Browsing by Author "Chen, W"

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    Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation.
    (PLoS Genet, 2014-04) Janbon, G; Ormerod, KL; Paulet, D; Byrnes, EJ; Yadav, V; Chatterjee, G; Mullapudi, N; Hon, C; Billmyre, RB; Brunel, F; Bahn, Y; Chen, W; Chen, Y; Chow, EWL; Coppée, J; Floyd-Averette, A; Gaillardin, C; Gerik, KJ; Goldberg, J; Gonzalez-Hilarion, S; Gujja, S; Hamlin, JL; Hsueh, Y; Ianiri, G; Jones, S; Kodira, CD; Kozubowski, L; Lam, W; Marra, M; Mesner, LD; Mieczkowski, PA; Moyrand, F; Nielsen, K; Proux, C; Rossignol, T; Schein, JE; Sun, S; Wollschlaeger, C; Wood, IA; Zeng, Q; Neuvéglise, C; Newlon, CS; Perfect, JR; Lodge, JK; Idnurm, A; Stajich, JE; Kronstad, JW; Sanyal, K; Heitman, J; Fraser, JA; Cuomo, CA; Dietrich, FS
    Cryptococcus neoformans is a pathogenic basidiomycetous yeast responsible for more than 600,000 deaths each year. It occurs as two serotypes (A and D) representing two varieties (i.e. grubii and neoformans, respectively). Here, we sequenced the genome and performed an RNA-Seq-based analysis of the C. neoformans var. grubii transcriptome structure. We determined the chromosomal locations, analyzed the sequence/structural features of the centromeres, and identified origins of replication. The genome was annotated based on automated and manual curation. More than 40,000 introns populating more than 99% of the expressed genes were identified. Although most of these introns are located in the coding DNA sequences (CDS), over 2,000 introns in the untranslated regions (UTRs) were also identified. Poly(A)-containing reads were employed to locate the polyadenylation sites of more than 80% of the genes. Examination of the sequences around these sites revealed a new poly(A)-site-associated motif (AUGHAH). In addition, 1,197 miscRNAs were identified. These miscRNAs can be spliced and/or polyadenylated, but do not appear to have obvious coding capacities. Finally, this genome sequence enabled a comparative analysis of strain H99 variants obtained after laboratory passage. The spectrum of mutations identified provides insights into the genetics underlying the micro-evolution of a laboratory strain, and identifies mutations involved in stress responses, mating efficiency, and virulence.
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    Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes
    (JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2015-09) Fang, S; Wang, Y; Chun, YS; Liu, H; Ross, MI; Gershenwald, JE; Cormier, JN; Royal, RE; Lucci, A; Schacherer, CW; Reveille, JD; Chen, W; Sui, D; Bassett, RL; Wang, L-E; Wei, Q; Amos, CI; Lee, JE
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    beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity through interaction with phosphorylated dishevelled proteins.
    (Proc Natl Acad Sci U S A, 2001-12-18) Chen, W; Hu, LA; Semenov, MV; Yanagawa, S; Kikuchi, A; Lefkowitz, RJ; Miller, WE
    One aspect of the function of the beta-arrestins is to serve as scaffold or adapter molecules coupling G-protein coupled receptors (GPCRs) to signal transduction pathways distinct from traditional second messenger pathways. Here we report the identification of Dishevelled 1 and Dishevelled 2 (Dvl1 and Dvl2) as beta-arrestin1 (betaarr1) interacting proteins. Dvl proteins participate as key intermediates in signal transmission from the seven membrane-spanning Frizzled receptors leading to inhibition of glycogen synthase kinase-3beta (GSK-3beta), stabilization of beta-catenin, and activation of the lymphoid enhancer factor (LEF) transcription factor. We find that phosphorylation of Dvl strongly enhances its interaction with betaarr1, suggesting that regulation of Dvl phosphorylation and subsequent interaction with betaarr1 may play a key role in the activation of the LEF transcription pathway. Because coexpression of the Dvl kinases, CK1epsilon and PAR-1, with Dvl synergistically activates LEF reporter gene activity, we reasoned that coexpression of betaarr1 with Dvl might also affect LEF-dependent gene activation. Interestingly, whereas betaarr1 or Dvl alone leads to low-level stimulation of LEF (2- to 5-fold), coexpression of betaarr1 with either Dvl1 or Dvl2 leads to a synergistic activation of LEF (up to 16-fold). Additional experiments with LiCl as an inhibitor of GSK-3beta kinase activity indicate that the step affected by betaarr1 is upstream of GSK-3beta and most likely at the level of Dvl. These results identify betaarr1 as a regulator of Dvl-dependent LEF transcription and suggest that betaarr1 might serve as an adapter molecule that can couple Frizzled receptors and perhaps other GPCRs to these important transcription pathways.
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    Magnetic levitation of metamaterial bodies enhanced with magnetostatic surface resonances
    (Physical Review B - Condensed Matter and Materials Physics, 2012-02-27) Urzhumov, Y; Chen, W; Bingham, C; Padilla, W; Smith, DR
    We propose that macroscopic objects built from negative-permeability metamaterials may experience resonantly enhanced magnetic force in low-frequency magnetic fields. Resonant enhancement of the time-averaged force originates from magnetostatic surface resonances (MSRs), which are analogous to the electrostatic resonances of negative-permittivity particles, well known as surface plasmon resonances in optics. We generalize the classical problem of the MSR of a homogeneous object to include anisotropic metamaterials and consider the most extreme case of anisotropy, where the permeability is negative in one direction but positive in the others. It is shown that deeply subwavelength objects made of such indefinite (hyperbolic) media exhibit a pronounced magnetic dipole resonance that couples strongly to uniform or weakly inhomogeneous magnetic field and provides strong enhancement of the magnetic force, enabling applications such as enhanced magnetic levitation. © 2012 American Physical Society.