Whole genome analysis of a Vietnamese trio Hai, Dang Thanh; Thanh, Nguyen Dai; Trang, Pham Thi Minh ...
Journal of biosciences,
03/2015, Volume:
40, Issue:
1
Journal Article
Peer reviewed
ABSTRACT
We here present the first whole genome analysis of an anonymous Kinh Vietnamese (KHV) trio whose genomes were deeply sequenced to 30-fold average coverage. The resulting short reads covered ...99.91% of the human reference genome (GRCh37d5). We identified 4,719,412 SNPs and 827,385 short indels that satisfied the Mendelian inheritance law. Among them, 109,914 (2.3%) SNPs and 59,119 (7.1%) short indels were novel. We also detected 30,171 structural variants of which 27,604 (91.5%) were large indels. There were 6,681 large indels in the range 0.1–100 kbp occurring in the child genome that were also confirmed in either the father or mother genome. We compared these large indels against the DGV database and found that 1,499 (22.44%) were KHV specific.
De novo
assembly of high-quality unmapped reads yielded 789 contigs with the length ≥300 bp. There were 235 contigs from the child genome of which 199 (84.7%) were significantly matched with at least one contig from the father or mother genome. Blasting these 199 contigs against other alternative human genomes revealed 4 novel contigs. The novel variants identified from our study demonstrated the necessity of conducting more genome-wide studies not only for Kinh but also for other ethnic groups in Vietnam.
The development of targeted therapeutics for neuroblastoma, the third most common tumor in children, has been limited by a poor understanding of growth signaling mechanisms unique to the peripheral ...nerve precursors from which tumors arise. In this study, we combined genetics with gene-expression analysis in the peripheral sympathetic nervous system to implicate arginase 1 and GABA signaling in tumor formation in vivo. In human neuroblastoma cells, either blockade of ARG1 or benzodiazepine-mediated activation of GABA-A receptors induced apoptosis and inhibited mitogenic signaling through AKT and MAPK. These results suggest that ARG1 and GABA influence both neural development and neuroblastoma and that benzodiazepines in clinical use may have potential applications for neuroblastoma therapy.
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•Arg1 and GABA gene expression correlates with neuroblastoma formation in mice•GABA gene expression correlates with survival in human neuroblastomas•Both activation of GABA-A and inhibition of ARG1 block the growth of neuroblastoma cells•A benzodiazepine inhibits AKT and ERK and induces apoptosis in neuroblastoma cells
Neuroblastoma is a pediatric tumor of peripheral neural tissue. Hackett et al. now link Arg1 and GABA with genetic susceptibility to neuroblastoma formation in mice. Expression of GABA genes correlates with survival in human tumors. GABA activation and ARG1 inhibition block the growth of neuroblastoma cells. These results identify therapeutic targets in neuroblastoma and suggest a role for these pathways in neural growth.
This study investigated arsenic (As) concentrations in existing drinking water sources in Hanam province, Vietnam. Sand-filtered groundwater, piped water, raw groundwater, and a type of drinking ...water mostly sourced from rainwater (hereafter referred to as the “stored rainwater”) are commonly used for drinking purposes in this area. It was found that all water sources contained different levels of toxic As. The highest levels were found in raw groundwater, followed by sand-filtered water, piped water, and stored rainwater. More than 50% of the stored rainwater samples contained As levels above the WHO recommendation value. As such, the daily As uptake in local residents from this kind of stored rainwater may be larger than previously considered because they consume stored rainwater as an alternative drinking water source. Relatively high levels of As in the stored rainwater samples also suggested that residents possibly mix rain and groundwater in rainwater containers in order to meet their daily water demand.
The paper analyzed the evolution of policies to reduce GHG emissions reduction in Vietnam, primarily to fulfill its transparency commitment under the UNFCCC and the Paris Agreement. The uncertainty ...in the transparency rules of the Paris Agreement will be considered to sketch-out the most likely options for developing national policies to meet the future transparency requirements. The key actors and factors in Vietnam impacted by the policies are illustrated. To analyze the extent of penetration of transparency actions and future potentials provided these options, the progress of building congruence toward domesticating international norms of climate change in Vietnam by empirical assessment of the readiness to implement the ETF is conducted. In their turns, the way each relevant stakeholder responded to newly introduced requirements has a profound impact on policy making and enforcement in Vietnam and can represent a typical example of how the community react to a shift in transparency frameworks. Besides, the paper explores how the transparency policies will imply on the monitoring the transition to a low carbon economy in Vietnam under those reactions and the recommend the way forwards that the country may adopt to make its climate change commitment achieved and benefit significantly from the process.
