ShorterLab
@ShorterLab
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Countering deleterious phase transitions in ALS/FTD, PD, AD, and related disorders @Penn @PennMedicine @bb_upenn @BMBGGUPENN @PGGUPenn @PennNGG @CAMBUpenn
University of Pennsylvania
Joined January 2012
FUS Mislocalization Rewires a Cortical Gene Network to Drive Cognitive and Behavioral Impairment in ALS:
medrxiv.org
Cognitive and behavioral impairment affects up to half of individuals with amyotrophic lateral sclerosis (ALS), but their molecular origin remains unresolved. Here, we identify mislocalization of the...
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M102, a combined NRF2 and HSF-1 activator for neuroprotection in amyotrophic lateral sclerosis
biorxiv.org
M102 is a central nervous system (CNS) penetrant small molecule electrophile which activates in vivo the NFE2-related factor 2 antioxidant response element (NRF2-ARE) pathway, as well as transcript...
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tRNA as an assembly chaperone for a macromolecular transcription-processing complex:
nature.com
Nature Structural & Molecular Biology - Here, the authors solve a series of cryo-electron microscopy structures that show how transfer RNAs (tRNAs) can guide the assembly of the multisubunit...
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The aging factor EPS8 induces disease-related protein aggregation through RAC signaling hyperactivation:
nature.com
Nature Aging - Aging is a risk factor for neurodegenerative diseases associated with protein aggregation. Here the authors identify age-related hyperactivation of EPS8/RAC signaling in C. elegans...
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Reversible compromise of physiological resilience by accumulation of heteroplasmic mtDNA mutations | Science
science.org
Somatically acquired mitochondrial DNA mutations accumulate with age, but the mechanisms and consequences are poorly understood. Here we show that transient injuries induce a burst of persistent...
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Lewy body dementia promotion by air pollutants | Science
science.org
Evidence links air pollution to dementia, yet its role in Lewy body dementia (LBD) remains unclear. In this work, we showed in a cohort of 56.5 million individuals across the United States that fine...
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For “U” the bell tolls: Pseudouridine evades TLR detection: Molecular Cell
cell.com
TLRs detect pathogen-derived uridine but not endogenous pseudouridine, which promotes host defense without autoimmunity. This principle is critical for the safe design of mRNA-based therapeutics, but...
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Pseudouridine RNA avoids immune detection through impaired endolysosomal processing and TLR engagement: Cell
cell.com
Toll-like receptors (TLRs) 7 and 8 detect RNA degradation products to sense infection. However, modified nucleosides common in self-RNA—most notably pseudouridine—evade recognition. This study finds...
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Rethinking RNA-binding proteins: Riboregulation challenges prevailing views: Cell
cell.com
The advent of system-wide proteomic approaches has largely expanded the number of RNA-binding proteins (RBPs). This review discusses how recent discoveries are transforming our understanding of...
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