A bZIP containing upstream open reading frame (uORF) is involved in integrated stress response (ISR) in plants

Bich Ngoc Vu,Jae Yong Yoo,Ki Seong Ko,Young Eun Lee,Ha Na Choi,Yoo Na Lee,Mi Hui Jang,Kyun Oh Lee 한국당과학회 2022 한국당과학회 학술대회 Vol.2022 No.07

To cope with multiple stresses caused by various biotic and abiotic stimuli and consequently increased accumulation of misfolded proteins, eukaryotic cells activate a series of adaptive mechanisms that are known as the unfolded protein response (UPR). In response to cellular stresses, phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α) attenuates general protein synthesis. However, it also favors the selective translation of mRNAs with upstream open reading frames (uORFs) such as ATF4, a key regulator of the integrated stress response (ISR), in mammalian cells. The ISR is an evolutionarily conserved translational and transcriptional program initiated upon phosphorylation of eIF2α. However, no studies to date have been conducted on the ISR mediated by phosphorylation of eIF2α, and key regulators responsible for the ISR have not been identified in plants. In this study, we performed in silico analysis to investigate functional orthologs of the ATF4, and confirmed that some genes belong to bZIP family containing uORFs in the 5′UTR are potential candidates. However, it is not well understood whether they are involved in plant ISR mediated by phosphorylation of eIF2α. During prolonged ER stress, transcription of these genes increased by 2-3 fold. Arabidopsis plants overexpressing showed a more sensitive phenotype than Col-0 and knockout mutant plants under tunicamycin-induced ER stress condition, while plants overexpressing with uORF did not show any difference. In addition, the expression level of bZIP GFP fusion protein without uORF is increased under ER stress conditions compare to normal conditions. These results suggest that uORF-containing bZIP genes may have a role in plant ISR. * Corresponding

Students' Knowledge and Attitudes Towards Smoke-Free Universities: Changes Since Enactment of Vietnamese Tobacco Control Legislation

Nguyen, Ngoc Bich,Cook, Margaret,Johnstone, Kelly,Capra, Mike,Vu, Thi Hoang Lan Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.no.sup1

Background: In 2013, legislation in Vietnam regulated smoking in public areas. Included was a ban on indoor smoking at universities. Objective: Since awareness and attitude are moderators of the effectiveness of smoke-free policy, ou aim was to assess changes in students' knowledge and attitude tosecond hand smoke (SHS) and awareness and support of smoke-free legislation at four Vietnamese universities, one year after legislative changes. Methods: A two-phase cross sectional study of undergraduate students using self-administered questionnaires (based on the Global Adult Tobacco Survey and the Thrasher survey) was conducted at the introduction of the legislation and one year thereafter. Results: One-year post legislation there were significant increases in knowledge of smoke-free legislation and awareness of universities as smoke-free environments. There was a significant increase in knowledge of harmful effects of SHS on diseases such as examples in the heart and lung, including lung cancer, and miscarriage. Students expressed strong support of smoke-free environments in universities, hospitals, schools, workplaces, public transport, libraries, cinemas and theatres; support was also increased post legislation. Changes were seen in attitude to SHS, and rights of non-smokers and smokers. Conclusions: Positive changes have occurred in knowledge and attitude toward smoke-free environments and SHS in universities since enactment of Vietnamese tobacco control legislation.

Spectrum of Lysosomal Storage Disease Targeted for Newborn Screening in Vietnam

Dung, Vu Chi,Ngoc, Can Thi Bich,Khanh, Nguyen Ngoc,Mai, Do Thi Thanh,Thao, Bui Phuong,Mai, Tran Thi Chi,Ha, Nguyen Thu,Huong, Nguyen Thi Mai,Nam, Nguyen Hoang,Hai, Le Thanh,Tomatsu, Shunji,Yoo, Han-Wo Association for Research of MPS and Rare Diseases 2017 Journal of mucopolysaccharidosis and rare disease Vol.3 No.1

The Effect of Institutions on Productivity Spillovers from FDI to Domestic Firms: Evidence in Vietnam

