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Pre-exposure antibody prophylaxis protects macaques from severe influenza

5 months ago
Science, Volume 387, Issue 6733, Page 534-541, January 2025.
Masaru Kanekiyo, Rebecca A. Gillespie, Kristine Cooper, Vanessa Guerra Canedo, Priscila M. S. Castanha, Amarendra Pegu, Eun Sung Yang, Luke Treaster, Gabin Yun, Megan Wallace, Gwenddolen Kettenburg, Connor Williams, Jeneveve Lundy, Stacey Barrick,…

Ancient genomics and the origin, dispersal, and development of domestic sheep

5 months ago
Science, Volume 387, Issue 6733, Page 492-497, January 2025.
Kevin G. Daly, Victoria E. Mullin, Andrew J. Hare, Áine Halpin, Valeria Mattiangeli, Matthew D. Teasdale, Conor Rossi, Sheila Geiger, Stefan Krebs, Ivica Medugorac, Edson Sandoval-Castellanos, Mihriban Özbaşaran, Güneş Duru, Sevil Gülcür, Nadja Pöllath,…

Increased plasma DOPA decarboxylase levels in Lewy body disorders are driven by dopaminergic treatment

5 months ago
DOPA Decarboxylase (DDC) has been proposed as a cerebrospinal fluid (CSF) biomarker with increased concentrations in Lewy body disorders (LBDs) and highest levels in patients receiving dopaminergic treatment. Here we evaluate plasma DDC, measured by proximity extension assay, and the effect of dopaminergic treatment in three independent LBD (with a focus on dementia with Lewy bodies (DLB) and Parkinson's disease (PD)) cohorts: an autopsy-confirmed cohort (n = 71), a large multicenter,...
Katharina Bolsewig

Oligodendrocytes in Alzheimer's disease pathophysiology

5 months ago
Our understanding of Alzheimer's disease (AD) has transformed from a purely neuronal perspective to one that acknowledges the involvement of glial cells. Despite remarkable progress in unraveling the biology of microglia, astrocytes and vascular elements, the exploration of oligodendrocytes in AD is still in its early stages. Contrary to the traditional notion of oligodendrocytes as passive bystanders in AD pathology, emerging evidence indicates their active participation in and reaction to...
Shreeya Kedia

The ubiquitin-conjugating enzyme UBE2D maintains a youthful proteome and ensures protein quality control during aging by sustaining proteasome activity

5 months ago
Ubiquitin-conjugating enzymes (E2s) are key for protein turnover and quality control via ubiquitination. Some E2s also physically interact with the proteasome, but it remains undetermined which E2s maintain proteostasis during aging. Here, we find that E2s have diverse roles in handling a model aggregation-prone protein (huntingtin-polyQ) in the Drosophila retina: while some E2s mediate aggregate assembly, UBE2D/effete (eff) and other E2s are required for huntingtin-polyQ degradation. UBE2D/eff...
Liam C Hunt

Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior T cells for cancer immunotherapy

5 months ago
Cellular therapies are living drugs whose efficacy depends on persistence and survival. Expansion of therapeutic T cells employs hypermetabolic culture conditions to promote T cell expansion. We show that typical in vitro expansion conditions generate metabolically and functionally impaired T cells more reliant on aerobic glycolysis than those expanding in vivo. We used dichloroacetate (DCA) to modulate glycolytic metabolism during expansion, resulting in elevated mitochondrial capacity,...
Andrew T Frisch

Convergence of orphan quality control pathways at a ubiquitin chain-elongating ligase

5 months ago
Unassembled and partially assembled subunits of multi-protein complexes have emerged as major quality control clients, particularly under conditions of imbalanced gene expression such as stress, aging, and aneuploidy. The factors and mechanisms that eliminate such orphan subunits to maintain protein homeostasis are incompletely defined. Here, we show that the UBR4-KCMF1 ubiquitin ligase complex is required for the efficient degradation of multiple unrelated orphan subunits from the chaperonin,...
Sara Carrillo Roas