Results 231 to 240 of about 1,051,372 (350)

First Generation Proteolysis Targeting Chimeras (PROTACs) for the Treatment of Progeria

open access: yesAdvanced Science, EarlyView.
We report the first PROTACs designed to degrade progerin, introducing a novel therapeutic approach for progeria. The best compound, UCM‐18142, significantly reduces progerin levels and improves key disease phenotypes in patient‐derived cells and in the LmnaG609G/G609G mouse model, paving the way for new treatment strategies targeting the root cause of ...
Jon Macicior‐Michelena   +5 more
wiley   +1 more source

Kinesin‐Induced Buckling Reveals the Limits of Microtubule Self‐Repair

open access: yesAdvanced Science, EarlyView.
This study shows that kinesin‐driven buckling induces extensive microtubule lattice damage that often exceeds intrinsic self‐repair and leads to filament failure. While curvature, motor motility, and force individually cause limited damage, their combination overwhelms repair.
Shweta Nandakumar   +9 more
wiley   +1 more source

ZMAT1 Promotes Osteoclastogenesis Through TRIM46 Mediated YAP1 Degradation and Inhibits Osteoblastogenesis

open access: yesAdvanced Science, EarlyView.
Zmat1 deficiency mitigates pathological bone loss by impairing osteoclastogenesis and promoting osteoblastogenesis. Mechanistically, in osteoclasts, Zmat1 loss relieves transcriptional repression of the E3 ligase TRIM46, promoting YAP1 degradation and inhibiting osteoclastogenic genes.
Xinyu Chang   +13 more
wiley   +1 more source

Haplotype‐Resolved 3D Genomic Landscapes and Their Impacts on Agronomic Traits in Grapevine

open access: yesAdvanced Science, EarlyView.
This study presents a haplotype‐resolved 3D genomic landscape of grapevine, revealing that structural variations (SVs) are closely associated with phased topologically associating domain (TAD) boundary transitions. These rearrangements coordinate with allele‐specific DNA methylation (ASM) and allele‐biased gene expression (ASE) to shape key agronomic ...
Yanling Peng   +18 more
wiley   +1 more source

Promoter Hypermethylation‐Induced Silencing of FXYD1 Drives Breast Cancer Metastasis via DDX5‐Mediated Wnt/β‐Catenin Pathway Activation

open access: yesAdvanced Science, EarlyView.
This study identifies FXYD1 as an epigenetically silenced tumor suppressor in breast cancer. DNA methylation turns off the gene FXYD1 in breast cancer, and low levels predict worse outcomes. Restoring FXYD1 limits breast cancer cells proliferation and metastasis. In the nucleus, FXYD1 recruits the E3 ligase MAEA to K63‐ubiquitinate DDX5 for proteasomal
Ping Wen   +11 more
wiley   +1 more source

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