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Genome-Wide Association Study in Thai Tsunami Survivors Identified Risk Alleles for Posttraumatic Stress Disorder  [PDF]
Nuntika Thavichachart, Taisei Mushiroda, Thongchai Thavichachart, Ongart Charoensook, Anchalee Prasansuklab, Prathan Rutchatajumroon, Sookjaroen Tangwongchai, Puangsoi Worakul, Buranee Kanchanatawan, Siriluck Suppapitiporn, Atapol Sughondhabirom, Chutima Roomruangwong, Wasun Chantratita, Atsushi Takahashi, Michiaki Kubo, Naoyuki Kamatani, Yusuke Nakamura
Open Journal of Genetics (OJGen) , 2015, DOI: 10.4236/ojgen.2015.52004
Abstract: Posttraumatic stress disorder (PTSD) is a psychiatric disorder found in individuals afflicted by a traumatic event. Multiple environmental and genetic factors can contribute to PTSD susceptibility. Since it is rare to find members of the same family afflicted by the same catastrophic event, it is not practical to determine PTSD susceptibility genes by a gene linkage analysis. A natural disaster, such as the 2004 Tsunami, provided us with a rare chance for a genetic analysis of PTSD. To identify SNPs associated with PTSD susceptibility, we conducted a genome-association study (GWAS) in Thai-Tsunami survivors. Initial phase of the study with 396 chronic PTSD patients and 457 controls, we identified top ninety SNPs (P < 1 × 10-4), which were further assessed in the second phase with 395 chronic PTSD patients and 798 controls. Two SNPs (rs267950 and rs954406), were identified in the second phase, and subjected to fine mapping using a data set from both phases. SNP rs267943 showed the strongest association with PTSD susceptibility and was in complete linkage disequilibrium with SNP rs267950 with P = 6.15 × 10-8, OR = 1.46 and 95% CI = 1.19 - 1.79, reaching genome-wide significance. SNP rs267943 is located on chromosome 5 in the intron of the death-associated protein 1 (DAP1) gene and, when linked to a synthetic promoter, could regulate transcription. To our knowledge, this is the first GWAS for PTSD susceptibility in an Asian population which could provide an important insight into the genetic contribution of PTSD and may lead to new treatment strategies for PTSD.
Influence of DAP1 Genotype and Psychosocial Factors on Posttraumatic Stress Disorder in Thai Tsunami Survivors: A GxE Approach  [PDF]
Nuntika Thavichachart, Prathan Rutchatajumroon, Taisei Mushiroda, Anchalee Prasansuklab, Sookjaroen Tangwongchai, Puangsoi Worakul, Buranee Kanchanatawan, Siriluck Suppapitiporn, Atapol Sughondhabirom, Chutima Roomruangwong, Ongart Charoensook, Wasun Chantratita, Atsushi Takahashi, Michiaki Kubo, Naoyuki Kamatani, Yusuke Nakamura
Open Journal of Genetics (OJGen) , 2019, DOI: 10.4236/ojgen.2019.93005
Abstract: Background: Posttraumatic Stress Disorder (PTSD) is a psychiatric disorder found in individuals afflicted by a traumatic event including the natural disaster. “Tsunami” occurred in Andaman coast of Thailand on December 26, 2004, in which 33.6% of survivors were diagnosed as PTSD. This study aimed to explore the single nucleotide polymorphism (SNP). rs267943 genotype is located on chromosome 5 in the intron of the death-associated protein 1 (DAP1) gene and psychosocial factors for PTSD. Methods: Participants (N = 1970) were recruited from volunteers who have complete data both of DAP1 gene and psychosocial factor. Results: Using a binary logistic regression model, significant gene-environment interactions were found for the single nucleotide polymorphism (SNP) rs267943 and psychosocial factors including depression (adj. OR = 6.0, 95% CI = 4.29 - 8.39), neurotic personality (adj. OR = 2.73, 95% CI = 2.18 - 3.42), planning (adj. OR = 1.52, 95% CI = 1.20 - 1.93), use of emotional support (adj. OR = 1.32, 95% CI = 1.21 - 1.94) with statistical significant p < 0.001 and self-distraction (adj. OR = 1.52, 95% CI = 1.15 - 1.85) with statistical significant p < 0.05. Conclusion: This study demonstrated that GxE studies can be utilized to shed light on the origins of PTSD.
