Using full-length sequences of all known alphaviruses, we produced a robust and comprehensive phylogeny of the Alphavirus genus, presenting a more complete evolutionary history of these viruses compared to previous studies based on partial sequences. Our phylogeny suggests the origin of the alphaviruses occurred in the southern oceans and spread equally through the Old and New World. Since lice appear to be involved in aquatic alphavirus transmission, it is possible that we are missing a louse-borne branch of the alphaviruses. Complete genome sequencing of
all members of the genus also revealed conserved residues forming the structural basis of the El and E2 protein dimers.”
“Neurotensin (NT), a neuropeptide abundant in the ventral Gemcitabine chemical structure midbrain, is known to act as a key regulator of the mesolimbic dopamine (DA) system, originating in the ventral tegmental area (VTA). NT activates metabotropic receptors coupled to Gq heterotrimeric G proteins, a signaling pathway often triggering endocannabinoid (EC) Protein Tyrosine Kinase inhibitor production in the brain. Because ECs act as negative
regulators of many glutamate synapses and have also been shown recently to gate LTP induction in the VTA, we examined the hypothesis that NT regulates glutamate-mediated synaptic inputs to VTA DA neurons. We performed whole cell patch-clamp recordings in VTA DA neurons in TH-EGFP transgenic mouse brain slices and found that NT induces a long-lasting decrease of the EPSC amplitude that was mediated by the type 1 NT receptor. An antagonist of the CB1 EC receptor blocked this decrease. This effect of NT was not OICR-9429 order dependent on intracellular calcium, but required G-protein activation and phospholipase
C. Blockade of the CB1 receptor after the induction of EPSC depression reversed synaptic depression, an effect not mimicked by blocking NT receptors, thus suggesting the occurrence of prolonged EC production and release. The EC responsible for synaptic depression was identified as 2-arachidonoylglycerol, the same EC known to gate LTP induction in VIA DA neurons. However, blocking NT receptors during LTP induction did not facilitate LTP induction, suggesting that endogenously released NT is not a major source of EC production during LIP inducing stimulations. (C) 2012 Elsevier Ltd. All rights reserved.”
“Whilst the deleterious effects of alcohol on retrospective remembering have been widely documented, no study has yet objectively determined alcohol’s effects on prospective memory (PM)-remembering to do something in the future.
With this aim, the present study determined the acute effects of alcohol upon PM using a laboratory measure that simulates the PM tasks in everyday life-’Virtual Week’aEuro”"both (a) in its standard form with regular, irregular, event-based and time-based PM tasks; and (b) an adapted version which enabled exploration of how future event simulation at encoding impacted upon subsequent PM.