Association of nicotinic acetylcholine receptor subunit alpha-4 polymorphisms with smoking behaviors in Chinese male smokers

Background it has been reported that the nicotinic acetylcholine receptor subunit a4 gene （CHRNA4） might be associated with smoking behaviors in the previous studies. Up to now, there are few reports on the relationship between CHRNA4 and smoking initiation, in this study, we tried to explore the role of two polymorphisms in CHRNA4 （rs1044396 and rs1044397） in smoking initiation and nicotine dependence in Chinese male smokers. Methods Nine hundred and sixty-six Chinese male lifetime nonsmokers and smokers were assessed by the Fagerstr6m test for nicotine dependence （FTND）, smoking quantity （SQ） and the heaviness of smoking index （HSI）.

Putative nicotinic acetylcholine receptor subunits express differentially through the life cycle of codling moth, Cydia pomonella （Lepidoptera： Tortricidae）

Nicotinic acetylcholine receptors （nAChRs） are the targets of neonicotinoids and spinosads, two insecticides used in orchards to effectively control codling moth, Cydia pomonella （L.） （Lepidoptera： Tortricidae）. Orchardists in Washington State are concerned about the possibility of codling moth field populations developing resistance to these two insecticides. In an effort to help mitigate this issue, we initiated a project to identify and characterize codling moth nAChR subunits expressed in heads. This study had two main goals; （i） identify transcripts from a codling moth head transcriptome that encode for nAChR subunits, and （ii） determine nAChR subunit expression profiles in various life stages of codling moth. From a codling moth head transcriptome, 24 transcripts encoding for 12 putative nAChR subunit classes were identified and verified by PCR amplification, cloning, and sequence determination. Characterization of the deduced protein sequences encoded by putative nAChR transcripts revealed that they share the distinguishing features of the cys-loop ligand-gated ion channel superfamily with 9 α-type subunits and 3 β- type subunits identified. Phylogenetic analysis comparing these protein sequences to those of other insect nAChR subunits supports the identification of these proteins as nAChR subunits. Stage expression studies determined that there is clear differential expression of many of these subunits throughout the codling moth life cycle. The information from this study will be used in the future to monitor for potential target-site resistance mechanisms to neonicotinoids and spinosads in tolerant codling moth populations.

Clinical significance of detection of antibodies to fetal and adult acetylcholine receptors in myasthenia gravis

Objective To evaluate the frequency, distribution and clinical significance of the antibodies to the fetal and/or adult acetylcholine receptor （AChR） in patients with myasthenia gravis （MG）. Methods AChR antibodies were detected by cell-based assay in the serum of ocular MG （OMG） （n = 90） and generalized MG （GMG） patients （n = 110）. The fetal-type （2α： β： γ： δ） and adult-type （2α： β： ε： δ） AChR were used as antigens, and their relevance to disease presentation was assessed. Results The overall frequencies of anti-adult and anti-fetal AChR antibodies were similar in all 200 patients examined, with 14 having serum specific to the AChR-γ subunit, and 22 to the AChR-ε subunit. The overall sensitivity when using the fetal and adult AChR antibodies was higher than that when using the fetal AChR antibody only （P = 0.015）. Compared with OMG patients, the mean age at disease onset and the positive ratio of antibodies to both isoforms of the AChR were significantly higher in patients who subsequently progressed to GMG. Older patients and patients with both anti-fetal and anti-adult AChR antibodies had a greater risk for developing generalized disease [odds ratio （OR）, 1.03; 95% confidence interval （CI）, 1.01–1.06 and OR, 5.09; 95% CI, 2.23–11.62]. Conclusion Using both fetal-and adult-type AChRs as the antigens may be more sensitive than using either subtype. Patients with serum specific to both isoforms are at a greater risk of progressing to GMG. Patients with disease onset at an advanced age appear to have a higher frequency of GMG conversion.

Stability of motor endplates is greater in the biceps than in the interossei in a rat model of obstetric brachial plexus palsy

The time window for repair of the lower trunk is shorter than that of the upper trunk in patients with obstetric brachial plexus palsy. The denervated intrinsic muscles of the hand become irreversibly atrophic much faster than the denervated biceps. However, it is unclear whether the motor endplates of the denervated interosseous muscles degenerate more rapidly than those of the denervated biceps. In this study, we used a rat model of obstetric brachial plexus palsy of the right upper limb. C5–6 was lacerated distal to the intervertebral foramina, with concurrent avulsion of C7–8 and T1, with the left upper limb used as the control. Bilateral interossei and biceps were collected at 5 and 7 weeks. Immunofluorescence was used to assess the morphology of the motor endplates. Real-time quantitative polymerase chain reaction and western blot assay were used to assess mRNA and protein expression levels of acetylcholine receptor subunits(α, β and δ), rapsyn and β-catenin. Immunofluorescence microscopy showed that motor endplates in the denervated interossei were fragmented, while those in the denervated biceps were morphologically intact with little fragmentation. The number and area of motor endplates, relative to the control side, were significantly lower in the denervated interossei compared with the denervated biceps. mRNA and protein expression levels of acetylcholine receptor subunits(α, β and δ) were significantly lower, whereas β-catenin protein expression was higher, in the denervated interossei compared with the denervated biceps. The protein expression of rapsyn was higher in the denervated biceps than in the denervated interossei at 7 weeks. Our findings demonstrate that motor endplates of interossei are destabilized, whereas those of the biceps remain stable, in the rat model of obstetric brachial plexus palsy. All procedures were approved by the Experimental Animal Ethics Committee of Fudan University, China(approval No. DF-187) in January 2016.