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The contributing genetic factors of vertigo remain poorly characterized, particularly in individuals of non-European ancestries. Here we show the genetic landscape of vertigo in an Asian population-based cohort. In a two-stage genome-wide association study (N case = 6199; N control  = 54,587), we identify vertigo-associated genomic loci in DROSHA and ZNF91/LINC01224, with the latter replicating the findings in European ancestries. Gene-based association testing corroborates these findings. Interestingly, both genes are enriched in cerebellum, a key structure receiving sensory input from the vestibular system. Subjects carrying risk alleles from lead SNPs of DROSHA and ZNF91 incur a 1.74-fold risk of vertigo than those without. Moreover, composite clinical-polygenic risk scores allow differentiation between patients and controls, yielding an area under receiver operating characteristic curve of 0.69. This study identified novel genomic loci for vertigo in an Asian population-based cohort, which may help identifying high risk subjects and provide mechanistic insight in understanding the pathogenesis of vertigo., (© 2024. The Author(s).)

Kiwiberry ( Actinidia arguta ) is a perennial fruit tree belonging to the family Actinidiaceae. Kiwiberries are known to have an extremely high concentration of sugars, phenolics, flavonoids, and vitamin C, and possess delicious taste and health-promoting properties. Numerous studies have focused on kiwiberry fruits, demonstrating that they possess a higher phytochemical content and greater antioxidant activities than other berry fruits. The purpose of this study was to compare the phytochemical content and antioxidant potential of leaf, stem, root, and fruit extracts from twelve kiwiberry cultivars grown in Wonju, Korea, characterized by a Dwa climate (Köppen climate classification). In most kiwiberry cultivars, the total phenolic (TPC) and total flavonoid (TFC) phytochemical content was significantly higher in leaf and stem tissues, while the roots exhibited higher antioxidant activity. In fruit tissues, the TPC and TFC were higher in unripe and ripe kiwiberry fruits, respectively, and antioxidant activity was generally higher in unripe than ripe fruit across most of the cultivars. Based on our results, among the 12 kiwiberry cultivars, cv. Daebo and cv. Saehan have a significantly higher phytochemical content and antioxidant activity in all of the tissue types, thus having potential as a functional food and natural antioxidant.

Background: Meta-analysis is a statistical method that combines the results of multiple studies to increase statistical power. When multiple studies participating in a meta-analysis utilize the same public dataset as controls, the summary statistics from these studies become correlated. To solve this challenge, Lin and Sullivan proposed a method to provide an optimal test statistic adjusted for the correlation. This method quickly became the standard practice. However, we identified an unexpected power asymmetry phenomenon in this standard framework. This can lead to unbalanced power for detecting protective minor alleles and risk minor alleles., Results: We found that the power asymmetry of the current framework is mainly due to the errors in approximating the correlation term. We then developed a meta-analysis method based on an accurate correlation estimator, called PASTRY (A method to avoid Power ASymmeTRY). PASTRY outperformed the standard method on both simulated and real datasets in terms of the power symmetry., Conclusions: Our findings suggest that PASTRY can help to alleviate the power asymmetry problem. PASTRY is available at https://github.com/hanlab-SNU/PASTRY ., (© 2023. The Author(s).)

Objective: Congenital hyperinsulinism (CHI) is a group of clinically and genetically heterogeneous disorders characterized by dysregulated insulin secretion. The aim of the study was to elucidate genetic etiologies of Taiwanese children with the most severe diazoxide-unresponsive CHI and analyze their genotype-phenotype correlations., Methods: We combined Sanger with whole exome sequencing (WES) to analyze CHI-related genes. The allele frequency of the most common variant was estimated by single-nucleotide polymorphism haplotype analysis. The functional effects of the ATP-sensitive potassium (K ATP ) channel variants were assessed using patch clamp recording and Western blot., Results: Nine of 13 (69%) patients with ten different pathogenic variants (7 in ABCC8 , 2 in KCNJ11 and 1 in GCK ) were identified by the combined sequencing. The variant ABCC8 p.T1042QfsX75 identified in three probands was located in a specific haplotype. Functional study revealed the human SUR1 (hSUR1)-L366F K ATP channels failed to respond to intracellular MgADP and diazoxide while hSUR1-R797Q and hSUR1-R1393C K ATP channels were defective in trafficking. One patient had a de novo dominant mutation in the GCK gene (p.I211F), and WES revealed mosaicism of this variant from another patient., Conclusion: Pathogenic variants in K ATP channels are the most common underlying cause of diazoxide-unresponsive CHI in the Taiwanese cohort. The p.T1042QfsX75 variant in the ABCC8 gene is highly suggestive of a founder effect. The I211F mutation in the GCK gene and three rare SUR1 variants associated with defective gating (p.L366F) or traffic (p.R797Q and p.R1393C) K ATP channels are also associated with the diazoxide-unresponsive phenotype., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Tsai, Chang, Chen, Fann, Chang, Liu, Wu, Chiu, Hsu, Yang, Lai, Tsai, Yang and Chen.)

Oplopanax elatus and Aralia cordata , commonly referred to as "Dureub" in Korea, are generally used as medicinal or food raw materials. Although O. elatus , a rare and endangered plant, is typically sold at high prices, the more abundant A. cordata is comparatively inexpensive. Given their common names and morphological root similarities, both plants can easily be confused, thereby providing potential opportunities for fraudulent use in food products. Species-specific molecular markers that can be used for quantitative real-time PCR (qPCR) analysis were developed. Verification of the six primer pairs revealed a correlation coefficient greater than 0.99, with a slope between -3.33 and -3.56. The assay confirmed specificity based on an analysis of 14 non-target plant species and verified its practicality using 10 commercial products with reliability based on a blind test. Thus, qPCR assays can contribute to food safety and protect consumer rights and interests., Supplementary Information: The online version of this article contains supplementary material available 10.1007/s10068-023-01313-1., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interest., (© The Korean Society of Food Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

To reduce overcrowding in emergency departments (ED), which is a serious international problem, it is important to reduce the length of ED stay (ED LOS) of emergency patients. In particular, due to the COVID 19 pandemic, psychiatric emergency patients spent much longer in ED. This study was conducted to identify the characteristics of psychiatric emergency patients who visited the ED during the COVID-19 pandemic and to identify factors affecting ED LOS. This retrospective study was conducted on adult patients aged 19 years or older who visited a psychiatric emergency center operated by an ED from 1 May 2020 to 31 April 2021 because of the COVID-19 pandemic. In this study, the average ED LOS of psychiatric emergency patients was 7.8 h. Factors affecting ED LOS for over 12 h were isolation (OR = 2.39, CI = 1.409-4.052), unaccompanied police officers (OR = 2.106, CI = 1.338-3.316), night-time visits (OR = 2.127, CI = 1.357-3.332), use of sedatives (OR = 1.671, CI = 1.030-2.713), and restraints (OR = 1.968, CI = 1.172-4.895). The ED LOS of psychiatric emergency patients is longer than that of general emergency patients, and a long ED LOS causes ED overcrowding. To reduce the ED LOS of psychiatric emergency patients, they must be accompanied by a police officer when visiting the ED, and the treatment process should be reorganized so that a psychiatrist can promptly intervene. Furthermore, it is necessary to reorganize the isolation guidelines and admission criteria for mental emergency patients.

