SUMMARY IDH1 and IDH2 mutations occur frequently in gliomas and acute myeloid leukemia, leading to simultaneous loss and gain of activities in the production of α-ketoglutarate (α-KG) and 2-hydroxyglutarate (2-HG), respectively. Here we demonstrate that 2-HG is a competitive inhibitor of multiple α-KG-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (5mC) hydroxylases. 2-HG occupies the same space as α-KG does in the active site of histone demethylases. Ectopic expression of tumor-derived IDH1 and IDH2 mutants inhibits histone demethylation and 5mC hydroxylation. In glioma, IDH1 mutations are associated with increased histone methylation and decreased 5-hydroxylmethylcytosine (5hmC). Hence, tumor-derived IDH1 and IDH2 mutations reduce α-KG and accumulate an α-KG antagonist, 2-HG, leading to genome-wide histone and DNA methylation alterations.

Hypoxia-inducible factor 1 (HIF-1) plays a central role in cellular adaptation to changes in oxygen availability. Recently, prolyl hydroxylation was identified as a key regulatory event that targets the HIF-1alpha subunit for proteasomal degradation via the pVHL ubiquitination complex. In this report, we reveal an important function for ARD1 in mammalian cells as a protein acetyltransferase by direct binding to HIF-1alpha to regulate its stability. We present further evidence showing that ARD1-mediated acetylation enhances interaction of HIF-1alpha with pVHL and HIF-1alpha ubiquitination, suggesting that the acetylation of HIF-1alpha by ARD1 is critical to proteasomal degradation. Therefore, we have concluded that the role of ARD1 in the acetylation of HIF-1alpha provides a key regulatory mechanism underlying HIF-1alpha stability.

is due to increased vagal output to the heart (40). However, breathing measurements were not made during spontaneous or heat-induced seizures in either of these DS mouse models, so it is unclear whether abnormal breathing contributes to SUDEP. Here we studied patients with DS and mice with an Scn1a R1407X/+ mutation (39) to evaluate a potential role of postictal breathing dysfunction in SUDEP.

A new class of highly thin, deformable, and safety‐reinforced plastic crystal polymer electrolytes (N‐PCPEs) is demonstrated as an innovative solid electrolyte for potential use in high‐performance flexible lithium‐ion batteries with aesthetic versatility and robust safety. The unusual N‐PCPEs are fabricated by combining a plastic crystal polymer electrolyte with a porous polyethylene terephthalate (PET) nonwoven. Herein, the three‐dimensional reticulated plastic crystal polymer electrolyte matrix is formed directly inside the PET nonwoven skeleton via in‐situ UV‐crosslinking of ethoxylated trimethylolpropane triacrylate (ETPTA) monomer, under co‐presence of plastic crystal electrolyte. The PET nonwoven is incorporated as a compliant skeleton to enhance mechanical/dimensional strength of N‐PCPE. Owing to this structural uniqueness, the N‐PCPE shows significant improvements in the film thickness and deformability with maintaining advantageous features (such as high ionic conductivity and thermal stability) of the PCE. Based on structural/physicochemical characterization of N‐PCPE, its potential application as a solid electrolyte for flexible lithium‐ion batteries is explored by scrutinizing the electrochemical performance of cells. The high ionic conductance of N‐PCPE, along with its excellent deformability, plays a viable role in improving cell performance (particularly at high current densities and also mechanically deformed states). Notably, the cell assembled with N‐PCPE exhibits stable electrochemical performance even under a severely wrinkled state, without suffering from internal short‐circuit failures between electrodes.

Forthcoming flexible/wearable electronic devices with shape diversity and mobile usability garner a great deal of attention as an innovative technology to bring unprecedented changes in our daily lives. From the power source point of view, conventional rechargeable batteries (one representative example is a lithium-ion battery) with fixed shapes and sizes have intrinsic limitations in fulfilling design/performance requirements for the flexible/wearable electronics. Here, as a facile and efficient strategy to address this formidable challenge, we demonstrate a new class of printable solid-state batteries (referred to as "PRISS batteries"). Through simple stencil printing process (followed by ultraviolet (UV) cross-linking), solid-state composite electrolyte (SCE) layer and SCE matrix-embedded electrodes are consecutively printed on arbitrary objects of complex geometries, eventually leading to fully integrated, multilayer-structured PRISS batteries with various form factors far beyond those achievable by conventional battery technologies. Tuning rheological properties of SCE paste and electrode slurry toward thixotropic fluid characteristics, along with well-tailored core elements including UV-cured triacrylate polymer and high boiling point electrolyte, is a key-enabling technology for the realization of PRISS batteries. This process/material uniqueness allows us to remove extra processing steps (related to solvent drying and liquid-electrolyte injection) and also conventional microporous separator membranes, thereupon enabling the seamless integration of shape-conformable PRISS batteries (including letters-shaped ones) into complex-shaped objects. Electrochemical behavior of PRISS batteries is elucidated via an in-depth analysis of cell impedance, which provides a theoretical basis to enable sustainable improvement of cell performance. We envision that PRISS batteries hold great promise as a reliable and scalable platform technology to open a new concept of cell architecture and fabrication route toward flexible power sources with exceptional shape conformability and aesthetic versatility.