Different Responses of Two Genes Associated with Disease Resistance Loci in Maize (Zea mays L.) to 3-allyloxy-1,2-benzothiazole 1,1-dioxide

Probenazole (3-allyloxy-1,2-benzothiazole 1,1-dioxide, PBZ) is a bactericide and fungicide that acts by inducing plant defense systems. It has been shown to induce the expression of NBS-LRR genes like RPR1 (rice probenazole-response gene) in rice (Oryza sativa L.) and systemic acquired resistance (SAR)-like disease resistance. Two maize (Zea mays L.) genes Zmnbslrr1 (a NBS-LRR gene, cloned from a disease resistance analog PIC11 based) and Zmgc1 , (a putative guanylyl cyclase-like gene) have both been associated with quantitative resistance loci (QTL) for resistance to Fusarium graminearum . PIC11 was associated with Fusarium stalk rot and ZmGC1 showed resistance to Gibberella ear rot caused by F. graminearum . The objectives of the current study here were to characterize the Zmnbslrr1 gene and to determine whether it and Zmgc1 respond to the inducer PBZ. The transcript abundance of Zmnbslrr1 expression was significantly reduced in corn seedlings of the Gibberella ear rot resistant genotype CO387 48 h after PBZ treatment. In contrast, the transcript abundance of the maize Zmgc1 gene increased more than 10-fold 8h after the treatment. Therefore, the two genes do not appear to be coordinately regulated by PBZ

Sputum YKL-40 Levels and Pathophysiology of Asthma and Chronic Obstructive Pulmonary Disease.

Background: Recent evidence suggests that YKL-40, also called chitinase-3-like-1 protein, is involved in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). Details of sputum YKL-40 in asthma and COPD, however, remain unknown. Objectives: To clarify associations of sputum YKL-40 levels with clinical indices in asthma and COPD. Methods: Thirty-nine patients with asthma, 14 age-matched never-smokers as controls, 45 patients with COPD, and 7 age-matched smokers as controls were recuited for this study. Sputum YKL-40 levels were measured and YKL-40 expression in sputum cells was evaluated by immunocytochemistry. Results: Sputum YKL-40 levels were higher in patients with COPD (346 ± 325 ng/ml) than in their smoker controls (125 ± 122 ng/ml; p < 0.05), but were not significantly different between patients with asthma (117 ± 170 ng/ml) and their controls (94 ± 44 ng/ml; p = 0.15). In patients with asthma only, sputum YKL-40 levels were positively correlated with disease severity (r = 0.34, p = 0.034) and negatively correlated with pre- and postbronchodilator %FEV(1) (r = -0.47 and -0.42, respectively; p < 0.01) and forced mid-expiratory flow (r = -0.48 and -0.46, respectively, p < 0.01). Sputum YKL-40 levels were positively correlated with sputum neutrophil counts in asthma (r = 0.55, p < 0.001) and with neutrophil and macrophage counts in COPD (r = 0.45 and 0.65, respectively, p < 0.01). YKL-40 was expressed in the cytoplasm of sputum neutrophils and macrophages in all groups. Conclusions: Elevated sputum YKL-40 reflects airflow obstruction in asthma whereas the roles of YKL-40 in the proximal airways in COPD remain to be elucidated

Phamacogenomics of Clozapine-Induced Agranulocytosis

Background: Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine. Methods: To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects. Results: We identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 × 10−9, odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 × 10−8, OR = 10.7) and confirmed this association by comparing with an independent clozapine-tolerant control group (n = 380, p = 2.97 × 10−5, OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA. Conclusions: Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated

Consciousness Level and Off‐Hour Admission Affect Discharge Outcome of Acute Stroke Patients: A J‐ASPECT Study