Sargassum is one of the most important brown algal genera that can be used as food and raw material for medicinal purpose, and has various beneficial effects. As the classification of Sargassum species is currently based on their morphological characteristics, organellar genome sequences of Sargassum would provide important information for accurate identification of species and developing species-specific markers. We sequenced the complete organellar genomes of six Sargassum species, including the first complete chloroplast genome sequences of S. fulvellum, S. serratifolium, S. macrocarpum, and S. siliquastrum, and the first complete mitochondrial genome sequences of S. fulvellum, S. serratifolium, and S. macrocarpum. The chloroplast genomes of the 6 Sargassum species contained 139 protein-coding genes (PCGs), and the mitochondrial genomes possessed 37 PCGs. A comparative study was performed between the newly sequenced organellar genomes and 44 other species belonging to class Phaeophyceae. Phylogenetic relationships using PCGs shared by Phaeophyceae species were constructed with IQ-TREE 2 using the maximum likelihood method. In addition, we developed real-time PCR markers based on SNPs to distinguish the 6 Sargassum species. Our results provide useful information for establishing phylogenetic relationships between brown algae., (© 2022. The Author(s).)

Background: Cluster headache is a highly debilitating neurological disorder with considerable inter-ethnic differences. Genome-wide association studies (GWAS) recently identified replicable genomic loci for cluster headache in Europeans, but the genetic underpinnings for cluster headache in Asians remain unclear. The objective of this study is to investigate the genetic architecture and susceptibility loci of cluster headache in Han Chinese resided in Taiwan., Methods: We conducted a two-stage genome-wide association study in a Taiwanese cohort enrolled from 2007 through 2022 to identify the genetic variants associated with cluster headache. Diagnosis of cluster headache was retrospectively ascertained with the criteria of International Classification of Headache Disorders, third edition. Control subjects were enrolled from the Taiwan Biobank. Genotyping was conducted with the Axiom Genome-Wide Array TWB chip, followed by whole genome imputation. A polygenic risk score was developed to differentiate patients from controls. Downstream analyses including gene-set and tissue enrichment, linkage disequilibrium score regression, and pathway analyses were performed., Results: We enrolled 734 patients with cluster headache and 9,846 population-based controls. We identified three replicable loci, with the lead SNPs being rs1556780 in CAPN2 (odds ratio = 1.59, 95% CI 1.42‒1.78, p = 7.61 × 10 -16 ), rs10188640 in MERTK (odds ratio = 1.52, 95% CI 1.33‒1.73, p = 8.58 × 10 -13 ), and rs13028839 in STAB2 (odds ratio = 0.63, 95% CI 0.52‒0.78, p = 2.81 × 10 -8 ), with the latter two replicating the findings in European populations. Several previously reported genes also showed significant associations with cluster headache in our samples. Polygenic risk score differentiated patients from controls with an area under the receiver operating characteristic curve of 0.77. Downstream analyses implicated circadian regulation and immunological processes in the pathogenesis of cluster headache., Conclusions: This study revealed the genetic architecture and novel susceptible loci of cluster headache in Han Chinese residing in Taiwan. Our findings support the common genetic contributions of cluster headache across ethnicities and provide novel mechanistic insights into the pathogenesis of cluster headache., (© 2022. The Author(s).)

Agastache rugosa and Pogostemon cablin are used as medicinal herbs and aromatic plants and belong to the family Lamiaceae . Despite differences in composition and physicochemical properties, both plants are frequently sold as the medical substance "Kwakhyang" in some Asian countries. Molecular markers were established to distinguish between the two plants using quantitative real-time PCR. Species-specific primers were designed in the nuclear internal transcribed spacer region of ribosomal DNA and in the chloroplast genes matK , rbcL , and rpoB . Six primer sets were tested, the correlation coefficient was higher than 0.99, and the slope was approximately - 3.36 to - 3.58. Efficiency ranged from 90.13 to 98.52%. The developed real-time PCR assay was validated with 14 off-target species, and its reliability was verified through blind testing of 14 commercial products. The assay developed here may help protect consumer rights, and the designed primers can be used to distinguish between the target species., Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01176-y., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Korean Society of Food Science and Technology 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Artemisia capillaris and Artemisia iwayomogi are well-known herbal medicines which are used as hepatotherapeutic drugs. These two herbal species can be confused with each other, owing to their morphological similarity and similar Korean common names of "Injinho" and "Haninjin," respectively. Molecular markers to distinguish between the two plants were developed. Six primer sets were designed and verified, and their efficiencies were found to range from 90.28 to 98.29%. The developed primer sets had significant correlation coefficient values between the cycle threshold values and the logarithm of DNA concentration for their target species (R 2  > 0.98), with slopes ranged from - 3.3637 to - 3.5793. The specificity of the quantitative polymerase chain reaction (qPCR) was confirmed with 14 other species. Additionally, 16 commercial medicinal herbs and 40 blind samples were tested to evaluate their reliability. Collectively, the findings indicate that developed qPCR-based target-specific primer sets have potential applicability toward protection of consumers' rights., Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01166-0., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Korean Society of Food Science and Technology 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: Acral lentiginous melanoma is the most common subtype of cutaneous melanoma in Asian countries. This study aims to clarify the associations between certain histologic and immunohistochemical parameters, and identify their prognostic values., Methods: We assessed several histologic features and conducted immunohistochemical study of programmed cell death ligand 1 (clone 22C3) and CD8/CD4 in 61 Taiwanese patients with Stage III/IV, non-BRAF acral lentiginous melanomas., Results: A total of 41 males and 20 females were included, with a median age of 74 years. The majority of tumors occurred at nonungual locations (86.9%), with 'foot' being the most frequently affected site (85.2%). Positive programmed cell death ligand 1 staining (combined positive score ≥ 10) was significantly associated with the status of tumor-infiltrating lymphocytes (P = 0.036). Lack of skin ulceration was linked to the immunoexpression of CD8/CD4-high (P = 0.004). A superior clinical outcome was found in the tumor-infiltrating lymphocytes-present group (P = 0.011), and among which, CD8/CD4-high was significantly correlated with better survival (P < 0.001). Combined survival analysis revealed that the PD-L1(-) TIL(+) CD8/CD4-high subgroup was associated with favorable prognosis, and cases with PD-L1(+) TIL(-) showed the worst disease specific survival (P < 0.001). In the univariate analysis, lymphovascular invasion (P = 0.002), skin ulceration (P = 0.002), tumor-infiltrating lymphocytes (P = 0.015) and CD8/CD4 status (P < 0.001) were significant prognostic factors. At the multivariate level, the statuses of CD8/CD4-low (P < 0.001) and lymphovascular invasion (P = 0.014) represented the independent poor prognosticators., Conclusion: For advanced, non-BRAF acral lentiginous melanomas, comprehensive assessments of these microscopic traits, along with CD8/CD4 and PD-L1 immunoprofiles, may help guide the clinicians and patients through treatment decisions., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Assessing aquifer vulnerability is crucial for preventing groundwater pollution. In this study, aquifer vulnerability to fecal coliform (FC) pollution was assessed using auxiliary environmental data in the Pingtung Plain, Taiwan. Moreover, key environmental factors inducing different fecal pollution levels were determined. First, 23 explanatory variables on land uses, population density, livestock and poultry densities, sanitary condition, antecedent precipitation, groundwater quality, aquifer characteristics, and subsurface hydrology were obtained using geographic information systems in 2014. As dependent variables, groundwater FCs were also simultaneously obtained. Then, multi-threshold logistic regression (LR) was adopted to model aquifer vulnerability assessment after cross validation. The thresholds of aquifer vulnerability causing risks of incidental ingestion were analyzed by risk assessment. Risks to human health were acceptable for a low-level threshold and exceeded the acceptable level for medium- and high-level thresholds when residents incidentally ingested FC-polluted groundwater. Finally, key environmental factors inducing low, medium, and high levels of groundwater FC pollution were characterized. The key environmental factors for the LR with low- and medium-level thresholds were sand and gravel soil textures of unsaturated aquifers and antecedent 3-day cumulative precipitation, and those for the LR with high-level thresholds were chicken farming, urban land use, and ratio of tap water use. Thus, the multi-threshold LR indicated that environmental factors must be ranked for assessing aquifer vulnerability., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Restless legs syndrome is a highly prevalent comorbidity of migraine; however, its genetic contributions remain unclear., Objectives: To identify the genetic variants of restless legs syndrome in migraineurs and to investigate their potential pathogenic roles., Methods: We conducted a two-stage genome-wide association study (GWAS) to identify susceptible genes for restless legs syndrome in 1,647 patients with migraine, including 264 with and 1,383 without restless legs syndrome, and also validated the association of lead variants in normal controls unaffected with restless legs syndrome (n = 1,053). We used morpholino translational knockdown (morphants), CRISPR/dCas9 transcriptional knockdown, transient CRISPR/Cas9 knockout (crispants) and gene rescue in one-cell stage embryos of zebrafish to study the function of the identified genes., Results: We identified two novel susceptibility loci rs6021854 (in VSTM2L) and rs79823654 (in CCDC141) to be associated with restless legs syndrome in migraineurs, which remained significant when compared to normal controls. Two different morpholinos targeting vstm2l and ccdc141 in zebrafish demonstrated behavioural and cytochemical phenotypes relevant to restless legs syndrome, including hyperkinetic movements of pectoral fins and decreased number in dopaminergic amacrine cells. These phenotypes could be partially reversed with gene rescue, suggesting the specificity of translational knockdown. Transcriptional CRISPR/dCas9 knockdown and transient CRISPR/Cas9 knockout of vstm2l and ccdc141 replicated the findings observed in translationally knocked-down morphants., Conclusions: Our GWAS and functional analysis suggest VSTM2L and CCDC141 are highly relevant to the pathogenesis of restless legs syndrome in migraineurs., (© 2022. The Author(s).)

