Browsing by Author "Wang, W"

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    Atmospheric neutrino oscillation analysis with subleading effects in Super-Kamiokande I, II, and III
    (Physical Review D - Particles, Fields, Gravitation and Cosmology, 2010-05-20) Wendell, R; Ishihara, C; Abe, K; Hayato, Y; Iida, T; Ikeda, M; Iyogi, K; Kameda, J; Kobayashi, K; Koshio, Y; Kozuma, Y; Miura, M; Moriyama, S; Nakahata, M; Nakayama, S; Obayashi, Y; Ogawa, H; Sekiya, H; Shiozawa, M; Suzuki, Y; Takeda, A; Takenaga, Y; Takeuchi, Y; Ueno, K; Ueshima, K; Watanabe, H; Yamada, S; Yokozawa, T; Hazama, S; Kaji, H; Kajita, T; Kaneyuki, K; McLachlan, T; Okumura, K; Shimizu, Y; Tanimoto, N; Vagins, MR; Dufour, F; Kearns, E; Litos, M; Raaf, JL; Stone, JL; Sulak, LR; Wang, W; Goldhaber, M; Bays, K; Casper, D; Cravens, JP; Kropp, WR; Mine, S; Regis, C; Smy, MB; Sobel, HW; Ganezer, KS; Hill, J; Keig, WE; Jang, JS; Kim, JY; Lim, IT; Albert, J; Fechner, M; Scholberg, K; Walter, CW; Tasaka, S; Learned, JG; Matsuno, S; Watanabe, Y; Hasegawa, T; Ishida, T; Ishii, T; Kobayashi, T; Nakadaira, T; Nakamura, K; Nishikawa, K; Nishino, H; Oyama, Y; Sakashita, K; Sekiguchi, T; Tsukamoto, T; Suzuki, AT; Minamino, A; Nakaya, T; Fukuda, Y; Itow, Y; Mitsuka, G; Tanaka, T; Jung, CK; Lopez, G; McGrew, C; Yanagisawa, C; Tamura, N; Ishino, H; Kibayashi, A; Mino, S; Mori, T; Sakuda, M; Toyota, H; Kuno, Y; Yoshida, M; Kim, SB
    We present a search for nonzero θ13 and deviations of sin2θ23 from 0.5 in the oscillations of atmospheric neutrino data from Super-Kamiokande I, II, and III. No distortions of the neutrino flux consistent with nonzero θ13 are found and both neutrino mass hierarchy hypotheses are in agreement with the data. The data are best fit at Δm2=2.1×10-3eV2, sin2θ13=0.0, and sin2θ23=0.5. In the normal (inverted) hierarchy θ13 and Δm2 are constrained at the one-dimensional 90% C.L. to sin2θ13<0.04(0.09) and 1.9(1.7)×10 -3<Δm2<2.6(2.7)×10-3eV2. The atmospheric mixing angle is within 0.407≤sin2θ23≤0.583 at 90% C.L. © 2010 The American Physical Society.
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    Conflicts in mangrove protected areas through the actor-centred power framework - Insights from China
    (Forest Policy and Economics, 2024-01) Wang, W; Zhai, D; Li, X; Fang, H; Yang, Y
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    Daily House Price Indexes: Construction, Modeling, and Longer-Run Predictions
    (Economic Research Initiatives at Duke (ERID), 2013-06-11) Bollerslev, T; Patton, AJ; Wang, W
    We construct daily house price indexes for ten major U.S. metropolitan areas. Our calculations are based on a comprehensive database of several million residential property transactions and a standard repeat-sales method that closely mimics the procedure used in the construction of the popular monthly Case-Shiller house price indexes. Our new daily house price indexes exhibit similar characteristics to other daily asset prices, with mild autocorrelation and strong conditional heteroskedasticity, which are well described by a relatively simple multivariate GARCH type model. The sample and model-implied correlations across house price index returns are low at the daily frequency, but rise monotonically with the return horizon, and are all commensurate with existing empirical evidence for the existing monthly and quarterly house price series. A simple model of daily house price index returns produces forecasts of monthly house price changes that are superior to various alternative forecast procedures based on lower frequency data, underscoring the informational advantages of our new more finely sampled daily price series.
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    Disrupted junctional membrane complexes and hyperactive ryanodine receptors after acute junctophilin knockdown in mice.