Research Article Abstracts in Two Related Disciplines: Rhetorical Variation between Linguistics and Applied Linguistics
Watinee Suntara,Siriluck Usaha
English Language Teaching , 2013, DOI: 10.5539/elt.v6n2p84
Abstract: The previous studies on abstracts (e.g., Santos, 1996; Samraj, 2002; Pho, 2008) illustrate that disciplinary variation in research article abstracts is discernible. However, the studies of abstracts from two related disciplines are still limited. The present study aimed to explore the rhetorical moves of abstracts in the fields of linguistics and applied linguistics by investigating 200 abstracts published between 2009-2012. Hyland’s (2000) model of five rhetorical moves was chosen as the analytical framework for the rhetorical structure. Findings indicated that there were three conventional moves in abstracts in linguistics, while there were four conventional moves in abstracts in applied linguistics. The findings have significant pedagogical implications for academic writing for novice writers in the two disciplines.
A Measure of EFL Public Speaking Class Anxiety: Scale Development and Preliminary Validation and Reliability
Kriangkrai Yaikhong,Siriluck Usaha
English Language Teaching , 2012, DOI: 10.5539/elt.v5n12p23
Abstract: The present study contributes to developing a Public Speaking Class Anxiety Scale (PSCAS) to measure anxiety in the EFL public speaking class in the Thai context. Items were adopted from previous scales: Foreign Language Classroom Anxiety Scale (FLCAS) by Horwitz et al. (1986); Personal Report of Communication Apprehension (PRCA-24) and Personal Report of Public Speaking Anxiety (PRPSA-34) by McCroskey (1970); and Speaker Anxiety Scale (SA) by Clevenger and Halvorson (1992) based on their critical appraisals. Some minor changes in wordings of adopted items were made to a preliminary PSCAS and were validated. The preliminary PSCAS yielded an internal consistency of .84 using Cronbach’s alpha coefficient when administered to 76 participants and was factor-analyzed to establish the construct and the final version. The factor analysis revealed that the PSCAS included the components of communication apprehension, test anxiety, fear of negative evaluation, and comfort in using English in a public speaking class.
Thai EFL Students’ Writing Errors in Different Text Types: The Interference of the First Language
Somchai Watcharapunyawong,Siriluck Usaha
English Language Teaching , 2013, DOI: 10.5539/elt.v6n1p67
Abstract: This study aimed at analyzing writing errors caused by the interference of the Thai language, regarded as the first language (L1), in three writing genres, namely narration, description, and comparison/contrast. 120 English paragraphs written by 40 second year English major students were analyzed by using Error Analysis (EA).The results revealed that the first language interference errors fell into 16 categories: verb tense, word choice, sentence structure, article, preposition, modal/auxiliary, singular/plural form, fragment, verb form, pronoun, run-on sentence, infinitive/gerund, transition, subject-verb agreement, parallel structure, and comparison structure, respectively, and the number of frequent errors made in each type of written tasks was apparently different. In narration, the five most frequent errors found were verb tense, word choice, sentence structure, preposition, and modal/auxiliary, respectively, while the five most frequent errors in description and comparison/contrast were article, sentence structure, word choice, singular/plural form, and subject-verb agreement, respectively. Interestingly, in the narrative and descriptive paragraphs, comparison structure was found to be the least frequent error, whereas it became the 10th frequent error in comparison/contrast writing. It was apparent that a genre did affect writing errors as different text types required different structural features. It could be concluded that to enhance students’ grammatical and lexical accuracy, a second language (L2) writing teacher should take into consideration L1 interference categories in different genres.