Dry mouth is a rather common unpleasant adverse drug reaction (ADR) to lithium treatment in bipolar disorders that often lead to poor adherence or early dropout. The aim of this study was to identify the genetic variants of dry mouth associated with lithium treatment in patients with bipolar I (BPI) disorder. In total, 1242 BPI patients who had ever received lithium treatment were identified by the Taiwan Bipolar Consortium for this study. The proportions of patients who experienced impaired drug compliance during lithium medication were comparable between those only with dry mouth and those with any other ADR (86% and 93%, respectively). Dry mouth appeared to be the most prevalent (47.3%) ADR induced by lithium treatment. From the study patients, 921 were included in a genome-wide association study (GWAS), and replication was conducted in the remaining 321 patients. The SNP rs10135918, located in the immunoglobulin heavy chain locus (IGH), showed the strongest associations in the GWAS ( p = 2.12 × 10 -37 ) and replication groups ( p = 6.36 × 10 -13 ) (dominant model) for dry mouth with a sensitivity of 84.9% in predicting dry mouth induced by lithium. Our results may be translated into clinical recommendation to help identify at-risk individuals for early identification and management of dry mouth, which will improve medication adherence.

Atractylodes lancea rhizomes are commonly consumed in east Asia as traditional medical herbs. However, in Korea, because of their morphological similarity, A. lancea rhizomes can be contaminated with those of Scopolia japonica imported from China. To detect adulteration with S. japonica in the complex products of A. lancea , we developed two PCR-based DNA markers, multiplex PCR and quantitative real-time PCR. The sensitivity of the multiplex PCR primer combinations and real-time PCR was confirmed with a series of DNA concentrations (0.01-10 ng/µL). The specificity of the developed PCR assays was confirmed with 14 other species. In addition, 14 commercial A. lancea medicinal herbs and 20 blind samples were tested with the developed PCR assays to demonstrate the reliability. Taken together, the developed multiplex and real-time PCR-based target-specific primer sets may be useful for detecting the target species and have the potential to contribute to food safety and consumer health care., Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-021-01008-5., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Korean Society of Food Science and Technology 2021.)

Glycosylation is important for biological functions of proteins and greatly affected by diseases. Exploring the glycosylation profile of the protein-specific glycosylation and/or the site-specific glycosylation may help understand disease etiology, differentiate diseases and ultimately develop therapeutics. Patients with multiple sclerosis (MS) and patients with neuromyelitis optica spectrum disorder (NMOSD) are sometimes difficult to differentiate due to the similarity in their clinical symptoms. The disease-related glycosylation profiles of MS and NMOSD have not yet been well studied. Here, we analyzed site-specific glycan profiles of serum proteins of these patients by using a recently developed mass spectrometry technique. A total of 286 glycopeptides from 49 serum glycoproteins were quantified and compared between healthy controls (n = 6), remitting MS (n = 45) and remitting NMOSD (n = 23) patients. Significant differences in the levels of site-specific N-glycans on inflammation-associated components [IgM, IgG1, IgG2, complement components 8b (CO8B) and attractin], central nerve system-damage-related serum proteins [apolipoprotein D (APOD), alpha-1-antitrypsin, plasma kallikrein and ADAMTS-like protein 3] were observed among three study groups. We furthered demonstrated that site-specific N-glycans on APOD on site 98, CO8B on sites 243 and 553 are potential markers to differentiate MS from NMOSD with an area under receiver operating curve value > 0.75. All these observations indicate that remitting MS or NMOSD patients possess a unique disease-associated glyco-signature in their serum proteins. We conclude that monitoring one's serum protein glycan profile using this high-throughput analysis may provide an additional diagnostic criterion for differentiating diseases, monitoring disease status and estimating response-to-treatment effect., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study aimed to distinguish between Korean and Chinese red pepper powder (RPP) using inorganic elemental analysis data combined with orthogonal partial least squares-discriminant analysis (OPLS-DA). Elemental concentrations were obtained for 31 Korean and 31 Chinese RPP samples that were collected in Korea. Energy dispersive X-ray fluorescence spectroscopy detected 11 elements in these samples. Rb and Cl concentrations were selected as the variables which best allowed distinguishing between Korean and Chinese RPP using an S-plot from OPLS-DA. Rb and Cl concentrations in the Korean RPP samples were ≤ 1.6 mg/100 g (measured by inductively coupled plasma-optical emission spectroscopy) and ≤ 215 mg/100 g, respectively. A blind trial demonstrated that Korean RPP containing ≥ 50 g/100 g of Chinese RPP could be identified by applying predetermined ranges of Rb and Cl concentrations, suggesting that analysis of these two elements is a possible approach to distinguish between Korean and Chinese RPP., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Korean Society of Food Science and Technology 2021.)

