Function and Specificity in Signaling Pathway of Two Map Kinases Erk1 and Erk2 in Dictyostelium

MAPKs are associated with several human diseases. However, studying MAPK signaling pathways in higher eukaryotes is challenging due to presence of several MAPKs. Dictyostelium, whose genome encodes only two MAPKs ERK1 and ERK2, therefore offers many advantages in this respect. Our purpose in this research is to define the function and the specificity in signaling pathway of ERK1 and ERK2 through characterizing G protein-mediated pathways and searching for ERK-associated proteins. We used immunoprecipitation, pull-down assays and genetic analyses to examine the interactions of ERKs with wild-type and mutated Ga subunits. We also created ERK mutants and performed the complementation, suppression and epistasis tests to determine role of ERKs in Ga subunit-mediated pathways. To search for ERK-associated proteins, His6-tagged ERK1 and ERK2 complexes were isolated and then subjected to mass spectrometry analysis. Cellular distribution of the transcription factors (STATs), expression of the cell type-specific genes (ecmA, ecmB) and the knockout of the phosphodiesterase RegA were used to determine the involvement of these ERK-associated proteins in ERK pathways. Findings and Conclusions: Our results showed that the Ga4 subunit interacts with ERK2 and the Ga5 subunit associates with ERK1 through the D-motifs. The Ga4-ERK2 interaction contributes to spore development while the Ga5-ERK1 interaction regulates cell viability and tip morphogenesis. We also indicated that ERK1 and ERK2 have different roles in Ga subunit-mediated pathways. Genetic analyses of the ERK-associated proteins revealed that both ERK1 and ERK2 negatively regulate RegA; the Ga5 subunit-ERK1 pathway controls nuclear localization of STATc ultimately resulting in repression of ecmA while the Ga2/Ga4 subunits-ERK2 pathways regulate function of STATa and expression of ecmB through down regulating RegA.Department of Biochemistry and Molecular Biolog

A dynamic model of profit of residential projects in Vietnam

It is difficult to estimate the profit of residential projects as there are a number of complicated relationships among key profit factors. This study develops a dynamic model of the profit of residential projects in Ho Chi Minh City, Vietnam, utilizing a system dynamic approach, to examine the profit of residential projects in the long term. Five key profit factors, including the Urban Population, Buyer Capacity, Housing Supply, Housing Economics, and Housing Finance factors, are used to develop the dynamic model. Simulation results reveal that the average profit of residential projects in Ho Chi Minh City, Vietnam, in the next 20 years, is 35%, with a minimum and maximum profit of 19% and 41%, respectively. Scenario analyses recommend that a 30% down payment, a 25-year payment period, and a debt to equity ratio of 40% are the best strategies that residential companies should use to maximize profit in the long term. It is also recommended that debt to equity ratio and house price should be maintained in the early years to assist low-income households. The developed model can be used as a starting point to develop a software that allows developers to examine strategies by simply inputting their available data

A Passivity-based Control Combined with Sliding Mode Control for a DC-DC Boost Power Converter

In this paper, a passivity-based control combined with sliding mode control for a DC-DC boost power converter is proposed. Moreover, a passivity-based control for a DC-DC boost power converter is also proposed. Using a co-ordinate transformation of state variables and control input, a DC-DC boost power converter is passive. A new plant is zero-state observable and the equilibrium point at origin of this plant is asymptotically stable. Then, a passivity-based control is applied to this plant such that the capacitor voltage is equal to the desired voltage. Additionally, the sliding mode control law is chosen such that the derivative of Lyapunov function is negative semidefinite. Finally, a passivity-based control combined with sliding mode control law is applied to this plant such that the capacitor voltage is equal to the desired voltage. The simulation results of the passivity-based control, the sliding mode control and the passivity-based control combined with sliding mode control demonstrate the effectiveness and show that the capacitor voltage is kept at the desired voltage when the desired voltage, the input voltage E and the load resistor R are changed. The results show that compared with the passivity-based control, the passivity-based control combined with sliding mode control has better performance such as shorter settling time, 8.5 ms when R changes and it has smaller steady-state error, which is indicated by the value of integral absolute error (IAE), 0.0679 when the desired voltage changes. The paper has limitations such as the assumed circuit parameters

