The frequency of the known mitochondrial variants associated with drug-induced toxicity in a Korean population.

BACKGROUND: Few studies have annotated the whole mitochondrial DNA (mtDNA) genome associated with drug responses in Asian populations. This study aimed to characterize mtDNA genetic profiles, especially the distribution and frequency of well-known genetic biomarkers associated with diseases and drug-induced toxicity in a Korean population. METHOD: Whole mitochondrial genome was sequenced for 118 Korean subjects by using a next-generation sequencing approach. The bioinformatic pipeline was constructed for variant calling, haplogroup classification and annotation of mitochondrial mutation. RESULTS: A total of 681 variants was identified among all subjects. The MT-TRNP gene and displacement loop showed the highest numbers of variants (113 and 74 variants, respectively). The m.16189T > C allele, which is known to reduce the mtDNA copy number in human cells was detected in 25.4% of subjects. The variants (m.2706A > G, m.3010A > G, and m.1095T > C), which are associated with drug-induced toxicity, were observed with the frequency of 99.15%, 30.51%, and 0.08%, respectively. The m.2150T > A, a genotype associated with highly disruptive effects on mitochondrial ribosomes, was identified in five subjects. The D and M groups were the most dominant groups with the frequency of 34.74% and 16.1%, respectively. CONCLUSIONS: Our finding was consistent with Korean Genome Project and well reflected the unique profile of mitochondrial haplogroup distribution. It was the first study to annotate the whole mitochondrial genome with drug-induced toxicity to predict the ADRs event in clinical implementation for Korean subjects. This approach could be extended for further study for validation of the potential ethnic-specific mitochondrial genetic biomarkers in the Korean population.

Comparison of multivariate linear regression and a machine learning algorithm developed for prediction of precision warfarin dosing in a Korean population.

BACKGROUND: Personalized warfarin dosing is influenced by various factors including genetic and non-genetic factors. Multiple linear regression (LR) is known as a conventional method to develop predictive models. Recently, machine learning approaches have been extensively implemented for warfarin dosing due to the hypothesis of non-linear association between covariates and stable warfarin dose. OBJECTIVE: To extend the multiple linear regression algorithm for personalized warfarin dosing in a Korean population and compare with a machine learning--based algorithm. METHOD: From this cohort study, we collected information on 650 patients taking warfarin who achieved steady state including demographic information, indications, comorbidities, comedications, habits, and genetic factors. The dataset was randomly split into training set (90%) and test set (10%). The LR and machine learning (gradient boosting machine [GBM]) models were developed on the training set and were evaluated on the test set. RESULT: LR and GBM models were comparable in terms of accuracy of ideal dose (75.38% and 73.85%), correlation (0.77 and 0.73), mean absolute error (0.58 mg/day and 0.64 mg/day), and root mean square error (0.82 mg/day and 0.9 mg/day), respectively. VKORC1 genotype, CYP2C9 genotype, age, and weight were the highest contributors and could obtain 80% of maximum performance in both models. CONCLUSION: This study shows that our LR and GMB models are satisfactory to predict warfarin dose in our dataset. Both models showed similar performance and feature contribution characteristics. LR may be the appropriate model due to its simplicity and interpretability.

Higher Photochemical Quenching and Better Maintenance of Carbon Dioxide Fixation Are Key Traits for Phosphorus Use Efficiency in the Wheat Breeding Line, RAC875.

Maintaining carbohydrate biosynthesis and C assimilation is critical under phosphorus (P) deficiency as inorganic P (Pi) is essential for ATP synthesis. Low available P in agricultural soils occurs worldwide and fertilizer P sources are being depleted. Thus, identifying biosynthetic traits that are favorable for P use efficiency (PUE) in crops is crucial. This study characterized agronomic traits, gas exchange, and chlorophyll traits of two wheat genotypes that differ in PUE. RAC875 was a P efficient genotype and Wyalkatchem was a P inefficient genotype. The plants were grown in pots under growth room conditions at two P levels; 10 mg P kg-1 soil (low P) and 30 mg P kg-1 soil (adequate P) and gas exchange and chlorophyll fluorescence were measured at the vegetative and booting stages using a portable photosynthesis system (LI-6800, LI-COR, United States). Results showed significant differences in some agronomic traits between the two wheat genotypes, i.e., greater leaf size and area, and a higher ratio of productive tillers to total tillers in RC875 when compared with Wyalkatchem. The CO2 response curve showed Wyalkatchem was more severely affected by low P than RAC875 at the booting stage. The relative ratio of the photosynthetic rate at low P to adequate P was also higher in RAC875 at the booting stage. Photochemical quenching (qP) in RAC875 was significantly higher when compared with Wyalkatchem at the booting stage. Maintaining CO2 fixation capacity under low P and higher qP would be associated with P efficiency in RAC875 and measuring qP could be a potential method to screen for P efficient wheat.

