[Effects of the Transformation from Natural Alpine Grassland to Mixed Artificial Grassland on the Characteristics of Soil Microbial Community].

This study aimed to analyze the effects of the transformation from natural alpine grassland (NAG) to mixed artificial grassland (MAG) on the characteristics of soil microbial community. We used Illumina Miseq high-throughput sequencing technology to investigate the soil microbial community of natural grassland and mixed artificial grassland. The results showed that plant diversity and the content of soil organic matter decreased significantly from NAG to MAG. In total, 29 and 11 phyla bacteria and fungi were detected, respectively. Compared with that in NAG, the Shannon indexes of the bacterial community increased significantly in MAG (from 9.51 to 9.89), whereas these differences were not significant between the NAG and MAG fungal community. The structure and composition of the soil microbial community showed significant differences between NAG and MAG. In addition, Mantel test results suggested that soil total organic matter, total nitrogen, and soil moisture were significantly correlated with variations in the bacterial community, and soil total organic matter and soil moisture were significantly correlated with variations in fungal community. The results of linear discriminant analysis (LEfSe) indicated that Atribacteria and Ascomycota microorganisms could be considered as the indicator groups for NAG, whereas Gemmata and Trichocomaceae microorganisms could be considered as the indicator groups for MAG. Tax4Fun2 results showed that the transition from NAG to MAG affected the utilization of different carbon sources by bacteria.

Twins methods quantitatively explore the genetic impact on children and adolescents brain gray matter volume.

The gray matter volumes of 58 pairs of twins ranging in age from 12 to 18 were measured by MRI to explore the genetic and environmental impacts on gray matter volume in twin children and adolescents. By means of A/C/E structural equation modeling, it was found that the gray matter volume in children and adolescents was jointly affected by genetic (A: 0.89) and environmental factors while genetic factors play a greater role. The gray matter volume in frontal lobe, parietal lobe, occipital lobe and lateral temporal lobe was mainly affected by genetics (A: 0.7-0.89), where as the gray matter volume in medial temporal lobe and cingulate cortex was affected by both genetics and environment.

[Effect of Risperidone on BDNF-TrkB Signaling Pathway in Rat Brain].

OBJECTIVE: To investigate the effect of risperidone on the expression of brain-derived neurotrophic factor (BDNF) and its receptors, tyrosine kinase receptor (TrkB) and P75 neurotrophin receptor (P75NTR) in rat brain. METHODS: Sixteen SD rats were divided into two groups (n = 8 for each group). The rats in experimental group were treated with risperidone [0.25 mg/(kg · d)] for 14 d, while the control group was given placebo. Total RNA sample in prefrontal cortex, temporal cortex and hippocampus was extracted, and the expression of BDNF, TrkB and P75NTR mRNA were determined by quantitative real-time PCR. RESULTS: The treatment of risperidone significantly up-regulated the expressions of BDNF and TrkB in prefrontal cortex, temporal cortex and hippocampus, while the expression of P75NTR was not significantly changed. CONCLUSION: Risperidone upregulated BDNF-TrkB signaling, but not BDNF-P75NTR signaling, which may be helpful for the further pharmacological study of risperidone.

Activated protease receptor-2 induces GATA6 expression to promote survival in irradiated colon cancer cells.

BACKGROUND AND AIMS: The resistance to irradiation is common and a great drawback in the treatment of cancer with radiotherapy; the underlying mechanism is unclear. GATA binding protein 6 (GATA6) is associated with the pathogenesis of cancer. This study aims to investigate the role of GATA6 on compromising irradiation effect on HT55 and HT29 cells, 2 colorectal cancer cell lines. METHODS: Human colon cancer cell lines, HT55 and HT29 cells, were treated with irradiation in the culture. Apoptosis of HT55 and HT29 cells was determined by flow cytometry. The expression of PAR2 and GATA6 in HT55 and HT29 cells was analyzed by real time RT-PCR and Western blotting. The gene silence and gene over expression were employed to observe the effect of GATA6 on p53 expression in HT55 and HT29 cells. RESULTS: The results showed that HT55 and HT29 cells expressed protease-activated receptor-2 (PAR2). Irradiation induced 38.6% HT55 cell and 33.8% HT29 cell apoptosis, which reduced to 4.2% and 5.6%, respectively after activation of PAR2. Exposure to irradiation increased the expression of GATA6; the latter played a critical role in suppression of p53 expression in HT55 and HT29 cells. Inhibition of GATA6 significantly increased the effect of irradiation on HT55 and HT29 cells. CONCLUSIONS: Activation of PAR2 compromises the effect of irradiation on inducing colorectal cancer cell apoptosis, which can be prevented by inhibition of GATA6 expression.

