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Despite abundant expression of DNA methyltransferases (Dnmts) in brain, the regulation and behavioral role of DNA methylation remain poorly understood. We found that Dnmt3a expression was regulated in mouse nucleus accumbens (NAc) by chronic cocaine use and chronic social defeat stress. Moreover, NAc-specific manipulations that block DNA methylation potentiated cocaine reward and exerted antidepressant-like effects, whereas NAc-specific Dnmt3a overexpression attenuated cocaine reward and was pro-depressant. On a cellular level, we found that chronic cocaine use selectively increased thin dendritic spines on NAc neurons and that DNA methylation was both necessary and sufficient to mediate these effects. These data establish the importance of Dnmt3a in the NAc in regulating cellular and behavioral plasticity to emotional stimuli.

Negative affect is critical for conferring vulnerability to opiate addiction as reflected by the high comorbidity of opiate abuse with major depressive disorder (MDD). Rodent models implicate amygdala prodynorphin (Pdyn) as a mediator of negative affect; however, evidence of PDYN involvement in human negative affect is limited. Here, we found reduced PDYN mRNA expression in the postmortem human amygdala nucleus of the periamygdaloid cortex (PAC) in both heroin abusers and MDD subjects. Similar to humans, rats that chroni-cally self-administered heroin had reduced Pdyn mRNA expression in the PAC at a time point associated with a negative affective state. Using the in vivo functional imaging technology DREAMM (DREADD-assisted metabolic mapping, where DREADD indicates designer receptors exclusively activated by designer drugs), we found that selective inhibition of Pdyn-expressing neurons in the rat PAC increased metabolic activity in the extended amygdala, which is a key substrate of the extrahypothalamic brain stress system. In parallel, PAC-specific Pdyn inhibition provoked negative affect-related physiological and behavioral changes. Altogether, our transla-tional study supports a functional role for impaired Pdyn in the PAC in opiate abuse through activation of the stress and negative affect neurocircuitry implicated in addiction vulnerability., Introduction Chronic negative emotional states are a compelling motivation for relapse to most drugs of abuse, especially opiates (1). The cluster of symptoms that make up these negative emotional states [...]

In order to solve the problem that the vehicles within the university campus are increasing steadily and a large number of outside vehicles drive through the campus arbitrarily and park disorderly. In this paper, a campus intelligent vehicle management system based on ETC is designed, and the ETC technology is introduced. On the basis of analyzing the system’s hardware architecture and workflow, a design model of lane is given. Finally, it discusses the communication theory of Winsock, customs a format of data frame and proposes a Winsock-based intelligent data synchronization algorithm. The daily traffic volume has been decreased by 65% since the system is put into operation in a university.

There remains debate regarding the impact of cannabis on neuropsychiatric disorders. Here, we examined the effects of cannabidiol (CBD), a nonpsychoactive constituent of cannabis, on heroin self-administration and drug-seeking behavior using an experimental rat model. CBD (5-20 mg/kg) did not alter stable intake of heroin self-administration, extinction behavior, or drug seeking induced by a heroin prime injection. Instead, it specifically attenuated heroin-seeking behavior reinstated by exposure to a conditioned stimulus cue. CBD had a protracted effect with significance evident after 24 h and even 2 weeks after administration. The behavioral effects were paralleled by neurobiological alterations in the glutamatergic and endocannabinoid systems. Discrete disturbances of AMPA GluR1 and cannabinoid type-1 receptor expression observed in the nucleus accumbens associated with stimulus cue-induced heroin seeking were normalized by CBD treatment. The findings highlight the unique contributions of distinct cannabis constituents to addiction vulnerability and suggest that CBD may be a potential treatment for heroin craving and relapse. [ABSTRACT FROM AUTHOR]

Background Identifying Streptococcus pneumoniae (Sp) serotypes by urinary antigen detection assay (UAD) is the most sensitive and specific way to evaluate the changing epidemiology of non-bacteremic community-acquired pneumonia (CAP) and efficacy of pneumococcal vaccines. We first described an UAD to detect the Sp serotypes 1,-3,-4,-5,-6A,-6B,-7F,-9V,-14,-18C,-19A,-19F,-23F covered by the 13-valent Sp conjugate vaccine PCV13. To assess the pneumococcal disease burden of additional serotypes, a UAD-2 assay was developed to diagnose 11 additional Sp serotypes (-2,-8,-9N,-10A,-11A,-12F,-15B,-17F,-20,-22F,-33F). Methods UAD-2 specificity was achieved by capturing highly purified pneumococcal polysaccharides with serotype-specific monoclonal antibodies using Luminex technology. Assay qualification assessed accuracy, precision, and sample linearity. Serotype positivity was based on cutoffs determined by non-parametric statistical evaluation of urine samples from individuals without pneumococcal disease. Clinical sensitivity and specificity of the positivity cutoffs were assessed in a clinical validation. Results The UAD-2 was shown to be specific and reproducible. Clinical validation using urine samples from invasive disease patients demonstrated assay sensitivity and specificity of 92.2% and 95.9%, respectively compared with a gold standard of isolating and typing (by Quellung) Sp bacteria from patient samples. Analysis of 11,087 CAP patients showed a UAD-2 and UAD-1 serotype prevalence of 4.33% and 4.60%, respectively (bacteremic and non-bacteremic CAP combined). Conclusion The qualified/clinically validated UAD-2 method has applicability in understanding the epidemiology of nonbacteremic Sp CAP as well as assessing vaccine efficacy of future pneumococcal conjugate vaccines. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background & objectives: Fluoroquinolone has a broad spectrum of antimicrobial activity, and is widely used for gonorrhoea treatment. However, its efficacy can be compromised by the drug-resistance property of Neisseria gonorrhoeae isolates. Most resistant eases of N. gonorrhoeae are associated with mutations in the quinolone-resistance-determining-region (QRDR) within genes of gyrA and parC. This study was undertaken to describe resistance profile of N. gonorrhoeae to fluoroquinolones in Shanghai, P.R. of China, and also associated resistance mutations in gyrA and parC. Methods: Eighty N. gonorrhoeae isolates were collected from Shanghai Skin Disease & Sexually Transmitted Disease Hospital or DongFang Hospital during April 2005 to April 2006 in Shanghai, P.R. of China. The minimum inhibitory concentrations (MIC) of fluoroquinolones for these isolates were determined by an agar dilution method. Mutation patterns within gyrA and parC were determined by direct sequencing or by using established restriction fragment length polymorphisms (RFLP) methods. Results: Ninety five per cent (76 of 80) of isolates were resistant, 3.75 per cent (3 of 80) intermediate resistant, and 1.25 per cent (1 of 80) were sensitive to fluoroquinolone drug ciprofloxacin. Sequencing and RFLP analysis of gyrA and parC revealed that all resistant isolates had dual mutations of S91F and D95A/G/N in gyrA. Some isolates had an extra mutation within parC either of D86N, S87N or E91A/G. Mutation patterns for gyrA and pare were significantly (P<0.05) associated with MICs level. Interpretation & conclusions: Mutations of S91F and D95A/G/N in gyrA combined with S87N in parC was the most prevalent mutation pattern of fluoroquinolone resistant N. gonorrhoeae isolates. This mutation pattern was associated with a high level of quinolone resistance (MIC >16.0 µg/ml) which can serve as a maker for quinolone-resistance prediction in Shanghai, P.R. of China. [ABSTRACT FROM AUTHOR]