1,356 research outputs found

    Mass Hierarchy, Mixing, CP-Violation and Higgs Decay---or Why Rotation is Good for Us

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    The idea of a rank-one rotating mass matrix (R2M2) is reviewed detailing how it leads to ready explanations both for the fermion mass hierarchy and for the distinctive mixing patterns between up and down fermion states, which can be and have been tested against experiment and shown to be fully consistent with existing data. Further, R2M2 is seen to offer, as by-products: (i) a new solution of the strong CP problem in QCD by linking the theta-angle there to the Kobayashi-Maskawa CP-violating phase in the CKM matrix, and (ii) some novel predictions of possible anomalies in Higgs decay observable in principle at the LHC. A special effort is made to answer some questions raised.Comment: 47 pages, 9 figure

    Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

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    Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

    The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver

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    LKB1 is a master kinase that regulates metabolism and growth through adenosine monophosphate-activated protein kinase (AMPK) and 12 other closely related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. Here we report that the salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressors downstream of LKB1 in the liver. The selective SIK inhibitor HG-9-91-01 promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive mutant SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation or activity. Collectively, we demonstrate that the LKB1-SIK pathway functions as a key gluconeogenic gatekeeper in the liver

    A Nonabelian Yang-Mills Analogue of Classical Electromagnetic Duality

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    The classic question of a nonabelian Yang-Mills analogue to electromagnetic duality is here examined in a minimalist fashion at the strictly 4-dimensional, classical field and point charge level. A generalisation of the abelian Hodge star duality is found which, though not yet known to give dual symmetry, reproduces analogues to many dual properties of the abelian theory. For example, there is a dual potential, but it is a 2-indexed tensor TμνT_{\mu\nu} of the Freedman-Townsend type. Though not itself functioning as such, TμνT_{\mu\nu} gives rise to a dual parallel transport, A~μ\tilde{A}_\mu, for the phase of the wave function of the colour magnetic charge, this last being a monopole of the Yang-Mills field but a source of the dual field. The standard colour (electric) charge itself is found to be a monopole of A~μ\tilde{A}_\mu. At the same time, the gauge symmetry is found doubled from say SU(N)SU(N) to SU(N)×SU(N)SU(N) \times SU(N). A novel feature is that all equations of motion, including the standard Yang-Mills and Wong equations, are here derived from a `universal' principle, namely the Wu-Yang (1976) criterion for monopoles, where interactions arise purely as a consequence of the topological definition of the monopole charge. The technique used is the loop space formulation of Polyakov (1980).Comment: We regret that, due to a technical hitch, parts of the reference list were mixed up. This is the corrected version. We apologize to the authors whose papers were misquote

    Chemical Genetic Screen for AMPKα2 Substrates Uncovers a Network of Proteins Involved in Mitosis

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    The energy-sensing AMP-activated protein kinase (AMPK) is activated by low nutrient levels. Functions of AMPK, other than its role in cellular metabolism, are just beginning to emerge. Here we use a chemical genetics screen to identify direct substrates of AMPK in human cells. We find that AMPK phosphorylates 28 previously unidentified substrates, several of which are involved in mitosis and cytokinesis. We identify the residues phosphorylated by AMPK in vivo in several substrates, including protein phosphatase 1 regulatory subunit 12C (PPP1R12C) and p21-activated protein kinase (PAK2). AMPK-induced phosphorylation is necessary for PPP1R12C interaction with 14-3-3 and phosphorylation of myosin regulatory light chain. Both AMPK activity and PPP1R12C phosphorylation are increased in mitotic cells and are important for mitosis completion. These findings suggest that AMPK coordinates nutrient status with mitosis completion, which may be critical for the organism's response to low nutrients during development, or in adult stem and cancer cells.National Institutes of Health (U.S.) (Grant R01-GM068762

    Identification of Impact Craters in Foils from the Stardust Interstellar Dust Collector

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    The Stardust Interstellar Dust Collection tray provides the first opportunity for the direct laboratory-based measurement of contemporary interstellar dust. The total exposed surface of the tray was approximately 0.1 square meters, including 153 square centimeters of Al foil in addition to the silica aerogel tiles that are the primary collection medium. Preliminary examination of aerogel tiles has already revealed 16 tracks from particle impacts with an orientation consistent with an interstellar origin, and to date four of the particles associated with these tracks have a composition consistent with an extraterrestrial origin. Tentative identification of impact craters on three foil samples was also reported previously. Here we present the definitive identification of 20 impact craters on five foils

    Preliminary Examination of the Interstellar Collector of Stardust

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    The findings of the Stardust spacecraft mission returned to earth in January 2006 are discussed. The spacecraft returned two unprecedented and independent extraterrestrial samples: the first sample of a comet and the first samples of contemporary interstellar dust. An important lesson from the cometary Preliminary Examination (PE) was that the Stardust cometary samples in aerogel presented a technical challenge. Captured particles often separate into multiple fragments, intimately mix with aerogel and are typically buried hundreds of microns to millimeters deep in the aerogel collectors. The interstellar dust samples are likely much more challenging since they are expected to be orders of magnitudes smaller in mass, and their fluence is two orders of magnitude smaller than that of the cometary particles. The goal of the Stardust Interstellar Preliminary Examination (ISPE) is to answer several broad questions, including: which features in the interstellar collector aerogel were generated by hypervelocity impact and how much morphological and trajectory information may be gained?; how well resolved are the trajectories of probable interstellar particles from those of interplanetary origin?; and, by comparison to impacts by known particle dimensions in laboratory experiments, what was the mass distribution of the impacting particles? To answer these questions, and others, non-destructive, sequential, non-invasive analyses of interstellar dust candidates extracted from the Stardust interstellar tray will be performed. The total duration of the ISPE will be three years and will differ from the Stardust cometary PE in that data acquisition for the initial characterization stage will be prolonged and will continue simultaneously and parallel with data publications and release of the first samples for further investigation
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