Polymorphisms of genes in neurotransmitter systems were associated with alcohol use disorders in a Tibetan population.

Studies of linkage and association in various ethnic populations have revealed many predisposing genes of multiple neurotransmitter systems for alcohol use disorders (AUD). However, evidence often is contradictory regarding the contribution of most candidate genes to the susceptibility of AUD. We, therefore, performed a case-control study to investigate the possible associations of genes selected from multiple neurotransmitter systems with AUD in a homogeneous Tibetan community population in China. AUD cases (N = 281) with an alcohol use disorder identification test (AUDIT) score ≥10, as well as healthy controls (N = 277) with an AUDIT score ≤5, were recruited. All participants were genotyped for 366 single nucleotide polymorphisms (SNPs) of 34 genes selected from those involved in neurotransmitter systems. Association analyses were performed using PLINK version 1.07 software. Allelic analyses before adjustment for multiple tests showed that 15 polymorphisms within seven genes were associated with AUD (p<0.05). After adjustment for the number of SNPs genotyped within each gene, only the association of a single marker (rs10044881) in HTR4 remained statistically significant. Haplotype analysis for two SNPs in HTR4 (rs17777298 and rs10044881) showed that the haplotype AG was significantly associated with the protective effect for AUD. In conclusion, the present study discovered that the HTR4 gene may play a marked role in the pathogenesis of AUD. In addition, this Tibetan population sample marginally replicated previous evidence regarding the associations of six genes in AUD.

Cortical surface area correlates with STON2 gene Ser307Pro polymorphism in first-episode treatment-naïve patients with schizophrenia.

BACKGROUND: Evidence shows that STON2 gene is associated with synaptic function and schizophrenia. This study aims to explore the relationship between two functional polymorphisms (Ser307Pro and Ala851Ser) of STON2 gene and the cortical surface area in first-episode treatment-naïve patients with schizophrenia and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: Magnetic resonance imaging of the whole cortical surface area, which was computed by an automated surface-based technique (FreeSurfer), was obtained from 74 first-episode treatment-naïve patients with schizophrenia and 55 healthy controls. Multiple regression analysis was performed to investigate the effect of genotype subgroups on the cortical surface area. A significant genotype-by-diagnosis effect on the cortical surface area was observed. Pro-allele carriers of Ser307Pro polymorphism had larger right inferior temporal surface area than Ser/Ser carriers in the patients with schizophrenia; however, no significant difference was found in the same area in the healthy controls. The Ala851Ser polymorphism of STON2 gene was not significantly associated with the cortical surface area in patients with schizophrenia and healthy controls. CONCLUSIONS/SIGNIFICANCE: The present study demonstrated that the functional variant of the STON2 gene could alter cortical surface area on the right inferior temporal and contribute to the pathogenesis of schizophrenia.

[Genome-wide linkage scan for an ethnic Han Chinese pedigree affected with schizophrenia].

OBJECTIVE: To perform genome-wide linkage analysis for an ethnic Han Chinese pedigree with schizophrenia in order to locate the susceptibility genes. METHODS: Genomic DNA was extracted from 4 mL of peripheral blood using conventional phenol-chloroform method. Illumina Infinium Linkage 24 BeadChips chip was used for determining the genotypes through detection of single nucleotide polymorphisms (SNPs). After processing the raw data using Illumina BeadStudio software, two-point nonparametric linkage analysis and two-point parametric linkage analysis were performed with Merlin software. RESULTS: By two-point nonparametric linkage analysis, 27 sites with high LOD scores (LOD=0.63-0.75, P U+003C 0.05) were identified. Among these, 3 SNPs(rs993694, rs992690 rs1861577) were located in 12p12.3 region, whilst the remainders were located in 4p12-q22 region. Two-point parametric linkage analysis under a dominant model has yielded almost identical results. CONCLUSION: Chromosomal regions 4p12-q22 and 12p12.3 probably contain susceptibility genes for schizophrenia.

[Association study of the 5-HTT polymorphism and posttraumatic stress disorder in adolescents].

