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Understanding taste is key for optimizing the palatability of seaweeds and other non-animal-based foods rich in protein. The lingual papillae in the mouth hold taste buds with taste receptors for the five gustatory taste qualities. Each taste bud contains three distinct cell types, of which Type II cells carry various G protein-coupled receptors that can detect sweet, bitter, or umami tastants, while type III cells detect sour, and likely salty stimuli. Upon ligand binding, receptor-linked intracellular heterotrimeric G proteins initiate a cascade of downstream events which activate the afferent nerve fibers for taste perception in the brain. The taste of amino acids depends on the hydrophobicity, size, charge, isoelectric point, chirality of the alpha carbon, and the functional groups on their side chains. The principal umami ingredient monosodium l-glutamate, broadly known as MSG, loses umami taste upon acetylation, esterification, or methylation, but is able to form flat configurations that bind well to the umami taste receptor. Ribonucleotides such as guanosine monophosphate and inosine monophosphate strongly enhance umami taste when l-glutamate is present. Ribonucleotides bind to the outer section of the venus flytrap domain of the receptor dimer and stabilize the closed conformation. Concentrations of glutamate, aspartate, arginate, and other compounds in food products may enhance saltiness and overall flavor. Umami ingredients may help to reduce the consumption of salts and fats in the general population and increase food consumption in the elderly.
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Glucocorticoids (GCs) such as prednisolone are potent immunosuppressive drugs but suffer from severe adverse effects, including the induction of insulin resistance. Therefore, development of so-called Selective Glucocorticoid Receptor Modulators (SGRM) is highly desirable. Here we describe a non-steroidal Glucocorticoid Receptor (GR)-selective compound (Org 214007-0) with a binding affinity to GR similar to that of prednisolone. Structural modelling of the GR-Org 214007-0 binding site shows disturbance of the loop between helix 11 and helix 12 of GR, confirmed by partial recruitment of the TIF2-3 peptide. Using various cell lines and primary human cells, we show here that Org 214007-0 acts as a partial GC agonist, since it repressed inflammatory genes and was less effective in induction of metabolic genes. More importantly, in vivo studies in mice indicated that Org 214007-0 retained full efficacy in acute inflammation models as well as in a chronic collagen-induced arthritis (CIA) model. Gene expression profiling of muscle tissue derived from arthritic mice showed a partial activity of Org 214007-0 at an equi-efficacious dosage of prednisolone, with an increased ratio in repression versus induction of genes. Finally, in mice Org 214007-0 did not induce elevated fasting glucose nor the shift in glucose/glycogen balance in the liver seen with an equi-efficacious dose of prednisolone. All together, our data demonstrate that Org 214007-0 is a novel SGRMs with an improved therapeutic index compared to prednisolone. This class of SGRMs can contribute to effective anti-inflammatory therapy with a lower risk for metabolic side effects.
Today, we live in a world where every time we turn on our smartphones, we are inextricably tied by data, laws and flowing bytes to different countries. A world in which personal expressions are framed and mediated by digital platforms, and where new kinds of currencies, financial exchange and even labor bypass corporations and governments. Simultaneously, the same technologies increase governmental powers of surveillance, allow corporations to extract ever more complex working arrangements and do little to slow the construction of actual walls along actual borders. On the one hand, the agency of individuals and groups is starting to approach that of nation states; on the other, our mobility and hard-won rights are under threat. What tools do we need to understand this world, and how can art assist in envisioning and enacting other possible futures?This publication investigates the new relationships between states, citizens and the stateless made possible by emerging technologies. It is the result of a two-year EU-funded collaboration between Aksioma (SI), Drugo More (HR), Furtherfield (UK), Institute of Network Cultures (NL), NeMe (CY), and a diverse range of artists, curators, theorists and audiences. State Machines insists on the need for new forms of expression and new artistic practices to address the most urgent questions of our time, and seeks to educate and empower the digital subjects of today to become active, engaged, and effective digital citizens of tomorrow.Contributors: James Bridle, Max Dovey, Marc Garrett, Valeria Graziano, Max Haiven, Lynn Hershman Leeson, Francis Hunger, Helen Kaplinsky, Marcell Mars, Tomislav Medak, Rob Myers, Emily van der Nagel, Rachel O’Dwyer, Lídia Pereira, Rebecca L. Stein, Cassie Thornton, Paul Vanouse, Patricia de Vries, Krystian Woznicki.
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