Exploring the Complexity of Protein-Level Dosage Compensation that Fine-Tunes Stoichiometry of Multiprotein Complexes

Proper control of gene expression levels upon various perturbations is a fundamental aspect of cellular robustness. Protein-level dosage compensation is one mechanism buffering perturbations to stoichiometry of multiprotein complexes through accelerated proteolysis of unassembled subunits. Although N-terminal acetylation- and ubiquitin-mediated proteasomal degradation by the Ac/N-end rule pathway enables selective compensation of excess subunits, it is unclear how widespread this pathway contributes to stoichiometry control. Here we report that dosage compensation depends only partially on the Ac/N-end rule pathway. Our analysis of genetic interactions between 18 subunits and 12 quality control factors in budding yeast demonstrated that multiple E3 ubiquitin ligases and N-acetyltransferases are involved in dosage compensation. We find that N-acetyltransferases-mediated compensation is not simply predictable from N-terminal sequence despite their sequence specificity for N-acetylation. We also find that the compensation of Pop3 and Bet4 is due in large part to a minor N-acetyltransferase NatD. Furthermore, canonical NatD substrates histone H2A/H4 were compensated even in its absence, suggesting N-acetylation-independent stoichiometry control. Our study reveals the complexity and robustness of the stoichiometry control system. Author summary Quality control of multiprotein complexes is important for maintaining homeostasis in cellular systems that are based on functional complexes. Proper stoichiometry of multiprotein complexes is achieved by the balance between protein synthesis and degradation. Recent studies showed that translation efficiency tends to scale with stoichiometry of their subunits. On the other hand, although protein N-terminal acetylation- and ubiquitin-mediated proteolysis pathway is involved in selective degradation of excess subunits, it is unclear how widespread this pathway contributes to stoichiometry control due to the lack of a systematic investigation using endogenous proteins. To better understand the landscape of the stoichiometry control system, we examined genetic interactions between 18 subunits and 12 quality control factors (E3 ubiquitin ligases and N-acetyltransferases), in total 114 combinations. Our data suggest that N-acetyltransferases are partially responsible for stoichiometry control and that N-acetylation-independent pathway is also involved in selective degradation of excess subunits. Therefore, this study reveals the complexity and robustness of the stoichiometry control system. Further dissection of this complexity will help to understand the mechanisms buffering gene expression perturbations and shaping proteome stoichiometry

Global Zero Emission Scenario: Role of Innovative Technologies

AbstractThis study investigated a zero emission scenario with following two originalities compared to various existing studies. One is that we based on A1T society of SRES (Special Report on Emissions Scenario) of IPCC (Intergovernmental Panel on Climate Change) compared to existing studies on those of B1 or B2. The second one is that various innovative and radical technologies were considered and incorporated, such as biomass energy with CCS (BECCS), and advanced nuclear technologies including hydrogen or synfuel production. We applied a global modeling, whose energies, materials, and biomass and foods supply costs were minimized by linear programing with time horizon up to 2150. We found following features of energy supply structure in A1T scenario. Since the electric demand in A1T scenario in 2100 is two times larger than the others, 1) renewable energy which solely produce electricity, nuclear, and fossil energy with CCS (FECCS) especially coal are main sources of electricity, 2) renewable which can supply heat, namely BECCS and geothermal, satisfies the sector, and 3) hydrogen from coal is introduced in transport sector. It can be concluded that the zero emission energy systems with global economic growth will be possible, by development and deployment of ambitious advanced energy technologies

Local Lunar Gravity Field Analysis over the South Pole-aitken Basin from SELENE Farside Tracking Data

We present a method with which we determined the local lunar gravity field model over the South Pole-Aitken (SPA) basin on the farside of the Moon by estimating adjustments to a global lunar gravity field model using SELENE tracking data. Our adjustments are expressed in localized functions concentrated over the SPA region in a spherical cap with a radius of 45deg centered at (191.1 deg E, 53.2 deg S), and the resolution is equivalent to a 150th degree and order spherical harmonics expansion. The new solution over SPA was used in several applications of geophysical analysis. It shows an increased correlation with high-resolution lunar topography in the frequency band l = 40-70, and admittance values are slightly different and more leveled when compared to other, global gravity field models using the same data. The adjustments expressed in free-air anomalies and differences in Bouguer anomalies between the local solution and the a priori global solution correlate with topographic surface features. The Moho structure beneath the SPA basin is slightly modified in our solution, most notably at the southern rim of the Apollo basin and around the Zeeman crate

Ectopic Calcification as Discernible Manifestation in Neonates with Pseudohypoparathyroidism Type 1a

The diagnosis of pseudohypoparathyroidism type 1a (PHP1a) is challenging, because both the osteodystrophy, such as brachydactyly and round face, and the symptomatic hypocalcemia usually develop beyond infancy. Although ectopic calcification may be an early sign of PHP1a, there are no systematic reviews regarding the time of its appearance. We here report on two PHP1a patients who presented with subcutaneous calcification in neonatal period

Diminished Gastric Resection Preserves Better Quality of Life in Patients with Early Gastric Cancer

Using the Postgastrectomy Syndrome Assessment Scale (PGSAS)-45, we compared the surgical outcomes and the quality of life (QOL) between patients undergoing limited gastrectomies and those undergoing conventional gastrectomies. In Oomoto Hospital between January 2004 and December 2013, a total of 124 patients who met the eligibility criteria were enrolled. Using the main outcome measures of PGSAS-45, we compared 4 types of limited gastrectomy procedures (1/2 distal gastrectomy [1/2DG] in 21 patients; pylorus-preserving gastrectomy [PPG] in 15 patients; segmental gastrectomy [SG] in 26 patients; and local resection [LR] in 13 patients) with conventional gastrectomy (total gastrectomy [TG] in 24 patients and 2/3 or more distal gastrectomy [WDG] in 25 patients). The TG group showed the worst QOL in almost all items of the main outcome measures. The 1/2DG, PPG, and SG groups showed better QOL than the WDG group in many of the main outcome measures, including the body weight ratio, total symptom score, ingested amount of food per meal, and the dissatisfaction for daily life subscale. The LR group showed a better intake of food than the 1/2DG, PPG, and SG groups. The body weight ratio of the LR group was better than that of the SG group. Diminished gastric resection preserved better QOL in patients with early gastric cancer