Genetic signatures of Mycobacterium tuberculosis Nonthaburi genotype revealed by whole genome analysis of isolates from tuberculous meningitis patients in Thailand.

Genome sequencing plays a key role in understanding the genetic diversity of Mycobacterium tuberculosis (M.tb). The genotype-specific character of M. tb contributes to tuberculosis severity and emergence of drug resistance. Strains of M. tb complex can be classified into seven lineages. The Nonthaburi (NB) genotype, belonging to the Indo-Oceanic lineage (lineage 1), has a unique spoligotype and IS6110-RFLP pattern but has not previously undergone a detailed whole genome analysis. In addition, there is not much information available on the whole genome analysis of M. tb isolates from tuberculous meningitis (TBM) patients in public databases. Isolates CSF3053, 46-5069 and 43-13838 of NB genotype were obtained from the cerebrospinal fluids of TBM Thai patients in Siriraj Hospital, Bangkok. The whole genomes were subjected to high throughput sequencing. The sequence data of each isolate were assembled into draft genome. The sequences were also aligned to reference genome, to determine genomic variations. Single nucleotide polymorphisms (SNPs) were obtained and grouped according to the functions of the genes containing them. They were compared with SNPs from 1,601 genomes, representing the seven lineages of M. tb complex, to determine the uniqueness of NB genotype. Susceptibility to first-line, second-line and other antituberculosis drugs were determined and related to the SNPs previously reported in drug-resistant related genes. The assembled genomes have an average size of 4,364,461 bp, 4,154 genes, 48 RNAs and 64 pseudogenes. A 500 base pairs deletion, which includes ppe50, was found in all isolates. RD239, specific for members of Indo Oceanic lineage, and RD147c were identified. A total of 2,202 SNPs were common to the isolates and used to classify the NB strains as members of sublineage 1.2.1. Compared with 1,601 genomes from the seven lineages of M. tb complex, mutation G2342203C was found novel to the isolates in this study. Three mutations (T28910C, C1180580T and C152178T) were found only in Thai NB isolates, including isolates from previous study. Although drug susceptibility tests indicated pan-susceptibility, non-synonymous SNPs previously reported to be associated with resistance to anti-tuberculous drugs; isoniazid, ethambutol, and ethionamide were identified in all the isolates. Non-synonymous SNPs were found in virulence genes such as the genes playing roles in apoptosis inhibition and phagosome arrest. We also report polymorphisms in essential genes, efflux pumps associated genes and genes with known epitopes. The analysis of the TBM isolates and the availability of the variations obtained will provide additional resources for global comparison of isolates from pulmonary tuberculosis and TBM. It will also contribute to the richness of genomic databases towards the prediction of antibiotic resistance, level of virulence and of origin of infection

An Examination of Psychological Factors Influencing Investment Decisions: The Moderating Role of Regret Aversion in Traditional and Alternative Investments

This study aims to examine the influence of psychological factors on stock and cryptocurrency investment decisions, with regret aversion as a moderator. Data has been collected through a structured survey questionnaire, and a total of 270 samples were used in PLS-SEM (Partial Least Square-Structural Equation Model) to analyze. The results revealed that risk perception has a significant positive influence on both stock and cryptocurrency investment decisions. Financial stress was found to have a significant negative influence on stock investment decisions, while having no influence on cryptocurrency investment decisions. Similarly, financial literacy was found to have a significant positive influence on stock investment decisions, but no significant influence on cryptocurrency investment decisions. Unexpectedly, regret aversion shows no significant influence on the relationship between risk perception, financial stress, financial literacy, and stock and cryptocurrency investment decisions. This study provides fresh insights that help understand how investor in Norway make their investment decision

Synthetic curcuminoid analogues abrogate oxidationinduced cell death and promote myogenic differentiation of C2C12 mouse myoblasts

Purpose: To investigate the ability of two synthetic curcuminoid analogues, 6-(4-hydroxy-3-methoxyphenethyl)-5-(3-(4-hydroxy-3-methoxyphenyl)propanoyl)-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (compound A) and 6-(4-hydroxy-3-methoxyphenethyl)-4-(4-hydroxy-3-methoxyphenyl)-5-(3-(4- hydroxy-3-methoxyphenyl)propanoyl)-3,4-dihydropyrimidin-2(1H)-one (compound B), to protect against oxidation-induced cell death and the potential to enhance proliferation and differentiation of C2C12 myoblast cells.Methods: Antioxidant activity of curcuminoid analogues was evaluated by DPPH assay. The cytotoxic activity of the compounds (0 - 25 mM) on C2C12 myoblasts was determined by MTT assay while the effect on cell proliferation was assessed by BrdU uptake. Myoblast cell differentiation was measured by the formation of myotubes and myosin heavy chain (MHC) protein expression using immunofluorescence staining and Western blotting, respectively.Results: Both curcuminoid analogues exhibited strong anti-oxidant activity of up to 3-fold greater than that of ascorbic acid, and were non-toxic to C2C12 myoblasts at concentrations up to 25 mM. Furthermore, these curcuminoid analogues mitigated myoblast cell death induced by oxidative stress. Notably, both analogues (10 nM) had no effect on cell proliferation. However, only compound A significantly enhanced myoblast differentiation comparable to the effects of dihydrotestosterone (1 μM) and estradiol (10 nM).Conclusion: The results suggest that compound A may serve as a lead compound for the development of suitable therapeutic agents for muscle injuries and diseases.Keywords: Curcuminoid analogues, Antioxidant, Cell proliferation, Cell differentiation, Myoblast