The search for susceptibility genes underlying the heterogeneous bipolar disorder has been inconclusive, often with irreproducible results. There is a hope that narrowing the phenotypes will increase the power of genetic analysis. Early-onset bipolar disorder is thought to be a genetically homogeneous subtype with greater symptom severity. We conducted a genome-wide association study (GWAS) for this subtype in bipolar I (BPI) disorder. Study participants included 1779 patients of Han Chinese descent with BPI disorder recruited by the Taiwan Bipolar Consortium. We conducted phenotype assessment using the Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry and prepared a life chart with graphic depiction of lifetime clinical course for each of the BPI patient recruited. The assessment of onset age was based on this life chart with early onset defined as ≤20 years of age. We performed GWAS in a discovery group of 516 early-onset and 790 non-early-onset BPI patients, followed by a replication study in an independent group of 153 early-onset and 320 non-early-onset BPI patients and a meta-analysis with these two groups. The SNP rs11127876, located in the intron of CADM2, showed association with early-onset BPI in the discovery cohort (P = 7.04 × 10 -8 ) and in the test of replication (P = 0.0354). After meta-analysis, this SNP was demonstrated to be a new genetic locus in CADM2 gene associated with early-onset BPI disorder (P = 5.19 × 10 -8 ).

Rivers are an important urban water resource. This study adopted multivariate linear regression (MLR) and logistic regression (LR) with multiple thresholds to assess river fecal pollution in the Tamsui River watershed using auxiliary environmental data. First, environmental data between 2015 and 2017 on land use, antecedent precipitation, population density, sewerage infrastructure, and river water quality were obtained using geographic information systems and served as explanatory variables. River fecal coliforms (FC), the dependent variable, were also collected for the same period. Then, MLR was used to establish an overall prediction model after validation, and to determine significant factors influencing the level of river fecal pollution. Finally, after stratifying the fecal pollution as low, medium, and high levels, LR with multiple thresholds was employed to explore key factors affecting different FC pollution levels. The study results revealed that land use type and river water quality (other than FC) strongly affected river FC pollution. The discharge of household sewage and wastewater from urban areas was a major source of river FC pollution, particularly for low and medium pollution levels, while farmland land use was negatively correlated with the medium and high levels of river FC pollution in the highly urbanized watershed. Biochemical oxygen demand and suspended solids were highly correlated with medium and high pollution levels in river water.

A pig-specific real-time PCR assay based on the mitochondrial ND5 gene was developed to detect porcine material in food and other products. To optimize the performance of assay, seven commercial TaqMan master mixes and two real-time PCR platforms (Applied Biosystems StepOnePlus and Bio-rad CFX Connect) were used to evaluate the limit of detection (LOD) as well as the PCR efficiency and specificity. The LODs and PCR efficiencies for the seven master mixes on two platforms were 0.5-5 pg/reaction and 84.96%-108.80%, respectively. Additionally, non-specific amplifications of DNA from other animal samples (human, dog, cow, and chicken) were observed for four master mixes. These results imply that the sensitivity and specificity of a real-time PCR assay may vary depending on master mix and platform used. The best combination of master mix and real-time PCR platform can accurately detect 0.5 pg porcine DNA, with a PCR efficiency of 100.49%., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

Turmeric, or Curcuma longa , is commonly consumed in the South East Asian countries as a medical product and as food due to its therapeutic properties. However, with increasing demand for turmeric powder, adulterated turmeric powders mixed with other cheap starch powders, such as from corn or cassava, are being distributed by food suppliers for economic benefit. Here, we developed molecular markers using quantitative real-time PCR to identify adulteration in commercial turmeric powder products. Chloroplast genes, such as matK, atpF , and ycf2 , were used to design species-specific primers for C. longa and Zea mays . Of the six primer pairs designed and tested, the correlation coefficients (R 2 ) were higher than 0.99 and slopes were -3.136 to -3.498. The efficiency of the primers was between 93.14 and 108.4%. The specificity of the primers was confirmed with ten other species, which could be intentionally added to C. longa powders or used as ingredients in complex turmeric foods. In total, 20 blind samples and 10 commercial C. longa food products were tested with the designed primer sets to demonstrate the effectiveness of this approach to detect the addition of Z. mays products in turmeric powders. Taken together, the real-time PCR assay developed here has the potential to contribute to food safety and the protection of consumer's rights.

Background: Many single nucleotide polymorphisms (SNPs) have been reported to be associated with migraine susceptibility. However, evidences for their associations with migraine endophenotypes or subtypes are scarce. We aimed to investigate the associations of pre-identified migraine susceptibility loci in Taiwanese with migraine endophenotypes or subtypes, including chronic migraine and allodynia., Methods: The associations of six SNPs identified from our previous study, including TRPM8 rs10166942, LRP1 rs1172113, DLG2 rs655484, GFRA1 rs3781545, UPP2 rs7565931, and GPR39 rs10803531, and migraine endophenotypes, including chronic migraine and allodynia were tested. Significant associations in the discovery cohort were validated in the replication cohort. The adjusted odds ratios (aOR) were calculated after controlling for confounders., Results: In total, 1904 patients (mean age 37.5 ± 12.2 years old, female ratio: 77.7%) including 1077 in the discovery cohort and 827 in the replication cohort were recruited. Of them, 584 (30.7%) had chronic migraine. Of the 6 investigated SNPs, TRPM8 rs10166942 T allele-carrying patients were more likely to have chronic migraine than non-T allele carriers in both discovery and replication cohorts and combined samples (33.7% vs. 25.8%, p = 0.004, aOR = 1.62). In addition, T allele carriers reported more allodynic symptoms than non-T allele carriers (3.5 ± 3.7 vs. 2.6 ± 2.8, p < 0.001). However, allodynia severity did not differ between episodic and chronic migraine patients. No further correlations between genetic variants and endophenotypes were noted for the other SNPs., Conclusions: TRPM8 may contribute to the pathogenesis of chronic migraine. However, our study did not support allodynia as a link between them. The underlying mechanisms deserve further investigations.

