Huntington disease oligodendrocyte maturation deficits revealed by single-nucleus RNAseq are rescued by thiamine-biotin supplementation.

The complexity of affected brain regions and cell types is a challenge for Huntington's disease (HD) treatment. Here we use single nucleus RNA sequencing to investigate molecular pathology in the cortex and striatum from R6/2 mice and human HD post-mortem tissue. We identify cell type-specific and -agnostic signatures suggesting oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs) are arrested in intermediate maturation states. OL-lineage regulators OLIG1 and OLIG2 are negatively correlated with CAG length in human OPCs, and ATACseq analysis of HD mouse NeuN-negative cells shows decreased accessibility regulated by OL maturation genes. The data implicates glucose and lipid metabolism in abnormal cell maturation and identify PRKCE and Thiamine Pyrophosphokinase 1 (TPK1) as central genes. Thiamine/biotin treatment of R6/1 HD mice to compensate for TPK1 dysregulation restores OL maturation and rescues neuronal pathology. Our insights into HD OL pathology spans multiple brain regions and link OL maturation deficits to abnormal thiamine metabolism.

Ultraflexible Transparent Film Heater Made of Ag Nanowire/PVA Composite for Rapid-Response Thermotherapy Pads.

Ultraflexible transparent film heaters have been fabricated by embedding conductive silver (Ag) nanowires into a thin poly(vinyl alcohol) film (AgNW/PVA). A cold-pressing method was used to rationally adjust the sheet resistance of the composite films and thus the heating powers of the AgNW/PVA film heaters at certain biases. The film heaters have a favorable optical transmittance (93.1% at 26 Ω/sq) and an outstanding mechanical flexibility (no visible change in sheet resistance after 10 000 bending cycles and at a radius of curvature ≤1 mm). The film heaters have an environmental endurance, and there is no significant performance degradation after being kept at high temperature (80 °C) and high humidity (45 °C, 80% humidity) for half a year. The efficient Joule heating can increase the temperature of the film heaters (20 Ω/sq) to 74 °C in ∼20 s at a bias of 5 V. The fast-heating characteristics at low voltages (a few volts) associated with its transparent and flexibility properties make the poly(dimethylsiloxane)/AgNW/PVA composite film a potential candidate in medical thermotherapy pads.

Decreased Coenzyme Q10 Levels in Multiple System Atrophy Cerebellum.

In familial and sporadic multiple system atrophy (MSA) patients, deficiency of coenzyme Q10 (CoQ10) has been associated with mutations in COQ2, which encodes the second enzyme in the CoQ10 biosynthetic pathway. Cerebellar ataxia is the most common presentation of CoQ10 deficiency, suggesting that the cerebellum might be selectively vulnerable to low levels of CoQ10 To investigate whether CoQ10 deficiency represents a common feature in the brains of MSA patients independent of the presence of COQ2 mutations, we studied CoQ10 levels in postmortem brains of 12 MSA, 9 Parkinson disease (PD), 9 essential tremor (ET) patients, and 12 controls. We also assessed mitochondrial respiratory chain enzyme activities, oxidative stress, mitochondrial mass, and levels of enzymes involved in CoQ biosynthesis. Our studies revealed CoQ10 deficiency in MSA cerebellum, which was associated with impaired CoQ biosynthesis and increased oxidative stress in the absence of COQ2 mutations. The levels of CoQ10 in the cerebella of ET and PD patients were comparable or higher than in controls. These findings suggest that CoQ10 deficiency may contribute to the pathogenesis of MSA. Because no disease modifying therapies are currently available, increasing CoQ10 levels by supplementation or upregulation of its biosynthesis may represent a novel treatment strategy for MSA patients.