Serum NGAL to Clinically Distinguish Cholangiocarcinoma from Benign Biliary Tract Diseases
Kawin Leelawat,Siriluck Narong,Jerasak Wannaprasert,Surang Leelawat
International Journal of Hepatology , 2011, DOI: 10.4061/2011/873548
Abstract: Aim. To determine whether the serum level of NGAL can discriminate cholangiocarcinoma from benign biliary tract disease in patients. Methods. This study was performed according to a prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) design. A total of 50 cholangiocarcinoma and 50 benign biliary tract disease cases were randomly selected from a cohort of consecutive cases of biliary tract diseases. Their sera were measured for the levels of NGAL and the widely used serum cholangiocarcinoma marker, carbohydrate antigen 19-9 (CA19-9). Results. The serum CA19-9 and NGAL levels were significantly elevated in cholangiocarcinoma patients (CA19-9: <.001, NGAL: <.001). The area under the curve (AUC) of a receiver operating characteristic (ROC) curve analysis for the diagnosis of cholangiocarcinoma of CA19-9 and NGAL was 0.81 and 0.79, respectively. Conclusion. The diagnostic accuracy of serum NGAL and CA19-9 makes them good candidates for use as biomarkers to discriminate cholangiocarcinoma patients from benign biliary tract disease patients.
A Substitution in the Ligand Binding Domain of the Porcine Glucocorticoid Receptor Affects Activity of the Adrenal Gland
Eduard Murani, Henry Reyer, Siriluck Ponsuksili, Stephan Fritschka, Klaus Wimmers
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0045518
Abstract: Glucocorticoids produced in the adrenal cortex under the control of the hypothalamic-pituitary axis play a vital role in the maintenance of basal and stress-related homeostasis and influence health and well-being. To identify loci affecting regulation of the hypothalamic-pituitary-adrenal (HPA) axis in the pig we performed a genome-wide association study for two parameters of acute and long-term adrenal activity: plasma cortisol level and adrenal weight. We detected a major quantitative trait locus at the position of the glucocorticoid receptor gene (NR3C1) – a key regulator of HPA axis activity. To determine the causal variant(s), we resequenced the coding region of NR3C1 and found three missense single nucleotide polymorphisms (SNPs). SNP c.1829C>T, leading to a p.Ala610Val substitution in the ligand binding domain, showed large (about 0.6× and 1.2× phenotypic standard deviations for cortisol level and adrenal weight, respectively), and highly significant (2.1E-39≤log10(1/p)≤1.7E+0) negative effects on both traits. We were able to replicate the association in three commercial pig populations with different breed origins. We analyzed effects of the p.Ala610Val substitution on glucocorticoid-induced transcriptional activity of porcine glucocorticoid receptor (GR) in vitro and determined that the substitution introduced by SNP c.1829C>T increased sensitivity of GR by about two-fold. Finally, we found that non-coding polymorphisms in linkage disequilibrium with SNP c.1829C>T have only a minor effect on the expression of NR3C1 in tissues related to the HPA axis. Our findings provide compelling evidence that SNP c.1829C>T in porcine NR3C1 is a gain-of-function mutation with a major effect on the activity of the adrenal gland. Pigs carrying this SNP could provide a new animal model to study neurobiological and physiological consequences of genetically based GR hypersensitivity and adrenal hypofunction.
Risk factors for the onset and persistence of neck pain in undergraduate students: 1-year prospective cohort study
Siriluck Kanchanomai, Prawit Janwantanakul, Praneet Pensri, Wiroj Jiamjarasrangsi
BMC Public Health , 2011, DOI: 10.1186/1471-2458-11-566
Abstract: A prospective study was carried out in healthy undergraduate students. At baseline, a self-administered questionnaire and standardized physical examination were used to collect data on biopsychosocial factors. At 3, 6, 9, and 12 months thereafter, follow-up data were collected on the incidence of neck pain. Those who reported neck pain on ≥ 2 consecutive follow-ups were categorized as having persistent neck pain. Two regression models were built to analyze risk factors for the onset and persistence of neck pain.Among the recruited sample of 684 students, 46% reported the onset of neck pain between baseline and 1-year follow-up, of whom 33% reported persistent neck pain. The onset of neck pain was associated with computer screen position not being level with the eyes and mouse position being self-rated as suitable. Factors that predicted persistence of neck pain were position of the keyboard being too high, use of computer for entertainment < 70% of total computer usage time, and students being in the second year of their studies.Neck pain is quite common among undergraduate students. This study found