Background-Poor outcomes have been reported for stroke patients admitted outside of regular working hours. However, few studies have adjusted for case severity. In this nationwide assessment, we examined relationships between hospital admission time and disabilities at discharge while considering case severity. Methods and Results-We analyzed 35 685 acute stroke patients admitted to 262 hospitals between April 2010 and May 2011 for ischemic stroke (IS), intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). The proportion of disabilities/death at discharge as measured by the modified Rankin Scale (mRS) was quantified. We constructed 2 hierarchical logistic regression models to estimate the effect of admission time, one adjusted for age, sex, comorbidities, and number of beds; and the second adjusted for the effect of consciousness levels and the above variables at admission. The percentage of severe disabilities/death at discharge increased for patients admitted outside of regular hours (22.8%, 27.2%, and 28.2% for working-hour, off-hour, and nighttime; P<0.001). These tendencies were significant in the bivariate and multivariable models without adjusting for consciousness level. However, the effects of off-hour or nighttime admissions were negated when adjusted for consciousness levels at admission (adjusted OR, 1.00 and 0.99; 95% CI, 1.00 to 1.13 and 0.89 to 1.10; P=0.067 and 0.851 for off-hour and nighttime, respectively, versus working-hour). The same trend was observed when each stroke subtype was stratified. Conclusions-The well-known off-hour effect might be attributed to the severely ill patient population. Thus, sustained stroke care that is sufficient to treat severely ill patients during off-hours is important

Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders

Bipolar disorder (BPD) and major depressive disorder (MDD) are primary major mood disorders. Recent studies suggest that they share certain psychopathological features and common risk genes, but unraveling the full genetic architecture underlying the risk of major mood disorders remains an important scientific task. The public genome-wide association study (GWAS) data sets offer the opportunity to examine this topic by utilizing large amounts of combined genetic data, which should ultimately allow a better understanding of the onset and development of these illnesses. Genome-wide meta-analysis was performed by combining two GWAS data sets on BPD and MDD (19,637 cases and 18,083 controls), followed by replication analyses for the loci of interest in independent 12,364 cases and 76,633 controls from additional samples that were not included in the two GWAS data sets. The single-nucleotide polymorphism (SNP) rs10791889 at 11q13.2 was significant in both discovery and replication samples. When combining all samples, this SNP and multiple other SNPs at 2q11.2 (rs717454), 8q21.3 (rs10103191), and 11q13.2 (rs2167457) exhibited genome-wide significant association with major mood disorders. The SNPs in 2q11.2 and 8q21.3 were novel risk SNPs that were not previously reported, and SNPs at 11q13.2 were in high LD with potential BPD risk SNPs implicated in a previous GWAS. The genome-wide significant loci at 2q11.2 and 11q13.2 exhibited strong effects on the mRNA expression of certain nearby genes in cerebellum. In conclusion, we have identified several novel loci associated with major mood disorders, adding further support for shared genetic risk between BPD and MDD. Our study highlights the necessity and importance of mining public data sets to explore risk genes for complex diseases such as mood disorders

Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders

Bipolar disorder (BPD) and major depressive disorder (MDD) are primary major mood disorders. Recent studies suggest that they share certain psychopathological features and common risk genes, but unraveling the full genetic architecture underlying the risk of major mood disorders remains an important scientific task. The public genome-wide association study (GWAS) data sets offer the opportunity to examine this topic by utilizing large amounts of combined genetic data, which should ultimately allow a better understanding of the onset and development of these illnesses. Genome-wide meta-analysis was performed by combining two GWAS data sets on BPD and MDD (19,637 cases and 18,083 controls), followed by replication analyses for the loci of interest in independent 12,364 cases and 76,633 controls from additional samples that were not included in the two GWAS data sets. The single-nucleotide polymorphism (SNP) rs10791889 at 11q13.2 was significant in both discovery and replication samples. When combining all samples, this SNP and multiple other SNPs at 2q11.2 (rs717454), 8q21.3 (rs10103191), and 11q13.2 (rs2167457) exhibited genome-wide significant association with major mood disorders. The SNPs in 2q11.2 and 8q21.3 were novel risk SNPs that were not previously reported, and SNPs at 11q13.2 were in high LD with potential BPD risk SNPs implicated in a previous GWAS. The genome-wide significant loci at 2q11.2 and 11q13.2 exhibited strong effects on the mRNA expression of certain nearby genes in cerebellum. In conclusion, we have identified several novel loci associated with major mood disorders, adding further support for shared genetic risk between BPD and MDD. Our study highlights the necessity and importance of mining public data sets to explore risk genes for complex diseases such as mood disorders