Huynh Quoc Vu,Pham Thi Bich Ngoc,Nguyen Le Hoang Thuy To Quyen 사람과세계경영학회 2022 Global Business and Finance Review Vol.27 No.3

Purpose: The purpose of this study is to investigate the impact of formal institutions and their components on productivity spillovers from FDI enterprises to domestic firms’ TFP in developing countries like Vietnam. Design/methodology/approach: The study, conducted in two steps to explore the relationship, is to estimate the firm's TFP in accordance with the semi-parametric method of Levisohn and Petrin (2003). Regression is in accordance with the equation with panel data and adjusted by Driscoll and Kraay standard errors. An unbalanced panel data, related to more than 61,600 Vietnamese manufacturing firms from 2012 to 2017, is combined with the Provincial Institutional Quality Survey (PAPI index) and IO table. Findings: The local institutions have a positive impact on promoting learning ability and increasing productivity of domestic firms, especially small and medium enterprises (SMEs) that take better advantage of this effect. Vertical linkages with FDI enterprises assist local firms to increase productivity while horizontal linkages bring in negative effects. Domestic enterprises with high productivity (in the top 25%) receive positive spillover effects from horizontal linkages and vertical linkages and gain positive impacts of the institution on productivity whereas the group of low-productivity enterprises records negative impacts. This research highlights those enterprises operating in the region where institutions have transparency, accountability, participation in comments and effective corruption control can absorb spillovers and improve their productivity as well as the transparency and corruption control are recognized as having a positive impact through horizontal linkages. Research limitations/implications: With the limitation of research data being conducted only on manufacturing enterprises, there is a lack of data on the impact of service enterprises. The study only stops at understanding the impact of formal institutional effects on productivity spillovers whereas informal institutional effects will be studied in the future. Furthermore, the productivity spillovers of FDI enterprises are explored in general besides other FDI forms that will have different productivity spillovers like offshore. From the results of this study, the governments of developing countries should improve their institutions to encourage local enterprises to take the advantage of spillover effects from FDI enterprises as well as pay more attention to regional factors by supplementing development priority policies based on the capacity of each region. Institutional quality at provincial level has a positive impact on productivity spillovers; consequently, it is essential to have policies for further institutional improvement. Originality/value: This is the first research paper on the impact of the institutional factor at provincial level on firm’s productivity in developing countries like Vietnam. Theoretically, the impact of formal institutions on spillover effects from FDI enterprises is also clarified. In addition, our findings have implications for local economic development policies: vertical linkages promote domestic firms to increase their productivity while horizontal linkages of FDI enterprises in the same industry generate adverse impacts. This paper suggests some feasible solutions for SMEs in developing countries towards their productivity improvement.

P58IPK facilitates plant recovery from ER stress by enhancing protein synthesis

고기성,유재용,김경화,황보영,Vu Bich Ngoc,이영은,최하나,이유나,윤지희,박지예,정우식,홍종찬,정명선,정현석,정수경,박정미,이균오 한국식물생명공학회 2022 Plant biotechnology reports Vol.16 No.6

P58IPK has been implicated in eukaryotic ER stress responses and viral pathogenesis, however, its biological functions and molecular mechanism in plants are unclear. Prolonged ER stress produced by tunicamycin (TM) increased P58IPK mRNA and protein levels in Arabidopsis. Although the growth of 2×35S:P58IPK-myc plants was less severely inhibited than that of Col-0 plants, TM inhibited the growth of p58ipk-2 mutants more severely than that of Col-0 plants. Under prolonged ER stress conditions, the unfolded protein response (UPR)-related genes were expressed at a higher level in the p58ipk-2 mutants than in Col-0 plants. Protein synthesis inhibition by TM in 2×35S:P58IPK-myc plants was lower than in Col-0 plants under prolonged ER stress conditions, however, not signifcantly diferent in p58ipk-2 mutants. The GST-P58IPK protein exhibited both chaperone and RNA-binding activities in a dose-dependent manner. P58IPK has been shown to interact with ribosomes, allowing for enhanced protein production on the ER membrane. Following ER stress, 2×35S:P58IPK-myc plants recovered better than Col-0, but p58ipk-2 mutants recovered less than Col-0. These fndings reveal that P58IPK can promote protein translation in association with ribosomes and contribute to stress recovery in Arabidopsis when induced during the last phase of ER stress

