradis, Abdellah Mansouri, Tarik Asselah   +17 more
wiley   +1 more source

Targeting the HSPA8‐CMA‐ATP6V1A Axis Triggers Lysosomal Hyperacidification and Catastrophic Vacuolation in Prostate Cancer

Advanced Science, EarlyView.
Our experimental evidence supports a model in which ALO targets the HSPA8‐CMA‐ATP6V1A axis to induce lysosomal hyperacidification and initiate osmotic and lipidomic stress. These changes are associated with LMP and loss of lysosomal integrity in prostate cancer cells.
Bingzheng An, Ze Gao, Shuo Chen, Liwei Meng, Chen Zhang, Kefan Song, Haochen Cui, Lei Yan, Zhiqing Fang   +8 more
wiley   +1 more source

Adipocyte Myoglobin Is a Determinant of Energy Expenditure and a Potential Target to Limit Obesity

Advanced Science, EarlyView.
Myoglobin, known as a muscle oxygen‐carrying protein, is shown to play a key role in fat cells that burn energy. Loss of myoglobin reduces the body's ability to generate heat and increases obesity risk, while restoring it improves metabolism. The study identifies myoglobin as a regulator of fat burning and a potential target to enhance energy ...
Christian Strehlau, Helen Broghammer, Claudia Gebhardt, Anne Hoffmann, Tobias Hagemann, Şeyma Midilli, Rachel S. Zimmer, Kristin Schubert, Vasiliki Karagiannakou, Anastasia Georgiadi, Mario Ost, Martin Krüger, Lisa Roth, Kerstin Krause, Nora Klöting, Maria Keller, Martin Wabitsch, Rima Nuwayhid, Roland H. Stimson, Michael Stumvoll, Matthias Blüher, Juliane Weiner, John T. Heiker   +22 more
wiley   +1 more source

Targeting WDR12 Unleashes T‐Cell‐Mediated Antitumor Activity in Melanoma by Destabilizing CD276

Advanced Science, EarlyView.
WDR12 cooperates with the chaperonin subunit CCT7 to maintain CD276 stability on tumor cells, suppressing T‐cell activity and promoting immune escape. SU14813, a small‐molecule WDR12 inhibitor, reduces CD276 stability and relieves CD276‐mediated T‐cell suppression.
Jie Pan, Ruimin Chang, Meng Zhang, Qian Dong, Guanxiong Zhang, Xiang Chen, Mingliang Chen, Lixia Lu, Xiaowei Liang, Yeye Guo, Juan Su   +10 more
wiley   +1 more source

Inhibition and Formation of Amyloid Fibrils in the Bulk and at the Interface of Biomolecular Condensates

Angewandte Chemie, EarlyView.
In this review, we discuss how biomolecular condensates can inhibit amyloid aggregation in their interior, while still facilitating fibril formation at the interface between the dense and dilute phases, where molecular and mesoscale properties are likely optimal to promote protein aggregation.
Marcell Papp, Chiara Morelli, Sarah Khawaja, Paolo Arosio   +3 more
wiley   +2 more sources

Molecular and Cellular Hallmarks of Age‐Related Vestibular Hair Cell Degeneration

Advanced Science, EarlyView.
This study utilizes single‐cell RNA‐seq transcriptomes, advanced imaging, and electrophysiology to examine universal and cell‐type‐specific aging signatures of vestibular hair cells. The study shows that impaired hair bundle function is a key driver of age‐related vestibular dysfunction.
Samadhi Kulasooriya, Huizhan Liu, Sarath Vijayakumar, Celia Bloom, Zhenhang Xu, Shu Tu, Benjamin J. Borgmeier, Mi Zhou, Litao Tao, Bechara Kachar, David Z. He   +10 more
wiley   +1 more source