Serotonin (5-hydroxytryptamine; 5-HT) plays key roles in sleep-wakefulness regulation. Evidence indicates that 5-HT2 receptors are involved mainly in non-rapid eye movement sleep (NREMS) regulation and respiratory control. Here, we investigated the relative contribution of 5-HT(2A), 5-HT(2B), and 5-HT(2C) receptor subtypes to NREMS and breathing during sleep, using 5-HT2 subtype-selective ligan...

Reaction of dialkyl acetylenedicarboxylates 1a-c andpyrrole derivatives 2a-e in the presence of triphenylphosphite (TPP) was investigated and the effect of the pyrrole substitution was established. Diastereoselectivity is observed with pyrroles, 2a,b, yieldingphosphonate ester derivatives 3a-f and 4,and their relative configuration is determined by 1H/13C and 31</...

Brome mosaic virus (BMV), a positive-strand RNA virus in the alphavirus-like superfamily, encodes RNA replication proteins 1a and 2a. 1a contains a C-terminal helicase-like domain and an N-terminal domain implicated in viral RNA capping, and 2a contains a central polymerase-like domain. 1a and 2a colocalize in an endoplasmic reticulum (ER)-associated replication complex that is the site of BMV-...

BACKGROUND Atherosclerosis is a chronic inflammatory disease of the arterial vessel wall. The A(2A) receptor (A(2A)R) plays a central role in many antiinflammatory effects of adenosine. However, the role of A(2A)R in atherosclerosis is not clear. METHODS AND RESULTS The knockout of A(2A)R in apolipoprotein E-deficient (Apoe(-/-)/A(2A)R(-/-)) mice led to an increase in body weight and levels o...

6-Carbethoxy-5-(3'-bromophenyl)-3-aryl-2-cyclohexenones 2a-j were obtained from the1-Aryl-3-(3'-bromophenyl)-2-propene-1-ones 1a-j by Micheal addition of ethyl acetoacetate, followed by internal Claisen condensation. Reaction of 2a-j with hydrazine hydrate afforded the corresponding 6-Aryl-4-(3'-bromophenyl)-3-oxo-2,3a,4,5-tetrahydro-2H-indazoles 3a-j. The structures of newly synthesized compou...

The distribution and function of the 5-hydroxytryptamine (5-HT(2A)) receptor were investigated in the intestines of wild-type (5-HT(2A) +/+) and knockout (5-HT(2A) -/-) mice. In 5-HT(2A) +/+ mice, rats, and guinea pigs, 5-HT(2A) receptor immunoreactivity was found on circular and longitudinal smooth muscle cells, neurons, enterocytes, and Paneth cells. Muscular 5-HT(2A) receptors were concentra...

Unlike all other picornaviruses, the primary cleavage of the hepatitis A virus (HAV) polyprotein occurs at the 2A/2B junction and is carried out by the only proteinase encoded by the virus, 3C(pro). The resulting P1-2A capsid protein precursor is subsequently cleaved by 3C(pro) to generate VP0, VP3, and VP1-2A, which associate as pentamers. An unidentified cellular proteinase acting at the VP1/...

2A is an oligopeptide sequence mediating a ribosome 'skipping' effect, producing an apparent 'cleavage' of polyproteins. First identified and characterized in picornaviruses, '2A-like' sequences are found in other mammalian viruses and a wide range of insect viruses. Databases were analysed using a motif conserved amongst 2A/2A-like sequences. The newly identified 2A-like sequences (30 aa) were...

Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. The Janus kinase (JAK) family of non-receptor protein tyrosine kinases constitute a novel type of signal-transduction pathway which is activated in re...

6-carbethoxy-5-(3&apos;-bromophenyl)-3-aryl-2-cyclohexenones 2a-j were obtained from the1-aryl-3-(3&apos;-bromophenyl)-2-propene-1-ones 1a-j by micheal addition of ethyl acetoacetate, followed by internal claisen condensation. reaction of 2a-j with hydrazine hydrate afforded the corresponding 6-aryl-4-(3&apos;-bromophenyl)-3-oxo-2,3a,4,5-tetrahydro-2h-indazoles 3a-j. the structures of newly syn...