Alterations in cellular ubiquitin (Ub) homeostasis, known as Ub stress, feature and affect cellular responses in multiple conditions, yet the underlying mechanisms are incompletely understood. Here we report that autophagy receptor p62/sequestosome-1 interacts with E2 Ub conjugating enzymes, UBE2D2 and UBE2D3. Endogenous p62 undergoes E2-dependent ubiquitylation during upregulation of Ub homeostasis, a condition termed as Ub stress, that is intrinsic to Ub overexpression, heat shock or prolonged proteasomal inhibition by bortezomib, a chemotherapeutic drug. Ubiquitylation of p62 disrupts dimerization of the UBA domain of p62, liberating its ability to recognize polyubiquitylated cargoes for selective autophagy. We further demonstrate that this mechanism might be critical for autophagy activation upon Ub stress conditions. Delineation of the mechanism and regulatory roles of p62 in sensing Ub stress and controlling selective autophagy could help to understand and modulate cellular responses to a variety of endogenous and environmental challenges, potentially opening a new avenue for the development of therapeutic strategies against autophagy-related maladies.
Study results suggest the value of incorporating community HCWs' recommendation for seasonal influenza vaccination into existing primary public health programs to increase vaccination coverage among high risk groups in China.
We report an effective method for the synthesis of a core-shell Si/C nanocomposite, and its application as anode material for lithium ion (Li-ion) batteries. Polyacrylonitrile (PAN)-coated Si nanoparticles are formed by emulsion polymerization, and this precursor is heat-treated under argon to generate a Si/C core-shell nanocomposite. The conductive carbon shell envelops the silicon nanoparticles and suppresses aggregation of the nanoparticles during cycling. Meanwhile, the carbon shell combines closely with the nanocores, and significantly enhances the kinetics of lithium intercalation and de-intercalation, as well as the apparent diffusion coefficient of Li-ions. Consequently, the core-shell Si/C nanocomposite exhibits better electrochemical performance than pure Si nanoparticles, indicating that this is a promising approach to improve cyclability and kinetics of nano-anode materials for Li-ion batteries.
Influenza, caused by the influenza virus, is a respiratory infectious disease that can severely affect human health. Influenza viruses undergo frequent antigenic changes, thus could spread quickly. Influenza causes seasonal epidemics and outbreaks in public gatherings such as schools, kindergartens, and nursing homes. Certain populations are at risk for severe illness from influenza, including pregnant women, young children, the elderly, and people in any ages with certain chronic diseases.
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