ACE2, the Receptor that Enables Infection by SARS-CoV-2: Biochemistry,Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.     

Angiotensin I‐converting enzyme inhibitory and Ca‐binding activities of peptides prepared from tuna cooking juice and spleen proteases

Tuna cooking juice is a by‐product from the tuna canning industry. In this study, tuna cooking juice was hydrolysed by proteases extracted from the spleen. Tuna cooking juice showed the highest ACE inhibitory and Ca‐binding activities after hydrolysis for 270 and 180 min, respectively. The hydrolysate was further fractionated by ultrafiltration. The permeate exhibited highest ACE inhibitory and Ca‐binding activities when passed through 1 and 5 kDa cut‐off membranes, respectively. Gel filtration chromatography was used to determine the MW of bioactive peptides that exhibited highest ACE inhibitory and Ca‐binding activities. Those peptides that exhibited highest ACE inhibitory and Ca‐binding activities were the MW range of 238–829 Da and 1355–1880 Da, respectively. These results suggest that the tuna cooking juice and the spleen protease extract are a potential source of bioactive peptides that can be utilised as bioactive ingredients in functional food and nutraceuticals.     

低差错平底特性的非规则LDPC码的设计

介绍了非规则LDPC码的发展并给出了其优势及缺点，重点论述用ACE算法来构造非规则LDPC码从而降低其差错平底特性。对降低非规则LDPC码的差错平底特性的其它方法提出了展望。     

Separation of di- and tripeptides with solvent extraction and an emulsion liquid membrane

The extraction equilibria of various di- and tripeptides with di-2-ethylhexylphosphoric acid (D2EHPA) were studied at low pH values. The complex extracted to organic phase consisted of one molecule of peptide and two molecules of D2EHPA dimer. The extraction constants of the peptides correlated well with the distribution coefficients of peptides between 1-octanol and water, which is a measure of hydrophobicity. The permeation rates of peptides through an emulsion liquid membrane were examined by using D2EHPA as a carrier, Span 80 as an emulsifier and kerosene as a diluent. The rates varied considerably with peptide type, depending upon the hydrophobicity.     

Working memory in mild Alzheimer's disease and early Parkinson's disease.

Alzheimer's disease (AD) and Parkinson's disease (PD) impair working memory (WM). It is unclear, however, whether the deficits seen early in the course of these diseases are similar. To address this issue, the authors compared the performance of 22 patients with mild AD, 20 patients with early PD and without dementia, and 112 control participants on tests of inhibition, short-term memory, and 2 commonly administered tests of WM. The results suggest that although mild AD and early PD both impair WM, the deficits may be related to the interruption of different processes that contribute to WM performance. Early PD disrupted inhibitory processes, whereas mild AD did not. The WM deficits seen in patients with AD may be secondary to deficits in other cognitive capacities, including semantic memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contributions of source and inhibitory mechanisms to age-related retroactive interference in verbal working memory.

Determining contributions of source-monitoring and inhibitory function to age-related forgetting has been an elusive goal for cognitive theorists. Five studies used a verbal working memory paradigm to examine mechanisms accounting for disproportionate retroactive interference (RI) experienced with adult aging. Participants distinguished studied target-word pairs from interfering pairs that were read aloud. Source-monitoring and inhibitory task components varied through manipulations of response requirements. RI effects were primarily due to source-monitoring failures rather than to inhibitory failures. Removing both source and inhibitory components eliminated age differences in RI. When source monitoring was emphasized, RI continued to be observed in all age groups but disproportionately for older adults. Process dissociation analyses of memory found recollection decreases and familiarity increases consistent with source failures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prebiotic synthesis of sequential peptides on the Hadean beach by a molecular engine working with nitrogen oxides as energy sources

Addressing the still open question of the prebiotic origin of sequential macromolecules (peptides, nucleic acids) on the primitive Earth, we describe a molecular engine (the primary pump), which works at ambient temperature and continuously generates, elongates and complexifies sequential peptides. This new scenario is based on a cyclic reaction sequence, whose keystep is the activation of amino acids into their N‐carboxyanhydrides (NCA) through nitrosation by NOx. This process could have taken place on tidal beaches; it requires a buffered ocean, emerged land and a nitrosating atmosphere. With the help of geochemical studies and computer simulations of atmosphere photochemistry, we show that the primitive Earth during the Hadean may have satisfied all these requirements. © 2001 Society of Chemical Industry.     

Fractionation and characterisation for antioxidant activity of hydrolysed whey protein

Whey protein isolate (WPI) was hydrolysed for 1 h using Alcalase, Protamex and Flavourzyme. Native WPI, hydrolysed WPI and two commercial WPI hydrolysates were subjected to fractionation by size exclusion chromatography. Antioxidant activity of WPI fractions was measured with a liposome‐oxidising system (50 µM FeCl₃/0.1 µM ascorbate, pH 7.0). Lipid oxidation was measured as thiobarbituric acid‐reactive substances (TBARS). Gel electrophoresis and amino acid analysis were run to identify the peptide composition. The influence of amino acid composition on antioxidant activity was evaluated using multivariate analysis methods (correlation analysis, principal component analysis, multiple linear regression and discriminant analysis). TBARS assays indicated the presence of antioxidant activity in all protein fractions, including non‐hydrolysed WPI. For native and hydrolysed WPI samples the first fraction (> 45 kDa) showed a higher TBARS inhibition effect (24–27%) when compared with lower‐molecular‐weight fractions and hydrolysate mixtures. In contrast, for commercial WPI hydrolysates a higher inhibitory effect was found in most of the lower‐molecular‐weight fractions (30–55%). The ability of WPI fractions to delay lipid oxidation was found to be related to the prevalence of histidine and hydrophobic amino acids. Copyright © 2004 Society of Chemical Industry     

EDELCA电力公司梯级调度自动发电控制系统

真正意义上的梯级调度自动发电控制（AGC）在国内尚属空白,委内瑞拉EDELCA电力公司的梯级联合调度已有30多年的经验,其AGC选择ACE（区域偏差控制）为控制方式,考虑各种复杂因素,控制功能针对不同的机组特性和运行情况有很大的灵活性。梯级调度AGC具有其自身的功能特点、目标函数、控制状态、参数及模式。