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41.
42.
Flax secoisolariciresinol diglucoside (SDG) lignan is a natural phytoestrogen for which a positive role in metabolic diseases is emerging. Until recently however, much less was known about SDG and its monoglucoside (SMG) biosynthesis. Lately, flax UGT74S1 was identified and characterized as an enzyme sequentially glucosylating secoisolariciresinol (SECO) into SMG and SDG when expressed in yeast. However, the amino acids critical for UGT74S1 glucosyltransferase activity were unknown. A 3D structural modeling and docking, site-directed mutagenesis of five amino acids in the plant secondary product glycosyltransferase (PSPG) motif, and enzyme assays were conducted. UGT74S1 appeared to be structurally similar to the Arabidopsis thaliana UGT72B1 model. The ligand docking predicted Ser357 and Trp355 as binding to the phosphate and hydroxyl groups of UDP-glucose, whereas Cys335, Gln337 and Trp355 were predicted to bind the 7-OH, 2-OCH3 and 17-OCH3 of SECO. Site-directed mutagenesis of Cys335, Gln337, His352, Trp355 and Ser357, and enzyme assays revealed an alteration of these binding sites and a significant reduction of UGT74S1 glucosyltransferase catalytic activity towards SECO and UDP-glucose in all mutants. A complete abolition of UGT74S1 activity was observed when Trp355 was substituted to Ala355 and Gly355 or when changing His352 to Asp352, and an altered metabolite profile was observed in Cys335Ala, Gln337Ala, and Ser357Ala mutants. This study provided for the first time evidence that Trp355 and His352 are critical for UGT74S1’s glucosylation activity toward SECO and suggested the possibility for SMG production in vitro. 相似文献
43.
Antonia L. Dow Tiffany V. Lin Elena H. Chartoff David Potter Donna L. McPhie Ashlee V. Van’t Veer Allison T. Knoll Kristen N. Lee Rachael L. Neve Tarun B. Patel Dost Ongur Bruce M. Cohen William A. Carlezon Jr 《PloS one》2015,10(3)
Both the development and relief of stress-related psychiatric conditions such as major depression (MD) and post-traumatic stress disorder (PTSD) have been linked to neuroplastic changes in the brain. One such change involves the birth of new neurons (neurogenesis), which occurs throughout adulthood within discrete areas of the mammalian brain, including the dorsal hippocampus (HIP). Stress can trigger MD and PTSD in humans, and there is considerable evidence that it can decrease HIP neurogenesis in laboratory animals. In contrast, antidepressant treatments increase HIP neurogenesis, and their efficacy is eliminated by ablation of this process. These findings have led to the working hypothesis that HIP neurogenesis serves as a biomarker of neuroplasticity and stress resistance. Here we report that local alterations in the expression of Sprouty2 (SPRY2), an intracellular inhibitor of growth factor function, produces profound effects on both HIP neurogenesis and behaviors that reflect sensitivity to stressors. Viral vector-mediated disruption of endogenous Sprouty2 function (via a dominant negative construct) within the dorsal HIP of adult rats stimulates neurogenesis and produces signs of stress resilience including enhanced extinction of conditioned fear. Conversely, viral vector-mediated elevation of SPRY2 expression intensifies the behavioral consequences of stress. Studies of these manipulations in HIP primary cultures indicate that SPRY2 negatively regulates fibroblast growth factor-2 (FGF2), which has been previously shown to produce antidepressant- and anxiolytic-like effects via actions in the HIP. Our findings strengthen the relationship between HIP plasticity and stress responsiveness, and identify a specific intracellular pathway that could be targeted to study and treat stress-related disorders. 相似文献
44.
Ying Pei Alice S. Tarun Ashley M. Vaughan Rob W. Herman Joanne M. B. Soliman Alyssa Erickson‐Wayman Stefan H. I. Kappe 《Molecular microbiology》2010,75(4):957-971
Plasmodium parasites possess a single pyruvate dehydrogenase (PDH) enzyme complex that is localized to the plastid‐like organelle known as the apicoplast. Unlike most eukaryotes, Plasmodium parasites lack a mitochondrial PDH. The PDH complex catalyses the conversion of pyruvate to acetyl‐CoA, an important precursor for the tricarboxylic acid cycle and type II fatty acid synthesis (FAS II). In this study, using a rodent malaria model, we show that the PDH E1α and E3 subunits colocalize with the FAS II enzyme FabI in the apicoplast of liver stages but are not significantly expressed in blood stages. Deletion of the E1α or E3 subunit genes of Plasmodium yoelii PDH caused no defect in blood stage development, mosquito stage development or early liver stage development. However, the gene deletions completely blocked the ability of the e1α‐ and e3‐ parasites to form exo‐erythrocytic merozoites during late liver stage development, thus preventing the initiation of a blood stage infection. This phenotype is similar to that observed for deletions of genes involved in FAS II elongation. The data strongly support the hypothesis that the sole role of PDH is to provide acetyl‐CoA for FAS II. 相似文献
45.
