Assessment of gene-covariate interactions by incorporating covariates into association mapping

The HLA region is considered to be the main genetic risk factor for rheumatoid arthritis. Previous research demonstrated that HLA-DRB1 alleles encoding the shared epitope are specific for disease that is characterized by antibodies to cyclic citrullinated peptides (anti-CCP). In the present study, we incorporated the shared epitope and either anti-CCP antibodies or rheumatoid factor into linkage disequilibrium mapping, to assess the association between the shared epitope or antibodies with the disease gene identified. Incorporating the covariates into the association mapping provides a mechanism 1) to evaluate gene-gene and gene-environment interactions and 2) to dissect the pathways underlying disease induction/progress in quantitative antibodies

Splint therapy for disc displacement with reduction of the temporomandibular joint. Part I: Modified mandibular splint therapy

AbstractThe aims of this preliminary study were to present a modified mandibular splint together with a treatment regimen and to evaluate their effects on the treatment of reciprocal joint sounds of the temporomandibular joint (TMJ). The study participants were recruited from 312 consecutive patients in the temporomandibular disorder clinic of a medical center in Taiwan from January 2003 to December 2003. From among these, 59 cases with typical reciprocal clicking were selected for this study. All participants were treated with a modified mandibular splint and then followed up for 6 months. Successful treatment was defined as leading to the disappearance of the joint sounds of TMJ, as described by patients. Based on clinical evaluation, the overall success rate was 71.2% (42/59) with minimal temporary complications. Patients with clicking at less than 3.5cm of interincisal opening had a success rate of 92.5%, which was higher than the success rate of patients with clicking at a mouth opening of 3.5cm or more. This study showed that a modified mandibular splint can be used to treat reciprocal clicking of the TMJ effectively and encouraged us to conduct further study on the efficacy of this splint to treat disc displacement with reduction of TMJ using magnetic resonance imaging examination

Predicting customer lifetime value for hypermarket private label products

This study develops a model to predict customer lifetime value for hypermarket private label products. It examines the relationships among store awareness, store image variables (i.e., service quality, price/value, convenience, and product quality), private label image, repurchase intention, and customer lifetime value and investigates the moderating role of image fit. The originality of this study lies in filling the gap of previous research on antecedents of private label customers’ behavior by considering store awareness, image fit, and customer lifetime value. Partial least squares structural equation modeling was used to analyze data. The results indicate the following. Store image variables (except product quality) and store awareness affect repurchase intention directly or indirectly through private label image. Image fit moderates the relationships between store image variables (except product quality) and private label image. Private label image facilitates customer lifetime value. This study provides several theoretical and practical implications for hypermarket private label product developments

Melatonin acts synergistically with pazopanib against renal cell carcinoma cells through p38 mitogen-activated protein kinase-mediated mitochondrial and autophagic apoptosis

Background Mounting evidence indicates that melatonin has possible activity against different tumors. Pazopanib is an anticancer drug used to treat renal cell carcinoma (RCC). This study tested the anticancer activity of melatonin combined with pazopanib on RCC cells and explored the underlying mechanistic pathways of its action. Methods The 786-O and A-498 human RCC cell lines were used as cell models. Cell viability and tumorigenesis were detected with the MTT and colony formation assays, respectively. Apoptosis and autophagy were assessed using TUNEL, annexin V/propidium iodide, and acridine orange staining with flow cytometry. The expression of cellular signaling proteins was investigated with western blotting. The in vivo growth of tumors derived from RCC cells was evaluated using a xenograft mouse model. Results Together, melatonin and pazopanib reduced cell viability and colony formation and promoted the apoptosis of RCC cells. Furthermore, the combination of melatonin and pazopanib triggered more mitochondrial, caspase-mediated, and LC3-II-mediated autophagic apoptosis than melatonin or pazopanib alone. The combination also induced higher activation of the p38 mitogen-activated protein kinase (p38MAPK) in the promotion of autophagy and apoptosis by RCC cells than melatonin or pazopanib alone. Finally, tumor xenograft experiments confirmed that melatonin and pazopanib cooperatively inhibited RCC growth in vivo and predicted a possible interaction between melatonin/pazopanib and LC3-II. Conclusion The combination of melatonin and pazopanib inhibits the growth of RCC cells by inducing p38MAPK-mediated mitochondrial and autophagic apoptosis. Therefore, melatonin might be a potential adjuvant that could act synergistically with pazopanib for RCC treatment

Secondary Metabolites from the Leaves of Aquilaria agallocha

Twelve compounds, including three flavonoids, 5-hydroxy-4¢,7- dimethoxyflavone (1) [22], luteolin-7,3¢,4¢-trimethyl ether (2) and 5,3¢- dihydroxy-7,4¢-dimethoxyflavone (3), five benzenoids, methylparaben (4), vanillic acid (5), p-hydroxybenzoic acid (6), syringic acid (7), and isovanillic acid (8) and four steroids, b-sitosterol (9), stigmasterol (10), b-sitostenone (11) and stigmasta-4,22-dien-3- one (12) were isolated from the leaves of Aquilaria agallocha (Thymelaeaceae). All of these compounds (1-12) were obtained for the first time from the leaves of this plant