OBJECTIVE: To study the association between 5-HTTVNTR polymorphism and posttraumatic stress disorder (PTSD) in Chinese Han adolescents after the Wenchuan Earthquake, and investigation of the genetic mechanism of PTSD. METHODS: Polymerase chain reaction (PCR) was used to detect the distributive frequency of 5-HTTVNTR polymorphism of 236 PTSD patients (patient group) and 234 normal people (control group), Plink version 1.07 was used to analyze the genotyping results. RESULTS: The frequency of 5-HTTVNTR allele 12 in PTSD group was significantly higher than control group (93.2% vs. 88.9%, chi2 = 5.42, P = 0.020). The 12/12 genotype in PTSD group and control group was 88.1% and 79.7%; 10/12 genotype was 10.2% and 19.6%; 10/10 genotype was 1.7% and 1.7%. The distributive frequency of all three genotypes (12/12, 10/12, 10/10) showed statistically significant (P = 0.023). CONCLUSION: The allele 12 of 5-HTTVNTR may increase the risk of PTSD in Chinese Han adolescents, 12/12 genotype may be the susceptibility gene, and heterozygote 10/12 may act as the protective factor of PTSD.

[Association study of NOS1 gene polymorphisms and schizophrenia].

OBJECTIVE: To assess the association between nitric oxide synthase 1 (NOS1) gene polymorphisms and schizophrenia. METHODS: Twenty eight tag single nucleotide polymorphisms (SNPs) of NOS1 in 382 schizophrenic patients and 448 healthy individuals sampled from Chinese Han population were analyzed by a Illumina GoldenGate Genotyping Assay. RESULTS: One SNP (rs1520811) was found to be associated with schizophrenia, which however becomes negative after Bonferroni correction (P>0.05). Further analysis has failed to identify any association between particular haplotypes and the disease. CONCLUSION: Our results did not support a significant association between NOS1 gene polymorphisms and schizophrenia.

[Genome-wide association study with memory measures as a quantitative trait locus for schizophrenia].

OBJECTIVE: To assess the association between gene polymorphisms and memory function through a genome-wide association study (GWAS) of schizophrenia and control group. Memory cognition was used as a quantitative trait (QT). METHODS: Ninty-eight subjects with chronic schizophrenia and 60 matched controls were genotyped with HumanHap660 Bead Array. The results were correlated with quantitative traits including memory and memory delay. RESULTS: Five candidate genes, including RASGRF2 (rs401758, P = 8.03×10(-5)), PLCG2 (rs7185362, P= 4.54×10(-5)), LMO1 (rs484161, P=9.80×10(-7), CSMD1 (rs2469383, P= 2.77×10(-6)) and PRKG1 (rs7898516, P=6.94×10(-5)) were associated with memory cognition deficits. CONCLUSION: Using memory cognition as a quantitative trait, this Genome- wide association study has identified 5 susceptibility loci. With their association with nervous system development, neuronal growth, axon guidance and plasticity, brain development, above loci may play a role in the development of memory dysfunction in schizophrenia.

Gender-specific interactions between alcohol metabolism genes and severity of quantitative alcohol-related-traits in a Tibetan population.

Association between genes influencing alcohol metabolism and alcohol use disorders (AUD) has been extensively studied, but the effect of interactions between these genes and AUD have rarely been tested. Our previous case-control study in a Tibetan population noted that the positive association between c2 allele of cytochrome P4502E1 (CYP2E1) gene and AUD might only exist in males who are homozygotes for 1 alleles of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B) genes, but this interaction did not reach statistical significance. Using the same set of data, the present study was aimed at exploring interactions between these genes and quantitative alcohol-related-trait scores (QARTs), and whether these are influenced by gender. The sample included 383 AUD cases with the alcohol use disorders identification test (AUDIT) score ≥10 and 350 normal controls with the AUDIT score ≤5. QARTs were measured using three factors from AUDIT. Possible associations of QARTs with interactions among genotypes of ALDH2 1/ 2, ADH1B1/2 and CYP2E1 c1/c2 and sex were analyzed in AUD cases and normal controls separately. The subjects with 2 alleles of ALDH2 or/and ADH1B had significantly lower scores of alcohol intake among controls but had significantly higher scores of alcohol related problems among cases. The score of alcohol intake in male cases who are homozygous for ALDH2 1 and ADH1B 1 and with CYP2E1 c2 allele was significantly higher than that of other cases. These findings suggest that interactions between genes influencing alcohol metabolism are influenced by gender and might affect QARTs differently between the milder-/non-drinkers and AUD cases.