Rudra Nath Chatterjee Tarun K. Bhattacharya Meenakshi Dange U. Rajkumar 《Biochemical genetics》2010,48(9-10):727-736
To measure genetic relatedness between populations, for breeding purposes, we analyzed 170 birds from six crossbred populations of three pure lines of White Leghorn chickens, using 14 microsatellite markers. All the microsatellites were polymorphic, with 2–6 alleles. The mean number of alleles per locus was 3.21. The effective number of alleles varied from 1.14 to 3.94. The observed heterozygosity varied from 0.133 to 1.00, with a mean of 0.748. The F IS values were mostly negative, with an average of ?0.345. The mean F ST value was 0.056. The Nm values ranged from 1.91 to 42.17. The highest genetic identity was observed between IWI × IWK and IWK × IWI. The relation between any two groups of crosses was more than 85%. The results suggest that the crossbred populations were very closely related. 相似文献
46.
47.
B Samanta G Mez? K P Das A C Ghose F Hudecz P C Sen 《The journal of peptide research》2005,65(4):445-449
Protein kinase (PK) A catalytic (PKAcat) subunit was purified to homogeneity from bovine lens using a 100-kDa cut-off membrane filtration followed by different chromatographic procedures. The molecular weight of PKAcat was found to be 41 kDa. The kinase phosphorylates histone IIIs and other synthetic modified peptides of VRKRTLRRL with different amino acid environment. The extent of phosphorylation depends not only on the presence of Ser or Thr (phosphorylating residues) but also on other surrounding amino acid residues. Although some peptides compete in phosphorylating histone, they are not very significant. The result suggests that the extent of phosphorylation depends on the amino acid residue(s) surrounding phosphorylable residue(s) on the peptide. 相似文献
48.
49.
Ágnes Baross Allen D Delaney H Irene Li Tarun Nayar Stephane Flibotte Hong Qian Susanna Y Chan Jennifer Asano Adrian Ally Manqiu Cao Patricia Birch Mabel Brown-John Nicole Fernandes Anne Go Giulia Kennedy Sylvie Langlois Patrice Eydoux JM Friedman Marco A Marra 《BMC bioinformatics》2007,8(1):1-18
Background
Genomic deletions and duplications are important in the pathogenesis of diseases, such as cancer and mental retardation, and have recently been shown to occur frequently in unaffected individuals as polymorphisms. Affymetrix GeneChip whole genome sampling analysis (WGSA) combined with 100 K single nucleotide polymorphism (SNP) genotyping arrays is one of several microarray-based approaches that are now being used to detect such structural genomic changes. The popularity of this technology and its associated open source data format have resulted in the development of an increasing number of software packages for the analysis of copy number changes using these SNP arrays.Results
We evaluated four publicly available software packages for high throughput copy number analysis using synthetic and empirical 100 K SNP array data sets, the latter obtained from 107 mental retardation (MR) patients and their unaffected parents and siblings. We evaluated the software with regards to overall suitability for high-throughput 100 K SNP array data analysis, as well as effectiveness of normalization, scaling with various reference sets and feature extraction, as well as true and false positive rates of genomic copy number variant (CNV) detection.Conclusion
We observed considerable variation among the numbers and types of candidate CNVs detected by different analysis approaches, and found that multiple programs were needed to find all real aberrations in our test set. The frequency of false positive deletions was substantial, but could be greatly reduced by using the SNP genotype information to confirm loss of heterozygosity. 相似文献50.
Ira Vashisht Prashant Mishra Tarun Pal Sreekrishna Chanumolu Tiratha Raj Singh Rajinder Singh Chauhan 《Planta》2015,241(5):1269-1270