Incorporation of the ␣5 nicotinic acetylcholine receptor (nAChR) subunit can greatly influence nAChR function without altering receptor number. Although few animal studies have assessed the role of the ␣5 nAChR in nicotine-mediated behaviors, recent evidence suggests an association between polymorphisms in the ␣5 nAChR gene and nicotine dependence phenotypes in humans. Thus, additional studies are imperative to elucidate the role and function of the ␣5 nAChR subunit in nicotine dependence. Using ␣5(Ϫ/Ϫ) mice, the current study aimed to examine the role of ␣5 nAChRs in the initial pharmacological effects of nicotine, nicotine reward using the conditioned place preference model, and the discriminative effects of nicotine using a two-lever drug discrimination model. 86 Rb ϩ efflux and 125 I-epibatidine binding assays were conducted to examine the effect of ␣5 nAChR subunit deletion on expression and activity of functional nAChRs. Results show that ␣5(Ϫ/Ϫ) mice are less sensitive to the initial effects of nicotine in antinociception, locomotor activity, and hypothermia measures and that the ␣5 nAChR is involved in nicotine reward. Alternatively, ␣5(Ϫ/Ϫ) mice did not differ from wild-type littermates in sensitivity to the discriminative stimulus effects of nicotine. Furthermore, deletion of the ␣5 nAChR subunit resulted in a statistically significant decrease in function in the thalamus and hindbrain, but the decreases noted in spinal cord were not statistically significant. Receptor number was unaltered in all areas tested. Taken together, results of the study suggest that ␣5 nAChRs are involved in nicotine-mediated behaviors relevant to development of nicotine dependence.

The large number of single nucleotide polymorphism (SNP) markers available in the public databases makes studies of association and fine mapping of disease loci very practical. To provide information for researchers who do not follow SNP genotyping technologies but need to use them for their research, we review here recent developments in the fields. We start with a general description of SNP typing protocols and follow this with a summary of current methods for each step of the protocol and point out the unique features and weaknesses of these techniques as well as comparing the cost and throughput structures of the technologies. Finally, we describe some popular techniques and the applications that are suitable for these techniques.

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We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values ≤0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3 828 611–rs10043986, r2 = 0.008; rs10043986–rs4704591, r2 = 0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case–control samples, 11 380 cases and 15 021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR) = 1.11, 95% confidence interval (CI) = 1.04–1.18, P = 8.2 × 10−4 and rs4704591, OR = 1.07, 95% CI = 1.03–1.11, P = 3.0 × 10−4). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR = 1.11, 95% CI = 1.03–1.17, P = 0.0026 and rs4704591, OR = 1.07, 95% CI = 1.02–1.11, P = 0.0015). Furthermore, haplotype conditioned analyses indicated that the association signals observed at these two markers are independent. On the basis of these results, we concluded that CMYA5 is associated with schizophrenia and further investigation of the gene is warranted.

Honokiol, a well-tolerated natural product, can inhibit the proliferation of cancer cells. But its water insolubility hampers its systemic administration for therapy of cancer. As a drug delivery system, the pegylated liposome (PEGL) can increase the water solubility and targeting of the drug. Honokiol has been successfully encapsulated by PEGL in our laboratory. We wondered whether the combination treatment with pegylated liposomal honokiol (H-PEGL) and cisplatin (DDP) could improve the antitumor efficacy in ovarian carcinoma. H-PEGL could introduce apoptosis of SKOV3 cells in vitro, which was quantified by flow cytometric analysis, and the cellular morphologic changes were determined by propidium iodide staining. In a human ovarian carcinoma mouse model, combination treatment with H-PEGL (0.4 mg/day for 30 days; intraperitoneal) and DDP (5 mg/kg on days 7, 11, 15, 19; intraperitoneal) acted synergistically to inhibit tumor growth by 91.48% without notable toxicity, but H-PEGL and DDP alone only inhibit tumor growth by 66.83% and 52.5% as compared to the NaCl solution control, respectively. Assessment of microvessel density and apoptosis index by CD31 and terminal deoxynucleotidyl transferase-mediated nick end labeling immunohistochemistry respectively suggested that the antitumor activity of H-PEGL is mediated by angiogenesis inhibition and introduction of apoptosis. Our results showed us a splendid prospect of the clinical application of combination treatment on patients suffering from ovarian cancer with H-PEGL and DDP.