In higher plants, the post-translational modification of target proteins via the attachment of molecules such as ubiquitin (Ub) mediates a variety of cellular functions via the Ub/26S proteasome system. Here, a really interesting new gene (RING)-H2 type E3 ligase, which regulates target proteins via the Ub/26S proteasome system, was isolated from a rice plant, and its other grass orthologs were examined to determine the evolution of its molecular function during speciation. The gene encoding Oryza sativa cytoplasmic-localized RING finger protein 1 (OsCLR1) was highly expressed under salt and drought stresses. By contrast, the three grass orthologs, SbCLR1 from Sorghum bicolor, ZmCLR1 from Zea mays and TaCLR1 from Triticum aestivum, showed different responses to these stresses. Despite these differences, all four orthologs exhibited E3 ligase activity with cytosol-targeted localization, demonstrating conserved molecular functions. Although OsCLR1-overexpressing plants showed higher survival rates under both salt and drought stresses than that of the wild type (WT) plants, this pattern was not observed in the other orthologs. In addition, OsCLR1-overexpressing plants exhibited lower germination rates in ABA than that of WT plants, whereas the three ortholog CLR1-overexpressing plants showed rates similar to the WT plants. These results indicate the positive regulation of OsCLR1 in response to salt and drought in an ABA-dependent manner. Despite the molecular functions of the three CLR1 orthologs remaining largely unknown, our results provide an insight into the evolutionary fate of CLR1 grass orthologs during speciation after the divergence from a common ancestor., (� The Author(s) 2019. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The Wellcome Trust Case Control Consortium (WTCCC) study was a large genome-wide association study that aimed to identify common variants associated with seven diseases. That study combined two control datasets (58C and UK Blood Services) as shared controls. Prior to using the combined controls, the WTCCC performed analyses to show that the genomic content of the control datasets was not significantly different. Recently, the analysis of human leukocyte antigen (HLA) genes has become prevalent due to the development of HLA imputation technology. In this project, we extended the between-control homogeneity analysis of the WTCCC to HLA. We imputed HLA information in the WTCCC control dataset and showed that the HLA content was not significantly different between the two control datasets, suggesting that the combined controls can be used as controls for HLA fine-mapping analysis based on HLA imputation.

Genomic global positioning system (GPS) applies the multilateration technique commonly used in the GPS to genomic data. In the framework we present here, investigators calculate genetic distances from their samples to reference samples, which are from data held in the public domain, and share this information with others. This sharing enables certain types of genomic analysis, such as identifying sample overlaps and close relatives, decomposing ancestry, and mapping of geographical origin without disclosing personal genomes. Thus, our method can be seen as a balance between open data sharing and privacy protection.

Disrupted-in-schizophrenia 1 (DISC1) was reported to be associated with schizophrenia. In a previous study, we found significant association with schizophrenia patients with deficient sustained attention assessed by continuous performance test (CPT). This study aimed to identify risk polymorphisms in this specific neurocognitive subgroup and investigate the expression of different isoforms of DISC1. A total of 83 genetic variants were identified through direct sequencing in 50 controls and 100 schizophrenia patients. Fourteen variants were genotyped in 600 controls and 912 patients. Patients were subgrouped by familial loading (multiplex or simplex) and performance on CPT. The frequency of AA genotype of rs11122324 at the 3'-UTR of Es and Esv1 isoforms and of rs2793091 at intron 4 were significantly higher in multiplex schizophrenia patients than those in controls (corrected p < 0.05). In further subgrouping, the frequency of AA genotype of the two SNPs were significantly higher in multiplex schizophrenia patients with deficient sustained attention than those in controls (corrected p < 0.005). The mRNA expression levels of two extra-short isoforms (Es and Esv1) in the EBV-transformed lymphocytes of schizophrenia were significantly higher than those of controls. Luciferase reporter assays demonstrated that the A-allele of rs11122324 significantly upregulated DISC1 extra-short isoforms transcription compared with the G-allele. We found two SNPs (rs11122324 and rs2793091) of DISC1 may be specifically associated with multiplex schizophrenia patients with deficient sustained attention. The SNP rs11122324 may be a risk polymorphism, which may have functional influence on the transcription of Es and Esv1 through increasing their expression.

Rivers are an important urban resource, and water quality influences the use of river water. Thus, analyzing spatiotemporal variations in river water quality is crucial for sustainable use and management of water resources in a highly urbanized region. This study employed river pollution index (RPI) data obtained in 2013 to assess spatiotemporal variations in river water quality for sustainable environmental and recreational management in the highly urbanized Danshui River basin. First, ordinary kriging was adopted to analyze monthly RPI distributions. Subsequently, different percentiles of monthly estimated RPI distributions were probabilistically determined at a river segment. Finally, three measurement methods of local uncertainty, namely-conditional variance, local entropy, and interquartile range-were used to characterize spatiotemporal variations in river water quality in the Danshui River basin. Assessment results revealed that more highly polluted river water quality resulted in higher seasonal variations. Moreover, high and very high seasonal variations were mainly concentrated in urban river segments, whereas low and very low seasonal variations were primarily located in upstream river segments. Thus, to achieve sustainable development goals, artificial wetlands should be established at downstream and midstream urban riverbanks and urban recreational activities should be developed in upstream riverbank parks in the Danshui River basin before the comprehensive improvement of river water quality.

River cruising ships move along river courses, and thus health risks to passengers may vary spatially due to the accidental exposure of river fecal pollution. This study performed a spatial dynamic assessment of health risks for river cruises in the highly urbanized Tamsui River Basin. First, the spatial distributions of river Escherichia coli (E. coli) were probabilistically characterized using indicator kriging (IK). Moreover, the current river cruise information was surveyed to obtain cruise routes and transit times. Then, to explore the parametric uncertainty of quantitative microbial risk assessment (QMRA), the ingestion rate (IR) for boating was determined using Monte Carlo simulation (MCS). Moreover, river E. coli distributions were estimated using nonparametric MCS according to multi-threshold IK estimates. Eventually, after combining the distribution of the joint probability of the IR and E. coli in QMRA, the β-Poisson dose-response function was adopted to analyze risks to river cruise passengers at discretized segments of cruise routes. Health risks to river cruise passengers were integrated at the discretized segments to explore suitable recreational strategies for river cruises. The research results indicate that all health risks do not exceed a daily target level of 8 illnesses per 1000 exposures for single-trip cruise routes. However, health risks to passengers can exceed this level for round-trip cruise routes along highly polluted urban river courses.

Several studies have reported individual benefits of yogurt and exercise on health; however, their combined effects remain unclear. Twenty-four healthy individuals participated in the study and were randomly assigned to the following four groups: control, yogurt, exercise, and combination. The participants consumed yogurt and exercised for 2 weeks, and we examined the combined effects of yogurt and exercise on physiological biomarkers. Individually, yogurt and exercise did not exert a significant effect on biomarkers of depression or cardiovascular disease, although vitamin D levels increased in the exercise group. However, in the combination group, serotonin levels increased, while levels of triglycerides and high-sensitivity C-reactive protein, which are biomarkers for cardiovascular diseases, decreased. In conclusion, the results of the study showed that, in healthy individuals, a combination of yogurt and exercise led to greater increases in serotonin levels and reductions in triglyceride and high-sensitivity C-reactive protein levels, relative to those observed for yogurt or exercise alone; therefore, this combination could have implications for the prevention of depression and cardiovascular disease.