[The effect of genetic and environmental factors on externalizing behaviors of twin children].

OBJECTIVE: To explore the effect of genetic and environmental factors on externalizing behaviors of children. METHODS: A total of 168 twin pairs aged 6-16 years were recruited. Their parents completed Achenbach Child Behavior Checklist (CBCL) to evaluate the children's externalizing behaviors. The parents also completed FACESII-CV and GHQ-12 to assess their family environment. Structural equation modeling was performed to evaluate the effects of additive genetic factors (A), common environmental factors (C) and individual-specific environmental factors (E) on the externalizing behaviors. RESULTS: The effect of A, C, and E on externalizing behaviors were 0.39 (95% CI: 0.22-0.62), 0.51 (95% CI: 0.28-0.67), and 0.10 (95% Cl: 0.07-0.15), respectively. Significant correlations were found between the children's externalizing behaviors and the total GHQ-12 scores of their fathers and mothers (r = 0.24, P < 0.05; r = 0.30, P < 0.05). The externalizing behaviors were also correlated with family adaptability (r = 0.27, P< 0.01). The logistic regression identified mother's habits, such as smoking and drinking as risk factors of their children's externalizing behaviors. CONCLUSION: Externalizing behaviors are mainly affected by shared environmental factors. Externalizing behaviors are related to general mental health of fathers and mothers and the family adaptability.

[A twin study on intelligence and processing speed heritability of children and adolescent].

OBJECTIVE: To explore the effects of the genetic and environmental factors on intelligence of children and adolescent from the Southwest China Prospective Twin Registry (SCPT). METHODS: The intelligence was investigated by using the Wechsler Intelligence Scale for Children (C-WISC) in 333 twin pairs aged 6-16 years. The effects of genetic and environmental factors on IQ were analyzed by using structural equation modeling (SEM) and correlation analysis method. The effects in different sex and age groups in this population were also investigated. RESULTS: Genetic influence accounted for 0.43 of total IQ variance and 0.37 of verbal IQ in 6-16 years old children and adolescent, but there was no significant genetic effect on performance IQ. The heritability of children aged 10-16 years was higher than that of those aged 6-10 years (total IQ: 0.82 vs 0.00, verbal IQ: 0.80 vs 0.00, performance IQ:0.51 vs 0.00). In males the heritability of verbal IQ (0.47) was higher than that in females (0.05). The shared environmental influences accounted fo r the majority of variance of performance IQ in both males and females. CONCLUSION: There is moderate heritability on the total IQ and verbal IQ, while shared environmental factors played important roles on the variance of performance IQ. The heritability of IQ, verbal IQ and performance IQ are higher in older children and adolescent than that in younger children.

[Expression of Toll-like receptors in thymus of myasthenia gravis patients].

OBJECTIVE: To investigate the expression of Toll-like receptors (TLRs) in thymus of myasthenia gravis (MG) patients and the relationship with clinical features. METHODS: Thymic specimens of 36 patients received extended thymectomy for MG were divided into three groups by pathological type: 13 thymoma tissues (thymoma group) and 13 thymic tissues adjacent to thymomas (parathymoma group) from 13 cases of MG patients with thymomas, and 23 thymic tissues from MG patients without thymomas (MG nonthymoma group). Twenty-one normal thymic specimens from cardiac surgery were used as controls. The levels of TLR2-4 mRNA were examined by RT-PCR, then the levels of TLR4 mRNA were assayed by real time RT-PCR and their relationship with clinical features were analyzed. RESULTS: The levels of TLR4 mRNA among the different groups had significant differences, while there was no difference in TLR2 and TLR3 levels. The real time RT-PCR showed that the level of TLR4 mRNA in nonthymoma group was significantly higher than that in control group(0.8544+/- 0.1200 vs 0.6851+/- 0.1524, P=0.018). And so is parathymoma group compared with the thymoma group (0.8214+/- 0.1019 vs 0.7101+/- 0.0916, P=0.005). No significant difference of TLR4 mRNA level was found between the parathymoma and nonthymoma groups. Nevertheless, the expression of TLR4 in both groups was increased compared with control group. The levels of TLR4 mRNA had positive correlation with Osserman type(R=0.609; P=0.004) . CONCLUSION: TLR4 may play a key role in the pathogenesis of MG. It was the thymic tissues adjacent to thymomas but not thymomas themselves participated in the onset of MG.

Functional polymorphism of CYP2E1 gene and alcohol use disorders in a Tibetan population.