Understanding multistage experiments

Abstract: Current advanced manufacturing processes are composed of multiple complex stages which prohibit experimenters from conveniently employing traditional statistical experimental designs due to restrictions on randomisation. In this paper, we demonstrate, and summarise how split plot design and its variants have been used for multistage experimentation, and present several multistage experiment scenarios with comments for practitioners and researchers

WASP: a Web-based Allele-Specific PCR assay designing tool for detecting SNPs and mutations

BACKGROUND: Allele-specific (AS) Polymerase Chain Reaction is a convenient and inexpensive method for genotyping Single Nucleotide Polymorphisms (SNPs) and mutations. It is applied in many recent studies including population genetics, molecular genetics and pharmacogenomics. Using known AS primer design tools to create primers leads to cumbersome process to inexperience users since information about SNP/mutation must be acquired from public databases prior to the design. Furthermore, most of these tools do not offer the mismatch enhancement to designed primers. The available web applications do not provide user-friendly graphical input interface and intuitive visualization of their primer results. RESULTS: This work presents a web-based AS primer design application called WASP. This tool can efficiently design AS primers for human SNPs as well as mutations. To assist scientists with collecting necessary information about target polymorphisms, this tool provides a local SNP database containing over 10 million SNPs of various populations from public domain databases, namely NCBI dbSNP, HapMap and JSNP respectively. This database is tightly integrated with the tool so that users can perform the design for existing SNPs without going off the site. To guarantee specificity of AS primers, the proposed system incorporates a primer specificity enhancement technique widely used in experiment protocol. In particular, WASP makes use of different destabilizing effects by introducing one deliberate 'mismatch' at the penultimate (second to last of the 3'-end) base of AS primers to improve the resulting AS primers. Furthermore, WASP offers graphical user interface through scalable vector graphic (SVG) draw that allow users to select SNPs and graphically visualize designed primers and their conditions. CONCLUSION: WASP offers a tool for designing AS primers for both SNPs and mutations. By integrating the database for known SNPs (using gene ID or rs number), this tool facilitates the awkward process of getting flanking sequences and other related information from public SNP databases. It takes into account the underlying destabilizing effect to ensure the effectiveness of designed primers. With user-friendly SVG interface, WASP intuitively presents resulting designed primers, which assist users to export or to make further adjustment to the design. This software can be freely accessed at http://bioinfo.biotec.or.th/WASP

Study of large and highly stratified population datasets by combining iterative pruning principal component analysis and structure

<p>Abstract</p> <p>Background</p> <p>The ever increasing sizes of population genetic datasets pose great challenges for population structure analysis. The Tracy-Widom (TW) statistical test is widely used for detecting structure. However, it has not been adequately investigated whether the TW statistic is susceptible to type I error, especially in large, complex datasets. Non-parametric, Principal Component Analysis (PCA) based methods for resolving structure have been developed which rely on the TW test. Although PCA-based methods can resolve structure, they cannot infer ancestry. Model-based methods are still needed for ancestry analysis, but they are not suitable for large datasets. We propose a new structure analysis framework for large datasets. This includes a new heuristic for detecting structure and incorporation of the structure patterns inferred by a PCA method to complement STRUCTURE analysis.</p> <p>Results</p> <p>A new heuristic called EigenDev for detecting population structure is presented. When tested on simulated data, this heuristic is robust to sample size. In contrast, the TW statistic was found to be susceptible to type I error, especially for large population samples. EigenDev is thus better-suited for analysis of large datasets containing many individuals, in which spurious patterns are likely to exist and could be incorrectly interpreted as population stratification. EigenDev was applied to the iterative pruning PCA (ipPCA) method, which resolves the underlying subpopulations. This subpopulation information was used to supervise STRUCTURE analysis to infer patterns of ancestry at an unprecedented level of resolution. To validate the new approach, a bovine and a large human genetic dataset (3945 individuals) were analyzed. We found new ancestry patterns consistent with the subpopulations resolved by ipPCA.</p> <p>Conclusions</p> <p>The EigenDev heuristic is robust to sampling and is thus superior for detecting structure in large datasets. The application of EigenDev to the ipPCA algorithm improves the estimation of the number of subpopulations and the individual assignment accuracy, especially for very large and complex datasets. Furthermore, we have demonstrated that the structure resolved by this approach complements parametric analysis, allowing a much more comprehensive account of population structure. The new version of the ipPCA software with EigenDev incorporated can be downloaded from <url>http://www4a.biotec.or.th/GI/tools/ippca</url>.</p

Intelligent robot of inclined assembly sequence planning in Industrial 4.0

In the industry 4.0, the Cyber-physical system (CPS) is one of the most important core which makes the manufacturing process more intelligent. Intelligent assembly operation is an important key in intelligent manufacturing of CPS. To complete the intelligent assembly operation, the cooperation between assembly robotic arm and assembly sequence planning (ASP) is necessary. However, the ASP and writing robotic codes manually is time consuming and requires professional knowledge and experience. Because the Local Coordinate System (LCS) is often ignored when checking for interference. If product have inclined interference and without considering LCS and causing and infeasible ASP. Therefore, this paper proposes a LCCPIAS (Local Coordinate Cyber-Physical Intelligent Assembly System) system to achieve three objective functions. First, this paper presents a dual-projected-based interference analysis approach (DPIAA) that analyzes the relations between components. Second, this paper generates optimal assembly sequence automatically to let the assembly sequence more suitable for the robotic arm to perform the assembly operation. The last one is LCS can recognize inclined interference between components and generate feasible ASP. Furthermore, this paper uses CAD model to verify that the DPIAA is faster and consider LCS interference can solve inclined interference problem. In the future assembly factory, the proposed method can help to realize intelligent manufacturing