RING (Really Interesting New Gene) finger proteins play crucial roles in abiotic stress responses in plants. We report the RING finger E3 ligase gene, an Oryza sativa salt, ABA and drought stress-induced RING finger protein 1 gene (OsSADR1). We demonstrated that although OsSAR1 possesses E3 ligase activity, a single amino acid substitution (OsSADR1C168A) in the RING domain resulted in no E3 ligase activity, suggesting that the activity of most E3s is specified by the RING domain. Additional assays substantiated that OsSADR1 interacts with three substrates-no E3 ligase acti and OsPIRIN, and mediates their proteolysis via the 26S proteasome pathway. For OsSADR1, approximately 62% of the transient signals were in the cytosol and 38% in the nucleus. However, transiently expressed OsSADR1 was primarily expressed in the nucleus (70%) in 200 mM salt-treated rice protoplasts. The two nucleus-localized proteins (OsSNAC2 and OsGRAS44) interacted with OsSADR1 in the cytosol and nucleus. Heterogeneous overexpression of OsSADR1 in Arabidopsis resulted in sensitive phenotypes for salt- and mannitol-responsive seed germination and seedling growth. With ABA, OsSADR1 overexpression in plants produced highly tolerant phenotypes, with morphological changes in root length and stomatal closure. The ABA-tolerant transgenic plants also showed hypersensitivity phenotypes under severe water deficit conditions. Taken together, OsSADR1 may act as a regulator in abiotic stress responses by modulating target protein levels.

The Jiaosi Hot Spring Region is one of the most famous tourism destinations in Taiwan. The spring water is processed for various uses, including irrigation, aquaculture, swimming, bathing, foot spas, and recreational tourism. Moreover, the multipurpose uses of spring water can be dictated by the temperature of the water. To evaluate the suitability of spring water for these various uses, this study spatially characterized the spring water temperatures of the Jiaosi Hot Spring Region by integrating ordinary kriging (OK), sequential Gaussian simulation (SGS), and Geographic information system (GIS). First, variogram analyses were used to determine the spatial variability of spring water temperatures. Next, OK and SGS were adopted to model the spatial uncertainty and distributions of the spring water temperatures. Finally, the land use (i.e., agriculture, dwelling, public land, and recreation) was determined using GIS and combined with the estimated distributions of the spring water temperatures. A suitable development strategy for the multipurpose uses of spring water is proposed according to the integration of the land use and spring water temperatures. The study results indicate that the integration of OK, SGS, and GIS is capable of characterizing spring water temperatures and the suitability of multipurpose uses of spring water. SGS realizations are more robust than OK estimates for characterizing spring water temperatures compared to observed data. Furthermore, current land use is almost ideal in the Jiaosi Hot Spring Region according to the estimated spatial pattern of spring water temperatures.

Chronic arsenic (As) exposure continues to be a public health problem of major concern worldwide, affecting hundreds of millions of people. A long-term groundwater quality survey has revealed that 20% of the groundwater in southern Taiwan's Pingtung Plain is clearly contaminated with a measured As concentration in excess of the maximum level of 10 µg/L recommended by the World Health Organization. The situation is further complicated by the fact that more than half of the inhabitants in this area continue to use groundwater for drinking. Efforts to assess the health risk associated with the ingestion of As from the contaminated drinking water are required in order to determine the priorities for health risk management. The conventional approach to conducting a human health risk assessment may be insufficient for this purpose, so this study adopts a geostatistical Kriging method to perform a spatial analysis of the health risk associated with ingesting As through drinking groundwater in the Pingtung Plain. The health risk is assessed based on the hazard quotient (HQ) and target cancer risk (TR) established by the U.S. Environmental Protection Agency. The results show that most areas where the HQ exceeds 1 are in the southwestern part of the study area. In addition, the high-population density townships of Daliao, Linyuan, Donggang, Linbian, Jiadong, and Fangliao presently have exceedingly high TR values that are two orders of magnitude higher than the acceptable standard. Thus, the use of groundwater for drinking in these townships should be strictly avoided. A map that delineates areas with high TR values and high population densities is provided. The findings broaden the scope of the spatial analysis of human health risk and provide a basis for improving the decision-making process., Competing Interests: The authors declare no conflicts of interest.

In the Pingtung Plain of southern Taiwan, elevated levels of NO₃ - -N in groundwater have been reported. Therefore, efforts for assessing groundwater vulnerability are required as part of the critical steps to prevent and control groundwater pollution. This study makes a groundwater vulnerability assessment for the Pingtung Plain using an improved overlay and index-based DRASTIC model. The improvement of the DRASTIC model is achieved by reassigning the weighting coefficients of the factors in this model with the help of a discriminant analysis statistical method. The analytical results obtained from the improved DRASTIC model provide a reliable prediction for use in groundwater vulnerability assessment to nitrate pollution and can correctly identify the groundwater protection zones in the Pingtung Plain. Moreover, the results of the sensitivity analysis conducted for the seven parameters in the improved DRASTIC model demonstrate that the aquifer media (A) is the most sensitive factor when the nitrate-N concentration is below 2.5 mg/L. For the cases where the nitrate-N concentration is above 2.5 mg/L, the aquifer media (A) and net recharge (R) are the two most important factors., Competing Interests: The authors declare no conflict of interest.

Groundwater is widely used for drinking, irrigation, and aquaculture in the Pingtung Plain, Southwestern Taiwan. The overexploitation and poor quality of groundwater in some areas of the Pingtung Plain pose great challenges for the safe use and sustainable management of groundwater resources. Thus, establishing an effective management plan for multi-purpose groundwater utilization in the Pingtung Plain is imperative. Considerations of the quality of the groundwater and potential impact on the aquifer of groundwater exploitation are paramount to multi-purpose groundwater utilization management. This study proposes a zonal management plan for the multi-purpose use of groundwater in the Pingtung Plain. The zonal management plan is developed by considering the spatial variability of the groundwater quality and the impact on the aquifer, which is defined as the ratio of the actual groundwater extraction rate to transmissivity. A geostatistical Kriging approach is used to spatially delineate the safe zones based on the water quality standards applied in the three groundwater utilization sectors. Suitable zones for the impact on the aquifer are then spatially determined. The evaluation results showing the safe water quality zones for the three types of utilization demands and suitable zones for the impact on aquifer are integrated to create a zonal management map for multi-purpose groundwater utilization which can help government administrators to establish a water resource management strategy for safe and sustainable use of groundwater to meet multi-purpose groundwater utilization requirements in the Pingtung Plain.

