1,128 research outputs found

    PLD1 (phospholipase D1, phosphatidylcholine-specific)

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    Review on PLD1 (phospholipase D1, phosphatidylcholine-specific), with data on DNA, on the protein encoded, and where the gene is implicated

    Gut microbe-derived extracellular vesicles induce insulin resistance, thereby impairing glucose metabolism in skeletal muscle

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    Gut microbes might influence host metabolic homeostasis and contribute to the pathogenesis of type 2 diabetes (T2D), which is characterized by insulin resistance. Bacteria-derived extracellular vesicles (EVs) have been suggested to be important in the pathogenesis of diseases once believed to be noninfectious. Here, we hypothesize that gut microbe-derived EVs are important in the pathogenesis of T2D. In vivo administration of stool EVs from high fat diet (HFD)-fed mice induced insulin resistance and glucose intolerance compared to regular diet (RD)-fed mice. Metagenomic profiling of stool EVs by 16S ribosomal DNA sequencing revealed an increased amount of EVs derived from Pseudomonas panacis (phylum Proteobacteria) in HFD mice compared to RD mice. Interestingly, P. panacis EVs blocked the insulin signaling pathway in both skeletal muscle and adipose tissue. Moreover, isolated P. panacis EVs induced typical diabetic phenotypes, such as glucose intolerance after glucose administration or systemic insulin injection. Thus, gut microbe-derived EVs might be key players in the development of insulin resistance and impairment of glucose metabolism promoted by HFD.11148Ysciescopu

    Targeting of highly conserved Dengue virus sequences with anti-Dengue virus trans-splicing group I introns

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    <p>Abstract</p> <p>Background</p> <p>Dengue viruses (DENV) are one of the most important viral diseases in the world with approximately 100 million infections and 200,000 deaths each year. The current lack of an approved tetravalent vaccine and ineffective insecticide control measures warrant a search for alternatives to effectively combat DENV. The <it>trans</it>-splicing variant of the <it>Tetrahymena thermophila </it>group I intron catalytic RNA, or ribozyme, is a powerful tool for post-transcriptional RNA modification. The nature of the ribozyme and the predictability with which it can be directed makes it a powerful tool for modifying RNA in nearly any cell type without the need for genome-altering gene therapy techniques or dependence on native cofactors.</p> <p>Results</p> <p>Several anti-DENV Group I <it>trans</it>-splicing introns (Ξ±DENV-GrpIs) were designed and tested for their ability to target DENV-2 NGC genomes <it>in situ</it>. We have successfully targeted two different uracil bases on the positive sense genomic strand within the highly conserved 5'-3' cyclization sequence (CS) region common to all serotypes of DENV with our Ξ±DENV-GrpIs. Our ribozymes have demonstrated ability to specifically <it>trans</it>-splice a new RNA sequence downstream of the targeted site <it>in vitro </it>and in transfected insect cells as analyzed by firefly luciferase and RT-PCR assays. The effectiveness of these Ξ±DENV-GrpIs to target infecting DENV genomes is also validated in transfected or transformed Aedes mosquito cell lines upon infection with unattenuated DENV-2 NGC.</p> <p>Conclusions</p> <p>Analysis shows that our Ξ±DENV-GrpIs have the ability to effectively <it>trans</it>-splice the DENV genome <it>in situ</it>. Notably, these results show that the Ξ±DENV-GrpI 9v1, designed to be active against all forms of Dengue virus, effectively targeted the DENV-2 NGC genome in a sequence specific manner. These novel Ξ±DENV-GrpI introns provide a striking alternative to other RNA based approaches for the transgenic suppression of DENV in transformed mosquito cells and tissues.</p

    Identification and characterization of seed-specific transcription factors regulating anthocyanin biosynthesis in black rice

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    Black rice is rich in anthocyanin and is expected to have more healthful dietary potential than white rice. We assessed expression of anthocyanin in black rice cultivars using a newly designed 135Β K Oryza sativa microarray. A total of 12,673 genes exhibited greater than 2.0-fold up- or down-regulation in comparisons between three rice cultivars and three seed developmental stages. The 137 transcription factor genes found to be associated with production of anthocyanin pigment were classified into 10 groups. In addition, 17 unknown and hypothetical genes were identified from comparisons between the rice cultivars. Finally, 15 out of the 17 candidate genes were verified by RT-PCR analysis. Among the genes, nine were up-regulated and six exhibited down-regulation. These genes likely play either a regulatory role in anthocyanin biosynthesis or are related to anthocyanin metabolism during flavonoid biosynthesis. While these genes require further validation, the results here underline the potential use of the new microarray and provide valuable insight into anthocyanin pigment production in rice

    Non-surgical treatment of primary female urethral cancer

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    Primary carcinomas of the female urethra are extremely rare, with an annual incidence of less than ten in one million. Currently, there is no consensus regarding management of this malignancy. However, there have been several case reports demonstrating the efficacy of chemoradiation in the treatment of female urethral cancer. In this report we present two cases of female primary urethral adenocarcinoma that were treated by concomitant chemotherapy and external beam radiotherapy, followed by interstitial brachytherapy