Identification of three novel mutations in PCNT in vietnamese patients with microcephalic osteodysplastic primordial dwarfism type II

Thu Hien Nguyen,Ngoc‑Lan Nguyen,Chi Dung Vu,Can Thi Bich Ngoc,Ngoc Khanh Nguyen,Huy Hoang Nguyen 한국유전학회 2021 Genes & Genomics Vol.43 No.2

Background Primordial dwarfsm (PD) is a group of genetically heterogeneous disorders related to developmental disabilities occurring in the uterus and prolongs during all stages of life, resulting in short stature, facial deformities and abnormal brain. Objective To determine the exact cause of the disease in two Vietnamese patients priory diagnosed with PD by severe preand postnatal growth retardation with marked microcephaly and some bone abnormalities. Methods Whole-exome sequencing was performed for the two patients and mutations in genes related to PD were screened. Sanger sequencing was applied to examine the mutations in the patients of their families. Results Three novel mutations in the PCNT gene which have not been reported previously were identifed in the two patients. Of which, two frameshift mutations (p.Thr479Profs*6 and p.Glu2742Alafs*8) were detected in patient I and one stop-gained mutation (p.Gln1907*) was detected in the patient II. These mutations may result in a truncated PCNT protein, leading to an inactivated PACT domain corresponding to residue His3138–Trp3216 of PCNT protein. Therefore, the three mutations may cause a defciency of protein functional activity and result in the phenotypes of primordial dwarfsm in the two patients. Conclusions Clinical presentations in combination with genetic analyses supported an accurate diagnosis of the two patients with microcephalic osteodysplastic primordial dwarfsm type II (MOPD II). In addition, these results have important implications for prenatal genetic screening and genetic counseling for the families.

Changes in Vietnamese Male Smokers' Reactions Towards New Pictorial Cigarette Pack Warnings Over Time

Tran, Thu Ngan,Le, Vu Anh,Nguyen, Thi Tuyet My,Nguyen, Ngoc Bich Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.no.sup1

Printing of pictorial health warnings (PHWs) on cigarette packages became obligatory by the Vietnam Law on Prevention and Control of Tobacco Harm in May 2013. Literature from high-income countries suggests that PHWs motivate smokers to quit smoking although their long-term effects have been questioned due to reduction of impact over time. This study aimed to assess the salience of PHWs and smokers' reactions towards PHWs over time. In May 2014 and May 2015, a cross-sectional questionnaire-based household survey was administered to respectively 1,462 and 1,509 Vietnamese male smokers aged 18 to 35. The result showed that salience of the PHWs 2 years after the implementation was higher than at the point of 1 year after the implementation. The proportion of respondents who tried to avoid noting the PHWs was reduced from 35% in wave 1 to 23% in wave 2. However, "Tried to avoid looking/thinking about the PHWs" increased 1.5 times the odds of presenting quit intention compared to those respondents who did not try to avoid looking/thinking about the PHWs (OR=1.5; 95%CI: 1.2-2.0). In conclusion, avoidance regarding PHWs may not work as a barrier when aiming at a higher level of quit intention. Salience of the PHWs may increase in the period shortly after their introduction onto packs but can be expected to decrease with time. In other words, it might be advisable to change or renew PHWs after a period of implementation to maintain their beneficial effects.

Mesenchymal Stem Cell Transplantation for Ischemic Diseases: Mechanisms and Challenges

Van Nguyen Thi-Tuong,Vu Ngoc Bich,Van Pham Phuc 한국조직공학과 재생의학회 2021 조직공학과 재생의학 Vol.18 No.4

