Coding mutations in NUS1 contribute to Parkinson's disease.

Whole-exome sequencing has been successful in identifying genetic factors contributing to familial or sporadic Parkinson's disease (PD). However, this approach has not been applied to explore the impact of de novo mutations on PD pathogenesis. Here, we sequenced the exomes of 39 early onset patients, their parents, and 20 unaffected siblings to investigate the effects of de novo mutations on PD. We identified 12 genes with de novo mutations (MAD1L1, NUP98, PPP2CB, PKMYT1, TRIM24, CEP131, CTTNBP2, NUS1, SMPD3, MGRN1, IFI35, and RUSC2), which could be functionally relevant to PD pathogenesis. Further analyses of two independent case-control cohorts (1,852 patients and 1,565 controls in one cohort and 3,237 patients and 2,858 controls in the other) revealed that NUS1 harbors significantly more rare nonsynonymous variants (P = 1.01E-5, odds ratio = 11.3) in PD patients than in controls. Functional studies in Drosophila demonstrated that the loss of NUS1 could reduce the climbing ability, dopamine level, and number of dopaminergic neurons in 30-day-old flies and could induce apoptosis in fly brain. Together, our data suggest that de novo mutations could contribute to early onset PD pathogenesis and identify NUS1 as a candidate gene for PD.

[Screening and identification of DPP-4 inhibitors from Xiaokean formula by a fluorescent probe].

Fluorescent bio-probes have attracted increasing attentions in studies for screening bioactive compounds from traditional Chinese medicines. In this study, a new-type fluorescent probe with the function of aggregation-induced emission (AIE) was used to screen dipeptidyl peptidase-4 (DPP-4) inhibitor from Xiaokean formula, which has been clinically used for the treatment of type 2 diabetes mellitus. Potential DPP-4 inhibitors were screened by the fluorescent probe, with diprotin A as the positive control; totally 43 components were isolated from Xiaokean formula by systematic separation. The results showed that 13 components can exert inhibitory effects on DPP-4 activity; 16 compounds were further identified by liquid chromatography-mass spectrometry (LC-MS) from those active components. The inhibitory effects of 14 compounds were further verified, while five of them showed significant inhibition against DPP-4. Salvianolicacid C, ginsenoside Rg5 and timosaponin AI inhibited DPP-4 activity at the concentration of 5-50 µmol•L⁻¹ in a dose-dependent manner. Thus, our study provided a successful example for screening bioactive compounds from traditional Chinese medicines by using a novelfluorescent probe.

Multi-medium distributions of HCHs, DDTs, and PCBs in typical petrochemical industrial area and surrounding regions of Jilin Province, Northeast China.

The levels of DDTs, HCHs and PCBs in topsoil, cereal and irrigation water from typical industrial and agricultural areas of Jilin Province in Northeastern China were evaluated by using gas chromatography coupled with an electron capture detector. The amount of ∑OCPs and ∑(7)PCBs found in topsoils ranged from 24.7 to 98.0 and 17.2 to 98.7 ng g(-1), respectively. The geometric means of ∑HCHs, ∑DDTs and ∑(7)PCBs in rice stem samples were 28.9, 32.4 and 49.0 ng g(-1), respectively. The average level of total OCPs concentration in rice field water in Meihekou area (0.849 ng g(-1)) is higher than that in Jilin area (0.178 ng g(-1)) and all OCPs concentrations in rice field water met the water quality standards for Grade I regulated by China's national environmental quality standard of surface water.

[Detection of respiratory syncytial virus in children with respiratory tract infections by nucleic acid amplification fluorogenic quantitative assay].

OBJECTIVE: Nucleic acid amplification (PCR) fluorogenic quantitative assay is used for the diagnosis of respiratory syncytial virus (RSV) infection. This study was designed to explore the sensitivity of PCR fluorogenic quantitative assay for ascertaining respiratory RSV infection and RSV infection conditions by detecting the presence of RSV-RNA related sequences in children. METHODS: Bronchial and nasopharyngeal secretions specimens from 261 hospitalized children with respiratory tract infections from January 2007 to October 2008 were collected. Respiratory syncytial virus nucleic acid (RNA) in the specimens was measuredby PCR fluorogenic quantitative assay. Blood RSV-IgM was detected by enzyme linked immunosorbent assay (ELISA). The sensitivity for ascertaining respiratory RSV infection was compared between the two assays. RESULTS: The RSV-RNA positive rate ascertained by PCR fluorogenic quantitative assay (38.7%) was significantly higher than blood RSV-IgM positive rate (21.1%) (p<0.01). The RSV-RNA positive rate (43.6%) in children at ages of less than 6 months was significantly higher than that in children at ages of 1 to three years (32.1%) (p<0.01). The RSV-RNA positive rate in children with bronchiolitis (58.5%) was the highest, followed by bronchopneumonia (38.2%) and acute bronchitis (20.0%). CONCLUSIONS: The sensitivity of PCR fluorogenic quantitative assay for ascertaining respiratory RSV infection is higher. RSV is a major pathogen of lower respiratory tract infections in infants and young children. A higher rate of RSV infection is associated with a younger age. RSV infection is the most common in children with bronchiolitis.

[Association of the progress of chronic periodontitis with interleukin-1B-511 genetic polymorphisms].

OBJECTIVE: To study the natural progress of different degree chronic periodontitis and its association with IL-1B-511 genetic polymorphisms. METHODS; 100 subjects with chronic periodontitis were selected and examined at baselined and in the 6 month and in 1 year on attatchment loss at 6 sites of each tooth. DNA samples were obtained with buccal swabbing technique and were further analyzed for IL-1B-511 genotype polymorphisms using PCR-RFLP-based method in all subjects. RESULTS: The mean AL increases were 1.43 mm within 1 year. Among 100 subjects, 16 patients with moderate progression (0 mm < AL increase/a year < or = 1.0 mm), 84 patients with rapid progression of periodontal disease (AL increase/ a year > 1.0 mm). There was no significant difference for the distribution and frequency of IL-1B-511 genotype and alleles between the AL increase/ a year > 1.0 mm group and AL increase/a year < or = 1.0 mm group. The progression of periodontal disease (AL increase/a year > 1.0 mm group) was significantly higher in the non-severe chronic periodontitis group than in the severe group (P < 0.05). The percentage of molar was higher as far as the rapid-progress sites (AL increase > 2.0 mm both in the 6th and the 12th months examination) were concerned than that of premolar and anterior (P < 0.05). The number of progressed sites in the severe group was higher than the non-severe chronic periodontitis group (P < 0.05). CONCLUSION: The progress of chronic periodontits varies individually. No specific relationship was found between the progression of chronic periodontitis and IL-1 gene polymorphisms.