D-amino acid oxidase (DAO) has been reported to be associated with schizophrenia. This study aimed to search for genetic variants associated with this gene. The genomic regions of all exons, highly conserved regions of introns, and promoters of this gene were sequenced. Potentially meaningful single-nucleotide polymorphisms (SNPs) obtained from direct sequencing were selected for genotyping in 600 controls and 912 patients with schizophrenia and in a replicated sample consisting of 388 patients with schizophrenia. Genetic associations were examined using single-locus and haplotype association analyses. In single-locus analyses, the frequency of the C allele of a novel SNP rs55944529 located at intron 8 was found to be significantly higher in the original large patient sample (p = 0.016). This allele was associated with a higher level of DAO mRNA expression in the Epstein-Barr virus-transformed lymphocytes. The haplotype distribution of a haplotype block composed of rs11114083-rs2070586-rs2070587-rs55944529 across intron 1 and intron 8 was significantly different between the patients and controls and the haplotype frequencies of AAGC were significantly higher in patients, in both the original (corrected p < 0.0001) and replicated samples (corrected p = 0.0003). The CGTC haplotype was specifically associated with the subgroup with deficits in sustained attention and executive function and the AAGC haplotype was associated with the subgroup without such deficits. The DAO gene was a susceptibility gene for schizophrenia and the genomic region between intron 1 and intron 8 may harbor functional genetic variants, which may influence the mRNA expression of DAO and neurocognitive functions in schizophrenia.

The Tamsui River watershed situated in Northern Taiwan provides a variety of water recreational opportunities such as riverbank park activities, fishing, cruising, rowing, sailing, and swimming. However, river water quality strongly affects water recreational quality. Moreover, the health of recreationists who are partially or fully exposed to polluted river water may be jeopardized. A river pollution index (RPI) composed of dissolved oxygen, biochemical oxygen demand, suspended solids, and ammonia nitrogen is typically used to gauge the river water quality and regulate the water body use in Taiwan. The purpose of this study was to probabilistically determine the RPI categories in the Tamsui River watershed and to assess the urban water recreational quality on the basis of the estimated RPI categories. First, according to various RPI categories, one-dimensional indicator kriging (IK) was adopted to estimate the occurrence probabilities of the RPI categories. The maximum occurrence probability among the categories was then employed to determine the most suitable RPI category. Finally, the most serious categories and seasonal variations of RPI were adopted to evaluate the quality of current water recreational opportunities in the Tamsui River watershed. The results revealed that the midstream and downstream sections of the Tamsui River and its tributaries with poor river water quality afford low water recreational quality, and water recreationists should avoid full or limited exposure to these bodies of water. However, the upstream sections of the Tamsui River watershed with high river water quality are suitable for all water recreational activities.

In order to develop rice mutants for crop improvement, we applied γ-irradiation mutagenesis and selected a rice seed color mutant (MT) in the M14 targeting-induced local lesions in genome lines. This mutant exhibited differences in germination rate, plant height, and root length in seedlings compared to the wild-type plants. We found 1645 different expressed probes of MT by microarray hybridization. To identify the modified metabolic pathways, we conducted integrated genomic analysis such as weighted correlation network analysis with a module detection method of differentially expressed genes (DEGs) in MT on the basis of large-scale microarray transcriptional profiling. These modules are largely divided into three subnetworks and mainly exhibit overrepresented gene ontology functions such as oxidation-related function, ion-binding, and kinase activity (phosphorylation), and the expressional coherences of module genes mainly exhibited in vegetative and maturation stages. Through a metabolic pathway analysis, we detected the significant DEGs involved in the major carbohydrate metabolism (starch degradation), protein degradation (aspartate protease), and signaling in sugars and nutrients. Furthermore, the accumulation of amino acids (asparagine and glutamic acid), sucrose, and starch in MT were affected by gamma rays. Our results provide an effective approach for identification of metabolic pathways associated with useful agronomic traits in mutation breeding.

Graves' disease is the leading cause of hyperthyroidism affecting 1.0-1.6% of the population. Antithyroid drugs are the treatment cornerstone, but may cause life-threatening agranulocytosis. Here we conduct a two-stage association study on two separate subject sets (in total 42 agranulocytosis cases and 1,208 Graves' disease controls), using direct human leukocyte antigen genotyping and SNP-based genome-wide association study. We demonstrate HLA-B*38:02 (Armitage trend Pcombined=6.75 × 10(-32)) and HLA-DRB1*08:03 (Pcombined=1.83 × 10(-9)) as independent susceptibility loci. The genome-wide association study identifies the same signals. Estimated odds ratios for these two loci comparing effective allele carriers to non-carriers are 21.48 (95% confidence interval=11.13-41.48) and 6.13 (95% confidence interval=3.28-11.46), respectively. Carrying both HLA-B*38:02 and HLA-DRB1*08:03 increases odds ratio to 48.41 (Pcombined=3.32 × 10(-21), 95% confidence interval=21.66-108.22). Our results could be useful for antithyroid-induced agranulocytosis and potentially for agranulocytosis caused by other chemicals.

Accurately classifying the spatial features of the water temperatures and discharge rates of hot springs is crucial for environmental resources use and management. This study spatially characterized classifications of the water temperatures and discharge rates of hot springs in the Tatun Volcanic Region of Northern Taiwan by using indicator kriging (IK). The water temperatures and discharge rates of the springs were first assigned to high, moderate, and low categories according to the two thresholds of the proposed spring classification criteria. IK was then used to model the occurrence probabilities of the water temperatures and discharge rates of the springs and probabilistically determine their categories. Finally, nine combinations were acquired from the probability-based classifications for the spatial features of the water temperatures and discharge rates of the springs. Moreover, various combinations of spring water features were examined according to seven subzones of spring use in the study region. The research results reveal that probability-based classifications using IK provide practicable insights related to propagating the uncertainty of classifications according to the spatial features of the water temperatures and discharge rates of the springs. The springs in the Beitou (BT), Xingyi Road (XYR), Zhongshanlou (ZSL), and Lengshuikeng (LSK) subzones are suitable for supplying tourism hotels with a sufficient quantity of spring water because they have high or moderate discharge rates. Furthermore, natural hot springs in riverbeds and valleys should be developed in the Dingbeitou (DBT), ZSL, Xiayoukeng (XYK), and Macao (MC) subzones because of low discharge rates and low or moderate water temperatures.

Background/aim: Despite great effort to elucidate the process of acquired gefitinib resistance (AGR) in order to develop successful chemotherapy, the precise mechanisms and genetic factors of such resistance have yet to be elucidated., Materials and Methods: We performed a cross-platform meta-analysis of three publically available microarray datasets related to cancer with AGR. For the top 100 differentially expressed genes (DEGs), we clustered functional modules of hub genes in a gene co-expression network and a protein-protein interaction network. We conducted a weighted correlation network analysis of total DEGs in microarray dataset GSE 34228. The identified DEGs were functionally enriched by Gene Ontology (GO) function and KEGG pathway., Results: We identified a total of 1,033 DEGs (510 up-regulated, 523 down-regulated, and 109 novel genes). Among the top 100 up- or down-regulated DEGs, many genes were found in different types of cancers and tumors. Through integrative analysis of two systemic networks, we selected six hub DEGs (Pre-B-cell leukemia homeobox1, Transient receptor potential cation channel subfamily C member 1, AXL receptor tyrosine kinase, S100 calcium binding protein A9, S100 calcium binding protein A8, and Nucleotide-binding oligomerization domain containing 2) associated with calcium homeostasis and signaling, apoptosis, transcriptional regulation, or chemoresistance. We confirmed a correlation of expression of these genes in the microarray dataset., Conclusion: Our study may lead to comprehensive insights into the complex mechanism of AGR and to novel gene expression signatures useful for further clinical studies., (Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.)

