Carbohydrate Recognition by an Architecturally Complex α-N-Acetylglucosaminidase from Clostridium perfringens

CpGH89 is a large multimodular enzyme produced by the human and animal pathogen Clostridium perfringens. The catalytic activity of this exo-α-d-N-acetylglucosaminidase is directed towards a rare carbohydrate motif, N-acetyl-β-d-glucosamine-α-1,4-d-galactose, which is displayed on the class III mucins deep within the gastric mucosa. In addition to the family 89 glycoside hydrolase catalytic module this enzyme has six modules that share sequence similarity to the family 32 carbohydrate-binding modules (CBM32s), suggesting the enzyme has considerable capacity to adhere to carbohydrates. Here we suggest that two of the modules, CBM32-1 and CBM32-6, are not functional as carbohydrate-binding modules (CBMs) and demonstrate that three of the CBMs, CBM32-3, CBM32-4, and CBM32-5, are indeed capable of binding carbohydrates. CBM32-3 and CBM32-4 have a novel binding specificity for N-acetyl-β-d-glucosamine-α-1,4-d-galactose, which thus complements the specificity of the catalytic module. The X-ray crystal structure of CBM32-4 in complex with this disaccharide reveals a mode of recognition that is based primarily on accommodation of the unique bent shape of this sugar. In contrast, as revealed by a series of X-ray crystal structures and quantitative binding studies, CBM32-5 displays the structural and functional features of galactose binding that is commonly associated with CBM family 32. The functional CBM32s that CpGH89 contains suggest the possibility for multivalent binding events and the partitioning of this enzyme to highly specific regions within the gastrointestinal tract

Effects of Tariffication: Tariffs and Quotas under Monopolistic Competition

Recent rounds of GATT and later WTO have advocated widespread tariffication, meaning that existing non-tariff barriers be converted into import equivalent tariffs. From an economic point of view, the effects of such tariffication are not entirely clear. The paper presents a trade model with monopolistic competition to examine the welfare effects of tariffication. The ranking of pre- and post-tariffication welfare crucially depends on the nature of the initial trade barrier and the tariff tool applied. Tariffication using a specific (ad valorem) tariff results in the same (reduced) welfare level compared to an initial sold quota, whereas welfare is increased (the same) compared to an initial shared quota. Copyright Springer Science+Business Media, LLC 2007Trade policy, Tariffication, Specific tariff, Ad valorem tariff, Quota, Tariff rate quotas, VER, F02, F12, F13,

Other Worlds. When Worldbuilding and Roleplay Feed Speculation

Games inherently deal with exploring alternative worlds. Worlds where players can experience other roles and have in-game, first-hand experiences by suspending our disbelief. This chapter digs into those features and peculiarities that make games and game design such good spaces where to imagine alternative pasts, presents, and futures for triggering reflection and imagining possibilities. Being situated in the trend of future-oriented design practices, where fictional worlds, what-ifs, and their surroundings nurture design, the reasoning frames the game’ worldbuilding activity and its potentialities in terms of envisioning and speculation from a twofold perspective—that of players and game designers. In doing so, it investigates the peculiar traits that make this practice compelling, challenging, and fruitful for feeding innovation. Relying on which features and strategies can games embed reflections on the complex challenges we are facing today, will face tomorrow, or in the long run? How can the game design activity stimulate designers towards more aware, responsible, inclusive and diversity-oriented processes of envisioning, speculation, creation