Complementary medicine, which refers to therapies that are not part of conventional medicine, comprising both evidence-based and non-evidence-based interventions, is increasingly used following a ...diagnosis of cancer. We aimed to investigate out-of-pocket spending patterns on complementary medicine and its association with adverse financial outcomes following cancer in middle-income countries in southeast Asia.
In this prospective cohort study, data on newly diagnosed patients with cancer were derived from the ASEAN Costs in Oncology (ACTION) cohort study, a prospective longitudinal study in 47 centres located in eight countries in southeast Asia. The ACTION study measured household expenditures on complementary medicine in the immediate year after cancer diagnosis. Participants were given cost diaries at baseline to record illness-related payments that were directly incurred and not reimbursed by insurance over the 12-month period after study recruitment. We assessed incidence of financial catastrophe (out-of-pocket cancer-related costs ≥30% of annual household income), medical impoverishment (reduction in annual household income to below poverty line following subtraction of out-of-pocket cancer-related costs), and economic hardship (inability to make necessary household payments) at 1 year.
Between March, 2012, and September, 2013, 9513 participants were recruited into the ACTION cohort study, of whom 4754 (50·0%) participants were included in this analysis. Out-of-pocket expenditures on complementary medicine were reported by 1233 households. These payments constituted 8·6% of the annual total out-of-pocket health costs in lower-middle-income countries and 42·9% in upper-middle-income countries. Expenditures on complementary medicine significantly increased risks of financial catastrophe (adjusted odds ratio 1·52 95% CI 1·23–1·88) and medical impoverishment (1·75 1·36–2·24) at 12 months in upper-middle-income countries only. However, the risks were significantly higher for economically disadvantaged households, irrespective of country income group.
Integration of evidence-supported complementary therapies into mainstream cancer care, along with interventions to address use of non-evidence-based complementary medicine, might help alleviate any associated adverse financial impacts.
None.
The current study is mainly focused on discovering the combinative influence of gender roles and occupation on negotiation performances in the context of Vietnam. The target participants are blue ...collar and white-collar workers who are working in Ho Chi Minh city. Qualitative approach is employed for the current research because this is an exploratory research on negotiation performances. Structured interview is utilized to gather data on gender roles, occupation and negotiation performances. The structure interview is divided into the three-stage procedure with pre-negotiation stage, negotiation stage and post-negotiation stage and each stage has identified research subjects. The collected data from three types of documents including pre-negotiation survey, post-negotiation survey and the final agreement form are examined using thematic analysis.
The class III receptor tyrosine kinase FLT3 is expressed on the blasts of >90% of patients with B-lineage acute lymphoblastic leukemias (ALL). In addition, it is expressed at extremely high levels in ...ALL patients with mixed lineage leukemia rearrangements or hyperdiploidy and is sometimes mutated in these same patients. In this report, we investigate the effects of treating ALL cell lines and primary samples with human anti-FLT3 monoclonal antibodies (mAb) capable of preventing binding of FLT3 ligand. In vitro studies, examining the ability of two anti-FLT3 mAbs (IMC-EB10 and IMC-NC7) to affect FLT3 activation and downstream signaling in ALL cell lines and primary blasts, yielded variable results. FLT3 phosphorylation was consistently inhibited by IMC-NC7 treatment, but in some cell lines, IMC-EB10 actually stimulated FLT3 activation, possibly as a result of antibody-mediated receptor dimerization. Through antibody-dependent, cell-mediated cytotoxicity, such an antibody could still prove efficacious against leukemia cells in vivo. In fact, IMC-EB10 treatment significantly prolonged survival and/or reduced engraftment of several ALL cell lines and primary ALL samples in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. This occurred even when IMC-EB10 treatment resulted in FLT3 activation in vitro. Moreover, fluorescence-activated cell sorting and PCR analysis of IMC-EB10-treated NOD/SCID mice surviving 150 days post-leukemic cell injection revealed that FLT3 immunotherapy reduced leukemic engraftment below the level of detection in these assays (<0.001%). Furthermore, in vivo IMC-EB10 treatment did not select for resistant cells, because cells surviving IMC-EB10 treatment remain sensitive to IMC-EB10 cytotoxicity upon retransplantation. In vivo studies involving either partial depletion or activation of natural killer (NK) cells show that most of the cytotoxic effect of IMC-EB10 is mediated through NK cells. Therefore, such an antibody, either naked or conjugated to radioactive isotopes or cytotoxic agents, may prove useful in the therapy of infant ALL as well as childhood and adult ALL patients whose blasts typically express FLT3.
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