Physical interaction and functional coupling between ACDP4 and the intracellular ion chaperone COX11, an implication of the role of ACDP4 in essential metal ion transport and homeostasis

Divalent metal ions such as copper, manganese, and cobalt are essential for cell development, differentiation, function and survival. These essential metal ions are delivered into intracellular domains as cofactors for enzymes involved in neuropeptide and neurotransmitter synthesis, superoxide metabolism, and other biological functions in a target specific fashion. Altering the homeostasis of these essential metal ions is known to connect to a number of human diseases including Alzheimer disease, amyotrophic lateral sclerosis, and pain. It remains unclear how these essential metal ions are delivered to intracellular targets in mammalian cells. Here we report that rat spinal cord dorsal horn neurons express ACDP4, a member of Ancient Conserved Domain Protein family. By screening a pretransformed human fetal brain cDNA library in a yeast two-hybrid system, we have identified that ACDP4 specifically interacts with COX11, an intracellular metal ion chaperone. Ectopic expression of ACDP4 in HEK293 cells resulted in enhanced toxicity to metal ions including copper, manganese, and cobalt. The metal ion toxicity became more pronounced when ACDP4 and COX11 were co-expressed ectopically in HEK293 cells, suggesting a functional coupling between them. Our results indicate a role of ACDP4 in metal ion homeostasis and toxicity. This is the first report revealing a functional aspect of this ancient conserved domain protein family. We propose that ACDP is a family of transporter protein or chaperone proteins for delivering essential metal ions in different mammalian tissues. The expression of ACDP4 on spinal cord dorsal horn neurons may have implications in sensory neuron functions under physiological and pathological conditions

Molecular cloning and characterization of the mouse Acdp gene family

BACKGROUND: We have recently cloned and characterized a novel gene family named ancient conserved domain protein (ACDP) in humans. To facilitate the functional study of this novel gene family, we have cloned and characterized Acdp, the mouse homologue of the human ACDP gene family. RESULTS: The four Acdp genes (Acdp1, Acdp2, Acdp3 and Acdp4) contain 3,631 bp, 3,244 bp, 2,684 bp and 2,743 bp of cDNA sequences, and encode deduced proteins of 951, 874, 713 and 771 amino acids, respectively. The mouse Acdp genes showed very strong homologies (>90%) in both nucleotide and amino acid sequences to their human counterparts. In addition, both nucleotide and amino acid sequences within the Ancient Conserved Domain (ACD) are highly conserved in many different taxonomic species. Particularly, Acdp proteins showed very strong AA homologies to the bacteria CorC protein (35% AA identity with 55% homology), which is involved in magnesium and cobalt efflux. The Acdp genes are widely expressed in all tissues tested except for Acdp1, which is only highly expressed in the brain with low levels of expression in kidney and testis. Immunostaining of Acdp1 in hippocampus neurons revealed a predominant localization on the plasma membrane. CONCLUSION: The Acdp genes are evolutionarily conserved in diverse species and ubiquitously expressed throughout development and adult tissues suggesting that Acdp may be an essential gene. Acdp showed strong homology to bacteria CorC protein and predominantly localized on the plasma membrane. These results suggest that Acdp is probably a family of proteins involved in ion transport in mammalian cell

Coordinated control strategy of reactive power compensation based on a flexible distribution network transformer

In order to solve the problem of the power quality caused by distributed power access to the distribution network, this paper proposes a coordinated control strategy of reactive power compensation based on a flexible distribution transformer. First, the working principle of the flexible distribution transformer is analyzed, and the mathematical model of energy acquisition and the regulation converter of the flexible distribution transformer are studied as well. The device-level control strategies of energy acquisition and regulation converters are proposed, respectively. Then, in order to maintain the stability of the bus voltage and quickly respond to the reactive power changes of the system, a coordinated control strategy for the reactive power compensation of flexible distribution transformers is proposed. The priority herein is to maximize the reactive power compensation capacity of the energy harvesting converter. When the energy harvesting converter reaches the compensation upper limit, the control converter is used for reactive power compensation to further suppress the grid voltage fluctuation. Finally, it is verified through simulations that the flexible distribution transformer can realize the reactive power compensation of the distribution network and effectively improve the power quality of the distribution network

Air-SAGD technology for super-heavy oil reservoirs

The air oxidation of super-heavy oil at low temperature was studied in laboratory and its influences on oil viscosity, component and steam sweep efficiency before and after air-injection were analyzed. The feasibility, operation mode and air flooding effect at the late stage of steam assisted gravity drainage (SAGD) were investigated by numerical simulation. The experimental results show for vertical-horizontal well pair SAGD test area of Xing VI Formation in Block Du 84 of Liaohe Oilfield, the low temperature oxidation occurred between 150–250 °C (steam chamber temperature), the oil viscosity increased greatly after low temperature oxidation, consequently, the oil displacement efficiency dropped sharply. Three development methods in the late stage of SAGD were simulated, i.e., steam + air low temperature oxidation, only air low temperature oxidation and only air high temperature oxidation. By comparing production dynamic curves and residual oil distribution etc., high temperature oxidation reduced the heat loss in late stage of SAGD, recovered the residual oil effectively, and prolonged reservoir development time. Key words: super heavy oil, SAGD, air injection, low temperature oxidation, high temperature oxidatio

A new technology of 3D scaled physical simulation for high-pressure and high-temperature steam injection recovery

