Inversion of allosteric effect of arginine on N-acetylglutamate synthase,a molecular marker for evolution of tetrapods

Background  

The efficient conversion of ammonia, a potent neurotoxin, into non-toxic metabolites was an essential adaptation that allowed animals to move from the aquatic to terrestrial biosphere. The urea cycle converts ammonia into urea in mammals, amphibians, turtles, snails, worms and many aquatic animals and requires N-acetylglutamate (NAG), an essential allosteric activator of carbamylphosphate synthetase I (CPSI) in mammals and amphibians, and carbamylphosphate synthetase III (CPSIII) in fish and invertebrates. NAG-dependent CPSI and CPSIII catalyze the formation of carbamylphosphate in the first and rate limiting step of ureagenesis. NAG is produced enzymatically by N-acetylglutamate synthase (NAGS), which is also found in bacteria and plants as the first enzyme of arginine biosynthesis. Arginine is an allosteric inhibitor of microbial and plant NAGS, and allosteric activator of mammalian NAGS.     

Consignment contracts with retail competition

Consignment contracts have been widely employed in many industries. Under such contracts, items are sold at a retailer’s but the supplier retains the full ownership of the inventory until purchased by consumers; the supplier collects payment from the retailer based on actual units sold. We investigate how competition among retailers influences the supply chain decisions and profits under different consignment arrangements, namely a consignment price contract and a consignment contract with revenue share. First, we investigate how these two consignment contracts and a price only contract compare from the perspective of each supply chain partner. We find that the retailers benefit more from a consignment price contract than from a consignment contract with revenue share or a price only contract, regardless of the level of retailer differentiation. The supplier’s most beneficial contact, however, critically depends upon the level of retailer differentiation: a consignment contract with revenue share is preferable for the supplier if retailer differentiation is strong; otherwise a consignment price contract is preferable. Second, we study how retailer differentiation affects the profits of all supply chain partners. We find that less retailer differentiation improves the supplier’s profit for both types of consignment contract. Moreover, less retailer differentiation improves profits of the retailers in a consignment price contract, but not necessarily in a consignment contract with revenue share.     

Thioether and Ether Furofuran Lignans: Semisynthesis,Reaction Mechanism,and Inhibitory Effect against α-Glucosidase and Free Radicals

The transformation of sesame lignans is interesting because the derived products possess enhanced bioactivity and a wide range of potential applications. In this study, the semisynthesis of 28 furofuran lignans using samin (5) as the starting material is described. Our methodology involved the protonation of samin (5) to generate an oxocarbenium ion followed by the attack from two different nucleophiles, namely, thiols (RSH) and alcohols (ROH). The highly diastereoselective thioether and ether furofuran lignans were obtained, and their configurations were confirmed by 2D NMR and X-ray crystallography. The mechanism underlying the reaction was studied by monitoring ¹H NMR and computational calculations, that is, the diastereomeric α- and β-products were equally formed through the S_N1-like mechanism, while the β-product was gradually transformed via an S_N2-like mechanism to the α-congener in the late step. Upon evaluation of the inhibitory effect of the synthesized lignans against α-glucosidases and free radicals, the lignans 7f and 7o of the phenolic hydroxyl group were the most potent inhibitors. Additionally, the mechanisms underlying the α-glucosidase inhibition of 7f and 7o were verified to be of a mixed manner and noncompetitive inhibition, respectively. The results indicated that both 7f and 7o possessed promising antidiabetic activity, while simultaneously inhibiting α-glucosidases and free radicals.