Genotypic Variation in the Root and Shoot Metabolite Profiles of Wheat (Triticum aestivum L.) Indicate Sustained, Preferential Carbon Allocation as a Potential Mechanism in Phosphorus Efficiency.

Changes in the levels of plant metabolites in response to nutrient deficiency is indicative of how plants utilize scarce resources. In this study, changes in the metabolite profile of roots and shoots of wheat genotypes differing in phosphorus use efficiency (PUE) was investigated. Under low P supply and at 28 days after sowing (DAS), the wheat breeding line, RAC875 (P efficient) produced 42% more shoot biomass than the wheat variety, and Wyalkatchem (P inefficient). Significant changes in the metabolite profile in leaves and roots were observed under low P supply and significant genotypic variation was evident. Under low P supply, an increase in raffinose and 1-kestose was evident in roots of both wheat genotypes, with RAC875 accumulating more when compared to Wyalkatchem. There was no significant increase in raffinose and 1-kestose in leaves when plants were grown under P deficiency. P deficiency had no significant impact on the levels of sucrose, maltose, glucose and fructose in both genotypes, and while phosphorylated sugars (glucose-6-P and fructose-6-P) remained unchanged in RAC875, in Wyalkatchem, glucose-6-P significantly decreased in roots, and fructose-6-P significantly decreased in both leaves and roots. Glycerol-3-P decreased twofold in roots of both wheat genotypes in response to low P. In roots, RAC875 exhibited significantly lower levels of fumarate, malate, maleate and itaconate than Wyalkatchem, while low P enhanced organic acid exudation in RAC875 but not in Wyalkatchem. RAC875 showed greater accumulation of aspartate, glutamine and ß-alanine in leaves than Wyalkatchem under low P supply. Greater accumulation of raffinose and 1-kestose in roots and aspartate, glutamine and ß-alanine in leaves appears to be associated with enhanced PUE in RAC875. Glucose-6-P and fructose-6-P are important for glycolysis, thus maintaining these metabolites would enable RAC875 to maintain carbohydrate metabolism and shoot biomass under P deficiency. The work presented here provides evidence that differences in metabolite profiles can be observed between wheat varieties that differ in PUE and key metabolic pathways are maintained in the efficient genotype to ensure carbon supply under P deficiency.

Growth in children infected with HIV receiving anti-retroviral therapy in Vietnam.

BACKGROUND: There are currently two markers used to monitor treatment response to anti-retroviral therapy (ART) in HIV-infected children: CD4 T-cell count and HIV viral load; but analysis of these could be challenging in resource-poor countries. The aim of this study was therefore to determine whether change in growth parameters such as weight-for-age Z score (WAZ), height-for-age Z score (HAZ) and body mass index-for-age Z score (BMIZ) is associated with treatment response in HIV-infected children. METHODS: This was a nested case-control study, in which the data were collected at enrolment and then periodically every 6 months for a total 36 month follow up of 107 HIV-infected children enrolled and treated at National Hospital of Pediatrics, Vietnam. RESULTS: At treatment initiation, WAZ, HAZ and BMIZ were not significantly higher in the treatment success (TS) group compared with the treatment failure (TF) group. After ART initiation, WAZ and HAZ increased, and this was significant in the TS group (from -1.5 to -0.54, P < 0.01 and from -2.06 to -0.84, P < 0.01, respectively). Low HAZ was significantly associated with TF (HR, 0.71; 95% CI: 0.54-0.92). CONCLUSION: Height-for-age Z score was the most sensitive growth parameter in prediction of the treatment response. In order to use growth parameters, particularly HAZ as a prognosis marker for TF in clinical practice, further research should be conducted to evaluate the role of growth parameters and their effects on treatment response.

Elevation of immunoglobulin levels is associated with treatment failure in HIV-infected children in Vietnam.

BACKGROUND: HIV-infected children suffer from higher levels of treatment failure compared to adults. Immunoactivation, including humoral immunoactivation reflected by increased immunoglobulin levels, is believed to occur early during HIV infection. Therefore, we wanted investigate alteration in immunoglobulin levels in association with treatment response in HIV-infected children. METHODS: A nested case-control study was conducted using clinical data collected from 68 HIV-infected children enrolled at the National Hospital of Pediatrics, Vietnam. RESULTS: The results showed that immunoglobulin levels, CD4 T-cell counts, CD4 T-cell percentage, and HIV load were significantly higher in the treatment-failure group than the treatment-success group at treatment initiation. IgG and IgA levels were negatively correlated with CD4 T-cell counts (P=0.049 and P<0.01, respectively) and positively correlated with HIV load (P=0.04 and P=0.02, respectively). In addition, IgG and IgA levels were independently associated with treatment response, analyzed by Cox regression analysis (HR 1.19 [P=0.049] and HR 1.69 [P<0.01], respectively). CONCLUSION: Elevation of IgA levels occurred early during HIV infection, and might have a prognostic role in treatment response.

