Tobacco use has one of the highest rates of addiction and relapse of any abused drug. Paradoxically, however, in animal models of reinforcement nicotine appears weak compared to other abused drugs. We report here that acetaldehyde, a major component of tobacco smoke, enhances nicotine self-administration. Juvenile and adult male rats were implanted with intravenous catheters and tested for self-administration 4 days later at postnatal day 27 or 90, respectively. Animals were tested, without prior response training, in five daily 3-h sessions where each nose-poke delivered an intravenous injection followed by a 60-s timeout. Animals (11-13/group) were offered one of the following solutions: nicotine (30 mg/kg/injection), acetaldehyde (16 mg/kg/inj), nicotine (30 mg/kg/inj) þ acetaldehyde (16 mg/kg/inj), or saline. The youngest animals responded significantly more for nic þ acet than for saline or for either drug alone. Responding at the reinforced hole was significantly higher than at the nonreinforced hole or at the reinforced hole during noncontingent injections of nic þ acet. Tests with receptor antagonists indicated that these drug effects are mediated by central, but not peripheral, nicotinic receptors. There was an age-related decline in self-administration of nic þ acet, but not for cocaine. Taken together, these results indicate that acetaldehyde, at the low concentrations found in tobacco smoke, interacts with nicotine to increase responding in a stringent self-administration acquisition test where nicotine alone is only weakly reinforcing, and that adolescent animals are more sensitive to these actions than adults. Animal models of tobacco addiction could be improved by combining acetaldehyde, and possibly other smoke components, with nicotine to more accurately reflect the pharmacological profile of tobacco smoke.

Vertebrates diverged from other chordates ~500 Myr ago and experienced successful innovations and adaptations, but the genomic basis underlying vertebrate origins are not fully understood. Here we suggest, through comparison with multiple lancelet (amphioxus) genomes, that ancient vertebrates experienced high rates of protein evolution, genome rearrangement and domain shuffling and that these rates greatly slowed down after the divergence of jawed and jawless vertebrates. Compared with lancelets, modern vertebrates retain, at least relatively, less protein diversity, fewer nucleotide polymorphisms, domain combinations and conserved non-coding elements (CNE). Modern vertebrates also lost substantial transposable element (TE) diversity, whereas lancelets preserve high TE diversity that includes even the long-sought RAG transposon. Lancelets also exhibit rapid gene turnover, pervasive transcription, fastest exon shuffling in metazoans and substantial TE methylation not observed in other invertebrates. These new lancelet genome sequences provide new insights into the chordate ancestral state and the vertebrate evolution.

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In this paper, the problem of finite-time H 1 control is addressed for a class of discrete-time switched nonlinear systems with time delay. The concept of H 1 finite-time boundedness is first introduced for discrete-time switched delay systems. Next, a set of switching signals are designed by using the average dwell time approach, under which some delay-dependent sufficient conditions are derived to guarantee the H 1 finite-time boundedness of the closed-loop system. Then, a finite-time H 1 state feedback controller is also designed by solving such conditions. Furthermore, the problem of uniform finite-time H 1 stabilization is also resolved. All the conditions are cast into linear matrix inequalities, which can be easily checked by using recently developed algorithms for solving linear matrix inequalities. A numerical example and a water-quality control system are provided to demonstrate the effectiveness of the main results.FINITE-TIME H 1 CONTROL 915 its system state does not exceed some prescribed bound for bounded initial states. It is known that finite-time stability and Lyapunov asymptotic stability are independent concepts; a finite-time stable system may not be Lyapunov asymptotically stable and vice versa.In the presence of exogenous disturbances, the concept of finite-time boundedness was introduced in [13]. In [14], the problem of finite-time state feedback stabilization for discrete-time linear system was investigated. Sufficient conditions ensuring finite-time stability for nonlinear quadratic systems were derived in [15]. For a class of linear singular impulsive systems with or without exogenous disturbances, the finite-time impulsive stabilization problem was considered in [16][17][18] via the matrix inequality method. In [19], the concepts of finite-time stability and finite-time boundedness were extended to switched linear systems, and some sufficient conditions were provided such that the switched linear systems were finite-time bounded and uniformly finite-time bounded. Recently, the problems of finite-time weighted L 2 gain for switched delay systems with disturbances were handled in [20]. Furthermore, in [21], the finite-time H 1 control was considered for continuous-time switched linear systems with time-varying delay. Using the switched Lyapunov function approach proposed in [4], solutions to the problem of finite-time H 1 control was presented in [22] for a class of discrete-time switched nonlinear systems. More recently, the problem of finite-time dynamic output feedback stabilization was addressed in [23]. It should be pointed out that so far, no attention has been paid to the H 1 finite-time control problem of switched delay systems, especially in a discrete-time context.In this paper, we focus upon the problem of finite-time H 1 control for discrete-time switched nonlinear systems with time delay. Because of the existence of time delay and nonlinear disturbances, this problem is apparently hard to tackle. The main contributions in this paper lie in three aspects. First, the concepts o...

Inflammation and maternal or fetal infections have been suggested as risk factors for schizophrenia (SZ) and bipolar disorder (BP). It is likely that such environmental effects are contingent on genetic background. Here, in a genome-wide approach, we test the hypothesis that such exposures increase the risk for SZ and BP and that the increase is dependent on genetic variants. We use genome-wide genotype data, plasma IgG antibody measurements against Toxoplasma gondii, Herpes simplex virus type 1, Cytomegalovirus, Human Herpes Virus 6 and the food antigen gliadin as well as measurements of C-reactive protein (CRP), a peripheral marker of inflammation. The subjects are SZ cases, BP cases, parents of cases and screened controls. We look for higher levels of our immunity/infection variables and interactions between them and common genetic variation genome-wide. We find many of the antibody measurements higher in both disorders. While individual tests do not withstand correction for multiple comparisons, the number of nominally significant tests and the comparisons showing the expected direction are in significant excess (permutation p=0.019 and 0.004 respectively). We also find CRP levels highly elevated in SZ, BP and the mothers of BP cases, in agreement with existing literature, but possibly confounded by our inability to correct for smoking or body mass index. In our genome-wide interaction analysis no signal reached genome-wide significance, yet many plausible candidate genes emerged. In a hypothesis driven test, we found multiple interactions among SZ-associated SNPs in the HLA region on chromosome 6 and replicated an interaction between CMV infection and genotypes near the CTNNA3 gene reported by a recent GWAS. Our results support that inflammatory processes and infection may modify the risk for psychosis and suggest that the genotype at SZ-associated HLA loci modifies the effect of these variables on the risk to develop SZ.