Chromosome Walking in the Petunia Inflata Self-Incompatibility ( S -) Locus and Gene Identification in an 881-kb Contig Containing S 2 -RNase

Self-incompatibility (SI) in the Solanaceae, Rosaceae and Scrophulariaceae is controlled by the polymorphic S locus, which contains two separate genes encoding pollen and pistil determinants in SI interactions. The S-RNase gene encodes the pistil determinant, whereas the pollen determinant gene, named the pollen S gene, has not yet been identified. Here, we set out to construct an integrated genetic and physical map of the S locus of Petunia inflata and identify any additional genes located at this locus. We first conducted chromosome walking at the S 2 locus using BAC clones that contained either S 2 -RNase or one of the nine markers tightly linked to the S locus. Ten separate contigs were constructed, which collectively spanned 4.4 Mb. To identify additional genes located at the S 2 locus, a 328-kb region (part of an 881-kb BAC contig) containing S 2 -RNase was completely sequenced. Approximately 76% of the region contained repetitive sequences, including transposon-like sequences. Other than S 2 -RNase , an F-box gene, named PiSLF 2 ( S 2 -allele of P. inflata S -locus F-box gene), was the only predicted gene whose deduced amino acid sequence was similar to the sequences of known proteins in the database. Two different cDNA selection methods were used to identify additional genes in the 881-kb contig; 11 groups of cDNA clones were identified in addition to those for S 2 -RNase and PiSLF 2 . RT-PCR analysis of expression profiles and PCR analysis of BAC clones and genomic DNA confirmed that seven of these 11 newly identified genes were located in the 881-kb contig.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43454/1/11103_2004_Article_DO00000142.pd

Metabolic syndrome and abdominal fat are associated with inflammation, but not with clinical outcomes, in peritoneal dialysis patients

BACKGROUND: In the general population, metabolic syndrome (MetS) is correlated with visceral fat and a risk factor for cardiovascular disease (CVD); however, little is known about the significance of abdominal fat and its association with inflammation and medication use in peritoneal dialysis (PD) patients. We investigated the relationship of visceral fat area (VFA) with C-reactive protein (CRP) levels and medication use in PD patients and followed their clinical outcomes. METHODS: In a prospective study from February 2009 to February 2012, we assessed diabetes mellitus (DM) status, clinical and PD-associated characteristics, medication use, CRP levels, components of MetS, and VFA in 183 PD patients. These patients were categorized into 3 groups based on MetS and DM status: non-MetS (group 1, n = 73), MetS (group 2, n = 65), and DM (group 3, n = 45). VFA was evaluated by computed tomography (CT) and corrected for body mass index (BMI). RESULTS: Patients in group 1 had smaller VFAs than patients in groups 2 and 3 (3.2 ± 1.8, 4.6 ± 1.9, and 4.9 ± 2.0 cm(2)/[kg/m(2)], respectively, P < 0.05) and lower CRP levels (0.97 ± 2.31, 1.27 ± 2.57, and 1.11 ± 1.35 mg/dL, respectively, P < 0.05). VFA increased with the number of criteria met for MetS. After adjusting for age, body weight, and sex, CRP and albumin levels functioned as independent positive predictors of VFA; on other hand, the use of renin-angiotensin system blockers was inversely correlated with VFA in PD patients without DM. In the survival analysis, DM patients (group 3) had the poorest survival among the 3 groups, but no significant differences were found between groups 1 and 2. CONCLUSION: This study showed that VFA and MetS are associated with CRP levels but cannot predict survival in PD patients without DM. The complex relationship of nutritional parameters to VFA and MetS may explain these results. The type of antihypertensive medication used was also associated with the VFA. The mechanisms behind these findings warrant further investigation

Imaging Neurovascular Function and Functional Recovery after Stroke in the Rat Striatum Using Forepaw Stimulation

Negative functional magnetic resonance imaging (fMRI) response in the striatum has been observed in several studies during peripheral sensory stimulation, but its relationship between local field potential (LFP) remains to be elucidated. We performed cerebral blood volume (CBV) fMRI and LFP recordings in normal rats during graded noxious forepaw stimulation at nine stimulus pulse widths. Albeit high LFP–CBV correlation was found in the ipsilateral and contralateral sensory cortices (r=0.89 and 0.95, respectively), the striatal CBV responses were neither positively, nor negatively correlated with LFP (r=0.04), demonstrating that the negative striatal CBV response is not originated from net regional inhibition. To further identify whether this negative CBV response can serve as a marker for striatal functional recovery, two groups of rats (n=5 each) underwent 20- and 45-minute middle cerebral artery occlusion (MCAO) were studied. No CBV response was found in the ipsilateral striatum in both groups immediately after stroke. Improved striatal CBV response was observed on day 28 in the 20-minute MCAO group compared with the 45-minute MCAO group (P<0.05). This study shows that fMRI signals could differ significantly from LFP and that the observed negative CBV response has potential to serve as a marker for striatal functional integrity in rats