Treatment with modafinil significantly attenuated the performance decrements seen for several parameters including

cognitive-psychomotor speed, visual attention and reaction times both with progressive hours awake and when working at adverse circadian phases. Subjective alertness and sleep parameters were similar between treatment groups, but modafinil-treated participants had fewer bouts of inadvertent sleep during scheduled waking. Modafinil reduced the neurobehavioral impairment associated with work, both during prolonged wakefulness SU5402 and at adverse circadian phases, without adversely affecting subjective alertness or subsequent sleep. These features suggest that modafinil might be a particularly relevant countermeasure against the deleterious

effects of prolonged work hours, shift work, and transmeridian travel. Neuropsychopharmacology (2010) 35, 1910-1920; doi: 10.1038/npp.2010.63; published online 26 May 2010″
“Interferon (IFN) signaling is initiated by the recognition of viral components by host pattern recognition receptors. Dengue virus (DEN) triggers IFN-beta induction through a molecular mechanism involving the cellular RIG-I/MAVS signaling pathway. Here we report that the MAVS protein level is reduced in DEN-infected cells and that caspase-1 and caspase-3 cleave MAVS at residue D429. In addition to its well-known function in IFN induction, MAVS is also a proapoptotic molecule that triggers disruption of the mitochondrial membrane potential and activation of caspases. Although different domains are required for the induction of cytotoxicity and IFN, caspase cleavage at residue 429 abolished S63845 order both functions of MAVS. The apoptotic role of MAVS in viral infection and double-stranded RNA (dsRNA) stimulation was

demonstrated in cells with reduced endogenous MAVS expression induced by RNA interference. Even though IFN-beta promoter activation was largely suppressed, DEN production was not affected greatly in MAVS knockdown cells. Instead, DEN-and dsRNA-induced cell death and caspase activation were delayed and attenuated in N-acetylglucosamine-1-phosphate transferase the cells with reduced levels of MAVS. These results reveal a new role of MAVS in the regulation of cell death beyond its well-known function of IFN induction in antiviral innate immunity.”
“There is shared genetic risk for dependence on multiple substances, and the nicotinic receptor gene cluster on chromosome 15 harbors multiple polymorphisms that associate to this risk. Here, we report the results of an association study with 21 SNPs genotyped across the CHRNA5, CHRNA3, and CHRNB4 loci on chromosome 15q25.1. The sample consists of a discovery set (N = 1858) of European-American and African-American (AA) families, ascertained on the basis of a sibling pair with cocaine and/or opioid dependence, and a case-control replication sample (N = 3388) collected for association studies of alcohol, cocaine, and opioid dependence.