In order to solve the problems of existing physical simulation experiment device for thermal recovery, such as great heat loss, low precision in internal pressure control of physical model and insufficient process monitoring, a new experiment device for high-pressure and high-temperature (HPHT) 3D scaled physical simulation is developed independently, and the relevant experiment technical route is presented. By using thermal fluid simulation, PID auto-control and 3D graphics, the following problems are solved: (1) the heat loss scaled simulation technology is applied for HPHT thermal recovery model, to control the heat dissipating capacity of the model top and bottom and realize the continuous growth of the steam chamber; (2) HPHT 3D formation temperature/pressure simulation technology is applied to keep the model pressure and temperature stable, ensuring temperature difference at each point in high-pressure chamber less than ± 2 °C; (3) 3D data field on-line monitoring and visual analysis technology is applied to monitor and control the reservoir performance at real time. By using this experiment device, 3D scaled physical simulation experiment is performed for commingled thermal recovery of extremely heavy oil by horizontal/vertical wells as well as SAGD of super heavy oil by dual horizontal wells. The evolution of steam chamber is depicted and the knowledge on SAGD mechanism by dual horizontal wells and the production performance is deeply studied. 摘要: 为了解决现有热采物理模拟装置模型热损失大、模型内压控制精度低、实验过程监控不足等问题 自主研制成功了新型高温高压三维比例物理模拟实验装置并提出了注蒸汽采油高温高压三维比例物理模拟实验技术路线。该装置采用热流数值模拟、PID自动控制及三维数据场平面设计方法 重点解决了以下难题并形成特色技术°采用高温高压热采模型热损失比例模化技术 比例控制模型顶底散热量 实现汽腔持续发育 °采用高温高压三维地层温/压模拟技术 实现模型压力均匀稳定控制 高压舱内各点温差小于±2 ࠓ °采用模型三维数据场在线监测与可视化分析技术 实时监测与调控油藏动态。利用该实验装置开展了特稠油水平井与直井组合热采及超稠油双水平井SAGD 蒸汽辅助重力泄油三维比例物理模拟实验研究 完整刻画了汽腔发育规律 深化了对双水平井SAGD开采机理和生产动态规律的认识。图5参13 关键词注蒸汽采油 比例物理模拟 三维模型 高温高压 蒸汽辅助重力泄油-图分类号TE345 文献标识码A Key words: steam injection recovery, scaled physical simulation, 3D physical model, high-pressure and high-temperature, steam assisted gravity drainage (SAGD

Prostasin:A possible candidate gene for human hypertension

BACKGROUND Prostasin, a serine protease, is suggested to be a novel mechanism regulating the epithelial sodium channel (ENaC) expressed in the distal nephron. This study aimed to evaluate whether the human prostasin gene is a novel candidate gene underlying blood pressure (BP) elevation. METHODS In a sample of healthy African-American (AA) and European-American (EA) twin subjects aged 17.6 +/- 3.3 years (n = 920,45% AAs), race-specific tagging single-nucleotide polymorphisms (tSNPs) were identified to tag all the available SNPs +/- 2 kb up- and downstream of the prostasin gene from HapMap at r(2) of 0.8-1.0. Selection yielded four tSNPs in AAs and one in EAs, with one tSNP (rs12597511:C to T) present in both AAs and EAs. RESULTS For 12597511, CT and TT genotypes exhibited higher systolic BP (SBP) than CC genotype (115.9 +/- 1.1 mm Hg vs. 113.7 +/- 0.6 mm Hg, P = 0.025 (AAs); and 110.7 +/- 0.5 mm Hg vs. 109.6 +/- 0.6 mm Hg, P = 0.115 (EAs)). CT and TT genotypes compared with CC genotype showed a significant increase in diastolic BP (DBP) in both racial groups (62.5 +/- 0.7 mm Hg vs. 60.4 +/- 0.4 mm Hg, P = 0.003 (AAs); and 58.2 +/- 0.3 mm Hg vs. 56.7 +/- 0.4 mm Hg, P = 0.007 (EAs)). Furthermore, there was an increase in radial pulse wave velocity (PWV) in subjects with CT and TT genotype as compared with those with CC genotype (6.5 +/- 0.1 vs. 6.1 +/- 0.1 m/s, P <0.0001) (EAs); and 6.7 +/- 0.1 vs. 6.6 +/- 0.1 m/s P = 0.354 (AAs)). Analyses combining AAs and EAs consistently demonstrated a statistical significance of rs12597511 on all the phenotypes including SBP/DBP and PWV. CONCLUSION Genetic variation of the prostasin gene may be implicated in the development of hypertension in youths

Proteomic analysis of SUMO4 substrates in HEK293 cells under serum starvation-induced stress.

The substrates of SUMO4, a novel member for the SUMO gene family, were characterized in HEK293 cells cultured under serum starvation by proteomic analysis. We identified 90 SUMO4 substrates including anti-stress proteins such as antioxidant enzymes and molecular chaperones or co-chaperones. The substrates also include proteins involved in the regulation of DNA repair and synthesis, RNA processing, protein degradation, and glucose metabolism. Several SUMO4-associated transcription factors were characterized by Western blot analyses. AP-1 was selected for in vitro conjugation assays to confirm SUMO4 sumoylation of these transcription factors. Further functional analyses of the transcription factors suggested that SUMO4 sumoylation represses AP-1 and AP-2alpha transcriptional activity, but enhances GR DNA binding capacity. These results demonstrate that SUMO4 sumoylation may play an important role in the regulation of intracellular stress.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe