Genetic analysis of IREB2, FAM13A and XRCC5 variants in Chinese Han patients with chronic obstructive pulmonary disease

Recently, variants (rs2568494, rs2869967 and rs3821104) in the IREB2, FAM13A and XRCC5 genes were found to be associated with chronic obstructive pulmonary disease (COPD) in non-Asian populations by genome-wide association study (GWAS) analysis. To evaluate whether variants in these genes are related to COPD in Chinese Han population, we investigated COPD patients of Chinese Han ethnicity from Mainland China. Significant differences in genotypic distributions (χ² = 6.319, p = 0.042 for rs2869967; χ² = 6.062, p = 0.048 for rs3821104) and allele distributions (χ² = 4.014, p = 0.045 for rs2869967; χ² = 5.607, p = 0.018 for rs3821104) were observed between patients and control subjects for variants rs2869967 and rs3821104, whereas no statistically significant associations for genotypic and allelic distribution between IREB2 rs2568494 and COPD phenotype (p > 0.05) were identified. Our results support that FAM13A rs2869967 and XRCC5 rs3821104 are associated with COPD in Chinese Han population.     

Intramolecular interaction between the DEP domain of RGS7 and the Gbeta5 subunit

The R7 family of RGS proteins (RGS6, -7, -9, -11) is characterized by the presence of three domains: DEP, GGL, and RGS. The RGS domain interacts with Galpha subunits and exhibits GAP activity. The GGL domain permanently associates with Gbeta5. The DEP domain interacts with the membrane anchoring protein, R7BP. Here we provide evidence for a novel interaction within this complex: between the DEP domain and Gbeta5. GST fusion of the RGS7 DEP domain (GST-R7DEP) binds to both native and recombinant Gbeta5-RGS7, recombinant Gbetagamma complexes, and monomeric Gbeta5 and Gbeta1 subunits. Co-immunoprecipitation and FRET assays supported the GST pull-down experiments. GST-R7DEP reduced FRET between CFP-Gbeta5 and YFP-RGS7, indicating that the DEP-Gbeta5 interaction is dynamic. In transfected cells, R7BP had no effect on the Gbeta5/RGS7 pull down by GST-R7DEP. The DEP domain of RGS9 did not bind to Gbeta5. Substitution of RGS7 Glu-73 and Asp-74 for the corresponding Ser and Gly residues (ED/SG mutation) of RGS9 diminished the DEP-Gbeta5 interaction. In the absence of R7BP both the wild-type RGS7 and the ED/SG mutant attenuated muscarinic M3 receptor-mediated Ca2+ mobilization. In the presence of R7BP, wild-type RGS7 lost this inhibitory activity, whereas the ED/SG mutant remained active. Taken together, our results are consistent with the following model. The Gbeta5-RGS7 molecule can exist in two conformations: "closed" and "open", when the DEP domain and Gbeta5 subunit either do or do not interact. The closed conformation appears to be less active with respect to its effect on Gq-mediated signaling than the open conformation.     

Chloride channel activity of vascular smooth muscle in the spontaneous hypertensive rats

To characterize the activity of the Ca2+-activated Cl- channels in vascular smooth muscle (VSM) of the spontaneous hypertensive rats (SHR), the isolated mesenteric vascular beds and tail artery strips were preparated from SHR and Wistar rats aged 7-8 weeks. The changes in contractile response to norepinphrine (NE) were taken as an index of vascular mortion. Results showed that the contractile responses of mesenteric arteries and tail arteries to NE in SHR were significantly greater than that in Wistar rats. The inhibition magnitude of the contractile response by Ca2+-activated Cl- channel blocker, niflumic acid in SHR was significantly less than that in Wistar rats. Decreasing the extracellular Cl- concentration increased the contractile response to NE significantly, but the amplitude of enhanced contractile response in SHR was greater than that in Wistar rats. It can be concluded that NE-induced contraction was enhanced in SHR, which is partly due to an increase in Cl- efflux through the Ca2+-activated Cl- channels. The chloride channel activity may be increased in association with the elevation of blood pressure.     

Effects of enhanced atmospheric ammonia on photosynthetic characteristics of two maize (<Emphasis Type=Italic>Zea mays</Emphasis> L.) cultivars with various nitrogen supply across long-term growth period and their diurnal change patterns