    SH2 domains serve as lipid binding modules for pTyr-signaling proteins

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    The Src-homology 2 (SH2) domain is a protein interaction domain that directs myriad phosphotyrosine (pY)-signaling pathways. Genome-wide screening of human SH2 domains reveals that similar to 90% of SH2 domains bind plasma membrane lipids and many have high phosphoinositide specificity. They bind lipids using surface cationic patches separate from pY-binding pockets, thus binding lipids and the pY motif independently. The patches form grooves for specific lipid headgroup recognition or flat surfaces for non-specific membrane binding and both types of interaction are important for cellular function and regulation of SH2 domain-containing proteins. Cellular studies with ZAP70 showed that multiple lipids bind its C-terminal SH2 domain in a spatiotemporally specific manner and thereby exert exquisite spatiotemporal control over its protein binding and signaling activities in T cells. Collectively, this study reveals how lipids control SH2 domain-mediated cellular protein-protein interaction networks and suggest a new strategy for therapeutic modulation of pY-signaling pathways.112620Ysciescopu

    Determination of EGFR Endocytosis Kinetic by Auto-Regulatory Association of PLD1 with mu 2

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    Background: Upon ligand binding, cell surface signaling receptors are internalized through a process tightly regulated by endocytic proteins and adaptor protein 2 (AP2) to orchestrate them. Although the molecular identities and roles of endocytic proteins are becoming clearer, it is still unclear what determines the receptor endocytosis kinetics which is mainly regulated by the accumulation of endocytic apparatus to the activated receptors. Methodology/Principal Findings: Here we employed the kinetic analysis of endocytosis and adaptor recruitment to show that ??2, a subunit of AP2 interacts directly with phospholipase D (PLD)1, a receptor-associated signaling protein and this facilitates the membrane recruitment of AP2 and the endocytosis of epidermal growth factor receptor (EGFR). We also demonstrate that the PLD1-??2 interaction requires the binding of PLD1 with phosphatidic acid, its own product. Conclusions/Significance: These results suggest that the temporal regulation of EGFR endocytosis is achieved by auto-regulatory PLD1 which senses the receptor activation and triggers the translocation of AP2 near to the activated receptor.open3

    Impact of the Resident Microbiota on the Nutritional Phenotype of Drosophila melanogaster

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    Background: Animals are chronically infected by benign and beneficial microorganisms that generally promote animal health through their effects on the nutrition, immune function and other physiological systems of the host. Insight into the host-microbial interactions can be obtained by comparing the traits of animals experimentally deprived of their microbiota and untreated animals. Drosophila melanogaster is an experimentally tractable system to study host-microbial interactions. Methodology/Principal Findings: The nutritional significance of the microbiota was investigated in D. melanogaster bearing unmanipulated microbiota, demonstrated by 454 sequencing of 16S rRNA amplicons to be dominated by the a-proteobacterium Acetobacter, and experimentally deprived of the microbiota by egg dechorionation (conventional and axenic flies, respectively). In axenic flies, larval development rate was depressed with no effect on adult size relative to conventional flies, indicating that the microbiota promotes larval growth rates. Female fecundity did not differ significantly between conventional and axenic flies, but axenic flies had significantly reduced metabolic rate and altered carbohydrate allocation, including elevated glucose levels. Conclusions/Significance: We have shown that elimination of the resident microbiota extends larval development and perturbs energy homeostasis and carbohydrate allocation patterns of of D. melanogaster. Our results indicate that th

    Allelopathic effects of Ulva pertusa, Corallina pilulifera and Sargassum thunbergii on the growth of the dinoflagellates Heterosigma akashiwo and Alexandrium tamarense

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    The allelopathic effects of fresh tissue, dry powder and aqueous extracts of three macroalgae, Ulva pertusa, Corallina pilulifera and Sargassum thunbergii, on the growth of the dinoflagellates Heterosigma akashiwo and Alexandrium tamarense were evaluated using coexistence culture systems in which concentrations of the three macroalga were varied. The results of the coexistence assay showed that the growth of the two microalgae was strongly inhibited by using fresh tissue, dry powder and aqueous extracts of the three macroalga; the allelochemicals were lethal to H. akashiwo at relatively higher concentrations of the three macroalga. The macroalgae showing the most allelopathic effect on H. akashiwo and A. tamarense using fresh tissue were U. pertusa and S. thunbergii, using dry powder were S. thunbergii and U. pertusa, and using aqueous extracts were U. pertusa and C. pilulifera. We also examined the potential allelopathic effect on the two microalgae of culture filtrate of the three macroalga; culture medium filtrate initially exhibited no inhibitory effects when first added but inhibitory effects became apparent under semi-continuous addition, which suggested that continuous release of small quantities of rapidly degradable allelochemicals from the fresh macroalgal tissue were essential to effectively inhibit the growth of the two microalgae
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