In a previous study, we identified a number of genes induced by chilling using a microarray approach. In order to investigate the molecular mechanism underlying chilling tolerance and possible crosstalk with other abiotic stresses, we selected a rice gene, OsChI1 (Os01g61160), for further analysis. The OsChI1 gene encodes a putative laccase precursor protein. In accordance with our previous results, its transcript is highly accumulated during a 12-day period of chilling treatment. Higher expression of the OsChI1 gene was also detected in roots and tissues at the vegetative and productive stages. In addition, we also observed increased transcript levels of the OsChI1 gene during dehydration and high salinity conditions. Transient expression of OsChI1 proteins tagged with fluorescence protein in rice protoplasts revealed that OsChI1 is localized in the plasma membrane. The Arabidopsis transgenic plants overexpressing OsChI1-EGFP resulted in an increased tolerance to drought and salinity stress. In silico analysis of OsChI1 suggests that several genes coexpressed with OsChI1 in the root during various abiotic stresses, such as chilling, drought and salt stress, may play an important role in the ROS signaling pathway. Potential roles of OsChI1 in response to abiotic stresses are discussed., (Copyright © 2014 Elsevier B.V. All rights reserved.)

It is common to observe the clustering of chronic hepatitis B surface antigen (HBsAg) carriers in families. Intra-familial transmission of hepatitis B virus (HBV) could be the reason for the familial clustering of HBsAg carriers. Additionally, genetic and gender factors have been reported to be involved. We conducted a three-stage genome-wide association study to identify genetic factors associated with chronic HBV susceptibility. A total of 1,065 male controls and 1,623 male HBsAg carriers were included. The whole-genome genotyping was done on Illumina HumanHap550 beadchips in 304 healthy controls and HumanHap610 beadchips in 321 cases. We found that rs9277535 (HLA-DPB1, P = 4.87×10(-14)), rs9276370 (HLA-DQA2, P = 1.9×10(-12)), rs7756516 and rs7453920 (HLA-DQB2, P = 1.48×10(-11) and P = 6.66×10(-15) respectively) were significantly associated with persistent HBV infection. A novel SNP rs9366816 near HLA-DPA3 also showed significant association (P = 2.58×10(-10)). The "T-T-G-G-T" haplotype of the five SNPs further signified their association with the disease (P = 1.48×10(-12); OR = 1.49). The "T-T" haplotype composed of rs7756516 and rs9276370 was more prevalent in severe disease subgroups and associated with non-sustained therapeutic response (P = 0.0262). The "G-C" haplotype was associated with sustained therapeutic response (P = 0.0132; OR = 2.49). We confirmed that HLA-DPB1, HLA-DQA2 and HLA-DQB2 loci were associated with persistent HBV infection in male Taiwan Han-Chinese. In addition, the HLA-DQA2 and -DQB2 complex was associated with clinical progression and therapeutic response.

In order to better understand the biological systems that are affected in response to cosmic ray (CR), we conducted weighted gene co-expression network analysis using the module detection method. By using the Pearson's correlation coefficient (PCC) value, we evaluated complex gene-gene functional interactions between 680 CR-responsive probes from integrated microarray data sets, which included large-scale transcriptional profiling of 1000 microarray samples. These probes were divided into 6 distinct modules that contained 20 enriched gene ontology (GO) functions, such as oxidoreductase activity, hydrolase activity, and response to stimulus and stress. In particular, modules 1 and 2 commonly showed enriched annotation categories such as oxidoreductase activity, including enriched cis-regulatory elements known as ROS-specific regulators. These results suggest that the ROS-mediated irradiation response pathway is affected by CR in modules 1 and 2. We found 243 ionizing radiation (IR)-responsive probes that exhibited similarities in expression patterns in various irradiation microarray data sets. The expression patterns of 6 randomly selected IR-responsive genes were evaluated by quantitative reverse transcription polymerase chain reaction following treatment with CR, gamma rays (GR), and ion beam (IB); similar patterns were observed among these genes under these 3 treatments. Moreover, we constructed subnetworks of IR-responsive genes and evaluated the expression levels of their neighboring genes following GR treatment; similar patterns were observed among them. These results of network-based analyses might provide a clue to understanding the complex biological system related to the CR response in plants., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In order to develop a rice population with improved important traits such as flowering time, we developed 2,911 M2 targeting-induced local lesions in genomes (TILLING) lines by irradiating rice seeds with γ-rays. In all, 15 M3 lines were obtained from 3 different M2 lines that exhibited an early-maturing phenotype: these plants matured approximately 25 days faster than wild-type (WT) plants. To identify genome-wide DNA polymorphisms, we performed whole-genome resequencing of both the plant types, i.e., WT and early-maturing TILLING 1 (EMT1), and obtained mapped reads of 118,488,245 bp (99.53 %) and 128,489,860 bp (99.72 %), respectively; Nipponbare was used as the reference genome. We obtained 63,648 and 147,728 single nucleotide polymorphisms (SNPs) and 33,474 and 31,082 insertions and deletions (InDels) for the WT and EMT1, respectively. Interestingly, there was a higher number of SNPs (2.6-fold) and slightly lower number of InDels (0.9-fold) in EMT1 than in WT. The expression of at least 202 structurally altered genes was changed in EMT1, and functional enrichment analysis of these genes revealed that their molecular functions were related to flower development. These results might provide a critical insight into the regulatory pathways of rice flowering.

Groundwater supplies over 50% of drinking water in Kinmen. Approximately 16.8% of groundwater samples in Kinmen exceed the drinking water quality standard (DWQS) of NO3 (-)-N (10 mg/L). The residents drinking high nitrate-polluted groundwater pose a potential risk to health. To formulate effective water quality management plan and assure a safe drinking water in Kinmen, the detailed spatial distribution of nitrate-N in groundwater is a prerequisite. The aim of this study is to develop an efficient scheme for evaluating spatial distribution of nitrate-N in residential well water using logistic regression (LR) model. A probability-based nitrate-N contamination map in Kinmen is constructed. The LR model predicted the binary occurrence probability of groundwater nitrate-N concentrations exceeding DWQS by simple measurement variables as independent variables, including sampling season, soil type, water table depth, pH, EC, DO, and Eh. The analyzed results reveal that three statistically significant explanatory variables, soil type, pH, and EC, are selected for the forward stepwise LR analysis. The total ratio of correct classification reaches 92.7%. The highest probability of nitrate-N contamination map presents in the central zone, indicating that groundwater in the central zone should not be used for drinking purposes. Furthermore, a handy EC-pH-probability curve of nitrate-N exceeding the threshold of DWQS was developed. This curve can be used for preliminary screening of nitrate-N contamination in Kinmen groundwater. This study recommended that the local agency should implement the best management practice strategies to control nonpoint nitrogen sources and carry out a systematic monitoring of groundwater quality in residential wells of the high nitrate-N contamination zones.