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61.
Singh KhD Kirubakaran P Nagarajan S Sakkiah S Muthusamy K Velmurgan D Jeyakanthan J 《Journal of molecular modeling》2012,18(1):39-51
To date, no suitable vaccine or specific antiviral drug is available to treat Chikungunya viral (CHIKV) fever. Hence, it is
essential to identify drug candidates that could potentially impede CHIKV infection. Here, we present the development of a
homology model of nsP2 protein based on the crystal structure of the nsP2 protein of Venezuelan equine encephalitis virus
(VEEV). The protein modeled was optimized using molecular dynamics simulation; the junction peptides of a nonstructural protein
complex were then docked in order to investigate the possible protein–protein interactions between nsP2 and the proteins cleaved
by nsP2. The modeling studies conducted shed light on the binding modes, and the critical interactions with the peptides provide
insight into the chemical features needed to inhibit the CHIK virus infection. Energy-optimized pharmacophore mapping was
performed using the junction peptides. Based on the results, we propose the pharmacophore features that must be present in
an inhibitor of nsP2 protease. The resulting pharmacophore model contained an aromatic ring, a hydrophobic and three hydrogen-bond
donor sites. Using these pharmacophore features, we screened a large public library of compounds (Asinex, Maybridge, TOSLab,
Binding Database) to find a potential ligand that could inhibit the nsP2 protein. The compounds that yielded a fitness score
of more than 1.0 were further subjected to Glide HTVS and Glide XP. Here, we report the best four compounds based on their
docking scores; these compounds have IDs of 27943, 21362, ASN 01107557 and ASN 01541696. We propose that these compounds could
bind to the active site of nsP2 protease and inhibit this enzyme. Furthermore, the backbone structural scaffolds of these
four lead compounds could serve as building blocks when designing drug-like molecules for the treatment of Chikungunya viral
fever. 相似文献
62.
Dubey JP Huong LT Lawson BW Subekti DT Tassi P Cabaj W Sundar N Velmurugan GV Kwok OC Su C 《The Journal of parasitology》2008,94(1):68-71
The prevalence of Toxoplasma gondii in free-ranging chickens (Gallus domesticus) is a good indicator of the prevalence of the parasite's oocysts in soil because chicken feed from the ground. The prevalence of T. gondii in free-range chickens from Ghana, Indonesia, Italy, Poland, and Vietnam was determined using the modified agglutination test (MAT). Antibodies to T. gondii were found in 41 (64%) of 64 chickens from Ghana, 24 (24.4%) of 98 chickens from Indonesia, 10 (12.5%) of 80 chickens from Italy, 6 (30%) of 20 chickens from Poland, and 81 (24.2%) of 330 chickens from Vietnam. Hearts and brains of chickens were bioassayed for T. gondii. Viable T. gondii was isolated from 2 chickens from Ghana, 1 chicken from Indonesia, 3 chickens from Italy, 2 chickens from Poland, and 1 chicken from Vietnam. Toxoplasma gondii isolates from 9 chickens were genotyped using 10 PCR-RFLP markers including SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico. A total of 7 genotypes was identified; the 3 isolates from chickens from Italy were clonal type II, and the others were nonclonal. This is the first report of genetic characterization of T. gondii isolates from animals from these countries. 相似文献
63.
Dubey JP Velmurugan GV Ulrich V Gill J Carstensen M Sundar N Kwok OC Thulliez P Majumdar D Su C 《International journal for parasitology》2008,38(8-9):1057-1063
Clinical toxoplasmosis is most severe in congenitally-infected hosts. In humans, transmission of Toxoplasma gondii from the mother to the foetus is considered to be most efficient during the last trimester of pregnancy but clinical congenital toxoplasmosis is more severe if transmission occurs during the first trimester. However, there are no data on the rate of congenital transmission of T. gondii with respect to gestational age in any host during natural infection. In the present study, attempts were made to isolate T. gondii by bioassay in mice inoculated with tissues from foetuses of 88 naturally-exposed white-tailed deer from Iowa and Minnesota. Viable T. gondii was isolated from foetuses of six of 61 deer in early pregnancy (45-85 days of gestation) from Iowa and foetuses of nine of 27 deer from Minnesota in mid-gestation (130-150 days) of a gestational period of 7 months. The 15 T. gondii isolates obtained from foetal deer were PCR-restriction fragment length polymorphism genotyped using polymorphisms at 10 nuclear markers including SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and an apicoplast marker, Apico. Five genotypes were revealed, including the clonal Type II and III lineages, and three non-clonal genotypes. DNA sequencing analysis of representative isolates at loci SAG2, c22-8, L358 and PK1 revealed that the three non-clonal genotypes are closely related to the clonal Type I, II and III lineages. It is very likely that these non-clonal genotypes were derived from genetic crosses among the three clonal Type I, II and III lineages. The most common genotype was Type II, commonly found in humans in North America and Europe, suggesting the possible link of transmission from game animals to humans. 相似文献
64.
High density lipoprotein (HDL) reverses palmitic acid induced energy metabolism imbalance by switching CD36 and GLUT4 signaling pathways in cardiomyocyte 下载免费PDF全文
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66.
