BACKGROUND We have demonstrated that anorexia nervosa is underpinned by overwhelming adrenal sympathetic activity which abolishes the neural sympathetic branch of the peripheral autonomic nervous system. This physiological disorder is responsible for gastrointestinal hypomotility, hyperglycemia, raised systolic blood pressure, raised heart rate, and other neuroendocrine disorders. Therefore, we...

The influenza A virus M2 protein is a pH-gated and amantadine-inhibited proton channel important for the virus life cycle. Proton conduction by M2 is known to involve water; however direct experimental evidence of M2-water interaction is scarce. Using (1)H spin diffusion solid-state NMR, we have now determined the water accessibility of the M2 transmembrane domain (M2-TM) in virus-envelope-mime...

A chemo- and regioselective gold-catalyzed tandem 6-endo-dig cyclization/enyne cycloisomerization/1,2-migration process for the synthesis of decorated peptidomimetics is developed. Various migrating groups such as aryl, heteroaryl alkyl are tolerated in this method under mild conditions. This protocol successfully utilized to modify various oligopeptides, including substrates bearing drug amant...

The M2 protein of influenza A viruses forms a tetrameric proton channel that is targeted by the amantadine class of antiviral drugs. A S31N mutation in the transmembrane (TM) domain of the protein has caused widespread amantadine resistance in most of the currently circulating flu viruses. Recently, a new family of compounds based on amantadine- and aryl-substituted isoxazole were discovered to...

The M2 proton channel of influenza A is the target of the antiviral drugs amantadine and rimantadine, whose effectiveness has been abolished by a single-site mutation of Ser31 to Asn in the transmembrane domain of the protein. Recent high-resolution structures of the M2 transmembrane domain obtained from detergent-solubilized protein in solution and crystal environments gave conflicting drug bi...

The influenza A H1N1 viruses, initially isolated from pigs in Ireland in 1991, were genetically distinct from previously identified human and swine H1N1 viruses, and appear to be the result of introduction of an avian virus distinct from those circulating in pigs in other European countries. The first Irish H3N2 swine isolates were genetically closely related to human H3N2 viruses. In contrast,...

Influenza virus A/Hong Kong/1774/99, isolated from a young child with mild influenza, was shown to be similar in its antigenic and genetic characteristics to H3N2 viruses circulating in pigs in Europe during the 1990s and in particular to be closely related to viruses isolated from two children in the Netherlands in 1993. Similar viruses had previously not been identified outside Europe. Althou...