Modulation of the M2 muscarinic acetylcholine receptor activity with monoclonal anti-M2 receptor antibody fragments

Antibodies directed against the second extracellular loop of G protein-coupled receptors are known to have functional activities. From a partial agonist monoclonal antibody directed against the M2 muscarinic receptor, we constructed and produced a single chain variable fragment with high affinity for its target epitope. The fragment is able to recognize its receptor on Chinese hamster ovary cells transfected with the M2 muscarinic acetylcholine receptor to block the effect of carbachol on this receptor and to exert an inverse agonist activity on the basal activity of the receptor. The antibody fragment is also able to increase the basal rhythm of cultured neonatal rat cardiomyocytes and to inhibit in a non-competitive manner the negative chronotropic effect of carbachol. This antibody fragment is able to exert its inverse agonist activity in vivo on mouse heart activity. The immunological strategy presented here could be useful to develop specific allosteric inverse agonist reagents for G protein-coupled receptors

How Bürgi computed the sines of all integer angles simultaneously in 1586

We present an algorithm discovered by Jost Bürgi around 1586, lost until 2013, and proven in 2015. Bürgi’s method needs only sums of integers and divisions by 2 to compute simultaneously and with any desired accuracy the sines of the nth parts of the right angle. We explain why it works with a new proof using polygons and discrete Fourier transforms

Early Italian Computing Machines and Their Inventors

International audienceNineteen centuries of Italian inventors and inventions in the field of aids to arithmetic and algebraic computing, before the electronic computer era, are reviewed; most of them forgotten or still unknown. Not meant to be a complete or ultimate treatise on the topic, this paper hopefully wants to be a starting point for more multidisciplinary research of Italian history of technology