    (Circulation, 2011-03) Van Oort, RJ; Garbino, A; Wang, W; Dixit, SS; Landstrom, AP; Gaur, N; De Almeida, AC; Skapura, DG; Rudy, Y; Burns, AR; Ackerman, MJ; Wehrens, XHT
    Excitation-contraction coupling in striated muscle requires proper communication of plasmalemmal voltage-activated Ca2+ channels and Ca2+ release channels on sarcoplasmic reticulum within junctional membrane complexes. Although previous studies revealed a loss of junctional membrane complexes and embryonic lethality in germ-line junctophilin-2 (JPH2) knockout mice, it has remained unclear whether JPH2 plays an essential role in junctional membrane complex formation and the Ca(2+)-induced Ca(2+) release process in the heart. Our recent work demonstrated loss-of-function mutations in JPH2 in patients with hypertrophic cardiomyopathy.To elucidate the role of JPH2 in the heart, we developed a novel approach to conditionally reduce JPH2 protein levels using RNA interference. Cardiac-specific JPH2 knockdown resulted in impaired cardiac contractility, which caused heart failure and increased mortality. JPH2 deficiency resulted in loss of excitation-contraction coupling gain, precipitated by a reduction in the number of junctional membrane complexes and increased variability in the plasmalemma-sarcoplasmic reticulum distance.Loss of JPH2 had profound effects on Ca2+ release channel inactivation, suggesting a novel functional role for JPH2 in regulating intracellular Ca2+ release channels in cardiac myocytes. Thus, our novel approach of cardiac-specific short hairpin RNA-mediated knockdown of junctophilin-2 has uncovered a critical role for junctophilin in intracellular Ca2+ release in the heart.
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    Junctophilin-2 is necessary for T-tubule maturation during mouse heart development.
    (Cardiovascular research, 2013-10) Reynolds, JO; Chiang, DY; Wang, W; Beavers, DL; Dixit, SS; Skapura, DG; Landstrom, AP; Song, L-S; Ackerman, MJ; Wehrens, XHT
    AIMS:Transverse tubules (TTs) provide the basic subcellular structures that facilitate excitation-contraction (EC) coupling, the essential process that underlies normal cardiac contractility. Previous studies have shown that TTs develop within the first few weeks of life in mammals but the molecular determinants of this development have remained elusive. This study aims to elucidate the role of junctophilin-2 (JPH2), a junctional membrane complex protein, in the maturation of TTs in cardiomyocytes. METHODS AND RESULTS:Using a novel cardiac-specific short-hairpin-RNA-mediated JPH2 knockdown mouse model (Mus musculus; αMHC-shJPH2), we assessed the effects of the loss of JPH2 on the maturation of the ventricular TT structure. Between embryonic day (E) 10.5 and postnatal day (P) 10, JPH2 mRNA and protein levels were reduced by >70% in αMHC-shJPH2 mice. At P8 and P10, knockdown of JPH2 significantly inhibited the maturation of TTs, while expression levels of other genes implicated in TT development remained mostly unchanged. At the same time, intracellular Ca(2+) handling was disrupted in ventricular myocytes from αMHC- shJPH2 mice, which developed heart failure by P10 marked by reduced ejection fraction, ventricular dilation, and premature death. In contrast, JPH2 transgenic mice exhibited accelerated TT maturation by P8. CONCLUSION:Our findings suggest that JPH2 is necessary for TT maturation during postnatal cardiac development in mice. In particular, JPH2 may be critical in anchoring the invaginating sarcolemma to the sarcoplasmic reticulum, thereby enabling the maturation of the TT network.
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    Mutation E169K in junctophilin-2 causes atrial fibrillation due to impaired RyR2 stabilization.