Identifying Key Factors influencing cost variation of construction projects in Ho Chi Minh City

Cost variation is one of the most concerns of the stakeholders in the construction projects, because it always presents in every construction projects, especially in Vietnam. However, the factors that make the project cost variation are not easy to identify. This study aimed to identify the key factors that influence to the project cost variation. A survey questionnaire was used to collect data from construction practitioners. The analysis results show that there are five groups of factors that influence to project cost variation: Government policies, nature, resources, fraud and theft, and ability of stakeholders. Recommendations are also mentioned to deal with the project cost variation

The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis

Proteins responsible for Pi homeostasis are critical for all life. In Saccharomyces cerevisiae, extracellular [Pi] is “sensed” by the inositol-hexakisphosphate kinase (IP6K) that synthesizes the intracellular inositol pyrophosphate 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) as follows: during a period of Pi starvation, there is a decline in cellular [ATP]; the unusually low affinity of IP6Ks for ATP compels 5-InsP7 levels to fall in parallel (Azevedo, C., and Saiardi, A. (2017) Trends. Biochem. Sci. 42, 219–231. Hitherto, such Pi sensing has not been documented in metazoans. Here, using a human intestinal epithelial cell line (HCT116), we show that levels of both 5-InsP7 and ATP decrease upon [Pi] starvation and subsequently recover during Pi replenishment. However, a separate inositol pyrophosphate, 1,5-bisdiphosphoinositol 2,3,4,6-tetrakisphosphate (InsP8), reacts more dramatically (i.e. with a wider dynamic range and greater sensitivity). To understand this novel InsP8 response, we characterized kinetic properties of the bifunctional 5-InsP7 kinase/InsP8 phosphatase activities of full-length diphosphoinositol pentakisphosphate kinases (PPIP5Ks). These data fulfil previously published criteria for any bifunctional kinase/phosphatase to exhibit concentration robustness, permitting levels of the kinase product (InsP8 in this case) to fluctuate independently of varying precursor (i.e. 5-InsP7) pool size. Moreover, we report that InsP8 phosphatase activities of PPIP5Ks are strongly inhibited by Pi (40–90% within the 0–1 mm range). For PPIP5K2, Pi sensing by InsP8 is amplified by a 2-fold activation of 5-InsP7 kinase activity by Pi within the 0–5 mm range. Overall, our data reveal mechanisms that can contribute to specificity in inositol pyrophosphate signaling, regulating InsP8 turnover independently of 5-InsP7, in response to fluctuations in extracellular supply of a key nutrient

Key factors influencing on Vietnamese construction performance

Together with the economic development, Vietnamese construction industry also develops very fast and occupies a large portion in economics. However, there are still many problems such as wastes, loses, low quality or low productivity relating to construction activities need to be improved. This paper aims at finding out the factors that influence on the performance of construction sites. A survey was carried out and found out 25 key factors that influence on the performance of construction sites. These factors are divided into six groups such as management, human resources, technology, finance, material/equipment and design after factor analysis. By ranking the importance of factors, this paper helps the contractors to focus on the most important factors to upgrade their competency