Ischemic diseases are conditions associated with the restriction or blockage of blood supply to specific tissues. These conditions can cause moderate to severe complications in patients, and can lead to permanent disabilities. Since they are blood vessel-related diseases, ischemic diseases are usually treated with endothelial cells or endothelial progenitor cells that can regenerate new blood vessels. However, in recent years, mesenchymal stem cells (MSCs) have shown potent bioeffects on angiogenesis, thus playing a role in blood regeneration. Indeed, MSCs can trigger angiogenesis at ischemic sites by several mechanisms related to their trans-differentiation potential. These mechanisms include inhibition of apoptosis, stimulation of angiogenesis via angiogenic growth factors, and regulation of immune responses, as well as regulation of scarring to suppress blood vessel regeneration when needed. However, preclinical and clinical trials of MSC transplantation in ischemic diseases have shown some limitations in terms of treatment efficacy. Such studies have emphasized the current challenges of MSC-based therapies. Treatment efficacy could be enhanced if the limitations were better understood and potentially resolved. This review will summarize some of the strategies by which MSCs have been utilized for ischemic disease treatment, and will highlight some challenges of those applications as well as suggesting some strategies to improve treatment efficacy.

N-acetylglucosaminyltransferase (GnTII) is required for adaptation to abiotic stresses in plant

Jae Yong Yoo,Ki Seong Ko,Bich Ngoc Vu,Seok Han Yoon,Kyun Oh Lee 한국당과학회 2021 한국당과학회 학술대회 Vol.2021 No.01

The most abundant N-glycan in plants is the paucimannosidic N-glycan with core β 1,2-xylose and α1,3-fucose residues (XylMan3FucGlcNAc2). Here, we investigated the physiological significance in Arabidopsis thaliana of α-1,6-mannosyl-glycoprotein 2--N-acetylglucosaminyltransferase (EC 2.4.1.143, N-acetylglucosaminyltransferase II [GnTII]), which transfers N-acetylglucosamine (GlcNAc) residue from the nucleotide sugar donor UDP-GlcNAc to the α1,6-mannose residue of the di-antennary N-glycan acceptor in the Golgi apparatus. We assessed the phenotypic effects of a loss-of-function mutation (gnt2-1) in GnTII, and used quantitative PCR (qPCR) to examine gene expression and callose deposition assays under stress conditions. Prolonged stress from tunicamycin or NaCl treatment enhanced GnTII expression in the wild type and caused severely disrupted development and abnormal callose deposition in root tissues in the gnt2-1 mutant. Lack of the 6-arm β1,2-linked GlcNAc residue in the N-glycans promoted the unfolded protein response (UPR) upon prolonged endoplasmic reticulum (ER) stress in gnt2-1. Thus, GnTII's promotion of the 6-arm GlcNAc addition to N-glycans is important for plant growth and development under stress conditions.

Production of an enzyme for treatment of Gaucher's disease using plants

Yoo Na Lee,Ki Seong Ko,Jae Yong Yoo,Bich Ngoc Vu,Young Eun Lee,Ha Na Choi,Mi Hui Jang,Kyun Oh Lee 한국당과학회 2022 한국당과학회 학술대회 Vol.2022 No.07

Gaucher's disease is a metabolic disorder in which a functional deficiency of an enzyme occurs due to a mutation in the gene encoding glucocerebrosidase (GC), resulting in multiple organ malfunctions. Gaucher's disease is being treated with enzyme replacement therapy, which compensates for the enzyme deficiency by administering activated GCs produced in mammalian cells. However, there is a potential of contamination by pathogenic viruses or prions in the mammalian cell-based manufacturing method, as well as a high production cost. In this study, GCs were expressed in plants that produce customized N-glycans to overcome the limitations of the mammalian cell-based production system and to produce a safe treatment drug for Gaucher's disease. A human cDNA library was used to clone a region expressing a GC gene, and sequence analysis was performed. In addition, a binary vector was created and introduced into plants using Agrobacterium to insert the sequence-confirmed GC gene. Plants into which the GC gene was introduced were selected using an antibiotic-containing media, and the presence or absence of the GC gene introduction into the transformed plants was confirmed using polymerase chain reaction (PCR). Furthermore, proteins were collected from the plant leaves into which the gene was inserted, and GC expression levels in the transformed plants were measured using a GC antibody. Finally, a single cloned plant was selected through the antibiotic-resistant isolate ratio. These findings suggest that employing plants, it is possible to overcome the disadvantages of the present mammalian cell-based manufacturing method, decreasing the production cost of pricey Gaucher's disease therapy, and effectively generating safer enzyme treatment.