Metagenomic insights into lignocellulose-degrading genes through Illumina-based de novo sequencing of the microbiome in Vietnamese native goats' rumen.

The scarcity of enzymes having an optimal activity in lignocellulose deconstruction is an obstacle for industrial-scale conversion of cellulosic biomass into biofuels. With the aim of mining novel lignocellulolytic enzymes, a ~9 Gb metagenome of bacteria in Vietnamese native goats' rumen was sequenced by Illumina platform. From the data, 821 ORFs encoding carbohydrate esterases (CEs) and polysaccharide lyases (PLs) serving for lignocellulose pre-treatment, 816 ORFs encoding 11 glycoside hydrolase families (GHs) of cellulases, and 2252 ORFs encoding 22 GHs of hemicellulases, were mined. The carbohydrate binding module (CBM) was also abundant with 763 ORFs, of which 480 ORFs are located with lignocellulolytic enzymes. The enzyme modularity analysis showed that CBMs are usually present in endoglucanase, endo 1,3-beta-D-glucosidase, and endoxylanase, whereas fibronectin 3-like module (FN3) mainly represents in GH3 and immunoglobulin-like domain (Ig) was located in GH9 only. Every domain located in each ORF was analyzed in detail to contribute enzymes' modularity which is valuable for modelling, to study the structure, and for recombinant production. With the aim of confirming the annotated results, a mined ORF encoding CBM63 was highly expressed in E. coli in soluble form. The purified recombinant CBM63 exhibited no cellulase activity, but enhanced a commercial cellulase activity in the destruction of a paper filter.

Clinical characteristics of pediatric HIV-1 patients treated with first-line antiretroviral therapy in Vietnam: a nested case-control study.

OBJECTIVES: Over the past decades, Vietnam has made great strides in reducing the rate of mortality in HIV-related deaths, due to increased access of antiretroviral therapy (ART); however, given the significantly high level of treatment failure (TF), it is essential to identify markers that describe the failure of ART in HIV-1 infected children. METHODS: A nested case-control study was conducted with clinical data collected from 101 HIV-infected children [26 TF and 75 treatment success (TS)] at National Hospital of Pediatrics, Vietnam (2008-2012). RESULTS: The results showed that certain factors including height, weight, vaccination with Hepatitis B, and platelet were significantly different between TF and TS before starting the treatment. In addition, age to start the treatment, CD4 percentage, and opportunistic infection were found to significantly predict treatment outcome most frequently, implying the importance of clinical markers in the treatment response by Cox regression analysis. CONCLUSIONS: There is an inherent complexity within clinical markers that is challenging to determine HIV-pediatric failure and further research is needed to build a complete picture to guide clinical, evidence-based practice.

Leaf photosynthesis of 'Cat Hoa Loc' mango (Mangifera indica L.) and 'Nam Roi' pummelo (Citrus grandis (L.) Osbeck.) in the rainy season.

With an EARS--Plant photosynthesis meter we determined gross photosynthesis (P) of leaves of 'Cat Hoa Loc' mango on 4 years old trees planted in the Fruit Tree Experiment and Production Station, Campus 2, Department of Crop Science, College of Agriculture, Can Tho University in the rainy season of the year 2000. The same experiment was conducted on 'Nam Roi' pummelo on a farm located in the Binh Minh district, Vinh Long province. In the rainy season the calculated gross photosynthesis of 'Cat Hoa Loc' mango leaves at flowering stage was higher than that at the vegetative stage. However, the photosynthetically active radiation and quantum yield of 'Cat Hoa Loc' mango leaves in both stages did not reach the light saturation point when compared with values from estimated equation of photosynthetic light curve. The same holds true for 'Nam Roi' pummelo in the vegetative stage.

[Human chlamydia infections (authors' transl)]. / Infections humaines à Chlamydia. Etude d'une technique de diagnostic rapide.

Human Chlamydia infections have diverse clinical presentations and various biological methods are used for their diagnosis. Despite progress in laboratory techniques, theses methods are relatively slow: inoculation of chick embryos requires 4 to 12 days, cell culture from 2 to 3 days and indirect immunofluorescence a whole morning. Counter immunoelectrophoresis seems to have a future, as it is rapid (45 minutes), easy to perform, highly sensitive and applicable to routine examinations.