TORC1 regulates autophagy induction in response to proteotoxic stress in yeast and human cells

Misfolded and aggregated proteins are eliminated to maintain protein homeostasis. Autophagy contributes to the removal of protein aggregates. However, if and how proteotoxic stress induces autophagy is poorly understood. Here we show that proteotoxic stress after treatment with azetidine-2-carboxylic acid (AZC), a toxic proline analog, induces autophagy in budding yeast. AZC treatment attenuated target of rapamycin complex 1 (TORC1) activity, resulting in the dephosphorylation of Atg13, a key factor of autophagy. By contrast, AZC treatment did not affect target of rapamycin complex 2 (TORC2). Proteotoxic stress also induced TORC1 inactivation and autophagy in fission yeast and human cells. This study suggested that TORC1 is a conserved key factor to cope with proteotoxic stress in eukaryotic cells

Low fat intake is associated with pathological manifestations and poor recovery in patients with hepatocellular carcinoma

BACKGROUND: This study aimed to clarify whether dietary deviation is associated with pathological manifestations in hepatocellular carcinoma (HCC) patients. METHODS: Dietary intake was estimated in 35 HCC cases before and after hospitalization by referencing digital camera images of each meal. Pathological conditions were evaluated in nitrogen balance, non-protein respiratory quotient (npRQ), neuropsychiatric testing and recovery speed from HCC treatment. RESULTS: On admission, nitrogen balance and npRQ were negative and less than 0.85, respectively. Five patients were judged to have suffered from minimal hepatic encephalopathy that tended to be associated with a lowered value of npRQ (p = 0.082). The energy from fat intake showed a tendency of positive correlation with npRQ (p = 0.11), and the patients with minimal hepatic encephalopathy took significantly fewer energy from fat (p = 0.024). The energy difference from fat between diets at home versus those in the hospital showed a significant positive correlation with npRQ change after admission (p = 0.014). The recovery speed from invasive treatments for HCC showed a significant negative correlation with npRQ alteration after admission (p = 0.0002, r = −0.73). CONCLUSIONS: These results suggest the lower fat intake leads to deterioration of energy state in HCC patients, which associates with poor recovery from invasive treatments and various pathological manifestations

Mg-implanted vertical GaN junction barrier Schottky rectifiers with low on resistance, low turn-on voltage, and nearly ideal nondestructive breakdown voltage

Vertical GaN junction barrier Schottky (JBS) diodes with superior electrical characteristics and nondestructive breakdown were realized using selective-area p-type doping via Mg ion implantation and subsequent ultra-high-pressure annealing. Mg-ion implantation was performed into a 10 μm thick Si-doped GaN drift layer grown on a free-standing n-type GaN substrate. We fabricated the JBS diodes with different n-type GaN channel widths Ln = 1 and 1.5 μm. The JBS diodes, depending on Ln, exhibited on-resistance (RON) between 0.57 and 0.67 mΩ cm2, which is a record low value for vertical GaN Schottky barrier diodes (SBDs) and high breakdown (BV) between 660 and 675 V (84.4% of the ideal parallel plane BV). The obtained low RON of JBS diodes can be well explained in terms of the RON model, which includes n-type GaN channel resistance, spreading current effect, and substrate resistance. The reverse leakage current in JBS diodes was relatively low 103–104 times lower than in GaN SBDs. In addition, the JBS diode with lower Ln exhibited the leakage current significantly smaller (up to reverse bias 300 V) than in the JBS diode with large Ln, which was explained in terms of the reduced electric field near the Schottky interface. Furthermore, the JBS diodes showed a very high current density of 5.5 kA/cm2, a low turn-on voltage of 0.74 V, and no destruction against the rapid increase in the reverse current approximately by two orders of magnitude. This work demonstrated that GaN JBS diodes can be strong candidates for low loss power switching applications