very few proposed risk factors that predicted onset and persistence of neck pain. The future health of undergraduate students deserves consideration. However, there is still much uncertainty about factors leading to neck pain and more research is needed on this topic.Neck pain is common among adults, affecting 14-71% of adults at some point in their lives [1]. Its 1-year prevalence in adults ranges at 16-75% [1]. A substantial 19-37% proportion of neck pain patients will develop chronic neck pain [2,3]. Neck pain causes considerable personal discomfort due to pain, disability, and impaired quality of life, and may affect work. The economic consequences of treating disabling neck pain are significant [4-6]. Bernaard et al [7] recently postulated that the total yearly cost of neck and upper limb symptoms in the Netherlands due to decreased productivity, sick leave, chroni
Inhibition of PI3K increases oxaliplatin sensitivity in cholangiocarcinoma cells
Kawin Leelawat, Siriluck Narong, Wandee Udomchaiprasertkul, Surang Leelawat, Sumalee Tungpradubkul
Cancer Cell International , 2009, DOI: 10.1186/1475-2867-9-3
Abstract: After exposing the cholangiocarcinoma cell lines RMCCA1 and KKU100 to oxaliplatin, the levels of Akt and mTOR phosphorylation increased, as shown by western blot analysis. The WST-1 cell proliferation assay showed increased inhibition of cell growth under high concentrations of oxaliplatin. The combination of oxaliplatin with LY294002, an inhibitor of PI3K, resulted in a remarkable arrest of cell proliferation. Deactivation of mTOR by RAD001 was also synergistic with oxaliplatin, although to a lesser extent. The combination of oxaliplatin and a PI3K inhibitor also resulted in a significant induction of apoptosis, as demonstrated by the TUNEL assay.Activation of PI3K might protect cholangiocarcinoma cells from oxaliplatininduced cytotoxicity. Although the inhibition of PI3K and the inhibition of mTOR both enhance oxaliplatin-induced cytotoxicity, PI3K inhibition has a greater effect. Targeting the PI3K pathway may be a useful approach to improve the chemotherapeutic sensitivity of cholangiocarcinoma.Cholangiocarcinoma is a cancer characterized by early vascular invasion and metastasis. Patients with cholangiocarcinoma are often diagnosed at advanced stage. Threeyear survival rates of 35% to 50% can be achieved only in a subset of patients, who have negative histological margins at the time of surgery [1]. Palliative therapeutic approaches consisting of percutaneous and endoscopic biliary drainage have usually been used for these patients, since there is no effective chemotherapeutic treatment for this type of cancer [2]. A novel agent, oxaliplatin, has been extensively used as chemotherapeutic agent in treating solid tumors [3,4]. Oxaliplatin is a diaminocyclohexane platinum compound that acts like cisplatin to induce DNA adducts formation. Although early studies suggested that oxaliplatin might be used as an active agent against cholangiocarcinoma [5,6], more recent data indicated that cholangiocarcinoma cells were resistant to oxaliplatin [7]. Therefore, elucidatin
Gene expression analysis of mammary tissue during fetal bud formation and growth in two pig breeds – indications of prenatal initiation of postnatal phenotypic differences
Kunsuda Chomwisarutkun, Eduard Murani, Siriluck Ponsuksili, Klaus Wimmers
BMC Developmental Biology , 2012, DOI: 10.1186/1471-213x-12-13
Abstract: The expression of 11,731 probe sets was analysed between the two stages within and among breeds. The analysis showed the largest distinction of samples of the breed GL at 63 dpc from all other samples. According to Ingenuity Pathways Analysis transcripts with abundance at the four comparisons made (GL63-GL91, PI63-PI93, GL63-PI63 and GL91-PI91) were predominantly assigned to biofunctions relevant to `cell maintenance, proliferation, differentiation and replacement′, `organismal, organ and tissue development′ and `genetic information and nucleic acid processing′. Moreover, these transcripts almost exclusively belong to canonical pathways related to signaling rather than metabolic pathways. The accumulation of transcripts that are up-regulated in GL compared to PI indicate a higher proliferating activity in GL, whereas processes related to differentiation, maturation and maintenance of cells are more prominent in PI. Differential expression was validated by quantitative RT-PCR of five genes (GAB1, MAPK9, PIK3C2B, PIK3C3 and PRKCH) that are involved in several relevant signaling pathways.The results indicate that mammary complex development in PI precedes GL. The differential expression between the two breeds at fetal stages likely reflects the prenatal initiation of postnatal phenotypes concerning the number and shape as well as functionality of teats.
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