We investigated the effect of enhanced atmospheric ammonia (NH₃) in combination with low and high nitrogen (LN and HN, respectively) growth medium on photosynthetic characteristics of two maize (Zea mays L.) cultivars (NE5 with high- and SD19 with low N-use efficiency) across long-term growth period and their diurnal change patterns exposed to 10 nl l⁻¹ and 1,000 nl l⁻¹ NH₃ fumigation in open-top chambers (OTCs). Regardless of the level of N in medium, increased NH₃ concentration promoted maximum net photosynthetic rate (P _max) and apparent quantum yield (AQY) of both cultivars at earlier growth stages, but inhibited P _max of NE5 from silking to maturity stage and that of SD19 at maturity stage only above the ambient concentration. Greater positive/less negative responses were predominant in the LN than in the HN treatment, especially for SD19. Dark respiration rate (R _D) remained more enhanced in the LN than in the HN treatment for SD19 as well as increased in the LN while decreased in the HN treatment for NE5 at their silking stage, following exposure to elevated NH₃ concentration. Additionally, enhanced atmospheric NH₃ increased net photosynthetic rate (P _N) and stomatal conductance (g _s) but reduced intercellular CO₂ concentration (C _i) of both cultivars with either the LN or HN treatment during the diurnal period at tasseling stage. The diurnal change patterns of P _N and g _s showed bimodal curve type and those of C _i presented single W-curve type for NE5, when NH₃ concentration was enhanced. As for SD19, single-peak curve type was showed for both P _N and g _s while single V-curve type for C _i. All results supported the hypothesis that appropriately enhanced atmospheric NH₃ can increase assimilation of CO₂ by improving photosynthesis of maize plant, especially at earlier growth stages and after photosynthetic “noon-break” point. These impacts of elevated NH₃ concentration were more beneficial for SD19 as compared to those for NE5, especially in the LN supply environment.     

Novel potent agonist [(pF)Phe4,Aib7,Aib11,Arg14,Lys15]N/OFQ-NH2 and antagonist [Nphe1,(pF)Phe4,Aib7,Aib11,Arg14,Lys15]N/OFQ-NH2 of nociceptin/orphanin FQ receptor

Two novel ligands for the nociceptin/orphanin FQ (N/OFQ) receptor (NOP), [(pF)Phe4,Aib7, Aib11,Arg14,Lys15]N/OFQ-NH2 (peptide-1) and [Nphe1,(pF)Phe4,Aib7,Aib11,Arg14,Lys15]N/OFQ-NH2 (peptide-2), have been generated by combining different modifications of N/OFQ sequence. In the present study, we investigated the actions of two analogues and compared them with those of N/OFQ in four assays. Peptide-1 mimicked N/OFQ effects in mouse vas deferens and mouse colon and showed similar maximal effects but higher potency relative to N/OFQ. The effects of peptide-1 were sensitive to NOP receptor selective antagonist ([Nphe1]N/OFQ(1-13)-NH2) but not to naloxone in vitro. Peptide-1 (25 pmol, i.c.v.) mimicked the pronociceptive action of N/OFQ (2.5 nmol, i.c.v.) in mouse tail withdrawal assay, displaying higher potency and longer lasting effects. In anesthetized rats, peptide-1 (1 nmol/kg, i.v.) produced a marked decrease in mean arterial pressure, which was comparable to that evoked by i.v. N/OFQ (100 nmol/kg). Peptide-2 did not produce any effect per se but antagonized N/OFQ actions in mouse vas deferens and mouse colon assays. Peptide-2 is active in vivo where it prevented the pronociceptive effect induced by 2.5 nmol N/OFQ i.c.v. in the mouse tail withdrawal assay. Furthermore, peptide-2 at 5 nmol produced alone a robust and long lasting antinociceptive effect. Moreover, peptide-2 (10 and 40 nmol/kg i.v.) didn't produce any effect per se but antagonized hypotensive actions produced by i.v. administration of N/OFQ. Collectively, these findings demonstrate that [(pF)Phe4,Aib7,Aib11, Arg14,Lys15]N/OFQ-NH2 behaves as a highly potent NOP receptor agonist which produces long lasting effects in vivo and [Nphe1,(pF)Phe4,Aib7,Aib11,Arg14,Lys15]N/OFQ-NH2 acts as a pure and competitive antagonist of the NOP receptor.     

山西庞泉沟银露梅群落物种多样性的海拔格局

采用样地调查的方法, 对山西庞泉沟银露梅(Potentilla glabra)群落的结构特征、物种多样性随海拔梯度的变化以及沿海拔梯度群落的相似性进行了研究, 并通过R语言对群落α多样性指数间的相关性进行了分析。结果表明: (1) 银露梅群落各层的α多样性指数除生态优势度指数(D)沿海拔梯度的变化不明显外, 其它各指数的变化基本一致。银露梅群落在海拔 1 700-1 900 m与2 100-2 300 m区间内, 灌木层和草本层的α多样性指数均较高, 在海拔1 900-2 000 m区间则较低。另外, 银露梅群落各α多样性指数间除J₂外均呈显著正相关。(2) 随着海拔间隔的增加, 灌木层和草本层的4个β多样性指数的变化均呈上升趋势, 并且草本层随海拔间隔的增加β多样性指数整体比灌木层高。(3) 银露梅群落Jaccard相似性指数随着海拔间隔的增大逐渐减小, 而当海拔达到2 300 m以上时, 群落间的相似性升高, 群落相对稳定。