    (Journal of the American College of Cardiology, 2013-11) Beavers, DL; Wang, W; Ather, S; Voigt, N; Garbino, A; Dixit, SS; Landstrom, AP; Li, N; Wang, Q; Olivotto, I; Dobrev, D; Ackerman, MJ; Wehrens, XHT
    This study sought to study the role of junctophilin-2 (JPH2) in atrial fibrillation (AF).JPH2 is believed to have an important role in sarcoplasmic reticulum (SR) Ca(2+) handling and modulation of ryanodine receptor Ca(2+) channels (RyR2). Whereas defective RyR2-mediated Ca(2+) release contributes to the pathogenesis of AF, nothing is known about the potential role of JPH2 in atrial arrhythmias.Screening 203 unrelated hypertrophic cardiomyopathy patients uncovered a novel JPH2 missense mutation (E169K) in 2 patients with juvenile-onset paroxysmal AF (pAF). Pseudoknock-in (PKI) mouse models were generated to determine the molecular defects underlying the development of AF caused by this JPH2 mutation.PKI mice expressing E169K mutant JPH2 exhibited a higher incidence of inducible AF than wild type (WT)-PKI mice, whereas A399S-PKI mice expressing a hypertrophic cardiomyopathy-linked JPH2 mutation not associated with atrial arrhythmias were not significantly different from WT-PKI. E169K-PKI but not A399A-PKI atrial cardiomyocytes showed an increased incidence of abnormal SR Ca(2+) release events. These changes were attributed to reduced binding of E169K-JPH2 to RyR2. Atrial JPH2 levels in WT-JPH2 transgenic, nontransgenic, and JPH2 knockdown mice correlated negatively with the incidence of pacing-induced AF. Ca(2+) spark frequency in atrial myocytes and the open probability of single RyR2 channels from JPH2 knockdown mice was significantly reduced by a small JPH2-mimicking oligopeptide. Moreover, patients with pAF had reduced atrial JPH2 levels per RyR2 channel compared to sinus rhythm patients and an increased frequency of spontaneous Ca(2+) release events.Our data suggest a novel mechanism by which reduced JPH2-mediated stabilization of RyR2 due to loss-of-function mutation or reduced JPH2/RyR2 ratios can promote SR Ca(2+) leak and atrial arrhythmias, representing a potential novel therapeutic target for AF.
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    NASH: Toward End-to-End Neural Architecture for Generative Semantic Hashing.
    (CoRR, 2018) Shen, D; Su, Q; Chapfuwa, P; Wang, W; Wang, G; Carin, L; Henao, R
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    Redox rhythm reinforces the circadian clock to gate immune response.
    (Nature, 2015-07-23) Zhou, M; Wang, W; Karapetyan, S; Mwimba, M; Marques, J; Buchler, NE; Dong, X
    Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism's metabolic activities. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant's redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism.
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    Reduced junctional Na+/Ca2+-exchanger activity contributes to sarcoplasmic reticulum Ca2+ leak in junctophilin-2-deficient mice.
    (American journal of physiology. Heart and circulatory physiology, 2014-11) Wang, W; Landstrom, AP; Wang, Q; Munro, ML; Beavers, D; Ackerman, MJ; Soeller, C; Wehrens, XHT
    Expression silencing of junctophilin-2 (JPH2) in mouse heart leads to ryanodine receptor type 2 (RyR2)-mediated sarcoplasmic reticulum (SR) Ca(2+) leak and rapid development of heart failure. The mechanism and physiological significance of JPH2 in regulating RyR2-mediated SR Ca(2+) leak remains elusive. We sought to elucidate the role of JPH2 in regulating RyR2-mediated SR Ca(2+) release in the setting of cardiac failure. Cardiac myocytes isolated from tamoxifen-inducible conditional knockdown mice of JPH2 (MCM-shJPH2) were subjected to confocal Ca(2+) imaging. MCM-shJPH2 cardiomyocytes exhibited an increased spark frequency width with altered spark morphology, which caused increased SR Ca(2+) leakage. Single channel studies identified an increased RyR2 open probability in MCM-shJPH2 mice. The increase in spark frequency and width was observed only in MCM-shJPH2 and not found in mice with increased RyR2 open probability with native JPH2 expression. Na(+)/Ca(2+)-exchanger (NCX) activity was reduced by 50% in MCM-shJPH2 with no detectable change in NCX expression. Additionally, 50% inhibition of NCX through Cd(2+) administration alone was sufficient to increase spark width in myocytes obtained from wild-type mice. Additionally, superresolution analysis of RyR2 and NCX colocalization showed a reduced overlap between RyR2 and NCX in MCM-shJPH2 mice. In conclusion, decreased JPH2 expression causes increased SR Ca(2+) leakage by directly increasing open probability of RyR2 and by indirectly reducing junctional NCX activity through increased dyadic cleft Ca(2+). This demonstrates two novel and independent cellular mechanisms by which JPH2 regulates RyR2-mediated SR Ca(2+) leak and heart failure development.