OBJECTIVE: To investigate the relationship between the CYP2E1*c1/*c2 polymorphism and alcohol use disorders, and the potential influence of the CYP2E1*c1/*c2 polymorphism on the severity and dimensions of alcohol use disorders in Tibetan. METHODS: Three hundred and forty Tibetans with Alcohol Use Disorders Identification Test (AUDIT) score >or=10 and another 315 matched control subjects with AUDIT score

[Examining the comorbidity of attention deficit and hyperactivity disorder and conduct disorder in a population-based twin sample].

OBJECTIVE: To examine three possible causes of the relationship between attention deficit and hyperactivity disorder and conduct disorder: additive genetic factors(A), common environmental factors(C) and individual-specific environmental factors(E). METHODS: One hundred and forty pairs of twins from the Southwestern China Twin Registry were examined with the parent-rated Strength and Difficulties Questionnaire (SDQ). The cross-twin within-variable, within-twin cross-variable and cross-twin cross-variable correlations were calculated. Using structural equation modelling, bivariate models were fitted. The best fitting model was chosen based on likelihood and parsimony. RESULTS: The observed phenotypic correlation between HYPER and COND was 0.44 (95% CI: 0.09, 0.27), with genetic factors accounting for about 70% of the observed correlation. Bivariate model fitting quantified the genetic correlation between HYPER and COND at 0.76 (95% CI: 0.31, 1) and the individual-specific environmental correlation at 0.28 (95% CI: 0.02, 0.51). CONCLUSION: In children, three different genetic factors may exist: one that solely affects the liability to hyperactivity behaviour, one that has only an effect on conduct behaviour and one that influences both hyperactivity and conduct behaviour. Our results suggests that most of the environmental factors that increase the risk of hyperactivity behaviour do not influence conduct behaviour and vice versa.

[Association analysis of the parkin gene in patients with sporadic Parkinson's disease from a Han population of Sichuan province].

OBJECTIVE: To determine whether there are any associations between the -258T/G polymorphism of the promoter and the IVS3 -20T/C polymorphism in parkin gene and Parkinson's disease (PD) from a Han population in Sichuan province. METHODS: Polymerase chain reaction (PCR), restriction fragment length polymorphism, denaturing high performance liquid chromatography(dHPLC) and sequence analysis were used to determine the genotype of each subject. The -258T/G polymorphism and IVS3 -20T/C polymorphism were analysed in 198 patients with sporadic PD and 187 healthy controls, matched for age and gender. RESULTS: There were significant differences in allele frequency of the -258T/G polymorphism between PD patients and controls, with the G allele more common in cases than controls (52.5% vs 43.3%; chi square is 6.17, P< 0.025, OR is 1.45, 95% CI 1.04-1.86). There were also significant differences in G allele frequency between PD patients with onset age over 50 years old and controls(chi square is 9.048, P< 0.01, OR is 1.57, 95% CI:1.08-2.06). The frequency of TG+GG genotype was significantly higher in PD patients than in controls (78.79% vs 69.51%; chi square is 3.854, P< 0.05, OR is 1.63, 95% CI:0.88-2.38). In addition, there were significant differences in age of onset between PD patients with different genotypes (P< 0.05). The average age of onset in group of GG genotype was later about 5 years compared with the group of TT or TG genotype. The frequency of CC genotype in IVS3 -20T/C polymorphism was much higher than that of TC genotype. No TT genotype was found. CONCLUSION: This study suggests that the parkin promoter -258T/G polymorphism might be a risk factor for late onset PD in Sichuan. CC genotype for IVS3 -20T/C polymorphism is common in Sichuan Han population. No TT genotype for IVS3 -20T/C polymorphism is found in Sichuan Han population.

[Gln192Arg polymorphism of the paraoxonase-1 gene is not associated with Alzheimer's disease in Chinese].

OBJECTIVE: To explore the relationship between paraoxonase-1 (PON1) gene Gln192Arg polymorphism and sporadic Alzheimer's disease (AD) in Chinese. METHODS: A total of 165 AD patients and 174 age-matched control subjects were enrolled in this study for examination of PON1 Gln192Arg and apolipoprotein E gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The distribution of PON1 allelic and genotypic frequencies did not significantly differ between AD patients and the control subjects, even after the stratification by ApoE-epsilon4 status. CONCLUSION: Gln192Arg polymorphism of the PON1 gene is not associated with sporadic AD in Chinese.