MUTATION ANALYSIS OF DJ-1 GENE IN VIETNAMESE PARKINSON’S DISEASE PATIENTS

Parkinson’s disease (PD) is a degenerative condition of the brain of uncertain cause that mainly affects older people. Shaking is a distinctive feature of the disease, but slowness, poverty of movement and stiffness interfere with everyday life. A large number of known pathogenic mutations of genes related to PD have been identified. The DJ-1 gene, one of PARK genes, is considered as the primary cause of PD in different populations. The analysis of mutation frequency of the DJ-1 gene in Vietnamese PD patients is necessary to clarify the pathogenic associations of PD with the DJ-1 gene and to understand the pathogenesis and genetic mechanisms of PD. In this study, genomic DNA was extracted from peripheral blood of 30 PD patients (mean age 64.11 ± 7.31 years) and 20 controls and directed Sanger sequencing of one fragment of DJ-1 gene, containing the introns 4 and 5 as well as exon 5. The obtained results showed that there were 13 heterozygous or homozygous point mutations in introns 4 and 5. The late-onset sporadic PD (LOPD) patient carried a single homozygous mutation in intron 5 (IVS5+31GA), and others had a heterozygous mutation, all of unknown significance.  Moreover, both the Ala86Glu and Gly95Leu mutations in exon 5 were present in one LOPD patient suggesting possible change of functional protein. Analysis of these mutations were shown the nonsynonymous and uncertain significant mutation, therefore they may not be related to pathogenic mutations of PD. Further research is needed to study the contribution of the novel found mutation in other PARK genes to the pathogenesis of Vietnamese PD patients

Establishing and validating noninvasive prenatal testing procedure for fetal aneuploidies in Vietnam

Noninvasive prenatal testing (NIPT) for fetal aneuploidies has been widely adopted in developed countries. Despite the sharp decrease in the cost of massively parallel sequencing, the technical know-how and skilled personnel are still one of the major limiting factors for applying this technology to NIPT in low-income settings. Here, we present the establishment and validation of our NIPT procedure called triSure for detection of fetal aneuploidies.We established the triSure algorithm based on the difference in proportion of fetal and maternal fragments from the target chromosome to all chromosomes. Our algorithm was validated using a published data set and an in-house data set obtained from high-risk pregnant women in Vietnam who have undergone amniotic testing. Several other aneuploidy calling methods were also applied to the same data set to benchmark triSure performance.The triSure algorithm showed similar accuracy to size-based method when comparing them using published data set. Using our in-house data set from 130 consecutive samples, we showed that triSure correctly identified the most samples (overall sensitivity and specificity of 0.983 and 0.986, respectively) compared to other methods tested including count-based, sized-based, RAPIDR and NIPTeR.We have demonstrated that our triSure NIPT procedure can be applied to pregnant women in low-income settings such as Vietnam, providing low-risk screening option to reduce the need for invasive diagnostic tests

Improvement in neoantigen prediction via integration of RNA sequencing data for variant calling

IntroductionNeoantigen-based immunotherapy has emerged as a promising strategy for improving the life expectancy of cancer patients. This therapeutic approach heavily relies on accurate identification of cancer mutations using DNA sequencing (DNAseq) data. However, current workflows tend to provide a large number of neoantigen candidates, of which only a limited number elicit efficient and immunogenic T-cell responses suitable for downstream clinical evaluation. To overcome this limitation and increase the number of high-quality immunogenic neoantigens, we propose integrating RNA sequencing (RNAseq) data into the mutation identification step in the neoantigen prediction workflow.MethodsIn this study, we characterize the mutation profiles identified from DNAseq and/or RNAseq data in tumor tissues of 25 patients with colorectal cancer (CRC). Immunogenicity was then validated by ELISpot assay using long synthesis peptides (sLP).ResultsWe detected only 22.4% of variants shared between the two methods. In contrast, RNAseq-derived variants displayed unique features of affinity and immunogenicity. We further established that neoantigen candidates identified by RNAseq data significantly increased the number of highly immunogenic neoantigens (confirmed by ELISpot) that would otherwise be overlooked if relying solely on DNAseq data.DiscussionThis integrative approach holds great potential for improving the selection of neoantigens for personalized cancer immunotherapy, ultimately leading to enhanced treatment outcomes and improved survival rates for cancer patients