Bharath Kumar Velmurugan Lohanathan Bharathi Priya Paramasivan Poornima Li-Jen Lee Rathinasamy Baskaran 《Journal of cellular physiology》2019,234(6):8443-8454
Engineering/reprogramming differentiated adult somatic cells to gain the ability to differentiate into any type of cell lineage are called as induced pluripotent stem cells (iPSCs). Offering unlimited self-renewal and differentiation potential, these iPSC are aspired to meet the growing demands in the field of regenerative medicine, tissue engineering, disease modeling, nanotechnology, and drug discovery. Biomaterial fabrication with the rapid evolution of technology increased their versatility and utility in regenerative medicine and tissue engineering, revolutionizing the stem cell biology research with the property to guide the process of proliferation, differentiation, and morphogenesis. Combining traditional culture platforms of iPSC with biomaterials aids to overcome the limitations associated with derivation, proliferation, and maturation, thereby could improve the clinical translation of iPSC. The present review discusses in brief about the reprogramming techniques for the derivation iPSC and details on several biomaterial guided differentiation of iPSC to different cell types with specific relevance to tissue engineering/regenerative medicine. 相似文献
67.
Bharath Kumar Velmurugan Chi-Ru Chan Ching-Feng Weng 《Journal of cellular physiology》2019,234(9):16125-16135
In this present study, Oreochromis mossambicus tilapia were transferred to cold water at 12°C for various time intervals (1, 4, 8, 24, and 48 hr) and its innate immune response was analyzed by studying cellular and humoral parameters. In vivo, alternative complement pathway activity in blood plasma was rapidly increased at 1 hr of cold water (12°C) exposure. Lysozyme activity and cortisol levels of plasma were increased at 4 and 1 hr, respectively. Surprisingly, only plasma cortisol levels remained unchanged through 24 hr of cold water transfer. Phagocytic ability, phagocytic capacity, and respiratory burst (RB) activity of head kidney (HK) leukocytes and splenocytes showed no any significant changes. In peripheral blood leukocytes, phagocytic capacity, and RB activity were increased at 24 hr of cold water exposure. The expressions of genes involved innate immunity in splenocytes and HK leukocytes of tilapia cold water exposure were analyzed, messenger RNA (mRNA) expressions of HSP70, HSP90, and immunoglobulin M failed to change upon exposure to cold stress. Major histocompatibility complex-I and II mRNAs were significantly increased in tilapia splenocytes at 1 hr of cold water transferred. Whereas myxovirus (Mx) expression was increased in splenocytes and HK leukocytes of tilapia after 1 hr of cold water exposed. Our result reveals that the exposure of tilapia to acute cold stress condition significantly enhances plasma acid phosphatase activity and both phagocytic capacity and RB activity. Furthermore, cold stress significantly stimulates Mx gene expression in splenocytes and HK leukocytes. 相似文献
68.
The use of pesticides in agriculture can make their way into the earth and wash into the amphibian system causing ecological stress. This study aims to understand the changes occurring in gill tissues as a result of fenvalerate exposure using Fourier-transform infrared spectroscopy. The intensity ratio of the selected bands I1545/I1657, I2924/I2853, and I1045/I1545 measures changes in proteins, lipids, and carbohydrates. Curve-fitting analysis was performed in the selected band region to analyze the quantitative changes of proteins, lipids, and carbohydrates. The band area ratio of CH3/asCH2+ sCH2 shows the absence of a long chain of fatty acids due to fenvalerate treatment. The band area ratio of asCH2/sCH2 increases for higher sublethal concentrations, which shows the lower disorder of lipid acyl chain flexibility. A decrease in lipids was found in lower sublethal concentrations. The secondary structure of proteins affirms β sheet development. Carbohydrate metabolism of gill tissues demonstrates a decrease in glycogen contents. A further decrease in glycogen content and an increase in lactic acid were observed when presented to a fenvalerate concentration. PCA plots indicate distinct variations among the biochemical parameters of the gill tissues. This study provides a quantitative examination of assessing pesticide toxicity in aquatic environments. 相似文献
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The 2μm Plasmid Stability System: Analyses of the Interactions among Plasmid- and Host-Encoded Components 下载免费PDF全文
Soundarapandian Velmurugan Yong-Tae Ahn Xian-Mei Yang Xu-Li Wu Makkuni Jayaram 《Molecular and cellular biology》1998,18(12):7466-7477
The stable inheritance of the 2μm plasmid in a growing population of Saccharomyces cerevisiae is dependent on two plasmid-encoded proteins (Rep1p and Rep2p), together with the cis-acting locus REP3 (STB). In this study we demonstrate that short carboxy-terminal deletions of Rep1p and Rep2p severely diminish their normal capacity to localize to the yeast nucleus. The nuclear targeting, as well as their functional role in plasmid partitioning, can be restored by the addition of a nuclear localization sequence to the amino or the carboxy terminus of the shortened Rep proteins. Analyses of deletion derivatives of the Rep proteins by using the in vivo dihybrid genetic test in yeast, as well as by glutathione S-transferase fusion trapping assays in vitro demonstrate that the amino-terminal portion of Rep1p (ca. 150 amino acids long) is responsible for its interactions with Rep2p. In a monohybrid in vivo assay, we have identified Rep1p, Rep2p, and a host-encoded protein, Shf1p, as being capable of interacting with the STB locus. The Shf1 protein expressed in Escherichia coli can bind with high specificity to the STB sequence in vitro. In a yeast strain deleted for the SHF1 locus, a 2μm circle-derived plasmid shows relatively poor stability. 相似文献